FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sarkar, S Svoboda, M De Beaumont, R Freedman, AS AF Sarkar, S Svoboda, M De Beaumont, R Freedman, AS TI The role of AKT and RAFTK in beta 1 integrin mediated survival of precursor B-acute lymphoblastic leukemia cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE integrin; leukemia; kinase; adhesion ID FOCAL TYROSINE KINASE; ACTIVATED PROTEIN-KINASE; ADHESION KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; ANTIGEN RECEPTOR; STROMAL CELLS; PHOSPHORYLATION; STIMULATION; P130(CAS); APOPTOSIS AB In this study, we report that the related adhesion focal tyrosine kinase RAFTK, is an upstream kinase in beta1 integrin mediated activation of Akt. Stimulation through beta1 integrins by fibronectin reversed apoptosis induced by adriamycin. Inhibitors of phosphatidylinositol 3-kinase (PI3 kinase)/Akt (LY 294002), tyrosine kinases (Herbimycin-A) and the cytotoxic agent adriamycin induced apoptosis of REH cells. beta1 integrin ligation induced activation of Akt, and tyrosine phosphorylation of RAFTK and FAK, but not SYK in REH cells. This suggested that RAFTK and FAK activation might be linked to Akt activation. Evidence that RAFTK is a modulator of Akt came from phorbol myristic acetate (PMA) stimulation. RAFTK and Akt were activated but FAK was not. Using fibroblasts from FAK -/- mice, which express high levels of RAFTK, fibronectin plating enhanced Akt activation. Pretreatment of REH cells with a PI3 kinase/Akt inhibitor LY 294002 did not inhibit RAFTK tyrosine phosphorylation showing that RAFTK is upstream of PI3k/Akt. Further evidence for a link between RAFTK tyrosine phosphorylation and Akt activation was the observation that the p85 subunit of PI3 kinase associated with RAFTK following integrin ligation in REH cells. These results suggest that RAFTK plays an antiapoptotic role through the activation of Akt. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Sarkar, Sibaji/0000-0002-2204-3031 FU NCI NIH HHS [CA81494] NR 48 TC 16 Z9 20 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 AUG PY 2002 VL 43 IS 8 BP 1663 EP 1671 DI 10.1080/1042819021000003009 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 580FF UT WOS:000177223900018 PM 12400610 ER PT J AU McLean, MA Busza, AL Wald, LL Simister, RJ Barker, GJ Williams, SR AF McLean, MA Busza, AL Wald, LL Simister, RJ Barker, GJ Williams, SR TI In vivo GABA+ measurement at 1.5T using a PRESS-localized double quantum filter SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE GABA; human brain; 1H-MRS; spectral editing; multiple quantum filter ID MAGNETIC-RESONANCE-SPECTROSCOPY; GAMMA-AMINOBUTYRIC-ACID; HUMAN BRAIN; SEIZURE CONTROL; EPILEPSY; HOMOCARNOSINE; VIGABATRIN; SUPPRESSION; ARTIFACTS; SPECTRA AB A point-resolved spectroscopy (PRESS)-localized double quantum filter was implemented on a 1.5T clinical scanner for the estimation of gamma-amino butyric acid (GABA) concentrations in vivo. Several calibrations were found to be necessary for consistent results to be obtained. The apparent filter yield was approximately 38%; filter strength was sufficient to reduce the singlet metabolite peaks in vivo to below the level of the noise. Metabolite-nulled experiments were performed, which confirmed that significant overlap occurred between macromolecule signals and the GABA resonance at 3.1 ppm. Although the multiplet arm at 2.9 ppm was confirmed to be relatively free of contamination with macromolecules, some contribution from these and from peptides is likely to remain; therefore, the term GABA+ is used. GABA+ concentrations were estimated relative to creatine (Cr) at the same echo time (TE) in a group of controls, studied on two occasions. The GABA+ concentration in 35-ml regions of interest (ROIs) in the occipital lobe was found to be 1.4 +/- 0.2 mM, with scan-rescan repeatability of 38%. C1 Natl Soc Epilepsy, MRI Unit, Gerrards Cross SL9 0RJ, Bucks, England. Neurol Inst, Dept Clin & Expt Epilepsy, London, England. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. UCL, Inst Neurol, Dept Neuroinflammat, London, England. Univ Manchester, Imaging Sci & Biomed Engn, Manchester, Lancs, England. RP McLean, MA (reprint author), Natl Soc Epilepsy, MRI Unit, Chalfont St Peter, Gerrards Cross SL9 0RJ, Bucks, England. EM m.mclean@ion.ucl.ac.uk RI Barker, Gareth/C-9616-2009; McLean, Mary/L-5128-2014; Wald, Lawrence/D-4151-2009; Williams, Stephen/C-8945-2011 OI Barker, Gareth/0000-0002-5214-7421; McLean, Mary/0000-0002-3752-0179; Williams, Stephen/0000-0001-5940-1675 FU Multiple Sclerosis Society [491] NR 29 TC 29 Z9 33 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD AUG PY 2002 VL 48 IS 2 BP 233 EP 241 DI 10.1002/mrm.10208 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 577UK UT WOS:000177080300003 PM 12210931 ER PT J AU Potosky, AL Warren, JL Riedel, ER Klabunde, CN Earle, CC Begg, CB AF Potosky, AL Warren, JL Riedel, ER Klabunde, CN Earle, CC Begg, CB TI Measuring complications of cancer treatment using the SEER-Medicare data SO MEDICAL CARE LA English DT Article; Proceedings Paper CT SEER-Medicare Workshop CY NOV, 2000 CL BETHESDA, MARYLAND DE neoplasms; outcome assessment; adverse effects; acute complications; chronic complications; measurement; SEER; Medicare ID ADMINISTRATIVE DATA; PROSTATE-CANCER; CLAIMS DATA; OUTCOMES; MORTALITY; ACCURACY; SURGERY; VOLUME; CARE AB BACKGROUND. The linkage of SEER registry data with Medicare claims allows the longitudinal tracking of health care and outcomes for patients after a cancer diagnosis. One category of outcomes amenable to research using Medicare claims is complications of cancer treatments: the unintentional, adverse side effects or sequelae of interventions used to treat or palliate cancer patients. RESEARCH DESIGN. The authors review some of the methods and limitations of using Medicare claims to identify both acute and chronic complications of cancer treatments, and present an original analysis comparing survey based and claims-based complications following radical prostatectomy for prostate cancer to illustrate some of the potential limitations inherent in using claims for this purpose. RESULTS. Utility of the Medicare claims for identifying postdischarge complications varies by the patient type, the initial treatment used, and any subsequent treatment of complications. For patients undergoing surgical interventions, Medicare claims can be used to identify most acute inpatient complications. However, claims data cannot be used as effectively in the long-term to capture chronic complications, particularly when the complication does not consistently prompt an intervention. CONCLUSION. Researchers who use the SEER-Medicare-linked database to assess long-term complications of cancer treatments should exercise caution when designing and interpreting studies. Ideally, for studies of most chronic complications of cancer care, validation studies similar to the one performed here would provide valuable additional evidence to assess the credibility of conclusions based on claims data. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Potosky, AL (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN Room 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 17 TC 71 Z9 71 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2002 VL 40 IS 8 SU S BP 62 EP 68 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581NY UT WOS:000177300200009 ER PT J AU Nattinger, AB Schapira, MM Warren, JL Earle, CC AF Nattinger, AB Schapira, MM Warren, JL Earle, CC TI Methodological issues in the use of administrative claims data to study surveillance after cancer treatment SO MEDICAL CARE LA English DT Article; Proceedings Paper CT SEER-Medicare Workshop CY NOV, 2000 CL BETHESDA, MARYLAND DE cancer surveillance; Medicare claims data; Tumor Registry data ID BREAST-CANCER; MEDICARE BENEFICIARIES; COLORECTAL-CANCER; FOLLOW-UP; MAMMOGRAPHY; CARE AB BACKGROUND. Administrative claims databases linked to tumor registry data provide an excellent opportunity for studying the follow-up care of cancer patients. RESEARCH DESIGN. Methodological principles of study design are reviewed, using examples drawn from the recently published literature. RESULTS. Most follow-up care is outpatient-based. Therefore, in studies using Medicare claims, the patient should be eligible,for Medicare Part B and should not be enrolled in a Medicare HMO. In studies of surveillance testing, it may be appropriate to exclude subjects who are near death, in a hospice, or in whom a new or recurrent cancer develops. The definition of the period for measurements of surveillance testing requires consideration, as does periodicity in patterns of testing. Several analytic methods can be employed, from proportions undergoing testing to survival analysis methods. Measurement of 'surveillance tests' among control subjects (those without cancer) may be useful for comparison with cancer patients. To date, administrative claims data have been most useful in studies investigating the quality of, and disparities in, cancer care. CONCLUSION. With appropriate attention to methodological issues, linked tumor registry and administrative databases can provide important insights into the quality of survivorship care for cancer. C1 Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Nattinger, AB (reprint author), Div Gen Internal Med, FEC Med Off Bldg,Suite 4200,9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 13 TC 21 Z9 21 U1 0 U2 1 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 AUG PY 2002 VL 40 IS 8 SU S BP 69 EP 74 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581NY UT WOS:000177300200010 ER PT J AU Earle, CC Nattinger, AB Potosky, AL Lang, K Mallick, R Berger, M Warren, JL AF Earle, CC Nattinger, AB Potosky, AL Lang, K Mallick, R Berger, M Warren, JL TI Identifying cancer relapse using SEER-Medicare data SO MEDICAL CARE LA English DT Article; Proceedings Paper CT SEER-Medicare Workshop CY NOV, 2000 CL BETHESDA, MARYLAND DE cancer; health services research; administrative data ID CHEMOTHERAPY AB INTRODUCTION. Tumor registries capture valid information at the time of cancer diagnosis, but often do not conduct longitudinal follow-up evaluations. However, investigators may be interested in questions relating to subsequent relapsed disease. Linking administrative data to registry data, as in the creation of the SEER (Surveillance, Epidemiology, and End Results) and Medicare data set, can provide the ability to infer the occurrence of relapse in selected situations. METHODS. The authors created different algorithms to detect relapse of acute myelogenous leukemia (AML). A retrospective cohort of patients with AML was identified, and both their billing data and medical records were obtained. The algorithms were then applied to the billing data, the results were compared with medical record review. RESULTS. Eighty-nine patients were identified, of whom 22 were treated for relapsed AML. The sensitivity of the best algorithm for detecting relapse was 86%, and the specificity 99%, with a positive predictive value of 95% and a negative predictive value of 96%. CONCLUSIONS. Identification of relapse from SEER-Medicare data using clinical algorithms is feasible for cancers where a majority of patients receive treatment for relapse, without a "watch and wait" strategy, and where that treatment is with a modality that can be detected in billing data (ie, intravenous chemotherapy, radiation, surgery, or all three). Optimal analytic situations are ones in which the investigator is mostly interested in positive predictive value, less interested in sensitivity, and wants to evaluate outcomes among those patients who receive treatment for their relapsed disease. However, the accuracy of such an approach for cancers other than AML has not yet been established. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Med Coll Wisconsin, Madison, WI USA. NCI, Appl Res Program, Bethesda, MD USA. Boston Hlth Econ, Boston, MA USA. Wyeth Ayerst Res, Madison, NJ USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. NR 9 TC 59 Z9 60 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2002 VL 40 IS 8 SU S BP 75 EP 81 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 581NY UT WOS:000177300200011 ER PT J AU Killoran, JH Giraud, JY Chin, L AF Killoran, JH Giraud, JY Chin, L TI A dosimetric comparison of two multileaf collimator designs SO MEDICAL PHYSICS LA English DT Article DE MLC dosimetry; MLC design ID PENUMBRA; FIELDS AB We present the results of measurements designed to compare two different multileaf collimator (MLC) designs using a novel evaluation technique. The MLC designs evaluated were: a "single-focused" MLC (SF-MLC) mounted below the jaws, and a "double-focused" MLC, which is a complete replacement for the lower jaws. The ability of each MLC to conform isodose lines to a prescribed field edge (PFE) was evaluated using film dosimetry. Circular fields, centered on axis and off axis, were used because they produce a range of "angles of approach" between the MLC leaves and the PFE. They also have the advantage that for an ideal field shaping system the resulting isodoses are concentric perfect circles, a well-defined basis for evaluation. The amplitude of the oscillations of the 50% isodose line about the PFE and the penumbra width as determined by the 20%, 80%, and 90% isodose lines was examined. We observe that the 50% isodose line oscillates around the PFE with greater amplitude for SF-MLC. We attribute this, at least in part, to the rounded ends of the SF-MLC leaves. However, the SF-MLC has a noticeably sharper penumbra, which we attribute to its position further from the source. We conclude that these results are relevant for accurate dosimetric modeling of these devices. (C) 2002 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Childrens Hosp,Dept Radiat Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02215 USA. CHU Grenoble, Serv Cancerol Radiotherapie, F-38053 Grenoble, France. RP Harvard Univ, Sch Med, Childrens Hosp,Dept Radiat Oncol, Dana Farber Canc Inst,Brigham & Womens Hosp, Boston, MA 02215 USA. EM jkilloran@lroc.harvard.edu NR 14 TC 15 Z9 17 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD AUG PY 2002 VL 29 IS 8 BP 1752 EP 1758 DI 10.1118/1.1485976 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 584VR UT WOS:000177489900014 PM 12201422 ER PT J AU Hayashi, T Hideshima, T Akiyama, M Richardson, P Schlossman, RL Chauhan, D Munshi, NC Waxman, S Anderson, KC AF Hayashi, T Hideshima, T Akiyama, M Richardson, P Schlossman, RL Chauhan, D Munshi, NC Waxman, S Anderson, KC TI Arsenic trioxide inhibits growth of human multiple myeloma cells in the bone marrow microenvironment SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; NF-KAPPA-B; INDUCED APOPTOSIS; DRUG-RESISTANCE; PLASMA-CELLS; DENDRITIC CELLS; KINASE PATHWAY; STROMAL CELLS; INTERLEUKIN-6; LINES AB Multiple myeloma (MM) remains incurable with current therapies, and novel biologically based therapies are urgently needed. Thalidomide and its analogues, as well as proteasome inhibitors, are examples of such novel agents that target both the myeloma cell and its microenvironment and can overcome classical drug resistance. In this study we demonstrate that arsenic trioxide (As2O3) mediates anti-MM activity both directly on tumor cells and indirectly by inhibiting production of myeloma growth and survival factors in the bone marrow (BM) microenvironment. Specifically, As2O3 at clinically achievable levels (2-5 muM) induces apoptosis even of drug-resistant MM cell lines and patient cells via caspase-9 activation, enhances the MM cell apoptosis induced by dexamethasone, and can overcome the antiapoptotic effects of interleukin 6. As2O3, also acts in the BM microenvironment to decrease MM cell binding to BM stromal cells, inhibits interleukin 6 and vascular endothelial growth factor secretion induced by MM cell adhesion, and blocks proliferation of MM cells adherent to BM stromal cells. These studies provide the rationale for clinical trials of As2O3, either alone or together with dexamethasone, to overcome classical drug resistance and improve outcome in patients with MM. C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Mt Sinai Canc Ctr, Div Med Oncol, New York, NY 10029 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1R01 CA 85748-01A1]; PHS HHS [P0-1 78378] NR 59 TC 109 Z9 126 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2002 VL 1 IS 10 BP 851 EP 860 PG 10 WC Oncology SC Oncology GA 607BN UT WOS:000178770700011 PM 12492118 ER PT J AU DiFiglia, M AF DiFiglia, M TI Huntingtin fragments that aggregate go their separate ways SO MOLECULAR CELL LA English DT Review ID NEURONAL INTRANUCLEAR INCLUSIONS; PROTEIN; BRAIN AB N-terminal region of mutant huntingtin forms intranuclear and cytoplasmic aggregates in neurons that may contribute to neuronal death in Huntington's disease. Lunkes et al. (2002) show that different endoprotease-cleaved huntingtin fragments form nuclear and cytoplasmic inclusions. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02114 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St, Charlestown, MA 02114 USA. NR 11 TC 18 Z9 20 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG PY 2002 VL 10 IS 2 BP 224 EP 225 DI 10.1016/S1097-2765(02)00609-3 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 586LD UT WOS:000177584700006 PM 12191468 ER PT J AU Bastepe, M Gunes, Y Perez-Villamil, B Hunzelman, J Weinstein, LS Juppner, H AF Bastepe, M Gunes, Y Perez-Villamil, B Hunzelman, J Weinstein, LS Juppner, H TI Receptor-mediated adenylyl cyclase activation through XL alpha s, the extra-large variant of the stimulatory G protein alpha-subunit SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MOUSE GNAS LOCUS; HEREDITARY OSTEODYSTROPHY; PARATHYROID-HORMONE; GENE; EXPRESSION; TRANSCRIPTS; ANTISENSE; PSEUDOHYPOPARATHYROIDISM; METHYLATION; RESIDUES AB XLalphas, the large variant of the stimulatory G protein a subunit (Gsalpha), is derived from GNAS1 through the use of an alternative first exon and promoter. Gsa and XLalphas have distinct amino-terminal domains, but are identical over the carboxyl-terminal portion encoded by exons 2-13. XLalphas can mimic some functions of Gsalpha, including betagamma interaction and adenylyl cyclase stimulation. However, previous attempts to demonstrate coupling of XLalphas to typically Gs-coupled receptors have not been successful. We now report the generation of murine cell lines that carry homozygous disruption of Gnas exon 2, and are therefore null for endogenous XLalphas and Gsalpha (Gnas(E2-/E2-)). Gnas(E2-/E2-) cells transfected with plasmids encoding XLalphas and different heptahelical receptors, including the beta2-adrenergic receptor and receptors for PTH, TSH, and CRF, showed agonist-mediated cAMP accumulation that was indistinguishable from that observed with cells transiently coexpressing Gsalpha and these receptors. Our findings thus indicate that XLalphas is capable of functionally coupling to receptors that normally act via Gsalpha. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,WEL 5, Boston, MA 02114 USA. FU PHS HHS [R01 46718-06] NR 40 TC 86 Z9 87 U1 2 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD AUG PY 2002 VL 16 IS 8 BP 1912 EP 1919 DI 10.1210/me.2002-0054 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 577WV UT WOS:000177086400016 PM 12145344 ER PT J AU Bracy, JL Iacomini, J AF Bracy, JL Iacomini, J TI Engraftment of genetically modified bone marrow cells in sensitized hosts SO MOLECULAR THERAPY LA English DT Article DE transplantation; tolerance; B cells; carbohydrate; xenotransplantation; Gal(alpha 1,3)Gal ID HUMAN NATURAL ANTIBODIES; RETROVIRAL GENE-THERAPY; ANTI-GAL ANTIBODY; MIXED CHIMERISM; XENOGRAFT REJECTION; B-CELLS; XENOTRANSPLANTATION; INDUCTION; EPITOPES; MICE AB Expression of retrovirally transduced genes in bone marrow-derived cells can be used to establish stable long-term B- and T-cell tolerance. To determine whether preexisting antibodies may prohibit the use of gene therapy to establish tolerance, we examined the extent to which preexisting antibodies specific for the carbohydrate antigen Galalpha1-3Galbeta1-4GlcNAc-R (alphaGal) could affect engraftment and development of bone marrow progenitors expressing the enzyme UDPgalactose: beta-D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha(1-3)galactosyltransferase (E.C. 2.4.1.151), or simply alphaGT, which synthesizes the alphaGal epitope. Groups of alphaGT knockout mice (GT(o) mice) lacking alphaGal were presensitized to alphaGal by immunization and then lethally irradiated and reconstituted with varying numbers of alphaGT-transduced syngeneic bone marrow cells. Whereas unimmunized controls were reconstituted with as few as 2 X 10(6) transduced cells, a significant fraction of immunized mice reconstituted with 2 x 10(6) or 4 x 10(6) alphaGT-transduced cells failed to undergo bone marrow engraftment and died. Immunized mice in which radiation protection was achieved failed to express alphaGal. However, radiation protection and expression of alphaGal on bone marrow-derived cells, resulting in tolerance, could be achieved by increasing the number of transduced cells used to reconstitute immunized mice. Thus, although high levels of preexisting antibodies can be a significant barrier to engraftment, this barrier can be overcome by increasing the number of transduced cells used for reconstitution. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI44268, R01 AI43619, T32 AI 07529] NR 25 TC 5 Z9 5 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 AUG PY 2002 VL 6 IS 2 BP 252 EP 257 DI 10.1006/mthe.2002.0651 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 582TX UT WOS:000177368200018 PM 12161192 ER PT J AU Pelletier, L Stern, CA Pypaert, M Sheff, D Ngo, HM Roper, N He, CY Hu, K Toomre, D Coppens, I Roos, DS Joiner, KA Warren, G AF Pelletier, L Stern, CA Pypaert, M Sheff, D Ngo, HM Roper, N He, CY Hu, K Toomre, D Coppens, I Roos, DS Joiner, KA Warren, G TI Golgi biogenesis in Toxoplasma gondii SO NATURE LA English DT Article ID CELL-CYCLE; APPARATUS; COMPLEX; ER; MAINTENANCE; DYNAMICS; MITOSIS; STAGE; EXIT AB Two models have been put forward to explain the growth of new Golgi during the cell cycle. The first suggests that a new Golgi grows out of the endoplasmic reticulum by de novo synthesis(1). The second suggests that a pre-existing Golgi is needed for the growth of a new one, that is, the Golgi is an autonomously replicating organelle(2). To resolve this issue, we have exploited the simplicity of the apicomplexan parasite Toxoplasma gondii(3), which has only a single Golgi stack(4). Here we show, by using video fluorescence microscopy and three-dimensional reconstructions of serial thin sections, that the Golgi grows by a process of lateral extension followed by medial fission. Further fission leads to the inheritance by each daughter of a pair of Golgi structures, which then coalesce to re-form a single Golgi. Our results indicate that new Golgi grow by autonomous duplication and raise the possibility that the Golgi is a paired structure that is analogous to centrioles(5). C1 Yale Univ, Sch Med, Ludwig Inst Canc Res, Dept Cell Biol, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06520 USA. Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. RP Warren, G (reprint author), Yale Univ, Sch Med, Ludwig Inst Canc Res, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA. RI Sheff, David/A-1269-2007; He, Cynthia/H-9789-2012 NR 29 TC 113 Z9 123 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 1 PY 2002 VL 418 IS 6897 BP 548 EP 552 DI 10.1038/nature00946 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 579EE UT WOS:000177162800044 PM 12152082 ER PT J AU Perez, JM Josephson, L O'Loughlin, T Hogemann, D Weissleder, R AF Perez, JM Josephson, L O'Loughlin, T Hogemann, D Weissleder, R TI Magnetic relaxation switches capable of sensing molecular interactions SO NATURE BIOTECHNOLOGY LA English DT Article ID NANOPARTICLE PROBES; MULTIPLE SAMPLES; DNA; NMR; BIOSENSOR; POLYNUCLEOTIDES; NANOCRYSTALS AB Highly sensitive, efficient, and high-throughput biosensors are required for genomic and proteomic data acquisition in complex biological samples and potentially for in vivo applications. To facilitate these studies, we have developed biocompatible magnetic nanosensors that act as magnetic relaxation switches (MRS) to detect molecular interactions in the reversible self-assembly of disperse magnetic particles into stable nanoassemblies. Using four different types of molecular interactions (DNA-DNA, protein-protein, protein-small molecule, and enzyme reactions) as model systems, we show that the MRS technology can be used to detect these interactions with high efficiency and sensitivity using magnetic relaxation measurements including magnetic resonance imaging (MRI). Furthermore, the magnetic changes are detectable in turbid media and in whole-cell lysates without protein purification. The developed magnetic nanosensors can be used in a variety of biological applications such as in homogenous assays, as reagents in miniaturized microfluidic systems, as affinity ligands for rapid and high-throughput magnetic readouts of arrays, as probes for magnetic force microscopy, and potentially for in vivo imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. FU NCI NIH HHS [P50 CA86355] NR 31 TC 548 Z9 557 U1 23 U2 160 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2002 VL 20 IS 8 BP 816 EP 820 DI 10.1038/nbt720 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 579MU UT WOS:000177182500033 PM 12134166 ER PT J AU Jeon, NL Baskaran, H Dertinger, SKW Whitesides, GM Van de Water, L Toner, M AF Jeon, NL Baskaran, H Dertinger, SKW Whitesides, GM Van de Water, L Toner, M TI Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device SO NATURE BIOTECHNOLOGY LA English DT Article ID POLYMORPHONUCLEAR LEUKOCYTES; CHEMOKINES; CELLS; ASSAY; SEPARATION; CYTOKINES; RECEPTORS; MIGRATION; SYSTEMS; AGAROSE AB Although a wealth of knowledge about chemotaxis has accumulated in the past 40 years, these studies have been hampered by the inability of researchers to generate simple linear gradients instantaneously and to maintain them at steady state. Here we describe a device microfabricated by soft lithography and consisting of a network of microfluidic channels that can generate spatially and temporally controlled gradients of chemotactic factors. When human neutrophils are positioned within a microchannel, their migration in simple and complex interleukin-8 (IL-8) gradients can be tested. The cells exhibit strong directional migration toward increasing concentrations of IL-8 in linear gradients. Neutrophil migration halts abruptly when cells encounter a sudden drop in the chemoattractant concentration to zero ("cliff" gradient). When neutrophils are challenged with a gradual increase and decrease in chemoattractant ("hill" gradient), however, the cells traverse the crest of maximum concentration and migrate further before reversing direction. The technique described in this paper provides a robust method to investigate migratory cells under a variety of conditions not accessible to study by earlier techniques. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. RP Toner, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13322]; NIGMS NIH HHS [GM 56442] NR 38 TC 469 Z9 476 U1 5 U2 80 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2002 VL 20 IS 8 BP 826 EP 830 DI 10.1038/nbt712 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 579MU UT WOS:000177182500035 PM 12091913 ER PT J AU Sagot, I Rodal, AA Moseley, J Goode, BL Pellman, D AF Sagot, I Rodal, AA Moseley, J Goode, BL Pellman, D TI An actin nucleation mechanism mediated by Bni1 and profilin SO NATURE CELL BIOLOGY LA English DT Article ID YEAST ARP2/3 COMPLEX; IN-VIVO; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE EXCHANGE; FISSION YEAST; PROTEIN; POLYMERIZATION; ACTIVATION; FILAMENTS; ROLES AB Formins are required for cell polarization and cytokinesis, but do not have a defined biochemical activity. In Saccharomyces cerevisiae, formins and the actin-monomer-binding protein profilin are specifically required to assemble linear actin structures called 'actin cables'. These structures seem to be assembled independently of the Arp2/3 complex, the only well characterized cellular mediator of actin nucleation. Here, an activated yeast formin was purified and found to promote the nucleation of actin filaments in vitro. Formin-dependent actin nucleation was stimulated by profilin. Thus, formin and profilin mediate actin nucleation by an Arp2/3-independent mechanism. These findings suggest that distinct actin nucleation mechanisms may underlie the assembly of different actin cytoskeletal structures. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Hematol, Childrens Hosp, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Brandeis Univ, Rosenstiel Med Ctr, Dept Biol, Waltham, MA 02454 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst,Childrens Hosp, 44 Binney ST, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM61345] NR 30 TC 327 Z9 332 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2002 VL 4 IS 8 BP 626 EP 631 DI 10.1038/ncb834 PG 6 WC Cell Biology SC Cell Biology GA 579WK UT WOS:000177201100020 PM 12134165 ER PT J AU Vetter, DE Li, CE Zhao, LY Contarino, A Liberman, MC Smith, GW Marchuk, Y Koob, GF Heinemann, SF Vale, W Lee, KF AF Vetter, DE Li, CE Zhao, LY Contarino, A Liberman, MC Smith, GW Marchuk, Y Koob, GF Heinemann, SF Vale, W Lee, KF TI Urocortin-deficient mice show hearing impairment and increased anxiety-like behavior SO NATURE GENETICS LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; RAT OLIVOCOCHLEAR NEURONS; TYPE-2 CRF RECEPTORS; GENE-RELATED PEPTIDE; LATERAL-LINE ORGAN; GUINEA-PIG; HORMONE RECEPTOR-2; UROTENSIN-I; MAMMALIAN COCHLEA; BASILAR-MEMBRANE AB Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of urocortin, we have generated mice carrying a null mutation of the urocortin gene. Urocortin-deficient mice have normal basal feeding behavior and stress responses, but show heightened anxiety-like behaviors in the elevated plus maze and open-field tests. In addition, hearing is impaired in the mutant mice at the level of the inner ear, suggesting that urocortin is involved in the normal development of cochlear sensory-cell function. These results provide the first example of a function for any peptidergic system in hearing. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. Scripps Res Inst, Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Lee, KF (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Contarino, Angelo/C-9429-2014; koob, george/P-8791-2016 FU NIDCD NIH HHS [P30 DC005209] NR 44 TC 108 Z9 111 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2002 VL 31 IS 4 BP 363 EP 369 DI 10.1038/ng914 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 578XV UT WOS:000177147100010 PM 12091910 ER PT J AU Apostolou, I Sarukhan, A Klein, L von Boehmer, H AF Apostolou, I Sarukhan, A Klein, L von Boehmer, H TI Origin of regulatory T cells with known specificity for antigen SO NATURE IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; IN-VIVO; THYMIC EPITHELIUM; EFFECTOR FUNCTION; TRANSGENIC MICE; IMMUNE-RESPONSE; B-CELLS; RECEPTOR; SELECTION; UNRESPONSIVENESS AB T cell receptor agonists can induce the differentiation of regulatory T (T-R) cells. We report here that the immunoglobulin kappa-controlled expression of an agonist in different cell types correlated with the phenotype of the generated TR cells. We found that aberrant expression on thymic stroma yielded predominantly CD4(+)CD25(+) T-R cells, which-under physiological conditions-may be induced by ectopically expressed organ-specific antigens and thus prevent organ-specific autoimmunity. Expression of the agonist antigen by nonactivated hematopoietic cells produced mostly CD4(+)CD25(-) T-R cells. This subset can be derived from mature monospecific T cells without "tutoring" by other T cells and can be generated in the absence of a functioning thymus. Suppression of CD4(+)T cell proliferative responses by both CD25(+) and CD25(-) subsets was interleukin 10 (IL-10)-independent and was overcome by IL-2. These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Fac Necker, INSERM, U345, F-75730 Paris 15, France. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 NR 40 TC 625 Z9 646 U1 2 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2002 VL 3 IS 8 BP 756 EP 763 DI 10.1038/ni816 PG 8 WC Immunology SC Immunology GA 578LF UT WOS:000177118500015 PM 12089509 ER PT J AU Freeman, GJ Sharpe, AH Kuchroo, VK AF Freeman, GJ Sharpe, AH Kuchroo, VK TI Protect the killer: CTLs need defenses against the tumor SO NATURE MEDICINE LA English DT Editorial Material ID B7 FAMILY; LYMPHOCYTES; ACTIVATION; RECEPTOR; MEMBER; B7-H1 AB Evasion of the immune system is an all too common feature of cancer. A new study suggests one evasion mechanism: induction of T-cell apoptosis through B7-H1, a molecule expressed on the surface of many tumor cells ( pages 793 - 800). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 12 TC 7 Z9 9 U1 2 U2 3 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 AUG PY 2002 VL 8 IS 8 BP 787 EP 789 DI 10.1038/nm0802-787 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 579WJ UT WOS:000177200900020 PM 12152031 ER PT J AU Ahveninen, J Kahkonen, S Pennanen, S Liesivuori, J Ilmoniemi, RJ Jaaskelainen, IP AF Ahveninen, J Kahkonen, S Pennanen, S Liesivuori, J Ilmoniemi, RJ Jaaskelainen, IP TI Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans SO NEUROIMAGE LA English DT Article DE attention; auditory cortex; event-related potentials; electroencephalography; magnetoencephalography; mismatch negativity; P3; P3a; RON; serotonin; tryptophan depletion ID EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; SELECTIVE ATTENTION; HEALTHY-VOLUNTEERS; EVOKED-POTENTIALS; SENSORY MEMORY; CORTEX; BRAIN; DOPAMINE; ETHANOL AB Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21-30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity. (C) 2002 Elsevier Science (USA). C1 Univ Helsinki, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Psychol, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, Helsinki, Finland. Kuopio Reg Inst Occupat Hlth, Occupat Hyg & Toxicol Sect, FIN-70701 Kuopio, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Helsinki Brain Res Ctr, Helsinki, Finland. RP Ahveninen, J (reprint author), Univ Helsinki, Cognit Brain Res Unit, POB 13, FIN-00014 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013; Ilmoniemi, Risto/E-9704-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618 NR 64 TC 39 Z9 40 U1 0 U2 7 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 AUG PY 2002 VL 16 IS 4 BP 1052 EP 1061 DI 10.1006/nimg.2002.1142 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 584AK UT WOS:000177444900019 PM 12202092 ER PT J AU Baird, AA Kagan, J Gaudette, T Walz, KA Hershlag, N Boas, DA AF Baird, AA Kagan, J Gaudette, T Walz, KA Hershlag, N Boas, DA TI Frontal lobe activation during object permanence: Data from near-infrared spectroscopy SO NEUROIMAGE LA English DT Article ID DEVELOPMENTAL-CHANGES; NEWBORN-INFANTS; BRAIN-FUNCTION; CORTEX; STIMULATION; PERFORMANCE; TOMOGRAPHY; HEMOGLOBIN; MONKEYS; ABBAR AB The ability to create and hold a mental schema of an object is one of the milestones in cognitive development. Developmental scientists have named the behavioral manifestation of this competence object permanence. Convergent evidence indicates that frontal lobe maturation plays a critical role in the display of object permanence, but methodological and ethical constrains have made it difficult to collect neurophysiological evidence from awake, behaving infants. Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy- and deoxyhemoglobin and total hemoglobin concentration within a prescribed region. The evidence described in this report reveals that the emergence of object permanence is related to an increase in hemoglobin concentration in frontal cortex. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Dept Psychol, Lab Infant Study, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. RP Baird, AA (reprint author), Harvard Univ, Dept Psychol, Lab Infant Study, 33 Kirkland St, Cambridge, MA 02138 USA. NR 24 TC 90 Z9 93 U1 1 U2 38 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 AUG PY 2002 VL 16 IS 4 BP 1120 EP 1126 DI 10.1006/nimg.2002.1170 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 584AK UT WOS:000177444900025 PM 12202098 ER PT J AU Bonmassar, G Purdon, PL Jaaskelainen, IP Chiappa, K Solo, V Brown, EN Belliveau, JW AF Bonmassar, G Purdon, PL Jaaskelainen, IP Chiappa, K Solo, V Brown, EN Belliveau, JW TI Motion and ballistocardiogram artifact removal for interleaved recording of EEG and EPs during MRI SO NEUROIMAGE LA English DT Article DE adaptive filtering; ballistocardiogram (BCG); interleaved VEPs and fMRI; visual evoked potentials; VEP; EEG; MRI; brain mapping; epilepsy ID TRIGGERED FUNCTIONAL MRI; MAGNETIC-RESONANCE SPECTROSCOPY; EVOKED-POTENTIALS; CORTICAL ACTIVITY; EPILEPSY; FMRI; LOCALIZATION; BRAIN; PATIENT; CORTEX AB Artifacts generated by motion (e.g., ballistocardiac) of the head inside a high magnetic field corrupt recordings of EEG and EPs. This paper introduces a method for motion artifact cancellation. This method is based on adaptive filtering and takes advantage of piezoelectric motion sensor information to estimate the motion artifact noise. This filter estimates the mapping between motion sensor and EEG space, subtracting the motion-related noise from the raw EEG signal. Due to possible subject motion and changes in electrode impedance, a time-varying mapping of the motion versus EEG is required. We show that this filter is capable of removing both ballistocardiogram and gross motion artifacts, restoring EEG alpha waves (8-13 Hz), and visual evoked potentials (VEPs). This adaptive filter outperforms the simple band-pass filter for alpha detection because it is also capable of reducing noise within the frequency band of interest. In addition, this filter also removes the transient responses normally visible in the EEG window after echo planar image acquisition, observed during interleaved EEG/fMRI recordings. Our adaptive filter approach can be implemented in real-time to allow for continuous monitoring of EEG and fMRI during clinical and cognitive studies. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, NMR Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Bonmassar, G (reprint author), Harvard Univ, Sch Med, NMR Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 FU NCRR NIH HHS [P41 RR14075]; NINDS NIH HHS [NIH R01 NS37462] NR 43 TC 131 Z9 135 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 AUG PY 2002 VL 16 IS 4 BP 1127 EP 1141 DI 10.1006/nimg.2002.1125 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 584AK UT WOS:000177444900026 PM 12202099 ER PT J AU Sharma, N Standaert, DG AF Sharma, N Standaert, DG TI Inherited movement disorders SO NEUROLOGIC CLINICS LA English DT Review ID LINKED DYSTONIA-PARKINSONISM; HALLERVORDEN-SPATZ-SYNDROME; DOPA-RESPONSIVE DYSTONIA; PAROXYSMAL KINESIGENIC CHOREOATHETOSIS; PROGRESSIVE SUPRANUCLEAR PALSY; IDIOPATHIC TORSION DYSTONIA; CYCLOHYDROLASE-I GENE; HUNTINGTONS-DISEASE; WILSONS-DISEASE; ALPHA-SYNUCLEIN AB The inherited movement disorders comprise a rapidly growing category of human disease. Advances in genetics have led to the identification of the gene mutation in Huntington's disease and three different gene mutations, which may lead to Parkinson's disease. In addition, gene mutations have been identified in less common movement disorders including Wilson's disease, Hallervorden-Spatz syndrome, paroxysmal kinesogenic choreo-athetosis, neuroacanthocytosis, and some forms of dystonia. This article summarizes what is known about the genetic mutations that cause these movement disorders, as well as the clinical features of each disease and the symptomatic treatments currently available. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 NR 110 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD AUG PY 2002 VL 20 IS 3 BP 759 EP + AR PII S0733-8619(01)00014-7 DI 10.1016/S0733-8619(01)00014-7 PG 21 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 607DL UT WOS:000178776200008 PM 12432829 ER PT J AU Cannon, SC AF Cannon, SC TI An expanding view for the molecular basis of familial periodic paralysis SO NEUROMUSCULAR DISORDERS LA English DT Review DE Andersen's syndrome; ion channels; myotonia; paramyotonia; skeletal muscle ID SODIUM-CHANNEL MUTATIONS; SKELETAL-MUSCLE; PARAMYOTONIA-CONGENITA; SLOW INACTIVATION; ANDERSENS-SYNDROME; K+ CURRENT; R528H; GENE; ACTIVATION; PARAMETERS AB The periodic paralyses are rare disorders of skeletal muscle characterized by episodic attacks of weakness due to intermittent failure of electrical excitability. Familial forms of periodic paralysis are all caused by mutations in genes coding for voltage-gated ion channels. New discoveries in the past 2 years have broadened our views on the diversity of phenotypes produced by mutations of a single channel gene and have led to the identification of potassium channel mutations, in addition to those previously found in sodium and calcium channels. This review focuses on the clinical features, molecular genetic defects, and pathophysiologic mechanisms that underlie familial periodic paralysis. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wellman 423,50 Blossom St, Boston, MA 02114 USA. NR 43 TC 49 Z9 55 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD AUG PY 2002 VL 12 IS 6 BP 533 EP 543 AR PII S0960-8966(02)00007-X DI 10.1016/S0960-8966(02)00007-X PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 584JP UT WOS:000177463700001 PM 12117476 ER PT J AU Orlando, LR Dunah, AW Standaert, DG Young, AB AF Orlando, LR Dunah, AW Standaert, DG Young, AB TI Tyrosine phosphorylation of the metabotropic glutamate receptor mGluR5 in striatal neurons SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 4th International Meeting on Metabotropic Glutamate Receptors CY SEP 15-20, 2002 CL TAORIMINA, ITALY DE metabotropic; mGluR; phosphorylation; striatum; Immunoprecipitation; neuronal culture ID D-ASPARTATE RECEPTOR; LONG-TERM POTENTIATION; PROTEIN-KINASE-C; POSTSYNAPTIC DENSITY FRACTION; RAT BASAL GANGLIA; NMDA RECEPTORS; HIPPOCAMPAL-NEURONS; CALMODULIN-BINDING; MESSENGER-RNA; ION CHANNELS AB Protein phosphorylation, controlled by the coordinated actions of phosphatases and kinases, is an important regulatory mechanism in synaptic transmission and other neurophysiological processes. Ionotropic glutamate receptors are known targets of phosphorylation on serine, threonine and tyrosine residues, with functional consequences for cell excitability, plasticity and toxicity. While phosphorylation of metabotropic glutamate receptors (mGluRs) also impacts critical cellular processes, there has been no evidence for direct tyrosine phosphorylation of mGluRs. In the present study, anti-phosphotyrosine and specific mGluR antibodies were used to detect tyrosine-phosphorylated mGluRs in rat brain. In particular, we found that mGluR5 is an abundant phosphotyrosine protein in vivo as well as in primary striatal neurons and tissue slices in vitro. The protein phosphatase inhibitor pervanadate robustly increased the amount of tyrosine-phosphorylated mGluR5, suggesting the receptor is subject to an endogenous, active cycle of phosphorylation and dephosphorylation. Furthermore, NMDA treatment also increased the amount of tyrosine-phosphorylated mGluR5, suggesting these endogenous phosphorylation regulatory mechanisms can be used to mediate crosstalk between synaptic glutamate receptors. While mGluR5-stimulated phosphoinositide hydrolysis appears to be unaltered by pervanadate treatment, tyrosine phosphorylation of mGluR5 may be important in trafficking, anchoring, or signaling of the receptor through G protein-independent pathways. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Orlando, LR (reprint author), Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG13617] NR 61 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD AUG PY 2002 VL 43 IS 2 BP 161 EP 173 AR PII S0028-3908(02)00113-2 DI 10.1016/S0028-3908(02)00113-2 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 597UG UT WOS:000178238700005 PM 12213270 ER PT J AU Orlando, LR Ayala, R Young, AB Tsai, LH AF Orlando, LR Ayala, R Young, AB Tsai, LH TI Phosphorylation of the C-terminal tail of mGluR5 SO NEUROPHARMACOLOGY LA English DT Meeting Abstract CT 4th International Meeting on Metabotropic Glutamate Receptors CY SEP 15-20, 2002 CL TAORIMINA, ITALY C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD AUG PY 2002 VL 43 IS 2 MA 104 BP 302 EP 302 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 597UG UT WOS:000178238700120 ER PT J AU Elman, I Goldstein, DS Green, AI Eisenhofer, G Folio, CJ Holmes, CS Pickar, D Breier, A AF Elman, I Goldstein, DS Green, AI Eisenhofer, G Folio, CJ Holmes, CS Pickar, D Breier, A TI Effects of risperidone on the peripheral noradrenegic system in patients with schizophrenia: A comparison with clozapine and placebo SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; catecholamine; spillover; clearance; DHPG; tritium-labeled norepinephrine ID EARLY-ONSET SCHIZOPHRENIA; PLASMA NOREPINEPHRINE; NEGATIVE SYMPTOMS; TREATMENT RESPONSE; BIOGENIC-AMINES; HEART-FAILURE; CATECHOLAMINES; NORADRENALINE; NEUROLEPTICS; RELEASE AB Risperidone is an atypical antipsychotic drug that increases plasma norepinephrine (NE) levels, but the mechanism behind this effect is unclear. We measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE (H-3-NE) in risperidone-treated patients and compared their data with those from patients treated with clozapine or placebo. NE levels in risperidone patients were significantly higher than in placebo patients, but lower than in clozapine patients. Neither drug, however, had significant effect on plasma levels of the main neuronal metabolite of NE, dihydroxyphenylglycol (DHPG), suggesting that adrenoceptors blockade alone would not explain the NE findings. The rate of release of endogenous NE into the bloodstream (spillover) was elevated in both risperidone and clozapine patients in a manner that paralleled their NE levels; the NE clearance in both groups did not differ from placebo. Following H-3-NE infusion in risperidone-treated individuals, production of H-3-DHPG was normal, as it was in the clozapine group, suggesting that risperidone does not impede neuronal uptake or intraneuronal metabolism of NE by monoamine oxidase. Our data suggest that both risperidone and clozapine elevate plasma NE levels via enhanced neurotransmitter spillover, with risperidone producing a smaller effect. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Commonwealth Res Ctr, Boston, MA USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Comprehens NeuroSci Inc, Washington, DC USA. Lilly Res Labs, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 15 Parkman St WACC-812, Boston, MA 02114 USA. NR 63 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 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2002 VL 27 IS 2 BP 293 EP 300 AR PII S0893-133X(02)00314-7 DI 10.1016/S0893-133X(02)00314-7 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 566AE UT WOS:000176402600017 PM 12093603 ER PT J AU Hoh, BL Chapman, PH Loeffler, JS Carter, BS Ogilvy, CS AF Hoh, BL Chapman, PH Loeffler, JS Carter, BS Ogilvy, CS TI Results of multimodality treatment for 141 patients with brain arteriovenous malformations and seizures: Factors associated with seizure incidence and seizure outcomes SO NEUROSURGERY LA English DT Article DE anticonvulsant; arteriovenous malformations; epilepsy; multimodality; radiosurgery; seizures; surgery ID STEREOTAXIC RADIOSURGERY; EPILEPSY; MANAGEMENT; THERAPY AB OBJECTIVE: Previous reports of seizure outcomes after arteriovenous malformation (AVM) treatment have involved single-treatment modality (surgery, radiosurgery, or embolization) series. Such series reflect only selected lesions, of certain sizes, locations, and other clinical and anatomic characteristics, that are amenable to the single therapy, limiting the analysis of those factors. We report the results of AVM treatment using a multimodality approach that we think encompasses a broader spectrum of treatable brain AVMs. We tested for factors associated with seizure presentation and seizure outcomes. METHODS: Between 1991 and 1999, the multidisciplinary neurovascular unit at Massachusetts General Hospital treated 424 patients with brain AVMs. Treatment consisted of surgical resection, radiosurgery, or embolization, either alone or in combination. One hundred forty-one, patients (33%) experienced seizures before treatment. We studied the following factors: sex, age, AVM size, AVM location, occurrence of intracranial hemorrhage, seizure type, duration of seizure history, treatment modality, and AVM obliteration. We tested for statistical associations between these factors and seizure presentation and outcomes. Clinical follow-up monitoring was via mailed questionnaires. RESULTS: When we compared the 141 patients with seizures with the 283 patients who did not experience seizures (total of 424 patients), male sex, age of less than 65 years, AVM size of more than 3 cm, and temporal lobe AVM location were statistically associated with seizures (P < 0.01, P < 0.05, P < 0.0001, and P < 0.01, respectively). Posterior fossa and deep locations were statistically associated, with no seizures (P < 0.0001). One hundred ten (78%) of the 141 patients who experienced seizures before treatment responded to the mailed questionnaires, with a mean follow-up period of 2.9 years. A detailed comparison of responders and nonresponders demonstrated no statistically significant differences in pertinent characteristics. As determined with the Engel Seizure Outcome Scale, there were 73 (66%) Class I (free of disabling seizures) 11 (10%) Class II (rare disabling seizures), 1 (0.9%) Class III (worthwhile improvement), and 22 (20%) Class IV: (no worthwhile improvement) outcomes. Three patients died during the follow-up period. We tested for factors associated with Engel Class I outcomes. Sex, age, and AVM size were not associated with Class I outcomes. Short seizure history, association of seizures with intracranial hemorrhage, generalized tonicoclonic seizure type, deep and posterior fossa AVM locations, surgical resection, and complete AVM obliteration were statistically associated with Class I outcomes (P < 0.0001, P < 0.05, P < 0.05, P < 0.05, P < 0.001, and P < 0.001 respectively). When only completely obliterated AVMs were considered, there were no statistically significant differences between surgery, radiosurgery, and embolization. CONCLUSION: Certain factors, as identified in an analysis of a wide spectrum of treatable brain AVMs, can facilitate predictions of the incidence of seizure presentation with AVMs, as well as seizure outcomes after multimodality treatment. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Radiat Oncol Serv, Boston, MA 02115 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Brain Aneurysm AVM Ctr, 55 Fruit St,VBK-710, Boston, MA 02114 USA. NR 38 TC 76 Z9 80 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2002 VL 51 IS 2 BP 303 EP 309 DI 10.1227/01.NEU.0000020570.78483.9E PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 581CK UT WOS:000177273400005 PM 12182768 ER PT J AU Selker, RG Shapiro, WR Burger, P Blackwood, MS Deutsch, M Arena, VC Van Gilder, JC Wu, J Malkin, MG Mealey, J Neal, JH Olson, J Robertson, JT Barnett, GH Bloomfield, S Albright, R Hochberg, FH Hiesiger, E Green, S AF Selker, RG Shapiro, WR Burger, P Blackwood, MS Deutsch, M Arena, VC Van Gilder, JC Wu, J Malkin, MG Mealey, J Neal, JH Olson, J Robertson, JT Barnett, GH Bloomfield, S Albright, R Hochberg, FH Hiesiger, E Green, S CA Brain Tumor Cooperative Grp TI The Brain Tumor Cooperative Group NIH Trial 87-01: A randomized comparison of surgery, external radiotherapy, and carmustine versus surgery, interstitial radiotherapy boost, external radiation therapy, and carmustine SO NEUROSURGERY LA English DT Article DE chemotherapy; interstitial radiation; malignant glioma; quality assurance ID RECURSIVE PARTITIONING ANALYSIS; MALIGNANT GLIOMAS; INITIAL MANAGEMENT; I-125 IMPLANTS; STEREOTAXIC RADIOSURGERY; GLIOBLASTOMA-MULTIFORME; BEAM RADIOTHERAPY; CLINICAL-TRIAL; I125 IMPLANTS; NECK-CANCER AB OBJECTIVE: The objective of the Brain Tumor Cooperative Group NIH Trial 87-01 trial was to investigate the effect of additional implanted radiation therapy in newly diagnosed patients with pathologically confirmed malignant gliomas. METHODS: The study involved a randomized comparison of surgery, external beam radiotherapy, and carmustine (BCNU) versus surgery, external beam therapy, interstitial radiotherapy boost, and BCNU in newly diagnosed malignant gliomas. I-125 was chosen as best suited for this effort because it allowed preimplantation planning and postimplantation quality assurance review. Two hundred ninety-nine patients met the eligibility criteria and were randomized into the two arms of the study between December 1987 and April 1994. Follow-up continued for an additional 3 years. Twenty-nine patients were identified as having committed protocol violations and were excluded, resulting in 270 subjects in the Valid Study Group. One hundred thirty-seven patients received external beam radiation and BCNU, and 133 underwent the I-125 implantation plus external beam radiation and BCNU therapy. RESULTS: The overall median survival for the Valid Study Group was 64.3 weeks. The median survival for patients receiving additional therapy of I-125 was 68.1 weeks, and median survival for those receiving only external beam radiation and BCNU was 58.8 weeks. The cumulative proportion surviving between the two treatment groups was not statistically significantly different (log-rank test, P = 0.101). As in other studies in the literature, age, Karnofsky score, and pathology were predictors of mortality. Additional analyses incorporating an adjustment for these prognostic variables, either in a stratified analysis or Cox proportional hazards model, did not result in statistically significant differences in the cumulative proportion of patients surviving between the two treatment groups. CONCLUSION: We conclude that there is no long-term survival advantage of in I-125 creased radiation dose with seeds in newly diagnosed glioma patients. C1 Western Penn Hosp, Western Penn Canc Inst, Ctr Neurooncol, Pittsburgh, PA 15224 USA. Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Western Penn Hosp, Ctr Neurooncol, Dept Radiat Phys, Pittsburgh, PA 15224 USA. Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Iowa, Dept Neurosurg, Iowa City, IA USA. Tufts Univ New England Med Ctr, Dept Neurosurg, Boston, MA 02111 USA. Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Indiana Univ, Dept Neurosurg, Indianapolis, IN 46204 USA. Marshfield Clin Fdn Med Res & Educ, Dept Neurosurg, Marshfield, WI USA. Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA. Univ Tennessee, Dept Neurosurg, Memphis, TN USA. Cleveland Clin, Dept Neurol, Cleveland, OH 44106 USA. W Virginia Univ, Dept Neurosurg, Morgantown, WV 26506 USA. Univ Cincinnati, Barrett Canc Ctr, Cincinnati, OH USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NYU, Ctr Med, Dept Neurosurg, New York, NY USA. Case Western Reserve Univ, Dept Biostat, Cleveland, OH 44106 USA. RP Selker, RG (reprint author), Western Penn Hosp, Western Penn Canc Inst, Ctr Neurooncol, 4800 Friendship Ave, Pittsburgh, PA 15224 USA. OI Arena, Vincent/0000-0002-1634-7207 FU NCI NIH HHS [2-U10CA-36012-04, 2-U10CA-36012-04A1] NR 65 TC 121 Z9 127 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2002 VL 51 IS 2 BP 343 EP 355 DI 10.1227/01.NEU.0000020571.12840.F9 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 581CK UT WOS:000177273400013 PM 12182772 ER PT J AU Barker, FG AF Barker, FG TI Efficacy of prophylactic antibiotic therapy in spinal surgery: A meta-analysis SO NEUROSURGERY LA English DT Article DE meta-analysis; prophylactic antibiotic therapy; spinal surgery ID CEREBROSPINAL-FLUID SHUNTS; RANDOMIZED CLINICAL-TRIAL; DESIGN AFFECTS OUTCOMES; 2X2 CONTINGENCY-TABLES; ANTIMICROBIAL PROPHYLAXIS; WOUND INFECTIONS; UNDERLYING RISK; ODDS RATIO; CLEAN NEUROSURGERY; TREATMENT BENEFIT AB OBJECTIVE: There is considerable variation in practice regarding the use of prophylactic antibiotic therapy in spinal operations. To date, individual studies have not demonstrated a significant benefit for prophylactic antibiotic therapy in spinal operations. METHODS: Systematic database searches for randomized prospective trials of prophylactic antibiotic therapy in spinal surgery, general neurosurgery, and orthopedic surgery were performed. Random-effects meta-analysis and Bayesian meta-regressions of treatment benefits versus baseline infection rates and other trial characteristics were performed. RESULTS: Six prospective randomized trials or trial subgroups, enrolling 843 patients, were identified, i.e., one spinal surgery trial, four general neurosurgery trials, and one general orthopedic surgery trial. No individual trial demonstrated a statistically significant effect of prophylactic antibiotic therapy for spinal surgery patients. Raw pooled infection rates were 2.2% (10 of 451 patients) with antibiotics and 5.9% (23 of 392 patients) without antibiotics. Individual trial infection rates ranged from 1.2 to 8.5%. The pooled odds ratio was 0.37 (95% confidence interval, 0.17-0.78), favoring antibiotic treatment (P < 0.01). There was no significant heterogeneity in treatment efficacy among the trials. Bayesian meta-regression was Used to test whether antibiotics were less effective in trials with low baseline infection rates and whether an optimal antibiotic regimen could be identified. There was no significant difference in antibiotic treatment effects in trials with lower baseline infection rates, in trials using antibiotics with gram-negative coverage in addition to gram-positive coverage, or,in trials using multiple-dose versus single-dose regimens. Nonrandomized studies of antibiotic therapy in spinal surgery yielded greater treatment effect estimates than did randomized trials, but not significantly so. CONCLUSION: Prophylactic antibiotic therapy is beneficial for spinal surgery, even when expected infection rates without antibiotic treatment are low. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Fruit St, Boston, MA 02114 USA. NR 75 TC 79 Z9 84 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2002 VL 51 IS 2 BP 391 EP 400 DI 10.1227/01.NEU.0000019872.28255.D1 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 581CK UT WOS:000177273400023 PM 12182777 ER PT J AU Livingston, EH Ko, CY AF Livingston, EH Ko, CY TI Use of the health and activities limitation index as a measure of quality of life in obesity SO OBESITY RESEARCH LA English DT Article DE quality of life; activity limitations; National Health Interview Survey; activities of daily living; health status ID OF-LIFE; SUBJECTS SOS; OVERWEIGHT; WEIGHT; PREVALENCE; IMPACT; HEIGHT; ADULTS AB Objective: Obesity reduces the quality of life (QOL); however, quantification of obesity's impact on QOL is cumbersome. Utility indices reduce QOL measurements to a single numerical value that can be used in the calculation of Quality-Adjusted Life-Years and the cost effectiveness for obesity treatment. The purpose of this investigation is to assess the sensitivity of the Health and Activities Limitation Index (HALex) utility index to obesity. Research Methods and Procedures: The answers to five questions regarding an individual's self-perception of his or her health status and information about limitation in daily and work activities were collected from 32,440 adults in the 1998 National Health Information Survey. Answers to the questions were scored and converted to a utility index score ranging from 0 (near-death state) to 1 (perfect health) with no limitations. Average values for indices corresponding to differing body mass indices were obtained and significance determined by ANOVA. Results: The utility index for normal weight males and females was 0.86 +/- 0.19 and fell to 0.68 +/- 0.27 for superobese males and 0.60 +/- 0.28 in superobese females. Utility indices fell linearly with increasing body mass index and were lower for respondents having obesity-related comorbid conditions known to reduce the quality of life. Discussion: There is a statistically significant decrease in the QOL with increasing obesity, slightly worse for women compared with men. The Health and Activities Limitation Index can quantitate the effect obesity and its complications have on quality of life. C1 Univ Calif Los Angeles, Bariatr Surg Program, UCLA Gen Surg, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. RP Livingston, EH (reprint author), Univ Calif Los Angeles, Bariatr Surg Program, UCLA Gen Surg, 10833 Conte,72-215 CHS, Los Angeles, CA 90095 USA. NR 23 TC 26 Z9 27 U1 0 U2 5 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 AUG PY 2002 VL 10 IS 8 BP 824 EP 832 DI 10.1038/oby.2002.111 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 584JT UT WOS:000177464000015 PM 12181392 ER PT J AU Akpek, EK Jabs, DA Tessler, HH Joondeph, BC Foster, CS AF Akpek, EK Jabs, DA Tessler, HH Joondeph, BC Foster, CS TI Successful treatment of serpiginous choroiditis with alkylating agents SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY NOV, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol ID WEGENERS GRANULOMATOSIS; BEHCETS-DISEASE; CLINICAL COURSE; NEOVASCULARIZATION; CYCLOPHOSPHAMIDE; RECOMMENDATIONS; CHOROIDOPATHY; CHLORAMBUCIL; THERAPY AB Objective: To describe the management and long-term outcomes of patients with serpiginous choroiditis treated with alkylating agents. Design: Retrospective, noncomparative case series. Participants: Nine patients with active, vision-threatening serpiginous choroiditis who had progressive inflammation while on steroids and/or immunosuppressive agents other than alkylating agents treated at three tertiary care uveitis referral centers. Methods: Patients received systemic immunosuppression with an alkylating agent, either chlorambucil or cyclophosphamide. Prednisone also was given initially and was tapered and discontinued. Main Outcome Measures: Visual acuity, clinical disease activity, duration of treatment, duration of drug-free disease remission, and side effects of alkylating agent therapy. Results: No patients had recurrences while on therapy. No further visual loss was encountered after starting the therapy. Six of the patients regained vision. All but two patients achieved prolonged drug-free remissions, ranging in duration between 15 and 96 months (median, 78 months). Side effects included transient bone marrow suppression, nausea, and fatigue. Secondary malignancy was encountered in one patient, whose carcinoma of the urinary bladder was treated successfully. Conclusions: Adequate immunosuppression with alkylating agents may favorably alter the long-term prognosis of patients with serpiginous choroiditis. (C) 2002 by the American Academy of Ophthalmology. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. Wayne State Univ, Dept Ophthalmol, Kresge Eye Inst, Detroit, MI USA. Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol, Chicago, IL USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Jabs, DA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. NR 41 TC 33 Z9 38 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 AUG PY 2002 VL 109 IS 8 BP 1506 EP 1513 AR PII S0161-6420(02)01097-7 DI 10.1016/S0161-6420(02)01097-7 PG 8 WC Ophthalmology SC Ophthalmology GA 578ZR UT WOS:000177151400028 PM 12153803 ER PT J AU Miserocchi, E Waheed, NK Dios, E Christen, W Merayo, J Roque, M Foster, CS AF Miserocchi, E Waheed, NK Dios, E Christen, W Merayo, J Roque, M Foster, CS TI Visual outcome in herpes simplex virus and varicella zoster virus uveitis - A clinical evaluation and comparison SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 22-25, 2000 CL DALLAS, TEXAS SP Amer Acad Ophthalmol ID NATURAL-HISTORY; EYE DISEASE; STROMAL KERATITIS; CONTROLLED TRIAL; ORAL ACYCLOVIR; OPHTHALMICUS; COMPLICATIONS; EPIDEMIOLOGY; ROCHESTER; INFECTION AB Purpose: To compare clinical characteristics and outcomes in patients with uveitis caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). Design: Retrospective comparative study. Participants: Forty patients with HSV uveitis and 24 patients with VZV uveitis. Methods: A retrospective study of 40 patients with HSV and 24 patients with VZV uveitis was performed. The patients were followed between May 1987 and September 1999 (median follow-up time, 46 months). The diagnosis of HSV uveitis was made clinically and serologically, and the diagnosis of VZV uveitis was made clinically. Main Outcome Measures: Clinical presentation of the disease, ocular complications, visual acuity, surgical and medical treatments needed. Results: Both populations were comparable for gender and age at disease onset. The course of the disease tended to be remitting and recurrent in HSV patients and chronic in VZV patients (P = 0.046). The most frequent ocular complication in both groups was secondary glaucoma (54% HSV, 38% VZV). Twenty-five percent of VZV patients developed posterior pole complications (cystoid macular edema, epiretinal membrane, papillitis, retinal fibrosis, and detachment) compared with 8% of HSV patients (P = 0.069). Treatment modalities selected were generally similar in the two groups, although periocular and systemic steroids were required more frequently in HSV patients (60% versus 25%; P = 0.01). Surgical procedures were required with similar frequency in both populations. The percentage of eyes that were legally blind at end of follow-up was also comparable (HSV, 20%; VZV, 21%). The visual outcome was similar in the studied populations. Conclusions: This study represents the only direct comparison of HSV and VZV uveitis patients reported in the literature. HSV patients were more likely to be treated with periocular and systemic steroids, and VZV patients were more likely to develop posterior pole complications (a finding of borderline significance). Other parameters evaluated in this study were not statistically different in the two patient groups. (C) 2002 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv,Dept Ophthalmol, 243,Charles St, Boston, MA 02114 USA. NR 33 TC 29 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 2002 VL 109 IS 8 BP 1532 EP 1537 AR PII S0161-6420(02)01113-2 DI 10.1016/S0161-6420(02)01113-2 PG 6 WC Ophthalmology SC Ophthalmology GA 578ZR UT WOS:000177151400032 PM 12153807 ER PT J AU Torriani, M Rosenthal, DI AF Torriani, M Rosenthal, DI TI Percutaneous radiofrequency treatment of osteoid osteoma SO PEDIATRIC RADIOLOGY LA English DT Editorial Material DE bone neoplasms; computed tomography (CT); radiofrequency (RF) ablation; osteoma AB Osteoid osteoma is a small osteogenic tumor usually found in the lower extremity of children and young adults. Although these lesions are benign and rarely progress, they present distinctive pain symptoms that frequently require medical intervention. This article reviews surgical, medical, and percutaneous techniques for treatment of osteoid osteoma, emphasizing the value of percutaneous radiofrequency treatment. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 16 TC 32 Z9 33 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD AUG PY 2002 VL 32 IS 8 BP 615 EP 618 DI 10.1007/s00247-002-0727-2 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 584EJ UT WOS:000177454000022 PM 12200642 ER PT J AU Biederman, J Lopez, FA Boellner, SW Chandler, MC AF Biederman, J Lopez, FA Boellner, SW Chandler, MC TI A randomized, double-blind, placebo-controlled, parallel-group study of SLI381 (Adderall XR) in children with attention-deficit/hyperactivity disorder SO PEDIATRICS LA English DT Article DE attention-deficit/hyperactivity disorder; amphetamine; Adderall XR; randomized; controlled trial ID DEFICIT HYPERACTIVITY DISORDER; METHYLPHENIDATE; YOUTHS; ADHD AB Objective. SLI381 (Adderall XR) is a 2-component extended-release capsule formulation of Adderall designed to produce a therapeutic effect that lasts throughout the day with 1 morning dose. The primary objective of this study was to assess the efficacy and safety of SLI381 compared with placebo in the treatment of attention-deficit/hyperactivity disorder (ADHD) in children in a naturalistic school and home setting. A secondary objective was to assess the diurnal variation in responses based on morning and afternoon assessments. Methods. A multicenter, randomized, double-blind, parallel-group, placebo-controlled trial was conducted at 47 sites. After a 1-week washout of any previous stimulant medication, patients were randomized to receive single-daily morning doses of placebo or SLI381 10 mg, 20 mg, or 30 mg for 3 weeks. Participants aged 6 to 12 years inclusive who satisfied Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria diagnosis of ADHD were included. The primary efficacy parameter was the Conners Global Index Scale for Teachers. Secondary efficacy parameters included the Conners Global Index Scale for Parents, the Clinical Global Impressions Scale for improvement, and the Parent Global Assessment for improvement. Safety was assessed by recording adverse events, laboratory tests, and vital signs at each visit during the study. Physical examinations and electrocardiograms were performed at the screening and the end of the study. Results. Five hundred eighty-four children were randomized, 563 were included in the intent-to-treat population, and 509 completed the entire study. Intention-to-treat analysis of Conners Global Index Scale for Teachers and Conners Global Index Scale for Parents scores revealed significant improvement in morning, afternoon, and late afternoon behavior for all active treatment groups versus placebo. All active treatment groups showed significant dose-related improvement in behavior from baseline. Both the Clinical Global Impressions Scale for improvement and Parent Global Assessment for improvement showed all doses of SLI381 to be superior to placebo at treatment end and both confirmed the dose-response relationship between improvement and the SLI381 dose. The incidence of spontaneously reported adverse events was low and similar for active treatments and placebo. Conclusions. SLI381 produced consistent, dose-related improvements on all measures of efficacy. The extended-release nature of the SLI381 formulation was shown by continued, significant improvement in afternoon assessments by teachers and afternoon and late afternoon assessments by parents. The time course and therapeutic effects of SLI381 suggests that this medication is an efficacious once-daily treatment for children with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Childrens Dev Ctr, Maitland, FL USA. Clin Study Ctr, Little Rock, AR USA. N Carolina Neuropsychiat, Chapel Hill, NC USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,ACC 725, Boston, MA 02114 USA. NR 21 TC 111 Z9 112 U1 5 U2 19 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2002 VL 110 IS 2 BP 258 EP 266 DI 10.1542/peds.110.2.258 PG 9 WC Pediatrics SC Pediatrics GA 581DA UT WOS:000177274800017 PM 12165576 ER PT J AU Roman, T Szobot, C Martins, D Biederman, J Rohde, LA Hutz, MH AF Roman, T Szobot, C Martins, D Biederman, J Rohde, LA Hutz, MH TI Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder SO PHARMACOGENETICS LA English DT Article DE ADHD; methylphenidate; dopamine transporter gene ID DEFICIT HYPERACTIVITY DISORDER; ASSOCIATION; DAT1 AB This study aims to evaluate whether a previously reported association between homozygosity for the 10-repeat allele of the dopamine transporter gene (10/10) and poor response to methylphenidate (MPH) would be replicated in a sample of Brazilian attention deficit/hyperactivity disorder (ADHD) boys. In a blind naturalistic study, 50 male ADHD youths were treated with MPH. Efficacy of the medication was measured by means of the 10-item Conners Abbreviated Rating Scale (ABRS), and the Children's Global Assessment Scale (CGAS). While 75% (15/20) of the youths without 10/10 genotype demonstrated an improvement higher than 50% in the ABRS scores with MPH, only 47% (14/30) of the subjects with 10/10 genotype achieved the same level of improvement with medication (one-tailed P=0.04). In addition, the group without this genotype had significantly higher increase in the CGAS scores than the other group (one-tailed P < 0.01). Our findings support an association between homozygosity for the 10-repeat allele at dopamine transporter gene locus and poor response to MPH. C1 Univ Fed Rio Grande Sul, Serv Psiquiatria Infancia & Adolescencia, Hosp Clin Porto Alegre, ADHD Outpatient Clin,Child & Adolescent Psychiat, BR-90035003 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Genet, BR-90035003 Porto Alegre, RS, Brazil. Harvard Univ, Sch Med, Pediat Psychopharmacol Unit, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Rohde, LA (reprint author), Univ Fed Rio Grande Sul, Serv Psiquiatria Infancia & Adolescencia, Hosp Clin Porto Alegre, ADHD Outpatient Clin,Child & Adolescent Psychiat, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. RI Rohde, Luis Augusto/A-6426-2008; Roman, Tatiana/C-1300-2010; OI Rohde, Luis Augusto/0000-0002-4552-4188; Hutz, Mara/0000-0002-9146-1229 NR 15 TC 96 Z9 100 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD AUG PY 2002 VL 12 IS 6 BP 497 EP 499 DI 10.1097/00008571-200208000-00011 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 586AK UT WOS:000177559600011 PM 12172219 ER PT J AU Han, R Baden, HP Brissette, JL Weiner, L AF Han, R Baden, HP Brissette, JL Weiner, L TI Redefining the skin's pigmentary system with a novel tyrosinase assay SO PIGMENT CELL RESEARCH LA English DT Article DE melanogenesis; melanocyte; epidermis; hair follicle; tyrosinase ID DHICA-OXIDASE ACTIVITY; MOUSE TYROSINASE; HAIR FOLLICLE; ALBINO MUTATION; CDNA; FIBROBLASTS; EXPRESSION; MICE; IDENTIFICATION; TRICHOHYALIN AB In mammalian skin, melanin is produced by melanocytes and transferred to epithelial cells, with the epithelial cells thought to receive pigment only and not generate it. Melanin formation requires the enzyme tyrosinase, which catalyzes multiple reactions in the melanin biosynthetic pathway. Here, we reassess cutaneous melanogenesis using tyramide-based tyrosinase assay (TTA), a simple test for tyrosinase activity in situ. In the TTA procedure, tyrosinase reacts with biotinyl tyramide, causing the substrate to deposit near the enzyme. These biotinylated deposits are then visualized with streptavidin conjugated to a fluorescent dye. In the skin and eye, TTA was highly specific for tyrosinase and served as a sensitive indicator of pigment cell distribution and status. In clinical skin samples, the assay detected pigment cell defects, such as melanocytic nevi and vitiligo, providing confirmation of medical diagnoses. In murine skin, TTA identified a new tyrosinase-positive cell type - the medullary cells of the hair - providing the first example of cutaneous epithelial cells with a melanogenic activity. Presumably, the epithelial tyrosinase originates in melanocytes and is acquired by medullary cells during pigment transfer. As tyrosinase by itself can generate pigment from tyrosine, it is likely that medullary cells produce melanin de novo. Thus, we propose that melanocytes convert medullary cells into pigment cells by transfer of the melanogenic apparatus, an unusual mechanism of differentiation that expands the skin's pigmentary system. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Brissette, JL (reprint author), Cutaneous Biol Res Ctr, MGH-E,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [R01 AR45284] NR 45 TC 32 Z9 36 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD AUG PY 2002 VL 15 IS 4 BP 290 EP 297 DI 10.1034/j.1600-0749.2002.02027.x PG 8 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 570MN UT WOS:000176662200007 PM 12100495 ER PT J AU Leaf, A Xiao, YF Kang, JX AF Leaf, A Xiao, YF Kang, JX TI Interactions of n-3 fatty acids with ion channels in excitable tissues SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID RAT CARDIAC MYOCYTES; NA+ CHANNELS; VENTRICULAR-FIBRILLATION; GRAMICIDIN CHANNELS; BILAYER DEFORMATIONS; LOCAL-ANESTHETICS; POINT MUTATIONS; LONG-CHAIN; BLOCK; ARRHYTHMIAS AB In summary, we have shown that the conventional explanation for the site of action of a ligand which alters the conductance of a membrane ion channel is that the ligand interacts or binds with the ion channel protein, changing its conductance, is inadequate to explain the primary site of action of the antiarrhythmic n-3 PUFAs. We have shown that when a neutral asparagine is replaced by a positively charged lysine in the N406 amino acid site in the alpha-subunit of the human cardiac sodium channel, the n-3 fatty acids lose their inhibitory action on the sodium current. The inadequacy of this finding to explain the primary site of action of the n-3 PUFAs is demonstrated by the inhibitory effect on all other cardiac ion channels, so far tested. We show that ion channels, which share no amino acid homology with the PUFAs, have their conductance also reduced in the presence of the PUFAs,Thus a more general conceptual framework or paradigm is needed to account for the broad action of the PUFAs on diverse different ion channels lacking amino acid homology. We have been testing the membrane tension hypothesis of Andersen and associates. (20-26) According to this hypothesis, the fatty acids are not acting directly on the ion channel protein but accumulating in the phospholipid membrane in immediate juxtaposition to the site in the membrane where the ion channel protein penetrates the membrane phospholipid bilayer. This alters membrane tensions exerted by the phospholipid membrane on the ion channel, which in turn causes conformational changes in the ion channel, altering the conductance of the ion channel. Our preliminary data seem to support this membrane tension hypothesis. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Bldg 149,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 29 TC 30 Z9 30 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG-SEP PY 2002 VL 67 IS 2-3 BP 113 EP 120 DI 10.1054/plef.407 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 598ZW UT WOS:000178308600009 PM 12324229 ER PT J AU Laposata, M Hasaba, A Best, CA Yoerger, DM McQuillan, BM Salem, RO Refaai, MA Soderberg, BL AF Laposata, M Hasaba, A Best, CA Yoerger, DM McQuillan, BM Salem, RO Refaai, MA Soderberg, BL TI Fatty acid ethyl esters: recent observations SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID NONOXIDATIVE ETHANOL-METABOLISM; HEPG2 CELLS; HUMAN SERUM; ALBUMIN; LIPOPROTEINS; INGESTION; MARKERS; OLEATE; ORGANS; PLASMA AB Fatty acid ethyl esters (FAEE), esterification products of fatty acids and ethanol, have been shown to be mediators of ethanol-induced cell injury and their presence in the blood and tissues is a marker of ethanol intake. Recently it has been shown that FAEE are produced within seconds of infusion of ethanol into the heart, when using a protocol similar to that used for myocardial ablation. This raises the possibility that the mechanism for the death of myocytes in cardiac ablation involves the generation of toxic FAEE. It has also been recently demonstrated that chronic alcoholics have a high concentration of a specific FAEE species-ethyl oleate. The use of the serum ethyl oleate concentration may be helpful in differentiating binge drinkers from chronic alcoholics. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Clin Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Gray Bldg,Room 235, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013 OI McQuillan, Brendan/0000-0002-2130-8114 NR 21 TC 7 Z9 9 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG-SEP PY 2002 VL 67 IS 2-3 BP 193 EP 196 DI 10.1054/plef.418 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 598ZW UT WOS:000178308600021 PM 12324241 ER PT J AU Rosen, MI Rosenheck, RA Shaner, A Eckman, T Gamache, G Krebs, C AF Rosen, MI Rosenheck, RA Shaner, A Eckman, T Gamache, G Krebs, C TI Veterans who may need a payee to prevent misuse of funds for drugs SO PSYCHIATRIC SERVICES LA English DT Article ID REPRESENTATIVE PAYEE; MENTAL-ILLNESS AB Objective: This study sought to determine the possible need for a payee among Department of Veterans Affairs (VA) inpatients with substance use disorders who receive public support payments. Methods: A total of 290 veterans hospitalized in VA psychiatric units completed a survey designed to identify patients who may be in need of a payee because of excessive expenditures for substances of abuse. Level 1 screening identified patients with a general likelihood of needing a payee because they received public support payments, did not have a payee, and had a substance abuse diagnosis. Level 2 screening identified level 1 patients for whom there was further evidence of need for a payee because, in addition to spending substantial amounts of money on substances of abuse, they reported either difficulty meeting basic material needs or substantial harm from substance use. Results: Of 290 patients surveyed, 78 (27 percent) met level 1 criteria. Altogether, 35 patients (45 percent of level 1 patients and 13 percent of all surveyed patients) met the more specific level 2 criteria, indicating that they were likely to be in need of a payee. As expected, veterans who met the level 2 criteria were more likely than those meeting only the level 1 criteria to have both self-rated and clinician-rated difficulties managing money. However, clinicians did not rate these veterans as more likely to benefit from a payee. Conclusions: A substantial proportion of veterans who have not been assigned a payee may need one. More effective approaches to money management in this population are needed. C1 Vet Affairs Connecticut Healthcare Syst, Dept Psychiat, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Calif State Univ Los Angeles, Sch Med, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dual Diagnosis Treatment Program, Los Angeles, CA USA. Univ Massachusetts, Amherst, MA 01003 USA. Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. RP Rosen, MI (reprint author), Vet Affairs Connecticut Healthcare Syst, Dept Psychiat, 116A,950 Campbell Ave, West Haven, CT 06516 USA. NR 10 TC 14 Z9 14 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD AUG PY 2002 VL 53 IS 8 BP 995 EP 1000 DI 10.1176/appi.ps.53.8.995 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 579KL UT WOS:000177177100015 PM 12161675 ER PT J AU Fava, M Farabaugh, AH Sickinger, AH Wright, E Alpert, JE Sonawalla, S Nierenberg, AA Worthington, JJ AF Fava, M Farabaugh, AH Sickinger, AH Wright, E Alpert, JE Sonawalla, S Nierenberg, AA Worthington, JJ TI Personality disorders and depression SO PSYCHOLOGICAL MEDICINE LA English DT Article ID ATYPICAL DEPRESSION; MAJOR DEPRESSION; FLUOXETINE; BORDERLINE; PHARMACOTHERAPY; OUTPATIENTS; PHENELZINE; IMIPRAMINE; PLACEBO; TRAITS AB Background. Personality disorders (PDs) were assessed among depressed out-patients by clinical interview before and after antidepressant treatment with fluoxetine to assess the degree of stability of PD diagnoses and determine whether changes in PD diagnoses across treatment are related to the degree of improvement in depressive symptoms. Method. Three hundred and eighty-four out-patients (55% women; mean age = 39(.)9 +/- 10(.)5) with major depressive disorder (MDD) diagnosed with the SCID-P were enrolled into an 8 week trial of open treatment with fluoxetine 20 mg/day. The SCID-II was administered to diagnose PDs at baseline and endpoint. Results. A significant proportion (64%) of our depressed out-patients met criteria for at least one co-morbid personality disorder. Following 8 weeks of fluoxetine treatment, there was a significant reduction in the proportion of patients meeting criteria for avoidant, dependent, passive- aggressive, paranoid and narcissistic PDs. From baseline to endpoint, there was also a significant reduction in the mean number of criteria met for paranoid, schizotypal, narcissistic, borderline, avoidant, dependent, obsessive-compulsive, passive aggressive and self-defeating personality disorders. While changes in cluster diagnoses were not significantly related to improvement in depressive symptoms, there were significant relationships between degree of reduction in depressive symptoms (percentage change in HAM-D-17 scores) and degree of change in the number of criteria met for paranoid, narcissistic, borderline and dependent personality disorders. Conclusions. Personality disorder diagnoses were found to be common among untreated outpatients with major depressive disorder. A significant proportion of these patients no longer met criteria for personality disorders following antidepressant treatment, and changes in personality disorder traits were significantly related to degree of improvement in depressive symptoms in some but not all personality disorders. These findings suggest that the lack of stability of PD diagnoses among patients with current MDD may be attributable in part to a direct effect of antidepressant treatment on behaviours and attitudes that comprise PDs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH-48-483-05] NR 27 TC 58 Z9 60 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 2002 VL 32 IS 6 BP 1049 EP 1057 DI 10.1017/S0033291702005780 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 586TE UT WOS:000177600500010 PM 12214786 ER PT J AU Mullins, ME Schaefer, PW Sorensen, AG Halpern, EF Ay, H He, J Koroshetz, WJ Gonzalez, RG AF Mullins, ME Schaefer, PW Sorensen, AG Halpern, EF Ay, H He, J Koroshetz, WJ Gonzalez, RG TI CT and conventional and diffusion-weighted MR imaging in acute stroke: Study in 691 patients at presentation to the emergency department SO RADIOLOGY LA English DT Article DE brain, CT; brain, infarction; brain, ischemia; brain, MR ID ACUTE ISCHEMIC STROKE; MAGNETIC-RESONANCE; THROMBOLYTIC THERAPY; WATER DIFFUSION; PLASMINOGEN-ACTIVATOR; CEREBRAL INFARCTION; TIME-COURSE; BRAIN; PERFUSION; EXPERIENCE AB PURPOSE: To compare the diagnostic accuracy of computed tomography (CT) and magnetic resonance (MR) imaging in a consecutive series of patients at presentation to the emergency department with symptoms of acute stroke. MATERIALS AND METHODS: Clinical data and images obtained in 691 consecutive patients with suspected acute stroke were examined. Results of first and second head CT and brain diffusion-weighted (DW) and conventional MR imaging were compared with each other and with the final neurologic discharge diagnosis. RESULTS: Five hundred seventy-three patients underwent CT at presentation, with 42% sensitivity (95% CI: 37%, 46%) and 91% specificity (95% CI: 82%, 96%). A total of 173 patients underwent a second CT examination, with 77% sensitivity (95% CI: 70%, 84%) and 79% specificity (95% CI: 49%, 95%). Of 498 MR images, 411 were DW, with 94% sensitivity (95% CI: 1%, 96%) and 97% specificity (95% CI: 88%, 100%), and 87 were conventional, with 70% sensitivity (95% CI: 58%, 81%) and 94% specificity (95% CI: 70%, 100%). By using DW MR imaging in the early period (<6 hours after presentation to emergency department), a 97% sensitivity (95% CI: 92%, 100%) and a 100% specificity (95% CI: 69%, 100%) were achieved, compared with 58% (29%-84%) and 100% (16%-100%), respectively, with conventional MR imaging, and 40% (35%-45%) and 92% (84%-97%), respectively, with CT. Negative predictive value was higher with DW MR imaging (73%) than with conventional (42%) MR imaging or CT (24%). In studies conducted within 12 hours, DW MR imaging achieved substantially superior accuracy than did CT. After 12 hours, accuracy was equivalent. CONCLUSION: In the diagnosis of stroke in the early period (<12 hours after presentation), DW MR imaging is superior to conventional MR imaging and CT. (C) RSNA, 2002. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroradiol Div, 55 Fruit St,GRB285, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13213]; NINDS NIH HHS [NS38477, NS34626] NR 45 TC 173 Z9 178 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2002 VL 224 IS 2 BP 353 EP 360 DI 10.1148/radiol.2242010873 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 576UY UT WOS:000177025400010 PM 12147827 ER PT J AU Mahmood, U Tung, CH Tang, Y Weissleder, R AF Mahmood, U Tung, CH Tang, Y Weissleder, R TI Feasibility of in vivo multichannel optical imaging of gene expression: Experimental study in mice SO RADIOLOGY LA English DT Article DE experimental study; genes and genetics; neoplasms, experimental studies ID FLUORESCENT CONTRAST AGENTS; NEAR-INFRARED SPECTROSCOPY; IN-VIVO; COHERENCE TOMOGRAPHY; TUMORS; REPORTER; PROBES; LIGHT; MODEL; MEDIA AB PURPOSE: To develop and test a multichannel reflectance imaging system for small animals on the basis of a previously developed single-channel setup. MATERIALS AND METHODS: The imaging system was composed of modular parts, including a light source, excitation filters, emission filters, and a charged-coupled device for recording images. On the basis of generated excitation and absorption spectra of green fluorescent protein (GFP), tricarbocyanine 5.5 (Cy5.5), and indocyanine green (ICG), filters were selected to allow spectral separation and optimize resultant recorded signal. The system was tested by using a combination of the fluorochromes to confirm spectral separation. In vivo tests were performed in nude mice with tumors that expressed cathepsin B, which could be evaluated by using a Cy5.5-based activatable probe and GFP. For each in vivo tumor type and channel, statistical analysis was performed on the basis of signal intensity in the region of interest. RESULTS: The different fluorochromes were readily distinguished with the system; characteristics such as power were determined for all wavelengths. The system demonstrated a linear response for GFP, a monotonic response for Cy5.5 over a range of more than three orders of magnitude of concentration, and a more complex response for ICG. In vivo analysis demonstrated the ability to image GFP expression and cathepsin B expression separately in tumors: As expected, marked differences were observed in GFP-expression imaging between tumor types (1,363 arbitrary units [AU] +/- 236 [SD] vs 110 AU +/- 11 for GFP-positive and GFP-negative tumors, respectively; P < .001), whereas similar cathepsin B expression (1,070 AU 285 vs 1,168 AU 367; P > .5) was observed. Histologic analysis confirmed in vivo findings. CONCLUSION: Imaging multiple gene expressions simultaneously in vivo by using optical imaging is feasible. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, CNY149-5403,Bldg 149,13th St, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 22 TC 49 Z9 50 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2002 VL 224 IS 2 BP 446 EP 451 DI 10.1148/radiol.2242011589 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 576UY UT WOS:000177025400022 PM 12147841 ER PT J AU Scott, JA AF Scott, JA TI Pulmonary perfusion patterns and pulmonary arterial pressure SO RADIOLOGY LA English DT Article DE computers, neural network; hypertension, pulmonary; lung, radionuclide studies; radionuclide imaging ID ARTIFICIAL NEURAL-NETWORK; FRACTAL ANALYSIS; LUNG SCANS; EMBOLISM; DIAGNOSIS; HYPERTENSION; EMPHYSEMA; IMAGES AB PURPOSE: To use artificial intelligence methods to determine whether quantitative parameters describing the perfusion image can be synthesized to make a reasonable estimate of the pulmonary arterial (PA) pressure measured at angiography. MATERIALS AND METHODS: Radionuclide perfusion images were obtained in 120 patients with normal chest radiographs who also underwent angiographic PA pressure measurement within 3 days of the radionuclide study. An artificial neural network (ANN) was constructed from several image parameters describing statistical and boundary characteristics of the perfusion images. With use of a leave-one-out cross-validation technique, this method was used to predict the PA systolic pressure in cases on which the ANN had not been trained. A Pearson correlation coefficient was determined between the predicted and measured PA systolic pressures. RESULTS: ANN predictions correlated with measured pulmonary systolic pressures (r = 0.846, P < .001). The accuracy of the predictions was not influenced by the presence of pulmonary embolism. None of the 51 patients with predicted PA pressures of less than 29 mm Hg had pulmonary hypertension at angiography. All 13 patients with predicted PA pressures greater than 48 mm Hg had pulmonary hypertension at angiography. CONCLUSION: Meaningful information regarding PA pressure can be derived from noninvasive radionuclide perfusion scanning. The use of image analysis in concert with artificial intelligence methods helps to reveal physiologic information not readily apparent at visual image inspection. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 55 Fruit St, Boston, MA 02114 USA. NR 21 TC 9 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2002 VL 224 IS 2 BP 513 EP 518 DI 10.1148/radiol.2242011353 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 576UY UT WOS:000177025400031 PM 12147850 ER PT J AU El-Serag, HB Johanson, JF AF El-Serag, HB Johanson, JF TI Risk factors for the severity of erosive esophagitis in Helicobacter pylori-negative patients with gastroesophageal reflux disease SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE erosive esophagitis; gastroesophageal reflux disease; risk factors ID ENDOSCOPIC ASSESSMENT; HIATUS-HERNIA; SYMPTOMS; PREVALENCE; ADENOCARCINOMA; POPULATION AB Background: The risk factors for the varying grades of erosive esophagitis (EE) severity could be better understood. For that reason, we evaluated the risk factors associated with EE in patients with gastroesophageal reflux disease. Methods: We determined the presence and severity of EE (using the Los Angeles Classification) in patients with negative serology Helicobacter pylori who underwent esophagogastroduodenoscopy as part of screening in four prospective, multicenter, randomized. double-blind comparative trials of once-daily esomeprazole and omeprazole for the acute healing of erosive esophagitis. We also examined the baseline characteristics of enrolled patients, and identified risk factors for severe disease using a multivariable logistic regression model. Results: Erosive esophagitis was documented in 6709 patients of a total of 10,294 patients who underwent endoscopy; of these, 34% had grade A, 39% had grade B, 20% had grade C, and 7% had grade D disease. The majority of patients were male (61%) and Caucasian (93%) with a mean age of 46 years. In the regression model, the following were significant independent risk factors for severe (grades C and D) versus mild erosive esophagitis (grades A and 13): severe heartburn (adjusted odds ratio 1.79); prolonged heartburn >5 years in duration (1.16); obesity (1.21); the presence of hiatus hernia (2.13); male gender (1.97); and Caucasian ethnicity (1.53). Conclusion: In this large sample of patients with predominantly H. pylori-negative gastroesophageal reflux disease, risk factors for severe erosive esophagitis were the duration and severity of heartburn, and obesity. C1 Baylor Coll Med, Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Houston VA Med Ctr, Gastroenterol & Hlth Serv Res, Houston, TX USA. Rockford Gastroenterol Associates, Rockford, IL USA. RP El-Serag, HB (reprint author), Baylor Coll Med, Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 22 TC 64 Z9 67 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD AUG PY 2002 VL 37 IS 8 BP 899 EP 904 DI 10.1080/003655202760230847 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 591BD UT WOS:000177859100006 PM 12229963 ER PT J AU Hoch, B Juknevicius, I Liapis, H AF Hoch, B Juknevicius, I Liapis, H TI Glomerular injury associated with hepatitis C infection: A correlation with blood and tissue HCV-PCR SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE glomerulonephritis; hepatitis C virus; polymerase chain reaction ID CRYOGLOBULINEMIC MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; VIRUS-INFECTION; MEMBRANOUS GLOMERULONEPHRITIS; MIXED CRYOGLOBULINEMIA; FIBRILLARY GLOMERULONEPHRITIS; RENAL-TRANSPLANTATION; MONONUCLEAR-CELLS; VIRAL-INFECTION; DISEASE; COMBINATION AB Membranoproliferative glomerulonephritis, with or without cryoglobulinemia, and membranous glomerulonephritis are the best characterized glomerulonephropathies associated with hepatitis C virus (HCV) infection. Other more unusual patterns of glomerular injury, including IgA nephropathy, focal segmental glomerulosclerosis, crescentic glomerulonephritis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, and thrombotic microangiopathy, have also been associated with HCV infection, but primarily on an anecdotal basis. It remains uncertain whether the patterns of glomerular injury seen in HCV infected patients, particularly the unusual patterns, represent a disease process specifically related to HCV infection or whether they represent nonspecific patterns of injury due to other causes that happen to occur in HCV-infected patients. We examine this issue by reviewing the epidemiological and pathological evidence in the literature that either supports or refutes a specific relationship between HCV and the pattern of glomerular injury. We also include our experience with 31 HCV-infected patients. In addition, the pathogenesis of HCV-associated glomerulonephropathies is discussed with an emphasis on the significance of detecting HCV in renal biopsies by reverse transcriptase-polymerase chain reaction. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Washington Univ, Div Nephrol, St Louis, MO USA. Washington Univ, Dept Pathol & Immunol & Internal Med, St Louis, MO USA. RP Hoch, B (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit ST, Boston, MA 02114 USA. NR 58 TC 14 Z9 16 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 AUG PY 2002 VL 19 IS 3 BP 175 EP 187 DI 10.1053/sdia.2002.34249 PG 13 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 582AB UT WOS:000177326600007 PM 12180637 ER PT J AU Kandziora, F Pflugmacher, R Kleemann, R Duda, G Wise, DL Trantolo, DJ Lewandrowski, KU AF Kandziora, F Pflugmacher, R Kleemann, R Duda, G Wise, DL Trantolo, DJ Lewandrowski, KU TI Biomechanical analysis of biodegradable interbody fusion cages augmented with poly(propylene glycol-co-fumaric acid) SO SPINE LA English DT Article DE interbody fusion; biodegradable implant system; biomechanical analysis ID SPINAL INSTRUMENTATION; CANINE MODEL; FIXATION; IMPLANT; COMPLICATIONS; POLYMER; CEMENT; DEVICE; SYSTEM AB Study Design. Three different types of biodegradable poly(L-lactide-co-D,L-lactide) cages with and without augmentation of a biodegradable poly(propylene glycol-cofumaric acid) scaffold were compared with autograft and metallic cages of the same design and size by determining the stiffness and failure load of the L4-L5 motion segment of cadaveric human spines. Objectives. To determine how these devices limit the range of motion in the lumbar spine compared with a metallic cage. If biomechanically equivalent, biodegradable spinal fusion systems ultimately could reduce local stress shielding and diminish the incidence of clinical complications, including device-related osteopenia, implant loosening, and breakage. Summary of Background Data. Previous studies in dogs and humans have demonstrated vertebral body osteopenia as a result of instrumented spine fusions. To the authors' knowledge, neither an in vitro nor an in vivo biomechanical analysis of a biodegradable interbody fusion system has been performed. Methods. Forty-eight L4-L5 motion segments were isolated from 22 male and 26 female human donors with an average age of 49.6+/-2.7 years (range 36-55 years). Cages of similar dimensions and design, including a threaded, hollow, porous titanium BAK cage and three different BIO cages (BIO cage 1, pure polymer; BIO cage 2, polymer plus hydroxyapatite buffer; BIO cage 3, polymer plus nano-sized hydroxyapatite), produced from the same poly(L-lactide-co-D,L-lactide) polymer were tested in a comparative analysis to intact motion segment, interbody implantation of autograft, and a BIO cage augmented with an expandable biodegradable foam-scaffold fashioned from poly(propylene glycol-cofumaric acid). Results. All cages were able to increase stiffness and failure load of the unstable motion segment significantly (P<0.01). In comparison with the bone graft, the BAK cage (P<0.01) and BIO cages 1 and 3 (P<0.05) were able to increase stiffness and failure load. There was no significant difference between BIO cage 2 and the bone graft. Augmentation of BIO cage 1 with the foaming PPF scaffold resulted in higher stiffness and similar failure load as seen with the BAK cage. Conclusion. By comparison, the in vitro lumbar spinal motion segment stiffness and failure load produced by implantation of a biodegradable interbody fusion cage augmented with an expandable PPF scaffold is similar to that of the titanium BAK cage. This suggests that biodegradable anterior interbody fusion systems could be further developed for clinical applications. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Humboldt Univ, Univ Klinikum Charite, Unfall & Wiederherstellungschirurg, Berlin, Germany. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St St, Cambridge, MA 02138 USA. EM dtrantolo@aol.com RI Duda, Georg/H-2085-2016 OI Duda, Georg/0000-0001-7605-3908 FU NIAMS NIH HHS [AR 45062]; NIDCR NIH HHS [1 R43 DE 12290-01A1] NR 32 TC 20 Z9 21 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD AUG 1 PY 2002 VL 27 IS 15 BP 1644 EP 1651 DI 10.1097/00007632-200208010-00010 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 581XN UT WOS:000177320200009 PM 12163726 ER PT J AU Zhou, XH AF Zhou, XH TI Inferences about population means of health care costs SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review ID ESTIMATING MEDICAL COSTS; CONFIDENCE-INTERVALS; DISTRIBUTIONS; SAMPLES AB The analysis of health care costs is complicated by the skewed and heteroscedastic nature of their distribution with possibly additional zero values. Statistical methods that do not adjust for these features can lead to incorrect conclusions. This paper reviews recent developments in statistical methods for the analysis of health care costs; our focus is on population means. C1 Indiana Univ, Sch Med, Dept Med, Div Biostat,RG 4101, Indianapolis, IN 46202 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. RP Zhou, XH (reprint author), Indiana Univ, Sch Med, Dept Med, Div Biostat,RG 4101, 1050 Wishard Blvd, Indianapolis, IN 46202 USA. FU NIMH NIH HHS [R01MH58875] NR 22 TC 14 Z9 14 U1 0 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD AUG PY 2002 VL 11 IS 4 BP 327 EP 339 DI 10.1191/0962280202sm290ra PG 13 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 585WU UT WOS:000177548200004 PM 12197300 ER PT J AU Dijkhuizen, RM Asahi, M Wu, O Rosen, BR Lo, EH AF Dijkhuizen, RM Asahi, M Wu, O Rosen, BR Lo, EH TI Rapid breakdown of microvascular barriers and subsequent hemorrhagic transformation after delayed recombinant tissue plasminogen activator treatment in a rat embolic stroke model SO STROKE LA English DT Article DE blood-brain barrier; cerebral hemorrhage; cerebral ischemia, focal; magnetic resonance imaging; thrombolytic therapy; rats ID BLOOD-BRAIN-BARRIER; RT-PA TREATMENT; FOCAL CEREBRAL-ISCHEMIA; THROMBOEMBOLIC STROKE; INTRACEREBRAL HEMORRHAGE; INJURY; MATRIX-METALLOPROTEINASE-9; THROMBOLYSIS; APPEARANCE; VOLUME AB Background and Purpose-Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) after stroke increases risk of hemorrhagic transformation, particularly in areas with blood-brain barrier leakage. Our aim was to characterize acute effects of rtPA administration on the integrity of microvascular barriers. Methods-Stroke was induced in spontaneously hypertensive rats by unilateral embolic middle cerebral artery occlusion. Six hours after stroke, rtPA was intravenously administered (n=10). Controls received saline (n=4). Extravasation of the large-diameter contrast agent monocrystalline iron oxide nanocolloid (MION) was assessed with susceptibility contrast-enhanced MRI during rtPA injection. In addition, we performed perfusion MRI and diffusion-weighted MRI. After MRI, 2 hours after rtPA treatment, intracerebral hemorrhage was quantified with a spectrophotometric hemoglobin assay. Results-Late rtPA treatment resulted in increased hemorrhage volume (8.4 +/- 1.7 versus 2.9 +/- 0.9 muL in controls; P<.05). In MION-injected animals, during rtPA administration, transverse relaxation rate change (DeltaR(2)*) increased from 12.4 +/- 6.0 to 31.6 +/- 19.2 s(-1) (P<0.05) in areas with subsequent hemorrhage. Significant DeltaR(2)* changes were absent in nonhemorrhagic areas, in animals without injected MION, and in saline-treated animals. Thrombolytic therapy did not improve perfusion in regions with hemorrhagic transformation (cerebral blood flow index was 22.8 +/- 19.7% [of contralateral] at 0.5 hours before and 22.4 +/- 18.0% at 1 hour after rtPA administration). Conclusions-The DeltaR(2)* changes during rtPA delivery in MION-injected animals indicate extravasation of MION, which reflects increased permeability of the blood-brain barrier. This implies that late rtPA treatment rapidly aggravates early ischemia-induced damage to microvascular barriers, thereby enhancing hemorrhagic transformation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. RP Dijkhuizen, RM (reprint author), Univ Utrecht, Ctr Med, Image Sci Inst, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. RI Dijkhuizen, Richard/A-6506-2008; OI Dijkhuizen, Rick/0000-0002-4623-4078 FU NCI NIH HHS [P01-CA48729]; NCRR NIH HHS [P41-RR14075]; NHLBI NIH HHS [R01-HL39810]; NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS38731, R29-NS32806] NR 30 TC 70 Z9 77 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2002 VL 33 IS 8 BP 2100 EP 2104 DI 10.1161/01.STR.0000023534.37670.F7 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 581XM UT WOS:000177320100040 PM 12154270 ER PT J AU Lightner, AM Jordan, TH Bunnett, NW Grady, EF Kirkwood, KS AF Lightner, AM Jordan, TH Bunnett, NW Grady, EF Kirkwood, KS TI Recombinant human neutral endopeptidase ameliorates pancreatic elastase-induced lung injury SO SURGERY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Society-of-University-Surgeons CY FEB 14-16, 2002 CL HONOLULU, HAWAII SP Soc Univ Surg ID INHIBITORY-KAPPA-B; SUBSTANCE-P; NEUROGENIC INFLAMMATION; MODULATION; ENZYMES AB Background. Genetic deletion of neutral endopeptidase (NEP), a cell-surface metalloprotease that degrades proinflammatory peptides, exacerbates lung injury induced by pancreatic elastase in a model of pancreatitis-associated lung injury. We tested 3 hypotheses: (1) genetic deletion of NEP prolongs lung recovery after elastase injections; (2) elastase-mediated lung injury is associated with down-regulation of NEP; and (3) pretreatment of NEP and (+/+) animals with recombinant human NEP (rhNEP) reduces pulmonary damage in this model. Methods. NEP (+/+) or (-/-) mice were injected with pancreatic elastase (0.085 U/g/dose intraperitoneally) or saline carrier at t = 0 hours and t = 1 hour. Some mice were pretreated with rhNEP (3 mg/kg intraperitoneally). Serum elastase, lung histologic score, myeloperoxidase, and NEP activities were measured at 4, 8, or 12 hours. Results. AEP (-/-) mice had worse pulmonary inflammation at 4 and 8 hours versus (+/+) mice. Lung AEP activity was similar in elastase-treated and control (+/+) animals. Pretreatment with rhNEP reduced myeloperoxidase and improved histology at 4 hours in NEP (-/-) and (+/+) mice. Conclusions. Pancreatic elastase induces lung injury that is worse and prolonged in NEP (-/-) mice. Pretreatment with rhNEP ameliorates this injury. Thus, upregulation of NEP is a potential therapeutic approach for pancreatitis-associated lung injury. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Kirkwood, KS (reprint author), 533 Parnassus Ave,Room U-372, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [R01-DK-52388, T32 DK-07573-12, R01 DK-46285-05] NR 25 TC 5 Z9 6 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 AUG PY 2002 VL 132 IS 2 BP 193 EP 199 DI 10.1067/msy.2002.125309 PG 7 WC Surgery SC Surgery GA 590YG UT WOS:000177851900012 PM 12219011 ER PT J AU Grikscheit, TC Ogilvie, JB Ochoa, ER Alsberg, E Mooney, D Vacanti, JP AF Grikscheit, TC Ogilvie, JB Ochoa, ER Alsberg, E Mooney, D Vacanti, JP TI Tissue-engineered colon exhibits function in vivo SO SURGERY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the Society-of-University-Surgeons CY FEB 14-16, 2002 CL HONOLULU, HAWAII SP Soc Univ Surg ID POUCH-ANAL ANASTOMOSIS; ULCERATIVE-COLITIS; ILEAL RESERVOIR AB Background. Postcolectomy morbidities include important changes in enterohepatic circulation, stool microbiology, and absorption. The surgical substitution of an ileal pouch for the absent colon also has a number of serious complications. We report in vivo colon replacement by tissue-engineered colon (TEC) in lieu of an ileal pouch. Methods. End-ileostomies were created in 22 male Lewis rats. In 11 animals, side-to-side ileum-TEC anastomosis was performed I cm from the stoma. This group was compared with end-ileostomy alone. Serial weights were measured, and animals were harvested sequentially for assessment of histologic signs of pouchitis. Transit times, stool dry and wet weights, and serum and stool colon Junction markers were collected. Results. Animals survived 41 days. Weight loss was more than 1.5 times greater in the end-ileostomy alone group compared with the ileum-TEC group. Transit times were significantly longer in the ileum-TEC group than the end-ileostomy alone group, with lower stool moisture content and higher total serum bile acids. Animals without TEC had statistically significant hyponatremia, elevated serum urea nitrogen, and lower stool short. chain fatty acids (13.5 mumol/kg vs 84.2) with an abnormal distribution. Conclusions. TEC successfully recapitulates some major physiologic functions of native large intestine in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Integrat Med & Innovat Technol, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Integrat Med & Innovat Technol, Dept Pathol, Boston, MA 02114 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 42 Z9 43 U1 0 U2 5 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 AUG PY 2002 VL 132 IS 2 BP 200 EP 204 DI 10.1067/msy.2002.125310 PG 5 WC Surgery SC Surgery GA 590YG UT WOS:000177851900013 PM 12219012 ER PT J AU Vangel, MG AF Vangel, MG TI Lot acceptance and compliance testing using the sample mean and an extremum SO TECHNOMETRICS LA English DT Article DE acceptance testing; category B sampling plan; NBS handbook 133; saddlepoint AB In industry, one sometimes compares a sample mean and minimum, or a mean and maximum, to reference values to determine whether a lot should be accepted. Particularly prominent examples of such procedures are "Category B" sampling plans for checking the net contents of packaged goods. Because the exact joint distribution of an extremum and the mean of a sample is usually complicated, establishing these reference values using statistical considerations typically involves crude approximations or simulation, even under the assumption of normality. The purpose of this article is to use the saddlepoint method to develop a fairly simple and very accurate approximation to the joint cumulative distribution function (cdf) of the mean and an extremum of a normal sample. This approximation can be used to establish statistically based acceptance criteria or to evaluate the performance of sampling plans based on criteria derived in other ways. These uses are illustrated with examples. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Vangel, MG (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. NR 6 TC 5 Z9 6 U1 1 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0040-1706 J9 TECHNOMETRICS JI Technometrics PD AUG PY 2002 VL 44 IS 3 BP 242 EP 249 DI 10.1198/004017002188618428 PG 8 WC Statistics & Probability SC Mathematics GA 606LD UT WOS:000178734700004 ER PT J AU Lin, AE AF Lin, AE TI The heart of Turner syndrome: Small matters SO TERATOLOGY LA English DT Editorial Material ID ASSOCIATION; DISEASE C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Lin, AE (reprint author), 36 Fieldstone Rd, Westwood, MA 02090 USA. NR 16 TC 2 Z9 3 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 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 2002 VL 66 IS 2 BP 63 EP 64 DI 10.1002/tera.10063 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 578HG UT WOS:000177110900006 PM 12210008 ER PT J AU Gouveia, CH Schultz, JJ Jackson, DJ Williams, GR Brent, GA AF Gouveia, CH Schultz, JJ Jackson, DJ Williams, GR Brent, GA TI Thyroid hormone gene targets in ROS 17/2.8 osteoblast like cells identified by differential display analysis SO THYROID LA English DT Article ID ENDOCHONDRAL BONE-FORMATION; MYOSIN ISOZYME TRANSITIONS; RAT-LIVER; CHONDROCYTE DIFFERENTIATION; POSTNATAL-DEVELOPMENT; MESSENGER-RNA; EXPRESSION; RECEPTORS; GROWTH; NUCLEAR AB Thyroid hormone plays an important role in bone development and metabolism. We used a polymerase chain reaction (PCR)-based mRNA differential display (DD) analysis to obtain a profile of thyroid hormone-responsive genes in osteoblast-like cells (ROS 17/2.8). ROS 17/2.8 cells were treated with 10(-8) M triiodothyronine (T-3) for 2 and 24 hours. Total RNA was isolated, reverse-transcribed, and amplified using a total of 72 combinations (2 hours) and 240 combinations (24 hours) of 5' and 3' primers. At the 2-hour time point, 1 true-positive novel clone was identified and shown to be the mitochondrial gene, subunit 6 of ATP synthase (ATPase-6). At the 24-hour time point, 3 differentially expressed (DE) mRNAs were confirmed as true-positives including; nonmuscle alkali myosin light chain (NM aMLC), ATPase-6, and one novel clone. T-3-induction of ATPase-6 mRNA in ROS 17/2.8 cells was seen at 2 and 4 hours, but was maximal at 24 hours (2.1-fold). T-3 induction of ATPase-6 mRNA was increased to fourfold in ROS 17/2.8 cells cultured at a low density. NM aMLC mRNA was modestly upregulated by T-3 in ROS 17/2.8 cells by 1.4-fold, and induction was augmented at low cell density to 1.7-fold. T-3 action on NM aMLC and on the mitochondrial gene ATPase 6, represent novel targets and potential mediators of thyroid hormone action on bone. Cell type, and the extent of cell differentiation, influences T-3 regulation of genes in osteoblast-derived cells. C1 VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 89364] NR 47 TC 6 Z9 8 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 AUG PY 2002 VL 12 IS 8 BP 663 EP 671 DI 10.1089/105072502760258631 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586BB UT WOS:000177561300003 PM 12225634 ER PT J AU Kang, YH Berthiaume, F Yarmush, ML AF Kang, YH Berthiaume, F Yarmush, ML TI Long-term stable cultures of rat hepatocytes: An in vitro model to study acute and chronic hepatic inflammation SO TISSUE ENGINEERING LA English DT Article ID TUMOR-NECROSIS-FACTOR; CYTOKINE GENE-EXPRESSION; ACUTE-PHASE RESPONSE; NITRIC-OXIDE; FACTOR-ALPHA; INTERLEUKIN-1 RECEPTOR; SANDWICH CONFIGURATION; PROTEIN-SYNTHESIS; MESSENGER-RNA; MITOCHONDRIAL RESPIRATION AB Engineered tissues provide an opportunity to investigate important physiological processes difficult to study in whole perfused organs and animal models. For example, a hepatocyte culture model consisting of rat hepatocytes cultured in a collagen sandwich configuration, which exhibits stable differentiated liver-specific functions, may be useful to investigate liver pathophysiology. To investigate systemic inflammation-related hepatic failure, we chronically exposed hepatocytes to the inflammatory mediators interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) for up to 4 weeks. IL-6 (2.5 ng/mL) transiently suppressed albumin (-90%) and chronically increased fibrinogen (+6-fold) production. IL-6 inhibited urea synthesis at 2.5 ng/mL and stimulated it at 0.025 ng/mL. IL-1beta (10 ng/mL) inhibited albumin (-90%, urea (-40 to 50%), and IL-6-stimulated fibrinogen (-90%) secretion. The inhibitory effect of IL-1beta on urea secretion was dose-dependent. Furthermore, IL-1beta transiently stimulated nitric oxide (NO) synthesis; however, NO did not mediate the effect of IL-1beta on albumin and fibrinogen production, and played a minor role in IL-1beta-mediated urea synthesis suppression. In conclusion, IL-1beta and IL-6 exert, via a direct effect on hepatocytes, long-term inhibitory effects on hepatic functions that are potentially important for the survival of the host, which may contribute to hepatic dysfunction in prolonged inflammatory states. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, GRB 1401,55 Fruit St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIGMS NIH HHS [R01 GM58125] NR 63 TC 18 Z9 19 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 2002 VL 8 IS 4 BP 681 EP 693 DI 10.1089/107632702760240599 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 584MR UT WOS:000177470800015 PM 12202007 ER PT J AU Lin, TM Ko, K Moore, RW Simanainen, U Oberley, TD Peterson, RE AF Lin, TM Ko, K Moore, RW Simanainen, U Oberley, TD Peterson, RE TI Effects of aryl hydrocarbon receptor null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Toxicology CY MAR 19-23, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Toxicol DE 2,3,7,8-tetrachlorodibenzo-p-dioxin; in utero; lactational exposure; TCDD; aryl hydrocarbon receptor null mutation; AhRKO mice; prostate; seminal vesicles; gene expression; development; mice ID MALE-RATS; SECRETORY PROTEIN; AH RECEPTOR; IN-UTERO; MOUSE; EXPRESSION; INUTERO; GENE; LACKING; CLONING AB Experiments were conducted to determine the effects of aryl hydrocarbon receptor (AhR) null mutation and in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, alone and in combination, on prostate and seminal vesicle development in C57BL/6 mice. AhR heterozygous (Ahr(+/-)) mice were mated, and pregnant females were dosed orally on gestation day 13 with TCDD (5 mug/kg) or vehicle. Pups underwent necropsy on postnatal days (PNDs) 35 and 90. Comparison of vehicle-exposed AhR knockout (AhRKO;Ahr(-/-)) with wild-type (Ahr(+/+)) pups revealed that the AhR is necessary for normal dorsolateral prostate, anterior prostate, and seminal vesicle development but apparently not for ventral prostate development. In wild-type mice,in utero and lactational TCDD exposure reduced ventral prostate weight by 79-87% and mRNA expression for its major androgen-dependent secretory protein (MP25) by 99%. Yet high levels of mRNA for a secretory protein normally produced primarily by the lateral prostate (PSP94) were expressed. These effects were predominantly AhR dependent because TCDD had little if any effect in AhRKO mice. TCDD reduced dorsolateral prostate weight in wild-type but not AhRKO mice and had no significant effect on expression of mRNA for PSP94 or for probasin, a major androgen-dependent secretory protein. The PSP94 results suggest that TCDD may have caused a respecification of prostatic gene expression. TCDD reduced anterior prostate weight by more than half, and expression of mRNA for its major androgen-dependent secretory protein (renin-1) was greatly reduced. These effects were AhR dependent. Seminal vesicle weight was reduced by TCDD in wild-type mice but was increased in AhRKO mice on PND 35 and decreased on PND 90 (relative weight only). Androgen receptor mRNA levels were not significantly altered in any prostate lobe, and all organs appeared histologically normal in all groups. Serum testosterone concentrations were unchanged, and modest reductions in serum 5alpha-androstane-3alpha,17beta-diol concentrations could not account for the effects on sex organs. Collectively, these results indicate that the AhR signaling pathway plays a role in normal accessory sex organ development and thatin utero and lactational TCDD exposure disrupts development of these organs via spatially and perhaps temporally specific mechanisms. C1 Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA. Univ Wisconsin, Endocrinol Reprod Physiol Program, Madison, WI 53705 USA. Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53705 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Peterson, RE (reprint author), Univ Wisconsin, Sch Pharm, 777 Highland Ave, Madison, WI 53705 USA. FU NIEHS NIH HHS [ES01332, P30 ES09090] NR 24 TC 79 Z9 82 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2002 VL 68 IS 2 BP 479 EP 487 DI 10.1093/toxsci/68.2.479 PG 9 WC Toxicology SC Toxicology GA 580GC UT WOS:000177226000027 PM 12151645 ER PT J AU Boll, W Rapoport, I Brunner, C Modis, Y Prehn, S Kirchhausen, T AF Boll, W Rapoport, I Brunner, C Modis, Y Prehn, S Kirchhausen, T TI The mu 2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppO sorting signals at distinct sites SO TRAFFIC LA English DT Article DE Alzheimer's; AP-2 adaptor; clathrin; endocytosis; membrane traffic ID EPIDERMAL GROWTH-FACTOR; LOW-DENSITY-LIPOPROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; PROTEIN COMPLEX AP-2; TRANS-GOLGI NETWORK; CD4 DOWN-REGULATION; CYTOPLASMIC DOMAIN; LDL RECEPTOR; COATED PITS; HIV-1 NEF AB The endocytic sorting signal on the low-density lipoprotein receptor for clathrin-mediated internalization is the sequence FDNPVY in the receptor's cytosolic tail. We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the mu2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting). We show that recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppO sorting signal, another tyrosine-based sequence also recognized by mu2-adaptin. These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA. Humboldt Univ, Inst Biochem, D-10115 Berlin, Germany. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM36548] NR 54 TC 58 Z9 60 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD AUG PY 2002 VL 3 IS 8 BP 590 EP 600 DI 10.1034/j.1600-0854.2002.30808.x PG 11 WC Cell Biology SC Cell Biology GA 574TL UT WOS:000176905600008 PM 12121421 ER PT J AU Zubair, AC Silberstein, L Ritz, J AF Zubair, AC Silberstein, L Ritz, J TI Adult hematopoietic stem cell plasticity SO TRANSFUSION LA English DT Article ID BONE-MARROW CELLS; CD34(+) CELLS; IN-VIVO; NOD/SCID MICE; DIFFERENTIATE; HEPATOCYTES; ENGRAFTMENT; BRAIN; TRANSPLANTATION; EXPRESSION C1 Dana Farber Canc Inst, Joint Program Transfus Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Zubair, AC (reprint author), Dana Farber Canc Inst, Joint Program Transfus Med, 530 Mayer Bldg,44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 30 TC 6 Z9 10 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2002 VL 42 IS 8 BP 1096 EP 1101 DI 10.1046/j.1537-2995.2002.00156.x PG 6 WC Hematology SC Hematology GA 585RM UT WOS:000177538400022 PM 12385424 ER PT J AU Cosimi, AB AF Cosimi, AB TI Calcineurin inhibitors are not antagonistic to tolerance induction SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Immunosuppression CY DEC 06-08, 2001 CL SAN DIEGO, CALIFORNIA ID DONOR SPLEEN-CELLS; ALLOGRAFT TOLERANCE; RENAL-ALLOGRAFTS; CYCLOSPORINE-A; IMMUNOSUPPRESSION; TRANSPLANTATION; RECIPIENTS; MECHANISM; BLOCKADE; RELEVANT C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 18646]; NIAID NIH HHS [R01 AI 37692] NR 18 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 2002 VL 34 IS 5 BP 1376 EP 1377 DI 10.1016/S0041-1345(02)02954-8 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 582UN UT WOS:000177369700004 PM 12176403 ER PT J AU Rabkin, JM Rosen, HR Corless, CL Olyaei, AJ AF Rabkin, JM Rosen, HR Corless, CL Olyaei, AJ TI Tacrolimus is associated with a lower incidence of cardiovascular complications in liver transplant recipients SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Immunosuppression CY DEC 06-08, 2001 CL SAN DIEGO, CALIFORNIA ID MANAGEMENT; DISEASE C1 Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Dept Surg, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 9 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 2002 VL 34 IS 5 BP 1557 EP 1558 AR PII S0041-1345(02)03020-8 DI 10.1016/S0041-1345(02)03020-8 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 582UN UT WOS:000177369700084 PM 12176483 ER PT J AU Baid, S Tolkoff-Rubin, N Farrell, ML Delmonico, FL Williams, WW Hayden, D Ko, D Cosimi, AB Pascual, M AF Baid, S Tolkoff-Rubin, N Farrell, ML Delmonico, FL Williams, WW Hayden, D Ko, D Cosimi, AB Pascual, M TI Tacrolimus-associated posttransplant diabetes mellitus in renal transplant recipients: Role of hepatitis C infection SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 2nd International Congress on Immunosuppression CY DEC 06-08, 2001 CL SAN DIEGO, CALIFORNIA ID VIRUS-INFECTION; IMMUNOSUPPRESSION; CYCLOSPORINE; RISK C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Baid, S (reprint author), Massachusetts Gen Hosp, Renal Unit, 100 Charles River Plaza,5th Floor, Boston, MA 02114 USA. NR 10 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 2002 VL 34 IS 5 BP 1771 EP 1773 AR PII S0041-1345(02)03060-9 DI 10.1016/S0041-1345(02)03060-9 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 582UN UT WOS:000177369700170 PM 12176569 ER PT J AU Bogdanov, A Weissleder, R AF Bogdanov, Alexei, Jr. Weissleder, Ralph TI In vivo imaging of gene delivery and expression SO TRENDS IN BIOTECHNOLOGY LA English DT Review AB Recent progress in the development of high-resolution imaging techniques and reporter probes is expected to revolutionize molecular imaging research in animal models of human disease and, ultimately, clinical practice. These developments provide inroads to continuous monitoring and quantitation of gene delivery and gene expression during experimental gene therapy. Furthermore, techniques using novel imaging transgenes and reporter probes enable imaging of the regulation of gene expression in living animals. This could significantly aid the development of therapeutics targeted at individual populations of cells or even specific molecules. C1 [Bogdanov, Alexei, Jr.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. RP Bogdanov, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02115 USA. EM bogdanov@helix.mgh.harvard.edu FU National Cancer Institute; Schering AG FX We acknowledge Angelique Louie, Juri Gelovani, Sanjiv Gambhir, Dawid Schellingerhout, James McArthur and Kurt Zinn for providing the images used in this review. We also acknowledge financial support from National Cancer Institute grants and Schering AG. NR 33 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD AUG PY 2002 VL 20 IS 8 BP S11 EP S18 AR PII S0167-7799(02)02007-3 DI 10.1016/S0167-7799(02)02007-3 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA V26HH UT WOS:000208536200003 ER PT J AU Samad, TA Sapirstein, A Woolf, CJ AF Samad, TA Sapirstein, A Woolf, CJ TI Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID CYTOSOLIC PHOSPHOLIPASE A(2); PROSTAGLANDIN-E SYNTHASE; ANTIINFLAMMATORY DRUGS; MESSENGER-RNA; UP-REGULATION; SPINAL-CORD; INFLAMMATORY PAIN; MOLECULAR-BIOLOGY; ARACHIDONIC-ACID; IMMUNE-RESPONSES AB Advances in our understanding of the synthesis, regulation and function of prostanoids have led to a new appreciation of their actions in health and disease. Prostanoid synthesis is essential for the generation of inflammatory pain and this depends not only on prostanoid production at the site of inflammation, but also on the actions of prostanoids synthesized within the central nervous system (CNS). Moreover, central prostanoid synthesis is controlled both by neural and humoral signals, the latter being a novel form of input to the CNS. Diverse compounds that act along the pathway of prostanoid synthesis and action, both in the periphery and in the CNS, might provide increased benefit for treating inflammatory pain hypersensitivity and its associated sickness syndrome, with a reduced risk of adverse effects. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Samad, TA (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. NR 65 TC 138 Z9 144 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD AUG PY 2002 VL 8 IS 8 BP 390 EP 396 AR PII S1471-4914(02)02383-3 DI 10.1016/S1471-4914(02)02383-3 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 581FN UT WOS:000177280600006 PM 12127725 ER PT J AU Rowitch, DH Lu, QR Kessaris, N Richardson, WD AF Rowitch, DH Lu, QR Kessaris, N Richardson, WD TI An 'oligarchy' rules neural development SO TRENDS IN NEUROSCIENCES LA English DT Review ID CHICK SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE DIFFERENTIATION; SONIC HEDGEHOG; TRANSCRIPTION FACTOR; STEM-CELLS; PROGENITOR-CELL; MOTOR-NEURON; CLONAL ANALYSIS; BHLH PROTEINS AB Recent reports show that Olig genes, which encode the basic helix-loop-helix Olig transcription factors, are essential for development of oligodendrocytes. Surprisingly, Olig function is also required for formation of somatic motor neurons. These findings alter our views of how the oligodendrocyte lineage is generated and raise further questions about the underlying developmental relationships between neurons and glia. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. UCL, Dept Biol, London WC1E 6BT, England. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM david_rowitch@dfci.harvard.edu RI Richardson, William/C-1762-2008; Kessaris, Nicoletta/C-7249-2008 OI Richardson, William/0000-0001-7261-2485; Kessaris, Nicoletta/0000-0003-1191-6009 NR 50 TC 114 Z9 120 U1 2 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD AUG PY 2002 VL 25 IS 8 BP 417 EP 422 DI 10.1016/S0166-2236(02)02201-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 576HU UT WOS:000176998500016 PM 12127759 ER PT J AU Sullivan, MP Yalla, SV AF Sullivan, MP Yalla, SV TI Physiology of female micturition SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID EXTERNAL URETHRAL SPHINCTER; URINARY-BLADDER FUNCTION; NITRIC-OXIDE SYNTHASE; HORMONE-RELATED PROTEIN; GENE-RELATED PEPTIDE; SMOOTH-MUSCLE; MECHANICAL STRETCH; RECEPTOR DENSITY; PRESSURE PROFILE; RABBIT URETHRA AB Micturition is a dynamic physiologic process consisting of alternating storage and expulsion phases and is accomplished by complex interactions among innervation, smooth muscle, connective tissue, urothelium and supportive structures. Although our current understanding of the anatomy and physiology of the lower urinary tract is far from complete, intensive research over the last decade has dramatically improved our appreciation of the neural, biomechanical, biochemical, and morphologic properties of the bladder and urethra, as well as the hormonal influences and unique pelvic and perineal anatomy of women. Continued research related to the physiology of female micturition promises to offer new insights into the complex bladder-urethral interactions and to provide a basis for developing better management strategies for a variety of voiding dysfunctions in women. C1 VA Boston Healthcare Syst, Boston, MA 02132 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Sullivan, MP (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 91 TC 6 Z9 7 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 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD AUG PY 2002 VL 29 IS 3 BP 499 EP + AR PII S0094-0143(02)00068-X DI 10.1016/S0094-0143(02)00068-X PG 17 WC Urology & Nephrology SC Urology & Nephrology GA 618KU UT WOS:000179417900002 PM 12476515 ER PT J AU MacNeill, BD Pomerantseva, I Lowe, HC Oesterle, SN Vacanti, JP AF MacNeill, BD Pomerantseva, I Lowe, HC Oesterle, SN Vacanti, JP TI Toward a new blood vessel SO VASCULAR MEDICINE LA English DT Article DE atherosclerosis; bypass; coronary artery disease; revascularization; tissue engineering ID HUMAN-ENDOTHELIAL-CELLS; GENE-TRANSFER; IN-VITRO; SMOOTH-MUSCLE; POLYTETRAFLUOROETHYLENE GRAFTS; INTIMAL HYPERPLASIA; TISSUE; ARTERIES; CULTURE; MODEL AB Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting (CABG), in which grafts are used to bypass atherosclerotic vessels and restore blood flow to the ischemic myocardium. The grafts used include healthy arteries or veins harvested from a separate site. Results with arterial grafts have been superior to venous grafts; promoting the practice of total arterial revascularization using only arterial grafts. Suitable arterial grafts, however, are scarce and harvest procedures add to morbidity and cost. Tissue engineering combines the principles of engineering with life sciences for the development of biological substitutes and restore, maintain or improve tissue function. Advances in this field have included the development of tissue-engineered blood vessels, with the potential to serve as arterial grafts, conduits or fistulae. This review describes the history of tissue engineering arteries, the techniques used, and progress to date. The source of cells and the future direction of this field are explored. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tissue Engn Labs, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 55 TC 22 Z9 24 U1 0 U2 5 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD AUG PY 2002 VL 7 IS 3 BP 241 EP 246 DI 10.1191/1358863x02vm433ra PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 637MP UT WOS:000180516400011 PM 12553747 ER PT J AU Dzik, WH AF Dzik, WH TI Cardinal signs of reactions: Hypotension following blood transfusion SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 27th Congress of the international-Society-of-Blood-Transfusion CY AUG 24-29, 2002 CL VANCOUVER, CANADA SP Int Soc Blood Transfusion C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv J224, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv J224, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2002 VL 83 SU 1 BP 145 EP 146 DI 10.1111/j.1423-0410.2002.tb05289.x PG 2 WC Hematology SC Hematology GA 607UZ UT WOS:000178810300036 PM 12617125 ER PT J AU Kuter, DJ AF Kuter, DJ TI Apoptosis in platelets during ex vivo storage SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 27th Congress of the international-Society-of-Blood-Transfusion CY AUG 24-29, 2002 CL VANCOUVER, CANADA SP Int Soc Blood Transfusion C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 6 TC 14 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2002 VL 83 SU 1 BP 311 EP 313 DI 10.1111/j.1423-0410.2002.tb05325.x PG 3 WC Hematology SC Hematology GA 607UZ UT WOS:000178810300072 PM 12617160 ER PT J AU Dzik, WH Mincheff, M Puppo, F AF Dzik, WH Mincheff, M Puppo, F TI An alternative mechanism for the immunosuppressive effect of transfusion SO VOX SANGUINIS LA English DT Article; Proceedings Paper CT 27th Congress of the international-Society-of-Blood-Transfusion CY AUG 24-29, 2002 CL VANCOUVER, CANADA SP Int Soc Blood Transfusion ID INGESTED APOPTOTIC CELLS; GROWTH-FACTOR-BETA; RED-CELLS; BLOOD; MACROPHAGES; LEUKOCYTES; STORAGE; SURGERY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Dzik, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, J-224, Boston, MA 02114 USA. NR 15 TC 4 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD AUG PY 2002 VL 83 SU 1 BP 417 EP 419 DI 10.1111/j.1423-0410.2002.tb05344.x PG 3 WC Hematology SC Hematology GA 607UZ UT WOS:000178810300091 PM 12617178 ER PT J AU Cheah, WK Arici, C Ituarte, PHG Siperstein, AE Duh, QY Clark, OH AF Cheah, WK Arici, C Ituarte, PHG Siperstein, AE Duh, QY Clark, OH TI Complications of neck dissection for thyroid cancer SO WORLD JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT International Surgical Week Conference CY AUG 26-30, 2001 CL BRUSSELS, BELGIUM ID FOLLOW-UP; PAPILLARY; CARCINOMA; AUTOTRANSPLANTATION AB Prophylactic and therapeutic neck dissections are used to control or eliminate local nodal disease in patients with thyroid cancer. The purpose of this study was to evaluate the results and complications of neck dissection. From 1992 to 1999 a series of 115 consecutive neck dissections were performed in 74 patients (32 men, 42 women; mean age 48 years) with thyroid cancer and nodal metastases. Operations included central compartment, lateral modified, and suprahyoid dissection with and without total or completion thyroidectomy. Sixty-four percent of the patients had papillary, 4% follicular, and 32% medullary thyroid cancer. Complications included transient hypocalcemia (23%) defined by a postoperative serum calcium level of < 2.0 mmol/L (8.0 mg/dl), one neck hematoma (0.9%), and one cardiac death (0.9%). There were no permanent recurrent nerve palsies. Hypocalcemia occurred more frequently when neck dissection was combined with total thyroidectomy than without it (p < 0.005). In this group, the incidence of hypocalcemia was higher after central, than lateral, neck dissection. When neck dissection was performed without thyroidectomy, there was no difference in the rates of hypocalcemia between central, lateral, or central with lateral neck dissection (p = NS). Hypocalcemia did not increase with repeated neck dissections (p = NS). Permanent hypoparathyroidism occurred in 0.9%. There were no complications after suprahyoid dissection. The median duration of hospitalization was I day. Therapeutic neck dissection or repeated neck dissection can be performed relatively safely in patients with thyroid cancer. Hypocalcemia occurs most frequently, when neck dissection is combined with total thyroidectomy. C1 Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, San Francisco, CA 94143 USA. Cleveland Clin Fdn, Dept Gen Surg, Cleveland, OH 44195 USA. Univ Calif San Francisco, Dept Surg, San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Clark, OH (reprint author), Univ Calif San Francisco, Dept Surg, Mt Zion Med Ctr, 1600 Divisadero St, San Francisco, CA 94143 USA. NR 11 TC 94 Z9 98 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD AUG PY 2002 VL 26 IS 8 BP 1013 EP 1016 DI 10.1007/s00268-002-6670-4 PG 4 WC Surgery SC Surgery GA 582VN UT WOS:000177372000022 PM 12045861 ER PT J AU Syed, S Weiss, GR AF Syed, S Weiss, GR TI Management of locally advanced bladder cancer: early vs deferred chemotherapy SO WORLD JOURNAL OF UROLOGY LA English DT Article DE bladder cancer; transitional cell carcinoma; prognostic factors; chemotherapy ID TRANSITIONAL-CELL-CARCINOMA; EPIDERMAL-GROWTH-FACTOR; METASTATIC UROTHELIAL CANCER; P53 NUCLEAR OVEREXPRESSION; RADICAL CYSTECTOMY; NEOADJUVANT CHEMOTHERAPY; TUMOR PROGRESSION; PHASE-II; RANDOMIZED TRIAL; URINARY-BLADDER AB Locally advanced bladder cancer is associated with a high risk of local recurrence and distant metastases. Clinical and pathologic variables have been useful in predicting outcome in patients with muscle-invasive bladder cancer. Recently, a number of molecular prognostic markers have been identified that help predict tumor aggressiveness, response to chemotherapy, and survival. Transitional cell carcinoma is a chemosensitive tumor. The early use of chemotherapy to reduce the risk of recurrence and improve survival has been the focus of many randomized clinical trials. Unfortunately, the majority of studies have failed to show a survival advantage for chemotherapy-treated patients. Well-designed prospective trials that target high-risk patients, defined by clinical, pathological, and molecular features, and incorporate new more tolerable chemotherapeutic agents are needed to clarify the benefit of early chemotherapy. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Div Med Oncol, San Antonio, TX 78284 USA. RP Weiss, GR (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. NR 75 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD AUG PY 2002 VL 20 IS 3 BP 175 EP 182 DI 10.1007/s00345-002-0277-0 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 588CV UT WOS:000177683900006 PM 12196901 ER PT J AU Ohiro, Y Garkavtsev, I Kobayashi, S Sreekumar, KR Nantz, R Higashikubo, BT Duffy, SL Higashikubo, R Usheva, A Gius, D Kley, N Horikoshi, N AF Ohiro, Y Garkavtsev, I Kobayashi, S Sreekumar, KR Nantz, R Higashikubo, BT Duffy, SL Higashikubo, R Usheva, A Gius, D Kley, N Horikoshi, N TI A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF) SO FEBS LETTERS LA English DT Article DE p53; target gene; cloning; apoptosis; oxidoreductase; transcription ID WILD-TYPE P53; CELL-CYCLE ARREST; P53-DEPENDENT APOPTOSIS; POTENTIAL MEDIATOR; PROMOTES APOPTOSIS; DNA-DAMAGE; PROTEIN; DOMAIN; EXPRESSION; INHIBITOR AB The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. GPC Biotech Inc, Waltham, MA 02451 USA. NCI, Radiat Oncol Sci Program, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Horikoshi, N (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. RI Ohiro, Yoichi/A-5470-2012 FU NCI NIH HHS [CA75556]; NHLBI NIH HHS [R01 HL062458, HL62458] NR 57 TC 51 Z9 57 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 31 PY 2002 VL 524 IS 1-3 BP 163 EP 171 AR PII S0014-5793(02)03049-1 DI 10.1016/S0014-5793(02)03049-1 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 580DM UT WOS:000177219500031 PM 12135761 ER PT J AU Chen, ZH Ge, YL Landman, N Knag, JX AF Chen, ZH Ge, YL Landman, N Knag, JX TI Decreased expression of the mannose 6-phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells SO BMC CANCER LA English DT Article ID TUMOR-NECROSIS-FACTOR; 6-PHOSPHATE RECEPTOR; FACTOR-ALPHA; FACTOR-BETA; SUPPRESSOR GENE; GROWTH-FACTOR-2 RECEPTOR; HEPATOCELLULAR-CARCINOMA; M6P/IGF2 RECEPTOR; CATHEPSIN-D; CARCINOGENESIS AB Background: Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. Methods: In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. Results: Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. Conclusions: These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Knag, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. FU NCI NIH HHS [CA79553] NR 43 TC 47 Z9 47 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JUL 30 PY 2002 VL 2 AR 18 DI 10.1186/1471-2407-2-18 PG 9 WC Oncology SC Oncology GA 631TP UT WOS:000180183100001 PM 12149131 ER PT J AU Meade, CA Deng, YP Fusco, FR Del Mar, N Hersch, S Goldowitz, D Reiner, A AF Meade, CA Deng, YP Fusco, FR Del Mar, N Hersch, S Goldowitz, D Reiner, A TI Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE immunohistochemistry; Huntington's disease; ubiquitin; animal disease models; light microscopy; confocal microscopy ID HUNTINGTONS-DISEASE GENE; PARVALBUMIN-IMMUNOREACTIVE NEURONS; CATALYZED REPORTER DEPOSITION; MEDIAL GANGLIONIC EMINENCE; N-TERMINAL HUNTINGTIN; EXPANDED CAG REPEAT; PROJECTION NEURONS; MOUSE MODEL; NUCLEAR-LOCALIZATION; MUTANT HUNTINGTIN AB The cellular localization and development of neuronal intranuclear inclusions (NIIs) in cortex and striatum of R6/2 HD transgenic mice were studied to ascertain the relationship of NIIs to symptom formation in these mice and gain clues regarding the possible relationship of NII formation to neuropathology in Huntington's disease (HD). All NIIs observed in R6/2 mice were ubiquitinated, and no evidence was observed for a contribution to them from wild-type huntingtin; they were first observed in cortex and striatum at 3.5 weeks of age. In cortex, NIIs increased rapidly in size and prevalence after their appearance. Generally, cortical projection neurons developed NIIs more rapidly than cortical interneurons containing calbindin or parvalbumin. Few cortical somatostatinergic interneurons, however, formed NIIs. In striatum, calbindinergic projection neurons and parvalbuminergic interneurons rapidly formed NIIs, but they formed more gradually in cholinergic interneurons and few somatostatinergic interneurons developed NIIs. Striatal NIIs tended to be smaller than those in cortex. The early accumulation of NIIs in cortex and striatum in R6/2 mice is consistent with the early appearance of motor and learning abnormalities in these mice, and the eventual pervasiveness of NIIs at ages at which severe abnormalities are evident is consistent with their contribution to a neuronal dysfunction underlying the abnormalities. That cortex develops larger NIIs than striatum, however, is inconsistent with the preferential loss of striatal neurons in HD but is consistent with recent evidence of early morphological abnormalities in cortical neurons in HD. That calbindinergic and parvalbuminergic striatal neurons develop large NIIs is consistent with a contribution of nuclear aggregate formation to their high degree of vulnerability in HD. (C) 2002 Wiley-Liss, Inc. C1 Univ Tennessee, Dept Anat & Neurobiol, Hlth Sci Ctr, Memphis, TN 38163 USA. IRCCS, Fdn Santa Lucia, Lab Expt Neurorehabil, Basal Gaglia Unit, I-00179 Rome, Italy. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Meade, CA (reprint author), Univ Tennessee, Dept Anat & Neurobiol, Hlth Sci Ctr, 855 Monroe Ave, Memphis, TN 38163 USA. FU NINDS NIH HHS [R01 NS028721, NS 19620, NS 28721] NR 146 TC 68 Z9 68 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 29 PY 2002 VL 449 IS 3 BP 241 EP 269 DI 10.1002/cne.10295 PG 29 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 567RB UT WOS:000176497500004 PM 12115678 ER PT J AU Rosen, HR Marousek, G Chou, SW AF Rosen, HR Marousek, G Chou, SW TI A longitudinal analysis of T-cell epitope-coding regions of hepatitis C virus after liver transplantation SO TRANSPLANTATION LA English DT Article ID CHOLESTATIC HEPATITIS; RECIPIENTS; EVOLUTION; VARIANTS; RNA; RECURRENCE; INFECTION; TRACKING; DISEASE; DONORS AB Background. Hepatitis C virus (HCV)-related liver failure is the single leading indication for orthotopic liver transplantation (OLT) worldwide. The mechanisms that underlie the observed differences in natural history of HCV recurrence remain poorly understood. We have previously demonstrated that differential T-cell responses correlate with histologic severity after OLT. We hypothesized that amino acid substitutions within critical T-cell epitopes could lead to increased severity of HCV disease. Methods. We determined the peptide sequences from sequential serum-derived viral RNA by reverse transcription and direct polymerase chain reaction sequence analysis from 32 HCV genotype 1-infected patients with well-characterized outcomes after liver transplantation. Serum samples were analyzed for HCV sequence the day of OLT and at least one time point post-OLT. To construct evolutionary relationships among the different patient samples, phylogenetic analyses of core and NS3 sequences were performed using a matrix fed into a neighbor-joining tree algorithm. Results. The phylogenetic analyses revealed remarkable conservation within a given individual and no significant differences when comparing patients with severe versus mild recurrence. Accordingly, the synonymous mutation rate was consistently greater than the nonsynonymous substitution rate. The nine epitopic regions analyzed were also preserved so that, with the exception of one patient with mild recurrence, none of the patients demonstrated a shift in viral peptide sequence. Conclusions. HCV core and NS3 viral peptide sequences are identical before and after OLT in most patients, suggesting that the prevalent sequence is preserved in most cases, and viral variants are competent to establish infection after OLT. Although these results do not support viral mutation as a dominant pathogenic mechanism after OLT, other viral regions need to be analyzed. C1 Portland Vet Affairs Med Ctr, Dept Med, Portland, OR USA. Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol & Liver Transplantat &, Portland, OR USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, SW US Vet Hosp 3710, P3-G1, Portland, OR 97207 USA. NR 31 TC 8 Z9 8 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 JUL 27 PY 2002 VL 74 IS 2 BP 209 EP 216 AR UNSP 0041-1337/02/7402-209/0 DI 10.1097/00007890-200207270-00011 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 580CN UT WOS:000177217100011 PM 12151733 ER PT J AU Eiland, MM Ramanathan, L Gulyani, S Gilliland, M Bergmann, BM Rechtschaffen, A Siegel, JM AF Eiland, MM Ramanathan, L Gulyani, S Gilliland, M Bergmann, BM Rechtschaffen, A Siegel, JM TI Increases in amino-cupric-silver staining of the supraoptic nucleus after sleep deprivation SO BRAIN RESEARCH LA English DT Article DE sleep deprivation; supraoptic nucleus; neuronal degeneration; amino cupric silver; disk-over-water ID DIAGONAL BAND; BODY-TEMPERATURE; NEUROHYPOPHYSEAL HORMONES; NEURONAL DEGENERATION; CEREBROSPINAL-FLUID; CHOLINERGIC INPUT; RAT; VASOPRESSIN; STIMULATION; NEUROENDOCRINE AB Sleep deprived rats undergo a predictable sequence of physiological changes, including changes in skin condition, increased energy expenditure, and altered thermoregulation. Amino-cupric-silver staining was used to identify sleep deprivation related changes in the brain. A significant increase in staining was observed in the supraoptic nucleus (SON) of the hypothalamus of rats with high sleep loss (>45 h) vs. their yoked controls. Follow-up experiments showed that staining was not significantly different in rats sleep deprived for less than 45 h, suggesting that injurious sleep deprivation-related processes occur above a threshold quantity of sleep loss. These anatomical changes suggest that the effects of sleep deprivation may be related to protein metabolism in certain brain regions. (C) 2002 Elsevier Science BY All rights reserved. C1 Greater Los Angeles VA Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Chicago, Chicago, IL 60637 USA. RP Siegel, JM (reprint author), Greater Los Angeles VA Healthcare Syst, Neurobiol Res 151A3,16111 Plummer St, Sepulveda, CA 91343 USA. FU NINDS NIH HHS [NS14610]; PHS HHS [59594] NR 72 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 26 PY 2002 VL 945 IS 1 BP 1 EP 8 AR PII S0006-8993(02)02448-4 DI 10.1016/S0006-8993(02)02448-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 580FK UT WOS:000177224300001 PM 12113945 ER PT J AU Hara, K Maruki, Y Long, XM Yoshino, K Oshiro, N Hidayat, S Tokunaga, C Avruch, J Yonezawa, K AF Hara, K Maruki, Y Long, XM Yoshino, K Oshiro, N Hidayat, S Tokunaga, C Avruch, J Yonezawa, K TI Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action SO CELL LA English DT Article ID P70 S6 KINASE; MESSENGER-RNA TRANSLATION; PROTEIN PHOSPHATASE 2A; MAMMALIAN TARGET; AMINO-ACID; PHAS-I; FISSION YEAST; EIF-4E BP1; WD-REPEAT; PHOSPHORYLATION AB mTOR controls cell growth, in part by regulating p70 S6 kinase alpha (p70alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha. The binding of raptor to mTOR is necessary for the mTOR-catalyzed phosphorylation of 4EBP1 in vitro, and it strongly enhances the mTOR kinase activity toward p70alpha. Rapamycin or amino acid withdrawal increases, whereas insulin strongly inhibits, the recovery of 4EBP1 and raptor on 7-methyl-GTP Sepharose. Partial inhibition of raptor expression by RNA interference (RNAi) reduces mTOR-catalyzed 4EBP1 phosphorylation in vitro. RNAi of C. elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo. C1 Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. RP Hara, K (reprint author), Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. FU NCI NIH HHS [R01 CA73818B 06] NR 57 TC 980 Z9 1024 U1 7 U2 61 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 26 PY 2002 VL 110 IS 2 BP 177 EP 189 DI 10.1016/S0092-8674(02)00833-4 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 578EV UT WOS:000177105200006 PM 12150926 ER PT J AU Gladysheva, IP Sazonova, IY Chowdhry, SA Liu, L Turner, RB Reed, GL AF Gladysheva, IP Sazonova, IY Chowdhry, SA Liu, L Turner, RB Reed, GL TI Chimerism reveals a role for the streptokinase beta-domain in nonproteolytic active site formation, substrate, and inhibitor interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN BINDING REGION; RECOMBINANT STAPHYLOKINASE; MONOCLONAL-ANTIBODY; ACTIVATION; COMPLEX; MECHANISM; FIBRIN; ALPHA-2-ANTIPLASMIN; MICROPLASMIN; GENERATION AB Streptokinase (SK) and staphylokinase form cofactorenzyme complexes that promote the degradation of fibrin thrombi by activating human plasminogen. The unique abilities of streptokinase to nonproteolytically activate plasminogen or to alter the interactions of plasmin with substrates and inhibitors may be the result of high affinity binding mediated by the streptokinase beta-domain. To examine this hypothesis, a chimeric streptokinase, SKbetaswap, was created by swapping the SK beta-domain with the homologous beta-domain of Streptococcus uberis Pg activator (SUPA or PauA, SK uberis), a streptokinase that cannot activate human plasminogen. SKbetaswap formed a tight complex with microplasminogen with an affinity comparable with streptokinase. The SKbetaswap-plasmin complex also activated human plasminogen with catalytic efficiencies (k(cat)/K-m = 16.8 versus 15.2 muM(-1) min(-1)) comparable with streptokinase. However, SKbetaswap was incapable of nonproteolytic active site generation and activated plasminogen by a staphylokinase mechanism. When compared with streptokinase complexes, SKbetaswap-plasmin and SKbetaswap-microplasmin complexes had altered affinities for low molecular weight substrates. The SKbetaswap-plasmin complex also was less resistant than the streptokinase-plasmin complex to inhibition by alpha(2)-antiplasmin and was readily inhibited by soybean trypsin inhibitor. Thus, in addition to mediating high affinity binding to plasmin(ogen), the streptokinase beta-domain is required for nonproteolytic active site generation and specifically modulates the interactions of the complex with substrates and inhibitors. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave,II-127, Boston, MA 02115 USA. OI Gladysheva, Inna/0000-0002-2501-9029 FU NHLBI NIH HHS [HL-57314] NR 45 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 2002 VL 277 IS 30 BP 26846 EP 26851 DI 10.1074/jbc.M202999200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 577HR UT WOS:000177055900020 PM 12016220 ER PT J AU Wurster, AL Rodgers, VL White, MF Rothstein, TL Grusby, MJ AF Wurster, AL Rodgers, VL White, MF Rothstein, TL Grusby, MJ TI Interleukin-4-mediated protection of primary B cells from apoptosis through Stat6-dependent up-regulation of Bcl-xL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; ANTIGEN-RECEPTOR ENGAGEMENT; CONSTITUTIVE ACTIVATION; BCL-X(L) EXPRESSION; NUCLEAR EXPRESSION; SURFACE IGM; IL-4; STAT6; GENE; LYMPHOCYTES AB Apoptosis is an integral aspect of B lymphocyte development and homeostasis and is regulated by the engagement of antigen costimulatory and cytokine receptors. Although it is well established that interleukin 4 (IL-4) is a potent anti-apoptotic cytokine for B lymphocytes, little is known about the IL-4-induced molecular events regulating cell survival. Stat6 is rapidly activated after IL-4 stimulation, but its role in B lymphocyte apoptosis has not been explored. In this report we demonstrate that Stat6 is a critical signaling molecule for IL-4 in protecting primary B cells from passive and Fas-induced cell death. We show that expression of the Bcl-2 family member, Bcl-xL, is induced maximally by IL-4 and anti-IgML-4 in a Stat6-dependent manner. Additionally, we demonstrate that bcl-xL transcription is likely to be directly activated through a Stat6 binding site in the bcl-xL-flanking region. Finally, reconstitution of Stat6-deficient splenic B cells with Bcl-xL was able to protect those cells from Fas-induced cell death. These results suggest that the anti-apoptotic activity of IL-4 in B cells is mediated through the activation of Stat6 and subsequent transcription of Bcl-xL. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Microbiol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Evans Mem Dept Clin Res, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Grusby, MJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. FU NIAID NIH HHS [AI 40181, AI 40171] NR 52 TC 87 Z9 90 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 26 PY 2002 VL 277 IS 30 BP 27169 EP 27175 DI 10.1074/jbc.M201207200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 577HR UT WOS:000177055900061 PM 12023955 ER PT J AU Maser, RS DePinho, RA AF Maser, RS DePinho, RA TI Connecting chromosomes, crisis, and cancer SO SCIENCE LA English DT Review ID TELOMERASE-DEFICIENT MICE; MAMMARY EPITHELIAL-CELLS; IMMORTAL HUMAN-CELLS; HUMAN TUMOR-CELLS; TO-END FUSIONS; LIFE-SPAN; COLORECTAL CARCINOGENESIS; PREMALIGNANT LESIONS; CATALYTIC SUBUNIT; HUMAN FIBROBLASTS AB Cancer is a disease of impaired genome stability. The molecular forces that maintain genome integrity and sense altered chromosome structure are invariably subverted in cancer cells. Here, we explore the contrasting contributions of telomeres in the initiation and suppression of cancer and review the evidence supporting a role for telomere dysfunction as a mechanism driving the radical chromosomal aberrations that typify cancer genomes. Recent work suggests that passage of cells through crisis in the setting of deactivated DNA damage checkpoints provides a mutational mechanism that can generate the diverse genetic alterations required for cancer initiation. A greater understanding of telomere-induced crisis and the cell's crisis management mechanisms should guide the rational development of new therapeutics for cancer and other disorders. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St,M413, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012 NR 93 TC 408 Z9 419 U1 3 U2 19 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 2002 VL 297 IS 5581 BP 565 EP 569 DI 10.1126/science.297.5581.565 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577GY UT WOS:000177054200040 PM 12142527 ER PT J AU Howlett, NG Taniguchi, T Olson, S Cox, B Waisfisz, Q de Die-Smulders, C Persky, N Grompe, M Joenje, H Pals, G Ikeda, H Fox, EA D'Andrea, AD AF Howlett, NG Taniguchi, T Olson, S Cox, B Waisfisz, Q de Die-Smulders, C Persky, N Grompe, M Joenje, H Pals, G Ikeda, H Fox, EA D'Andrea, AD TI Biallelic inactivation of BRCA2 in Fanconi anemia SO SCIENCE LA English DT Article ID MITOMYCIN-C RESISTANCE; DNA-REPAIR; BREAST-CANCER; GENE; MUTATIONS; MICE; RECOMBINATION; PROTEINS; CELLS; RAD51 AB Fanconi anemia ( FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 BT Amsterdam, Netherlands. Univ Limburg, Acad Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. Sapporo Med Univ, Sch Med, Dept Pathol, Chuo Ku, Sapporo, Hokkaido 0608557, Japan. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Pals, Gerard/A-5198-2011 FU NHLBI NIH HHS [P01HL54785, R01HL52725]; NIDDK NIH HHS [R01DK43889] NR 31 TC 723 Z9 744 U1 3 U2 15 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 2002 VL 297 IS 5581 BP 606 EP 609 DI 10.1126/science.1073834 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577GY UT WOS:000177054200052 PM 12065746 ER PT J AU Kim, DH Feinbaum, R Alloing, G Emerson, FE Garsin, DA Inoue, H Tanaka-Hino, M Hisamoto, N Matsumoto, K Tan, MW Ausubel, FM AF Kim, DH Feinbaum, R Alloing, G Emerson, FE Garsin, DA Inoue, H Tanaka-Hino, M Hisamoto, N Matsumoto, K Tan, MW Ausubel, FM TI A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity SO SCIENCE LA English DT Article ID C-ELEGANS; DROSOPHILA; INTERFERENCE; EXPRESSION; MUTATIONS; RNA AB A genetic screen for Caenorhabditis elegans mutants with enhanced susceptibility to killing by Pseudomonas aeruginosa led to the identification of two genes required for pathogen resistance: sek-1, which encodes a mitogen-activated protein (MAP) kinase kinase, and nsy-1, which encodes a MAP kinase kinase kinase. RNA interference assays and biochemical analysis established that a p38 ortholog, pmk-1, functions as the downstream MAP kinase required for pathogen defense. These data suggest that this MAP kinase signaling cassette represents an ancient feature of innate immune responses in evolutionarily diverse species. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Japan Sci & Technol Corp, CREST, Chikusa Ku, Nagoya, Aichi 4648602, Japan. Nagoya Univ, Grad Sch Sci, Dept Mol Biol, Nagoya, Aichi 4648602, Japan. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM48707] NR 24 TC 384 Z9 407 U1 2 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 2002 VL 297 IS 5581 BP 623 EP 626 DI 10.1126/science.1073759 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577GY UT WOS:000177054200057 PM 12142542 ER PT J AU Browder, T Folkman, J Hahnfeldt, P Heymach, J Hlatky, L Kieran, M Rogers, MS AF Browder, T Folkman, J Hahnfeldt, P Heymach, J Hlatky, L Kieran, M Rogers, MS TI Antiangiogenic therapy and p53 SO SCIENCE LA English DT Editorial Material ID GROWTH-FACTOR; ANGIOGENESIS; EXPRESSION C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Browder, T (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RI Rogers, Michael/A-9814-2009 OI Rogers, Michael/0000-0002-5250-8434 NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 26 PY 2002 VL 297 IS 5581 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577GY UT WOS:000177054200002 ER PT J AU Smith, EE Rosand, J Knudsen, KA Hylek, EM Greenberg, SM AF Smith, EE Rosand, J Knudsen, KA Hylek, EM Greenberg, SM TI Leukoaraiosis is associated with warfarin-related hemorrhage following ischemic stroke SO NEUROLOGY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; RISK-FACTORS; ATRIAL-FIBRILLATION; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; ANTICOAGULANT TREATMENT; COMPLICATIONS; MULTICENTER; OUTPATIENTS AB Background and Objectives: Prior ischemic stroke is a risk factor for intracerebral hemorrhage (ICH) in patients taking warfarin, but the mechanism is not known. This study investigates radiographic and clinical characteristics of patients with warfarin-related ICH following ischemic stroke. Methods: In this case-control study, the authors selected all patients with warfarin-related ICH and previous symptomatic ischemic stroke from a prospective cohort of consecutive patients with ICH. Control subjects were similarly aged patients with history of symptomatic stroke randomly chosen from an anticoagulant therapy unit. The 26 eligible ICH cases and 56 controls were compared for vascular risk factors, stroke characteristics, and extent of leukoaraiosis (graded in anterior and posterior brain regions on a validated scale of 0 to 4). Results: The presence and severity of leukoaraiosis on CT scan correlated strongly with the occurrence of ICH. Leukoaraiosis was seen in 24 of 26 cases (92%) compared with 27 of 56 controls (48%), yielding an odds ratio of 12.9 (95% CI 2.8 to 59.8). Other clinical factors associated with ICH included an international normalized ratio >3.0, history of multiple previous strokes, and the presence of carotid artery stenosis. The relationship between leukoaraiosis and ICH persisted in multivariable analyses controlling for these risk factors as well as hypertension and diabetes mellitus. Conclusions: Leukoaraiosis is an independent risk factor for warfarin-related ICH in survivors of ischemic stroke, including those in the commonly employed range of anticoagulation. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. OI Smith, Eric/0000-0003-3956-1668 FU NIA NIH HHS [AG00725] NR 24 TC 126 Z9 129 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 23 PY 2002 VL 59 IS 2 BP 193 EP 197 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 574EL UT WOS:000176875400009 PM 12136056 ER PT J AU Arboleda-Velasquez, JF Lopera, F Lopez, E Frosch, MP Sepulveda-Falla, D Gutierrez, JE Vargas, S Medina, M de Arrieta, CM Lebo, RV Slaugenhaupt, SA Betensky, RA Villegas, A Arcos-Burgos, M Rivera, D Restrepo, JC Kosik, KS AF Arboleda-Velasquez, JF Lopera, F Lopez, E Frosch, MP Sepulveda-Falla, D Gutierrez, JE Vargas, S Medina, M de Arrieta, CM Lebo, RV Slaugenhaupt, SA Betensky, RA Villegas, A Arcos-Burgos, M Rivera, D Restrepo, JC Kosik, KS TI C455R notch3 mutation in a Colombian CADASIL kindred with early onset of stroke SO NEUROLOGY LA English DT Article AB Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the notch3 epidermal growth factor-like repeats. A Colombian kindred carries a novel C455R mutation located in the predicted ligand-binding domain. Stroke occurred in the patients at an unusually early age (median age: 31 years) in comparison to the more frequent onset in the fourth decade of life in other CADASIL populations, including a second Colombian kindred with an R1031C mutation. C1 Harvard Univ, Sch Med, Ctr Neurol Dis, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. George Washington Univ, Wilson Lab, Washington, DC USA. Univ Antioquia, Grp Neurociencias Antioquia, Medellin, Colombia. Univ Antioquia, Grp Genet Poblaic Mutacarciogenesis & Epidemiol G, Medellin, Colombia. RP Kosik, KS (reprint author), Harvard Inst Med, 77 Ave Louis Pasteur, Boston, MA 02115 USA. OI Sepulveda-Falla, Diego/0000-0003-0176-2042; Medina, Miguel/0000-0002-7016-5340 NR 10 TC 37 Z9 39 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 23 PY 2002 VL 59 IS 2 BP 277 EP 279 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 574EL UT WOS:000176875400024 PM 12136071 ER PT J AU Dudley, DD Manis, JP Zarrin, AA Kaylor, L Tian, M Alt, FW AF Dudley, DD Manis, JP Zarrin, AA Kaylor, L Tian, M Alt, FW TI Internal IgH class switch region deletions are position-independent and enhanced by AID expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTIDINE DEAMINASE AID; CELL-LINE; B-CELLS; RECOMBINATION; HYPERMUTATION; CLEAVAGE; SITES AB Ig heavy chain class switch recombination (CSR) involves a recombination/deletion mechanism that exchanges the expressed C-H gene with a downstream C-H gene. CSR is mediated by highly repetitive switch (S) region sequences and requires the activation-induced deaminase (AID). The S region 5' of the Cmu gene (Six) can undergo high-frequency internal deletions in normal B cells and B cell lines activated for CSR, although the relationship of these deletions and CSR has not been elucidated. In this study, we introduced constitutively transcribed Smu or Sgamma2b regions into a pro-B cell line that can be activated for AID expression, CSR, and enclogenous Smu deletions. We find that randomly integrated S region transcription units in these cells also undergo increased levels of internal rearrangements after cellular activation, indicating that the deletion process is independent of location within the Ig heavy chain locus and potentially AID-promoted. To test the latter issue, we generated hybridomas from wild-type and AID-deficient activated B cells and assayed them for internal Smu deletions and S region mutations. These studies demonstrated that efficient intra-S region recombination depends on AID expression and that internal S region deletions are accompanied by frequent mutations, indicating that most S region deletions occur by the same mechanism as CSR. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Genet,Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Genet,Howard Hughes Med Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [T32 AI007512, U19 AI031541, AI07512, AI31541, P01 AI031541] NR 33 TC 63 Z9 63 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 23 PY 2002 VL 99 IS 15 BP 9984 EP 9989 DI 10.1073/pnas.152333499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 577DG UT WOS:000177042400070 PM 12114543 ER PT J AU Grundy, SM Vega, GL McGovern, ME Tulloch, BR Kendall, DM Fitz-Patrick, D Ganda, OP Rosenson, RS Buse, JB Robertson, DD Sheehan, JP AF Grundy, SM Vega, GL McGovern, ME Tulloch, BR Kendall, DM Fitz-Patrick, D Ganda, OP Rosenson, RS Buse, JB Robertson, DD Sheehan, JP CA Diabetes Multicenter Res Grp TI Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes - Results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID EXTENDED-RELEASE NIACIN; CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; HYPERCHOLESTEROLEMIC PATIENTS; NICOTINIC-ACID; VA-HIT; GEMFIBROZIL; EVENTS; INTERVENTION; PREVENTION AB Background: Diabetic dyslipidemia is characterized by high triglyceride levels; low high-density lipoprotein cholesterol levels; small, dense low-density lipoprotein particles; and high free fatty acid levels. Niacin reduces concentrations of triglyceride-rich and small low-density lipoprotein particles while increasing high-density lipoprotein cholesterol levels. It also lowers levels of free fatty acids and lipoprotein(a). However, the use of niacin in patients with diabetes has been discouraged because high doses can worsen glycemic control. We evaluated the efficacy and safety of once-daily extended-release (ER) niacin in patients with diabetic dyslipidemia. Methods: During a 16-week, double-blind, placebo-controlled trial, 148 patients were randomized to placebo (n=49) or 1000 (n=45) or 1500 mg/d (n=52) of ER niacin. Sixty-nine patients (47%) were also receiving concomitant therapy with statins. Results: Dose-dependent increases in high-density lipoprotein cholesterol levels (+19% to +24% [P<.05] vs placebo for both niacin dosages) and reductions in triglyceride levels (-13% to -28% [P<.05] vs placebo for the 1500-mg ER niacin) were observed. Baseline and week 16 values for glycosylated hemoglobin levels were 7.13% and 7.11%, respectively, in the placebo group; 7.28% and 7.35%, respectively, in the 1000-mg ER niacin group (P=.16 vs placebo); and 7.2% and 7.5%, respectively, in the 1500-mg ER niacin group (P=.048 vs placebo). Four patients discontinued participation because of inadequate glucose control. Rates of adverse event rates other than flushing were similar for the niacin and placebo groups. Four patients discontinued participation owing to flushing (including 1 receiving placebo). No hepatotoxic effects or myopathy were observed. Conclusion: Low doses of ER niacin (1000 or 1500 mg/d) are a treatment option for dyslipidemia in patients with type 2 diabetes. C1 Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX USA. Kos Pharmaceut, Miami, FL USA. Diagnost Clin Houston, Houston, TX USA. Int Diabet Ctr, St Louis Pk, MN USA. EW Med Res Inst, Honolulu, HI USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Prevent Cardiol Clin, Chicago, IL 60614 USA. Univ N Carolina, Sch Med, Diabet Care Ctr, Chapel Hill, NC 27599 USA. Atlanta Diabet Assoc, Atlanta, GA USA. N Coast Inst Diabet & Endocrinol, Westlake, OH USA. RP Grundy, SM (reprint author), Univ Texas, SW Med Ctr, Ctr Human Nutr, 5323 Harry Hines Blvd,Room Y3206, Dallas, TX USA. NR 26 TC 328 Z9 341 U1 2 U2 8 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 JUL 22 PY 2002 VL 162 IS 14 BP 1568 EP 1576 DI 10.1001/archinte.162.14.1568 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 573GW UT WOS:000176821800003 PM 12123399 ER PT J AU Menzin, J Lang, K Earle, CC Kerney, D Mallick, R AF Menzin, J Lang, K Earle, CC Kerney, D Mallick, R TI The outcomes and costs of acute myeloid leukemia among the elderly SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; SOUTHWEST-ONCOLOGY-GROUP; BREAST-CANCER; PHASE-III; CONSOLIDATION THERAPY; REMISSION INDUCTION; PROGNOSTIC FACTORS; OLDER PATIENTS; DOUBLE-BLIND AB Background: The incidence of acute myeloid leukemia (AML) among the elderly can be expected to grow as the population continues to age. However, data on current treatment practices and costs for this form of cancer are sparse. Methods: We used a retrospective inception cohort design and data from a linkage between 11 Surveillance, Epidemiology, and End Results cancer registries and Medicare administrative claims. We evaluated survival, use of health care resources, use of chemotherapy, and Medicare payments among adults 65 years and older with an initial diagnosis of AML between January 1, 1991, and December 31, 1996. Results: A total of 2657 elderly patients with AML and complete Medicare claims data were identified. The prognosis for these patients was poor, with median survival estimated to be 2 months and a 2-year survival rate of 6%. Mean+/-SE total Medicare payments were $41594+/-$870 (in 1998 US dollars), 84% of which was attributed to inpatient payments. In the 2 years after the AML diagnosis, 790 patients (30%) underwent chemotherapy treatment. These patients had costs almost 3 times higher than those of other patients, and their median survival was 6 months longer. The use of hospice care was rare (17% of patients). Conclusions: Among the elderly, AML is associated with a poor prognosis and substantial costs during the relatively few remaining months of life. Moreover, most patients do not receive active treatment with chemotherapy or hospice services. Further work is needed to characterize this disease and the patient-related factors that influence treatment decisions and associated health outcomes. C1 Boston Hlth Econ Inc, Waltham, MA 02451 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wyeth Ayerst Res, Collegeville, PA USA. RP Menzin, J (reprint author), Boston Hlth Econ Inc, 20 Fox Rd, Waltham, MA 02451 USA. NR 35 TC 156 Z9 162 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 22 PY 2002 VL 162 IS 14 BP 1597 EP 1603 DI 10.1001/archinte.162.14.1597 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 573GW UT WOS:000176821800007 PM 12123403 ER PT J AU Jeon, CJ Kong, JH Strettoi, E Rockhill, R Stasheff, SF Masland, RH AF Jeon, CJ Kong, JH Strettoi, E Rockhill, R Stasheff, SF Masland, RH TI Pattern of synaptic excitation and inhibition upon direction-selective retinal ganglion cells SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE kinesin; GABA; receptor ID STARBURST AMACRINE CELLS; COMPLEX RECEPTIVE-FIELDS; RABBIT RETINA; GLYCINE RECEPTOR; BIPOLAR CELLS; GABA(A) RECEPTORS; MAMMALIAN RETINA; ALPHA-1 SUBUNIT; SPINAL-CORD; RAT RETINA AB The distributions of excitatory and inhibitory synapses upon the dendritic arbor of a direction-selective retinal ganglion cell were compared by triple-labeling techniques. The dendrites were visualized by confocal microscopy after injection of Lucifer yellow. Excitatory inputs from bipolar cells were located by using antibodies against kinesin II, a component of synaptic ribbons. Inhibitory inputs were identified by antibodies against gamma-aminobutyric acid-A receptors. The combined images were examined by visual inspection and by formal, automated analyses, in a search for anisotropies that might contribute to a directional preference of the ganglion cell. Within the limits of our analysis, none was found. If an anatomic specialization underlies direction selectivity, it appears to lie in the geometry and spatial positioning of the neurons afferent to the ganglion cell and/or the microcircuitry among its afferent synapses. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02114 USA. Kyungpook Natl Univ, Dept Biol, Taegu 702701, South Korea. CNR, Area Ric, Italian Natl Res Council, Inst Neurophysiol, I-56100 Pisa, Italy. RP Masland, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. FU NIEHS NIH HHS [R01 ES 12654-01A1]; NINDS NIH HHS [NS-01701-09]; Telethon [E.0833] NR 47 TC 47 Z9 48 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD JUL 22 PY 2002 VL 449 IS 2 BP 195 EP 205 DI 10.1002/cne.10288 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 565TY UT WOS:000176386600008 PM 12115689 ER PT J AU Malhotra, A White, DP AF Malhotra, A White, DP TI Obstructive sleep apnoea SO LANCET LA English DT Review ID POSITIVE AIRWAY PRESSURE; APNEA-HYPOPNEA SYNDROME; GENIOGLOSSAL ELECTROMYOGRAM RESPONSES; COST-EFFECTIVENESS ANALYSIS; PROSPECTIVE PARALLEL TRIAL; PLACEBO-CONTROLLED TRIAL; SOFT PALATAL MUCOSA; APNOEA/HYPOPNOEA-SYNDROME; MUSCLE ACTIVATION; NEGATIVE-PRESSURE AB Obstructive sleep apnoea is a disease of increasing importance because of Its neurocognitive and cardiovascular sequelae. Abnormalities in the anatomy of the pharynx, the physiology of the upper airway muscle dilator, and the stability of ventilatory control are important causes of repetitive pharyngeal collapse during sleep. Obstructive sleep apnoea can be diagnosed on the basis of characteristic history (snoring, daytime sleepiness) and physical examination (increased neck circumference), but overnight polysomnography is needed to confirm presence of the disorder. Repetitive pharyngeal collapse causes recurrent arousals from sleep, leading to sleepiness and increased risk of motor vehicle and occupational accidents. The surges in hypoxaemia, hypercapnia, and catecholamine associated with this disorder have now been implicated in development of hypertension, but the association between obstructive sleep apnoea and myocardial infarction, stroke, and congestive heart failure is not proven. Continuous positive airway pressure, the treatment of choice for obstructive sleep apnoea, reduces sleepiness and Improves hypertension. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Malhotra, A (reprint author), RF 486,221 Longwood Bldg, Boston, MA 02115 USA. NR 123 TC 478 Z9 503 U1 5 U2 93 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 20 PY 2002 VL 360 IS 9328 BP 237 EP 245 DI 10.1016/S0140-6736(02)09464-3 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 576DX UT WOS:000176988500028 PM 12133673 ER PT J AU Isenberg, G Doerhoefer, S Hoekstra, D Goldmann, WH AF Isenberg, G Doerhoefer, S Hoekstra, D Goldmann, WH TI Membrane fusion induced by the major lipid-binding domain of the cytoskeletal protein talin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ACTIN-BINDING; ADHESION PLAQUES; PLASMA-MEMBRANE; LEADING-EDGE; N-TERMINUS; PEPTIDES; VINCULIN; CELLS; ACTIVATION; HYDROPHOBICITY AB Secondary structure predictions have led to the identification of a major membrane-anchoring domain of the cytoskeletal protein talin spanning from amino acid 385 to 406. Using a synthetically derived peptide of this region, researchers have shown that it inserts into POPC/POPG phospholipid membranes with a partition coefficient of K-app = 1.1 +/- 0.2 x 10(5) M-1 and has an average molar reaction enthalpy of DeltaH = -2.5 kcal/mol. as determined by monolayer expansion technique and isothermic titration calorimetry [J. Biol. Chem. 275, 17954]. We applied resonance energy transfer (RET) assays to analyze the fusogenic properties of this peptide by lipid mixing and used liposomes containing carboxyfluorescein to measure the contents leakage. We directly Visualized talin peptide-induced vesicle membrane fusion using cryo-electron microscopy. This is the first example of a cytoskeletal protein domain that can trigger membrane fusion that might be of importance for understanding membrane targeting and motile events at the leading edge of the cell. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich, Dept Biophys E22, D-85748 Garching, Germany. Univ Groningen, Dept Physiol Chem, NL-9713 AV Groningen, Netherlands. RP Goldmann, WH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Bldg 149,13th St,Rm 8200, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 46 TC 11 Z9 11 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 19 PY 2002 VL 295 IS 3 BP 636 EP 643 AR PII S0006-291X(02)00714-3 DI 10.1016/S0006-291X(02)00714-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 574UM UT WOS:000176908000011 PM 12099686 ER PT J AU Wallington, CL Peters, DM Gelb, CR Peterfreund, RA AF Wallington, CL Peters, DM Gelb, CR Peterfreund, RA TI Orphanin FQ/nociceptin and mu-opioid receptor mRNA levels in human SH-SY5Y neuroblastoma cells: effects of activating the cAMP-PKA signal transduction pathway SO BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 17-21, 1998 CL ORLANDO, FLORIDA SP Amer Soc Anesthesiol DE mRNA; mu-opioid receptor; orphanin FQ/nociceptin receptor; cAMP; protein kinase A; SH-SY5Y neuroblastoma cell ID MESSENGER-RNA LEVELS; ASTROCYTE-ENRICHED CULTURES; D-ASPARTATE RECEPTOR; PROTEIN-KINASE-C; DOWN-REGULATION; INTERLEUKIN-1-BETA-MEDIATED REGULATION; ADENYLYL-CYCLASE; UP-REGULATION; SPINAL-CORD; GENE AB Responses to opioid agonists vary, depending on past opioid exposure and the physiological state. The intracellular signaling pathway mediated by cAMP and protein kinase A (PKA) has been linked to regulation of opioid receptor responsiveness. The role of the cAMP-PKA pathway in regulating opioid receptor gene expression is incompletely defined. mu-Opioid receptor (MuOR) and orphanin FQ/nociceptin receptor (ORL1) transcripts were measured after activating this pathway in human neuroblastoma cells. Human SH-SY5Y neuroblastoma cells were maintained in continuous monolayer culture. Cells were incubated with combinations of agents which activate the cAMP-PKA signal transduction pathway, including forskolin and choleratoxin (CTX). MuOR and ORL1 transcript levels were measured by hybridization to specific probes. Activation of the cAMP-PKA signal transduction pathway with forskolin in the presence of phosphodiesterase inhibitors was associated with a time-dependent decrease in the level of MuOR mRNA; partial recovery was observed with prolonged incubations. Forskolin effects were mimicked by CTX, but not by dideoxyforskolin. The PKA inhibitor H89 blunted the actions of forskolin. However, forskolin responses persisted despite coincubation with protein synthesis inhibitors. ORL1 transcript levels did not significantly change, but vasoactive intestinal polypeptide (VIP) transcripts exhibited substantial increases, in the presence of forskolin or CTX. These observations support a role for cAMP in regulating MuOR responsiveness through actions at the level of receptor gene expression. ORL1 transcript levels are not effected, suggesting that the cAMP-PKA pathway has differential effects on the expression of mRNA for different, but biochemically closely related, opioid receptor subtypes. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Beecher Mem Lab,Clin, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Beecher Mem Lab,Clin, 55 Fruit St, Boston, MA 02114 USA. NR 38 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 19 PY 2002 VL 944 IS 1-2 BP 73 EP 81 AR PII S0006-8993(02)02720-8 DI 10.1016/S0006-8993(02)02720-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 580FH UT WOS:000177224100008 PM 12106667 ER PT J AU Thakkar, MM Winston, S McCarley, RW AF Thakkar, MM Winston, S McCarley, RW TI Orexin neurons of the hypothalamus express adenosine Al receptors SO BRAIN RESEARCH LA English DT Article DE immunohistochemistry; lateral hypothalamus; sleep-wakefulness ID BASAL FOREBRAIN; PROLONGED WAKEFULNESS; BEHAVIORAL STATE; SLEEP; MODULATION; MICRODIALYSIS; AROUSAL; SYSTEM; RATS; NARCOLEPSY AB Adenosine is a putative sleep factor with effects mainly mediated by the At receptor. Recent studies have implicated the hypothalamic orexin/hypocretin-containing neurons in the control of sleep-wakefulness. To help determine if adenosine might play a role in the control of orexin neurons, immunohistochemistry was used to characterize the distribution of adenosine At receptor protein on the orexinergic neurons. About 30% of orexin-containing neurons were labeled. The data supports the presence of adenosine At receptors on orexinergic neurons and suggests a possible substrate for a functional role of adenosine in the regulation of orexinergic activity. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Brockton VA Med Ctr, Dept Psychiat,VA Boston Healthcare Syst, Brockton, MA 02401 USA. RP Thakkar, MM (reprint author), Harvard Univ, Sch Med, Brockton VA Med Ctr, Dept Psychiat,VA Boston Healthcare Syst, Brockton, MA 02401 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [K01MH01798, R37MH39683] NR 27 TC 35 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 19 PY 2002 VL 944 IS 1-2 BP 190 EP 194 AR PII S0006-8993(02)02873-1 DI 10.1016/S0006-8993(02)02873-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 580FH UT WOS:000177224100020 PM 12106679 ER PT J AU Hannun, YA Obeid, LM AF Hannun, YA Obeid, LM TI The ceramide-centric universe of lipid-mediated cell regulation: Stress encounters of the lipid kind. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID HEREDITARY SENSORY NEUROPATHY; KINASE-C-ZETA; SACCHAROMYCES-CEREVISIAE; SERINE PALMITOYLTRANSFERASE; NEUTRAL SPHINGOMYELINASE; INDUCED APOPTOSIS; COMPLEX-III; KAPPA-B; SPHINGOLIPIDS; MITOCHONDRIA C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [CA 87584]; NIA NIH HHS [AG 16583]; NIGMS NIH HHS [GM43285, GM62887] NR 58 TC 570 Z9 596 U1 2 U2 16 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 JUL 19 PY 2002 VL 277 IS 29 BP 25847 EP 25850 DI 10.1074/jbc.R200008200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574UV UT WOS:000176908700003 PM 12011103 ER PT J AU Andrews, HN Mullan, PB McWilliams, S Sebelova, S Quinn, JE Gilmore, PM McCabe, N Pace, A Koller, B Johnston, PG Haber, DA Harkin, DP AF Andrews, HN Mullan, PB McWilliams, S Sebelova, S Quinn, JE Gilmore, PM McCabe, N Pace, A Koller, B Johnston, PG Haber, DA Harkin, DP TI BRCA1 regulates the interferon gamma-mediated apoptotic response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; POLYMERASE-II HOLOENZYME; BREAST-CANCER CELLS; GENE-EXPRESSION; IFN-GAMMA; TRANSCRIPTIONAL ACTIVATION; CYCLE; PHOSPHORYLATION; COMPLEX; PROTEIN AB BRCA1 is a tumor suppressor gene implicated in transcriptional regulation. We have generated cell lines with inducible expression of BRCA1 as a tool to identify downstream targets that may be important mediators of BRCA1 function. Oligonucleotide array-based expression profiling identified 11 previously described interferon regulated genes that were up-regulated following inducible expression of BRCA1. Northern blot analysis revealed that a subset of the identified targets including IRF-7, MxA, and ISG-54 were synergistically up-regulated by BRCA1 in the presence of interferon gamma (IFN-gamma) but not interferons alpha or beta. Importantly, IFN-gamma-mediated induction of IRF-7 and MxA was attenuated in the BRCA1 mutant cell line HCC1937, an effect that was rescued following reconstitution of exogenous wild type BRCA1 in these cells. Furthermore, reconstituted BRCA1 sensitized HCC1937 cells to IFN-gamma-induced apoptotic cell death. This study identifies BRCA1 as a component of the IFN-gamma-regulated signaling pathway and suggests that BRCA1 may play a role in the regulation of IFN-gamma-mediated apoptosis. C1 Queens Univ Belfast, Dept Oncol, Canc Res Ctr, Belfast BT9 7AB, Antrim, North Ireland. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Harkin, DP (reprint author), Queens Univ Belfast, Dept Oncol, Canc Res Ctr, Belfast City Hosp, Univ Floor,Lisburn Rd, Belfast BT9 7AB, Antrim, North Ireland. NR 42 TC 52 Z9 52 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 2002 VL 277 IS 29 BP 26225 EP 26232 DI 10.1074/jbc.M201316200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574UV UT WOS:000176908700053 PM 12011077 ER PT J AU Rattenholl, A Pappano, WN Koch, M Keene, DR Kadler, KE Sasaki, T Timpl, R Burgeson, RE Greenspan, DS Bruckner-Tuderman, L AF Rattenholl, A Pappano, WN Koch, M Keene, DR Kadler, KE Sasaki, T Timpl, R Burgeson, RE Greenspan, DS Bruckner-Tuderman, L TI Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYSTROPHIC EPIDERMOLYSIS-BULLOSA; MAMMALIAN TOLLOID-LIKE; C-PROTEINASE; I PROCOLLAGEN; MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; ANTIPARALLEL DIMER; FIBROGENIC CELLS; GAMMA-2 CHAIN; TISSUE FORM AB Collagen VII is the major structural component of the anchoring fibrils at the dermal-epidermal junction in the skin. It is secreted by keratinocytes as a precursor, procollagen VII, and processed into mature collagen during polymerization of the anchoring fibrils. We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA down arrow DTAG within the NC-2 domain. Mammalian tolloid-like (mTLL)-1 and -2, two other proteases of the astacin enzyme family, were able to process procollagen VII at the same site in vitro. Immunohistochemical and genetic evidence supported the involvement of these enzymes in cleaving type VII procollagen in vivo. Both BMP-1 and mTLL-1 are expressed in the skin and in cultured cutaneous cells. A naturally occurring deletion in the human COL7A1 gene, 8523del14, which is associated with dystrophic epidermolysis bullosa and eliminates the BMP-1 consensus sequence, abolished processing of procollagen VII, and in mutant skin procollagen VII accumulated at the dermal-epidermal junction. On the other hand, deficiency of BMP-1 in the skin of knockout mouse embryos did not prevent processing of procollagen VII to mature collagen, suggesting that mTLL-1 and/or mTLL-2 can substitute for BMP-1 in the processing of procollagen VII in situ. C1 Univ Munster, Dept Dermatol, D-48149 Munster, Germany. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Cambridge, MA 02139 USA. Shriners Hosp Children, Portland, OR 97201 USA. Univ Manchester, Sch Biol Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England. Max Planck Inst Biochem, D-82152 Martinsried, Germany. RP Bruckner-Tuderman, L (reprint author), Univ Munster, Dept Dermatol, Von Esmarch Str 58, D-48149 Munster, Germany. OI Greenspan, Daniel/0000-0001-8096-7446 FU NIAMS NIH HHS [AR47746]; NIGMS NIH HHS [GM63471] NR 58 TC 80 Z9 82 U1 1 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 JUL 19 PY 2002 VL 277 IS 29 BP 26372 EP 26378 DI 10.1074/jbc.M203247200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574UV UT WOS:000176908700073 PM 11986329 ER PT J AU D'Souza, I Schellenberg, GD AF D'Souza, I Schellenberg, GD TI Tau exon 10 expression involves a bipartite intron 10 regulatory sequence and weak 5 ' and 3 ' splice sites. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRE-MESSENGER-RNA; FAMILIAL FRONTOTEMPORAL DEMENTIA; MICROTUBULE-ASSOCIATED PROTEINS; FTDP-17 MUTATIONS; NEURODEGENERATIVE DISORDERS; U1 SNRNP; GENE; CHROMOSOME-17; PARKINSONISM; PHOSPHORYLATION AB tau mutations that deregulate alternative exon 10 (E10) splicing cause frontotemporal dementia with parkinsonism chromosome 17-type by several mechanisms. Previously we showed that E10 splicing involved exon splicing enhancer sequences at the Wand 3' ends of E10, an exon splicing silencer, a weak 5' splice site, and an intron splicing silencer (ISS) within intron 10 (I10). Here, we identify additional regulatory sequences in I10 using both non-neuronal and neuronal cells. The ISS sequence extends from I10 nucleotides 11-18, which is sufficient to inhibit use of a weakened 5' splice site of a heterologous exon. Furthermore, ISS function is location-independent but requires proximity to a weak 5' splice site. Thus, the ISS functions as a linear sequence. A new cis-acting element, the intron splicing modulator (ISM), was identified immediately downstream of the ISS at I10 positions 19-26. The ISM and ISS form a bipartite regulatory element, within which the ISM functions when the ISS is present, mitigating E10 repression by the ISS. Additionally, the 3' splice site of E10 is weak and requires exon splicing enhancer elements for efficient E10 inclusion. Thus far, tau FTDP-17 splicing mutations affect six predicted cis-regulatory sequences. C1 Univ Washington, Div Gerontol, Dept Med, Seattle, WA 98195 USA. Univ Washington, Div Geriatr Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Univ Washington, Div Gerontol, Dept Med, Seattle, WA 98195 USA. FU NIA NIH HHS [R01 AG11762] NR 48 TC 56 Z9 56 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 19 PY 2002 VL 277 IS 29 BP 26587 EP 26599 DI 10.1074/jbc.M203794200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574UV UT WOS:000176908700100 PM 12000767 ER PT J AU Lee, SS Ruvkun, G AF Lee, SS Ruvkun, G TI Longevity - Don't hold your breath SO NATURE LA English DT Editorial Material ID CALORIC RESTRICTION; SACCHAROMYCES-CEREVISIAE; OXIDATIVE STRESS; GENE-EXPRESSION; LIFE-SPAN C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lee, SS (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. NR 13 TC 10 Z9 11 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 18 PY 2002 VL 418 IS 6895 BP 287 EP 288 DI 10.1038/418287a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 574BF UT WOS:000176868000028 PM 12124610 ER PT J AU Krane, SM AF Krane, SM TI Genetic control of bone remodeling - Insights from a rare disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INHIBITS OSTEOCLASTOGENESIS; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; PAGETS-DISEASE; OSTEOPROTEGERIN; CBFA1; MUTATIONS; RANK; OPG C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Krane, SM (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 21 TC 8 Z9 9 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 18 PY 2002 VL 347 IS 3 BP 210 EP 212 DI 10.1056/NEJMe020066 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 574BR UT WOS:000176869000010 PM 12124412 ER PT J AU Callus, BA Mathey-Prevot, B AF Callus, BA Mathey-Prevot, B TI SOCS36E, a novel Drosophila SOCS protein, suppresses JAK/STAT and EGF-R signalling in the imaginal wing disc SO ONCOGENE LA English DT Article DE Drosophila; EGF-R; JAK-STAT; signalling; SOCS ID NEGATIVE REGULATOR; SH2 DOMAIN; PATHWAY; BOX; ACTIVATION; RECEPTORS; EMBRYOS; REVEALS; ENCODES; MEMBERS AB We have cloned a novel SOCS gene from Drosophila, socs36E, which is most homologous to the mammalian socs-5 gene. Socs36E is expressed zygotically, predominantly during embryogenesis, in a highly dynamic pattern. In vivo expression of SOCS36E in transgenic flies results in several adult phenotypes. Engrailed-GAL4 directed expression causes loss of the wing anterior cross vein, humeral outgrowths, absence of halteres and eye pigmentation defects. Expression of SOCS36E under apterous-GAL4 control resulted in outstretched wings. Full penetrance of these phenotypes required the presence of the SH2 and SOCS-box domains of SOCS36E. The observed phenotypes were consistent with defects in JAK/STAT or EGF-R signalling and were exacerbated jak (hopscotch), din flies heterozygous for either the d-stat (stat92E) or d-egf-r (der) genes. Conversely, inactivating one copy of the d-cbl gene, a negative regulator of the d-EGF-R, partially rescued the wing phenotypes. These genetic interactions imply that SOCS36E can suppress activities of the JAK/STAT and EGF-R signalling pathways in the wing disc and suggest that SOCS36E interacts with multiple pathways in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia. RP Callus, BA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL 62434-01] NR 26 TC 80 Z9 81 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 18 PY 2002 VL 21 IS 31 BP 4812 EP 4821 DI 10.1038/sj.onc.1205618 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 571KJ UT WOS:000176716300010 PM 12101419 ER PT J AU Partridge, AH Winer, EP AF Partridge, AH Winer, EP TI Informing clinical trial participants about study results SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; DECISION-MAKING; COMMUNITY; ILLNESS; WOMEN C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 91 Z9 91 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 17 PY 2002 VL 288 IS 3 BP 363 EP 365 DI 10.1001/jama.288.3.363 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 573AK UT WOS:000176807000029 PM 12117402 ER PT J AU Goldhirsch, A Coates, AS Collins, J Thurlimann, B Senn, HJ Holmberg, S Lindtner, J Veronesi, A Cortes-Funes, H Castiglione-Gertsch, M Nasi, ML Egli, G Rabaglio, M Maibach, R Gerber, MI Hiltbrunner, A Gelber, R Price, K Bonetti, M Peterson, H Zahrieh, D Zelen, M Gelber, S O'Neill, A Litman, H Hinkle, R Isley, M Blacher, L Lippert, S Celano, J Gusterson, B Bettelheim, R Reed, R Viale, G Mallon, E Bernhard, J Hurny, C Gusset, H Mathys, N Cliffe, B Crivellari, D Monfardini, S Galligioni, E Magri, MD Veronesi, A Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Roncadin, M Arcicasa, M Coran, F Morassut, S Simoncini, E Marini, G Marpicati, P Braga, M Grigolato, P Lucini, L Foladore, S Foghin, L Pamich, G Bianchi, C Marino, B Murgia, A Milan, V Goldhirsch, A Colleoni, M Martinelli, G Orlando, L Nole, F Luini, A Orecchia, R Viale, G Peccatori, F de Braud, F Costa, A Zurrida, S Veronesi, P Sacchini, V Galimberti, V Intra, M Veronesi, U Ravaioli, A Tassinari, D Oliverio, G Barbanti, F Rinaldi, P Gianni, L Drudi, G Antimi, M Minelli, M Bellini, V Porzio, R Pernazza, E Santeusanio, G Spagnoli, LG Magazu, M Fosser, V Morandi, P Scalco, G Balli, M Gion, M Meli, S Torsello, G Fey, MF Castiglione-Gertsch, M Dreher, E Schneider, H Aebi, S Ludin, J Beck, G Haenel, A Luthi, JM Altermatt, HJ Nandedkar, M Buser, K Senn, HJ Thurlimann, B Oehlschlegel, C Ries, G Topfer, M Lorenz, U Schiltknecht, O Spati, B Ehrsam, A Bamert, M Jungi, WF Cavalli, F Pagani, O Neuenschwander, H Bronz, L Sessa, C Ghielmini, M Rusca, T Rey, P Bernier, J Pedrinis, E Gyr, T Leidi, L Pastorelli, G Caccia, G Goldhirsch, A Herrmann, R Rochlitz, CF Harder, JF Kochli, O Eppenberger, U Thorhorst, J Piguet, D Siegenthaler, P Barrelet, V Baumann, RP Pestalozzi, B Sauter, C Fink, D Fehr, M Haller, U Metzger, U Huguenin, P Caduff, R Perey, L Leyvraz, S Anani, P Gomez, F Wellman, D Chapuis, G De Grandi, P Reymond, P Gillet, M Delaloye, JF Alberto, P Bonnefoi, H Schafer, P Krauer, F Forni, M Aapro, M Egeli, R Megevand, R Jacot-des-Combes, E Schindler, A Borisch, B Diebold, S Egli, F Forrer, P Willi, A Steiner, R Allemann, J Ruedi, T Leutenegger, A Torre, UD Forbes, JF Lindsay, D Wilson, A Simes, RJ Dhillon, H Collins, J Snyder, R Abdi, E Basser, R Burns, WI Chipman, M Chirgwin, J Drummond, R Francis, P Green, M Gregory, P Hart, S Henderson, M Kitchen, P McLennan, R Murphy, C Neil, S Pitcher, M Richardson, G Rodger, A Schwarz, M Mitchell, P Joseph, D Griffiths, J Stanley, R Jeal, P Olver, I Zalcberg, J Lindeman, G Finkelde, D Goss, G Steele, M Mann, B Read, A Russell, I Stewart, J Underhill, C Reading, D Kay, RG Harvey, BJ Benjamin, CS Thompson, P Bierre, A Hochstein, B Lethaby, A Webber, J Porter, D Malden, T Van Hazel, G Forbes, JF Stewart, J Jackson, D Gourlay, R Bishop, J Cox, S Ackland, S Bonaventura, A Hamilton, C Denham, J O'Brien, P Back, M Brae, S Muragasu Lewis, C Olver, IN Keefe, D Brown, M Gill, PG Taylor, A Yeoh, E Abdi, E Cleary, J Parnis, F Byrne, M Van Hazel, G Dewar, J Buck, M Sterrett, G Ingram, D Hastrich, D Joseph, D Cameron, F Tattersall, MHN Coates, AS Niesche, F West, R Renwick, S Donovan, J Duval, P Simes, RJ Ng, A Glenn, D North, RA Beith, J O'Connor, RG Rice, M Stevens, G Grassby, J Pendlebury, S McLeod, C Boyer, M Sullivan, A Hobbs, J Lind, D Kennedy, I Round, G Long, J Rudenstam, CM Wallgren, A Ottosson-Lonn, S Hultborn, R Colldahl-Jaderstrom, G Cahlin, E Mattsson, J Holmberg, SB Ivarson, L Ruusvik, O Niklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Salander, H Andersson, C Heideman, M Hessman, Y Nelzen, O Claes, G Ramhult, T Svensson, JH Liedberg, P Suuzkula, M Persson, S Dent, DM Gudgeon, A Murray, E Werner, ID Steynor, P Toop, J McEvoy, E Vorobiof, D Chasen, M Fotheringham, G de Muelenaere, G Skudowitz, B Mohammed, C Rosengarten, A Lindtner, J Erzen, D Majdic, E Stabuc, B Plesnicar, A Golouh, R Lamovec, J Jancar, J Vrhoved, I Kramberger, M Cortes-Funes, H Mendiola, D Hornedo, J Colomer, R Vigo, FC Miranda, P Sierra, A Martinez-Tello, F Garzon, A Alonso, S Ferrero, A AF Goldhirsch, A Coates, AS Collins, J Thurlimann, B Senn, HJ Holmberg, S Lindtner, J Veronesi, A Cortes-Funes, H Castiglione-Gertsch, M Nasi, ML Egli, G Rabaglio, M Maibach, R Gerber, MI Hiltbrunner, A Gelber, R Price, K Bonetti, M Peterson, H Zahrieh, D Zelen, M Gelber, S O'Neill, A Litman, H Hinkle, R Isley, M Blacher, L Lippert, S Celano, J Gusterson, B Bettelheim, R Reed, R Viale, G Mallon, E Bernhard, J Hurny, C Gusset, H Mathys, N Cliffe, B Crivellari, D Monfardini, S Galligioni, E Magri, MD Veronesi, A Buonadonna, A Massarut, S Rossi, C Candiani, E Carbone, A Volpe, R Roncadin, M Arcicasa, M Coran, F Morassut, S Simoncini, E Marini, G Marpicati, P Braga, M Grigolato, P Lucini, L Foladore, S Foghin, L Pamich, G Bianchi, C Marino, B Murgia, A Milan, V Goldhirsch, A Colleoni, M Martinelli, G Orlando, L Nole, F Luini, A Orecchia, R Viale, G Peccatori, F de Braud, F Costa, A Zurrida, S Veronesi, P Sacchini, V Galimberti, V Intra, M Veronesi, U Ravaioli, A Tassinari, D Oliverio, G Barbanti, F Rinaldi, P Gianni, L Drudi, G Antimi, M Minelli, M Bellini, V Porzio, R Pernazza, E Santeusanio, G Spagnoli, LG Magazu, M Fosser, V Morandi, P Scalco, G Balli, M Gion, M Meli, S Torsello, G Fey, MF Castiglione-Gertsch, M Dreher, E Schneider, H Aebi, S Ludin, J Beck, G Haenel, A Luthi, JM Altermatt, HJ Nandedkar, M Buser, K Senn, HJ Thurlimann, B Oehlschlegel, C Ries, G Topfer, M Lorenz, U Schiltknecht, O Spati, B Ehrsam, A Bamert, M Jungi, WF Cavalli, F Pagani, O Neuenschwander, H Bronz, L Sessa, C Ghielmini, M Rusca, T Rey, P Bernier, J Pedrinis, E Gyr, T Leidi, L Pastorelli, G Caccia, G Goldhirsch, A Herrmann, R Rochlitz, CF Harder, JF Kochli, O Eppenberger, U Thorhorst, J Piguet, D Siegenthaler, P Barrelet, V Baumann, RP Pestalozzi, B Sauter, C Fink, D Fehr, M Haller, U Metzger, U Huguenin, P Caduff, R Perey, L Leyvraz, S Anani, P Gomez, F Wellman, D Chapuis, G De Grandi, P Reymond, P Gillet, M Delaloye, JF Alberto, P Bonnefoi, H Schafer, P Krauer, F Forni, M Aapro, M Egeli, R Megevand, R Jacot-des-Combes, E Schindler, A Borisch, B Diebold, S Egli, F Forrer, P Willi, A Steiner, R Allemann, J Ruedi, T Leutenegger, A Torre, UD Forbes, JF Lindsay, D Wilson, A Simes, RJ Dhillon, H Collins, J Snyder, R Abdi, E Basser, R Burns, WI Chipman, M Chirgwin, J Drummond, R Francis, P Green, M Gregory, P Hart, S Henderson, M Kitchen, P McLennan, R Murphy, C Neil, S Pitcher, M Richardson, G Rodger, A Schwarz, M Mitchell, P Joseph, D Griffiths, J Stanley, R Jeal, P Olver, I Zalcberg, J Lindeman, G Finkelde, D Goss, G Steele, M Mann, B Read, A Russell, I Stewart, J Underhill, C Reading, D Kay, RG Harvey, BJ Benjamin, CS Thompson, P Bierre, A Hochstein, B Lethaby, A Webber, J Porter, D Malden, T Van Hazel, G Forbes, JF Stewart, J Jackson, D Gourlay, R Bishop, J Cox, S Ackland, S Bonaventura, A Hamilton, C Denham, J O'Brien, P Back, M Brae, S Muragasu Lewis, C Olver, IN Keefe, D Brown, M Gill, PG Taylor, A Yeoh, E Abdi, E Cleary, J Parnis, F Byrne, M Van Hazel, G Dewar, J Buck, M Sterrett, G Ingram, D Hastrich, D Joseph, D Cameron, F Tattersall, MHN Coates, AS Niesche, F West, R Renwick, S Donovan, J Duval, P Simes, RJ Ng, A Glenn, D North, RA Beith, J O'Connor, RG Rice, M Stevens, G Grassby, J Pendlebury, S McLeod, C Boyer, M Sullivan, A Hobbs, J Lind, D Kennedy, I Round, G Long, J Rudenstam, CM Wallgren, A Ottosson-Lonn, S Hultborn, R Colldahl-Jaderstrom, G Cahlin, E Mattsson, J Holmberg, SB Ivarson, L Ruusvik, O Niklasson, LG Dahlin, S Karlsson, G Lindberg, B Sundback, A Bergegardh, S Salander, H Andersson, C Heideman, M Hessman, Y Nelzen, O Claes, G Ramhult, T Svensson, JH Liedberg, P Suuzkula, M Persson, S Dent, DM Gudgeon, A Murray, E Werner, ID Steynor, P Toop, J McEvoy, E Vorobiof, D Chasen, M Fotheringham, G de Muelenaere, G Skudowitz, B Mohammed, C Rosengarten, A Lindtner, J Erzen, D Majdic, E Stabuc, B Plesnicar, A Golouh, R Lamovec, J Jancar, J Vrhoved, I Kramberger, M Cortes-Funes, H Mendiola, D Hornedo, J Colomer, R Vigo, FC Miranda, P Sierra, A Martinez-Tello, F Garzon, A Alonso, S Ferrero, A CA Int Breast Canc Study Grp IBCSG TI Endocrine responsiveness and tailoring adjuvant therapy for postmenopausal lymph node-negative breast cancer: A randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; INTERNATIONAL CONSENSUS PANEL; SUMMING-UP EVIDENCE; CLINICAL-TRIALS; CHEMOTHERAPY; ESTROGEN; RECEPTOR; TAMOXIFEN; TUMORS; CYCLOPHOSPHAMIDE AB Background: The role of adjuvant chemotherapy in postmenopausal patients with lymph node-negative breast cancer is controversial. After demonstrating the efficacy of chemotherapy combined with tamoxifen for postmenopausal patients with lymph node-positive disease, the International Breast Cancer Study Group launched a randomized trial (Trial IX) to evaluate the role of adjuvant chemotherapy preceding treatment with tamoxifen for patients with lymph node-negative disease. Methods: After stratification by estrogen receptor (ER) status, patients were randomly assigned to receive three 28-day courses of "classical" adjuvant CMF chemotherapy (cyclophosphamide at 100 mg/m(2) on days 1-14, orally; methotrexate at 40 mg/m(2) on days I and 8, intravenously; and 5-fluorouracil at 600 mg/m(2) on days I and 8, intravenously) followed by tamoxifen (20 mg/day, orally for 57 months) (CMF-->tamoxifen) or to receive tamoxifen alone (20 mg/day, orally for 60 months). We enrolled 1669 eligible patients, 382 (23%) with ER-negative tumors, 1217 (73%) with ER-positive tumors, and 70 (4%) with unknown ER status. The median follow-up was 71 months. All statistical tests were two-sided. Results: The added benefit of CMF followed by tamoxifen over tamoxifen alone was statistically significantly dependent on ER status (tests for interaction: P =.01 for disease-free survival [DFS] and P =.07 for overall survival [OS]), For patients with ER-negative tumors, the addition of CMF statistically significantly improved DFS (5-year DFS = 84% for CMF-->tamoxifen versus 69% for tamoxifen alone; difference = 15%; 95% confidence interval [CI] = 6% to 24%; risk ratio [RR] = 0.52; 95% CI = 0.34 to 0.79; P =.003) and OS (5-year OS = 89% for CMF-->tamoxifen versus 81% for tamoxifen alone; difference = 8%; 95% CI = 0% to 16%; RR = 0.51; 95% CI = 0.30 to 0.87; P =.01). By contrast, for patients with ER-positive tumors, addition of CMF provided no benefit in terms of DFS (5-year DFS = 84% for CMF-->tamoxifen versus 85% for tamoxifen alone; difference = -1; 95% CI = -6% to 4%; RR = 0.99, 95% CI = 0.75 to 1.30; P = .92) or OS (5-year OS = 95% for CMF-->tamoxifen versus 93%, for tamoxifen alone; difference = 2%; 95% CI=-1% to 5%, RR=0.95; 95% CI=0.64 to 1.40; P = .80). Conclusions: Postmenopausal patients with lymph node-negative breast cancer benefited substantially from adjuvant chemotherapy if their cancer was ER-negative (i.e., endocrine-nonresponsive). In contrast, if their cancer was ER-positive (i.e., endocrine-responsive), they obtained no benefit from the combination treatment compared with tamoxifen alone. C1 IBCSG, Coordinating Ctr, CH-3008 Bern, Switzerland. Inselspital Bern, CH-3010 Bern, Switzerland. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. European Inst Oncol, IBCSG Sci Comm, Milan, Italy. Inst Oncol Svizzera Italiana, Bellinzona, Switzerland. Univ Sydney, Dubbo Base Hosp, Royal Prince Alfred Hosp, IBCSG Sci Comm, Sydney, NSW 2006, Australia. Canc Council Australia, Sydney, NSW, Australia. IBCSG, Qual Life Off, Bern, Switzerland. RP Castiglione-Gertsch, M (reprint author), IBCSG, Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM meastiglione@sakk.ch RI gusterson, barry/D-3752-2009; Colomer, Ramon/C-5142-2008; Aebi, Stefan/F-2004-2010; Olver, Ian/I-1518-2015; Cameron, Fergus/N-9535-2015; OI Colomer, Ramon/0000-0002-6393-3444; Aebi, Stefan/0000-0002-3383-9449; Olver, Ian/0000-0001-5478-1576; Bonetti, Marco/0000-0003-2304-4180 NR 51 TC 78 Z9 78 U1 3 U2 9 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 JUL 17 PY 2002 VL 94 IS 14 BP 1054 EP 1065 PG 12 WC Oncology SC Oncology GA 573UH UT WOS:000176849400007 ER PT J AU Baden, LR Rubin, RH AF Baden, LR Rubin, RH TI Fever, neutropenia, and the second law of thermodynamics SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Infect Dis Div, Boston, MA 02115 USA. RP Baden, LR (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Infect Dis Div, 75 Francis St, Boston, MA 02115 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 16 PY 2002 VL 137 IS 2 BP 123 EP 124 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 575VN UT WOS:000176969300007 PM 12118968 ER PT J AU Saint, S Lipsky, BA Goold, SD AF Saint, S Lipsky, BA Goold, SD TI Indwelling urinary catheters: A one-point restraint? SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID TRACT INFECTION; PHYSICAL RESTRAINTS; MEDICAL PATIENTS; BACTERIURIA; PREVALENCE C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48109 USA. RP Saint, S (reprint author), Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Room 7E08,300 NIB Campus Box 0429, Ann Arbor, MI 48109 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114; Goold, Susan Dorr/0000-0002-0258-9774 NR 21 TC 91 Z9 93 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 16 PY 2002 VL 137 IS 2 BP 125 EP 127 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 575VN UT WOS:000176969300008 PM 12118969 ER PT J AU Greco, JB Sakaie, KE Westmoreland, S He, J Aminipour, S Seghal, P Cheng, LL Lee, PL Lackner, A Gonzalez, RG AF Greco, JB Sakaie, KE Westmoreland, S He, J Aminipour, S Seghal, P Cheng, LL Lee, PL Lackner, A Gonzalez, RG TI In vivo and ex vivo NMR in the study of the pathogenesis of AIDS dementia. SO BIOCHEMISTRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. New England Reg Primate Res Ctr, Div Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 16 PY 2002 VL 41 IS 28 MA 148 BP 8994 EP 8994 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 572LW UT WOS:000176777000167 ER PT J AU O'Donnell, CJ Chazaro, I Wilson, PWF Fox, C Hannan, MT Kiel, DP Cupples, LA AF O'Donnell, CJ Chazaro, I Wilson, PWF Fox, C Hannan, MT Kiel, DP Cupples, LA TI Evidence for heritability of abdominal aortic calcific deposits in the Framingham Heart Study SO CIRCULATION LA English DT Article DE atherosclerosis; calcification; abdominal aorta; genetics; heritability ID CORONARY-ARTERY CALCIFICATION; RISK-FACTORS; VASCULAR CALCIFICATION; DISEASE; POLYMORPHISM; AGGREGATION; FAMILIES; LESIONS; GENE AB Background-Atherosclerosis is a systemic disease that underlies clinical cardiovascular disease. The radiographic finding of abdominal aortic calcific deposits is an indicator of the presence of aortic atherosclerosis and an independent predictor of cardiovascular disease events. Little is known about the heritability of aortic calcification. Methods and Results-Original Framingham Heart Study cohort participants (2151) in 1109 extended pedigrees had a lateral lumbar radiograph. The presence and severity of abdominal aortic calcific (AAC) deposits at the levels of the first through fourth lumbar vertebrae was graded by a previously validated rating scale. Correlation coefficients were calculated in pairs of siblings, parent-offspring, and spouses. Age-, sex-, and multivariable-adjusted correlation coefficients for AAC were 0.52 for parent-offspring pairs and 0.20 for sibling pairs. In contrast, the multivariable-adjusted correlation for AAC in spouse pairs was -0.02. Using variance component methods implemented in SOLAR, the estimated heritability for age-, sex-, and multivariable-adjusted AAC was 0.49 (P<0.001). Thirty-one percent of the overall variance in AAC deposits was due to measured covariates, and 49% to heritable factors. Conclusions-In our large, population-based sample, heritable factors play a role in the presence and extent of abdominal aortic calcification. Thus, a substantial proportion of the variation in AAC is due to additive effects of genes, which have yet to be characterized. Measures of aortic atherosclerosis may provide heritable quantitative phenotypes for the genetic dissection of the complex condition of atherosclerosis in human populations. C1 Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Natl Heart Lung & Blood Inst, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI Cupples, L. Adrienne/0000-0003-0273-7965; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [AR/AG 41398] NR 28 TC 52 Z9 53 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 JUL 16 PY 2002 VL 106 IS 3 BP 337 EP 341 DI 10.1161/01.CIR.0000022663.26468.5B PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 575JZ UT WOS:000176944300014 PM 12119250 ER PT J AU Kratz, A Lewandrowski, KB Januzzi, JL Flood, JG Lee-Lewandrowski, E AF Kratz, A Lewandrowski, KB Januzzi, JL Flood, JG Lee-Lewandrowski, E TI Comparison of cardiac marker concentrations in healthy blood donors and hospital patients without acute coronary syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TROPONIN-I; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; CLINICAL-SIGNIFICANCE; PROGNOSTIC VALUE; ELEVATION; METAANALYSIS; BENEFIT AB Concentrations of the cardiac markers troponin I and T and creatine kinase-MB were markedly (up to 26 times) higher in, in-hospital patients without acute coronary syndromes than in healthy blood donors. A significant percentage of noncardiac in-hospital patients (8% to 19%) would have had "elevated" cardiac marker concentrations if the 99th percentile cutoffs derived from the donor population had been used. These data stress the importance of the use of the appropriate reference population for the determination of thresholds for cardiac markers. C1 Massachusetts Gen Hosp, Clin Labs, Div Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Lee-Lewandrowski, E (reprint author), Massachusetts Gen Hosp, Clin Labs, Div Lab Med, 55 Fruit St,GRB 5 Chem, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 U1 0 U2 1 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 JUL 15 PY 2002 VL 90 IS 2 BP 177 EP + AR PII S0002-9149(02)02447-5 DI 10.1016/S0002-9149(02)02447-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575DF UT WOS:000176930800021 PM 12106854 ER PT J AU Choo, JK Abernethy, WB Hutter, AM AF Choo, JK Abernethy, WB Hutter, AM TI Electrocardiographic observations in professional football players SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ABNORMALITIES AB Analysis of electrocardiograms in >1,200 professional American football players shows that abnormalities are very common. ST- and T-wave abnormalities are more common in black players and ventricular conduction delays are more common in white players. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Hutter, AM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, 15 Parkman St,WACC 467, Boston, MA 02114 USA. NR 8 TC 32 Z9 32 U1 0 U2 1 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 JUL 15 PY 2002 VL 90 IS 2 BP 198 EP + AR PII S0002-9149(02)02454-2 DI 10.1016/S0002-9149(02)02454-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 575DF UT WOS:000176930800028 PM 12106861 ER PT J AU Lee, SJ Klein, JP Barrett, AJ Ringden, O Antin, JH Cahn, JY Carabasi, MH Gale, RP Giralt, S Hale, GA Ilhan, O McCarthy, PL Socie, G Verdonck, LF Weisdorf, DJ Horowitz, MM AF Lee, SJ Klein, JP Barrett, AJ Ringden, O Antin, JH Cahn, JY Carabasi, MH Gale, RP Giralt, S Hale, GA Ilhan, O McCarthy, PL Socie, G Verdonck, LF Weisdorf, DJ Horowitz, MM TI Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; BLOOD PROGENITOR-CELL; CHRONIC PHASE; HIGH-RISK; SURVIVAL; CYCLOSPORINE; PREDNISONE; PREDICTORS; DONOR AB Chronic graft-versus-host disease (cGVHD) is the leading cause of late treatment-related deaths among recipients of allogeneic bone marrow and blood transplants. However, cGVHD is also associated with fewer relapses. We sought to determine whether severity of cGVHD predicts the magnitude of these effects. One impediment to such an analysis is the current limited/extensive grading system for cGVHD because this classification was designed to identify patients likely to benefit from systemic immune suppression and does not capture the severity of multiorgan involvement. We, therefore, first developed a grading system predictive for survival by using data from 1827 HLA-matched sibling allotransplant recipients reported to the International Bone Marrow Transplant Registry (IBMTR). We found Karnofsky performance score, diarrhea, weight loss, and cutaneous and oral involvement to be independent prognostic variables, from which we generated a grading scheme. We tested this scheme, the limited/extensive classification system, and a classification based on clinical impression of overall cGVHD severity (mild/moderate/severe) in parallel analyses of 1092 HLA-matched sibling transplant recipients from the IBMTR and 553 recipients of unrelated donor marrow from the National Marrow Donor Program. Presence of cGVHD was associated with fewer relapses (relative risk [RR], 0.5-0.6) but more treatment-related mortality (RR, 1.8-2.8) in the 3 analyses. No grading scheme correlated cGVHD severity with relapse rates, but all schemes predicted treatment-related mortality. Survival and disease-free survival of the most favorable cGVHD group in each scheme were similar, or better, than those of patients without cGVHD; these patients may not need aggressive or extended immune suppression. (Blood. 2002; 100:406-414). (C) 2002 by The American Society of Hematology. C1 Med Coll Wisconsin, Graft Vs Host Dis Working Comm Int Bone Marrow Tr, Hlth Policy Inst, Milwaukee, WI 53226 USA. Natl Marrow Donor Program, Coordinating Ctr, Minneapolis, MN USA. Dana Farber Canc Ctr, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Huddinge Hosp, S-14186 Huddinge, Sweden. Hop Jean Minjoz, F-25030 Besancon, France. Univ So Calif, Norris Canc Ctr, Los Angeles, CA USA. Ctr Adv Studies Leukemia, Los Angeles, CA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Ibni Sina Hosp, Ankara, Turkey. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Hop St Louis, Paris, France. Univ Utrecht Hosp, Utrecht, Netherlands. Fairview Univ, Med Ctr, Minneapolis, MN USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM stephanie_lee@dfci.harvard.edu FU NCI NIH HHS [CA75267-03, P01-CA-40053]; PHS HHS [U24-76518] NR 33 TC 271 Z9 284 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2002 VL 100 IS 2 BP 406 EP 414 DI 10.1182/blood.V100.2.406 PG 9 WC Hematology SC Hematology GA 571WB UT WOS:000176741200005 PM 12091329 ER PT J AU Ballen, KK Becker, PS Emmons, RVB Fitzgerald, TJ Hsieh, CC Liu, Q Heyes, C Clark, Y Levy, W Lambert, JF Chiafari, F Szymanski, I Rososhansky, S Popovsky, MA Stewart, FM Quesenberry, PJ AF Ballen, KK Becker, PS Emmons, RVB Fitzgerald, TJ Hsieh, CC Liu, Q Heyes, C Clark, Y Levy, W Lambert, JF Chiafari, F Szymanski, I Rososhansky, S Popovsky, MA Stewart, FM Quesenberry, PJ TI Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; STEM-CELL TRANSPLANTATION; UMBILICAL-CORD BLOOD; MIXED HEMATOPOIETIC CHIMERISM; CHRONIC MYELOID-LEUKEMIA; PLACENTAL-BLOOD; UNRELATED DONORS; PHARMACOLOGICAL IMMUNOSUPPRESSION; GRAFT AB Allogeneic stem cell transplantation is curative for certain cancers, but the high doses of chemotherapy/radiotherapy lead to toxicity. Here, we treat patients with refractory cancer with 100 cGy total body irradiation (TBI) followed by infusion of nonmobilized pheresed allogeneic peripheral blood cells. Twenty-five patients, with a median age of 47 years, with refractory cancers were enrolled. Eighteen patients received sibling and 7 received unrelated cord blood cells. Donor chimerism was assessed at weeks 1, 2, 3, 4, and 8 after transplantation. Seven patients with solid tumors received a sibling transplant and 6 received a cord blood transplant; none achieved donor chimerism, but 1 treated at the higher dose level of 1 x 108 CD3(+) cells/kg had a transient nodal 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, including one patient with transient 5% donor chimerism. The development of chimerism correlated with hematologic malignancy (P <.001), total previous myelotoxic chemotherapy (P <.001), T-cell dose (P=.03), and graft-versus-host disease (P=.01). Tumor response correlated with donor chimerism (P=.01). Engraftment was achieved In patients with hematologic malignancies who had been heavily pretreated, suggesting the degree of immunosuppression may be a determinant of engraftment. Low-dose TBI and allogeneic lymphocyte Infusion may Induce remission In patients with refractory hematologic malignancy. (Blood. 2002; 100:442-450). (C) 2002 by The American Society of Hematology. C1 Univ Massachusetts Mem Hlth Care, Ctr Canc, Worcester, MA USA. Univ Massachusetts Mem Hlth Care, Dept Med, Worcester, MA USA. Univ Massachusetts Mem Hlth Care, Dept Radiat Oncol, Worcester, MA USA. Univ Massachusetts Mem Hlth Care, Dept Pathol, Worcester, MA USA. Baltimore Rh Typing Lab, Baltimore, MD USA. American Red Cross, Cord Blood Program, Dedham, MA USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 45 TC 38 Z9 41 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 JUL 15 PY 2002 VL 100 IS 2 BP 442 EP 450 DI 10.1182/blood.V100.2.442 PG 9 WC Hematology SC Hematology GA 571WB UT WOS:000176741200010 PM 12091334 ER PT J AU Brander, C Raje, N O'Connor, PG Davies, F Davis, J Chauhan, D Hideshima, T Martin, J Osmond, D Kedes, DH Walker, BD Scadden, DT Anderson, KC AF Brander, C Raje, N O'Connor, PG Davies, F Davis, J Chauhan, D Hideshima, T Martin, J Osmond, D Kedes, DH Walker, BD Scadden, DT Anderson, KC TI Absence of biologically important Kaposi sarcoma-associated herpesvirus gene products and virus-specific cellular immune responses in multiple myeloma SO BLOOD LA English DT Article ID PRIMARY EFFUSION LYMPHOMA; BONE-MARROW; SEXUAL TRANSMISSION; DENDRITIC CELLS; DNA-SEQUENCES; INFECTION; HHV8 AB Kaposi sarcoma-associated herpesvirus (KSHV) has been associated with several diseases, but the association between KSHV and multiple myeloma (MM) remains controversial. To address this issue, we studied patients with MM for the presence of viral RNA transcripts as well as KSHV-specific cellular immune responses, Highly sensitive reverse transcription-polymerase chain reaction assays for detection of viral transcripts of KSHV open reading frame (ORF) 26, ORF72, and ORF74 did not detect viral gene transcripts in long-term cultures of bone marrow stromal cells from 23 patients with MM. Moreover, sensitive assays for KSHV ORF65-specific and ORF73-specific cytotoxic T-lymphocyte (CTL) activity that readily and routinely detect CTLs specific for ORF65 and ORF73 in patients positive for human immunodeficiency virus and KSHV did not show any specific responses In 16 patients with MM, despite the presence of positive Epstein-Barr virus-specific CTLs In all cases. These data therefore do not show a biologically Important association between ongoing KSHV Infection and MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Virginia, Myles H Thaler Ctr AIDS Res, Dept Microbiol, Charlottesville, VA USA. Univ Virginia, Myles H Thaler Ctr AIDS Res, Dept Med, Charlottesville, VA USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 16 TC 25 Z9 25 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 JUL 15 PY 2002 VL 100 IS 2 BP 698 EP 700 DI 10.1182/blood.V100.2.698 PG 3 WC Hematology SC Hematology GA 571WB UT WOS:000176741200044 PM 12091368 ER PT J AU D'Amico, AV Saegaert, T Chen, MH Renshaw, AA George, D Oh, W Kantoff, PW AF D'Amico, AV Saegaert, T Chen, MH Renshaw, AA George, D Oh, W Kantoff, PW TI Initial decline in hemoglobin during neoadjuvant hormonal therapy predicts for early prostate specific antigen failure following radiation and hormonal therapy for patients with intermediate and high-risk prostate cancer SO CANCER LA English DT Article DE prostatic neoplasms; prostate specific antigen; anemia; radiation therapy; outcome ID RADIOTHERAPY; CERVIX AB BACKGROUND. Declines in serum hemoglobin (Hgb) levels occur from the use of androgen suppression therapy (AST) in the treatment of prostate cancer patients. We studied whether time to prostate specific antigen (PSA) failure following external beam radiation therapy (RT) and AST could be predicted by the rate of decline in the Hgb level following the administration of neoadjuvant AST or by the Hgb level at presentation or at the start of RT. METHODS. The study cohort comprised 110 intermediate or high-risk prostate cancer patients who were managed using three-dimensional conformal RT (70 Gy) and 6 months of AST (2 months neoadjuvant, concurrent, and adjuvant). A Cox regression multivariable analysis was performed to evaluate the ability of the rate of decline of the Hgb from baseline to the start of RT, baseline PSA level, Gleason score, percent positive biopsies, and T-category to predict time to PSA failure. RESULTS. A decline in the Hgb level of 1 g/dL or more during the first month of AST was the only significant predictor of time to PSA failure (P = 0.02) on multivariable analysis. The relative risk of PSA failure (95% confidence interval) for patients with a decline in Hgb level during the first month (greater than or equal to 1 g/dL vs. < 1 g/dL) was 6.3 (2.4, 8.3) and the 3-year estimate of PSA outcome was 66% versus 82% (P = 0.04), respectively. There were no imbalances in the pretreatment prognostic factors or length of follow-up in each of these groups. CONCLUSION. A decline of 1 g/dL or more in Hgb level during the first month of neoadjuvant AST was a predictor of early PSA failure following RT and AST in intermediate and high-risk prostate cancer patients. (C) 2002 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 15 TC 9 Z9 9 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 JUL 15 PY 2002 VL 95 IS 2 BP 275 EP 280 DI 10.1002/cncr.10673 PG 6 WC Oncology SC Oncology GA 575CH UT WOS:000176928100011 PM 12124826 ER PT J AU D'Amico, AV Whittington, R Malkowicz, SB Cote, K Loffredo, M Schultz, D Chen, MH Tomaszewski, JE Renshaw, AA Wein, A Richie, JP AF D'Amico, AV Whittington, R Malkowicz, SB Cote, K Loffredo, M Schultz, D Chen, MH Tomaszewski, JE Renshaw, AA Wein, A Richie, JP TI Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era SO CANCER LA English DT Article DE radical prostatectomy (RIP); conventional dose radiation therapy (RT); prostate carcinoma; prostate specific antigen (PSA); survival ID PRETREATMENT NOMOGRAM; CANCER; RADIOTHERAPY; RECURRENCE; SURVIVAL; BIOPSIES; UTILITY AB BACKGROUND. To the authors' knowledge, consensus is lacking regarding the relative long-term efficacy of radical prostatectomy (RP) versus conventional-dose external beam radiation therapy (RT) in the treatment of patients with clinically localized prostate carcinoma. METHODS. A retrospective cohort study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000 was performed. The primary endpoint was prostate specific antigen (PSA) survival stratified by treatment received and high-risk, intermediate-risk, or low-risk group based on the serum PSA level, biopsy Gleason score, 1992 American joint Commission on Cancer clinical tumor category, and percent positive prostate biopsies. RESULTS. Estimates of 8-year PSA survival (95% confidence interval [95% CI]) for low-risk patients (T1c,T2a, a PSA level less than or equal to 10 ng/mL, and a Gleason score less than or equal to 6) were 88% (95% CI, 85, 90) versus 78% (95% CI, 72, 83) for RP versus patients treated with RT, respectively. Eight-year estimates of PSA survival also favored RP for intermediate-risk patients (T2b or Gleason score 7 or a PSA level > 10 and less than or equal to 20 ng/mL) with < 34% positive prostate biopsies, being 79% (95% CI, 73, 85) versus 65% (95% CI, 58, 72), respectively. Estimates of PSA survival in high-risk (T2c or PSA level > 20 ng/mL or Gleason score 8) and intermediate-risk patients with at least 34% positive prostate biopsies initially favored RT, but were not significantly different after 8 years. CONCLUSIONS. intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of PSA survival that were not found to be significantly different. (C) 2002 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Connecticut, Dept Biostat, Farmington, CT USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 19 TC 185 Z9 192 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 2002 VL 95 IS 2 BP 281 EP 286 DI 10.1002/cncr.10657 PG 6 WC Oncology SC Oncology GA 575CH UT WOS:000176928100012 PM 12124827 ER PT J AU Fowler, FJ Collins, MM Corkery, EW Elliott, DB Barry, MJ AF Fowler, FJ Collins, MM Corkery, EW Elliott, DB Barry, MJ TI The impact of androgen deprivation on quality of life after radical prostatectomy for prostate carcinoma SO CANCER LA English DT Article DE androgen deprivation; prostate carcinoma; quality of life; prostate specific antigen (PSA) ID OF-LIFE; UROLOGIST BELIEFS; NATIONAL SURVEY; ANTIGEN ERA; CANCER; THERAPY; MEN; PROGRESSION; ELEVATION AB BACKGROUND. Androgen deprivation is commonly prescribed for men with a rising prostate specific antigen level after radical prostatectomy, despite scant evidence regarding its efficacy and side effects. In the current study, the authors compared measures of health-related quality of life (HRQOL) in men who were treated with androgen deprivation after radical prostatectomy with those for men who underwent surgery but were not treated with androgen deprivation. METHODS. Medicare Provider and Analysis and Review (MedPAR) files were used to identify men who had undergone radical prostatectomies between 1991-1992. Medicare Part B data then were used to select two samples: men who subsequently were androgen deprived and those who were not. In 1999, a mail survey was administered that addressed a range of disease-related and treatment-related issues, including HRQOL. Age-adjusted comparisons of responses to seven multi-item measures of HRQOL were performed. RESULTS. The overall response rate was 82%. On all seven HRQOL measures (impact of cancer and treatment, concern regarding body image, mental health, general health, activity, worries about cancer and dying, and energy), there were statistically significant decrements associated with androgen deprivation. CONCLUSIONS. Patients and physicians must weigh the price patients pay with regard to HRQOL against the uncertain benefits of early androgen deprivation. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 22 TC 56 Z9 57 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 2002 VL 95 IS 2 BP 287 EP 295 DI 10.1002/cncr.10656 PG 9 WC Oncology SC Oncology GA 575CH UT WOS:000176928100013 PM 12124828 ER PT J AU Bonham, M Arnold, H Montgomery, B Nelson, PS AF Bonham, M Arnold, H Montgomery, B Nelson, PS TI Molecular effects of the herbal compound PC-SPES: Identification of activity pathways in prostate carcinoma SO CANCER RESEARCH LA English DT Article ID ANDROGEN RECEPTOR; CANCER-CELLS; IN-VITRO; EXPRESSION; PROLIFERATION; MODULATION; INDUCTION; APOPTOSIS; LINES AB Clinical trials of the herbal preparation PC-SPES have demonstrated substantial responses in patients with advanced prostate cancer. Biochemical assays and clinical observations suggest that the effects of PC-SPES are mediated at least in part through estrogenic activity, although the mechanism(s) remains largely undefined. In this study, we used cDNA microarray analysis to identify gene expression changes in LNCaP prostate carcinoma cells exposed to PC-SPES and estrogenic agents including diethylstilbestrol. PC-SPES altered the expression of 156 genes after 24 h of exposure. Of particular interest, transcripts encoding cell cycle-regulatory proteins, alpha- and beta-tubulins, and the androgen receptor were down-regulated by PC-SPES. A comparison of gene expression profiles resulting from these treatments indicates that PC-SPES exhibits activities distinct from those attributable to diethylstilbestrol and suggests that alterations in specific genes involved in modulating the cell cycle, cell structure, and androgen response may be responsible for PC-SPES-mediated cytotoxicity. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med & Oncol, Seattle, WA 98108 USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Mailstop D4-100,1100 Fairview Ave N, Seattle, WA 98109 USA. FU NCI NIH HHS [T32 CA09437, CA75173-01A1] NR 23 TC 59 Z9 66 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2002 VL 62 IS 14 BP 3920 EP 3924 PG 5 WC Oncology SC Oncology GA 574CU UT WOS:000176871500005 PM 12124319 ER PT J AU Gazzoli, I Loda, M Garber, J Syngal, S Kolodner, RD AF Gazzoli, I Loda, M Garber, J Syngal, S Kolodner, RD TI A hereditary nonpolyposis colorectal carcinoma case associated with hypermethylation of the MLH1 gene in normal tissue and loss of heterozygosity of the unmethylated allele in the resulting microsatellite instability-high tumor SO CANCER RESEARCH LA English DT Article ID DNA METHYLATION; CELL-LINES; CANCER; PROMOTER; HMLH1; EXPRESSION; BINDING; INACTIVATION; AGE AB Fourteen suspected hereditary nonpolyposis colorectal carcinoma cases with microsatellite unstable (microsatellite instability-high; MSI-H) tumors but no germ-line MSH2, MSH6, or MLH1 mutations were examined for hypermethylation of CpG sites in the critical promoter region of W HI. The methylation patterns were determined using methylation-specific PCR and by sequence analysis of sodium bisulfite-treated genomic DNA. In one case, DNA hypermethylation of one allele was detected in DNA isolated from blood. In the MSI-H tumor from this case, the unmethylated MLH1 allele was eliminated by loss of heterozygosity, and the methylated allele was retained. This biallelic inactivation resulted in loss of expression of MLH1 in the tumor as confirmed by immunohistochemistry. These results suggest a novel mode of germ-line inactivation of a cancer susceptibility gene. C1 Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Gazzoli, I (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, CMME 3019,9500 Gilman Dr, La Jolla, CA 92093 USA. FU NCI NIH HHS [CA23100, CA06516] NR 24 TC 140 Z9 145 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2002 VL 62 IS 14 BP 3925 EP 3928 PG 4 WC Oncology SC Oncology GA 574CU UT WOS:000176871500006 PM 12124320 ER PT J AU Hartmann, C Johnk, L Kitange, G Wu, YH Ashworth, LK Jenkins, RB Louis, DN AF Hartmann, C Johnk, L Kitange, G Wu, YH Ashworth, LK Jenkins, RB Louis, DN TI Transcript map of the 3.7-mb D19S112-D19S246 candidate tumor suppressor legion on the long arm of chromosome 19 SO CANCER RESEARCH LA English DT Article ID DOMAIN-CONTAINING PROTEINS; EXPRESSED SEQUENCE TAGS; HUMAN OVARIAN-CANCER; HUMAN GLIOMAS; OLIGODENDROGLIAL TUMORS; MOLECULAR-CLONING; HOMEOBOX GENE; 19Q; 19Q13.3; REGION AB Allelic losses of the q13.3 region of chromosome 19 have been documented in malignant gliomas, neuroblastomas, and ovarian carcinomas, strongly suggesting the presence of a 19q13.3 tumor suppressor gene. Deletion mapping in tumors over the past decade has narrowed the candidate region considerably but has produced partially conflicting results, with some small candidate regions defined only by isolated tumors with deletions. Mutation and expression screening of genes from the most likely candidate regions has failed to identify the gene of interest, perhaps because of the conflicting deletion mapping data. The recently increased public availability of human genomic sequence, combined with improved bioinformatics capabilities, has now made it possible to map much larger candidate regions in considerable detail. We have manually generated a transcript map that spans most of the 19q13.3 tumor suppressor candidate region, from D19S219 to D19S246, with a resolution and quality superior to that of computer-generated maps. These results are presented in the hope that an improved map of the candidate region will facilitate further widespread screening and eventual identification of the gene or genes deleted in human gliomas, neuroblastomas, and ovarian cancers. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Mayo Clin & Mayo Fdn, Div Lab Genet, Rochester, MN 55905 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. Joint Genome Inst, Dept Energy, Walnut Creek, CA USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol, CNY6,149 13th St, Charlestown, MA 02129 USA. EM louis@helix.mgh.harvard.edu RI Hartmann, Christian/D-1882-2010 FU NCI NIH HHS [CA69285, CA85799] NR 50 TC 49 Z9 52 U1 0 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 JUL 15 PY 2002 VL 62 IS 14 BP 4100 EP 4108 PG 9 WC Oncology SC Oncology GA 574CU UT WOS:000176871500034 PM 12124348 ER PT J AU Rossi, F MacLean, HE Yuan, W Francis, RO Semenova, E Lin, CS Kronenberg, HM Cobrinik, D AF Rossi, F MacLean, HE Yuan, W Francis, RO Semenova, E Lin, CS Kronenberg, HM Cobrinik, D TI p107 and p130 coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE chondrocyte; chondrogenesis; p107; p130; hypertrophic differentiation; Cbfa1 ID RETINOBLASTOMA GENE FAMILY; HORMONE-RELATED PEPTIDE; LIMB CARTILAGE DIFFERENTIATION; EARLY MOUSE DEVELOPMENT; II PROCOLLAGEN; MESSENGER-RNA; CHICK LIMB; CHONDROCYTE DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; CBFA1-DEFICIENT MICE AB During endochondral bone development, both the chondrogenic differentiation of mesenchyme and the hypertrophic differentiation of chondrocytes coincide with the proliferative arrest of the differentiating cells. However, the mechanisms by which differentiation is coordinated with cell cycle withdrawal, and the importance of this coordination for skeletal development, have not been defined. Through analysis of mice lacking the pRB-related p107 and p130 proteins, we found that p107 was required in prechondrogenic condensations for cell cycle withdrawal and for quantitatively normal alpha1(II) collagen expression. Remarkably, the p107-dependent proliferative arrest of mesenchymal cells was not needed for qualitative changes that are associated with chondrogenic differentiation, including production of Alcian blue-staining matrix and expression of the collagen 1113 isoform. In chondrocytes, both p107 and p130 contributed to cell cycle exit, and p107 and p130 loss was accompanied by deregulated proliferation, reduced expression of Cbfa1, and reduced expression of Cbfa1-dependent genes that are associated with hypertrophic differentiation. Moreover, Cbfa1 was detected, and hypertrophic differentiation occurred, only in chondrocytes that had undergone or were undergoing a proliferative arrest. The results suggest that Cbfa1 links a p107- and p130-mediated cell cycle arrest to chondrocyte terminal differentiation. (C) 2002 Elsevier Science (USA). C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Inst Canc Genet, New York, NY 10032 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cobrinik, D (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168 St, New York, NY 10032 USA. FU NICHD NIH HHS [HD-35156]; NIDDK NIH HHS [DK-47038] NR 48 TC 53 Z9 53 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2002 VL 247 IS 2 BP 271 EP 285 DI 10.1006/dbio.2002.0691 PG 15 WC Developmental Biology SC Developmental Biology GA 573LG UT WOS:000176830700004 PM 12086466 ER PT J AU Ceron, J van den Heuvel, S AF Ceron, J van den Heuvel, S TI G1 regulation in Caenorhabditis elegans. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RI van den Heuvel, Sander/B-8892-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2002 VL 247 IS 2 MA 179 BP 477 EP 477 PG 1 WC Developmental Biology SC Developmental Biology GA 573LG UT WOS:000176830700171 ER PT J AU Hwang, I Sheen, J AF Hwang, I Sheen, J TI Two-component circuitry in Arabidopsis cytokinin signal transduction. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2002 VL 247 IS 2 MA 211 BP 484 EP 484 PG 1 WC Developmental Biology SC Developmental Biology GA 573LG UT WOS:000176830700199 ER PT J AU Li, E Oh, SP AF Li, E Oh, SP TI Gene-dosage-sensitive genetic interactions between iv, nodal, and ActRIIB genes in the left-right asymmetric patterning. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Univ Florida, Dept Physiol, Gainesville, FL USA. Massachusetts Gen Hosp, CVRC, Boston, 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2002 VL 247 IS 2 MA 319 BP 508 EP 508 PG 1 WC Developmental Biology SC Developmental Biology GA 573LG UT WOS:000176830700295 ER PT J AU Oh, SP Yeo, CY Lee, YJ Schrewe, H Lee, SJ Whitman, M Li, E AF Oh, SP Yeo, CY Lee, YJ Schrewe, H Lee, SJ Whitman, M Li, E TI Gene-dosage-sensitive compensatory mechanism of activin type II receptors for mediating GDF11 and nodal signals for anteroposterior and left-right patternings. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 Univ Florida, Dept Physiol, Gainesville, FL USA. Harvard Univ, Sch Med, Boston, MA USA. Max Planck Inst, Berlin, Germany. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2002 VL 247 IS 2 MA 354 BP 516 EP 516 PG 1 WC Developmental Biology SC Developmental Biology GA 573LG UT WOS:000176830700327 ER PT J AU Goldberg, Z Vogt Sionov, R Berger, M Zwang, Y Perets, R Van Etten, RA Oren, M Taya, Y Haupt, Y AF Goldberg, Z Vogt Sionov, R Berger, M Zwang, Y Perets, R Van Etten, RA Oren, M Taya, Y Haupt, Y TI Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation SO EMBO JOURNAL LA English DT Article DE c-Abl; Mdm2; p53; tyrosine phosphorylation ID TUMOR-SUPPRESSOR PROTEIN; DAMAGE-INDUCED PHOSPHORYLATION; ATM-DEPENDENT PHOSPHORYLATION; NUCLEAR EXPORT SIGNAL; RING-FINGER DOMAIN; DNA-DAMAGE; ATAXIA-TELANGIECTASIA; APOPTOTIC RESPONSE; CELLULAR-RESPONSE; KINASE AB The p53 tumor suppressor is inhibited and destabilized by Mdm2. However, under stress conditions, this downregulation is relieved, allowing the accumulation of biologically active p53. Recently we showed that c-Abl is important for p53 activation under stress conditions. In response to DNA damage, c-Abl protects p53 by neutralizing the inhibitory effects of Mdm2. In this study we ask whether this neutralization involves a direct interplay between c-Abl and Mdm2, and what is the contribution of the c-Abl kinase activity? We demonstrate that the kinase activity of c-Abl is required for maintaining the basal levels of p53 expression and for achieving maximal accumulation of p53 in response to DNA damage. Importantly, c-Abl binds and phosphorylates Mdm2 in vivo and in vitro. We characterize Hdm2 (human Mdm2) phosphorylation at Tyr394. Substitution of Tyr394 by Phe394 enhances the ability of Mdm2 to promote p53 degradation and to inhibit its transcriptional and apoptotic activities. Our results suggest that phosphorylation of Mdm2 by c-Abl impairs the inhibition of p53 by Mdm2, hence defining a novel mechanism by which c-Abl activates p53. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Natl Canc Ctr, Res Inst, Tokyo 104, Japan. RP Haupt, Y (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. FU NCI NIH HHS [CA72465] NR 73 TC 126 Z9 131 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 15 PY 2002 VL 21 IS 14 BP 3715 EP 3727 DI 10.1093/emboj/cdf384 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 572PT UT WOS:000176784700016 PM 12110584 ER PT J AU Suit, H AF Suit, H TI Contributions of L. H. Gray to radiation physics, biology, and oncology SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Biographical-Item C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 302, 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 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2002 VL 53 IS 4 BP 795 EP 797 AR PII S0360-3016(02)02852-3 DI 10.1016/S0360-3016(02)02852-3 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 575BF UT WOS:000176925400002 PM 12095544 ER PT J AU Suit, H AF Suit, H TI The Gray Lecture 2001: Coming technical advances in radiation oncology SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE advances; radiation technology; protons ID PROTON-BEAM RADIOTHERAPY; ATOMIC-BOMB SURVIVORS; THERAPY; CANCER AB Purpose: To review the current limits on the efficacy of radiotherapy (RT) due to technical factors and to assess the potential for major improvements in technology. Methods and Materials: The method of this review was to assess the efficacy of current RT in general terms; strategies for improving RT; historical record of technological advances; rationale for further reductions of treatment volume; and importance of defining and excluding nontarget tissues from the target volume. The basis for the interest in proton beam RT is developed, and the relative dose distributions of intensity-modulated radiotherapy (IMRT) and intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton and the first proposal that protons be used in RT is described. This is followed by a brief mention of the clinical outcome studies of proton RT. Likely technical advances to be integrated into advanced proton RT are considered, specifically, four-dimensional treatment planning and delivery. Finally, the increment in cost of some of these developments is presented. Results: For definitive RT, dose limits are set by the tolerance of normal tissues/structures adjacent or near to the target. Using imaging fusion of CT, MRI, positron emission tomography, magnetic resonance spectroscopic imaging, and other studies will result in improved definition of the target margins. Proton beams are likely, to replace photon beams because of their physical characteristics. Namely, for each beam path, the dose deep to the target is zero, across the target it is uniform, and proximal to the target it is less. Proton therapy can use as many beams, beam angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can photon plans. The ability for much greater accuracy in defining the target position in space and then maintaining the target in a constant position in the radiation beam despite target movement between and during dose fractions will be possible. The cost of proton RT will be modestly higher than comparable high technology photon therapy. Conclusion: The technology of RT is clearly experiencing intense and rapid technical developments as pertains to treatment planning and dose delivery. It is predicted that radical dose RT will move to proton beam technology and that the treatment will be four dimensional (the fourth dimension is time). The impact will be higher tumor control probability and reduced frequency and severity of treatment-related morbidity. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 302, Boston, MA 02114 USA. NR 42 TC 84 Z9 93 U1 0 U2 6 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 JUL 15 PY 2002 VL 53 IS 4 BP 798 EP 809 AR PII S0360-3016(02)02851-1 DI 10.1016/S0360-3016(02)02851-1 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 575BF UT WOS:000176925400003 PM 12095545 ER PT J AU Lieberfarb, ME Schultz, D Whittington, R Malkowicz, B Tomaszewski, JE Weinstein, M Wein, A Richie, JP D'Amico, AV AF Lieberfarb, ME Schultz, D Whittington, R Malkowicz, B Tomaszewski, JE Weinstein, M Wein, A Richie, JP D'Amico, AV TI Using PSA, biopsy Gleason score, clinical stage, and the percentage of positive biopsies to identify optimal candidates for prostate-only radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE prostate cancer; radical prostatectomy; radiation therapy; prostate-specific antigen; outcome ID RADICAL PROSTATECTOMY; CANCER; UTILITY AB Purpose: An identification of prostate cancer patients most likely to benefit from prostate-only radiation was made based upon the pretreatment prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, percentage of positive biopsies, and the 5-year postoperative PSA outcome. Methods: Between 1989 and 2000, 2099 patients underwent radical prostatectomy for clinically localized prostate cancer. The primary end points were pathologic evidence of seminal vesicle invasion (SVI), extracapsular extension (ECE) with or without positive surgical margins, and the 5-year postoperative PSA outcome. Results: Pretreatment PSA, biopsy Gleason score, and clinical stage were used to assign patients to low-, intermediate-, and high-risk groups. These risk groups were stratified by the percentage of positive biopsies and the primary pathologic and biochemical outcomes examined. The rates of SVI, ECE with positive margin, and no biochemical evidence of disease (bNED) for low-risk patients with less than or equal to50% positive biopsies were 2%, 7%, and 93%, respectively. Patients with >50% positive biopsies had higher rates of SVI and ECE (5% and 11%, respectively) and 52% bNED (p < 0.0001). For intermediate-risk patients with &LE;17% positive biopsies, the rates of SVI, ECE with positive margin, and bNED were 3%, 9%. and 90%, respectively. As the percentage of positive biopsies increased above 17% in intermediate- risk patients, there was a statistically significant increase in SVI and ECE and a significant decrease in bNED. Conclusions: Low-risk patients with &LE;50% positive biopsies and intermediate-risk patients with &LE;17% positive biopsies had a very low risk of SVI and ECE with positive surgical margins. Given that the presence of SVI and ECE with positive surgical margins was uncommon (<10%) with a greater than or equal to90% PSA failure-free survival after radical prostatectomy, these patients may be optimal candidates for radiation therapy directed at the prostate only (prostate gland + 1.5-cm margin). (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Millersville Univ Pennsylvania, Dept Math, Millersville, PA 17551 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lieberfarb, ME (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 15 TC 22 Z9 23 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 JUL 15 PY 2002 VL 53 IS 4 BP 898 EP 903 AR PII S0360-3016(02)02812-2 DI 10.1016/S0360-3016(02)02812-2 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 575BF UT WOS:000176925400013 PM 12095555 ER PT J AU Hurwitz, MD Kaplan, ID Hansen, JL Prokopios-Davos, S Topulos, GP Wishnow, K Manola, J Bornstein, BA Hynynen, K AF Hurwitz, MD Kaplan, ID Hansen, JL Prokopios-Davos, S Topulos, GP Wishnow, K Manola, J Bornstein, BA Hynynen, K TI Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE hyperthermia; toxicity; thermometry; prostate cancer; rectum ID THERAPY ONCOLOGY GROUP; TERM FOLLOW-UP; RANDOMIZED TRIAL; PLUS HYPERTHERMIA; PELVIC TUMORS; RADIOTHERAPY; CARCINOMA; RECURRENT; THERMORADIOTHERAPY; COMPLICATIONS AB Purpose: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer. Methods and Materials: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation h androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40degreesC in 19 patients, 41degreesC in 3 patients, and 42degreesC in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter. Results: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40degreesC. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40degreesC (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups. Conclusion: Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax,and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner. (C) 2002 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02215 USA. RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. FU NCI NIH HHS [P-01 CA 31303] NR 18 TC 9 Z9 9 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 JUL 15 PY 2002 VL 53 IS 4 BP 913 EP 918 AR PII S0360-3016(02)02809-2 DI 10.1016/S0360-3016(02)02809-2 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 575BF UT WOS:000176925400015 PM 12095557 ER PT J AU Moy, TI Silver, PA AF Moy, TI Silver, PA TI Requirements for the nuclear export of the small ribosomal subunit SO JOURNAL OF CELL SCIENCE LA English DT Article DE ribosome; nuclear export; in situ hybridization ID MESSENGER-RNA EXPORT; SACCHAROMYCES-CEREVISIAE; PORE COMPLEX; POLY(A)(+) RNA; PROTEIN EXPORT; IMPORTIN-BETA; IN-VIVO; NUCLEOCYTOPLASMIC TRAFFICKING; CONDITIONAL ALLELE; BINDING-PROTEINS AB Eukaryotic ribosome biogenesis requires multiple steps of nuclear transport because ribosomes are assembled in the nucleus while protein synthesis occurs in the cytoplasm. Using an in situ RNA localization assay in the yeast Saccharomyces cerevisiae, we determined that efficient nuclear export of the small ribosomal subunit requires Yrb2, a factor involved in Crm1-mediated export. Furthermore, in cells lacking YRB2, the stability and abundance of the small ribosomal subunit is decreased in comparison with the large ribosomal subunit. To identify additional factors affecting small subunit export, we performed a large-scale screen of temperature-sensitive mutants. We isolated new alleles of several nucleoporins and Ran-GTPase regulators. Together with further analysis of existing mutants, we show that nucleoporins previously shown to be defective in ribosomal assembly are also defective in export of the small ribosomal subunit. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. NR 64 TC 58 Z9 58 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUL 15 PY 2002 VL 115 IS 14 BP 2985 EP 2995 PG 11 WC Cell Biology SC Cell Biology GA 581TC UT WOS:000177308300018 PM 12082158 ER PT J AU Donaldson, SS Hudson, MM Lamborn, KR Link, MP Kun, L Billett, AL Marcus, KC Hurwitz, CA Young, JA Tarbell, NJ Weinstein, HJ AF Donaldson, SS Hudson, MM Lamborn, KR Link, MP Kun, L Billett, AL Marcus, KC Hurwitz, CA Young, JA Tarbell, NJ Weinstein, HJ TI VAMP and low-dose, involved-field radiation for children and adolescents with favorable, early-stage Hodgkin's disease: Results of a prospective clinical trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEDIATRIC-ONCOLOGY; CHEMOTHERAPY; THERAPY; MOPP; IRRADIATION; ETOPOSIDE AB Purpose: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. Patients and Methods: One hundred ten patients with clinical stages I and 11, favorable (nonbulky) Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. Results: With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin's disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. Conclusion: Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin's disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and 11 favorable Hodgkin's disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy. (C) 2002 by American Society of Clinical Oncology. C1 Stanford Univ, Sch Med, Dept Radiat Oncol, Med Ctr, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Med Ctr, San Francisco, CA 94143 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Portland, ME USA. RP Donaldson, SS (reprint author), Stanford Univ, Sch Med, Dept Radiat Oncol, Med Ctr, M-C 5302, Stanford, CA 94305 USA. EM sarah@reyes.stanford.edu NR 23 TC 62 Z9 66 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2002 VL 20 IS 14 BP 3081 EP 3087 DI 10.1200/JCO.2002.12.101 PG 7 WC Oncology SC Oncology GA 574ZF UT WOS:000176920000007 PM 12118021 ER PT J AU Friedmann, AM Hudson, MM Weinstein, HJ Donaldson, SS Kun, L Tarbell, NJ Link, MP AF Friedmann, AM Hudson, MM Weinstein, HJ Donaldson, SS Kun, L Tarbell, NJ Link, MP TI Treatment of unfavorable childhood Hodgkin's disease with VEPA and low-dose, involved-field radiation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PEDIATRIC-ONCOLOGY; PREDNISOLONE CHEMOTHERAPY; FRENCH SOCIETY; ETOPOSIDE; THERAPY; VINBLASTINE; CANCER; ABVD; MOPP AB Purpose: Between January 1990 and April 1993, 56 pediatric patients with Hodgkin's disease were treated an a single-arm trial at three institutions with a regimen designed to maintain high cure rates while minimizing the potential late effects of treatment, such as infertility, second malignant neoplasms, and cardiopulmonary injury. Patients and Methods: The regimen used combined-modality therapy with six cycles of vinblastine, etoposide, prednisone, and doxorubicin (VEPA) chemotherapy and low-close, involved-field radiation. Unfavorable features comprised bulky presentations of localized (stage I or 11) disease or advanced (stage III or IV) Hodgkin's disease. Results: Of 56 patients enrolled, 26 (46%) had unfavorable presentations of stage I/II disease and 30 (54%) had advanced (stage III/IV) disease. Seventy-nine percent of the patients are alive without disease at a median follow-up time of 8.9 years from diagnosis. Nineteen patients had events at a median of 1.5 years (range, 0.4 to 7.9 years) from diagnosis, 17 patients relapsed, one died of cardiomyopathy, and one died of accidental injuries. Survival and event-free survival (EFS) estimates at 5 years for the entire cohort were 81.9% (SE, 5.2%) and 67.8% (SE, 6.3%), respectively. Five-year EFS by stage was 100% for stage 1, 79.2% (SE, 8.3%) for stage 11, 70% (SE, 14.5%) for stage III, and 49.5% (SE, 11.3%) for stage IV patients. Conclusion: Combined-modality therapy with VEPA chemotherapy and low-dose, involved-field radiation is adequate for disease control of early-stage patients with unfavorable features, but it is inferior to other standard regimens for advanced-stage patients. (C) 2002 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM afriedmann@partners.org NR 22 TC 38 Z9 41 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2002 VL 20 IS 14 BP 3088 EP 3094 DI 10.1200/JCO.2002.03.051 PG 7 WC Oncology SC Oncology GA 574ZF UT WOS:000176920000008 PM 12118022 ER PT J AU Mathew, A Medoff, BD Carafone, AD Luster, AD AF Mathew, A Medoff, BD Carafone, AD Luster, AD TI Cutting edge: Th2 cell trafficking into the allergic lung is dependent on chemoattractant receptor signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE; RECRUITMENT; LYMPHOCYTE; INDUCTION AB Th2 cells are recruited to the lung where they mediate the asthma phenotype. Since the molecular mechanisms regulating Th2 cell trafficking remain unknown, we sought to determine whether trafficking of Th2 cells into the lung is mediated by Galphai-coupled chemoattractant receptors. We show here that in contrast to untreated Th2 cells, pertussis toxin-treated Th2 cells were unable to traffic into the lung, airways, or lymph nodes following Ag challenge and therefore were unable to induce allergic inflammation in vivo. Pertussis toxin-treated Th2 cells were functional cells, however, and when directly instilled into the airways of mice, bypassing their need to traffic to the lung, were able to induce airway eosinophilic inflammation. These studies conclusively demonstrate that trafficking of Th2 cells into the lung is an active process dependent on chemoattractant receptors. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 8th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [F32-HL10375]; NIAID NIH HHS [F32-AI50399, R01-AI40618] NR 11 TC 43 Z9 43 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2002 VL 169 IS 2 BP 651 EP 655 PG 5 WC Immunology SC Immunology GA 572BK UT WOS:000176753500005 PM 12097366 ER PT J AU Gemma, C Mesches, MH Sepesi, B Choo, K Holmes, DB Bickford, PC AF Gemma, C Mesches, MH Sepesi, B Choo, K Holmes, DB Bickford, PC TI Diets enriched in foods with high antioxidant activity reverse age-induced decreases in cerebellar beta-adrenergic function and increases in proinflammatory cytokines SO JOURNAL OF NEUROSCIENCE LA English DT Article DE aging; cerebellum; cytokines; antioxidants; norepinephrine; inflammation ID RADICAL ABSORBENCY CAPACITY; SIGNAL-TRANSDUCTION; F344 RATS; DEFICITS; ALPHA; ACQUISITION; EXPRESSION; IMPAIRMENT; ASSAY AB Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar beta-adrenergic receptor function. We examined whether this effect was related to the antioxidant capacity of the food supplement and whether an antioxidant-rich diet reduced the levels of proinflammatory cytokines in the cerebellum. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage or supplied in the rat chow daily for 14 d. Electrophysiologic techniques revealed a significant decrease in beta-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple (a food with intermediate ORAC) had an intermediate effect on cerebellar beta-adrenergic receptor physiology, and cucumber (low ORAC) had no effect, indicating that the reversal of beta-adrenergic receptor function decreases might be related to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis factor-alpha (TNFalpha) and TNFbeta was also examined. RNase protection assays revealed increased levels of these cytokines in the aged cerebellum. Spirulina and apple significantly downregulated this age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that one mechanism by which these diets work is by modulation of an age-related increase in inflammatory responses. Malondialdehyde (MDA) was measured as a marker of oxidative damage. Apple and spirulina but not cucumber decreased MDA levels in the aged rats. In summary, the improved beta-adrenergic receptor function in aged rats induced by diets rich in antioxidants is related to the ORAC dose, and these diets reduce proinflammatory cytokine levels. C1 Univ S Florida, Coll Med, Dept Neurosurg, Ctr Aging & Brain Repair, Tampa, FL 33612 USA. James A Haley Vet Adm Med Ctr, Tampa, FL 33612 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. RP Bickford, PC (reprint author), Univ S Florida, Coll Med, Dept Neurosurg, Ctr Aging & Brain Repair, MDC-78,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. RI Bickford, Paula/J-5970-2012; Marion-Poll, Frederic/D-8882-2011 OI Bickford, Paula/0000-0001-9657-7725; Marion-Poll, Frederic/0000-0001-6824-0180 FU NIA NIH HHS [AG00728, AG04418] NR 29 TC 74 Z9 81 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 15 PY 2002 VL 22 IS 14 BP 6114 EP 6120 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 573PR UT WOS:000176840500035 PM 12122072 ER PT J AU Arelin, K Kinoshita, A Whelan, CM Irizarry, MC Rebeck, GW Strickland, DK Hyman, BT AF Arelin, K Kinoshita, A Whelan, CM Irizarry, MC Rebeck, GW Strickland, DK Hyman, BT TI LRP and senile plaques in Alzheimer's disease: colocalization with apolipoprotein E and with activated astrocytes SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer; LRP; astrocyte; apoE; PDAPP mice ID RECEPTOR-RELATED PROTEIN; AMYLOID-BETA-PEPTIDE; ALPHA-2-MACROGLOBULIN RECEPTOR; TRANSGENIC MICE; MACROGLOBULIN RECEPTOR; NEURONAL CULTURES; PRECURSOR PROTEIN; MICROGLIAL CELLS; HUMAN BRAIN; LIPOPROTEIN AB The low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor which is present on senile plaques in Alzheimer's disease (AD). It is suggested to play an important role in the balance between amyloid beta (Abeta) synthesis and clearance mechanisms. One of its ligands, apolipoprotein E (apoE), is also present on senile plaques and has been implicated as a risk factor for AD, potentially affecting the deposition, fibrillogenesis and clearance of Abeta. Using immunohistochemistry we show that LRP was present only on cored, apoE-containing senile plaques, in both PDAPP transgenic mice and human AD brains. We detected strong LRP staining in neurons and in reactive astrocytes, and immunostaining of membrane-bound LRP showed colocalization with line astrocytic processes surrounding senile plaques. LRP was not present in plaques in young transgenic mice or in plaques of APOE-knockout mice. As LRP ligands associated with Abeta deposits in AD brain may play an important role in inducing levels of LRP in both neurons and astrocytes, our findings support the idea that apoE might be involved in upregulation of LRP (present in fine astrocytic processes) and act as a local scaffolding protein for LRP and Abeta. The upregulation of LRP would allow increased clearance of LRP ligands as well as clearance of AP/ApoE complexes. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Dept Neurol, Charlestown, MA 02129 USA. Amer Red Cross, Holland Lab, Dept Vasc Biol, Rockville, MD 20855 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, Dept Neurol, 114 16th St,Room 2009, Charlestown, MA 02129 USA. NR 49 TC 53 Z9 54 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL 15 PY 2002 VL 104 IS 1 BP 38 EP 46 AR PII S0169-328X(02)00203-6 DI 10.1016/S0169-328X(02)00203-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 581BZ UT WOS:000177272400005 ER PT J AU Lin, TS Zahrieh, D Weller, E Alyea, EP Antin, JH Soiffer, RJ AF Lin, TS Zahrieh, D Weller, E Alyea, EP Antin, JH Soiffer, RJ TI Risk factors for cytomegalovirus reactivation after CD6+T-cell-depleted allogeneic bone marrow transplantation SO TRANSPLANTATION LA English DT Article ID T-CELL DEPLETION; IDENTIFY PATIENTS; VIRUS INFECTIONS; CMV INFECTION; RECIPIENTS; DONOR; DISEASE; ANTIGENEMIA; PREVENTION; LEUKEMIA AB Background Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Recipients of T-cell-depleted (TCD) transplants may be more susceptible to CMV infection as a result of the reduction in transferred T cell immunity. We sought to determine the effect of prior donor and patient CMV exposure on the incidence of CMV infection after TCD allogeneic HSCT. Methods. We retrospectively examined CMV antigen testing results in all patients who had undergone CD6+ TCD related and unrelated donor allogeneic HSCT at our institution from 1996 to 1999. All 124 patients who had documented donor and recipient CMV serologies pretransplant and had undergone CMV antigen testing before day +100 posttransplant were included in the analysis. Results. Forty-one percent of seropositive recipients and 1% of seronegative recipients developed evidence of CMV reactivation (odds ratio 54.1, 95% confidence interval [CI] 6.9-424.1, P<0.001). Prior donor CMV exposure did not place seronegative recipients at increased risk of CMV conversion. Multivariable analysis indicated that prior donor CMV exposure significantly reduced the risk of CMV reactivation in seropositive recipients by 81% (odds ratio 0.19, 95% CI 0.04-0.91, P=0.04). Grades II to IV acute graft-versus-host disease (GVHD) was associated with CMV conversion (P=0.04) when seropositive recipients underwent HSCT from CMV-negative donors, but not when the donor was CMV-seropositive (P=0.54). Conclusions. The CMV serology status of the recipient, rather than the donor, was the primary determinant of risk for CMV conversion after TCD allogeneic HSCT. Despite CD6+ T-cell depletion, immunity against CMV seemed to be transferred with the donor graft and protected seropositive HSCT recipients from CMV reactivation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Lin, TS (reprint author), Ohio State Univ, Div Hematol & Oncol, 320 W 10th Ave, Columbus, OH 43210 USA. FU NIAID NIH HHS [AI29530] NR 31 TC 19 Z9 20 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 JUL 15 PY 2002 VL 74 IS 1 BP 49 EP 54 AR UNSP 0041-1337/02/7401-49/0 DI 10.1097/00007890-200207150-00009 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 576HP UT WOS:000176998100009 PM 12134098 ER PT J AU Egger, M May, M Chene, G Phillips, AN Ledergerber, B Dabis, F Costagliola, D Monforte, AD de Wolf, F Reiss, P Lundgren, JD Justice, AC Staszewski, S Leport, C Hogg, RS Sabin, CA Gill, MJ Salzberger, B Sterne, JAC AF Egger, M May, M Chene, G Phillips, AN Ledergerber, B Dabis, F Costagliola, D Monforte, AD de Wolf, F Reiss, P Lundgren, JD Justice, AC Staszewski, S Leport, C Hogg, RS Sabin, CA Gill, MJ Salzberger, B Sterne, JAC CA ART Cohort Collaboration TI Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies SO LANCET LA English DT Article ID HIV-INFECTED PATIENTS; CD4 CELL COUNT; IMMUNODEFICIENCY-VIRUS-INFECTION; INTRAVENOUS-DRUG-USERS; VIROLOGICAL RESPONSE; VIRAL LOAD; CLINICAL PROGRESSION; PROTEASE INHIBITOR; CONTROLLED-TRIAL; TYPE-1 RNA AB Background Insufficient data are available from single cohort studies to allow estimation of the prognosis of HIV-1 infected, treatment-naive patients who start highly active antiretroviral therapy (HAART). The ART Cohort Collaboration, which includes 13 cohort studies from Europe and North America, was established to fill this knowledge gap. Methods We analysed data on 12 574 adult patients starting HAART with a combination of at least three drugs. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. We considered progression to a combined endpoint of a new AIDS-defining disease or death, and to death alone. The prognostic model that generalised best was a Weibull model, stratified by baseline CD4 cell count and transmission group. Findings During 24 310 person-years of follow up, 1094 patients developed AIDS or died and 344 patients died. Baseline CD4 cell count was strongly associated with the probability of progression to AIDS or death: compared with patients starting HAART with less than 50 CD4 cells/muL, adjusted hazard ratios were 0.74 (95% CI 0.62-0.89) for 50-99 cells/muL, 0.52 (0.44-0.63) for 100-199 cells/muL, 0.24 (0.20-0.30) for 200-349 cells/muL, and 0.18 (0.14-0.22) for 350 or more CD4 cells/muL. Baseline HIV-1 viral load was associated with a higher probability of progression only if 100000 copies/mL or above. Other independent predictors of poorer outcome were advanced age, infection through injection-drug use, and a previous diagnosis of AIDS. The probability of progression to AIDS or death at 3 years ranged from 3.4% (2.8-4.1) in patients in the lowest-risk stratum for each prognostic variable, to 50% (43-58) in patients in the highest-risk strata. Interpretation The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART. Our findings have important implications for clinical management and should be taken into account in future treatment guidelines. C1 Univ Bern, Dept Social & Prevent Med, CH-3012 Bern, Switzerland. Univ Bristol, Dept Social Med, Bristol, Avon, England. Univ Victor Seglen, INSERM, U330, Bordeaux, France. UCL Royal Free & Univ Coll Med Sch, Dept Primary Care & Populat Sci, London, England. Univ Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland. Ctr Hosp Univ Pitie Salpetriere, INSERM, EMI 0214, Paris, France. Univ Milan, Inst Infect & Trop Dis, Milan, Italy. Univ Amsterdam, Acad Med Ctr, HIV Monitoring Fdn, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Natl AIDS Therpay Evaluat Ctr, NL-1105 AZ Amsterdam, Netherlands. Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept Infect Dis Epidemiol, London, England. Hvidovre Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark. VA Pittsburgh Healthcare Syst, Gen Internal Med Sect, Pittsburgh, PA USA. Univ Frankfurt, Zentrum Inneren Med, Frankfurt, Germany. Hop Bichat Claude Bernard, Serv Malad Infect & Trop, F-75877 Paris 18, France. BC Ctr Excellence HIV AIDS, Div Epidemiol & Populat Hlth, Vancouver, BC, Canada. Univ Calgary, Div Infect Dis, Calgary, AB, Canada. Klinikum Univ Regensburg, Innere Med Klin 1, Regensburg, Germany. RP Egger, M (reprint author), Univ Bern, Dept Social & Prevent Med, CH-3012 Bern, Switzerland. EM egger@ispm.unibe.ch RI Sabin, Caroline/C-2464-2008; Phillips, Andrew/B-4427-2008; Hogg, Robert/B-2783-2012; SHCS, all/G-4072-2011; May, Margaret/E-8099-2013; Infektiologie, USZ/A-6921-2011; SHCS, int. coll. A/G-4083-2011; chene, genevieve/H-8665-2014; Costagliola, Dominique/H-5849-2011; Gill, John/G-7083-2016; Ledergerber, Bruno/B-5656-2009; OI Phillips, Andrew/0000-0003-2384-4807; May, Margaret/0000-0002-9733-1003; Costagliola, Dominique/0000-0003-0765-0869; Gill, John/0000-0002-8546-8790; Ledergerber, Bruno/0000-0002-6881-4401; Lundgren, Jens/0000-0001-8901-7850; Hogg, Robert/0000-0003-3463-5488 FU Medical Research Council [G0100221] NR 49 TC 987 Z9 1020 U1 8 U2 71 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 13 PY 2002 VL 360 IS 9327 BP 119 EP 129 DI 10.1016/S0140-6736(02)09411-4 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 573PB UT WOS:000176839100010 PM 12126821 ER PT J AU Sharpless, NE DePinho, RA AF Sharpless, NE DePinho, RA TI p53: Good cop/bad cop SO CELL LA English DT Review ID STRESS-RESPONSE; LIFE-SPAN; CANCER; MICE; TELOMERASE; SIR2; NAD AB Activation of the p53 transcription factor in response to a variety of cellular stresses, including DNA damage and oncogene activation, initiates a program of gene expression that blocks the proliferative expansion of damaged cells. While the beneficial impact of the anticancer function of p53 is well established, several recent papers suggest that p53 activation may in some circumstances act in a manner detrimental to the long-term homeostasis of the organism. Here, we discuss the significant participation of p53 in three non-mutually exclusive theories of human aging involving DNA damage, telomere shortening, and oxidative stress. These "good cop/bad cop" functions of p53 appear to place it at the nexus of two opposing forces, cancer and aging. By extension, this relationship implies that therapies aimed to reduce cancer and postpone aging, and thereby increase longevity, will necessarily work either upstream or downstream, but not on the level of, p53. C1 Harvard Univ, Dept Adult Oncol, Dana Farber Canc Inst, Dept Med & Genet,Sch Med, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Dept Adult Oncol, Dana Farber Canc Inst, Dept Med & Genet,Sch Med, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 20 TC 183 Z9 190 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 12 PY 2002 VL 110 IS 1 BP 9 EP 12 DI 10.1016/S0092-8674(02)00818-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 573PU UT WOS:000176840700003 PM 12150992 ER PT J AU Wijelath, ES Murray, J Rahman, S Patel, Y Ishida, A Strand, K Aziz, S Cardona, C Hammond, WP Savidge, GF Rafii, S Sobel, M AF Wijelath, ES Murray, J Rahman, S Patel, Y Ishida, A Strand, K Aziz, S Cardona, C Hammond, WP Savidge, GF Rafii, S Sobel, M TI Novel vascular endothelial growth factor binding domains of fibronectin enhance vascular endothelial growth factor biological activity SO CIRCULATION RESEARCH LA English DT Article DE vascular endothelial growth factor; fibronectin; binding domains; integrins; endothelial cells ID ACTIVATED PROTEIN-KINASE; EXTRACELLULAR-MATRIX; CELL-PROLIFERATION; ALPHA(V)BETA(3) INTEGRIN; FACTOR RECEPTOR-2; ANGIOGENESIS; MIGRATION; TYROSINE; VEGF; PHOSPHORYLATION AB Interactions between integrins and growth factor receptors play a critical role in the development and healing of the vasculature. This study mapped two binding domains on fibronectin (FN) that modulate the activity of the angiogenic factor, vascular endothelial growth factor (VEGF). Using solid-phase assays and surface plasmon resonance analysis, we identified two novel VEGF binding domains within the N- and C-terminus of the FN molecule. Native FN bound to VEGF enhanced endothelial cell migration and mitogen-activated protein (MAP) kinase activity, but FN that is devoid of the VEGF binding domains failed to do so. Coprecipitation studies confirmed a direct physical association between VEGF receptor-2 (Flk-1) and the FN integrin, a,p, which required intact FN because FN fragments lacking the VEGF binding domains failed to support receptor association. Thrombin-activated platelets released intact VEGF/FN complexes, which stimulated endothelial cell migration and could be inhibited by soluble high affinity VEGF receptor I and antibodies to alpha(5)beta(1) integrin. This study demonstrates that FN is potentially a physiological cofactor for VEGF and provides insights into mechanisms by which growth factor receptors and integrins cooperate to influence cellular behavior. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Hope Heart Inst, Dept Mol Biol, Seattle, WA USA. Univ Washington, Sch Med, Div Vasc Surg, Seattle, WA 98195 USA. St Thomas Hosp, GKT Med Sch, Coagulat Res Lab, London, England. Univ Colorado, Div Cardiothorac Surg, Denver, CO USA. Cornell Univ Med Coll, Div Hematol Oncol, New York, NY USA. RP Wijelath, ES (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,Res Serv 151, Seattle, WA 98108 USA. RI Rahman, Sharif/D-3229-2009 FU NHLBI NIH HHS [HL39903] NR 40 TC 153 Z9 158 U1 0 U2 9 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 JUL 12 PY 2002 VL 91 IS 1 BP 25 EP 31 DI 10.1161/01.RES.0000026420.22406.79 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 575JX UT WOS:000176944100006 PM 12114318 ER PT J AU Addona, GH Husain, SS Stehle, T Miller, KW AF Addona, GH Husain, SS Stehle, T Miller, KW TI Geometric isomers of a photoactivable general anesthetic delineate a binding site on adenylate kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE MONOPHOSPHATE KINASES; HUMAN SERUM-ALBUMIN; RESOLUTION; IDENTIFICATION; MECHANISM; SPECIFICITY; HALOTHANE; MOLECULES; PROTEINS; CAVITY AB General anesthetics are a class of drugs whose mode of action is poorly understood. Here, two photoactivable general anesthetics, n-octan-1-ol geometric isomers bearing a diazirine group on either the third or seventh carbon (3- and 7-azioctanol, respectively), were used to locate and delineate an anesthetic site on adenylate kinase. Each photoincorporated at a mole ratio of 1:1 as determined by mass spectrometry. The photolabeled kinase was subjected to tryptic digest, and the fragments were separated by chromatography and sequenced by mass spectrometry. 3-Azioctanol photolabeled His-36, whereas its isomer, 7-azioctanol, photolabeled Asp-41. Inspection of the known structure of adenylate kinase shows that the side chains of these residues are within similar to5 Angstrom of each other. This distance matches the separation of the 3- and 7-positions of an extended aliphatic chain. The alkanol site so-defined spans two domains of adenylate kinase. His-36 is part of the CORE domain, and Asp-41 belongs to the nucleotide monophosphate binding domain. Upon ligand binding the nucleotide monophosphate binding domain rotates relative to the CORE domain, causing a conformational change that might be expected to affect alkanol binding. Indeed, the substrate-mimicking inhibitor adenosine-(5')-pentaphospho-(5')-adenosine (Ap5A) reduced the photoincorporation of 3- [H-3]azioctanol by 75%. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM 58448] NR 38 TC 16 Z9 16 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 JUL 12 PY 2002 VL 277 IS 28 BP 25685 EP 25691 DI 10.1074/jbc.M201303200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 571YP UT WOS:000176747000108 PM 11976328 ER PT J AU Chiarugi, A Moskowitz, MA AF Chiarugi, A Moskowitz, MA TI Cell biology: PARP-1 - A perpetrator of apoptotic cell death? SO SCIENCE LA English DT Editorial Material ID POLY(ADP-RIBOSE) POLYMERASE-1; NERVOUS-SYSTEM; MITOCHONDRIA; PROTEINS; NAD(+) C1 Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy. Univ Massachusetts, Dept Cellular & Mol Physiol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02029 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02029 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurosci Ctr, Charlestown, MA 02029 USA. RP Chiarugi, A (reprint author), Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy. RI Moskowitz, Michael/D-9916-2011 NR 17 TC 84 Z9 91 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 12 PY 2002 VL 297 IS 5579 BP 200 EP 201 DI 10.1126/science.1074592 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 571UT UT WOS:000176738100024 PM 12114611 ER PT J AU Helfgott, SM Smith, RN AF Helfgott, SM Smith, RN TI A 21-year-old man with arthritis during treatment for hyperthyroidism - Propylthiouracil-induced, ANCA-positive vasculitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; CHURG-STRAUSS-SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIMYELOPEROXIDASE ANTIBODIES; MICROSCOPIC POLYANGIITIS; GLOMERULONEPHRITIS; MYELOPEROXIDASE; AUTOANTIBODIES; GRANULOMATOSIS; NEUTROPHILS C1 Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Helfgott, SM (reprint author), Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. NR 38 TC 13 Z9 15 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 JUL 11 PY 2002 VL 347 IS 2 BP 122 EP 130 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 572HC UT WOS:000176767300008 PM 12110741 ER PT J AU Yeni, PG Hammer, SM Carpenter, CCJ Cooper, DA Fischl, MA Gatell, JM Gazzard, BG Hirsch, MS Jacobsen, DM Katzenstein, DA Montaner, JSG Richman, DD Saag, MS Schechter, M Schooley, RT Thompson, MA Vella, S Volberding, PA AF Yeni, PG Hammer, SM Carpenter, CCJ Cooper, DA Fischl, MA Gatell, JM Gazzard, BG Hirsch, MS Jacobsen, DM Katzenstein, DA Montaner, JSG Richman, DD Saag, MS Schechter, M Schooley, RT Thompson, MA Vella, S Volberding, PA TI Antiretroviral treatment for adult HIV infection in 2002 - Updated recommendations of the international AIDS Society-USA panel SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITOR THERAPY; STRUCTURED TREATMENT INTERRUPTIONS; CD4 CELL COUNT; RANDOMIZED CONTROLLED TRIAL; TRIPLE-DRUG THERAPY; PLASMA VIRAL LOAD; HIV-1-INFECTED PATIENTS; VIROLOGICAL RESPONSE; INSULIN-RESISTANCE AB Objective New information warrants updated recommendations for the 4 central issues in antiretroviral therapy: when to start, what drugs to start with, when to change, and what to change to. These updated recommendations are intended to guide practicing physicians actively involved in human immunodeficiency virus (HIV)- and acquired immunodeficiency syndrome (AIDS)-related care. Participants In 1995, physicians with specific expertise in HIV-related basic science and clinical research, antiretroviral therapy, and HIV patient care were invited by the International AIDS Society-USA to serve on a volunteer panel. In 1999, others were invited to broaden international representation. The 17-member panel met regularly in closed meetings between its last report in 2000 and April 2002 to review current data. The effort was sponsored and funded by the International AIDS Society-USA, a not-for-profit physician education organization. Evidence and Consensus Process The full panel was convened in late 2000 and assigned 7 section committees. A section writer and 3 to 5 section committee members (each panel member served on numerous sections) identified relevant evidence and prepared draft recommendations. Basic science, clinical research, and epidemiologic data from the published literature and abstracts from recent (within 2 years) scientific conferences were considered by strength of evidence. Extrapolations from basic science data and expert opinion of the panel members were included as evidence. Draft sections were combined and circulated to the entire panel and discussed in a series of full-panel conference calls until consensus was reached. Final recommendations represent full consensus agreement of the panel. Conclusions Because of increased awareness of the activity and toxicity of current drugs, the threshold for initiation of therapy has shifted to a later time in the course of HIV disease. However, the optimal time to initiate therapy remains imprecisely defined. Availability of new drugs has broadened options for therapy initiation and management of treatment failure, which remains a difficult challenge. C1 Int AIDS Soc USA, San Francisco, CA 94129 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ New S Wales, Sydney, NSW, Australia. Univ Miami, Sch Med, Miami, FL USA. Univ Barcelona, Hosp Clin, Barcelona, Spain. Chelsea & Westminster Hosp, London, England. Harvard Univ, Sch Med, Boston, MA USA. Hop Bichat Claude Bernard, Dept Infect Dis, X Bichat Med Sch, F-75877 Paris 18, France. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Calif San Diego, La Jolla, CA 92093 USA. San Diego VA Healthcare Syst, San Diego, CA USA. Univ Alabama, Birmingham, AL USA. Univ Fed Rio de Janeiro, BR-21941 Rio De Janeiro, Brazil. Univ Colorado, Sch Med, Denver, CO USA. AIDS Res Consortium Atlanta, Atlanta, GA USA. Ist Super Sanita, I-00161 Rome, Italy. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Yeni, PG (reprint author), Int AIDS Soc USA, 1001 B OReilly Ave, San Francisco, CA 94129 USA. RI Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 NR 187 TC 570 Z9 580 U1 0 U2 22 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 JUL 10 PY 2002 VL 288 IS 2 BP 222 EP 235 DI 10.1001/jama.288.2.222 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 571HC UT WOS:000176711100023 PM 12095387 ER PT J AU Wong, GC Morrow, DA Murphy, S Kraimer, N Pai, R James, D Robertson, DH Demopoulos, LA DiBattiste, P Cannon, CP Gibson, CM AF Wong, GC Morrow, DA Murphy, S Kraimer, N Pai, R James, D Robertson, DH Demopoulos, LA DiBattiste, P Cannon, CP Gibson, CM CA TACTICS-TIMI 18 Study Grp TI Elevations in troponin T and I are associated with abnormal tissue level perfusion - A TACTICS-TIMI 18 substudy SO CIRCULATION LA English DT Article DE angina; perfusion; troponin; angiography; thrombosis ID ACUTE CORONARY SYNDROMES; NO-REFLOW PHENOMENON; ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; RISK STRATIFICATION; ANGIOGRAPHIC FINDINGS; CLINICAL OUTCOMES; FLOW; INTERVENTION; MORTALITY AB Background-Cardiac troponin T (cTnT) and I elevations are associated with a higher risk of adverse events, a higher incidence of multivessel disease, complex lesions, and visible thrombus in the setting of non-ST elevation (NSTE) acute coronary syndromes (ACS). Other pathophysiological mechanisms underlying troponin elevation remain unclear. Methods and Results-We evaluated the relationship between troponin elevation and tissue level perfusion using the TIMI myocardial perfusion grade (TMPG) in 3 10 patients with NSTE-ACS in the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction (TACTICS-TIMI) 18 trial. TMPG 0/1 ("closed" microvasculature) was observed more frequently in cTnT-positive patients both before (58.1% versus 42.1%; P=0.007) and after percutaneous coronary intervention (55.4% versus 35.6%; P=0.004). cTnT levels were higher among patients with TMPG 0/1 versus patients with TMPG 2/3 (0.50 versus 0.31 ng/mL; P=0.006). cTnT-positive patients were more likely to have thrombus (42.5% versus 29.3%), tighter stenoses (72.0% versus 64.8%), and higher rates of TIMI flow grade 0/1 (15.6% versus 7.0%; all P<0.05). TMPG 0/1 remained independently associated with cTnT elevation (odds ratio, 1.81; P=0.02), even after adjusting for epicardial TIMI flow grade, presence of thrombus, and prior myocardial infarction. TMPG 0/1 flow both before and after intervention was associated with increased risk of death or myocardial infarction at 6 months. Conclusions-Similar to what has been observed in the setting of ST-elevation myocardial infarction, abnormal tissue level perfusion is also associated with adverse outcomes in the NSTE-ACS setting. Independent of the presence of thrombus and abnormal flow in the epicardial artery, impaired tissue level perfusion is associated with a 1.8-fold increased risk of cTnT elevation. C1 TIMI Study Grp, Boston, MA USA. Merck & Co Inc, W Point, PA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA. NR 26 TC 80 Z9 84 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 9 PY 2002 VL 106 IS 2 BP 202 EP 207 DI 10.1161/01.CIR.0000021921.14653.28 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 573GG UT WOS:000176820500020 PM 12105159 ER PT J AU Chang, AN Cantor, AB Fujiwara, Y Lodish, MB Droho, S Crispino, JD Orkin, SH AF Chang, AN Cantor, AB Fujiwara, Y Lodish, MB Droho, S Crispino, JD Orkin, SH TI GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; HEART MORPHOGENESIS; HEMATOPOIETIC-CELLS; MICE LACKING; COFACTOR; DIFFERENTIATION; MOUSE; GENE; PRECURSORS; EXPRESSION AB The function of GATA transcription factors in diverse developmental contexts depends in part on physical interaction with cofactors of the Friend of GATA (FOG) family. However, previous studies indicate that FOG-1 may play a GATA-1-independent role in early megakaryopoiesis, suggesting that FOG proteins might act in a GATA factor-independent manner. Here, we have generated mouse knock-in (KI) mutants harboring a critical valine-to-glycine substitution in the amino-terminal zinc fingers of GATA-1 and GATA-2 to ablate FOG interaction. In contrast to male GATA-1(KI) (GATA-1 is located on the X-chromosome) or GATA-2(KI/KI) mice, compound GATA-1(KI) GATA-2(KI/KI) mutant mice display complete megakaryopoietic failure, a phenocopy of FOG-1(-/-) mice. We conclude that FOG-1 requires an interaction with either GATA-1 or -2 as part of its essential role in early megakaryopoiesis. On the basis of these and previous reports, we infer that GATA factor dependence is a critical aspect of FOG protein function. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. OI Crispino, John/0000-0002-8182-8306 NR 33 TC 125 Z9 129 U1 0 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 JUL 9 PY 2002 VL 99 IS 14 BP 9237 EP 9242 DI 10.1073/pnas.142302099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 572LE UT WOS:000176775400031 PM 12077323 ER PT J AU Bent, S Saint, S AF Bent, S Saint, S TI The optimal use of diagnostic testing in women with acute uncomplicated cystitis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID URINARY-TRACT INFECTION; CLINICAL-PRACTICE GUIDELINE; RISK-FACTORS; YOUNG-WOMEN; MANAGEMENT; ASSOCIATION; BACTERIURIA; STRATEGIES; SYMPTOMS AB Acute uncomplicated cystitis is a common and costly disorder in women, and there is considerable variation in the diagnostic strategies currently used in clinical practice. Because the diagnosis of cystitis can be established in most patients using the history alone, the clinician's responsibility is to determine which patients require additional diagnostic testing. Patients with typical symptoms (i.e., dysuria, frequency, urgency, hematuria), without risk factors for complicated infection or pyelonephritis, and without a history of vaginal discharge, have a very high probability of cystitis and are appropriate candidates for empiric treatment. It is more difficult, however, to rule out infection in patients with suspected cystitis. Because the prevalence of culture-proven infection is very high in women who present with greater than or equal to 1 symptom, and because the treatment threshold for this condition is low, a urine culture is generally required to rule out infection in patients with atypical symptoms, even in the presence of a negative dipstick test. In population-based, before-and-after studies, use of diagnostic algorithms has been shown to significantly decrease the use of urinalysis, urine culture, and office visits while increasing the percentage of patients who receive recommended antibiotics. These strategies have substantially reduced the cost of managing cystitis without an increase in adverse events or a decrease in patient satisfaction. Randomized controlled trials are needed to more closely examine the outcomes, costs of care, and patient satisfaction from different diagnostic and management strategies. (C) 2002 by Excerpta Medica, Inc. C1 San Francisco VAMC, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Ann Arbor Vet Adm Med Ctr, Hlth Serv Res & Dev Field Program, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Internal Med, Patient Safety Enhancement Program,Hlth Syst, Ann Arbor, MI USA. RP Bent, S (reprint author), San Francisco VAMC, Gen Internal Med Sect, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. NR 36 TC 22 Z9 22 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL 8 PY 2002 VL 113 SU 1A BP 20S EP 28S AR PII S0002-9343(02)01056-2 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 572BV UT WOS:000176754300004 PM 12113868 ER PT J AU Bortfeld, T Jokivarsi, K Goitein, M Kung, J Jiang, SB AF Bortfeld, T Jokivarsi, K Goitein, M Kung, J Jiang, SB TI Effects of intra-fraction motion on IMRT dose delivery: statistical analysis and simulation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID MODULATED RADIATION-THERAPY; INCORPORATING ORGAN MOTION; MULTILEAF COLLIMATOR; INTENSITY MODULATION; GATED RADIOTHERAPY; CANCER; TUMOR AB There has been some concern that organ motion, especially intra-fraction organ motion due to breathing, can negate the potential merit of intensity-modulated radiotherapy (IMRT). We wanted to find out whether this concern is justified. Specifically, we wanted to investigate whether IMRT delivery techniques with moving parts, e.g., with a multileaf collimator (MLC), are particularly sensitive to organ motion due to the interplay between organ motion and leaf motion. We also wanted to know if, and by how much, fractionation of the treatment can reduce the effects. We performed a statistical analysis and calculated the expected dose values and dose variances for volume elements of organs that move during the delivery of the IMRT. We looked at the overall influence of organ motion during the course of a fractionated treatment. A linear-quadratic model was used to consider fractionation effects. Furthermore, we developed software to simulate motion effects for IMRT delivery with an MLC, with compensators, and with a scanning beam. For the simulation we assumed a sinusoidal motion in an isocentric plane. We found that the expected dose value is independent of the treatment technique. It is just a weighted average over the path of motion of the dose distribution without motion. If the treatment is delivered in several fractions, the distribution of the dose around the expected value is close to a Gaussian. For a typical treatment with 30 fractions, the standard deviation is generally within 1% of the expected value for MLC delivery if one assumes a typical motion amplitude of 5 mm (1 cm peak to peak). The standard deviation is generally even smaller for the compensator but bigger for scanning beam delivery. For the latter it can be reduced through multiple deliveries ('paintings') of the same field. In conclusion, the main effect of organ motion in IMRT is an averaging of the dose distribution without motion over the path of the motion. This is the same as for treatments with conventional beams. Additional effects that are specific to the IMRT delivery technique appear to be relatively small, except for the scanning beam. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 31 TC 313 Z9 316 U1 2 U2 15 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUL 7 PY 2002 VL 47 IS 13 BP 2203 EP 2220 AR PII S0031-9155(02)34249-0 DI 10.1088/0031-9155/47/13/302 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 578FM UT WOS:000177106800002 PM 12164582 ER PT J AU Hettiaratchy, S Butler, PEM AF Hettiaratchy, S Butler, PEM TI Face transplantation - fantasy or the future? SO LANCET LA English DT Editorial Material ID INDUCTION; TOLERANCE C1 Royal Free Hosp, Dept Plast Surg, London NW3 20G, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Butler, PEM (reprint author), Royal Free Hosp, Dept Plast Surg, London NW3 20G, England. NR 6 TC 51 Z9 55 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 6 PY 2002 VL 360 IS 9326 BP 5 EP 6 DI 10.1016/S0140-6736(02)09361-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 569JR UT WOS:000176599700005 PM 12114034 ER PT J AU Goetz, MB Feikin, DR Lennox, JL O'Brien, WA Elie, CM Butler, JC Breiman, RF AF Goetz, MB Feikin, DR Lennox, JL O'Brien, WA Elie, CM Butler, JC Breiman, RF TI Viral load response to a pneumococcal conjugate vaccine, polysaccharide vaccine or placebo among HIV-infected patients SO AIDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFLUENZA VACCINATION; DOUBLE-BLIND; CONTROLLED TRIAL; IMMUNIZATION; REPLICATION; ACTIVATION; ADULTS; INDIVIDUALS; CHILDREN AB We determined the HIV viral load in 66 adults randomly assigned to receive pneumococcal immunization with one or two doses of protein conjugate vaccine, one dose of polysaccharide vaccine, one dose of each, or placebo. Second doses were given 8 weeks after the first. Mean baseline viral load and CD4 cell count were 3.41 copies/ml (log(10)) and 457 cells/mul, respectively. We found no change in viral load during 24 weeks of follow-up for any vaccine or combination of vaccines or placebo. C1 VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Natl Ctr Infect Dis, Resp Dis Branch, Div Bacterial & Mycot Dis, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Emory Univ, Atlanta, GA 30322 USA. Grady Infect Dis Program, Atlanta, GA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Goetz, MB (reprint author), VA Greater Los Angeles Hlthcare Syst, Los Angeles, CA USA. RI Lennox, Jeffrey/D-1654-2014; OI Lennox, Jeffrey/0000-0002-2064-5565; Goetz, Matthew/0000-0003-4542-992X NR 19 TC 10 Z9 10 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 JUL 5 PY 2002 VL 16 IS 10 BP 1421 EP 1423 DI 10.1097/00002030-200207050-00015 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 571LX UT WOS:000176719800015 PM 12131220 ER PT J AU Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH AF Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH TI Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury SO BRAIN RESEARCH LA English DT Article DE brain microdialysis; glucose; glutamate; traumatic brain injury ID TRAUMATIC BRAIN INJURY; HUMAN HEAD-INJURY; GLUTAMATE RELEASE; RAT; BW619C89; DAMAGE; ANTAGONISTS; LAMOTRIGINE; ASPARTATE; MECHANISM AB Increases in brain interstitial excitatory amino acid (EAA(1)) concentrations after ischemia are ameliorated by use-dependent Na+ channel antagonists and by supplementing interstitial glucose, but the regulation of EAA(1) after traumatic brain injury (TBI) is unknown. We studied the regulation of EAA(1), after TBI using the controlled cortical impact model in rats. To monitor changes in EAA(1), microdialysis probes were placed in the cortex adjacent to the contusion and in the ipsilateral hippocampus. Significant increases in dialysate EAA, after TBI were found compared to levels measured in sham controls. Treatment with the use-dependent Na+ channel antagonist 619C89 (30 mg/kg i.v.) did not significantly decrease dialysate glutamate compared to vehicle controls in hippocampus (10.4 +/- 2.4 vs. 11.9 +/- 1.6 muM), but there was significant decrease in dialysate glutamate in cortex after 619C89 treatment (19.3 +/- 3 vs. 12.6 +/- 1.1 muM, P<0.05). Addition of 30 mM glucose to the dialysate, a treatment that decreases EAA(1) after ischemia, had no significant effect upon dialysate glutamate after TBI in cortex (20.0 +/- 4.9 vs. 11.7 +/- 3.4 μM) or in hippocampus (10.9 +/- 2.0 vs. 8.9 +/- 2.4 μM). These results suggest that neither increased release of EAAs due to Na+ channel-mediated depolarization nor failure of glutamate reuptake due to glucose deprivation can explain the majority of the increase in EAA(1) following TBI. Published by Elsevier Science B.V. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA 15213 USA. Vernalis Ltd, Wokingham, England. Vet Affairs Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Graham, SH (reprint author), Univ Pittsburgh, Dept Neurol, 526 S BST, Pittsburgh, PA 15213 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS30318] NR 27 TC 29 Z9 37 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 5 PY 2002 VL 943 IS 1 BP 15 EP 22 AR PII S0006-8993(02)02471-X DI 10.1016/S0006-8993(02)02471-X PG 8 WC Neurosciences SC Neurosciences & Neurology GA 576TK UT WOS:000177021000003 PM 12088834 ER PT J AU Lishko, PV Martemyanov, KA Hopp, JA Arshavsky, VY AF Lishko, PV Martemyanov, KA Hopp, JA Arshavsky, VY TI Specific binding of RGS9-G beta 5L to protein anchor in photoreceptor membranes greatly enhances its catalytic activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACCELERATING PROTEIN; ROD OUTER SEGMENTS; VERTEBRATE PHOTORECEPTORS; RGS; TRANSDUCIN; PHOTOTRANSDUCTION; PHOSPHODIESTERASE; PURIFICATION; ACTIVATION; ADAPTATION AB The complex between the short splice variant of the ninth member of the RGS protein family and the long splice variant of type 5 G protein beta subunit (RGS9-Gbeta5L) plays a critical role in regulating the duration of the light response in vertebrate photoreceptors by activating the GTPase activity of the photoreceptor-specific G protein, transducin. RGS9-Gbeta5L is tightly associated with the membranes of photoreceptor outer segments; however, the nature of this association remains unknown. Here we demonstrate that rod outer segment membranes contain a limited number of sites for high affinity RGS9-Gbeta5L binding, which are highly sensitive to proteolysis. In membranes isolated from bovine rod outer segments, all of these sites are occupied by the endogenous RGS9-Gbeta5L, which prevents the binding of exogenous recombinant RGS9-Gbeta5L to these sites. However, treating membranes with urea or high pH buffers causes either removal or denaturation of the endogenous RGS9-Gbeta5L, allowing for high affinity binding of recombinant RGS9-Gbeta5L to these sites. This binding results in a striking similar to70-fold increase in the RGS9-Gbeta5L ability to activate transducin GTPase. The DEP (disheveled/EGL-10/pleckstrin) domain of RGS9 plays a crucial role in the RGS9-Gbeta5L membrane attachment, as evident from the analysis of membrane-binding properties of deletion mutants lacking either N- or C-terminal parts of the RGS9 molecule. Our data indicate that specific association of RGS9-Gbeta5L with photoreceptor disc membranes serves not only as a means of targeting it to an appropriate subcellular compartment but also serves as an important determinant of its catalytic activity. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. FU NEI NIH HHS [EY-12859] NR 25 TC 53 Z9 53 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 JUL 5 PY 2002 VL 277 IS 27 BP 24376 EP 24381 DI 10.1074/jbc.M203237200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 569PV UT WOS:000176611800054 PM 12006596 ER PT J AU Linseman, DA McClure, ML Bouchard, R Laessig, TA Ahmadi, FA Heidenreich, KA AF Linseman, DA McClure, ML Bouchard, R Laessig, TA Ahmadi, FA Heidenreich, KA TI Suppression of death receptor signaling in cerebellar Purkinje neurons protects neighboring granule neurons from apoptosis via an insulin-like growth factor I-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; CYTOCHROME-C RELEASE; CELL-DEATH; IGF-I; GENE-EXPRESSION; RAT CEREBELLUM; NERVOUS-SYSTEM; FAS LIGAND; SURVIVAL; BCL-2 AB Neuronal apoptosis contributes to the progression of neurodegenerative disease. Primary cerebellar granule neurons are an established in vitro model for investigating neuronal death. After removal of serum and depolarizing potassium, granule neurons undergo apoptosis via a mechanism that requires intrinsic (mitochondrial) death signals; however, the role of extrinsic (death receptor-mediated) signals is presently unclear. Here, we investigate involvement of death receptor signaling in granule neuron apoptosis by expressing adenoviral, AU1-tagged, dominant-negative Fas-associated death domain (Ad-AU1-DeltaFADD). Ad-AU1-DeltaFADD decreased apoptosis of granule neurons from 65 +/- 5 to 27 +/- 2% (n = 7, p < 0.01). Unexpectedly, immunocytochemical staining for AU1 revealed that <5% of granule neurons expressed DeltaFADD. In contrast, DeltaFADD was expressed in >95% of calbindin-positive Purkinje neurons (similar to2% of the cerebellar culture). Granule neurons in proximity to DeltaFADD-expressing Purkinje cells demonstrated markedly increased survival. Both granule and Purkinje neurons expressed insulin-like growth factor-I (IGF-I) receptors, and DeltaFADD-mediated survival of granule neurons was inhibited by an IGF-I receptor blocking antibody. These results demonstrate that the selective suppression of death receptor signaling in Purkinje neurons is sufficient to rescue neighboring granule neurons that depend on Purkinje cell-derived IGF-I. Thus, the extrinsic death pathway has a profound but indirect effect on the survival of cerebellar granule neurons. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol C236, 4200 E Ninth Ave, Denver, CO 80262 USA. FU NINDS NIH HHS [NS38619-01A1] NR 52 TC 24 Z9 25 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 JUL 5 PY 2002 VL 277 IS 27 BP 24546 EP 24553 DI 10.1074/jbc.M201098200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 569PV UT WOS:000176611800076 PM 11964396 ER PT J AU Orkin, SH Morrison, SJ AF Orkin, SH Morrison, SJ TI Stem-cell competition SO NATURE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Michigan, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Howard Hughes Med Inst, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 13 TC 40 Z9 53 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 4 PY 2002 VL 418 IS 6893 BP 25 EP 27 DI 10.1038/418025a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 569JL UT WOS:000176599200020 PM 12097889 ER PT J AU Antin, JH AF Antin, JH TI Long-term care after hematopoietic-cell transplantation in adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC GRAFT; RISK-FACTORS; STEM-CELL; THYROID-DYSFUNCTION; AVASCULAR NECROSIS; RECIPIENTS; SURVIVORS; LEUKEMIA C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Adult Oncol Stem Cell Transplantat Program, Boston, MA 02115 USA. RP Antin, JH (reprint author), Brigham & Womens Hosp, Dept Med, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 52 Z9 57 U1 1 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 JUL 4 PY 2002 VL 347 IS 1 BP 36 EP 42 DI 10.1056/NEJMcp010518 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 569HA UT WOS:000176594500008 PM 12097539 ER PT J AU Roberts, D Schwartz, RS AF Roberts, D Schwartz, RS TI Clotting and hemorrhage in the placenta - A delicate balance SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID THROMBOPHILIA; PREGNANCY; LESIONS; FETAL; WOMEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roberts, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 28 Z9 30 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 JUL 4 PY 2002 VL 347 IS 1 BP 57 EP 59 DI 10.1056/NEJMe020061 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 569HA UT WOS:000176594500012 PM 12097543 ER PT J AU Lundberg, AS Randell, SH Stewart, SA Elenbaas, B Hartwell, KA Brooks, MW Fleming, MD Olsen, JC Miller, SW Weinberg, RA Hahn, WC AF Lundberg, AS Randell, SH Stewart, SA Elenbaas, B Hartwell, KA Brooks, MW Fleming, MD Olsen, JC Miller, SW Weinberg, RA Hahn, WC TI Immortalization and transformation of primary human airway epithelial cells by gene transfer SO ONCOGENE LA English DT Article DE transformation; lung cancer; immortalization; ras oncogene ID LARGE T-ANTIGEN; TELOMERASE ACTIVITY; RAS ONCOGENE; LIFE-SPAN; NEOPLASTIC TRANSFORMATION; CELLULAR SENESCENCE; CLONAL GROWTH; TUMOR-CELLS; HUMAN-LUNG; IN-VITRO AB One critical step in the development of a cancerous cell is its acquisition of an unlimited replicative lifespan, the process termed immortalization. Experimental model systems designed to study cellular transformation ex vivo have relied to date on the in vitro selection of a subpopulation of cells that have become immortalized through treatment with chemical or physical mutagens and the selection of rare clonal variants. In this study, we describe the direct immortalization of primary human airway epithelial cells through the successive introduction of the Simian Virus 40 Early Region and the telomerase catalytic subunit hTERT. Cells immortalized in this way are now responsive to malignant transformation by an introduced H-ras or K-ras oncogene. These immortalized human airway epithelial cells, which have been created through the stepwise introduction of genetic alterations, provide a novel experimental model system with which to study further the biology of the airway epithelial cell and to dissect the molecular basis of lung cancer pathogenesis. C1 Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Childrens Hosp, Dept Pathol, Boston, MA 02215 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Randell, SH (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. RI Stewart, Sheila/C-5213-2012 NR 44 TC 149 Z9 154 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 4 PY 2002 VL 21 IS 29 BP 4577 EP 4586 DI 10.1038/sj.onc.1205550 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 567GH UT WOS:000176476700012 PM 12085236 ER PT J AU Hirose, J Kawashima, H Willis, MS Springer, TA Hasegawa, H Yoshie, O Miyasaka, M AF Hirose, J Kawashima, H Willis, MS Springer, TA Hasegawa, H Yoshie, O Miyasaka, M TI Chondroitin sulfate B exerts its inhibitory effect on secondary lymphoid tissue chemokine (SLC) by binding to the C-terminus of SLC SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE chemokine; secondary lymphoid tissue chemokine (SLC); CC chemokine receptor (CCR) 7; glycosaminoglycan; chondroitin sulfate B; chondroitin sulfate E ID HIGH ENDOTHELIAL VENULES; ROLLING T-LYMPHOCYTES; HEPARAN-SULFATE; GLYCOSAMINOGLYCAN-BINDING; CELLULAR-RESPONSES; PROTEOGLYCANS; EXPRESSION; ADHESION; ARREST; CELLS AB We previously reported that certain glycosaminoglycans (GAGs) bind secondary lymphoid tissue chemokine (SLC, CCL21) and that the SLC-binding GAGs, including chondroitin sulfate B (CS B), negatively modulate the function of SLC, although the mechanism remains unknown [J. Biol. Chem. 276 (2001) 5228]. To gain insight into the mechanism of inhibition, we used a C-terminally truncated SLC (SLC-T) that lacked clusters of basic amino acid residues that have been implicated in GAG binding. While SLC-T failed to bind any GAGs, it induced prominent intracellular Ca2+ mobilization in CC chemokine receptor (CCR) 7-expressing cells, as did wild-type SLC. However, the SLC-T-induced Ca2+ influx was not inhibited by CS B, unlike the SLC-induced Ca2+ influx. These results demonstrate the requirement of the C-terminus of SLC for the inhibition of chemokine responses by CS B; that is, CS B exerts its inhibitory effect by binding to the C-terminus of SLC, thus defining the mode of action of CS B on certain chemokines. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Osaka Univ, Grad Sch Med C8, Suita, Osaka 5650871, Japan. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Ehime Univ, Sch Med, Dept Internal Med, Shigenobu, Ehime 7910295, Japan. Kinki Univ, Sch Med, Dept Microbiol, Osaka 5898511, Japan. RP Miyasaka, M (reprint author), Osaka Univ, Grad Sch Med C8, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 28 TC 32 Z9 34 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JUL 3 PY 2002 VL 1571 IS 3 BP 219 EP 224 AR PII S030404165(02)00232-5 DI 10.1016/S0304-4165(02)00232-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 616JB UT WOS:000179299700007 PM 12090936 ER PT J AU Morrow, DA Antman, EM Sayah, A Schuhwerk, KC Giugliano, RP deLemos, JA Waller, M Cohen, SA Rosenberg, DG Cutler, SS McCabe, CH Walls, RM Braunwald, E AF Morrow, DA Antman, EM Sayah, A Schuhwerk, KC Giugliano, RP deLemos, JA Waller, M Cohen, SA Rosenberg, DG Cutler, SS McCabe, CH Walls, RM Braunwald, E CA Early Retavase Thrombolysis Myocar TI Evaluation of the time saved by prehospital initiation of reteplase for ST-elevation myocardial infarction - Results of the Early Retavase-Thrombolysis In Myocardial Infarction (ER-TIMI) 19 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID SEGMENT RESOLUTION; FIBRINOLYTIC THERAPY; REPERFUSION THERAPY; RANDOMIZED TRIAL; OF-CARDIOLOGY; TASK-FORCE; IMPACT; ELECTROCARDIOGRAPHY; METAANALYSIS; MORTALITY AB OBJECTIVES The Early Retavase-Thrombolysis In Myocardial Infarction (ER-TIMI) 19 trial tested the feasibility of prehospital initiation of the bolus fibrinolytic reteplase (rPA) and determined the time saved by prehospital rPA in the setting of contemporary emergency cardiac care. BACKGROUND Newer bolus fibrinolytics have undergone only limited evaluation for prehospital administration. In addition, as door-to-drug times have decreased, the relevance of findings from prior trials of prehospital fibrinolysis has become less certain. METHODS Patients (n = 315) with ST-elevation myocardial infarction (STEMI) were enrolled in 20 emergency medical systems in North America. The time from emergency medical service (EMS) arrival to administration of a fibrinolytic was compared between study patients receiving prehospital rPA and sequential control patients from 6 to 12 months before the study who received a fibrinolytic in the hospital. RESULTS Acute myocardial infarction was confirmed in 98%. The median time from EMS arrival to initiation of rPA was 31 min (25th to 75th percentile, 24 min to 37 min). The time from EMS arrival to in-hospital fibrinolytic for 630 control patients was 63 min (25th to 75th percentile, 48 min to 89 min), resulting in a time saved of 32 min (p < 0.0001). By 30 min after first medical contact, 49% of study patients had received the first bolus of fibrinolytic compared with only 5% of controls (p < 0.0001). In-hospital mortality was 4.7%. Intracranial hemorrhage occurred in 1.0%. CONCLUSIONS Prehospital administration of rPA is a feasible approach to accelerating reperfusion in patients with STEMI. Valuable time savings can be achieved in the setting of contemporary transport and door-to-drug times and may translate into an improvement in clinical outcomes. (C) 2002 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Boston, MA USA. Good Samaritan Hosp, Dept Emergency Med, Brockton, MA USA. SW Texas State Univ, Dept Med, Dallas, TX USA. Centocor Inc, Malvern, PA USA. Univ Florida, Div Cardiol, Miami, FL USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 37 TC 95 Z9 102 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 3 PY 2002 VL 40 IS 1 BP 71 EP 77 AR PII S0735-1097(02)01936-8 DI 10.1016/S0735-1097(02)01936-8 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 569XT UT WOS:000176628500009 PM 12103258 ER PT J AU Nemoto, S Hamawaki, M De Freitas, G Carabello, BA AF Nemoto, S Hamawaki, M De Freitas, G Carabello, BA TI Differential effects of the angiotensin-converting enzyme inhibitor lisinopril versus the beta-adrenergic receptor blocker atenolol on hemodynamics and left ventricular contractile function in experimental mitral regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VOLUME-OVERLOAD HYPERTROPHY; HEART-FAILURE; CARDIAC-MUSCLE; WALL STRESS; DYSFUNCTION; CARDIOMYOPATHY; PERFORMANCE; THERAPY; GROWTH AB OBJECTIVES The goal of this study was to determine the therapeutic efficacy of anglotensin-converting enzyme (ACE) inhibitors and beta-adrenergic receptor blockers in experimental chronic mitral regurgitation (MR), gaining knowledge using methods difficult to apply in humans. BACKGROUND Both ACE inhibitors and beta-blockers are cornerstones in the treatment of human congestive heart failure. However, the roles of these treatments for chronic MR is unclear. METHODS Mitral regurgitation was created in 11 closed-chest dogs. Three months after the creation, the ACE inhibitor lisinopril 20 mg was given orally daily. After three months of lisinopril therapy, the beta-blocker atenolol was added to lisinopril for another three months. Atenolol was begun at a dose of 12.5 mg daily and increased gradually to 100 mg daily. Hemodynamics and left ventricular (LV) function were assessed throughout the study. RESULTS Regurgitant fraction was consistently >50% over the course of this study. Pulmonary capillary wedge pressure and LV end-diastolic pressure were significantly increased after three months of MR and decreased during both lisinopril and the combined therapy in which it was not different from baseline. Left ventricular contractility measured by the end-systolic stiffness constant was depressed from 3.66 +/- 0.20 to 2.65 +/- 0.12 (p < 0.05) at three months of MR and rose insignificantly after lisinopril treatment (2.99 +/- 0.17). When atenolol was added, it rose significantly and returned to normal (3.50 +/- 0.22, p < 0.05). CONCLUSIONS Although lisinopril significantly reduced preload, its effect on LV contractility was insignificant in experimental MR. Conversely, atenolol, when added to lisinopril, achieved maximum hemodynamic benefit and also restored LV contractility. (C) 2002 by the American College of Cardiology Foundation. C1 Med Univ S Carolina, Dept Med, Dept Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs, Charleston, SC USA. RP Carabello, BA (reprint author), Houston Vet Affairs Med Ctr, Med Serv 3, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [R0-1 HL38185] NR 29 TC 58 Z9 59 U1 0 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 JUL 3 PY 2002 VL 40 IS 1 BP 149 EP 154 AR PII S0735-1097(02)01926-5 DI 10.1016/S0735-1097(02)01926-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 569XT UT WOS:000176628500020 PM 12103269 ER PT J AU Burbea, M Dreier, L Dittman, JS Grunwald, ME Kaplan, JM AF Burbea, M Dreier, L Dittman, JS Grunwald, ME Kaplan, JM TI Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C-elegans SO NEURON LA English DT Article ID LONG-TERM FACILITATION; CAENORHABDITIS-ELEGANS; AMPA RECEPTORS; SYNAPTIC TRANSMISSION; DEUBIQUITINATING ENZYME; NERVOUS-SYSTEM; INTERNALIZATION; ENDOCYTOSIS; NEURONS; DEGRADATION AB Regulated delivery and removal of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) from postsynaptic elements has been proposed as a mechanism for regulating synaptic strength. Here we test the role of ubiquitin in regulating synapses that contain a C. elegans GluR, GLR-1. GLR-1 receptors were ubiquitinated in vivo. Mutations that decreased ubiquitination of GLR-1 increased the abundance of GLR-1 at synapses and altered locomotion behavior in a manner that is consistent with increased synaptic strength. By contrast, overexpression of ubiquitin decreased the abundance of GLR-1 at synapses and decreased the density of GLR-1-containing synapses, and these effects were prevented by mutations in the unc-11 gene, which encodes a clathrin adaptin protein (AP180). These results suggest that ubiquitination of GLR-1 receptors regulates synaptic strength and the formation or stability of GLR-1 -containing synapses. C1 Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8, Boston, MA 02114 USA. FU NINDS NIH HHS [F32 NS41705, NS32196] NR 52 TC 196 Z9 208 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 3 PY 2002 VL 35 IS 1 BP 107 EP 120 DI 10.1016/S0896-6273(02)00749-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 569KP UT WOS:000176601800014 PM 12123612 ER PT J AU Mulley, AG Sepucha, K AF Mulley, AG Sepucha, K TI Making good decisions about breast cancer chemoprevention SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED TRIAL; RISK; TAMOXIFEN; WOMEN; PERCEPTIONS; PREVENTION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Mulley, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Stanford St, Boston, MA 02114 USA. NR 19 TC 12 Z9 12 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 2 PY 2002 VL 137 IS 1 BP 52 EP 54 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 569VA UT WOS:000176622000008 PM 12093247 ER PT J AU Spertus, JA Jones, P McDonell, M Fan, V Fihn, SD AF Spertus, JA Jones, P McDonell, M Fan, V Fihn, SD TI Health status predicts long-term outcome in outpatients with coronary disease SO CIRCULATION LA English DT Article DE mortality; coronary disease; angina; Seattle Angina Questionnaire; risk factors ID BYPASS GRAFT-SURGERY; QUALITY-OF-LIFE; ARTERY DISEASE; FUNCTIONAL STATUS; MORTALITY; IDENTIFICATION; VALIDITY; TESTS AB Background-Although patient-reported health status measures have been used as end points in clinical trials, they are rarely used in other settings. Demonstrating that they independently predict mortality and hospitalizations among Outpatients with coronary disease could emphasize their clinical value. Methods and Results-This stud evaluated the prognostic utility of the Seattle Angina Questionnaire (SAQ), a disease- specific health status measure for patients with coronary artery disease. Patients were enrolled in a prospective cohort study from 6 Veterans Affairs General Internal Medicine Clinics. All patients reporting coronary artery disease who completed a SAQ and had I year of follow-up were analyzed (n=5558). SAQ predictor variables were the physical limitation, angina stability, angina frequency, and quality-of-life scores. The primary outcome was 1-year all-cause mortality, and a secondary outcome was hospitalization for acute coronary syndrome (ACS). Lower SAQ scores were associated with increased risks of mortality and ACS admissions. Prognostic models controlling for demographic and clinical characteristics demonstrated significant independent mortality risk with lower SAQ physical limitation scores-, odds ratios for mild. moderate, and severe limitation were 1.5, 2.0, and 4.0 versus minimal limitation (P<0.001). Odds ratios for mild, moderate, and severe angina frequency were 0.8, 1.2, and 1.6 (P=0.078). The odds ratios for ACS admission among those with mild, moderate, and severe angina frequency were 1.4, 2.0, and 2.2, respectively (P=0.016). Conclusions-SAQ scores are independently associated with 1-year mortality and ACS among outpatients with coronary disease and may serve a valuable role in the risk stratification of such patients. C1 St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Washington, Dept Med, Seattle, WA USA. VA Puget Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. RP Spertus, JA (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. NR 17 TC 269 Z9 275 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 2 PY 2002 VL 106 IS 1 BP 43 EP 49 DI 10.1161/01.CIR.0000020688.24874.90 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 573GF UT WOS:000176820400012 PM 12093768 ER PT J AU Duda, JE Giasson, BI Mahon, ME Miller, DC Golbe, LI Lee, VMY Trojanowski, JQ AF Duda, JE Giasson, BI Mahon, ME Miller, DC Golbe, LI Lee, VMY Trojanowski, JQ TI Concurrence of alpha-synuclein and tau brain pathology in the Contursi kindred SO ACTA NEUROPATHOLOGICA LA English DT Article DE neuropathology; alpha-synuclein; Parkinson's disease; histopathology; Lewy bodies ID NEURODEGENERATIVE DISEASES; PARKINSONS-DISEASE; IN-VITRO; NEUROPATHOLOGY; ANTIBODIES; MUTATION; MUTANT AB Previous genetic analysis of the familial Parkinson's disease Contursi kindred led to the identification of an Ala53Thr pathogenic mutation in the alpha-synuclein gene. We have re-examined one of the original brains from this kindred using new immunohistochemical reagents, thioflavin S staining and immunoelectron microscopy. Surprisingly, we uncovered a dense burden of alpha-synuclein neuritic pathology and rare Lewy bodies. Immunoelectron microscopy demonstrated fibrillar (alpha-synuclein-immunoreactive aggregates. Unexpected tau neuritic and less frequent perikaryal inclusions were also observed. Some inclusions were comprised of both proteins with almost complete spatial disparity. We suggest that it is important to recognize that the neurodegenerative process caused by the Ala53Thr mutation in alpha-synuclein is not identical to that seen in typical idiopathic Parkinson's disease brains. C1 Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. NYU, Dept Pathol, Div Neuropathol, Sch Med, New York, NY 10016 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. RP Trojanowski, JQ (reprint author), Univ Penn, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Sch Med, 3rd Floor,Maloney Bldg, Philadelphia, PA 19104 USA. NR 14 TC 166 Z9 168 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD JUL PY 2002 VL 104 IS 1 BP 7 EP 11 DI 10.1007/s00401-002-0563-3 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 569AP UT WOS:000176577400002 PM 12070658 ER PT J AU Hurt, RD Wolter, TD Rigotti, N Hays, JT Niaura, R Durcan, MJ Gonzales, D Sachs, DPL Johnston, JA Offord, KP AF Hurt, RD Wolter, TD Rigotti, N Hays, JT Niaura, R Durcan, MJ Gonzales, D Sachs, DPL Johnston, JA Offord, KP TI Bupropion for pharmacologic relapse prevention to smoking - Predictors of outcome SO ADDICTIVE BEHAVIORS LA English DT Article DE bupropion; smoking; relapse prevention; nicotine dependence ID NICOTINE DEPENDENCE; CESSATION AB The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion. Smokers (N = 784) who were interested in stopping smoking were enrolled in a 7-week, open-label bupropion phase. Abstinent subjects at the end of treatment and eligible to proceed (N = 429) were randomized to active bupropion or placebo through Week 52 and then followed for an additional year. The best overall predictor of less relapse to smoking was assignment to active bupropion. In aggregate, the results indicate that bupropion can be prescribed to diverse populations of smokers with expected comparable results. There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase. Predictors of successful relapse prevention included lower baseline smoking rates, a Fagerstrom Tolerance Questionnaire score of < 6, and initiation of smoking at an older age. These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Nicotine Res Ctr, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Providence, RI 02912 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Palo Alto Ctr Pulm Dis Prevent, Palo Alto, CA USA. RP Hurt, RD (reprint author), Mayo Clin & Mayo Fdn, Nicotine Res Ctr, 200 1st St SW, Rochester, MN 55905 USA. NR 15 TC 38 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 2002 VL 27 IS 4 BP 493 EP 507 AR PII S0306-4603(01)00188-5 DI 10.1016/S0306-4603(01)00188-5 PG 15 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 584JN UT WOS:000177463600003 PM 12188588 ER PT J AU Johnson, JL Fava, JL Velicer, WF Monroe, AD Emmons, K AF Johnson, JL Fava, JL Velicer, WF Monroe, AD Emmons, K TI Testing stage effects in an ethnically diverse sample SO ADDICTIVE BEHAVIORS LA English DT Article DE stage of change; ethnically diverse; smoking cessation; effect size predictions ID HEALTH BEHAVIOR-CHANGE; TRANSTHEORETICAL MODEL; SMOKING CESSATION; SELF-EFFICACY; DECISIONAL BALANCE; INTEGRATIVE MODEL; SMOKERS; INTERVENTION; PROGRAMS AB The Transtheoretical Model (TTM) has been extensively validated in representative samples of adult smokers. Stage effects, i.e., the patterned relationships between Stage of Change (SOC) and other TTM variables, have been reported in a variety of samples. This study describes reliability data for the TTM variables and tests the stage effects with an ethnically diverse sample of 296 parents with young children. On the basis of theory and previous empirical evidence from a general population, it is possible to make quantitative predications about the magnitude of the expected effect sizes for the Decisional Balance, Situational Temptations, and Processes of Change subscales. For each variable, both a test of significance and a comparison with the expected effect sizes is reported. Results indicated significant stage differences for 8 of the 11 TTM subscales, and all quantitative predictions were confirmed. This study supports the use of TTM measures in an ethnically diverse sample. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Rhode Isl, Canc Prevent Res Ctr, Kingston, RI 02881 USA. Mem Hosp Rhode Isl, Pawtucket, RI 02860 USA. Brown Univ, Providence, RI 02912 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Johnson, JL (reprint author), Univ Rhode Isl, Canc Prevent Res Ctr, 2 Chafee Rd, Kingston, RI 02881 USA. FU NCI NIH HHS [R01 CA73242] NR 30 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JUL-AUG PY 2002 VL 27 IS 4 BP 605 EP 617 AR PII S0306-4603(01)00196-4 DI 10.1016/S0306-4603(01)00196-4 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 584JN UT WOS:000177463600010 PM 12188595 ER PT J AU Verghese, VJ Ayub, K Qureshi, W Taupo, T Graham, DY AF Verghese, VJ Ayub, K Qureshi, W Taupo, T Graham, DY TI Low-salt bowel cleansing preparation (LoSo Prep) as preparation for colonoscopy: a pilot study SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ORAL SODIUM-PHOSPHATE; GLYCOL-ELECTROLYTE LAVAGE; POLYETHYLENE-GLYCOL; BARIUM ENEMA; FLEXIBLE SIGMOIDOSCOPY; SERUM ELECTROLYTES; CASTOR-OIL; BISACODYL; PATIENT; SODA AB Background: Currently available colon cleansing preparations are often poorly tolerated. Aims: To evaluate the efficacy of a low-volume, low-salt preparation for colonoscopy. Methods: This was a pilot study in patients scheduled for colonoscopy. The preparation consisted of 34 g of magnesium citrate and four bisacodyl tablets the day before the procedure, and one bisacodyl suppository on the morning of the procedure. Results: Twenty patients (age range, 49-81 years; all males) were entered into the study. There were no significant side-effects associated with the preparation. All rated the taste as 'tolerable or better'. The examination was considered to be adequate, with no limitations, in 17 patients (85%), and was scored as good to excellent (no solid stool) in 11 (55%), acceptable (small amounts of solid stool) in six (30%) and poor in three (15%: two in-patients and one out-patient). Importantly, two of the failures then received a standard polyethylene glycol preparation and again failed to show adequate colon preparation. Conclusions: This pilot study showed that the low-salt colon cleansing preparation was an effective alternative preparation for colonoscopy. C1 Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 34 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD JUL PY 2002 VL 16 IS 7 BP 1327 EP 1331 DI 10.1046/j.1365-2036.2002.01295.x PG 5 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 577UU UT WOS:000177081200016 PM 12144583 ER PT J AU Wood, BJ Razavi, P AF Wood, BJ Razavi, P TI Virtual endoscopy: A promising new technology SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID COLORECTAL-CANCER; CT COLONOGRAPHY; BARIUM ENEMA; COLONOSCOPY; CARCINOMA; COLON; BRONCHOSCOPY; MAMMOGRAPHY; POLYPS; SCREEN AB Growing evidence shows that early detection of cancer can substantially reduce mortality, necessitating screening programs that encourage patient compliance. Radiology is already established as a screening tool, as in mammography for breast cancer and ultrasonography for congenital anomalies. Advanced processing of helical computed tomographic data sets permits three-dimensional and virtual endoscopic models. Such models are noninvasive and require minimal patient preparation, making them ideal for screening. Virtual endoscopy has been used to evaluate the colon, bronchi, stomach, blood vessels, bladder, kidney, larynx, and paranasal sinuses. The most promising role for virtual endoscopy is in screening patients for colorectal cancer. The technique has also been used to evaluate the tracheobronchial tree for bronchogenic carcinoma. Three-dimensional and virtual endoscopy can screen, diagnose, evaluate and assist determination of surgical approach, and provide surveillance of certain malignancies. Copyright (C) 2002 American Academy of Family Physicians. C1 NIH, Ctr Clin, Special Procedures Div, Diagnost Radiol Dept, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wood, BJ (reprint author), NIH, Ctr Clin, Special Procedures Div, Diagnost Radiol Dept, Room 1C-660,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 16 Z9 19 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL 1 PY 2002 VL 66 IS 1 BP 107 EP 112 PG 6 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 571XV UT WOS:000176745200009 PM 12126025 ER PT J AU Orford, JL Sesso, HD Stedman, M Gagnon, D Vokonas, P Gaziano, JM AF Orford, JL Sesso, HD Stedman, M Gagnon, D Vokonas, P Gaziano, JM TI A comparison of the Framingham and European Society of Cardiology coronary heart disease risk prediction models in the Normative Aging Study SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 73rd Annual Scientific Sessions of the American-Heart-Association CY NOV 12-15, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc ID CARDIOVASCULAR-DISEASE; PRIMARY PREVENTION; TASK-FORCE; MORTALITY; ATHEROSCLEROSIS; INFLAMMATION; POPULATION; DECLINE; TRENDS; MEN AB Background A number of prediction models have been developed in an attempt to accurately identify patients at increased risk of a first coronary heart disease event. We sought to determine the ten-year incidence of coronary heart disease events in a healthy cohort with measurable risk factors, and to compare these results with the predicted number of events by use of both the Framingham and European Society of Cardiology risk prediction models. Methods We compared the predicted and observed number of events in 5 risk categories in 1393 subjects aged 30 to 74 years who were enrolled in the Normative Aging Study. Results The risk prediction models reliably stratify populations with regards to relative risk of coronary heart disease events and there is reasonable agreement between the 2 models (weighted K = 0.46, P <.01). The Framingham model underestimated the absolute risk of coronary heart disease events in the low-risk group, and both risk prediction models overestimated the absolute risk of events in the high- or very-high-risk groups (Framingham c-statistic = 0.60, European Society of Cardiology c-statistic = 0.58). Conclusions Despite simplification, the accuracy of the European model was not significantly different from the Framingham model. But the accuracy of absolute risk prediction, particularly at the extremes of risk, is imperfect. Refinement and validation of these risk prediction models is important because they affect the management of individual patients and the allocation of community resources. C1 MAVERIC, VA Boston Healthcare Syst, Boston, MA 02130 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Gaziano, JM (reprint author), MAVERIC, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. OI Gagnon, David/0000-0002-6367-3179; Stedman, Margaret/0000-0001-9271-8332 NR 39 TC 34 Z9 40 U1 1 U2 3 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 JUL PY 2002 VL 144 IS 1 BP 95 EP 100 DI 10.1067/mhj.2002.123317 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573AV UT WOS:000176807900015 PM 12094194 ER PT J AU Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA TI Variation in the risk of onset of acute myocardial infarction during the menstrual cycle SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CASE-CROSSOVER DESIGN; PREMENOPAUSAL WOMEN; HEART-DISEASE; ANGINA; VARIANT AB Of the 669 women interviewed for the Determinants of Myocardial Infarction Onset Study, 11 of 21 women with ongoing menstrual cycles had the onset of acute myocardial infarction during the early follicular phase of the menstrual cycle, corresponding to a threefold higher risk. In younger women at otherwise relatively low risk, the early portion of the menstrual cycle appears to be associated with particular susceptibility to myocardial infarction. C1 Beth Israel Deaconess Med Ctr, Div Gen Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Social Behav, Boston, MA 02115 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [K23AA00299] NR 14 TC 17 Z9 17 U1 0 U2 1 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 JUL 1 PY 2002 VL 90 IS 1 BP 49 EP + AR PII S0002-9149(02)02386-X DI 10.1016/S0002-9149(02)02386-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570AE UT WOS:000176635000012 PM 12088780 ER PT J AU Murphy, SA Gibson, CM Van de Werf, F McCabe, CH Cannon, CP AF Murphy, SA Gibson, CM Van de Werf, F McCabe, CH Cannon, CP TI Comparison of errors in estimating weight and in dosing of single-bolus tenecteplase with tissue plasminogen activator (TIMI 10B and ASSENT I) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; B-10 TRIAL; SAFETY AB In the Thrombolysis In Myocardial Infarction (TIMI) 10B and the Assessment of the Safety of a New Thrombolytic (ASSENT) I trials, we found that errors in estimating weight were uncommon, especially those that would lead to a dose change (3% to 5%). Dosing errors were infrequent among tenecteplase-treated patients, and no adverse outcomes were seen among patients who received an incorrect dose, suggesting a broad safety profile for the new single-bolus agent, tenecteplase. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Clin Res Inst, Cambridge, MA 02138 USA. Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. RP Murphy, SA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 4 Z9 4 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 JUL 1 PY 2002 VL 90 IS 1 BP 51 EP + AR PII S0002-9149(02)02387-1 DI 10.1016/S0002-9149(02)02387-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570AE UT WOS:000176635000013 PM 12088781 ER PT J AU Hoffmann, U Dirisamer, A Heher, S Kostner, K Widhalm, K Neunteufl, T AF Hoffmann, U Dirisamer, A Heher, S Kostner, K Widhalm, K Neunteufl, T TI Relation of peripheral flow-mediated vasodilatation and coronary arterial calcium in young patients with heterozygous familial hypercholesterolemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ULTRAFAST COMPUTED-TOMOGRAPHY; ENDOTHELIAL DYSFUNCTION; CHILDREN; ATHEROSCLEROSIS; THERAPY; ADULTS AB The relation of peripheral flow-mediated vasodilation and coronary arterial calcium was studied in young patients with heterozygous familial hypercholesterolemia (FH) using high-resolution ultrasound and multi-detector computed tomography (MDCT). We found that peripheral flow mediated vasodilation, a precursor of atherosclerosis, is altered in young heterozygous patients with FH. This alteration occurs before coronary arterial or aortic root calcium can be detected by MDCT and is independently related to hypercholesterolemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Univ Hosp Vienna, Dept Diagnost Radiol, Vienna, Austria. Univ Hosp Vienna, Dept Cardiol, Vienna, Austria. Univ Hosp Vienna, Dept Pediat, Vienna, Austria. RP Hoffmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 100 Charles River Plaza Suite 400, Boston, MA 02114 USA. RI Kostner, Karam/F-5167-2010 NR 16 TC 9 Z9 11 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 JUL 1 PY 2002 VL 90 IS 1 BP 70 EP + AR PII S0002-9149(02)02393-7 DI 10.1016/S0002-9149(02)02393-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 570AE UT WOS:000176635000019 PM 12088787 ER PT J AU Bartels, SJ Coakley, E Oxman, TE Constantino, G Oslin, D Chen, HT Zubritsky, C Cheal, K Durai, UNB Gallo, JJ Llorente, M Sanchez, H AF Bartels, SJ Coakley, E Oxman, TE Constantino, G Oslin, D Chen, HT Zubritsky, C Cheal, K Durai, UNB Gallo, JJ Llorente, M Sanchez, H TI Suicidal and death ideation in older primary care patients with depression, anxiety, and at-risk alcohol use SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID QUALITY-OF-LIFE; MAJOR DEPRESSION; SOCIAL SUPPORT; COMORBID ANXIETY; SEX-DIFFERENCES; DISORDERS; VALIDATION; PREVALENCE; POPULATION; INTERVIEW AB The authors identified correlates of active suicidal ideation and passive death ideation in older primary cart, patients with depression, anxiety and at-risk alcohol use. Participants included 2,240 older primary care patients (age 65+), who were identified in three mutually exclusive groups on the basis of responses to the Paykel suicide questions: No Ideation, Death Ideation, and Suicidal Ideation. Chi-square, ANOVA, and polytomous logistic regression analyses were used to identify characteristics associated with suicidal ideation. The highest amount of suicidal ideation was associated with co-occurring major depression and anxiety disorder (18%), and the lowest proportion occurred in at-risk alcohol use (3%). Asians have the highest (57%) and African Americans have the lowest (27%) proportion of suicidal or death ideation. Fewer social supports and more severe symptoms were associated with greater overall ideation. Death ideation was associated with the greatest medical comorbidity and highest service utilization. Contrary to previous report,,;, authors failed to find that active suicidal ideation was associated with increased contact,,; with healthcare providers. Accordingly, targeted assessment and preventive services should be emphasized for geriatric outpatients with co-occurring depression and anxiety social isolation, younger age, and Asian or Caucasian race. C1 Dartmouth Coll Sch Med, Dept Psychiat, Lebanon, NH USA. John Snow Inc, Boston, MA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Sunset Pk Family Hlth Ctr, Brooklyn, NY USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. VA Chicago Hlth Care Syst, Chicago, IL USA. Univ Illinois, Dept Psychiat, Chicago, IL USA. Univ Penn, Dept Family Practice & Community Med, Philadelphia, PA 19104 USA. Univ Miami, Sch Med, Miami VA Med Ctr, Ctr Geriatr Res Educ & Clin, Miami Beach, FL USA. RP Bartels, SJ (reprint author), New Hampshire Dartmouth Psychiat Res Ctr, 2 Whipple Pl,Suite 202, Lebanon, NH 03766 USA. NR 47 TC 99 Z9 101 U1 3 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 417 EP 427 DI 10.1176/appi.ajgp.10.4.417 PG 11 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 571KR UT WOS:000176717000008 PM 12095901 ER PT J AU Cook, JM Pearson, JL Thompson, R Black, BS Rabins, PV AF Cook, JM Pearson, JL Thompson, R Black, BS Rabins, PV TI Suicidality in older African Americans - Findings from the EPOCH study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID PUBLIC-HOUSING RESIDENTS; MENTAL-HEALTH-CARE; CAGE QUESTIONNAIRE; LIFE SATISFACTION; DEPRESSION; POPULATION; ALCOHOLISM; SYMPTOMS; IDEATION; PROGRAM AB The authors examined the current frequency of suicidality and associated characteristics in a sample of 835 African-American older adult residents of six urban public housing developments who consented to participate in an intervention trial of mobile outreach. The frequency of passive and active suicidal ideation was 2.5% and 1.4%, respectively Characteristics of individuals with both active and passive suicidality included elevated anxiety, social dysfunction, somatic symptoms, low social support, lack of a confidant, and low religiosity. Characteristics those with passive, but not active, ideation also included older age, lower levels of education, elevated depressive symptoms, poorer cognitive functioning, and having recently discussed emotional problems with a healthcare provider The characteristics of those reporting active, but not passive, ideation included having a history of mental health treatment and reporting no instrumental support. Multivariate analyses indicated that depression and religiosity were uniquely associated with passive suicidal ideation, and life satisfaction and religiosity were uniquely associated with active suicidal ideation. The authors discuss implications of these findings and offer suggestions for research and clinical practice. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. NIMH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Cook, JM (reprint author), Philadelphia VA Med Ctr, 116A,Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM cook_j@mail.trc.upenn.edu RI Thompson, Richard/G-5408-2011 OI Thompson, Richard/0000-0003-0127-513X FU NIMH NIH HHS [MH 42412, MH 48673, MH P50 43703] NR 45 TC 34 Z9 34 U1 1 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 437 EP 446 DI 10.1176/appi.ajgp.10.4.437 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 571KR UT WOS:000176717000010 PM 12095903 ER PT J AU Feil, D Chuang, K Sultzer, DL AF Feil, D Chuang, K Sultzer, DL TI Valproate-induced hyperammonemia as a cause of altered mental status SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID ACID-INDUCED HYPERAMMONEMIA; ENCEPHALOPATHY; CARNITINE; PATIENT AB The authors describe valproate-induced hyperammonemia and mental status changes in an 88-year-old man, the first known reported case in an elderly patient. They discuss this underrecognized complication of valproate use and the implications for treating elderly patients, in whom valproate use is increasing. C1 VA Greater Los Angeles Healthcare Syst, Div Geriatr Psychiat, Los Angeles, CA 90073 USA. RP Feil, D (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza,Room C8-852, Los Angeles, CA 90024 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 476 EP 478 PG 3 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 571KR UT WOS:000176717000014 PM 12095907 ER PT J AU Kramer, HM Curhan, G AF Kramer, HM Curhan, G TI The association between gout and nephrolithiasis: The National Health and Nutrition Examination Survey III, 1988-1994 SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE kidney stones; Third National Health and Nutrition Examination Survey (NHANES III); gout; epidemiology ID URIC-ACID NEPHROLITHIASIS; STONE FORMATION; KIDNEY-STONES; RISK; PATHOGENESIS; HYPERTENSION AB Background: Gout, an inflammatory arthritis, reportedly afflicts more than 2 million men and women in the United States. Previous reports have suggested an association between gout and kidney stone disease; however, these studies did not adjust for such important potential confounders as obesity and the presence of hypertension. To our knowledge, no published study has examined the independent association between gout and kidney stone disease. Methods: We used a national probability sample of the US population to determine the independent association between reported gout and history of kidney stone disease. Results: Among men and women 20 years and older, 5.6% (10 million) reported the previous passage of a kidney stone and 2.7% (5.1 million) reported a diagnosis of gout by a physician. Moreover, 8.6% of individuals who reported the passage of a kidney stone on two or more occasions had a history of gout. Conversely, the prevalence of previous kidney stones in subjects with reported gout was 13.9%. In the age-adjusted model, gout was associated with an increased odds ratio (OR) for previous kidney stones (OR, 1.97; 95% confidence interval [CI], 1.37 to 2.83). After further adjustment for sex, race, body mass index, and presence of hypertension, the OR for previous kidney stones in individuals with gout decreased to 1.49 (95% CI, 1.04 to 2.14). Conclusion: Showing an independent association between kidney stone disease and gout strongly suggests that they share common underlying pathophysiological mechanisms. Identification of these mechanisms may lead to improved preventive strategies for both conditions. (C) 2002 by the National Kidney Foundation, Inc. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Unit, Boston, MA 02114 USA. RP Curhan, G (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK59583] NR 23 TC 158 Z9 171 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2002 VL 40 IS 1 BP 37 EP 42 DI 10.1053/ajkd.2002.33911 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 585KM UT WOS:000177524000007 PM 12087559 ER PT J AU Mueller, W Hartmann, C Hoffmann, A Lanksch, W Kiwit, J Tonn, J Veelken, J Schramm, J Weller, M Wiestler, OD Louis, DN von Deimling, A AF Mueller, W Hartmann, C Hoffmann, A Lanksch, W Kiwit, J Tonn, J Veelken, J Schramm, J Weller, M Wiestler, OD Louis, DN von Deimling, A TI Genetic signature of oligoastrocytomas correlates with tumor location and denotes distinct molecular subsets SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PCV CHEMOTHERAPY; ANAPLASTIC OLIGODENDROGLIOMAS; NEURAL PROGENITORS; CHROMOSOME 1P; MIXED GLIOMAS; BRAIN-TUMORS; IN-VIVO; ASTROCYTOMAS; 19Q; SURVIVAL AB Oligoastrocytomas are heterogeneous tumors that have molecular features that overlap with either oligodendrogliomas or astrocytomas. Differences in the frequency of chromosomal losses of 1p and 19q in oligodendrogliomas are related to tumor location, with a low rate of allelic loss in tumors of the temporal and a high rate in tumors of the frontal, parietal, and occipital lobes. To test the possibility of regional molecular heterogeneity in oligoastrocytoma, we examined a series of 203 gliomas including 68 oligoastrocytomas and two control groups of 73 oligodendrogliomas and 62 astrocytomas for allelic losses of chromosomal arms 1p and 19q, and TP53 mutations, and compared these data with tumor localization. Common molecular alterations were found in oligodendrogliomas and oligoastrocytoma arising in extratemporal sites. In respect to the molecular parameters analyzed, temporal oligoastrocytomas were either indistinguishable from astrocytoma or similar to temporal oligodendrogliomas. Oligodendroglial neoplasms can thus be separated into three molecular subsets, two of which include lesions with the morphological features of oligodendrogliomas and oligoastrocytomas and one resembling temporal oligoastrocytoma. Molecular subclassification thus unifies previous findings about prognosis, behavior, response to therapy, genotype, and location in oligodendroglial tumors. C1 Humboldt Univ, Dept Neuropathol, Berlin, Germany. Humboldt Univ, Dept Neurosurg, Berlin, Germany. Helios Kliniken GmbH, Dept Neurosurg, Buch, Germany. Univ Munich, Dept Neurosurg, Munich, Germany. Vivantes Klinikum Neukolln, Dept Neurosurg, Berlin, Germany. Univ Bonn, Med Ctr, Dept Neurosurg, D-5300 Bonn, Germany. Univ Tubingen, Dept Neurol, D-7400 Tubingen, Germany. Univ Bonn, Med Ctr, Dept Neuropathol, D-5300 Bonn, Germany. Massachusetts Gen Hosp, Mol Neurooncol & Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP von Deimling, A (reprint author), Inst Neuropathol, Charite, Campus Virchow Klinkum,Augustenburgerpl 1, D-13353 Berlin, Germany. RI von Deimling, Andreas/F-7774-2013; Hartmann, Christian/D-1882-2010 OI von Deimling, Andreas/0000-0002-5863-540X; FU NCI NIH HHS [CA57683, R01 CA057683] NR 38 TC 119 Z9 124 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 JUL PY 2002 VL 161 IS 1 BP 313 EP 319 DI 10.1016/S0002-9440(10)64183-1 PG 7 WC Pathology SC Pathology GA 571LF UT WOS:000176718300035 PM 12107116 ER PT J AU Jost, P Fasshauer, M Kahn, CR Benito, M Meyer, M Ott, V Lowell, BB Klein, HH Klein, J AF Jost, P Fasshauer, M Kahn, CR Benito, M Meyer, M Ott, V Lowell, BB Klein, HH Klein, J TI Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE beta-adrenoceptor; adipose tissue; insulin resistance; CGP-12177 ID ADIPOSE-TISSUE; KNOCKOUT MICE; PUTATIVE BETA-4-ADRENOCEPTOR; BETA(1)-ADRENERGIC RECEPTORS; PROTEIN-KINASE; GLUCOSE-UPTAKE; ADRENOCEPTOR; STIMULATION; AGONISTS; OBESITY AB Cross talk between adrenergic and insulin signaling systems may represent a fundamental molecular basis of insulin resistance. We have characterized a newly established beta(3)-adrenoceptor-deficient (beta(3)-KO) brown adipocyte cell line and have used it to selectively investigate the potential role of novel-state and typical beta-adrenoceptors (beta-AR) on insulin signaling and action. The novel-state beta(1)-AR agonist CGP-12177 strongly induced uncoupling protein-1 in beta(3)-KO brown adipocytes as opposed to the beta(3)-selective agonist CL-316,243. Furthermore, CGP-12177 potently reduced insulin-induced glucose uptake and glycogen synthesis. Neither the selective beta(1)- and beta(2)-antagonists metoprolol and ICI-118,551 nor the nonselective antagonist propranolol blocked these effects. The classical beta(1)-AR agonist dobutamine and the beta(2)-AR agonist clenbuterol also considerably diminished insulin-induced glucose uptake. In contrast to CGP-12177 treatment, these negative effects were completely abrogated by metoprolol and ICI-118,551. Stimulation with CGP-12177 did not impair insulin receptor kinase activity but decreased insulin receptor substrate-1 binding to phosphatidylinositol (PI) 3-kinase and activation of protein kinase B. Thus the present study characterizes a novel cell system to selectively analyze molecular and functional interactions between novel and classical beta-adrenoceptor types with insulin action. Furthermore, it indicates insulin receptor-independent, but PI 3-kinase- dependent, potent negative effects of the novel beta(1)-adrenoceptor state on diverse biological end points of insulin action. C1 Med Univ Lubeck, Dept Internal Med 1, D-23538 Lubeck, Germany. Univ Leipzig, Dept Internal Med 3, D-04103 Leipzig, Germany. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Complutense Madrid, Fac Farm, E-28040 Madrid, Spain. RP Klein, J (reprint author), Med Univ Lubeck, Dept Internal Med 1, Ratzeburger Allee 160, D-23538 Lubeck, Germany. NR 27 TC 14 Z9 16 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2002 VL 283 IS 1 BP E146 EP E153 DI 10.1152/ajpendo.00531.2001 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 562HH UT WOS:000176191000020 PM 12067855 ER PT J AU Roubenoff, R Grinspoon, S Skolnik, PR Tchetgen, E Abad, L Spiegelman, D Knox, T Gorbach, S AF Roubenoff, R Grinspoon, S Skolnik, PR Tchetgen, E Abad, L Spiegelman, D Knox, T Gorbach, S TI Role of cytokines and testosterone in regulating lean body mass and resting energy expenditure in HIV-infected men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; WEIGHT-LOSS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; MONONUCLEAR-CELLS; LIPODYSTROPHY; VIRUS; INTERLEUKIN-1-BETA; ASSOCIATION; RESISTANCE AB Although catastrophic weight loss is no longer common in HIV-infected men, we hypothesized that a more gradual process of cachexia [loss of lean body mass (LBM) without severe weight loss, often accompanied by elevated resting energy expenditure (REE)] is still common and is driven by excessive production of the catabolic cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). We performed a longitudinal analysis of an ongoing cohort study of nutritional status in 172 men with HIV infection. LBM loss of >1 kg occurred in 35% of the cohort, and LBM loss of >5% occurred in 12.2% over 8 mo of observation, but classical wasting (loss of approximate to10% of weight) was rare (2%). Both TNF-alpha (-150 g LBM.ng(-1).m(-1), P < 0.02) and IL-1β production (-130 g LBM.ng(-.1.)ml(-1), P < 0.01) by peripheral blood mononuclear cells predicted loss of LBM. A rise in REE of >200 kcal/day was found in 17.7% of the subjects regardless of weight change. IL-1beta (+9 kcal/day per ng/ml, P < 0.002) and TNF-α (+10 kcal/day per ng/ml, P < 0.02) production predicted DeltaREE. Serum free testosterone was inversely associated with TNF-alpha production and was not an independent predictor of either DeltaLBM or DeltaREE after adjustment for cytokine production. Even though weight loss was rare in this cohort of patients treated with highly active antiretroviral therapy, loss of LBM was common and was driven by catabolic cytokines and not by inadequate dietary intake or hypogonadism. C1 Tufts Univ, Jean Mayer USDA HNRCA, Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. Tufts Univ, Jean Mayer USDA HNRCA, Dept Community Hlth, Boston, MA 02111 USA. Tufts Univ, Jean Mayer USDA HNRCA, Dept Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Roubenoff, R (reprint author), Tufts Univ, Jean Mayer USDA HNRCA, Exercise Physiol & Sarcopenia Lab, 711 Washington St, Boston, MA 02111 USA. FU NCRR NIH HHS [M01-RR-00054, M01-RR-01066]; NIAID NIH HHS [P30 AI-42853]; NIDA NIH HHS [DA-11598-02]; NIDDK NIH HHS [DK-45734] NR 32 TC 44 Z9 45 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JUL PY 2002 VL 283 IS 1 BP E138 EP E145 DI 10.1152/ajpendo.00426.2001 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 562HH UT WOS:000176191000019 PM 12067854 ER PT J AU Werner, J Saghir, M Warshaw, AL Lewandrowski, KB Laposata, M Iozzo, RV Carter, EA Schatz, RJ Fernandez-del Castillo, C AF Werner, J Saghir, M Warshaw, AL Lewandrowski, KB Laposata, M Iozzo, RV Carter, EA Schatz, RJ Fernandez-del Castillo, C TI Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pathophysiology; ethanol metabolism; fatty acid ethyl ester ID ACID ETHYL-ESTERS; TRYPSINOGEN-ACTIVATION; LYSOSOMAL-ENZYMES; DUCT OBSTRUCTION; ACETALDEHYDE; CHOLECYSTOKININ; STIMULATION; SECRETION; ZYMOGEN; DAMAGE AB The mechanism by which alcohol injures the pancreas remains unknown. Recent investigations suggest a role for fatty acid ethyl ester (FAEE), a nonoxidative metabolite of ethanol, in the pathogenesis of alcohol pancreatitis. In this study, we characterized ethanol-induced injury in rats and evaluated the contribution of oxidative and nonoxidative ethanol metabolites in this form of acute pancreatitis. Pancreatic injury in rats was assessed by edema, intrapancreatic trypsinogen activation, and microscopy after infusing ethanol with or without inhibitors of oxidative ethanol metabolism. Plasma and tissue levels of FAEE and ethanol were measured and correlated with pancreatic injury. Ethanol infusion generated plasma and tissue FAEE and, in a dose-dependent fashion, induced a pancreas-specific injury consisting of edema, trypsinogen activation, and formation of vacuoles in the pancreatic acini. Inhibition of the oxidation of ethanol significantly increased both FAEE concentration in plasma and pancreas and worsened the pancreatitis-like injury. This study provides direct evidence that ethanol, through its nonoxidative metabolic pathway, can produce pancreas-specific toxicity in vivo and suggests that FAEE are responsible for the development of early pancreatic cell damage in acute alcohol-induced pancreatitis. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WAC-336,15 Parkman St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA-39481-14] NR 46 TC 68 Z9 68 U1 0 U2 1 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 JUL PY 2002 VL 283 IS 1 BP G65 EP G73 DI 10.1152/ajpgi.00419.2001 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 562EZ UT WOS:000176185600009 PM 12065293 ER PT J AU Zhou, HZ Karliner, JS Gray, MO AF Zhou, HZ Karliner, JS Gray, MO TI Moderate alcohol consumption induces sustained cardiac protection by activating PKC-epsilon and Akt SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart; ischemia; reperfusion; ethanol; signaling ID PROTEIN-KINASE-C; ISCHEMIA-REPERFUSION INJURY; K-ATP CHANNELS; IN-VIVO; MYOCARDIAL-INFARCTION; MOUSE HEART; MICE; INHIBITION; APOPTOSIS; MORTALITY AB C57BL/6 mice were fed 18% ethanol (vol/vol) in drinking water for 12 wk. Isovolumic hearts were subjected to 20 min of ischemia and 30 min of reperfusion on a Langendorff apparatus. There were no differences in baseline hemodynamic function between hearts from ethanol (EtOH)-fed mice and controls. However, prior alcohol consumption doubled recovery of left ventricular developed pressure (68 +/- 8 vs. 33 +/- 8 mmHg for controls; n = 10, P < 0.05) and reduced creatine kinase release by half (0.26 +/- 0.04 vs. 0.51 +/- 0.08 U.min(-1).g wet wt(-1) for controls; n = 10, P < 0.05). EtOH feeding doubled expression of activated protein kinase C epsilon (PKC)epsilon (n = 6, P < 0.05); whereas PKC inhibition blocked protection during ischemia-reperfusion. EtOH feeding also increased expression of Akt three- to fivefold (n = 6, P < 0.05), whereas PKC inhibition prevented increases in Akt kinase activity. We conclude that signaling pathways involving PKC-epsilon are critical for sustained EtOH-mediated cardioprotection and that Akt may be a downstream effector of resistance to myocardial reperfusion injury. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. RP Gray, MO (reprint author), San Francisco Gen Hosp, Div Cardiol 5G1, 1001 Potrero Ave, San Francisco, CA 94110 USA. FU NIAAA NIH HHS [AA-11135] NR 47 TC 66 Z9 66 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUL PY 2002 VL 283 IS 1 BP H165 EP H174 DI 10.1152/ajpheart.00408.2001 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 561RL UT WOS:000176156400021 PM 12063287 ER PT J AU Natarajan, S Lipsitz, SR Nietert, PJ AF Natarajan, S Lipsitz, SR Nietert, PJ TI Self-report of high cholesterol - Determinants of validity in US adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE awareness; health surveys; hypercholesterolemia; sensitivity and specificity ID CARDIOVASCULAR-DISEASE RISK; UNITED-STATES ADULTS; EPIDEMIOLOGIC RESEARCH; LOGISTIC-REGRESSION; PLASMA-CHOLESTEROL; PROSPECTIVE COHORT; BLOOD CHOLESTEROL; DIAGNOSTIC-TESTS; DECISION-MAKING; VALIDATION AB Background: Hypercholesterolemia is a major cardiovascular risk factor, and cholesterol awareness is important in both clinical practice and in public health. We evaluated the validity of self-reported hypercholesterolemia and identified determinants of validity. Methods: The study design was a cross-sectional survey, from 1988 to 1994, of adult participants (N=8236) from the Third National Health and Nutrition Examination Survey for whom self-report of hypercholesterolemia and serum measurement were available. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for self-reported hypercholesterolemia were calculated using total cholesterol greater than or equal to5.17 mmol/L (200 mg/dL) and/or taking cholesterol-lowering medication as the criterion standard. Results: Overall test characteristics for self-report were sensitivity, 51%; specificity, 89%; PPV, 87%; and NPV, 55%. Sensitivity of self-report was higher among older subjects and non-Hispanic whites, specificity was higher among subjects with >12 years of education, PPV was higher in older subjects, and NPV was higher in younger subjects and in those with >12 years of education. Using higher cholesterol thresholds to define hypercholesterolemia led to higher sensitivity, lower specificity, lower PPV, and higher NPV. Sociodemographic and anthropometric predictors of validity were identified by logistic regression. Conclusions: Due to low sensitivity, self-reported hypercholesterolemia should be used with caution, both during the patient encounter and for surveillance of trends in hypercholesterolemia in the absence of measured cholesterol levels. Specificity is consistently much higher than sensitivity. The high PPV may be of use in certain clinical situations. Such validation studies should form the foundation for future research based on self-report. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & epidemiol, Charleston, SC 29425 USA. RP Natarajan, S (reprint author), 135 Cannon St,Suite 403,POB 250837, Charleston, SC 29425 USA. OI Nietert, Paul/0000-0002-3933-4986 FU NHLBI NIH HHS [HL 69800, HL52329, HL61769] NR 41 TC 33 Z9 34 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2002 VL 23 IS 1 BP 13 EP 21 AR PII S0749-3797(02)00446-4 DI 10.1016/S0749-3797(02)00446-4 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 573BG UT WOS:000176809000003 PM 12093418 ER PT J AU Sachs, GS Grossman, F Ghaemi, SN Okamoto, A Bowden, CL AF Sachs, GS Grossman, F Ghaemi, SN Okamoto, A Bowden, CL TI Combination of a mood stabilizer with risperidone or haloperidol for treatment of acute mania: A double-blind, placebo-controlled comparison of efficacy and safety SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; ANTIPSYCHOTIC AGENTS; CONTROLLED TRIAL; RATING-SCALE; CLOZAPINE; OLANZAPINE; LITHIUM; INDUCTION; HYPOMANIA; RESISTANT AB Objective: The study assessed the efficacy and safety of risperidone as an adjunctive agent to mood stabilizers in the treatment of acute mania. Method: This 3-week randomized, double-blind, placebo-controlled study included 156 bipolar disorder patients with a current manic or mixed episode who received a mood stabilizer (lithium or dival-proex) and placebo, risperidone, or halo-Peridol. The primary efficacy measure was the Young Mania Rating Scale. Other assessments used the Brief Psychiatric Rating Scale, the Clinical Global impression scale, and safety measures. Results: The trial was discontinued by 25 (49%) of the 51 placebo group patients, 18 (35%) of the 52 risperidone group patients, and 28 (53%) of the 53 haloperidol group patients, Mean modal doses were 3.8 mg/day (SD=1.8) of risperidone and 6,2 mg/day (SD=2.9) of haloperidol. Significantly greater reductions in Young Mania Rating Scale scores at endpoint and over time were seen in the risperidone group and in the haloperidol group, compared with the placebo group. Young Mania Rating Scale total scores improved with risperidone and with haloperidol both in patients with psychotic features and in those without Psychotic features at baseline. Extrapyramidal Symptom Rating Scale total scores at endpoint were significantly higher in the haloperidol patients than in the placebo patients, Antiparkinsonian medications were received by 8%, 17%, and 38% of patients in the placebo, risperidone, and haloperidol groups, respectively. Conclusions: Risperidone plus a mood stabilizer was more efficacious than a mood stabilizer alone, and as efficacious as haloperidol plus a mood stabilizer, for the rapid control of manic symptoms and was well tolerated. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. Cambridge Hosp, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. RP Sachs, GS (reprint author), 50 Staniford St,Suite 580, Boston, MA 02114 USA. NR 41 TC 296 Z9 300 U1 3 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2002 VL 159 IS 7 BP 1146 EP 1154 DI 10.1176/appi.ajp.159.7.1146 PG 9 WC Psychiatry SC Psychiatry GA 570UE UT WOS:000176676000011 PM 12091192 ER PT J AU Perlis, RH Sachs, GS Lafer, B Otto, MW Faraone, SV Kane, JM Rosenbaum, JF AF Perlis, RH Sachs, GS Lafer, B Otto, MW Faraone, SV Kane, JM Rosenbaum, JF TI Effect of abrupt change from standard to low serum levels of lithium: A reanalysis of double-blind lithium maintenance data SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIPOLAR DISORDER; GRADUAL DISCONTINUATION; PROPHYLACTIC LITHIUM; DEPRESSIVE DISORDERS; AFFECTIVE-ILLNESS; RECURRENCE; RISK; WITHDRAWAL; MORBIDITY; EFFICACY AB Objective: Growing evidence suggests that abrupt lithium discontinuation increases the risk of recurrence for patients with bipolar disorder. To assess the effect of abrupt change in lithium dose, the authors reanalyzed data from a previously reported, randomized, double-blind trial of standard- versus low-dose lithium for maintenance therapy in bipolar disorder. Method: In the original study, serum lithium levels were obtained during a 2-month open stabilization period for 94 patients with bipolar disorder who were then randomly assigned to be maintained on a low (serum level=0.4-0.6 meq/liter) or a standard (0.8-1.0 meq/liter) level of lithium therapy. Patients were then followed for up to 182 weeks. This reanalysis examined the potential confounding influence of prerandomization lithium level and change in lithium level on the outcome of subjects assigned to a standard or low maintenance dose of lithium. Results: In a Cox proportional hazards model incorporating pre- and postrandomization lithium levels and the interaction of these factors, only the interaction term remained significantly associated with time to recurrence. Conclusions: The findings indicate that change in serum lithium level may be a more powerful predictor of recurrence of bipolar disorder than the absolute assignment to a low or a standard dose of lithium and suggest that an abrupt decrease in lithium level should be avoided. This reanalysis did not directly address optimal maintenance lithium levels but raises questions about the original study's finding of superiority for lithium levels greater than or equal to0.8 meq/liter. The results underscore the importance of accounting for the possible confounding effects of changes in the intensity of pharmacotherapy in studies of maintenance therapies for bipolar disorder. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015; OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999; Faraone, Stephen/0000-0002-9217-3982 NR 27 TC 51 Z9 52 U1 1 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2002 VL 159 IS 7 BP 1155 EP 1159 DI 10.1176/appi.ajp.159.7.1155 PG 5 WC Psychiatry SC Psychiatry GA 570UE UT WOS:000176676000012 PM 12091193 ER PT J AU Levitt, JJ McCarley, RW Dickey, CC Voglmaier, MM Niznikiewicz, MA Seidman, LJ Hirayasu, Y Ciszewski, AA Kikinis, R Jolesz, FA Shenton, ME AF Levitt, JJ McCarley, RW Dickey, CC Voglmaier, MM Niznikiewicz, MA Seidman, LJ Hirayasu, Y Ciszewski, AA Kikinis, R Jolesz, FA Shenton, ME TI MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 152nd Annual Meeting of the American-Psychiatric-Association CY MAY 15-20, 1999 CL WASHINGTON, D.C. SP Amer Psychiat Assoc ID BASAL GANGLIA; SCHIZOPHRENIC-PATIENTS; VENTRICULAR VOLUME; PREFRONTAL CORTEX; BRAIN; PERFORMANCE; MOTOR; HALOPERIDOL; ACTIVATION; CLOZAPINE AB Objective: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. Method. Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. Results: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. Conclusions: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Clin Neurosci Div,Lab Neurosci,Dept Psychiat, Brockton, MA 02301 USA. Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab,MRI Div, Boston, MA 02115 USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat 116A, 940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [P41 RR 13218-01, 1R01 RR 11747-01A1, P41 RR013218]; NIMH NIH HHS [MH 01110, MH 40799, MH 50740, R01 MH040799, R01 MH050740, R01 MH050740-14] NR 37 TC 93 Z9 94 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2002 VL 159 IS 7 BP 1190 EP 1197 DI 10.1176/appi.ajp.159.7.1190 PG 8 WC Psychiatry SC Psychiatry GA 570UE UT WOS:000176676000017 PM 12091198 ER PT J AU Greene, RW Biederman, J Zerwas, S Monuteaux, MC Goring, JC Faraone, SV AF Greene, RW Biederman, J Zerwas, S Monuteaux, MC Goring, JC Faraone, SV TI Psychiatric comorbidity, family dysfunction, and social impairment in referred youth with oppositional defiant disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; CONDUCT DISORDER; ADJUSTMENT INVENTORY; PRESCHOOL BOYS; CHILDREN; ADHD; ADOLESCENTS; TEMPERAMENT; SAMPLE; PREVALENCE AB Objective: The authors sought to achieve an improved understanding of the diagnosis of oppositional defiant disorder independent of its association with conduct disorder. Method: Family interactions, social functioning, and psychiatric comorbidity were compared in clinically referred male and female subjects with oppositional defiant disorder alone (N=643) or with comorbid conduct disorder (N=262) and a psychiatric comparison group with neither oppositional defiant disorder nor conduct disorder (N=695). Results: Oppositional defiant disorder youth with or without conduct disorder were found to have significantly higher rates of comorbid psychiatric disorders and significantly greater family and social dysfunction relative to psychiatric comparison subjects. Differences between subjects with oppositional defiant disorder alone and those with comorbid conduct disorder were seen primarily in rates of mood disorders and social impairment. Oppositional defiant disorder was a significant correlate of adverse family and social outcomes when comorbid disorders (including conduct disorder) were controlled. Conclusions: These results support the validity of the oppositional defiant disorder diagnosis as a meaningful clinical entity independent of conduct disorder and highlight the extremely detrimental effects of oppositional defiant disorder on multiple domains of functioning in children and adolescents. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, ACC-725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 39 TC 135 Z9 142 U1 7 U2 29 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2002 VL 159 IS 7 BP 1214 EP 1224 DI 10.1176/appi.ajp.159.7.1214 PG 11 WC Psychiatry SC Psychiatry GA 570UE UT WOS:000176676000021 PM 12091202 ER PT J AU Celedon, JC Litonjua, AA Ryan, L Weiss, ST Gold, DR AF Celedon, JC Litonjua, AA Ryan, L Weiss, ST Gold, DR TI Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE antibiotic use; asthma; early life ID EARLY-CHILDHOOD; RESPIRATORY-TRACT; HAY-FEVER; CHILDREN; ATOPY; RISK; INFECTIONS; INCREASE; HISTORY AB Five retrospective studies have reported an association between antibiotic use in early life and asthma in childhood. We studied the relationship between the use of oral antibiotics in the first year of life and asthma, allergic rhinitis, and eczema at age 5 years among 448 children with a parental history of atopy monitored from birth. After adjustment for potential confounders, we found no significant association between antibiotic use in the first year of life and asthma (odds ratio [OR] for one versus no courses of antibiotics, 0.5; 95% confidence interval [CI] for OR, 0.2 to 1.5; OR for two or more versus no courses of antibiotics, 1.0; 95% CI for OR, 0.5 to 2.2), recurrent wheezing, allergic rhinitis, or eczema at age 5 years. There was no significant association between antibiotic use in the first year of life and having at least one of three atopic diseases (asthma, allergic rhinitis, or eczema) at age 5 years (OR for one versus no courses of antibiotics, 0.7, 95% CI, 0.4 to 1.4; OR for two or more versus no courses of antibiotics, 0.9; 95% CI, 0.5 to 1.4). Our findings do not support the hypothesis that antibiotic use in early life is associated with the subsequent development of asthma and atopy in childhood. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Celedon, JC (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIAID NIH HHS [AIEHS35786] NR 17 TC 86 Z9 89 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2002 VL 166 IS 1 BP 72 EP 75 DI 10.1164/rccm.2109074 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 569GD UT WOS:000176592000018 PM 12091174 ER PT J AU Sahani, D Saini, S Pena, C Nichols, S Prasad, SR Hahn, PF Halpern, EF Tanabe, KK Mueller, PR AF Sahani, D Saini, S Pena, C Nichols, S Prasad, SR Hahn, PF Halpern, EF Tanabe, KK Mueller, PR TI Using multidetector CT for preoperative vascular evaluation of liver neoplasms: Technique and results SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY NOV, 2000 CL CHICAGO, ILLINOIS SP Radiolog Soc N Amer ID HELICAL COMPUTED-TOMOGRAPHY; HEPATIC ARTERIAL INFUSION; COLORECTAL-CANCER; SPIRAL CT; RESECTION; TRANSPLANTATION; CHEMOTHERAPY; ANGIOGRAPHY; VEIN; CANDIDATES AB OBJECTIVE. The purpose of our study was to evaluate the performance of CT angiography using multidetector CT (MDCT) for preoperative vascular evaluation in candidates who were scheduled for liver neoplasm resection. SUBJECTS AND METHODS. Forty-two consecutive subjects with malignant liver tumors scheduled for resection were studied with multiphase MDCT. The first 22 subjects underwent both multiphase MDCT angiography and catheter angiography before surgery. The subsequent 20 subjects underwent only preoperative CT angiography. Postprocessing was performed, and the images were analyzed for the depiction of arterial, portal vein, and hepatic vein anatomy and for the identification of important vascular variants. The postprocessing findings were compared and correlated with the findings from catheter angiography (22/42) or intraoperative sonography (42/42) and surgery (42/42). RESULTS. Arterial anomalies were detected on the images of 17 of 42 patients, including a replaced right hepatic artery in five, replaced left hepatic artery in six, accessory right and left hepatic arteries in two, common trunk for the celiac and superior mesenteric arteries in one, and early bifurcation of the celiac artery in one. In 22 patients in whom catheter angiography confirmation was available, the number of arteries and almost all the significant anomalies were correctly identified on CT angiography (accuracy, 97%; sensitivity, 94%; specificity, 100%). In the subset of 20 patients who underwent MDCT angiography without catheter angiography confirmation, all clinically relevant information was provided by CT angiography. The portal and hepatic vein anatomy and the relationships of the liver tumors to the neighboring venous structures were shown on CT. CONCLUSION. Multidetector CT provides valuable preoperative information about hepatic vascular architecture and can be used as a noninvasive alternative to catheter angiography before oncologic liver surgery. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. RP Sahani, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234-E,55 Fruit St, Boston, MA 02114 USA. NR 26 TC 69 Z9 95 U1 0 U2 2 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 JUL PY 2002 VL 179 IS 1 BP 53 EP 59 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565GG UT WOS:000176361000011 PM 12076905 ER PT J AU Mullins, ME Lev, MH Schellingerhout, D Koroshetz, WJ Gonzalez, RG AF Mullins, ME Lev, MH Schellingerhout, D Koroshetz, WJ Gonzalez, RG TI Influence of availability of clinical history on detection of early stroke using unenhanced CT and diffusion-weighted MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTEROBSERVER AGREEMENT; RADIOLOGY; ERROR; VARIABILITY; INFARCTION; ACCURACY; THERAPY; SIGNS AB OBJECTIVE. The radiologic diagnosis of stroke requires accurate detection and appropriate interpretation of relevant imaging findings; both detection and interpretation may be influenced by knowledge of the patient's presentation. In our study, we evaluated the effect of the availability of clinical history on the sensitivity for stroke detection using unenhanced CT and diffusion-weighted MR imaging. MATERIALS AND METHODS. The records of 733 consecutive patients with a clinically based admission diagnosis of early stroke were reviewed. Among the criteria for inclusion in our study were the availability of an unenhanced CT scan (561 cases) or diffusion-weighted MR imaging examination (409 cases) obtained at admission and a discharge diagnosis indicating whether a patient had actually had a stroke. The radiology requisition forms, available at the time of image interpretation, were classified as either indicating or not indicating a clinical suspicion of early stroke. Sensitivity, specificity, and accuracy of stroke detection were computed, stratified by the presence or absence of an available history indicating suspicion of stroke. Results were compared using the Fisher's exact two-tailed test. RESULTS. Unenhanced CT sensitivity was 52% (specificity, 95%) for the suspicion-of-stroke group and 38% (specificity, 89%) for the no-suspicion-of-stroke group (p = 0.008). Diffusion-weighted MR imaging sensitivity was 95% (specificity, 94%) for the suspicion-of-stroke group and 94% (specificity, 98%) for the no-suspicion-of-stroke group (p = 0.822). CONCLUSION. Availability of a clinical history indicating that early stroke is suspected significantly improves the sensitivity for detecting strokes on unenhanced CT without reducing specificity. In contradistinction, the availability of such a history did not significantly improve the sensitivity for detecting stroke using diffusion-weighted MR imaging. Whenever possible, relevant clinical history should be made available to physicians interpreting emergency CT scans of the head. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. NR 24 TC 39 Z9 41 U1 0 U2 2 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 JUL PY 2002 VL 179 IS 1 BP 223 EP 228 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565GG UT WOS:000176361000042 PM 12076941 ER PT J AU Livingston, EH Harwell, JD AF Livingston, EH Harwell, JD TI The medicolegal aspects of proctoring SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE medical staff; privileges; national Practitioners Data Bank; Health Care Quality Improvement Act AB Virtually every medical staff ensures surgeons technical competency by requiring a proctoring process. However. rarely do medical staff bylaws specify the relationship between completion of proctoring and acquisition of medical staff privileges. For this reason surgeons failing to acquire privileges because of adverse proctor evaluations might be subject to National Practitioners Data Bank reporting. Few proctors understand what their responsibilities are should they witness malpractice being committed. In the State of California, case law has demonstrated that proctors are immune from liability should they allow substandard practices to continue and fail to intervene on the patient's behalf. Alternatively, if the proctor intervenes on a Good Samaritan basis they are most likely protected from malpractice liability. We recommend the implementation of two processes to avoid legal pitfalls: (1) Liability can be minimized if proctoring consents are obtained that clearly delineate the proctor's responsibilities during the operation. (2) Medical staff bylaws should clearly specify the temporal relationship between application of privileges, duration of proctoring process and final acquisition of clinical privileges. (C) 2002 Excerpta Medica, Inc. All rights reserved. C1 VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Gen Surg, Los Angeles, CA 90095 USA. RP Livingston, EH (reprint author), VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. NR 5 TC 8 Z9 8 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2002 VL 184 IS 1 BP 26 EP 30 AR PII S0002-9610(02)00888-7 DI 10.1016/S0002-9610(02)00888-7 PG 5 WC Surgery SC Surgery GA 578KT UT WOS:000177117100006 PM 12135714 ER PT J AU Yantiss, RK Chang, HK Farraye, FA Compton, CC Odze, RD AF Yantiss, RK Chang, HK Farraye, FA Compton, CC Odze, RD TI Prevalence and prognostic significance of acinar cell differentiation in pancreatic endocrine tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pancreatic endocrine tumor; acinar cell carcinoma; immunohistochemistry; lipase; trypsin; chymotrypsin; chromogranin A; synaptophysin; Leu-7; neuron specific enolase; Ki67 ID INTRAHEPATIC BILE-DUCTS; ALPHA-AMYLASE; PERIBILIARY GLANDS; CARCINOMA; EXPRESSION; LIPASE; CLONING; TRYPSIN; IDENTIFICATION; ISOENZYMES AB We have noted that many histologically and immunohistochemically confirmed pancreatic endocrine tumors show immunophenotypic evidence of acinar cell differentiation, but the clinical relevance of this finding is unknown. We performed this study to evaluate the prevalence and prognostic significance of exocrine differentiation by immunohistochemistry in pancreatic endocrine tumors that do not show morphologic features of acinar cell differentiation. Routinely processed tissue sections from 87 pancreatic endocrine tumors were immunohistochemically stained with monoclonal antibodies against acinar (lipase. chymotrypsin. trypsin) and endocrine cell markers (chromogranin A, neuron-specific enolase, synaptophysin, Leu-7) and for the proliferation-associated peptide Ki67. The degree of staining with each marker was graded on a three-tier scale for acinar markers (grade 0, <5%; grade 1, 5-10%: grade 2, 11-25%; and grade 3, >25%) and on a four-tier scale for endocrine markers (grade 0, <5%; grade 1.5-25%; grade 2, 26-50%; grade 3, 51-75%; and grade 4, >75%), and the results were correlated with clinical outcome (mean follow-up 53 months), Greater than 75% of the tumor cells stained for chromogranin A, neuron-specific enolase, synaptophysin, and Leu-7 in 100%, 96%, 93%. and 27% of cases, respectively. Overall, 66% of tumors stained positively for at least one acinar cell marker, 31% stained for at least two acinar cell markers, and 13% stained for all three acinar cell markers. Forty-seven percent stained for lipase (23 grade 1, 11 grade 2. seven grade 3), 37% for trypsin (22 grade 1, three grade 2, seven grade 3), and 25% stained for chymotrypsin (13 grade 1, five grade 1 four grade 3). No correlation was noted between the presence or extent of expression of any single or combination of acinar cell markers and clinical outcome, However, higher tumor stage correlated with a poor clinical outcome (p = 0.002). and location in the tail of the pancreas was associated with a longer interval to tumor recurrence (p = 0.03). The presence of synaptophysin (p = 0.03) and Leu-7 expression (p = 0.03) correlated significantly with less aggressive clinical behavior. An association was observed between increased Ki67 labeling and poorer clinical outcome, but this was not statistically significant (p > 0.05). In conclusion, immunophenotypic evidence of acinar cell differentiation is common in pancreatic endocrine tumors, but this feature does not have any relevance to clinical prognosis. However, in addition to tumor stage, location in the pancreatic tail and the immunohistochemical expression of synaptophysin and/or Leu-7 may be useful prognostic indicators in patients with these lesions. C1 Univ Massachusetts, Mem Med Ctr, Dept Pathol, Worcester, MA 01655 USA. Kosin Univ, Med Ctr, Pusan, South Korea. Boston Univ, Med Ctr, Boston, MA 02215 USA. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Yantiss, RK (reprint author), Univ Massachusetts, Mem Med Ctr, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 47 TC 29 Z9 30 U1 1 U2 2 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 JUL PY 2002 VL 26 IS 7 BP 893 EP 901 DI 10.1097/00000478-200207000-00007 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 569UR UT WOS:000176621200007 PM 12131156 ER PT J AU Yang, XMJ Wu, CL Woda, BA Dresser, K Tretiakova, M Fanger, GR Jiang, Z AF Yang, XMJ Wu, CL Woda, BA Dresser, K Tretiakova, M Fanger, GR Jiang, Z TI Expression of alpha-methylacyl-CoA racemase (P504S) in atypical adenomatous hyperplasia of the prostate SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE adenosis; prostate; cancer; precursor; P504S; immunohistochemistry ID INTRAEPITHELIAL NEOPLASIA; HISTOLOGIC FEATURES; NEEDLE-BIOPSY; CARCINOMA; ADENOSIS; SPECIMENS; CANCER; BENIGN AB Atypical adenomatous hyperplasia (AAH) of the prostate, also known as adenosis, is characterized by a proliferation of prostatic glands with abnormal architectural patterns, but Without significant cytologic atypia. In some cases it may be difficult to distinguish AAH from prostatic carcinoma. Additionally, it is not clear whether AAH is a precursor lesion of prostatic adenocarcinoma. P504S, a protein highly expressed in prostatic adenocarcinoma, has been recently shown to be a marker of prostate cancer, The goal of this study is to examine the expression of P504S in AAH by immunohistochemistry, A total of 80 prostate specimens, including 40 cases of AAH (prostatectomy N = 30, biopsy N = 6. transurethral resection N = 4), 20 cases of prostatic adenocarcinomas, and 20 cases of benign prostatic hyperplasia. were studied. Immuohistochemistry for a prostate cancer marker alpha-methylacyl-CoA racemase (P504S) and a basal cell-specific marker 34betaE12 was performed in all the cases. The 34betaE12 stain confirmed the presence of patchy basal cells in all 40 cases of AAH. P504S was undetectable in the majority of AAHs (33 of 40, 82.5%), focally expressed in four of 40 (10.0%), or diffusely positive only in three of 40 (7.5%) cases of AAH. Interestingly, two of seven P504S-positive AAHs were found adjacent to adenocarcinoma. In contrast, all benign prostatic hyperplasias (20 of 20, 100%) were negative for P504S, and all 20 cases of prostatic carcinomas (100%) showed a diffuse P504S staining pattern, These findings suggest that AAH is a heterogenous entity. The biologic significance of P504S expression in a small subset of AAH remains to be determined. Because most cases of AAH are negative for P504S, immunostaining of P504S is also of diagnostic value in distinguishing the majority of AAHs from prostatic adenocarcinoma. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Labs, Boston, MA USA. Corixa Corp, Seattle, WA USA. RP Jiang, Z (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave, Worcester, MA 01655 USA. NR 20 TC 99 Z9 119 U1 1 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 JUL PY 2002 VL 26 IS 7 BP 921 EP 925 DI 10.1097/00000478-200207000-00011 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 569UR UT WOS:000176621200011 PM 12131160 ER PT J AU Toursarkissian, B Shireman, PK Harrison, A D'Ayala, M Schoolfield, J Sykes, MT AF Toursarkissian, B Shireman, PK Harrison, A D'Ayala, M Schoolfield, J Sykes, MT TI Major lower-extremity amputation: Contemporary experience in a single Veterans Affairs institution SO AMERICAN SURGEON LA English DT Article ID ISCHEMIA; AMPUTEE AB Our objective is to describe our current experience with major lower-extremity amputation secondary to vascular disease. We conducted a retrospective review of sequential amputations over a 3-year period at one Veterans Affairs institution. One hundred thirteen amputations were performed in 99 men (age 70 +/- 11 years). Seventy-five per cent were diabetic and 23 per cent were on dialysis. Fifty-six per cent were primary amputations. The final AKA/BKA (above-knee to below-knee amputation) ratio was 3:2 and was not related to prior bypass, ethnicity, or dialysis status (P > 0.5). Forty-three per cent of amputations were BKAs in diabetics versus 26 per cent in nondiabetics (P = 0.08). The in-hospital and 30-day mortality rates were 2.6 and 8 per cent and were not related to amputation level (P = 0.76). Forty per cent experienced postoperative complications that were most frequently wound related (22%). Wound complications were more frequent with BKA than AKA (P = 0.04). At an average follow-up of 10 +/- 8 months only 65 per cent were alive. Although 51 per cent were discharged to rehabilitation units only 26 per cent regularly wore a prosthesis with 23 per cent ambulating. BKA patients were more likely to ambulate than AKA (34% vs 9%; P = 0.001), and dialysis patients were less likely to ambulate than nondialysis patients (5% vs 25%; P < 0.02). During follow-up 17 per cent of patients discharged with an intact contralateral limb required amputation of that limb and 7 per cent had bypass surgery on that limb. Complication rates were higher in African Americans and Hispanics than in whites (59%, 45%, and 23%, respectively; P < 0.001), although mortality and ambulation rates were similar. Despite an acceptable perioperative mortality complication rates remain high especially in nonwhites. One-year mortality is high. Low rehabilitation rates especially in dialysis patients mandate further efforts in this regard. Vigilant follow-up of the contralateral limb is essential. C1 Audie Murphy Vet Hosp, Sect Vasc Surg, San Antonio, TX USA. RP Toursarkissian, B (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 13 TC 30 Z9 30 U1 1 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD JUL PY 2002 VL 68 IS 7 BP 606 EP 610 PG 5 WC Surgery SC Surgery GA 573AN UT WOS:000176807300010 PM 12132742 ER PT J AU Garrison, HG Maio, RF Spaite, DW Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR AF Garrison, HG Maio, RF Spaite, DW Desmond, JS Gregor, MA O'Malley, PJ Stiell, IG Cayten, CG Chew, JL MacKenzie, EJ Miller, DR TI Emergency Medical Services Outcomes Project III (EMSOP III): The role of risk adjustment in out-of-hospital outcomes research SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID GLASGOW-COMA-SCALE; CARDIAC-ARREST; PREHOSPITAL CARE; INJURED PATIENTS; NATIONAL SURVEY; TRAUMA PATIENTS; INTENSIVE-CARE; TIME; MORTALITY; SURVIVAL AB The purpose of the Emergency Medical Services Outcomes Project (EMSOP) is to develop a foundation and framework for out-of-hospital outcomes research. Fundamental to that purpose is the identification of priority conditions, risk-adjustment measures (RAMs), and outcome measures. In this third EMSOP article, we examine the topic of risk adjustment, discuss the relevance of risk adjustment for out-of-hospital outcomes research, and recommend RAMS that should be evaluated for potential use in emergency medical services (EMS) research. Risk adjustment allows better judgment about the effectiveness and quality of alternative therapies; it fosters a better comparison of potentially dissimilar groups of patients. By measuring RAMS, researchers account for an important source of variation in their studies. Core RAMS are those measures that might be necessary for out-of-hospital outcomes research involving any EMS condition. Potential core RAMS that should be evaluated for their feasibility, validity, and utility in out-of-hospital research include patient age and sex, race and ethnicity, vital signs, level of responsiveness, Glasgow Coma Scale, standardized time intervals, and EMS provider impression of the presenting condition. Potential core RAMS that could be obtained through linkage to other data sources and that should be evaluated for their feasibility, validity, and utility include principal diagnosis and patient comorbidity. We recommend that these potential core RAMS be systematically evaluated for use in risk adjustment of out-of-hospital patient groups that might be used for outcomes research. C1 E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC 27858 USA. Univ Michigan, Med Ctr, Dept Emergency Med, Ann Arbor, MI 48109 USA. Univ Arizona, Coll Med, Dept Emergency Med, Tucson, AZ USA. Massachusetts Gen Hosp, Pediat Emergency Serv, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Emergency Med Serv Children, Boston, MA USA. Univ Ottawa, Div Emergency Med, Ottawa, ON, Canada. New York Med Coll, Inst Trauma & Emergency Care, Valhalla, NY 10595 USA. EMSSTAR Grp, Annapolis, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. HealthSpan Transportat Serv & Allina Hlth Syst, St Paul, MN USA. RP Garrison, HG (reprint author), E Carolina Univ, Brody Sch Med, Dept Emergency Med, Greenville, NC 27858 USA. OI Spaite, Daniel/0000-0003-2601-6476; Stiell, Ian/0000-0002-2583-6408 NR 63 TC 0 Z9 0 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2002 VL 40 IS 1 BP 81 EP 90 DI 10.1067/mem.2002.124758 PG 10 WC Emergency Medicine SC Emergency Medicine GA 569GE UT WOS:000176592100013 ER PT J AU Cooper, DKC AF Cooper, DKC TI Xenotransplant cardiac chimera: Immune tolerance of adult stem cells - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2002 VL 74 IS 1 BP 24 EP 24 AR PII S0003-4975(02)03691-3 DI 10.1016/S0003-4975(02)03691-3 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 569VF UT WOS:000176622500006 ER PT J AU Goodacre, BW Savage, C Zwischenberger, JB Wittich, GR vanSonnenberg, E AF Goodacre, BW Savage, C Zwischenberger, JB Wittich, GR vanSonnenberg, E TI Salinoma window technique for mediastinal lymph node biopsy SO ANNALS OF THORACIC SURGERY LA English DT Article AB Computed tomographic-guided transthoracic needle biopsy can access virtually all mediastinal lymph node stations, but is limited by the potential for pneumothorax and bleeding. To avoid these possible complications, the extrapleural "salinoma" technique was used for computed tomographic-guided mediastinal biopsies in 15 patients. Sampling methods were coaxial (8), tandem (5), and single pass (2). Diagnostic yield was 93% with no significant bleeding or pneumothorax. The salinoma technique permits biopsy of deep mediastinal lesions to stage pulmonary malignancies, while providing a technique that limits complications. C1 Univ Texas, Med Branch, Div Cardiothorac Surg, Dept Surg, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Radiol, Galveston, TX 77555 USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Victoria Gen Hosp, Victoria, BC, Canada. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX USA. RP Zwischenberger, JB (reprint author), Univ Texas, Med Branch, Div Cardiothorac Surg, Dept Surg, 301 Univ Blvd, Galveston, TX 77555 USA. NR 5 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2002 VL 74 IS 1 BP 276 EP 277 AR PII S0003-4975(02)03560-9 DI 10.1016/S0003-4975(02)03560-9 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 569VF UT WOS:000176622500077 PM 12118788 ER PT J AU Duan, Z Lamendola, DE Yusuf, RZ Penson, RT Preffer, FI Seiden, MV AF Duan, Z Lamendola, DE Yusuf, RZ Penson, RT Preffer, FI Seiden, MV TI Overexpression of human phosphoglycerate kinase 1 (PGK1) induces a multidrug resistance phenotype SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the American-Association-for-Cancer-Research CY APR 01-05, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Canc Res DE multidrug resistance; PGK-1; paclitaxel; P-glycoprotein; ATP ID BREAST-CANCER CELLS; P-GLYCOPROTEIN; INDUCED APOPTOSIS; OVARIAN-CANCER; TAXOL RESISTANCE; EXPRESSION; PACLITAXEL; CDNA; MECHANISMS; BAX AB Background: Multidrug resistance is a significant barrier to the development of successful cancer treatment. To identify genetic alterations that are directly involved in paclitaxel resistance, a functional cloning strategy was developed. Materials and Methods: Using mRNA from paclitaxel resistant human ovarian cancer cell line SW626(TR), a cDNA library was established in a pCMV-Script vector that permits expression of cDNA inserts in mammalian cells. Transfection of the pCMV-Script/ SW626(TR) cDNA library into the paclitaxel-sensitive human osteogenic sarcoma cell line, U-20S, resulted in several paclitaxel-resistant clones. Results: DNA sequencing of clone C16 demonstrates complete. homology to human phosphoglycerate kinase 1 (PGK1) Retransfection of the PGK1 insert into U-20S confers a multidrug resistant phenotype, characterized by a 30-fold increase in paclitaxel resistance, and cross-resistance to vincristine, adriamycin and mitoxantrone, but not methotrexate or cisplatin. Enzymatic analysis of the PGK1 transfectants demonstrates an increase in PGK1 activity as compared to the parental cell line, U-20S. Northern and Western analysis of PGK1 transfectants reveals no change in MDR-1 expression compared with the parental cell line. In addition, co-culture of PGK1 transfectants with verapamil only partially reverses the multidrug resistant phenotype. Rhodamine 123 studies are also consistent with an MDR-1 independent mechanism of increased drug efflux. Conclusion: Together this data suggests that PGK1 can induce a multidrug resistant phenotype through an MDR-1 independent mechanism. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 37 TC 55 Z9 58 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2002 VL 22 IS 4 BP 1933 EP 1941 PG 9 WC Oncology SC Oncology GA 580WP UT WOS:000177259900001 PM 12174867 ER PT J AU Goldstein, G Minshew, NJ Allen, DN Seaton, BE AF Goldstein, G Minshew, NJ Allen, DN Seaton, BE TI High-functioning autism and schizophrenia - A comparison of an early and late onset neurodevelopmental disorder SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE autism; schizophrenia; cognition ID COGNITIVE HETEROGENEITY; PROFILES; DEFICITS; SUBTYPES; CHILDREN AB Autism and schizophrenia are separate neurodevelopmental disorders that share a number of interpersonal and cognitive deficits. The symptoms of autism first appear during early life while schizophrenic symptoms do not typically appear until adolescence at the earliest. Efforts have been made to characterize the pattern of cognitive function in both disorders, and certain resemblances have become apparent such as deficits in abstract reasoning and the more complex aspects of memory and language. The present study provided a comparison of cognitive function between the two disorders. The autistic sample consisted of well-diagnosed individuals with high-functioning autism (IQ greater than or equal to 70). The schizophrenic sample was divided into four subgroups using Ward's method of cluster analysis. Participants received the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the Halstead Category Test, the Trail Making test, and the Wisconsin Card Sorting test (WCST). The profile of the autism sample was compared with the four schizophrenia cluster profiles. The autism group resembled only one of the schizophrenia clusters, with both showing elevations on the WAIS-R Information and Block Design subtests and depressions on Comprehension and Digit Symbol. It was concluded that individuals with high-functioning autism have a cognitive profile that resembles that of an empirically derived subgroup of schizophrenia patients but that does not resemble profiles found in other schizophrenia subgroups. The pattern itself, marked by a relatively depressed score on the Comprehension subtest among the Verbal subtests and a relatively elevated score on Block Design among the Performance subtests, has been characterized in the past as a prototypic profile for high-functioning autism. (C) 2002 National Academy of Neuropsychology. Published by Elsevier Science Ltd. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Nevada, Las Vegas, NV 89154 USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr,151R, Pittsburgh, PA 15206 USA. EM ggold@nb.net NR 42 TC 46 Z9 49 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD JUL PY 2002 VL 17 IS 5 BP 461 EP 475 AR PII S0887-6177(01)00129-9 DI 10.1016/S0887-6177(01)00129-9 PG 15 WC Psychology, Clinical; Psychology SC Psychology GA 567PL UT WOS:000176493100004 PM 14592000 ER PT J AU Martinez, MI Sanchez-Carpintero, I North, PE Mihm, MC AF Martinez, MI Sanchez-Carpintero, I North, PE Mihm, MC TI Infantile hemangioma - Clinical resolution with 5% imiquimod cream SO ARCHIVES OF DERMATOLOGY LA English DT Article ID IMMUNE-RESPONSE MODIFIER; INFANCY; ANTIANGIOGENESIS; CARCINOMA; THERAPY C1 Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. Clin Americas, San Juan, PR USA. Univ Navarra Clin, Navarra, Spain. Harvard Univ, Boston, MA 02115 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Sanchez-Carpintero, I (reprint author), Massachusetts Gen Hosp, Div Dermatopathol, Warren 827, Boston, MA 02114 USA. NR 19 TC 62 Z9 73 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2002 VL 138 IS 7 BP 881 EP 884 DI 10.1001/archderm.138.7.881 PG 4 WC Dermatology SC Dermatology GA 569RA UT WOS:000176614900001 PM 12071813 ER PT J AU McCauley, LA Joos, SK Barkhuizen, A Shuell, T Tyree, WA AF McCauley, LA Joos, SK Barkhuizen, A Shuell, T Tyree, WA TI Chronic fatigue in a population-based study of Gulf War veterans SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE Chronic Fatigue Syndrome; diagnosis; Gulf War; illness behavior ID COGNITIVE-BEHAVIOR-THERAPY; SELF-REPORTED EXPOSURES; PRIMARY-CARE; UNEXPLAINED ILLNESS; PREVALENCE; DEFINITION; SYSTEM AB Fatigue has been associated with illness in veterans of the Gulf War; however, few studies have confirmed self-reported fatigue by using clinical evaluation, and symptomatic veterans have not been evaluated with established criteria for Chronic Fatigue Syndrome (CFS). The authors describe the frequency and clinical characteristics of CFS in a sample of veterans residing in the northwestern United States. The sample was selected randomly from U.S. Department of Defense databases of troops deployed to southwest Asia during the Gulf War. The selected individuals were invited to participate in a clinical case-control study of unexplained illness. Of 799 survey respondents eligible for clinical evaluation, 178 had fatigue symptoms. Of the 130 veterans who were evaluated clinically, 103 had unexplained fatigue, and 44 veterans met the 1994 U.S. Centers for Disease Control criteria for CFS. In this population, the authors estimated a minimum prevalence of any unexplained fatigue to be 5.1%, and of CFS to be 2.2%. The estimated prevalence was greater among females than among males. Cases were similar to healthy controls, as determined by laboratory tests and physical findings. In comparison to several clinical studies of CFS patients, the authors of this study found a lower proportion of veterans who reported a sudden onset of symptoms (19%) vs. a gradual onset (50%). Although it has previously been suggested that veterans of the Gulf War suffer from higher rates of chronic fatigue than the general population, the study results described herein-on the basis of clinical examination of a population-based sample of veterans-actually indicate that an increased rate may indeed exist. Gulf War veterans with unexplained fatigue should be encouraged to seek treatment so that the impact of these symptoms on overall quality of life can be reduced. C1 Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Hlth Serv Res & Dev Dep Med, Portland, OR USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Div Med Informat & Outcome Res, Portland, OR USA. Concordia Univ, Math & Sci Dept, Portland, OR USA. Good Samaritan Reg Med Ctr, Phoenix, AZ USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Portland Vet Affairs Med Ctr, Neurol Serv, Portland, OR USA. RP McCauley, LA (reprint author), Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. NR 32 TC 19 Z9 20 U1 2 U2 2 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 2002 VL 57 IS 4 BP 340 EP 348 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 634UM UT WOS:000180359800012 PM 12530602 ER PT J AU Spencer, T Biederman, J Coffey, B Geller, D Crawford, M Bearman, SK Tarazi, R Faraone, SV AF Spencer, T Biederman, J Coffey, B Geller, D Crawford, M Bearman, SK Tarazi, R Faraone, SV TI A double-blind comparison of desipramine and placebo in children and adolescents with chronic tic disorder and comorbid attention-deficit/hyperactivity disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; SUDDEN-DEATH; TRICYCLIC ANTIDEPRESSANTS; LONGITUDINAL DATA; SCALE; CLONIDINE; SYMPTOMS; SEVERITY; PARENT AB Background: Currently, there is no consensus on the best therapeutic approach to chronic tic disorders and comorbid attention-deficit/hyperactivity disorder (ADHD). To address this issue, we evaluated the tolerability and efficacy of the noradrenergic tricyclic antidepressant desipramine hydrochloride in the treatment of children and adolescents with chronic tic disorders and comorbid ADHD. Methods: Forty-one children and adolescents with chronic tic disorders, including Tourette disorder and comorbid ADHD, were studied in a 6-week, double-blind, placebo-controlled, parallel trial. Desipramine was titrated weekly up to 3.5 mg/kg per day, We rated ADHD and tic symptoms weekly and monitored adverse effects, laboratory findings, and cardiovascular parameters. Results: Treatment with desipramine (mean total daily dose, 3.4 mg/kg per day) was well tolerated without meaningful adverse effects. Desipramine significantly reduced core symptoms of ADHD (ADHD Rating Scale 42% decrease from baseline relative to placebo, P < .001), with equal response in inattentive symptoms and hyperactive/impulsive symptoms (P < .001 for both). The ADHD response rate was robust (71% vs 0% desipramine vs placebo, P < .001). Likewise, desipramine significantly reduced tic symptoms (Yale Global Tic Severity Scale 30% decrease from baseline relative to placebo, P < .001), with equal response in motor and phonic tic symptoms (P < .01 for both). The tic response rate was substantial (58% vs 5%; desipramine vs placebo, P < .001). There were small but statistically significant differences between desipramine and placebo in heart rate and blood pressure. Conclusions: Treatment with desipramine was well tolerated and was associated with robust clinically significant reductions in tic and ADHD symptoms in children and adolescents with chronic tic disorders and ADHD diagnoses. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. McLean Hosp, Obsess Compuls Disorders Clin, Belmont, MA 02178 USA. McLean Hosp, Tourettes Disorders Clin, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R29 MH57511] NR 41 TC 63 Z9 66 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2002 VL 59 IS 7 BP 649 EP 656 DI 10.1001/archpsyc.59.7.649 PG 8 WC Psychiatry SC Psychiatry GA 571KG UT WOS:000176716100008 PM 12090818 ER PT J AU Leverenz, JB Agustin, CM Tsuang, D Peskind, ER Edland, SD Nochlin, D DiGiacomo, L Bowen, JD McCormick, WC Teri, L Raskind, MA Kukull, WA Larson, EB AF Leverenz, JB Agustin, CM Tsuang, D Peskind, ER Edland, SD Nochlin, D DiGiacomo, L Bowen, JD McCormick, WC Teri, L Raskind, MA Kukull, WA Larson, EB TI Clinical and neuropathological characteristics of hippocampal sclerosis - A community-based study SO ARCHIVES OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE CERAD; COMMON PATHOLOGICAL FEATURE; APOLIPOPROTEIN-E; DEGENERATIVE DEMENTIA; CASE SERIES; RARE CAUSE; CONSORTIUM; ESTABLISH; DIAGNOSIS; REGISTRY AB Background: Hippocampal sclerosis (HS) is a neuropathologic finding characterized by neuronal loss and gliosis in the CA-1 and subiculum of the hippocampus. Previous studies of HS have shown that this is a common postmortem finding in elderly subjects with dementia. However, these studies were from selected samples and therefore are not necessarily representative of patients seen in the general medical community. Objectives: To examine the clinical and pathologic characteristics of HS in a community-based case series of dementia and to compare these characteristics with those observed in subjects with Alzheimer disease (AD) from the same study sample. Methods: One hundred thirty-four autopsy cases were available from a community-based registry of dementia. Sixteen cases (12%) had a postmortem diagnosis of HS. Thirty-two comparison control cases with a neuropathologic diagnosis of AD were selected from the same files. Each case of HS was reviewed for HS neuropathologic features, including severity, distribution, and additional pathologic processes. Blinded review of clinical characteristics for the HS and control groups was performed to assess risk factors. Results: There was a wide range of severity and distribution of HS lesions between cases and substantial variability in lesion severity and age within individual cases. Serial neuropsychologic and behavioral assessments revealed similar clinical features and rates of dementia progression between HS and AD groups. Of all neuropsychologic tests performed at enrollment, only enhanced performance on Trails A differentiated the HS from the AD group (64 seconds, 0 errors vs 114 seconds, 0.6 errors; Pless than or equal to.05). The number of AD cases with at least 1 apolipoprotein epsilon4 allele was significantly greater than the HS cases (61% vs 31%; chi(2)=3.81, Pless than or equal to.05). Although medical record review indicated higher frequencies of clinical stroke and neuroradiologic white matter abnormalities in the HS group, risk factors for vascular disease and neuropathologic evidence of cerebrovascular disease did not differ between the groups. Conclusions: Our results suggest that HS is a frequent pathologic finding in community-based dementia. Individuals with HS have similar initial symptoms and rates of dementia progression to those with AD and therefore are frequently misclassified as having AD. Our clinical and pathologic findings suggest that HS has characteristics of a progressive disorder although the underlying cause remains elusive. C1 NW Network Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Nursing, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Div Neuropathol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. RP Leverenz, JB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way,116 MIRECC, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [U01AG06781, AG05136, AG06781, R01AG10845] NR 43 TC 63 Z9 65 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2002 VL 59 IS 7 BP 1099 EP 1106 DI 10.1001/archneur.59.7.1099 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 571JP UT WOS:000176714500005 PM 12117357 ER PT J AU Hatton, MP Rubin, PAD AF Hatton, MP Rubin, PAD TI Chronic lymphocytic leukemia of the orbit SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LYMPHOMA; INFILTRATION; OBSTRUCTION; INVOLVEMENT C1 Massachusetts Eye & Ear Infirm, Dept Oculoplast Orbit & Cosmet Surg, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Dept Oculoplast Orbit & Cosmet Surg, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2002 VL 120 IS 7 BP 990 EP 991 PG 2 WC Ophthalmology SC Ophthalmology GA 570ZG UT WOS:000176689900022 PM 12096979 ER PT J AU Gliklich, RE Wang, PC AF Gliklich, RE Wang, PC TI Validation of the snore outcomes survey for patients with sleep-disordered breathing SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID DAYTIME SLEEPINESS; HEALTH-STATUS; APNEA; QUESTIONNAIRE; POPULATION; REDUCTION; SURGERY; ADULTS; SF-36; SCALE AB Objective: To develop and validate a self-reported outcomes measure for patients with sleep-disordered breathing-the Snore Outcomes Survey. Design: Item areas of the SOS were developed by an expert panel. Consecutive patients were enrolled into the study in a prospective manner. Patients received the SOS, the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Medical Outcomes Study 36-Item Short-Form Health Survey, and standard overnight polysomnography at baseline and after 4 months of continuous positive airway pressure therapy. Setting: A tertiary care, academic otolaryngology and sleep disorders referral center. Patients: One hundred fifty-six adult patients presenting with a chief complaint of snoring or sleep-disordered breathing to the Massachusetts Eye and Ear Infirmary, Boston. Main Outcome Measures: Test-retest reliability, intrasurvey reliability, internal consistency, validity, and standardized response means of the SOS. Results: Overall, reliability of the SOS was excellent (test-retest reliability r=0.86; P<.001; Cronbach alpha coefficient, 0.85). The SOS index significantly correlated with the Epworth Sleepiness Scale (r=-0.42; P<.001) and the global Pittsburgh Sleep Quality Index score (r=-0.38; P<.001), as well as with the number of recorded arterial oxygen saturation levels below 85% (r=-0.46; P=.02). The SOS index was sensitive to clinical changes after intervention (standardized response mean, 0.57). Conclusion: The SOS is a reliable and valid instrument for assessing sleep-related health status for patients with snoring and sleep-disordered breathing and for measuring change in health status following therapy. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 33 Z9 35 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2002 VL 128 IS 7 BP 819 EP 824 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 571JM UT WOS:000176714300018 PM 12117343 ER PT J AU Howanitz, PJ Renner, SW Walsh, MK AF Howanitz, PJ Renner, SW Walsh, MK TI Continuous wristband monitoring over 2 years decreases identification errors - A college of American pathologists Q-tracks study SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID EVALUATING LABORATORY PERFORMANCE; TRANSFUSION ERRORS; CONFERENCE-XXVIII; QUALITY ISSUES; HEALTH-CARE; Q-PROBES; HOSPITALS; SCALE AB Context.-Identification of patients is one of the first steps in ensuring the accuracy of laboratory results. In the United States, hospitalized patients wear wristbands to aid in their identification, but wristbands errors are frequently found. Objective.-To investigate if continuous monitoring of wristband errors by participants of the College of American Pathologists (CAP) Q-Tracks program results in lower wristband error rates. Setting.-A total of 217 institutions voluntarily participating in the CAP Q-Tracks interlaboratory quality improvement program in 1999 and 2000. Design.-Participants completed a demographic form, answered a questionnaire, collected: wristband data, and at the end of the year, best and most improved performers answered another questionnaire seeking suggestions for improvement. Each institution's phlebotomists inspected wristbands for errors before performing phlebotomy and recorded the number of patients with wristband errors. On a monthly basis, participants submitted data to the CAP for data processing, and at the end of each quarter, participants received summarized comparisons. At the end of each year, participants also received a critique of the results along with suggestions for improvement. Main Outcome Measures.-The percentage of wristband errors by quarter, types of wristband errors, and suggestions for improvement. Results.-During 2 years, 1757 730 wristbands were examined, and 45197 wristband errors were found. The participants' mean wristband error rate for the first quarter in 1999 was 7.40%; by the eighth quarter, the mean wristband error rate had fallen to 3.05% (P < .001). Continuous improvement occurred in each quarter for participants in the 1999 and 2000 program and in 7 of 8 quarters for those who participated in both 1999 and 2000. Missing wristbands accounted for 71.6% of wristband errors, and best performers usually had wristband error rates under 1.0%. The suggestion for improvement provided by the largest number of best and most improved performers was that phlebotomists should refuse to perform phlebotomy on a patient when a wristband error is detected. Conclusions.-The wristband error rate decreased markedly when this rate was monitored continuously using the CAP Q-Tracks program. The Q-Tracks program provides a useful tool for improving the quality of services in anatomic pathology and laboratory medicine. C1 Suny Downstate Med Ctr, Dept Pathol, Brooklyn, NY 11203 USA. W Los Angeles Vet Adm Med Ctr, Dept Lab Med, Los Angeles, CA USA. Coll Amer Pathologists, Dept Biostat, Northfield, IL USA. RP Howanitz, PJ (reprint author), Suny Downstate Med Ctr, Dept Pathol, Box 25,450 Clarkson Ave, Brooklyn, NY 11203 USA. NR 34 TC 55 Z9 57 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JUL PY 2002 VL 126 IS 7 BP 809 EP 815 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 573UM UT WOS:000176849900007 PM 12088450 ER PT J AU Naeser, MA Hahn, KAK Lieberman, BE Branco, KF AF Naeser, MA Hahn, KAK Lieberman, BE Branco, KF TI Carpal tunnel syndrome pain treated with low-level laser and microamperes transcutaneous electric nerve stimulation: A controlled study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 2nd World Congress Meeting of the World Association-for-Laser-Therapies CY SEP 05, 1998 CL KANSAS CITY, MISSOURI SP Assoc Laser Therapies DE acupuncture; carpal tunnel syndrome; lasers; pain; rehabilitation; transcutaneous electric nerve stimulation ID HUMAN MEDIAN NERVE; IRRADIATION; THERAPY; CONDUCTION; ACUPUNCTURE; MANAGEMENT AB Objective: To investigate whether real or sham low-level laser therapy (LLLT) plus microamperes transcutaneous electric nerve stimulation (TENS) applied to acupuncture points significantly reduces pain in carpal tunnel syndrome (CTS). Design: Randomized, double-blind, placebo-control, crossover trial. Patients and staff administered outcome measures blinded. Setting: Outpatient, university-affiliated Department of Veterans Affairs medical center. Participants: Eleven mild to moderate CTS cases (nerve conduction study, clinical examination) who failed standard medical or surgical treatment for 3 to 30 months. Intervention: Patients received real and sham treatment series (each for 3-4wk), in a randomized order. Real treatments used red-beam laser (continuous wave, 15mW, 632.8nm) on shallow acupuncture points on the affected hand, infrared laser (pulsed, 9.4W, 904nm) on deeper points on upper extremity and cervical paraspinal areas, and microamps TENS on the affected wrist. Devices were painless, noninvasive, and produced no sensation whether they were real or sham. The hand was treated behind a hanging black curtain without the patient knowing if devices were on (real) or off (sham). Main Outcome Measures: McGill Pain Questionnaire (MPQ) score, sensory and motor latencies, and Phalen and Tinel signs. Results: Significant decreases in MPQ score, median nerve sensory latency, and Phalen and Tinel signs after the real treatment series but not after the sham treatment series. Patients could perform their previous work (computer typist, handyman) and were stable for I to 3 years. Conclusions: This new, conservative treatment was effective in treating CTS pain; larger studies are recommended. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Rehabil Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Rehabil Med Serv, Boston, MA USA. VA Boston Healthcare Syst, Psychol Res Serv, Boston, MA USA. Acupuncture Healthcare Serv, Westport, MA USA. RP Naeser, MA (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. NR 60 TC 72 Z9 74 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2002 VL 83 IS 7 BP 978 EP 988 DI 10.1053/apmr.2002.33096 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 569KC UT WOS:000176600700016 PM 12098159 ER PT J AU Veves, A Sheehan, P Pham, HT AF Veves, A Sheehan, P Pham, HT CA Promogran Diabetic Foot Ulcer Stud TI A randomized, controlled trial of promogran (a collagen/oxidized regenerated cellulose dressing) vs standard treatment in the management of diabetic foot ulcers SO ARCHIVES OF SURGERY LA English DT Article ID HUMAN-SKIN; COLLAGEN; COST AB Hypothesis: Promogran, a wound dressing consisting of collagen and oxidized regenerated cellulose, is more effective that standard care in treating chronic diabetic plantar ulcers. Design: Randomized, prospective, controlled multicenter trial. Setting: University teaching hospitals and primary care centers. Patients: A total of 276 patients from 11 centers were enrolled in the study. The mean age of the patients was 58.3 years (range, 23-85 years). All patients had at least I diabetic foot ulcer. Interventions: Patients were randomized to receive Promogran (n = 138) or moistened gauze (control groups n = 138) and a secondary dressing. Dressings were changed when clinically required. The maximum follow-up for each patient was 12 weeks. Main Outcome Measure: Complete healing of the study ulcer (wound). Results: After 12 weeks of treatment, 51 (37.0%) Promogran-treated patients had complete wound closure compared with 39 (28.3%) control patientss, but this difference was not statistically significant (P = .12). The difference in healing between treatment groups achieved borderline significance in the subgroup of patients with wounds of less than 6 months' duration. In patients with ulcers of less than 6 months' duration, 43 (45%) of 95 Promogran-treated patients healed compared with 29 (33%) of 89 controls (P = .056). In the group with wounds of at least 6 months' duration, similar numbers of patients healed in the control (10/49 [20%]) and the Promogran (8/43 [19%] P = .83) groups. No differences were seen in the safety measurements between groups. Patients and investigators expressed a strong preference for Promogran compared with moistened gauze. Conclusions: Promogran was comparable to moistened gauze in promoting wound healing in diabetic foot ulcers. It showed an additional efficacy for ulcers of less than 6 months' duration that was of marginal statistical significance. Furthermore, Promogran had a safety profile that was similar to that of moistened gauze, with greater user satisfaction. Therefore, Promogran may be a useful adjunct in the management of diabetic foot ulceration, especially in ulcers of less than 6 months' duration. C1 Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. Hosp Joint Dis & Med Ctr, Diabet Food & Ankle Ctr, New York, NY USA. RP Veves, A (reprint author), Joslin Beth Israel Deaconess Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. OI Pham, Hau/0000-0003-4583-9873 NR 25 TC 150 Z9 152 U1 3 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 2002 VL 137 IS 7 BP 822 EP 827 DI 10.1001/archsurg.137.7.822 PG 6 WC Surgery SC Surgery GA 571JU UT WOS:000176714900015 PM 12093340 ER PT J AU Bagby, SP LeBard, LS Luo, ZM Speth, RC Ogden, BE Corless, CL AF Bagby, SP LeBard, LS Luo, ZM Speth, RC Ogden, BE Corless, CL TI Angiotensin II type 1 and 2 receptors in conduit arteries of normal developing microswine SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE neural AT2R; quantitative autoradiography; vascular renin-angiotensin system; developing aorta; CGP 42112 ID MESSENGER-RNA; RAT FETUS; EXPRESSION; AT(2); ATHEROSCLEROSIS; LOCALIZATION; PATHWAYS; ONTOGENY; DISEASE; SYSTEM AB Objective-To identify vascular cells capable of responding to angiotensin II (Ang II) generated in conduit arteries, we examined the. Ang II type I receptor (ATIR) and Ang II type 2 receptor, (AT2R) in the thoracic aorta (TA) and abdominal aorta (AA) and branches in 90-day fetal, 3-week postnatal, and 6-month adult microswine. Methods and Results-By autoradiography (I-125-[Sar(1)Ile(8)]-Ang II with or without AT1R- or AT2R-selective analogues or I-125-CGP 42112), there were striking rostrocaudal differences in (1),AT2R binding at all ages (prominent in AA wall and branches, sparse in TA wall and branches) and (2) a non-AT2R binding site for CGP 42112 (consistently evident in postnatal TA and branches but absent in AA and branches). Furthermore, patterns of AT2R distribution in infradiaphragmatic arteries were developmentally distinct. In fetal AAs, high-density AT2Rs occupied the inner 60% of the medial-endothelial wall. In postnatal AAs, AT2Rs were sparse in the medial-endothelial wall but prominent in a circumferential smooth muscle a-actin-negative cell layer at the medial-adventitial border, occupying approximate to20% to 25% of the AA cross-sectional area. ATIR density in the TA and AA medial-endothelial wall increased with age, whereas AT2R density decreased after birth. Conclusions-A novel AT2R-positive cell layer confined to postnatal infradiaphragmatic arteries physically links adventitial and medial layers, appears optimally positioned to transduce AT2R-dependent functions of local Ang II, and suggests that adventitial Ang II may elicit regionally distinct vascular responses. C1 Oregon Hlth Sci Univ, Div Nephrol, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Nephrol, Dept Comparat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Nephrol, Dept Pathol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Washington State Univ, Coll Vet Med, Dept Vet & Comparat Anat Pharmacol & Physiol, Pullman, WA 99164 USA. RP Bagby, SP (reprint author), Oregon Hlth Sci Univ, Div Nephrol, Dept Med, 3314 SW US Vet Hosp Rd,Suite 262, Portland, OR 97201 USA. FU NICHD NIH HHS [P01 HD-34430] NR 32 TC 12 Z9 12 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2002 VL 22 IS 7 BP 1113 EP 1121 DI 10.1161/01.ATV.0000022382.61262.3E PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 575ZQ UT WOS:000176978700013 PM 12117725 ER PT J AU Park, YB Ahn, CW Choi, HK Lee, SH In, BH Lee, HC Nam, CM Lee, SK AF Park, YB Ahn, CW Choi, HK Lee, SH In, BH Lee, HC Nam, CM Lee, SK TI Atherosclerosis in rheumatoid arthritis - Morphologic evidence obtained by carotid ultrasound SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; INTIMA-MEDIA THICKNESS; B-MODE ULTRASOUND; ARTERIAL-WALL; COMMUNITIES; MORTALITY; PLAQUE; ABNORMALITIES; PLASMA AB Objective. Recent studies have suggested increased cardiovascular disease among patients with rheumatoid arthritis (RA). We undertook this study to obtain morphologic evidence of subclinical atherosclerosis in RA patients. Methods. We used high-resolution B-mode ultrasound to compare carotid artery intima-media wall thickness (IMT) between 53 postmenopausal women with RA and 53 controls matched by age, sex, and menopause status. No subject in either group had a history of atherosclerosis or its complications. We investigated the association between IMT and relevant clinical and therapeutic variables, including the impact of low-dose corticosteroid therapy (less than or equal to10 mg/day prednisolone). Results. The mean+/-SD IMT of the left and right common carotid arteries in RA patients was significantly greater than that in controls (0.77+/-0.09 mm versus 0.68+/-0.14 mm; P<0.001). Early RA (duration &LE;1 year) was associated with lesser IMT than was RA of longer duration (0.72&PLUSMN;0.03 mm versus 0.78&PLUSMN;0.01 mm; P<0.04). Prednisolone use was not associated with increased IMT (0.78+/-0.02 mm in nonusers versus 0.76+/-0.01 mm in users; P=0.38). Conclusion. Our data indicate that RA patients have an ultrasonic marker of early atherosclerosis consistent with an increased risk for atherosclerosis. C1 Yonsei Univ, Coll Med, Dept Internal Med, Div Rheumatol, Seoul, South Korea. Yonsei Univ, Coll Med, Inst Immunol & Immunol Dis, BK21 Project Med Sci, Seoul, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lee, SK (reprint author), Yonsei Univ, Coll Med, Dept Internal Med, Div Rheumatol, CPO Box 8044, Seoul, South Korea. NR 33 TC 175 Z9 180 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2002 VL 46 IS 7 BP 1714 EP 1719 DI 10.1002/art.10359 PG 6 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200003 PM 12124853 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL St Clair, EW Gilkeson, GS TI Hormonal and reproductive risk factors for development of systemic lupus erythematosus - Results of a population-based, case-control study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PREMATURE OVARIAN FAILURE; AUTOIMMUNE-DISEASE; MATERNAL BLOOD; BREAST-CANCER; ORAL-CONTRACEPTIVES; GENDER DIFFERENCES; REVISED CRITERIA; SERUM PROLACTIN; INTERVIEW DATA; HYPERPROLACTINEMIA AB Objective. Estrogen and prolactin may accelerate the progression of murine systemic lupus erythematosus (SLE). In humans, 85% of lupus patients are women, which also suggests the importance of hormonal factors in disease pathogenesis. The purpose of this study was to examine hormonal and reproductive risk factors for lupus among women. Methods. This population-based, case-control study included 240 female SLE patients diagnosed between January 1, 1995 and July 31, 1999 who fulfilled the American College of Rheumatology classification criteria. Female controls (n=321) were identified through driver's license records. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) as measures of association, adjusting for age, state, race, and education. Analyses were limited to exposures before diagnosis. Results. Breast-feeding was associated with a decreased risk of developing SLE (OR 0.6, 95% CI 0.4-0.9), with a statistically significant trend for number of babies breast-fed and total weeks of breast-feeding. There were no associations with number of pregnancies or live births. Natural menopause occurred earlier in women with subsequent development of SLE compared with controls (P<0.001). There was little association between SLE and current use or duration of use of hormone replacement therapy or oral contraceptives, and no association with previous use of fertility drugs. Conclusion. We found little evidence that estrogen- or prolactin-related exposures are associated with an increased risk of lupus. The reduced risk observed among women who had breast-fed one or more babies should be examined in other studies. Early natural menopause, rather than decreasing risk of SLE because of reduced estrogen exposure, may be a marker of susceptibility to development of SLE. C1 NIEHS, Epidemiol Branch A3 05, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Greenville, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch A3 05, POB 12233, Res Triangle Pk, NC 27709 USA. NR 54 TC 94 Z9 102 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2002 VL 46 IS 7 BP 1830 EP 1839 DI 10.1002/art.10365 PG 10 WC Rheumatology SC Rheumatology GA 572KK UT WOS:000176773200017 PM 12124867 ER PT J AU Sutherland, FWH Perry, TE Nasseri, BA Wang, J Kaushal, S Guleserian, KJ Martin, DP Vacant, JP Mayer, JE AF Sutherland, FWH Perry, TE Nasseri, BA Wang, J Kaushal, S Guleserian, KJ Martin, DP Vacant, JP Mayer, JE TI Advances in the mechanisms of cell delivery to cardiovascular scaffolds: Comparison of two rotating cell culture systems SO ASAIO JOURNAL LA English DT Article ID CULTIVATION; CARTILAGE; TISSUE AB Having a reliable method of delivering cells to polymer scaffolds in vitro is fundamental to the development of tissue engineered structures. This paper compares the efficacy of two rotating systems for this purpose. Ten conduits, measuring 40 mm by 10 mm, were fabricated from polyglycolic acid mesh and poly-4-hydrobutyrate. Five conduits were placed in a rotating wall vessel (RWV, Synthecon Inc., Houston, TX), developed by the National Aeronautics and Space Administration (NASA); five conduits were also placed in rotating individual sealed tubes (RISTs). Medium in the RWV was left unchanged for the duration of the experiment; medium in the RISTs required daily change. Samples of the discarded medium and samples from the RWV were analyzed for pH, pCO(2), pO(2), and lactate concentration. Constructs were assayed for DNA content as a surrogate for cell number. In the RWV, pH, pCO(2),, and pO(2) remained stable, while the lactate concentration gradually increased. The measure of pO(2) did not differ significantly between the RWV and the RISTs, but the pH was lower and the pCO(2) and the lactate concentration measurements were higher in the RIST system at each time point (p = 0.001). After 6 days (p = 0.001), the total DNA per conduit was 226 +/- 7 mug for the conduits seeded in the RISTs and 396 +/- 18 mug for the conduits in the RWV, suggesting that the RWV is superior to the RIST system for delivering cells to polymer scaffolds. C1 Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Tepha Inc, Boston, MA USA. RP Mayer, JE (reprint author), Childrens Hosp, Dept Cardiovasc Surg, 300 Longwood Ave, Boston, MA 02115 USA. FU PHS HHS [5R01 H16,043-03] NR 4 TC 14 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JUL-AUG PY 2002 VL 48 IS 4 BP 346 EP 349 DI 10.1097/00002480-200207000-00003 PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 573BN UT WOS:000176809600003 PM 12141461 ER PT J AU Neragi-Miandoab, S Guerrero, JL Vlahakes, GJ AF Neragi-Miandoab, S Guerrero, JL Vlahakes, GJ TI Autologous blood sequestration using a double venous reservoir bypass circuit and polymerized hemoglobin prime SO ASAIO JOURNAL LA English DT Article ID CARDIOPULMONARY BYPASS; CARDIAC-SURGERY; WHOLE-BLOOD; TRANSFUSION; CIRCULATION; PLATELETS; SUBSTITUTE; TRIAL; MODEL AB Cardiac surgery often necessitates transfusion of homologous blood. Hemoglobin based oxygen carrying solutions (HBOCs) transport oxygen, suggesting use in cardiopulmonary bypass. HBOC was used in a novel oxygenator double-reservoir circuit that permits acute sequestration of a portion of the autologous blood volume during bypass. Two groups of seven mongrel dogs each were studied in an experimental bypass model using global myocardial ischemia and cardioplegia protection: HBOC group, initial venous return drained to a separate reservoir and hypothermic bypass was conducted with HBOC containing perfusate in a second bypass reservoir; Control group, crystalloid prime in a conventional circuit. Hemodynamics and metabolic and hematologic parameters were measured before and 60 min after aortic clamp removal and reinfusion of sequestered autologous blood. Blood gases, base excess, hematocrit, total hemoglobin, and platelet counts were measured. In the HBOC group, metabolic acidosis did not occur, and ventricular function was preserved. Net conservation of platelets was noted at study conclusion: control 33 +/- 13 x 10(3) per mm(3) versus HBOC 48 +/- 13 x 10(3), p < 0.05. HBOC based priming in a double venous reservoir system permits bypass at very low hematocrit, with preservation of cardiac function. Net conservation of the platelet mass occurs, a portion of which is not exposed to the deleterious effects of hypothermia and cardiopulmonary bypass. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Med Sch, Boston, MA 02138 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,BUL119, Boston, MA 02114 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JUL-AUG PY 2002 VL 48 IS 4 BP 407 EP 411 DI 10.1097/00002480-200207000-00015 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 573BN UT WOS:000176809600015 PM 12141473 ER PT J AU Bohne, A Wilhelm, S Keuthen, NJ Baer, L Jenike, MA AF Bohne, A Wilhelm, S Keuthen, NJ Baer, L Jenike, MA TI Skin picking in German students - Prevalence, phenomenology, and associated characteristics SO BEHAVIOR MODIFICATION LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; NEUROTIC EXCORIATIONS; TRICHOTILLOMANIA; PERFECTIONISM; DERMATOLOGIST; FLUOXETINE; BEHAVIOR; SEEKING AB Severe skin picking (SP) is a repetitive, intentionally performed behavior that causes noticeable tissue damage and results in clinically significant distress or impairment. To date, SP has received little attention in the psychiatric literature. This study was conducted to further investigate SP and its characteristics in a German student population, The participants (N = 133) completed various self-report questionnaires. More than 90% (n = 122) reported occasional SP, with six students (4.6%) endorsing significant impairment from recurrent, self-injurious SP. SP was triggered by specific cutaneous stimuli, situations, and emotions. The students primarily squeezed (85%) and scratched (77.4%) the skin, with a primary focus on the face (94.7%) and cuticles (52.6%). About 20% (n = 26) ate the picked tissue after-ward. Results suggest SP is an underrecognized problem that occurs on a continuum ranging from mild to severe with generally stable clinical characteristics across cultures. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Marburg, D-35032 Marburg, Germany. RP Bohne, A (reprint author), Univ Marburg, D-35032 Marburg, Germany. RI Citations, TLC SAB/C-4006-2011 NR 49 TC 53 Z9 55 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2002 VL 26 IS 3 BP 320 EP 339 DI 10.1177/01445502026003002 PG 20 WC Psychology, Clinical SC Psychology GA 560XT UT WOS:000176107200002 PM 12080904 ER PT J AU Deckersbach, T Wilhelm, S Keuthen, NJ Baer, L Jenike, MA AF Deckersbach, T Wilhelm, S Keuthen, NJ Baer, L Jenike, MA TI Cognitive-behavior therapy for self-injurious skin picking - A case series SO BEHAVIOR MODIFICATION LA English DT Article ID HABIT-REVERSAL AB Self-injurious skin picking is characterized by repetitive, ritualistic, or impulsive skin picking that leads to tissue damage and causes significant distress or impairment in daily functioning. Little is known about effective behavioral or cognitive-behavioral treatments for self-injurious skin picking. As described by Azrin and colleagues, habit reversal is a promising behavioral treatment for modifying nervous habits or tics. To the authors' knowledge, only one case series currently exists in the literature that shows self-injurious skin picking, in the absence of an underlying dermatological condition or without psychiatric comorbidity can be successfully treated with habit reversal. In the current article, the authors describe the implementation and outcome of cognitive-behavior therapy for three patients with severe self-injurious skin picking, two of which had psychiatric comorbidity. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 26 TC 25 Z9 25 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD JUL PY 2002 VL 26 IS 3 BP 361 EP 377 DI 10.1177/01445502026003004 PG 17 WC Psychology, Clinical SC Psychology GA 560XT UT WOS:000176107200004 PM 12080906 ER PT J AU Pascual-Leone, A Manoach, DS Birnbaum, R Goff, DC AF Pascual-Leone, A Manoach, DS Birnbaum, R Goff, DC TI Motor cortical excitability in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE TMS; motorcortex; cortical excitability; human; neuroleptic medications ID TRANSCRANIAL MAGNETIC STIMULATION; RECEPTOR SUBUNIT EXPRESSION; MESSENGER-RNA LEVELS; VOLUNTARY CONTRACTION; PARKINSONS-DISEASE; NMDA RECEPTOR; CORTEX EXCITABILITY; ANTIPSYCHOTIC-DRUGS; COIL ORIENTATION; CONSCIOUS HUMANS AB Background: Transcranial magnetic stimulation (TMS) provides a method to examine cortico-cortical motor excitability and hemispheric asymmetry in unmedicated and medicated schizophrenia patients. Methods: Fourteen right-handed schizophrenia patients (seven on conventional neuroleptics and seven medication-free) were compared with seven right-handed, age- and gender-matched normal control subjects. Motor threshold for induction of motor-evoked potentials (MEPs) and bihemispheric intracortical inhibition and facilitation were measured with single-pulse and paired-pulse TMS. Results: Medicated patients showed an approximately 5% higher motor thresholds in both hemispheres than unmedicated patients and control subjects. Normal control subjects had a nearly 10% higher threshold for the left than the right hemisphere, whereas the opposite was true for the patient groups (5-10% higher threshold on the right than the left). Medicated patients showed significantly decreased intracortical inhibition relative to unmedicated patients and control subjects. This difference was more pronounced for the right than for the left hemisphere. Conclusions: Treatment with conventional neuroleptics is associated with increased motor threshold and decreased intracortical inhibition, whereas unmedicated patients did not differ from normal control subjects on these measures; however, schizophrenia may be characterized by a reversed pattern of interhemispheric corticospinal excitability. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Lab Magnet Brain Stimulat, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. RP Goff, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 25 Staniford St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01-MH54245, R01-MH5790] NR 50 TC 50 Z9 53 U1 2 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 JUL 1 PY 2002 VL 52 IS 1 BP 24 EP 31 AR PII S0006-3223(02)01317-3 DI 10.1016/S0006-3223(02)01317-3 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 564YG UT WOS:000176340700004 PM 12079727 ER PT J AU Rojas, DC Bawn, SD Carlson, JP Arciniegas, DB Teale, PD Reite, ML AF Rojas, DC Bawn, SD Carlson, JP Arciniegas, DB Teale, PD Reite, ML TI Alterations in tonotopy and auditory cerebral asymmetry in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE magnetoencephalography; evoked potentials; auditory cortex ID CORTEX; FREQUENCY; MAGNETOENCEPHALOGRAPHY; ABNORMALITIES; ORGANIZATION; DYSFUNCTION; HEMISPHERE; FIELD; M100 AB Background: Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiologic imaging research has documented a structure-function disassociation in the auditory system in schizophrenia. This study examines whether the most fundamental level of auditory, cortical organization, tonotopy, is altered in schizophrenia. Methods: The tonotopic organization for five tone frequencies in 19 patients with schizophrenia and 22 comparison subjects was evaluated using magnetoencephalography. Auditory evoked magnetic field dipole locations were examined for the N100m component for each frequency. Results: The expected linear relationship between depth and frequency was found in the comparison subjects but not in the schizophrenia group (p < .004). In addition, normal anterior-posterior asymmetry of the N100m was found to be reduced at all five stimulation frequencies employed in the study (p < .04). No relationships between clinical symptom ratings and either tonotopy or asymmetry were observed. Conclusions: This finding suggests that the tonotopic organization of the auditory cortex in schizophrenia is disturbed and may help explain the relatively poor behavioral performance of schizophrenia patients oil simple frequency discrimination tasks. Alterations in fundamental sensory organization may underlie or interact with higher order cognitive mechanisms to produce changes in cognitive task performance. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Rojas, DC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Box C268-68 CPH,4200 E 9th Ave, Denver, CO 80262 USA. RI Arciniegas, David/A-3792-2009; Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616 FU NIMH NIH HHS [MH60214] NR 31 TC 30 Z9 31 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2002 VL 52 IS 1 BP 32 EP 39 AR PII S0006-3223(01)01365-8 DI 10.1016/S0006-3223(01)01365-8 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 564YG UT WOS:000176340700005 PM 12079728 ER PT J AU Milberg, W AF Milberg, W TI Human neuropsychology SO BIOLOGICAL PSYCHOLOGY LA English DT Book Review C1 VA Boston Healthcare, GRECC, Boston, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA 02130 USA. RP Milberg, W (reprint author), VA Boston Healthcare, GRECC, 182JP,150 S Huntington Ave, Boston, MA 02130 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD JUL PY 2002 VL 60 IS 1 BP 75 EP 77 AR PII S0301-0511(02)00013-3 DI 10.1016/S0301-0511(02)00013-3 PG 3 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 578VW UT WOS:000177142600006 ER PT J AU Borenstein, JT Terai, H King, KR Weinberg, EJ Kaazempur-Mofrad, MR Vacanti, JP AF Borenstein, JT Terai, H King, KR Weinberg, EJ Kaazempur-Mofrad, MR Vacanti, JP TI Microfabrication technology for vascularized tissue engineering SO BIOMEDICAL MICRODEVICES LA English DT Article DE tissue engineering; MEMS; microfabrication; microfluidics ID FIBROBLASTS; MORPHOMETRY; FABRICATION; SYSTEMS AB This work describes the application of advanced microfabrication technologies including silicon micromachining and polymer replica molding towards the field of tissue engineering of complex tissues and organs. As a general approach, tissue engineering of skin, bone and cartilage using cell transplantation on biodegradable matrices has achieved great success. However, such techniques encounter difficulties when applied to complex tissues and vital organs. The principal limitation for such applications is the lack of an intrinsic blood supply for the tissue engineered organ, which experiences significant cell death when the tissue thickness is increased above the 1-2 mm range. In this work, the concept of microfabricated scaffolds is introduced, with the goal of producing organ templates with feature resolution oft micron, well in excess of that necessary to fashion the capillaries which comprise the microcirculation of the organ. Initial efforts have resulted in high resolution biocompatible polymer scaffolds produced by replica molding from silicon micromachined template wafers. These scaffolds have been successfully seeded with endothelial cells in channels with dimensions as small as the capillaries. C1 Charles Stark Draper Lab Inc, MEMS Technol Grp, Cambridge, MA 02139 USA. MIT, Dept Engn Mech, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Ctr Integrat Med & Innovat Technol, Cambridge, MA USA. RP Borenstein, JT (reprint author), Charles Stark Draper Lab Inc, MEMS Technol Grp, Cambridge, MA 02139 USA. NR 26 TC 239 Z9 245 U1 5 U2 53 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1387-2176 J9 BIOMED MICRODEVICES JI Biomed. Microdevices PD JUL PY 2002 VL 4 IS 3 BP 167 EP 175 DI 10.1023/A:1016040212127 PG 9 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA 589TN UT WOS:000177776600002 ER PT J AU Helander, KG Widehn, S Helander, HF AF Helander, KG Widehn, S Helander, HF TI Kinetic studies of glutaraldehyde binding in liver SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Biological Stain Commission (BSC) CY JUN 07, 2002 CL ROCKVILLE, MARYLAND SP Biol Stain Commiss DE electron microscopy; fixation; glutaraldehyde; immunohistochemistry; kinetics; light microscopy; liver AB To study the kinetics of glutaraldehyde fixation, fresh rabbit liver cubes were immersed in 3% buffered H-3-glutaraldehyde for various periods of time. Following weighing and a brief rinse in water, the tissues were solubilized, and the radioactivity was measured in a scintillation counter. Binding of the isotope was half-maximal after approximately 4 h and a plateau was reached after approximately 20 h. We also investigated the reversibility of glutaraldehyde fixation. Fixed liver cubes were weighed and immersed in water for various periods of time, and after solubilization, the radioactivity was determined. After rinsing for 48 h, approximately 95% of the radioactivity was lost from the tissue specimens, indicating that fixation with glutaraldehyde is largely reversible. Light and electron microscopy of specimens rinsed for 1 and 48 h showed essentially similar morphology. Rinsing for 48 h restored some of the immunoreactivity that was absent after rinsing for only 1 h. C1 Univ Calif Los Angeles, W Los Angeles VA Hosp, Lab Membrane Biol, Los Angeles, CA 90073 USA. Gothenburg Univ, Dept Biomed Lab Sci, S-41345 Gothenburg, Sweden. Gothenburg Univ, Dept Pathol, S-41345 Gothenburg, Sweden. RP Helander, KG (reprint author), Univ Gothenburg, Dept Biomed Lab Sci, POB 419, S-40530 Gothenburg, Sweden. FU NIDDK NIH HHS [DK46917, DK58333] NR 9 TC 3 Z9 3 U1 2 U2 8 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD JUL PY 2002 VL 77 IS 4 BP 207 EP 212 DI 10.1080/714028200 PG 6 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA 618PC UT WOS:000179425600005 PM 12503730 ER PT J AU Krackhardt, AM Harig, S Witzens, M Broderick, R Barrett, P Gribben, JG AF Krackhardt, AM Harig, S Witzens, M Broderick, R Barrett, P Gribben, JG TI T-cell responses against chronic lymphocytic leukemia cells: implications for immunotherapy SO BLOOD LA English DT Article ID FOLLICULAR LYMPHOMA-CELLS; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; NORMAL B-CELLS; IMMUNE-RESPONSES; GAMMA PRODUCTION; DENDRITIC CELLS; INDUCTION; VACCINATION; MALIGNANCIES AB Chronic lymphocytic, leukemia (CLL) cells are ineffective antigen-presenting cells (APCs) although CD40-activated CLL cells can stimulate proliferation of autologous and allogeneic T cells. We examined the antigen-presenting capacity of CD40-, activated CLL cells as well as dendritic cells pulsed with apoptotic bodies of CLL cells to generate autologous and allogeneic immune responses against CLL cells. Both APC types were capable of generating T-cell lines that proliferate specifically in response to unstimulated CLL cells. Whereas cytotoxic responses against stimulated and unstimulated CLL cells could be repeatedly generated by allogeneic healthy donors, autologous cytotoxic immune responses against CD40-activated and native CLL cells were rarely detected. However, T cells isolated from patients with CLL could recognize and lyse allogeneic stimulated and unstimulated CLL cells, demonstrating that cytotoxic T cells from these tumor-bearing patients are functionally intact. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Gribben, JG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [81534] NR 42 TC 61 Z9 62 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 JUL 1 PY 2002 VL 100 IS 1 BP 167 EP 173 DI 10.1182/blood.V100.1.167 PG 7 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400024 PM 12070023 ER PT J AU Kogan, SC Ward, JM Anver, MR Berman, JJ Brayton, C Cardiff, RD Carter, JS de Coronado, S Downing, JR Fredrickson, TN Haines, DC Harris, AW Harris, NL Hiai, H Jaffe, ES MacLennan, ICM Pandolfi, PP Pattengale, PK Perkins, AS Simpson, RM Tuttle, MS Wong, JF Morse, HC AF Kogan, SC Ward, JM Anver, MR Berman, JJ Brayton, C Cardiff, RD Carter, JS de Coronado, S Downing, JR Fredrickson, TN Haines, DC Harris, AW Harris, NL Hiai, H Jaffe, ES MacLennan, ICM Pandolfi, PP Pattengale, PK Perkins, AS Simpson, RM Tuttle, MS Wong, JF Morse, HC TI Bethesda proposals for classification of nonlymphoid hematopoietic neoplasms in mice SO BLOOD LA English DT Article ID MYELOID-LEUKEMIA AB The hematopathology subcommittee of the Mouse Models of Human Cancers Consortium recognized the need for a classification of murine hematopoietic neoplasms that would allow investigators to diagnose lesions as well-defined entities according to accepted criteria. Pathologists and investigators worked cooperatively to develop proposals for the classification of lymphoid and nonlymphoid hematopoietic neoplasms. It is proposed here that nonlymphoid hematopoietic neoplasms of mice be classified in 4 broad categories: nonlymphoid leukemias, nonlymphoid hematopoietic sarcomas, myeloid dysplasias, and myeloid proliferations (nonreactive). Criteria for diagnosis and subclassification of these lesions include peripheral blood findings, cytologic features of hematopoietic tissues, histopathology, immunophenotyping, genetic features, and clinical course. Differences between murine and human lesions are reflected in the terminology and methods used for classification. This classification will be of particular value to investigators seeking to develop, use, and communicate about mouse models of human hematopoietic neoplasms. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Apelon Inc, Alameda, CA USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA. Childrens Hosp Los Angeles, Dept Pathol, Los Angeles, CA 90027 USA. Baylor Coll Med, Ctr Comparat Med, Houston, TX 77030 USA. Kyoto Univ, Grad Sch Med, Dept Pathol & Biol Dis, Kyoto, Japan. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Cornell Univ, Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NCI, Canc Diag Program, Ctr Bioinformat, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. NCI, Tumor Pathol Sect, Frederick, MD 21701 USA. NCI, SAIC, Frederick, MD 21701 USA. NIAID, Infect Dis Pathogenesis Branch, Rockville, MD USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Univ Birmingham, Sch Med, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Melbourne, Vic, Australia. Yale Univ, Dept Pathol, New Haven, CT 06510 USA. RP Kogan, SC (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 2340 Sutter St,Rm N-361,Box 0128, San Francisco, CA 94143 USA. EM skogan@cc.ucsf.edu OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA75986, CA84221, N01-CO-56000] NR 16 TC 267 Z9 273 U1 1 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 JUL 1 PY 2002 VL 100 IS 1 BP 238 EP 245 DI 10.1182/blood.V100.1.238 PG 8 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400034 PM 12070033 ER PT J AU Morse, HC Anver, MR Fredrickson, TN Haines, DC Harris, AW Harris, NL Jaffe, ES Kogan, SC MacLennan, ICM Pattengale, PK Ward, JM AF Morse, HC Anver, MR Fredrickson, TN Haines, DC Harris, AW Harris, NL Jaffe, ES Kogan, SC MacLennan, ICM Pattengale, PK Ward, JM TI Bethesda proposals for classification of lymphoid neoplasms in mice SO BLOOD LA English DT Article ID B-CELL LYMPHOMAS; MARGINAL ZONE; C57BL/6 MICE; IMMUNODEFICIENCY SYNDROME; NATURAL-KILLER; MURINE AIDS; T-CELLS; LEUKEMIA; MOUSE; MODEL AB A consensus system for classification of mouse lymphoid neoplasms according to their histopathologic and genetic features has been an elusive target for investigators involved in understanding the pathogenesis of spontaneous cancers or modeling human hematopoietic diseases in mice. An international panel of scientists with expertise in mouse and human hematopathology joined with the hematopathology subcommittee of the Mouse Models for Human Cancers Consortium to develop criteria for definition and classification of these diseases together with a standardized nomenclature. The fundamental elements contributing to the scheme are clinical features, morphology, immunophenotype, and genetic characteristics. The resulting classification has numerous parallels to the World Health Organization classification of human lymphoid tumors while recognizing differences that may be species specific. The classification should facilitate communications about mouse models of human lymphoid diseases. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Pathol Histotechnol Lab, SAIC Frederick, NIH, Frederick, MD 21701 USA. NCI, Vet & Tumor Pathl Sect, Ctr Canc Res, NIH, Frederick, MD 21701 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Birmingham, Sch Med, Birmingham, W Midlands, England. RP Morse, HC (reprint author), 7 Ctr Dr,Rm 7-304,MSC 0760, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [N01-CO56000] NR 46 TC 228 Z9 233 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 JUL 1 PY 2002 VL 100 IS 1 BP 246 EP 258 DI 10.1182/blood.V100.1.246 PG 13 WC Hematology SC Hematology GA 567GQ UT WOS:000176477400035 PM 12070034 ER PT J AU Lee, M Martin-Ruiz, C Graham, A Court, J Jaros, E Perry, R Iversen, P Bauman, M Perry, E AF Lee, M Martin-Ruiz, C Graham, A Court, J Jaros, E Perry, R Iversen, P Bauman, M Perry, E TI Nicotinic receptor abnormalities in the cerebellar cortex in autism SO BRAIN LA English DT Article DE autism; cerebellum; cholinergic system; nicotinic receptors; muscarinic receptors ID POSTERIOR-FOSSA; BRAIN-STEM; ACETYLCHOLINE-RECEPTORS; INFANTILE-AUTISM; CHOLINE-ACETYLTRANSFERASE; MUSCARINIC RECEPTORS; PRENATAL DEVELOPMENT; COGNITIVE DEFICITS; CORPUS-CALLOSUM; BASAL FOREBRAIN AB Autism is a common developmental disorder associated with structural and inferred neurochemical abnormalities of the brain. Cerebellar abnormalities frequently have been identified, based on neuroimaging or neuropathology. Recently, the cholinergic neurotransmitter system has been implicated on the basis of nicotinic receptor loss in the cerebral cortex. Cerebellar cholinergic activities were therefore investigated in autopsy tissue from a series of autistic individuals. The presynaptic cholinergic enzyme, choline acetyltransferase, together with nicotinic and muscarinic receptor subtypes were compared in the cerebellum from age-matched mentally retarded autistic (eight), normal control (10) and non-autistic mentally retarded individuals (11). The nicotinic receptor binding the agonist epibatidine (the high affinity receptor subtype, consisting primarily of alpha3 and alpha4, together with beta2 receptor subunits) was significantly reduced by 40-50% in the granule cell, Purkinje and molecular layers in the autistic compared with the normal group (P < 0.05). There was an opposite increase (3-fold) in the nicotinic receptor binding α-bungarotoxin (to the α7 subunit) which reached significance in the granule cell layer (P < 0.05). These receptor changes were paralleled by a significant reduction (P < 0.05) and non-significant increase, respectively, of α4 and α7 receptor subunit immunoreactivity measured using western blotting. Immunohistochemically loss of α(4) reactivity was apparent from Purkinje and the other cell layers, with increased α7 reactivity in the granule cell layer. There were no significant changes in choline acetyltransferase activity, or in muscarinic M1 and M2 receptor subtypes in autism. In the non-autistic mentally retarded group, the only significant abnormality was a reduction in epibatidine binding in the granule cell and Purkinje layers. In two autistic cases examined histologically, Purkinje cell loss was observed in multiple lobules throughout the vermis and hemispheres. This was more severe in one case with epilepsy, which also showed vermis folial malformation. The case with less severe Purkinje cell loss also showed cerebellar white matter thinning and demyelination. These findings indicate a loss of the cerebellar nicotinic α4 receptor subunit in autism which may relate to the loss of Purkinje cells, and a compensatory increase in the α7 subunit. It remains to be determined how these receptor abnormalities are involved in neurodevelopment in autism and what is the relationship to mental function. Since nicotinic receptor agonists enhance attentional function and also induce an elevation in the high affinity receptor, nicotinic therapy in autism may be worth considering. C1 Newcastle Gen Hosp, Dept Neuropathol, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. MRC Univ Newcastle Tyne Dev Clin Brain Ageing, Newcastle Upon Tyne, Tyne & Wear, England. Cure Autism Now, Los Angeles, CA USA. Harvard Univ, Sch Med, Childrens Neurol Serv, Massachusetts Gen Hosp, Boston, MA USA. RP Perry, E (reprint author), Newcastle Gen Hosp, Dept Neuropathol, MRC Bldg,Westgate Rd, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. NR 81 TC 123 Z9 125 U1 5 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2002 VL 125 BP 1483 EP 1495 DI 10.1093/brain/awf160 PN 7 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 572PE UT WOS:000176783500006 PM 12076999 ER PT J AU Miller, KW Richards, CD Roth, SH Urban, BW AF Miller, KW Richards, CD Roth, SH Urban, BW TI Molecular and basic mechanisms of anaesthesia SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Edwards 505, Boston, MA 02114 USA. UCL, Dept Physiol, London WC1E 6JJ, England. Univ Calgary, Fac Med, Dept Pharmacol & Therapeut, Calgary, AB T2N 4N1, Canada. Univ Calgary, Fac Med, Dept Anesthesia, Calgary, AB T2N 4N1, Canada. Univ Klinikum Bonn, Klin Anasthesiol & Spezielle Intens Med, D-53127 Bonn, Germany. RP Miller, KW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Edwards 505, Blossom St, Boston, MA 02114 USA. NR 2 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUL PY 2002 VL 89 IS 1 BP 1 EP 2 DI 10.1093/bja/aef192 PG 2 WC Anesthesiology SC Anesthesiology GA 573JE UT WOS:000176825400001 PM 12173222 ER PT J AU Miller, KW AF Miller, KW TI The nature of sites of general anaesthetic action SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthesia, general; anaesthesia, binding sites ID NICOTINIC ACETYLCHOLINE-RECEPTOR; NUCLEOSIDE MONOPHOSPHATE KINASES; CAENORHABDITIS-ELEGANS; ANESTHETIC BINDING; GLYCINE RECEPTORS; LIGAND-BINDING; SERUM-ALBUMIN; XENON COMPLEX; ION-CHANNEL; T4 LYSOZYME C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM5848] NR 74 TC 76 Z9 85 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUL PY 2002 VL 89 IS 1 BP 17 EP 31 DI 10.1093/bja/aef167 PG 15 WC Anesthesiology SC Anesthesiology GA 573JE UT WOS:000176825400003 PM 12173229 ER PT J AU Tulpule, A Groopman, J Saville, MW Harrington, W Friedman-Kien, A Espina, BM Garces, C Mantelle, L Mettinger, K Scadden, DT Gill, PS AF Tulpule, A Groopman, J Saville, MW Harrington, W Friedman-Kien, A Espina, BM Garces, C Mantelle, L Mettinger, K Scadden, DT Gill, PS TI Multicenter trial of low-dose paclitaxel in patients with advanced AIDS-related Kaposi sarcoma SO CANCER LA English DT Article DE paclitaxel; Paxene; AIDS; Kaposi sarcoma; chemotherapy ID PHASE-II; VINCRISTINE; BLEOMYCIN; DAUNORUBICIN; DOXORUBICIN; REGRESSION; INFECTION; THERAPY AB BACKGROUND. Treatment options are limited for patients with advanced acquired immunodeficieny syndrome (AIDS)-related Kaposi sarcoma (AIDS-KS) whose disease has progressed after receiving therapy with liposomal anthracyclines or combination chemotherapy with doxorubicin (Adriamycin), bleomycin, and vincristine (ABV). This study was performed to assess the safety and efficacy of a novel dose and schedule of paclitaxel in patients with AIDS-KS who failed to respond to previous systemic chemotherapy. METHODS. This was an open-label, multicenter Phase II study. Eligible patients had advanced AIDS-KS consisting of at least 25 mucocutaneous lesions, visceral disease, or lymphedema, and had failed to respond to at least one previous systemic chemotherapy regimen. Patients were treated with paclitaxel at a dose of 100 mg/m(2) given intravenously over 3 hours, every 2 weeks. Primary efficacy end points were tumor response, time to progression, time to treatment failure, and survival. Quality of life and adverse events were evaluated using the Symptom Distress Scale (SDS) and the World Health Organization Toxicity Criteria, respectively. RESULTS. One hundred and seven male patients with advanced AIDS-KS were enrolled from nine participating sites. The median entry CD4+ lymphocyte count was 41/mm(3) (range 0-1139). Previous treatment regimens included A13V in 52, liposomal daunorubicin in 49, and liposomal doxorubicin in 40 patients. Forty-one patients (38%) received two or more previous chemotherapy regimens. Protease inhibitor use during the study was reported by 82 (77%) patients overall; 47 patients (44%) were receiving a protease inhibitor before study entry. Complete or partial response was documented in 60 patients (56%) The median duration of response was 8.9 months. Major response rate was similar when comparing patients not on a protease inhibitor at the time of response (59%) with patients on a protease inhibitor at time of response (54%). However, protease inhibitor use had a significant impact on survival (P = 0.04). Grade 4 neutropenia was reported in 35% of patients; other life-threatening side effects were uncommon. Significant improvements were seen in the total quality of life scores measured by the SDS, including significant improvement in KS-related symptoms such as faciat disease, tumor-associated edema, and pulmonary involvement. CONCLUSION. Paclitaxel given every 2 weeks induces major tumor regression in the majority of patients with advanced KS who failed to respond to previous systemic chemotherapy. Paclitaxel is associated with significant improvement in quality of life with acceptable toxicity and should be considered as an effective treatment option for patients with advanced KS. (C) 2002 American Cancer Society. C1 Univ So Calif, Sch Med, Kenneth Norris Canc Hosp & Res Inst, Dept Med,Div Hematol, Los Angeles, CA 90033 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Miami, Med Ctr, Sylvester Canc Ctr, Miami, FL 33152 USA. NYU, Med Ctr, New York, NY 10016 USA. Baker Norton Pharmaceut Inc, Miami, FL USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. RP Gill, PS (reprint author), Univ So Calif, Sch Med, Kenneth Norris Canc Hosp & Res Inst, Dept Med,Div Hematol, 1441 Eastlake Ave MC 9172, Los Angeles, CA 90033 USA. OI Friedman Kien, Alvin/0000-0002-5854-2852 NR 26 TC 77 Z9 79 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 JUL 1 PY 2002 VL 95 IS 1 BP 147 EP 154 DI 10.1002/cncr.10634 PG 8 WC Oncology SC Oncology GA 569XK UT WOS:000176627800020 PM 12115328 ER PT J AU Elkahloun, AG Gaudet, J Robinson, GS Sgroi, DC AF Elkahloun, AG Gaudet, J Robinson, GS Sgroi, DC TI In situ gene expression analysis of cancer using loser capture microdissection, Microarrays and real time quantitative PCR SO CANCER BIOLOGY & THERAPY LA English DT Review DE laser capture microdissection; gene expression; microarrays; real-time quantitative PCR ID BREAST-CANCER; MOLECULAR ANALYSIS; CDNA MICROARRAYS; EPITHELIAL-CELLS; MESSENGER-RNA; LASER; CARCINOMA; PATTERNS; HYBRIDIZATION; PROFILES AB The simultaneous development of laser capture microdissection (LCM) and high-throughput mRNA analysis platforms has provided a significant technological advance in the world of cancer biology. The combination of such technologies provides a unique and powerful opportunity to directly assess the in situ molecular genetic events that are associated with initiation and progression of human malignancies. Despite these technological advances, the integration of LCM with high-throughput gene expression analysis has been met with various challenges. The goal of this review is to highlight some of the obstacles that we have faced and continue to face as we try to optimally apply LCM to in situ gene expression analysis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Pharmacia Corp, St Louis, MO 63198 USA. RP Sgroi, DC (reprint author), Harvard Univ, Sch Med, Dept Pathol, Charlestown Navy Yard, Boston, MA 02129 USA. NR 36 TC 22 Z9 23 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2002 VL 1 IS 4 BP 354 EP 358 PG 5 WC Oncology SC Oncology GA 645TW UT WOS:000180996300006 PM 12432245 ER PT J AU Hahn, WC AF Hahn, WC TI Senescence, telomere shortening and telomere maintenance SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE telomerase; Li-Fraumeni syndrome; replicative lifespan; chromosomal instability ID EPITHELIAL-CELLS; IMMORTAL CELLS; LIFE-SPAN; INACTIVATION; CANCER; INSTABILITY; MECHANISMS; GROWTH C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. FU NCI NIH HHS [K01 CA94223] NR 21 TC 5 Z9 6 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2002 VL 1 IS 4 BP 398 EP 400 PG 3 WC Oncology SC Oncology GA 645TW UT WOS:000180996300015 PM 12432254 ER PT J AU Pardee, AB AF Pardee, AB TI Role reversal for anticancer agents SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE cancer; chemotherapy; checkpoint; flavopiridol; paclitaxel ID BREAST-CANCER CELLS; INDUCED APOPTOSIS; KINASE; FLAVOPIRIDOL C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Harvard Univ, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 14 TC 9 Z9 10 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2002 VL 1 IS 4 BP 426 EP 427 PG 2 WC Oncology SC Oncology GA 645TW UT WOS:000180996300021 PM 12432260 ER PT J AU Rubin, JB Rowitch, DH AF Rubin, JB Rowitch, DH TI Medulloblastoma: A problem of developmental biology SO CANCER CELL LA English DT Article C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rubin, JB (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 9 TC 46 Z9 47 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2002 VL 2 IS 1 BP 7 EP 8 DI 10.1016/S1535-6108(02)00090-9 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UA UT WOS:000178352500004 PM 12150819 ER PT J AU Fantin, VR Berardi, MJ Scorrano, L Korsmeyer, SJ Leder, P AF Fantin, VR Berardi, MJ Scorrano, L Korsmeyer, SJ Leder, P TI A novel mitochondriotoxic small molecule that selectively inhibits tumor cell growth SO CANCER CELL LA English DT Article ID PERMEABILITY TRANSITION PORE; BOVINE HEART MITOCHONDRIAL; CARCINOMA-CELLS; FACTOR RECEPTOR; PHASE-I; LIVER-MITOCHONDRIA; ANTITUMOR-ACTIVITY; LIPOPHILIC CATION; ANTICANCER AGENTS; RHODACYANINE DYE AB Tumorigenesis results from events that impinge on a variety of collaborating metabolic pathways. To assess their role in this process, we utilized a cell-based assay to perform a high-throughput, chemical library screen. In so doing, we identified F16, a small molecule that selectively inhibits proliferation of mammary epithelial, neu-overexpressing cells, as well as a variety of mouse mammary tumor and human breast cancer cell lines. F16 belongs to a group of structurally similar molecules with a delocalized positive charge. The compound is accumulated in mitochondria of responsive cells, driven by the membrane potential, and it compromises their functional integrity. Mitochondrial hyperpolarization is a shared feature of many tumor cell lines, explaining the broad action spectrum of this novel delocalized lipophilic cation. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Leder, P (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 NR 58 TC 137 Z9 146 U1 3 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2002 VL 2 IS 1 BP 29 EP 42 DI 10.1016/S1535-6108(02)00082-X PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UA UT WOS:000178352500008 PM 12150823 ER PT J AU Ramaswamy, S Nakamura, N Sansal, I Bergeron, L Sellers, WR AF Ramaswamy, S Nakamura, N Sansal, I Bergeron, L Sellers, WR TI A novel mechanism of gene regulation and tumor suppression by the transcription factor FKHR SO CANCER CELL LA English DT Article ID FACTOR-BINDING PROTEIN-1; INSULIN-RESPONSE UNIT; CAENORHABDITIS-ELEGANS; FAMILY MEMBER; KINASE-B; PHOSPHOENOLPYRUVATE CARBOXYKINASE; GLIOMA-CELLS; DNA-DAMAGE; FACTOR AFX; FORKHEAD AB The mammalian DAF-16-like transcription factors, FKHR, FKHRL1, and AFX, function as key regulators of insulin signaling, cell cycle progression, and apoptosis downstream of phosphoinositide 3-kinase. Gene activation through binding to insulin response sequences (IRS) has been thought to be essential for mediating these functions. However, using transcriptional profiling, chromatin immunoprecipitation, and functional experiments, we demonstrate that rather than activation of IRS regulated genes (Class I transcripts), transcriptional repression of D-type cyclins (in Class 111) is required for FKHR mediated inhibition of cell cycle progression and transformation. These data suggest that a novel mechanism of FKHR-mediated gene regulation is linked to its activity as a suppressor of tumor growth. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Millennium Pharmaceut, Div Oncol, Cambridge, MA 02139 USA. RP Sellers, WR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA85912] NR 44 TC 273 Z9 276 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUL PY 2002 VL 2 IS 1 BP 81 EP 91 DI 10.1016/S1535-6108(02)00086-7 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UA UT WOS:000178352500012 PM 12150827 ER PT J AU Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Chauhan, D Richardson, P Munshi, NC Anderson, KC AF Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Chauhan, D Richardson, P Munshi, NC Anderson, KC TI Cytokines modulate telomerase activity in a human multiple myeloma cell line SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; GROWTH-FACTOR-I; INDUCED APOPTOSIS; DRUG-RESISTANCE; PLASMA-CELLS; KINASE; INTERLEUKIN-6; INHIBITION; ACTIVATION; SURVIVAL AB Telomerase is a ribonucleoprotein DNA polymerase that elongates the telomeres of chromosomes to compensate for losses that occur with each round of DNA replication and maintain chromosomal stability. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) are proliferative and survival factors for human multiple myeloma (MM) cells. To date, however, the effects of IGF-1 and IL-6 on telomerase activity and associated sequelae in MM cells have not been characterized. In this study, we evaluated the effects of IGF-1 and IL-6 on telomerase activity in MM cell lines (MM.1S, U266, and RPMI 8226), as well as patient MM cells. We show that these cytokines up-regulate telomerase activity without alteration of human telomerase reverse transcriptase (hTERT) protein expression. We also demonstrate that increased telomerase activity triggered by these cytokines is mediated by phosphatidylinositol 3'-kinase (PI3k)/Akt/nuclear factor kappaB (NFkappaB) signaling. We confirm involvement of PI3k/Akt/NFkappaB signaling because the PI3k inhibitors wortmannin and LY294002 or the inhibitor of NFkappaB (IkappaB) kinase inhibitor PS-1145 block constitutive and cytokine-induced up-regulation of telomerase activity. Furthermore, we show that dexamethasone (Dex) reduces telomerase activity through the inhibition of hTERT expression before the induction of apoptosis. Importantly, IGF-1 and IL-6 abrogate Dex-induced down-regulation of telomerase activity and apoptosis. The protective effect of those cytokines against Dex-induced down-regulation of telomerase activity is blocked by both wortmannin and PS-1145, whereas the protection against Dex-induced apoptosis is blocked by wortmannin but not PS-1145. Therefore, our results demonstrate that telomerase activity is related not only to transcriptional regulation of hTERT by NFkappaB but also to post-transcriptional regulation because of phosphorylation of hTERT by Akt kinase. These studies therefore demonstrate that telomerase activity is associated with cell growth, survival, and drug resistance in MM cells. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 43 TC 134 Z9 138 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2002 VL 62 IS 13 BP 3876 EP 3882 PG 7 WC Oncology SC Oncology GA 569BL UT WOS:000176579500049 PM 12097303 ER PT J AU Houser, SL Askenase, PW Palazzo, E Bloch, KJ AF Houser, SL Askenase, PW Palazzo, E Bloch, KJ TI Valvular heart disease in patients with hypocomplementemic urticarial vasculitis syndrome associated with Jaccoud's arthropathy SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE heart valve; hypocomplementemic vasculitis syndrome arthropathy ID DEFICIENCY; ARTHRITIS AB Background: Since 1973, more than 75 patients with hypocomplementemic urticarial vasculitis syndrome (HUVS) were reported, but valvular heart disease does not seem to have been noted in these patients. Since 1993, however, five patients with HUVS accompanied by Jaccoud's arthropathy (JA) were found to have serious valvular heart disease. Methods: To characterize the cardiac valvulopathy of the third patient with HUVS/JA to have undergone valve replacement, this Study included the use of routine and special tissue stains, as well as immunohistochemical staining. We compared gross and histologic findings of this patient's valve to those of two other patients with this complex syndrome Who underwent valve replacement. Pathologic findings of these latter two patients were described in separate earlier reports. Results: Histologic examination of the resected valves in all three patients showed an acute necrotizing endocarditis and fibrin deposition on the surface of valve leaflets. Beneath the surfaces of the leaflets, there was evidence of chronic inflammation, consisting of lymphocytes and histiocytes. A fibrocalcific degenerative change was also present in all three valves. Positive staining for IgG, IgA, IgM, and light-chain determinant-bearing proteins was detected primarily at the valve surface in special Studies of the aortic valve of the patient described in the current report. Conclusion: Patients with HUVS and associated JA should be evaluated for the presence of valvular heart disease. The latter is probably a nonheumatic, inflammatory, and degenerative process, mediated by immune complex, as well as cellular immune mechanisms. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Cardiovasc Pathol Sect, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Hop Xavier Bichat, Med Sch Xavier Bichat, Dept Rheumatol, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Clin Immunol Unit, Boston, MA 02114 USA. RP Houser, SL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Cardiovasc Pathol Sect, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 15 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 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JUL-AUG PY 2002 VL 11 IS 4 BP 210 EP 216 AR PII S1054-8807(02)00107-2 DI 10.1016/S1054-8807(02)00107-2 PG 7 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 584XW UT WOS:000177494900002 PM 12140126 ER PT J AU Halgren, E Boujon, C Clarke, J Wang, C AF Halgren, E Boujon, C Clarke, J Wang, C TI Rapid distributed fronto-parieto-occipital processing stages during working memory in humans SO CEREBRAL CORTEX LA English DT Review ID CONTINGENT NEGATIVE-VARIATION; HUMAN HIPPOCAMPAL-FORMATION; POSITRON EMISSION TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; DEPTH-RECORDED POTENTIALS; MEDIAL TEMPORAL-LOBE; PREFRONTAL CORTEX; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; RHESUS-MONKEY AB Cortical potentials were recorded from implanted electrodes during a difficult working memory task requiring rapid storage, modification and retrieval of multiple memoranda. Synchronous event-related potentials were generated in distributed occipital, parietal, Rolandic and prefrontal sites beginning similar to130 ms after stimulus onset and continuing for >500 ms. Coherent phase-locked, event-related oscillations supported interaction between these dorsal stream structures throughout the task period. The Rolandic structures generated early as well as sustained potentials to sensory stimuli in the absence of movement. Activation peaks and phase lags between synaptic populations suggested that perceptual processing occurred exclusively in the visual association cortex from similar to90 to 130 ms, with its results projected to fronto-parietal areas for interpretation from similar to130 to 280 ms. The direction of interaction then appeared to reverse from similar to300 to 400 ms, consistent with mental arithmetic being performed by fronto-parietal areas operating upon a visual scratch pad in the dorsolateral occipital cortex. A second reversal, from similar to420 to 600 ms, may have represented an updating of memoranda stored in fronto-parietal sites. Lateralized perisylvian oscillations suggested an articulatory loop. Anterior cingulate activity was evoked by feedback signals indicating errors. These results indicate how a fronto-centro-parietal 'central executive' might interact with an occipital visual scratch pad, perisylvian articulatory loop and limbic monitor to implement the sequential stages of a complex mental operation. C1 CHU Pontchaillou, INSERM, CJF90 12, F-35033 Rennes, France. RP Halgren, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Nucl Med Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS18741, R01 NS018741] NR 121 TC 70 Z9 73 U1 3 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 2002 VL 12 IS 7 BP 710 EP 728 DI 10.1093/cercor/12.7.710 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 562YT UT WOS:000176227100004 PM 12050083 ER PT J AU Sydora, BC Wagner, N Lohler, J Yakoub, G Kronenberg, M Muller, W Aranda, R AF Sydora, BC Wagner, N Lohler, J Yakoub, G Kronenberg, M Muller, W Aranda, R TI beta 7 Integrin expression is not required for the localization of T cells to the intestine and colitis pathogenesis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE beta 7 integration; colitis; T cells; trafficking ID INFLAMMATORY-BOWEL-DISEASE; L-SELECTIN; SCID MICE; ULCERATIVE-COLITIS; CD4(+); CD45RB(HIGH); LYMPHOCYTES; ADHESION; PREVENTS; PATCHES AB beta7 Integrins have been shown to have an important role in the localization of T cells to the intestine. Utilizing two different experimental mouse models of inflammatory bowel disease (IBD), this study was undertaken to determine if beta7 integrin expression is critical for T cell localization to the intestine and colitis pathogenesis. Transfer of CD4(+) CD45RB(high) cells into immunodeficient mice results in colitis. To examine the role of beta7 integrins, donor cells were obtained from beta7 integrin gene-deficient animals and disease induction was examined following transfer into severe combined immunodeficiency (SCID) mice. Additionally, beta7 integrin gene-deficient animals were crossed to IL-2-deficient mice and the onset of spontaneous colitis that normally occurs in IL-2-deficient animals was examined. No differences in the onset or severity of spontaneous colitis was noted in animals that were deficient in both beta7 integrin and IL-2. In contrast, the onset of colitis in recipients of T cells from beta7 integrin-deficient donors was delayed significantly. In mice receiving beta7 integrin negative cells, the initial lack of colitis appeared to correlate with fewer numbers of CD3(+) beta7 integrin -/- donor lymphocytes present in the host colon. The eventual development of disease, however, was associated with increased numbers of donor beta7 integrin -/- lymphocytes. These results show that beta7 integrin expression is not absolutely required for T cell localization to the intestine and colitis pathogenesis. C1 Univ Cologne, Inst Genet, D-5000 Cologne 41, Germany. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Bonn, Dept Paediat, D-5300 Bonn, Germany. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, Hamburg, Germany. La Jolla Inst Allergy & Immunol, La Jolla, CA 92093 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sydora, BC (reprint author), Univ Alberta, Div Gastroenterol, 519 NRB,11315 87 Ave, Edmonton, AB T6G 2C2, Canada. RI Muller, Werner/B-9044-2008 OI Muller, Werner/0000-0002-1297-9725 FU NIDDK NIH HHS [P01 DK046763, P01 DK46763] NR 26 TC 35 Z9 36 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2002 VL 129 IS 1 BP 35 EP 42 DI 10.1046/j.1365-2249.2002.01892.x PG 8 WC Immunology SC Immunology GA 567ZP UT WOS:000176518200006 PM 12100020 ER PT J AU Zorn, E Wang, KS Hochberg, EP Canning, C Alyea, EP Soiffer, RJ Ritz, J AF Zorn, E Wang, KS Hochberg, EP Canning, C Alyea, EP Soiffer, RJ Ritz, J TI Infusion of CD4+ donor lymphocytes induces the expansion of CD8+ donor T cells with cytolytic activity directed against recipient hematopoietic cells SO CLINICAL CANCER RESEARCH LA English DT Article ID BONE-MARROW TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST DISEASE; CHRONIC MYELOID-LEUKEMIA; CLASS-I MOLECULES; BCR-ABL; IMMUNE RECONSTITUTION; LEUKOCYTE INFUSIONS; FREE SURVIVAL AB Purpose: Donor lymphocyte infusions (DLIs) provide effective therapy for patients with relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation. Previous studies have suggested that depletion of CD8+ T cells from the infused donor lymphocytes can reduce the incidence of graft-versus-host disease associated with DLI without reducing antileukemia activity. In this situation however, the immune effector cells responsible for tumor rejection have not been identified. The goal of this study was to characterize these effector populations. Experimental Design: We studied three representative patients with relapsed chronic myeloid leukemia who achieved complete molecular remission after receiving CD8+ T-cell-depleted DLI from HLA-identical sibling donors. Effector T cells were characterized in patient samples after in vitro stimulation and functional assessment. T-cell clones relevant to the immune response were then isolated and further characterized. Results: Analysis of peripheral blood samples collected after DLI indicated the presence of a high frequency of circulating host-reactive cytolytic CD8+ T cells secreting IFN-gamma. These HLA class I-restricted CTLs were specific for recipient minor histocompatibility antigens (mHAs) because they did not recognize target cells of donor origin. One CTL clone was further expanded in vitro and shown to recognize a broadly expressed mHA presented by HLA-B5701. Using a molecular approach, we demonstrated that this clone was expanded in peripheral blood and marrow after DLI. It was not detected before DLI. Conclusions: These results indicate that CD4+ DLI elicits a potent allogeneic response mediated by mHA-specific CD8+ T cells. C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 66996]; NIAID NIH HHS [AI 29530] NR 42 TC 42 Z9 44 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2002 VL 8 IS 7 BP 2052 EP 2060 PG 9 WC Oncology SC Oncology GA 571VR UT WOS:000176740300005 PM 12114403 ER PT J AU Mauvais-Jarvis, F Kulkarni, RN Kahn, CR AF Mauvais-Jarvis, F Kulkarni, RN Kahn, CR TI Knockout models are useful tools to dissect the pathophysiology and genetics of insulin resistance SO CLINICAL ENDOCRINOLOGY LA English DT Review ID PANCREATIC BETA-CELLS; DEPENDENT DIABETES-MELLITUS; ADIPOSE-TISSUE; MICE LACKING; RECEPTOR SUBSTRATE-1; PHOSPHOINOSITIDE 3-KINASE; TARGETED DISRUPTION; MOLECULAR MECHANISMS; GLUCOSE-HOMEOSTASIS; MUSCLE AB OBJECTIVE The development of type 2 diabetes is linked to insulin resistance coupled with a failure of pancreatic beta-cells to compensate by adequate insulin secretion. DESIGN Here, we review studies obtained from genetically engineered mice that provide novel insights into the pathophysiology of insulin resistance. RESULTS Knockout models with monogenic impairment in insulin action have highlighted the potential role for insulin signalling molecules in insulin resistance at a tissue-specific level. Polygenic models have strengthened the idea that minor defects in insulin secretion and insulin action, when combined, can lead to diabetes, emphasizing the importance of interactions of different genetic loci in the production of diabetes. Knockout models with tissue-specific alterations in glucose or lipid metabolism have dissected the individual contributions of insulin-responsive organs to glucose homeostasis. They have demonstrated the central role of fat as an endocrine tissue in the maintenance of insulin sensitivity and the development of insulin resistance. Finally, these models have shown the potential role of impaired insulin action in pancreatic beta-cells and brain in the development of insulin deficiency and obesity. C1 Hop St Louis, Dept Endocrinol & Diabet, F-75010 Paris, France. Univ Paris 07, Sch Med, Inst Cochin Genet Mol, CNRS,UPR 1524, Paris, France. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mauvais-Jarvis, F (reprint author), Hop St Louis, Dept Endocrinol & Diabet, 1 Ave Claude Vellefaux, F-75010 Paris, France. NR 65 TC 54 Z9 56 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 2002 VL 57 IS 1 BP 1 EP 9 DI 10.1046/j.1365-2265.2002.01563.x PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 570BU UT WOS:000176638800001 PM 12100063 ER PT J AU Gurrera, RJ AF Gurrera, RJ TI Is neuroleptic malignant syndrome a neurogenic form of malignant hyperthermia? SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE neuroleptic malignant syndrome; sympathetic nervous system; genetic defects; intracellular calcium regulation ID CREATINE-KINASE ACTIVITY; CENTRAL CORE DISEASE; SYMPATHETIC-NERVE ACTIVITY; CA2+-INDUCED CA2+ RELEASE; RYANODINE RECEPTOR GENE; INDUCED CALCIUM-RELEASE; SKELETAL-MUSCLE FIBERS; SARCOPLASMIC-RETICULUM; SODIUM-CHANNEL; CATECHOLAMINE SECRETION AB Neuroleptic malignant syndrome is a rare and potentially lethal disorder associated with the use of antipsychotic medications. Heightened vigilance on the part of clinical providers has reduced morbidity and mortality caused by this disorder over the past decade, but there is still no consensus regarding its diagnosis, pathophysiology, or treatment. Efforts to demonstrate a direct link between neuroleptic malignant syndrome and malignant hyperthermia have been unsuccessful, indicating mutually distinct etiologies despite striking clinical similarities. This paper concisely reviews essential aspects of electromechanical transduction in muscle and nerve cells and current knowledge concerning the pathophysiology of malignant hyperthermia and neuroleptic malignant syndrome. Utilizing this conceptual framework, the author proposes that neuroleptic malignant syndrome may be caused by a spectrum of inherited defects in genes that are responsible for a variety of calcium regulatory proteins within sympathetic neurons or the higher order assemblies that regulate them. In this proposed model, neuroleptic malignant syndrome may be understood as a neurogenic form of malignant hyperthermia. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02401 USA. VA Boston Healthcare Syst, Boston, MA USA. VA Boston Healthcare Syst, Brockton, MA USA. RP Gurrera, RJ (reprint author), Psychiat 116A,940 Belmont St, Brockton, MA 02301 USA. NR 162 TC 25 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUL-AUG PY 2002 VL 25 IS 4 BP 183 EP 193 DI 10.1097/01.WNF.0000017321.88078.D1 PG 11 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 581UE UT WOS:000177311200001 PM 12151905 ER PT J AU Gerber, A Warner, JJP AF Gerber, A Warner, JJP TI Thermal capsulorrhaphy to treat shoulder instability SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MONOPOLAR RADIOFREQUENCY ENERGY; EHLERS-DANLOS-SYNDROME; JOINT CAPSULE; GLENOHUMERAL JOINT; IN-VIVO; MULTIDIRECTIONAL INSTABILITY; OVINE MODEL; LASER; COLLAGEN; ANTERIOR AB The contemporary therapeutic approach of glenohumeral instability is directed at the restoration of anatomy. Thermal capsular modification to treat shoulder instability is a relatively recent modality. Early successful clinical applications have led to a wide use of this low demanding technique. Currently, however, the indications for thermal capsulorrhaphy are defined poorly, clinical outcome has not been shown to be superior to conventional stabilization procedures, and long-term effects on joint biology and mechanics are not known. Based on a critical review of the literature and personal clinical experience, the authors conclude that additional experimental and clinical investigations are necessary to add this procedure to the accepted modalities applied for the treatment of shoulder instability. C1 Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, 275 Cambridge St,POB 403, Boston, MA 02114 USA. RI Gerber Popp, Ariane/O-2781-2014 OI Gerber Popp, Ariane/0000-0002-6798-3676 NR 67 TC 10 Z9 10 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 JUL PY 2002 IS 400 BP 105 EP 116 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 588LT UT WOS:000177703500013 PM 12072752 ER PT J AU Donati, D Giacomini, S Gozzi, E Salphale, Y Mercuri, M Mankin, HJ Springfield, DS Gebhardt, MC AF Donati, D Giacomini, S Gozzi, E Salphale, Y Mercuri, M Mankin, HJ Springfield, DS Gebhardt, MC TI Allograft arthrodesis treatment of bone tumors: A two-center study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MASSIVE ALLOGRAFTS; GRAFTS; RESECTION AB The current study consists of an outcome review of a consecutive series of 92 patients with knee arthrodesis using an allograft, done for malignant or aggressive tumors in two centers on different continents during a period of 18 years (mean followup, 5 +/- 4 years). The data were compiled by creating a computerized file using the information provided by both centers. Seventy-five of the patients (81%) had high-grade nonmetastatic tumors (Stage II), mostly osteosarcoma. In addition seven (8%) had metastases at outset (Stage III) and the remaining 10 (11%) had benign disease, mostly giant cell tumor or revision procedures for failed allograft or total joint replacement. Seventy-two patients (78%) had distal femoral lesions (78%) whereas the proximal tibia was the site of the tumor in 20 patients (22%). The average age of the patients was 23 +/- 16 years; 51 were males and 41 were females. Tumor complications were a major problem for patients in the series. Thirty-four percent of the patients died, 47% had metastases develop, and 9% had a local recurrence. Allograft complications included an infection rate of 20%, a fracture rate of 25%, and a nonunion rate of 44%. Repeat surgery was required for more than 50% of the patients with 26 requiring one additional operation, 11 requiring two, and 10 requiring three or more operations. Nineteen of the patients required an amputation (20%), only four of which were for recurrent tumor. When these data were compared with data for a control series of 880 patients with allografts other than allograft arthrodeses, the complications were greater and the outcome less successful, suggesting that other approaches should be considered unless there are special indications for this procedure. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ist Ortoped Rizzoli, Bologna, Italy. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, 604 Orthopaed, Boston, MA 02114 USA. NR 24 TC 26 Z9 29 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 JUL PY 2002 IS 400 BP 217 EP 224 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 588LT UT WOS:000177703500026 PM 12072765 ER PT J AU Sheridan, R AF Sheridan, R TI Force or finesse: Maintaining functional residual capacity while practicing lung-protective ventilation SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE acute respiratory distress syndrome; respiratory failure; mechanical ventilation; oxygenation ID RESPIRATORY-DISTRESS SYNDROME; RECRUITMENT; FAILURE; DERECRUITMENT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2002 VL 30 IS 7 BP 1670 EP 1671 DI 10.1097/00003246-200207000-00055 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 573PY UT WOS:000176841100055 PM 12131007 ER PT J AU Dell'Italia, LJ Husain, A AF Dell'Italia, LJ Husain, A TI Dissecting the role of chymase in angiotensin II formation and heart and blood vessel diseases SO CURRENT OPINION IN CARDIOLOGY LA English DT Review ID ACTIVATED MAST-CELLS; CORONARY ATHEROMATOUS EROSION; INTERNAL THORACIC ARTERY; CONVERTING-ENZYME; MYOCARDIAL-INFARCTION; FORMING PATHWAYS; INTERSTITIAL FLUID; VASCULAR CHYMASE; ALPHA-CHYMASE; ATHEROSCLEROTIC AORTA AB Inhibition of angiotensin II action or its formation by angiotensin-converting enzyme has been highly successful in the treatment of cardiovascular diseases. Since the identification of chymase as a major angiotensin II-forming enzyme in the human heart and its vessels more than a decade ago, numerous studies have sought to understand the importance of this enzyme in tissue angiotensin II formation and in the pathogenesis of hypertension, congestive heart failure, and vascular disease. Recent studies show that chymase and angiotensin-converting enzyme regulate angiotensin II production in distinct tissue compartments and that, in the pathogenesis of cardiovascular diseases, chymase-de pendent effects extend beyond its ability to regulate tissue angiotensin II levels. C1 Univ Alabama, Univ Stn, Birmingham Vet Affairs Med Ctr, Dept Med,Div Cardiovasc Dis, Birmingham, AL USA. Victor Chang Cardiac Res Inst, Enzyme Res Unit, Sydney, NSW 2010, Australia. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiol, MCLM 834, 1918 Univ Blvd, Birmingham, AL 35295 USA. RI Husain, Ahsan/J-6861-2012 OI Husain, Ahsan/0000-0003-3426-3469 NR 77 TC 56 Z9 58 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD JUL PY 2002 VL 17 IS 4 BP 374 EP 379 DI 10.1097/01.HCO.0000018700.85782.AB PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 582PK UT WOS:000177360200009 PM 12151872 ER PT J AU Gilliland, DG Griffin, JD AF Gilliland, DG Griffin, JD TI Role of FLT3 in leukemia SO CURRENT OPINION IN HEMATOLOGY LA English DT Review ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; RECEPTOR TYROSINE KINASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; GROWTH-FACTOR RECEPTOR; LYMPHOMA CELL-LINES; HEMATOPOIETIC-CELLS; TRANSGENIC MICE; HEMATOLOGIC MALIGNANCIES AB FLT3 is the most frequently mutated gene in cases of acute myelogenous leukemia (AML). About 30 to 35% of patients have either internal tandem duplications (ITDs) in the juxtamembrane domain or mutations in the activating loop of FLT3. FLT3 mutations occur in a broad spectrum of FAB subtypes in adult and pediatric AML and are particularly common in acute promyelocytic leukemia (APL). FLT3 mutations confer a poor prognosis in most retrospective studies. The consequence of either FLT3-ITD or activating loop mutations, which occur predominantly at position D835, is constitutive activation of the tyrosine kinase; FLT3 mutants confer factor-independent growth to Ba/F3 and 32D cells and activate similar transduction pathways as the native receptor in response to ligand, including the STAT, RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3' kinase (Pl3K)/AKT pathways. Injection of FLT3-ITD transformed cells, such as Ba/F3 or 32D, into syngeneic recipient mice results in a leukemia-like syndrome, and expression in primary murine bone marrow cells in a retroviral transduction assay results in a myeloproliferative disorder. Mutations that abrogate FLT3 kinase activity result in loss of transforming properties in these assays. Further, FLT3-selective inhibitors impair transformation of primary AML cells that harbor these mutations, and also inhibit FLT3 transformed hematopoietic cell lines, and leukemias induced by activated FLT3 mutants in murine models. Collectively, these data indicate that FLT3 may be a viable therapeutic target for treatment of AML. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle,Room 418, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA66996]; NIDDK NIH HHS [P01 DK50654] NR 119 TC 144 Z9 148 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 274 EP 281 DI 10.1097/00062752-200207000-00003 PG 8 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000003 PM 12042700 ER PT J AU Ernst, P Wang, J Korsmeyer, SJ AF Ernst, P Wang, J Korsmeyer, SJ TI The role of MLL in hematopoiesis and leukemia SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; FUSION PROTEINS; HISTONE H3; SET DOMAIN; MAMMALIAN TRITHORAX; HOMEOTIC GENE; MUTANT MICE; LYSINE 9; LEUKEMOGENESIS; BROMODOMAIN AB The MLL gene, also called HRX or ALL-1, was originally identified as a recurrent chromosomal translocation in particular subtypes of acute lymphocytic leukemia (ALL) and acute myelogenous leukemia (AML). Reciprocal rearrangements of the MLL gene are most common in infant ALL and secondary AML. Because of the unique association with infant leukemia and the intriguingly immature and mixed lineage phenotype of leukemic cells, the authors speculate that the wild-type MLL gene plays an important role early in the development of the hematopoietic system. This article reviews recent progress in understanding the function of the wild-type MLL protein, with particular consideration of potential functions within the developing hematopoietic system. Murine gain- and loss-of-function models have provided clues to the normal functions of MLL and altered functions of oncogenic MLL fusion proteins. Biochemical and genetic approaches using other model organisms have also elucidated mechanisms by which these functions are achieved. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Med, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA68484] NR 41 TC 100 Z9 102 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 282 EP 287 DI 10.1097/00062752-200207000-00004 PG 6 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000004 PM 12042701 ER PT J AU Armstrong, SA Hsieh, JJD Korsmeyer, SJ AF Armstrong, SA Hsieh, JJD Korsmeyer, SJ TI Genomic approaches to the pathogenesis and treatment of acute lymphoblastic leukemias SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; RECEPTOR TYROSINE KINASE; CHROMOSOMAL TRANSLOCATIONS; DROSOPHILA-TRITHORAX; BONE-MARROW; CELL; GENE; EXPRESSION; HEMATOPOIESIS; FUSION AB During the past 2 years, gene expression-profiling technology has been used to characterize multiple tumor types. These studies represent the initial attempts to understand cancer at the whole genome level and have given us our first glimpse into what can be learned from such analysis. This technology is beginning to be applied to the study of human leukemias. Recent studies focusing on lymphoblastic leukemia have provided insight into classification and pathogenesis. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat, Cambridge, MA 02138 USA. RP Korsmeyer, SJ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA68484, K08 CA92551] NR 43 TC 6 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2002 VL 9 IS 4 BP 339 EP 344 DI 10.1097/00062752-200207000-00012 PG 6 WC Hematology SC Hematology GA 573FQ UT WOS:000176819000012 PM 12042709 ER PT J AU Bluher, M Michael, MD Peroni, OD Ueki, K Carter, N Kahn, BB Kahn, CR AF Bluher, M Michael, MD Peroni, OD Ueki, K Carter, N Kahn, BB Kahn, CR TI Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance SO DEVELOPMENTAL CELL LA English DT Article ID CULTURED RAT ADIPOCYTES; OB GENE-EXPRESSION; TARGETED DISRUPTION; DIABETES-MELLITUS; LEPTIN SECRETION; CELL-SIZE; PLASMA LEPTIN; RESISTANCE; MUSCLE; METABOLISM AB Insulin signaling in adipose tissue plays an important role in lipid storage and regulation of glucose homeostasis. Using the Cre-loxP system, we created mice with fat-specific disruption of the insulin receptor gene (FIRKO mice). These mice have low fat mass, loss of the normal relationship between plasma leptin and body weight, and are protected against age-related and hypothalamic lesion-induced obesity, and obesity-related glucose intolerance. FIRKO mice also exhibit polarization of adipocytes into populations of large and small cells, which differ in expression of fatty acid synthase, C/EBPalpha, and SREBP-1. Thus, insulin signaling in adipocytes is critical for development of obesity and its associated metabolic abnormalities, and abrogation of insulin signaling in fat unmasks a heterogeneity in adipocyte response in terms of gene expression and triglyceride storage. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrine, Diabet Unit, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 43051, DK 56116] NR 43 TC 435 Z9 453 U1 3 U2 21 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2002 VL 3 IS 1 BP 25 EP 38 DI 10.1016/S1534-5807(02)00199-5 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 572HY UT WOS:000176769500007 PM 12110165 ER PT J AU Miyamoto, T Iwasaki, H Reizis, B Ye, M Graf, T Weissman, IL Akashi, K AF Miyamoto, T Iwasaki, H Reizis, B Ye, M Graf, T Weissman, IL Akashi, K TI Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment SO DEVELOPMENTAL CELL LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAIN; RECEPTOR-ALPHA-GENE; MOUSE BONE-MARROW; TRANSCRIPTION FACTOR; PROGENITOR CELLS; ERYTHROID-DIFFERENTIATION; PRECEDES COMMITMENT; B-LYMPHOPOIESIS; PRECURSOR CELLS; PROTEIN LMO2 AB We demonstrate here that "promiscuous" expression of myeloid or lymphoid genes precedes lineage commitment in hematopoiesis. Prospectively purified single common myeloid progenitors (CMPs) coexpress myelo-erythroid but not lymphoid genes, whereas single common lymphoid progenitors (CLPs) coexpress T and B lymphoid but not myeloid genes. Genes unrelated to the adopted lineage are downregulated in bipotent and monopotent descendants of CMPs and CLPs. Promiscuous gene expression does not alter the biological potential of multipotent progenitors: CMPs with an activated endogenous M lysozyme locus yield normal proportions of myelo-erythroid colonies, and CLPs expressing the pre-T cell receptor of gene differentiate into normal numbers of B cells. Thus, the accessibility for multiple myeloid or lymphoid programs promiscuously may allow flexibility in fate commitments at these multipotent stages. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Palo Alto, CA 94305 USA. Stanford Univ, Sch Med, Dept Biol, Palo Alto, CA 94305 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Graf, Thomas/B-4252-2015 OI Graf, Thomas/0000-0003-2774-4117 FU NCI NIH HHS [CA 86065]; NIAID NIH HHS [AI47458]; NIDDK NIH HHS [DK553074] NR 72 TC 306 Z9 313 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2002 VL 3 IS 1 BP 137 EP 147 DI 10.1016/S1534-5807(02)00201-0 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 572HY UT WOS:000176769500016 PM 12110174 ER PT J AU Oh, SP Li, E AF Oh, SP Li, E TI Gene-dosage-sensitive genetic interactions between inversus viscerum (iv), nodal, and activin type IIB receptor (ActRIIB) genes in asymmetrical patterning of the visceral organs along the left-right axis SO DEVELOPMENTAL DYNAMICS LA English DT Article DE activin receptor; inversus viscerum; nodal; laterality; isomerism; heterotaxy ID SITUS-INVERSUS; CRANIOFACIAL DEVELOPMENT; MOUSE; MICE; EXPRESSION; MALFORMATIONS; PATHWAY; GASTRULATION; REQUIREMENT; ANOMALIES AB We have shown previously that mice deficient in the activin type IIB receptor (ActRIIB) exhibit right isomerism, which is characterized by mirror-image symmetrical right lungs, complex cardiac malformations, and hypoplasia of the spleen. These observations led us to hypothesize that the signaling of a TGF-beta family member by means of ActRIIB is necessary for the determination of the left-sidedness of the visceral organs. To test this hypothesis, we examined laterality defects in mice carrying mutations in both ActRIIB and inversus viscerum (iv) genes, because iv(-/-) mice display a spectrum of laterality defects, including situs inversus, right isomerism, and left isomerism. We found that all mice homozygous for both iv and ActRIIB mutations displayed the right isomerism. The phenotype of right isomerism in the double mutants was also more severe than that in ActRIIB(-/-) mice as shown by persistent left inferior vena cava, right atrial isomerism, and hypoplasia of spleen. Interestingly, the incidence of right isomerism also increased significantly in iv(-/-);ActRIIB(+/-) and iv(+/-);ActRIIB(-/-) mice compared with homozygous mice carrying either of single gene mutations. A mechanism of the genetic modulation between ActRIIB and iv genes may be that iv modulates the asymmetric expression of a TGF-beta family member that signals through activin type II receptors, ActRIIA and ActRIIB, to specify the "left-sidedness." Nodal is the most likely candidate. We show here that the penetrance and severity of the right isomerism is significantly elevated in nodal(+/-); ActRIIB(-/-) mice, compared with ActRIIB(-/-) mice. Furthermore, the chimeric mice derived from nodal(-/-) ES cells displayed right isomerism, indistinguishable from that in (iv-/-; ActRIIB(-/-)) mice. We propose that iv functions to establish asymmetric expression of nodal in a gene-dosage-sensitive manner and that nodal signals through the activin type II receptors to specify the left-sidedness by means of a threshold mechanism. (C) 2002 Wiley-Liss, Inc. C1 Univ Florida, Coll Med, Dept Physiol & Funct Genomics, Gainesville, FL 32610 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Charlestown, MA USA. RP Oh, SP (reprint author), Univ Florida, Coll Med, Dept Physiol & Funct Genomics, POB 100274, Gainesville, FL 32610 USA. FU NHLBI NIH HHS [HL64024]; NICHD NIH HHS [HD35286] NR 54 TC 18 Z9 19 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD JUL PY 2002 VL 224 IS 3 BP 279 EP 290 DI 10.1002/dvdy.10103 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 569AG UT WOS:000176576700003 PM 12112458 ER PT J AU Musi, N Hirshman, MF Nygren, J Svanfeldt, M Bavenholm, P Rooyackers, O Zhou, GC Williamson, JM Ljunqvist, O Efendic, S Moller, DE Thorell, A Goodyear, LJ AF Musi, N Hirshman, MF Nygren, J Svanfeldt, M Bavenholm, P Rooyackers, O Zhou, GC Williamson, JM Ljunqvist, O Efendic, S Moller, DE Thorell, A Goodyear, LJ TI Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes SO DIABETES LA English DT Article ID ANTIDIABETIC DRUG METFORMIN; GLUCOSE-TRANSPORT; INSULIN-RESISTANCE; RESPIRATORY-CHAIN; MECHANISM; RECEPTOR; TRANSLOCATION; METABOLISM; EXERCISE; MICE AB Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK alpha2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK alpha2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK alpha2. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Karolinska Inst, Ctr Gastrointestinal Dis, Ersta Hosp, Stockholm, Sweden. Huddinge Univ Hosp, Dept Surg, S-14186 Huddinge, Sweden. Karolinska Hosp & Inst, Div Med, Stockholm, Sweden. Karolinska Hosp & Inst, Dept Emergency & Cardiovasc Med, Stockholm, Sweden. Huddinge Univ Hosp, Dept Anesthesiol & Intens Care, S-14186 Huddinge, Sweden. Merck Res Labs, Dept Metab Disorders, Rahway, NJ USA. Karolinska Hosp & Inst, Div Mol Med, Stockholm, Sweden. Karolinska Hosp & Inst, Dept Endocrinol, Stockholm, Sweden. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR 45670] NR 62 TC 424 Z9 450 U1 4 U2 33 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2074 EP 2081 DI 10.2337/diabetes.51.7.2074 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200011 PM 12086935 ER PT J AU Jensen, CC Cnop, M Hull, RL Fujimoto, WY Kahn, SE AF Jensen, CC Cnop, M Hull, RL Fujimoto, WY Kahn, SE CA Amer Diabetes Assoc GENNID Study G TI beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the US SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; JAPANESE-AMERICAN MEN; HOMEOSTASIS MODEL ASSESSMENT; INSULIN-RESISTANCE ATHEROSCLEROSIS; SERUM PROINSULIN LEVELS; NON-HISPANIC WHITES; AFRICAN-AMERICANS; VISCERAL ADIPOSITY; FAT DISTRIBUTION; FASTING GLUCOSE AB First-degree relatives of individuals with type 2 diabetes are at increased risk of developing hyperglycemia. To examine the prevalence and pathogenesis of abnormal glucose homeostasis in these subjects, 531 first-degree relatives with no known history of diabetes (aged 44.1 +/- 0.7 years; BMI 29.0 +/- 0.3 kg/m(2)) underwent an oral glucose tolerance test (OGTT). Newly identified diabetes was found in 19% (n = 100), and impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) was found in 36% (n = 191). Thus, only 45% (n = 240) had normal glucose tolerance (NGT). The homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin sensitivity; P-cell function was quantified as the ratio of the incremental insulin to glucose responses over the first 30 min during the OGTT (DeltaI(30)/DeltaG(30)). This latter measure was also adjusted for insulin sensitivity as it modulates beta-cell function ([DeltaI(30)/DeltaG(30)]/HOMA-IR). Decreasing glucose tolerance was associated with increasing insulin resistance (HOMA: NGT 12.01 +/- 0.54 pmol/mmol; IFG/IGT 16.14 +/- 0.84; diabetes 26.99 +/- 2.62; P < 0.001) and decreasing beta-cell function (DeltaI(30)/DeltaG(30): NGT 157.7 +/- 9.7 pmol/mmol; IFG/IGT 100.4 +/- 5.4; diabetes 57.5 +/- 7.3; P < 0.001). Decreasing beta-cell function was also identified when adjusting this measure for insulin sensitivity ([DeltaI(30)/DeltaG(30)/HOMA-IR). In all four ethnic groups (African-American, n = 55; Asian-American, n = 66; Caucasian, n = 217; Hispanic-American, n = 193), IFG/IGT and diabetic subjects exhibited progressively increasing insulin resistance and decreasing beta-cell function. The relationships of insulin sensitivity and beta-cell function to glucose disposal, as measured by the incremental glucose area under the curve (AUCg), were examined in the whole cohort. Insulin sensitivity and AUCg were linearly related so that insulin resistance was associated with poorer glucose disposal (r(2) = 0.084, P < 0.001). In contrast, there was a strong inverse curvilinear relationship between P-cell function and AUCg such that poorer insulin release was associated with poorer glucose disposal log[DeltaI(30)/DeltaG(30)]: r(2) = 0.29, P < 0.001; log[(DeltaI(30)/DeltaG(30))/HOMA-IR]: r(2) = 0.45, P < 0.001). Thus, abnormal glucose metabolism is common in first-degree relatives of subjects with type 2 diabetes. Both insulin resistance and impaired beta-cell function are associated with impaired glucose metabolism in all ethnic groups, with beta-cell function seeming to be more important in determining glucose disposal. C1 VA Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Med Ctr 151, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK 02654, DK 17047] NR 60 TC 182 Z9 189 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2170 EP 2178 DI 10.2337/diabetes.51.7.2170 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200023 PM 12086947 ER PT J AU Ng, DPK Canani, L Araki, S Smiles, A Moczulski, D Warram, JH Krolewski, AS AF Ng, DPK Canani, L Araki, S Smiles, A Moczulski, D Warram, JH Krolewski, AS TI Minor effect of GLUT1 polymorphisms on susceptibility to diabetic nephropathy in type 1 diabetes SO DIABETES LA English DT Article ID GLUCOSE-TRANSPORTER GENE; RAT MESANGIAL CELLS; IGF-I; EXPRESSION; INSULIN; HYPERGLYCEMIA; COMPLICATIONS; POPULATION; ACTIVATION; MELLITUS AB Elevation of intracellular glucose in mesangial cells as mediated by GLUT1 may be important in initiating cellular mechanisms that cause diabetic nephropathy. To determine whether DNA sequence differences in GLUT1 confer susceptibility to this complication, single-nucleotide polymorphisms (SNPs) in this gene were examined using a large case-control study. SNPs examined included the known XbaI (intron 2) and HaeIII SNPs (exon 2). Four novel SNPs located in three putative enhancers were also investigated. Homozygosity for the XbaI(-) allele was associated with diabetic nephropathy (odds ratio 1.83 [95% CI 1.01-3.33]). Furthermore, homozygosity for the A allele for a novel SNP (enhancer-2 SNP 1) located in a putative insulin-responsive enhancer-2 was associated with diabetic nephropathy (2.38 [1.16-4.90]). Patients who were homozygous for risk alleles at both XbaI SNP and enhancer-2 SNP 1 [i.e., homozygosity for XbaI(-)/A haplotype] also had an increased risk of diabetic nephropathy (2.40 [1.13-5.07]). Because enhancer-2 SNP I may directly control GLUT1 expression, the strong linkage disequilibrium between the two SNPs likely accounts for Xbal SNP being associated with diabetic nephropathy. In conclusion, our study confirms that SNPs at the GLUT1 locus are associated with susceptibility to diabetic nephropathy in type 1 diabetes. Although these SNPs confer a considerable personal risk for diabetic nephropathy, they account for a limited proportion of cases among type I diabetic patients. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU NIDDK NIH HHS [DK 41526] NR 29 TC 30 Z9 33 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2264 EP 2269 DI 10.2337/diabetes.51.7.2264 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200035 PM 12086959 ER PT J AU Menzaghi, C Ercolino, T Di Paola, R Berg, AH Warram, JH Scherer, PE Trischitta, V Doria, A AF Menzaghi, C Ercolino, T Di Paola, R Berg, AH Warram, JH Scherer, PE Trischitta, V Doria, A TI A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome SO DIABETES LA English DT Article ID TYPE-2 DIABETES-MELLITUS; PROTEIN; ADIPOSE; GENE; PLASMA; EXPRESSION; SENSITIVITY; CALPAIN-10; DISEASE; CLONING AB Adiponectin is a protein secreted by adipocytes that modulates insulin action. To assess whether variants of this gene contribute to the prevalence of insulin resistance in Caucasians, we genotyped 413 nondiabetic individuals for two single nucleotide polymorphisms (SNPs) at this locus. The two SNPs (45T-->G and 276G-->T) were chosen because of their association with type 2 diabetes in Japanese. Whereas each polymorphism was significantly associated with some correlate of insulin resistance, the haplotype defined by the two together was strongly associated with many components of the insulin resistance syndrome. Homozygotes for the risk haplotype had higher body weight (P = 0.03), waist circumference (P = 0.004), systolic (P = 0.01) and diastolic (P = 0.003) blood pressure, fasting glucose (P = 0.02) and insulin (P = 0.005) levels, homeostasis model assessment (HOMA) for insulin resistance (P = 0.003), and total to HDL cholesterol ratio (P = 0.01). Homozygotes also had significantly lower plasma levels of adiponectin (P = 0.03), independent of sex, age, and body weight. In an independent study group of 614 Caucasians, including 310 with type 2 diabetes, the risk haplotype was confirmed to be associated with increased body weight (P = 0.03) but not with type 2 diabetes per se. We conclude that variability at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome, but given the nature of the two SNPs, the risk haplotype is most probably a marker in linkage disequilibrium with an as yet unidentified polymorphism that affects plasma adiponectin levels and insulin sensitivity. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Dept Med,Res Div, Boston, MA 02215 USA. Osped Casa Sollievo Sofferenza, Unit Endocrinol, San Giovanni Rotondo, Italy. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Ctr Diabet Res & Training, Bronx, NY 10467 USA. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Doria, A (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Dept Med,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016; OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X; Menzaghi, Claudia/0000-0002-7438-8955 FU NIDDK NIH HHS [DK 36836, R01 DK 47475, R01 DK 55523] NR 39 TC 296 Z9 326 U1 0 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2002 VL 51 IS 7 BP 2306 EP 2312 DI 10.2337/diabetes.51.7.2306 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 569RP UT WOS:000176616200041 PM 12086965 ER PT J AU Cornish, JW Herman, BH Ehrman, RN Robbins, SJ Childress, AR Bead, V Esmonde, CA Martz, K Poole, S Caruso, FS O'Brien, CP AF Cornish, JW Herman, BH Ehrman, RN Robbins, SJ Childress, AR Bead, V Esmonde, CA Martz, K Poole, S Caruso, FS O'Brien, CP TI A randomized, double-blind, placebo-controlled safety study of high-dose dextromethorphan in methadone-maintained male inpatients SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE heroin dependence; dextromethorphan; NMDA; methadone; addiction; pharmacotherapy ID NMDA RECEPTOR ANTAGONISTS; CONDITIONING FACTORS; OPIATE WITHDRAWAL; OPIOID TOLERANCE; MORPHINE; DRUG; PREFERENCE; ADDICTION; MK-801; MICE AB The NMDA antagonist dextromethorphan hydrobromide (DM) may be useful in the treatment of opioid dependence, particularly as a means of reducing tolerance to methadone during replacement therapy. As a prelude to clinical efficacy studies, a randomized, double-blind, placebo-controlled study examined the safety of DM in combination with methadone in inpatient, opiate-dependent volunteers. Male participants received daily methadone (50-70 mg/day) and either DM (n = 10) or placebo (n = 5) during the 12-day active medication phase of the study. DM participants received doses of 120, 240, and 480 mg/day in increasing order (4 days each). DM at high doses caused mild elevations of heart rate, blood pressure, temperature, and plasma bromide. However, none of these effects was clinically significant. DM caused no significant changes in respiration, pupil diameter, or subjective drug effects measured by standard scales. Participants in the DM group reported many more adverse events than did subjects on placebo (173 vs. 21), but these effects were not clinically serious. The most commonly reported side effects were sleepiness and drowsiness. Several participants reported intoxicating effects at the highest dose. Overall, DM was well-tolerated by the methadone-maintained opiate-dependent subjects studied here. These results support the further exploration of DM as an adjunct medication during methadone replacement therapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIDA, Div Treatment Res & Dev, Bethesda, MD 20892 USA. Arcadia Univ, Glenside, PA 19038 USA. Ridgeview Stat, Bluemont, VA 20135 USA. ENDO Pharmaceut Inc, Chadds Ford, PA 19317 USA. RP Cornish, JW (reprint author), Univ Penn, Dept Psychiat, Ctr Studies Addict, 3535 Market St,4th Floor, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P60-DA-05186] NR 23 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2002 VL 67 IS 2 BP 177 EP 183 AR PII S0376-8716(02)00025-X DI 10.1016/S0376-8716(02)00025-X PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 576TW UT WOS:000177022600008 PM 12095667 ER PT J AU Ehrman, RN Robbins, SJ Bromwell, MA Lankford, ME Monterosso, JR O'Brien, CP AF Ehrman, RN Robbins, SJ Bromwell, MA Lankford, ME Monterosso, JR O'Brien, CP TI Comparing attentional bias to smoking cues in current smokers, former smokers, and non-smokers using a dot-probe task SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cigarette smoking; attention; dot-probe task; reaction time ID CONDITIONING FACTORS; ANXIETY; THREAT; REACTIVITY; DEPENDENCE; DEPRESSION; ABSTINENCE; AWARENESS; BEHAVIOR; DISORDER AB Much evidence documents that individuals with emotional and drug-use disorders demonstrate biased attention toward stimuli associated with their disorder. This bias appears to diminish following successful treatment. Two studies examined whether current cigarette smokers show biased attention toward smoking-related images compared with non-smokers (Studies 1 and 2) and whether this bias is less pronounced in former smokers (Study 2). Attentional bias toward cigarette-related photographs was examined using the dot-probe task. Pairs of images (one smoking-related) appeared side by side for 500 ins on a computer screen prior to the presentation of a probe (an asterisk) replacing one of the photographs. Subjects struck a key as quickly as possible to indicate the probe location. Attentional bias was defined as faster reaction times when the probe replaced the smoking-related image. In both studies, current smokers displayed significantly greater attentional bias toward cigarette stimuli than did non-smokers. Former smokers in Study 2 displayed an intermediate level of bias, but did not differ significantly in bias score from either of the other groups. These results support further use of the dot-probe task as a measure of attentional bias in non-abstinent smokers and in individuals undergoing smoking cessation treatment. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Arcadia Univ, Dept Psychol, Glenside, PA 19038 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Ehrman, RN (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [P60-DA-05186] NR 38 TC 128 Z9 135 U1 5 U2 28 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL 1 PY 2002 VL 67 IS 2 BP 185 EP 191 AR PII S0376-8716(02)00065-0 DI 10.1016/S0376-8716(02)00065-0 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 576TW UT WOS:000177022600009 PM 12095668 ER PT J AU Albuquerque, CA Smith, KR Saywers, TE Johnson, C Cock, ML Harding, R AF Albuquerque, CA Smith, KR Saywers, TE Johnson, C Cock, ML Harding, R TI Relation between oligohydramnios and spinal flexion in the human fetus SO EARLY HUMAN DEVELOPMENT LA English DT Article DE fetus; spine; amniotic fluid; oligohydramnios ID FETAL BREATHING MOVEMENTS; PRETERM PREMATURE RUPTURE; AMNIOTIC-FLUID VOLUME; PULMONARY HYPOPLASIA; LUNG EXPANSION; MEMBRANES; SHEEP; GROWTH AB Background: Oligohydramnios, a severe reduction in the volume of amniotic fluid, is associated with fetal lung hypoplasia but underlying processes are nuclear. Studies in sheep Suggest that oligohydramnios may lead to lung hypoplasia by causing increased flexion of the fetal spine, but this has not been demonstrated in the human, which has a different uterine anatomy. Aims: Our aims were to quantify spinal flexion in the human fetus and to determine the relationship between oligohydramnios and the degree of spinal flexion. Subjects and methods: In 35 pregnancies, we used ultrasonography to assess amniotic fluid volume and to image the fetal spine so as to provide an index of mean spinal radius between the upper thoracic and lumbar spine. In 17 pregnancies with evidence of oligohydramnios resulting from premature rupture of membranes (mean+/-SEM gestation 28.8+/-1.4 weeks), the mean radius of fetal spinal curvature between the upper thorax and sacrum was compared with values from 18 control fetuses with normal amounts of amniotic fluid (at 28.9+/-1.6 weeks). Results: In each fetus, the spine could be imaged and the mean radius Of Curvature calculated. Oligohydramnios was associated with a significantly increased degree of fetal spinal flexion compared to controls. Conclusion: In human pregnancy, oligohydramnios is associated with increased flexion of the fetal spine, which is likely due to reduced uterine volume. This Could contribute to the development of fetal lung hypoplasia, fetal immobility and other fetal anomalies. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia. Deaconess Med Ctr, Spokane, WA USA. RP Harding, R (reprint author), Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia. OI cock, megan/0000-0001-7757-8781 NR 28 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JUL PY 2002 VL 68 IS 2 BP 119 EP 126 AR PII S0378-3782(02)00022-1 DI 10.1016/S0378-3782(02)00022-1 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 585LW UT WOS:000177527100005 PM 12113997 ER PT J AU Storre, J Elsasser, HP Fuchs, M Ullmann, D Livingston, DM Gaubatz, S AF Storre, J Elsasser, HP Fuchs, M Ullmann, D Livingston, DM Gaubatz, S TI Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6 SO EMBO REPORTS LA English DT Article ID POLYCOMB-GROUP; FAMILY; GENE; TRANSCRIPTION; PROLIFERATION; PROTEINS; MEMBER; MICE; REPRESSOR; BINDING AB E2F transcription factors play an important role in regulating mammalian cell proliferation. E2F6, the most recently identified E2F family member, is a transcriptional repressor. In an effort to ascertain the in vivo biological function of E2F6, we have generated an E2f6 mutant mouse strain. Mice lacking E2F6 are viable and healthy. Surprisingly, E2f6-1- embryonic fibroblasts proliferate normally. However, Uf6-1- animals display overt homeotic transformations of the axial skeleton that are strikingly similar to the skeletal transformations observed in polycomb mutant mice. This observation is compatible with the recent finding that endogenous E2F6 and one or more mammalian polycomb proteins are components of the same multiprotein complex. The accumulated evidence suggests that, during development E2F6 participates in the recruitment of polycomb proteins to specific target promoters. C1 Univ Marburg, Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany. Univ Marburg, Dept Cell Biol, D-35037 Marburg, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gaubatz, S (reprint author), Univ Marburg, Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany. NR 25 TC 57 Z9 59 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JUL PY 2002 VL 3 IS 7 BP 695 EP 700 DI 10.1093/embo-reports/kvf141 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 578MM UT WOS:000177121500021 PM 12101104 ER PT J AU Liu, YY Tachiki, KH Brent, GA AF Liu, YY Tachiki, KH Brent, GA TI A targeted thyroid hormone receptor a gene dominant-negative mutation (P398H) selectively impairs gene expression in differentiated embryonic stem cells SO ENDOCRINOLOGY LA English DT Article ID RETINOIC ACID; NERVOUS-SYSTEM; RAT-BRAIN; POSTNATAL-DEVELOPMENT; RESPONSE ELEMENT; ASTROGLIAL CELLS; ALPHA-RECEPTOR; IN-VITRO; MICE; BETA AB Thyroid hormone and retinoic acid (RA) are essential for normal neural development in vivo, yet all in vitro differentiation strategies of embryonic stem (ES) cells use only RA. We developed a novel differentiation strategy of mouse ES cells using T-3. A dominant-negative knock-in point mutation (P398H) was introduced into the thyroid hormone receptor a gene to determine the influence of T-3 on ES cell differentiation. Differentiation promoted by T-3 (1 nM), RA (1 mum), or combined T-3/RA was assessed in wild-type (wt) and mutant (in) ES cells on the basis of neuronal-specific gene expression and cell cycle. T-3 alone stimulated neural differentiation in a similar fashion as that seen with RA in both wtES and mES cells. Expression of neurogranin and Ca2+/calmodulin-dependent kinase IV mRNA (identified in vivo as T-3-regulated genes), however, was markedly reduced in mES, compared with wtES cells. RA treatment enhanced apoptosis, significantly greater than that seen with T-3 stimulation. T-3 treatment given with RA significantly reduced the apoptotic effects of RA, an effect not seen in mES cells. T-3-induced ES cell neural differentiation of thyroid hormone a mutant and wtES cells provides an in vitro model to study T-3-dependent gene regulation in neural development. This system could also be used to identify novel T-3-regulated genes. The modulation of the apoptotic effects of RA by T-3 may have implications for stem cell therapy. C1 Univ Calif Los Angeles, Mol Endocrinol Lab,Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Mol Endocrinol Lab,Dept Physiol, Vet Affairs Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Res Serv,Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Res Serv,Dept Physiol, Vet Affairs Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, Mol Endocrinol Lab,Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Sch Med, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 61 TC 30 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2002 VL 143 IS 7 BP 2664 EP 2672 DI 10.1210/en.143.7.2664 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568PE UT WOS:000176550400027 PM 12072400 ER PT J AU Gyurko, R Leupen, S Huang, PL AF Gyurko, R Leupen, S Huang, PL TI Deletion of exon 6 of the neuronal nitric oxide synthase gene in mice results in hypogonadism and infertility SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE SECRETION; RAT; OVULATION; DISRUPTION; RELEASE; FERTILIZATION; HYPOTHALAMUS; INVOLVEMENT; EXPRESSION; MEDIATOR AB Nitric oxide (NO) has been recognized as a modulator in reproductive functions, but it is not clear whether NO is required for fertility. The first line of mice deficient in neuronal NO synthase (referred to herein as KN1 mice) reproduce normally. However, residual neuronal NO synthase (nNOS) activity is detected in KN1 mice due to the expression of beta- and gamma-nNOS splice variants. We generated a new line of nNOS knockout mice (KN2) lacking exon 6, which codes for the heme-binding domain of nNOS. KN2 mice are viable, but mated homozygotes do not produce litters, indicating that either one or both sexes are infertile, Male KN2 mice show decreased gonad weights, but sperm counts are normal. KN2 males do not display mating behavior, and consequently do not leave vaginal plugs when housed with wild-type (WT) females. KN2 females show decreased ovary weight, and histology reveals decreased corpus luteum counts. RIAs show that KN2 males have decreased plasma FSH, whereas KN2 females have increased levels of plasma LH and increased hypothalamic GnRH content. Experimental ovarian transplantation suggests that central, rather than ovarian, processes are influenced by nNOS, as KN2 ovaries ovulate at near-normal rates under WT hormonal control, whereas WT ovaries transplanted into KN2 mice have decreased ovulation rates. We observed pyloric stenosis in KN2 mice, but plasma leptin levels are normal, and no ketones are found, indicating that hypogonadism is not a result of malnutrition. We conclude that nNOS is required for normal central hormonal regulation of reproductive function. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-57818]; NINDS NIH HHS [NS-33335] NR 35 TC 95 Z9 96 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2002 VL 143 IS 7 BP 2767 EP 2774 DI 10.1210/en.143.7.2767 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 568PE UT WOS:000176550400039 PM 12072412 ER PT J AU Chang, LT Koutrakis, P Catalano, PJ Suh, HH AF Chang, LT Koutrakis, P Catalano, PJ Suh, HH TI Predicting 24-hr personal PM2.5 exposures: Assessing the relative importance of 24-hr and 1-hr ambient PM2.5 concentrations, 1-hr personal PM2.5 exposures, and time activity data SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 867 BP S235 EP S236 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600800 ER PT J AU Duty, SM Silva, MJ Barr, DB Brock, JW Ryan, L Chen, Z Herrick, RF Christiani, D Hauser, R AF Duty, SM Silva, MJ Barr, DB Brock, JW Ryan, L Chen, Z Herrick, RF Christiani, D Hauser, R TI Urinary phthalate monoesters at general population exposure levels are associated with altered semen quality. SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Androl Lab, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Biostat, Cambridge, MA USA. Harvard Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RI Ryan, Louise/A-4562-2009; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 OI Ryan, Louise/0000-0001-5957-2490; NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 657 BP S197 EP S197 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600611 ER PT J AU Garshick, E Laden, F Hart, JE Caron, AM Smith, TJ AF Garshick, E Laden, F Hart, JE Caron, AM Smith, TJ TI Epidemiologic and exposure assessment study of the association of particulate exposure and lung cancer in the trucking industry. SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 849 BP S232 EP S232 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600782 ER PT J AU Heff, A Laden, F Garshick, E Natkin, J Hart, JE Smith, TJ AF Heff, A Laden, F Garshick, E Natkin, J Hart, JE Smith, TJ TI The accelerometer as a tool to distinguish between driving on open highways and on local roads SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Med Sch, Brighams & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 792 BP S221 EP S221 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600729 ER PT J AU Heff, A Laden, F Garshick, E Natkin, J Hart, JE Smith, TJ AF Heff, A Laden, F Garshick, E Natkin, J Hart, JE Smith, TJ TI An integrated air sampling sysstem for field use SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. Harvard Univ, Med Sch, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 779 BP S219 EP S219 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600718 ER PT J AU Laden, F Garshick, E Hart, JE Caron, AM Smith, TJ AF Laden, F Garshick, E Hart, JE Caron, AM Smith, TJ TI Factors influencing elemental carbon exposure in the US trucking industry SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 105 BP S98 EP S98 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600113 ER PT J AU Proctor, SP Tsaih, SW Spiro, A Sparrow, D Aro, A McDonald, K Hu, H AF Proctor, SP Tsaih, SW Spiro, A Sparrow, D Aro, A McDonald, K Hu, H TI Bone lead and changes in cognitive test outcomes in the normative aging study SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Publ Hlth & Med, Boston, MA 02215 USA. VA Boston Healthcare Sys, Boston Environm Hazards Ctr, Boston, MA USA. VA Boston Healthcare Sys, Natl Ctr PTSD, Boston, MA USA. Harvard Univ, Sch Med, B&W Hosp, Dept Med,Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Cambridge, MA 02138 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 754 BP S214 EP S215 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600696 ER PT J AU Mangoni, AA Koelling, TM Meyer, GS Akins, CW Fifer, MA AF Mangoni, AA Koelling, TM Meyer, GS Akins, CW Fifer, MA TI Outcome following mitral valve replacement in patients with mitral stenosis and moderately reduced left ventricular ejection fraction SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE mitral valve; mitral stenosis; mural valve replacement; clinical outcome; congestive heart failure ID PERFORMANCE; COMMISSUROTOMY; REGURGITATION; DYSFUNCTION; SURVIVAL AB Background: Some patients with mitral stenosis (MS) have moderately reduced left ventricular (LV) ejection fraction (EF), due to either depressed myocardial contractility or alterations in loading conditions. The effect of moderately reduced LV EF on outcome after mitral valve replacement (MVR) is not known. Methods: We studied 16 consecutive patients with LV EF less than or equal to0.50 and MS without significant mitral reguritation or other valvular or coronary artery disease (Group I). We selected four controls with LV EF >0.50 for each patient, matched for time of surgery (Group II, n = 64). Mean EF in Groups I and II was 0.45 and 0.66. respectively. We compared short- and long-term outcome between the two groups. Results: There were no perioperative deaths. Group I patients had a higher incidence of in-hospital postoperative heart failure (25% vs. 6%. P = 0.02). Mean follow-up was 9 years in both groups. Mean New York Heart Association class improved from 2.4 to 1.7 in both groups. Group I patients had a higher incidence of heart failure deaths (13% vs. 2%. P = 0.03) and admissions (40% vs. 13%, P = 0.01). There were. however. no differences between Groups I and II in overall mortality (27% vs. 21%), rate of cardiac admissions (69% vs. 53%). or mean Specific Activity Scale Score (2.5 vs. 2.5). Conclusions: Although patients with MS and moderately reduced LV EF are at higher risk for heart failure after MVR, overall mortality is not different from that of patients with normal EF Moderate depression of LV EF should not be a contraindication to MVR for MS. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cardiac Surg Div, Boston, MA 02115 USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, 15 Parkman St,WACC Suite 478, Boston, MA 02114 USA. RI Mangoni, Arduino/F-8000-2010 NR 23 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD JUL PY 2002 VL 22 IS 1 BP 90 EP 94 AR PII S1010-7940(02)00218-X DI 10.1016/S1010-7940(02)00218-X PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 578TR UT WOS:000177136500017 PM 12103379 ER PT J AU Kregenow, DA Swenson, ER AF Kregenow, DA Swenson, ER TI The lung and carbon dioxide: implications for permissive and therapeutic hypercapnia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ALVEOLAR EPITHELIAL-CELLS; NITRIC-OXIDE; ENDOTHELIAL-CELLS; INTRACELLULAR PH; INSPIRED CO2; BLOOD-FLOW; INJURY; REPERFUSION; PULMONARY C1 Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Swenson, ER (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,Box 358280,S-111-PULM, Seattle, WA 98108 USA. NR 60 TC 41 Z9 42 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JUL PY 2002 VL 20 IS 1 BP 6 EP 11 DI 10.1183/09031936.02.00400802 PG 6 WC Respiratory System SC Respiratory System GA 579QD UT WOS:000177188600003 PM 12166583 ER PT J AU Andersen, NS Donovan, JW Zuckerman, A Pedersen, L Geisler, C Gribben, JG AF Andersen, NS Donovan, JW Zuckerman, A Pedersen, L Geisler, C Gribben, JG TI Real-time polymerase chain reaction estimation of bone marrow tumor burden using clonal immunoglobulin heavy chain gene and bcl-1/JH rearrangements in mantle cell lymphoma SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MINIMAL RESIDUAL DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; QUANTITATIVE PCR; CHROMOSOMAL TRANSLOCATION; T(14-18)-POSITIVE CELLS; FOLLICULAR LYMPHOMA; MULTIPLE-MYELOMA; PROBES; QUANTIFICATION; T(11-14) AB Objective. In mantle cell lymphoma (MCL), detection of minimal residual disease in bone marrow (BM) samples by qualitative polymerase chain reaction (PCR) is insufficient to predict relapse. The aim of this study was to evaluate whether a quantitative estimation of tumor burden in consecutive BM samples from MCL patients was feasible and of clinical value. Materials and Methods. In combination with standard qualitative PCR, we developed a sensitive and accurate real-time PCR for detection of bcl-1/JH (joining region) rearrangement and used a recently described real-time PCR analysis of clonal immunoglobulin rearrangement. To assess clinical utility, we quantified tumor cells in 27 BM samples from three MCL patients undergoing combined CHOP (cyclophosphamide, doxorubicin [hydroxydaunomycin], vincristine [Oncovin], prednisone) and anti-CD20 antibody treatment and three MCL patients undergoing up-front autologous stem cell transplantation. Results. The approach is capable of detecting tumor cells over a wide range of BM contamination compared to qualitative PCR analysis alone. Tumor burden in consecutive BM samples decreases during therapy and either increases or stabilizes at low levels in patients who relapse or remain in continuous clinical remission, respectively. Conclusions. Dynamic range estimation of BM tumor burden is feasible in MCL patients undergoing therapy using clonal immunoglobulin heavy chain gene and bcl-1/JH rearrangement-based real-time PCR. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Andersen, NS (reprint author), Rigshosp, Dept Hematol L4041, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. NR 17 TC 20 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2002 VL 30 IS 7 BP 703 EP 710 AR PII S0301-472X(02)00807-X DI 10.1016/S0301-472X(02)00807-X PG 8 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 576ZC UT WOS:000177036200011 PM 12135667 ER PT J AU Gupta, D Podar, K Tai, YT Lin, B Hideshima, T Akiyama, M LeBlanc, R Catley, L Mitsiades, N Mitsiades, C Chauhan, D Munshi, NC Anderson, KC AF Gupta, D Podar, K Tai, YT Lin, B Hideshima, T Akiyama, M LeBlanc, R Catley, L Mitsiades, N Mitsiades, C Chauhan, D Munshi, NC Anderson, KC TI beta-lapachone, a novel plant product, overcomes drug resistance in human multiple myeloma cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID PROSTATE-CANCER CELLS; INDUCED APOPTOSIS; MEDIATED APOPTOSIS; TRYPANOSOMA-CRUZI; TOPOISOMERASE-I; INTERLEUKIN-6; INHIBITOR; DEXAMETHASONE; ACTIVATION; INDUCTION AB Objective. To evaluate the anti-tumor potential of beta-lapachone in multiple myeloma (MM) cell lines (U266, RPM18226, and MMAS); MM cell lines resistant to dexamethasone (MM.1R), melphalan (RPM18226/LR5), doxorubicin (RPM18226/DOX40), and mitoxantrone (RPM18226/MR20); and MM cells from patients (MM1-MM4). Materials and Methods. Cytotoxicity of beta-lapachone was assessed by MTT and [H-3]-thymidine uptake assays. Apoptosis was analyzed using propidium iodide staining, DNA fragmentation, TUNEL assay, caspase-9 colorimetric assay, and immunoblotting for caspase-3, poly (ADPribose) polymerase (PARP), and caspase-8 cleavage products. Paracrine growth of MM cells was assessed by [H-3]-thymidine uptake in cultures of bone marrow stromal cells (BMSCs) and MM cells. Interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) secretion in the culture supernatants was measured by specific enzyme-linked immunosorbent assays (ELISAs). Results. beta-lapachone showed significant cytotoxicity in MM cells (IC50: 4-8 muM). In contrast, normal peripheral blood mononuclear cells (PBMCs) and BMSCs from MM patients were relatively resistant (IC50: 8-16 muM). IL-6 did not protect against beta-lapachone-induced apoptosis in MMAS cells, and dexamethasone showed additive cytotoxicity. beta-lapachone also decreased binding of MMAS cells to BMSCs; abrogated IL-6 and VEGF secretion triggered by adhesion of BMSCs to MMAS cells; reduced proliferation of MMAS cells adherent to BMSCs; and decreased intracellular adhesion molecule-1 (ICAM-1) expression on MMAS cells. Furthermore, beta-lapachone induced typical PARP cleavage, increased caspase-9 proteolytic activity, and activation of caspase-3, without activation of caspase-8 in U266 cells. Conclusion. These studies provide a framework for clinical evaluation of beta-lapachone to improve the outcome for patients with MM. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P0-1 78378] NR 39 TC 23 Z9 24 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2002 VL 30 IS 7 BP 711 EP 720 AR PII S0301-472X(02)00839-1 DI 10.1016/S0301-472X(02)00839-1 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 576ZC UT WOS:000177036200012 PM 12135668 ER PT J AU Heinz, M Huang, CA Emery, DW Giovino, MA LeGuern, A Kurilla-Mahon, B Theodore, P Arn, JS Sykes, M Mulligan, R Down, JD Sachs, DH Goodell, MA AF Heinz, M Huang, CA Emery, DW Giovino, MA LeGuern, A Kurilla-Mahon, B Theodore, P Arn, JS Sykes, M Mulligan, R Down, JD Sachs, DH Goodell, MA TI Use of CD9 expression to enrich for porcine hematopoietic progenitors SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; STEM-CELLS; MONOCLONAL-ANTIBODIES; TRANSPLANTATION; WORKSHOP; ANTIGENS; MOUSE; ASSAY AB Objective. The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. Materials and Methods. We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSQ-containing murine SP and therefore represents a putative pig stem cell population. We screened a panel of monoclonal antibodies for those that allowed positive or negative enrichment of porcine SP cells and tested one of these for enrichment of hematopoietic progenitors in short-term and long-term in vitro assays. We then screened an expression library to clone the gene whose product is recognized by this antibody. Results. Among a panel of 35 monoclonal lines screened, we found three that were useful for positive enrichment of SP cells and seven for negative enrichment. The 4-6 monoclonal line, allowing around 10-fold negative enrichment of SP cells, recognized the product of the porcine CD9 gene. Hematopoietic progenitors measured by short-term colony-forming unit and long-term cobblestone area-forming cell assays were around 10-fold enriched in the CD9(negative/low) fraction and were significantly depleted in the CDDhigh fraction. Conclusions. The antibody against the porcine CD9 gene product may be of use for enrichment of porcine hematopoietic stem cells. This approach to identify novel markers for enrichment of hematopoietic progenitors may be applicable to other mammalian species. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77098 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. BioTransplant Inc, Boston, MA USA. RP Goodell, MA (reprint author), Baylor Coll Med, Ctr Cell & Gene Therapy, 1 Baylor Plaza, Houston, TX 77098 USA. OI Goodell, Margaret/0000-0003-1111-2932 FU NCI NIH HHS [R01 CA79988]; NHLBI NIH HHS [R01 HL54038, R01 HL63440] NR 22 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2002 VL 30 IS 7 BP 809 EP 815 AR PII S0301-472X(02)00835-4 DI 10.1016/S0301-472X(02)00835-4 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 576ZC UT WOS:000177036200024 PM 12135680 ER PT J AU Klein, RL Hamby, ME Gong, Y Hirko, AC Wang, S Hughes, JA King, MA Meyer, EM AF Klein, RL Hamby, ME Gong, Y Hirko, AC Wang, S Hughes, JA King, MA Meyer, EM TI Dose and promoter effects of adeno-associated viral vector for green fluorescent protein expression in the rat brain SO EXPERIMENTAL NEUROLOGY LA English DT Article DE adeno-associated virus; dose response; gene therapy; gene transfer; green fluorescent protein; IRES; primary neuronal cultures; promoter; WPRE ID ADENOASSOCIATED VIRUS VECTORS; POSTTRANSCRIPTIONAL REGULATORY ELEMENT; CONVECTION-ENHANCED DELIVERY; CENTRAL-NERVOUS-SYSTEM; MEDIATED GENE-TRANSFER; NEUROTROPHIC FACTOR; AAV VECTOR; TRANSDUCTION; TYPE-2; PURIFICATION AB Previous studies demonstrated that the rat neuron-specific enolase (NSE) promoter is effective for transgene expression in the brain in a variety of adeno-associated virus-2 vectors. This study evaluated the dose response and longer time course of this promoter and compared it to two cytomegalovirus/chicken beta-actin hybrid (CBA) promoter-based systems. NSE promoter-driven green fluorescent protein (GFP)-expressing neurons were found at doses as low as 107 particles, with expression increasing in a dose-dependent manner over a 3.3-log range. Bicistronic expression of GFP via an internal ribosome entry site coupled to the NSE promoter was also dose dependent, although the potency was decreased by 3.4-fold. The number of GFP-expressing neurons was stable for at least 25 months. The CBA promoter increased the numbers of GFP-expressing cells versus the NSE promoter, although the expression pattern remained neuronal and persisted for at least 18 months. The CBA promoter permitted detection of cells distal to the injection site that had retrogradely transported the vector from their terminal areas. Incorporating the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) into a CBA promoter vector induced greater expression levels in the hippocampus, as measured by stereological estimates of cell numbers and by Western blots, which demonstrated an 11-fold increase. Incorporation of the WPRE also improved transgene expression in primary neuronal cultures. The increased efficiency obtained with vector elements such as the CBA promoter and the WPRE may enhance the ability to genetically modify larger portions of the brain while requiring smaller doses and volumes. (C) 2002 Elsevier Science (USA). C1 Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Vet Adm Gainesville Med Ctr, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Neurosci, Gainesville, FL 32610 USA. Univ Florida, Coll Pharm, Dept Pharmaceut, Gainesville, FL 32610 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Klein, RL (reprint author), Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA. FU NIA NIH HHS [P01 AG10485]; NINDS NIH HHS [R01 NS37432] NR 28 TC 106 Z9 109 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2002 VL 176 IS 1 BP 66 EP 74 DI 10.1006/exnr.2002.7942 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 574VV UT WOS:000176911000006 PM 12093083 ER PT J AU Dedeoglu, A Ferrante, RJ Andreassen, OA Dillmann, WH Beal, MF AF Dedeoglu, A Ferrante, RJ Andreassen, OA Dillmann, WH Beal, MF TI Mice overexpressing 70-kDa heat shock protein show increased resistance to malonate and 3-nitropropionic acid SO EXPERIMENTAL NEUROLOGY LA English DT Article DE 3-NP; HSP-70; Huntington's disease; malonate ID MITOCHONDRIAL TOXIN; OVER-EXPRESSION; INDUCIBLE HSP70; ISCHEMIC-INJURY; STRESS; HEAT-SHOCK-PROTEIN-70; APOPTOSIS; CELLS; PROTECTION AB Heat shock proteins (HSPs) are induced in response to oxidative stress, hypoxia-ischemia, and neuronal injury and play a protective role. Malonate and 3-nitropropionic acid (3-NP) are well-characterized animal models of Huntington's Disease (HD). They inhibit succinate dehydrogenase, inducing mitochondrial dysfunction, which triggers the generation of superoxide radicals, secondary excitotoxicity, and apoptosis. In this study, we examined whether the 70-kDa heat shock protein (HSP-70) is protective against neurotoxicity induced by malonate and 3-NP. Homozygous and heterozygous HSP-70 overexpressing mice (HSP-70+/+, HSP-70+/-) and wild-type controls received 3-NP or malonate and striatal lesion sizes were evaluated by stereology. Compared to HSP70+/+ and HSP-70+/-, wild-type controls showed significantly larger striatal lesions following 3-NP or malonate injections. These findings support the idea that HSP-70 has a neuroprotective role that may be useful in the treatment of neurodegenerative diseases. (C) 2002 Elsevier Science (USA). C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Vet Adm Med Ctr, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. RP Dedeoglu, A (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. OI Dedeoglu, Alpaslan/0000-0003-1156-0874; Andreassen, Ole A./0000-0002-4461-3568 FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS 38180, NS35255, NS37102] NR 24 TC 39 Z9 42 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2002 VL 176 IS 1 BP 262 EP 265 DI 10.1006/exnr.2002.7933 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 574VV UT WOS:000176911000027 PM 12093104 ER PT J AU Scott, DR Marcus, EA Weeks, DL Sachs, G AF Scott, DR Marcus, EA Weeks, DL Sachs, G TI Mechanisms of. acid resistance due to the urease system of Helicobacter pylori SO GASTROENTEROLOGY LA English DT Article ID HEAT-SHOCK PROTEIN; NEGATIVE MUTANT; LOCALIZATION; PH; EXPRESSION; STOMACH; PURIFICATION; COLONIZATION; AUTOLYSIS; MUSTELAE AB Background & Aims: Helicobacter pylori, a neutralophile, uses acid neutralization by urease to combat gastric acidity, allowing gastric colonization. Both acute and chronic acid resistance mechanisms are present. Acute mechanisms of acid adaptation could be due to surface urease, increased inner-membrane urea permeability via Urel, or both. Slower mechanisms may involve increased nickel insertion into apoenzyme, posttranscriptional regulation, or increased enzyme synthesis. The aim of this Study was to further define regulation I of urease under acidic conditions. Methods: Surface-bound urease was analyzed by, Measurement of free and bound urease after centrifugation through a step gradient and by quantitative urease immunostaining of intact and fixed bacteria. Changes in urease Synthesis or assembly were determined by incubation Of the organisms at pH 5.5 or 7.0 in the absence and presence of chloramphenicol, urea, or. nickel chelator and in urel-positive and -negative organisms. Results: The amount of surface urease was below detection limits with either centrifugation washing or immunostaining. Total bacterial urease activity was increased 3-5-fold by incubation at pH 5.5 in the presence of chloramphenicol but not in nickel-free medium or in urel knockout organism. There was also a 3-fold increase in survival of acid shock in acid-adapted organisms. Conclusions: Surface-bound urease is too low,to contribute to acid resistance. Acidic medium pH induces Urel-dependent nickel incorporation into apoenzyme. This augmentation of urease activity,increases survival in acid and is part of the gastric colonization strategy of the organism. C1 Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP Scott, DR (reprint author), Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. FU NIDDK NIH HHS [DK46917]; PHS HHS [53462, 17294, 41301] NR 39 TC 84 Z9 87 U1 0 U2 13 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 JUL PY 2002 VL 123 IS 1 BP 187 EP 195 DI 10.1053/gast.2002.34218 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 570VD UT WOS:000176678600024 PM 12105847 ER PT J AU Glatzle, J Sternini, C Robin, C Zittel, TT Wong, H Reeve, JR Raybould, HE AF Glatzle, J Sternini, C Robin, C Zittel, TT Wong, H Reeve, JR Raybould, HE TI Expression of 5-HT3 receptors in the rat gastrointestinal tract SO GASTROENTEROLOGY LA English DT Article ID GUINEA-PIG INTESTINE; 5-HYDROXYTRYPTAMINE TYPE-3 RECEPTORS; GATED ION-CHANNEL; INTERSTITIAL-CELLS; FUNCTIONAL EXPRESSION; MYENTERIC NEURONS; MOLECULAR-CLONING; PHARMACOLOGICAL CHARACTERIZATION; IMMUNONEUTRALIZING ACTIVITY; SEROTONIN RECEPTORS AB Background & Aims: Functional effects mediated via the 5-hydroxytryptamine(3) receptor (5-HT3R) can be elicited from both extrinsic and intrinsic neurons innervating the gastrointestinal (GI) tract. Clinically, 5-HT3 antagonists are important in the treatment of emesis and have been used for the treatment of symptoms in functional bowel disease. The aim of the present study was to elucidate the cellular sites of 5-HT3R expression in the rat GI tract using immunohistochemistry. Methods: Immunohistochemistry was performed in fixed cryostat sections and whole mounts of stomach and intestine of fasted rats, using an affinity-purified antibody directed to a 19-amino acid sequence of the cytoplasmic loop of the 5-HT3R. Results: 5-HT3R immunoreactivity was localized to numerous neurons of the myenteric and submucosal plexus, concentrated primarily near the neuronal plasma membrane, and to fibers in the circular and longitudinal muscles, submucosa, and mucosa. 5-HT3R immunoreactivity was also expressed by interstitial cells of Cajal and a few endocrine cells. Numerous 5-HT3R-positive myenteric neurons were cholinergic, and few neurons coexpressed VIP or SP immunoreactivity. Fibers immunoreactive for 5-HT3R in the duodenal but not ileal mucosa were markedly reduced by subdiaphragmatic vagotomy or chemical denervation of vagal afferents. Conclusions: These findings indicate that 5-HT(3)Rs are expressed by distinct cells in the GI tract, including functionally distinct classes of neurons, interstitial cells of Cajal, and endocrine cells. The effects of serotonin mediated by 5-HT3Rs involve the activation of neuronal and nonneuronal pathways. C1 Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Ctr Res & Educ, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Ctr Res & Educ, Dept Neurobiol, Los Angeles, CA USA. Vet Adm Greater Los Angeles Allied Hlth Serv, Los Angeles, CA USA. Univ Tubingen Hosp, Dept Gen Surg, Tubingen, Germany. RP Raybould, HE (reprint author), Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, 1321 Haring Hall, Davis, CA 95616 USA. FU NIDDK NIH HHS [DK41301, DK41004, DK57037, DK35740] NR 57 TC 91 Z9 97 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2002 VL 123 IS 1 BP 217 EP 226 DI 10.1053/gast.2002.34245 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 570VD UT WOS:000176678600027 PM 12105850 ER PT J AU Williams, JW Pignone, M Ramirez, G Stellato, CP AF Williams, JW Pignone, M Ramirez, G Stellato, CP TI Identifying depression in primary care: a literature synthesis of case-finding instruments SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE depressive disorder; sensitivity; specificity; diagnosis; mass screening ID GENERAL HEALTH QUESTIONNAIRE; RANDOMIZED CLINICAL-TRIAL; DIAGNOSING MENTAL-DISORDERS; MEDICAL OUTPATIENTS; SCREENING INSTRUMENT; SCALE GDS15; VALIDATION; RECOGNITION; MANAGEMENT; INVENTORY AB We evaluated the usefulness of case-finding instruments for identifying patients with major depression or dysthymia in primary care settings using English language literature from Medline, a specialized trials registry and bibliographies of selected papers. Studies were done in primary care settings with unselected patients and compared case-finding instruments with accepted diagnostic criterion standards for major depression were selected. A total of 16 case-finding instruments were assessed in 38 studies. More than 32,000 patients received screening with a case-finding instrument; approximately 12,900 of these received criterion standard assessment. Case-finding instruments ranged in length from 1 to 30 questions. Average administration times ranged from less than 2 min to 6 min. Median sensitivity for major depression was 85% (range 50% to 97%); median specificity was 74% (range 51% to 98%). No significant differences between instruments were found. However for individual instruments, estimates of sensitivity and specificity varied significantly between studies. For the combined diagnoses of major depression or dysthymia, overall sensitivity was 79% (CI, 74% to 83%) and overall specificity 75% (CI, 70% to 81%). Stratified analyses showed no significant effects on overall instrument performance for study methodology, criterion standard choice, or patient characteristics. We found that multiple instruments with reasonable operating characteristics are available to help primary care clinicians identify patients with major depression. Because operating characteristics of these instruments are similar, selection of a particular instrument should depend on issues such as feasibility, administration and scoring times, and the instruments' ability to serve additional purposes, such as monitoring severity or response to therapy. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Vet Evidence Based Res Disseminat & Implementat, S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Internal Med, San Antonio, TX USA. Univ N Carolina, Sch Med, Dept Gen Internal Med, Chapel Hill, NC USA. RTI UNC Evidence Based Practice Ctr, Chapel Hill, NC USA. San Antonio Evidence Based Practice Ctr, San Antonio, TX USA. RP Williams, JW (reprint author), Dept Vet Affairs Med Ctr, HSR&D, Ctr Hlth Serv Res Primary Care, Durham, NC USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 81 TC 149 Z9 154 U1 3 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JUL-AUG PY 2002 VL 24 IS 4 BP 225 EP 237 AR PII S0163-8343(02)00195-0 DI 10.1016/S0163-8343(02)00195-0 PG 13 WC Psychiatry SC Psychiatry GA 570VP UT WOS:000176679900005 PM 12100833 ER PT J AU Roig, J Mikhailov, A Belham, C Avruch, J AF Roig, J Mikhailov, A Belham, C Avruch, J TI Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression SO GENES & DEVELOPMENT LA English DT Article DE NIMA; NEK; Ran; RCC1; cdc2/MPF; mitosis ID CELL-CYCLE CONTROL; ASPERGILLUS-NIDULANS; PROTEIN-KINASE; CHROMATIN CONDENSATION; NUCLEAR TRANSPORT; SPINDLE; MITOSIS; CHECKPOINT; GENE; IDENTIFICATION AB The protein kinase NIMA is an indispensable pleiotropic regulator of mitotic progression in Aspergillus. Although several mammalian NIMA-like kinases (Neks) are known, none appears to have the broad importance for mitotic regulation attributed to NIMA. Nercc1 is a new NIMA-like kinase that regulates chromosome alignment and segregation in mitosis. Its NIMA-like catalytic domain is followed by a noncatalytic tail containing seven repeats homologous to those of the Ran GEF, RCC1, a Ser/Thr/Pro-rich segment, and a coiled-coil domain. Nercc1 binds to another NIMA-like kinase, Nek6, and also binds specifically to the Ran GTPase through both its catalytic and its RCC1-like domains, preferring RanGDP in vivo. Nercc1 exists as a homooligomer and can autoactivate in vitro by autophosphorylation. Nercc1 is a cytoplasmic protein that is activated during mitosis and is avidly phosphorylated by active p34(Cdc2). Microinjection of anti-Nercc1 antibodies in prophase results in spindle abnormalities and/or chromosomal misalignment. In Ptk2 cells the outcome is prometaphase arrest or aberrant chromosome segregation and aneuploidy, whereas in CFPAC-1 cells prolonged arrest in prometaphase is the usual response. Nercc1 and its partner Nek6 represent a new signaling pathway that regulates mitotic progression. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Roig, Joan/0000-0002-3872-4712 FU NIDDK NIH HHS [DK17776, R37 DK017776] NR 42 TC 90 Z9 92 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUL 1 PY 2002 VL 16 IS 13 BP 1640 EP 1658 DI 10.1101/gad.972202 PG 19 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 570VH UT WOS:000176679100005 PM 12101123 ER PT J AU Letko, E Bhol, K Colon, J Foster, CS Ahmed, AR AF Letko, E Bhol, K Colon, J Foster, CS Ahmed, AR TI Biology of interleukin-5 in ocular cicatricial pemphigoid SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID SERUM LEVELS; MAST-CELLS; EOSINOPHILS; ANTIBODIES; FIBROSIS AB Background: Ocular cicatricial pemphigoid (OCP) is an autoimmune disease characterized by the presence of autoantibodies, T-cell dysregulation, and abnormal serum levels of cytokines such as interleukin-6, interieukin-1, and tumor necrosis factor-alpha. The purpose of the present study was to investigate levels of interleukin-5 (IL-5) in the sera, eosinophil counts in the peripheral blood, and eosinophil and mast cell counts in the inflamed conjunctivae of patients with active OCP. Methods: Seven patients diagnosed in the active phase of OCP presenting with chronic cicatrizing conjunctivitis were studied. The serum levels of IL-5 were compared to a group of seven age-, race-, and sex-matched normal human subjects. Eosinophil and mast cell counts in the patients' conjunctivae were compared to those in normal conjunctivae harvested during cataract surgery from seven normal individuals. In addition, eosinophil counts in peripheral blood of patients with active OCP were compared to those in normal individuals. Results: The mean serum level of IL-5 in patients with active OCP was higher (67.23 pg/ml, range 46.33-98.26 pg/ml) than that in normal individuals (12.18 pg/ml, range 7.66-18.86). The difference was statistically significant (P<0.001). On light microscopy the biopsied conjunctivae stained with hematoxylin and eosin revealed statistically significant differences (P<0.001) in the mean numbers of eosinophils in the substantia propria between the patients with active OCP (6.8 cells/cm(2), range 4.8-8.2 cells/cm(2)) and normal controls (0.91 cells/cm(2), range 0.4-1.8 cells/cm2). The average number of mast cells found in the substantia propria of the biopsied conjunctivae was statistically significantly higher in patients with OCP (13.79 cells/cm(2), range 6.6-19.4) than in normal individuals (4.34 cells/cm(2), range 3.2-7.8; P<0.01). The average number of eosinophils in the peripheral blood of patients with active OCP (6.6x10(7)/1, range 2.9 - 9.3x10(7)/1) was statistically significantly higher (P<0.01) than in normal controls (2.09x10(7)/1, range 0 - 4.5x10(7)/1). The results suggest that IL-5 may play an important role in the pathogenesis of OCP. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. NE Baptist Hosp, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Uveitis & Immunol Serv, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. NR 17 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUL PY 2002 VL 240 IS 7 BP 565 EP 569 DI 10.1007/s00417-002-0497-4 PG 5 WC Ophthalmology SC Ophthalmology GA 583WJ UT WOS:000177433600012 PM 12136288 ER PT J AU Montoya, AG Sorrentino, R Lukas, SE Price, BH AF Montoya, AG Sorrentino, R Lukas, SE Price, BH TI Long-term neuropsychiatric consequences of "ecstasy" (MDMA): A review SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; (ECSTASY)-INDUCED SEROTONIN NEUROTOXICITY; AMPHETAMINE DESIGNER DRUGS; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; COGNITIVE PERFORMANCE; PARKINSONS-DISEASE; RECREATIONAL USERS; MEMORY IMPAIRMENT; BRAIN; PHARMACOLOGY AB The recreational drug "ecstasy" (3,4-methylenedioxymethamphetamine, or MDMA) is widely used by young people throughout the world. Experimental studies indicate that MDMA damages serotonergic neurons in animals and possibly in humans. Repeated use may induce long-term neurotoxic effects, with cognitive and behavioral implications. We reviewed both the preclinical and the clinical literature to assess the evidence for persistent neuropsychiatric sequelae in humans. We focused on studies of chronic recreational use and reports of presence or absence of neurological, psychiatric, and psychological problems related to MDMA exposure. These investigations show repeated use of ecstasy to be associated with sleep, mood, and anxiety disturbances, elevated impulsiveness, memory deficits, and attention problems, which may persist for up to 2 years after cessation. In a subset of humans, particularly adolescents, depletion of serotonin by MDMA use may hasten or enhance vulnerability to a wide array of neuropsychiatric problems. Together, the studies reviewed provide substantial evidence that MDMA causes neuronal damage in animals and humans. Additional research is necessary to determine whether the MDMA-induced destruction of serotonergic neurons can have long-term and possibly permanent neuropsychiatric consequences in humans. C1 McLean Hosp, Dept Neurol, Belmont, MA 02478 USA. McLean Hosp, Behav Psychopharmacol Res Lab, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. RP Price, BH (reprint author), McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA. NR 88 TC 63 Z9 63 U1 5 U2 22 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 212 EP 220 DI 10.1093/hrp/10.4.212 PG 9 WC Psychiatry SC Psychiatry GA 575ED UT WOS:000176932900002 PM 12119307 ER PT J AU Dechant, E Jellinek, M Goodwin, J Prince, JB AF Dechant, E Jellinek, M Goodwin, J Prince, JB TI Processing acute traumatic grief: Exacerbation of posttraumatic stress disorder after September 11 in a 9-year-old boy SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BEHAVIORAL-INHIBITION; PTSD; CHILDREN; CHILDHOOD; SERTRALINE; EFFICACY; PLACEBO; SAFETY; TRIAL C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. N Shore Med Ctr, Salem, MA USA. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77550 USA. RP Dechant, E (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, WACC 725,55 Fruit St, Boston, MA 02114 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 231 EP 241 DI 10.1093/hrp/10.4.231 PG 11 WC Psychiatry SC Psychiatry GA 575ED UT WOS:000176932900004 PM 12119309 ER PT J AU Golomb, M AF Golomb, M TI Psychiatric symptoms in metabolic and other genetic disorders: Is our "organic" workup complete? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID CARDIO-FACIAL SYNDROME; 22Q11 DELETION SYNDROME; REDUCTASE-ACTIVITY; CLINICAL-FEATURES; SCHIZOPHRENIA; HOMOCYSTINURIA; SPECTRUM; PHENYLKETONURIA; PREVALENCE; PORPHYRIA C1 Massachusetts Gen Hosp, Dept Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Golomb, M (reprint author), Massachusetts Gen Hosp, Dept Pediat, Genet & Teratol Unit, Fruit St, Boston, MA 02114 USA. NR 45 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD JUL-AUG PY 2002 VL 10 IS 4 BP 242 EP 248 DI 10.1093/hrp/10.4.242 PG 7 WC Psychiatry SC Psychiatry GA 575ED UT WOS:000176932900005 PM 12119310 ER PT J AU Moriguchi, H Uemura, T Kobayashi, M Chung, RT Sato, C AF Moriguchi, H Uemura, T Kobayashi, M Chung, RT Sato, C TI Management strategies using pharmacogenomics in patients with severe HCV-1b infection: A decision analysis SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; SENSITIVITY-DETERMINING REGION; NONSTRUCTURAL 5A REGION; CHRONIC LIVER-DISEASE; COST-EFFECTIVENESS; HEPATOCELLULAR-CARCINOMA; GENOTYPE 1B; INTERFERON THERAPY; AMERICAN PATIENTS; NS5A REGION AB The management of interferon (IFN) therapy for histologically severe chronic hepatitis C vim genotype 1b (HCV-1b [F3]) is controversial. A decision analysis using the Markov decision analysis model was performed for 6 disease management strategies by using clinical data from a Japanese teaching hospital and available published data. The results of base case analyses showed that IFN monotherapy was considered favorable for patients aged 40 to 60 years with HCV-1b (B). For the sensitivity analyses, to support the results of base case analyses, HCV-1b (173) patient quality-of-life (QOL) score must be 0.5 or greater for those 40 to 50 years old and 0.4 to 0.5 or greater for those 60 years old. When patients with HCV-1b (B) were judged as nonresponsive (NR) after IFN monotherapy, the transition probabilities of liver diseases at 40, 50, and 60 years of age had to be such that the progression of liver diseases was controlled at an annual rate of 7.51% to 8.82% or lower, 7.77% to 8.27% or lower, and 6.39% to 6.60% or lower, respectively, and the sustained virologic response (SVR) rate for IFN monotherapy must be 3.0% to 5.51% or greater, 5.57% to 5.93% or greater, and 10.6% to 11.21% or greater, respectively. It is likely that IFN monotherapy could be applied to patients with HCV-1b (173) aged 40 years at a dose of at least 432 MU. However, IFN monotherapy did not appear useful for patients with HCV-1b (B) aged 50 and 60 years if they had no amino acid mutation in NS5A 2209 to 2248 and HCV RNA levels exceeded 1.0 mEq/mL. In conclusion, use of decision analysis models can help in therapeutic decisions for patients with HCV-1b. C1 Univ Tokyo, Div Adv Med Technol & Intellectual Property Policy, Adv Sci & Technol Res Ctr, Meguro Ku, Tokyo 1538904, Japan. Crecon Res & Consulting Inc, Hlth Econ Res Grp, Tokyo, Japan. Keio Univ, Sch Med, Dept Prevent Med & Publ Hlth, Tokyo, Japan. Tokyo Med & Dent Univ, Fac Med, Dept Analyt Hlth Sci, Tokyo 113, Japan. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Moriguchi, H (reprint author), Univ Tokyo, Div Adv Med Technol & Intellectual Property Policy, Adv Sci & Technol Res Ctr, Meguro Ku, 4-6-1 Komaba, Tokyo 1538904, Japan. NR 50 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2002 VL 36 IS 1 BP 177 EP 185 DI 10.1053/jhep.2002.33895 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 568GP UT WOS:000176534300022 PM 12085363 ER PT J AU Perrillo, RP Lai, CL Liaw, YF Dienstag, JL Schiff, ER Schalm, SW Heathcote, EJ Brown, NA Atkins, M Woessner, M Gardner, SD AF Perrillo, RP Lai, CL Liaw, YF Dienstag, JL Schiff, ER Schalm, SW Heathcote, EJ Brown, NA Atkins, M Woessner, M Gardner, SD TI Predictors of HBeAg loss after lamivudine treatment for chronic hepatitis B SO HEPATOLOGY LA English DT Article ID TERM FOLLOW-UP; ALPHA-INTERFERON THERAPY; E-ANTIGEN SEROCONVERSION; CHRONIC ACTIVE HEPATITIS; CONTROLLED TRIAL; VIRUS-INFECTION; ALFA AB Elevated alanine transaminase (ALT) levels and low serum hepatitis B virus (HBV) DNA predict a higher likelihood of hepatitis B e antigen (HBeAg) loss in patients with chronic hepatitis B treated with interferon. Predictors of HBeAg loss in patients treated with lamivudine are not known. The objective of this analysis of 4 lamivudine-controlled Phase III trials was to determine patient-dependent or laboratory variables that predict HBeAg loss. Predictors of HBeAg loss in patients treated with interferon, lamivudine plus interferon, or placebo are also described. A total of 805 adults with chronic hepatitis B were treated either with lamivudine (n = 406), matching placebo (n = 196), interferon (n = 68), or the combination of lamivudine plus interferon (n = 135). Demographic and baseline disease characteristics were used in stepwise multivariate analyses to identify features that were predictive of lamivudine-induced HBeAg loss. HBeAg loss correlated with increased pretreatment ALT levels in all groups. The rate of HBeAg loss was highest among patients with pretreatment ALT levels greater than 5 times the upper limit of normal (ULN) and was most pronounced in the lamivudine group (56%). Multivariate modeling indicated that elevated baseline ALT levels (P < .001) and histologic activity index (HAI) score (P < .001) were important predictors of HBeAg loss in response to lamivudine. The effect of pretreatment ALT levels on HBeAg loss was similar for Asians and Caucasians. In conclusion, elevated pretreatment ALT levels and/or active histologic disease were the most important predictors of lamivudine-induced HBeAg loss. Asians and Caucasians had similar rates of response to lamivudine at comparable ALT levels. C1 Alton Ochsner Med Fdn & Ochsner Clin, Sect Gastroenterol & Hepatol, New Orleans, LA 70121 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Res & Dev Ltd, Greenford, Middx, England. Novirio Pharmaceut Inc, Cambridge, MA USA. Toronto Western Hosp, Div Gastroenterol, Toronto, ON M5T 2S8, Canada. Erasme Univ Hosp, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands. Vet Affairs Med Ctr, Miami, FL 33125 USA. Univ Miami, Med Ctr, Ctr Liver Dis, Miami, FL 33152 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Chang Gung Univ, Chang Gung Mem Hosp, Liver Res Unit, Taipei, Taiwan. Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. RP Perrillo, RP (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Sect Gastroenterol & Hepatol, 1514 Jefferson Highway, New Orleans, LA 70121 USA. RI Liaw, Yun-Fan /B-4305-2009; Lai, Ching Lung/C-4298-2009 FU NCRR NIH HHS [M01 RR 01066] NR 25 TC 209 Z9 218 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2002 VL 36 IS 1 BP 186 EP 194 DI 10.1053/jhep.2002.34294 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 568GP UT WOS:000176534300023 PM 12085364 ER PT J AU Kim, WR Brown, RS Terrault, NA El-Serag, H AF Kim, WR Brown, RS Terrault, NA El-Serag, H TI Burden of liver disease in the United States: Summary of a workshop SO HEPATOLOGY LA English DT Article ID NONALCOHOLIC FATTY LIVER; C VIRUS-INFECTION; NUTRITION EXAMINATION SURVEYS; PRIMARY BILIARY-CIRRHOSIS; SINGLE-CENTER EXPERIENCE; CHRONIC HEPATITIS-C; CRYPTOGENIC CIRRHOSIS; WILSONS-DISEASE; NATURAL-HISTORY; AUTOIMMUNE HEPATITIS C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Kim, WR (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 72 TC 302 Z9 310 U1 0 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2002 VL 36 IS 1 BP 227 EP 242 DI 10.1053/jhep.2002.34734 PG 16 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 568GP UT WOS:000176534300028 PM 12085369 ER PT J AU Pileri, SA Grogan, TM Harris, NL Banks, P Campo, E Chan, JKC Favera, RD Delsol, G De Wolf-Peeters, C Falini, B Gascoyne, RD Gaulard, P Gatter, KC Isaacson, PG Jaffe, ES Kluin, P Knowles, DM Mason, DY Mori, S Muller-Hermelink, HK Piris, MA Ralfkiaer, E Stein, H Su, IJ Warnke, RA Weiss, LM AF Pileri, SA Grogan, TM Harris, NL Banks, P Campo, E Chan, JKC Favera, RD Delsol, G De Wolf-Peeters, C Falini, B Gascoyne, RD Gaulard, P Gatter, KC Isaacson, PG Jaffe, ES Kluin, P Knowles, DM Mason, DY Mori, S Muller-Hermelink, HK Piris, MA Ralfkiaer, E Stein, H Su, IJ Warnke, RA Weiss, LM TI Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases SO HISTOPATHOLOGY LA English DT Review DE dendritic cell neoplasms; histiocytic sarcoma; malignant histiocytosis; Langerhans cell tumour and sarcoma; interdigitating dendritic cell sarcoma; follicular dendritic cell sarcoma; mononuclear-phagocytic system; reticuloendothelial system; dendritic cell; malignant lymphoma; immunohistochemistry ID PLASMACYTOID T-CELLS; EPSTEIN-BARR-VIRUS; CHRONIC MYELOPROLIFERATIVE DISORDERS; MACROPHAGE DIFFERENTIATION ANTIGEN; INTERDIGITATING RETICULUM CELLS; PARAFFIN WAX SECTIONS; IN-SITU HYBRIDIZATION; REED-STERNBERG CELLS; MALIGNANT HISTIOCYTOSIS; MONOCLONAL-ANTIBODIES AB Neoplasms of histiocytes and dendritic cells are rare, and their phenotypic and biological definition is incomplete. Seeking to identify antigens detectable in paraffin-embedded sections that might allow a more complete, rational immunophenotypic classification of histiocytic/dendritic cell neoplasms, the International Lymphoma Study Group (ILSG) stained 61 tumours of suspected histiocytic/dendritic cell type with a panel of 15 antibodies including those reactive with histiocytes (CD68, lysozyme (LYS)), Langerhans cells (CD1a), follicular dendritic cells (FDC: CD21, CD35) and S100 protein. This analysis revealed that 57 cases (93%) fit into four major immunophenotypic groups (one histiocytic and three dendritic cell types) utilizing six markers: CD68, LYS, CD1a, S100, CD21, and CD35. The four (7%) unclassified cases were further classifiable into the above four groups using additional morphological and ultrastructural features. The four groups then included: (i) histiocytic sarcoma (n =18) with the following phenotype: CD68 (100%), LYS (94%), CD1a (0%), S100 (33%), CD21/35 (0%). The median age was 46 years. Presentation was predominantly extranodal (72%) with high mortality (58% dead of disease (DOD)). Three had systemic involvement consistent with `malignant histiocytosis'; (ii) Langerhans cell tumour (LCT) (n =26) which expressed: CD68 (96%), LYS (42%), CD1a (100%), S100 (100%), CD21/35 (0%). There were two morphological variants: cytologically typical (n =17) designated LCT; and cytologically malignant (n =9) designated Langerhans cell sarcoma (LCS). The LCS were often not easily recognized morphologically as LC-derived, but were diagnosed based on CD1a staining. LCT and LCS differed in median age (33 versus 41 years), male:female ratio (3.7:1 versus 1:2), and death rate (31% versus 50% DOD). Four LCT patients had systemic involvement typical of Letterer-Siwe disease; (iii) follicular dendritic cell tumour/sarcoma (FDCT) (n =13) which expressed: CD68 (54%), LYS (8%), CD1a (0%), S100 (16%), FDC markers CD21/35 (100%), EMA (40%). These patients were adults (median age 65 years) with predominantly localized nodal disease (75%) and low mortality (9% DOD); (iv) interdigitating dendritic cell tumour/sarcoma (IDCT) (n =4) which expressed: CD68 (50%), LYS (25%), CD1a (0%), S100 (100%), CD21/35 (0%). The patients were adults (median 71 years) with localized nodal disease (75%) without mortality (0% DOD). In conclusion, definitive immunophenotypic classification of histiocytic and accessory cell neoplasms into four categories was possible in 93% of the cases using six antigens detected in paraffin-embedded sections. Exceptional cases (7%) were resolvable when added morphological and ultrastructural features were considered. We propose a classification combining immunophenotype and morphology with five categories, including Langerhans cell sarcoma. This simplified scheme is practical for everyday diagnostic use and should provide a framework for additional investigation of these unusual neoplasms. C1 Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pathol, Tucson, AZ 85724 USA. Univ Bologna, Serv Pathol Anat & Hematopathol, I-40126 Bologna, Italy. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Clin Hosp, Serv Anat Pathol, Barcelona, Spain. Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Columbia Univ, Dept Pathol, New York, NY USA. Toulouse Univ, Cent Lab Pathol Anat, Toulouse, France. Univ Louvain, Dept Pathol, Louvain, Belgium. Univ Perugia, Inst Haematol, I-06100 Perugia, Italy. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. Univ Oxford, Dept Cellular Sci, Oxford, England. UCL, Dept Histopathol, London, England. NCI, Bethesda, MD 20892 USA. Univ Gottingen, Dept Pathol, D-3400 Gottingen, Germany. Cornell Univ, Dept Pathol, New York, NY USA. Univ Tokyo, Dept Pathol, Tokyo, Japan. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Virgen Salud Hosp, Serv Anat Pathol, Toledo, Spain. Univ Copenhagen, Dept Pathol, Herlev, Denmark. Benjamin Franklin Univ, Inst Pathol, Berlin, Germany. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan, Taiwan. City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA. RP Grogan, TM (reprint author), Univ Arizona, Hlth Sci Ctr, Coll Med, Dept Pathol, 1501 N Campbell Ave,POB 245043, Tucson, AZ 85724 USA. EM pileri@almadns.unibo.it; TMGrogan@U.Arizona.edu RI Su, Ih-Jen/B-2655-2010; OI Piris, Miguel A/0000-0001-5839-3634; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA32102-18, CA34233] NR 88 TC 319 Z9 363 U1 2 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JUL PY 2002 VL 41 IS 1 BP 1 EP 29 DI 10.1046/j.1365-2559.2002.01418.x PG 29 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 571XW UT WOS:000176745300001 PM 12121233 ER PT J AU Hadjikhani, N de Gelder, B AF Hadjikhani, N de Gelder, B TI Neural basis of prosopagnosia: An fMRI study SO HUMAN BRAIN MAPPING LA English DT Article DE prosopagnosia; face recognition; object recognition; brain plasticity; fMRI ID HUMAN VISUAL-CORTEX; HUMAN EXTRASTRIATE CORTEX; SURFACE-BASED ANALYSIS; HUMAN FACE PERCEPTION; OCCIPITOTEMPORAL CORTEX; FUNCTIONAL-ANALYSIS; AREAS; RECOGNITION; SYSTEM; REPRESENTATIONS AB Brain imaging research has identified at least two regions in human extrastriate cortex responding selectively to faces. One of these is located in the mid-fusiform gyrus (FFA), the other in the inferior occipital gyrus (IOG). We studied activation of these areas using fMRI in three individuals with severely impaired face recognition (one pure developmental and two childhood prosopagnosics). None of the subjects showed the normal pattern of higher fMRI activity to faces than to objects in the FFA and JOG or elsewhere. Moreover, in two of the patients, faces and objects produced similar activations in the regions corresponding to where the FFA and IOG are found in normal subjects. Our study casts light on the important role of FFA and JOG in the network of areas involved in face recognition, and indicates limits of brain plasticity. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Tilburg Univ, Cognit Neurosci Lab, NL-5000 LE Tilburg, Netherlands. FC Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands. RP Hadjikhani, N (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 NR 38 TC 82 Z9 83 U1 1 U2 13 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD JUL PY 2002 VL 16 IS 3 BP 176 EP 182 DI 10.1002/hbm.10043 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 569TU UT WOS:000176619000005 PM 12112771 ER PT J AU Nath, SK Kelly, JA Reid, J Lam, T Gray-McGuire, C Namjou, B Aston, CE Harley, JB AF Nath, SK Kelly, JA Reid, J Lam, T Gray-McGuire, C Namjou, B Aston, CE Harley, JB TI SLEB3 in systemic lupus erythematosus (SLE) is strongly related to SLE families ascertained through neuropsychiatric manifestations SO HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY GENE; LOD SCORES; REVISED CRITERIA; LINKAGE ANALYSIS; GENOME SCAN; CLASSIFICATION; DISEASES; MODELS; POWER AB Seizures and psychosis are neuropsychiatric (NP) manifestations of a large number of systemic lupus erythematosus (SLE) patients. Since NP manifestations were part of the SLE phenotype for some, but not all SLE affecteds, we hypothesized that those SLE patient families with NP manifestations might be more genetically homogeneous at loci important to NP-related SLE, and hence have increased power to detect linkage. We identified 23 families of European-American (EA) origin and 20 families of African-American (AA) origin, in which at least one SLE patient in each family was diagnosed with the presence of NP manifestations. A total of 318 microsatellite markers at an average marker density of I I cM were genotyped. Uncertainty of the genetic model led us to perform the initial genome scan by a multipoint non-parametric allele sharing linkage method. Once the evidence of linkage was suggestive, we then performed parametric model-based linkage by maximizing the relevant parameters to define a parsimonious genetic model. We found the maximum multipoint parametric LOD score was 5.19 and the non-parametric linkage score (Zlr) was 3.12 (P=9x10(-4)) for EA NP pedigrees at 4p16, previously identified as SLEB3. The segregation behavior of this linked locus suggests a dominant mode of inheritance with an almost 100% homogeneous genetic effect in these pedigrees. The results demonstrated a significant increase of LOD score to detect SLEB3 when the families were further ascertained through NP, compared with the analysis of all EA SLE families together. C1 Oklahoma Med Res Fdn, Artrhrit & Immunol Res Program, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. Univ Oklahoma, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Ctr Med, Oklahoma City, OK USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Nath, SK (reprint author), Oklahoma Med Res Fdn, Artrhrit & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NCRR NIH HHS [RR15577]; NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR45231, AR-1-2253, AR42460] NR 30 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2002 VL 111 IS 1 BP 54 EP 58 DI 10.1007/s00439-002-0743-1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 580CX UT WOS:000177218000008 PM 12136236 ER PT J AU Chen, SYJ Carroll, JD Messenger, JC AF Chen, SYJ Carroll, JD Messenger, JC TI Quantitative analysis of reconstructed 3-D coronary arterial tree and intracoronary devices SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE 3-D reconstruction; angiography; angioplasty; intracoronary devices; vasculature ID ANGIOGRAPHIC VISUALIZATION; BASIC PRINCIPLES; RESTENOSIS; VALIDATION; DIMENSIONS; MOTION; STENT; CINEANGIOGRAMS; QUANTIFICATION; ARTERIOGRAPHY AB Traditional quantitative coronary angiography is performed on two-dimensional (2-D) projection views. These views are chosen by the angiographer to minimize vessel overlap and foreshortening. With 2-D projection views that are acquired in this nonstandardized. fashion, however, there is no way to know or estimate how much error occurs in the QCA process. Furthermore, coronary arteries possess a curvilinear shape and undergo a cyclical deformation due to their attachment to the myocardium. Therefore, it is necessary to obtain three-dimensional (3-D) information to best describe and quantify the dynamic curvilinear nature of the human coronary artery. Using a patient-specific 3-D coronary reconstruction algorithm and routine angiographic images, a new technique is proposed to describe: 1) the curvilinear nature of 3-D coronary arteries and intracoronary devices; 2) the magnitude of the arterial deformation caused by intracoronary devices and due to heart motion; and 3) optimal view(s) with respect to the desired "pathway" for delivering intracoronary devices. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Cardiol, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80262 USA. RP Chen, SYJ (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Div Cardiol, 4200 E 9th Ave, Denver, CO 80262 USA. FU NHLBI NIH HHS [HL60220-01A2] NR 40 TC 43 Z9 47 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2002 VL 21 IS 7 BP 724 EP 740 DI 10.1109/TMI.2002.801151 PG 17 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 599UH UT WOS:000178353200002 PM 12374311 ER PT J AU Solymar, DC Agarwal, S Bassing, CH Alt, FW Rao, A AF Solymar, DC Agarwal, S Bassing, CH Alt, FW Rao, A TI A 3 ' enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells SO IMMUNITY LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; HUMAN T-CELLS; COORDINATE REGULATOR; TRANSGENIC MICE; C-MAF; EXPRESSION; DIFFERENTIATION; INTERLEUKIN-4; SEQUENCE; BINDING AB Differentiation of naive T cells into mature Th2 cells is associated with the appearance of a complex pattern of DNase I hypersensitive (DH) sites within the IL-4/IL-13 cytokine gene cluster. We show here that targeted deletion of an inducible DH site, V-A, and the adjacent conserved DH site V (CNS-2) selectively compromises IL-4 gene transcription by differentiated Th2 cells and mast cells. In mast cells, the deletion abrogates IL-4 mRNA induction, an effect mimicked by deletion of the transcription factor NFAT1 (NFATc2), which binds DH site VA. In T cells, the deletion impairs a process of response maturation, defined by progressive increases in IL-4 levels as Th2 differentiation proceeds. These results identify an essential enhancer which regulates IL-4 gene expression in two important cell lineages in vivo. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI35714, AI20047, AI44432] NR 53 TC 92 Z9 94 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2002 VL 17 IS 1 BP 41 EP 50 DI 10.1016/S1074-7613(02)00334-5 PG 10 WC Immunology SC Immunology GA 579PR UT WOS:000177187500005 PM 12150890 ER PT J AU Lee, CK Raz, R Gimeno, R Gertner, R Wistinghausen, B Takeshita, K DePinho, RA Levy, DE AF Lee, CK Raz, R Gimeno, R Gertner, R Wistinghausen, B Takeshita, K DePinho, RA Levy, DE TI STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation SO IMMUNITY LA English DT Article ID COLONY-STIMULATING FACTOR; EMBRYONIC STEM-CELLS; FACTOR-RECEPTOR; TARGETED DISRUPTION; MYELOID DIFFERENTIATION; SIGNAL-TRANSDUCTION; CHRONIC NEUTROPENIA; DEFICIENT MICE; GRANULOCYTE; ACTIVATION AB STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3. C1 NYU, Sch Med, Dept Pathol, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. NYU, Sch Med, Dept Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Levy, DE (reprint author), NYU, Sch Med, Dept Pathol, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. OI Lee, Chien-Kuo/0000-0001-8189-6045 NR 45 TC 146 Z9 151 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2002 VL 17 IS 1 BP 63 EP 72 DI 10.1016/S1074-7613(02)00336-9 PG 10 WC Immunology SC Immunology GA 579PR UT WOS:000177187500007 PM 12150892 ER PT J AU Husain, Z Alper, CA Yunis, EJ Dubey, DP AF Husain, Z Alper, CA Yunis, EJ Dubey, DP TI Complex expression of natural killer receptor genes in single natural killer cells SO IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN-LIKE RECEPTORS; IG-LIKE RECEPTOR; MHC CLASS-I; LY49 RECEPTORS; NK CELLS; REPERTOIRE; LECTIN; ACQUISITION; INDIVIDUALS; PHENOTYPES AB Human natural killer (NK) cells express several inhibitory and non-inhibitory NK receptors per cell. Understanding the expression patterns of these receptor genes in individual cells is important to understanding their function. Using a single-cell reverse transcription-polymerase chain reaction (RT-PCR) method, we analysed the expression of nine NK receptor genes in 38 resting CD56(+) NK cells from peripheral blood of normal donors. We observed highly diverse patterns of receptor expression in these cells. No NK receptor is expressed universally in every CD56(+) NK cell. The expressed receptor types per cell varied from two to eight. We specifically analysed the distribution of inhibitory (DL) and non-inhibitory (DS) killer immunoglobulin-like receptors (KIR). The frequency of individual receptor expression varied from 26% for 2DS2 to 68% for both 2DL1 and 2DL4. A comparison of the coexpression of DL and DS receptors showed a significant association in the expression of 2DL2 and 2DS2 (chi(2) =16.6; P <0.001) genes but no association between 2DL1 and 2DS1 or between 3DL1 and 3DS1 genes. Coexpression analysis of the 2DL1 and 2DL2 genes in 2DL4(+) and 2DL4(-) cells showed a strong association in 2DL4(+) but not in 2DL4(-) cells, suggesting a differential effect of the 2DL4 gene on the expression of 2DL1 and 2DL2 genes. Single-cell RT-PCR is a powerful tool to study multiple receptor gene expression ex vivo in individual NK cells and provides information about the expression pattern of KIR receptors that may suggest mechanisms of gene expression responsible for generation of the KIR repertoire. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Dubey, DP (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583, P01 HL029583] NR 29 TC 24 Z9 28 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2002 VL 106 IS 3 BP 373 EP 380 DI 10.1046/j.1365-2567.2002.01444.x PG 8 WC Immunology SC Immunology GA 568CX UT WOS:000176525800011 PM 12100725 ER PT J AU Angelakopoulos, H Loock, K Sisul, DM Jensen, ER Miller, JF Hohmann, EL AF Angelakopoulos, H Loock, K Sisul, DM Jensen, ER Miller, JF Hohmann, EL TI Safety and shedding of an attenuated strain of Listeria monocytogenes with a deletion of actA/plcB in adult volunteers: a dose escalation study of oral inoculation SO INFECTION AND IMMUNITY LA English DT Article ID TO-CELL SPREAD; EXPERIMENTALLY INFECTED GOATS; HELICOBACTER-PYLORI UREASE; IN-VITRO; INTRACELLULAR GROWTH; HEPATIC INVOLVEMENT; PHOSPHOLIPASE-C; IMMUNE-RESPONSE; VACCINE; INDUCTION AB Listeria monocytogenes is an intracellular bacterial pathogen which causes bacteremia and has a tropism for the central nervous system and a propensity to cause maternofetal infection. L. monocytogenes has been shown to be an effective prophylactic and a therapeutic vaccine vector for viral and tumor antigens in animal models. L. monocytogenes mutants lacking the ActA protein, which is essential for intracellular movement, are attenuated but retain immunogenicity in mice. Given the pathogenic potential of L. monocytogenes, we created an attenuated mutant strain bearing double deletions in the actA and plcB virulence genes for an initial clinical safety study of a prototype L. monocytogenes vector in adults. Twenty healthy volunteers received single escalating oral doses (10(6) to 10(9) CFU, 4 volunteers per dose cohort) of this attenuated L. monocytogenes, designated LH1169. Volunteers were monitored in the hospital for 14 days with frequent clinical checks and daily blood and stool cultures, and they were monitored for six additional weeks as outpatients. There were no positive blood cultures and no fevers attributable to the investigational inoculation. Most volunteers shed vaccine bacteria for 4 days or less, without diarrhea. One volunteer had a late positive stool culture during outpatient follow-up. Three volunteers had abnormal liver function test results temporally associated with inoculation; one could be reasonably attributed to another cause. In the highest-dose cohort, humoral, mucosal, and cellular immune responses to the investigational organism were detected in individual volunteers. Attenuated L. monocytogenes can be studied in adult volunteers without serious long-term health sequelae. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 94270 USA. RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM ehohmann@partners.org FU NCI NIH HHS [R01 CA084008, R01CA84008]; NCRR NIH HHS [M01 RR001066, M01RR01066-21]; NIAID NIH HHS [R01 AI045137, R01AI45137] NR 63 TC 78 Z9 85 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3592 EP 3601 DI 10.1128/IAI.707.3592-3601.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600034 PM 12065500 ER PT J AU Shapiro, EL Ginzberg, R AF Shapiro, EL Ginzberg, R TI Parting gifts: Termination rituals in group therapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article AB A Patient's termination from group therapy is a powerful experience for the departing Patient, the therapist, and all group members. Unless the feelings evoked are channeled into constructive expression, they may undermine this potentially valuable phase of both the departing patient's group treatment and the life of the group as a whole. A termination ritual, styled by a particular patient according to his or her own need, therapy goals, and personality may help the patient achieve a more clearly defined sense of self. The authors suggest that the group therapist's careful attunement to and thorough exploration of the significance of any termination ritual or gift will help to extract maximum therapeutic benefit for the departing member and the group as a whole. C1 Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Shapiro, EL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Psychoanalyt Studies, 15 Parkman St,ACC 805, Boston, MA 02114 USA. NR 20 TC 8 Z9 8 U1 1 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2002 VL 52 IS 3 BP 319 EP 336 DI 10.1521/ijgp.52.3.319.45507 PG 18 WC Psychology, Clinical SC Psychology GA 562AJ UT WOS:000176175000001 PM 12082674 ER PT J AU Ulman, KH AF Ulman, KH TI The ghost in the group room: Countertransferential pressures associated with conjoint individual and group psychotherapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID DILEMMAS AB Conjoint individual and group therapy is a commonly used, effective psychotherapeutic treatment. The relationship between the conjoint therapists signficantly influences the treatment. This article examines countertransference dilemmas of the group and individual therapists arising from the real and fantasied conjoint relationship. Case examples illustrate specific countertransference dilemmas. Therapists are encouraged to consider the Possibility of difficulties with each potential conjoint treatment. Consultation and supervision are recommended to heap the conjoint therapists identify and manage countertransference Pressures. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Grp Psychotherapy, Boston, MA 02114 USA. RP Ulman, KH (reprint author), 17 Elm St, Boxford, MA 01921 USA. NR 30 TC 6 Z9 6 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JUL PY 2002 VL 52 IS 3 BP 387 EP 407 DI 10.1521/ijgp.52.3.387.45516 PG 21 WC Psychology, Clinical SC Psychology GA 562AJ UT WOS:000176175000005 PM 12082678 ER PT J AU Griffiths, CT Parker, LM Lee, S Finkler, NJ AF Griffiths, CT Parker, LM Lee, S Finkler, NJ TI The effect of residual mass size on response to chemotherapy after surgical cytoreduction for advanced ovarian cancer: Long-term results SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE chemosensitivity of residual tumor; ovarian cancer ID COMBINATION CHEMOTHERAPY; DEBULKING SURGERY; CARCINOMA; CISPLATIN; PROGNOSIS; SURVIVAL; CYCLOPHOSPHAMIDE; TRIAL AB We report an observational study of chemotherapeutic regression of ovarian tumor implants according to decrements in residual mass size after surgical cytoreduction. Cytoreductive operations were attempted on 74 consecutive patients with stages IIIB-IV disease referred for this purpose. Thirty-two patients had received one to four courses of preoperative chemotherapy (22 responses, no progressions). Postoperative chemotherapy followed current protocols at Dana Farber Cancer Institute (n=61) or referring institutions (n=13); 57 regimens contained cisplatin. Postchemotherapy response was assessed clinically or by second-look procedures. Negative findings were considered a complete remission. Masses >1 cm were excised from 62 patients. Twelve patients were inoperable. Twenty-eight patients had complete remissions and the correlation between these and decrements in residual mass size was highly significant (P <0.0001). Complete remissions had a uniform effect and were the only outcome predictive of survival. Preoperative treatment greatly facilitated cytoreduction but only masses 0-0.2 cm were senstitive to postoperative chemotherapy. Masses 0.5 cm or less were optimal. They made up 77% of operable patients and supplied 25 (89%) of the complete remissions. Cytoreduction is not always required but even large-volume disease in the upper abdomen can be safely excised. The concept that masses larger than 10 cm indicate general chemoresistance has not been sustained. C1 Florida Hosp Canc Inst, Orlando, FL 32805 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Finkler, NJ (reprint author), Florida Hosp Canc Inst, Orlando, FL 32805 USA. NR 33 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD JUL-AUG PY 2002 VL 12 IS 4 BP 323 EP 331 DI 10.1046/j.1525-1438.2002.01150.x PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 577WQ UT WOS:000177085900002 PM 12144679 ER PT J AU Young, RH AF Young, RH TI Simple clefts, complex problems: Reflections on glandular lesions of the uterine cervix SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Editorial Material ID ECTOPIC PROSTATIC TISSUE; ADENOID BASAL CARCINOMA; MALIGNUM; ADENOCARCINOMA; HYPERPLASIA; METAPLASIA; ENDOMETRIOSIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 35 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2002 VL 21 IS 3 BP 212 EP 216 DI 10.1097/00004347-200207000-00002 PG 5 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 565JH UT WOS:000176366000002 ER PT J AU Halabi, M Oliva, E Mazal, PR Breitenecker, G Young, RH AF Halabi, M Oliva, E Mazal, PR Breitenecker, G Young, RH TI Prostatic tissue in mature cystic teratomas of the ovary: A report of four cases, including one with features of prostatic adenocarcinoma, and cytogenetic studies SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; dermoid cyst; prostatic tissue; prostatic adenocarcinoma; FISH ID UTERINE CERVIX; ORIGIN AB Four cases of mature cystic teratoma that contained prostatic tissue are reported. The ovarian tumors occur-red in patients from 17 to 38 (mean 31) years of age and had no unusual clinical or gross aspects. The microscopic findings for the most part were typical of a mature cystic teratoma, but they also contained foci of prostatic tissue that ranged from 0.2 to 1.9 cm in greatest dimension. In these areas there was a lobular arrangement of medium-sized acini lined by cuboidal to columnar cells with pale cytoplasm and round nuclei with inconspicuous nucleoli except focally in one case a noted below. Basal cells were seen focally. The prostatic acini lay in a paucicellular fibromuscular stroma, In two cases thick layers of disorganized smooth muscle covered by transitional-like pseudostratified epithelium, resulting in an appearance resembling fetal bladder wall, were present next to the prostatic glands. One tumor also contained prostatic-type acini. which haphazardly infiltrated the stroma over an area approximately 5 mm in maximal dimension. The acini, a few of which contained intraluminal flocculent eosinophilic material, were lined by cells with eosinophilic to amphophilic focally granular cytoplasm and had nuclei that were enlarged compared with the benign-appearing, prostatic-type acini in the four cases and had focally prominent nucleoli. Basal cells were not identified in these infiltrating glands, Grading this focus according to the approach in the prostate, the morphology was that of a Gleason grade 3 of 5 adenocarcinoma. Immunohistochemical stains of the putative prostatic epithelial cells confirmed their nature by showing immunoreactivity for prostatic-specific antigen in the lining epithelial cells in all four cases and for prostatic-specific acid phosphatase in the one case tested. The high molecular cytokeratin stain, 34betaE12, highlighted basal cells to a variable extent in the three cases containing only benign prostatic tissue. Material was not available to immunostain for basal cells in the case with carcinoma, Cytogenetic studies were performed in two cases and showed that the great majority of the nuclei of the nonprostatic and prostatic tissue had an XX karyotype but from 3% to 5% of the nuclei displayed trisomy for the X chromosome. A small number of cases of prostatic tissue in ovarian teratomas have previously been documented but none had morphologic features of carcinoma. C1 Gen Hosp Ried, Dept Pathol, A-4910 Ried, Austria. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Univ Vienna, Vienna Gen Hosp, Dept Clin Pathol, A-1010 Vienna, Austria. RP Halabi, M (reprint author), Gen Hosp Ried, Dept Pathol, Schlossberg 1, A-4910 Ried, Austria. NR 32 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 2002 VL 21 IS 3 BP 261 EP 267 DI 10.1097/00004347-200207000-00009 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 565JH UT WOS:000176366000009 PM 12068172 ER PT J AU Steinhauer, SR Siegle, GJ Condray, R Carter, CC Thase, ME AF Steinhauer, SR Siegle, GJ Condray, R Carter, CC Thase, ME TI Pupillary dilation, cognition, and psychiatric disorder: Insights to brain function SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2002 VL 45 IS 1-2 BP 43 EP 43 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 578AP UT WOS:000177095500100 ER PT J AU Pekary, AE Sattin, A Meyerhoff, JL Chilingar, M AF Pekary, AE Sattin, A Meyerhoff, JL Chilingar, M TI Mood stabilizers increase TRH receptor levels in rat brain SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Res & Psychiat Serv, VA Greater Los Angeles Healtcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2002 VL 45 IS 1-2 BP 154 EP 154 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 578AP UT WOS:000177095500391 ER PT J AU D'Amico, AV Keshaviah, A Manola, J Cote, K Loffredo, M Iskrzytzky, O Renshaw, AA AF D'Amico, AV Keshaviah, A Manola, J Cote, K Loffredo, M Iskrzytzky, O Renshaw, AA TI Clinical utility of the percentage of positive prostate biopsies in predicting prostate cancer-specific and overall survival after radiotherapy for patients with localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; survival; tumor volume; radiotherapy ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; RECURRENCE; NOMOGRAM; ANTIGEN AB Purpose: To determine whether the percentage of positive prostate biopsies provides clinically relevant information to a previously established risk stratification system with respect to the end points of prostate cancer-specific survival (PCSS) and overall survival after radiotherapy for patients with clinically localized prostate cancer. Methods and Materials: A Cox regression multivariable analysis was used to evaluate the ability of the percentage of positive prostate biopsies to predict PCSS and overall survival for 381 men who underwent radiotherapy for localized prostate cancer during the prostate-specific antigen era. Results: At a median follow-up of 4.3 years (range 0.8-13.3), the presence of less than or equal to50% positive biopsies vs. >50% positive biopsies provided a clinically relevant stratification of the 7-year estimates of PCSS (100% vs. 57%, p = 0.004) in intermediate-risk patients. Moreover, all patients could be stratified into a minimal or high-risk cohort on the basis of the 10-year estimates of PCSS (100% vs. 55%, p < 0.0001) and overall survival (87% vs. 40%, p = 0.02) by incorporating the percentage of positive prostate biopsy information into a previously established risk stratification system. Conclusion: The clinically relevant stratification of PCSS using the percentage of positive prostate biopsies in intermediate-risk patients confirms previous findings based on prostate-specific antigen outcome. These data provide evidence to support the ability to stratify newly diagnosed patients with clinically localized disease into a minimal-risk (low-risk + low biopsy volume [&LE;50%] intermediate-risk) or high-risk (high biopsy volume [>50%] intermediate-risk + high-risk) cohort for prostate cancer-specific death after conventional dose radiotherapy. Additional follow-up and independent validation are needed to confirm these findings. (C) 2002 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. NR 13 TC 29 Z9 30 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 JUL 1 PY 2002 VL 53 IS 3 BP 581 EP 587 AR PII S0360-3016(02)02797-9 DI 10.1016/S0360-3016(02)02797-9 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 568JR UT WOS:000176539100009 PM 12062600 ER PT J AU Zacks, DN Ezra, E Terada, Y Michaud, N Connolly, E Gragoudas, ES Miller, JW AF Zacks, DN Ezra, E Terada, Y Michaud, N Connolly, E Gragoudas, ES Miller, JW TI Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: Angiographic and histologic characterization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MACULAR DEGENERATION; NORMAL RETINA; BENZOPORPHYRIN; PHASE-1 AB PURPOSE. To develop a model of verteporfin photodynamic therapy (PDT) for experimental choroidal neovascularization CNV in the rat. METHODS. A laser injury model was used to induce experimental CNV in rats. The transit and accumulation of the photosensitizer verteporfin was assessed angiographically in CNV lesions. to determine the optimal time for delivery of light energy. The CNV lesions were then treated with verteporfin PDT, with two doses of verteporfin (3.0 and 6.0 mg/m(2)) and four activating doses of light energy (10, 25, 50, and 100 J/cm(2)). Closure of the CNV was assessed both angiographically and histologically. Verteporfin PDT was also performed on areas of normal choroid and retina at the two verteporfin doses and four light energy doses. The effect of these treatments on these structures was also assessed angiographically and histologically. RESULTS. Peak verteporfin intensities in the CNV were detected at 15 to 20 minutes after intravenous injection. Rates of closure of the CNV varied as a function of the dose of verteporfin and of the activating light energy. Angiographic closure of the CNV correlated with damage to the neovascular complex, as seen with light and electron microscopy. Damage to areas of normal choroid and retina treated with verteporfin PDT also varied as a function of the verteporfin and light energy doses. CONCLUSIONS. Verteporfin PDT for experimental CNV in the rat is a feasible, effective, and reproducible model that can be used for testing the efficacy of adjunctive therapy to verteporfin PDT. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 19 TC 54 Z9 58 U1 0 U2 7 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2002 VL 43 IS 7 BP 2384 EP 2391 PG 8 WC Ophthalmology SC Ophthalmology GA 567JU UT WOS:000176482300046 PM 12091441 ER PT J AU Cohen, LS Soares, CN Otto, MW Sweeney, BH Liberman, RF Harlow, BL AF Cohen, LS Soares, CN Otto, MW Sweeney, BH Liberman, RF Harlow, BL TI Prevalence and predictors of premenstrual dysphoric disorder (PMDD) in older premenopausal women - The Harvard Study of Moods and Cycles SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE PMS; prevalence; predictors; premenstrual dysphoric disorder; PMDD ID DEPRESSIVE DISORDER; NONCLINICAL SAMPLE; CIGARETTE-SMOKING; MAJOR DEPRESSION; SEEKING BEHAVIOR; SYMPTOMS; ANXIETY; HISTORY AB Background: Consistent data on the prevalence and predictors of premenstrual dysphoric disorder (PMDD) in the general population are lacking. Methods: Premenstrual symptoms of 4164 women (aged 36-44 years) were retrospectively assessed by the Moos Premenstrual Inventory. From this original sample, 976 subjects were further interviewed at which time demographic and lifestyle characteristics, gynecologic history, and medical conditions were examined. The Structured Clinical Interview for DSM-IV Axis I disorders (SCID) was used to assess past and current psychiatric morbidity. Additionally, 513 of these women completed a prospective evaluation of premenstrual symptoms by using the Daily Rating of Severity of Problems Form (DRSP). Results: The diagnosis of PMDD was confirmed in 33 of 513 women (6.4%) who completed the prospective evaluation with daily records. Fourteen subjects (2.7%) met criteria for PMDD without a previous history of depression. PMDD was associated with lower education (odds ratio [OR] = 2.3, confidence interval [CI] = 1.1-4.9), a history of major depression (OR = 3.6, CI = 1.7-7.4), and current cigarette smoking (OR = 4.1, CI = 1.5-11.1). In addition, women not working outside the home were significantly less likely to meet criteria for PMDD (OR = 0.2, CI = 0.1-0.9). Limitations: Only 513 of 976 women agreed to have:their symptoms documented prospectively. Symptoms were assessed over the course of one menstrual cycle. Conclusions: This study indicates a significant prevalence of PMDD in a large community-based sample. Given the associated impairment in social and occupational functioning seen in PMDD, these prevalence data provide a strong rationale for enhanced recognition and treatment of the disorder. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Cohen, LS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. FU NIMH NIH HHS [R01-MH-50013] NR 35 TC 82 Z9 84 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 2002 VL 70 IS 2 BP 125 EP 132 AR PII S0165-0327(01)00458-X DI 10.1016/S0165-0327(01)00458-X PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 580FC UT WOS:000177223600003 PM 12117624 ER PT J AU Foy, BD AF Foy, BD TI Adolescents, alcohol, and substance abuse: Reaching teens through brief interventions. SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Book Review C1 Washington Univ, St Louis, MO USA. Student Hlth & Counseling Ctr, St Louis, MO USA. Boston VA & Boston Univ, Clin Intership Program, Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. RP Foy, BD (reprint author), Campus Box 1201,1 Brookings Dr, St Louis, MO 63130 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD JUL PY 2002 VL 51 IS 1 BP 48 EP COVER3 PG 2 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 590MW UT WOS:000177827500010 ER PT J AU Sakamoto, K Goodyear, LJ AF Sakamoto, K Goodyear, LJ TI Exercise effects on muscle insulin signaling and action - Invited review: Intracellular signaling in contracting skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Review DE exercise; insulin signaling; mitogen-activated protein kinase; AMP-activated protein kinase; phosphatidylinositol 3-kinase ID ACTIVATED PROTEIN-KINASE; JUN NH2-TERMINAL KINASE; ACETYL-COA CARBOXYLASE; GLYCOGEN-SYNTHASE KINASE-3; INDUCED GLUCOSE-TRANSPORT; INDUCED CARDIAC-HYPERTROPHY; ACUTE RESISTANCE EXERCISE; INITIATION-FACTOR 2B; MAP KINASE; MALONYL-COA AB Physical exercise is a significant stimulus for the regulation of multiple metabolic and transcriptional processes in skeletal muscle. For example, exercise increases skeletal muscle glucose uptake, and, after exercise, there are increases in the rates of both glucose uptake and glycogen synthesis. A single bout of exercise can also induce transient changes in skeletal muscle gene transcription and can alter rates of protein metabolism, both of which may be mechanisms for chronic adaptations to repeated bouts of exercise. A central issue in exercise biology is to elucidate the underlying molecular signaling mechanisms that regulate these important metabolic and transcriptional events in skeletal muscle. In this review, we summarize research from the past several years that has demonstrated that physical exercise can regulate multiple intracellular signaling cascades in skeletal muscle. It is now well established that physical exercise or muscle contractile activity can activate three of the mitogen-activated protein kinase signaling pathways, including the extracellular signal-regulated kinase 1 and 2, the c-Jun NH2-terminal kinase, and the p38. Exercise can also robustly increase activity of the AMP-activated protein kinase, as well as several additional molecules, including glycogen synthase kinase 3, Akt, and the p70 S6 kinase. A fundamental goal of signaling research is to determine the biological consequences of exercise-induced signaling through these molecules, and this review also provides an update of progress in this area. 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. NR 160 TC 153 Z9 165 U1 2 U2 6 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 JUL PY 2002 VL 93 IS 1 BP 369 EP 383 DI 10.1152/japplphysiol.00167.2002 PG 15 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 563JV UT WOS:000176253300048 PM 12070227 ER PT J AU de Boer, JF Milner, TE AF de Boer, JF Milner, TE TI Review of polarization sensitive optical coherence tomography and Stokes vector determination SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Review DE optical coherence tomography; polarization; birefringence; turbid media; multiple scattering ID BIOLOGICAL TISSUE; BIREFRINGENCE CHARACTERIZATION; MUELLER MATRICES; LIGHT; REFLECTOMETER; ELLIPSOMETRY; INVIVO; MEDIA AB Polarization sensitive optical coherence tomography (PS-OCT) provides depth resolved measurements of the polarization state of light reflected from turbid media such as tissue. The theory and calculation of the Stokes vector of light reflected from turbid media is described and application of PS-OCT to contemporary biomedical imaging problems is given. Measurement of the depth resolved Stokes parameters allows determination of the degree of polarization and optical axis orientation in turbid media that can be modeled as a linear retarder. Effect of multiple scattering and speckle on the accuracy and noise of the computed Stokes parameters is discussed. Future directions for development of PS-OCT instrumentation for biological and medical applications is given. (C) 2002 Society of Photo-Optical Instrumentation Engineers. C1 Univ Texas, Biomed Engn Dept, Austin, TX 78712 USA. RP de Boer, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 41 TC 266 Z9 269 U1 9 U2 50 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD JUL PY 2002 VL 7 IS 3 BP 359 EP 371 DI 10.1117/1.1483879 PG 13 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 584RR UT WOS:000177482700011 PM 12175285 ER PT J AU Mankin, HJ Isaacson, KB Cullen, KJ AF Mankin, HJ Isaacson, KB Cullen, KJ TI A happy outcome to a bad problem SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article C1 Massachusetts Gen Hosp, Orthopaed Oncol & Reprod Endocrinol Serv, Boston, MA 02114 USA. Georgetown Univ Hosp, Hematol Oncol Serv, Washington, DC 20007 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol & Reprod Endocrinol Serv, Gray 604, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 JUL PY 2002 VL 84A IS 7 BP 1251 EP 1253 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 572KE UT WOS:000176772700024 PM 12107329 ER PT J AU Tashjian, AH Chabner, BA AF Tashjian, AH Chabner, BA TI Commentary on clinical safety of recombinant human parathyroid hormone 1-34 in the treatment of osteoporosis in men and postmenopausal women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material ID OVARIECTOMIZED CYNOMOLGUS MONKEYS; INCREASES BONE-FORMATION; CORTICAL BONE; HUMAN PARATHYROID-HORMONE-(1-34); PRIMARY HYPERPARATHYROIDISM; THYROID-GLAND; INTERMITTENT TREATMENT; COMBINATION THERAPY; SEQUENTIAL ADDITION; MACACA-FASCICULARIS C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Tashjian, AH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave,Bldg 1,Room 1202, Boston, MA 02115 USA. NR 78 TC 76 Z9 79 U1 0 U2 2 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 JUL PY 2002 VL 17 IS 7 BP 1151 EP 1161 DI 10.1359/jbmr.2002.17.7.1151 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 566KL UT WOS:000176427200003 PM 12096828 ER PT J AU Jongnarangsin, K Mela, T AF Jongnarangsin, K Mela, T TI Implantable Cardioverter defibrillator sensing failure due to endocardial R wave electrical alternans SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE electrical alternans; implantable cardioverter defibrillator; undersensing; ventricular tachycardia ID VENTRICULAR-FIBRILLATION; ANTIARRHYTHMIC DRUGS; GAIN; SYSTEM AB A 71-year-old patient underwent routine singlechamber implantable cardioverter defibrillator (ICD) generator replacement. During detibrillation threshold testing, ventricular tachyeardia was induced but the ICD failed twice to properly detect the tachycardia due to endocardial R wave alternans and sensing of every other beat. The problem was resolved by inserting a separate sensing/pacing lead positioned further away from the existing ICD lead. C1 Harvard Univ, Cardiac Arrhythmia Serv, Div Cardiol, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Mela, T (reprint author), Harvard Univ, Cardiac Arrhythmia Serv, Div Cardiol, Massachusetts Gen Hosp,Med Sch, 75 Fruit St, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JUL PY 2002 VL 13 IS 7 BP 702 EP 704 DI 10.1046/j.1540-8167.2002.00702.x PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 573VP UT WOS:000176852700016 PM 12139297 ER PT J AU Singhal, AB Wang, XY Sumii, T Mori, T Lo, EH AF Singhal, AB Wang, XY Sumii, T Mori, T Lo, EH TI Effects of normobaric hyperoxia in a rat model of focal cerebral ischemia-reperfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE oxygen free radical; oxidative stress; heat shock protein; reperfusion; blood-brain barrier; neuroprotection ID BLOOD-BRAIN-BARRIER; HYPERBARIC-OXYGEN; HEME OXYGENASE-1; ARTERY OCCLUSION; LIPID-PEROXIDATION; PROTEIN OXIDATION; STROKE; GERBIL; FLOW; PERMEABILITY AB Recent studies suggest that normobaric hyperoxia can be beneficial, if administered during transient stroke. However, increased oxygenation theoretically may increase oxygen free-radical injury, particularly during reperfusion. In the present study, the authors assessed the benefit and risks of hyperoxia during focal cerebral ischemia and reperfusion. Rats were subjected to hyperoxia (FIO2 100%) or normoxia (FIO2 30%) during 2-hour filament occlusion and 1-hour reperfusion of the middle cerebral artery. At 24 hours, the hyperoxia group showed 70% (total) and 92% (cortical) reduction in infarct volumes as compared to the normoxia group. Levels of oxidative stress were evaluated using three indirect methods. First, since oxygen free radicals increase blood-brain barrier (BBB) damage, Evan's blue dye extravasation was quantified to assess BBB damage. Second, the expression of heme oxygenase-1 (HO-1), a heat shock protein inducible by oxidative stress, was assessed using Western blot techniques. Third, an immunoblot technique ("OxyBlot") was used to assess levels of protein carbonyl formation as a marker of oxidative stress-induced protein denaturation. At 24 hours, Evan's blue dye extravasation per average lesion volume was similar between groups. There were no significant differences in HO-1 induction and protein carbonyl formation between groups, in the ipsilateral or contralateral hemispheres, at 6 hours and at 24 hours. These results indicate that hyperoxia treatment during focal cerebral ischemia-reperfusion is neuroprotective, and does not increase oxidative stress. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, CNY 2401,13th St,Bldg 149, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R29-NS32806, R01-NS38731, R01-NS37074] NR 41 TC 128 Z9 132 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2002 VL 22 IS 7 BP 861 EP 868 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 570ZE UT WOS:000176689700011 PM 12142571 ER PT J AU Ferraro, MJ AF Ferraro, MJ TI The rise of fluoroquinolone resistance: Fact or fiction SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 41st Interscience Conference on Antimicrobial Agents and Chemotherapy CY DEC 16-20, 2001 CL CHICAGO, ILLINOIS DE fluoroquinolones; quinolones; ketolide; resistance to quinolones; PROTEKT; telithromycin ID GRAM-NEGATIVE BACILLI; COMMUNITY-ACQUIRED PNEUMONIA; IN-VITRO ACTIVITY; STREPTOCOCCUS-PNEUMONIAE; RESPIRATORY-TRACT; PENICILLIN-RESISTANT; NORTH-AMERICA; KETOLIDE; HMR-3647; SUSCEPTIBILITIES AB Fluoroquinolone antibiotics have been available since the 1980s when ciprofloxacin and norfloxacin were licensed. Structural revisions of the quinolone molecule have provided new compounds that were well suited to the treatment of upper and lower community-acquired respiratory tract infections, having good activity against Streptococcus pneumoniae. Nevertheless, it was only a matter of time before the pneumococcus developed effective resistance against these new agents. There are populations of fluoroquinolone-resistant S. pneumoniae and, more worryingly, many of these strains are also resistant to penicillin and to macrolides. Surveillance studies such as PROTEKT (Prospective, Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) can provide an early warning system and, with the provision of global surveillance on a local level, can assist in the selection of empirical antibiotic treatment. The new ketolide antibiotic, telithromycin, has excellent activity against the major community-acquired respiratory pathogens (including atypical/intracellular organisms), and has the advantage of retaining its activity against strains of S. pneumoniae that are resistant to penicillin, macrolides and fluoroquinolones. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Clin Microbiol, Boston, MA 02114 USA. RP Ferraro, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Clin Microbiol, Boston, MA 02114 USA. NR 39 TC 5 Z9 5 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD JUL PY 2002 VL 14 SU 3 BP 31 EP 41 PG 11 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 617HY UT WOS:000179357300005 PM 12418559 ER PT J AU Moellering, RC AF Moellering, RC CA Consensus Working Grp TI Clinical and public health implications of macrolide-resistant Streptococcus pneumoniae SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 41st Interscience Conference on Antimicrobial Agents and Chemotherapy CY DEC 16-20, 2001 CL CHICAGO, ILLINOIS DE macrolides; macrolide resistance; erythromycin resistance; S. pneumoniae; treatment failure; community-acquired pneumonia; respiratory tract infections ID COMMUNITY-ACQUIRED PNEUMONIA; INITIAL ANTIMICROBIAL THERAPY; GROUP-A STREPTOCOCCI; OTITIS-MEDIA; HAEMOPHILUS-INFLUENZAE; UNITED-STATES; IN-VITRO; DECREASED SUSCEPTIBILITY; PNEUMOCOCCAL RESISTANCE; MORAXELLA-CATARRHALIS AB Macrolide resistance among Streptococcus pneumoniae is a growing global concern, although its specific impact on public health is not currently well defined. A Consensus Working Group was convened in March 2001 to address whether credible, scientific data substantiate macrolide resistance in S. pneumoniae as: (i) producing significant morbidity; (ii) creating attendant health and economic burdens; (iii) constituting a public health threat; and (iv) warranting intervention, including development of new antibiotics with efficacy against these strains. Despite the limitations of available clinical data, concern about the possibility of treatment failure with macrolides is being expressed in clinical practice and in formal treatment guidelines, threatening the important role of these agents in the treatment of respiratory tract infections. Further studies are required to monitor and control macrolide resistance and evaluate settings in which macrolide treatment failures are occurring, and new therapeutic interventions are needed. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. GR Micro Ltd, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. Summa Hlth Syst, Akron, OH USA. Med Ctr, Boston, MA USA. Miriam Hosp, Providence, RI 02906 USA. Vet Adm Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. MRL Inc, Focus, Herndon, VA USA. Talbot Advisors LLC, Wayne, PA USA. RP Moellering, RC (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 110 Francis St,Suite 6A, Boston, MA 02215 USA. NR 83 TC 14 Z9 14 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD JUL PY 2002 VL 14 SU 3 BP 42 EP 56 PG 15 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA 617HY UT WOS:000179357300006 PM 12418560 ER PT J AU Finkelstein, JS Sowers, M Greendale, GA Lee, MLT Neer, RM Cauley, JA Ettinger, B AF Finkelstein, JS Sowers, M Greendale, GA Lee, MLT Neer, RM Cauley, JA Ettinger, B TI Ethnic variation in bone turnover in pre- and early perimenopausal women: Effects of anthropometric and lifestyle factors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EARLY POSTMENOPAUSAL WOMEN; HIP FRACTURE INCIDENCE; MINERAL DENSITY; BIOCHEMICAL MARKERS; PREMENOPAUSAL WOMEN; RACIAL-DIFFERENCES; PHYSICAL-ACTIVITY; LIFE-STYLE; WHITE; AMERICAN AB Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Little is known, however, about ethnic variation in bone turnover. We measured serum osteocalcin (OC) and urinary N-telopeptide of type I collagen (NTX) levels in 2313 pre- or early perimenopausal women who were Caucasian (n = 1140), African-American (n = 651), Chinese (n = 247), or Japanese (n = 275) and were participating in the Study of Women's Health Across the Nation. Serum OC and urinary NTX levels were compared before and after adjustment for a series of lifestyle and anthropometrie variables that can affect bone turnover. Unadjusted serum OC levels were highest in Caucasian women (P < 0.001 vs. all other groups), higher in African-American than Chinese women (P = 0.006), and similar in Chinese and Japanese women (P = 0.203) and African-American and Japanese women (P = 0.187). Unadjusted serum OC levels were 11-24% higher in Caucasians than in the other groups. Adjustment for covariates did not alter the ethnic pattern of serum OC levels. Unadjusted urinary NTX levels were statistically significantly higher in Caucasian and African-American women than in Chinese women (P < 0.001) for both comparisons. Unadjusted urinary NTX levels were higher in Caucasian than in Japanese women (P = 0.071) and higher in Japanese than in Chinese women (P = 0.055), but these differences were of borderline statistical significance. Unadjusted urinary NTX levels were 9-18% higher in African-Americans and Caucasians than in the other groups. Among Caucasians, there were significant geographic regional variations in both serum OC and urinary NTX levels, with higher levels in women from the Northeast and the Midwest than in women from California. These data demonstrate significant ethnic differences in bone turnover in pre- and early perimenopausal women. Although these differences in adult bone turnover may explain some of the known ethnic variation in BMD, ethnic patterns of adult bone turnover do not parallel patterns of BMD. Other factors, such as differences in bone accretion, are likely responsible for much of the ethnic variation in adult BMD. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM jfinkelstein@partners.org RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [U01 AG 12495, U01 AG 12531, U01 AG 12539, U01 AG 12546, U01 AG 12553, U01 AG 12554]; NIDDK NIH HHS [K24 DK 02759]; NINR NIH HHS [U01 NR 04061] NR 31 TC 54 Z9 55 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2002 VL 87 IS 7 BP 3051 EP 3056 DI 10.1210/jc.87.7.3051 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700010 PM 12107200 ER PT J AU Finkelstein, JS Lee, MLT Sowers, M Ettinger, B Neer, RM Kelsey, JL Cauley, JA Huang, MH Greendale, GA AF Finkelstein, JS Lee, MLT Sowers, M Ettinger, B Neer, RM Kelsey, JL Cauley, JA Huang, MH Greendale, GA TI Ethnic variation in bone density in premenopausal and early perimenopausal women: Effects of anthropometric and lifestyle factors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HIP FRACTURE INCIDENCE; MINERAL DENSITY; RACIAL-DIFFERENCES; BLACK-WOMEN; WHITE WOMEN; VITAMIN-D; PHYSICAL-ACTIVITY; BODY HABITUS; JAPANESE; AMERICAN AB Bone mineral density (BMD) and fracture rates vary among women of differing ethnicities. Most reports suggest that BMD is highest in African-Americans, lowest in Asians, and intermediate in Caucasians, yet Asians have lower fracture rates than Caucasians. To assess the contributions of anthropometric and lifestyle characteristics to ethnic differences in BMD, we assessed lumbar spine and femoral neck BMD by dual-energy x-ray absorptiometry in 2277 (for the lumbar spine) and 2330 (for the femoral neck) premenopausal or early perimenopausal women (mean age, 46.2 yr) participating in the Study of Women's Health Across the Nation. Forty-nine percent of the women were Caucasian, 28% were African-American, 12% were Japanese, and 11% were Chinese. BMDs were compared among ethnic groups before and after adjustment for covariates. Before adjustment, lumbar spine and femoral neck BMDs were highest in African-American women, next highest in Caucasian women, and lowest in Chinese and Japanese women. Unadjusted lumbar spine and femoral neck BMDs were 7-12% and 14-24% higher, respectively, in African-American women than in Caucasians, Japanese, or Chinese women. After adjustment, lumbar spine and femoral neck BMD remained highest in African-American women, and there were no significant differences between the remaining groups. When BMD was assessed in a subset of women weighing less than 70 kg and then adjusted for covariates, lumbar spine BMD became similar in African-American, Chinese, and Japanese women and was lowest in Caucasian women. Adjustment for bone size increased values for Chinese women to levels equal to or above those of Caucasian and Japanese women. Among women of comparable weights, there are no differences in lumbar spine BMD among African-American, Chinese, and Japanese women, all of whom have higher BMDs than Caucasians. Femoral neck BMD is highest in African-Americans and similar in Chinese, Japanese, and Caucasians. These findings may explain why Caucasian women have higher fracture rates than African-Americans and Asians. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Univ Calif Los Angeles, Sch Med, Dept Geriatr, Los Angeles, CA 90095 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM jfinkelstein@partners.org RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NCRR NIH HHS [RR 1066]; NIA NIH HHS [U01 AG 12539, U01 AG 12531, U01 AG 12546, U01 AG 12553, U01 AG 12554]; NIDDK NIH HHS [K24 DK 02759]; NINR NIH HHS [U01 NR 04061] NR 46 TC 132 Z9 140 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 JUL PY 2002 VL 87 IS 7 BP 3057 EP 3067 DI 10.1210/jc.87.7.3057 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700011 PM 12107201 ER PT J AU Cherrier, MM Anawalt, BD Herbst, KL Amory, JK Craft, S Matsumoto, AM Bremner, WJ AF Cherrier, MM Anawalt, BD Herbst, KL Amory, JK Craft, S Matsumoto, AM Bremner, WJ TI Cognitive effects of short-term manipulation of serum sex steroids in healthy young men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TESTOSTERONE LEVELS; POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT; GONADOTROPIN-LEVELS; SPATIAL COGNITION; BASAL FOREBRAIN; ANDROGEN LEVELS; WORKING-MEMORY; ALZHEIMER-TYPE; VERBAL MEMORY AB We examined the effects of sex steroids on cognitive functioning by exogenously manipulating circulating T levels in a group of healthy young men. Thirty-two men were randomized to receive 8 wk of treatment including: 1) im T enanthate 100 mg/wk plus daily oral placebo (T); 2) im placebo/wk plus 125 mug daily oral levonorgestrel (LNG); 3) im T enanthate 100 mg/wk plus 125 mug daily oral LNG (T + LNG); 4) im placebo/wk plus daily oral placebo. Cognitive functions were assessed at baseline and twice during treatment. Serum T and E2 levels were significantly increased in the T and T + LNG groups compared with baseline (P < 0.01) and T levels were significantly decreased in the LNG group (P < 0.05). Verbal memory significantly decreased in the LNG group (P < 0.01) and was maintained by coadministration of T in the T + LNG group. Divided attention was unaffected in the LNG group but improved significantly in the T + LNG group. In summary, decreased serum T levels induced by LNG or direct effects of the progestin, LNG, adversely affects verbal memory in normal young men. These results suggest that short-term changes in sex steroid levels have effects on cognitive function in healthy young men. C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Educ & Clin Ctr, Dept Geriatr Res, Seattle, WA 98108 USA. RP Cherrier, MM (reprint author), Univ Washington, Sch Med, Dept Psychiat, Box 356560,1959 NE Pacific, Seattle, WA 98195 USA. EM cherrier@u.washington.edu FU NIA NIH HHS [K01 AG 00858] NR 49 TC 39 Z9 39 U1 2 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 JUL PY 2002 VL 87 IS 7 BP 3090 EP 3096 DI 10.1210/jc.87.7.3090 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 578GU UT WOS:000177109700016 PM 12107206 ER PT J AU Fox, JG Shen, ZL Xu, SL Feng, Y Dangler, CA Dewhirst, FE Paster, BJ Cullen, JM AF Fox, JG Shen, ZL Xu, SL Feng, Y Dangler, CA Dewhirst, FE Paster, BJ Cullen, JM TI Helicobacter marmotae sp nov isolated from livers of woodchucks and intestines of cats SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; A/JCR MICE; CHRONIC COLITIS; AFLATOXIN B-1; B6C3F(1) MICE; INBRED MICE; INFECTION; CARCINOGENESIS; BACTERIUM; TUMORS AB Woodchucks (Marmota monax) have a high incidence of hepatocellular carcinoma (HCC) associated with chronic infection with woodchuck hepatitis virus (WHV) and serve as a model of hepatitis B virus-associated HCC in humans. Helicobacter hepaticus, an enterohepatic helicobacter in mice, is known to cause hepatocellular adenomas and carcinomas in susceptible mouse strains. In long-term chemical bioassays conducted with B6C3F(1) mice, H. hepaticus has been regarded as a confounding factor because of its tumor-promoting activity. In order to determine if woodchucks harbor a Helicobacter sp. that might play a role in potentiating hepatic inflammation or neoplasia, a study was undertaken to determine whether woodchucks' livers were infected with a Helicobacter sp. Frozen liver samples from 20 (17 WHV-infected and 3 noninfected) woodchucks, 10 with WHV-associated hepatic tumors and 10 without tumors, were cultured by microaerobic techniques and analyzed by using genus- and species-specific helicobacter PCR primers. A 1,200-bp Helicobacter sp.-specific sequence was amplified from 14 liver samples. Southern hybridization confirmed the specific identity of the PCR products. Nine of the 10 livers with tumors had positive Helicobacter sp. identified by PCR, whereas 5 of the 10 livers without tumors were positive. By use of 16S rRNA species-specific primers for H. marmotae, two additional liver samples from the nontumor group had positive PCR amplicons confirmed by Southern hybridization. A urease-, catalase-, and oxidase-positive bacterium was isolated from one liver sample from a liver tumor-positive woodchuck. By 16S rRNA analysis and biochemical and phenotypic characteristics, the organism was classified as a novel Helicobacter sp. Subsequently, four additional bacterial strains isolated from feces of cats and characterized by biochemical, phenotypic, and 16S rRNA analysis were determined to be identical to the woodchuck isolate. We propose the name Helicobacter marmotae sp. nov. for these organisms. Further studies are required to ascertain if this novel Helicobacter sp. plays a tumor promotion role in hepadnavirus-associated tumors in woodchucks or causes enterohepatic disease in cats. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01-CA67529, R01 CA067529, P01 CA26723]; NCRR NIH HHS [T32 RR007036, RR07036]; NIDCR NIH HHS [R01 DE010374, R01 DE10374]; PHS HHS [R01A150952] NR 38 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2002 VL 40 IS 7 BP 2513 EP 2519 DI 10.1128/JCM.40.7.2513-2519.2002 PG 7 WC Microbiology SC Microbiology GA 569MH UT WOS:000176605800032 PM 12089272 ER PT J AU Raskind, MA Thompson, C Petrie, EC Dobie, DJ Rein, RJ Hoff, DJ McFall, ME Peskind, ER AF Raskind, MA Thompson, C Petrie, EC Dobie, DJ Rein, RJ Hoff, DJ McFall, ME Peskind, ER TI Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PREFRONTAL CORTEX; SLEEP; PTSD; NOREPINEPHRINE; MECHANISM AB Background: Preclinical and clinical observations suggest that the centrally active alpha(1)-adrenergic antagonist prazosin might alleviate trauma content nightmares and other symptoms in combat veterans with chronic posttraumatic stress disorder (PTSD). Method: In this retrospective chart review study, we analyzed data from 59 consecutive combat veterans with previously treatment-resistant chronic PTSD (DSM-IV criteria) and severe intractable trauma content nightmares to whom prazosin had been prescribed. Nightmare severity was quantified using the recurrent distressing dreams item of the Clinician Administered PTSD Scale (CAPS). Change in overall PTSD severity exclusive of nightmares was estimated by assigning a Clinical Global Impressions-Change scale (CGI-C) score based on chart review. Results: Mean +/- SEM recurrent distressing dreams item scores improved significantly (7.0 +/- 0.2 to 3.5 +/- 0.3, p < .0001) in the 36 patients who completed at least 8 weeks of prazosin treatment at their maximum titrated dose. The mean maximum prazosin dose achieved in these 36 patients was 9.6 +/- 0.9 mg/day. Recurrent distressing dreams scores also improved in the total group who filled their prazosin prescriptions (N = 51)(7.1 +/- 0.2 to 4.2 +/- 0.3, p < .0001). In a comparison group of 8 patients who did not fill their prazosin prescriptions but continued in outpatient treatment, there was no significant change in CAPS recurrent distressing dreams score (6.8 +/- 0.5 to 6.7 +/- 0.4). There also was at least some improvement in CGI-C ratings of overall PTSD severity exclusive of nightmares in a substantial majority of patients receiving prazosin, but not in the 8 comparison subjects. There were no serious adverse effects attributable to prazosin. Conclusion: These observations suggest that prazosin may relieve symptomatic distress in PTSD, and they provide rationale for placebo-controlled trials of prazosin for PTSD trauma content nightmares and other PTSD symptoms. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv, NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, NW Network Mental Illness Res Educ & Clin Ctr, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 62 Z9 64 U1 0 U2 4 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 JUL PY 2002 VL 63 IS 7 BP 565 EP 568 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 575NT UT WOS:000176954500005 PM 12143911 ER PT J AU Chinman, M Kloos, B O'Connell, M Davidson, L AF Chinman, M Kloos, B O'Connell, M Davidson, L TI Service providers' views of psychiatric mutual support groups SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID SELF-HELP GROUPS; MENTAL-HEALTH PROFESSIONALS; UNITED-STATES; PERSPECTIVES; POPULATION; MOVEMENTS; CONSUMER AB Despite evidence that mutual support groups can be beneficial for those with serious mental illnesses, professionals have been reluctant to utilize this resource. We surveyed over 400 providers across several disciplines and settings within the state of Connecticut's public mental health system to assess their attitudes and practices regarding the use of mutual support groups for their patients. We found that being a rehabilitation worker and possessing more advanced training, greater numbers of years in their setting and discipline, and personal experience with psychiatric disorders or mutual support were associated with more favorable attitudes and behaviors toward mutual support. In addition, traditional 12-step groups (e.g., Alcoholics Anonymous) were viewed more favorably than psychiatric mutual support groups. Implications for educational efforts about the benefits of mutual support for those with serious mental illnesses are discussed. (C) 2002 Wiley Periodicals, Inc. C1 W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Chinman, M (reprint author), W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,MIRECC 210A, Los Angeles, CA 90073 USA. NR 49 TC 19 Z9 19 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 2002 VL 30 IS 4 BP 349 EP 366 DI 10.1002/jcop.10010 PG 18 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 564AL UT WOS:000176291400002 ER PT J AU Thomsen, TW Brown, DFM Nadel, ES AF Thomsen, TW Brown, DFM Nadel, ES TI Pediatric tremors SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID INDUCED MOVEMENT-DISORDERS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Affliated Emergency Med Residency, Dept Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 8 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 JUL PY 2002 VL 23 IS 1 BP 75 EP 78 AR PII S0736-4679(02)00470-5 DI 10.1016/S0736-4679(02)00470-5 PG 4 WC Emergency Medicine SC Emergency Medicine GA 592VX UT WOS:000177958500013 PM 12217475 ER PT J AU Lee, CC Kim, SH Crupi, RS AF Lee, CC Kim, SH Crupi, RS TI Emergency department presentation of spontaneous rupture of hepatocellular carcinoma SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID INTRAPERITONEAL HEMORRHAGE; EMBOLIZATION C1 Flushing Hosp & Med Ctr, Ctr Med, Dept Emergency Med, Flushing, NY 11355 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Lee, CC (reprint author), Flushing Hosp & Med Ctr, Ctr Med, Dept Emergency Med, 45th Ave Parsons Blvd, Flushing, NY 11355 USA. NR 12 TC 1 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD JUL PY 2002 VL 23 IS 1 BP 83 EP 85 AR PII S0736-4679(02)00466-3 DI 10.1016/S0736-4679(02)00466-3 PG 3 WC Emergency Medicine SC Emergency Medicine GA 592VX UT WOS:000177958500015 PM 12217477 ER PT J AU Ji, H Pettit, A Ohmura, K Ortiz-Lopez, A Duchatelle, V Degott, C Gravallese, E Mathis, D Benoist, C AF Ji, H Pettit, A Ohmura, K Ortiz-Lopez, A Duchatelle, V Degott, C Gravallese, E Mathis, D Benoist, C TI Critical roles for interleukin 1 and tumor necrosis factor at in antibody-induced arthritis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transgenic; cytokine; knockout; inflammatory; TNF ID COLLAGEN-INDUCED ARTHRITIS; AMELIORATES JOINT DISEASE; ANTIGEN-INDUCED ARTHRITIS; RECEPTOR-DEFICIENT MICE; RHEUMATOID-ARTHRITIS; T-CELL; FACTOR-ALPHA; TNF-ALPHA; INTERLEUKIN-6-DEFICIENT MICE; INFLAMMATORY RESPONSE AB in spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also required, although seemingly less critically than IL-1, because a proportion of TNF-alpha-deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFalpha for bone destruction. The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Univ Strasbourg 1, Inst Natl Sante & Rech, Ctr Natl Rech Sci, Inst Genet & Biol Mol & Cellulaire, F-67404 Strasbourg, France. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Inst Med, New England Baptist Bone & Joint Inst, Boston, MA 02215 USA. Hop Beaujon, Serv Anat & Cytol Pathol, F-92118 Clichy, France. RP Mathis, D (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Pettit, Allison/G-2591-2010 OI Pettit, Allison/0000-0003-4707-7892 FU NIAMS NIH HHS [1R01 AR/AI46580-01] NR 54 TC 213 Z9 221 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 JUL 1 PY 2002 VL 196 IS 1 BP 77 EP 85 DI 10.1084/jem.20020439 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 569TJ UT WOS:000176618100007 PM 12093872 ER PT J AU Ye, QR Press, B Kissler, S Yang, XF Lu, LR Bassing, CH Sleckman, BP Jansson, M Panoutsakopoulou, V Trimble, LA Alt, FW Cantor, H AF Ye, QR Press, B Kissler, S Yang, XF Lu, LR Bassing, CH Sleckman, BP Jansson, M Panoutsakopoulou, V Trimble, LA Alt, FW Cantor, H TI T cell costimulation through CD28 depends on induction of the Bcl-x gamma isoform: Analysis of Bcl-x gamma-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Bcl-x gamma; CD28; T cell; costimulation; EAE ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CYCLE PROGRESSION; ACTIVATION; PROLIFERATION; EXPRESSION; SURVIVAL; BCL-X(L); LYMPHOCYTES; APOPTOSIS; DEATH AB The molecular basis of CD28-dependent costimulation of T cells is poorly understood. Bcl-xgamma is a member of the Bcl-x family whose expression is restricted to activated T cells and requires CD28-dependent ligation for full expression. We report that Bcl-xgamma-deficient (Bcl-xgamma(-/-)) T cells display defective proliferative and cytokine responses to CD28-dependent costimulatory signals, impaired memory responses to proteolipid protein peptide (PLP), and do not develop PLP-induced experimental autoimmune encephalomyelitis (EAE). In contrast, enforced expression of Bcl-xgamma largely replaces the requirement for B7-dependent ligation of CD28. These findings identify the Bcl-xgamma cytosolic protein as an essential downstream link in the CD28-dependent signaling pathway that underlies T cell costimulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet,Childrens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, 44 Binney St,SM 722, Boston, MA 02115 USA. RI Lu, Linrong/A-1429-2013; OI , /0000-0003-3062-7800; Lu, Linrong/0000-0002-0171-4115 FU NIAID NIH HHS [R01 AI020047, AI07386, AI10468, AI20047, AI35714, AI48125, F32 AI010468, P01 AI035714, R01 AI048125, R37 AI020047, T32 AI007386]; PHS HHS [A112184, A13600] NR 31 TC 13 Z9 14 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 JUL 1 PY 2002 VL 196 IS 1 BP 87 EP 95 DI 10.1084/jem.20012084 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 569TJ UT WOS:000176618100008 PM 12093873 ER PT J AU Cohen, PL Caricchio, R Abraham, V Camenisch, TD Jennette, JC Roubey, RAS Earp, HS Matsushima, G Reap, EA AF Cohen, PL Caricchio, R Abraham, V Camenisch, TD Jennette, JC Roubey, RAS Earp, HS Matsushima, G Reap, EA TI Delayed apoptotic cell clearance and lupus-like autoimmunity in mice lacking the c-mer membrane tyrosine kinase SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmunity; Lupus Erythematosus, systemic; phagocytosis; apoptosis; macrophages ID RECEPTOR; PHAGOCYTOSIS; ANTIGENS; IDENTIFICATION; ANTIBODIES; GAS6; GENE AB Mice lacking the membrane tyrosine kinase c-mer have been shown to have altered macrophage cytokine production and defective phagocytosis of apoptotic cells despite normal phagocytosis of other particles. We show here that c-mer-deficient mice have impaired clearance of infused apoptotic cells and that they develop progressive lupus-like autoimmunity, with antibodies to chromatin, DNA, and IgG. The autoimmunity appears to be driven by endogenous antigens, with little polyclonal B cell activation. These mice should be an excellent model for studying the role of apoptotic debris as an immunogenic stimulus for systemic autoimmunity. C1 Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Mayo Clin, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol Immunol, Chapel Hill, NC 27599 USA. AlphaVax, Durham, NC 27709 USA. RP Cohen, PL (reprint author), Univ Penn, Dept Med, Div Rheumatol, 421 Curie Blvd,Suite 757, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [R01 AI47780] NR 24 TC 361 Z9 377 U1 1 U2 9 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 JUL 1 PY 2002 VL 196 IS 1 BP 135 EP 140 DI 10.1084/jem.20012094 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 569TJ UT WOS:000176618100013 PM 12093878 ER PT J AU Kilbourne, AM Justice, AC Rollman, BL McGinnis, KA Rabeneck, L Weissman, S Smola, S Schultz, R Whittle, J Rodriguez-Barradas, M AF Kilbourne, AM Justice, AC Rollman, BL McGinnis, KA Rabeneck, L Weissman, S Smola, S Schultz, R Whittle, J Rodriguez-Barradas, M TI Clinical importance of HIV and depressive symptoms among veterans with HIV infection SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV/AIDS; symptoms; depression ID QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; HOMOSEXUAL MEN; CES-D; HEALTH; DISEASE; AIDS; PROGRESSION; DECLINE; PREDICTORS AB OBJECTIVE: To compare the clinical importance (association with illness severity and survival) of depressive and HIV symptoms among veterans with HIV infection. DESIGN: Cross-sectional study; survival analysis. SETTING: Infectious Disease Clinics at 3 VA Medical Centers. PARTICIPANTS: HIV-infected patients (N = 881) and their health care providers from June 1999 through July 2000. MEASUREMENTS AND MAIN RESULTS: Depressive symptoms were assessed using the 10-item Centers for Epidemiologic Studies Depression Scale (CES-D). Patient baseline survey included an HIV Symptom Index measuring the frequency and bother of 20 common symptoms. Providers were surveyed on patients' illness severity, and survival data were obtained from VA death records. Of 881 patients, 46% had significant depressive symptoms (CES-D greater than or equal to10). Increasing depression symptom severity was associated with increasing HIV symptom frequency (P < .001) and bother (P < .001). Multiple regression results revealed that having moderate or severe depressive symptoms was not associated with provider-reported illness severity or survival. However, HIV symptoms were significantly associated with provider-reported illness severity (P < .01) and survival (P = .05), after adjusting for moderate and severe depressive symptoms, CD4 cell count/mm(3) , viral load, age, race, and antiretroviral use. CONCLUSIONS: Depression, while common in this sample, was not associated with illness severity or mortality after adjusting for HIV symptoms. HIV symptoms are associated with severity of illness and survival regardless of patients' severity of depressive symptoms. This suggests that equal medical consideration should be given to HIV symptoms presented by HIV-infected patients regardless of their depression status, rather than automatically attributing medical complaints to depression. C1 VA Pittsburgh Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. Univ Toronto, Dept Med, Div Gastroenterol, Toronto, ON, Canada. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Hosp St Raphael, New Haven, CT USA. Univ Kansas, Med Ctr, Dept Internal Med Geriatr & Gen Med, Kansas City, KS 66103 USA. VA Med Ctr, Kansas City, KS USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Ctr Hlth Equ Res & Promot, 130-U Univ Drive C, Pittsburgh, PA 15240 USA. NR 43 TC 85 Z9 85 U1 3 U2 4 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 JUL PY 2002 VL 17 IS 7 BP 512 EP 520 DI 10.1046/j.1525-1497.2002.10803.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 575AQ UT WOS:000176923700003 PM 12133141 ER PT J AU Jupiter, JB Ring, D Weitzel, PP AF Jupiter, JB Ring, D Weitzel, PP TI Surgical treatment of redisplaced fractures of the distal radius in patients older than 60 years SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE wrist; distal radius; internal fixation; osteoporosis ID COLLES FRACTURE; HEALTH AB Twenty patients aged 60 years or older (average age, 68 y) presented to our institution with a distal radius fracture made complex by virtue of displacement after a closed reduction and cast or external fixation immobilization. Ten of the fractures were volarly angulated and 10 were dorsally angulated. Fifteen patients' hands had associated soft-tissue swelling. Surgical exposure and stable internal fixation were undertaken to both realign the fracture as well as enable functional rehabilitation. The final functional result and radiographic results were physician rated and patient rated by using the Patient Rated Wrist Evaluation (PRWE). The patients' overall activity level was quantified and compared with population norms by using the Physical Activity Scale for the Elderly (PASE). At an average follow-up visit of 38 months, all the fractures healed and none of the implants loosened or broke. The functional results were excellent in 7, good in 11, and fair in 2. The average PRWE score was 14, which compares favorably with prior studies of adult patients of all ages treated for a distal radius fracture. The PASE score averaged 177, representing a return to preoperative activity levels in 17 of 20 patients. Complications included loss of alignment, tendon rupture, transient radial sensory neuritis, and nonfatal pulmonary embolism in 1 patient each. Six plates were removed because of soft-tissue irritation. Copyright (C) 2002 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand Surg Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA. NR 42 TC 64 Z9 67 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JUL PY 2002 VL 27A IS 4 BP 714 EP 723 DI 10.1053/jhsu.2002.34007 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 574TW UT WOS:000176906500024 PM 12132101 ER PT J AU Rosen, HR Ribeiro, RR Weinberger, L Wolf, S Chung, MJ Gretch, DR Perelson, AS AF Rosen, HR Ribeiro, RR Weinberger, L Wolf, S Chung, MJ Gretch, DR Perelson, AS TI Early hepatitis C viral kinetics correlate with long-term outcome in patients receiving high dose induction followed by combination interferon and ribavirin therapy SO JOURNAL OF HEPATOLOGY LA English DT Article DE early hepatitis C viral kinetics; long-term outcome; high dose induction; combination interferon and ribavirin therapy ID PLUS RIBAVIRIN; HCV RNA; VIRUS; INFECTION; GENOTYPE-1; CLEARANCE; EFFICACY; DYNAMICS; ALFA AB Background/Aims: The majority of patients with genotype 1 do not respond to interferon (IFN) plus ribavirin. Limited data exist on the use of induction followed by combination therapy. Methods: In this prospective study of 28 patients infected with genotype 1, randomization involved either daily or twice daily high dose IFN for 6 weeks, followed by standard therapy of 3 million units three times a week in combination with ribavirin for an additional 42 weeks. Hepatitis C virus (HCV) RNA was quantitated before and frequently during treatment. Results: The best correlate of response was 3 (the infected cell loss rate). Sixteen patients continued on the study because they had at least a 2 log drop in their HCV RNA levels by week 12; all but one were PCR negative for HCV RNA at 48 weeks, and 14 of these 16, patients continued to be PCR negative at 72 weeks. Both African-Americans in our trial failed to respond to therapy, and differences were evident during the induction phase. Conclusions: This randomized study of induction IFN therapy followed by combination IFN plus ribavirin yielded the highest rate of sustained response (50%) reported to date in chronically HCV-infected patients with genotype 1. The predictive value of the infected cell loss rate needs to be evaluated prospectively in larger studies, particularly in patients receiving pegylated IFN. (C) 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. C1 Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Div Mol Microbiol & Immunol, Portland, OR 97201 USA. Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. Univ Washington, Viral Hepatitis Lab, Seattle, WA 98195 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp,P3-G1, Portland, OR 97207 USA. FU NCRR NIH HHS [5 M01 RR00334, RR06555] NR 26 TC 35 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUL PY 2002 VL 37 IS 1 BP 124 EP 130 AR PII S0168-8278(02)00114-9 DI 10.1016/S0168-8278(02)00114-9 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 573UN UT WOS:000176850100017 PM 12076871 ER PT J AU Faunce, DE Stein-Streilein, J AF Faunce, DE Stein-Streilein, J TI NKT cell-derived RANTES recruits APCs and CD8(+) T cells to the spleen during the generation of regulatory T cells in tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTORS; SYSTEMIC TOLERANCE; EXPRESSION; LYMPHOCYTES; ACTIVATION; RESPONSES; ALPHA; BETA; MICE AB The induction of peripheral tolerance via immune privileged sites such as the eye requires splenic colocalization of NKT cells and CD1d(+) tolerogenic F4/80(+) APCs, both of which are needed for the generation of CD8(+)-regulatory T (Tr) cells. Whereas tolerogenic APCs secrete the chemokine macrophage-inflammatory protein-2 for the purpose of recruiting NKT cells, the signals responsible for recruiting potential Tr cells and additional APCs to the spleen are not known. Here we examined the ability of CD1d-stimulated NKT cells to produce chemokines that can recruit other cells needed for tolerance. Our results show that NKT cells stimulated by either CD1d-transfected fibroblasts in vitro or CD1d(+) tolerogenic APCs both in vivo and ex vivo produced RANTES in a CD1d-dependent manner. The requirement for RANTES in tolerance was demonstrated by studies in which RANTES blockade in vivo prevented not only APC accumulation in the spleen but also the generation of CD8(+) Tr cells that suppress Th1 immunity. Thus, CD1d-restricted NKT cells provide critical signals for orchestrating the accumulation of cells needed for tolerance induction. These data expand our current knowledge of RANTES beyond its role in Th1 immune responses to show its importance in tolerance induction and add a novel aspect to our understanding of the role of NKT cells in tolerance. Understanding the precise mechanisms involved in tolerance induction may lead to more effective therapeutic strategies for autoimmunity and graft rejection. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, NEI, Training Program Mol Bases Eye Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Pulm & Crit Care,Dept Med, Boston, MA 02115 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NEI NIH HHS [EY07021-01, EY11983-01, EY13306] NR 28 TC 83 Z9 88 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2002 VL 169 IS 1 BP 31 EP 38 PG 8 WC Immunology SC Immunology GA 565GA UT WOS:000176360400006 PM 12077225 ER PT J AU Yang, SX Linette, GP Longerich, S Haluska, FG AF Yang, SX Linette, GP Longerich, S Haluska, FG TI Antimelanoma activity of CTL generated from peripheral blood mononuclear cells after stimulation with autologous dendritic cells pulsed with melanoma gp100 peptide G209-2M is correlated to TCR avidity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; MHC CLASS-I; ANTIGEN GP100; SYNTHETIC PEPTIDES; REACTIVE CTL; ADOPTIVE IMMUNOTHERAPY; METASTATIC MELANOMA; MULTIPLE EPITOPES; FINE SPECIFICITY AB Anchor residue-modified peptides derived from tumor-associated Ag have demonstrated success in engendering immune responses in clinical studies. However, tumor regression does not always correlate with immune responses. One hypothesis to explain this is that CTL resulting from such immunization approaches are variable in antitumor potency. In the present study, we evaluated this hypothesis by characterizing the activity of tumor-associated Ag-specific CTL. We chose an anchor residue-modified peptide from gp100, G209-2M, and used peptide-pulsed dendritic cells to generate CTL from PBMC of HLA-A2(+) normal donors. The specificities and avidities of the resulting CTL were evaluated. The results demonstrate that CTL generated by G209-2M can be classified into three categories: G209-2M-specific CTL which are cytotoxic only to G209-2M-pulsed targets; peptide-specific CTL which recognize both G209 and G209-2M peptides but not melanomas; and melanoma-reactive CTL which recognize peptide-pulsed targets as well as HLA-A2(+)gp100(+) melanomas. CTL that kill only peptide-pulsed targets require a higher peptide concentration to mediate target lysis, whereas CTL that lyse melanomas need a lower peptide concentration. Increasing peptide density on melanomas by loading exogenous G209 peptide enhances their sensitivity to peptide-specific CTL. High avidity CTL clones also demonstrate potent antimelanoma activity in melanoma model in nude mice. Injection of G209 peptide around transplanted tumors significantly enhances the antitumor activity of low avidity CTL. These results suggest that peptide stimulation causes expansion of T cell populations with a range of avidities. Successful immunotherapy may require selective expansion of the higher-avidity CTL and intratumor injection of the peptide may enhance the effect of peptide vaccines. C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Dept Hematol Oncol, Jackson Bldg,GRJ 1021,55 Fruit St, Boston, MA 02114 USA. NR 52 TC 54 Z9 55 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2002 VL 169 IS 1 BP 531 EP 539 PG 9 WC Immunology SC Immunology GA 565GA UT WOS:000176360400066 PM 12077285 ER PT J AU Meijer, SL Dols, A Urba, WJ Hu, HM Smith, JW Vetto, J Wood, W Doran, T Chu, Y Sayaharuban, P Alvord, WG Fox, BA AF Meijer, SL Dols, A Urba, WJ Hu, HM Smith, JW Vetto, J Wood, W Doran, T Chu, Y Sayaharuban, P Alvord, WG Fox, BA TI Adoptive cellular therapy with tumor vaccine draining lymph node lymphocytes after vaccination with HLA-B7/beta(2)-microglobulin gene-modified autologous tumor cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE adoptive immunotherapy; tumor vaccine; melanoma; renal cell cancer ID T-CELLS; IMMUNOTHERAPY; INTERLEUKIN-2; CANCER; EXPRESSION; GENERATION; TOXICITY; MELANOMA; TYPE-1; DNA AB Adoptive immunotherapy with anti-CD3-expanded lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors. This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-expanded tumor vaccine draining lymph node lymphocytes (TVDLN) in patients with metastatic melanoma and renal cell cancer (RCC). To facilitate the generation of tumor-specific lymphocytes in the TVDLN, autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7, a modification that has the potential to enhance the immunogenicity of the tumor cells. After vaccination with gene-modified tumor cells, patients' lymph nodes were harvested; TVDLN lymphocytes were activated and expanded ex vivo with anti-CD3 and interleukin-2 (IL-2), and adoptively transferred to patients in combination with systemic IL-2. Twenty patients, nine with melanoma and I I with RCC were treated. Tumor was harvested successfully in all 20 patients. Ex vivo gene transfer was performed using lipofection with a lipid: DNA plasmid complex containing the genes for HLA-B7 and beta2-microglobulin. The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53% (range 0.3%-12.1%). Lymph nodes were harvested from all 20 patients with a mean of 53 x 107 and 60 x 107 cells obtained from the gene-modified and unmodified tumor vaccine sites, respectively. Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines. No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes. Typical IL-2-related toxicities were observed in all patients. No objective tumor regressions were observed. MHC class I restricted, tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients. C1 Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR 97213 USA. Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Mol & Tumor Immunol, Portland, OR 97213 USA. Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Oregon Canc Ctr, Portland Vet Affairs Med Ctr, Dept Surg, Portland, OR 97201 USA. Frederick Canc Res Facil, Comp Serv, Frederick, MD USA. Frederick Canc Res Facil, Stat Serv, Frederick, MD USA. RP Fox, BA (reprint author), Providence Portland Med Ctr, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, 4805 NE Glisan St, Portland, OR 97213 USA. FU NCI NIH HHS [R21 CA76078] NR 20 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2002 VL 25 IS 4 BP 359 EP 372 DI 10.1097/01.CJI.0000018062.31201.75 PG 14 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 578GL UT WOS:000177109000008 PM 12142559 ER PT J AU Fraenkel, PG Rutkove, SB Matheson, JK Fowkes, M Cannon, ME Patti, ME Atkins, MB Gollob, JA AF Fraenkel, PG Rutkove, SB Matheson, JK Fowkes, M Cannon, ME Patti, ME Atkins, MB Gollob, JA TI Induction of myasthenia gravis, myositis, and insulin-dependent diabetes mellitus by high-dose interleukin-2 in a patient with renal cell cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-2; autoimmunity; myasthenia gravis; renal cell cancer ID ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; HYPOTHYROIDISM; AUTOANTIBODIES; IMMUNOTHERAPY; ASSAY; ANTIBODIES; CARCINOMA; THERAPY AB Interleukin-2 is an effective agent against renal cell carcinoma and melanoma, but it has been associated with autoimmune sequelae such as hypothyroidism and vitiligo. A 64-year-old man with non-insulin-dependent diabetes and metastatic renal cell carcinoma developed insulin-dependent diabetes after his first cycle of therapy with high-dose (HD) interleukin-2. After additional therapy with interleukin-2, the patient developed generalized myasthenia gravis (MG) and polymyositis, both of which responded to treatment with corticosteroids and plasmapheresis. To investigate the role of IL-2 in the development of these autoimmune complications, autoantibody titers were assayed from serum obtained before and after IL-2 treatment and after treatment with corticosteroids plus plasmapheresis. Before IL-2 treatment, the patient had antibodies directed against insulin, islet cell antigens, and striated muscle. Acetylcholine receptor antibody levels were normal before starting IL-2. After treatment with IL-2, the patient developed acetylcholine receptor binding antibodies and exhibited an increase in the striated muscle antibody titer from 1:40 to 1:160. Recovery from the MG and polymyositis was associated with substantial decreases in the acetylcholine receptor and striated muscle antibody titers. These findings suggest that HD IL-2 accelerated the progression of latent autoimmune diabetes and myositis in this patient whose tolerance to islet cell antigens and striated muscle had already been broken and precipitated a break in tolerance to the acetylcholine receptor resulting in the development of MG. This case demonstrates the importance of prompt recognition of IL-2-induced MG and shows how this complication can be successfully managed with aggressive therapy. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Gollob, JA (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Kirstein Bldg,Room E-KS-158,330 Brookline Ave, Boston, MA 02215 USA. OI Fraenkel, Paula/0000-0001-8894-0117 NR 26 TC 13 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2002 VL 25 IS 4 BP 373 EP 378 DI 10.1097/01.CJI.0000022256.21966.35 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 578GL UT WOS:000177109000009 PM 12142560 ER PT J AU Lilly, CM Silverman, ES Sheffer, AL AF Lilly, CM Silverman, ES Sheffer, AL TI Systemic capillary leak syndrome, leukotrienes, and anaphylaxis SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article DE edema; hypotension; seafood allergy; montelukast; zafirlukast; zileuton ID HYPOVOLEMIC SHOCK; MONOCLONAL IGG; RARE CAUSE; EDEMA; PERMEABILITY; TERBUTALINE; HYPERPERMEABILITY; PATIENT; ASTHMA AB The association of cysteinyl leukotrienes with plasma exudation allowed the authors to form the hypothesis that rates of leukotriene excretion would be increased in the acute phase of systemic capillary leak syndrome (SCLS) and that leukotriene-modifier therapy would reduce the frequency and severity of life-threatening episodes. The authors report the association of SCLS in 3 cases, 1 with seafood-induced anaphylaxis. Rates of urinary leukotriene excretion were greater during the evolution of an episode than after resolution. In a third case, the rate of urinary leukotriene excretion was significantly higher when symptoms were evolving than when they were absent (230 +/- 17 vs 110 +/- 6 pg/mg, P < 0.001). Treatment with a leukotriene receptor (cys-LT1) antagonist eliminated episodes in 1 patient. Treatment with the 5-lipoxygenase inhibitor zileuton was completely effective in another patient and prevented life-threatening episodes in the patient with SCLS after seafood exposure. The authors' finding that allergen exposure-associated episodes of SCLS were eliminated by allergen avoidance implies that anaphylaxis; can present as SCLS. The acute phase of all 3 forms of SCLS (paraprotein associated, anaphylaxis associated, and idiopathic) is associated with increased excretion of cystinyl leukotrienes, and leukotriene-modifier treatment appears to control the disease. C1 Brigham & Womens Hosp, Div Resp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Div Resp, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD JUL-AUG PY 2002 VL 17 IS 4 BP 189 EP 194 DI 10.1177/0885066602017004006 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 702NJ UT WOS:000184229700006 ER PT J AU Detmar, M Streit, M Perruzzi, CA Koteliansky, VE de Fougerolles, AA Senger, DR AF Detmar, M Streit, M Perruzzi, CA Koteliansky, VE de Fougerolles, AA Senger, DR TI The alpha 1 beta 1 and alpha 2 beta 1 integrins provide critical support for VEGF signaling, endothelial cell migration, and tumor angiogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Biogen Inc, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2002 VL 119 IS 1 MA 017 BP 210 EP 210 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100016 ER PT J AU Chung, J Yano, K Lee, M Seo, J Kim, K Cho, K Eun, H Detmar, M AF Chung, J Yano, K Lee, M Seo, J Kim, K Cho, K Eun, H Detmar, M TI Retinoic acid differentially modulates the microvascular alterations associated with intrinsic aging vs. photoaging of the skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Med, Seoul, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Kim, Kyu Han/E-7814-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2002 VL 119 IS 1 MA 027 BP 212 EP 212 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100027 ER PT J AU Hirakawa, S Schacht, V Hong, Y Detmar, M AF Hirakawa, S Schacht, V Hong, Y Detmar, M TI Selective isolation and characterization of cultured human dermal lymphatic endothelial cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 028 BP 212 EP 212 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100030 ER PT J AU Hawighorst, T Skobe, M Streit, M Hong, Y Riccardi, L Brown, LF Detmar, M AF Hawighorst, T Skobe, M Streit, M Hong, Y Riccardi, L Brown, LF Detmar, M TI Tie2 receptor activation by angiopoietin-1 enhances vessel maturation and suppresses squamous cell carcinoma growth SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 033 BP 213 EP 213 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100033 ER PT J AU Hong, Y Streit, M Oura, H Janes, L Riccard, L Detmar, M Hawighorst, T AF Hong, Y Streit, M Oura, H Janes, L Riccard, L Detmar, M Hawighorst, T TI Thrombospondin-2 overexpression in the skin of transgenic mice reduces the susceptibility to chemically induced multistep carcinogencesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 058 BP 217 EP 217 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100060 ER PT J AU Silva, J Oura, H Yano, IK Hawighorst, T Carmeliet, P Detmar, M AF Silva, J Oura, H Yano, IK Hawighorst, T Carmeliet, P Detmar, M TI Suppression of multistage skin carcinogenesis in mice deficient for placental growth factor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. Katholieke Univ Leuven, Univ Ziekenhuis Leuven, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 100 BP 224 EP 224 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100102 ER PT J AU Wilcox-Adelman, SA Denhez, F Goetinck, PF AF Wilcox-Adelman, SA Denhez, F Goetinck, PF TI Syndecan-4 modulates focal adhesion kinase phosphorylation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 121 BP 228 EP 228 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100122 ER PT J AU Ahmed, A Kumari, S Foster, C AF Ahmed, A Kumari, S Foster, C TI Recombinant antigen (IC3.4) in the development of ELISA to detect ocular cicatricial pemphigoid autoantibody SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 155 BP 233 EP 233 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100154 ER PT J AU Yawalkar, N Jones, D Ferenczi, K Kupper, TS AF Yawalkar, N Jones, D Ferenczi, K Kupper, TS TI Profound loss of T cell receptor repertoire complexity in cutaneous T cell lymphoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, DFCI, BWH, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 175 BP 237 EP 237 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100176 ER PT J AU Nori, S Swindells, K Diaz, FR Valderrama, J Hicks, S Huzaira, M Tachihara, R Tannous, Z Goldgeier, MH Gonzalez, S AF Nori, S Swindells, K Diaz, FR Valderrama, J Hicks, S Huzaira, M Tachihara, R Tannous, Z Goldgeier, MH Gonzalez, S TI Sensitivity and specificity of near infrared reflectance confocal scanning laser microscopy for in vivo diagnosis of basal cell carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Dermatol & Dermatol Surg, Rochester, NY 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 187 BP 239 EP 239 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100188 ER PT J AU Swindells, K Burnett, N Rius-Diaz, F Raju, B Srinivasan, MA Gonzalez, E Gonzalez, S AF Swindells, K Burnett, N Rius-Diaz, F Raju, B Srinivasan, MA Gonzalez, E Gonzalez, S TI Reflectance confocal microscopy may differentiate acute allergic and irritant contact dermatitis in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA USA. MIT, Lab Human & Machine Hapt, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Dermatol, Contact Dermatitis Unit, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 194 BP 240 EP 240 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100197 ER PT J AU Chren, M Sahay, A Sands, L Maddock, L Lindquist, K AF Chren, M Sahay, A Sands, L Maddock, L Lindquist, K TI Recurrent nonmelanoma skin cancers: Variation in performance rates of therapies SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 235 BP 247 EP 247 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100236 ER PT J AU Petersen, M Jorgensen, C Tandeski, T Chen, M Morgan, J Krueger, G AF Petersen, M Jorgensen, C Tandeski, T Chen, M Morgan, J Krueger, G TI Transgene expression by human fibroblasts in vivo is under hierarchical regulation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. Univ So Calif, Pasadena, CA USA. Massachusetts Gen Hosp, Shriners Burns Inst, Res Unit, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 366 BP 268 EP 268 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100367 ER PT J AU Tandeski, T Jorgensen, C Chen, M Morgan, J Petersen, M Krueger, G AF Tandeski, T Jorgensen, C Chen, M Morgan, J Petersen, M Krueger, G TI Survival of genetically modified fibroblasts in vivo as a function of cloning, transduction and cellular lifespan SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. Univ So Calif, Pasadena, CA USA. Massachusetts Gen Hosp, Shriners Burns Inst, Res Unit, 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 395 BP 273 EP 273 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100394 ER PT J AU Calautti, E Grossi, M Dotto, G AF Calautti, E Grossi, M Dotto, G TI Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in keratinocyte cell-cell adhesion SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 430 BP 279 EP 279 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100432 ER PT J AU Mammucari, C Oh, H Nenci, A Cabodi, S Cohen, SN Dotto, G AF Mammucari, C Oh, H Nenci, A Cabodi, S Cohen, SN Dotto, G TI Negative regulation of cell growth and differentiation by TSG101 through association of p21Cip1/WAF1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUL PY 2002 VL 119 IS 1 MA 462 BP 284 EP 284 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100463 ER PT J AU Brissette, JL Baxter, RM Li, J Weiner, L Viel, A AF Brissette, JL Baxter, RM Li, J Weiner, L Viel, A TI Dual roles for the nude gene in epithelial self-renewal SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 531 BP 296 EP 296 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100530 ER PT J AU Hurwitz, D Friedman, J Boyd, A King, S Moreno, R Rich, B Kupper, T AF Hurwitz, D Friedman, J Boyd, A King, S Moreno, R Rich, B Kupper, T TI Decreased marine graft-vs.-host disease caused by T cells from aged donors is not related to E-selectin binding activity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, DFCI, Harvard Skin Dis Res Ctr, Boston, MA 02115 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 628 BP 312 EP 312 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100628 ER PT J AU Leshem, O Kawai, T Milinkovic, M Taubman, M Sackstein, R AF Leshem, O Kawai, T Milinkovic, M Taubman, M Sackstein, R TI Ca++ independent T cell adherence to inflamed gingival epithelium detected by a shear-dependent lymphocyte adherence assay SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 BWH, Boston, MA USA. Forsyth Inst, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 626 BP 312 EP 312 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100627 ER PT J AU Razzaque, MS Foster, C Ahmed, A AF Razzaque, MS Foster, C Ahmed, A TI IL-4 induces m-CSF by conjunctival fibroblasts: Possible role in the recruitment of macrophages in cicatricial pemphigoid SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 637 BP 314 EP 314 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100635 ER PT J AU Chen, J Wu, A Pathak, MA Rius-Diaz, F Mihm, CM Goukassian, DA Gonzalez, S AF Chen, J Wu, A Pathak, MA Rius-Diaz, F Mihm, CM Goukassian, DA Gonzalez, S TI Dietary lutein and zeaxanthin partially prevent UVB-induced skin carcinogenesis in Skh-1 hairless mouse model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 767 BP 335 EP 335 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100761 ER PT J AU Wu, A Pathak, MA Sifakis, M Goukassian, DA Gonzalez, S AF Wu, A Pathak, MA Sifakis, M Goukassian, DA Gonzalez, S TI Oral administration of lutein modulates cell proliferation induced by acute UVB radiation in the SHK-1 hairless mouse animal model SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 769 BP 336 EP 336 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100765 ER PT J AU Han, R Baden, HP Brissette, JL Weiner, L AF Han, R Baden, HP Brissette, JL Weiner, L TI Redefining the skin's pigmentary system with a novel tyrosinase assay SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 790 BP 339 EP 339 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100787 ER PT J AU Lin, CB Babiarz, L Liebel, F Price, RE Fisher, DE Gendimenico, GJ Seiberg, M AF Lin, CB Babiarz, L Liebel, F Price, RE Fisher, DE Gendimenico, GJ Seiberg, M TI Modulation of microphthalmia-associated transcription factor expression alters skin pigmentation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Johnson & Johnson Consumer Prod Inc, Skin Res Ctr, Skillman, NJ 08558 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2002 VL 119 IS 1 MA 792 BP 339 EP 339 PN 2 PG 1 WC Dermatology SC Dermatology GA 583UG UT WOS:000177428100788 ER PT J AU Wong, H Schotz, MC AF Wong, H Schotz, MC TI The lipase gene family SO JOURNAL OF LIPID RESEARCH LA English DT Review DE homology; lipolytic; chimera; triglyceride; phospholipid; HDL; VLDL ID RECEPTOR-RELATED PROTEIN; HUMAN PANCREATIC LIPASE; SITE-DIRECTED MUTAGENESIS; ALPHA/BETA-HYDROLASE FOLD; HUMAN LIPOPROTEIN-LIPASE; HEPATIC LIPASE; HEPARIN-BINDING; TRIGLYCERIDE LIPASE; PHOSPHOLIPASE A(1); MOLECULAR-MODEL AB Development of the lipase gene family spans the change in science that witnessed the birth of contemporary techniques of molecular biology. Amino acid sequencing of enzymes gave way to cDNA cloning and gene organization, augmented by in vitro expression systems and crystallization. This review traces the origins and highlights the functional significance of the lipase gene family, overlaid on the background of this technical revolution. The gene family initially consisted of three mammalian lipases [pancreatic lipase (PL), lipoprotein lipase, and hepatic lipase] based on amino acid sequence similarity and gene organization. Family size increased when several proteins were subsequently added based on amino acid homology, including PL-related proteins 1 and 2, phosphatidylserine phospholipase A1, and endothelial lipase. The physiological function of each of the members is discussed as well as the region responsible for lipase properties such as enzymatic activity, substrate binding, heparin binding, and cofactor interaction. Crystallization of several lipase gene family members established that the family belongs to a superfamily of enzymes, which includes esterases and thioesterases. This superfamily is related by tertiary structure, rather than amino acid sequence, and represents one of the most populous families found in nature. C1 W Los Angeles Vet Affairs Healthcare Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Wong, H (reprint author), W Los Angeles Vet Affairs Healthcare Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL-28481] NR 64 TC 159 Z9 171 U1 1 U2 20 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 JUL PY 2002 VL 43 IS 7 BP 993 EP 999 DI 10.1194/jlr.R200007-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 574DL UT WOS:000176873100001 PM 12091482 ER PT J AU Tubiana-Rufi, N Megarbane, A Maassen, J Polak, M Lacombe, D Kahn, CR Silveira, EL D'Abronzo, FH Grigorescu, F O'Rahilly, S AF Tubiana-Rufi, N. Megarbane, A. Maassen, J. Polak, M. Lacombe, D. Kahn, C. R. Silveira, E. L. D'Abronzo, F. H. Grigorescu, F. O'Rahilly, S. TI Genotype-phenotype relationships in Berardinelli-Seip congenital lipodystrophy (vol 39, pg 722, 2002) SO JOURNAL OF MEDICAL GENETICS LA English DT Correction C1 [Tubiana-Rufi, N.] Hop Robert Debre, Serv Endocrinol Pediat, F-75019 Paris, France. [Megarbane, A.] Univ St Joseph, Unite Genet Med, Beirut, Lebanon. [Maassen, J.] Leiden Univ, Silvius Lab, Med Ctr, Leiden, Netherlands. [Polak, M.] Univ Paris 08, INSERM, U457, Paris, France. [Lacombe, D.] Hop Pellegrin Enfants, Serv Genet Med, Bordeaux, France. [Kahn, C. R.] Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. [Grigorescu, F.] IURC, Montpellier, France. [O'Rahilly, S.] Addenbrookes Hosp, Dept Med & Clin Biochem, Cambridge, England. RP Tubiana-Rufi, N (reprint author), Hop Robert Debre, Serv Endocrinol Pediat, F-75019 Paris, France. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUL PY 2002 VL 39 IS 7 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA V28HS UT WOS:000208672500007 ER PT J AU Muller, JG Thompson, JT Edmonson, AM Rackley, MS Kasahara, H Izumo, S McQuinn, TC Menick, DR O'Brien, TX AF Muller, JG Thompson, JT Edmonson, AM Rackley, MS Kasahara, H Izumo, S McQuinn, TC Menick, DR O'Brien, TX TI Differential regulation of the cardiac sodium calcium exchanger promoter in adult and neonatal cardiomyocytes by Nkx2.5 and serum response factor SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Nkx2.5; cardiac sodium-calcium exchanger; serum response factor; adult cardiomyocytes; neonatal cardiomyocytes ID ATRIAL-NATRIURETIC-FACTOR; ACTIN GENE-TRANSCRIPTION; DNA-BINDING TARGETS; CSX/NKX2.5 HOMEOPROTEIN; NA+-CA2+ EXCHANGER; HOMEODOMAIN FACTOR; HEART DEVELOPMENT; TINMAN HOMOLOG; HOMEOBOX GENES; EXPRESSION AB J. G. MOLLER, J. T. THOMPSON, A. M. EDMONSON, M. S. RACKLEY, H. KASAHARA, S. IZUMO, T. C. MCQUINN, D. R. MENICK AND T. X. O'BRIEN. Differential Regulation of the Cardiac Sodium Calcium Exchanger Promoter in Adult and Neonatal Cardiomyocytes by Nkx2.5 and Serum Response Factor. Journal of Molecular and Cellular Cardiology (2002) 34, 807-821. Nkx2.5 and serum response factor (SRF) are critically important transcription factors in cardiac morphogenesis. They arc also widely expressed in adult cardiomyocytes, but there is little data to indicate their possible role in adult cardiac cells. In this paper we demonstrate that the interaction of Nkx2.5 and SRF in cardiac-specific gene regulation is different between neonatal and adult cardiomyocytes. Our experimental model utilizes transient transfection and adenovirus mediated gene transfer of the proximal promoter fragment of the cardiac isoform of the sodium-calcium exchanger gene (NCX1). This promoter construct (NCX:184) contains a single Nkx2.5-response element (NKE) and a single serum response element (CArG). In rat neonatal cardiomyocytes NCX184 activity is substantially induced with Nkx2.5 or SRF and additively with both. Mutagenesis of these NKE and CArG elements demonstrated the specificity of the interactions, which was confirmed with gel retardation analysis of cardiac ventricular tissue. In contrast, in adult cardiomyocytes, co-infection of Nkx2.5 and SRF adenovirus vectors showed Nkx2.5 induction but SRF did not have additive effects on NCX1 promoter regulation. As opposed to NCX1, the proximal atrial natriuretic factor (ANF) promoter was regulated identically in response to SRF and Nkx2.5 in both adult and neonatal cardiomyocytes. These results show that Nkx2.5-SRF interactions are capable of producing different transcriptional responses in adult versus neonatal cardiomyocytes, implying important differences in NCX1 promoter tertiary complex formation dependent on developmental stage. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Div Pediat Cardiol, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Cardiovasc, Boston, MA 02215 USA. Univ Florida, Coll Med, Dept Physiol & Funct Genom, Gainesville, FL 32611 USA. RP O'Brien, TX (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, 96 Jonathan Lucas St,Suite 816,POB 250623, Charleston, SC 29425 USA. EM obriente@musc.edu FU NHLBI NIH HHS [T32-HL-07260, HL-48788, HL-55284] NR 43 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUL PY 2002 VL 34 IS 7 BP 807 EP 821 DI 10.1006/jmcc.2002.2019 PG 15 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 579YR UT WOS:000177207100015 PM 12099720 ER PT J AU Norris, PJ Rosenberg, ES AF Norris, PJ Rosenberg, ES TI CD4+T helper cells and the role they play in viral control SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE human immunodeficiency virus 1; T helper cell ID CD4(+) T-CELLS; IMMUNODEFICIENCY VIRUS-INFECTION; CELLULAR IMMUNE-RESPONSES; EPSTEIN-BARR-VIRUS; STRUCTURED TREATMENT INTERRUPTIONS; NEUTRALIZING ANTIBODY-RESPONSE; CHRONIC HIV-1 INFECTION; LONG-TERM SURVIVORS; LYMPHOCYTE-T; INFLUENZA-VIRUS AB The natural history of untreated HIV-1 infection is characterized by progressive erosion of the immune system with eventual loss of viral control. T helper cell responses to HIV-1 are typically weak or absent in chronically HIV-1 infected individuals. CD4(+) T helper cell responses have been shown to be important in a number of experimental viral infection systems, and here we explore the ways in which T helper cells might aid in the control of viruses in general and HIV-1 in particular. We first review the relationship between T helper cells and other arms of the immune system. We then focus on the role T helper cells play in viral control in murine and nonhuman primate models, and finally review what is known of CD4(+) T helper cell function in HIV-1 infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Norris, PJ (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. NR 95 TC 29 Z9 30 U1 3 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JUL PY 2002 VL 80 IS 7 BP 397 EP 405 DI 10.1007/s00109-002-0337-3 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 581LZ UT WOS:000177295000004 PM 12110945 ER PT J AU Safren, SA Gershuny, BS Marzol, P Otto, MW Pollack, MH AF Safren, SA Gershuny, BS Marzol, P Otto, MW Pollack, MH TI History of childhood abuse in panic disorder, social phobia, and generalized anxiety disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; SYMPTOMS; TRAUMA; INTELLIGENCE AB The authors examined the prevalence of self-reported childhood physical or sexual abuse in a sample of adult patients presenting for treatment of panic disorder, social phobia, or generalized anxiety disorder. Regardless of the presence of comorbid anxiety disorders or comorbid depression, patients with panic disorder had significantly higher rates of past childhood physical or sexual abuse than patients with social phobia. Patients with generalized anxiety disorder had intermediate rates of past physical or sexual abuse that were not significantly different from the other two diagnostic groups. Anxiety disorder patients with a history of childhood abuse were also more likely to have comorbid major depression than those without. These findings are discussed in terms of biological and behavioral factors that may influence the development of anxiety disorders after the experience of a traumatic event. C1 Harvard Univ, Sch Med, MGH Psychiat, Boston, MA 02114 USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, MGH Psychiat,WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 23 TC 57 Z9 57 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2002 VL 190 IS 7 BP 453 EP 456 DI 10.1097/01.NMD.0000022445.62652.82 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 577KV UT WOS:000177060800005 PM 12142846 ER PT J AU Gluck, M Ehrhart, J Jayatilleke, E Zeevalk, GD AF Gluck, M Ehrhart, J Jayatilleke, E Zeevalk, GD TI Inhibition of brain mitochondrial respiration by dopamine: involvement of H2O2 and hydroxyl radicals but not glutathione-protein-mixed disulfides SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dopamine; glutathione; glutathione-protein-mixed disulfides; mitochondria; Parkinson's disease; peroxide ID ELECTRON-TRANSPORT CHAIN; COMPLEX I DEFICIENCY; PARKINSONS-DISEASE; MONOAMINE-OXIDASE; HYDROGEN-PEROXIDE; OXIDIZED GLUTATHIONE; OXIDATIVE STRESS; METABOLISM; INACTIVATION; REDUCTION AB Examination of the downstream mediators responsible for inhibition of mitochondrial respiration by dopamine (DA) was investigated. Consistent with findings reported by others, exposure of rat brain mitochondria to 0.5 mm DA for 15 min at 30degreesC inhibited pyruvate/glutamate/malate-supported state-3 respiration by 20%. Inhibition was prevented in the presence of pargyline and clorgyline demonstrating that mitochondrial inhibition arose from products formed following MAO metabolism and could include hydrogen peroxide (H2O2), hydroxyl radical, oxidized glutathione (GSSG) or glutathione-protein mixed disulfides (PrSSG). As with DA, direct incubation of intact mitochondria with H2O2 (100 mum) significantly inhibited state-3 respiration. In contrast, incubation with GSSG (1 mm) had no effect on O-2 consumption. Exposure of mitochondria to 1 mm GSSG resulted in a 3.3-fold increase in PrSSG formation compared with 1.4- and 1.5-fold increases in the presence of 100 mum H2O2 or 0.5 mm DA, respectively, suggesting a dissociation between PrSSG formation and effects on respiration. The lack of inhibition of respiration by GSSG could not be accounted for by inadequate delivery of GSSG into mitochondria as increases in PrSSG levels in both membrane-bound (2-fold) and intramatrix (3.5-fold) protein compartments were observed. Furthermore, GSSG was without effect on electron transport chain activities in freeze-thawed brain mitochondria or in pig heart electron transport particles (ETP). In contrast, H2O2 showed differential effects on inhibition of respiration supported by different substrates with a sensitivity of succinate > pyruvate/malate > glutamate/malate. NADH oxidase and succinate oxidase activities in freeze-thawed mitochondria were inhibited with IC50 approximately 2-3-fold higher than in intact mitochondria. ETPs, however, were relatively insensitive to H2O2 . Co-administration of desferrioxamine with H2O2 had no effect on complex I-associated inhibition in intact mitochondria, but attenuated inhibition of rotenone-sensitive NADH oxidase activity by 70% in freeze-thawed mitochondria. The results show that DA-associated inhibition of respiration is dependent on MAO and that H-2 O-2 and its downstream hydroxyl radical rather than increased GSSG and subsequent PrSSG formation mediate the effects. C1 UMDNJ, Robert Wood Johnson Med Sch, Dept Neurol, Piscataway, NJ 08854 USA. Bronx Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. RP Zeevalk, GD (reprint author), UMDNJ, Robert Wood Johnson Med Sch, Dept Neurol, Bldg UBHC,Rm 401D,675 Hoes Lane, Piscataway, NJ 08854 USA. FU NINDS NIH HHS [NS 36157] NR 51 TC 43 Z9 43 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 1 BP 66 EP 74 DI 10.1046/j.1471-4159.2002.00938.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 566QC UT WOS:000176438900008 PM 12091466 ER PT J AU Zhang, XP Chen, J Graham, SH Du, LN Kochanek, PM Draviam, R Guo, FL Nathaniel, PD Szabo, C Watkins, SC Clark, RSB AF Zhang, XP Chen, J Graham, SH Du, LN Kochanek, PM Draviam, R Guo, FL Nathaniel, PD Szabo, C Watkins, SC Clark, RSB TI Intranuclear localization of apoptosis-inducing factor (AIF) and large scale dna fragmentation after traumatic brain injury in rats and in neuronal cultures exposed to peroxynitrite SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; brain injury; controlled cortical impact; DNA damage; programmed cell death ID CORTICAL IMPACT INJURY; PROGRAMMED CELL-DEATH; HEAD-INJURY; DENTATE GYRUS; ACTIVATION; BCL-2; CASPASE-3; CLEAVAGE; PROTEASE; EXPRESSION AB Programmed cell death occurs after ischemic, excitotoxic, and traumatic brain injury (TBI). Recently, a caspase-independent pathway involving intranuclear translocation of mitochondrial apoptosis-inducing factor (AIF) has been reported in vitro; but whether this occurs after acute brain injury was unknown. To address this question adult rats were sacrificed at various times after TBI. Western blot analysis on subcellular protein fractions demonstrated intranuclear localization of AIF in ipsilateral cortex and hippocampus at 2-72 h. Immunocytochemical analysis showed AIF labeling in neuronal nuclei with DNA fragmentation in the ipsilateral cortex and hippocampus. Immunoelectronmicroscopy verified intranuclear localization of AIF in hippocampal neurons after TBI, primarily in regions of euchromatin. Large-scale DNA fragmentation (similar to50 kbp), a signature event in AIF-mediated cell death, was detected in ipsilateral cortex and hippocampi by 6 h. Neuron-enriched cultures exposed to peroxynitrite also demonstrated intranuclear AIF and large-scale DNA fragmentation concurrent with impaired mitochondrial respiration and cell death, events that are inhibited by treatment with a peroxynitrite decomposition catalyst. Intranuclear localization of AIF and large-scale DNA fragmentation occurs after TBI and in neurons under conditions of oxidative/nitrosative stress, providing the first evidence of this alternative mechanism by which programmed cell death may proceed in neurons after brain injury. C1 Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15260 USA. Safar Ctr Resuscitat Res, Dept Neurol, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Pediat, Pittsburgh, PA USA. Safar Ctr Resuscitat Res, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA USA. Vet Affairs Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Inotek Corp, Beverly, MA USA. RP Clark, RSB (reprint author), Safar Ctr Resuscitat Res, Dept Anesthesiol & Crit Care Med, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU NINDS NIH HHS [P50 NS 30318, R01 NS 38620] NR 49 TC 183 Z9 188 U1 0 U2 3 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 JUL PY 2002 VL 82 IS 1 BP 181 EP 191 DI 10.1046/j.1471-4159.2002.00975.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 566QC UT WOS:000176438900021 PM 12091479 ER PT J AU Kiyashchenko, LI Mileykovskiy, BY Maidment, N Lam, HA Wu, MF John, J Peever, J Siegel, JM AF Kiyashchenko, LI Mileykovskiy, BY Maidment, N Lam, HA Wu, MF John, J Peever, J Siegel, JM TI Release of hypocretin (orexin) during waking and sleep states SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hypocretin; orexin; microdialysis; sleep-waking cycle; motor activity; cataplexy ID LOCUS-COERULEUS NEURONS; BEHAVIORAL ORGANIZATION; RETICULAR-FORMATION; UNRESTRAINED CAT; GABA RELEASE; A LEVELS; RAT; NARCOLEPSY; HYPOTHALAMUS; CYCLE AB Hypocretin (Hcrt or orexin) somas are located in the hypothalamus and project widely to forebrain and brainstem regions, densely innervating monoaminergic and cholinergic cells. Loss of Hcrt function results in the sleep disorder narcolepsy. However, the normal pattern of Hcrt release across the sleep-wake cycle is unknown. We monitored Hcrt-1 release in the basal forebrain, perifornical hypothalamus, and locus ceruleus (LC) across the sleep-wake cycle using microdialysis in freely moving cats and a sensitive solid phase radioimmunoassay. We found that the peptide concentration in dialysates from the hypothalamus was significantly higher during active waking (AW) than during slow-wave sleep (SWS). Moreover, Hcrt-1 release was significantly higher during rapid eye movement (REM) sleep than during SWS in the hypothalamus and basal forebrain. We did not detect a significant difference in release across sleep-waking states in the LC, perhaps because recovered levels of the peptide were lower at this site. Because there was a trend toward higher levels of Hcrt-1 release during AW compared with quiet waking (QW) in our 10 min dialysis samples, we compared Hcrt-1 levels in CSF in 2 hr AW and QW periods. Hcrt-1 release into CSF was 67% higher during AW than during QW. Elevated levels of Hcrt during REM sleep and AW are consistent with a role for Hcrt in the central programming of motor activity. C1 Univ Calif Los Angeles, Dept Psychiat, Vet Adm Greater Los Angeles Healthcare Syst Sepul, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, North Hills, CA 91343 USA. Russian Acad Sci, Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, Vet Adm Greater Los Angeles Healthcare Syst Sepul, 16111 Plummer St, North Hills, CA 91343 USA. FU NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610] NR 48 TC 198 Z9 204 U1 2 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 2002 VL 22 IS 13 BP 5282 EP 5286 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 569JK UT WOS:000176599100006 PM 12097478 ER PT J AU Cao, GD Pei, W Ge, HL Liang, QH Luo, YM Sharp, FR Lu, AG Ran, RQ Graham, SH Chen, J AF Cao, GD Pei, W Ge, HL Liang, QH Luo, YM Sharp, FR Lu, AG Ran, RQ Graham, SH Chen, J TI In vivo delivery of a Bcl-xL fusion protein containing the TAT protein transduction domain protects against ischemic brain injury and neuronal apoptosis SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cerebral ischemia; stroke; protein transduction; Bcl-2; caspase-3; cytochrome c ID FOCAL CEREBRAL-ISCHEMIA; CELL-DEATH; CYTOCHROME-C; DNA FRAGMENTATION; TRANSGENIC MICE; CASPASE-9 ACTIVATION; ARTERY OCCLUSION; NERVOUS-SYSTEM; CNS NEURONS; IN-VIVO AB Bcl-xL is a well characterized death-suppressing molecule of the Bcl-2 family. Bcl-xL is expressed in embryonic and adult neurons of the CNS and may play a critical role in preventing neuronal apoptosis that occurs during brain development or results from diverse pathologic stimuli, including cerebral ischemia. In this study, we used a novel approach to study the potential neuroprotective effect of Bcl-xL as a therapeutic agent in the murine model of focal ischemia/reperfusion. We created a Bcl-xL fusion protein, designated as PTD-HA-Bcl-xL, which contains the protein transduction domain (PTD) derived from the human immunodeficiency TAT protein. We demonstrated that this fusion protein is highly efficient in transducing into primary neurons in cultures and potently inhibited staurosporin-induced neuronal apoptosis. Furthermore, intraperitoneal injection of PTD-HA-Bcl-xL into mice resulted in robust protein transduction in neurons in various brain regions within 1-2 hr, and decreased cerebral infarction (up to similar to40%) in a dose-dependent manner, as determined at 3 d after 90 min of focal ischemia. PTD-HA-Bcl-xL was effective even when it was administered after the completion of ischemia (up to 45 min), and the protective effect was independent of the changes in cerebral blood flow or other physiological parameters. Finally, as shown by immunohistochemistry, Western blotting, and substrate-cleavage assays, PTD-HA-Bcl-xL attenuated ischemia-induced caspase-3 activation in ischemic neurons. These results thus confirm the neuroprotective effect of Bcl-xL against ischemic brain injury and provide the first evidence that the PTD can be used to efficiently transduce a biologically active neuroprotectant in experimental cerebral ischemia. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Disorders, Pittsburgh, PA 15261 USA. Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH 45267 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15261 USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS35965, NS36736, NS38560] NR 47 TC 303 Z9 323 U1 0 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 1 PY 2002 VL 22 IS 13 BP 5423 EP 5431 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 569JK UT WOS:000176599100022 PM 12097494 ER PT J AU Lo, EH Wang, XY Cuzner, ML AF Lo, EH Wang, XY Cuzner, ML TI Extracellular proteolysis in brain injury and inflammation: Role for plasminogen activators and matrix metalloproteinases SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE blood-brain barrier; brain injury; cell death; demyelination; ECM; inflammation; neuroprotection ID CENTRAL-NERVOUS-SYSTEM; FOCAL CEREBRAL-ISCHEMIA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS LESIONS; SERINE-PROTEASE INHIBITOR; LONG-TERM POTENTIATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; OXYGEN-GLUCOSE DEPRIVATION; REDUCES INFARCT SIZE; TPA-DEFICIENT MICE AB The role of intracellular proteases (e.g., calpains and caspases) in the pathophysiology of neuronal cell death has been extensively investigated. More recently, accumulating data have suggested that extracellular proteolysis also plays a critical role. The two major systems that modify the extracellular matrix in brain are the plasminogen activator (PA) and matrix metalloproteinase (MMP) axes. This Mini-Review delineates major pathways of PA and MMP action after stroke, brain trauma, and chronic inflammation. Deleterious effects include the disruption of blood-brain barrier integrity, amplification of inflammatory infiltrates, demyelination, and possibly interruption of cell-cell and cell-matrix interactions that may trigger cell death. In contrast, PA-MMP actions may contribute to extracellular proteolysis that mediates parenchymal and angiogenic recovery after brain injury. As the mechanisms of deleterious vs. potentially beneficial PA and MMP actions become better defined, it is hoped that new therapeutic targets will emerge for ameliorating the sequelae of brain injury and inflammation. (C) 2002 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Neuroprotect Res Lab, Massachusetts Gen Hosp,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neuroprotect Res Lab, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. Univ Coll, Inst Neurol, Dept Neuroinflammat, London, England. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS38731, R01-NS40529, R01-NS37074] NR 150 TC 218 Z9 226 U1 1 U2 9 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 JUL 1 PY 2002 VL 69 IS 1 BP 1 EP 9 DI 10.1002/jnr.10270 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 567RA UT WOS:000176497400001 PM 12111810 ER PT J AU Mesiwala, AH Goodkin, R AF Mesiwala, AH Goodkin, R TI Reversible ischemia detected by diffusion-weighted magnetic resonance imaging - Case illustration SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material DE diffusion-weighted imaging; ischemia; subdural hematoma; magnetic resonance imaging C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Goodkin, R (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUL PY 2002 VL 97 IS 1 BP 230 EP 230 DI 10.3171/jns.2002.97.1.0230 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 570NU UT WOS:000176665000039 PM 12134924 ER PT J AU Chang, BL Lee, JL Pearson, ML Kahn, KL Elliott, MN Rubenstein, LL AF Chang, BL Lee, JL Pearson, ML Kahn, KL Elliott, MN Rubenstein, LL TI Evaluating quality of nursing care - The gap between theory and practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID PROSPECTIVE PAYMENT SYSTEM; HOSPITAL CHARACTERISTICS; REHABILITATION; ASSOCIATION; OUTCOMES; STROKE; NURSES; UNIT AB The purpose of this article is to determine whether nursing practice, as judged by nurse peer reviewers, varies by type or location of hospital and to assess which aspects of practice tend to be most at variance with nursing theory. This article provides a framework of continued quality assessment and improvement that is based on prior research. Trained nurse peer reviewers carried out structured implicit review, which utilized their professional judgment to evaluate the process of nursing care for patients admitted to acute hospitals with heart failure or cerebrovascular accident. Findings show significant variations in the quality of nursing care and support the continued development of nursing quality assessment and improvement initiatives directed at reducing the gap between nursing theory and practice. C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Vet Adm Greater Los Angeles, Los Angeles, CA USA. RP Chang, BL (reprint author), Univ Calif Los Angeles, Sch Nursing, Factor Bldg,Rm 5-238,Box 956918, Los Angeles, CA 90095 USA. FU NINR NIH HHS [R01-NR03681] NR 62 TC 10 Z9 12 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUL-AUG PY 2002 VL 32 IS 7-8 BP 405 EP 418 DI 10.1097/00005110-200207000-00009 PG 14 WC Nursing SC Nursing GA 585RV UT WOS:000177539100009 PM 12177562 ER PT J AU Kales, SN Soteriades, ES Christoudias, SG Tucker, SA Nicolaou, M Christiani, DC AF Kales, SN Soteriades, ES Christoudias, SG Tucker, SA Nicolaou, M Christiani, DC TI Firefighters' blood pressure and employment status on hazardous materials teams in Massachusetts: A prospective study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID UNITED-STATES; JOB STRAIN; HYPERTENSION; FITNESS; RISK; FRAMINGHAM; MORBIDITY; MORTALITY; DUTY; INCAPACITATION AB We evaluated the association between hypertension and changes in employment status in 334 hazardous materials firefighters. Firefighters were categorized by blood pressure (BP) at baseline (1996 or 1997) and the subsequent follow-up examinations (1997, 1998, and 1999). They were followed up for a maximum of 4 years for possible adverse outcomes (death, placement on "injured-on-duty" status, termination of duty, resignation, retirement, or incident cardiovascular disease). In several analytic models, we found that firefighters with stage II hypertension (BP greater than or equal to 160/100 mm Hg) were consistently 2 to 3 times more likely to experience an adverse outcome compared with those with normal BP. Cox proportional-hazards regression was used to adjust for age, body mass index, smoking, cholesterol, and antihypertensive medication. In these models, the hazard ratio for stage II hypertension was 3.2 (95% confidence interval [CI], 1.50 to 7.04, P = 0.003) and for untreated stage II hypertension, it was 4.6 (95% CI, 2.08 to 10.11 P = 0.0002). Firefighters with a BP greater than or equal to 160/100 min Hg should receive further evaluation and demonstrate improved BP control before being determined fit for duty. C1 Cambridge Hosp, Dept Med Occupat & Environm Hlth, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care unit, Boston, MA USA. Olympus Specialty & Rehabil Hosp, Ctr Occupat & Environm Med, Braintree, MA USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med Occupat & Environm Hlth, 1493 Cambridge St, Cambridge, MA 02139 USA. FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [OH03729] NR 39 TC 14 Z9 15 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2002 VL 44 IS 7 BP 669 EP 676 DI 10.1097/01.jom.0000023251.57933.bb PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 573RU UT WOS:000176845300013 PM 12134531 ER PT J AU Levine, MH Yates, KE Kaban, LB AF Levine, MH Yates, KE Kaban, LB TI Nerve growth factor is expressed in rat femoral vein SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgery CY SEP 22, 2000 CL SAN FRANSICAO, CALIFORNIA SP Amer Assoc Oral & Maxillofacial Surg ID AUTOGENOUS VEIN; REGENERATION; REPAIR; LAMININ; CONDUITS; GRAFTS; TUBE AB Purpose: Entubulization is a well known method of nerve repair for defects too large to be reconstructed by direct suturing without tension. Vein grafts and alloplastic tubes have been used for entubulization in peripheral and cranial nerves, but the mechanism by which they promote healing is poorly understood. The overall hypothesis of this laboratory is that nerve growth factor (NGF) plays an important role in nerve regeneration after entubulization with a vein graft. The purpose of this pilot study was to localize NGF protein expression in the rat femoral vein. Materials and Methods: Sciatic nerves and femoral veins were harvested from adult male Sprague-Dawley rats. Femoral arteries were also collected and used for comparison and validation of the analysis. All specimens were fixed in paraformaldehyde and embedded in paraffin. Specimens were either stained with hematoxylin and eosin or used for immunohistochemical reaction with anti-NGF antibody. Results: Sciatic nerve was used as a positive control to identify the monofasicular architecture with hematoxylin and eosin and to document the positive immunohistochemical reaction. NGF immunoreactivity was present in the tunica intima and tunica adventitia of femoral vein and artery but not in the tunica media. Conclusion: The results of this pilot study indicate that NGF is detectable in both the intimal and adventitial layers of the rat femoral vein and artery but not in the smooth muscle wall. These findings suggest that vein grafts could potentially promote nerve regeneration by supplying NGF to the injured nerve. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. NR 42 TC 14 Z9 19 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2002 VL 60 IS 7 BP 729 EP 733 DI 10.1053/joms.2002.33237 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 567QQ UT WOS:000176496100002 PM 12089682 ER PT J AU Kim, Y Flynn, TR Donoff, RB Wong, DW Todd, R AF Kim, Y Flynn, TR Donoff, RB Wong, DW Todd, R TI The gene: The polymerase chain reaction and its clinical application SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ENZYMATIC AMPLIFICATION; DNA; PCR; MUTAGENESIS; CHROMOSOME; ABSCESSES; SEQUENCES; INVITRO; CANCER AB Chromosomal DNA transfers and stores information regarding the structure and function of the cell. Genetic information, encoded within sequences of nucleotides that compose DNA, is grouped into functional units called genes. Genetic diseases are caused by changes in the chromosomal DNA, leading to a change in the quantity or function of the protein gene product. In the past, genetic diagnosis was limited by the availability of sufficient quantity and quality of DNA and the absence of an efficient amplification procedure. The polymerase chain reaction (PCR), an inexpensive, rapid, and accurate means of amplifying DNA, is already making a major contribution to the diagnostic sciences. PCR techniques have been widely used in diverse applications, including molecular analysis of microbial pathogens, inheritable diseases and syndromes, and neoplasms. The purpose of this article is to 1) Review gene structure and function, 2) review principles of PCR technology and its applications in molecular biology, and 3) discuss an experimental clinical application of PCR to identify novel infectious agents responsible for odontogenic infections. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Dent, Dept Oral Pathol, Los Angeles, CA 90024 USA. RP Todd, R (reprint author), Harvard Sch Dent Med, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [P30 DE 11814, K02 DE 00456, P01 DE 11983, P01 DE 12467, R29 DE 11983] NR 31 TC 17 Z9 18 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2002 VL 60 IS 7 BP 808 EP 815 DI 10.1053/jams.2002.33251 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 567QQ UT WOS:000176496100018 PM 12089698 ER PT J AU Bragdon, CR Malchau, H Yuan, XH Perinchief, R Karrholm, J Borlin, N Estok, DM Harris, WH AF Bragdon, CR Malchau, H Yuan, XH Perinchief, R Karrholm, J Borlin, N Estok, DM Harris, WH TI Experimental assessment of precision and accuracy of radio stereometric analysis for the determination of polyethylene wear in a total hip replacement model SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE radiostereometric analysis; polyethylene wear ID MIGRATION AB The purpose of this study was to develop and testa phantom model based on actual total hip replacement (THR) components to simulate the true penetration of the femoral h cad resulting fro in polyethylene car, This Model was used to Study both the accuracy and the precision of radiostereometric analysis, RSA, in measuring wear. We also used this model to evaluate optimum tantalum bead configuration for this particular cup design when used in a clinical setting. A physical model of a total hip replacement (a phantom) was constructed which Could simulate progressive. three-dimensional (3-D) penetration of the femoral head into the polyethylene component of a THR. Using it coordinate Measuring machine (CMM) the positioning of the femoral head using the phantom was measured to be accurate to within 7 mum The accuracy and precision of an RSA analysis system was determined from five repeat examinations of the phantom using various experimental set-ups of the phantom. The accuracy of the radiostereometric analysis, in this optimal experimental set-up studied was 33 mum for the medial direction, 22 mum for the superior direction, 86 mum for the posterior direction and 55 mum for the resultant 3-D vector length. The corresponding precision at the 95% confidence interval of the test results for repositioning the phantom five times. measured 8.4 mum for the medial direction, 5.5 mum for the superior direction. 16.0 mum for the posterior direction. and 13 5 mum for the resultant 3-D vector length. This in vitro model is proposed as a useful tool for developing a standard for the evaluation of radiostereometric and other radiographic methods used to measure in vivo wear. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd, All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Gothenburg, Inst Surg Sci, Dept Orthoped, Gothenburg, Sweden. Umea Univ, Dept Comp Sci, Umea, Sweden. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. OI Borlin, Niclas/0000-0002-7657-6917 NR 24 TC 94 Z9 96 U1 0 U2 7 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 JUL PY 2002 VL 20 IS 4 BP 688 EP 695 AR PII S0736-0266(01)00171-1 DI 10.1016/S0736-0266(01)00171-1 PG 8 WC Orthopedics SC Orthopedics GA 579RL UT WOS:000177191600008 PM 12168656 ER PT J AU Cho, DR Shanbhag, AS Hong, CY Baran, GR Goldring, SR AF Cho, DR Shanbhag, AS Hong, CY Baran, GR Goldring, SR TI The role of adsorbed endotoxin in particle-induced stimulation of cytokine release SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE endotoxin; cytokines; wear debris; orthopaedic implant; particles ID TUMOR-NECROSIS-FACTOR; TOTAL HIP REPLACEMENTS; TOLL-LIKE RECEPTORS; BONE-RESORPTION; IN-VITRO; PARTICULATE DEBRIS; TITANIUM PARTICLES; SURFACE-AREA; LIPOPOLYSACCHARIDE; MACROPHAGES AB Numerous in vitro models have demonstrated the capacity of wear particles to stimulate the release of soluble pro-inflammatory products with the ability to induce local bone resorption. Recent observations have demonstrated that binding of lipopolysaccharide (LPS) to particulate wear debris can significantly modulate the pattern of cell response in the in vitro models. These findings raise concerns over the possible role of LPS in the pathogenesis of aseptic loosening after total joint replacements, and also indicates the importance of controlling for possible confounding effects of LPS contamination in the in vitro models used to study the reactive nature of wear debris. Our studies were undertaken to rigorously analyze the effects of particle-associated LPS on cell responses and to assess the efficacy of different treatment protocols to inactivate LPS associated with different particulate materials. Particles of cobalt-chrome alloy, titanium-6-aluminum 4-vanadium, titanium nitride and silica were pretreated with LPS and exposed to multiple treatment protocols. When cells were treated with "as-received" particles prepared by washing in ethanol, small amounts of TNF-alpha, IL-1beta, and IL-1alpha were detected. In contrast, all particle species pretreated with LPS produced marked increases in TNF-alpha, IL-1alpha, and IL-1beta release, as well as upregulation of corresponding mRNA levels even after ethanol washing. Boiling the LPS-pretreated particles in 1% acetic acid or autoclaving and baking the particles also markedly reduced and in some instances abolished the effect of the LPS-pretreatment. This indicates that LPS binds to the surface of particles of diverse composition and that the bound LPS is biologically active. Treatment protocols to inactivate particle-associated LPS demonstrated significant differences in efficacy. When the most rigorous treatments were utilized, essentially all LPS activity could be eliminated. Particles treated with these methods retained some capacity to stimulate cytokine release, but activities were markedly reduced. These results provide further evidence indicating that LPS contamination of particulate materials can markedly enhance their biological activity. This potential confounding effect needs to be carefully monitored and controlled in the in vitro model systems used to evaluate wear particles. Furthermore, the presence of particle-associated endotoxin at the bone implant interface in vivo could markedly enhance the adverse biological activity of particulate wear debris. (C) 2002 Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Rheumatol Div, New England Bone & Joint Inst,Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Biomat Lab, Boston, MA 02114 USA. Natl Taiwan Univ, Sch Dent, Taipei 10016, Taiwan. Temple Univ, Ctr Adv Res & Educ Biomat, Philadelphia, PA 19122 USA. RP Goldring, SR (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Rheumatol Div, New England Bone & Joint Inst,Harvard Inst Med, 4 Blackfan Circle,2nd Floor, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR45472] NR 60 TC 59 Z9 60 U1 1 U2 6 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 JUL PY 2002 VL 20 IS 4 BP 704 EP 713 AR PII S0736-0266(01)00179-6 DI 10.1016/S0736-0266(01)00179-6 PG 10 WC Orthopedics SC Orthopedics GA 579RL UT WOS:000177191600010 PM 12168658 ER PT J AU Mithofer, K Lhowe, DW Altman, GT AF Mithofer, K Lhowe, DW Altman, GT TI Delayed presentation of acute compartment syndrome after contusion of the thigh SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE compartment syndrome; thigh; contusion; delayed; lower extremity; fasciotomy ID FASCIOTOMY; DIAGNOSIS AB Acute compartment syndrome has been described as a result of thigh contusion in several contact sports. and emergent fasciotomy has routinely been recommended. However. recent data suggest that thigh contusions in athletes presenting with isolated elevation of compartment pressures in the absence of neurovascular deficits may be treated expectantly. We describe a case of anterior thigh contusion, which initially presented with isolated compartmental hypertension without neurovascular symptoms. Under nonoperative treatment the patient developed delayed acute compartment syndrome from persistent muscular hemorrhage ten days after the initial trauma, requiring operative treatment. This case demonstrates that expanding hematoma formation may result in delayed increase of intramuscular pressures and compromise of myoneural perfusion in patients with severe thigh contusions. Early evacuation of the hematoma may help to prevent late development of compartment syndrome and reduce the risk for long-term complications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Mithofer, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, GRB 606,15 Parkman St, Boston, MA 02114 USA. NR 18 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD JUL PY 2002 VL 16 IS 6 BP 436 EP 438 DI 10.1097/00005131-200207000-00014 PG 3 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 569LQ UT WOS:000176604200014 PM 12142836 ER PT J AU Choi, YS Billings, JA AF Choi, YS Billings, JA TI Opioid antagonists: A review of their role in palliative care, focusing on use in opioid-related constipation SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Review DE narcotic antagonists; naloxone; naltrexone; nalmephene; opioid-related disorders; constipation; gastrointestinal motility; nausea/vomiting; pruritus; respiratory depression; substace-related disorders ID INDUCED RESPIRATORY DEPRESSION; CECAL TRANSIT-TIME; QUATERNARY NARCOTIC-ANTAGONISTS; PATIENT-CONTROLLED ANALGESIA; MORPHINE-INDUCED INHIBITION; OPIATE RECEPTOR-BINDING; LOW-DOSE NALOXONE; ORAL NALOXONE; GASTROINTESTINAL TRANSIT; EPIDURAL MORPHINE AB Opioid, antagonists have well-established indications in the reversal of life-threatening opioid toxicity, but also hold considerable promise for other applications in palliative care practice, particularly management of opioid-related constipation. We briefly review current understanding of opioid receptors, focusing on their complex role in gastrointestinal physiology. We summarize the pharmacology, conventional indications, and clinical usage of three major groups of opioid antagonists, including a promising new peripherally acting agent, methylnaltrexone, which is not commercially available. We suggest an an approach to administering opioid antagonists for reduction of life-threatening opioid toxicity in patients with pain. The literature on opioid-induced constipation and its treatment with opioid-antagonists is reviewed in detail. Finally, other potential uses of opioid antagonists in palliative care are described, especially strategies for reducing such opioid, side effects as nausea. and pruritus and for improving analgesia or reducing tolerance by concomitantly administrating both an opioid agonist and low dosages of an antagonist. C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Korea Univ, Coll Med, Seoul 136701, South Korea. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, FND 600,55 Fruit St, Boston, MA 02114 USA. NR 203 TC 70 Z9 75 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2002 VL 24 IS 1 BP 71 EP 90 AR PII S0885-3924(02)00424-4 DI 10.1016/S0885-3924(02)00424-4 PG 20 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 580WT UT WOS:000177260200015 PM 12183097 ER PT J AU Bonner-Weir, S Sharma, A AF Bonner-Weir, S Sharma, A TI Pancreatic stem cells SO JOURNAL OF PATHOLOGY LA English DT Review DE regeneration; islets of Langerhans; pancreatic duct ID EPITHELIAL PROGENITOR CELLS; KERATINOCYTE GROWTH-FACTOR; RAT PANCREAS; BETA-CELLS; ISLET NEOGENESIS; TRANSGENIC MICE; PRECURSOR CELLS; OVAL CELLS; ENDOCRINE PANCREAS; FACTOR-ALPHA AB beta-cell replacement therapy via islet transplantation has had renewed interest, due to the recent improved success. In order to make such a therapy available to more than a few of the thousands of patients with diabetes, new sources of insulin-producing cells must be readily available. The recent conceptual revolution of the presence of adult pluripotent stem cells in bone marrow and in most, if not all, organs suggests that adult stem cells may be a potential source of insulin-producing cells. Pancreatic stem/progenitor cells or markers for these cells have been sought in both islets and ducts. There is considerable evidence that such cells exist and several candidate cells have been reported. However, no clearly identifiable adult pancreatic stem cell has been found as yet. The putative pancreatic stem cells will be the focus of this review. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cellular Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cellular Biol, 1 Joslin Pl, Boston, MA 02215 USA. OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 66 TC 196 Z9 214 U1 2 U2 15 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD JUL PY 2002 VL 197 IS 4 BP 519 EP 526 DI 10.1002/path.1158 PG 8 WC Oncology; Pathology SC Oncology; Pathology GA 573MW UT WOS:000176834800011 PM 12115867 ER PT J AU Malaty, HM Haveman, T Graham, DY Fraley, JK AF Malaty, HM Haveman, T Graham, DY Fraley, JK TI Helicobacter pylori infection in asymptomatic children: Impact of epidemiologic factors on accuracy of diagnostic tests SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Helicobacter pylori infection; diagnostic methods; crowding; children ID UREA BREATH TEST; SOCIOECONOMIC-STATUS; CHILDHOOD; ACQUISITION; PREVALENCE; TRANSMISSION; STAIN AB Background: Childhood is a time of high risk for acquiring H. pylori infection. Accurate information on the epidemiology of the infection requires accurate diagnostic tests. Objective: To study the epidemiologic factors that influence the accuracy of diagnostic tests among asymptomatic children. Methods: Two rapid. noninvasive assays (FlexSure(R) whole-blood test and OraSure(R) saliva test) were evaluated using the C-13-urea breath test (C-13 -UBT) as the gold standard. The three diagnostic tests were conducted in children from 10 licensed day care centers from various locations in Houston. Texas. Demographic information and socioeconomic factors evaluated included age, gender, ethnicity, and crowded living conditions in each center. The three tests were conducted oil each child on the same day, We examined the effect of epidemiologic factors on the sensitivity, the specificity, and the positive and negative predictive values of both tests. Results: Thirty-two percent of the 243 asymptomatic children who participated in the study tested positive for H. pylori using C-13-UBT. Among all the children, the sensitivities of FlexSure and OraSure were 47% (95% confidence interval, 35-57%) and 65% (95% confidence interval. 54-73%). respectively. Both tests had greater than 95% specificity. Positive and negative predictive values for FlexSure were 86% and 80%, respectively, and 98% and 86% for OraSure. Among children attending the more crowded day care centers, the sensitivities of FlexSure and OraSure were 40% and 63%, respectively, compared with 100% sensitivity for FlexSure and 80% sensitivity for OraSure among children attending the less-crowded centers. FlexSure and OraSure tests had the highest sensitivities among the 6- to 10-year-olds. Ethnicity had no effect on the sensitivity or the specificity of either test. Conclusion: Epidemiologic factors influenced the accuracy of serologic tests for diagnosing H. pylori infection in children. The lowest sensitivities of both tests were among children who attended the more crowded centers and among the youngest and oldest age groups. reflecting an increased proportion of recent infections. The strategy for choosing a diagnostic test for H. pylori infection in children varies based on the epidemiologic characteristics of the studied population. (C) 2002 LippinCott Williams Wilkins, Inc. C1 Vet Affairs Med Ctr 111D, Dept Med, Houston, TX 77030 USA. Vet Affairs Med Ctr 111D, Div Mol Virol, Houston, TX 77030 USA. Vet Affairs Med Ctr 111D, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Malaty, HM (reprint author), Vet Affairs Med Ctr 111D, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 2002 VL 35 IS 1 BP 59 EP 63 DI 10.1097/01.MPG.0000016486.73596.4E PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 578DR UT WOS:000177102600012 PM 12142811 ER PT J AU Fuchs, JR Terada, S Ochoa, ER Vacanti, JP Fauza, DO AF Fuchs, JR Terada, S Ochoa, ER Vacanti, JP Fauza, DO TI Fetal tissue engineering: In utero tracheal augmentation in an ovine model SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Section on Surgery of the American-Academy-of-Pediatrics CY OCT 19-21, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Pediat, Surg Sect DE tissue engineering; cartilage; tracheal malformations; fetal surgery; congenital anomalies; transplantation ID SLIDE-TRACHEOPLASTY; RECONSTRUCTION; CARTILAGE; STENOSIS; REPLACEMENT; TRANSPLANTATION; INTERMEDIATE; CELLS; GRAFT AB Background/Purpose: This study was aimed at comparing fetal tissue engineering with autologous free grafting in an ovine model of in utero tracheal repair. Methods: Chondrocytes were isolated from both elastic and hyaline cartilage specimens harvested from fetal lambs and expanded in vitro. Cells were seeded dynamically onto biodegradable scaffolds, which then were maintained in a rotating bioreactor for 6 to 8 weeks. Constructs subsequently were implanted into fetal tracheas (n = 15), in a heterologous fashion (group 1). In group 11, fetuses (n = 5) received autologous free grafts of elastic cartilage harvested from the ear as tracheal implants. In vivo specimens were harvested for histologic analysis at different time-points postimplantation. Results: In the 12 of 15 surviving fetuses of group 1, all constructs were found to resemble normal hyaline cartilage, engraft well despite their heterologous origin, and display time-dependent epithelialization derived from the native trachea. All autologous free grafts were engrafted and epithelialized at birth, retaining histologic characteristics of elastic cartilage, but were more deformed than engineered constructs. Of the lambs allowed to reach term, 5 of 5 in the engineered group and 4 of 5 in the free graft group could breathe spontaneously. Conclusions: (1) Tissue-engineered cartilage, as well as autologous free grafts, can be implanted successfully into the fetal trachea, resulting in engraftment and function. (2) Engineered cartilage provides enhanced structural support after implantation into the fetal trachea when compared with free grafts. Prenatal tracheoplasty may prove useful for the treatment of severe congenital tracheal malformations. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Med Sch,Harvard Ctr Minimally Invas Surg, Ctr Integrat Med & Innovat Technol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Fauza, DO (reprint author), Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. NR 26 TC 40 Z9 42 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2002 VL 37 IS 7 BP 1000 EP 1006 DI 10.1043/jpsu.2002.33829 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 569NX UT WOS:000176609400020 PM 12077758 ER PT J AU Feschenko, MS Stevenson, E Nairn, AC Sweadner, KJ AF Feschenko, MS Stevenson, E Nairn, AC Sweadner, KJ TI A novel cAMP-stimulated pathway in protein phosphatase 2A activation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ELONGATION FACTOR-II; CYCLIC-AMP; KINASE-C; RETINOBLASTOMA PROTEIN; SIGNALING PATHWAY; STRUCTURAL BASIS; PHOSPHORYLATION; CELLS; IDENTIFICATION; INHIBITION AB Elevated cAMP in NRK-52E and L6 cells causes a marked reduction in the phosphorylation of numerous phosphoproteins, as detected initially with phosphoserine-specific antibodies. Here, we show that elevation of cAMP in NRK cells by forskolin/3-isobutyl-1-methylxanthine (IBMX) treatment decreased phosphorylation of substrates for different protein kinases, pointing to a common protein phosphatase as a target for cAMP-dependent regulation. Forskolin/IBMX treatment completely dephosphorylated a selective protein phosphatase 2A (PP2A) substrate, elongation factor-2 (EF-2), at its Ca2+ calmodulin-dependent kinase site, and decreased phosphorylation of substrates for cyclin-dependent kinases, including retinoblastoma (Rb) protein. As reported before, forskolin/IBMX also decreased phosphorylation of a protein kinase C substrate, the Na,K-ATPase. The cAMP-stimulated dephosphorylation was blocked by the protein phosphatases 1 (PP1) and PP2A inhibitor okadaic acid at concentrations selective for PP2A but was not blocked by tautomycin at concentrations selective for PP1. The data implicate PP2A as a cAMP-activated phosphatase. Contrary to expectation, we found evidence that cAMP-dependent activation of PP2A did not depend on protein kinase A (PKA). Pretreatment of cells with the PKA inhibitor H89 abolished PKA activity measured in cell extracts and significantly decreased cAMP-activated phosphorylation of a known PKA substrate, ARPP-19, in cells, but failed to block the cAMP-stimulated dephosphorylation of EF-2, Rb, and other proteins. This novel pathway of PP2A activation, acting on the time scale of minutes, represents yet another example of a cAMP-mediated, PKA-independent signaling mechanism. Because PP2A is active toward a variety of endogenous substrates, cAMP-stimulated dephosphorylation may have complicated the interpretation of many prior studies. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. RP Feschenko, MS (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149 13th St, Charlestown, MA 02129 USA. OI Nairn, Angus/0000-0002-7075-0195 FU NIDA NIH HHS [P01 DA010044]; NIGMS NIH HHS [GM 50402]; NINDS NIH HHS [NS 27653] NR 40 TC 66 Z9 67 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2002 VL 302 IS 1 BP 111 EP 118 AR UNSP 33589/990841 DI 10.1124/jpet.302.1.111 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 562DW UT WOS:000176183000015 PM 12065707 ER PT J AU Lomarev, M Denslow, S Nahas, Z Chae, JH George, MS Bohning, DE AF Lomarev, M Denslow, S Nahas, Z Chae, JH George, MS Bohning, DE TI Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE vagus nerve stimulation; depression; FMRI ID TRANSCRANIAL MAGNETIC STIMULATION; BLOOD-FLOW; RESISTANT DEPRESSION; REFRACTORY EPILEPSY; VAGAL-STIMULATION; THERAPY; SEIZURES; SPECT AB Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy patients, and may be helpful in treating depression. PET studies have shown that vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity) dependent changes in regional cerebral blood flow. We sought to use the newly developed VNS synchronized fMRI technique to examine whether VNS BOLD signal changes depend on the frequency of stimulation. Six adults with recurrent depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest, with the VNS device on for 7 s, and also, for comparison, while the patient listened to a tone for 7 s. In two separate back-to-back sessions, the VNS stimulation frequency was set to either 5 or 20 Hz. Data were transformed into Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS produced more acute activity changes from rest in regions similar to our initial VNS synchronized fMRI feasibility study in depression. Brain regions activated by hearing a tone were also greater when VNS was intermittently being applied at 20 Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain activity changes that depend on the frequency of stimulation or total dose, or both. In addition to the acute immediate effects of VNS on regional brain activity, this study suggests further that VNS at different frequencies likely has frequency or dose dependent modulatory effects on other brain activities (e.g. hearing a tone). (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. Inst Human Brain, St Petersburg, Russia. Catholic Univ Korea, Seoul, South Korea. RP Lomarev, M (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. NR 29 TC 73 Z9 73 U1 0 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 JUL-AUG PY 2002 VL 36 IS 4 BP 219 EP 227 AR PII S0022-3956(02)00013-4 DI 10.1016/S0022-3956(02)00013-4 PG 9 WC Psychiatry SC Psychiatry GA 577KR UT WOS:000177060500003 PM 12191626 ER PT J AU Pollack, MH Rapaport, MH Fayyad, R Otto, MW Nierenberg, AA Clary, CM AF Pollack, MH Rapaport, MH Fayyad, R Otto, MW Nierenberg, AA Clary, CM TI Early improvement predicts endpoint remission status in sertraline and placebo treatments of panic disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE panic disorder; sertraline; early improvement; remission; ROC analysis ID MULTICENTER TRIAL; DOUBLE-BLIND; DRUG; IMIPRAMINE; THERAPY AB The early identification of likely remitters and non-remitters to pharmacotherapy for panic disorder may have important implications for clinical treatment decisions. To address this question, combined data from two fixed-dose and two flexible dose placebo-controlled studies of sertraline treatment of panic disorder were examined. Patients (N=544) diagnosed with panic disorder, with or without agoraphobia, were treated with 50 mg of sertraline, 100 mg of sertraline, flexible dosages of sertraline, or placebo. Measures of early improvement included panic attack frequency (full + limited symptom attacks), anticipatory anxiety, the Hamilton Anxiety Rating Scale (HAM-A), and the Clinical Global Impression Improvement. (CGI-I) Scale. Improvement as reflected in CGI-I ratings and change from baseline in the HAM-A at weeks 1, 2, and 3 significantly (P<0.0001) predicted endpoint clinical remission (defined at endpoint as no full panic attacks and a CGI-Severity rating of 1 or 2). Improvements in panic attack frequency and anticipatory anxiety were not consistent predictors in multivariate predictive models. Receiver-Operator Curve analyses revealed good specificity (0.83) for change in CGI-1 at week 2, and good sensitivity (0.82) for change in HAM-A at week 3. Predictive success for HAM-A and CGI-I was not significantly different for fixed vs. flexible dose sertraline treatment, nor for sertraline vs. placebo treatment. The use of ROC analyses for examination of early response as a predictor of final remission holds promise for aiding clinicians in decision making regarding the need for alternative or supplemental treatment approaches during the course of pharmacotherapy for panic disorder. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anxiety Disorders Program,Dept Psychiat, Boston, MA 02114 USA. Univ Calif San Diego, Sch Med, San Diego Vet Affairs Healthcare Syst, Dept Psychiat, La Jolla, CA 92037 USA. Univ Calif San Diego, Sch Med, San Diego Vet Affairs Healthcare Syst, Psychiat Serv, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Program,Dept Psychiat, Boston, MA 02114 USA. Pfizer Inc, New York, NY 10017 USA. RP Pollack, MH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anxiety Disorders Program,Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 26 TC 21 Z9 21 U1 1 U2 1 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 JUL-AUG PY 2002 VL 36 IS 4 BP 229 EP 236 AR PII S0022-3956(02)00010-9 DI 10.1016/S0022-3956(02)00010-9 PG 8 WC Psychiatry SC Psychiatry GA 577KR UT WOS:000177060500004 PM 12191627 ER PT J AU Wambaugh, JL Doyle, PJ Martinez, AL Kalinyak-Fliszar, M AF Wambaugh, JL Doyle, PJ Martinez, AL Kalinyak-Fliszar, M TI Effects of two lexical retrieval cueing treatments on action naming in aphasia SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE anomia; aphasia; language; speech and language therapy; word-finding ID BRAIN-DAMAGED SUBJECTS; VERB RETRIEVAL; THERAPY; IMPAIRMENT; DEFICITS AB The effects of two cueing treatments, Phonological Cueing Treatment (PCT) and Semantic Cueing Treatment (SCT), were examined with three chronic speakers with aphasia. The effects of treatment on action naming were measured with the use of single-subject experimental designs. The participants had received PCT and SCT to improve object naming in a previous investigation and had responded positively to both treatments. In the current study, Speaker 1 received SCT, Speaker 2 received PCT, and Speaker 3 received both SCT and PCT. Action naming improved for Speakers 1 and 3, but not for Speaker 2. These findings indicate that PCT and SCT may have utility in facilitating action naming for some speakers with aphasia but that the effects of these treatments may vary across grammatical form classes (e.g., nouns versus verbs). C1 Salt Lake City Healthcare Syst, Dept Vet Affairs, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. VA Salt Lake City Healthcare Syst, Salt Lake City, UT USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Wambaugh, JL (reprint author), Dept Vet Affairs Med Ctr, 151 A Bldg 2,500 Foothill Blvd, Salt Lake City, UT 84148 USA. NR 22 TC 29 Z9 29 U1 0 U2 4 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 JUL-AUG PY 2002 VL 39 IS 4 BP 455 EP 466 PG 12 WC Rehabilitation SC Rehabilitation GA 612AL UT WOS:000179051000004 PM 17638143 ER PT J AU Connor, NP Conforti, ML Heisey, DM Vanderby, R Kunz, D Hartig, GK AF Connor, NP Conforti, ML Heisey, DM Vanderby, R Kunz, D Hartig, GK TI Augmented blood removal after medicinal leech feeding in congested tissue flaps SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE heparin; leech; mechanical device; microsurgery; reconstruction; venous congestion ID RELIEVE VENOUS CONGESTION; MECHANICAL LEECH; REPLANTATION; THERAPY AB Reconstructive microsurgery is performed to reattach, transfer, or transplant body tissues. Venous congestion is a complication that threatens the viability of the affected tissue and is often treated with medicinal leeches. Leech therapy has two phases: active bloodletting and passive bleeding from the leech wound after detachment, which can last for several hours. Unfortunately, the small blood volumes removed by medicinal leeches are generally ineffective in decongesting tissue. Our goal was to develop a device to augment blood removal during the passive-bleeding phase of leech therapy with the use of a porcine model of venous congestion. Results indicated that the use of the device resulted in significant increases in blood retrieval relative to reports of passive bleeding alone (141%, 156%, and 155% in 1, 2, and 3 hours, respectively). These results are an encouraging first step toward development of a mechanical device that completely replaces the use of medicinal leeches in modem medicine. C1 Univ Wisconsin, Ctr Clin Sci, Dept Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Hartig, GK (reprint author), Univ Wisconsin, Ctr Clin Sci, Dept Surg, 600 Highland Ave, Madison, WI 53792 USA. NR 27 TC 8 Z9 8 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2002 VL 39 IS 4 BP 505 EP 511 PG 7 WC Rehabilitation SC Rehabilitation GA 612AL UT WOS:000179051000008 PM 17638147 ER PT J AU Garber, SL Bunzel, R Monga, TN AF Garber, SL Bunzel, R Monga, TN TI Wheelchair utilization and satisfaction following cerebral vascular accident SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE follow-up; stroke; wheelchairs ID QUALITY-OF-LIFE; MINI-MENTAL-STATE; ASSISTIVE DEVICES; STROKE SURVIVORS; REHABILITATION; DEPRESSION; SCALE; PAIN AB The purpose of this cross-sectional descriptive study was to determine the extent to which wheelchairs prescribed during rehabilitation are used and perceived as satisfactorily meeting individual mobility, functional, psychological and social needs of veterans who have had a stroke. Forty-nine veterans were interviewed during a one-time visit to the Veterans Affairs Medical Center. Questionnaires on demographics, medical status, functional independence, cognition, social integration, depression, health status and well-being, and wheelchair use and satisfaction were administered. Fifteen participants (31%) no longer used their wheelchairs. Primary reasons included improved physical function (93%) and use of alternative mobility aids (87%). Use by continued wheelchair users ranged from less than 1 hour each day (29%) to more than 8 hours each day (3%). Participants who retained use of the wheelchair were satisfied with its performance. Continued use was associated with impaired mobility, physical dysfunction, and physical dependence. Participants who no longer used their wheelchairs had used them an average of 13 weeks. Medical and psychosocial problems unrelated to wheelchair use were common. Almost 45% of the participants had impaired socialization, 80% had severely compromised occupations, and 41 percent displayed mild to severe depression. Although wheelchair use declined for 31% of the participants, primarily as a result of improved physical function, it is evident that a number of wheelchairs were issued at great expense that were no longer needed. This finding, as well as the reporting of problems unrelated to wheelchair use, suggests the need for reevaluation of mobility and psychosocial needs during the years following rehabilitation for a stroke. C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Ctr Excellence Healthy Aging Disabil, Phys Med & Rehabil Serv,Dept VA Rehabil Res & Dev, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Garber, SL (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Ctr Excellence Healthy Aging Disabil, Phys Med & Rehabil Serv,Dept VA Rehabil Res & Dev, 580-128,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 53 TC 24 Z9 24 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 JUL-AUG PY 2002 VL 39 IS 4 BP 521 EP 533 PG 13 WC Rehabilitation SC Rehabilitation GA 612AL UT WOS:000179051000010 PM 17638149 ER PT J AU Robbins, J Langmore, S Hind, JA Erlichman, M AF Robbins, J Langmore, S Hind, JA Erlichman, M TI Dysphagia research in the 21st century and beyond: Proceedings from Dysphagia Experts Meeting, August 21, 2001 SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE clinical trials; deglutition disorder; group meetings; therapeutics ID PREDICTORS; PRESSURE AB Swallowing problems (dysphagia) can occur at any age but are most prevalent in elderly individuals and are a growing healthcare concern as the geriatric population expands. Without effective diagnosis and treatment, dysphagia may lead to serious medical conditions such as pneumonia, dehydration, and malnutrition. Experts in the field of dysphagia met on August 21, 2001, in Rockville, Maryland, to respond to this heightened healthcare need and to deter-mine the course of dysphagia research. Presentations at the meeting included epidemiological data, geriatric-specific issues, diagnostic techniques, risk factors for pneumonia, and recent relevant trials. The experts identified outstanding issues in dysphagia research, such as study design, population selection, and the standardization of diagnostic and treatment protocols. They designed a clinical trial that represents what they deem is one of the greatest needs in dysphagia research, providing a critical springboard for research endeavors with far-reaching implications. C1 William S Middleton Mem Vet Adm Med Ctr, CRECC, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. AHRQ, Rockville, MD USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, CRECC, 2500 Overlook Terrace,11G, Madison, WI 53705 USA. FU NIDCD NIH HHS [U01 DC0326]; NINDS NIH HHS [R01 NS24427] NR 13 TC 28 Z9 28 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2002 VL 39 IS 4 BP 543 EP 547 PG 5 WC Rehabilitation SC Rehabilitation GA 612AL UT WOS:000179051000012 PM 17638151 ER PT J AU Hung, AM Chertow, GM Young, BS Carey, S Johansen, KL AF Hung, AM Chertow, GM Young, BS Carey, S Johansen, KL TI Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis SO JOURNAL OF RENAL NUTRITION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Nephrol ID CHRONIC-RENAL-FAILURE; C-REACTIVE PROTEIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; RECOMBINANT-HUMAN-ERYTHROPOIETIN; AMBULATORY PERITONEAL-DIALYSIS; ALL-CAUSE MORTALITY; MAINTENANCE DIALYSIS; ENERGY-EXPENDITURE; NUTRITIONAL-STATUS; PLASMA-FIBRINOGEN AB Objective: To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients. Design: Cross-sectional analysis of cohort study. Setting: University-affiliated dialysis units, general clinical research center. Subjects: Multiethnic cohort of maintenance hemodialysis patients. Main Outcome Measures: Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile. Results: Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-a was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function. Conclusion: Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population. (C) 2002 by the National Kidney Foundation, Inc. C1 San Francisco VA Med Ctr, Div Nephrol 111J, San Francisco, CA 94121 USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94120 USA. RP Hung, AM (reprint author), San Francisco VA Med Ctr, Div Nephrol 111J, 4150 Clement St, San Francisco, CA 94121 USA. FU NCRR NIH HHS [RR-00083] NR 56 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD JUL PY 2002 VL 12 IS 3 BP 170 EP 176 DI 10.1053/jren.2002.33513 PG 7 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 570UM UT WOS:000176676800005 PM 12105814 ER PT J AU Gill, TJ McIrvin, E Kocher, MS Homa, K Mair, SD Hawkins, RJ AF Gill, TJ McIrvin, E Kocher, MS Homa, K Mair, SD Hawkins, RJ TI The relative importance of acromial morphology and age with respect to rotator cuff pathology SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SHOULDERS; TEARS AB The purpose of this study was to examine the relationship between patient age, acromial morphology, and rotator cuff pathology. Data on 523 patients who hod arthroscopic and/or open shoulder surgery were reviewed. Acromial morphology was classified by the system of Bigliani. All patients were categorized by postoperative diagnosis as having tendinitis of the rotator cuff, partial rotator cuff tear, complete rotator cuff tear, and non-rotator cuff-related pathology. Univariate analysis results for acromial morphology (P < .001), age (P < .001), and gender (P = .019) showed a significant association with rotator cuff pathology. Fifty percent of patients with rotator cuff tendinitis hod type I acromions, and 58% of patients with full-thickness rotator cuff tears hod type III acromions. Stratified univariate analysis revealed no significant association between acromial morphology and rotator cuff pathology in patients who were over 50 years old. Patients with full-thickness rotator cuff tears were significantly older than those with partial-thickness tears or tendinitis. A larger proportion of male patients than female patients had full-thickness rotator cuff tears. Multivariable logistic regression analysis identified acromial morphology, age, and gender as independent multivariate predictors of rotator cuff pathology. Age, acromial morphology, and gender all have an independent association with rotator cuff pathology. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Steadman Hawkins Sports Med Fdn, Vail, CO USA. Univ Kentucky, Lexington, KY USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, WACC 508,15 Parkman St, Boston, MA 02114 USA. NR 15 TC 32 Z9 34 U1 0 U2 3 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 JUL-AUG PY 2002 VL 11 IS 4 BP 327 EP 330 DI 10.1067/mse.2002.124425 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 589JN UT WOS:000177755300006 PM 12195249 ER PT J AU Davis, TM Carpenter, KM Malte, CA Carney, M Chambers, S Saxon, AJ AF Davis, TM Carpenter, KM Malte, CA Carney, M Chambers, S Saxon, AJ TI Women in addictions treatment: comparing VA and community samples SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE women; addictions treatment; gender-specific treatment; veterans; psychosocial issues ID DRUG-ABUSE TREATMENT; GENDER DIFFERENCES; SUBSTANCE-ABUSE; ALCOHOLISM-TREATMENT; TREATMENT RETENTION; GENERAL-POPULATION; SEX-DIFFERENCES; MEN; SERVICES; PREDICTORS AB Despite increasing awareness of gender issues in substance use treatment, women with substance use disorders (SUD) and gender-specific treatment remain understudied. This study examines differences, including identification of comorbid issues and patients' perceived treatment needs, between women in different SUD treatment settings: an intensive VA outpatient program (VA; N = 76) and a private residential/ outpatient program (Residence XII; N = 308). In both settings the Addiction Severity Index (ASI) was administered at intake; ASI data were collected from retrospective chart review. Results support previous findings that women entering SUD treatment endorse high rates of psychiatric and medical comorbidity, and past abuse. Women in VA SUD treatment experienced more impairment on indices of medical, psychiatric, and employment issues whereas the private agency sample had higher alcohol and family/social composite scores. The differences between and similarities among the two treatment groups have implications for design of women-specific SUD treatment programs. (C) 2002 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst Excellence Subst Ab, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98105 USA. Residence XII Chem Dependency Treatment Women, Kirkland, WA 98034 USA. RP Davis, TM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div S116ATC, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 40 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD JUL PY 2002 VL 23 IS 1 BP 41 EP 48 AR PII S0740-5472(02)00242-8 DI 10.1016/S0740-5472(02)00242-8 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 581JV UT WOS:000177289500005 PM 12127467 ER PT J AU Field, AE Austin, SB Frazier, AL Gillman, MW Camargo, CA Colditz, GA AF Field, AE Austin, SB Frazier, AL Gillman, MW Camargo, CA Colditz, GA TI Smoking, getting drunk, and engaging in bulimic behaviors: In which order are the behaviors adopted? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adolescents; smoking; bulimic behaviors; alcohol ID BODY-MASS INDEX; AGE-OF-ONSET; ADOLESCENT GIRLS; YOUNG ADOLESCENTS; WEIGHT CONCERNS; PROTECTIVE FACTORS; SCHOOL-STUDENTS; RISK BEHAVIORS; ALCOHOL-USE; INITIATION AB Objective: To assess the relation between beginning to binge-eat or purge, beginning to smoke, and getting drunk for the first time. Method: Prospective study of 11,358 girls and boys, 10 to 15 years of age, in an ongoing cohort study who completed questionnaires in 1997 and 1998. The outcome measures were beginning to engage in bulimic behaviors, beginning to smoke, and getting drunk for the first time between 1997 and 1998. Results: During 1 year, 4.3% of girls and 3.6% of boys started smoking, 5.3% of girls and 4.8% of boys started getting drunk, and 2.4% of girls and 0.6% of boys started engaging in bulimic behaviors. Among the girls, weight concerns in 1997 were predictive of beginning to smoke (odds ratio [OR] = 2.2), get drunk (OR = 1.7), purge (OR = 3.8), and binge-eat (OR = 2.6). Adolescents who reported smoking in 1997 were more likely than nonsmokers to get drunk for the first time (girls: OR = 5.7: boys: OR = 7.1). The reverse association, getting drunk as a predictor of starting to smoke, was of lesser magnitude (OR = 2.3-2.6). Conclusions: The three unhealthy behaviors were associated prospectively with each other. The results suggest that prevention efforts should target weight concerns and multiple risk behaviors. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Pilgrim Hlth Care, Cambridge, MA 02138 USA. RP Field, AE (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385-09]; NIDDK NIH HHS [DK 46200, DK-46834] NR 33 TC 37 Z9 38 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2002 VL 41 IS 7 AR UNSP 0890-8567/02/4107-0846 DI 10.1097/00004583-200207000-00018 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 566JQ UT WOS:000176424500017 PM 12108810 ER PT J AU Kratochvil, CJ Heiligenstein, JH Dittmann, R Spencer, TJ Biederman, J Wernicke, J Newcorn, JH Casat, C Milton, D Michelson, D AF Kratochvil, CJ Heiligenstein, JH Dittmann, R Spencer, TJ Biederman, J Wernicke, J Newcorn, JH Casat, C Milton, D Michelson, D TI Atomoxetine and methylphenidate treatment in children with ADHD: A prospective, randomized, open-label trial SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; methylphenidate; atomoxetine; nonstimulants; children ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CRITERION VALIDITY; HYPERACTIVITY; RELIABILITY AB Objective: To assess the comparability of atomoxetine, a new therapy for attention-deficit/hyperactivity disorder (ADHD) and methylpheniclate. (Atomoxetine was originally called tomoxetine. The name was recently changed in order to avoid any potential confusion with tamoxifen that might lead to errors in dispensing drug.) Method: Children with ADHD were randomized to open-label atomoxetine or methylpheniclate for 10 weeks. Response was assessed with the ADHD-IV Rating Scale. Results: Two hundred twenty-eight patients were randomized (atomoxetine n = 184, methylphenidate n = 44). Both drugs were associated with marked improvement in inattentive and hyperactive-impulsive symptom clusters as assessed by parents and investigators. No statistically significant differences between treatment groups were observed on the primary outcome measure (investigator-rated ADHD-IV Rating Scale total score: atomoxetine baseline: 39.4 [8.5], endpoint: 20.0 [13.9]: methylphenidate baseline: 37.6 [9.7], endpoint: 19.8 (16.6); p =.66). Safety and tolerability were also similar between the 2 drugs. Discontinuations due to adverse events were 10/184 (5.4%) for atomoxetine and 5/44 (11.4%) for methylpheniclate; p =.175. Conclusion: These data provide preliminary evidence that atomoxetine is associated with therapeutic effects comparable to those of methylphenidate. C1 Univ Nebraska, Med Ctr, Lincoln, NE 68583 USA. Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Carolinas Med Ctr, Charlotte, NC 28232 USA. Lilly Res Labs, Indianapolis, IN USA. RP Michelson, D (reprint author), Lilly Corp Ctr, DC 6026, Indianapolis, IN 46285 USA. OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 20 TC 171 Z9 180 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2002 VL 41 IS 7 AR UNSP 0890-8567/02/4107-0776 DI 10.1097/00004583-200207000-00008 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 566JQ UT WOS:000176424500008 PM 12108801 ER PT J AU Richardson, SK Tannous, ZS Mihm, MC AF Richardson, SK Tannous, ZS Mihm, MC TI Congenital and infantile melanoma: Review of the literature and report of an uncommon variant, pigment-synthesizing melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID MALIGNANT-MELANOMA; NEUROCUTANEOUS MELANOSIS; NEVOCELLULAR NEVI; MELANOCYTIC NEVI; CHILDREN; CHILDHOOD; RISK; ADOLESCENTS; AGE AB Congenital and infantile types of melanoma are uncommon conditions for which there are limited epidemiologic data. The number of reported cases is small with several ascribed etiologies. We review the literature and report the first documented case, to our knowledge, of pigment-synthesizing melanoma in an infant. Reported cases of congenital and infantile melanoma were identified and categorized on the basis of disease origin. Dermatopathologic specimens from an infant given a diagnosis of pigment-synthesizing melanoma are described. Disease arising from medium and large/giant congenital nevi was most common, whereas reports of de novo and transplacental disease were infrequent. Death of approximately 40% of patients was noted within 18 months of diagnosis. Male infants accounted for approximately 74% of cases. The most commonly affected anatomic sites were the head and neck. The prognosis for congenital and infantile melanoma is poor. The high incidence of head-and-neck involvement and male predominance for disease suggest dispositions for both anatomic disease localization and sex. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit, Boston, MA USA. RP Mihm, MC (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, 55 Fruit St,Warren 827, Boston, MA 02114 USA. NR 69 TC 52 Z9 54 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 JUL PY 2002 VL 47 IS 1 BP 77 EP 90 DI 10.1067/mjd.2002.120602 PG 14 WC Dermatology SC Dermatology GA 568TR UT WOS:000176560400012 PM 12077586 ER PT J AU Norman, DC AF Norman, DC TI Management of antibiotic-resistant bacteria SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE older; bacterial resistance; long-term care; pneumonia ID TERM-CARE FACILITY; STAPHYLOCOCCUS-AUREUS; NURSING-HOME; INFECTION; APPROPRIATENESS; COLONIZATION AB Optimizing the management of antibiotic resistance is an important strategy in improving outcomes for infectious diseases in older persons. Strategies that manage antibiotic resistance must take into account all clinical settings, because resistant pathogens previously seen only in acute care facilities are becoming increasingly common in long-term care facilities. Recently, modest improvement in therapeutic options for the treatment of infections due to resistant pathogens has become available because of the development of newer antibiotics. Some of these drugs are briefly discussed in this review, but the best strategy is to limit the potential for the development of resistance and transmission of these pathogens. This can best be accomplished by minimizing misuse of antibiotics and maximizing adherence to basic hygiene standards. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Norman, DC (reprint author), VA Greater Los Angeles Healthcare Syst, 11201 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2002 VL 50 IS 7 SU S BP S242 EP S246 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 572BY UT WOS:000176754600005 PM 12121520 ER PT J AU Belkin, GS AF Belkin, GS TI Bioethics in social context. SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Belkin, GS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JUL PY 2002 VL 57 IS 3 BP 373 EP 375 DI 10.1093/jhmas/57.3.373 PG 3 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 583LA UT WOS:000177408300021 ER PT J AU Esterman, M McGlinchey-Berroth, R Alexander, MP Milberg, W AF Esterman, M McGlinchey-Berroth, R Alexander, MP Milberg, W TI Triangular backgrounds shift line bisection performance in hemispatial neglect: The critical point SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE hemispatial neglect; line bisection; geometric illusions; perception ID VISUOSPATIAL NEGLECT; VISUAL NEGLECT; ATTENTION AB Isosceles triangular backgrounds influence line bisection performance in normal control participants and patients with hemispatial neglect. When the triangles are oriented asymmetrically with the vertex in 1 visual field, and the base in the other, the perceived midpoint of horizontal lines within the triangle is shifted towards the base, and away from the vertex. The current study examines this illusion further by systematically varying the extent of the triangle presented. With only fragments of the triangle in the background of the line, the vertex is the critical component driving the illusory shift in perceived midpoint, Patients with neglect and controls are equally sensitive to the illusion. Similar geometric illusions that are also intact in neglect, along with these results, suggest that preattentive, implicit visual processing is preserved in neglect and drives these illusions. C1 VA Boston Healthcare Syst, GRECC, Geriatr Neuropsychol Lab, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02118 USA. RP McGlinchey-Berroth, R (reprint author), VA Boston Healthcare Syst, GRECC JP182, 150 S Hunting Ave, Boston, MA 02130 USA. RI McGlinchey, Regina/R-1971-2016 FU NINDS NIH HHS [NS29342] NR 20 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JUL PY 2002 VL 8 IS 5 BP 721 EP 726 DI 10.1017/S1355617702801369 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 578FA UT WOS:000177105700010 PM 12164680 ER PT J AU Soloria, MR Asch, SM Globe, D Cunningham, WE AF Soloria, MR Asch, SM Globe, D Cunningham, WE TI The association of access to medical care with regular source of care and sociodemographic characteristics in patients with HIV and tuberculosis SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE HIV; TB; access to care ID QUALITY-OF-LIFE; VULNERABLE POPULATIONS; SERVICES; HOSPITALIZATIONS; COMMUNITY; OUTCOMES; DISEASE; LATINOS AB Purpose: To examine satisfaction with access to health care in two populations, one with HIV and one with TB, and examine the effect of having a regular doctor and sociodemographic characteristics. Design: Cross-Sectional survey. Patients: A sample of HIV inpatients hospitalized at seven Los Angeles sites (N = 217) and TB outpatients chosen randomly from the Los Angeles County TB Registry Census (N = 313). Analysis: We performed bivariate and multivariate regression analyses of satisfaction with access to care on gender, race/ethnicity, age, education, income, insurance, and having a regular doctor. Main Outcome Measures: A six-item scale of satisfaction with access to care (range 0-100; Cronbach's alpha 0.87), Results: The mean satisfaction with access score for the HIV sample was significantly lower than the TB sample (53.5 vs. 61.2, p<0.001). The HIV sample multivariate analysis (including all the variables) showed that increasing age (p<0.02) and having a regular doctor (p<0.002) were associated with better access, and that low income (p<0.005) was associated with poor access. In the TB sample analysis, only increasing age was associated with better satisfaction with access to care (p<0.01). Conclusion: HIV patients receiving care in the private sector reported less satisfaction with access to care compared to TB patients receiving care in the public health sector. The traditional factors of socio-economic status and having a regular doctor were associated with satisfaction with access-to-care in the HIV sample but not the TB sample. Our findings suggest that certain characteristics of the TB public health programs may explain these differences and suggests that, perhaps, the existence of a similar public health program for vulnerable low-income populations with HIV would improve their satisfaction with access, as well. C1 Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Gen Insternal Med & Hlth Serv, Los Angeles, CA 90024 USA. RP Soloria, MR (reprint author), Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90024 USA. NR 26 TC 2 Z9 2 U1 1 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUL PY 2002 VL 94 IS 7 BP 581 EP 589 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 573DW UT WOS:000176814900020 PM 12126284 ER PT J AU Levy, JH Goodnough, LT Greilich, PE Parr, GVS Stewart, RW Gratz, I Wahr, J Williams, J Comunale, ME Doblar, D Silvay, G Cohen, M Jahr, JS Vlahakes, GJ AF Levy, JH Goodnough, LT Greilich, PE Parr, GVS Stewart, RW Gratz, I Wahr, J Williams, J Comunale, ME Doblar, D Silvay, G Cohen, M Jahr, JS Vlahakes, GJ TI Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: Results of a randomized, double-blind trial SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID OXYGEN-TRANSPORT; EFFICACY; HEMODILUTION; SUBSTITUTES; CARRIER; SAFETY; MODEL AB Background: Blood loss leading to reduced oxygen-carrying capacity is usually treated with red blood cell transfusions. This study examined the hypothesis that a hemoglobin-based oxygen-carrying solution can serve as an initial alternative to red blood cell transfusion. Methods: In a randomized, double-blind efficacy trial of HBOC-201, a total of 98 patients undergoing cardiac surgery and requiring transfusion were randomly assigned to receive either red blood cell units or HBOC-201 (Hemopure; Biopure Corporation, Cambridge, Mass) for the first three postoperative transfusions. Patients were monitored before and after transfusion, at discharge, and at 3 to 4 weeks after the operation for subsequent red blood cell use, hemodynamics, and clinical laboratory parameters. Results: The use of HBOC-201 eliminated the need for red blood cell transfusions in 34% of cases (95% confidence interval 21%-49%). Patients in the HBOC group received a mean of 1.72 subsequent units of red blood cells; those who received red blood cells only received a mean of 2.19 subsequent units (P = .05). Hematocrit values were transiently lower in the HBOC group but were similar in the two groups at discharge and follow-up. Oxygen extraction was greater in the HBOC group (P = .05). Mean increases in blood pressure were greater in the HBOC group, but not significantly so. Conclusion: HBOC-201 may be an initial alternative to red blood cell transfusions for patients with moderate anemia after cardiac surgery. In a third of cases, HBOC-201 eliminated the need for red blood cell transfusion, although substantial doses were needed to produce this modest degree of blood conservation. C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Washington Univ, Sch Med, St Louis, MO USA. Dallas Vet Adm Med Ctr, Dallas, TX USA. Morristown Mem Hosp, Morristown, NJ USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Cooper Hosp Univ Med Ctr, Camden, NJ 08103 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Alabama, Birmingham, AL USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA 19102 USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,BUL119, Boston, MA 02114 USA. NR 18 TC 109 Z9 116 U1 2 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2002 VL 124 IS 1 BP 35 EP 42 DI 10.1067/mtc.2002.121505 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 573AY UT WOS:000176808200008 PM 12091806 ER PT J AU Fidler, PE Mackool, BT Schoenfeld, DA Malloy, M Schulz, JT Sheridan, RL Ryan, CM AF Fidler, PE Mackool, BT Schoenfeld, DA Malloy, M Schulz, JT Sheridan, RL Ryan, CM TI Incidence, outcome, and long-term consequences of herpes simplex virus type 1 reactivation presenting as a facial rash in intubated adult burn patients treated with acyclovir SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Burn-Association CY APR 18-21, 2001 CL BOSTON, MASSACHUSETTS SP Amer Burn Assoc DE burn injury; herpes; viral infection; outcome; rash ID RENAL-FAILURE; INFECTIONS; MORTALITY AB Background: Increased mortality, extensive visceral involvement, and necrotizing tracheobronchitis associated with herpes viruses have been reported after burns. It is unclear whether herpes presenting as a facial rash results in outcome changes after burns. Methods: A retrospective study characterizing the incidence, presentation, and outcome of 14 patients with facial herpes rashes out of 95 severely burned intubated adults was performed. Results: Facial rashes attributed to herpetic infections were found in at least 15% of patients. The problem was recognized during the second week after burn. There was no difference in mortality or length of stay noted between patients with or without the infection. Conclusion: The course of this infection was relatively benign in this group of acyclovir-treated patients. Even so, the lesions clearly contributed to patient discomfort and often produced fevers requiring costly investigations. Early recognition could help prevent diffuse spread of the lesions, decreasing patient discomfort and improving patient care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA USA. RP Ryan, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Bigelow 1302, Boston, MA 02114 USA. NR 19 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUL PY 2002 VL 53 IS 1 BP 86 EP 89 DI 10.1097/00005373-200207000-00017 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 573BR UT WOS:000176809900023 PM 12131395 ER PT J AU Freedland, SJ Wieder, JA Jack, GS Dorey, F deKernion, JB Aronson, WJ AF Freedland, SJ Wieder, JA Jack, GS Dorey, F deKernion, JB Aronson, WJ TI Improved risk stratification for biochemical recurrence after radical prostatectomy using a novel risk group system based on prostate specific antigen density and biopsy Gleason score SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostate-specific antigen; prostatectomy; prostatic neoplasms; risk ID INDEPENDENT PREDICTOR; PROGNOSTIC INDICATOR; CANCER; CARCINOMA; RADIOTHERAPY; SPECIMENS; THERAPY; RACE AB Purpose: Previous studies have suggested that prostate specific antigen (PSA) density is a significant independent predictor of biochemical failure after primary therapy. We determined whether pathological PSA density using surgical weight of the radical prostatectomy specimen was an independent predictor of adverse pathological features or biochemical recurrence after radical prostatectomy. We also examined whether combining pathological PSA density with biopsy Gleason score improved risk stratification compared with serum PSA and biopsy Gleason score for predicting PSA recurrence after prostatectomy. Materials and Methods: Multivariate analysis was used to determine whether pathological PSA density was an independent predictor of adverse pathology or PSA recurrence after radical prostatectomy in 325 patients treated at a Veterans Affairs medical center. Cutoff points of pathological PSA density were generated to identify patients at various risks for biochemical recurrence. These cutoffs were combined with biopsy Gleason cutoff points 2 to 6, 7 and 8 to 10 to generate a risk stratification system that was compared with a previous risk stratification system using PSA and biopsy Gleason score cutoff points. The validity of the risk stratification system using pathological PSA density and biopsy Gleason score was evaluated in another cohort of 490 patients treated with radical prostatectomy at a tertiary care medical center. Results: Pathological PS A density was an independent predictor of positive surgical margins (p < 0.001), nonorgan confined disease (p < 0.001), seminal vesicle invasion (p = 0.003) and biochemical recurrence after radical prostatectomy (p < 0.001). The cutoff points for pathological PSA density of less than 0.3, 0.3 to 0.7 and greater than 0.7 ng./ml./gm. separated patients into 3 distinct groups at increasing risk for biochemical failure after radical prostatectomy (p < 0.001). Pathological PSA density cutoffs combined with biopsy Gleason score cutoffs 2 to 6, 7 and 8 to 10 provided better risk stratification for biochemical failure than cutoffs based on a combination of PSA and biopsy Gleason score in patients treated at the Veterans Affairs (hazards ratio 3.04, confidence interval 2.25 to 4.11, p < 0.001) and tertiary care (hazards ratio 2.38, confidence interval 1.78 to 3.18, p < 0.001) medical centers. Conclusions: Pathological PSA density was a strong predictor of advanced pathology and biochemical failure after radical prostatectomy. Pathological PSA density combined with biopsy Gleason score defined a novel risk group system that improved risk stratification compared with a combination of PSA and biopsy Gleason score. These results were validated in another cohort of patients treated with radical prostatectomy at a tertiary care medical center. Further studies are required using PSA density values calculated from preoperative transrectal ultrasound measurements to determine whether a combination of PSA density and biopsy Gleason score provides significant pretreatment risk stratification. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. NR 19 TC 24 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 110 EP 115 AR UNSP 0022-5347/02/1681-0110/0 DI 10.1016/S0022-5347(05)64841-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600023 PM 12050502 ER PT J AU Bubolz, T Wasson, JH Lu-Yao, G Barry, MJ AF Bubolz, T Wasson, JH Lu-Yao, G Barry, MJ TI Treatments for prostate cancer in older men: 1984-1997 SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Healthstat, Princeton, NJ USA. Dartmouth Coll Sch Med, Hanover, NH 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 375 EP 376 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600114 ER PT J AU Penson, DF Albertsen, PC Nelson, PS Barry, M Stanford, JL AF Penson, DF Albertsen, PC Nelson, PS Barry, M Stanford, JL TI Determining cause of death in prostate cancer: Are death certificates valid? SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Univ Washington, Sch Med, US Dept Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 375 EP 375 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600113 ER PT J AU Smith, MR Finkelstein, JS McGovern, FJ Zietman, AL Fallon, MA Schoenfeld, DA Kantoff, PW AF Smith, MR Finkelstein, JS McGovern, FJ Zietman, AL Fallon, MA Schoenfeld, DA Kantoff, PW TI Changes in body composition during androgen deprivation therapy for prostate cancer SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 378 EP 379 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600119 ER PT J AU Porteus, MH Narkool, P Neuberg, D Guthrie, K Breslow, N Green, DM Diller, L AF Porteus, MH Narkool, P Neuberg, D Guthrie, K Breslow, N Green, DM Diller, L TI Characteristics and outcome of children with Beckwith-Wiedemann syndrome and Wilms' tumor: A report from the National Wilms Tumor Study Group SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Natl Wilms Tumor Study Grp, Seattle, WA 98195 USA. Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 382 EP 383 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600126 ER PT J AU Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS AF Collins, MM Pontari, MA O'Leary, MP Calhoun, EA Santanna, J Landis, JR Kusek, JW Litwin, MS CA Chronic Prostatis Collaborative TI Quality of life is impaired in men with chronic prostatitis. The chronic prostatitis collaborative research network SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Med Serv,Gen Med Unit, Boston, MA USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Northwestern Univ, Sch Med, Inst Hlth Serv & Hlth Policy Studies, Chicago, IL USA. NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RI Landis, J. Richard/A-9330-2010 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 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 395 EP 396 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600147 ER PT J AU Boppart, SA Herrmann, JM Pitris, C Stamper, DL Brezinski, ME Fujimoto, JG AF Boppart, SA Herrmann, JM Pitris, C Stamper, DL Brezinski, ME Fujimoto, JG TI Real-time optical coherence tomography for minimally invasive imaging of prostate ablation SO JOURNAL OF UROLOGY LA English DT Meeting Abstract C1 MIT, Dept Elect Engn & Comp Sci, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kings Coll, Dept Biol, Wilkes Barre, PA USA. RI Boppart, Stephen/C-7338-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2002 VL 168 IS 1 BP 401 EP 401 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 562LQ UT WOS:000176198600156 ER PT J AU Ahmed, M Lobo, SM Weinstein, J Kruskal, JB Gazelle, GS Halpern, EF Afzal, SK Lenkinski, RE Goldberg, SN AF Ahmed, M Lobo, SM Weinstein, J Kruskal, JB Gazelle, GS Halpern, EF Afzal, SK Lenkinski, RE Goldberg, SN TI Improved coagulation with saline solution pretreatment during radiofrequency tumor ablation in a canine model SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE neoplasms, therapy; radiofrequency (RF) ablation ID TISSUE ABLATION; THERMAL ABLATION; HEPATOCELLULAR-CARCINOMA; HEPATIC METASTASES; PORCINE LIVER; LESION SIZE; BLOOD-FLOW; IN-VITRO; EX-VIVO; ELECTRODE AB PURPOSE: To determine whether pretreatment with local NaCl injection can increase radiofrequency (RF)-induced coagulation in a large animal model. MATERIAL AND METHODS: Multiple canine venereal sarcomas (n = 25) were implanted subcutaneously in eight mildly immunosuppressed dogs (25 mg/kg cyclosporin A twice daily). Tumors were incubated for 8-12 weeks to a diameter of 4.2-6.3 cm (5.1 cm +/- 0.7). Internally cooled RF ablation (1-cm tip; 12 min; pulsed technique; 2,000-mA maximum) was performed. Tumors were pretreated with 6 mL of 18%, 24%, or 36% NaCl injected intratumorally under direct ultrasound guidance after RF electrode insertion, and this treatment was compared to RF treatment without NaCl injection and to 36% NaCl injection without RF ablation. Impedance measurements and remote thermometry were performed. These measurements and resultant coagulation were compared. RESULTS: Significantly greater RF heating (73degreesC +/- 11degreesC at 20 mm) was observed when the tumors were treated with 24% or 36% NaCl pretreatment, compared to the 47degreesC +/- 5degreesC observed when 18% or no NaCl was injected (P < .02). In the 36% NaCl group, the entire tumor (5.2 cm +/- 0.8 diameter) was completely ablated in every case, with coagulation extending several centimeters into the surrounding tissues. By comparison, control tumors (without NaCl injection) contained coagulation measuring 3.1 cm +/- 0.2, surrounded by viable, well-perfused tumor (P < .01), and 36% NaCl alone produced 2.7 cm +/- 0.6 of patchy necrosis. CONCLUSIONS: Pretreatment with intratumoral injection of small volumes of highly concentrated NaCl markedly increases RF heating and coagulation in a large animal tumor model. The complete destruction of tumors 5 cm in diameter or larger suggests that this substantial increase may be achieved for tumor ablation in clinical practice. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu RI Lenkinski, Robert/F-9045-2014; OI Lenkinski, Robert/0000-0001-7371-5048 FU NCI NIH HHS [R01-CA87992-01A1] NR 43 TC 62 Z9 66 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2002 VL 13 IS 7 BP 717 EP 724 DI 10.1016/S1051-0443(07)61850-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 580HG UT WOS:000177228700009 PM 12119331 ER PT J AU Chiba, S Un-No, M Neer, RM Okada, K Segre, GV Lee, K AF Chiba, S Un-No, M Neer, RM Okada, K Segre, GV Lee, K TI Parathyroid hormone induces interleukin-6 gene expression in bone stromal cells of young rats SO JOURNAL OF VETERINARY MEDICAL SCIENCE LA English DT Article DE interleukin-6; parathyroid hormone; stromal cell ID LEUKEMIA INHIBITORY FACTOR; IN-VIVO; OSTEOBLASTS; RESORPTION; LOCALIZATION; STIMULATION; OSTEOCLASTS; RECEPTOR AB To test the hypothesis that parathyroid hormone (PTH) regulates interleukin-6 (IL-6) expression locally in bone, the expression of IL-6 mRNA was examined by in situ hybridization after a subcutaneous injection of human PTH [1-84] (225 mug/kg) in 4-week old rats. Whereas IL-6 mRNA was not detected at the basal status, it was transiently detected in a subpopulation of stromal cells in the intertrabecular region of the metaphyses from 1/2 to 1 hr after PTH injection. Contrastingly, IL-6 transcripts were not detected in other cell populations at any time points examined. Since IL-6 is a known activator of osteoclasts, these results are consistent with the hypothesis that PTH stimulates the local IL-6 synthesis in stromal cells to indirectly activate osteoclasts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Iwate Univ, Fac Agr, Dept Vet Pathol, Morioka, Iwate 0208550, Japan. Chugai Pharmaceut Co Ltd, Safety Assessment Lab, Shizuoka 4128513, Japan. RP Chiba, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Fruit St, Boston, MA 02114 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU JAPAN SOC VET SCI PI TOKYO PA UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 103, JAPAN SN 0916-7250 J9 J VET MED SCI JI J. Vet. Med. Sci. PD JUL PY 2002 VL 64 IS 7 BP 641 EP 644 DI 10.1292/jvms.64.641 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 579HE UT WOS:000177171900019 PM 12185323 ER PT J AU Dorfman, T Popova, E Pizzato, M Gottlinger, HG AF Dorfman, T Popova, E Pizzato, M Gottlinger, HG TI Nef enhances human immunodeficiency virus type 1 infectivity in the absence of matrix SO JOURNAL OF VIROLOGY LA English DT Article ID CD4 DOWN-REGULATION; CELLULAR SERINE KINASE; PROVIRAL DNA-SYNTHESIS; HIV-1 NEF; VIRAL INFECTIVITY; ENVELOPE GLYCOPROTEINS; LYMPHOCYTE-ACTIVATION; VIRION INCORPORATION; T-LYMPHOCYTES; SURFACE CD4 AB Nef enhances the serine phosphorylation of the human immunodeficiency virus type 1 matrix (MA) protein, which suggests that MA may be a functional target of Nef. Using mutants that remain infectious despite the absence of most or all of MA, we show in the present study that the ability of Nef to enhance virus infectivity is not compromised even if MA is entirely replaced by a heterologous lipid anchor. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 42510, AI 28691, P30 AI028691, R01 AI042510] NR 56 TC 20 Z9 21 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 JUL PY 2002 VL 76 IS 13 BP 6857 EP 6862 DI 10.1128/JVI.76.13.6857-6862.2002 PG 6 WC Virology SC Virology GA 564BF UT WOS:000176293600049 PM 12050401 ER PT J AU Wang, Y Camp, SM Niwano, M Shen, X Bakowska, JC Breakefield, XO Allen, PD AF Wang, Y Camp, SM Niwano, M Shen, X Bakowska, JC Breakefield, XO Allen, PD TI Herpes simplex virus type 1/adeno-associated virus rep(+) hybrid amplicon vector improves the stability of transgene expression in human cells by site-specific integration SO JOURNAL OF VIROLOGY LA English DT Article ID ADENO-ASSOCIATED VIRUS; RECOMBINANT ADENOASSOCIATED VIRUS; PROTEIN-KINASE-C; GENE-TRANSFER; DNA-SEQUENCES; IN-VIVO; TYROSINE-HYDROXYLASE; TERMINAL REPEATS; RAT-BRAIN; REPLICATION AB Herpes simplex virus type 1 (HSV-1) amplicon vectors are promising gene delivery tools, but their utility in gene therapy has been impeded to some extent by their inability to achieve stable transgene expression. In this study, we examined the possibility of improving transduction stability in cultured human cells via site-specific genomic integration mediated by adeno-associated virus (AAV) Rep and inverted terminal repeats (ITRs). A rep(-) HSV/AAV hybrid amplicon vector was made by inserting a transgene cassette flanked with AAV ITRs into an HSV-1 amplicon backbone, and a rep(+) HSV/AAV hybrid amplicon was made by inserting rep68/78 outside the rep- vector 3' AAV ITR sequence. Both vectors also had a pair of loxP sites flanking the ITRs. The resulting hybrid amplicon vectors were successfully packaged and compared to a standard amplicon vector for stable transduction frequency (STF) in human 293 and Gli36 cell lines and primary myoblasts. The rep+, but not the rep-, hybrid vector improved STF in all three types of cells; 84% of Gli36 and 40% of 293 stable clones transduced by the rep(+) hybrid vector integrated the transgene into the AAVS1 site. Due to the difficulty in expanding primary myoblasts, we did not assess site-specific integration in these cells. A strategy to attempt further improvement of STF by "deconcatenating" the hybrid amplicon DNA via Cre-loxP recombination was tested, but it did not increase STF. These data demonstrate that introducing the integrating elements of AAV into HSV-1 amplicon vectors can significantly improve their ability to achieve stable gene transduction by conferring the AAV-Iike capability of site-specific genomic integration in dividing cells. C1 Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wang, Y (reprint author), Brigham & Womens Hosp, Dept Anesthesia, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-69246, P01 CA069246]; NIAMS NIH HHS [K01AR02148]; NINDS NIH HHS [NS-24279, P01 NS024279] NR 61 TC 43 Z9 45 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 JUL PY 2002 VL 76 IS 14 BP 7150 EP 7162 DI 10.1128/JVI.76.14.7150-7162.2002 PG 13 WC Virology SC Virology GA 567ZH UT WOS:000176517600029 PM 12072515 ER PT J AU Waters, G Caplan, D AF Waters, G Caplan, D TI Working memory and online syntactic processing in Alzheimer's disease: Studies with auditory moving window presentation SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; LANGUAGE COMPREHENSION; AMBIGUITY RESOLUTION; CAPACITY THEORY; AGE; DEPENDENCIES; CONSTRAINTS; DIFFICULTY; COMPLEXITY AB Twenty patients with dementia of the Alzheimer's type (DAT) and 20 controls were tested on six tests of working memory and a test of online auditory sentence comprehension in which listening times for each phrase in the sentence, as well as the time required for an end-of-sentence plausibility judgment, were measured. The sentences differed in syntactic complexity. Patients had lower working memory scores than controls and performed more poorly on the plausibility judgments. However, patients were not more affected than controls by the syntactic complexity of a sentence in these judgments, and both groups showed similar effects of syntactic structure in the listening-time data. The increase in listening times at syntactically capacity-demanding points in complex sentences, compared with comparable points in matched simpler sentences, did not correlate with measures of working memory. The results indicate that early-stage DAT patients are not impaired in their ability to assign syntactic structure and to use it to determine aspects of sentence meaning, despite their reduced working memories. This provides evidence for a specialization within working memory for syntactic processing. C1 Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Waters, G (reprint author), 635 Commonwealth Ave, Boston, MA 02215 USA. FU NIA NIH HHS [AG0096610] NR 55 TC 6 Z9 6 U1 3 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD JUL PY 2002 VL 57 IS 4 BP P298 EP P311 PG 14 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 571JA UT WOS:000176713200002 PM 12084781 ER PT J AU Han, WK Bailly, V Abichandani, R Thadhani, R Bonventre, JV AF Han, WK Bailly, V Abichandani, R Thadhani, R Bonventre, JV TI Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Nephrology CY OCT 10-16, 2000 CL TORONTO, CANADA SP Amer Soc Nephrol DE acute renal failure; acute tubular necrosis; contrast nephropathy; urinary biomarker; ischemia; dialysis; nephrotoxicity ID URINARY-EXCRETION; FAILURE; CELLS; ENZYMES; PATIENT AB Background. Traditional blood and urine markers for the diagnosis of various renal diseases are insensitive and nonspecific. Kidney Injury Molecule-1 (KIM-1) is a type 1 transmembrane protein, with an immunoglobulin and mucin domain, whose expression is markedly up-regulated in the proximal tubule in the post-ischemic rat kidney. The ectodomain of KIM-1 is shed from cells. The current studies were carried out to evaluate whether KIM-1 is present in human acute renal failure and might serve as a urinary marker of acute renal tubular injury. Methods. Kidney tissue samples from six patients with biopsy-proven acute tubular necrosis (ATN) were evaluated by immunohistochemistry for expression of KIM-1. Urine samples were collected from an additional thirty-two patients with various acute and chronic renal diseases, as well as from eight normal controls. Urinary KIM-1 protein was detected by immunoassay and was quantified by ELISA. Results. There was extensive expression of KIM-1 in proximal tubule cells in biopsies from 6 of 6 patients with confirmed ATN. The normalized urinary KIM-1 levels were significantly higher in patients with ischemic ATN (2.92 +/- 0.61 N = 7) compared to levels in patients with other forms of acute renal failure (0.63 +/- 0.17, P < 0.01; N = 16) or chronic renal disease (0.72 +/- 0.37, P < 0.01: N = 9). Adjusted for age, gender, length of time delay between the initial insult and sampling of the urine, a one-unit increase in normalized KIM-1 was associated with a greater than 12-fold (OR 12.4, 95% CI 1.2 to 119) risk for the presence of ATN. Concentrations of other urinary biomarkers, including total protein. gamma-glutamyltransferase, and alkaline phosphatase, did not correlate with clinical diagnostic groupings. Conclusions. A soluble form of human KIM-1 can be detected in the urine of patients with ATN and may serve as a useful biomarker for renal proximal tubule injury facilitating the early diagnosis of the disease and serving as a diagnostic discriminator. C1 Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Massachusetts Gen Hosp,Med Serv,Dept Med, Charlestown, MA USA. Biogen Corp, Cambridge, MA USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, 149 13th St,Suite 4002, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 39773] NR 26 TC 635 Z9 706 U1 11 U2 38 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2002 VL 62 IS 1 BP 237 EP 244 DI 10.1046/j.1523-1755.2002.00433.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 565YG UT WOS:000176397500026 PM 12081583 ER PT J AU Hoffman, WF Essink, B Hansen, TE AF Hoffman, WF Essink, B Hansen, TE TI Use of the clinical laboratory in the diagnosis and treatment of depression SO LABORATORY MEDICINE LA English DT Article ID IMMUNE-INFLAMMATORY MARKERS; MAJOR DEPRESSION; VALPROIC ACID; EXPERIENCE; DISORDERS; BLOOD; THROMBOCYTOPENIA; STRESS; PLASMA; RISK C1 Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. RP Hoffman, WF (reprint author), Portland VA Med Ctr, Div Mental Hlth, Portland, OR 97207 USA. NR 35 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 JUL PY 2002 VL 33 IS 7 BP 511 EP 514 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 565NK UT WOS:000176376200011 ER PT J AU Reardon, EJ AF Reardon, EJ TI Navigational risks associated with sinus surgery and the clinical effects of implementing a navigational system for sinus surgery SO LARYNGOSCOPE LA English DT Review DE computer-aided navigational; endoscopic; sinus surgery; electromagnetic ID ENDOSCOPIC INTRANASAL ETHMOIDECTOMY; FRAMELESS STEREOTAXIC INTEGRATION; IMAGE-GUIDANCE SYSTEMS; COMPUTED-TOMOGRAPHY; CEREBROSPINAL-FLUID; PARANASAL SINUSES; DECISION-MAKING; ADVERSE EVENTS; OPTIC-NERVE; INTRAOPERATIVE LOCALIZATION AB Objective: To evaluate the clinical effects of implementing the use of a navigational system in sinus surgery in a community hospital setting. Study Design: Retrospective record review. Methods: The hospital records of 800 patients who had undergone sinus surgery performed by 7 physicians at one institution over 11 years were reviewed and tabulated. The information was recorded in 2 groups of 400 with those in group A being treated before the availability of an electromagnetic sinus navigational system and those in group B being treated after the unit had been installed. The following data were collected: date, age, gender, informed consent, physician, additional procedures, sinuses entered, use of navigational system, revision status, setup time, operative time, and complications. The results of the two groups were analyzed statistically, and comparisons were made. Results/Conclusions: The patient populations in groups A and B were determined to have similar demographic profiles. Significantly more sinuses, specifically in the frontal location, were entered in group B compared with group A. Adjusted for the number of sinuses treated, the median operative times did not differ significantly between groups. Major and minor complication rates were similar in both groups and were consistent with the published literature. In a community hospital setting, once an electromagnetic guidance system became available, it was used in 92% of the cases performed by several otolaryngologists. Key Words: Computer-aided, navigational, endoscopic, sinus surgery, electromagnetic. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Carney Hosp, Boston, MA USA. RP Reardon, EJ (reprint author), 500 Congress St, Quincy, MA 02169 USA. EM Edward_Reardon@MEEI.Harvard.edu NR 168 TC 38 Z9 39 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUL PY 2002 VL 112 IS 7 SU 99 BP 1 EP 19 PN 2 PG 19 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 583GM UT WOS:000177398900001 PM 12169888 ER PT J AU Rosen, HR Schwartz, JM AF Rosen, HR Schwartz, JM TI Hepatitis C quasispecies and severity of recurrence: Cause, consequence, or coincidence? SO LIVER TRANSPLANTATION LA English DT Editorial Material ID LIVER-TRANSPLANTATION; HYPERVARIABLE REGION-1; SEQUENCE VARIATION; VIRUS-INFECTION; EVOLUTION; VARIANTS; RESPONSES; SERUM; HCV AB Recurrence of hepatitis C virus (HCV) infection after liver transplantation is almost universal and usually leads to chronic hepatitis with different degrees of severity. The pathogenic mechanisms underlying the variable outcome of HCV infection recurrence are not well defined, but recent data suggest that the dynamics of HCV quasispecies may be involved. HCV quasispecies evolution was traced by longitudinal single-strand conformation polymorphism, direct sequencing, and cloning analyses of pretransplant and posttransplant HCV-1b isolates from patients with histologically severe (seven cases) or mild or moderate (nine cases) HCV infection recurrence. Differences between the two groups of patients that concerned the level of viremia or the degree of HCV quasispecies complexity and diversity were not observed at any of the three time points analyzed. However, emergence of nucleotide and amino acid changes during the 12-month follow-up was significantly more frequent in patients with mild or moderate than in those with severe HCV infection recurrence. The ratio of nonsynonymous to synonymous nucleotide substitutions 12 months after transplantation was also greater in the former, suggesting that the HVR1 of HCV is under stronger selective pressure in these subjects. These findings suggest that the degree of amino acid diversification in the HVR1 of HCV, which probably reflects the strength of immune pressure on HCV, is inversely related to the histologic severity of HCV infection recurrence. C1 Oregon Hlth Sci Univ, Gastroenterol & Liver Transplantat Program, Portland VA Med Ctr, Portland, OR 97201 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Gastroenterol & Liver Transplantat Program, Portland VA Med Ctr, Portland, OR 97201 USA. NR 24 TC 3 Z9 3 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 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD JUL PY 2002 VL 8 IS 7 BP 646 EP 648 DI 10.1053/jlts.2002.0080646 PG 3 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 568HA UT WOS:000176535300015 PM 12089722 ER PT J AU Feinberg, DA Reese, TG Wedeen, VJ AF Feinberg, DA Reese, TG Wedeen, VJ TI Simultaneous echo refocusing in EPI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE simultaneous; EPI; SER; echo planar imaging AB A method to encode multiple two-dimensional Fourier transform (2D FT) images within a single echo train is presented. This new method, simultaneous echo refocusing (SER), is a departure from prior echo planar image (EPI) sequences which use repeated single-shot echo trains for multislice imaging. SER simultaneously acquires multiple slices in a single-shot echo train utilizing a shared refocusing process. The SER technique acquires data faster than conventional multislice EPI since it uses fewer gradient switchings and fewer preparation pulses such as diffusion gradients. SER introduces a new capability to simultaneously record multiple spatially separated sources of physiologic information in subsecond image acquisitions, which enables several applications that are dependent on temporal coherence in MRI data including velocity vector field mapping and brain activation mapping. (C) 2002 Wiley-Liss, Inc. C1 Adv MRI Technol LLC, Sebastopol, CA 95472 USA. Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Feinberg, DA (reprint author), Adv MRI Technol LLC, 652 Petaluma Ave,Suite J, Sebastopol, CA 95472 USA. FU NCRR NIH HHS [R01 RR13618]; NHLBI NIH HHS [R01 HL27-01A1] NR 9 TC 51 Z9 51 U1 1 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 JUL PY 2002 VL 48 IS 1 BP 1 EP 5 DI 10.1002/mrm.10227 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 570FU UT WOS:000176648900001 PM 12111925 ER PT J AU Dou, JG Reese, TG Tseng, WYI Wedeen, VJ AF Dou, JG Reese, TG Tseng, WYI Wedeen, VJ TI Cardiac diffusion MRI without motion effects SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; diffusion; myocardium; strain; motion effect; myocardial structure; dynamics ID MAGNETIC-RESONANCE; IN-VIVO; FIBER ARCHITECTURE; WATER DIFFUSION; STRAIN-RATES; MYOCARDIUM; KINEMATICS; HEART; NMR AB We present a method for diffusion tensor MRI in the beating heart that is insensitive to cardiac motion and strain. Using a stimulated echo pulse sequence with two electrocardiogram (ECG) triggers, diffusion-encoding bipolar gradient pulses are applied at identical phases in consecutive cardiac cycles. In this experiment, diffusion is encoded at a single phase in the cardiac cycle of less than 30 ms in duration. This encoding produces no phase shifts for periodic motion and is independent of intervening strains, Studies in a gel phantom with cyclic deformation confirm that by using this sequence we can map the diffusion tensor free of effects of cyclic motion. In normal human subjects, myocardial diffusion eigenvalues measured with the present method showed no significant change between acquisitions encoded at maximum contractile velocity (peak) vs. at myocardial standstill (end-systole), demonstrating motion independence of in vivo diffusion measurements. Diffusion tensor images acquired with the present method agree with registered data acquired with a previous cardiac diffusion MRI method that was shown to be valid in the normal heart, strongly supporting the validity of MRI diffusion measurement in the beating heart. Myocardial sheet and fiber dynamics measured during systole showed that normal human myocardial sheet orientations tilt toward the radial during systole, and fiber orientations tilt toward the longitudinal, in qualitative agreement with previous invasive studies in canines. These results demonstrate the technique's ability to measure myocardial diffusion accurately at any point in the cardiac cycle free of measurable motion effect, as if the heart were frozen at the point of acquisition. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Natl Taiwan Univ, Coll Med, Ctr Optoelect Biomed, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Dept Radiol, Taipei, Taiwan. RP Wedeen, VJ (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St,MS 2301, Charlestown, MA 02129 USA. OI Tseng, Wen-Yih Isaac/0000-0002-2314-6868 FU NHLBI NIH HHS [1R01-HL56737] NR 23 TC 85 Z9 86 U1 0 U2 4 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 JUL PY 2002 VL 48 IS 1 BP 105 EP 114 DI 10.1002/mrm.10188 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 570FU UT WOS:000176648900013 PM 12111937 ER PT J AU Fillit, HM Butler, RN O'Connell, AW Albert, MS Birren, JE Cotman, CW Greenough, WT Gold, PE Kramer, AF Kuller, LH Perls, TT Sahagan, BG Tully, T AF Fillit, HM Butler, RN O'Connell, AW Albert, MS Birren, JE Cotman, CW Greenough, WT Gold, PE Kramer, AF Kuller, LH Perls, TT Sahagan, BG Tully, T TI Achieving and maintaining cognitive vitality with aging SO MAYO CLINIC PROCEEDINGS LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; LONG-TERM-MEMORY; ANDROGEN-BEHAVIOR CORRELATIONS; ESTROGEN REPLACEMENT THERAPY; TRANSGENIC MOUSE MODEL; RAT VISUAL-CORTEX; ALZHEIMERS-DISEASE; RISK-FACTORS; CEREBROSPINAL-FLUID; HIPPOCAMPAL VOLUME AB Cognitive vitality is essential to quality of life and survival in old age. With normal aging, cognitive changes such as slowed speed of processing are common, but there is substantial interindividual, variability, and cognitive decline is clearly not inevitable. In this review, we focus on recent research investigating the association of various lifestyle factors and medical comorbidities with cognitive aging. Most of these factors are potentially modifiable or manageable, and some are protective. For example, animal and human studies suggest that lifelong learning, mental and physical exercise, continuing social engagement, stress reduction, and proper nutrition may be important factors in promoting cognitive vitality in aging. Manageable medical comorbidities, such as diabetes, hypertension, and hyperlipidemia, also contribute to cognitive decline in older persons. Other comorbidities such as smoking and excess alcohol intake may contribute to cognitive decline, and avoiding these activities may promote cognitive vitality in aging. Various therapeutics, including cognitive enhancers and protective agents such as antioxidants and anti-inflammatories, may eventually prove useful as adjuncts for the prevention and treatment of cognitive decline with aging. The data presented in this review should interest physicians who provide preventive care management to middle-aged and older individuals who seek to maintain cognitive vitality with aging. C1 Inst Study Aging Inc, New York, NY 10153 USA. Mt Sinai Med Ctr, Dept Geriatr Med & Neurobiol, New York, NY 10029 USA. Int Longev Ctr, New York, NY USA. Massachusetts Gen Hosp, Dept Psychiat & Neurol, Boston, MA 02114 USA. Univ Calif Los Angeles, Ctr Aging, Los Angeles, CA USA. Univ Calif Irvine, Dept Neurol Biol & Behav, Irvine, CA USA. Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. Univ Illinois, Dept Psychol & Neurosci Program, Urbana, IL 61801 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Boston Med Ctr, Boston, MA USA. Pfizer Inc, Groton, CT 06340 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Fillit, HM (reprint author), Inst Study Aging Inc, 767 5th Ave,Suite 4600, New York, NY 10153 USA. FU NIA NIH HHS [R37 AG025667] NR 237 TC 130 Z9 136 U1 6 U2 27 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 2002 VL 77 IS 7 BP 681 EP 696 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 569YG UT WOS:000176630300012 PM 12108606 ER PT J AU Chapko, MK Borowsky, SJ Fortney, JC Hedeen, AN Hoegle, M Maciejewski, ML Lukas, CV AF Chapko, MK Borowsky, SJ Fortney, JC Hedeen, AN Hoegle, M Maciejewski, ML Lukas, CV TI Evaluation of the Department of Veterans Affairs Community-Based Outpatient Clinics SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of Veterans Affairs Health Services Research and Development CY FEB 23, 2000 CL WASHINGTON, D.C. DE veterans; primary care; community clinics; quality of care; cost; utilization; satisfaction ID CARE AB OBJECTIVE. This paper describes the history of the Department of Veterans Affairs (VA) Community-Based Outpatient Clinics (CBOCs), CBOC Performance Evaluation Project, and characteristics of CBOCs within the VA, and summarizes the findings and implications of the CBOC Performance Evaluation Project. SUBJECTS. There were 139 CBOCs in operation at the end of fiscal year 1998. Ninety-eight percent of CBOCs offered primary health care, and 28% offered primary health care and primary mental health care. The average CBOC was 70.7 miles from its parent VAMC. Sixty-one percent of the CBOCs were located in urban areas and 39% were in rural areas. Sixty-four percent of the CBOCs were VA-staff and 36% were contract. RESULTS. The details of the project's findings are reported in four companion papers that describe, respectively, health care access and utilization, cost of care, patient perceptions of care, and quality of care in VA CBOCs. For most measures, CBOC performance was equivalent to their parent VAMCs. However, there were a few areas of potential concern: CBOCs had fewer patients that reported having one provider or team in charge of care; CBOC patients had fewer specialty visits; and CBOCs served a smaller percent of women and black persons. CONCLUSION. CBOCs appear to be performing comparably to their parent medical centers but will benefit from ongoing monitoring. C1 VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Minneapolis VAMC, Ctr Chron Dis Outcome Res, Hlth Serv Res & Dev, Minneapolis, MN USA. Univ Minnesota, Dept Med, Minneapolis, MN USA. Cent Arkansas Vet Healthcare Syst, Cent Mental Hlth & Outcomes Res, Hlth Serv Res & Dev, N Little Rock, AR USA. RP Chapko, MK (reprint author), VA Puget Sound Hlth Care Syst, Northwest Ctr Outcomes Res Older Adults, Hlth Serv Res & Dev, HSR&D 152 1660 S Columbian Way, Seattle, WA 98108 USA. NR 10 TC 36 Z9 36 U1 1 U2 2 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 JUL PY 2002 VL 40 IS 7 BP 555 EP 560 DI 10.1097/00005650-200207000-00001 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000001 PM 12142770 ER PT J AU Fortney, JC Borowsky, SJ Hedeen, AN Maciejewski, ML Chapko, MK AF Fortney, JC Borowsky, SJ Hedeen, AN Maciejewski, ML Chapko, MK TI VA Community-Based Outpatient Clinics - Access and utilization performance measures SO MEDICAL CARE LA English DT Article DE veterans; performance measures; access; utilization ID PREVENTIVE SERVICES; EARLY READMISSION; AMBULATORY CARE; UNITED-STATES; HEALTH-CARE; DISTANCE; HOSPITALIZATIONS; MANAGEMENT; VETERANS AB OBJECTIVES. The purpose of this study was to compare access and utilization performance measures between Community-Based Outpatient Clinics (CBOC) and primary care clinics at parent VA Medical Centers (VAMC) and between VA-staff CBOCs and contract CBOCs. METHODS. The study design was cross-sectional and retrospective. Performance measures were based on data routinely collected for administrative and research purposes by the VA. The sample included all primary care patients (n = 37,084) treated at the 38 CBOCs opened before 4/1/98 (30 VA-staff and 8 contract) and all primary care patients (n = 318,369) treated at the 32 parent VAMCs. Six months of service use data were used to derive the access and utilization performance measures. Multivariate regression analyses were used to control for observable casemix differences. RESULTS. CBOCs are attracting new high priority patients to the VA health care system. CBOC patients had more primary care encounters and fewer specialty encounters than patients in the primary care clinics of the parent VAMCs. VA-staffed CBOC patients had more primary care encounters and fewer specialty encounters than contract CBOC patients. CONCLUSIONS. CBOCs are helping the VA achieve its goals of attracting new patients and shifting the focus of care from the specialty to the primary care setting. C1 Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Hlt Serv Res & Dev, N Little Rock, AR USA. Univ Arkansas, Dept Psychiat, Ctr Mental Healthcare Res, Little Rock, AR 72204 USA. Minneapolis VAMC, Ctr Chron Dis Outcomes Res, Hlth Serv Res & Dev, Minneapolis, MN USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Fortney, JC (reprint author), VA HSR&D, CeMHOR, CAVHS, 152 NLR,2200 Ft Root Dr,Bldg 58, North Little Rock, AR 72114 USA. NR 26 TC 20 Z9 20 U1 1 U2 1 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 JUL PY 2002 VL 40 IS 7 BP 561 EP 569 DI 10.1097/00005650-200207000-00002 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000002 PM 12142771 ER PT J AU Hedeen, AN Heagerty, PJ Fortney, JC Borowsky, SJ Walder, DJ Chapko, MK AF Hedeen, AN Heagerty, PJ Fortney, JC Borowsky, SJ Walder, DJ Chapko, MK TI VA Community-Based Outpatient Clinics - Quality of care performance measures SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of Veterans Affairs Health Services Research and Development CY FEB 23, 2000 CL WASHINGTON, D.C. DE quality of care; performance measures; veterans; community clinics AB BACKGROUND. The Veterans Health Administration (VHA) recently initiated a system of Community-Based Outpatient Clinics (CBOCs) to enhance delivery of primary care to veterans. OBJECTIVE. The objective of this study was to compare quality of care provided to veterans at CBOCs and at traditional hospital-based VA Medical Center (VAMC) clinics. RESEARCH DESIGN. Quality of care was assessed using medical record data abstracted at CBOCs and VAMCs. The analysis used a logistic regression model that allowed for possible within-facility correlation and controlled for patient differences between facilities. SUBJECTS. The study included 4768 patients from 20 geographically diverse CBOCs and 2433 patients from the 20 VAMCs associated with these CBOCs. MEASURES. Quality of care was measured using 7 Prevention Index (PI) indicators and 9 Chronic Disease Care Index (CDCI) indicators, which assess compliance with nationally recognized guidelines for primary prevention, early disease detection, and care of patients with chronic disease. RESULTS. In the overall CBOC versus VAMC comparisons, performance was not significantly different on 15 of the 16 PI and CDCI indicators. In the comparisons between individual CBOCs and VAMCs pairs, 5 out of 20 CBOCs performed significantly below the affiliated VAMC on 4 or more indicators. CONCLUSIONS. These results suggest that CBOCs overall are providing a similar level of quality of care as VAMCs based on the PI and CDCI, although performance at several individual CBOCs fell below their affiliated VAMC on some indicators. Therefore, it appears that CBOCs are a valid approach for providing quality primary care to veterans. C1 VA Puget Sound Hlth Care Syst, NW Ctr Outcome Res Older Adults, Hlth Serv Res & Dev, Seattle, WA 98108 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Hlth Serv Res & Dev, N Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Ctr Mental Healthcare Res, N Little Rock, AR USA. Minneapolis VAMC, Ctr Chron Dis Outcomes Res, Hlth Serv Res & Dev, Minneapolis, MN USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Vet Hlth Adm, Off Qualit & Performance, Washington, DC USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Hedeen, AN (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcome Res Older Adults, Hlth Serv Res & Dev, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 15 TC 9 Z9 10 U1 16 U2 18 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 JUL PY 2002 VL 40 IS 7 BP 570 EP 577 DI 10.1097/00005650-200207000-00003 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000003 PM 12142772 ER PT J AU Borowsky, SJ Nelson, DB Fortney, JC Hedeen, AN Bradley, JL Chapko, MK AF Borowsky, SJ Nelson, DB Fortney, JC Hedeen, AN Bradley, JL Chapko, MK TI VA Community-Based Outpatient Clinics - Performance measures based on patient perceptions of care SO MEDICAL CARE LA English DT Article DE patient satisfaction; access to care; veterans ID SATISFACTION; DISSATISFACTION; DISENROLLMENT; ACCESS; PLAN AB BACKGROUND. The Department of Veterans Affairs (VA) recently initiated a system of Community- Based Outpatient Clinics (CBOCs) to enhance delivery of primary care to veterans. OBJECTIVE. The objective of this study was to determine the effect of CBOCs on patients' perceptions of care. RESEARCH DESIGN. The study design is a cross-sectional survey. SUBJECTS. This study compares 4,980 patients from 44 geographically diverse CBOCs to 4,159 patients from 36 parent VA Medical Center primary care clinics administratively and geographically associated with the CBOCs studied. MEASURES. Survey data were obtained from the 1998 VA National Outpatient Customer Satisfaction Survey which assesses eight multiitem scales addressing access and timeliness of care, education/information, patient preferences, emotional support, coordination of care, courtesy, and specialty care access. Each scale was evaluated based upon item responses that indicate a problem with care. The survey also contained SF-12 health status measures used for case-mix adjustment. RESULTS. Multivariate logistic regression controlling for patient health status measures revealed that CBOC patients reported fewer problems with care than VA-based patients on 7 of 8 scales though the absolute differences were small for most of the scales. The largest difference was observed for the access/timeliness scale. Significant differences between VA-staff and contract CBOCs were not observed. CONCLUSIONS. These results suggest that veterans participating in VA's initiative to provide primary care in community-based settings report no more than, and in some dimensions fewer problems with care compared with veterans who receive care in VAMC clinics. C1 VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Hlth Serv Res & Dev, Seattle, WA USA. Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Hlth Serv Res & Dev, N Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Ctr Mental Healthcare Res, Little Rock, AR USA. Minneapolis VAMC, Ctr Chron Dis Outcome Res, Health Serv Res & Dev, Minneapolis, MN USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Borowsky, SJ (reprint author), 3850 Pk Nicollet Clin Blvd, Minneapolis, MN 55416 USA. NR 16 TC 29 Z9 29 U1 0 U2 0 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 JUL PY 2002 VL 40 IS 7 BP 578 EP 586 DI 10.1097/00005650-200207000-00004 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000004 PM 12142773 ER PT J AU Maciejewski, ML Chapko, MK Hedeen, AN Fortney, JC AF Maciejewski, ML Chapko, MK Hedeen, AN Fortney, JC TI VA Community-Based Outpatient Clinics - Cost performance measures SO MEDICAL CARE LA English DT Article DE VA; community clinics; costs; performance measures ID MEDICARE CAPITATION PAYMENTS; HOSPITAL RESOURCES; CARE; QUALITY AB OBJECTIVE. To examine the direct costs of treating veterans in Community-Based Outpatient Clinics (CBOC) and primary care clinics operated by VA medical centers (VAMCs) between April 1998 and September 1998. RESEARCH DESIGN. In a retrospective observational study of patients in eighteen CBOCs and fourteen VAMCs, direct costs were compared. In addition, the costs of treating patients in new and established CBOCs were also examined. MEASURES. The three types of costs examined include direct cost per primary care visit, direct primary care cost per patient, and total direct cost per patient in ordinary least squares regressions with facility-specific random effects. Indirect costs for overhead and administration were excluded. All cost comparisons controlled for patient characteristics and case-mix differences via the Diagnostic Cost Group methodology. RESULTS. Results indicate that CBOC patients and VAMC patients had similar direct primary care costs on a per visit and per patient basis. Total direct costs for CBOC patients were lower compared with VAMC patients, because of lower specialty and ancillary care costs. Patients in new CBOCs had similar primary, specialty, ancillary and inpatient care costs when compared with patients in established CBOCs. CONCLUSION. Lower total costs for CBOC patients may be a consequence of substituting primary care at CBOCs for expensive specialty and ancillary care at VAMCs. CBOCs may be an alternative approach to providing care to veterans at a lower cost than traditional delivery models based in VA Medical Centers. C1 VA Puget Sound Hlth Care Syst, NW Ctr Outcome Res Older Adults, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Cent Arkansas Vet Healthcare Syst, Ctr Mental Hlth & Outcomes Res, Hlth Serv Res & Dev, N Little Rock, AR USA. Univ Arkansas Med Sci, Dept Psychiat, Ctr Mental Healthcare Res, Little Rock, AR USA. RP Maciejewski, ML (reprint author), VA Puget Sound Hlth Care Syst, NW Ctr Outcome Res Older Adults, 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 20 TC 14 Z9 14 U1 0 U2 0 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 JUL PY 2002 VL 40 IS 7 BP 587 EP 595 DI 10.1097/00005650-200207000-00005 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 572XJ UT WOS:000176800000005 PM 12142774 ER PT J AU Korthuis, PT Nekhlyudov, L Ziganshin, AU Sadigh, M Green, ML AF Korthuis, PT Nekhlyudov, L Ziganshin, AU Sadigh, M Green, ML TI Implementation of a cross-cultural evidence-based medicine curriculum SO MEDICAL TEACHER LA English DT Article AB While principles of evidence-based medicine (EBM) are increasingly prevalent in medical education curricula in Europe and North America, medical educators elsewhere face formidable barriers to its implementation. We sought to determine the feasibility of implementing a learner-centered, case-based EBM curriculum among academic physicians in Kazan, Russia, facilitated by residents participating in an international health elective. This article reports that implementation of an EBM curriculum is feasible during a resident international health elective and that mutually beneficial educational exchanges represent an opportunity for teaching the tenets of EBM abroad. C1 Yale Sch Med, Primary Care Internal Med Residency, New Haven, CT USA. RP Korthuis, PT (reprint author), Greater Los Angeles VA Syst, Bldg 500,Room 3233,11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. OI Ziganshin, Ayrat/0000-0002-9087-7927 NR 14 TC 4 Z9 4 U1 1 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0142-159X J9 MED TEACH JI Med. Teach. PD JUL PY 2002 VL 24 IS 4 BP 444 EP 446 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 577LR UT WOS:000177062800022 PM 12193334 ER PT J AU Mylonakis, E Paliou, M Hohmann, EL Calderwood, SB Wing, EJ AF Mylonakis, E Paliou, M Hohmann, EL Calderwood, SB Wing, EJ TI Listeriosis during pregnancy - A case series and review of 222 cases SO MEDICINE LA English DT Review ID SUCCESSFUL ANTEPARTUM TREATMENT; EPIDEMIC PERINATAL LISTERIOSIS; NEONATAL LISTERIOSIS; MONOCYTOGENES INFECTION; FETAL LISTERIOSIS; CROSS-INFECTION; OBSTETRIC COMPLICATION; 2ND TRIMESTER; EARLY-ONSET; OUTBREAK C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Brown Univ, Dept Med, Providence, RI 02912 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Newton Wellesley Hosp, Dept Med, Boston, MA USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,Gray 5,GRJ-504, Boston, MA 02114 USA. NR 137 TC 107 Z9 114 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 2002 VL 81 IS 4 BP 260 EP 269 DI 10.1097/01.md.0000027825.16955.8d PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 573RD UT WOS:000176843900002 PM 12169881 ER PT J AU Takahashi, K Gordon, J Liu, H Sastry, KN Epstein, JE Motwani, M Laursen, I Thiel, S Jensenius, JC Carroll, M Ezekowitz, RAB AF Takahashi, K Gordon, J Liu, H Sastry, KN Epstein, JE Motwani, M Laursen, I Thiel, S Jensenius, JC Carroll, M Ezekowitz, RAB TI Lack of mannose-binding lectin-A enhances survival in a mouse model of acute septic peritonitis SO MICROBES AND INFECTION LA English DT Article DE mannose-binding lectin (MBL); knockout; CLP; septic shock; TNF-alpha; IL-6; PMN ID INNATE IMMUNE-RESPONSE; ACUTE-PHASE REACTANT; SERINE-PROTEASE; COMPLEMENT PATHWAY; ACTIVATES COMPLEMENT; LABORATORY MODELS; CLASSICAL PATHWAY; HOST-DEFENSE; PIVOTAL ROLE; SEPSIS AB The mannose-binding lectin (MBL) (also known as the mannose-binding protein) is a serum protein that plays a role as an "ante-antibody" in innate immunity. In man, MBL is encoded by a single gene, whereas in mice there are two homologous proteins, MBL-A and MBL-C. In order to evaluate the relative roles of these two forms of MBL, we created MBL-A null mice that were MBL-C sufficient. We found MBL-A null mice had enhanced survival in a septic peritonitis model compared to wild-type mice and complement 3 null mice at 24 h, 48 h and 10 d (P < 0.05). Reconstitution of these mice with human MBL reversed the phenotype. Surviving mice had significantly decreased TNF-α and IL-6 levels in the blood and peritoneal cavity (P < 0.01). In vitro studies indicate that bacteria opsonized with MBL-A-deficient serum induced significantly less cytokine by peritoneal macrophages compared to those with wild-type serum. Our results indicate that MBL-A is a modulator of inflammation in vivo and in vitro in the mouse and that the role of MBL may extend beyond its role as an opsonin. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus C, Denmark. USN, Malaria Program, Med Res Ctr, Silver Spring, MD 20910 USA. Statens Serum Inst, DK-2300 Copenhagen S, Denmark. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA 02113 USA. RP Takahashi, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI 42788] NR 64 TC 68 Z9 68 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2002 VL 4 IS 8 BP 773 EP 784 AR PII S1286-4579(02)01597-6 DI 10.1016/S1286-4579(02)01597-6 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 580KT UT WOS:000177234300002 PM 12270724 ER PT J AU Harris, NR Whitt, SP Zilberberg, J Alexander, JS Rumbaut, RE AF Harris, NR Whitt, SP Zilberberg, J Alexander, JS Rumbaut, RE TI Extravascular transport of fluorescently labeled albumins in the rat mesentery SO MICROCIRCULATION LA English DT Article DE microvascular permeability; endothelial barrier; protein diffusion; reperfusion injury; nitric oxide ID ENDOTHELIAL CELL-INTERACTIONS; NITRIC-OXIDE PRODUCTION; HAMSTER-CHEEK POUCH; MICROVASCULAR PERMEABILITY; RECEPTOR ANTAGONIST; LEUKOCYTE ADHESION; ISCHEMIA; REPERFUSION; LEAKAGE; MICROCIRCULATION AB Objective: Fluorescently labeled albumin is used frequently as a tracer when monitoring microvascular permeability. Several fluorescent dyes are available for labeling protein, including fluorescein isothiocyanate (FITC) and Texas Red (TR). Because differences in leakage of dye-labeled proteins have been reported., the objective of the present study was to compare the accumulation of these two tracers in interstitium and lymph after the inflammatory event of ischemia-reperfusion. Methods: Anesthetized rats were injected intravenously with FITC-labeled albumin (FITC-alb) and TR-labeled albumin (TR-alb) before 30 minutes of mesenteric ischemia. Because the tracers leaked out of the microcirculation after reperfusion. accumulation in the surrounding buffer-superfused tissue. and in separate experiments. accumulation in lymph vessels, was defined as the ratio of tissue-to-plasma and lymph-to-plasma fluorescence. Results: Reperfusion induced a significant increase in tissue-to-plasma fluorescence of FITC-alb, however. no increase was observed for TR-alb. In contrast, lymph-to-plasma fluorescence of TR-alb tended to be greater than FITC-alb. Reperfusion-induced increases in tissue-to-plasma fluorescence of TR-alb occurred only when the superfusate was replaced with mineral oil. in which case tissue-to-plasma TR-alb fluorescence tended to be greater than FITC-alb. Conclusions: Measurement of fluorescently labeled albumin leak-age from mesenteric venules depends on the dye used to label the albumin and requires an assessment of losses from the extravascular measuring region. C1 Penn State Univ, Dept Bioengn, University Pk, PA 16802 USA. Univ Missouri, Pulm & Crit Care Div, Dept Internal Med, Columbia, MO USA. Louisiana State Univ, Ctr Hlth Sci, Dept Mol & Cellular Physiol, Shreveport, LA 71105 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Houston VA Med Ctr, Pulm & Crit Care Sect, Houston, TX 77030 USA. RP Harris, NR (reprint author), Penn State Univ, Dept Bioengn, 223 Hallowell Bldg, University Pk, PA 16802 USA. FU NHLBI NIH HHS [R01 HL064721, R01 HL-64721]; NIDDK NIH HHS [DK43785]; PHS HHS [R37 42528] NR 43 TC 8 Z9 8 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD JUL PY 2002 VL 9 IS 3 BP 177 EP 187 DI 10.1038/sj.mn.7800135 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 562UG UT WOS:000176216900003 PM 12080415 ER PT J AU Rumbaut, RE Huxley, VH AF Rumbaut, RE Huxley, VH TI Similar permeability responses to nitric oxide synthase inhibitors of venules from three animal species SO MICROVASCULAR RESEARCH LA English DT Article DE endothelium; rat; pig; frog; albumin; nitric oxide synthase; L-NMMA; L-NAME ID HYDRAULIC CONDUCTIVITY; L-NAME; ALBUMIN; LEAKAGE; FLOW; TRANSPORT; PROTEINS AB The influence of nitric oxide (NO) on microvascular permeability remains unclear. NO synthase (NOS) inhibitors have been reported to increase as well as to decrease permeability in different experimental models and animal species. We tested the hypothesis that NOS inhibitors influence venular permeability differently in amphibians and mammals. Permeability coefficients to albumin (P-s(alb)) were measured on in situ mesenteric venules of the frog and rat and excised pig coronary venules before and after exposure to NOS inhibitors. Despite individual variability in magnitude of responses, NOS inhibitors resulted in a reduction in p(s)(alb) in each species. Superfusion with 10(-5) M N-G -monomethyl-L-arginine (L-NMMA) reduced P-s(alb) of frog mescnteric venules by 42% (from a median of 11.4 X 10(-7)cm s(-1), n = 12, P < 0.01) and by 67% in porcine coronary venules (from 12.5 X 10(-7) cm s(-1), n = 5, P < 0.05). The response was attenuated in rat mesenteric venules; 10(-4) M N-G-nitro-L-arginine methyl ester (L-NAME) reduced p(s)(alb) by 23% (from 7.6 X 10(-7) cm s(-1), n = 9, P = 0.01). The inactive D-enantiomers of the NOS inhibitors were without effect on P-s(alb) in each model. In pig venules, perfusion with blood modified the permeability responses to L-NMMA, suggesting that effects of NO on permeability are modified by one or more elements of blood. These data support a role of nitric oxide release on venular permeability to albumin that is conserved among the three animal species. (C) 2002 Elsevier Science (USA). C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX 77030 USA. Univ Missouri, Dept Physiol, Columbia, MO 65212 USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe Blvd,Bldg 109,Room 114, Houston, TX 77030 USA. FU NHLBI NIH HHS [P01 HL-52490, R01 HL-64721, R37 HL-42528, R01 HL064721] NR 37 TC 25 Z9 25 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 2002 VL 64 IS 1 BP 21 EP 31 DI 10.1006/mvre.2002.2394 PG 11 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 569YN UT WOS:000176631000003 PM 12074627 ER PT J AU Mita, H Tsutsui, J Takekawa, M Witten, EA Saito, H AF Mita, H Tsutsui, J Takekawa, M Witten, EA Saito, H TI Regulation of MTK1/MEKK4 kinase activity by its N-terminal autoinhibitory domain and GADD45 binding SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; MAP KINASE; SIGNAL-TRANSDUCTION; SACCHAROMYCES-CEREVISIAE; YEAST; STRESS; PATHWAY; P38; PHOSPHORYLATION; IDENTIFICATION AB A variety of cellular stresses activate the stress-responsive mitogen-activated protein (MAP) kinases p38 and JNK. In this study, we studied the activation mechanism of a human MA-P kinase kinase kinase, MTK1 (also known as MEKK4), which mediates activation of both p38 and JNK. MTK1 has an extensive N-terminal noncatalytic domain composed of similar to1,300 amino acids. Full-length or near full-length MTK1 is catalytically inactive when expressed in Saccharomyces cerevisiae cells, as it is in mammalian cells. Deletion of a segment including positions 253 to 553 activates kinase, indicating that this segment contains the autoinhibitory domain. In the autoinhibited conformation, the MTK1 kinase domain cannot interact with its substrate, MKK6. By a functional complementation screening with yeast cells, GADD45 proteins (GADD45alpha, beta, and gamma) were identified as MTK1 activators. GADD45 proteins bind a site in MTK1 near the inhibitory domain and relieve autoinhibition. Mutants of full-length MTK1 were isolated that can interact with MKK6 in the absence of the activator GADD45 proteins. These MTK1 mutants are constitutively active, in both yeast and mammalian cells. A model of MTK1 autoinhibition by the N-terminal inhibitory domain and activation by GADD45 binding is presented. C1 Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. 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. RP Univ Tokyo, Inst Med Sci, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM h-saito@ims.u-tokyo.ac.jp FU NIGMS NIH HHS [GM-53415, GM-50909, GM-56699] NR 45 TC 111 Z9 115 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 13 BP 4544 EP 4555 DI 10.1128/MCB.22.13.4544-4555.2002 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 562UJ UT WOS:000176217100010 PM 12052864 ER PT J AU Andrechek, ER Hardy, WR Girgis-Gabardo, AA Perry, RLS Butler, R Graham, FL Kahn, RC Rudnicki, MA Muller, WJ AF Andrechek, ER Hardy, WR Girgis-Gabardo, AA Perry, RLS Butler, R Graham, FL Kahn, RC Rudnicki, MA Muller, WJ TI ErbB2 is required for muscle spindle and myoblast cell survival SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PERIPHERAL NERVOUS-SYSTEM; RECEPTOR GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; CARDIAC DEVELOPMENT; PROTEIN-KINASE; NEU-ONCOGENE; EGF RECEPTOR; MICE LACKING; NEUROMUSCULAR SYNAPSES AB Signaling mediated by ErbB2 is thought to play a critical role in numerous developmental processes. However, due to the embryonic lethality associated with the germ line inactivation of erbB2, its role in adult tissues remains largely obscure. Given the expression of ErbB2 at the neuromuscular junction, we have created a muscle-specific knockout to assess its role there. This resulted in viable mice with a progressive defect in proprioception due to loss of muscle spindles. Interestingly, a partial reduction of ErbB2 levels also reduced the number of muscle spindles. Although histological analysis of the muscle revealed an otherwise normal architecture, induction of muscle injury revealed a defect in muscle regeneration. Consistent with these observations, primary myoblasts lacking ErbB2 exhibit extensive apoptosis upon differentiation into myofibers. Taken together, these results illustrate a dual role for ErbB2 in both muscle spindle maintenance and survival of myoblasts. C1 McMaster Univ, Dept Biol, Inst Mol Biol & Biotechnol, Hamilton, ON L8S 4K1, Canada. McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON L8S 4K1, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Ottawa Hlth Res Inst, Ottawa, ON, Canada. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. RP Muller, WJ (reprint author), McMaster Univ, Dept Biol, Inst Mol Biol & Biotechnol, Hamilton, ON L8S 4K1, Canada. NR 53 TC 78 Z9 79 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2002 VL 22 IS 13 BP 4714 EP 4722 DI 10.1128/MCB.22.13.4714-4722.2002 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 562UJ UT WOS:000176217100025 PM 12052879 ER PT J AU Rheinwald, JG Hahn, WC Ramsey, MR Wu, JY Guo, ZY Tsao, H De Luca, M Catricala, C O'Toole, KM AF Rheinwald, JG Hahn, WC Ramsey, MR Wu, JY Guo, ZY Tsao, H De Luca, M Catricala, C O'Toole, KM TI A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HUMAN EPIDERMAL-KERATINOCYTES; ORAL PREMALIGNANT LESIONS; HUMAN MESOTHELIAL CELLS; HUMAN-FIBROBLASTS; TUMOR-SUPPRESSOR; CELLULAR SENESCENCE; MONOCLONAL-ANTIBODIES; RETROVIRAL VECTORS; DOWN-REGULATION AB With increasing frequency during serial passage in culture, primary human keratinocytes express p16(INK4A) (p16) and undergo senescence arrest. Keratinocytes engineered to express hTERT maintain long telomeres but typically are not immortalized unless, by mutation or other heritable event, they avoid or greatly reduce p16 expression. We have confirmed that keratinocytes undergo p16-related senescence during growth in culture, whether in the fibroblast feeder cell system or in the specialized K-sfm medium formulation, and that this mechanism can act as a barrier to immortalization following hTERT expression. We have characterized the p16-related arrest mechanism more precisely by interfering specifically with several regulators of cell cycle control. Epidermal, oral mucosal, corneal limbal, and conjunctival keratinocytes were transduced to express a p16-insensitive mutant cdk4 (cdk4(R24C)), to abolish p16 control, and/or a dominant negative mutant p53 (p53DD), to abolish p53 function. Expression of either cdk4(R24C) or p53DD alone had little effect on life span, but expression of both permitted cells to divide 25 to 43 population doublings (PD) beyond their normal limit. Keratinocytes from a p16(+/-) individual transduced to express p53DD alone displayed a 31-PD life span extension associated with selective growth of variants that had lost the wild-type p16 allele. Cells in which both p53 and p16 were nonfunctional divided rapidly during their extended life span but experienced telomere erosion and ultimately ceased growth with very short telomeres. Expression of hTERT in these cells immortalized them. Keratinocytes engineered to express cdk4(R24C) and hTERT but not p53DD did not exhibit an extended life span. Rare immortal variants exhibiting p53 pathway defects arose from them, however, indicating that the p53-dependent component of keratinocyte senescence is telomere independent. Mutational loss of p16 and p53 has been found to be a frequent early event in the development of squamous cell carcinoma. Our results suggest that such mutations endow keratinocytes with extended replicative potential which may serve to increase the probability of neoplastic progression. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Lab Photomed, Boston, MA 02114 USA. Ist Dermatopatico Immacolata, Lab Tissue Engn, Rome, Italy. San Gallicano Hosp, Rome, Italy. RP Rheinwald, JG (reprint author), Harvard Univ, Inst Med, Rm 664,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI De Luca, Michele/N-5883-2014 OI De Luca, Michele/0000-0002-0850-8445 FU NCI NIH HHS [CA 94223, K01 CA094223]; NIDCR NIH HHS [P01 DE 12467, P01 DE012467, R01 DE 13178, R01 DE013178] NR 79 TC 229 Z9 236 U1 0 U2 10 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 JUL PY 2002 VL 22 IS 14 BP 5157 EP 5172 DI 10.1128/MCB.22.14.5157-5172.2002 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 566VF UT WOS:000176448400018 PM 12077343 ER PT J AU Lobell, RB Liu, DM Buser, CA Davide, JP DePuy, E Hamilton, K Koblan, KS Lee, Y Mosser, S Motzel, SL Abbruzzese, JL Fuchs, CS Rowinsky, EK Rubin, EH Sharma, S Deutsch, PJ Mazina, KE Morrison, BW Wildonger, L Yao, SL Kohl, NE AF Lobell, RB Liu, DM Buser, CA Davide, JP DePuy, E Hamilton, K Koblan, KS Lee, Y Mosser, S Motzel, SL Abbruzzese, JL Fuchs, CS Rowinsky, EK Rubin, EH Sharma, S Deutsch, PJ Mazina, KE Morrison, BW Wildonger, L Yao, SL Kohl, NE TI Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl : protein transferase and geranylgeranyl : protein transferase type-1 SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RAS TRANSGENIC MICE; HUMAN TUMOR-GROWTH; FARNESYLTRANSFERASE INHIBITORS; N-RAS; I INHIBITORS; CELL-GROWTH; K-RAS; ANTITUMOR-ACTIVITY; PRENYLATION; GGTI-298 AB Farnesyl:protein transferase (FPTase) inhibitors were developed as anti-Ras drugs, but they fail to inhibit Ki-Ras activity because Ki-Ras can be modified by geranylgeranyl:protein transferase type-I (GGPTase-I). L-778,123, an inhibitor of FPTase and GGPTase-I, was developed in part because it can completely inhibit Ki-Ras prenylation. To support the clinical development of L-778,123, we developed pharmacodynamic assays using peripheral blood mononuclear cells (PBMCs) to measure the inhibition of prenylation of HDJ2 and Rap1A, proteins that are FPTase- and GGPTase-I substrates, respectively. We validated these assays in animal models and show that inhibition of HDJ2 prenylation in mouse PBMCs correlates with the concentration of FPTase inhibitors in blood. In dogs, continuous infusion of L-778,123 inhibited both HDJ2 and Rap1A prenylation in PBMCs, but we did not detect inhibition of Ki-Ras prenylation. We reported previously results from the first L-778,123 Phase I trial that showed a dose-dependent inhibition of HDJ2 farnesylation in PBMCs. In this report, we present additional analysis of patient samples from this trial and a second Phase I trial of L-778,123, and demonstrate the inhibition of both HDJ2 and Rap1A prenylation in PBMC samples. This study represents the first demonstration of GGPTase-I inhibition in humans. However, no inhibition of Ki-Ras prenylation by L-778,123 was detected in patient samples. These results confirm the pharmacologic profile of L-778,123 in humans as a dual inhibitor of FPTase and GGPTase-I, but indicate that the intended target of the drug, Ki-Ras, was not inhibited. C1 Merck Res Labs, Dept Canc Res, W Point, PA 19486 USA. Merck Res Labs, Dept Drug Metab, W Point, PA 19486 USA. Merck Res Labs, Dept Lab Anim Resources, W Point, PA 19486 USA. Merck Res Labs, Dept Clin Pharmacol, W Point, PA 19486 USA. Merck Res Labs, Dept Canc Res, Rahway, NJ 07065 USA. Merck Res Labs, Dept Drug Metab, Rahway, NJ 07065 USA. Merck Res Labs, Dept Lab Anim Resources, Rahway, NJ 07065 USA. Merck Res Labs, Dept Clin Pharmacol, Rahway, NJ 07065 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78245 USA. Univ Med & Dent New Jersey, Inst Canc, New Brunswick, NJ 08901 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Lobell, RB (reprint author), Merck Res Labs, Dept Canc Res, WP26-462, W Point, PA 19486 USA. NR 49 TC 70 Z9 73 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2002 VL 1 IS 9 BP 747 EP 758 PG 12 WC Oncology SC Oncology GA 607BM UT WOS:000178770600010 PM 12479371 ER PT J AU Mankodi, A Takahashi, MP Jiang, H Beck, CL Bowers, WJ Moxley, RT Cannon, SC Thornton, CA AF Mankodi, A Takahashi, MP Jiang, H Beck, CL Bowers, WJ Moxley, RT Cannon, SC Thornton, CA TI Expanded CUG repeats trigger aberrant splicing of CIC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy SO MOLECULAR CELL LA English DT Article ID PROTEIN-KINASE; CTG REPEAT; TRINUCLEOTIDE REPEAT; MOLECULAR-BASIS; CL CONDUCTANCE; MICE; EXPANSION; TRANSCRIPTS; RNA; MYOPATHY AB In myotonic dystrophy (dystrophia myotonica, DM), expression of RNAs that contain expanded CUG or CCUG repeats is associated with degeneration and repetitive action potentials (myotonia) in skeletal muscle. Using skeletal muscle from a transgenic mouse model of DM, we show that expression of expanded CUG repeats reduces the transmembrane chloride conductance to levels well below those expected to cause myotonia. The expanded CUG repeats trigger aberrant splicing of pre-mRNA for CIC-1, the main chloride channel in muscle, resulting in loss of CIC-1 protein from the surface membrane. We also have identified a similar defect in CIC-1 splicing and expression in two types of human DM. We propose that a transdominant effect of mutant RNA on RNA processing leads to chloride channelopathy and membrane hyperexcitability in DM. C1 Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Neurobiol, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. RP Thornton, CA (reprint author), Univ Rochester, Sch Med & Dent, Dept Neurol, Box 673,601 Elmwood Ave, Rochester, NY 14642 USA. FU NCRR NIH HHS [RR00044]; NIAMS NIH HHS [AR46806, AR42703, AR44069] NR 44 TC 353 Z9 364 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUL PY 2002 VL 10 IS 1 BP 35 EP 44 DI 10.1016/S1097-2765(02)00563-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 574XX UT WOS:000176916600008 PM 12150905 ER PT J AU Pal, PK Leung, J Hedrich, K Samii, A Lieberman, A Nausieda, PA Calne, DB Breakefield, XO Klein, C Stoessl, AJ AF Pal, PK Leung, J Hedrich, K Samii, A Lieberman, A Nausieda, PA Calne, DB Breakefield, XO Klein, C Stoessl, AJ TI [F-18]-dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism SO MOVEMENT DISORDERS LA English DT Article DE parkin; dopamine; Parkinson's disease; PET; genetics ID EARLY-ONSET PARKINSONISM; NIGROSTRIATAL DOPAMINERGIC SYSTEM; F-18 DOPA UPTAKE; IDIOPATHIC PARKINSONISM; FAMILIAL PARKINSONISM; JAPANESE FAMILIES; GENE; MUTATIONS; DISEASE; PET AB There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of F-18-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the Parkin gene. (C) 2002 Movement Disorder Society. C1 Univ British Columbia, Vancouver Hosp, Ctr Neurodegenerat Disorders, Vancouver, BC V6T 2B5, Canada. Univ British Columbia, Hlth Sci Ctr, Ctr Neurodegenerat Disorders, Vancouver, BC V6T 2B5, Canada. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Dept Human Genet, D-23538 Lubeck, Germany. Natl Parkinson Fdn, Miami, FL USA. St Josephs Hosp, NPF Ctr Excellence, Milwaukee, WI USA. RP Stoessl, AJ (reprint author), Univ British Columbia, Vancouver Hosp, Ctr Neurodegenerat Disorders, Purdy Pavilion 2221 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. FU NINDS NIH HHS [P50 NS38372] NR 34 TC 9 Z9 9 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2002 VL 17 IS 4 BP 789 EP 794 DI 10.1002/mds.10133 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 577UV UT WOS:000177081300022 PM 12210877 ER PT J AU Auchincloss, H Bonventre, JV AF Auchincloss, H Bonventre, JV TI Transplanting cloned cells into therapeutic promise - Therapeutic cloning promises to provide genetically matched replacement tissue, but non-self mitochondrial proteins derived from the recipient oocyte could render cloned tissue immunogenic. A new study examines this issue. SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 31 Z9 32 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2002 VL 20 IS 7 BP 665 EP 666 DI 10.1038/nbt0702-665 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 567QC UT WOS:000176494800016 PM 12089546 ER PT J AU Jauliac, S Lopez-Rodriguez, C Shaw, LM Brown, LF Rao, A Toker, A AF Jauliac, S Lopez-Rodriguez, C Shaw, LM Brown, LF Rao, A Toker, A TI The role of NFAT transcription factors in integrin-mediated carcinoma invasion SO NATURE CELL BIOLOGY LA English DT Article ID T-CELL ACTIVATION; ALPHA-6-BETA-4 INTEGRIN; CYCLOSPORINE-A; NUCLEAR FACTOR; CALCINEURIN; EXPRESSION; PROTEIN; LOCALIZATION; RECEPTORS; BREAST AB Integrins, receptors for extracellular matrix ligands, are critical regulators of the invasive phenotype(1). Specifically, the alpha(6)beta(4) integrin has been linked with epithelial cell motility, cellular survival and carcinoma invasion, hallmarks of metastatic tumours(2-4). Previous studies have also shown that antagonists of the NFAT (nuclear factor of activated T-cells) family of transcription factors(5,6) exhibit strong anti-tumour-promoting activity(7). This suggests that NFAT may function in tumour metastasis. Here, we investigate the involvement of NFAT in promoting carcinoma invasion downstream of the alpha(6)beta(4) integrin. We provide evidence that both NFAT1, and the recently identified NFAT5 isoform, are expressed in invasive human ductal breast carcinomas and participate in promoting carcinoma invasion using cell lines derived from human breast and colon carcinomas. NFAT1 and NFAT5 activity correlates with the expression of the alpha(6)beta(4) integrin. In addition, the transcriptional activity of NFAT5 is induced by alpha(6)beta(4) clustering in the presence of chemo-attractants, resulting in enhanced cell migration. These observations show that NFATs are targets of alpha(6)beta(4) integrin signalling and are involved in promoting carcinoma invasion, highlighting a novel function for this family of transcription factors in human cancer. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Div Canc Biol & Angiogenesis, Boston, MA 02215 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Toker, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Lopez-Rodriguez, C/G-4482-2014; OI Lopez-Rodriguez, C/0000-0002-2311-2406; Jauliac, Sebastien/0000-0002-1712-3416 FU NCI NIH HHS [CA42471, CA81325, CA82695]; NIDDK NIH HHS [DK64854] NR 27 TC 240 Z9 249 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 2002 VL 4 IS 7 BP 540 EP 544 DI 10.1038/ncb816 PG 5 WC Cell Biology SC Cell Biology GA 568UL UT WOS:000176562900021 PM 12080349 ER PT J AU Avni, O Lee, D Macian, F Szabo, SJ Glimcher, LH Rao, A AF Avni, O Lee, D Macian, F Szabo, SJ Glimcher, LH Rao, A TI T-H cell differentiation is accompanied by dynamic changes in histone acetylation of cytokine genes SO NATURE IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR; IN-VIVO; COORDINATE REGULATOR; LINEAGE COMMITMENT; IMMUNE-SYSTEM; CUTTING EDGE; TH1 CELLS; IL-4; EXPRESSION; STAT6 AB Naive T cells differentiate into effector cells upon stimulation with antigen, a process that is accompanied by changes in the chromatin structure of effector cytokine genes. Using histone acetylation to evaluate these changes, we showed that T cell receptor (TCR) stimulation results in early activation of the genes encoding both interleukin 4 and interferon-gamma. We found that continued culture in the presence of polarizing cytokines established a selective pattern of histone acetylation on both cytokine genes; this correlated with restricted access of the transcription factor NFAT1 to these gene regulatory regions as well as mutually exclusive gene expression by the differentiated T cells. Our data point to a biphasic process in which cytokine- driven signaling pathways maintain and reinforce chromatin structural changes initiated by the TCR. This process ensures that cytokine genes remain accessible to the relevant transcription factors and promotes functional cooperation of the inducible transcription factor NFAT with lineage-specific transcription factors such as GATA-3 and T-bet. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 55 TC 366 Z9 373 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2002 VL 3 IS 7 BP 643 EP 651 DI 10.1038/ni808 PG 9 WC Immunology SC Immunology GA 566RH UT WOS:000176441700014 PM 12055628 ER PT J AU Novina, CD Murray, MF Dykxhoorn, DM Beresford, PJ Riess, J Lee, SK Collman, RG Lieberman, J Shankar, P Sharp, PA AF Novina, CD Murray, MF Dykxhoorn, DM Beresford, PJ Riess, J Lee, SK Collman, RG Lieberman, J Shankar, P Sharp, PA TI siRNA-directed inhibition of HIV-1 infection SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; RNA-INTERFERENCE; C-ELEGANS; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; REV PROTEIN; AIDS VIRUS; DROSOPHILA; RECEPTOR; CELLS AB RNA interference silences gene expression through short interfering 21-23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Novina, CD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015; Dykxhoorn, Derek/D-1357-2015 FU NCI NIH HHS [P01-CA42063, P30-CA14051]; NIAID NIH HHS [AI 35502, AI45306, F32AI10523]; NIGMS NIH HHS [R37-GM34277, T32-GM07748] NR 45 TC 597 Z9 685 U1 5 U2 41 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2002 VL 8 IS 7 BP 681 EP 686 DI 10.1038/nm725 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 567QG UT WOS:000176495200028 PM 12042777 ER PT J AU Yoo, LI Chung, DC Yuan, JY AF Yoo, LI Chung, DC Yuan, JY TI LKB1 - A master tumour suppressor of the small intestine and beyond SO NATURE REVIEWS CANCER LA English DT Review ID PEUTZ-JEGHERS-SYNDROME; SERINE/THREONINE PROTEIN-KINASE; CELL-CYCLE ARREST; JUVENILE POLYPOSIS; GERMLINE MUTATIONS; GROWTH SUPPRESSION; CANCER SYNDROME; INCREASED RISK; GENE; LOCUS AB Peutz-Jeghers syndrome (PJS) is a rare, inherited intestinal polyposis syndrome that is associated with a significantly increased risk of several types of cancer - particularly those of the gastrointestinal and reproductive systems. Most cases of PJS have been associated with loss-of-function mutations in the ubiquitously expressed LKB1 gene, which encodes a serine/threonine kinase. Recent studies have begun to illustrate the molecular mechanisms by which LKB1 functions as an important new tumour suppressor. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. NR 54 TC 79 Z9 79 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2002 VL 2 IS 7 BP 529 EP 535 DI 10.1038/nrc843 PG 7 WC Oncology SC Oncology GA 636GV UT WOS:000180447000014 PM 12094239 ER PT J AU Kim, JYH Koralnik, IJ LeFave, M Segal, RA Pfister, LA Pomeroy, SL AF Kim, JYH Koralnik, IJ LeFave, M Segal, RA Pfister, LA Pomeroy, SL TI Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences SO NEURO-ONCOLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; SYRIAN GOLDEN-HAMSTER; LARGE T-ANTIGEN; SV40 LARGE-T; JC-VIRUS; SIMIAN VIRUS-40; BRAIN-TUMORS; DELETION MUTANTS; TRANSGENIC MICE; CHOROID-PLEXUS AB To address the hypothesis that medulloblastoma or supratentorial primitive neuroectodermal tumor (sPNET) can arise through infection by polyomaviruses, we examined genomic DNA isolated from 15 primary medulloblastoma and 5 sPNET biopsy specimens and from 2 medulloblastoma cell lines for the presence of DNA sequences from the polyomaviruses simian virus 40 (SV40), JC virus, and BK virus. These polyomaviruses have oncogenic potential in animals, and their DNA sequences have been detected in other surveys of various solid tumors, including childhood brain tumors. The tumor DNA samples were analyzed by Southern blot hybridization of polymerase chain reaction products that employed probes designed to detect specific polyomavirus sequences. Neither JC virus nor BK virus DNA sequences were detected in any of the specimens. None of the primary medulloblastoma or sPNET specimens contained SV40 sequences. However, SV40 DNA coding and noncoding sequences were detected in the D283-Med (medulloblastoma) cell line. Immunocytochemical studies of D283-Med revealed nuclear expression of SV40 large T antigen. In contrast to childhood ependymomas and choroid plexus tumors, medulloblastomas and sPNETs infrequently express evidence of polyomavirus infection. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. RP Pomeroy, SL (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 09172]; NICHD NIH HHS [HD 18348]; NINDS NIH HHS [NS 01919, NS 35701, NS 37757] NR 37 TC 28 Z9 30 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2002 VL 4 IS 3 BP 165 EP 170 DI 10.1215/15228517-4-3-165 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 565EB UT WOS:000176355100001 PM 12084346 ER PT J AU Adlkofer, F Aguzzi, A Baumeister, R Haass, C Silva, ODE DeStrooper, B Dotti, C Efthimiopoulos, S Gomez-Isla, T Growdon, J Hardy, J Hock, C Nitsch, R Lannfelt, L Pohlner, J Rossor, M Tovar, K Unsicker, K Wiltfang, J AF Adlkofer, F Aguzzi, A Baumeister, R Haass, C Silva, ODE DeStrooper, B Dotti, C Efthimiopoulos, S Gomez-Isla, T Growdon, J Hardy, J Hock, C Nitsch, R Lannfelt, L Pohlner, J Rossor, M Tovar, K Unsicker, K Wiltfang, J TI Early diagnosis of Alzheimer's disease and related dementia (DIADEM) - A research network funded by the European Union SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 VERUM Fdn, Munich, Germany. Univ Zurich, Inst Neuropathol, CH-8006 Zurich, Switzerland. Univ Munich, A Butenandt Inst, D-80539 Munich, Germany. Univ Aveiro, Dept Cellular Biol, P-3800 Aveiro, Portugal. Flanders Interuniv, Inst Biotechnol, Louvain, Belgium. Ottolenghi Sci Inst, Orbassano, Italy. Univ Athens, Dept Biol, GR-10679 Athens, Greece. Univ Navarra, Dept Neurosci, E-31080 Pamplona, Spain. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Mayo Clin Jacksonville, Ctr Neurosci, Jacksonville, FL 32224 USA. Univ Zurich, Div Psychiat Res, CH-8006 Zurich, Switzerland. Uppsala Univ, Dept Publ Hlth, S-75105 Uppsala, Sweden. Evotec NeuroSci GmbH, Hamburg, Germany. UCL, Neurol Inst, London WC1E 6BT, England. EleGene AG, Martinsried, Germany. Univ Heidelberg, Inst Cell Biol, D-6900 Heidelberg, Germany. EM prof.adlkofer@verum-foundation.de RI De Strooper, Bart/F-6507-2012; Aguzzi, Adriano/A-3351-2008; Efthimiopoulos, Spiros/H-3956-2013; da Cruz e Silva, Odete/F-4072-2010 OI De Strooper, Bart/0000-0001-5455-5819; Efthimiopoulos, Spiros/0000-0001-9244-4570; da Cruz e Silva, Odete/0000-0003-3718-9874 NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1405 BP S383 EP S383 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301381 ER PT J AU Baker, L Cholerton, B Sambamurti, K Gleason, C Asthana, S Watson, S Craft, S Hale, C AF Baker, L Cholerton, B Sambamurti, K Gleason, C Asthana, S Watson, S Craft, S Hale, C TI Estrogen alters plasma beta-amyloid (1-40) in postmenopausal women with AD SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Washington, Vet Affairs Puget Sound, Tacoma, WA USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Wisconsin, Sch Med, Madison, WI USA. Univ Washington, Vet Affairs Puget Sound, Seattle, WA 98195 USA. Univ Puget Sound, Vet Affairs Puget Sound, Tacoma, WA 98416 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 400 BP S106 EP S106 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300390 ER PT J AU Berezovska, O Ramdya, P Hyman, B AF Berezovska, O Ramdya, P Hyman, B TI Fluorescence resonance energy transfer analysis of interaction between PS1 and APP or Notch1 SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1041 BP S278 EP S278 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301021 ER PT J AU Blacker, D AF Blacker, D TI Ethical and legal issues in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 542 BP S145 EP S145 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300529 ER PT J AU Bonner, LT Li, G Hoff, DJ Raskind, MA AF Bonner, LT Li, G Hoff, DJ Raskind, MA TI Adrenergic antagonists for disruptive agitation in nursing home residents with Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 343 BP S90 EP S90 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300334 ER PT J AU Chang, Y Tanzi, RE Guenette, S AF Chang, Y Tanzi, RE Guenette, S TI Characterization of the subcellular localization of the APP-CTF,C83, in H4 neuroglioma cells overexpressing FE65L1 SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 703 BP S188 EP S188 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300687 ER PT J AU Cherny, R Carrington, D Masters, CL Opazo, C Bush, AI AF Cherny, R Carrington, D Masters, CL Opazo, C Bush, AI TI Clioquinol inhibits the copper-catalysed generation of H2O2 by A-beta SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Mental Hlth Res Inst Victoria, Melbourne, Vic, Australia. Ctr Regulac Celular & Patol, Santiago, Chile. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Ageing Unit, Charlestown, MA USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1187 BP S319 EP S319 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301166 ER PT J AU Cherny, R Carrington, D Masters, C Huang, XD Bush, A AF Cherny, R Carrington, D Masters, C Huang, XD Bush, A TI Clioquinol, inhibits copper-catalysed H2O2 production by A-beta SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Melbourne, Melbourne, Vic, Australia. Mental Hlth Res Inst Victoria, Melbourne, Vic, Australia. Ctr Regulac Celular & Patol, Santiago, Chile. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Ageing Unit, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 401 BP S106 EP S106 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300391 ER PT J AU Choi, EK Zaidi, NF Miller, JM Thomson, E Wasco, W Buxbaum, JD AF Choi, EK Zaidi, NF Miller, JM Thomson, E Wasco, W Buxbaum, JD TI Functional role phosphorylation of calsenilin in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Mt Sinai Sch Med, Lab Mol Neuropsychiat, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 790 BP S209 EP S210 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300772 ER PT J AU Fishel, M Tsuang, D O'Connell, J Peskind, E Raskind, M Leverenz, J Cook, D AF Fishel, M Tsuang, D O'Connell, J Peskind, E Raskind, M Leverenz, J Cook, D TI Psychosis in adult down syndrome patients: Clinical and neuropathologic characteristics SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, CHDD, Seattle, WA 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 563 BP S150 EP S150 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300550 ER PT J AU Forman, MS Giasson, BI Lee, VMY Trojanowski, JQ Duda, JE Miller, B AF Forman, MS Giasson, BI Lee, VMY Trojanowski, JQ Duda, JE Miller, B TI Convergence of tau and alpha-synuclein pathology in dementia patients: Chance event or mechanistically linked? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 500 BP S132 EP S132 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300489 ER PT J AU Goldstein, L Muffat, J Moir, R Goto, J Saunders, A Friedlich, A Huang, XD Coccia, J Faget, K Tanzi, R Bush, A Cherny, R Ericsson, M Delalle, I Newell, K Hedley-Whyte, ET Chylack, L AF Goldstein, L Muffat, J Moir, R Goto, J Saunders, A Friedlich, A Huang, XD Coccia, J Faget, K Tanzi, R Bush, A Cherny, R Ericsson, M Delalle, I Newell, K Hedley-Whyte, ET Chylack, L TI Beta-amyloid in the lens: A novel AD biomarker? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Aging Res Unit, Charlestown, MA USA. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Harvard Univ, Sch Med, Electron Microscopy Facil, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Neuropathol Div, Charlestown, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Ophthalm Res, Boston, MA USA. RI Muffat, Julien/P-2298-2014 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1523 BP S414 EP S414 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301495 ER PT J AU Hock, C Konietzko, U Papssotiropoulos, A Wollmer, A Streffer, J von Rotz, RC Davey, G Nitsch, RM Moritz, E AF Hock, C Konietzko, U Papssotiropoulos, A Wollmer, A Streffer, J von Rotz, RC Davey, G Nitsch, RM Moritz, E TI Vaccination therapy for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Zurich, Div Psychiat Res, Zurich, Switzerland. Massachusetts Gen Hosp, Dept Neurol, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 536 BP S143 EP S143 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300523 ER PT J AU Hyman, BT Bacskai, BJ Kajdasz, ST McLellan, ME Forsch, MP Debnath, ML Holt, DP Wang, YM Klunk, WE AF Hyman, BT Bacskai, BJ Kajdasz, ST McLellan, ME Forsch, MP Debnath, ML Holt, DP Wang, YM Klunk, WE TI Visualizing amyloid plaques SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Pittsburgh, Pittsburgh, PA USA. 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 559 BP S149 EP S149 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300546 ER PT J AU Ingelsson, M Fukumoto, H Newell, KV Hyman, BT Irizarry, MC AF Ingelsson, M Fukumoto, H Newell, KV Hyman, BT Irizarry, MC TI Biochemical and neuropathological measures in Alzheimer brain: Correlation of synaptophysin loss but not A beta levels with duration of disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1529 BP S416 EP S416 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301501 ER PT J AU Irizarry, M Fukumoto, H Cheung, B Hyman, B Tennis, M Growdon, J AF Irizarry, M Fukumoto, H Cheung, B Hyman, B Tennis, M Growdon, J TI Plasma A beta 40 and A beta 42 levels are not accurate diagnostic biomarkers for mild cognitive impairment (MCI) and Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp E, Alzheimer Dis Res Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Memory & Movement Disorders Unit, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1402 BP S383 EP S383 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301379 ER PT J AU Johnson, K Killiany, R Becker, JA Hilson, J Jones, K Albert, M AF Johnson, K Killiany, R Becker, JA Hilson, J Jones, K Albert, M TI Cerebral perfusion as a predictor of stability, decline and conversion to AD SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1303 BP S352 EP S352 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301282 ER PT J AU Kovacs, DM Ingano, LAM Ellis, BC Tanzi, RE Puglielli, L AF Kovacs, DM Ingano, LAM Ellis, BC Tanzi, RE Puglielli, L TI Sterol-dependent proteolysis of the APP N-terminus regulates beta generation SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet Aging Res Unit, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 532 BP S141 EP S141 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300519 ER PT J AU McMillan, P Cook, D Leverenz, J Kulstad, J Schellenberg, G Craft, S Ericksen, S Jin, LW Roth, R Kovacina, K AF McMillan, P Cook, D Leverenz, J Kulstad, J Schellenberg, G Craft, S Ericksen, S Jin, LW Roth, R Kovacina, K TI Reduced hippocampal insulin degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon 4 allele SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Stanford Univ, Sch Med, Stanford, CA 94305 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1468 BP S400 EP S400 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301443 ER PT J AU Moir, RD Romano, DM Saunders, AJ Tanzi, RE AF Moir, RD Romano, DM Saunders, AJ Tanzi, RE TI LRP-mediated clearance of redox modified Ab SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 2047 BP S557 EP S557 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465302006 ER PT J AU Puglielli, L Ellis, B Kovacs, DM AF Puglielli, L Ellis, B Kovacs, DM TI The second messenger ceramide regulates A beta generation SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 718 BP S191 EP S192 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300702 ER PT J AU Raskind, M Truyen, L AF Raskind, M Truyen, L TI Galantamine has cognitive benefits for patients with Alzheimer's disease after 36 months of continuous treatment SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Janssen Res Fdn, Titusville, NJ 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 429 BP S113 EP S114 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300419 ER PT J AU Religa, D London, H Styczynska, M Haroutunian, V AF Religa, D London, H Styczynska, M Haroutunian, V TI Amyloid beta pathology in Alzheimer disease and schizophrenia SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Polish Acad Sci, Dept Neurod Dis, MRC, Huddinge, Sweden. KI, NEUROTEC, Stockholm, Sweden. Karolinska Inst, Dept Clin Neurosci Occupat Therapy & Elderly Care, Huddinge, Sweden. Polish Acad Sci, Med Res Ctr, Dept Neurodegenerat Disorders, Warsaw, Poland. Mt Sinai Sch Med, Dept Psychiat, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Bronx, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 714 BP S190 EP S191 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465300698 ER PT J AU Rogers, J Goto, J Huang, XD Venti, A Moir, R Tanzi, R Bush, A AF Rogers, J Goto, J Huang, XD Venti, A Moir, R Tanzi, R Bush, A TI Iron oxidation and neuroprotection by secreted amyloid precursor protein SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1860 BP S509 EP S509 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301825 ER PT J AU Sperling, R Chua, E Rentz, D Bates, J Greve, D Dale, A Rosen, B Albert, M Schacter, D AF Sperling, R Chua, E Rentz, D Bates, J Greve, D Dale, A Rosen, B Albert, M Schacter, D TI Functional MRI studies in early sAlzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Memory Disorders Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Cambridge, MA 02138 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 2063 BP S562 EP S562 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465302022 ER PT J AU Ueda, K Xia, Y Masliah, E AF Ueda, K Xia, Y Masliah, E TI Apoe-deficiency leads to a progressive age-dependent blood brain barrier leakage and hydrocephalus SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1512 BP S411 EP S412 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301485 ER PT J AU Watson, GS Peskind, ER Asthana, S Purganan, K Wait, C Chapman, D Baker, LD Cholerton, B Schellenberg, G Craft, S AF Watson, GS Peskind, ER Asthana, S Purganan, K Wait, C Chapman, D Baker, LD Cholerton, B Schellenberg, G Craft, S TI ApoE genotype and age moderate insulin effects on CSF and serum apoE levels SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL-AUG PY 2002 VL 23 IS 1 SU 1 MA 1479 BP S403 EP S403 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 584KG UT WOS:000177465301453 ER PT J AU Alpert, N Badgaiyan, R Fischman, A AF Alpert, N Badgaiyan, R Fischman, A TI Detection of neuromodulatory changes in specific neurotansmitter systems: Experimental design and strategy SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 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 JUL PY 2002 VL 16 IS 3 SU S BP S53 EP S53 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 573YY UT WOS:000176861900054 ER PT J AU Minshew, NJ Meyer, J Goldstein, G AF Minshew, NJ Meyer, J Goldstein, G TI Abstract reasoning in autism: A dissociation between concept formation and concept identification SO NEUROPSYCHOLOGY LA English DT Article ID CARD SORTING TEST; CHILDREN; INDIVIDUALS; DIAGNOSIS AB The concept identification and concept formation aspects of abstract reasoning were examined in 90 nonmentally retarded individuals with autism and 107 normal controls. It was hypothesized that pronounced deficits would be found on concept formation tests, whereas performance on concept identification tests would be relatively intact. There was a significant difference between individuals with autism and individuals from a matched control group on all abstract reasoning tasks, but, with the exception of the Wisconsin Card Sorting Test (R. K. Heaton et al., 1993), differences on concept identification tests were not clinically significant. Factor analyses showed that concept formation and concept identification tasks loaded on separate factors in the autism group but not in the control group. Stepwise discriminant function analyses revealed that 2 tests of concept formation correctly classified 78.4% of cases, whereas concept identification tasks did not pass the tolerance test. C1 Vet Affairs Pittsburgh Healthcare Syst, Res Serv, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Goldstein, G (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Res Serv, 7180 Highland Dr,151R, Pittsburgh, PA 15206 USA. FU NICHD NIH HHS [HD35469]; NINDS NIH HHS [NS33355] NR 37 TC 99 Z9 99 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JUL PY 2002 VL 16 IS 3 BP 327 EP 334 DI 10.1037//0894-4105.16.3.327 PG 8 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 577RV UT WOS:000177076300004 PM 12146680 ER PT J AU Ogilvy, CS Hoh, BL Singer, RJ Putman, CM AF Ogilvy, CS Hoh, BL Singer, RJ Putman, CM TI Clinical and radiographic outcome in the management of posterior circulationaneurysms by use of direct surgical or endovascular techniques SO NEUROSURGERY LA English DT Article DE endovascular; Guglielmi detachable coils; outcome; posterior circulation aneurysms; rebleed; surgery ID GUGLIELMI DETACHABLE COILS; RUPTURED INTRACRANIAL ANEURYSMS; BASILAR TIP ANEURYSMS; UNRUPTURED ANEURYSMS; EMBOLIZATION; BIFURCATION AB OBJECTIVE: Posterior circulation aneurysms can be difficult lesions to treat surgically, and they have potential for high morbidity and mortality, particularly in elderly patients or those in poor neurological condition. In an effort to improve outcomes, our combined neurosurgical and neuroendovascular unit has used both surgical clipping and endovascular coiling techniques to treat posterior circulation aneurysms. Patients considered at high risk for surgery were managed with endovascular treatment. METHODS: From 1990 to 1998, 197 posterior circulation aneurysms in 189 patients were treated in our combined neurovascular unit. Of these aneurysms, 128 were ruptured, 63 were unruptured, and 6 had a distant history of rupture in patients who came to our center for delayed or repeat treatment. A total of 132 aneurysms were treated with surgical clipping (85 ruptured, 46 unruptured, and 1 with distant history of rupture) and 65 aneurysms were treated with endovascular coiling (43 ruptured, 17 unruptured, and 5 with distant history of rupture). Dissecting aneurysms of the vertebral or posteroinferior cerebellar arteries or aneurysms treated with proximal (Hunterian) occlusion were excluded from this analysis. Surgical risk was assessed using a previously described system (Massachusetts General Hospital [MGH] grade), which incorporates age, Hunt and Hess grade, size of lesion, and Fisher grade. RESULTS: Overall clinical outcomes at 1 year of follow-up wore 77.2% excellent or good, 10.2% fair, 4.1% poor, and 8.6% dead. Surgical treatment resulted in 95.6% complete aneurysm occlusion and 4.4% with residual aneurysm after surgical treatment, whereas endovascular treatment resulted in 32.3% complete occlusion, 26.2% with residual aneurysm, and 41.5% with partial occlusion. In most cases, however, treatment with Guglielmi detachable coils (Boston Scientific/Target, Fremont, CA) was performed for palliation rather than complete radiographic occlusion. Outcome was closely associated with NIGH grade with either treatment modality. Excellent/good outcomes were achieved in 96, 92.3, 82.9, 46.2, and 0% of surgically treated patients with MGH Grades of 0, 1, 2, 3, and 4, respectively. In comparison, excellent/good outcomes were achieved in 100, 84.2, 61.9, 0, and 50% of endovascularly treated patients with MGH Grades of 0, 1, 2, 3, and 4, respectively. CONCLUSION: A combined surgical and endovascular approach to posterior circulation aneurysms can achieve good outcomes in high-risk surgical patients treated by use of coiling techniques. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Intervent Neuroradiol, Boston, MA USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, V8K710,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 48 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2002 VL 51 IS 1 BP 14 EP 21 DI 10.1227/01.NEU.0000017189.09821.CA PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 569PU UT WOS:000176611700004 PM 12182412 ER PT J AU Smith, ER Carter, BS Ogilvy, CS AF Smith, ER Carter, BS Ogilvy, CS TI Proposed use of prophylactic decompressive craniectomy in poor-grade aneurysmal subarachnoid hemorrhage patients presenting with associated large sylvian hematomas SO NEUROSURGERY LA English DT Article DE aneurysm; craniectomy; decompression; hematoma; intracranial pressure; subarachnoid hemorrhage ID SPONTANEOUS INTRACEREBRAL HEMATOMAS; CEREBRAL-ARTERY INFARCTION; INTRACRANIAL-PRESSURE; HEMISPHERIC INFARCTION; SUBDURAL-HEMATOMA; BRAIN EDEMA; SURGERY; MANAGEMENT; STROKE; HEMICRANIECTOMY AB OBJECTIVE: As a group, patients who present in poor neurological grade after aneurysmal subarachnoid hemorrhage (SAH) often have poor outcomes. There may bel subgroups-of these patients, however, in which one pathological process predominates and for which the initiation of specific therapeutic interventions that target the predominant pathological process may result in improved outcome.,We report the use of prophylactic decompressive craniectomy in patients presenting in poor neurological condition after SAH from middle cerebral artery aneurysms with associated large sylvian fissure hematomas. Craniectomy allowed significant parenchymal swelling in the posthehemorrhagic period without increased intracranial pressure (ICP) or herniation syndrome. METHODS: Eight patients (mean age, 56.5 yr; age range, 42-66 yr) presented comatose with SAH (five Hunt and Hess, Grade IV, three Hunt and Hess Grade V). Radiographic evaluations demonstrated middle cerebral artery aneurysm and associated large sylvian fissure hematoma (mean clot volume, 121 ml; range, 30-175 ml). Patients were brought emergently to the operating room and treated with a modification of the pterional craniotomy And aneurysm clipping that included. a planned craniectomy and duraplasty. A large, reverse question mark scalp flap was created, followed by bone removal with, the following margins: anterior, frontal to the midpupillary line; posterior at least 2 cm behind-the external auditory meatus; superior up to. 2 cm lateral to the superior sagittal sinus; and inferior to the floor of the middle cranial fossa. Generous duraplasty was performed, using either pericranium or suitable, commercially available dural substitutes. RESULTS: All of the eight patients tolerated the craniectomy without operative complications. Postoperatively, all patients experienced immediate decreases in ICP to levels at or, below 20 mm Hg (presentation mean ICP, 31.6 mm Hg; postoperative mean ICP, 13.1 mm Hg). ICP control was sustained in seven of eight patients, with the one exception being due to a massive hemispheric infarction secondary to refractory vasospasm. Follow-up (greater than or equal to1 yr, except for one patient who died during the hospital stay) demonstrated that the craniectomy patients had a remarkably high number of good or excellent outcomes. The outcomes in the hemicraniectomy group were five good or excellent, one fair, and two poor or dead. CONCLUSION: The data gathered in this study demonstrate that decompressive craniectomy can be performed safely as part of initial management for a subcategory of patients with SAH who present with large sylvian fissure hematomas. In addition, the performance of decompressive craniectomy in the patients described in this article seemed to be associated with rapid and sustained control of ICP. Although the number of patients in this study is small, the data lend support to the hypothesis that decompressive craniectomy may be associated with good or excellent outcome in a carefully selected subset of patients with SAH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, VBK 710,55 Fruit St, Boston, MA 02114 USA. NR 59 TC 94 Z9 101 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUL PY 2002 VL 51 IS 1 BP 117 EP 124 DI 10.1227/01.NEU.0000017192.85679.38 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 569PU UT WOS:000176611700026 PM 12182408 ER PT J AU McDonald, C Carter, BS AF McDonald, C Carter, BS TI Medical management of increased intracranial pressure after spontaneous intracerebral hemorrhage SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID HEAD-INJURED PATIENTS; TRAUMATIC BRAIN INJURY; HYPERTONIC SALINE; MILD HYPOTHERMIA; CEREBRAL EDEMA; HYPERTENSION; MANNITOL; HYDROCEPHALUS AB The clinician is frequently faced with the patient who has suffered a spontaneous intracerebral hemorrhage. This article discusses the role of differing modes of intracranial pressure (ICP) management. ICP management can serve as either a primary therapeutic modality or an adjunct to other surgical efforts to control ICP (eg, direct hematoma evacuation). At the heart of all these management strategies is the notion that sustained increased ICP leads to further permanent neurologic injury. Because increased ICP is correlated with an increased volume of intracranial contents, all ICP therapies attempt to reduce the volume occupied by the intracranial contents while preserving maximum tissue perfusion and oxygenation. C1 Harvard Univ, Sch Med, Dept Neurol, S Shore Hosp, Weymouth, MA 02190 USA. Harvard Univ, Sch Med, Cerebrovasc Surg Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP McDonald, C (reprint author), Harvard Univ, Sch Med, Dept Neurol, S Shore Hosp, Weymouth, MA 02190 USA. NR 27 TC 3 Z9 3 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JUL PY 2002 VL 13 IS 3 BP 335 EP + AR PII S1042-3680(02)00016-5 DI 10.1016/S1042-3680(02)00016-5 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 605BD UT WOS:000178654800007 PM 12486922 ER PT J AU Picard, C AF Picard, C TI Family reflections on living through sudden death of a child SO NURSING SCIENCE QUARTERLY LA English DT Article DE cooperative inquiry; family; health as expanding consciousness; sudden infant death syndrome ID PATTERNS AB The author describes a method of cooperative inquiry into a family's experience of the sudden death of a child. Through the praxis method based on Newman's health as expanding consciousness, family members had an opportunity, individually and together, to explore the impact of this experience on subsequent family life over three generations. Members were given transcripts of all dialogues for further reflection. All writings were shared with all family members. Both process and content of the inquiry will illustrate the shared and unique ways in which this loss was expressed over time. Implications of the mode of inquiry will be discussed. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. RP Picard, C (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD JUL PY 2002 VL 15 IS 3 BP 242 EP 250 DI 10.1177/08918402015003011 PG 9 WC Nursing SC Nursing GA 565DW UT WOS:000176354500013 PM 12125536 ER PT J AU Smith, MR Fuchs, V Anderson, EJ Fallon, MA Manola, J AF Smith, MR Fuchs, V Anderson, EJ Fallon, MA Manola, J TI Measurement of body fat by dual-energy x-ray absorptiometry and bioimpedance analysis in men with prostate cancer SO NUTRITION LA English DT Article DE body composition; body fat; dual-energy x-ray absorptiometry; bioelectrical impedance; prostatatic neoplasms ID BIOELECTRICAL IMPEDANCE; VALIDATION; MASS; POPULATION; MUSCLE; RISK; DEXA AB OBJECTIVE: The aims of this study were to determine the percentage of body fat (%BF) by dual-energy x-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) using a standard adult equation and BIA using a standard geriatric equation in a population of older men with prostate cancer and to compare the results from these different methods. METHODS: We conducted a cross-sectional study in 38 men with locally advanced, node-positive. or recur-rent prostate cancer and no history of androgen-deprivation therapy. Bode composition was evaluated by DXA with the use of a Hologic 4500A densitometer and BIA. BIA %BF was calculated by using standard equations developed for adult and geriatric populations. RESULTS: %BF by DXA, BIA with the standard adult equation, BIA with the standard geriatric equation, and BIA with the a.-e-appropriate equation were 26.7 +/- 5.3%, 22.5 +/- 5.6%, 38.2 +/- 6.9%, and 35.4 +/- 9.6%. respectively. There were statistically significant differences between %BF by DXA and all BIA estimates. By using the methods described by Bland and Altman (Lancet 1986:1(84761):307). the standard adult equation showed the least bias and variability. CONCLUSIONS: In this group of men with prostate cancer, BIA with the standard adult equation provided a reasonable estimate of %BF compared with DXA. although the differences were statistically significant. BIA with the standard geriatric equation, however, markedly overestimated %BF compared with DXA, even when its use was restricted to elderly men. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mallinckrodt Gen Clin Res Ctr, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Inst Hlth Profess, Cox 640,100 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR 01066] NR 21 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JUL-AUG PY 2002 VL 18 IS 7-8 BP 574 EP 577 AR PII S0899-9007(02)00821-3 DI 10.1016/S0899-9007(02)00821-3 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 569GT UT WOS:000176593700007 PM 12093432 ER PT J AU Zellos, LS Sugarbaker, DJ AF Zellos, LS Sugarbaker, DJ TI Diffuse malignant mesothelioma of the pleural space and its management SO ONCOLOGY-NEW YORK LA English DT Article ID PHASE-II; MULTIMODALITY THERAPY; CONSECUTIVE PATIENTS; TRIMODALITY THERAPY; INTERLEUKIN-2; DIAGNOSIS; INTERFERON; CISPLATIN; EFFUSIONS; PATTERNS AB Diffuse malignant pleural mesothelioma is a rare and aggressive, malignancy of the pleura that is usually caused by exposure to asbestos. Between 2,000 and 3,000 new, cases are expected, to be diagnosed annually in the United States. Difficulties in diagnosis, staging, and treatment set this disease apart from other malignancies. The variable clinical presentation and problems, in establishing a definite histo-pathologic diagnosis result in significant delays in treatment.. Three histologic subtypes of the disease are described in this review: epithelial, sarcomatous, and mixed histologies. The Butchart, International Mesothelioma Interest Group, and Brigham. staging systems are the most commonly used-staging systems. The disease's natural history involves aggressive local,growth, invasion of vital mediastinal structures,, and death within 4 to 12 months without treatment. Single-modality therapy of any kind, has failed to. substantially, alter this. natural,history. Aggressive, multimodality regimens that include surgery, radiation, and chemotherapy have resulted in improved survival in properly selected patients. However, innovative therapies are still needed to prolong survival inpatients with early and advanced,disease. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Surg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 32 Z9 32 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 JUL PY 2002 VL 16 IS 7 BP 907 EP 913 PG 7 WC Oncology SC Oncology GA 577GG UT WOS:000177052700013 PM 12164558 ER PT J AU Krause, M Kwong, KK Xiong, J Gragoudas, ES Young, LHY AF Krause, M Kwong, KK Xiong, J Gragoudas, ES Young, LHY TI MRI of blood volume and cellular uptake of superparamagnetic iron in an animal model of choroidal melanoma SO OPHTHALMIC RESEARCH LA English DT Article DE nuclear magnetic resonance; melanoma; blood volume; choroid neoplasms; pathology; physiopathology; ferric compounds; diagnostic use; pharmacokinetics ID 10 LARGEST NUCLEOLI; UVEAL MELANOMA; MICROCIRCULATION ARCHITECTURE; SIMULATING LESIONS; CONTRAST AGENTS; CILIARY BODY; MAGNETIC-SUSCEPTIBILITY; MALIGNANT-MELANOMA; INTRAOCULAR TUMORS; IMAGING EVALUATION AB Functional magnetic resonance imaging (MRI), using monocrystalline iron oxide nanoparticles (MION) as a new intravascular contrast agent, was adapted for a rabbit model of pigmented choroidal melanoma. Three-dimensionally spoiled gradient recalled sequences were used for the quantitative assessment of blood volume and cellular uptake. In all ocular tissues studied, MION reduced the T-2-weighted signal intensity within 0.5 h and at 24 h (both p < 0.05) after the injection. In individual tumors, MION reduced the T-2-weighted signal intensity by 46-78% within 0.5 h and by 24-48% at 24 h. In addition, MION increased the T-1-weighted signal intensity in all tissues. T-2 yielded a higher sensitivity than T-1-weighted images. Functional MRI with MION is a noninvasive technique with regard to the eye, permitting measurement of blood volume and cellular uptake of the contrast agent. Further study is necessary to determine the feasibility of this technique for the tumor diagnosis and evaluation of tumor viability following treatments. Copyright (C) 2002 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Young, LHY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 10975] NR 67 TC 16 Z9 17 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 J9 OPHTHALMIC RES JI Ophthalmic Res. PD JUL-AUG PY 2002 VL 34 IS 4 BP 241 EP 250 DI 10.1159/000063883 PG 10 WC Ophthalmology SC Ophthalmology GA 598PM UT WOS:000178285700009 PM 12297697 ER PT J AU Alevizos, I Blaeser, B Gallagher, G Ohyama, H Wong, DTW Todd, R AF Alevizos, I Blaeser, B Gallagher, G Ohyama, H Wong, DTW Todd, R TI Odontogenic carcinoma: a functional genomic comparison with oral mucosal squamous cell carcinoma SO ORAL ONCOLOGY LA English DT Article DE DNA hybridization array; laser capture microdissection; squamous cell carcinoma ID PRIMARY INTRAOSSEOUS CARCINOMA; LASER-CAPTURE MICRODISSECTION; HYBRIDIZATION; EXPRESSION; ARRAYS; GENES; HEAD; NECK AB Intraosseous squamous cell carcinomas of the mandible arise de novo or secondary to a tumor transformed cyst epithelium. Current diagnostic tests frequently fail to distinguish between these tumors, leading to confusing, classification schemes. We report the functional genomic analysis of a mandibular odontogenic carcinoma. Malignant keratinocytes front the lesion were isolated using laser capture microdissection. Target sample generated from the total RNA of the LCM-procured cells was used to hybridize high-density oligonucleotide arrays. Functional genomic analysis of the odontogenic carcinoma database compared with four oral mucosal squamous cell carcinoma gene expression databases was performed. Preliminary results suggest a small subset of genes distinguish this odontogenic carcinoma from oral mucosal epidermoid carcinomas. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol, Boston, MA 02115 USA. Boston Univ, Goldman Sch Dent Med, Dept Oral Pathol, Boston, MA 02118 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Todd, R (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 1 Fruit ST, Boston, MA 02114 USA. FU NIDCR NIH HHS [P01 DE12467, R29 DE11983, K02 DE00456, P30 DE11814] NR 13 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD JUL PY 2002 VL 38 IS 5 BP 504 EP 507 AR PII S1368-8375(01)00093-8 DI 10.1016/S1368-8375(01)00093-8 PG 4 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 575HY UT WOS:000176941900015 PM 12110347 ER PT J AU Bharam, S Vrahas, MS Fu, FH AF Bharam, S Vrahas, MS Fu, FH TI Knee fractures in the athlete SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID TIBIAL PLATEAU FRACTURES; PATELLAR DISLOCATION; EMINENCE FRACTURES; FIXATION; DISTAL AB in comparison with other athletic knee injuries, fractures of the knee during competition are relatively rare. The incidence of sports-related fractures of the knee over a 10-year period from the Cleveland Clinic Foundation are shown in Table 1 [1]. When these injuries do occur, special attention is needed for a successful return to competition. Factors to consider for fracture management in these athletes are: the patient's sport and its functional requirements; the level of competition prior to injury; the patient's expectations the degree of soft tissue injury, and the method of fracture treatment [2]. A detailed rehabilitation and reconditioning program should also be included to restore muscle strength, endurance, and proprioception at preinjury level of performance. The evaluation and management of fibial plateau fractures, distal femur fractures, patella fractures, osteochondral fractures with acute patella dislocation, and knee fractures of the adolescent athlete will be discussed in this article. Return to sports criteria and implant removal will also be addressed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. UPMC, Ctr Sports Med, Pittsburgh, PA 15203 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bharam, S (reprint author), 36 7th Ave,Suite 502, New York, NY 10011 USA. NR 45 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD JUL PY 2002 VL 33 IS 3 BP 565 EP + AR PII S0030-5898(02)00019-6 DI 10.1016/S0030-5898(02)00019-6 PG 11 WC Orthopedics SC Orthopedics GA 608BP UT WOS:000178825500010 PM 12483952 ER PT J AU Wachter, BG Leonetti, JP Lee, JM Wurster, RD Young, MRI AF Wachter, BG Leonetti, JP Lee, JM Wurster, RD Young, MRI TI Silver nitrate injury in the rat sciatic nerve: A model of facial nerve, injury SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID CRUSH INJURY; RECOVERY; MORPHOMETRY; INDEX AB BACKGROUND: An unpublished communication of a permanent facial paralysis secondary to silver nitrate application in a postoperative mastoid cavity with a dehiscent facial nerve raises concern regarding its neurotoxicity. This study was performed to examine functional neural Injury and the morphology of nerve injury due to silver nitrate contact with a peripheral motor nerve. METHODS., Sprague-Dawley male rats were assigned to a sham surgery group or to a group where silver nitrate was applied directly to a surgically exposed sciatic nerve for 1, 5, or 10 seconds. Individual walking track data were collected on postoperative days (POD) 1, 4, 7, and 14, and the Sciatic Functional Index (SFI) was calculated to assess neural function. On POD 14, the cauterized nerve was harvested, and the histologic axon loss of each specimen was graded. RESULTS: In all experimental groups, the most severe functional loss was noted on POD 1. At POD 14 the greatest neural recovery was observed in the 1-second group, whereas the 5- and 10-second cautery groups demonstrated a significantly worse deficit. A moderate or greater degree of axon loss was observed in 50% of animals Injured for 1 second and nearly all animals injured for 5 or 10 seconds. CONCLUSION: Functional and neuropathologic data demonstrate that silver nitrate causes significant injury to the rat sciatic nerve. A 5-second cautery causes greater functional Impairment and more severe axonal loss than a 1-second Injury. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Res Serv, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Otolaryngol Head & Neck Surg, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Physiol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. RP Young, MRI (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Res Serv, 151-Z2,Bldg 1,Room A319, Hines, IL 60141 USA. NR 19 TC 8 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUL PY 2002 VL 127 IS 1 BP 48 EP 54 DI 10.1067/mhn.2002.126592 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 582WA UT WOS:000177373100008 PM 12161730 ER PT J AU DiMuzio, J Deschler, DG AF DiMuzio, J Deschler, DG TI Emergency department management of foreign bodies of the external auditory canal in children SO OTOLOGY & NEUROTOLOGY LA English DT Article DE foreign body; external auditory canal; pediatrics ID EAR AB Objective: To evaluate the management of foreign bodies in the external auditory canal (EAC) in pediatric patients by emergency department personnel. Setting: Tertiary care pediatric hospital emergency department. Study Design: A retrospective chart review of children with foreign bodies of the EAC over a 12-month period. Age, foreign body type, rate of successful removal, and complication rates were recorded, Foreign bodies were categorized into two groups: objects with smooth surfaces and not easily grasped (nongraspable) and objects with irregularly shaped surfaces and easily grasped (graspable). Results: Thirty-six patients were brought to the emergency department over a 12-month period with foreign bodies of the EAC. Their mean age was 6.5 years (range, 1-16 yr). Numerous foreign bodies were noted beads were the most common. Successful removal was achieved in 53% of cases, and one or more complications were recorded in 47%. When the foreign bodies were grouped into nongraspable and graspable objects, the success rate for the nongraspable group was 45%. with a complication rate of 70%, whereas for graspable objects the successful removal rate was 64%, with a complication rate of only 14%. The difference in complication rates was statistically significant (p < 0.001.) Conclusion: This study demonstrates that certain foreign bodies (graspable type) of the EAC in pediatric patients can be successfully managed by skilled emergency department personnel with low complication rates, whereas other foreign bodies (nongraspable types) may be better managed by early referral to an otolaryngologist. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Sch Osteopath Med, Dept Otolaryngol, Stratford, NJ 08084 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 21 Z9 21 U1 0 U2 1 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 JUL PY 2002 VL 23 IS 4 BP 473 EP 475 DI 10.1097/00129492-200207000-00014 PG 3 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 575JN UT WOS:000176943300015 PM 12170148 ER PT J AU Abou-Halawa, AS Poe, DS AF Abou-Halawa, AS Poe, DS TI Efficacy of increased gentamicin concentration for intratympanic injection therapy in Meniere's disease SO OTOLOGY & NEUROTOLOGY LA English DT Article DE intratympanic gentamicin; Meniere's disease ID UPDATE AB Objectives: Update of ongoing case series of intratympanic gentamicin use in intractable Meniere's disease. Comparison of the treatment results of two gentamicin concentrations: 30 mg/ml and 40 mg/ml. Study Design: Retrospective case-matched review of an ongoing protocol. Setting: Ambulatory visits in an office setting. Patients: Eighty-seven patients were included in this study according to the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) for reporting treatment results of Meniere's disease. Intervention: Intratympanic injection of a buffered gentamicin solution (30 mg/ml) was used in 44 patients (Group 1) in years 1992 to 1995. Stock gentamicin solution (40 mg/ml) was used in 43 patients (Group 2) in years 1996 to 1999. Treatment was titrated for each patient. and the hearing was strictly monitored. The endpoint of treatment was the complete cessation of vertigo spells. Main Outcome Measures: Hearing results, vertigo control scores. and ice water caloric testing responses were analyzed after 24 months of follow-up. Thirty-two patients from each group were selected for case-matched statistical analysis. Results: Four or fewer gentamicin injections were used in 70% of Group 1 patients and 96% of Group 2 patients, In Group 1, vertigo control was achieved in 81% of patients, and the hearing remained the same or was improved in 68% of patients. In Group 2. vertigo control was achieved in 72% of patients, and the hearing remained the same or was improved in 81% of patients. Treatment was aborted in four patients of Group 2 for early reversible hearing loss, and 31 of 39 patients (79%) who completed the protocol experienced lasting vertigo control. There was a trend for longer-lasting vertigo control in the Group 2 patients. Conclusion: It was concluded that increasing the gentamicin concentration to 40 mg/ml probably produces similar rates of vertigo control as those of the lower dose, at least initially, but requires fever injections, The higher dose did not increase the risk of hearing loss if treatment was stopped at the first indication of injury. A larger study is needed to confirm the trend of improved long-term hearing results in patients treated with the 40 mg/ml solution. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Suez Canal Univ, Fac Med, Ismailia, Egypt. RP Poe, DS (reprint author), Zero Emerson Pl,Suite 2C, Boston, MA 01124 USA. NR 23 TC 19 Z9 19 U1 0 U2 0 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 JUL PY 2002 VL 23 IS 4 BP 494 EP 502 DI 10.1097/00129492-200207000-00018 PG 9 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 575JN UT WOS:000176943300019 PM 12170152 ER PT J AU Rauch, SD AF Rauch, SD TI Immunologic and serologic testing in patients with Meniere's disease - Invited comment SO OTOLOGY & NEUROTOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD JUL PY 2002 VL 23 IS 4 BP 520 EP 521 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 575JN UT WOS:000176943300024 ER PT J AU Pfutzer, RH Tadic, SD Li, HS Thompson, BS Zhang, JY Ford, ME Eagon, PK Whitcomb, DC AF Pfutzer, RH Tadic, SD Li, HS Thompson, BS Zhang, JY Ford, ME Eagon, PK Whitcomb, DC TI Pancreatic cholesterol esterase, ES-10, and fatty acid ethyl ester synthase III gene expression are increased in the pancreas and liver but not in the brain or heart with long-term ethanol feeding in rats SO PANCREAS LA English DT Article DE cholesterol esterase; ethanol; fatty acid ethyl esters; gene expression; pancreatitis ID ALCOHOLIC PANCREATITIS; CARBOXYLESTER LIPASE; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; OXIDATIVE STRESS; CONSUMPTION; CELLS; CDNA; METABOLISM; PURIFICATION AB Introduction: Chronic alcohol consumption predisposes susceptible individuals to both acute and chronic pancreatitis. Aims: Our hypothesis was that alcohol increases the risk of pancreatitis by disrupting defense mechanisms and/or enhancing injury-associated pathways through altered gene expression. Hence, we studied the expression of pancreatic genes in rats chronically exposed to ethanol. Methodology: Male Wistar rats were pair-fed liquid diets without and with ethanol for 4 weeks. Total RNA was extracted from rat pancreas and other organs. The mRNA expression patterns among pancreatic samples from ethanol-fed rats and controls were compared with use of mRNA differential display. The differentially expressed cDNA tags were isolated, cloned, and sequenced. Results: One cDNA tag that was overexpressed in the pancreas showed 99% sequence homology to a rat pancreatic cholesterol esterase mRNA (CEL; Enzyme Commission number [EC] 3.1.1.13). The differential expression was confirmed by real-time PCR. Gene expression was also increased in the liver but not in the heart or brain of the alcohol-fed rats. Because CEL has fatty acid ethyl ester (FAEE)-generating activity and FAEEs play a major role in acute alcoholic pancreatitis, we determined the expression of other genes encoding for FAEE-generating enzymes and showed similar organ-specific expression patterns. Conclusion: Our results demonstrate that chronic ethanol consumption induced expression of FAEE-related genes in the pancreas and liver. This upregulation may be a central mechanism leading to acinar cell injury. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Genom Sci, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Hlth Care Syst, Div Gastroenterol, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), Whitcomb Ctr Genom Sci, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NIAAA NIH HHS [R01 AA-10885] NR 48 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD JUL PY 2002 VL 25 IS 1 BP 101 EP + DI 10.1097/01.MPA.0000020652.86805.47 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 569GB UT WOS:000176591700017 PM 12131779 ER PT J AU Butler, WE Khan, A Khan, SA AF Butler, WE Khan, A Khan, SA TI Posterior fossa ependymoma with intense but transient disseminated enhancement but not metastasis SO PEDIATRIC NEUROSURGERY LA English DT Article DE ependymoma; disseminated enhancement; craniospinal radiation therapy; local radiation therapy ID PROGNOSTIC FACTORS; INTRACRANIAL EPENDYMOMAS; RADIATION-THERAPY; STEREOTAXIC RADIOSURGERY; BRAIN-TUMORS; CHILDREN; CHILDHOOD; CHEMOTHERAPY; RADIOTHERAPY; IRRADIATION AB We report a pediatric patient with a posterior fossa ependymoma in whom the second of two magnetic resonance imaging (MRI) scans obtained preoperatively within a 10-day span showed intense but transient disseminated enhancement. However, following posterior fossa craniotomy for near total tumor resection, neither three MRI exams nor two craniospinal fluid samplings revealed evidence of disseminated disease. Concerned that the one MRI with disseminated enhancement indicated an elevated risk of leptomeningeal metastasis, we initiated craniospinal irradiation. However, we terminated this treatment after realizing that the bulk of the clinical evidence refuted the diagnosis of metastatic disease Copyright (C) 2002 S. KargerAG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv,Wang Ambulatory Care Ctr 331, Boston, MA 02114 USA. RP Butler, WE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv,Wang Ambulatory Care Ctr 331, 15 Parkman St, Boston, MA 02114 USA. NR 34 TC 3 Z9 3 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1016-2291 J9 PEDIATR NEUROSURG JI Pediatr. Neurosurg. PD JUL PY 2002 VL 37 IS 1 BP 27 EP 31 DI 10.1159/000065098 PG 5 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 577BM UT WOS:000177041700005 PM 12138216 ER PT J AU Suvak, MK Vogt, DS Savarese, VW King, LA King, DW AF Suvak, MK Vogt, DS Savarese, VW King, LA King, DW TI Relationship of war-zone coping strategies to long-term general life adjustment among Vietnam veterans: Combat exposure as a moderator variable SO PERSONALITY AND SOCIAL PSYCHOLOGY BULLETIN LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL SUPPORT; LONGITUDINAL ANALYSIS; POSITIVE PSYCHOLOGY; EMOTIONAL APPROACH; MODEL; PERSONALITY; PREVALENCE; RESISTANCE; APPRAISAL AB In this study, we examined long-term general life adjustment among members of one trauma-exposed population, Vietnam veterans, using data from a nationally representative sample. Our particular concern was the relationship between coping strategies used in the war zone and the outcomes of achievement, life satisfaction, and lifetime adaptation (the latter defined in terms of the absence of psychosocial problems in core life domains) as a function of level of combat exposure. Hierarchical multiple regression analyses supported a hypothesized quadratic interaction between problem focused coping and the outcomes of achievement and lifetime adaptation, with this form of coping most strongly related to adjustment (positively) at moderate levels of combat exposure. One aspect of emotion-focused coping, the use of wishful thinking, likewise interacted in a quadratic manner for the dependent variable of achievement, exhibiting its strongest association with adjustment (negatively) at moderate levels of combat exposure. The importance of interactions between coping and stressors, especially quadratic interactions, is emphasized. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Thomas Jefferson Univ, Philadelphia, PA USA. RP Suvak, MK (reprint author), VA Boston Healthcare Syst, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM suvakmi@yahoo.com NR 67 TC 28 Z9 28 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0146-1672 J9 PERS SOC PSYCHOL B JI Pers. Soc. Psychol. Bull. PD JUL PY 2002 VL 28 IS 7 BP 974 EP 985 DI 10.1177/01467202028007010 PG 12 WC Psychology, Social SC Psychology GA 567KU UT WOS:000176484600010 ER PT J AU Wu, TY Ronis, DL Pender, N Jwo, JL AF Wu, TY Ronis, DL Pender, N Jwo, JL TI Development of questionnaires to measure physical activity cognitions among Taiwanese adolescents SO PREVENTIVE MEDICINE LA English DT Article DE physical activity; questionnaire; Taiwan; adolescents; cognitions ID CONFIRMATORY FACTOR-ANALYSIS; HIGH-SCHOOL-STUDENTS; PERCEIVED BARRIERS; FIT INDEXES; EXERCISE; DETERMINANTS; VALIDITY; CHILDREN; BEHAVIORS; BELIEFS AB Background. Although a number of studies have investigated perceived self-efficacy, perceived benefits, and perceived barriers and their relationship to adolescents' participation in physical activity, the validity and reliability of the instruments used have not been consistently examined. The purpose of the present study was to develop culturally sensitive, reliable, and valid instruments to measure physical activity cognitions among Taiwanese adolescents. Methods. The items generated for the instruments were drawn from a comprehensive literature review and a focus group interview. The instruments were translated using the back-translation technique and evaluated by a panel of experts. Psychometric testing was performed and confirmed with convenience samples of 110 and 969 Taiwanese adolescents. Results. Psychometric testing demonstrated satisfactory internal consistency and validity of the instrument for this group of Taiwanese adolescents. Cronbach's a's ranged from 0.79 to 0.90. Construct validity was supported by exploring the factor structure of the instrument using confirmatory factor analysis and correlation with the outcome variable of physical activity. Conclusions. The study identified culturally sensitive items to measure physical activity cognitions in urban Taiwanese students in their early adolescence. Clinicians or practitioners can use the instruments developed and tested in this study for clinical assessment to identify risk factors for inactivity as well as for further research in similar populations. (C) 2002 American Health Foundation and Elsevier Science (USA). C1 Eastern Michigan Univ, Ypsilanti, MI 48197 USA. Univ Michigan, Ann Arbor, MI 48109 USA. US Dept Vet Affairs, Ann Arbor, MI USA. Natl Taiwan Normal Univ, Taipei, Taiwan. RP Wu, TY (reprint author), Eastern Michigan Univ, 328 Marshall, Ypsilanti, MI 48197 USA. NR 52 TC 14 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2002 VL 35 IS 1 BP 54 EP 64 DI 10.1006/pmed.2002.1049 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 569PQ UT WOS:000176611400008 PM 12079441 ER PT J AU Biederman, J Faraone, SV Monuteaux, MC AF Biederman, J Faraone, SV Monuteaux, MC TI Impact of exposure to parental attention-deficit hyperactivity disorder on clinical features and dysfunction in the offspring SO PSYCHOLOGICAL MEDICINE LA English DT Article ID RISK-FACTORS; CHILDREN; FAMILY; ADULTS; ADHD; COMORBIDITY; ADVERSITY; SYMPTOMS; BEHAVIOR; ISSUES AB Background. Although genes are known to influence the aetiology of ADHD, the impact of exposure to parental ADHD has received limited scientific scrutiny. This study investigated the impact of exposure to parental ADHD on clinical features and dysfunction in offspring. Methods. We studied 1099 offspring (53 % male, mean age 12(.)4 years) of non-ADHD, remitted ADHD, and persistent ADHD parents, using structured diagnostic interviews and a battery of cognitive and psychosocial measures. Offspring across these three groups were compared on clinical, cognitive and psychosocial outcomes, adjusting for exposure to other parental psychopathology, offspring ADHD status and social class. Results. Parental ADHD was associated with an increased risk for ADHD in offspring relative to no parental ADHD, but no significant differences were found between children of remitted versus persistent ADHD parents. Exposure to parental ADHD predicted higher levels of family conflict and lesser levels of family cohesion relative to families without parental ADHD, independent of other psychopathological conditions in parents or ADHD status. Significant interactions were detected in which parental ADHD had a deleterious impact on measures of school performance in offspring without ADHD but not in those with the disorder. Conclusions. These results find no support for the hypothesis that exposure to parental ADHD increases the risk for ADHD in children beyond that conveyed by the liability associated with the diagnosis in the parent. However, since exposure to parental ADHD was associated with a disruptive family environment, the identification and treatment of adults with ADHD may be an important component of the treatment plan of youth with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, 55 Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-O1A2, R01 MH57934] NR 46 TC 51 Z9 51 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2002 VL 32 IS 5 BP 817 EP 827 DI 10.1017/S0033291702005652 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 583FX UT WOS:000177397000005 PM 12171376 ER PT J AU Richardson, RD Engel, CC Hunt, SC McKnight, K McFall, M AF Richardson, RD Engel, CC Hunt, SC McKnight, K McFall, M TI Are veterans seeking veterans affairs' primary care as healthy as those seeking Department of Defense primary care? A look at Gulf War veterans' symptoms and functional status SO PSYCHOSOMATIC MEDICINE LA English DT Article DE Persian Gulf; healthy worker effect; health; functional status; PTSD; employment ID POSTTRAUMATIC-STRESS-DISORDER; SOMATOFORM DISORDERS; UNEMPLOYMENT; SERVICE; WOMEN AB Objective: This study compared Gulf War veterans seeking VA primary care with Gulf War veterans seeking treatment from a Department of Defense primary care clinic on measures of physical symptoms, psychiatric complaints, and functional status. Additionally, the association between employment status and health was examined. Methods: Analysis was based on the responses of consecutive patients attending the Gulf War Primary Care clinics at either the VA Puget Sound Health Care System in Seattle, WA (N = 223), or the Walter Reed Army Medical Center in Washington, DC (N = 153), between March 1998 and September 1999. Results: After controlling for demographic variables, Gulf War veterans who sought VA care reported significantly more anxiety and PTSD symptoms than active duty military personnel. The groups did not differ on somatic complaints or summary scores from the SF-36. Employment status was significantly, independently, and consistently associated with greater psychiatric symptoms, physical symptoms, and decreased functional status. Conclusions: Our findings reveal important differences in health status between veterans seeking primary care at a VA and a Department of Defense facility, differences that are in part related to employment status. Both groups report symptoms of psychiatric distress and decreased functional status, though VA patients are more impaired. Research findings based on clinical samples of veterans at VA sites may not generalize to Gulf War veterans still on active duty (and vice versa). C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. Univ Arizona, Dept Psychol, Tucson, AZ USA. VA Puget Sound Hlth Care Syst, CESATE, Seattle, WA USA. RP Richardson, RD (reprint author), VA Puget Sound Hlth Care Syst, 16 MHC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 42 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2002 VL 64 IS 4 BP 676 EP 683 DI 10.1097/01.PSY.0000021941.35402.18 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 575WZ UT WOS:000176972600018 PM 12140358 ER PT J AU Sonawalla, SB Papakostas, GI Petersen, TJ Yeung, AS Smith, MM Sickinger, AH Gordon, J Israel, JA Tedlow, JR Lamon-Fava, S Fava, M AF Sonawalla, SB Papakostas, GI Petersen, TJ Yeung, AS Smith, MM Sickinger, AH Gordon, J Israel, JA Tedlow, JR Lamon-Fava, S Fava, M TI Elevated cholesterol levels associated with nonresponse to fluoxetine treatment in major depressive disorder SO PSYCHOSOMATICS LA English DT Article ID LOW SERUM-CHOLESTEROL; GENERALIZED ANXIETY DISORDER; CORONARY-ARTERY DISEASE; PLASMA-LIPID LEVELS; PANIC DISORDER; ANXIOUS DEPRESSION; MEN; WOMEN; SYMPTOMS; SUICIDE AB Previous studies have suggested that patients with major depressive disorder may have lower cholesterol levels compared to healthy controls. The purpose of this study was to examine the relationship between pretreatment serum cholesterol levels and clinical response to treatment with fluoxetine among outpatients with major depression. Three hundred and twenty-two depressed outpatients meeting DSM-III-R criteria for major depressive disorder were enrolled in all 8-week, fixed-dose, open trial of fluoxetine 20 mg/day. Non sting serum cholesterol levels were obtained for all patients before starting fluoxetine. All patients were drug free for a minimum of 2 weeks prior to the onset of the study Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Rating Scale for Depression (HAM-D-17) score tit endpoint compared to baseline. Cholesterol levels were classified as either elevated (defined as a level equal to or greater than 200 mg/A) or nonelevated (defined as a level less than 200 mg/dL). Among the 322 outpatients, 51.6% were classified as having elevated and 48.4% as having nonelevated cholesterol levels at baseline (mean cholesterol level 238.6 +/- 33.4 mg/dL vs. 170.4 +/- 22.2 mg/dL, respectively). Depressed patients with elevated cholesterol levels did not significantly differ ill gender ratio but were Significantly older than depressed patients with nonelevated cholesterol levels (P < .0001). After adjusting for age, gender, and Body Mass Index (BMI), depressed patients with elevated cholesterol levels were significantly more likely to be nonresponders to fluoxetine treatment than were depressed patients with nonelevated cholesterol levels (P < 0.05). Elevated serum cholesterol levels appear to be associated with poorer response to fluoxetine treatment. Further studies tire needed to confirm our findings. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Sonawalla, SB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [R01-MH-48-483-05] NR 57 TC 34 Z9 36 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 2002 VL 43 IS 4 BP 310 EP 316 DI 10.1176/appi.psy.43.4.310 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 585EH UT WOS:000177510900006 PM 12189257 ER PT J AU Schmidt, ME Fava, M Zhang, SY Gonzales, J Raute, NJ Judge, R AF Schmidt, ME Fava, M Zhang, SY Gonzales, J Raute, NJ Judge, R TI Treatment approaches to major depressive disorder relapse - Part 1: Dose increase SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE long-term; depression; enteric-coated fluoxetine; relapse ID MANAGEMENT; FLUOXETINE; NONRESPONSE; STRATEGIES; EFFICACY; THERAPY AB Objective: Although continuing antidepressant treatment after patients have responded to medication has been shown to greatly reduce the risk of relapse, this risk is not eliminated. A number of theories have been proposed to account for this apparent loss of efficacy. A common initial approach to managing relapse is to increase the dose of antidepressant. We prospectively evaluated the likelihood of response to increasing the fluoxetine doses in patients relapsing during a long-term efficacy study of two fluoxetine dosing regimens. Method. Patients meeting the DSM-IV criteria for major depressive disorder with modified HAMD17 scores greater than or equal to18 and CGI-severity scores greater than or equal to4 were treated for 13 weeks with open-label 20 mg/day fluoxetine in a multicenter US study. Responders (n = 501) were randomized to 20 mg fluoxetine daily, placebo, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. If the patients relapsed during the continuation phase, they were offered a 25-week optional rescue treatment phase during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated, (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. The results of the rescue phase for the latter two groups who relapsed while on continuation treatment with fluoxetine are reported. Response was defined as a 50% reduction in the modified HAMD17 score since time of relapse and a CGI-severity score less than or equal to2. Additional efficacy analyses included HAMD and CGI-severity changes from baseline to endpoint. Safety measures included assessment of treatment-emergent adverse events, vital signs, and laboratory measures. Results: Overall, patients relapsing during the continuation treatment responded to an increased dose (57% of the 40-mg-daily group and 72% of the enteric-coated 90-mg-twice-weekly group). Mean modified HAMD17 scores decreased from a mean of approximately 20 to below 8 and were maintained for up to 6 months in the responders. Thirty-five percent of patients either did not respond or initially responded but again relapsed after augmentation of medication. Conclusions:The patients relapsing after initially responding to fluoxetine can benefit from an increase in fluoxetine dose. These results also generally support increasing dose as a first-line treatment strategy for a patient who has relapsed while taking a previously effective dose of an antidepressant. Increasing enteric-coated fluoxetine 90 mg once weekly to twice weekly appeared to be as well-tolerated and effective in restoring response as increasing a daily fluoxetine dose from 20 to 40 mg. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. RP Gonzales, J (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 2434, Indianapolis, IN 46285 USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 18 TC 39 Z9 40 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JUL-AUG PY 2002 VL 71 IS 4 BP 190 EP 194 DI 10.1159/000063643 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 577BB UT WOS:000177040700003 PM 12097783 ER PT J AU Fava, M Schmidt, ME Zhang, ZY Gonzales, J Raute, NJ Judge, R AF Fava, M Schmidt, ME Zhang, ZY Gonzales, J Raute, NJ Judge, R TI Treatment approaches to major depressive disorder relapse - Part 2: Reinitiation of antidepressant treatment SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE long-term; depression; enteric-coated fluoxetine; relapse ID PRIMARY-CARE; FLUOXETINE; DISCONTINUATION; MANAGEMENT; EFFICACY; THERAPY AB Background: Anecdotal reports concerning mood disorder patients suggest restarting drug treatment in patients who prematurely discontinue it may be associated with a diminished chance of response upon rechallenge. We evaluated the likelihood of response to reinitiation of fluoxetine treatment in patients relapsing after switching to placebo during a long-term efficacy study of two different dosing regimens of fluoxetine. Method. Patients who met the DSM-IV major depressive disorder criteria with modified HAMD17 scores greater than or equal to18 and CGI-Severity scores greater than or equal to4 were treated with open-label 20 mg/day fluoxetine for 13 weeks in a multicenter US study. Responders (n = 501) were randomized to placebo, 20 mg fluoxetine daily, or 90 mg enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. Patients relapsing during the continuation phase were offered 25 weeks of double-blind rescue treatment during which the study medication dose was increased as follows: (1) patients on placebo had treatment with fluoxetine 20 mg/day reinitiated; (2) patients on fluoxetine 20 mg/day had their dose increased to 40 mg/day, and (3) patients on a 90-mg weekly dose had their dose increased to 90 mg twice a week. Only the results of the rescue phase for the group who relapsed while on continuation treatment with placebo are reported here. Analyses included percentage of responders (50% reduction of modified HAMD17 and CGI-Severity less than or equal to2) and assessments of change from baseline to endpoint (HAMD, CGI-Severity). Safety measures included assessment of vital signs, laboratory measures, and treatment-emergent adverse events. Results: Of 122 patients assigned to placebo, 57 (47%) relapsed during continuation treatment. Fifty-five (96%) of these elected to enter double-blind rescue treatment. Overall, patients who relapsed upon switching to placebo responded well to reinitiation of fluoxetine (62%). The mean modified HAMD17 score decreased from 20 to less than 9 and was maintained for up to 6 months. Thirty-eight percent of patients either did not respond or initially responded but again relapsed after reinitiation of medication. Conclusion: This study suggests that patients who, after an initial response to fluoxetine, relapse upon switching to placebo have a relatively high probability of responding to the reinitiation of fluoxetine treatment. These results challenge the view that the efficacy of an agent prematurely discontinued is diminished when such an agent is restarted. They also generally support reinitiation of the same antidepressant as a 'first-line' treatment strategy in patients who relapsed after stopping a previously effective antidepressant. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St, Boston, MA 02114 USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 21 TC 24 Z9 25 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD JUL-AUG PY 2002 VL 71 IS 4 BP 195 EP 199 DI 10.1159/000063644 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 577BB UT WOS:000177040700004 PM 12097784 ER PT J AU Davis, PC O'Neill, MJ Yoder, IC Lee, SI Mueller, PR AF Davis, PC O'Neill, MJ Yoder, IC Lee, SI Mueller, PR TI Sonohysterographic findings of endometrial al and subendometrial conditions SO RADIOGRAPHICS LA English DT Article DE uterus, hemorrhage; uterus, US; uterine neoplasms; uterine neoplasms, US ID ASYMPTOMATIC POSTMENOPAUSAL WOMEN; BREAST-CANCER PATIENTS; TRANSVAGINAL SONOHYSTEROGRAPHY; TAMOXIFEN; ULTRASONOGRAPHY; SONOGRAPHY; US; HYSTEROSONOGRAPHY; ABNORMALITIES; HYSTEROSCOPY AB Sonohysterography has become the standard test in the evaluation of dysfunctional uterine and postmenopausal bleeding because it allows reliable differentiation between focal and diffuse endometrial and subendometrial lesions, with the most common being polyps and submucosal fibroids. An endometrial polyp usually appears as a well-defined homogeneous, polypoid lesion that is isoechoic to the endometrium with preservation of the endometrial-myometrial interface. Atypical polyps have cystic components, multiplicity, a broad base, and hypoecho-genicity or heterogeneity. Submucosal fibroids are usually broad-based, hypoechoic, well-defined, solid masses with shadowing and an overlying layer of echogenic endometrium that distorts the endometrial-myometrial interface. Atypical fibroids are pedunculated or have a multilobulated surface. The major advantage of sonohysterography is that it can accurately depict the percentage of the fibroid that projects into the endometrial cavity. Endometrial hyperplasia usually appears as diffuse thickening of the echogenic endometrial stripe without focal abnormality, but occasionally focal hyperplasia can be seen. Endometrial cancer is typically a diffuse process, but early cases can appear as a polypoid mass. Adhesions usually appear as mobile, thin, echogenic bands that bridge a normally distensible endometrial cavity, but occasionally thick, broadbased bands or complete obliteration of the endometrial cavity is seen. Although endometrial lesions have characteristic features, a wide range of appearances is possible, with significant overlap between entities. Radiologists should be familiar with the broad spectrum of findings that may be seen at sonohysterography in both benign and malignant processes to raise the appropriate level of concern and to direct the clinician toward the appropriate means of diagnostic biopsy or surgery. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Davis, PC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, White Bldg,Rm 270,55 Fruit St, Boston, MA 02114 USA. NR 26 TC 37 Z9 37 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 JUL-AUG PY 2002 VL 22 IS 4 BP 803 EP 816 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 572NF UT WOS:000176780900006 PM 12110711 ER PT J AU Evins, AE Amico, E Posever, TA Toker, R Goff, DC AF Evins, AE Amico, E Posever, TA Toker, R Goff, DC TI D-cycloserine added to risperidone in patients with primary negative symptoms of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE D-cycloserine; glutamate; glycine; negative symptoms; NMDA; schizophrenia ID PLACEBO-CONTROLLED TRIAL; HIGH-DOSE GLYCINE; CONVENTIONAL NEUROLEPTICS; XENOPUS OOCYTES; D-SERINE; CLOZAPINE; DYSFUNCTION; GLUTAMATE; RECEPTORS; SITE AB Background. D-Cycloserine, a partial agonist at the glycine recognition site of the NMDA receptor has previously been shown to improve negative symptoms when added to conventional antipsychotics and to worsen negative symptoms when added to clozapine. The purpose of this study was to examine the effects of D-cycloserine when added to risperidone on negative symptoms of schizophrenia. Method. Ten patients with schizophrenia who were treated with risperidone completed consecutive two week trials of placebo and four doses of D-cycloserine. Clinical assessments were videotaped and were scored by a rater who was blind to temporal sequence. Results. D-cycloserine at a dose of 50 mg/day was associated with significant reduction in negative symptoms (mean = 10%). Ratings of depression, extrapyramidal side effects, and cognitive function were unchanged. Serum concentrations of glutamate and serine increased significantly on this dose of D-cycloserine. Conclusions. This preliminary study suggests that combination of D-cycloserine, 50 mg/day, with risperidone may improve negative symptoms of schizophrenia over a narrow dose range. The degree of improvement appears to be intermediate between improvement of negative symptoms observed with combination of D-cycloserine with conventional antipsychotics and worsening of negative symptoms observed with combination of D-cycloserine with clozapine in previous trials of identical design. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Freedom Trail Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Freedom Trail Clin, Schizophrenia Res Program, Boston, MA 02114 USA. Tufts Univ, Sch Med, Lemuel Shattuck Hosp, Jamaica Plain, MA 02130 USA. Lemuel Shattuck Hosp, Bay Cove Mental Hlth Ctr, Jamaica Plain, MA 02130 USA. RP Evins, AE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 21 TC 87 Z9 88 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 1 PY 2002 VL 56 IS 1-2 BP 19 EP 23 AR PII S0920-9964(01)00220-1 DI 10.1016/S0920-9964(01)00220-1 PG 5 WC Psychiatry SC Psychiatry GA 567JJ UT WOS:000176481400003 PM 12084415 ER PT J AU Wirshing, DA Pierre, JM Marder, SR Saunders, CS Wirshing, WC AF Wirshing, DA Pierre, JM Marder, SR Saunders, CS Wirshing, WC TI Sexual side effects of novel antipsychotic medications SO SCHIZOPHRENIA RESEARCH LA English DT Article DE antipsychotic medication; clozapine; risperidone; haloperidol; fluphenazine; sexual side effects ID PROLACTIN LEVELS; SCHIZOPHRENIA; DYSFUNCTION; CLOZAPINE; RISPERIDONE AB Background: The novel antipsychotic medications offer a more favorable extrapyramidal side effect profile than conventional agents. It is uncertain that the novel antipsychotics have a benefit in terms of sexual side effects. Methods: We prospectively administered a survey of sexual functioning to 25 male patients with DSM-IV schizophrenia, taking conventional and novel antipsychotics. Contrasts were made between three treatment groups: clozapine (CLOZ), risperidone (RIS), and a combined haloperidol/fluphenazine (HAL/FLU) group. Results: A decrease in overall sexual functioning was reported in all medication groups (40-71 %). The majority of subjects taking RIS or HAL/FLU reported a decline in one or more aspects of sexual functioning. Examining specific aspects of sexual functioning revealed that, a decline in sexual interest was significantly less corm-non on CLOZ compared to RIS (0 vs. 64%; chi(2) = 6.1, df = 1, p = 0.01) or HAL/FLU (0 vs. 67%; chi(2) = 5.2, df = 1, p = 0.02), while a decline in the erectile frequency was significantly more common on RIS compared to CLOZ (40 vs. 93%; chi(2) = 6.2, df = 1, p = 0.01) or HAL/FLU (50 vs. 93%; chi(2) = 4.8, df = 1, p = 0.03) (0%). For enjoyment of orgasm and ejaculatory volume, significantly fewer CLOZ compared to RIS subjects reported a decline (20 vs. 86%; chi = 7.4, df = 1, p = 0.01). Conclusions: Sexual side effects are common clinically pertinent adverse effects associated with both novel and conventional antipsychotic medications. They deserve increased attention in clinical work and future research with emerging antipsychotic drugs. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Wirshing, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210B,Room 15, Los Angeles, CA 90073 USA. NR 14 TC 53 Z9 54 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL 1 PY 2002 VL 56 IS 1-2 BP 25 EP 30 AR PII S0920-9964(01)00271-7 DI 10.1016/S0920-9964(01)00271-7 PG 6 WC Psychiatry SC Psychiatry GA 567JJ UT WOS:000176481400004 PM 12084416 ER PT J AU Stone, RM AF Stone, RM TI Treatment of acute myeloid leukemia: State-of-the-art and future directions SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT Scientific Roundtable Meeting on Hematologic Malignacies CY DEC 06, 2001 CL RARITAN, NEW JERSEY SP Ortho Biotech Oncol ID BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; INTERMEDIATE-DOSE CYTARABINE; SOUTHWEST-ONCOLOGY-GROUP; TRANSFERASE INHIBITOR SCH66336; ACUTE NONLYMPHOCYTIC LEUKEMIA; COLONY-STIMULATING FACTOR; CYTOSINE-ARABINOSIDE; INTENSIVE CHEMOTHERAPY; POSTREMISSION THERAPY C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 66 TC 26 Z9 27 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JUL PY 2002 VL 39 IS 3 SU 2 BP 4 EP 10 DI 10.1053/shem.2002.35977 PG 7 WC Hematology SC Hematology GA 590GX UT WOS:000177812100002 PM 12214287 ER PT J AU Symons, SP Cullen, SP Buonanno, F Gonzalez, RG Lev, MH AF Symons, SP Cullen, SP Buonanno, F Gonzalez, RG Lev, MH TI Noncontrast conventional computed tomography in the evaluation of acute stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC STROKE; CEREBRAL-ARTERY INFARCTION; DIFFUSION-WEIGHTED MRI; EARLY CT SIGN; THROMBOLYTIC THERAPY; PROGNOSTIC VALUE; INTRAVENOUS THROMBOLYSIS; MAGNETIC-RESONANCE; CAROTID-ARTERY C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. NR 57 TC 9 Z9 9 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 185 EP 191 DI 10.1053/sroe.2002.34559 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300004 PM 12226897 ER PT J AU Cullen, SP Symons, SP Hunter, G Hamberg, L Koroshetz, W Gonzalez, RG Lev, MH AF Cullen, SP Symons, SP Hunter, G Hamberg, L Koroshetz, W Gonzalez, RG Lev, MH TI Dynamic contrast-enhanced computed tomography of acute ischemic stroke: CTA and CTP SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; TISSUE-PLASMINOGEN-ACTIVATOR; ACUTE HEMISPHERIC STROKE; PERFUSION-WEIGHTED MRI; HYPERACUTE STROKE; INTRAARTERIAL THROMBOLYSIS; ARTERY STROKE; ANGIOGRAPHY; THERAPY; ANGIOPLASTY C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, GRB 285,Fruit St, Boston, MA 02114 USA. NR 74 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 192 EP 205 DI 10.1053/sroe.2002.34560 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300005 PM 12226898 ER PT J AU Romero, J Schaefer, P McDonald, C Schwamm, L Gonzalez, RG AF Romero, J Schaefer, P McDonald, C Schwamm, L Gonzalez, RG TI Conventional magnetic resonance imaging of acute stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID INVERSION-RECOVERY FLAIR; ACUTE CEREBRAL INFARCTION; PULSE SEQUENCES; MR; HEMORRHAGE; BRAIN; ENHANCEMENT; ISCHEMIA; CT C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 21 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 206 EP 211 DI 10.1053/sroe.2002.34563 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300006 PM 12226899 ER PT J AU Yu, D Schaefer, PW Rordorf, G Gonzalez, RG AF Yu, D Schaefer, PW Rordorf, G Gonzalez, RG TI Magnetic resonance angiography in acute stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID ENHANCED MR-ANGIOGRAPHY; DIGITAL SUBTRACTION ANGIOGRAPHY; CAROTID-ARTERY STENOSIS; VESSELS; DISEASE C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 212 EP 218 DI 10.1053/sroe.2002.34567 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300007 PM 12226900 ER PT J AU Schaefer, PW Romero, JM Grant, PE Wu, O Sorensen, AG Koroshetz, W Gonzalez, RG AF Schaefer, PW Romero, JM Grant, PE Wu, O Sorensen, AG Koroshetz, W Gonzalez, RG TI Diffusion magnetic resonance imaging of acute ischemic stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; WEIGHTED MR; TIME-COURSE; ARTERY OCCLUSION; T2-WEIGHTED MRI; WATER DIFFUSION; LESION VOLUMES; BRAIN; COEFFICIENT; RAT C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. NR 57 TC 3 Z9 3 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 219 EP 229 DI 10.1053/sroe.2002.34568 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300008 PM 12226901 ER PT J AU Schaefer, PW Romero, JM Grant, PE Wu, O Sorensen, AG Koroshetz, W Gonzalez, RG AF Schaefer, PW Romero, JM Grant, PE Wu, O Sorensen, AG Koroshetz, W Gonzalez, RG TI Perfusion magnetic resonance imaging of acute ischemic stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; APPARENT DIFFUSION-COEFFICIENT; WEIGHTED MRI; HYPERACUTE STROKE; CONTRAST AGENTS; INFARCT GROWTH; PENUMBRA; PREDICTION; VOLUME; HEMODYNAMICS C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. NR 33 TC 4 Z9 6 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 230 EP 236 DI 10.1053/sroe.2002.34569 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300009 PM 12226902 ER PT J AU Rabinov, J Schwamm, L Putman, C Gonzalez, RG Koroshetz, W Pryor, J AF Rabinov, J Schwamm, L Putman, C Gonzalez, RG Koroshetz, W Pryor, J TI Image-guided vascular recanalization in acute stroke SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC STROKE; LOCAL INTRAARTERIAL THROMBOLYSIS; TISSUE PLASMINOGEN-ACTIVATOR; INTERNAL CAROTID-ARTERY; CT ANGIOGRAPHY; FIBRINOLYTIC THERAPY; TERRITORY STROKE; OCCLUSION; PROUROKINASE C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 44 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD JUL PY 2002 VL 37 IS 3 BP 237 EP 248 DI 10.1053/sroe.2002.34562 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 589FD UT WOS:000177747300010 PM 12226903 ER PT J AU Ahmed, A Allman, RM DeLong, JF Bodner, EV Howard, G AF Ahmed, A Allman, RM DeLong, JF Bodner, EV Howard, G TI Age-related underutilization of left ventricular function evaluation in older heart failure patients SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; ELDERLY PATIENTS; PRACTICE GUIDELINES; MEDICARE PATIENTS; PRIMARY-CARE; MANAGEMENT; ECHOCARDIOGRAPHY; QUALITY; CARDIOLOGY AB Background. Underutilization of left ventricular function (LVF) evaluation in older patients with heart failure has been well documented, but age-related variation in the use of LVF evaluation has not been. Methods. We studied age-related variation of LVF evaluation in older Medicare-beneficiaries discharged with a diagnosis of heart failure in 1994 in Alabama. Results. A total of 1,090 patients had a mean+/-SD age of 79+/-7.5 years; 60% were female and 18% were African American. Of these, 6360 (58%) had LVF evaluation. Compared with patients aged 65 to 74 years, those 75 to 84 years of age and those aged 85 and older were less likely to receive LVF evaluation. Age of 85 years and older was also independently associated with lower odds of LVF evaluation. Conclusion. The overall rate of LVF evaluation was low, and performance of evaluation decreased with patient age. Left ventricular function evaluation should be performed in all patients with heart failure. Considerable opportunities exist for improving care among hospitalized Medicare beneficiaries diagnosed with heart failure. C1 Univ Alabama, Div Gerontol & Geriatr Med, Dept Med, Sch Med Dept,Epidemiol & Int Hlth, Birmingham, AL USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Ctr Aging, Birmingham, AL 35294 USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Ctr Outcome & Effectiveness Res & Educ, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Clin Ctr, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Sect Geriatr, Heart Failure Clin, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Ahmed, A (reprint author), 1530 3rd Ave S,CH-19,Suite 219, Birmingham, AL 35294 USA. RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 NR 28 TC 9 Z9 9 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD JUL PY 2002 VL 95 IS 7 BP 695 EP 702 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 574CT UT WOS:000176871400009 PM 12144074 ER PT J AU Ahmed, A Allman, RM DeLong, JF Bodner, EV Howard, G AF Ahmed, A Allman, RM DeLong, JF Bodner, EV Howard, G TI Age-related underutilization of angiotensin-converting enzyme inhibitors in older hospitalized heart failure patients SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID PRACTICE GUIDELINES COMMITTEE; LEFT-VENTRICULAR DYSFUNCTION; ASSOCIATION TASK-FORCE; MEDICARE PATIENTS; AMERICAN-COLLEGE; MANAGEMENT; CARE; PATTERNS; QUALITY AB Background. The extent to which age plays a role in the underutilization of angiotensin-converting enzyme (ACE) inhibitors in heart failure patients has not been well studied. Methods. We studied age-related variation in the use of ACE inhibitors in older Medicare beneficiaries discharged alive in Alabama with a diagnosis of heart failure with left ventricular systolic dysfunction. Results. A total of 285 patients had a mean age +/-SD of 78+/-6.9 years; 59% were female and 21% were African American. Of the 285 patients, 181 (63%) were prescribed ACE inhibitors at discharge. Therapy with ACE inhibitors was initiated in 47% of the patients. Compared with patients 65 to 74 years, those 85 years and older had lower odds of receiving ACE inhibitors at discharge. Among patients not admitted on an ACE inhibitor, those 85 years and older also had lower odds of ACE inhibitor therapy being initiated. Conclusion. The overall rate of ACE inhibitor use was low, and age of 85 years and older was independently associated with lower use and initiation of ACE inhibitors. Opportunities remain to increase the use of ACE inhibitors in older patients with heart failure. C1 Univ Alabama, Div Gerontol & Geriatr Med, Dept Med, Sch Med,Dept Epidemiol & Int Hlth, Birmingham, AL 35487 USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Birmingham, AL 35487 USA. Univ Alabama, Dept Biostat, Sch Publ Hlth, Ctr Aging, Birmingham, AL 35487 USA. Univ Alabama, Ctr Outcome & Effectiveness Res & Educ, Birmingham, AL 35487 USA. Birmingham Vet Affairs Med Ctr, Sect Geriatr Heart Failure Clin, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. RP Ahmed, A (reprint author), 1530 3rd Ave S,CH-19, Birmingham, AL 35294 USA. RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 NR 33 TC 22 Z9 22 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD JUL PY 2002 VL 95 IS 7 BP 703 EP 710 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 574CT UT WOS:000176871400010 PM 12144075 ER PT J AU Wang, XY Mori, T Sumii, T Lo, EH AF Wang, XY Mori, T Sumii, T Lo, EH TI Hemoglobin-induced cytotoxicity in rat cerebral cortical neurons - Caspase activation and oxidative stress SO STROKE LA English DT Article DE apoptosis; cerebral hemorrhage; free radicals; neuroprotection; stroke; rats ID INDUCED CELL-DEATH; INTRACEREBRAL HEMORRHAGE; DNA FRAGMENTATION; ENDOTHELIAL-CELLS; NERVOUS-SYSTEM; APOPTOSIS; OXYHEMOGLOBIN; INHIBITION; BRAIN; ISCHEMIA AB Background and Purpose-Apoptotic-like pathways may contribute to brain cell death after intracerebral hemorrhage. In this study, we used a simplified in vitro model of hemoglobin neurotoxicity to map the caspase cascades involved and to document the role of oxidative stress. Methods-Primary neuronal cultures were obtained from rat cerebral cortex and exposed to hemoglobin to induce cell death. Cytotoxicity was assessed via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase (LDH assay). Activation of caspase-3, -8, and -9 was measured by Western blot and enzyme activity assays. Various caspase inhibitors (zVADfmk, zDEVDfmk, zIETDfmk, and zLEHDfmk) were tested for neuroprotective efficacy. The role of oxidative stress was assessed with the use of U83836E as a potent scavenger of free radicals. Results-Exposure of primary cortical neurons to hemoglobin induced a dose- and time-dependent cytotoxicity. Western blots showed upregulation of cleaved caspase-3. Enzyme assays showed an increase in caspase-9-like and caspase-3-like activity. However, caspase inhibition did not result in neuroprotection. In contrast, the free radical scavenger U83836E significantly reduced hemoglobin-induced neuronal death. Combination treatment with both U83836E and the broad spectrum caspase inhibitor zVADfmk did not yield additional protection. Conclusions-Upstream and downstream caspases were upregulated after hemoglobin-induced neurotoxicity in vitro, but only an antioxidant approach with a potent free radical scavenger significantly improved neuronal survival. These data suggest that in addition to the activation of caspase cascades, parallel pathways of oxidative stress may predominate in this model of hemoglobin neurotoxicity. C1 Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA USA. Harvard Med Sch, Program Neurosci, Charlestown, MA USA. RP Wang, XY (reprint author), Harvard Med Sch, Dept Neurol, Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01 NS-37074, R01 NS-38731, R01 NS-40529] NR 42 TC 91 Z9 93 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2002 VL 33 IS 7 BP 1882 EP 1888 DI 10.1161/01.STR.0000020121.41527.5D PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 571LY UT WOS:000176719900047 PM 12105370 ER PT J AU Bohmer, RMJ Newell, J Torchiana, DF AF Bohmer, RMJ Newell, J Torchiana, DF TI The effect of decreasing length of stay on discharge destination and readmission after coronary bypass operation SO SURGERY LA English DT Article ID CARDIAC OPERATIONS; INFORMATION; RECOVERY AB Background. Over the decade of the 1990s, hospital stay after operation declined in response to prospective payment and managed care. As a result, complications previously detected and treated in the hospital may have begun to occur after discharge. In addition, discharge to nursing homes and rehabilitation hospitals may have increased. To address these questions, we used a statewide database to look at the use of postacute care and the 30-day readmission and mortality after coronary bypass operation. Methods. A modification of the Commonwealth of Massachusetts Division of Health Care Finance and Policy discharge data to include a unique patient identifier allowed us to retrospectively track patient destination at discharge and study 30-day readmission to all hospitals in the state. Results. Over the 3-year period after the institution of the unique patient identifier (1993 to 1996), postoperative length of stay after coronary bypass operation decreased from 7.4 to 6 days (19%, P < .0005), but the 30-day readmission rate (17.7%) did not increase. Discharge to rehabilitation hospitals and skilled nursing facilities rose significantly (11.7% to 23.8%), especially in the Medicare population (17.2% to 38.5%). Mortality in the 30 days after discharge remained constant at 0.3%. Conclusions. A shorter postoperative length of stay did not appear to disadvantage coronary artery bypass patients by increasing their likelihood of readmission or death. Cost savings from reduced length of stay were offset by increased use of postacute services. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Comp Ctr, Boston, MA 02114 USA. Harvard Univ, Grad Sch Business Adm, Cambridge, MA 02138 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Fruit St,Room EDR-109, Boston, MA 02114 USA. NR 12 TC 31 Z9 31 U1 2 U2 2 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 JUL PY 2002 VL 132 IS 1 BP 10 EP 15 DI 10.1067/msy.2002.125358 PG 6 WC Surgery SC Surgery GA 577FU UT WOS:000177051500003 PM 12110788 ER PT J AU Warshaw, AL AF Warshaw, AL TI Forces for change in surgical training: Unintended consequences SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 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 JUL PY 2002 VL 132 IS 1 BP 100 EP 101 DI 10.1067/msy.2002.125788 PG 2 WC Surgery SC Surgery GA 577FU UT WOS:000177051500017 PM 12110802 ER PT J AU Bokhari, A Coull, BA Holmes, LB AF Bokhari, A Coull, BA Holmes, LB TI Effect of prenatal exposure to anticonvulsant drugs on dermal ridge patterns of fingers SO TERATOLOGY LA English DT Article ID FETAL-HYDANTOIN SYNDROME; PHALANGEAL HYPOPLASIA; TERATOGENICITY; ASYMMETRY; MALFORMATIONS; PREGNANCY; CHILDREN; LIMB; RISK AB Background: An altered frequency of specific dermal ridge patterns on fingertips, such as an increased number of arches, has been observed in children exposed in utero to anticonvulsants and other teratogens. Asymmetry of the distribution of dermal ridge patterns has been attributed to environmental exposures and genetic factors. Methods: We evaluated all of the dermal ridge patterns of 66 children who had been exposed to either the anticonvulsant phenytoin alone or phenytoin and phenobarbital. We determined the frequency of each pattern, concordance between the fingers on the left and right hands, sex differences and total ridge counts in the drug-exposed children and compared them to the findings in 716 unexposed comparison children. The frequency of each pattern was established in comparison to the most common type of pattern (ulnar loop), which showed that there were alterations in the frequency of arches, radial loops and whorls on specific fingers. Results: Eight (12.1%) of 66 children had three or more arch patterns, with all but one having been exposed to phenytoin and phenobarbital. Only one of these eight children was considered by the masked examiner to have fingernail hypoplasia. There was no evidence of asymmetry in the anticonvulsant-exposed children. There were minor differences in the distribution of total ridge count. Conclusions: Subtle differences in several dermal ridge patterns, not just arch patterns, were present in anticonvulsant-exposed children, primarily in those exposed to polytherapy: phenytoin and phenobarbital. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 11 Z9 11 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 2002 VL 66 IS 1 BP 19 EP 23 DI 10.1002/tera.10044 PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 570GW UT WOS:000176651400005 PM 12115776 ER PT J AU Manco-Johnson, MJ Grabowski, EF Hellgreen, M Kemahli, AS Massicotte, MP Muntean, W Peters, M Nowak-Gottl, U AF Manco-Johnson, MJ Grabowski, EF Hellgreen, M Kemahli, AS Massicotte, MP Muntean, W Peters, M Nowak-Gottl, U TI Laboratory testing for thrombophilia in pediatric patients - On behalf of the subcommittee for perinatal and pediatric thrombosis of the scientific and standardization committee of the International Society of Thrombosis and Haemostasis (ISTH) SO THROMBOSIS AND HAEMOSTASIS LA English DT Article C1 Mt States Hemophilia Ctr, Aurora, CO USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Sahlgrenska Hosp E, Dept Obstet Gynecol, Gothenburg, Sweden. Ankara Univ, Dept Pediat, TR-06100 Ankara, Turkey. Univ Toronto, Div Hematol Oncol, Toronto, ON, Canada. Graz Univ, Dept Pediat, Graz, Austria. Acad Med Ctr, Dept Pediat, Amsterdam, Netherlands. RP Nowak-Gottl, U (reprint author), Univ Munster, Paediat Hosp, Albert Schweitzer Str 33, D-48149 Munster, Germany. NR 4 TC 51 Z9 52 U1 0 U2 0 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 JUL PY 2002 VL 88 IS 1 BP 155 EP 156 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 574BE UT WOS:000176867800027 PM 12152657 ER EF