FN Thomson Reuters Web of Science™ VR 1.0 PT J AU de la Monte, SM Ganju, N Wands, JR AF de la Monte, SM Ganju, N Wands, JR TI Microtiter immunocytochemical ELISA assay SO BIOTECHNIQUES LA English DT Article ID CELL-SURFACE ANTIGENS; OXIDE SYNTHASE GENE; RECEPTOR; PHOSPHORYLATION; REGENERATION; ANTIBODIES; EXPRESSION; CELISA; IRS-1; RATS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brown Univ, Rhode Isl Hosp, Sch Med, Liver Res Ctr, 55 Claverick St, Providence, RI 02903 USA. EM delamonte@hot-mail.com FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-10102] NR 17 TC 23 Z9 23 U1 0 U2 0 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD JUN PY 1999 VL 26 IS 6 BP 1073 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 204HK UT WOS:000080758100015 PM 10376144 ER PT J AU Wetzler, M Dodge, RK Mrozek, K Carroll, AJ Tantravahi, R Block, AW Pettenati, MJ Le Beau, MM Frankel, SR Stewart, CC Szatrowski, TP Schiffer, CA Larson, RA Bloomfield, CD AF Wetzler, M Dodge, RK Mrozek, K Carroll, AJ Tantravahi, R Block, AW Pettenati, MJ Le Beau, MM Frankel, SR Stewart, CC Szatrowski, TP Schiffer, CA Larson, RA Bloomfield, CD TI Prospective karyotype analysis in adult acute lymphoblastic leukemia: The Cancer and Leukemia Group B experience SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; ACUTE LYMPHOCYTIC-LEUKEMIA; FOLLOW-UP; BCR-ABL; CLINICAL-SIGNIFICANCE; REMISSION INDUCTION; TRIAL; EXPRESSION; REGIMEN; CLASSIFICATION AB The Cancer and Leukemia Group B (CALGB) has been conducting a prospective cytogenetic companion study (CALGB 8461) to all CALGB treatment protocols for newly diagnosed adults with acute lymphoblastic leukemia (ALL). These protocols underwent a significant change in 1988 when a new intensive chemotherapy program was introduced (CALGB 8811). We asked whether karyotype continued to represent a significant prognostic factor in adult ALL patients after the change. A total of 256 patients had adequate pretreatment cytogenetic analyses: 67 before 1988 and 189 subsequently. The complete remission (CR) rate for the whole group was 80%. Patients with t(9;22), t(4;11), -7, or +8 had significantly lower probabilities of continuous CR and survival at 5 years (.11 and .12) than patients with a normal karyotype (.38 and .37) and patients with miscellaneous cytogenetic abnormalities (.52 and .49; P < .001 for each comparison). When analyzed by treatment period, the CR rate before CALGB 8811 was 63%; subsequently, it was 86% (P < .001). Patients with cytogenetic abnormalities other than t(9;22), t(4;11), -7, or +8 had better CR rates, disease-free survival (DFS), and survivals (P = .001, P = .04, and P = .004, respectively) after the change to the more intensive chemotherapy regimens. Patients with normal cytogenetics had improved CR rate but no improved DFS or survival, whereas no significant benefit for patients with t(9;22), t(4;11), -7, or +8 was seen. In a multivariate analysis, karyotype retained its prognostic significance for DFS but not for survival: it remained the most important factor for DFS. We conclude that cytogenetic analysis at diagnosis should be used to guide treatment decisions in adults with ALL. (C) 1999 by The American Society of Hematology. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Duke Univ, Med Ctr, Durham, NC USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Alabama, Birmingham, AL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. RP Wetzler, M (reprint author), Roswell Pk Canc Ctr, Div Med, Buffalo, NY 14263 USA. RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA16050, CA31946, CA77658] NR 34 TC 201 Z9 210 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 1999 VL 93 IS 11 BP 3983 EP 3993 PG 11 WC Hematology SC Hematology GA 200UM UT WOS:000080558500049 PM 10339508 ER PT J AU Kohn, SE Melvold, J AF Kohn, SE Melvold, J TI Effects of morphological complexity on phonological output deficits SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT Tennet IX - Theoretical and Experimental Neuropsychology Conference CY JUN 10-12, 1998 CL UNIV QUEBEC MONTREAL, MONTREAL, CANADA SP Univ Quebec Montreal, MRC Canada, Minist Ind & Commerce HO UNIV QUEBEC MONTREAL AB The single-word repetition of four aphasics (2 fluent and 2 nonfluent) was examined to explore the effects of derivational and inflectional affixes on phonological output disorders. While the performance of three of the four subjects declined with affixed (i.e., morphologically complex) targets, all four subjects showed similar effects of affix type on accuracy (e.g., inflectional morphology presented greater difficulty than derivational morphology). The error data, on the other hand, revealed differences between the fluent and nonfluent aphasics. For example, affix omissions were common errors for the nonfluent subjects, while affix substitutions were common for the fluent subjects. The implications for models of language processing, and the characterization of aphasic deficits, will be discussed. (C) 1999 Academic Press. C1 Moss Rehabil Res Inst, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kohn, SE (reprint author), Moss Rehabil Res Inst, Philadelphia, PA USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUN PY 1999 VL 40 IS 1 BP 156 EP 159 PG 4 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 208FU UT WOS:000080980900075 ER PT J AU Schwartz, DP Badier, JM Bihoue, P Bouliou, A AF Schwartz, DP Badier, JM Bihoue, P Bouliou, A TI Evaluation of a new MEG-EEG spatio-temporal localization approach using a realistic source model SO BRAIN TOPOGRAPHY LA English DT Article DE spatio-temporal localization; source model; MEG, EEG ID SHAPED HEAD; PRINCIPAL COMPONENTS; DIPOLE LOCALIZATION; ACCURACY; POTENTIALS; MRI AB This paper introduces a new technique for the localization of brain electromagnetic activity: a spatio-temporal fit (SPTF). This algorithm uses some properties of the principal component analysis and makes no assumptions about the number of sources to be located. It was applied to both simulated and real MEG/EEG signals and was compared to the well-known moving dipole fit (MDF) technique. For the simulations, we constructed extended sources, rather than single dipoles, that respected realistic anatomical and temporal properties. From these, we generated, under different noise conditions, MEG and EEG signals from which localization was performed. The real signals were auditory evoked fields. Firstly, it appeared that the SPTF was able to separate simultaneously activated sources even on strongly noisy signals while, most of the time, the MDF failed to give a clear description of the source configuration. Secondly, although we used the same head model to both generate the signals and locate the sources, localization for EEG was inferior to that for MEG. In conclusion, since in all test conditions the SPTF is found to be far superior to MDF,we suggest the use SPTF for the localization of equivalent dipoles. C1 Univ Rennes 1, UPRES EA Cortex Cerebral & Epilepsie, Rennes, France. Univ Mediterannee, Lab Neurophysiol & Neuropsychol, Marseille, France. Univ Mediterannee, INSERM, CJF 97 6, Marseille, France. RP Schwartz, DP (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St Rm 2301, Charlestown, MA 02129 USA. NR 34 TC 25 Z9 25 U1 1 U2 1 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0896-0267 J9 BRAIN TOPOGR JI Brain Topogr. PD SUM PY 1999 VL 11 IS 4 BP 279 EP 289 DI 10.1023/A:1022206603596 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221UF UT WOS:000081744600003 PM 10449259 ER PT J AU Runnels, JM Chen, N Ortel, B Kato, D Hasan, T AF Runnels, JM Chen, N Ortel, B Kato, D Hasan, T TI BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and beta(1) integrin expression in ovarian cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE BPD-MA; photosensitization; cellular adhesion; ECM proteins; OVCAR 3; ovarian cancer ID PHOTODYNAMIC THERAPY; VONWILLEBRAND-FACTOR; LIGHT DELIVERY; HEMATOPORPHYRIN; METASTASIS; MODULATION; BINDING; FIBRONECTIN; COLLAGEN; RELEASE AB Benzoporphyrin derivative monoacid (BPD-MA) photosensitization was examined for its effects on cellular adhesion of a human ovarian cancer cell line, OVCAR 3, to extracellular matrix (ECM) components. Mild BPD-MA photosensitization (similar to 85% cell survival) of OVCAR 3 transiently decreased adhesion to collagen IV, fibronectin, laminin and vitronectin to a greater extent than could be attributed to cell death. The loss in adhesiveness was accompanied by a loss of beta(1) integrin-containing focal adhesion plaques (FAPs), although beta(1) subunits were still recognized by monoclonal antibody directed against human beta(1) subunits, In vivo BPD-MA photosensitization decreased OVCAR 3 adhesiveness as well. Photosensitized adhesion was reduced in the presence of sodium azide and enhanced in deuterium oxide, suggesting mediation by singlet oxygen. Go-localization studies of BPD-MA and Rhodamine 123 showed that the photosensitizer was largely mitochondrial, but also exhibited extramitochondrial, intracellullar, diffuse cytosolic fluorescence. Taken together, these data show that intracellular damage mediated by BPD-PDT remote from the FAP site can affect cellular-ECM interactions and result in loss of FAP formation. This may have an impact on long-term effects of photodynamic therapy. The topic merits further investigation. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Gynecol Oncol Serv, Boston, MA 02114 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, WEL 224, Boston, MA 02114 USA. FU NIAMS NIH HHS [5RO1 AR40352] NR 64 TC 57 Z9 59 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1999 VL 80 IS 7 BP 946 EP 953 DI 10.1038/sj.bjc.6690448 PG 8 WC Oncology SC Oncology GA 197VK UT WOS:000080386300005 PM 10362101 ER PT J AU Mitsikostas, DD del Rio, MS Waeber, C Huang, ZH Cutrer, FM Moskowitz, MA AF Mitsikostas, DD del Rio, MS Waeber, C Huang, ZH Cutrer, FM Moskowitz, MA TI Non-NMDA glutamate receptors modulate capsaicin induced c-fos expression within trigeminal nucleus caudalis SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE AMPA kainate receptors; metabotropic glutamate receptors; meninges; trigeminal system; pain; migraine; headache ID METHYL-D-ASPARTATE; RAT SPINAL-CORD; GENE-RELATED PEPTIDE; SUBSTANCE-P; BRAIN-STEM; ELECTRICAL-STIMULATION; CORNEAL STIMULATION; GANGLION NEURONS; DRG NEURONS; CELL-DEATH AB 1 We examined the effects of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzol[f]quinoxaline-7-sulphonamide (NBQX), the kainate receptor antagonists gamma-(R-)-glutamylaminomethanesulphonic acid (GAMS) and 6,7,8,9-tetrahydro-5-nitro-1H-benz[g]indole-2,3-dione-3-oxime (NS-102), and the group III metabotropic glutamate receptor (mGluR) agonist 2-amino-4-phosphono-S-butanoic acid (L-AP4) on c-fos-like immunoreactivity (c-fos LI) in trigeminal caudalis (Sp5C), lateral reticular (LRt), medullary reticular (Md) and solitary tract (Sol) nuclei, after intracisternal injection of capsaicin in urethane anaesthetized Sprague-Dawley rats. 2 Few c-fos labelled cells were observed within Sp5C in capsaicin-vehicle treated animals. The number of positive c-fos cells increased by 17 fold after intracisternal capsaicin (5 nmol) administration. 3 Pretreatment with CNQX (0.02, 0.1, 0.6, 3 and 15 mg kg(-1)) or NBQX (0.01, 0.1 and 1 mg kg(-1)), administered intraperitoneally 15 min before capsaicin, significantly reduced labelled cells within Sp5C by a maximum of 45 and 34%, respectively. The number of c-fos LI cells within LRt, Md and Sol was not affected. Pretreatment with L-AP4 (1, 3 and 10 mg kg(-1)) decreased the number of Sp5C c-fos LI cells by a maximum of 30%, whereas GAMS (1 and 10 mg kg(-1)) and NS-102 (1 and 5 mg kg(-1)) did not show any significant effect. 4 These results suggest that blockade of AMPA receptors, but not kainate receptors, or the activation of group III mGluRs, decrease the response of Sp5C neurons to trigeminovascular activation. Thus, in addition to NMDA receptors, mGluRs and AMPA receptors may modulate cephalic pain and may provide a potential therapeutic target for antimigraine drugs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS 01803, NS 35611, P01 NS035611] NR 71 TC 56 Z9 57 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUN PY 1999 VL 127 IS 3 BP 623 EP 630 DI 10.1038/sj.bjp.0702584 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204ZF UT WOS:000080796000006 PM 10401552 ER PT J AU Berkey, CS Frazier, AL Gardner, JD Colditz, GA AF Berkey, CS Frazier, AL Gardner, JD Colditz, GA TI Adolescence and breast carcinoma risk SO CANCER LA English DT Article DE breast carcinoma; adolescence; menarche; body fatness; height; growth rate; peak height velocity ID FULL TERM PREGNANCY; UNITED-STATES; NURSES HEALTH; CANCER RISK; ALCOHOL-CONSUMPTION; RELATIVE WEIGHT; BODY-SIZE; HEIGHT; WOMEN; DISEASE AB BACKGROUND. Breast carcinoma risk may be modified by early life factors, including physical growth and development, diet, and life-style factors of preadolescence and adolescence, as well as genetic factors. METHODS. The authors tested their hypothesis that adolescent growth and development are related to breast carcinoma incidence by evaluating 65,140 women who participated in the Nurses' Health Study. During 16 years of follow-up, 806 women were diagnosed with breast carcinoma prior to menopause, and another 1485 were diagnosed after menopause. Because adolescent growth was not directly observed in this cohort, the peak height growth velocity for each participant was estimated by using a model from another longitudinal study. Finally, Cox proportional hazards regression models were used to study associations between breast carcinoma incidence and adolescent factors in the Nurses' Health Study. RESULTS. Later menarche (relative risk [RR] = 0.52 for > 15 vs. less than or equal to 11 years) and more body fatness at age 10 years (RR = 0.60 for fattest vs, leanest) were associated with a decreased risk of premenopausal breast carcinoma. The risk of postmenopausal breast carcinoma was lower for girls with later menarche (RR = 0.80), more body fat at age 10 years (RR = 0.72), and shorter adult height (RR = 1.29 for greater than or equal to 61 vs. less than or equal to 62 inches). Higher peak height growth velocity, derived from these 3 variables, was associated with increased risk of both premenopausal (RR = 1.31 for highest vs. lowest quintile) and postmenopausal (RR = 1.40) breast carcinoma. These analyses controlled for birth cohort, other possible risk factors from the adolescent period, and family history. These associations persisted after controlling for age at the birth of a first child, parity, adult adiposity, and age at menopause. Post-hoc analyses suggested that, although childhood body fatness was associated with lower risk, increasing body fatness between ages 10 and 20 years was not protective against either premenopausal or postmenopausal breast carcinoma. CONCLUSIONS. Earlier menarche, extremely lean body mass at age 10 years, and taller adult height were predictive of elevated breast carcinoma risk. The same three factors were also predictive of higher peak growth velocities during adolescence, lending credence to the hypothesis that more rapid adolescent growth may increase the risk of breast carcinoma development. Cancer 1999;85:2400-9. (C) 1999 American Cancer Society. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkey, CS (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA62252, CA40356]; NIDDK NIH HHS [DK 46200] NR 43 TC 131 Z9 131 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1999 VL 85 IS 11 BP 2400 EP 2409 DI 10.1002/(SICI)1097-0142(19990601)85:11<2400::AID-CNCR15>3.0.CO;2-O PG 10 WC Oncology SC Oncology GA 199WR UT WOS:000080507500015 PM 10357411 ER PT J AU Wright, JE Pardo, M Tretyakov, A Alperin, WL Trites, D Rosowsky, A AF Wright, JE Pardo, M Tretyakov, A Alperin, WL Trites, D Rosowsky, A TI Pharmacokinetics, antibiotic activity and there distribution of FTS23 in SCC VII tumor-bearing mice (vol 42, pg 300, 1998) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Correction C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wright, JE (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1999 VL 43 IS 6 BP 522 EP 522 PG 1 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 188UP UT WOS:000079867300014 ER PT J AU Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Atienzar, M Vallejo, M AF Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Atienzar, M Vallejo, M TI Detection of genomically-tagged cancer cells in different tissues at different stages of tumor development: lack of correlation with the formation of metastasis SO CANCER LETTERS LA English DT Article DE experimental colon adenocarcinoma; detection of tumor cells; polymerase chain reaction; metastasis ID POLYMERASE-CHAIN-REACTION; CARCINOMA; COLON; DIAGNOSIS; MODEL; BLOOD; RAT AB Genetic detection of tumor cells in blood, lymphatic nodes or bone marrow using reverse transcription and polymerase chain reaction (PCR) is quite attractive because it allows the early diagnosis of cancer dissemination. Unfortunately, this type of detection strategy cannot be applied to solid parenchymas, because they usually share with tumor cells the mRNA markers. To avoid this impediment, we have developed an experimental model of cancer using cells with a genome-associated tag. DHD/K12-PROb cancer cells were stably transfected with pcDNA3.1CAT. Approximately 10(6) transfected cells (DHD-CAT cells) were injected subcutaneously into the chest of BD-UC rats. Animals were divided into 11 groups according to the time between injection of tumor cells and euthanasia. An additional 'untagged group' was injected with untransfected cells (DHD-Wild), Blood and tissues samples were collected after euthanasia, Macroscopic and microscopic analysis was done. To detect circulating tumor cells or their presence in peripheral organs, we performed PCR with nested primers to amplify chloramphenicol acetyl transferase-encoding (CAT-encoding) DNA sequences. The minimum number of cells that yielded detectable cells routinely was 2 in 10(6). No modification of cancer aggressiveness was observed in DHD-CAT cells. DHD-CAT cells were detected by PCR in lung from the ist week after inoculation, in liver, spleen and kidney from the 3rd week and in the blood from the 5th week, All animals analyzed 12 weeks after injection showed lung metastases. Metastases in liver, spleen or kidney, either microscopic or macroscopic, were never detected. We have developed an experimental model of cancer based on genomic tagging of tumor cells that allows the detection of small numbers of cells in all organs and the blood. The presence of cancer cells in parenchymas detected with molecular technology does not correlate with the development of clinically relevant metastases. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Hosp Gen Albacete, Serv Cirug Gen, Expt Res Unit, Albacete 02006, Spain. Hosp Gen Albacete, Dept Gen Surg, Albacete 02006, Spain. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Reprod Endocrine Unit, Boston, MA 02115 USA. RP Garcia-Olmo, D (reprint author), Hosp Gen Albacete, Serv Cirug Gen, Expt Res Unit, Falco S-N, Albacete 02006, Spain. RI Garcia-Olmo, Dolores C./L-5733-2014 NR 17 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 1 PY 1999 VL 140 IS 1-2 BP 11 EP 20 DI 10.1016/S0304-3835(99)00046-4 PG 10 WC Oncology SC Oncology GA 206FV UT WOS:000080867400002 PM 10403536 ER PT J AU Tang, W Willers, H Powell, SN AF Tang, W Willers, H Powell, SN TI p53 directly enhances rejoining of DNA double-strand breaks with cohesive ends in gamma-irradiated mouse fibroblasts SO CANCER RESEARCH LA English DT Article ID HOMOLOGOUS RECOMBINATION; REPAIR; INVOLVEMENT; CELLS; GENE; INACTIVATION; RADIATION; CAFFEINE; DAMAGE AB The p53 gene regulates the cell cycle response to DNA damage, which may allow time for adequate DNA repair, We asked whether p53 could directly increase the repair of defined double-strand breaks (DSBs) by nonhomologous end-joining in gamma-irradiated mouse embryonic fibroblasts with differing p53 status. By using an episomal plasmid reactivation assay; we found that presence of wild-type p53 enhanced rejoining of DSBs with short complementary ends of single-stranded DNA. p53 appeared to be directly involved in this regulation, because rejoining enhancement was dependent on the presence of nonspecific DNA binding activity as mediated by the COOH-terminal domain and was independent of transactivating function. We hypothesize that tumor cells lacking p53 and normal cells with nad-type p53 may use different pathways for repair of radiation-induced DSBs. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. Univ Hamburg, Inst Biophys & Radiobiol, D-20246 Hamburg, Germany. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA58985] NR 24 TC 74 Z9 77 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 JUN 1 PY 1999 VL 59 IS 11 BP 2562 EP 2565 PG 4 WC Oncology SC Oncology GA 203NA UT WOS:000080712700012 PM 10363973 ER PT J AU Oesterle, SN Hayase, M Baim, DS Teirstein, PS Ramee, SR Whitlow, PL Webb, J Virmani, R AF Oesterle, SN Hayase, M Baim, DS Teirstein, PS Ramee, SR Whitlow, PL Webb, J Virmani, R TI An embolization containment device SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE embolization; no reflow; coronary artery disease; vein graft; carotid artery disease ID SAPHENOUS-VEIN GRAFTS; PERCUTANEOUS CORONARY INTERVENTION; LONG-TERM; BYPASS GRAFTS; BALLOON ANGIOPLASTY; NO-REFLOW; DISTAL EMBOLIZATION; FOLLOW-UP; RECANALIZATION; STENT AB A coaxial catheter system for containment of distal embolization is described, Utilizing a novel 0.014" hypotube with a distal elastomeric occlusion balloon, the PercuSurge GuardWire functions as a guidewire while trapping distal embolization resulting from more proximal intervention. The particulate debris is evacuated with a single operator exchange aspiration catheter (Export catheter) prior to deflation of the distal occlusion balloon, This animal study confirmed the feasibility of concept, The system was easily delivered through tortuous coronary anatomy. The GuardWire served as an adequate rail for delivery of dilatation balloons and a multitude of stents, There was no evidence of deep wall damage from low-pressure inflation and apposition of the distal occlusion balloon, Cathet Cardiovasc. Intervent 47:243-254 1999, (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Scripps Clin, La Jolla, CA USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ British Columbia, St Pauls Hosp, Vancouver, BC V5Z 1M9, Canada. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Oesterle, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 35 TC 30 Z9 30 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD JUN PY 1999 VL 47 IS 2 BP 243 EP 250 DI 10.1002/(SICI)1522-726X(199906)47:2<243::AID-CCD25>3.0.CO;2-Q PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201AC UT WOS:000080571600025 PM 10376514 ER PT J AU Lorenzo, HK Susin, SA Penninger, J Kroemer, G AF Lorenzo, HK Susin, SA Penninger, J Kroemer, G TI Apoptosis inducing factor (AIF): a phylogenetically old, caspase-independent effector of cell death SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE mitochondria; cytochrome c ID MITOCHONDRIAL PERMEABILITY TRANSITION; ASCORBATE-GLUTATHIONE CYCLE; CERAMIDE-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; CYTOCHROME-C RELEASE; CD4(+) T-CELLS; HYPERSENSITIVE RESPONSE; NUCLEAR APOPTOSIS; OXIDATIVE STRESS; TOBACCO PLANTS AB Although much emphasis has been laid on the role of caspase in cell death, recent data indicate that, in many instances, mammalian cell death is caspase-independent. Thus, in many examples of mammalian cell death the 'decision' between death and life is upstream or independent of caspase activation. Similarly, it is unclear whether PCD of plants and fungi involves the activation of caspase-like enzymes, and no caspase-like gene has thus far been cloned in these phyla, Apoptosis inducing factor (AIF) is a new mammalian, caspase-independent death effector which, upon apoptosis induction, translocates from its normal localization, the mitochondrial intermembrane space, to the nucleus, Once in the nucleus, AIF causes chromatin condensation and large scale DNA fragmentation to fragments of similar to 50 kbp, The AIF cDNA from mouse and man codes for a protein which possesses three domains (i) an amino-terminal presequence which is removed upon import into the intermembrane space of mitochondria; (ii) a spacer sequence of approximately 27 amino acids; and (iii) a carboxyterminal 484 amino acid oxidoreductase domain with strong homology to oxidoreductases from other vertebrates (X. laevis), non-vertebrate animals (C.elegans, D. melanogaster), plants, fungi, eubacteria, and archaebacteria, Functionally important amino acids involved in the interaction with the prosthetic groups flavin adenine nucleotide and nicotinamide adenine nucleotide are strongly conserved between AIF and bacterial oxidoreductase, Several eukaryotes possess a similar domain organisation in their AIF homologs, making them candidates to be mitochondrial oxidoreductases as well as caspase-independent death effecters. The phylogenetic implications of these findings are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. CNRS, UPR 420, F-94801 Villejuif, France. Univ Toronto, Dept Med Biphys & Immunol, Amgen Inst, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Med Biphys & Immunol, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada. RP Kroemer, G (reprint author), 19 Rue Guy Moquet,BP 8, F-94801 Villejuif, France. RI Kroemer, Guido/B-4263-2013; Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 NR 77 TC 350 Z9 374 U1 0 U2 11 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 1999 VL 6 IS 6 BP 516 EP 524 DI 10.1038/sj.cdd.4400527 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 203YZ UT WOS:000080736900005 PM 10381654 ER PT J AU Hiyama, H Reeves, SA AF Hiyama, H Reeves, SA TI Role for cyclin D1 in UVC-induced and p53-mediated apoptosis SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE cyclin D1; UVC; p53; apoptosis; cell cycle ID CELL-CYCLE; ECTOPIC EXPRESSION; HUMAN FIBROBLASTS; S-PHASE; RADIATION; INHIBITOR; GROWTH; P53; MEDIATOR; ARREST AB DNA damaging agents such as ultraviolet (UV) induce cell cycle arrest followed by apoptosis in cells where irreparable damage has occurred. Here we show that during early phase G1 arrest which occurs in UV-irradiated human U343 glioblastoma cells, there are (1) decreases in cyclin D1 and cdk4 levels which parallel a loss of S-phase promoting cyclin D1/cdk4 complexes, and (2) increases in p53 and p21 protein levels. We also show that the late phase UV-induced apoptosis of U343 cells occurs after cell cycle re-entry and parallels the reappearance of cyclin D1 and cdk4 and cyclin D1/cdk4 complexes. These findings suggest that cyclin D1 can abrogate UV-induced G1 arrest and that the p53-mediated apoptosis that occurs in these cells is dependent an cyclin D1 levels. We examined these possibilities using U343 cells that ectopically express cyclin D1 and found that indeed cyclin D1 can overcome the cell cycle arrest caused by UV. Moreover, the appearance of p53 protein and the induction of apoptosis in UV-irradiated cells was found to be dependent on the level of ectopically expressed cyclin D1. These findings, therefore, indicate that expression of cyclin D1 following DNA damage is essential for cell cycle re-entry and p53-mediated apoptosis. C1 Massachusetts Gen Hosp, Ctr Neurosci, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Reeves, SA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Neurosurg Serv, 149 13th St, Charlestown, MA 02129 USA. NR 15 TC 22 Z9 24 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 1999 VL 6 IS 6 BP 565 EP 569 DI 10.1038/sj.cdd.4400524 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 203YZ UT WOS:000080736900010 PM 10381651 ER PT J AU Schatz, J Craft, S Koby, M Siegel, MJ Resar, L Lee, RR Chu, JY Launius, G Dadash-Zadehm, M DeBaun, MR AF Schatz, J Craft, S Koby, M Siegel, MJ Resar, L Lee, RR Chu, JY Launius, G Dadash-Zadehm, M DeBaun, MR TI Neuropsychologic deficits in children with sickle cell disease and cerebral infarction: Role of lesion site and volume SO CHILD NEUROPSYCHOLOGY LA English DT Article ID FRONTAL-LOBE INJURY; HYPERACTIVITY DISORDER; ABNORMALITIES; CHILDHOOD AB Little is known about the correlation between the location and size of cerebral infarction in children and neuropsychologic deficits. We related lesion location and volume on magnetic resonance exams to neuropsychologic performance in 28 children with cerebral infarcts due to sickle cell disease. Seventeen healthy siblings served as a comparison group. Children with anterior cerebral infarcts (n = 7) showed deficits in attention and executive skills, whereas children with more widespread cerebral infarcts (n = 18) showed additional deficits in spatial skills. The volume of cerebral infarction was associated with spatial and language performance, but minimally related to performance in other cognitive domains. The location and volume of cerebral infarction are both important for defining the type and magnitude of cognitive sequelae in childhood stroke. C1 Washington Univ, St Louis, MO USA. Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. Johns Hopkins Univ, Med Ctr, Dept Pediat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. St Louis Univ, Med Ctr, Dept Radiol, St Louis, MO 63110 USA. Sinai Hosp, Dept Pediat, Baltimore, MD 21215 USA. Washington Univ, Sch Med, Dept Pediat, Div Pediat Hematol Oncol, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), St Louis Childrens Hosp, Campus Box 8116,1 Childrens Pl, St Louis, MO 63110 USA. NR 32 TC 31 Z9 31 U1 1 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD JUN PY 1999 VL 5 IS 2 BP 92 EP 103 DI 10.1076/chin.5.2.92.3170 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 237ME UT WOS:000082659500002 ER PT J AU Duerinckx, AJ Perloff, JK Currier, JW AF Duerinckx, AJ Perloff, JK Currier, JW TI Arteriovenous fistulas of the circumflex and right coronary arteries with drainage into an aneurysmal coronary sinus SO CIRCULATION LA English DT Article C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Adult Congenital Heart Dis Ctr, Los Angeles, CA 90024 USA. RP Duerinckx, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Radiol, 11301 Wilshire Blvd,Mail Route W114,MRI Bldg 507, Los Angeles, CA 90073 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 1 PY 1999 VL 99 IS 21 BP 2827 EP 2828 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 201AZ UT WOS:000080573600018 PM 10351979 ER PT J AU Hishii, M Kurnick, JT Ramirez-Montagut, T Pandolfi, F AF Hishii, M Kurnick, JT Ramirez-Montagut, T Pandolfi, F TI Studies of the mechanism of cytolysis by tumour-infiltrating lymphocytes SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE tumour-infiltrating lymphocytes; cytotoxicity; perforin; Fas/CD95; FasL; Bcl-2 apoptosis ID T-CELL-RECEPTOR; MEDIATED CYTOTOXICITY; HUMAN-MELANOMA; FAS-LIGAND; CTL CLONES; IN-VIVO; GENE REARRANGEMENTS; INDUCED APOPTOSIS; IMMUNE-RESPONSE; LYTIC PATHWAYS AB In order to determine the mechanism of tumour destruction by tumour-infiltrating lymphocytes (TIL), we examined the ability of both CD4(+) and CD8(+) effector TIL, and TIL clones, to manifest granzyme-mediated and Fas-mediated destruction of tumour targets. In many in vitro studies TIL have been shown to manifest anti-tumour reactivity, yet many tumours escape immunological destruction. To investigate the role of Fas expression and the concomitant sensitivity to the inducibility of apoptotic death, we derived TIL from four melanomas and one glioma. The glioma, and all but one of the melanomas, expressed Fas, but Fas-mediated apoptosis could only be detected if the targets were treated with cyclohexamide. The melanomas and the glioma all expressed detectable cytoplasmic Bcl-2 protein, known to exert anti-apoptotic activity. Lysis of tumours by CD8-enriched cultures and CD8(+) clones was Ca2+-dependent and could not be modified by an anti-Fas MoAb. In CD4-enriched cultures or CD4(+) clones with cytotoxic potential against tumour cells, cytotoxicity was also Ca2+-dependent. As Ca2+-dependent cytotoxicity is usually the result of secretion of perforin/granzyme- B, we investigated the presence of perforin in cytotoxic CD4(+) clones and demonstrated the presence of granular deposits of this enzyme in some of the CD4(+) clones. Although an anti-Fas MoAb did not block the lysis of melanoma targets by CD4(+) clones, the examination of Fas-dependent targets demonstrated that these clones also had the potential to kill by the Fas/Fas ligand system. These data suggest that the predominant mechanism in tumour killing by TIL appears to be perforin-granzyme-dependent, and that the solid tumour cell lines we studied are less susceptible to Fas-mediated apoptosis. As non-apoptotic pathways may enhance tumour immunogenicity, exploitation of the perforin-granzyme-dependent cytotoxic T lymphocyte (CTL) pathways may be important for achieving successful anti-tumour responses. C1 Massachusetts Gen Hosp, Pathol Res Lab, Boston, MA 02114 USA. Catholic Univ Rome, Chair Semeiot Med, Rome, Italy. RP Pandolfi, F (reprint author), Viale Univ 37, I-00185 Rome, Italy. FU NCI NIH HHS [CA51345]; NHLBI NIH HHS [HL-43793] NR 60 TC 34 Z9 39 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUN PY 1999 VL 116 IS 3 BP 388 EP 394 PG 7 WC Immunology SC Immunology GA 217QU UT WOS:000081511100002 PM 10361224 ER PT J AU Duska, LR Penson, R Supko, JG Finkelstein, DM Makastorsis, T Gallagher, J Borden, K Goodman, A Fuller, AF Nikrui, N Seiden, MV AF Duska, LR Penson, R Supko, JG Finkelstein, DM Makastorsis, T Gallagher, J Borden, K Goodman, A Fuller, AF Nikrui, N Seiden, MV TI A phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for relapsed epithelial ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; CONTINUOUS INTRAVENOUS-INFUSION; PLATINUM-RESISTANT; CREMOPHOR EL; NONLINEAR PHARMACOKINETICS; RANDOMIZED TRIAL; ORAL ETOPOSIDE; CYCLOPHOSPHAMIDE; CISPLATIN; CARCINOMA AB A Phase I study of paclitaxel and doxorubicin administered as concurrent 96-h continuous i,v, infusion was performed to determine the maximum tolerated dose (MTD), principal toxicities, and pharmacokinetics of this combination in women with relapsed epithelial ovarian cancer. The paclitaxel dose was fixed at 100 mg/m(2) (25 mg/m(2)/day for 4 days). The dose of doxorubicin was escalated from 30 mg/m(2) (7.5 mg/m(2)/day for 4 days) in increments of 10 mg/m(2) until dose-limiting toxicity was observed. All patients received granulocyte colony-stimulating factor 5 mu g/kg/day prophylactically. Apparent steady-state plasma levels of both drugs were determined in the final cohort of patients treated at the MTD, A total of 17 patients received 52 cycles of therapy. The median age was 58 years, and all patients had previously received one to five different regimens (median, 2) of chemotherapy, including both platinum and paclitaxel, The treatment was tolerated well, with grade 1-2 nausea being the most frequent side effect (73% of cycles). Anemia, neutropenia, thrombocytopenia, and mucositis became dose limiting at the fourth dose level, defining the MTD of doxorubicin in this regimen as 50 mg/m(2). There were four partial responses and one complete response in 15 evaluable patients. Apparent steady-state plasma concentrations (mean +/- SD) of paclitaxel and doxorubicin in the three patients treated at the MTD were 33.9 +/- 12.5 nM and 15.7 +/- 1.3 nM, respectively. Paclitaxel and doxorubicin by continuous infusion is a well-tolerated and active chemotherapy regimen for recurrent ovarian cancer. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox Bldg 640,100 Blossom St, Boston, MA 02114 USA. NR 33 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1299 EP 1305 PG 7 WC Oncology SC Oncology GA 206MR UT WOS:000080883800007 PM 10389912 ER PT J AU Hampl, M Hampl, JA Reiss, G Schackert, G Saeger, HD Schackert, HK AF Hampl, M Hampl, JA Reiss, G Schackert, G Saeger, HD Schackert, HK TI Loss of heterozygosity accumulation in primary breast carcinomas and additionally in corresponding distant metastases is associated with poor outcome SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; ALLELIC LOSS; ATAXIA-TELANGIECTASIA; LUNG CARCINOMAS; CANCER; PROGRESSION; REGIONS; BRCA1; 16Q; IDENTIFICATION AB The occurrence of distant metastases is the most feared manifestation of breast cancer, often occurring years after the primary surgery and associated dth poor survival. The dominant metastatic clone is characterized by an accumulation of genetic alterations, but it is not actually known at what stage of the metastatic cascade these alterations have occurred, We investigated allelic losses during breast cancer progression in a series of 17 primary breast carcinomas and 22 corresponding brain, liver, lung, and bone metastases (mean metastasis-free interval, 31 months) by analyzing 19 microsatellite markers on seven breast cancer- or metastasis-related chromosomal regions and correlated the incidence of combined loss of heterozygosity (LOH) with metastasis-free and postmetastatic survival, We found that, in comparison with the corresponding primary tumor, additional LOH events are frequently found in metastases and that the incidence of combined LOH in the primary tumor, plus the occurrence of additional LOH events in the distant metastases, correlated significantly with decreased postmetastatic survival. Combined LOH of the three breast cancer-related chromosomal regions alone or in combination with allelic loss at the p53 gene region seems to have a specific influence on the aggressive behavior of metastases, We hypothesize that the occurrence of additional LOH events is either involved in termination of dormancy of micrometastatic tumor cells at distant organ sites or acquired during further progression of metastases. C1 Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Gen Thorac & Vasc Surg, D-01307 Dresden, Germany. Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Neurosurg, D-01307 Dresden, Germany. Tech Univ Dresden, Med Fac Carl Gustav Carus, Dept Surg Res, D-01307 Dresden, Germany. RP Hampl, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,M 457, Boston, MA 02115 USA. RI Reiss, Gunter/A-3423-2010 OI Reiss, Gunter/0000-0002-0918-5940 NR 42 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 1999 VL 5 IS 6 BP 1417 EP 1425 PG 9 WC Oncology SC Oncology GA 206MR UT WOS:000080883800022 PM 10389927 ER PT J AU Dinovo, EC Lee, KD Shin, WY AF Dinovo, EC Lee, KD Shin, WY TI Correlation study between four i-Stat portable analyzers. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Pathol & Lab Med Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A29 EP A29 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500207 ER PT J AU Hughes, MP Bankson, DD Schwartz, MW Sindelar, DK AF Hughes, MP Bankson, DD Schwartz, MW Sindelar, DK TI Comparison of the DSL murine leptin ELISA with the Linco RIA method. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Metab, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A85 EP A86 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500411 ER PT J AU Khoury, RH Sluss, PM AF Khoury, RH Sluss, PM TI Serum follistatin level adjusted for degree of ovarian stimulation as a predictor of IVF outcome. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A86 EP A86 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500413 ER PT J AU Lee, KD Shin, WY Dinova, EC AF Lee, KD Shin, WY Dinova, EC TI Comparison Study of Accu-Chek Advantage and Precision QID meters with i-Stat as reference method using same finger tip capillary blood. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A33 EP A33 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500221 ER PT J AU Lewandrowski, KB Dan, L AF Lewandrowski, KB Dan, L TI Effects of small sample volumes and interfering substances on two glucose meters. SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 1999 VL 45 IS 6 SU S BP A4 EP A4 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 202XB UT WOS:000080676500127 ER PT J AU Wang, ZG Yunis, D Irigoyen, M Kitchens, B Bottaro, A Alt, FW Alper, CA AF Wang, ZG Yunis, D Irigoyen, M Kitchens, B Bottaro, A Alt, FW Alper, CA TI Discordance between IgA switching at the DNA level and IgA expression at the mRNA level in IgA-deficient patients SO CLINICAL IMMUNOLOGY LA English DT Article DE B lymphocytes; immunodeficiency diseases; MHC; isotype switching; gene regulation ID B-CELLS; LYMPHOCYTES; IGG1; INDIVIDUALS; GENES AB IgA deficiency is a common immune disorder in Caucasians and is associated with certain MHC conserved extended haplotypes, such as [HLA-BS, SC01, DR3], which presumably carry a susceptibility gene(s). We applied a competitive digestion-circularization PCR method to quantitate the number of switch (S)mu to S alpha rearrangements in peripheral B cells from IgA-deficient subjects homozygous for this haplotype and compared their number with the productive C alpha mRNA level to determine C alpha gene expression in IgA-switched B cells. Two types of defects, low expression of both secreted and membrane forms of productive C alpha mRNA in IgA-switched B cells and impaired IgA switching, were characterized in IgA-deficient subjects homozygous for [HLA-B8, SC01, DR3]. The former defect was also found in another noncarrier subject. It may directly cause low IgA secretion and reflects a blockade in post-IgA switch differentiation of B cells. These results suggest that the heterogeneity of defects in IgA deficiency is not simply ascribable to MHC susceptibility genes. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Wang, ZG (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL29583] NR 22 TC 23 Z9 23 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 1999 VL 91 IS 3 BP 263 EP 270 DI 10.1006/clim.1999.4702 PG 8 WC Immunology SC Immunology GA 202DA UT WOS:000080635800003 PM 10370371 ER PT J AU Hosono, O Homma, T Kobayashi, H Munakata, Y Nojima, Y Iwamoto, A Morimoto, C AF Hosono, O Homma, T Kobayashi, H Munakata, Y Nojima, Y Iwamoto, A Morimoto, C TI Decreased dipeptidyl peptidase IV enzyme activity of plasma soluble CD26 and its inverse correlation with HIV-1 RNA in HIV-1 infected individuals SO CLINICAL IMMUNOLOGY LA English DT Article DE soluble CD26; dipeptidyl peptidase IV; HIV-RNA ID T-CELL ACTIVATION; HUMAN-IMMUNODEFICIENCY-VIRUS; SYSTEMIC LUPUS-ERYTHEMATOSUS; ADENOSINE-DEAMINASE; IMMUNE-RESPONSE; SELECTIVE LOSS; ANTIGEN; TAT; RECEPTOR; PROTEIN AB Human plasma contains soluble CD26/dipeptidyl peptidase IV (sCD26/DPPIV) although its physiological significance remains unclear. To determine whether the plasma sCD26 levels have clinical relevance in HIV-1 infected individuals, the concentration and DPPIV enzyme activity of plasma sCD26 were measured, While there is no significant difference between the plasma levels of sCD26 in 90 HIV-1 infected individuals and in 79 uninfected controls, specific DPPIV enzyme activity of sCD26 was significantly decreased in HIV-1 infected individuals (P < 0.0001). Specific DPPIV enzyme activity was correlated with the levels of CD4(+) T cells (r = 0.247; P < 0.02), CD8(+) T cells (r = 0.236; P < 0.03), and adenosine deaminase (r = 0.227; P < 0.05) and had an inverse correlation with HIV-1 RNA (Spearman's r = 0.474; P = 0.0012). Furthermore, recombinant sCD26 enhanced the in vitro PPD-induced response of lymphocytes from HIV-l infected individuals with decreased specific DPPIV enzyme activity. These results suggest that the specific DPPIV enzyme activity of plasma sCD26 may contribute to the immunopathogenesis of HIV infection. (C) 1999 Academic Press. C1 Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo 1080071, Japan. Univ Tokyo, Inst Med Sci, AIDS Res Ctr, Minato Ku, Tokyo 1080071, Japan. Univ Tokyo, Inst Med Sci, Dept Infect Dis, Minato Ku, Tokyo 1080071, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Morimoto, C (reprint author), Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, 4-6-1 Shirokanedai, Tokyo 1080071, Japan. NR 52 TC 17 Z9 17 U1 3 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUN PY 1999 VL 91 IS 3 BP 283 EP 295 DI 10.1006/clim.1999.4711 PG 13 WC Immunology SC Immunology GA 202DA UT WOS:000080635800005 PM 10370373 ER PT J AU Mayer, KH Boswell, S Goldstein, R Lo, W Xu, C Tucker, L DePasquale, MP D'Aquila, R Anderson, DJ AF Mayer, KH Boswell, S Goldstein, R Lo, W Xu, C Tucker, L DePasquale, MP D'Aquila, R Anderson, DJ TI Persistence of human immunodeficiency virus in semen after adding indinavir to combination antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; SEXUAL TRANSMISSION; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; SEROPOSITIVE MEN; DISEASE STAGE; TYPE-1; HIV-1; ZIDOVUDINE; INFECTION AB Changes in human immunodeficiency virus (HIV) type 1 concentration and protease genotype were evaluated in semen specimens from 22 HN-positive men before and 6 months after the addition of indinavir to dual nucleoside therapy. Seminal HIV was detected by polymerase chain reaction analysis for DNA or RNA for 59% of men before combination treatment and persisted at 6 months for 31% of the men who initially had seminal HIV detected (P = .026). The maximum levels of cell-free RNA, cell-associated RNA, and proviral DNA in semen before treatment and at 6 months were 400,000 and 10,000 copies/mL, 70,000 and 27,000 copies/mL, and 80,000 and 3,000 copies/mL, respectively. Three of the four men with persistent seminal DNA had plasma viral loads of >10,000 copies/mL before treatment. One patient who became intolerant to indinavir had seminal HN RNA detected by PCR analysis after 6 months. Although none of the cultures of semen specimens from the four men with PCR analysis-detectable seminal DNA after 6 months yielded HIV, indinavir resistance mutations were identified in a seminal leukocyte DNA specimen from one patient, and a second patient whose therapy was switched to saquinavir had different protease inhibitor resistance mutations in seminal and blood leukocyte DNA specimens. HIV-1 protease inhibitor resistance mutants may emerge in the semen of patients receiving combination therapy. C1 Mem Hosp Rhode Isl, Div Infect Dis, Pawtucket, RI 02860 USA. Massachusetts Gen Hosp, Fenway Community Hlth Ctr, Brigham & Womens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Univ, Providence, RI 02912 USA. RP Mayer, KH (reprint author), Mem Hosp Rhode Isl, Div Infect Dis, Pawtucket, RI 02860 USA. FU NIAID NIH HHS [AI29193]; NICHD NIH HHS [HD33276]; PHS HHS [A135564] NR 40 TC 70 Z9 71 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1999 VL 28 IS 6 BP 1252 EP 1259 DI 10.1086/514775 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 207CD UT WOS:000080917000012 PM 10451162 ER PT J AU Otto, MW AF Otto, MW TI Psychological interventions in the age of managed care: A commentary on medical cost offsets SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Editorial Material DE cost effectiveness; cost offset; managed care; psychotherapy; mental health; cognitive-behavioral therapy ID DEPRESSION; METAANALYSIS AB This article provides a commentary on the Chiles, Lambert, and Hatch (this issue) meta-analytic review of the medical cost-offset literature. Emphasis is placed on the impact of managed care on their findings and on the field. Under conditions of closely monitored and/ or restricted care, cost offsets may be more difficult to achieve. Moreover, recent research indicates that specialty care for mental health may be more costly than management by primary care physicians. However, specialty care is associated with more optimal outcomes and greater cost-effectiveness. Attention to the value of care (cost-effectiveness) will help ensure that psychological interventions compete well in current fiscal environments. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC-815, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SUM PY 1999 VL 6 IS 2 BP 239 EP 241 DI 10.1093/clipsy/6.2.239 PG 3 WC Psychology, Clinical SC Psychology GA 210PQ UT WOS:000081114200010 ER PT J AU Lipsky, BA Unowsky, J Zhang, H Townsend, L Talbot, GH AF Lipsky, BA Unowsky, J Zhang, H Townsend, L Talbot, GH TI Treating acute bacterial exacerbations of chronic bronchitis in patients unresponsive to previous therapy: Sparfloxacin versus clarithromycin SO CLINICAL THERAPEUTICS LA English DT Article ID LOWER RESPIRATORY-TRACT; DOUBLE-BLIND; MULTICENTER; MANAGEMENT AB The optimal antibiotic therapy for patients with acute bacterial exacerbations of chronic bronchitis (ABECB) who have failed to respond to previous oral antimicrobial therapy is not known; however, newer macrolide and fluoroquinolone antibiotics may be appropriate. This multicenter, randomized, double-masked, double-dummy study was undertaken to compare the efficacy and tolerability of sparfloxacin with those of clarithromycin in the treatment of ABECB. In 43 centers in the United States, 298 patients (52% male; age range, 19 to 92 years) were randomly allocated to receive a 400-mg loading dose of sparfloxacin, followed by 200 mg once daily, or clarithromycin 500 mg twice daily, for a total of 10 days. Signs and symptoms of ABECB were assessed at each of 4 visits, including a follow-up visit approximately 1 month after the completion of therapy. Efficacy was determined on the basis of the clinical and bacteriologic response rates in the clinically assessable population. Tolerability was assessed on the basis of patient reports, clinical evaluations, and laboratory tests. Of the 266 clinically assessable patients, 109 (85.2%) of 128 patients receiving sparfloxacin and 115 (83.3%) of 138 patients receiving clarithromycin had a clinically successful outcome (cure or improvement). The bacteriologic success rate (eradication of pathogen) was 88.9% (64 of 72 isolates) in the sparfloxacin group and 84.7% (83 of 98 isolates) in the clarithromycin group. Adverse events possibly or probably related to study drug included photosensitivity in 12 (8.3%) and rash in 6 (4.1%) of 145 patients in the sparfloxacin group, and diarrhea in 10 (6.5%), taste perversion in 9 (5.9%), and nausea in 8 (5.2%) of 153 patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of patients with ABECB unresponsive to previous oral antimicrobial therapy. The overall rate of adverse events was comparable for the 2 study drugs, but the types of events differed. C1 VA Puget Sound Hlth Care Syst, Gen Internal Med Clin 111M, Med Serv, Seattle, WA 98108 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Gen Internal Med Clin 111M, Med Serv, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 22 TC 7 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUN PY 1999 VL 21 IS 6 BP 954 EP 965 DI 10.1016/S0149-2918(99)80017-4 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 215BC UT WOS:000081361200004 PM 10440620 ER PT J AU Oettinger, MA AF Oettinger, MA TI V(D)J recombination: on the cutting edge SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article ID CODING JOINT FORMATION; RAG2 PROTEINS; IN-VITRO; DNA TRANSPOSITION; CLEAVAGE; COMPLEX; 12/23-RULE; INTEGRATION; INITIATION; SEQUENCES AB The vertebrate immune system has evolved an elegant mechanism for generating an enormous diversity in antigen receptor binding specificity from a limited amount of genetic information. Recent advances are rapidly increasing our understanding of this unusual site-specific DNA rearrangement that assembles the antigen receptor genes during lymphoid development. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM48026] NR 40 TC 44 Z9 44 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD JUN PY 1999 VL 11 IS 3 BP 325 EP 329 DI 10.1016/S0955-0674(99)80044-1 PG 5 WC Cell Biology SC Cell Biology GA 205AM UT WOS:000080799100005 PM 10395566 ER PT J AU Xavier, R Seed, B AF Xavier, R Seed, B TI Membrane compartmentation and the response to antigen SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID PROTEIN-TYROSINE KINASES; GPI-ANCHORED PROTEINS; T-CELL ACTIVATION; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; LIVING CELLS; RECEPTOR; CAVEOLAE; DOMAINS; SURFACE AB Antigen-receptor engagement is a complex, highly orchestrated rearrangement of signaling molecules at, and adjacent to, the plasma membrane. Recent discoveries have shown that the plasma membrane itself is differentiated into microdomains of distinct lipid constituents and that the affiliation of lipid-modified proteins with those domains has important implications for antigen-receptor function. Disruption of lipid microdomains by a variety of methods attenuates TCR signal transduction. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Xavier, R (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 49 TC 99 Z9 100 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1999 VL 11 IS 3 BP 265 EP 269 DI 10.1016/S0952-7915(99)80043-0 PG 5 WC Immunology SC Immunology GA 205AE UT WOS:000080798400005 PM 10375560 ER PT J AU Cutrer, FM O'Donnell, A AF Cutrer, FM O'Donnell, A TI Recent advances in functional neuroimaging SO CURRENT OPINION IN NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; TRANSCRANIAL MAGNETIC STIMULATION; MIGRAINE ATTACKS; CLASSIC MIGRAINE; HEADACHE; CORTEX; PAIN; AURA AB New functional imaging techniques, including positron emission tomography, transcranial magnetic stimulation and functional magnetic resonance imaging, promise to allow the noninvasive study of haemodynamic, metabolic and activation parameters during acute migraine attacks in humans. These techniques are currently being applied to the study of the transient neurologic symptoms of the aura, as well as the painful headache phase of migraine. This review summarizes the most recent of these studies and discusses how they relate to the prevailing theories of migraine pathophysiology. (C) 1999 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Partners Headache Ctr, Boston, MA 02114 USA. RP Cutrer, FM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Partners Headache Ctr, MGH VBK 905,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD JUN PY 1999 VL 12 IS 3 BP 255 EP 259 DI 10.1097/00019052-199906000-00003 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 251XD UT WOS:000083470900003 PM 10499170 ER PT J AU Menaker, GM Wrone, DA Williams, RM Moy, RL AF Menaker, GM Wrone, DA Williams, RM Moy, RL TI Treatment of facial rhytids with a nonablative laser: A clinical and histologic study SO DERMATOLOGIC SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; PHOTOAGED SKIN; HIGH-ENERGY; DERMABRASION; COLLAGEN AB BACKGROUND. Current facial resurfacing modalities (laser, chemical peels, and dermabrasion) remove the epidermis and thus cause open wounds which carry significant risks and extended recovery periods. The nonablative laser is a novel Nd: YAG system designed to alleviate facial rhytids without injuring the epidermis. This new modality may offer patients rhytid removal without the risk seen in currently used resurfacing techniques. OBJECTIVE. TO describe a novel nonablative laser system and assess its safety profile and efficacy. METHODS. Ten patients received laser treatments of their periocular rhytids and postauricular skin. Clinical variables (rhytid severity, hyperpigmentation, hypopigmentation, scarring, and level of discomfort) were assessed at 1 and 3 months posttreatment,:Postauricular skin biopsies were taken both pre- and posttreatment for histologic analysis; RESULTS. Patient discomfort was minimal. Three months post- treatment, 4 of 10 patients showed a one-point improvement in periocular rhytid severity when judged on a six-point scale. The results were not statistically significant. Biopsy analysis showed a small posttreatment increase in the amount of dermal collagen in three patients. A small decrease in collagen was noted in one patient. Three patients. also showed a small posttreatment increase in the degree homogenization of dermal collagen. No change from baseline was noted in other assessed histological parameters. Complications observed included hyperpigmentation in three patients and pitted scarring in three patients. CONCLUSIONS. The nonablative laser gave clinically subtle and statistically insignificant improvement-in rhytid severity. Unfortunately its use was associated with complications that included hyperpigmentation and scarring. This technology may eventually offer patients a new resurfacing option, but its efficacy and complication rate must be improved first. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Menaker, GM (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 70 Blossom St, Boston, MA 02114 USA. NR 14 TC 117 Z9 122 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD JUN PY 1999 VL 25 IS 6 BP 440 EP 444 DI 10.1046/j.1524-4725.1999.08158.x PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 204XL UT WOS:000080790600004 PM 10469089 ER PT J AU Gu, ZY Reynolds, EM Song, JH Lei, H Feijen, A Yu, LA He, WW MacLaughlin, DT van den Eijnden-van Raaij, J Donahoe, PK Li, E AF Gu, ZY Reynolds, EM Song, JH Lei, H Feijen, A Yu, LA He, WW MacLaughlin, DT van den Eijnden-van Raaij, J Donahoe, PK Li, E TI The type I serine threonine kinase receptor ActRIA (ALK2) is required for gastrulation of the mouse embryo SO DEVELOPMENT LA English DT Article DE activin; BMP; serine threonine kinase receptor; gene targeting; mesoderm formation; gastrulation; mouse ID GROWTH-FACTOR-BETA; BONE-MORPHOGENETIC PROTEIN-4; MESODERM FORMATION; DEVELOPMENTAL EXPRESSION; ACTIVIN RECEPTORS; VISCERAL ENDODERM; PRIMITIVE STREAK; STEM-CELLS; GENE; INDUCTION AB ActRIA (or ALK2), one of the type I receptors of the transforming growth factor-beta (TGF-beta) superfamily, can bind both activin and bone morphogenetic proteins (BMPs) in conjunction with the activin and BMP type II receptors, respectively. In mice, ActRIA is expressed primarily in the extraembryonic visceral endoderm before gastrulation and later in both embryonic and extraembryonic cells during gastrulation. To elucidate its function in mouse development, we disrupted the transmembrane domain of ActRIA by gene targeting. We showed that embryos homozygous for the mutation were arrested at the early gastrulation stage, displaying abnormal visceral endoderm morphology and severe disruption of mesoderm formation. To determine in which germ layer ActRIA functions during gastrulation, we performed reciprocal chimera analyses. (1) Homozygous mutant ES cells injected into wild-type blastocysts were able to contribute to all three definitive germ layers in chimeric embryos. However, a high contribution of mutant ES cells in chimeras disrupted normal development at the early somite stage. (2) Consistent with ActRIA expression in the extraembryonic cells, wild-type ES cells failed to rescue the gastrulation defect in chimeras in which the extraembryonic ectoderm and visceral endoderm were derived from homozygous mutant blastocysts, Furthermore, expression of HNF4, a key visceral endoderm-specific transcription regulatory factor, was significantly reduced in the mutant embryos. Together, our results indicate that ActRIA in extraembryonic cells plays a major role in early gastrulation, whereas ActRIA function is also required in embryonic tissues during later development in mice. C1 Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Pediat Surg Res Lab, Boston, MA 02114 USA. Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. RP Li, E (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD1332]; NIGMS NIH HHS [GM52106] NR 48 TC 159 Z9 168 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 11 BP 2551 EP 2561 PG 11 WC Developmental Biology SC Developmental Biology GA 208YF UT WOS:000081019500023 PM 10226013 ER PT J AU Xavier-Neto, J Neville, CM Shapiro, MD Houghton, L Wang, GF Nikovits, W Stockdale, FE Rosenthal, N AF Xavier-Neto, J Neville, CM Shapiro, MD Houghton, L Wang, GF Nikovits, W Stockdale, FE Rosenthal, N TI A retinoic acid-inducible transgenic marker of sino-atrial development in the mouse heart SO DEVELOPMENT LA English DT Article DE mouse embryo; heart; sinus venosa; atrium; ventricle; retinoic acid ID ISOMYOSIN EXPRESSION PATTERNS; CARDIOMYOGENIC CELL LINEAGES; CHAMBER-SPECIFIC EXPRESSION; CHICKEN HEART; QUAIL EMBRYO; RXR-ALPHA; IMMUNOHISTOCHEMICAL ANALYSIS; MORPHOGENESIS; GENE; DIFFERENTIATION AB To study the specification of inflow structures in the heart we generated transgenic animals harboring the human alkaline phosphatase (HAP) gene driven by the proximal 840 bp of a quail SMyHC3 promoter, In transgenic mice, the SMyHC3-HAP reporter was expressed in posterior heart precursors at 8.25 dpc, in sinus venosa and in the atrium at 8.5 and 9.0 dpc, and in the atria from 10.5 dpe onwards. SMyHC3-HAP transgene expression overlapped synthesis and endogenous response to retinoic acid (RA) in the heart, as determined by antibodies directed against a key RA synthetic enzyme and by staining of RAREhsplacZ transgenic animals. A single pulse of all-trans RA administered to pregnant mice at 7.5, but not after 8.5, dpc induced cardiac dismorphology, ranging from complete absence of outflow tract and ventricles to hearts with reduced ventricles expressing both SMyHC3-HAP and ventricular markers. Blockade of RA synthesis with disulfiram inhibited RA-induced transcription and produced hearts lacking the atrial chamber. This study defines a novel marker for atrial-restricted transcription in the developing mouse heart. It also suggests that atrial-specific gene expression is controlled by localized synthesis of RA, and that exclusion of RA from ventricular precursors is essential for correct specification of the ventricles. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Sao Paulo, Fac Med, Inst Coracao, Mol Biol Lab, BR-05403000 Sao Paulo, Brazil. Harvard Univ, Museum Comparat Zool, Cambridge, MA 02138 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Rosenthal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG12316, AG14811]; NIAMS NIH HHS [AR41929] NR 42 TC 70 Z9 71 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 12 BP 2677 EP 2687 PG 11 WC Developmental Biology SC Developmental Biology GA 215DG UT WOS:000081366200010 PM 10331979 ER PT J AU Vyas, P McDevitt, MA Cantor, AB Katz, SG Fujiwara, Y Orkin, SH AF Vyas, P McDevitt, MA Cantor, AB Katz, SG Fujiwara, Y Orkin, SH TI Different sequence requirements for expression in erythroid and megakaryocytic cells within a regulatory element upstream of the GATA-1 gene SO DEVELOPMENT LA English DT Article DE GATA-1; cis-elements; cell lineage; transcriptional regulation; hematopoiesis; mouse ID TRANSCRIPTION FACTOR GATA-1; BINDING PROTEINS; TESTIS PROMOTER; MICE LACKING; STEM-CELLS; HEMATOPOIESIS; DOMAIN; MOUSE; LINEAGES; LEUKEMIA AB The lineage-restricted transcription factor GATA-1 is required for differentiation of erythroid and megakaryocytic cells, We have localized a 317 base pair cis-acting regulatory element, HS I, associated with a hematopoietic-specific DNase I hypersensitive site, which lies approx. 3.7 kilobases upstream of the murine hematopoietic-specific GATA-1 IE promoter. HS I directs high-level expression of reporter GATA-1/lacZ genes to primitive and definitive erythroid cells and megakaryocytes in transgenic mice. Comparative sequence analysis of HS I between human and mouse shows approx. 63% nucleotide identity with a more conserved core of 169 base pairs (86% identity). This core contains a GATA site separated by 10 base pairs from an E-box motif, The composite motif binds a multi-protein hematopoietic-specific transcription factor complex: which includes GATA-1, SCL/tal-1, E2A, Lmo2 and Ldb-1, Point mutations of the GATA site abolishes HS I function, whereas mutation of the E-box motif still allows reporter gene expression in both lineages. Strict dependence of HS I activity on a GATA site implies that assembly of a protein complex containing a GATA-factor, presumably GATA-1 or GATA-2, is critical to activating or maintaining its function. Further dissection of the 317 base pair region demonstrates that, whereas all 317 base pairs are required for expression in megakaryocytes, only the 5' 62 base pairs are needed for erythroid-specific reporter expression. These findings demonstrate differential lineage requirements for expression within the HS I element. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Hematol Oncol, Boston, MA 02115 USA. FU Medical Research Council [MC_U137961146]; NHLBI NIH HHS [K08-T32HL07623] NR 41 TC 110 Z9 110 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1999 VL 126 IS 12 BP 2799 EP 2811 PG 13 WC Developmental Biology SC Developmental Biology GA 215DG UT WOS:000081366200020 PM 10331989 ER PT J AU Feinbaum, R Ambros, V AF Feinbaum, R Ambros, V TI The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events in Caenorhabditis elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE heterochronic genes; lin-4 RNA; LIN-14; developmental timing; C-elegans ID HETEROCHRONIC GENES CONTROL; TEMPORAL PATTERN-FORMATION; C-ELEGANS; NEMATODE; PROTEIN; SWITCH; EXPRESSION; SEQUENCES; MUTANTS; ENCODES AB The lin-4 gene encodes a small RNA that is required to translationally repress lin-14 toward the end of the first larval stage of Caenorhabditis elegans development. To determine if the timing of LIN-14 protein down-regulation depends on the temporal profile of lin-4 RNA level, we analyzed the stage-specificity of lin-4 RNA expression during wild-type development and examined the phenotypes of transgenic worms that overexpress lin-4 RNA during the first larval stage. We found that lin-4 RNA first becomes detectable at approximately 12 h of wild-type larval development and rapidly accumulates to nearly maximum levels by 16 h. This profile of lin-4 RNA accumulation corresponded to the timing of LIN-14 protein down-regulation. Transgenic strains that express elevated levels of lin-4 RNA prior to 12 h of development display reduced levels of LIN-14 protein and precocious phenotypes consistent with abnormally early loss of lin-14 activity. These results indicate that the temporal profile of lin-4 RNA accumulation specifies the timing of LIN-14 down-regulation and thereby controls the timing of postembryonic developmental events. (C) 1999 Academic Press. C1 Dartmouth Coll, Dept Sci Biol, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Ambros, V (reprint author), Dartmouth Coll, Dept Sci Biol, Hanover, NH 03755 USA. FU NIGMS NIH HHS [GM15396, GM34028] NR 26 TC 104 Z9 106 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUN 1 PY 1999 VL 210 IS 1 BP 87 EP 95 DI 10.1006/dbio.1999.9272 PG 9 WC Developmental Biology SC Developmental Biology GA 207CN UT WOS:000080918000007 PM 10364429 ER PT J AU Griffin, ME Marcucci, MJ Cline, GW Bell, K Barucci, N Lee, D Goodyear, LJ Kraegen, EW White, MF Shulman, GI AF Griffin, ME Marcucci, MJ Cline, GW Bell, K Barucci, N Lee, D Goodyear, LJ Kraegen, EW White, MF Shulman, GI TI Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade SO DIABETES LA English DT Article; Proceedings Paper CT 58th Annual Meeting and Scientific Session of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, ILLINOIS SP Amer Diabet Assoc ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; SKELETAL-MUSCLE; GLUCOSE-METABOLISM; RAT; EXPRESSION; NIDDM AB To examine the mechanism by which free fatty acids (FFAs) induce insulin resistance in vivo, awake chronically catheterized rats underwent a hyperinsulinemic-euglycemic clamp with or without a 5-h preinfusion of lipid/heparin to raise plasma FFA concentrations. Increased plasma FFAs resulted in insulin resistance as reflected by a similar to 35% reduction in the glucose infusion rate (P < 0.05 vs. control). The insulin resistance was associated with a 40-50% reduction in C-13 nuclear magnetic resonance (NMR)-determined rates of muscle glycogen synthesis (P < 0.01 vs, control) and muscle glucose oxidation (P < 0.01 vs. control), which in turn could be attributed to a similar to 25% reduction in glucose transport activity as assessed by 2-[1,2-H-3]deoxyglucose uptake in vivo (P < 0.05 vs. control). This lipid-induced decrease in insulin-stimulated muscle glucose metabolism was associated with 1) a similar to 50% reduction in insulin-stimulated insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity (P < 0.05 vs. control), 3) a blunting in insulin-stimulated IRS-1 tyrosine phosphorylation (P < 0.05, lipid-infused versus glycerol-infused), and 3) a fourfold increase in membrane-bound, or active, protein kinase C (PKC) theta (P < 0.05 vs. control). me conclude that acute elevations of plasma FFA levels for 5 h induce skeletal muscle insulin resistance in vivo via a reduction in insulin-stimulated muscle glycogen synthesis and glucose oxidation that can be attributed to reduced glucose transport activity. These changes are associated with abnormalities in the insulin signaling cascade and may be mediated by FFA activation of PKC theta. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Garvan Inst Med Res, Sydney, NSW, Australia. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Dept Internal Med, FMP 104,Box 208020,333 Cedar St, New Haven, CT 06520 USA. RI Bell-Anderson, Kim/A-5588-2009 FU NIDDK NIH HHS [P30 DK45735, R01 DK040936, R01 DK40936] NR 22 TC 749 Z9 784 U1 4 U2 35 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1999 VL 48 IS 6 BP 1270 EP 1274 DI 10.2337/diabetes.48.6.1270 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 200YM UT WOS:000080567900009 PM 10342815 ER PT J AU Ahroni, JH Boyko, EJ Forsberg, RC AF Ahroni, JH Boyko, EJ Forsberg, RC TI Clinical correlates at plantar pressure among diabetic veterans SO DIABETES CARE LA English DT Article ID FOOT PRESSURES; ULCERATION; RISK; AMPUTATION; PREVENTION; ULCERS; FEET AB OBJECTIVE - To assess the relationship between diabetes characteristics, medical history foot deformity, sensory neuropathy, and plantar foot pressure. RESEARCH DESIGN AND METHODS - There were 517 subjects from a cohort of diabetic veterans enrolled in a prospective study of risk factors for foot complications who contributed 1,017 limbs for study; We interviewed subjects to collect data on demographics, diabetes characteristics, and medical history. A research nurse practitioner performed a directed physical exam of the lower extremities, assessing foot deformities and including quantitative sensory testing with a 5.07 monofilament. In-shoe foot-pressure measurements were obtained with F-scan insoles on subjects wearing their own footwear while walking 10 m at their usual pace. RESULTS - In univariate analyses, significant associations were seen between at least one measure of plantar pressure and body mass, sex, race, age, insulin use, certain foot deformities, plantar callus, and sensory neuropathy. Diabetes duration, HbA(1c), and history of foot ulcer or amputation were unrelated to plantar pressure. In multiple regression analyses, body mass measured as log (weight),insulin use, white race, male sex, plantar callus, and diabetes duration were significantly related to certain pressures. Foot deformities were related primarily to forefoot pressures. With high pressure at two or more sites defined as the outcome, only body mass remained statistically significant as a predictor of this outcome in a backwards elimination logistic regression model. CONCLUSIONS - High in-shoe plantar pressure in diabetic subjects can be predicted in part from readily available clinical characteristics. The mechanisms by which these characteristics may be related to plantar pressure require further study. C1 Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Sect, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Clin Fac, Seattle, WA 98195 USA. RP Ahroni, JH (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 23 TC 47 Z9 49 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1999 VL 22 IS 6 BP 965 EP 972 DI 10.2337/diacare.22.6.965 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198WN UT WOS:000080447400016 PM 10372250 ER PT J AU Meyer, JH Elashoff, JD Lake, R AF Meyer, JH Elashoff, JD Lake, R TI Gastric emptying of indigestible versus digestible oils and solid fats in normal humans SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gastric emptying; fats; solid; liquid; lipolysis ID PANCREATIC INSUFFICIENCY; LIQUID MEAL; LIPIDS; INGESTION AB Recent scintigraphic studies indicate that lipolytic products in the small intestine do not inhibit gastric emptying of fat as potently as previously suggested by studies that compared a liquid indigestible oil with a solid digestible fat. The older studies left open the confounding possibility that solid fats emptied differently than liquid oil. We studied eight normal subjects who ingested four meals in which fat was (1) liquid, digestible Crisco oil, (2) liquid, indigestible sucrose polyester oil, (3) digestible, solid Crisco, and (4) indigestible, solid olestra, Fats were labeled with iodine-123, and their gastric emptying was followed with a gamma camera, Indigestible fats (whether liquid or solid) emptied consistently faster than digestible fats (P < 0.005), although differences were small. Solid fats emptied about as rapidly as oils in the first hour; but more slowly thereafter (P < 0.01). A comparison of present scintigraphic with older studies suggested that solid fats were not well tracked by duodenal, marker-perfusion techniques, which misled previous investigators. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Cedars Sinai Med Ctr, Dept Biostat, Los Angeles, CA 90048 USA. Sepulveda VA Med Ctr, Dept Nucl Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Meyer, JH (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Rm 105,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 14 TC 17 Z9 17 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 1999 VL 44 IS 6 BP 1076 EP 1082 DI 10.1023/A:1026699401535 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 211LM UT WOS:000081162600002 PM 10389676 ER PT J AU Turner, WM Turner, KH Reif, S Gutowski, WF Gastfriend, DR AF Turner, WM Turner, KH Reif, S Gutowski, WF Gastfriend, DR TI Feasibility of multidimensional substance abuse treatment matching: automating the ASAM Patient Placement Criteria SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE addiction; algorithm; automation; criteria; matching; substance abuse ID ADDICTION SEVERITY INDEX; ALCOHOL DEPENDENCE; JUDGMENT; REHABILITATION; INPATIENT; DECISION; PERSPECTIVE; NALTREXONE; READINESS; NALOXONE AB The Patient Placement Criteria published by the American Society of Addiction Medicine (ASAM Criteria) established a non-proprietary standard for matching substance use disorder patients to treatment settings. Methods: Data from 593 substance dependent adults who were assessed using the: first computerized implementation of the ASAM Criteria were analyzed to determine whether the level of care assignments showed significant differences on a variety of clinical measures. Results: The algorithm showed acceptable discrimination between each of three ASAM Levels of Care across numerous clinical subscales. Conclusions: It is feasible to implement complex, :multidimensional criteria for substance abuse treatment that may improve reliability and facilitate validity studies. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Delta Sigma Measurement & Decis Grp, Orleans, MA 02653 USA. RP Gastfriend, DR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Addict Serv, 16 Parkman St, Boston, MA 02114 USA. FU NIDA NIH HHS [DA08781] NR 49 TC 18 Z9 18 U1 1 U2 1 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 JUN 1 PY 1999 VL 55 IS 1-2 BP 35 EP 43 DI 10.1016/S0376-8716(98)00178-1 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 202MK UT WOS:000080656100004 PM 10402147 ER PT J AU Kraemer, KL Conigliaro, J Saitz, R AF Kraemer, KL Conigliaro, J Saitz, R TI Managing alcohol withdrawal in the elderly SO DRUGS & AGING LA English DT Review ID BLIND CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL; UNITED-STATES; DELIRIUM-TREMENS; LIVER-DISEASE; DRUG-THERAPY; CHLORDIAZEPOXIDE LIBRIUM; KINDLING HYPOTHESIS; OXAZEPAM KINETICS; CLINICAL-TRIAL AB The alcohol withdrawal syndrome is common in elderly individuals who are alcohol dependent and who decrease or stop their alcohol intake. While there have been few clinical studies to directly support or refute the hypothesis that withdrawal symptom severity, delirium and seizures increase with advancing age, several observational studies suggest that adverse functional and cognitive complications during alcohol withdrawal do occur more frequently in elderly patients. Most elderly patients with alcohol withdrawal symptoms should be considered for admission to an inpatient setting for supportive care and management, However, elderly patients with adequate social support and without significant withdrawal symptoms at presentation, comorbid illness or past history of complicated withdrawal may be suitable for outpatient management. Although over 100 drugs have been described for alcohol withdrawal treatment, there have been no studies assessing the efficacy of these drugs specifically in elderly patients. Studies in younger patients support benzodiazepines as the most efficacious therapy for reducing withdrawal symptoms and the incidence of delirium and seizure. While short-acting benzodiazepines, such as oxazepam and lorazepam, may be appropriate for elderly patients given the risk for excessive sedation from long-acting benzodiazepines, they may be less effective in preventing seizures and more prone to produce discontinuation symptoms if not tapered properly. To ensure appropriate benzodiazepine treatment, dose and frequency should be individualised with frequent monitoring, and based on validated alcohol withdrawal severity measures. Selected patients who have a history of severe or complicated withdrawal symptoms may benefit from a fixed schedule of benzodiazepine provided that medication is held for sedation. P-Blockers, clonidine, carbamazepine and haloperidol may be used as adjunctive agents to treat symptoms not controlled by benzodiazepines. Lastly, the age of the patient should not deter clinicians from helping the patient achieve successful alcohol treatment and rehabilitation. C1 Univ Pittsburgh, Sch Med, Ctr Res Healthcare, Div Gen Internal Med,Dept Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare System, Sect Gen Med, Pittsburgh, PA USA. Boston Univ, Sch Med, Boston Med Ctr,Clin Addict Res & Educ Unit, Gen Internal Med Sect,Dept Med, Boston, MA 02118 USA. RP Kraemer, KL (reprint author), Univ Pittsburgh, Sch Med, Ctr Res Healthcare, Div Gen Internal Med,Dept Med, MUH E820,200 Lothrop St, Pittsburgh, PA 15213 USA. FU CSAP SAMHSA HHS [1T15-SP07773]; NIAAA NIH HHS [5K08-AA00235, 5R01-AA10870] NR 178 TC 18 Z9 19 U1 2 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD JUN PY 1999 VL 14 IS 6 BP 409 EP 425 DI 10.2165/00002512-199914060-00002 PG 17 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 205JG UT WOS:000080817100002 PM 10408740 ER PT J AU Casasnovas, JM Larvie, M Stehle, T AF Casasnovas, JM Larvie, M Stehle, T TI Crystal structure of two CD46 domains reveals an extended measles virus-binding surface SO EMBO JOURNAL LA English DT Article DE CD46; measles virus; membrane cofactor protein; short consensus repeat; virus-receptor interaction ID MEMBRANE COFACTOR PROTEIN; ACCELERATING FACTOR CD55; COMPLEMENT ACTIVATION; RECEPTOR CD46; SOLUBLE CD46; DISTINCT; SITES; MCP; HEMAGGLUTININ; LIGAND AB Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide, The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 Angstrom resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface, Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition, A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46. C1 Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden. Harvard Univ, Sch Med, Grad Program Biol & Biomed Sci, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Stehle, T (reprint author), Massachusetts Gen Hosp, Lab Dev Immunol, 55 Fruit St, Boston, MA 02114 USA. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 NR 50 TC 124 Z9 126 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1999 VL 18 IS 11 BP 2911 EP 2922 DI 10.1093/emboj/18.11.2911 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205NA UT WOS:000080826400001 PM 10357804 ER PT J AU Sun, ZYJ Dotsch, V Kim, M Li, J Reinherz, EL Wagner, G AF Sun, ZYJ Dotsch, V Kim, M Li, J Reinherz, EL Wagner, G TI Functional glycan-free adhesion domain of human cell surface receptor CD58: design, production and NMR studies SO EMBO JOURNAL LA English DT Article DE CD58; glycosylation; immunology; nuclear magnetic resonance; protein structure ID FUNCTION-ASSOCIATED ANTIGEN-3; TRIPLE-RESONANCE NMR; HUMAN LYMPHOCYTES-T; HUMAN CD2; MOLECULE CD2; MONOCLONAL-ANTIBODY; ALLOGRAFT SURVIVAL; PROTEIN STRUCTURES; CRYSTAL-STRUCTURE; GLYCOPROTEIN CD2 AB A general strategy is presented here for producing glycan-free forms of glycoproteins without loss of function by employing apolar-to-polar mutations of surface residues in functionally irrelevant epitopes, The success of this structure-based approach was demonstrated through the expression in Escherichia coli of a soluble 11 kDa adhesion domain extracted from the heavily glycosylated 55 kDa human CD58 ectodomain. The solution structure was subsequently determined and binding to its counter-receptor CD2 studied by NMR. This mutant adhesion domain is functional as determined by several experimental methods, and the size of its binding site has been probed by chemical shift perturbations in NMR titration experiments. The new structural information supports a 'hand-shake' model of CD2-CD58 interaction involving the GFCC'C " faces of both CD2 and CD58 adhesion domains. The region responsible for binding specificity is most likely localized on the C, C' and C " strands and the C-C' and C'-C " loops on CD58. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Wagner, G (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Doetsch, Volker/D-5697-2011 FU NIAID NIH HHS [AI37581, AI21226] NR 65 TC 33 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1999 VL 18 IS 11 BP 2941 EP 2949 DI 10.1093/emboj/18.11.2941 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205NA UT WOS:000080826400004 PM 10357807 ER PT J AU Koipally, J Renold, A Kim, J Georgopoulos, K AF Koipally, J Renold, A Kim, J Georgopoulos, K TI Repression by Ikaros and Aiolos is mediated through histone deacetylase complexes SO EMBO JOURNAL LA English DT Article DE Aiolos; Ikaros; lymphocytes; repression mechanisms; Sin3-HDAC ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTIONAL REPRESSION; CENTROMERIC HETEROCHROMATIN; FUSION PARTNER; GENE; ACETYLATION; INTERACTS; PROTEIN; DOMAIN; RECRUITMENT AB Here we show that the lymphoid lineage-determining factors Ikaros and Aiolos can function as strong transcriptional repressors. This function is mediated through two repression domains and is dependent upon the promoter context and cell type, Repression by Ikaros proteins correlates with hypo-acetylation of core histones at promoter sites and is relieved by histone deacetylase inhibitors. Consistent with these findings, Ikaros and its repression domains can interact in vivo and in vitro with the mSin3 family of co-repressors which bind to histone deacetylases. Based on these and our recent findings of associations between Ikaros and Mi-2-HDAC, we propose that Ikaros family members modulate gene expression during lymphocyte development by recruiting distinct histone deacetylase complexes to specific promoters. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Grad Program Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Basel, Bioctr, Dept Biochem, CH-4056 Basel, Switzerland. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI33062] NR 50 TC 220 Z9 224 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1999 VL 18 IS 11 BP 3090 EP 3100 DI 10.1093/emboj/18.11.3090 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 205NA UT WOS:000080826400018 PM 10357820 ER PT J AU Delbaere, A Sidis, Y Schneyer, AL AF Delbaere, A Sidis, Y Schneyer, AL TI Differential response to exogenous and endogenous activin in a human ovarian teratocarcinoma-derived cell line (PA-1): Regulation by cell surface follistatin SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-29, 1998 CL NEW ORLEANS, LA SP Endocrine Soc ID FOLLICULAR GRANULOSA-CELLS; HEPARAN-SULFATE; BINDING PROTEIN; II RECEPTORS; INHIBIN; SUBUNIT; PROTEOGLYCANS; ANTAGONIZES; COMPLEXES; GROWTH AB The activin/follistatin system is implicated in growth and differentiation of various cell types. Follistatin (FS), through binding and neutralizing activin, plays a major role in the regulation of activin bioavailability. We previously reported that ovarian PA1 cells constitutively secrete FS and show a decreased proliferation rate in response to exogenous activin only if cell surface associated FS is first removed by heparin treatment. These observations suggest that cell-associated FS prevents exogenous activin from accessing its receptor. We hypothesized that cell surface FS would differentially regulate the bioavailability of endogenous and exogenous activin in these cells. To examine the effect of endogenous activin, PA1 cells were stably transfected with an activin beta(A)-subunit complementary DNA (cDNA). The proliferation rate of five activin-secreting clones was measured by [H-3]thymidine incorporation and compared with the proliferation rate of untransfected cells. In clones secreting levels of activin ranging from 22.6 +/- 7.1 to 42.4 +/- 9.9 ng/ml, proliferation was decreased by 31-72% at 96 h of culture, whereas one cell line secreting lower levels of activin (0.4 +/- 0.1 ng/ml) proliferated similarly to the untransfected cells, in which activin was not detectable. To further assess activin signaling, wild-type PA1 cells and activin-secreting clones were transiently transfected with an activin response element-luciferase re-porter construct. Basal luciferase activity was 6-fold higher in activin-secreting clones than in wild-type PA1 cells. Exogenous activin (100 ng/ml) increased the transcriptional response of wild-type PA1 cells by 3-fold but did not increase reporter activity in activin secreting clones. Interestingly, the transcriptional response in activin secreting clones was always greater than the basal or activin-stimulated response in wild-type cells. Furthermore, we found that FS was removed from the cell surface by lipofectamine used for these transfections. Therefore, these results show that activation of the luciferase reporter gene occurs under conditions in which proliferation is affected, suggesting that the antiproliferative effect of activin could be due to direct stimulation of activin signaling pathways. In summary, as opposed to exogenous activin, endogenous activin decreased proliferation of PA1 cells even in the presence of cell surface associated FS. These results are consistent with a model in which FS acts as a barrier for exogenous (endocrine-paracrine) but not for endogenous (autocrine) activin. In addition, the higher PA1 cell responsiveness to endogenous compared with exogenous activin, suggests that activin overexpression in PA1 cells may up-regulate an activin signaling component, or down-regulate an activin signaling inhibitor. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Schneyer, AL (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Bartlett Hall Exstens 5,Fruit St, Boston, MA 02114 USA. EM schneyer.alan@MGH.Harvard.edu FU NICHD NIH HHS [P30-HD-23138, U54HD29164, R01HD31894] NR 29 TC 25 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2463 EP 2470 DI 10.1210/en.140.6.2463 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400004 PM 10342830 ER PT J AU Dharmarajan, AM Hisheh, S Singh, B Parkinson, S Tilly, KI Tilly, JL AF Dharmarajan, AM Hisheh, S Singh, B Parkinson, S Tilly, KI Tilly, JL TI Antioxidants mimic the ability of chorionic gonadotropin to suppress apoptosis in the rabbit corpus luteum in vitro: A novel role for superoxide dismutase in regulating bax expression SO ENDOCRINOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; BCL-2 GENE FAMILY; RIBONUCLEIC-ACID LEVELS; RAT OVARY; PSEUDOPREGNANT RABBITS; FOLLICULAR ATRESIA; OXIDATIVE STRESS; CORPORA-LUTEA; REGRESSION; GRANULOSA AB We have recently reported that members of the bcl-2 gene family are expressed and estradiol regulated in rabbit luteal cells during corpus luteum (CL) regression, and that estradiol and hCG are effective inhibitors of apoptosis in the rabbit CL in vivo and in vitro. As Bcl-2 and related proteins are known to regulate levels of reactive oxygen species or their intermediates in cells as one possible mechanism to control apoptosis, the present studies were designed to examine if oxidative stress plays a role in luteal cell apoptosis during CL regression in the rabbit. In the first set of experiments, healthy CL obtained from day 11 pseudopregnant rabbits were incubated in serum-free medium for 2 h in the absence or presence of superoxide dismutase (SOD; 1.5-150 U/ml), ascorbic acid (1-100 mM), N-acetyl-L-cysteine (25 and 50 mM), or catalase (10-1000 U/ml). Cells within CL incubated in medium alone exhibited extensive apoptosis (examined by analysis of extracted DNA using 3'-end labeling), and this onset of apoptosis was blocked in a dose-dependent fashion by treatment with SOD, ascorbic acid, N-acetyl-L-cysteine, or catalase. In the second set of experiments, expression of bax and bcl-x in CL after in vitro treatment without and with 100 U/ml SOD was examined. Although SOD treatment did not alter the levels of bcl-x messenger RNA (mRNA) over the 2-h incubation period, this antioxidant enzyme significantly reduced the levels of bax mRNA in incubated CL. In the final set of experiments, we observed that expression of mitochondrial- or manganese-containing SOD was significantly increased by treatment of isolated CL with 1 mu g/ml hCG in. vitro, whereas bax mRNA levels were significantly reduced under the same culture conditions. Collectively, these data indicate that the gonadotropin-mediated inhibition of apoptosis in rabbit luteal cells involves enhanced expression of the oxidative stress response gene, manganese-containing SOD, whose protein product may then function to protect luteal cells directly from the damaging effect of reactive oxygen species and/or indirectly by acutely down-regulating expression of Bax, a prooxidant member of the Bcl-2 protein family. C1 Univ Western Australia, Dept Anat & Human Biol, Nedlands, WA 6907, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Dharmarajan, AM (reprint author), Univ Western Australia, Dept Anat & Human Biol, Nedlands, WA 6907, Australia. EM dharma@anhb.uwa.edu.au FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226] NR 51 TC 43 Z9 48 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2555 EP 2561 DI 10.1210/en.140.6.2555 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400016 PM 10342842 ER PT J AU Robles, R Tao, XJ Trbovich, AM Maravei, DV Nahum, R Perez, GI Tilly, KI Tilly, JL AF Robles, R Tao, XJ Trbovich, AM Maravei, DV Nahum, R Perez, GI Tilly, KI Tilly, JL TI Localization, regulation and possible consequences of apoptotic protease-activating factor-1 (Apaf-1) expression in granulosa cells of the mouse ovary SO ENDOCRINOLOGY LA English DT Article ID BCL-2 GENE FAMILY; CYTOCHROME-C; RAT OVARY; DEATH; CASPASE-3; BAX; MITOCHONDRIA; MEMBERS; CED-4 AB The recent characterization of apoptotic protease-activating factor-1 (Apaf-1) in vertebrates as a putative homolog of the Caenorhabditis elegans gene, ced-4, indicates that the third major arm of the C. elegans programmed cell death machinery has also been conserved through evolution. Although apoptosis is now known to be important for ovarian follicular atresia in vertebrates, nothing is known of the role of Apaf-1 in ovarian function. Herein we show by immunohistochemical analysis that Apaf-1 is abundant in granulosa cells of early antral follicles whereas in vivo gonadotropin priming completely suppresses Apaf-1 expression and granulosa cell apoptosis. Western blot analysis of fractionated protein extracts prepared from granulosa cells before and after in vitro culture without hormonal support to induce apoptosis indicated that mitochondrial cytochrome c release, a biochemical step required for the activation of Apaf-1, occurs in granulosa cells cultured in vitro. Moreover, Western blot analysis of procaspase-3 processing, a principal downstream event set in motion by activated Apaf-1, indicated that healthy granulosa cells possess almost exclusively the inactive (pro-) form of the enzyme whereas granulosa cells deprived of hormonal support rapidly process procaspase-3 to the active enzyme. Lastly, we show that serum-starved granulosa cells activate caspase-3-like enzymes both prior to and after nuclear pyknosis, as revealed by a single-cell fluorescent caspase activity assay. These data, combined with previous observations regarding the role of homologs of the two other C. elegans cell death regulatory genes, ced-9 (Bcl-2 family members) and ced-3 (caspases), in atresia fully support the hypothesis that granulosa cell apoptosis is precisely coordinated by all three major arms of a cell death program conserved through evolution. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. EM jtilly@partners.org NR 18 TC 53 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2641 EP 2644 DI 10.1210/en.140.6.2641 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400027 PM 10342853 ER PT J AU Morita, Y Tilly, JL AF Morita, Y Tilly, JL TI Segregation of retinoic acid effects on fetal ovarian germ cell mitosis versus apoptosis by requirement for new macromolecular synthesis SO ENDOCRINOLOGY LA English DT Article ID BCL-2 GENE FAMILY; RECEPTOR-ALPHA; X-RECEPTORS; VITAMIN-A; DIFFERENTIAL EXPRESSION; MUTANT MICE; RAT TESTIS; IN-VITRO; MOUSE; SPERMATOGENESIS AB Retinoic acid (RA), a naturally occurring metabolite of vitamin A, plays an essential role in regulating cellular growth, differentiation, and death in a variety of tissues, particularly during fetal development. However, essentially nothing is known of the effects of RA on fetal gametogenesis. Using a recently validated system of culturing murine fetal ovaries, herein we sought to characterize the actions of RA on female germ cell proliferation and apoptosis during oogenesis. In the absence of trophic hormone support, approximately 90% of the oogonia and oocytes present in fetal ovaries at the start of culture underwent apoptosis over a 72 h culture period (P < 0.05), whereas provision of 0.01-1 mu M RA dose dependently maintained germ cell numbers. In fact, ovaries cultured with 0.1 mu M RA for 72 h possessed approximately 30% more oogonia and oocytes as compared with the preculture mean number (P < 0.05). Additional experiments, using in situ DNA 3'-end-labeling and cellular morphology to assess apoptosis coupled with 5-bromo-2'-deoxyuridine incorporation to assess proliferation, revealed that RA acts as both a mitogen and a survival factor for female germ cells. Furthermore, the ability of RA to stimulate germ cell proliferation in cultured fetal ovaries was completely suppressed (P < 0.05) by cotreatment with inhibitors of transcription (alpha-amanitin, 0.1 mu g/ml) or protein synthesis (cycloheximide, 1.0 mu g/ml), whereas RC1-mediated suppression of germ cell apoptosis was not affected by cotreatment with either macromolecular synthesis inhibitor (P > 0.05). Moreover, cotreatment of fetal ovaries with 5 mu M LY294002, an inhibitor of phosphatidylinositol 3'-kinase, had no effect on RA-promoted germ cell maintenance (P > 0.05). By comparison, the antiapoptotic effects of insulin-like growth factor I on germ cells in cultured fetal ovaries were significantly attenuated by cotreating ovaries with LY294002 (P < 0.05) but not with alpha-amanitin or cycloheximide (P > 0.05). Importantly, the effect of RA on the female germ line was also observed in vivo because a single oral administration of 100 mg/kg RA to timed-pregnant female mice resulted in a significantly (P < 0.05) larger endowment of primordial oocytes in female offspring. That these actions were mediated, at least in part, by specific retinoid receptors was demonstrated by the finding of retinoic acid receptor protein in fetal female gonocytes, as assessed by immunohistochemical localization experiments. Collectively, these data indicate that RA can function, in vitro and in, vivo, as a potent germ cell survival factor and mitogen during fetal oogenesis in the mouse. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226]; NIEHS NIH HHS [R01-ES-08430] NR 49 TC 55 Z9 57 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2696 EP 2703 DI 10.1210/en.140.6.2696 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400034 PM 10342860 ER PT J AU Lee, MM Seah, CC Masiakos, PT Sottas, CM Preffer, FI Donahoe, PK Maclaughlin, DT Hardy, MP AF Lee, MM Seah, CC Masiakos, PT Sottas, CM Preffer, FI Donahoe, PK Maclaughlin, DT Hardy, MP TI Mullerian-inhibiting substance type II receptor expression and function in purified rat Leydig cells SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; SERTOLI CELLS; SEXUAL-DIFFERENTIATION; STEROIDOGENIC ENZYMES; TRANSGENIC MICE; TESTIS; FETAL; GENE; ANDROGEN AB Mullerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Mullerian duct involution during male sexual differentiation. Mice with null mutations of the MIS ligand or receptor develop Leydig cell hyperplasia and neoplasia in addition to retained Mullerian ducts, whereas MIS-overexpressing transgenic mice have decreased testosterone concentrations and Leydig cell numbers. We hypothesized that MIS directly modulates Leydig cell proliferation and differentiated function in the maturing testis. Therefore, highly purified rat Leydig and Sertoli cells were isolated to examine cell-specific expression, binding, and function of the MIS type II receptor. These studies revealed that this receptor is expressed abundantly in progenitor (21-day) and immature (35-day) Leydig cells as well as in Sertoli cells. Prepubertal progenitor Leydig cells exhibit high affinity (K-d = 15 nM), saturable binding of MIS. No binding, however, is detected with either peripubertal immature Leydig cells or Sertoli cells at either age. Moreover, progenitor, but not immature Leydig cells, respond to MIS by decreasing DNA synthesis. These data demonstrate that functional MIS type II receptors are expressed in progenitor Leydig cells and support the hypothesis that MIS has a direct role in the regulation of postnatal testicular development. C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Rockefeller Univ, New York, NY 10021 USA. Populat Council, New York, NY USA. RP Massachusetts Gen Hosp, Pediat Endocrine Unit, Bartlett Hall Extens 410,55 Fruit St, Boston, MA 02114 USA. EM mlee@helix.mgh.harvard.edu OI Lee, Mary/0000-0002-7204-4884 NR 50 TC 55 Z9 59 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1999 VL 140 IS 6 BP 2819 EP 2827 DI 10.1210/en.140.6.2819 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 198JB UT WOS:000080419400047 PM 10342873 ER PT J AU Hisnanick, JJ Kymn, KO AF Hisnanick, JJ Kymn, KO TI Modeling economies of scale: the case of US electric power companies SO ENERGY ECONOMICS LA English DT Article DE electricity; economies of scale ID TECHNOLOGICAL-CHANGE; PRODUCTIVITY; GENERATION AB Modeling and validating the existence of technical progress within the neoclassical production function specification has been facilitated through the translog functional form. However, attempts to separate out the effects of technical progress and returns to scale has been limited. This study develops and presents a model for testing the existence of these two separate effects using data from a sample of US electric power companies. The analysis found that for these electric utilities there existed increasing returns to scale and technical progress that was energy using but capital-neutral. However, scale effects were found to be a dominant factor in lessening the impact of declining average productivity. (C) 1999 Elsevier Science B.V. All rights reserved. C1 US Dept Vet Affairs, Washington, DC 20420 USA. W Virginia Univ, Coll Business & Econ, Dept Econ, Morgantown, WV 26505 USA. RP Hisnanick, JJ (reprint author), US Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20420 USA. NR 20 TC 10 Z9 10 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0140-9883 J9 ENERG ECON JI Energy Econ. PD JUN PY 1999 VL 21 IS 3 BP 225 EP 237 DI 10.1016/S0140-9883(98)00019-X PG 13 WC Economics SC Business & Economics GA 205AP UT WOS:000080799300003 ER PT J AU Rollins, BJ AF Rollins, BJ TI Monocyte chemoattractant protein-1: its roles in immune modulation and pathophysiology SO EUROPEAN CYTOKINE NETWORK LA English DT Article; Proceedings Paper CT Euroconference of Institut Pasteur on Chemokines and Their Receptors - From Basic Research to Therapeutic Intervention CY MAR 11-13, 1999 CL INST PASTEUR, PARIS, FRANCE HO INST PASTEUR ID ENDOTHELIAL-CELLS; TRANSGENIC MICE; GENE-EXPRESSION; MCP-1; GLOMERULONEPHRITIS; ATHEROSCLEROSIS; RECRUITMENT; NEPHRITIS; ANTIBODY; MODEL C1 Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med, Bldg D930,44 Binney St, Boston, MA 02115 USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD JUN PY 1999 VL 10 IS 2 BP 269 EP 271 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 214KV UT WOS:000081327900023 ER PT J AU Lackner, JR DiZio, P Jeka, J Horak, F Krebs, D Rabin, F AF Lackner, JR DiZio, P Jeka, J Horak, F Krebs, D Rabin, F TI Precision contact of the fingertip reduces postural sway of individuals with bilateral vestibular loss SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE posture; somatosensation; vestibular; haptic; proprioception ID MODEL AB Contact of the hand with a stationary surface attenuates postural sway in normal individuals even when the level of force applied is mechanically inadequate to dampen body motion. We studied whether subjects without vestibular function would be able to substitute contact cues from the hand for their lost labyrinthine function and be able to balance as well as normal subjects in the dark without finger contact. We also studied the relative contribution of sight of the test chamber to the two groups. Subjects attempted to maintain a tandem Romberg stance for 25 s under three levels of fingertip contact: no contact; light-touch contact, up to 1 N (approximate to 100 g) force; and unrestricted contact force. Both eyes open and eyes closed conditions were evaluated. Without contact, none of the vestibular loss subjects could stand for more than a few seconds in the dark without falling; all the normals could. The vestibular loss subjects were significantly more stable in the dark with light touch of the index finger than the normal subjects in the dark without touch. They also swayed less in the dark with light touch than when permitted sight of the test chamber without touch, and less with sight and touch than just sight. The normal subjects swayed less in the dark with touch than without, and less with sight and touch than sight alone. These findings show that during quiet stance light touch of the index finger with a stationary surface can be as effective or even more so than vestibular function for minimizing postural sway. C1 Brandeis Univ, Ashton Graybiel Spatial Orientat Lab, Waltham, MA 02454 USA. Brandeis Univ, Ctr Complex Syst, Waltham, MA 02254 USA. Brandeis Univ, Ashton Graybiel Spatial Orientat Lab, Waltham, MA 02254 USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Good Samaritan Hosp, Dow Neurol Sci Inst, Portland, OR 97210 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. RP Lackner, JR (reprint author), Brandeis Univ, Ashton Graybiel Spatial Orientat Lab, MS 033, Waltham, MA 02454 USA. EM lackner@brandeis.edu FU NIA NIH HHS [R01AG11255]; PHS HHS [H133G30041] NR 21 TC 92 Z9 95 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUN PY 1999 VL 126 IS 4 BP 459 EP 466 DI 10.1007/s002210050753 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 210CH UT WOS:000081087200002 PM 10422708 ER PT J AU Hu, M Dutt, J Arrunategui-Correa, V Baltatzis, S Foster, CS AF Hu, M Dutt, J Arrunategui-Correa, V Baltatzis, S Foster, CS TI Cytokine mRNA in BALB/c mouse corneas infected with herpes simplex virus SO EYE LA English DT Article DE cytokine gene expression; herpes simplex virus; keratitis; mouse; tetrandrine ID STROMAL KERATITIS; MESSENGER-RNA; TNF-ALPHA; T-CELLS; MICE; TETRANDRINE; IL-6; INTERLEUKIN-6; EXPRESSION; RESPONSES AB Purpose To investigate cytokine mRNA expression and the influence of acyclovir and tetrandrine on that expression in the corneas of mice infected with herpes simplex virus type 1 (HSV-1). Methods Male BALB/c mice were infected in the right cornea with HSV-1. The corneas were harvested from control normal mice and from untreated, acyclovir-treated and tetrandrine-treated mice 14 days after infection. The infected corneas of each group were divided into inflamed and uninflamed depending on clinical observation. After total mRNA extraction from the corneas, gene expression of interleukin 1 beta (IL-1 beta), IL-6, tumour necrosis factor alpha (TNF-alpha) and transforming growth factor (beta (TGF-beta) was analysed by reverse transcription polymerase chain reaction. Results No mRNA expression of the cytokines was found in normal corneas. IL-1 beta and TNF-alpha mRNA was seen in inflamed corneas, while mRNA expression of IL-6 and relatively weaker TGF-beta mRNA expression were found both in inflamed corneas and in infected but uninflamed corneas treated with acyclovir. TNF-alpha mRNA was present in the uninflamed corneas of tetrandrine-treated mice. No influence of either agent was found on TGF-beta gene expression. Conclusions The results suggest that local IL-1 beta and TNF-alpha. gene expression is required for corneal inflammation, whereas IL-6 and TGF-beta may exert antiviral and inflammation regulatory activities in HSV corneal infection. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol Serv,Rhoads Mol Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol Serv,Hilles Immunol Lab, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol Serv,Rhoads Mol Lab, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 9 Z9 12 U1 0 U2 0 PU ROYAL COLL OPHTHALMOLOGISTS PI LONDON PA 17 CORNWALL TERRACE, LONDON NW1 4QW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JUN PY 1999 VL 13 BP 309 EP 313 PN 3A PG 5 WC Ophthalmology SC Ophthalmology GA 215GV UT WOS:000081374300005 PM 10624423 ER PT J AU Lezza, AMS Mecocci, P Cormio, A Beal, MF Cherubini, A Cantatore, P Senin, U Gadaleta, MN AF Lezza, AMS Mecocci, P Cormio, A Beal, MF Cherubini, A Cantatore, P Senin, U Gadaleta, MN TI Mitochondrial DNA 4977 bp deletion and OH(8)dG levels correlate in the brain of aged subjects but not Alzheimer's disease patients SO FASEB JOURNAL LA English DT Article DE aging; mtDNA; deletions; mtDNA oxidative damage; neurodegenerative disease ID OXIDATIVE DAMAGE; NUCLEAR-DNA; STRESS; REGIONS; DECAY; SITES AB The levels of mitochondrial DNA 4977 bp deletion (mtDNA(4977)) and mitochondrial DNA 8'-hydroxy-2'-deoxyguanosine (OH(8)dG) were determined in the same samples from two brain areas of healthy subjects and Alzheimer's disease (AD) patients, A positive correlation between the age-related increases of mtDNA(4977) and of OH(8)dG levels was found in the brain of healthy individuals. On the contrary, in both brain areas of AD patients, mtDNA(4977) levels were very low in the presence of high OH(8)dG amounts. These results might be explained assuming that the increase of OH(8)dG above a threshold level, as in AD patients, implies consequences for mtDNA replication and neuronal cell survival. C1 Univ Bari, Dept Biochem & Mol Biol, I-70125 Bari, Italy. Univ Perugia, Dept Gerontol & Geriatr, I-06122 Perugia, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gadaleta, MN (reprint author), Univ Bari, Dept Biochem & Mol Biol, Via Orabona 4, I-70125 Bari, Italy. EM m.n.gadaleta@biologia.uniba.it OI Cormio, Antonella/0000-0002-6029-1722; Cherubini, Antonio/0000-0003-0261-9897 NR 34 TC 57 Z9 59 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 1999 VL 13 IS 9 BP 1083 EP 1088 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 200NZ UT WOS:000080547700013 PM 10336891 ER PT J AU Li, N Zhai, Y Oberley, TD AF Li, N Zhai, Y Oberley, TD TI Two distinct mechanisms for inhibition of cell growth in human prostate carcinoma cells with antioxidant enzyme imbalance SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE human prostate carcinoma; cell redox; cell cycle; microtubules; free radicals ID MANGANESE SUPEROXIDE-DISMUTASE; NIH/3T3 FIBROBLASTS; HAMSTER-KIDNEY; OVEREXPRESSION; GLUTATHIONE; LOCALIZATION; TUMOR; DIFFERENTIATION; MODULATION; EXPRESSION AB The purpose of the present study was to determine whether manganese superoxide dismutase (MnSOD) overexpression in DU145 human prostate carcinoma cells affected cell reduction-oxidation state (cell redox) and to correlate changes in cell redox status with cell cycle progression and plating efficiency. One MnSOD-overexpressing cell line had no change in other antioxidant enzymes (AEs) (nonadapted clone), whereas a second MnSOD-overexpressing cell line studied had an increase in catalase (CAT) activity (adapted clone). Correlation of biochemical studies with cell cycle studies suggested that heteroploidy observed in the nonadapted MnSOD-overexpressing cell line may be due to increased intracellular peroxides with resultant disruption of the microtubule network, while a decreased mitotic rate was associated with decreased ATP levels in mitosis. In contrast, the decrease in cell growth in the adapted cell line was demonstrated to be due to a decrease in plating efficiency. Our results demonstrate complex effects of AE imbalance on cell growth of DU145 prostate cancer cells. (C) 1999 Elsevier Science Inc. C1 William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. Univ Wisconsin, Grad Sch, Mol Biol Lab, Madison, WI 53706 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. NR 42 TC 23 Z9 23 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN PY 1999 VL 26 IS 11-12 BP 1554 EP 1568 DI 10.1016/S0891-5849(99)00024-6 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 210VY UT WOS:000081126400025 PM 10401622 ER PT J AU Andres, PG Friedman, LS AF Andres, PG Friedman, LS TI Epidemiology and the natural course of inflammatory bowel disease SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ACTIVE ULCERATIVE-COLITIS; POPULATION-BASED COHORT; COLORECTAL-CANCER RISK; TERM FOLLOW-UP; CROHNS-DISEASE; TRANSDERMAL NICOTINE; CIGARETTE-SMOKING; CLINICAL CHARACTERISTICS; SUSCEPTIBILITY LOCI; JEWISH POPULATION AB Ulcerative colitis and Crohn's disease are inflammatory disorders of the gastrointestinal tract that are distributed unevenly within populations and throughout the world. Although the exact causes of inflammatory bowel disease (IBD) remain unknown, study of the epidemiology of IBD has provided insight into pathogenesis. This article examines the geographic, ethnic, and other trends of IBD; risk factors (including genetic and environmental); and the natural history of IBD. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Blake 456D,55 Fruit St, Boston, MA 02114 USA. NR 125 TC 180 Z9 187 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 1999 VL 28 IS 2 BP 255 EP + DI 10.1016/S0889-8553(05)70056-X PG 28 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207TX UT WOS:000080952800002 PM 10372268 ER PT J AU Sands, BE AF Sands, BE TI Novel therapies for inflammatory bowel disease SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID TUMOR-NECROSIS-FACTOR; ACTIVE CROHNS-DISEASE; DISTAL ULCERATIVE-COLITIS; RANDOMIZED CONTROLLED TRIAL; CHIMERIC MONOCLONAL-ANTIBODY; KERATINOCYTE GROWTH-FACTOR; CD4(+) T-CELLS; INTERCELLULAR-ADHESION MOLECULE-1; METRONIDAZOLE PLUS CIPROFLOXACIN; PLATELET-ACTIVATING-FACTOR AB Recent advances in our understanding of the basic processes that contribute to inflammatory bowel disease have led to the identification of new targets for therapy Novel therapies, which include agents in development and those newly introduced for use in the clinic, include both traditional compounds and a growing number of biologic response modifiers. This article places these novel therapies within a pathophysiologic framework, highlighting completely new targets and therapeutic modalities. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 825A, Boston, MA 02114 USA. FU NIDDK NIH HHS [R03DK52845] NR 218 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD JUN PY 1999 VL 28 IS 2 BP 323 EP + DI 10.1016/S0889-8553(05)70059-5 PG 30 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 207TX UT WOS:000080952800005 PM 10372271 ER PT J AU Bracher, GA Manocha, AP DeBanto, JR Gates, LK Slivka, A Whitcomb, DC Bleau, BL Ulrich, CD Martin, SP AF Bracher, GA Manocha, AP DeBanto, JR Gates, LK Slivka, A Whitcomb, DC Bleau, BL Ulrich, CD Martin, SP TI Endoscopic pancreatic duct stenting to treat pancreatic ascites SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID THERAPY; SOMATOSTATIN; PSEUDOCYSTS; MANAGEMENT AB Background: Management of pancreatic ascites with conservative medical therapy or surgery has met with limited success. Decompression of the pancreatic ductal system through transpapillary stent placement, an alternative strategy, has been reported in only a handful of cases of pancreatic ascites. Methods: We reviewed all cases from 1994 to 1997 in which patients with pancreatic ascites underwent an endoscopic retrograde pancreatogram documenting pancreatic duct disruption with subsequent placement of a transpapillary pancreatic duct stent. Clinical end points were resolution of ascites and need for surgery. Results: There were 8 castes of pancreatic ascites in which a 5F or 7F transpapillary pancreatic duct stent was placed as the initial drainage procedure. Pancreatic ascites resolved in 7 of 8 patients (88%) within 6 weeks. Ascites resolved in the eighth patient, a poor candidate for surgery following placement of a 5 mm expandable metallic pancreatic stent. No infections, alterations in ductal-morphology, or other complications related to stent placement were noted. There was no recurrence of pancreatic ascites or duct disruption at a mean follow-up of 14 months. Conclusions: Our experience doubles the number of reported cases in which transpapillary pancreatic stent placement safely obviated the need for surgical intervention in the setting of pancreatic ascites. This therapeutic endoscopic intervention should be seriously considered in the initial management of patients with pancreatic ascites. C1 Univ Cincinnati, Med Ctr, Div Digest Dis, Dept Med, Cincinnati, OH 45267 USA. Univ Kentucky, Dept Med, Div Digest Dis & Nutr, Lexington, KY 40506 USA. Univ Pittsburgh, Dept Med, Div Gastroenterol & Hepatol, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Midwest Multicenter Pancreat Study Grp, Pittsburgh, PA USA. RP Martin, SP (reprint author), Univ Cincinnati, Med Ctr, Div Digest Dis, Dept Med, Box 670595,231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 27 TC 48 Z9 51 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUN PY 1999 VL 49 IS 6 BP 710 EP 715 DI 10.1016/S0016-5107(99)70287-7 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 204JE UT WOS:000080760100007 PM 10343214 ER PT J AU Spillare, EA Robles, AI Wang, XW Shen, JC Yu, CE Schellenberg, GD Harris, CC AF Spillare, EA Robles, AI Wang, XW Shen, JC Yu, CE Schellenberg, GD Harris, CC TI p53-mediated apoptosis is attenuated in Werner syndrome cells SO GENES & DEVELOPMENT LA English DT Article DE DNA helicase; XPB; XPD; p53 carboxy-terminal domain ID SYNDROME PROTEIN; DNA HELICASES; SYNDROME GENES; IN-VIVO; P53; LOCALIZATION; EXONUCLEASE; MODULATION; MUTATIONS; CANCER AB The WRN DNA helicase is a member of the DExH-containing DNA helicase superfamily that includes XPB, XPD, and BLM. Mutations in WRN are found in patients with the premature aging and cancer susceptibility syndrome known as Werner syndrome (WS). p53 binds to the WRN protein in vivo and in vitro through its carboxyl terminus. WS fibroblasts have an attenuated p53-mediated apoptotic response, and this deficiency can be rescued by expression of wild-type WRN. These data support the hypothesis that p53 can induce apoptosis through the modulation of specific DExH-containing DNA helicases and may have implications for the cancer predisposition observed in WS patients. C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182B, Seattle Div, Seattle, WA 98108 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 FU NIA NIH HHS [AG05427, AG12019] NR 29 TC 135 Z9 140 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JUN 1 PY 1999 VL 13 IS 11 BP 1355 EP 1360 DI 10.1101/gad.13.11.1355 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 205TM UT WOS:000080836700001 PM 10364153 ER PT J AU Paradis, S Ailion, M Toker, A Thomas, JH Ruvkun, G AF Paradis, S Ailion, M Toker, A Thomas, JH Ruvkun, G TI A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans SO GENES & DEVELOPMENT LA English DT Article DE insulin signaling; dauer; PDK1 activation; PDK-1; life span ID GLYCOGEN-SYNTHASE KINASE-3; DEPENDENT PROTEIN-KINASE; C-ELEGANS; DAUER FORMATION; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOINOSITIDE-3-OH KINASE; TRANSCRIPTION FACTOR; LARVAL DEVELOPMENT; INTERACTING GENES; FAMILY MEMBER AB An insulin receptor-like signaling pathway regulates Caenorhabditis elegans metabolism, development, and longevity. Inactivation of the insulin receptor homolog DAF-2, the AGE-1 PI3K, or the AKT-1 and AKT-2 kinases causes a developmental arrest at the dauer stage. A null mutation in the daf-16 Fork head transcription factor alleviates the requirement for signaling through this pathway. We show here that a loss-of-function mutation in pdk-1, the C. elegans homolog of the mammalian Akt/PKB kinase PDK1, results in constitutive arrest at the dauer stage and increased life span; these phenotypes are suppressed by a loss of function mutation in daf-16. An activating mutation in pdk-1 or overexpression of wild-type pdk-1 relieves the requirement for AGE-1 PI3K signaling. Therefore, pdk-1 activity is both necessary and sufficient to propagate AGE-1 PI3K signals in the DAF-2 insulin receptor-like signaling pathway. The activating mutation in pdk-1 requires akt-1 and akt-2 gene activity in order to suppress the dauer arrest phenotype of age-1. This indicates that the major function of C. elegans PDK1 is to transduce signals from AGE-1 to AKT-1 and AKT-2. The activating pdk-1 mutation is located in a conserved region of the kinase domain; the equivalent amino acid substitution in human PDK1 activates its kinase activity to toward mammalian Akt/PKB. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Boston Biomed Res Inst, Signal Transduct Grp, Boston, MA 02114 USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA075134, R01CA75134]; NIA NIH HHS [R01 AG014161, R01AG14161] NR 58 TC 266 Z9 277 U1 1 U2 11 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 JUN 1 PY 1999 VL 13 IS 11 BP 1438 EP 1452 DI 10.1101/gad.13.11.1438 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 205TM UT WOS:000080836700008 PM 10364160 ER PT J AU Tuncer, ZS Bernstein, MR Goldstein, DP Berkowitz, RS AF Tuncer, ZS Bernstein, MR Goldstein, DP Berkowitz, RS TI Outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients with persistent gestational trophoblastic tumor SO GYNECOLOGIC ONCOLOGY LA English DT Article DE trophoblastic disease; pregnancy; chemotherapy ID DISEASE; CHEMOTHERAPY AB Objective. To determine the outcome of pregnancies occurring before completion of human chorionic gonadotropin follow-up in patients treated with chemotherapy for gestational trophoblastic tumor. Methods, Retrospective record review of patients with gestational trophoblastic tumor who conceived before standard hCG follow-up was completed during 1973-1998, Results. Forty-three patients treated for gestational trophoblastic tumors conceived before human chorionic gonadotropin follow-up was completed, The antecedent pregnancy was complete mole in 31 (72.1%) and partial mole in 12 (27.9%) patients. Of the 43 patients, 39 (90.7%) had stage I, 1 had stage II, and 3 had stage III disease. The mean interval from human chorionic gonadotropin remission to new pregnancy was 6.3 months (range 1-11 months), Ten patients underwent elective termination and four patients were lost to follow-up. Of the remaining 29 patients, 22 (75.9%) had term live births, 3 (10.3%) had preterm delivery, 3 had spontaneous abortion, and 1 (3.5%) had a repeat mole. Two cases of fetal anomalies were detected; one was inherited polydactyly and the other was hydronephrosis, One patient developed choriocarcinoma with lung involvement and underwent cesarean section at 28 weeks; a normal fetus was delivered and no choriocarcinoma was detected in the placenta. Conclusion, Pregnancies occurring in patients treated for gestational trophoblastic tumor before standard human chorionic gonadotropin follow-up is completed may continue under close clinical surveillance since the majority have a favorable outcome. However, patients should also be advised of the low but important risk of delayed diagnosis in case tumor relapse develops during early subsequent pregnancy. (C) 1999 Academic Press. C1 Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Gillette Ctr Wome, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Gillette Ctr Wome, 75 Francis St, Boston, MA 02115 USA. NR 14 TC 19 Z9 19 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1999 VL 73 IS 3 BP 345 EP 347 DI 10.1006/gyno.1999.5437 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 207DV UT WOS:000080920900002 PM 10366457 ER PT J AU Strobel, T Cannistra, SA AF Strobel, T Cannistra, SA TI beta 1-integrins partly mediate binding of ovarian cancer cells to peritoneal mesothelium in vitro SO GYNECOLOGIC ONCOLOGY LA English DT Article ID ADHESION; INTEGRINS; CARCINOMA; BETA-1; EXPRESSION; MIGRATION AB Ovarian cancer cells frequently metastasize by implanting onto the peritoneal mesothelial surface of the abdominal cavity. Although the CD44 molecule expressed by ovarian cancer cells is known to partly mediate this process, the role of other adhesion proteins such as beta 1-integrins has been previously difficult to demonstrate using the 4B4 anti-beta 1 neutralizing antibody. In view of the widespread expression of beta 1-integrins in ovarian cancer, however, we have further examined the potential role of this class of molecules in ovarian cancer cell implantation through the use of an alternative anti-beta 1 neutralizing antibody, MAB13. We now report that MAB13 is capable of inhibiting the binding of three separate human ovarian cancer cell lines (36M2, CAOV3, SKOV-3) to mesothelium (mean 37 +/- 4% inhibition, n = 21, P < 0.001). An additive inhibitory effect was observed when MAB13 was combined with anti-CD44 antibody (clone 515) (mean 63 +/- 3% inhibition, n = 19, P < 0.001), suggesting that binding occurs through two independent pathways involving both beta 1-integrins and CD44. Because fibronectin is an extracellular matrix ligand recognized by many types of integrins and is abundantly expressed on mesothelial cells, the inhibitory effects of MAB13 and 4B4 on ovarian cancer cell binding to fibronectin were directly compared. MAB13 inhibited ovarian cancer cell binding to fibronectin to a significantly greater degree than did 4B4, suggesting that the discordant effects of these two antibodies on mesothelial adhesion may be partly related to their differential ability to neutralizing fibronectin-mediated binding. Studies using anti-alpha 5 neutralizing antibody demonstrated that the alpha 5 beta 1 fibronectin receptor contributes to approximately 50% of integrin-mediated binding of 36M2 and CAOV3 cells (which express the alpha 5 chain in 54 and 58% of cells, respectively). Since the RGD sequence of fibronectin is a known recognition site for many types of integrins, including alpha 5 beta 1 and alpha nu beta 3, we performed binding in the continued presence of both anti-alpha 5 and RGD peptide in order to exclude other types of fibronectin-integrin interactions. The addition of RGD peptides at concentrations known to be capable of blocking fibronectin binding resulted in no additional inhibitory effect over that observed with anti-alpha 5 antibody alone, suggesting that alpha 5 beta 1 was the major receptor responsible for fibronectin-mediated ovarian cancer binding to mesothelium. These data demonstrate that ovarian cancer cell binding to peritoneal mesothelium is mediated by several adhesion pathways and that simultaneous inhibition of both beta 1-integrin and CD44 function may be necessary in order to significantly limit the intraabdominal spread of this tumor in vivo. (C) 1999 Academic Press. C1 Beth Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Cannistra, SA (reprint author), Beth Deaconess Med Ctr, Div Hematol Oncol, 330 Brookline Ave,KS 158, Boston, MA 02215 USA. NR 18 TC 115 Z9 123 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1999 VL 73 IS 3 BP 362 EP 367 DI 10.1006/gyno.1999.5388 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 207DV UT WOS:000080920900006 PM 10366461 ER PT J AU Feltmate, CM Duska, LR Chang, YC Flynn, CE Nikrui, N Kiggundu, E Goodman, A Fuller, AF McIntyre, JF AF Feltmate, CM Duska, LR Chang, YC Flynn, CE Nikrui, N Kiggundu, E Goodman, A Fuller, AF McIntyre, JF TI Predictors of recurrence in surgical stage II endometrial adenocarcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article ID CERVICAL INVOLVEMENT; PROGNOSTIC FACTORS; RISK-FACTORS; CARCINOMA; SURVIVAL; CANCER AB Objective. A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival. Methods, A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging, Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately. Results. Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2-9.6 years), Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%, The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis, Conclusion. This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease, LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Gillette Ctr Womens Canc, Div Gynecol Oncol, 100 Blossom St,Cox 1, Boston, MA 02144 USA. NR 13 TC 27 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1999 VL 73 IS 3 BP 407 EP 411 DI 10.1006/gyno.1999.5380 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 207DV UT WOS:000080920900013 PM 10366468 ER PT J AU Donovan, JT Prefontaine, M Gragoudas, ES AF Donovan, JT Prefontaine, M Gragoudas, ES TI Blindness as a consequence of a paraneoplastic syndrome in a woman with clear cell carcinoma of the ovary SO GYNECOLOGIC ONCOLOGY LA English DT Article ID MELANOCYTIC PROLIFERATION AB Background. Paraneoplastic syndromes are rare conditions associated with cancer that result in serious disease states at unique sites. In 1982, a report of bilateral diffuse uveal melanocytic proliferation associated with nonocular cancers which resulted in blindness was reported. We present a case of a woman with recurrent ovarian cancer who developed this paraneoplastic syndrome. Case. A 55-year-old woman had been diagnosed in 1990 with an ocular melanoma of her right eye and in 1994 with clear cell carcinoma of the ovary. With recurrence of ovarian cancer, new eye lesions were identified in both eyes. After enulcleation of her right eye, an ocular melanoma and diffuse bilateral melanocytic proliferation (BDUMP) were found. The sight in her left eye continued to deteriorate as other signs of BDUMP occurred in the eye. Within 1 month of diagnosis, the patient was blind. She subsequently succumbed to progression of ovarian cancer. Conclusion. Recurrent ovarian cancer is usually an intraabdominal disease that results in gastrointestinal dysfunction. This case illustrates a rare paraneoplastic syndrome associated with ovarian cancer that mimics metastatic disease to the eye, but has a different pathophysiology. (C) 1999 Academic Press. C1 Tufts Univ, Sch Med, Springfield, MA 01199 USA. Baystate Med Ctr, Div Gynecol Oncol, Springfield, MA 01199 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02144 USA. RP Donovan, JT (reprint author), Tufts Univ, Sch Med, Springfield, MA 01199 USA. NR 8 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUN PY 1999 VL 73 IS 3 BP 424 EP 429 DI 10.1006/gyno.1998.5332 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 207DV UT WOS:000080920900017 PM 10366472 ER PT J AU Fisher, CM AF Fisher, CM TI Late-life (migrainous) scintillating zigzags without headache: One person's 27-year experience SO HEADACHE LA English DT Article DE migraine; headache; visual aura; scintillating zigzags AB Background.-Episodes of typical scintillating zigzags similar to the visual aura of migraine may occur without headache, especially after the age of 50. There is no record of once individual's long-term experience. Present Material,This paper is a personal account of all 41 episodes of scintillating zigzags that occurred between the ages of 59 and 85. Observations were made on several aspects of the visual event itself-evolution, pattern, scotoma, coloration, duration, lateralization, etc. The chronological distribution of spells, circumstances of occurrence, time of day, the season, etc were noted. The study was observational in nature. Documentation of this experience could be of value clinically and scientifically. Results.-The spells occurred irregularly, unrelated to season, time of day, activity at onset, diet, and temperamental state. The characteristic appearance was a flickering zigzag line that began centrally and migrated to the periphery. The display, which was stereotyped, was achromatic. The average duration was 15 minutes. Both visual fields were equally involved, never at the same time. The details of the scintillating zigzag line are actually complex and an account of the observations of others and of the author is included here. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, 32 Fruit St, Boston, MA 02114 USA. NR 20 TC 10 Z9 10 U1 0 U2 2 PU AMER ASSOC STUDY HEADACHE PI MT ROYAL PA 19 MANTUA RD, MT ROYAL, NJ 08061 USA SN 0017-8748 J9 HEADACHE JI Headache PD JUN PY 1999 VL 39 IS 6 BP 391 EP 397 DI 10.1046/j.1526-4610.1999.3906391.x PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 237PF UT WOS:000082664700001 PM 11279916 ER PT J AU Linnan, LA Fava, JL Thompson, B Emmons, K Basen-Engquist, K Probart, C Hunt, MK Heimendinger, J AF Linnan, LA Fava, JL Thompson, B Emmons, K Basen-Engquist, K Probart, C Hunt, MK Heimendinger, J TI Measuring participatory strategies: instrument development for worksite populations SO HEALTH EDUCATION RESEARCH LA English DT Article ID WORKING WELL TRIAL; COMMUNITY COALITIONS; HEALTH PROMOTION; PROJECT; PROGRAM; HEART; PREVENTION; DIETARY AB A participatory strategies approach which involves employees in the planning and delivery of worksite health promotion programs was utilized in the 55 experimental worksites included in the national, NCI-funded Working Well Trial. According to study protocol, Employee Advisory Boards (EABs) were organized in each experimental worksite. This paper describes two substudies designed to develop and measure participatory strategies associated with the EABs in the Working Well Trial. Study 1 determined characteristics of the EABs, developed subscales and assessed the internal consistency of the scales. Study 2 used a confirmatory factor analysis to examine the structure of the developed questionnaire. The four subscales include: Autonomy/Independence, Management Involvement, Institutionalization/Commitment and Others Involvement. Results from Study 1 indicate that the four subscales of the 24-item instrument demonstrated strong internal consistency and three were sensitive enough to register differences by Study Center at the baseline. Study 2 results found that the EAB subscales again demonstrated good internal consistency, structural stability and acceptable sensitivity. An initial validity analysis was performed and yielded results which supported some but not all of the hypothesized associations. Implications for further refinement and application of this new instrument in worksite settings are explored. C1 Miriam Hosp, Div Behav Med, Providence, RI 02906 USA. Brown Univ, Providence, RI 02906 USA. Univ Rhode Isl, N Kingston, RI 02852 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Texas, Sch Publ Hlth, Houston, TX 77030 USA. Penn State Univ, University Pk, PA 16802 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20814 USA. RP Linnan, LA (reprint author), Miriam Hosp, Div Behav Med, 164 Summit Ave, Providence, RI 02906 USA. FU NCI NIH HHS [U01 CA51671, U01 CA51686, U01 CA51687] NR 49 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD JUN PY 1999 VL 14 IS 3 BP 371 EP 386 DI 10.1093/her/14.3.371 PG 16 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 205AL UT WOS:000080799000006 PM 10539228 ER PT J AU Friedman, LS AF Friedman, LS TI The risk of surgery in patients with liver disease SO HEPATOLOGY LA English DT Review ID MALIGNANT OBSTRUCTIVE-JAUNDICE; BILIARY-TRACT DISEASE; HEPATOCELLULAR-CARCINOMA; CIRRHOTIC-PATIENTS; ABDOMINAL OPERATIONS; HEPATIC RESECTION; RENAL DYSFUNCTION; EXPLORATORY LAPAROTOMY; SURGICAL CHALLENGE; BLOOD-FLOW C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Blake 456D, Boston, MA 02114 USA. NR 123 TC 105 Z9 112 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 JUN PY 1999 VL 29 IS 6 BP 1617 EP 1623 DI 10.1002/hep.510290639 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 200GN UT WOS:000080531400001 PM 10347099 ER PT J AU Allikmets, R Seddon, JM Bernstein, PS Hutchinson, A Atkinson, A Sharma, S Gerrard, B Li, W Metzker, ML Wadelius, C Caskey, CT Dean, M Petrukhin, K AF Allikmets, R Seddon, JM Bernstein, PS Hutchinson, A Atkinson, A Sharma, S Gerrard, B Li, W Metzker, ML Wadelius, C Caskey, CT Dean, M Petrukhin, K TI Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies SO HUMAN GENETICS LA English DT Article ID BEAVER DAM EYE; STARGARDT-DISEASE; RETINITIS-PIGMENTOSA; DYSTROPHY; ABCR; MUTATIONS AB Vitelliform macular dystrophy (VMD2, Best disease, MIM153700) is an early onset, autosomal, dominant macular degeneration characterized by the deposition of lipofuscin-like material within and below the retinal pigment epithelium (RPE); it is associated with degeneration of the RPE and overlying photoreceptors. Recently, we cloned the gene bestrophin, which is responsible for the disease, and identified a number of causative mutations in families with VMD2. Here, we report that the analysis of bestrophin in a collection of 259 age-related macular degeneration (AMD) patients provides evidence that mutations in the Best disease gene do not play a significant role in the predisposition of individuals to AMD. However, our results suggest that, in addition to Best disease, mutations within the bestrophin gene could be responsible for other forms of maculopathy with phenotypic characteristics similar to Best disease and for other diseases not included in the VMD category. C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Utah, Moran Eye Ctr, Dept Ophthalmol, Salt Lake City, UT 84132 USA. Merck Res Labs, Dept Human Genet, W Point, PA 19486 USA. Univ Uppsala Hosp, Clin Genet Unit, Dept Genet & Pathol, S-75185 Uppsala, Sweden. NCI, Frederick Canc Res & Dev Ctr, Lab Gen Divers, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, 2nd Floor,630 W 168th St, New York, NY 10032 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-56000]; NEI NIH HHS [EY11309, EY11600] NR 23 TC 95 Z9 99 U1 0 U2 8 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 JUN PY 1999 VL 104 IS 6 BP 449 EP 453 DI 10.1007/s004390050986 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 223RL UT WOS:000081854000002 PM 10453731 ER PT J AU Nahum, RT Eroglu, A Toth, TL Perez, G Isaacson, K Leykin, L AF Nahum, RT Eroglu, A Toth, TL Perez, G Isaacson, K Leykin, L TI Laser-assisted intracytoplasmic sperm injection in human oocytes SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Shriners Burns Hosp,Vincent IVF Unit, Massachusetts Gen Hosp,Vincent Mem Obstet & Gynec, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1999 VL 14 SU 1 MA P061 BP 171 EP 171 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223EN UT WOS:000081828000306 ER PT J AU Awwad, JT Sayegh, R Tao, XJ Hassan, T Awwad, ST Isaacson, K AF Awwad, JT Sayegh, R Tao, XJ Hassan, T Awwad, ST Isaacson, K TI The SCID (severe combined immunodeficiency) mouse: an experimental model for endometriosis SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Weizman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1999 VL 14 SU 1 MA P164 BP 223 EP 223 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223EN UT WOS:000081828000409 ER PT J AU De los Santos, MJ Anderson, DJ Xiao, L Turbay, D Yunis, EJ Hill, JA AF De los Santos, MJ Anderson, DJ Xiao, L Turbay, D Yunis, EJ Hill, JA TI Are interferon gamma (INF-gamma) gene polymorphisms associated with recurrent spontaneous abortion (RSA) in women with and without a T helper 1 (Th I) type immunity to trophoblast? SO HUMAN REPRODUCTION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Fearing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Reprod Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Immunogenet, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1999 VL 14 SU 1 MA P167 BP 224 EP 225 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 223EN UT WOS:000081828000412 ER PT J AU Trad, FS Toner, M Biggers, JD AF Trad, FS Toner, M Biggers, JD TI Effects of cryoprotectants and ice-seeding temperature on intracellular freezing and survival of human oocytes SO HUMAN REPRODUCTION LA English DT Article DE cryobiology; freezing; human; intracellular ice formation; oocyte ID INTRACYTOPLASMIC SPERM INJECTION; MOUSE OOCYTES; WATER PERMEABILITY; ACTIVATION-ENERGY; CRYOPRESERVATION; FERTILIZATION; 1,2-PROPANEDIOL; HEPATOCYTES; TRANSPORT; IMMATURE AB The accurate determination of the freezing conditions that promote intracellular ice formation (IIF) is crucial for designing cryopreservation protocols far cells. In this paper, the range of temperatures at which IIF occurs in human oocytes was determined. Fresh oocytes with a germinal vesicle, failed-to-fertilize (metaphase I and metaphase II stages) and polyspermic eggs were used for this study. The occurrence of IIF was first visualized at a cooling rate of 120 degrees C/min using a programmable thermal microscope stage connected to a videomicroscope. Then, with a cooling rate of 0.2 degrees C/min, the seeding temperature of the extracellular ice was modified to decrease the incidence of IIF and increase the survival rate of frozen-thawed human oocytes. After adding different cryoprotectants, the median temperature of IIF (T-MED) was decreased by similar to 23 degrees C in mouse and only by similar to 6.5 degrees C in human oocytes. Using 1.5 M propylene glycol and seeding temperatures of -8.0, -6.0 and -4.5 degrees C, the incidence of IIF was 22/28 (78%), 8/24 (33%) and 0/33 (0%) and the 24 h post-thaw survival rate was 10/31 (32 %), 19/34 (56%) and 52/56 (93%) respectively. The results show that IIF occurs more readily in human oocytes, and that ice seeding between -6 degrees C and -8 degrees C triggers IIF in a large number of human oocytes. Undesirable IIF can be prevented and survival rates maximized by raising the seeding temperature as close as possible to the melting point of the solution, which in our instrument was -4.5 degrees C. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn,Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn,Surg Serv, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Biggers, JD (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02215 USA. NR 47 TC 56 Z9 59 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1999 VL 14 IS 6 BP 1569 EP 1577 DI 10.1093/humrep/14.6.1569 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 206MN UT WOS:000080883300033 PM 10357978 ER PT J AU Bruce, IC White, MW Irlicht, LS O'Leary, SJ Dynes, S Javel, E Clark, GM AF Bruce, IC White, MW Irlicht, LS O'Leary, SJ Dynes, S Javel, E Clark, GM TI A stochastic model of the electrically stimulated auditory nerve: Single-pulse response SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE auditory nerve; cochlear implant; functional electrical stimulation; population response; sensory prosthesis; single-pulse response; stochastic threshold model ID THRESHOLD FLUCTUATIONS; EXCITATION PATTERNS; FIBERS; DISTRIBUTIONS; EXCITABILITY; REDUCTION; COCHLEA; NEURONS; RANVIER; RATES AB Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity, For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena, In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli, These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model. C1 Univ Melbourne, Bionic Ear Inst, Melbourne, Vic 3002, Australia. Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3002, Australia. N Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA. RP Bruce, IC (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 505 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Bruce, Ian/A-1232-2008; OI Bruce, Ian/0000-0002-5169-4538; O'Leary, Stephen/0000-0001-6926-2103 FU NIDCD NIH HHS [DC00361] NR 58 TC 80 Z9 80 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 1999 VL 46 IS 6 BP 617 EP 629 DI 10.1109/10.764938 PG 13 WC Engineering, Biomedical SC Engineering GA 199CN UT WOS:000080461900001 PM 10356868 ER PT J AU Bruce, IC Irlicht, LS White, MW O'Leary, SJ Dynes, S Javel, E Clark, GM AF Bruce, IC Irlicht, LS White, MW O'Leary, SJ Dynes, S Javel, E Clark, GM TI A stochastic model of the electrically stimulated auditory nerve: Pulse-train response SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE auditory nerve; cochlear implant; functional electrical stimulation; pulse-train response; population response; refractory effect; renewal process; sensory prosthesis; stochastic model ID THRESHOLD FLUCTUATIONS; FIBERS AB The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism, Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s, First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model, Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate; while the deterministic model predicts no variance at all. C1 Univ Melbourne, Bionic Ear Inst, Melbourne, Vic 3002, Australia. Univ Melbourne, Dept Otolaryngol, Melbourne, Vic 3002, Australia. N Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA. RP Bruce, IC (reprint author), Johns Hopkins Univ, Dept Biomed Engn, 505 Traylor Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Bruce, Ian/A-1232-2008; OI Bruce, Ian/0000-0002-5169-4538; O'Leary, Stephen/0000-0001-6926-2103 NR 26 TC 56 Z9 58 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 1999 VL 46 IS 6 BP 630 EP 637 DI 10.1109/10.764939 PG 8 WC Engineering, Biomedical SC Engineering GA 199CN UT WOS:000080461900002 PM 10356869 ER PT J AU Correia, JA Burnham, CA Kaufman, D Fischman, AJ AF Correia, JA Burnham, CA Kaufman, D Fischman, AJ TI Development of a small animal PET imaging device with resolution approaching 1 mm SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT 1998 Medical Imaging Conference CY NOV 12-14, 1998 CL TORONTO, CANADA ID SCANNER; TOMOGRAPH; DETECTOR; DESIGN AB The work presented here describes progress in the design and construction of a single-plane PET tomograph having spatial resolution approaching 1 mm. The system consists of a 12 cm diameter ring with 360 LSO detectors viewed by 30 photo-multiplier tubes. Thin (5 mm) crystals and a low energy threshold are used. Crystals are identified using both position arithmetic and energy criteria. To-date the system construction has been completed, system tuning carried out and imaging studies begun. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Correia, JA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 57 Z9 57 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 1999 VL 46 IS 3 BP 631 EP 635 DI 10.1109/23.775590 PN 2 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 216UA UT WOS:000081461200030 ER PT J AU Vonderheide, RH Hahn, WC Schultze, JL Nadler, LM AF Vonderheide, RH Hahn, WC Schultze, JL Nadler, LM TI The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes SO IMMUNITY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; POLYVALENT MELANOMA VACCINE; HUMAN EPITHELIAL-CELLS; IMMORTAL CELLS; LIFE-SPAN; IN-VITRO; GENE; LENGTH; CANCER; MAGE-3 AB The discovery of tumor-associated antigens (TAA) in certain human malignancies has prompted renewed efforts to develop antigen-specific immunotherapy of cancer. However, most TAA described thus far are expressed in one or a few tumor types, and, among patients with these types of tumors, TAA expression is not universal. Here, we characterize the telomerase catalytic subunit (hTERT) as a widely expressed TAA capable of triggering antitumor cytotoxic T lymphocyte (CTL) responses. More than 85% of human cancers exhibit strong telomerase activity, but normal adult tissues, with few exceptions, do not. In a human system, CD8(+) CTL specific for an hTERT peptide and restricted to MHC HLA-A2 lysed hTERT(+) tumors from multiple histologies. These findings identify hTERT as a potentially important and widely applicable target for anticancer immunotherapeutic strategies. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Vonderheide, RH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [P01-CA-66996] NR 34 TC 427 Z9 451 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 1999 VL 10 IS 6 BP 673 EP 679 DI 10.1016/S1074-7613(00)80066-7 PG 7 WC Immunology SC Immunology GA 212GU UT WOS:000081209600005 PM 10403642 ER PT J AU Bhan, AK Mizoguchi, E Smith, RN Mizoguchi, A AF Bhan, AK Mizoguchi, E Smith, RN Mizoguchi, A TI Colitis in transgenic and knockout animals as models of human inflammatory bowel disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL-RECEPTOR; INTESTINAL EPITHELIAL-CELLS; ALPHA-MUTANT MICE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ENTERIC BACTERIAL-ANTIGENS; NONOBESE DIABETIC MICE; GROWTH-FACTOR-BETA; ULCERATIVE-COLITIS; DEFICIENT MICE AB Spontaneous colitis in knockout (KO) and transgenic rodents provides experimental models to study the development of mucosal inflammation and inflammatory bowel disease (Crohn's disease and ulcerative colitis). Genetic and environmental factors, particularly the normal enteric flora, are important factors in the development of mucosal inflammation. The normal mucosal homeostasis is disrupted when there is either cytokine imbalance, abrogation of oral tolerance, alteration of epithelial barrier and function or loss of immunoregulatory cells. Some but not all immunodeficiencies, in the appropriate setting, lead to colitis. CD4(+) T cells have been identified as the pathogenic T cells in colitis, which mediate inflammation by either the Th1 or the Th2 pathway The Th1 pathway dominates most colitis models and in Crohn's disease. In contrast, the colitis in TCR alpha KO mice shares many features of ulcerative colitis including the dominance of Th2 pathway in colonic inflammation. A major benefit of these models is in the development of therapeutic strategies for the treatment of inflammatory bower disease. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, 100 Blossom St,Cox 503, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK47677] NR 135 TC 107 Z9 124 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 1999 VL 169 BP 195 EP 207 DI 10.1111/j.1600-065X.1999.tb01316.x PG 13 WC Immunology SC Immunology GA 222AT UT WOS:000081760600016 PM 10450518 ER PT J AU Hellman, J Warren, HS AF Hellman, J Warren, HS TI Antiendotoxin strategies SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID PERMEABILITY-INCREASING PROTEIN; HIGH-DENSITY-LIPOPROTEIN; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; GRAM-NEGATIVE BACTERIA; ENDOTOXIN-NEUTRALIZING PROTEIN; AMINO-TERMINAL FRAGMENT; MONOPHOSPHORYL LIPID-A; LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; ESCHERICHIA-COLI SEPSIS; SALMONELLA-TYPHIMURIUM LIPOPOLYSACCHARIDES AB Endotoxin is a potent stimulator of the inflammatory response and is believed to initiate the pathology in Gram-negative sepsis. Agents are being developed that bind and neutralize or block the effects of endotoxin, with the goal of improving outcome in the treatment of sepsis. Strategies discussed in this article include anti-LPS antibodies, LPS binding proteins and lipoproteins, poly myxin B conjugates, Lipid A analogues, and extracorporeal techniques for endotoxin removal. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp E, Infect Dis Unit, 5th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 158 TC 24 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 1999 VL 13 IS 2 BP 371 EP + DI 10.1016/S0891-5520(05)70080-5 PG 17 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 197WZ UT WOS:000080390500007 PM 10340172 ER PT J AU Dennehy, KC Bigatello, LM AF Dennehy, KC Bigatello, LM TI Pathophysiology of the acute respiratory distress syndrome SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID ACUTE LUNG INJURY; EUROPEAN CONSENSUS CONFERENCE; PULMONARY; ARDS; FAILURE; RECOVERY; SURVIVAL; TRIAL C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Dennehy, KC (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 1 EP 13 DI 10.1097/00004311-199903730-00004 PG 13 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200003 PM 10445170 ER PT J AU Hurford, WE AF Hurford, WE TI A note from the Editor-in-Chief SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Hurford, WE (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP XI EP XI PG 1 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200001 ER PT J AU Bigatello, LM Hess, D AF Bigatello, LM Hess, D TI Update on respiratory critical care - Preface SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Bigatello, LM (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, 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 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP XIII EP XIV PG 2 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200002 ER PT J AU Hess, DR Medoff, BD Fessler, MB AF Hess, DR Medoff, BD Fessler, MB TI Pulmonary mechanics and graphics during positive pressure ventilation SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID END-EXPIRATORY PRESSURE; RESPIRATORY-DISTRESS SYNDROME; CHEST-WALL MECHANICS; MEAN AIRWAY PRESSURE; VOLUME CURVE; SUPPORT VENTILATION; MATHEMATICAL-MODEL; PHYSIOLOGICAL DETERMINANTS; BRONCHODILATOR DELIVERY; DYNAMIC HYPERINFLATION C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. NR 74 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 15 EP 34 DI 10.1097/00004311-199903730-00005 PG 20 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200004 PM 10445171 ER PT J AU Hurford, WE AF Hurford, WE TI Cardiopulmonary interactions during mechanical ventilation SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID END-EXPIRATORY PRESSURE; LEFT-VENTRICULAR FUNCTION; RESPIRATORY-DISTRESS SYNDROME; ARTERY OCCLUSION PRESSURE; INTRATHORACIC PRESSURE; BLOOD-FLOW; PEEP; FAILURE; PERFORMANCE; DOGS C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Hurford, WE (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 52 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 35 EP 46 DI 10.1097/00004311-199903730-00006 PG 12 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200005 PM 10445172 ER PT J AU Kacmarek, RM AF Kacmarek, RM TI Ventilator-associated lung injury SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; HYALINE-MEMBRANE FORMATION; POSITIVE AIRWAY PRESSURE; MECHANICAL VENTILATION; PULMONARY-EDEMA; TIDAL VOLUME; PERMISSIVE HYPERCAPNIA; LIMITED VENTILATION; PROTECTIVE-VENTILATION C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. NR 67 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 47 EP 64 DI 10.1097/00004311-199903730-00007 PG 18 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200006 PM 10445173 ER PT J AU Kwo, J Bigatello, LM AF Kwo, J Bigatello, LM TI Ancillary therapies for acute respiratory distress syndrome SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID INHALED NITRIC-OXIDE; PARTIAL LIQUID VENTILATION; END-EXPIRATORY PRESSURE; ACUTE LUNG INJURY; CORTICOSTEROID RESCUE TREATMENT; PRONE POSITION; GAS-EXCHANGE; AEROSOLIZED SURFACTANT; LEUKOCYTE ADHESION; CLINICAL-TRIAL C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Kwo, J (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. NR 65 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 65 EP 83 DI 10.1097/00004311-199903730-00008 PG 19 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200007 PM 10445174 ER PT J AU Hess, DR AF Hess, DR TI Noninvasive positive pressure ventilation for acute respiratory failure SO INTERNATIONAL ANESTHESIOLOGY CLINICS LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; MECHANICAL VENTILATION; FACE MASK; SUPPORT VENTILATION; ACUTE EXACERBATIONS; NASAL VENTILATION; PROSPECTIVE TRIAL; LUNG-DISEASE; ASSISTANCE; INTUBATION C1 Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02114 USA. NR 50 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-5907 J9 INT ANESTHESIOL CLIN JI Int. Anesthesiol. Clin. PD SUM PY 1999 VL 37 IS 3 BP 85 EP 102 DI 10.1097/00004311-199903730-00009 PG 18 WC Anesthesiology SC Anesthesiology GA 222AZ UT WOS:000081761200008 PM 10445175 ER PT J AU Wells, A AF Wells, A TI EGF receptor SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE receptor protein tyrosine kinase (RPTK); tumor invasion; wound healing; organogenesis; signaling pathways ID EPIDERMAL GROWTH-FACTOR; CELL MOTILITY; ALPHA AB The receptor for the epidermal growth factor (EGF) and related ligands (EGFR), the prototypal member of the superfamily of receptors with intrinsic tyrosine kinase activity, is widely expressed on many cell types, including epithelial and mesenchymal lineages. Upon activation by at least five genetically distinct ligands (including EGF, transforming growth factor-alpha (TGF alpha) and heparin-binding EGF (HB-EGF)), the intrinsic kinase is activated and EGFR tyrosyl-phosphorylates itself and numerous intermediary effector molecules, including closely-related c-erbB receptor family members. This initiates myriad signaling pathways, some of which attenuate receptor signaling. The integrated biological responses to EGFR signaling are pleiotropic including mitogenesis or apoptosis, enhanced cell motility, protein secretion, and differentiation or dedifferentiation. In addition to being implicated in organ morphogenesis, maintenance and repair, upregulated EGFR signaling has been correlated in a wide variety of tumors with progression to invasion and metastasis. Thus, EGFR and its downstream signaling molecules are targets for therapeutic interventions in wound repair and cancer. Published by Elsevier Science Ltd. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham VAMC, Pathol Serv, Birmingham, AL 35294 USA. Birmingham VAMC, Lab Serv, Birmingham, AL 35294 USA. RP Wells, A (reprint author), Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. OI Wells, Alan/0000-0002-1637-8150 NR 15 TC 718 Z9 764 U1 6 U2 53 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD JUN PY 1999 VL 31 IS 6 BP 637 EP 643 DI 10.1016/S1357-2725(99)00015-1 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 211NL UT WOS:000081167100002 PM 10404636 ER PT J AU Zwillich, CW AF Zwillich, CW TI Obstructive sleep apnoea causes transient and sustained systemic hypertension SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Review ID APNEA PATIENTS; SYMPATHETIC ACTIVITY; ARTERIAL-PRESSURE; BLOOD-PRESSURE; STROKE VOLUME; POPULATION; MORTALITY; HYPOXIA; PULMONARY AB Apnoea with associated fall in arterial oxygen tension results in increased blood pressure and a striking surge in sympathetic activity, which can be measured as high catecholamine levels or increase in muscle sympathetic nerve activity. Following the termination of apnoea with resumption of breathing, sympathetic nerve activity decreases and blood pressure returns to lower values. Sympathetic mediated alternations in peripheral vascular resistance best explain these findings. Hypertension during wakefulness in untreated patients with apnoea is also associated with high sympathetic nervous system activity. Nasal continuous positive airway pressure (CPAP) has been shown to lower blood pressure in some hypertensive obstructive sleep apnoea (OSA) patients. Recently, previously untreated OSA patients exhibiting awake sympathetic hyperexcitation demonstrated striking attentuation of the response following initiation of effective CPAP therapy. Accordingly, the common problem of systemic hypertension found in untreated OSA appears to be mediated by sympathetic excitation and responds to effective CPAP therapy. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Zwillich, CW (reprint author), Denver VA Med Ctr, Med Serv, 1055 Clermont St, Denver, CO 80220 USA. NR 35 TC 6 Z9 6 U1 0 U2 0 PU MEDICOM INTERNATIONAL PI SURREY PA CHURSTON HOUSE, PORTSMOUTH RD, ESHER, SURREY KT10 9AD, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD JUN PY 1999 VL 53 IS 4 BP 301 EP 305 PG 5 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 212LL UT WOS:000081218100015 PM 10563076 ER PT J AU Sachs, RK Chen, AM Simpson, PJ Hlatky, LR Hahnfeldt, P Savage, JRK AF Sachs, RK Chen, AM Simpson, PJ Hlatky, LR Hahnfeldt, P Savage, JRK TI Clustering of radiation-produced breaks along chromosomes: modelling the effects on chromosome aberrations SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID IN-SITU HYBRIDIZATION; DOUBLE-STRAND BREAKS; STRUCTURE-DEPENDENT REPAIR; DOSE-RESPONSE CURVES; SHORT DNA FRAGMENTS; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; INCOMPLETE EXCHANGES; NOMENCLATURE SYSTEMS; HUMAN FIBROBLASTS AB Purpose: For high-LET radiations, and perhaps even for hard X-rays, DNA double-strand breaks (dsb) are clustered non-randomly along chromosomes; disproportionately, many inter-dsb segments are less than a few Mbp (10(6) base pairs). The implications of such dsb clustering for chromosome aberrations are analysed. Methods: Chromosome segments between different dsb within one dsb cluster are assumed too small to detect in the aberration assay. Enumeration or Monte-Carlo computer simulations are used to compute the relative frequencies of many observable aberration patterns: apparently simple or visibly complex. The theoretical predictions are compared with X-ray data for human fibroblasts, involving painted chromosomes 1, 2, 4, 5, 7 or 13. Results and conclusions: Surprisingly, cryptic dsb multiplicity does not affect the frequency ratios predicted for aberration patterns by a random breakage-and-rejoining model. The model is generally consistent with current data on many different types of aberrations, whether or not dsb usually occur in cryptic clusters. For a Revell-type exchange model, however, the predictions do depend on clustering configurations; they gradually approach the predictions of the breakage-and-rejoining model as average cluster multiplicity increases. The model is consistent with the data, for example with the ratio of visibly complex to apparently simple aberrations, only if there is considerable dsb clustering even at low-LET, with similar to 1.5 or more reactive dsb per cluster on average. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA USA. MRC, Radiat & Genome Stabil Unit, Didcot OX11 0RD, Oxon, England. Harvard Univ, JCRT, DFCI, Boston, MA 02215 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Evans Hall, Berkeley, CA USA. FU NIGMS NIH HHS [GM57245-01] NR 59 TC 36 Z9 38 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD JUN PY 1999 VL 75 IS 6 BP 657 EP 672 PG 16 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 208UT UT WOS:000081010800001 PM 10404995 ER PT J AU Strauss, EC Larson, KA Brenneise, I Foster, CS Larsen, GR Lee, NA Lee, JJ AF Strauss, EC Larson, KA Brenneise, I Foster, CS Larsen, GR Lee, NA Lee, JJ TI Soluble P-selectin glycoprotein ligand 1 inhibits ocular inflammation in a murine model of allergy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID IN-VIVO; LEUKOCYTE RECRUITMENT; NEUTROPHIL INFLUX; DEFICIENT MICE; EOSINOPHIL; EXPRESSION; RECEPTOR; OLIGOSACCHARIDES; ENDOTHELIUM; THERAPY AB PURPOSE. TO assess the anti-inflammatory modality of a soluble extracellular form of P-selectin glycoprotein Ligand 1 (sPSGL-1) in a mouse model of ocular allergic response. METHODS. Potential anti-inflammatory effects of sPSGL-1 were investigated in SWR/J mice sensitized by topical application of short ragweed pollen to the nasal mucosa followed by a challenge of the ocular mucosa with the same allergen. Five experimental groups were included in these studies: A, mice neither sensitized nor challenged with pollen (control group 1); B, animals sensitized but not challenged (control group 2); C, animals not sensitized but challenged (control group 3); D, animals sensitized and challenged; and E, sensitized animals treated with sPSGL-1 before pollen challenge. All experimental groups were evaluated for gross morphologic ocular changes, and histologic assessments were made to determine the onset/progression of inflammatory reactions and to look for evidence of eosinophil infiltration. RESULTS.,Mice sensitized and challenged with pollen developed clinical signs consistent with human allergic conjunctivitis. These signs correlate with histologic changes in the conjunctival epithelium and stroma (e.g., edema and extensive eosinophil infiltration). Moreover, the ocular changes also correlated with evidence of eosinophil degranulation. However, sensitized and challenged mice concurrently treated with sPSGL-1 displayed no inflammatory ocular changes associated with a ragweed-induced type-1 hypersensitivity reaction. The lack of ocular changes included the absence of histologic late-phase inflammatory changes of the conjunctiva and a 97% reduction in the induced eosinophil infiltrate. CONCLUSIONS. The antagonistic intervention of cell-cell interactions through the blockade of selectin-dependent leukocyte adhesion may offer novel therapeutic strategies to modulate inflammatory responses. The potent inhibitory effects on eosinophil recruitment and late-phase inflammation suggest a role for sPSGL-1 in the treatment of ocular allergic diseases. C1 Mayo Clin Scottsdale, SC Johnson Res Ctr, Dept Biochem & Mol Biol, Scottsdale, AZ 85259 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Inst Genet, Cambridge, MA USA. RP Lee, JJ (reprint author), Mayo Clin Scottsdale, SC Johnson Res Ctr, Dept Biochem & Mol Biol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. NR 37 TC 20 Z9 21 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1999 VL 40 IS 7 BP 1336 EP 1342 PG 7 WC Ophthalmology SC Ophthalmology GA 200GU UT WOS:000080531900004 PM 10359314 ER PT J AU Justice, AC Rabeneck, L Hays, RD Wu, AW Bozzette, SA AF Justice, AC Rabeneck, L Hays, RD Wu, AW Bozzette, SA CA Outcomes Comm AIDS Clinical Trials Grp TI Sensitivity, specificity, reliability, and clinical validity of provider-reported symptoms: A comparison with self-reported symptoms SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adverse drug reactions; symptoms; HIV infection; reliability; validity; functional status; global quality of life; survival ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; PATIENT COMPLIANCE; POLYPHARMACY; INFECTION; DISEASE; TRIALS AB Background: If symptoms are to be recognized and effectively addressed in clinical research, they must be collected using sensitive, specific, reliable, and clinically meaningful methods. Objective: To perform a comparison of self-administered symptom survey data with data from conventional provider-reports. Design/methods: Secondary data analysis of AIDS Clinical Trials Group Study 081 (ACTG 081), a randomized trial taking place in 33 sites comparing three approaches to prophylaxis for Pneumocystis carinii-related pneumonia that found no difference among treatment arms. The study was performed on 842 subjects with advanced HIV infection. No intervention was undertaken as a result of this study. ACTG 081 included data on functional status, global quality of life and survival, and two methods of symptom measurement: an open-ended, provider-reported symptom assessment (provider-report) and a self-administered symptom survey (self-report). Agreement was measured using kappa scores. Sensitivity and specificity were calculated using self-report as the standard. Reliability was measured by intersite variation and test-retest reliability (8 weeks later). Clinical validity was evaluated by testing expected associations with functional status, global quality of life, and survival. Results: Symptom data were available for 808 patients (96%). Patient and provider agreement was poor (mean kappa, 0.14; range, 0.07-0.25). Compared with self-report, providers underreported the presence and severity of symptoms (mean symptom count, 5.2 versus 1.3; mean severity score, 1.3 versus 0.74). provider-report demonstrated greater variability by site (R-2 associated with site, 0.02 versus 0.16) and poorer test-retest reliability (mean kappa, 0.34 versus 0.25). Provider-report severity scores were less strongly associated than were self-report with functional status (chi(2), 252 versus 80) global quality of life (R-2 for model, 0.57 versus 0.15), and survival (chi(2), 38 versus 24). Self-reported symptom severity was strongly correlated to patient-reported global quality of life (rho, 0.75; p < .0001). Conclusions: Provider-reported symptoms as currently collected within the ACTG are less sensitive and reproducible than a self-administered symptom survey. Provider reported severity scores are also more weakly associated with functional status, global quality of life, and survival. A self-reported symptom survey may provide a better method of symptom measurement for HIV research. C1 Dept Vet Affairs Med Ctr, Div Gen Internal Med & Hlth Care Res, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Baylor Coll Med, Dept Vet Affairs Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dev Field Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RAND Hlth Sci Program, Los Angeles, CA USA. Johns Hopkins Univ, Dept Hlth Policy & Management, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Vet Affairs San Diego Healthcare Syst, Dept Med, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RAND Hlth Sci Div, San Diego, CA USA. RP Justice, AC (reprint author), VA Pittsburgh Healthcare Syst, Gen Internal Med Sect, 11E,Univ Dr C, Pittsburgh, PA 15240 USA. RI Hays, Ronald/D-5629-2013 NR 17 TC 109 Z9 111 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD JUN 1 PY 1999 VL 21 IS 2 BP 126 EP 133 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 202JA UT WOS:000080647500008 PM 10360804 ER PT J AU Agarwal, S Viola, JPB Rao, A AF Agarwal, S Viola, JPB Rao, A TI Chromatin-based regulatory mechanisms governing cytokine gene transcription SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chromatin remodeling; DNA methylation; T-cell differentiation; T-cell activation; IL-4 ID T-CELL SUBSETS; HELPER TYPE-1 CELLS; IFN-GAMMA; REPRESS TRANSCRIPTION; EXPRESSION; DIFFERENTIATION; TH1; METHYLATION; ACTIVATION; REGION AB On initial contact with antigen, naive T cells differentiate and acquire effector characteristics, including the ability to transcribe specific cytokine genes rapidly and at high levels on subsequent exposure to antigen. Several effector T-cell subsets showing distinct patterns of cytokine gene transcription have been described. The patterns of cytokine expression in response to pathogenic challenges have a significant impact on the outcome of immune and inflammatory reactions. Here we review recent studies suggesting that the ability of naive T cells to differentiate into specific cytokine-expressing cells is regulated by epigenetic changes in the accessibility and chromatin structure of cytokine genetic loci. Antigen and cytokine stimulation of naive T cells activates diverse intracellular signaling pathways, which result in chromatin remodeling and demethylation of cytokine genes. These changes are likely to increase, in a stable and heritable fashion, the accessibility of these genes to the basal transcriptional machinery. Chromatin-based regulatory mechanisms may explain several features of cytokine gene expression in effector versus naive T cells, including their monoallelic expression, coordinate regulation, and stable maintenance in memory T cells. The hypothesis of epigenetic changes occurring during T-cell differentiation provides a framework for a comprehensive understanding of cytokine expression by T cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. INCA, Inst Nacl Canc, Ctr Pesquisa Basica, Program Med Expt, Rio De Janeiro, Brazil. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. NR 56 TC 43 Z9 46 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1999 VL 103 IS 6 BP 990 EP 999 DI 10.1016/S0091-6749(99)70168-5 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 207GT UT WOS:000080929500002 PM 10359875 ER PT J AU Christodoulopoulos, P Wright, E Frenkiel, S Luster, A Hamid, Q AF Christodoulopoulos, P Wright, E Frenkiel, S Luster, A Hamid, Q TI Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: Effect of topical corticosteroids SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergic rhinitis; chemokines; monocyte chemotactic proteins; eosinophils; topical corticosteroids ID CYTOKINE MESSENGER-RNA; INDUCED RHINITIS; TISSUE EOSINOPHILIA; CHEMOATTRACTANT PROTEIN-1; FLUTICASONE PROPIONATE; CC-CHEMOKINES; T-LYMPHOCYTES; EXPRESSION; CELLS; EOTAXIN AB Background: Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions. Objective: To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis. Methods: Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6), Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells, Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined. Results: MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epitheliun. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P < .001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils. Conclusion: Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-1, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis. C1 McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada. SMBD Jewish Gen Hosp, Dept Otolaryngol Head & Neck Surg, Montreal, PQ, Canada. McGill Univ, McGill Nasal Res Grp, Montreal, PQ, Canada. Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA USA. RP Hamid, Q (reprint author), McGill Univ, Meakins Christie Labs, 3626 St Urbain St, Montreal, PQ H2X 2P2, Canada. NR 28 TC 30 Z9 33 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 1999 VL 103 IS 6 BP 1036 EP 1044 DI 10.1016/S0091-6749(99)70176-4 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 207GT UT WOS:000080929500010 PM 10359883 ER PT J AU Kimura, T Ito, A Hancock, WW Maki, T AF Kimura, T Ito, A Hancock, WW Maki, T TI Islet mass plays a critical role in initiation, but not progression, of the diabetogenic process in NOD mice SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE pancreatectomy; islet transplantation; islet mass; diabetogenic process ID NONOBESE DIABETIC MICE; AUTOIMMUNE-DISEASE; GENETIC-CONTROL; MOUSE; PANCREATECTOMY; IMMUNOTHERAPY; INSULITIS; MELLITUS; CELLS AB Pancreatectomy (90%) at a preinsulitis age (7 weeks) protects NOD mice from diabetes while pancreatectomy at a mid-insulitis age (13 weeks) has no such protective effect. The present study examined the effects of islet transplantation in pancreatectomized diabetes-free NOD mice. Transplantation of syngeneic NOD islets as well as allogeneic C3H/He and C57BL/6 islets 3 weeks after pancreatectomy-induced spontaneous diabetes whereas transplantation of xenogeneic Sprague-Dawley rat islets or allogeneic C3H/He skin failed to induce diabetes, demonstrating that the diabetogenic antigen(s) of NOD islets is also expressed by islets of diabetes-resistant mouse strains but not by xenogeneic rat islets. Removal of NOD islet grafts by nephrectomy 7-14 days after transplantation had no effect on the subsequent chronic development of diabetes, while graft removal 3 days after transplantation completely abolished the diabetogenic effect of islet transplantation. Thus, activation of the diabetogenic response by islet isografting takes less than 7 days and the continuous presence of a large islet mass is not required:for progression to diabetes. While islet transplantation at 10 and 15 weeks of age caused diabetes, delayed islet transplantation at 23 and 35 weeks of age failed to induce diabetes in pancreatectomized diabetes-free NOD mice, suggesting that initiation of the diabetogenic autoimmune process must take place within a certain window of time. The pancreatectomy/islet transplantation model is excellent for studying the immunological events surrounding activation and progression of the diabetogenic autoimmune process and for identifying the diabetogenic islet antigen(s). (C) 1999 Academic Press. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Transplantat & Cellular Immunol Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Maki, T (reprint author), Res N Beth Israel Deaconess Med Ctr, POB 15707, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01DK48001] NR 24 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1999 VL 12 IS 4 BP 243 EP 249 DI 10.1006/jaut.1999.0283 PG 7 WC Immunology SC Immunology GA 200ME UT WOS:000080543400003 PM 10330295 ER PT J AU Semana, G Gausling, R Jackson, RA Hafler, DA AF Semana, G Gausling, R Jackson, RA Hafler, DA TI T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE antigens; peptides; epitopes; autoimmunity; diabetes; human; T lymphocytes ID TRANSGENIC MICE; IMMUNE-RESPONSE; INSULIN; IDDM; AUTOANTIGENS; RECOGNITION; MELLITUS; ANTIGENS; PEPTIDE; IMMUNODOMINANT AB We investigated the immune response to proinsulin, a potential autoantigen in IDDM secreted exclusively by pancreatic beta-cells. A total of 2,142 short-term cell lines were generated from 19 individuals; seven IDDM patients at the disease onset and 12 control subjects. No increase in the frequency of proinsulin reactive cells was observed in the IDDM group. To define proinsulin epitopes, proliferative responses of proinsulin-specific lines were examined against 10 overlapping 15 amino acid peptides encompassing the human proinsulin sequence. The predominant immune response was directed against the proinsulin p35-50 peptide located in the (C) connecting peptide between the alpha- and beta-chain of insulin. Recognition of the proinsulin p35-50 peptide could be shown by generating specific T cell clones against the peptide. However, unlike responses to other tissue-specific autoantigens there were only low proliferative responses to proinsulin as measured by H-3-thymidine incorporation. This low reactivity may be partially explained by the location of the p35-50 peptide in the C-peptide which is released into the circulation and therefore, may induce a clonal anergy of T reactive cells. However, the significantly higher H-3-thymidine incorporation after CD3-D28 triggering showed that peptide specific T cells were capable of a significant response with a stronger TCR signal. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. Joslin Diabet Ctr, Immunol Sect, Boston, MA 02215 USA. RP Semana, G (reprint author), Univ Rennes 1, Lab Univ Immunol, Fac Med, 2 Ave Professeur Leon Bernard,CS 34317, F-35043 Rennes, France. NR 33 TC 38 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1999 VL 12 IS 4 BP 259 EP 267 DI 10.1006/jaut.1999.0282 PG 9 WC Immunology SC Immunology GA 200ME UT WOS:000080543400005 PM 10330297 ER PT J AU Watnick, PI Fullner, KJ Kolter, R AF Watnick, PI Fullner, KJ Kolter, R TI A role for the mannose-sensitive hemagglutinin in biofilm formation by Vibrio cholerae El Tor SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TOXIN-COREGULATED PILI; GENETIC-ANALYSIS; COLONIZATION; PSEUDOMONAS; PATHOGENESIS; INITIATION; ATTACHMENT; MOTILITY AB While much has been learned regarding the genetic basis of host-pathogen interactions, less is known about the molecular basis of a pathogen's survival in the environment. Biofilm formation on abiotic surfaces represents a survival strategy utilized by many microbes. Here it is shown that Vibrio cholerae El Tor does not use the virulence-associated toxin-coregulated pilus to form biofilms on borosilicate but rather uses the mannose-sensitive hemagglutinin (MSHA) pilus, which plays no role in pathogenicity. In contrast, attachment of V. cholerae to chitin is shown to be independent of the MSHA pilus, suggesting divergent pathways for biofilm formation on nutritive and nonnutritive abiotic surfaces. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Kolter, R (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM58213, R01 GM058213]; PHS HHS [A107410-06] NR 23 TC 166 Z9 177 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 11 BP 3606 EP 3609 PG 4 WC Microbiology SC Microbiology GA 201NQ UT WOS:000080602000038 PM 10348878 ER PT J AU Zakharova, N Paster, BJ Wesley, I Dewhirst, FE Berg, DE Severinov, KV AF Zakharova, N Paster, BJ Wesley, I Dewhirst, FE Berg, DE Severinov, KV TI Fused and overlapping rpoB and rpoC genes in helicobacters, campylobacters, and related bacteria SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COMPLETE GENOME; PYLORI AB The genes coding for the beta (rpoB) and beta' (rpoC) subunits of RNA polymerase are fused in the gastric pathogen Helicobacter pylori but separate in other taxonomic groups. To better understand how the unique fused structure evolved, we determined DNA sequences at and around the rpoB-rpoC junction in 10 gastric and nongastric species of Helicobacter acid in members of the related genera Wolinella, Arcobacter, Sulfurospirillum, and Campylobacter. We found the fusion to be specific to Helicobacter and Wolinella genera; rpoB and rpoC overlap in the other genera. The fusion may have arisen by a frameshift mutation at the site of rpoB and rpoC overlap. Loss of good Shine-Dalgarno sequences might then have fixed the fusion in the Helicobacteraceae, even if fusion itself did not confer a selective advantage. C1 Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Severinov, KV (reprint author), Rutgers State Univ, Waksman Inst, 190 Frelinghuysen Rd, Piscataway, NJ 08854 USA. RI Severinov, Konstantin/C-8545-2016 FU NIAID NIH HHS [AI38166]; NIDCR NIH HHS [R01 DE010374, R01 DE011443]; NIDDK NIH HHS [DK48029]; NIGMS NIH HHS [R01 GM 59295, R01 GM059295] NR 8 TC 18 Z9 18 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1999 VL 181 IS 12 BP 3857 EP 3859 PG 3 WC Microbiology SC Microbiology GA 205YR UT WOS:000080849100036 PM 10368167 ER PT J AU Wilkerson, PW Levine, RA Yoganathan, AP AF Wilkerson, PW Levine, RA Yoganathan, AP TI Quantification of mitral regurgitation using corrected Doppler measurements SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID PROXIMAL FLOW-CONVERGENCE; ESTIMATING VOLUME FLOW; IN-VITRO; ORIFICE; AREA; REGION; PISA C1 Georgia Inst Technol, Inst Bioengn & Sci, Sch Biomed Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. Georgia Inst Technol, Inst Bioengn & Sci, Sch Mech Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiac Ultrasound Lab, Boston, MA 02111 USA. RP Wilkerson, PW (reprint author), Georgia Inst Technol, Inst Bioengn & Sci, Sch Biomed Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. FU NHLBI NIH HHS [HL53702, HL52009] NR 22 TC 2 Z9 2 U1 0 U2 0 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JUN PY 1999 VL 121 IS 3 BP 273 EP 280 DI 10.1115/1.2798320 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 208RW UT WOS:000081006300002 PM 10396692 ER PT J AU Li, G Kaufman, KR Chao, EYS Rubash, HE AF Li, G Kaufman, KR Chao, EYS Rubash, HE TI Prediction of antagonistic muscle forces using inverse dynamic optimization during flexion extension of the knee SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; JOINT FORCES; PHYSIOLOGICAL PREDICTION; ISOKINETIC EXERCISE; LOWER-EXTREMITIES; MODEL; LOAD; HIP; COCONTRACTION; MUSCULATURE AB This paper examined the feasibility of using different optimization criteria in inverse dynamic optimization to predict antagonistic muscle forces and joint reaction forces during isokinetic flexion/extension and isometric extension exercises of the knee. Both quadriceps and hamstrings muscle groups were included in this study. The knee joint motion included flexion/extension, varus/valgus, and internal/external rotations. Four linear, nonlinear, and physiological optimization criteria were utilized in the optimization procedure. All optimization criteria adopted in this paper were shown to be able to predict antagonistic muscle contraction during flexion and extension of the knee. The predicted muscle forces were compared in temporal patterns with EMG activities (averaged data measured from five subjects). Joint reaction forces were predicted to be similar using all optimization criteria. In comparison with previous studies, these results suggested that the kinematic information involved in the inverse dynamic optimization plays an important role in prediction of the recruitment of antagonistic muscles rather than the selection of a particular optimization criterion. Therefore, it might be concluded that a properly formulated inverse dynamic optimization procedure should describe the knee joint rotation in three orthogonal planes. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mayo Clin & Mayo Fdn, Orthopaed Biomech Lab, Rochester, MN 55905 USA. Johns Hopkins Univ, Orthopaed Biomech Lab, Baltimore, MD USA. RP Li, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02215 USA. OI Kaufman, Kenton/0000-0002-7311-3781 NR 45 TC 50 Z9 54 U1 0 U2 5 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JUN PY 1999 VL 121 IS 3 BP 316 EP 322 DI 10.1115/1.2798327 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 208RW UT WOS:000081006300008 PM 10396698 ER PT J AU Keller, RB Atlas, SJ Soule, DN Singer, DE Deyo, RA AF Keller, RB Atlas, SJ Soule, DN Singer, DE Deyo, RA TI Relationship between rates and outcomes of operative treatment for lumbar disc herniation and spinal stenosis SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NONSURGICAL MANAGEMENT; 1-YEAR OUTCOMES; SURGERY; VOLUME; SCIATICA AB Background Population-based variations in rates of operations for the treatment of lumbar disc herniation and spinal stenosis are well known, This variability may occur in part because of; differences in the threshold at which physicians recommend an operation, reflecting uncertainty about the optimum use of an operative procedure, To the best of our knowledge, no previous reports have indicated whether differences in population-based rates of operative treatment are associated with patient outcomes. Methods:The Maine Lumbar Spine Study is an ongoing prospective study of 655 patients who had a herniated lumbar disc dr spinal stenosis, The patients were enrolled by their physicians, who provided baseline demographic and treatment-related data. The patients completed baseline and follow-up questionnaires that focused On symptoms, function, satisfaction, and quality of life. Small-area variation analysis was used to develop three distinct so-called spine service areas in Maine. The outcomes (usually at four years; minimum, two years) were compared among these areas, in which a total of 250 patients had been managed operatively and had answered questionnaires. Results: Population-based rates of operative treatment derived from state,vide data that had been collected over five years in the state of Maine ranged from 38 percent below to 72 percent above the average rate in the state (a greater than fourfold difference). The outcomes for the patients who had been managed by surgeons in the lowest-rate area were superior to those for the patients in the two higher-rate areas. Seventy-nine percent (fifty-seven) of seventy-two patients in the lowest-rate area had marked or complete relief of pain in the lower extremity compared with 60 percent (eighteen) of thirty patients in the highest-rate area. The improvements in the Poland disability score (p less than or equal to 0,01), quality of life (p less than or equal to 0,01), and satisfaction (p less than or equal to 0.05) were significantly greater among the patients in the lowest-rate area. The patients in the higher-rate areas generally had;less severe symptoms and findings at baseline than those in the lowest-rate area did. Conclusions: Higher population-based rates of elective spinal operations may be associated with inferior outcomes. This variability is possibly related to differences in physicians' preferences with regard to recommending an operation and in their criteria for the selection of patients, Physicians cannot assume that their outcomes will be the same as those of others, and therefore they need to evaluate their own results. C1 Maine Med Assessment Fdn, Manchester, ME 04351 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Univ Washington, Dept Med & Hlth Serv, Seattle, WA 98195 USA. RP Keller, RB (reprint author), Maine Med Assessment Fdn, POB 249, Manchester, ME 04351 USA. FU AHRQ HHS [HS 06344, HS 08194] NR 17 TC 56 Z9 57 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 JUN PY 1999 VL 81A IS 6 BP 752 EP 762 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 207JE UT WOS:000080933100002 PM 10391540 ER PT J AU Seipel, K Medley, QG Kedersha, NL Zhang, XA O'Brien, SP Serra-Pages, C Hemler, ME Streuli, M AF Seipel, K Medley, QG Kedersha, NL Zhang, XA O'Brien, SP Serra-Pages, C Hemler, ME Streuli, M TI Trio amino-terminal guanine nucleotide exchange factor domain expression promotes actin cytoskeleton reorganization, cell migration and anchorage-independent cell growth SO JOURNAL OF CELL SCIENCE LA English DT Article DE Rho; Rac; Dbl homology; trio; actin cytoskeleton ID GTP-BINDING PROTEIN; RHO-FAMILY GTPASES; FOCAL ADHESIONS; STRESS FIBERS; RAS TRANSFORMATION; DBL FAMILY; TYROSINE-PHOSPHATASE; EXTRACELLULAR-MATRIX; SIGNALING PATHWAYS; HOMOLOGY DOMAIN AB Rho family GTPases regulate diverse cellular processes, including extracellular signal-mediated actin cytoskeleton reorganization and cell growth, The functions of GTPases are positively regulated by guanine nucleotide exchange factors, which promote the exchange of GDP for GTP, Trio is a complex protein possessing two guanine nucleotide exchange factor domains, each with adjacent pleckstrin homology and SH3 domains, a protein serine/threonine kinase domain with an adjacent immunoglobulin-like domain and multiple spectrin-like domains, To assess the functional role of the two Trio guanine nucleotide exchange factor domains, NIH 3T3 cell lines stably expressing the individual guanine nucleotide exchange factor domains were established and characterized, Expression of the amino-terminal guanine nucleotide exchange factor domain results in prominent membrane ruffling, whereas cells expressing the carboxy-terminal guanine nucleotide exchange factor domain have lamellae that terminate in miniruffles, Moreover, cells expressing the amino-terminal guanine nucleotide exchange factor domain display more rapid cell spreading, haptotactic cell migration and anchorage-independent growth, suggesting that Trio regulates both cell motility and cell growth, Expression of full-length Trio in COS cells also alters actin cytoskeleton organization, as well as the distribution of focal contact sites, These findings support a role for Trio as a multifunctional protein that integrates and amplifies signals involved in coordinating actin remodeling, which is necessary for cell migration and growth. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Seipel, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55547, CA75091]; NIGMS NIH HHS [GM46526] NR 72 TC 41 Z9 42 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 JUN PY 1999 VL 112 IS 12 BP 1825 EP 1834 PG 10 WC Cell Biology SC Cell Biology GA 214TJ UT WOS:000081343400003 PM 10341202 ER PT J AU Schon, M Benwood, J O'Connell-Willstaedt, T Rheinwald, JG AF Schon, M Benwood, J O'Connell-Willstaedt, T Rheinwald, JG TI Human sweat gland myoepithelial cells express a unique set of cytokeratins and reveal the potential for alternative epithelial and mesenchymal differentiation states in culture SO JOURNAL OF CELL SCIENCE LA English DT Article DE cultured cell; eccrine; apocrine; keratin; actin ID HUMAN EPIDERMAL-KERATINOCYTES; HUMAN MAMMARY-GLAND; INTERMEDIATE FILAMENT PROTEINS; MONOCLONAL-ANTIBODY; GROWTH-FACTOR; DUCT CELLS; TERMINAL DIFFERENTIATION; MESOTHELIAL CELLS; CYSTIC-FIBROSIS; SIZED FILAMENTS AB We have characterized precisely the cytokeratin expression pattern of sweat gland myoepithelial cells and have identified conditions for propagating this cell type and modulating its differentiation in culture. Rare, unstratified epithelioid colonies were identified in cultures initiated from several specimens of full-thickness human skin. These cells divided rapidly in medium containing serum, epidermal growth factor (EGF), and hydrocortisone, and maintained a closely packed, epithelioid morphology when co-cultured with 3T3 feeder cells. Immunocytochemical and immunoblot analysis disclosed that the cells differed from keratinocytes in that they were E-cadherin-negative, vimentin-positive, and expressed an unusual set of cytokeratins, K5, K7, K14, and K17, When subcultured without feeder cells, they converted reversibly to a spindle morphology and ceased K5 and K14 expression. Under these conditions, EGF deprivation induced flattening, growth arrest, and expression of alpha-smooth muscle actin (alpha-sma), Coexpression of keratins and alpha-sma is a hallmark of myoepithelial cells, a constituent of secretory glands. Immunostaining of skin sections revealed that only sweat gland myoepithelial cells expressed the same pattern of keratins and alpha-sma and lack of E-cadherin as the cell type we had cultured. Interestingly, our immunocytochemical analysis of ndk, a skin-derived cell line of uncertain identity, suggests that this line is of myoepithelial origin. Earlier immunohistochemical studies by others had found myoepithelial cells to be K7-negative. We tested five K7-specific antibodies that can recognize this protein in western blots and in the assembled keratin filaments of mesothelial cells. Three of these antibodies did not recognize the K7 present in myoepithelial cell filaments or in HeLa cell filaments, indicating that some K7 epitopes are masked when K7 pairs with K17 instead of with its usual keratin filament partner, K19. C1 Brigham & Womens Hosp, Dept Med, Div Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. RP Rheinwald, JG (reprint author), Brigham & Womens Hosp, Dept Med, Div Dermatol, 75 Francis St, Boston, MA 02115 USA. FU NIAMS NIH HHS [P30 AR42689] NR 52 TC 51 Z9 54 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 JUN PY 1999 VL 112 IS 12 BP 1925 EP 1936 PG 12 WC Cell Biology SC Cell Biology GA 214TJ UT WOS:000081343400012 PM 10341211 ER PT J AU Sneddon, WB Demay, MB AF Sneddon, WB Demay, MB TI Characterization of an enhancer required for 1,25-dihydroxyvitamin D-3-dependent transactivation of the rat osteocalcin gene SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE rat osteocalcin gene; VDRE ID DNA-SEQUENCES; TRANSCRIPTIONAL ACTIVATION; ESTROGEN-RECEPTOR; NUCLEAR RECEPTORS; HORMONE RECEPTOR; ELEMENT; IDENTIFICATION; PROTEINS; MEDIATOR; BIND AB The sequences in the rat osteocalcin gene that lie 3' to the vitamin D response element (VDRE) contain a GGTTTGG motif (-420 to -414) that is essential for transcriptional activation of osteocalcin-CAT (OC-CAT) fusion genes by 1,25(OH)(2)D-3. A second copy of this motif, present on the antisense strand is unable to compete for nuclear protein binding to the VDRE-associated motif, suggesting that the core element extends beyond the GGTTTGG motif. In order to examine the base requirements for both function and nuclear protein interactions with the VDRE-associated GGTTTGG enhancer motif, deletion and substitution of flanking sequences was performed in the context of both the native osteocalcin promoter and a heterologous viral promoter. These data demonstrate that the base requirements for protein-DNA interactions and transactivation are located between -430 and -414. The position of the clement with respect to the VDRE is flexible and insertion of additional copies either 5' or 3' to the VDRE further enhances transactivation, both in the context of the native osteocalcin promoter and a heterologous viral promoter. These data demonstrate that VDR-dependent transactivation of the rat osteocalcin gene requires not only the VDRE (-456 to -442) hut also sequences between -430 and -414. The protein(s) that interacts with these sequences is capable of enhancing transcription in both a position and orientation-independent fashion. J. Cell. Biochem. 73:400-407, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 36597] NR 27 TC 4 Z9 4 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUN 1 PY 1999 VL 73 IS 3 BP 400 EP 407 DI 10.1002/(SICI)1097-4644(19990601)73:3<400::AID-JCB11>3.0.CO;2-O PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188HG UT WOS:000079840300011 PM 10321839 ER PT J AU Mandeville, JB Marota, JJA Ayata, C Zaharchuk, G Moskowitz, MA Rosen, BR Weisskoff, RM AF Mandeville, JB Marota, JJA Ayata, C Zaharchuk, G Moskowitz, MA Rosen, BR Weisskoff, RM TI Evidence of a cerebrovascular postarteriole windkessel with delayed compliance SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE cerebral blood flow; brain; rat; forepaw ID CEREBRAL BLOOD-VOLUME; MAGNETIC-RESONANCE IMAGE; SENSORY STIMULATION; INTRINSIC SIGNALS; BRAIN ACTIVATION; CARBON-DIOXIDE; FUNCTIONAL MRI; FLOW; CONTRAST; OXYGENATION AB A pronounced temporal mismatch was observed between the responses of relative cerebral blood volume (rCBV) measured by magnetic resonance imaging and relative cerebral blood flow measured by laser-Doppler flowmetry in rat somatosensory cortex after electrical forepaw stimulation. The increase of relative cerebral blood flow after stimulus onset and decrease after stimulus cessation were accurately described with a single exponential time constant of 2.4 +/- 0.8 seconds. In contrast, rCBV exhibited two distinct and nearly sequential processes after both onset and cessation of stimulation. A rapid change of rCBV (1.5 +/- 0.8 seconds) occurring immediately after onset and cessation was not statistically different from the time constant for relative cerebral blood flow. However, a slow phase of increase (onset) and decrease (cessation) with an exponential time constant of 14 +/- 13 seconds began approximately 8 seconds after the rapid phase of CBV change. A modified windkessel model was developed to describe the temporal evolution of rCBV as a rapid elastic response of capillaries and veins followed by slow venous relaxation of stress. Venous delayed compliance was suggested as the mechanism for the poststimulus undershoot in blood oxygen-sensitive magnetic resonance imaging signal that has been observed in this animal model and in human data. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NCI NIH HHS [P01CA48729]; NHLBI NIH HHS [R01HL39810]; NIDA NIH HHS [DA09467] NR 42 TC 327 Z9 328 U1 3 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 JUN PY 1999 VL 19 IS 6 BP 679 EP 689 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TB UT WOS:000084948700012 PM 10366199 ER PT J AU Ostergaard, L Chesler, DA Weisskoff, RM Sorensen, AG Rosen, BR AF Ostergaard, L Chesler, DA Weisskoff, RM Sorensen, AG Rosen, BR TI Modeling cerebral blood flow and flow heterogeneity from magnetic resonance residue data SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE vascular models; residue detection; magnetic resonance imaging; cerebral blood flow; flow heterogeneity; humans ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-RESOLUTION MEASUREMENT; IMAGING BOLUS TRACKING; CONTRAST AGENTS; MR CONTRAST; SUSCEPTIBILITY; VOLUME; BRAIN; PERFUSION; HYPERCAPNIA AB Existing model-free approaches to determine cerebral blood flow by external residue detection show a marked dependence of flow estimates on tracer arrival delays and dispersion. In theory, this dependence can be circumvented by applying a specific model of vascular transport and tissue flow heterogeneity. The authors present a method to determine flow heterogeneity by magnetic resonance residue detection of a plasma marker. Probability density functions of relative flows measured in six healthy volunteers were similar among tissue types and volunteers, and were in qualitative agreement with literature measurements of capillary red blood cell and plasma velocities. Combining the measured flow distribution with a model of vascular transport yielded excellent model fits to experimental residue data. Fitted gray-to-white flow-rate ratios were in good agreement with PET literature values, as well as a model-free singular value decomposition (SVD) method in the same subjects, The vascular model was found somewhat sensitive to data noise, but showed far less dependence on vascular delay and dispersion than the model-free SVD approach. C1 Aarhus Univ Hosp, Dept Neuroradiol, DK-8000 Aarhus, Denmark. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard MIT Div Hlth Sci, Cambridge, MA USA. RP Ostergaard, L (reprint author), Aarhus Kommune Hosp, Dept Neuroradiol, Norrebrogade 44, DK-8000 Aarhus, Denmark. RI Ostergaard, Leif/A-9281-2008 OI Ostergaard, Leif/0000-0003-2930-6997 FU NCI NIH HHS [R01-CA40303, R01-CA66072]; NHLBI NIH HHS [R01-HL39810] NR 25 TC 89 Z9 89 U1 0 U2 1 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 JUN PY 1999 VL 19 IS 6 BP 690 EP 699 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 277TB UT WOS:000084948700013 PM 10366200 ER PT J AU Miller, KK Klibanski, A AF Miller, KK Klibanski, A TI Amenorrheic bone loss SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; FUNCTIONAL HYPOTHALAMIC-AMENORRHEA; QUANTITATIVE COMPUTED-TOMOGRAPHY; RECEPTOR GENE POLYMORPHISMS; X-RAY ABSORPTIOMETRY; FEMALE ATHLETE TRIAD; ADD-BACK THERAPY; GROWTH-FACTOR-I; MINERAL DENSITY C1 Massachusetts Gen Hosp, Dept Med, Clin Res Ctr, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Dept Med, Clin Res Ctr, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01-DK-52625] NR 153 TC 63 Z9 67 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1775 EP 1783 DI 10.1210/jc.84.6.1775 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000002 PM 10372663 ER PT J AU Orwoll, ES Nelson, HD AF Orwoll, ES Nelson, HD TI Does estrogen adequately protect postmenopausal women against osteoporosis: An iconoclastic perspective SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID REPLACEMENT THERAPY; OLDER WOMEN; BONE LOSS; FRACTURES; PREVENTION; AGE; HIP C1 Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland VA Med Ctr, Portland, OR 97201 USA. RP Orwoll, ES (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Unit, Portland VA Med Ctr, 3181 SW Sam Jackson Pk, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 14 TC 15 Z9 15 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1872 EP 1874 DI 10.1210/jc.84.6.1872 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000027 PM 10372678 ER PT J AU Perkins, RB Hall, JE Martin, KA AF Perkins, RB Hall, JE Martin, KA TI Neuroendocrine abnormalities in hypothalamic amenorrhea: Spectrum, stability, and response to neurotransmitter modulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; LUTEINIZING-HORMONE; ANOREXIA-NERVOSA; BETA-ENDORPHIN; NALTREXONE TREATMENT; ADRENERGIC SYSTEMS; OPIOID-PEPTIDES; ORAL CLONIDINE; FEMALE RAT AB To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12-24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns. The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. Conclusions: 1) HA. represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA. C1 Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Martin, KA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Bartlett Hall Extens 5,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01RR01066]; NICHD NIH HHS [U54HD29164, P30HD28138] NR 51 TC 42 Z9 46 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1905 EP 1911 DI 10.1210/jc.84.6.1905 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000034 PM 10372685 ER PT J AU Seminara, SB Hall, JE Taylor, AE Crowley, WF Martin, KA AF Seminara, SB Hall, JE Taylor, AE Crowley, WF Martin, KA TI The Reproductive Endocrine Associates of the Massachusetts General Hospital: Fifteen years of integrated clinical practice and investigation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; LIPOPROTEIN LIPID CONCENTRATIONS; HYPOGONADOTROPIC HYPOGONADISM; ASSISTED-REPRODUCTION; INSULIN-SECRETION; DEFICIENT MEN; WOMEN; INDUCTION C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 505,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [U54 HD029164, P30 HD028138, U54 HD028138] NR 35 TC 0 Z9 0 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1912 EP 1918 DI 10.1210/jc.84.6.1912 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000035 PM 10372686 ER PT J AU Hadigan, C Miller, K Corcoran, C Anderson, E Basgoz, N Grinspoon, S AF Hadigan, C Miller, K Corcoran, C Anderson, E Basgoz, N Grinspoon, S TI Fasting hyperinsulinemia and changes in regional body composition in human immunodeficiency virus-infected women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; PERIPHERAL LIPODYSTROPHY; PROTEASE INHIBITORS; HYPERLIPIDEMIA AB A novel lipodystrophy syndrome (characterized by insulin resistance, hypertriglyceridemia, and fat redistribution) has recently been described in human immunodeficiency virus (HIV)-infected patients. However, investigation of the Lipodystrophy syndrome has generally been limited to men; and a comprehensive evaluation of insulin, lipids, and regional body composition has not been performed in the expanding population of HIV-infected women. In this study, we assessed fasting insulin, Lipid levels, virologic parameters, and regional body composition, using dual-energy x-ray absorptiometry, in a cohort of 75 HIV-infected women (age, 25-46 yr), in comparison with 30 healthy weight-matched premenopausal control subjects. HIV-infected women demonstrated significant truncal adiposity (38.5 +/- 0.9 vs. 34.9 +/- 1.3%, P < 0.05) hyperinsulinemia (15.9 +/- 1.5 vs. 7.5 +/- 0.6 mu U/mL, P < 0.001) and an increased insulin-to-glucose ratio (0.2 +/- 0.02 vs. 0.1 +/- 0.03, P < 0.001), compared with control subjects. Insulin and the insulin-to-glucose ratio were increased, even among HIV-infected patients with low body weight (<90% of ideal body weight) (insulin, 13.3 +/- 2.8 mu U/mL, P < 0.01 vs. control; insulin/glucose, 0.2 +/- 0.04, P < 0.01 vs. control). Insulin and the insulin-to-glucose ratio were most significantly elevated among patients with increased truncal adiposity (insulin, 28.2 +/- 3.2 mu U/mL, P < 0.001 vs. control; insulin/glucose, 0.32 +/- 0.04, P < 0.001 vs. control). In contrast, no differences in insulin were seen in relation to protease inhibitor (PI) use. Similarly, HIV-infected women also demonstrated significant hypertriglyceridemia (144 +/- 15 vs. 66 +/- 23 mg/dL, P < 0.01 vs, controls), which was present even among low-weight patients (148 +/- 32 mg/dL, P < 0.001 vs. control) but was not related to truncal adiposity or PI usage. These data demonstrate significant hyperinsulinemia and truncal adiposity in HIV-infected women. Our data suggest that these metabolic abnormalities occur at baseline in HN-infected women, independent of PI use. However, these data do not rule out a direct effect of PI therapy on fat metabolism or indirect effects of PI therapy to further worsen glucose and lipid homeostasis in association with weight gain and disease recovery. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01-DK 54167, R01-DK49302] NR 17 TC 154 Z9 155 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1932 EP 1937 DI 10.1210/jc.84.6.1932 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000038 PM 10372689 ER PT J AU Meneilly, GS Veldhuis, JD Elahi, D AF Meneilly, GS Veldhuis, JD Elahi, D TI Disruption of the pulsatile and entropic modes of insulin release during an unvarying glucose stimulus in elderly individuals SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CONTINUOUS ENTERAL NUTRITION; DEPENDENT DIABETES-MELLITUS; PLASMA-GLUCOSE; ULTRADIAN OSCILLATIONS; C-PEPTIDE; SECRETION; HORMONE; PATTERNS; HUMANS; TOLERANCE AB Insulin is secreted in a pulsatile fashion with measurable orderliness (low entropy). Aging is characterized by alterations in pulsatile insulin release in the fasting state. We undertook the current studies to determine whether disruptions in pulsatile insulin release in response to sustained glucose infusion also accompany the age-related changes in carbohydrate metabolism. Healthy young (n = 10; body mass index, 23 +/- 1 kg/m(2); age, 23 +/- 1 yr) and old (n = 10; body mass index, 24 +/- 1 kg/m(2); age, 80 +/- 2 yr) volunteers underwent a 600-min hyperglycemic glucose clamp. During the entire 600 min, insulin was sampled every 10 min, and insulin release was evaluated by Cluster analysis. From 240-360 min, insulin was sampled every 1 min, and secretory pulse analysis was conducted using a multiparameter deconvolution technique. During the 1-min sampling interval, basal insulin secretion (P < 0.01), insulin production rate (P < 0.01), pulsatile mean and integrated insulin concentration (P < 0.01), insulin secretory burst mass (P < 0.01), and burst amplitude (P < 0.05) were reduced in the elderly. In addition, interpulse interval was increased in the aged (P < 0.05). In the 600-min studies, interpulse interval was greater in the aged (P < 0.01) and burst number (P < 0.01), basal concentration (P < 0.01), and burst increment (P < 0.05) were less. Approximate entropy, a measure of irregularity of insulin release, was increased in the aged, signifying the loss of orderliness of insulin secretion (P < 0.05). We conclude that in response to a sustained (10-h) glucose infusion, normal aging is characterized by a reduction in mass and amplitude of rapid insulin pulses and a decrease in the frequency, amplitude, and regularity of ultradian pulses. Whether these changes in insulin pulsatility contribute directly to the age-related changes in carbohydrate metabolism will require further clinical studies. C1 Univ British Columbia, Dept Med, Div Geriatr Med, Vancouver, BC V6T 2B5, Canada. Univ Virginia, Dept Med, Charlottesville, VA 22908 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Meneilly, GS (reprint author), 215 Hawken Dr, St Lucia, Qld 4067, Australia. EM gmeneillly@uq.net.au FU NIA NIH HHS [AG-00599, AG-147991]; NICHD NIH HHS [1K04 HD00634] NR 39 TC 34 Z9 34 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 1938 EP 1943 DI 10.1210/jc.84.6.1938 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000039 PM 10372690 ER PT J AU Grinspoon, S Miller, K Coyle, C Krempin, J Armstrong, C Pitts, S Herzog, D Klibanski, A AF Grinspoon, S Miller, K Coyle, C Krempin, J Armstrong, C Pitts, S Herzog, D Klibanski, A TI Severity of osteopenia in estrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; BONE-MINERAL DENSITY; PHYSICAL-ACTIVITY; BODY-COMPOSITION; OSTEOPOROSIS; MASS; ABSORPTIOMETRY; PROTEIN AB Reduced bone density is observed in over half of women with anorexia nervosa (AN), in whom the risk of fracture is significantly increased even at a young age. It is unknown to what extent low bone density in AN differs from other conditions of premenopausal osteoporosis and is related to estrogen deficiency and/or other factors, such as nutritional status. We therefore investigated bone loss in nutritionally replete and nutritionally deplete amenorrheic women by comparing patients with AN (n = 30) to age-matched subjects with hypothalamic amenorrhea (HA; n = 19) in whom duration of amenorrhea, prior estrogen use, and age of menarche were comparable. Healthy, age-matched, eumenorrheic women were studied as a control group (NL; n = 30). Weight and nutritionally dependent factors including (body mass index, 20.7 +/- 0.3 vs. 16.7 +/- 0.3 kg/m(2); P < 0.0001), insulin-like growth factor I (270 +/- 18 vs. 203 +/- 17 ng/mL; P < 0.01), percent body fat (26% vs. 19%; P < 0.0001), and lean body mass (38.7 +/- 1.1 vs. 34.3 +/- 0.8, P < 0.01) were significantly different between the HA and AN groups, respectively. The bone densities of the anterior-posterior (AP) spine, total hip, and total body measured by dual energy x-ray absortiometry were reduced in both amenorrheic groups compared to those in control subjects, but were significantly lower in women with AN than in those with HA. The t scores for AP spine and hip were -1.80 +/- 0.15 (AN), -0.80 +/- 0.22 (HA), and 0.28 +/- 0.19 SD (NL) for the AP spine and -1.62 +/- 0.17 (AN), -0.51 +/- 0.21 (HA), and 0.25 +/- 0.16 (NL) for the total hip, respectively (P < 0.01 for all comparisons). Among the amenorrheic subjects, duration of amenorrhea, age of menarche, and N-telopeptide were inversely correlated with bone density at all sites, whereas body mass index, insulinlike growth factor I, lean body mass, and fat intake were positively correlated with bone density at all sites measured. In multivariate regression analyses, bone density was most significantly related to lean body mass (P = 0.05 and P = 0.03 for the spine and hip, respectively), but not to the duration of amenorrhea or other indexes of estrogen status among patients with AN. In contrast, bone density of the lumbar spine was significantly related to weight and duration of amenorrhea among patients with HA. These data demonstrate that the severity of osteopenia in AN is greater than that in patients with HA and is critically dependent upon nutritional factors in addition to the degree or duration of estrogen deficiency itself. Lean body mass, independent of the duration or severity of estrogen deficiency, is an important predictor of bone loss among women with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorder Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [P32-DK-07028, R01-DK-52625] NR 34 TC 123 Z9 123 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 2049 EP 2055 DI 10.1210/jc.84.6.2049 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000059 PM 10372709 ER PT J AU Finkelstein, JS Schoenfeld, DA AF Finkelstein, JS Schoenfeld, DA TI Effects of gonadal suppression on the regulation of parathyroid hormone and 1,25-dihydroxyvitamin D secretion in women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID KIDNEY-CELL-CULTURES; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; BONE MASS; PRIMARY HYPERPARATHYROIDISM; TRANSDERMAL ESTROGEN; CALCIUM-ABSORPTION; OSTEOPOROSIS; METABOLISM; THERAPY AB Although a causal association between estrogen deficiency and bone loss has been established for many years, the mechanism by which estrogen deficiency leads to bone loss is unclear. Estrogen deficiency could induce bone loss either by a direct effect on bone cells to modify the production of bone-resorbing cytokines or by altering the production or response to calcium regulatory hormones such as PTH and 1,25-dihydroxyvitamin D. To assess the effects of ovarian hormones on calcium regulatory hormones, we evaluated the ability of calcium to suppress PTH secretion and the ability of PTH to increase serum 1,25-dihydroxyvitamin D and whole blood ionic calcium levels in women before and after GnRH analog-induced ovarian suppression. Sixteen women with endometriosis underwent iv infusion of calcium (1.1 mg calcium gluconate/cc in 5% dextrose) at a rate of 4 cc/kg.h (n = 7) or human PTH-(1-34) (Parathar) at a dose of 0.55 U/kg.h (n = 9) before and after 6 months of suppression of ovarian function with the GnRH analog nafarelin acetate (200 mu g, intranasally, twice daily). Initial infusions were performed between days 6-10 of the menstrual cycle. Serum PTH and whole blood ionic calcium levels were measured at -20, -10, and 0 min and then every 10 min for 2 h during iv calcium infusions. Whole blood ionic calcium and 1,25-dihydroxyvitamin D levels were measured every 6 h for 24 h during iv human PTH-(1-34) infusions. Serum estradiol levels were markedly suppressed by nafarelin therapy in both groups of women. The relationship between whole blood ionic calcium and serum PTH levels was similar before and during nafarelin-induced ovarian suppression. The net change and rate of rise in serum 1,25-dihydroxyvitamin D levels in response to PTH infusion were similar before and during nafarelin therapy. Peak whole blood ionic calcium and incremental increases in ionic calcium in response to PTH were similar before and during nafarelin therapy. Our data suggest that ovarian suppression does not alter the regulation of PTH secretion in response to calcium, the ability of PTH to stimulate 1,25-dihydroxyvitamin D formation, or the skeletal sensitivity to PTH. These findings suggest that alterations in calcium regulatory hormones by estrogen deficiency are unlikely to play a major role in the pathogenesis of estrogen deficiency bone loss. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Bulfinch 327,55 Fruit St, Boston, MA 02114 USA. EM finkelstein@helix.mgh.harvard.edu FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [R29-DK-43341] NR 39 TC 6 Z9 6 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 2151 EP 2156 DI 10.1210/jc.84.6.2151 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000074 PM 10372724 ER PT J AU Welt, CK Adams, JM Sluss, PM Hall, JE AF Welt, CK Adams, JM Sluss, PM Hall, JE TI Inhibin A and inhibin B responses to gonadotropin withdrawal depends on stage of follicle development SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; MESSENGER-RIBONUCLEIC-ACID; LUTEINIZING-HORMONE SURGE; SUBUNIT GENE-EXPRESSION; GRANULOSA-LUTEAL CELLS; HUMAN CORPUS-LUTEUM; ANTAGONIST NAL-GLU; STIMULATING-HORMONE; DIMERIC INHIBIN; PROGESTERONE SECRETION AB Previous studies demonstrate that inhibin A and B are differentially secreted across the menstrual cycle. To test the hypothesis that the responses of inhibin A and inhibin B to partial gonadotropin withdrawal are influenced by the stage of follicular development, a maximally suppressive dose of the Nal-Glu GnRH antagonist (150 mu g/kg) was administered to normal cycling women during the midfollicular (MFP; n = 8), late follicular (LFP; n = 6), and midluteal phase (MLP; n = 5) to assess ovarian responsiveness over a broad range of developmental stages. Administration of the GnRH antagonist resulted in a significant decrease in LH (75 +/- 5%, 63 +/- 3%, and 84 +/- 7%; P < 0.05) and FSH (23 +/- 9%, 32 +/- 5%, and 39 +/- 6%; P < 0.04) during the MFP, LFP, and MLP, respectively. During the MFP, partial withdrawal of gonadotropins resulted in disappearance of the dominant follicle on ultrasound accompanied by a decrease in estradiol (E-2; 64.9 +/- 11.4 to 23.9 +/- 3.3 pg/mL; P < 0.02) and inhibin B levels (121.6 +/- 14.8 to 28.4 +/- 4.8 pg/mL; P < 0.002) from baseline to near the limit of detection. Inhibin A was near the limit of detection in this cycle stage (0.8 +/- 0.1 IU/mL). When gonadotropins were withdrawn during the LFP, the size of the dominant follicle remained stationary in four of five subjects, and inhibin B (84.1 +/- 14.1 to 22.2 +/- 3.4 pg/mL; 71 +/- 5%; P < 0.02), inhibin A (4.4 +/- 1.1 to 1.3 +/- 0.5 IU/mL; 71 +/- 7%; P < 0.02), and E-2 (236.8 +/- 48.2 to 95.6 +/- 39.0 pg/mL; 61 +/- 12%; P < 0.02) decreased similarly. Time to ovulation was shorter in association with higher inhibin A (r = -0.67; P < 0.02) and E-2 (r = -0.79; P < 0.003), but there was no relation to inhibin B. During the MLP, decreased gonadotropin levels resulted in the disappearance of corpus luteum function with a significant decrease in inhibin A (9.0 +/- 0.4 to 0.7 +/- 0.1 IU/mL; 92 +/- 1%; P < 0.0001) in combination with decreased E-2 (150.4 +/- 22.9 to 23.8 +/- 4.2 pg/mL; 83 +/- 3%; P < 0.005) and progesterone (12.6 +/- 2.6 to 0.9 +/- 0.2 ng/mL; 92 +/- 2%; P < 0.01). Administration of a GnRH antagonist at precise stages of the menstrual cycle provides further evidence that differential regulation of inhibin A and inhibin B is critically dependent on the stage of follicular development. Inhibin B secretion is exquisitely sensitive to gonadotropin withdrawal during the MFP when inhibin A has not yet risen. Inhibin A and inhibin B decrease equally after GnRH antagonist administration during the LFP. However, before antagonist administration, the positive correlation between estradiol and inhibin A and time to ovulation and the lack of such a correlation with inhibin B suggest that the source of inhibin B secretion is different from that of inhibin A and E-2. The decrease in inhibin A secretion after antagonist administration during the luteal phase confirms gonadotropin-dependent secretion of dimeric inhibin A by the corpus luteum. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [P30-HD-28138, U54-HD-29164] NR 47 TC 65 Z9 67 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1999 VL 84 IS 6 BP 2163 EP 2169 DI 10.1210/jc.84.6.2163 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202VZ UT WOS:000080674000076 PM 10372726 ER PT J AU Peters, LL Jindel, HK Gwynn, B Korsgren, C John, KM Lux, SE Mohandas, N Cohen, CM Cho, MR Golan, DE Brugnara, C AF Peters, LL Jindel, HK Gwynn, B Korsgren, C John, KM Lux, SE Mohandas, N Cohen, CM Cho, MR Golan, DE Brugnara, C TI Mild spherocytosis and altered red cell ion transport in protein 4.2-null mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MURINE PALLID MUTATION; BLOOD-CELLS; HEREDITARY SPHEROCYTOSIS; MEMBRANE SKELETONS; CYTOPLASMIC DOMAIN; ANION TRANSPORT; BETA-SPECTRIN; BAND-3 AE1; BINDING; GENE AB Protein 4.2 is a major component of the red blood cell(RBC) membrane skeleton. We used targeted mutagenesis in embryonic stem (ES) cells to elucidate protein 4.2 functions in vivo. Protein 4.2-null (4.2(-/-)) mice have mild hereditary spherocytosis (HS). Scanning electron microscopy and ektacytometry confirm loss of membrane surface in 4.2(-/-) RBCs. The membrane skeleton architecture is intact, and the spectrin and ankyrin content of 4.2(-/-) RBCs are normal. Band 3 and band 3-mediated anion transport are decreased. Protein 4.2(-/-) RBCs show altered cation content (increased K+/decreased Na+) resulting in dehydration. The passive Na+ permeability and the activities of the Na-K-2Cl and K-Cl cotransporters, the Na/H exchanger, and the Gardos channel in 4.2(-/-) RBCs are significantly increased. Protein 4.2(-/-) RBCs demonstrate an abnormal regulation of cation transport by cell volume. Cell shrinkage induces a greater activation of Na/H exchange and Na-K-2Cl cotransport in 4.2(-/-) RBCs compared with controls. The increased passive Na+ permeability of 4.2(-/-) RBCs is also dependent on cell shrinkage. We conclude that protein 4.2 is important in the maintenance of normal surface area in RBCs and for normal RBC cation transport. C1 Jackson Lab, Bar Harbor, ME 04609 USA. St Elizabeths Med Ctr, Dept Biomed Res, Boston, MA 02135 USA. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. RP Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM luanne@aretha.jax.org RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 FU NCI NIH HHS [P30 CA034196]; NHLBI NIH HHS [HL-55321, P01 HL032262, R01 HL032854, R01 HL055321, R37 HL032854]; NIDDK NIH HHS [DK-26263, DK-34083, R01 DK026263, R01 DK034083, R01 DK050422, R37 DK026263] NR 52 TC 59 Z9 59 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 11 BP 1527 EP 1537 DI 10.1172/JCI5766 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VY UT WOS:000083468100008 PM 10359562 ER PT J AU Menaa, C Devlin, RD Reddy, SV Gazitt, Y Choi, SJ Roodman, GD AF Menaa, C Devlin, RD Reddy, SV Gazitt, Y Choi, SJ Roodman, GD TI Annexin II increases osteoclast formation by stimulating the proliferation of osteoclast precursors in human marrow cultures SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-BONE MARROW; TRANSFORMING GROWTH-FACTOR; CELLS; DIFFERENTIATION; IDENTIFICATION; INTERLEUKIN-1; RESORPTION; SURFACE; LINEAGE; GM AB Annexin II (AXII), a calcium-dependent phospholipid-binding protein, has been recently found to be an osteoclast (OCL) stimulatory factor that is also secreted by OCLs. In vitro studies showed that AXII induced OCL formation and bone resorption. However, the mechanism of action by which AXII acts as a soluble extracellular protein to induce OCL formation is unknown. In this paper, we demonstrate that AXII gene expression is upregulated by 1,25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] and that addition of AXII significantly increased OCL-like multinucleated cell formation. Time-course studies suggested that AXII acted on the proliferative stage of OCL precursors and that AXII increased thymidine incorporation in OCL precursors. Moreover, AXII enhanced the growth of CFU-GM, the earliest identifiable OCL precursor, when bone marrow cultures were treated with low concentrations of GM-CSF. This capacity of AXII to induce OCL precursor proliferation was due to induction of GM-CSF expression, because the addition of neutralizing antibodies to GM-CSF blocked the stimulatory effect of AXII on OCL formation. RT-PCR analysis using RNA from highly purified subpopulations of marrow cells demonstrated that T cells, especially CD4(+) T cells, produced GM-CSF in response to AXII. Furthermore, FACS(R) analysis of T-cell subpopulations treated with fluorescein-labeled AXII suggested that the CD4+, but not CD8(+), subpopulation of T cells express an AXII receptor. Taken together, these data suggest that AXII stimulates OCL formation by activating T cells through a putative receptor to secrete GMCSF. GM-CSF then expands the OCL precursor pool to enhance OCL formation. C1 Audie Murphy Vet Adm Hosp, Res Serv 151, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX 78284 USA. RP Roodman, GD (reprint author), Audie Murphy Vet Adm Hosp, Res Serv 151, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NCI NIH HHS [P01 CA040035, CA-40035]; NIA NIH HHS [R01 AG013625, AG-13625]; NIAMS NIH HHS [R01 AR041336, R01 AR044603, AR-44603] NR 27 TC 68 Z9 72 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 11 BP 1605 EP 1613 DI 10.1172/JCI6374 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VY UT WOS:000083468100016 PM 10359570 ER PT J AU Mohan, C Morel, L Yang, P Watanabe, H Croker, B Gilkeson, G Wakeland, EK AF Mohan, C Morel, L Yang, P Watanabe, H Croker, B Gilkeson, G Wakeland, EK TI Genetic dissection of lupus pathogenesis: a recipe for nephrophilic autoantibodies SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ANTI-DNA ANTIBODIES; HEPARAN-SULFATE PROTEOGLYCAN; CONGENIC MOUSE STRAINS; DRUG-INDUCED LUPUS; MURINE MODELS; T-CELLS; ERYTHEMATOSUS; MICE; MECHANISMS; LPR AB Sle1 and Sle3 are 2 loci that confer susceptibility to lupus nephritis in the NZM2410 strain of mice. Our previous work has shown that B6.NZMc1 mice, congenic for Sle1, exhibit loss of tolerance to chromatin but do not develop any pathogenic autoantibodies or disease. B6.NZMc7 mice, congenic for Sle3, exhibit low-grade polyclonal B- and T-cell activation, elevated CD4/CD8 ratios, and mildly penetrant glomerulonephritis. In contrast to these monocongenics, the present study reveals that B6.NZMc1 \ c7 mice, bicongenic for Sle1 and Sle3, exhibit splenomegaly, significantly expanded populations of activated B and CD4(+) T cells, and a robust, variegated IgG autoantibody response targeting multiple components of chromatin (including double-stranded DNA), intact glomeruli, and basement membrane matrix antigens. As one might predict, these mice, particularly the females, exhibit highly penetrant glomerulonephritis. These findings lend strong support to a two-step epistatic model for the formation of pathogenic, nephrophilic autoantibodies in lupus. Whereas loci such as Sle1 may serve to breach tolerance to chromatin, full-blown pathogenic maturation of the autoantibody response appears to require additional input from other loci (such as Sle3) and gender-based factors. C1 Univ Texas, SW Med Ctr, Simmons Arthritis Res Ctr, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75235 USA. Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. Ralph H Johnson Vet Affairs Med Coll, Med Res Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Mohan, C (reprint author), Univ Texas, SW Med Ctr, Simmons Arthritis Res Ctr, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NIAID NIH HHS [P01 AI-39824, P01 AI039824]; NIAMS NIH HHS [R01 AR044894, R29 AR-44894] NR 55 TC 130 Z9 130 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1999 VL 103 IS 12 BP 1685 EP 1695 DI 10.1172/JCI5827 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251VZ UT WOS:000083468200011 PM 10377175 ER PT J AU Hudspeth, MK Gerardo, SH Maiden, MFJ Citron, DM Goldstein, EJC AF Hudspeth, MK Gerardo, SH Maiden, MFJ Citron, DM Goldstein, EJC TI Characterization of Bacteroides forsythus strains from cat and dog bite wounds in humans and comparison with monkey and human oral strains SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GEL-ELECTROPHORESIS; SDS-PAGE; IDENTIFICATION AB Bacteroides forsythus strains recovered from cat and dog bite wound infections in humans (n = 3), monkey oral strains (n = 3), and the human oral ATCC 43037 type strain were characterized by using phenotypic characteristics, enzymatic tests, whole cell fatty acid analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, PCR fingerprinting, and 16S rDNA (genes coding for rRNA) sequencing. All three bite wound isolates grew on brucella agar supplemented with 5% sheep blood, vitamin K-1, and hemin, These strains, unlike the ATCC strain and previously described monkey oral and human clinical strains, did not require N-acetylmuramic acid supplementation for growth as pure cultures. However, their phenotypic characteristics, except for catalase production, were similar to those of previously identified strains. PCR fingerprinting analysis showed differences in band patterns from the ATCC strain. Also, SDS-PAGE and whole cell fatty acid analysis indicated that the dog and cat bite wound strains were similar but not identical to the human B. forsythus ATCC 43037 type strain and the monkey oral strains. The rDNA sequence analysis indicated that the three bite wound isolates had 99.93% homology with each other and 98.9 and 99.22% homology with the human ATCC 43037 and monkey oral strains, respectively, These results suggest that there are host-specific variations within each group. C1 Univ Calif Los Angeles, Med Ctr, R M Alden Res Lab, Santa Monica, CA 90404 USA. USN, Hlth Res Ctr, San Diego, CA 92186 USA. Forsyth Dent Ctr, Dept Periodontal Microbiol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Goldstein, EJC (reprint author), Univ Calif Los Angeles, Med Ctr, R M Alden Res Lab, 1250 16th St, Santa Monica, CA 90404 USA. NR 17 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1999 VL 37 IS 6 BP 2003 EP 2006 PG 4 WC Microbiology SC Microbiology GA 197BN UT WOS:000080344900060 PM 10325363 ER PT J AU Recht, A Gray, R Davidson, NE Fowble, BL Solin, LJ Cummings, FJ Falkson, G Falkson, HC Taylor, SG Tormey, DC AF Recht, A Gray, R Davidson, NE Fowble, BL Solin, LJ Cummings, FJ Falkson, G Falkson, HC Taylor, SG Tormey, DC TI Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: Experience of the Eastern Cooperative Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSITIVE BREAST-CANCER; MODIFIED RADICAL-MASTECTOMY; AXILLARY LYMPH-NODES; DOXORUBICIN-CYCLOPHOSPHAMIDE; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; RANDOMIZED TRIAL; LOCAL RECURRENCE; POSTMASTECTOMY RADIOTHERAPY; REGIONAL RECURRENCE AB Purpose: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. Patients and Methods: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time far patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). Results: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LEE, 254(13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF, Conclusion: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen, prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens. (C) 1999 by American Society of Clinical Oncology. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Roger Williams Canc Med Ctr, Providence, RI USA. Univ Pretoria, Sch Med, ZA-0002 Pretoria, South Africa. Rush Presbyterian Med Sch, Chicago, IL USA. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. AMC Canc Res Ctr, Denver, CO USA. RP Recht, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, E Campus,Finard Bldg B25,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA16116, CA18281, CA23318] NR 59 TC 281 Z9 301 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1999 VL 17 IS 6 BP 1689 EP 1700 PG 12 WC Oncology SC Oncology GA 206AA UT WOS:000080852800006 PM 10561205 ER PT J AU Gill, PS Tulpule, A Espina, BM Cabriales, S Bresnahan, J Ilaw, M Louie, S Gustafson, NF Brown, MA Orcutt, C Winograd, B Scadden, DT AF Gill, PS Tulpule, A Espina, BM Cabriales, S Bresnahan, J Ilaw, M Louie, S Gustafson, NF Brown, MA Orcutt, C Winograd, B Scadden, DT TI Paclitaxel is safe and effective in the treatment of advanced AIDS-related Kaposi's sarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PEGYLATED-LIPOSOMAL DOXORUBICIN; ACQUIRED IMMUNODEFICIENCY SYNDROME; VINCRISTINE; TRIAL; BLEOMYCIN; DAUNORUBICIN; CRITERIA; THERAPY; TAXOL AB Purpose: Liposomal anthracyclines are the present standard treatment for advanced AIDS-related Kaposi's sarcoma (KS). No effective therapies have been defined for use after treatment failure of these agents, A phase II trial was thus conducted with paclitaxel in patients with advanced KS ta assess safety and antitumor activity. Materials and Methods: A regimen of paclitaxel at a dose of 100 mg/m(2) was given every 2 weeks to patients with advanced AIDS-related KS. patients. were treated until complete remission, disease progression, or unacceptable toxicity occurred. Results: Fifty-six patients with advanced AIDS-related KS were accrued. Tumor-associated edema was present in 70% of patients and visceral involvement in 45%. Forty patients (71%) had received prior systemic therapy; 31 of these were resistant to an anthracycline., The median entry CD4(+) lymphocyte count was 20 cells/ mm(3) (range, 0 to 358). A median of 10 cycles (range, 1 ta 54+) of paclitaxel was administered. Fifty-nine percent of patients showed complete (n = 1) or partial response(n = 32) to paclitaxel. The median duration of response was 10.4 months (range, 2.8 to 26.7+ months) and the median survival was 15.4 months. The main side effects of therapy were grade 3 or 4 neutropenia in 61% of patients and mild-to-moderate alopecia in 87%. Conclusion: Paclitaxel at 100 mg/m(2) given every 2 weeks is active and well tolerated in the treatment of advanced and previously treated AIDS-related KS. The median duration of response is among the longest observed for any regimen or single agent reported far AIDS-related KS. Paclitaxel at this dosage and schedule is a treatment option for patients with advanced AIDS-related KS, including those who have experienced treatment failure of prior systemic therapy. (C) 1999 by American Society of Clinical Oncology. C1 Univ So Calif, Kenneth Norris Canc Hosp & Res Inst, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Kenneth Norris Canc Hosp & Res Inst, Dept Pharm, Los Angeles, CA 90033 USA. Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT USA. Harvard Univ, New England Deaconess Hosp, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gill, PS (reprint author), Univ So Calif, Kenneth Norris Canc Hosp & Res Inst, Dept Med, 1441 Eastlake Ave,MS-34, Los Angeles, CA 90033 USA. NR 28 TC 95 Z9 98 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1999 VL 17 IS 6 BP 1876 EP 1883 PG 8 WC Oncology SC Oncology GA 206AA UT WOS:000080852800029 PM 10561228 ER PT J AU Liu, G Darling, MLR Chan, J Jaklitsch, MT Skarin, AT AF Liu, G Darling, MLR Chan, J Jaklitsch, MT Skarin, AT TI Gynecomastia in a patient with lung cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; EXPRESSION C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Liu, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 NR 7 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN PY 1999 VL 17 IS 6 BP 1956 EP 1957 PG 2 WC Oncology SC Oncology GA 206AA UT WOS:000080852800038 PM 10561237 ER PT J AU Wirshing, DA Wirshing, WC Kysar, L Berisford, MA Goldstein, D Pashdag, J Mintz, J Marder, SR AF Wirshing, DA Wirshing, WC Kysar, L Berisford, MA Goldstein, D Pashdag, J Mintz, J Marder, SR TI Novel antipsychotics: Comparison of weight gain liabilities SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 19th Collegium-Internationale-Neuro-Psychopharmacologicum Congress CY JUN 27-JUL 01, 1994 CL WASHINGTON, D.C. SP Collegium Int Neuro Psychopharm ID FOOD-INTAKE; PSYCHOTROPIC-DRUGS; CLOZAPINE; SEROTONIN; RISPERIDONE; RECEPTORS; RATS; ANTAGONIST; ASTEMIZOLE; OBESITY AB Background: We performed a retrospective analysis of 122 clinical records of 92 male patients with DSM-III-R schizophrenia to examine the relative weight gain liabilities of clozapine, risperidone, olanzapine, and sertindole compared with haloperidol. We hypothesized that the unique pharmacodynamic profiles of these agents would contribute to different amounts and patterns of weight gain. Method: Data were analyzed to determine differences in weight gain during treatment among patients receiving 5 different drug treatments (clozapine [N = 20], olanzapine [N = 13], risperidone [N = 38], haloperidol [N = 43], and sertindole [N = 8]). Measures of maximal weight gain, final weight, and duration to maximal weight gain were calculated. Results: Repeated measures analyses of variance controlling for age, treatment duration, and initial weight revealed statistically significant differences between groups on all 3 measures. Clozapine and olanzapine had the greatest maximal weight gain liability (F = 4.13, df = 4,23; p = .01). Weight gain with clozapine, but not olanzapine or risperidone, appears to persist (as reflected by final weight) despite behavioral interventions (e.g., nutritional consultation, suggested exercise regimen; F = 5.69, df = 4,23; p = .003). Clozapine- and olanzapine-treated subjects appeared to gain weight over a prolonged period of time, whereas risperidone and sertindole-treated subjects had a more limited period of weight gain (F = 2.95, df = 4,25; P = .04). Conclusion: Clozapine and olanzapine caused the most weight gain, risperidone was intermediate, and sertindole had less associated weight gain than haloperidol. The relative receptor affinities of the novel antipsychotics for histamine H-1 appear to be the most robust correlate of these clinical findings. C1 VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Pepperdine Univ, Malibu, CA 90265 USA. RP Wirshing, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Rd B151-H,Bldg 210B,Room 15, Los Angeles, CA 90073 USA. NR 49 TC 426 Z9 442 U1 3 U2 11 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 JUN PY 1999 VL 60 IS 6 BP 358 EP 363 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 211XN UT WOS:000081187300001 PM 10401912 ER PT J AU Zajecka, J Amsterdam, JD Quitkin, FM Reimherr, FW Rosenbaum, JF Tamura, RN Sundell, KL Michelson, D Beasley, CM AF Zajecka, J Amsterdam, JD Quitkin, FM Reimherr, FW Rosenbaum, JF Tamura, RN Sundell, KL Michelson, D Beasley, CM TI Changes in adverse events reported by patients during 6 months of fluoxetine therapy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 49th Institute on Psychiatric Services CY OCT, 1997 CL WASHINGTON, D.C. ID SEROTONIN REUPTAKE INHIBITOR; MAINTENANCE THERAPIES; RECURRENT DEPRESSION; SERTRALINE AB Background: Although a period of 6 to 12 months of antidepressant therapy is recommended for most patients with depression, systematic examinations of the course of adverse events over time, the resolution of early-onset events, and the possible emergence of later-onset events are limited. We examined the safety of fluoxetine, 20 mg/day, in a large, prospective, long-term treatment trial, and we report a comparison of early- and late-onset adverse events and the course of adverse events over 26 weeks of treatment. Method: Adverse events were recorded at each visit in a uniform format by open-ended questioning, regardless of perceived causality. New or worsened events reported in either the first 4 weeks of treatment (early-reporting interval) or weeks 22 through 26 of treatment (late-reporting interval) were compared. Results: Patients (N = 299) whose depression (DSM-III-R) remitted with 12 weeks of fluoxetine treatment entered continuation therapy, and 174 completed 26 weeks of therapy. All events that occurred in greater than or equal to 5% of patients early in treatment decreased in frequency over time (p < .05), and no events occurred significantly more frequently during continuation therapy. No previously uncommon adverse events became common during long-term treatment. Conclusion: Common adverse events associated with initiating fluoxetine treatment in depressed patients, including nausea, insomnia, nervousness, and somnolence, resolve in the majority of patients and become significantly less frequent with continued treatment over a 6-month period. No adverse events present initially become more frequent late in treatment. Therapy with fluoxetine, 20 mg/day, is well tolerated over 6 months, and most adverse events observed early in treatment resolve. C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Rush Med Ctr, Dept Psychiat, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Michelson, D (reprint author), Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NR 20 TC 33 Z9 33 U1 0 U2 0 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 JUN PY 1999 VL 60 IS 6 BP 389 EP 394 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 211XN UT WOS:000081187300007 PM 10401918 ER PT J AU Wilens, TE Biederman, J Spencer, TJ Frazier, J Prince, J Bostic, J Rater, M Soriano, J Hatch, M Sienna, M Millstein, RB Abrantes, A AF Wilens, TE Biederman, J Spencer, TJ Frazier, J Prince, J Bostic, J Rater, M Soriano, J Hatch, M Sienna, M Millstein, RB Abrantes, A TI Controlled trial of high doses of pemoline for adults with attention-deficit/hyperactivity disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MINIMAL BRAIN-DYSFUNCTION; PSYCHIATRIC STATUS; DOUBLE-BLIND; FOLLOW-UP; CHILDREN; METHYLPHENIDATE; CHILDHOOD; PLACEBO; ABUSE AB Despite the increasing awareness of attention-deficit/hyperactivity disorder (ADHD) in adults, there are a limited number of controlled pharmacologic studies of this disorder. Because the stimulant medication magnesium pemoline (Cylert, Abbott Laboratories, Abbott Park, IL) has been found effective in treating ADHD in pediatric groups, me tested its efficacy in adults with ADHD using higher daily doses than those previously studied. We conducted a Id-week, double-blind, placebo-controlled, crossover design study of pemoline at a target daily dose of 3 mg/kg per day in 35 adult patients with DSM-III-R and -IV ADHD. We used standardized structured psychiatric instruments for diagnosis. To measure improvement, we used separate assessments of ADHD, depressive, and anxiety symptoms at baseline and at each biweekly visit. ADHD outcome was determined using the ADHD symptom checklist and Clinical Global Impression scales of Severity and Improvement. Of the 35 adults with ADHD who mere randomized in the trial, 27 (77%) completed the protocol. Treatment with pemoline in the final week of the 4-week active phase was best tolerated at doses substantially lower than the target dose of 3 mg/kg per day (mean dose, 2.2 mg/kg per day; mean +/- SD, 148 +/- 95 mg). Pemoline was significantly better at reducing ADHD symptoms compared with placebo (z = 2.4, p < 0.02). Using a predefined 30% reduction in symptoms as an indication of improvement, 50% of pemoline-treated subjects and 17% of subjects in the placebo group were considered positive responders (chi(2) = 7.1, p = 0.008). These results indicate that pemoline is moderately effective in the treatment of ADHD in adults. Although robust doses were targeted, most adults preferred more moderate dosing (120-160 mg/day). Given the Limited efficacy, tolerability, and concerns of hepatic dysfunction, pemoline should be considered as second-line medication for treating ADHD in adults. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. FU NIMH NIH HHS [K20 MH011175A03] NR 59 TC 47 Z9 47 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1999 VL 19 IS 3 BP 257 EP 264 DI 10.1097/00004714-199906000-00009 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 197BP UT WOS:000080345000008 PM 10350032 ER PT J AU Khoo, L Taylor, CR AF Khoo, L Taylor, CR TI Ultraviolet light therapy for atopic dermatitis SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE ultraviolet; ultraviolet light therapy for atopic dermatitis ID ORAL PSORALEN PHOTOCHEMOTHERAPY; UVB PHOTOTHERAPY; ECZEMA; PSORIASIS; PUVA AB Dr Lawrence Khoo and Dr Charles Taylor have reviewed the literature concerning ultraviolet light therapy for atopic dermatitis including conventional broad-band UVB, UVA, UVA-1 and narrow-band UVB. They have also examined the evidence for treatment of eczema with PUVA and ambient sunlight. This detailed review serves to bring residents and trainees up-to-date with the various phototherapies used to treat atopic eczema and in particular places narrow-band UVB firmly within this repertoire of therapies. Narrow-band UVB phototherapy has moved from being a research based phototherapy offered in a small number of specialized photodermatology units in Europe to being widely available in phototherapy units throughout the world. This rapid development is a reflection of the obvious efficacy of narrow-band UVB in the treatment of psoriasis and has close parallels with the development of PUVA. As with PUVA there is now accumulating evidence that narrow-band UVB phototherapy has a role in the treatment of recalcitrant cases of atopic dermatitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD JUN PY 1999 VL 10 IS 2 BP 133 EP 138 PG 6 WC Dermatology SC Dermatology GA 222CL UT WOS:000081765800010 ER PT J AU Rhew, DC Glassman, PA Goetz, MB AF Rhew, DC Glassman, PA Goetz, MB TI Improving pneumococcal vaccine rates - Nurse protocols versus clinical reminders SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pneumococcal vaccine; vaccinations; standing orders; reminders; feedback ID RANDOMIZED CONTROLLED TRIALS; PREVENTIVE CARE; METAANALYSIS; IMMUNIZATION; GUIDELINES; INFLUENZA; ADULTS AB OBJECTIVE: To compare the effectiveness of three interventions designed to improve the pneumococcal vaccination rate. DESIGN: A prospective controlled trial. SETTING: Department of Veterans Affairs ambulatory care clinic. PATIENTS/PARTICIPANTS: There were 3,502 outpatients with scheduled visits divided into three clinic teams (A, B, or C). INTERVENTIONS: During a la-week period, each clinic team received one intervention: (A) nurse standing orders with comparative feedback as well as patient and clinician reminders; (B) nurse standing orders with compliance reminders as well as patient and clinician reminders; and (C) patient and clinician reminders alone. Team A nurses (comparative feedback group) received information on their vaccine rates relative to those of team B nurses. Team B nurses (compliance reminders group) received reminders to vaccinate but no information on vaccine rates. MEASUREMENTS AND MAIN RESULTS: Team A nurses assessed more patients than team B nurses (39% vs 34%, p = .009). However, vaccination rates per total patient population were similar (22% vs 25%, p = .09). The vaccination rates for both team A and team B were significantly higher than the 5% vaccination rate for team C (p < .001). CONCLUSIONS: Nurse-initiated vaccine protocols raised vaccination rates substantially more than a physician and patient reminder system. The nurse-initiated protocol with comparative feedback modestly improved the assessment rate compared with the protocol with compliance reminders, but overall vaccination rates were similar. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Goetz, MB (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, 11301 Wilshire Blvd,111F, Los Angeles, CA 90073 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 21 TC 32 Z9 32 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 1999 VL 14 IS 6 BP 351 EP 356 DI 10.1046/j.1525-1497.1999.00353.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 206BD UT WOS:000080855400006 PM 10354255 ER PT J AU Santis, G Legrand V Hong, SS Davison, E Kirby I Imler, JL Finberg, RW Bergelson, JM Mehtali, M Boulanger, P AF Santis, G Legrand, V Hong, SS Davison, E Kirby, I Imler, JL Finberg, RW Bergelson, JM Mehtali, M Boulanger, P TI Molecular determinants of adenovirus serotype 5 fibre binding to its cellular receptor CAR SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TYPE-5 FIBER PROTEIN; COXSACKIE-B VIRUSES; SUBGROUP-C; ESCHERICHIA-COLI; DOMAIN; ATTACHMENT; VECTORS; CELLS; GENERATION; INFECTION AB Adenovirus (Ad) tropism is mediated in part through the fibre protein. The common coxsackie B virus and Ad receptor (CAR) was recently identified as the major receptor for subgroup C Ad serotype 5 (Ad5) and serotype 2 (Ad2) fibres, Effects of mutations in the Ad5 fibre gene were studied to assess domains of the fibre capsomer that could alter virus tropism without altering virus assembly and replication. All mutants that accumulated as fibre monomers failed to assemble with a penton base and proved lethal for Ad5 which suggests that the absence of infectious virions resulted in part from a defect in fibre penton base assembly. Cell binding capacity of all fibre mutants was investigated in cell binding competition experiments with adenovirions using CHO-CAR cells (CHO cells that have been transfected with CAR cDNA and express functional CAR). The results suggest that the R-sheet of the Ad5 fibre knob monomer contains binding motifs for CAR and that beta-strands E and F, or a region close to them, may also be involved in receptor recognition. C1 Guys Hosp, Dept Resp Med & Allergy, London SE1 9RT, England. Transgene SA, Dept Gene Therapy, F-67000 Strasbourg, France. Fac Med Montpellier, Inst Biol, CNRS UMR 5812, Lab Virol & Pathogenese Mol, F-34060 Montpellier, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Div Infect Dis & Immunol, Philadelphia, PA 19104 USA. RP Santis, G (reprint author), Guys Hosp, Dept Resp Med & Allergy, 5th Floor Thomas Guy House, London SE1 9RT, England. EM george.santis@kcl.ac.uk RI Finberg, Robert/E-3323-2010 FU Wellcome Trust NR 32 TC 59 Z9 60 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 1999 VL 80 BP 1519 EP 1527 PN 6 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 200LW UT WOS:000080542600023 PM 10374971 ER PT J AU Oken, BS Kishiyama, SS Kaye, JA Jones, DE AF Oken, BS Kishiyama, SS Kaye, JA Jones, DE TI Age-related differences in global-local processing: Stability of laterality differences but disproportionate impairment in global processing SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; HEALTHY OLDEST-OLD; SPATIAL-FREQUENCY; HIERARCHICAL STIMULI; ATTENTION; FOREST; BRAIN; TREES; TIME; IDENTIFICATION AB Visual processing of global and local features differentially engages the right and left hemispheres and requires different allocations of spatial attention. To further understand the decline in visual cognition and visual attention with age, we studied the performance of healthy young subjects and healthy elders on a global-local figures task. The results showed that elders processed global images more quickly when presented in the left visual field and local images in the right visual field, similarly to the young controls. However, we did observe a significant impairment in the elders' ability to process global figures compared with local figures, despite there being no overall difference between global and local processing speed among the young. It is thought that this age-related decline in global processing is related to the narrowed attentional field that can be demonstrated in other age-related visual processing declines such as visual search and useful field of view. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Oken, BS (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG08017, AG14877] NR 52 TC 19 Z9 20 U1 0 U2 8 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SUM PY 1999 VL 12 IS 2 BP 76 EP 81 DI 10.1177/089198879901200207 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 230WC UT WOS:000082273800006 PM 10483929 ER PT J AU Barnes, VL Musa, J Mitchell, RJ Barnes, JL AF Barnes, VL Musa, J Mitchell, RJ Barnes, JL TI Expression of embryonic fibronectin isoform EIIIA parallels alpha-smooth muscle actin in maturing and diseased kidney SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE fibronectin; alternative splicing; smooth muscle actin; mesangium; glomerulonephritis; interstitial nephritis; fibrosis ID HABU SNAKE-VENOM; ALTERNATIVELY SPLICED EIIIB; IMMUNE-COMPLEX NEPHRITIS; MESANGIAL CELL-MIGRATION; EXTRACELLULAR-MATRIX; TRANSFORMING GROWTH-FACTOR-BETA-1; PROLIFERATIVE GLOMERULONEPHRITIS; PULMONARY FIBROSIS; V-SEGMENT; RAT AB In this study we examined if an association exists between expression of an alternatively spliced "embryonic" fibronectin isoform EIIIA (Fn-EIIIA) and or-smooth muscle actin (alpha-SMA) in the maturing and adult rat kidney and in two unrelated models of glomerular disease, passive accelerated anti-glomerular basement membrane (GBM) nephritis and Habu venom (HV)-induced proliferative glomerulonephritis, using immunohistochemistry and in situ hybridization. Fn-EIIIA and alpha-SMA proteins were abundantly expressed in mesangium and in periglomerular and peritubular interstitium of 20-day embryonic and 7-day (D-7) postnatal kidneys in regions of tubule and glomerular development. Staining was markedly reduced in these structures in maturing juvenile (D-14) kidney and was largely lost in adult kidney. Expression of Fn-EIIIA and alpha-SMA was reinitiated in the mesangium and the periglomerular and peritubular interstitium in both models and was also observed in glomerular crescents in anti-GBM nephritis. Increased expression of Fn-EIIIA mRNA by in situ hybridization corresponded to the localization of protein staining. Dual labeling experiments verified co-localization of Fn-EIIIA and alpha-SMA, showing a strong correlation of staining between location and staining intensity during kidney development, maturation, and disease. Expression of EIIIA mRNA corresponded to protein expression in developing and diseased kidneys and was lost in adult kidney. These studies show a recapitulation of the co-expression of Fn-EIIIA and alpha-SMA in anti-GBM disease and suggest a functional link for these two proteins. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Med Res Serv, San Antonio, TX 78284 USA. Wilford Hall USAF Hosp, Dept Nephrol, San Antonio, TX USA. RP Barnes, JL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDDK NIH HHS [DK38758] NR 56 TC 17 Z9 17 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 1999 VL 47 IS 6 BP 787 EP 797 PG 11 WC Cell Biology SC Cell Biology GA 198YH UT WOS:000080451800008 PM 10330455 ER PT J AU Shih, VE Safran, AP Ropper, AH Tuchman, M AF Shih, VE Safran, AP Ropper, AH Tuchman, M TI Ornithine carbamoyltransferase deficiency: Unusual clinical findings and novel mutation SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article C1 Massachusetts Gen Hosp, Amino Acid Disorder Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Neurol Serv PC, Framingham, MA USA. St Elizabeths Med Ctr, Dept Neurol, Brighton, MA USA. Univ Minnesota Hosp & Clin, Biochem Genet Lab, Minneapolis, MN 55455 USA. Univ Minnesota Hosp & Clin, Metab Lab, Minneapolis, MN 55455 USA. RP Shih, VE (reprint author), Massachusetts Gen Hosp, Amino Acid Disorder Lab, Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [NS05096] NR 3 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD JUN PY 1999 VL 22 IS 5 BP 672 EP 673 DI 10.1023/A:1005502718790 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 204EL UT WOS:000080750600015 PM 10399103 ER PT J AU Goldberg, SL AF Goldberg, SL TI The arteries are small - The challenge is large SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Editorial Material ID BALLOON ANGIOPLASTY; STENT IMPLANTATION; CORONARY; TRIAL C1 W Los Angeles Vet Affairs Med Ctr, Cardiac Catheterizat Lab, Los Angeles, CA 90073 USA. RP Goldberg, SL (reprint author), W Los Angeles Vet Affairs Med Ctr, Cardiac Catheterizat Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD JUN PY 1999 VL 11 IS 6 BP 351 EP 352 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 225WW UT WOS:000081989800006 PM 10745547 ER PT J AU Ibbotson, SH Moran, MN Nash, JF Kochevar, IE AF Ibbotson, SH Moran, MN Nash, JF Kochevar, IE TI The effects of radicals compared with UVB as initiating species for the induction of chronic cutaneous photodamage SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE benzoyl peroxide; extracellular matrix; photoaging; photobiology ID CHRONIC SKIN DAMAGE; KERATINOCYTE CELL-LINE; PANOXYL GEL 5-PERCENT; HAIRLESS MOUSE SKIN; BENZOYL PEROXIDE; ULTRAVIOLET-RADIATION; TUMOR PROMOTERS; DERMAL DAMAGE; IN-VITRO; MICE AB There is substantial evidence that ultraviolet radiation induces the formation of reactive oxygen species which are implicated as toxic intermediates in the pathogenesis of photoaging. The aim of this study was to determine whether repeated topical treatment with benzoyl peroxide, a source of free radicals, produced the same cutaneous effects as chronic ultraviolet B radiation. Three concentrations of benzoyl peroxide (0.1, 1.5, 5.0% wt/wt) and three cumulative fluences of ultraviolet B radiation (0.9, 2.2, 5.1 J per cm(2)) used alone and in all combinations along with appropriate controls. Female SKH1 (hr/hr) albino hairless mice were treated 5 d per wk for 12 wk, Extracellular matrix molecules and histologic parameters were assessed. Ultraviolet B radiation induced a fluence-dependent and time-dependent increase in skin-fold thickness. Fluence dependence was seen for epidermal thickness, sunburn cell numbers, dermal thickness, glycosaminoglycan content, mast cell numbers, and skin-fold thickness. Benzoyl peroxide treatment alone caused less marked increases in epidermal and dermal measures compared with ultraviolet B under the conditions used. A benzoyl peroxide concentration-dependent increase was only observed for elastin content, although the highest concentration of benzoyl peroxide increased epidermal thickness and glycosaminoglycan content. A synergistic interaction between ultraviolet B and benzoyl peroxide was not found. These results indicate that repeated administration of benzoyl peroxide produces skin changes in the hairless mouse that qualitatively resemble those produced by ultraviolet B and suggest that common mechanisms may be involved. In addition, any potential synergistic effect of ultraviolet B and benzoyl peroxide was below the level of detection used in this study. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. Procter & Gamble Co, Sharon Woods Tech Ctr, Cincinnati, OH USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, WEL-224, Boston, MA 02114 USA. OI Ibbotson, Sally/0000-0001-5685-752X FU NIAMS NIH HHS [R01 AR43895] NR 41 TC 22 Z9 23 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1999 VL 112 IS 6 BP 933 EP 938 DI 10.1046/j.1523-1747.1999.00591.x PG 6 WC Dermatology SC Dermatology GA 203QC UT WOS:000080717500015 PM 10383741 ER PT J AU Guihan, M Weaver, FM Cowper, DC Nydam, T Miskevics, S AF Guihan, M Weaver, FM Cowper, DC Nydam, T Miskevics, S TI Using Department of Veterans Affairs administrative databases to examine long term care utilization for men and women veterans SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE long-term care; databases; nursing home; veterans ID FEMALE VETERANS AB We examined long term care (LTC) utilization by male and female veterans using administrative databases maintained by VA. Research questions included: (I) Which LTC services are utilized? (2) Do utilization patterns of older veterans differ from those of elderly persons in the general U.S. population? (3) Po LTC needs of veterans vary by gender? We were unable to track LTC utilization of individuals across administrative databases. Some databases could only provide information at the national level, or alternatively, were available only at local facilities, or only at the patient or program-level data-making it impossible to get a clear picture of all the services received by an individual. Those planning to use administrative databases to conduct research must: (I) take more time than expected; (2) be flexible/willing to compromise, (3) "ferret out" information, and (4) recognize that because of dynamism inherent in information systems, results may change over time. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL 60208 USA. RP Guihan, M (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0148-5598 J9 J MED SYST JI J. Med. Syst. PD JUN PY 1999 VL 23 IS 3 BP 201 EP 218 DI 10.1023/A:1020571504693 PG 18 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 248DP UT WOS:000083260300005 PM 10554736 ER PT J AU Sato, M Maulik, G Ray, PS Bagchi, D Das, DK AF Sato, M Maulik, G Ray, PS Bagchi, D Das, DK TI Cardioprotective effects of grape seed proanthocyanidin against ischemic reperfusion injury SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE proanthocyanidins; grape; red wine; antioxidant; ischemia reperfusion; peroxy radical; hydroxyl radical; heart; flavonoids ID FREE-RADICAL SCAVENGERS; CORONARY HEART-DISEASE; ANTIOXIDANT ACTIVITY; LIPID-PEROXIDATION; FLAVONOIDS; RISK; CONSUMPTION AB There is increasing evidence to indicate cardioprotective effects of red wine consumption. Such cardioprotective properties of wine have been attributed to certain polyphenolic constituents of grapes. The purpose of this investigation was to examine whether proanthocyanidins derived from grape seeds possess cardioprotective properties. Rats were randomly divided into two groups: grape-seed proanthocyanidin was administered orally to one group of rats (100 mg/kg/day) for 3 weeks while the other group served as control. After 3 weeks, rats were killed, hearts excised, mounted on the perfusion apparatus and perfused with Krebs-Hensereit bicarbonate (KHB) buffer. After stabilization hearts were perfused in the working mode for baseline measurements of contractile functions. Hearts were then subjected to 30 min of global ischemia followed by 2 h of reperfusion. Coronary perfusates were collected to monitor malonaldehyde formation, a presumptive marker for oxidative stress development. At the end of each experiment, the heart was processed for infarct size determination. Peroxyl radical scavenging activity of proanthocyanidin was determined by examining its ability to remove peroxyl radical generated by 2,2'-azobis (2-amidinopropane) dihydrochloride while hydroxyl radical scavenging activity was tested with its ability to reduce 7-OH .-coumarin-3-carboxylic acid. The results of our study demonstrated that proanthocyanidin-fed animals were resistant to myocardial ischemia reperfusion injury as evidenced by improved recovery of postischemic contractile functions. The proanthocyanidin-fed group revealed reduced extent of myocardial infarction compared to the control group, Fluorimetric study demonstrated the antioxidant property of proanthocyanidin as judged by its ability to directly scavenge peroxyl radicals. Taken together, the results of this study showed that grape seed-proanthocyanidins possess a cardioprotective effect against ischemia reperfusion injury, Such cardioprotective property, at least in part, map be attributed to its ability to directly scavenge peroxyl and hydroxyl radicals and to reduce oxidative stress developed during ischemia and reperfusion. (C) 1999 Academic Press. C1 Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Creighton Univ, Sch Pharm & Allied Hlth Profess, Omaha, NE 68178 USA. RP Das, DK (reprint author), Univ Connecticut, Sch Med, Dept Surg, Farmington, CT 06030 USA. FU NHLBI NIH HHS [HL 22559, HL 33889, HL 34360] NR 31 TC 128 Z9 148 U1 1 U2 7 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 JUN PY 1999 VL 31 IS 6 BP 1289 EP 1297 DI 10.1006/jmcc.1999.0961 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 205LF UT WOS:000080822000011 PM 10371703 ER PT J AU Schwarzschild, MA Cole, RL Meyers, MA Hyman, SE AF Schwarzschild, MA Cole, RL Meyers, MA Hyman, SE TI Contrasting calcium dependencies of SAPK and ERK activations by glutamate in cultured striatal neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glutamate; N-methyl-D-aspartate; c-Jun N-terminal kinase; extracellular-regulated kinase; calcium; sodium ID METHYL-D-ASPARTATE; NMDA RECEPTOR ACTIVATION; CENTRAL-NERVOUS-SYSTEM; PROTEIN-KINASE-C; GROWTH-FACTOR; NITRIC-OXIDE; CELL-DEATH; HIPPOCAMPAL-NEURONS; CORTICAL-NEURONS; GENE-EXPRESSION AB Stress-activated protein kinase (SAPK) and extracellular signal-regulated kinase (ERK), both members of the mitogen-activated protein kinase (MAPK) family, may in some circumstances serve opposing functions with respect to cell survival. However, SAPK and ERK can also be coordinately activated in neurons in response to glutamate stimulation of NMDA receptors. To explore the mechanisms of these MAPK activations, we compared the ionic mechanisms mediating SAPK and ERK activations by glutamate. In primary cultures of striatal neurons, glutamatergic activation of ERK and one of its transcription factor targets, CREB, showed a calcium dependence typical of NMDA receptor-mediated responses. In contrast, extracellular calcium was not required for glutamatergic, NMDA receptor-mediated activation of SAPK and phosphorylation of its substrate, c-Jun. Increasing extracellular calcium enhanced ERK activation but reversed SAPK activation, further distinguishing the calcium dependencies of these two NMDA receptor-mediated effects. Finally, reducing extracellular sodium prevented the glutamatergic activation of SAPK but only partially blocked that of ERK. These contrasting ionic dependencies suggest a mechanism by which NMDA receptor activation may, under distinct conditions, differentially regulate neuronal MAPKs and their divergent functions. C1 Massachusetts Gen Hosp, Dept Neurol, Lab Mol & Dev Neurosci, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Schwarzschild, MA (reprint author), Mol Neurobiol Lab, CNY-6616,MGH-E,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA07134, DA00257]; NINDS NIH HHS [NS01729] NR 52 TC 43 Z9 44 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1999 VL 72 IS 6 BP 2248 EP 2255 DI 10.1046/j.1471-4159.1999.0722248.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 198QE UT WOS:000080434800003 PM 10349832 ER PT J AU Li, QX Maynard, C Cappai, R McLean, CA Cherny, RA Lynch, T Culvenor, JG Trevaskis, J Tanner, JE Bailey, KA Czech, C Bush, AI Beyreuther, K Masters, CL AF Li, QX Maynard, C Cappai, R McLean, CA Cherny, RA Lynch, T Culvenor, JG Trevaskis, J Tanner, JE Bailey, KA Czech, C Bush, AI Beyreuther, K Masters, CL TI Intracellular accumulation of detergent-soluble amyloidogenic A beta fragment of Alzheimer's disease precursor protein in the hippocampus of aged transgenic mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid beta-protein; amyloid precursor protein; C100; transgenic mouse; processing ID C-TERMINAL FRAGMENT; CARBOXY-TERMINUS; HUMAN PLATELETS; FULL-LENGTH; PEPTIDE; EXPRESSION; BRAIN; RAT; NEUROTOXICITY; RECOGNITION AB To study amyloid beta-protein (A beta) production and aggregation in vivo, we created two transgenic (Tg) mouse lines expressing the C-terminal 100 amino acids of human amyloid precursor protein (APP): Tg C100.V717F and Tg C100,WT. Western blot analysis showed that human APP-C100 and A beta were produced in brain and some peripheral tissues and A beta was produced in serum. Using antibodies specific for the A beta C terminus we found that Tg C100.V717F produced a 1.6-fold increase in A beta 42/A beta 40 compared with Tg C100.WT. Approximately 30% of total brain A beta (similar to 122 ng/g of wet tissue) was water-soluble. The remaining 70% of A beta partitioned into the particulate fraction and was completely sodium dodecyl sulfate-soluble, In contrast, human Alzheimer's disease brain has predominantly sodium dodecyl sulfate-insoluble A beta. Immunohistochemistry with an A beta(5-8) antibody showed that A beta or A beta-containing fragments accumulated intracellularly in the hippocampus of aged Tg C100.V717F mice. The soluble A beta levels in Tg brain are similar to those in normal human brain, and this may explain the lack of microscopic amyloid deposits in the Tg mice. However, this mouse model provides a system to study the intracellular processing and accumulation of A beta or A beta-containing fragments and to screen for compounds directed at the gamma-secretase activity. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst Victoria, Parkville, Vic, Australia. Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat,Genet & Aging Unit, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. RP Masters, CL (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007 OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069 NR 52 TC 69 Z9 73 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1999 VL 72 IS 6 BP 2479 EP 2487 DI 10.1046/j.1471-4159.1999.0722479.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 198QE UT WOS:000080434800029 PM 10349858 ER PT J AU Delgutte, B Joris, PX Litovsky, RY Yin, TCT AF Delgutte, B Joris, PX Litovsky, RY Yin, TCT TI Receptive fields and binaural interactions for virtual-space stimuli in the cat inferior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INTERAURAL INTENSITY DIFFERENCES; PRIMARY AUDITORY-CORTEX; SOUND PRESSURE LEVEL; UNIT AZIMUTH SENSITIVITY; LATERAL SUPERIOR OLIVE; LOW-FREQUENCY CELLS; TIME DIFFERENCES; CENTRAL NUCLEUS; SPECTRAL CUES; RESPONSE PROPERTIES AB Receptive fields and binaural interactions for virtual-space stimuli in the cat inferior colliculus. J. Neurophysiol. 81: 2833-2851, 1999. Sound localization depends on multiple acoustic cues such as interaural differences in time (ITD) and level (ILD) and spectral features introduced by the pinnae. Although many neurons in the inferior colliculus (IC) are sensitive to the direction of sound sources in free field, the acoustic cues underlying this sensitivity are unknown. To approach this question, we recorded the responses of IC cells in anesthetized cats to virtual space CVS stimuli synthesized by filtering noise through head-related transfer functions measured in one cat. These stimuli not only possess natural combinations of ITD, ILD, and spectral cues as in free field but also allow precise control over each cue. VS receptive fields were measured in the horizontal and median vertical planes. The vast majority of cells were sensitive to the azimuth of VS stimuli in the horizontal plane for low to moderate stimulus levels. Two-thirds showed a "contra-preference'' receptive field, with a vigorous response on the contralateral side of an edge azimuth. The other third of receptive fields were tuned around a best azimuth. Although edge azimuths of contra-preference cells had a broad distribution, best azimuths of tuned cells were near the midline. About half the cells tested were sensitive to the elevation of VS stimuli along the median sagittal plane by showing either a peak or a trough at a particular elevation. In general receptive fields for VS stimuli were similar to those found in free-field studies of IC neurons, suggesting that VS stimulation provided the essential cues for sound localization. Binaural interactions for VS stimuli were studied by comparing responses to binaural stimulation with responses to monaural stimulation of the contralateral ear. A majority of cells showed either purely inhibitory (Br) or mixed facilitatory/inhibitory (BF&I) interactions. Others showed purely facilitatory (BF) or no interactions (monaural). Binaural interactions were correlated with azimuth sensitivity: most contra-preference cells had either BI or BF&I interactions, whereas tuned cells were usually BF. These correlations demonstrate the importance of binaural interactions for azimuth sensitivity. Nevertheless most monaural cells were azimuth-sensitive, suggesting that monaural cues also play a role. These results suggest that the azimuth of a high-frequency sound source is coded primarily by edges in azimuth receptive fields of a population of no-sensitive cells. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. RI Joris, Philip/D-9608-2011 OI Joris, Philip/0000-0002-9759-5375 FU NIDCD NIH HHS [DC-00116, DC-00119, P01 DC000116-25, P01 DC000119-26] NR 93 TC 67 Z9 71 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1999 VL 81 IS 6 BP 2833 EP 2851 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 208RR UT WOS:000081005800022 PM 10368401 ER PT J AU Irizarry, MC Ghaemi, SN Lee-Cherry, ER Gomez-Isla, T Binetti, G Hyman, BT Growdon, JH AF Irizarry, MC Ghaemi, SN Lee-Cherry, ER Gomez-Isla, T Binetti, G Hyman, BT Growdon, JH TI Risperidone treatment of behavioral disturbances in outpatients with dementia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID NEUROLEPTIC MALIGNANT SYNDROME; ALZHEIMERS-DISEASE; EXTRAPYRAMIDAL SYMPTOMS; REUPTAKE INHIBITORS; MOVEMENT-DISORDERS; CLOZAPINE; PSYCHOSIS; EFFICACY; SIGNS AB The authors retrospectively assessed the effectiveness and side effects of risperidone used to trent behavioral disturbances in elderly outpatients with dementia. In 41 patients treated with risperidone 1.8 +/- 1.4 mg/day, there was complete suppression of the target symptom in 15%, partial response in 41%, and no response in 44%. Risperidone appeared equally effective in treating agitation and psychosis. New or worsening extra-pyramidal side effects (EPS) occurred in 32%, associated with longer duration of treatment and possibly with concomitant use of serotonergic antidepressants. Risperidone was a useful adjunct in the treatment of agitation and psychosis in outpatients with dementia but teas limited by EPS in about one-third of patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. George Washington Univ, Dept Psychiat, Ctr Neurosci Med Progress & Soc, Washington, DC USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Alzheimer Dis Res Unit, CNY 6028,149 13th St, Cambridge, MA 02139 USA. RI Binetti, Giuliano/K-4519-2016 OI Binetti, Giuliano/0000-0003-2759-5844 FU NIA NIH HHS [AG05134, AG00793] NR 39 TC 25 Z9 25 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1999 VL 11 IS 3 BP 336 EP 342 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 222CG UT WOS:000081765400006 PM 10440009 ER PT J AU Montepare, J Koff, E Zaitchik, D Albert, M AF Montepare, J Koff, E Zaitchik, D Albert, M TI The use of body movements and gestures as cues to emotions in younger and older adults SO JOURNAL OF NONVERBAL BEHAVIOR LA English DT Article ID FACIAL EMOTION; LIFE-SPAN; RECOGNITION; EXPRESSION; IDENTIFICATION; LATERALIZATION; PERCEPTION; DISPLAYS; ANGER; AGE AB Eighty-two younger and older adults participated in a two-part study of the decoding of emotion through body movements and gestures. In the first part, younger and older adults identified emotions depicted in brief videotaped displays of young adult actors portraying emotional situations. In each display, the actors were silent and their faces were electronically blurred in order to isolate the body cues to emotion. Although both groups made accurate emotion identifications well above chance levels, older adults made more overall errors, and this was especially true for negative emotions. Moreover, their errors were more likely to reflect the misidentification of emotional displays as neutral in content. In the second part, younger and older adults rated the videotaped displays using scales reflecting several movement dimensions (e.g., form, tempo, force, and movement). The ratings of both age groups were in high agreement and provided reliable information about particular body cues to emotion. The errors made by older adults were linked to reactions to exaggerated or ambiguous body cues. C1 Massachusetts Gen Hosp, Charlestown, MA USA. Emerson Coll, Boston, MA 02116 USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Albert, M (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA USA. NR 34 TC 69 Z9 71 U1 4 U2 9 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0191-5886 J9 J NONVERBAL BEHAV JI J. Nonverbal Behav. PD SUM PY 1999 VL 23 IS 2 BP 133 EP 152 DI 10.1023/A:1021435526134 PG 20 WC Psychology, Social SC Psychology GA 233KW UT WOS:000082426900003 ER PT J AU Gerrity, TR Feussner, JR AF Gerrity, TR Feussner, JR TI Emerging research on the treatment of Gulf War veterans' illnesses SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article AB Much of what is known about Gulf War veterans' illnesses is a result of the investment in research by the federal government. Since 1993, the Research Working Group of the Federal Interagency Persian Gulf Veterans Coordinating Board has guided the federal research program. Based on this research, Hodgson and Kipin(1) conclude that the symptom-based conditions reported by Gulf War veterans could be treated through the use of a technique called cognitive behavioral therapy. This past year, the Department of Veterans Veterans Affairs launched the largest multisite, randomized, controlled treatment trial of the effectiveness of exercise and cognitive behavioral therapy in relieving the symptoms of ill Gulf War veterans, Despite this important step forward, the Department and its Research Working Group partners continue to explore all aspects of Gulf War veterans' illnesses. C1 Vet Hlth Adm, Off Res & Dev 12G, US Dept Vet Affairs, Washington, DC 20420 USA. RP Gerrity, TR (reprint author), Vet Hlth Adm, Off Res & Dev 12G, US Dept Vet Affairs, Washington, DC 20420 USA. NR 9 TC 5 Z9 6 U1 1 U2 1 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 JUN PY 1999 VL 41 IS 6 BP 440 EP 442 DI 10.1097/00043764-199906000-00009 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 206MQ UT WOS:000080883500009 PM 10390694 ER PT J AU Strack, S AF Strack, S TI Special series: Millon's evolving personality theory and measures SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Editorial Material C1 US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. RP Strack, S (reprint author), VA Ambulatory Care Ctr, Psychol Serv, 116B,351 E Temple St, Los Angeles, CA 90012 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUN PY 1999 VL 72 IS 3 BP 323 EP 329 DI 10.1207/S15327752JP720301 PG 7 WC Psychology, Clinical; Psychology, Social SC Psychology GA 218AG UT WOS:000081530700001 ER PT J AU Strack, S AF Strack, S TI Millon's normal personality styles and dimensions SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID ADJECTIVE CHECK LIST; MCMI-II; SCALES AB Millon's normal personality styles and dimensions emanate from the same evolutionary model he developed to explain personality pathology. For him, normal and abnormal personality lie along a continuum with no sharp demarcation to distinguish the two. The major difference is that normal individuals demonstrate adaptive flexibility in responding to their environment, whereas disordered persons exhibit rigid and maladaptive behavior.. In this article, I present a historical introduction to Millon's ideas on normality, descriptions of his normal personality styles and dimensions, up-to-date empirical findings, and avenues for future research. I conclude that, with additional validity data, Millon's model of normal personality may be suitable for an expanded Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) Axis II that allows for diagnosis of normal personality types when a complete personality disorder syndrome is absent. C1 US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. RP Strack, S (reprint author), VA Ambulatory Care Ctr, Psychol Serv, 116B,351 E Temple St, Los Angeles, CA 90012 USA. NR 38 TC 5 Z9 6 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUN PY 1999 VL 72 IS 3 BP 426 EP 436 DI 10.1207/S15327752JP720307 PG 11 WC Psychology, Clinical; Psychology, Social SC Psychology GA 218AG UT WOS:000081530700007 ER PT J AU Malament, KA Socransky, SS AF Malament, KA Socransky, SS TI Survival of Dicor glass-ceramic dental restorations over 14 years. Part II: Effect of thickness of Dicor material and design of tooth preparation SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the Academy-of-Prosthodontics CY MAY, 1996 CL NEWPORT BEACH, CALIFORNIA SP Acad Prosthodont ID STRENGTH; CROWNS; PORCELAIN AB Statement of problem. The influence of different restorative design features on the long-term survival of Dicor glass-ceramic restorations is not well understood. Purpose. This study examined the relationship of different types of restorations and methods of preparation with the survival of Dicor glass-ceramic restorations functioning in vivo. Material and methods. A total of 1444 Dicor glass-ceramic restorations were placed on the teeth of 417 adults. Failure was defined as a restoration that required remake because of material fracture. Survival of restorations of different types and with different methods of preparation was described by using Kaplan Meier survivor functions. Statistical significance between restoration type and preparation method was determined with the log rank test. Results. Probability of survival of a typical partial coverage restoration was 92% at 11.3 years. There was no statistically significant difference between the survival of inlay or onlay restorations. For the 91 cores used for pulpless teeth, none failed over a total cumulative monitoring period of 419 years. There was no significant difference in survival of acid-etched Dicor restorations that were placed on shoulder or chamfer preparations. Thickness measured at the midpoint of the labial, lingual, mesial, distal, and midocclusal surfaces did not relate to risk of failure. Conclusions. The majority of Dicor glass-ceramic partial coverage inlay and onlay restorations and cores survived over time. Survival of restorations with either chamfer or shoulder preparations did not differ whether the restoration was acid-etched. Thickness of the restoration measured at the midaxial point of each surface did not relate to survival. C1 Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Malament, KA (reprint author), 50 Staniford St, Boston, MA 02114 USA. NR 23 TC 79 Z9 84 U1 1 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUN PY 1999 VL 81 IS 6 BP 662 EP 667 DI 10.1016/S0022-3913(99)70104-6 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 207AF UT WOS:000080912600003 PM 10347353 ER PT J AU Maeda, F Nathan, JH AF Maeda, F Nathan, JH TI Understanding taijin kyofusho through its treatment, Morita therapy SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Editorial Material DE anthropophobia; Morita therapy; psychotherapy; taijin kyofusho AB This article presents a brief review of the definition, nosology, history, clinical features, and etiology of taijin kyofusho. Special attention is also given to Morita therapy for taijin kyofusho. The term taijin kyofusho literally means the disorder (sho) of fear (kyofu) of interpersonal relations (taijin). Morita therapy was developed by Masatake Morita in the 1910s to treat the Japanese mental disorders called shinkeishitsu and taijin kyofusho. It is suggested that taijin kyofusho is an excellent example of a mental disorder in which understanding its treatment is an integral part of its conceptualization. (C) 1999 Elsevier Science Inc. C1 BIDMC, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Maeda, F (reprint author), BIDMC, Dept Neurol, 330 Brookline Ave,KS452, Boston, MA 02215 USA. NR 22 TC 24 Z9 24 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 1999 VL 46 IS 6 BP 525 EP 530 PG 6 WC Psychiatry SC Psychiatry GA 212JG UT WOS:000081213100005 PM 10454167 ER PT J AU Islam, S Donahoe, PK Schnitzer, JJ AF Islam, S Donahoe, PK Schnitzer, JJ TI Tracheal ligation increases mitogen-activated protein kinase activity and attenuates surfactant protein B mRNA in fetal sheep lungs SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE tracheal ligation; fetal lung growth and development; pulmonary hypoplasia; tracheal occlusion; mitogen-activated protein kinase; growth factors; receptor tyrosine kinase ID CONGENITAL DIAPHRAGMATIC-HERNIA; IN-UTERO; PULMONARY HYPOPLASIA; THERAPY IMPROVES; GENE-EXPRESSION; IMMATURITY; OCCLUSION; CASCADES; PHOSPHORYLATION; REVERSES AB Background Tracheal ligation has been shown to accelerate fetal pulmonary growth in normal and hypoplastic lungs. Our aim was to study the effects of tracheal ligation on established molecular markers of growth and differentiation [mitogen-activated protein (MAP) kinase] and maturity [surfactant protein B (SPB) and fatty acid synthase (FAS)]. Materials and methods. Tracheal ligation was performed on four 100-day-gestation fetal sheep, with four age-matched fetuses undergoing maternal laparotomy and hysterotomy as control. Lungs from surviving fetuses (n = 2 in each group) were harvested after 4 days and frozen in liquid nitrogen. Protein lysates were prepared, and MAP kinase enzymatic assays [extracellular signal regulated protein kinase (ERK)-1 and -2] and Western blots were performed. Total RNA was isolated, and a fetal sheep lung cDNA library was created. The sheep SPB and FAS genes were cloned and sequenced. Northern blots were performed with the new clones, normalizing to beta-actin. Results. Tracheal ligation lungs contained a larger volume of fluid (40 ml) compared with age-matched controls (8 ml). MAP kinase enzymatic ERK-1 activity was increased and SPB mRNA expression was reduced in fetal lungs after tracheal ligation. Neither ERK-2 enzymatic activities and FAS mRNA nor ERK protein levels were affected by tracheal ligation, by Western blot analysis. Conclusion. Tracheal ligation-induced fetal lung growth may be mediated in part via the MAP kinase pathway. Expression of SPB mRNA is attenuated by tracheal ligation, whereas FAS, one of the key enzymes that synthesizes the lipid portion of surfactant, is not affected. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Pediat Surg Res Lab, Dept Surg,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schnitzer, JJ (reprint author), Harvard Univ, Sch Med, Pediat Surg Res Lab, Dept Surg,Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03132] NR 40 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN 1 PY 1999 VL 84 IS 1 BP 19 EP 23 DI 10.1006/jsre.1999.5593 PG 5 WC Surgery SC Surgery GA 200ZY UT WOS:000080571200004 PM 10334883 ER PT J AU Wilens, TE Biederman, J Millstein, RB Wozniak, J Hahesy, AL Spencer, TJ AF Wilens, TE Biederman, J Millstein, RB Wozniak, J Hahesy, AL Spencer, TJ TI Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adolescent; mania; bipolar disorder; substance abuse ID PROSPECTIVE FOLLOW-UP; PSYCHIATRIC-DISORDERS; CONDUCT DISORDER; MANIA; ADHD; ILLNESS; COMORBIDITY; TEMPERAMENT; MAGNITUDE; SAMPLE AB Objective: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child-versus adolescent-onset BPD with attention to comorbid psychopathology. Method: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (less than or equal to 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). Results: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p =.001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi(7)(2) = 9.7, p = 002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. Conclusions: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Child Psychiat Serv, ACC 725, Boston, MA 02114 USA. FU NIDA NIH HHS [DA-R2911315]; NIMH NIH HHS [MH-K2001175A04] NR 43 TC 74 Z9 74 U1 4 U2 6 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 JUN PY 1999 VL 38 IS 6 BP 680 EP 685 DI 10.1097/00004583-199906000-00014 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 200UQ UT WOS:000080558800014 PM 10361785 ER PT J AU Rohde, LA Biederman, J Busnello, EA Zimmermann, H Schmitz, M Martins, S Tramontina, S AF Rohde, LA Biederman, J Busnello, EA Zimmermann, H Schmitz, M Martins, S Tramontina, S TI ADHD in a school sample of Brazilian adolescents: A study of prevalence, comorbid conditions, and impairments SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; inattention; hyperactivity ID DEFICIT HYPERACTIVITY DISORDER; CHILD-BEHAVIOR CHECKLIST; GLOBAL ASSESSMENT SCALE; DIAGNOSTIC-CRITERIA; PSYCHIATRIC STATUS; ATTENTION; BOYS; PREDICTORS; CONDUCT; RISK AB Objective: To evaluate the prevalence, comorbid conditions, and impairments of attention-deficit/hyperactivity disorder (ADHD) among young adolescents in Porto Alegre, Brazil. Method: 1,013 students aged 12 to 14 years were evaluated at 64 state schools, using a screening instrument based on the 18 DSM-IV ADHD symptoms. All positive screened students (n = 99) and a random subset of negative screened subjects (n = 92) had a psychiatric evaluation carried out within a hospital setting or at home. Results: The prevalence of ADHD was estimated to be 5.8% (95% confidence interval = 3.2-10.6), and the comorbidity with other disruptive behavior disorders was high (47.8%). Youths with ADHD (n = 23) had significantly higher rates of school repetitions, suspensions, and expulsions (p <.01) than controls (n = 168). No association was identified between ADHD and alcohol, marijuana, and inhalent use. Conclusion: The results extend to adolescents well-documented findings in children, indicating that ADHD is quite prevalent in early adolescence and affected youths are at high risk for impairment and dysfunction in multiple domains. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Fed Rio Grande Sul, BR-90046900 Porto Alegre, RS, Brazil. RP Rohde, LA (reprint author), Hosp Clin Porto Alegre, Serv Psiquiatria Infancia & Adolescencia, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. RI Rohde, Luis Augusto/A-6426-2008 OI Rohde, Luis Augusto/0000-0002-4552-4188 NR 41 TC 126 Z9 153 U1 4 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 JUN PY 1999 VL 38 IS 6 BP 716 EP 722 DI 10.1097/00004583-199906000-00019 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 200UQ UT WOS:000080558800019 PM 10361790 ER PT J AU Jang, IK Brown, DFM Giugliano, RP Anderson, HV Losordo, D Nicolau, JC Dutra, OP Bazzino, O Viamonte, VM Norbady, R Liprandi, AS Massey, TJ Dinsmore, R Schwarz, RP AF Jang, IK Brown, DFM Giugliano, RP Anderson, HV Losordo, D Nicolau, JC Dutra, OP Bazzino, O Viamonte, VM Norbady, R Liprandi, AS Massey, TJ Dinsmore, R Schwarz, RP CA MINT Invest TI A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: Myocardial infarction with novastan and TPA (MINT) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID THROMBIN INHIBITION; RECOMBINANT HIRUDIN; ARTERIAL THROMBOSIS; THROMBOLYSIS; THERAPY; TRIAL; STREPTOKINASE; REPERFUSION; ASPIRIN; PATENCY AB OBJECTIVES This study examined the effect of a small-molecule, direct thrombin inhibitor, argatroban, on reperfusion induced by tissue plasminogen activator (TPA) in patients with acute myocardial infarction (AMI). BACKGROUND Thrombin plays a crucial role in thrombosis and thrombolysis. In vitro and in vivo studies have shown that argatroban has advantages over heparin for the inhibition of clot-bound thrombin and for the enhancement of thrombolysis with TPA. METHODS One hundred and twenty-five patients with AMI within 6 h were randomized to heparin, low-dose argatroban or high-dose argatroban in addition to TPA. The primary end point was the rate of thrombolysis in myocardial infarction (TIMI) grade 3 flow at 90 min. RESULTS TIMI grade 3 flow was achieved in 42.1% of heparin, 56.8% of low-dose argatroban (p = 0.20 vs. heparin) and 58.7% of high-dose argatroban patients (p = 0.13 vs. heparin). In patients presenting after 3 h, TIMI grade 3 flow was significantly more frequent in high-dose argatroban versus heparin patients: 57.1% versus 20.0% (p = 0.03 vs, heparin). Major bleeding was observed in 10.0% of heparin, and in 2.6% and 4.3% of low-dose and high-dose argatroban patients, respectively. The composite of death, recurrent myocardial infarction, cardiogenic shock or congestive heart failure, revascularization and recurrent ischemia at 30 days occurred in 37.5% of heparin, 32.0% of low-dose argatroban and 25.5% of high-dose argatroban patients (p = 0.23). CONCLUSIONS Argatroban, as compared with heparin, appears to enhance reperfusion with TPA in patients with AMI, particularly in those patients with delayed presentation. The incidences of major bleeding and adverse clinical outcome were lower in the patients receiving argatroban. (C) 1999 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Texas Heart Inst, Houston, TX 77025 USA. St Elizabeth Hosp, Boston, MA USA. Inst Mol Cardiovasc, Sao Jose Rio Preto, Brazil. Inst Cardiol Rio Grande Sul, Porto Alegre, RS, Brazil. Hosp Italiano, Buenos Aires, DF, Argentina. Hosp Espanol, Inst Cardiol & Cirugia Cardiovasc, Buenos Aires, DF, Argentina. Hosp Frances, Buenos Aires, DF, Argentina. Sanatorio Mitre, Buenos Aires, DF, Argentina. Coromed Inc, Troy, NY USA. Texas Biotechnol Corp, Houston, TX USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. RI Nicolau, Jose/E-1487-2012 NR 25 TC 77 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1999 VL 33 IS 7 BP 1879 EP 1885 DI 10.1016/S0735-1097(99)00107-2 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 210UM UT WOS:000081123100009 PM 10362188 ER PT J AU Hagan, MP Choi, NC Mathisen, DJ Wain, JC Wright, CD Grillo, HC AF Hagan, MP Choi, NC Mathisen, DJ Wain, JC Wright, CD Grillo, HC TI Superior sulcus lung tumors: Impact of local control on survival SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID RADIATION-THERAPY; PANCOAST TUMOR; PREOPERATIVE CHEMOTHERAPY; PULMONARY SULCUS; CANCER; IRRADIATION; MANAGEMENT; RADIOTHERAPY; RESECTION; CARCINOMA AB Objectives: Our goal was to assess patient survival and response to treatment for superior sulcus tumors treated with combined radiation therapy and surgery when possible, or,vith radiation alone when surgery was not possible. Methods: Seventy-three patients were treated for primary non-small cell carcinoma of the superior pulmonary sulcus, Thirty-four patients received combined resection and irradiation. Thirty-nine patients who had extensive primary disease, distant metastases, or who were medically unfit for surgery were treated with radiation alone, Thirty-one patients (91%) assigned to the resection/irradiation group completed treatment, Combined therapy patients routinely received 40 Gy before the operation, with additional postoperative irradiation based on the surgical findings, Results: Overall survival at 5 years was 19% and disease-specific survival was 20% for all patients. Overall survival and disease-specific survival at 5 years for the resection/irradiation group were 33% and 38%, respectively. Significant indicators of poor prognosis included unresected primary disease, low performance score, T4 stage, or positive node status. Eighty-two percent of the patients who received irradiation alone were treated with palliative intent. freedom from local-regional progression, achieved initially in 66% of these patients, was associated,vith a median survival of 8 months. Median survival for 7 patients considered for definitive irradiation was 25 months. During the first 18 months, distant failures occurred in approximately 35% of patients in each treatment group, Conclusions: Selection of medically fit patients with resectable disease for combined surgery and aggressive radiation therapy resulted in a high likelihood of local control, Overall survival for the resection/irradiation group was significantly poorer for patients with T4 stage, nodal disease, or Horner's syndrome. Distant metastases eventually developed in 56% of patients undergoing resection, Median survival in the resection/irradiation group was significantly prolonged for those patients who could tolerate high-dose radiation treatment. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. RP Hagan, MP (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, POB 980058,401 Coll St, Richmond, VA 23298 USA. NR 31 TC 35 Z9 35 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 1999 VL 117 IS 6 BP 1086 EP 1094 DI 10.1016/S0022-5223(99)70244-8 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 206FN UT WOS:000080866800006 PM 10343256 ER PT J AU Jannuzzi, JL Jang, IK AF Jannuzzi, JL Jang, IK TI Heparin induced thrombocytopenia: Diagnosis and contemporary antithrombin management SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE heparin; thrombocytopenia; antithrombin; r-hirudin; argatroban; HIT ID CARDIOPULMONARY BYPASS; THROMBOSIS; ASSAY; HIRUDIN; ANCROD AB Heparin-induced thrombocytopenia (HIT) may be complicated by severe thrombotic complications and death. Currently no specific laboratory test is available to make the diagnosis. When HIT is clinically suspected, heparin should be discontinued immediately. While no specific therapy for HIT exists, there is increasing evidence that acute antithrombin therapy may significantly reduce morbidity and mortality. Among several agents, the direct antithrombins, such as r-hirudin and argatroban, look the most promising for acute treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. NR 28 TC 1 Z9 1 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD JUN PY 1999 VL 7 IS 3 BP 259 EP 264 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 211LY UT WOS:000081163600005 ER PT J AU Jerath, MR Schomacker, KT Sheridan, RL Nishioka, NS AF Jerath, MR Schomacker, KT Sheridan, RL Nishioka, NS TI Burn wound assessment in porcine skin using indocyanine green fluorescence SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE burns; burn depth; indocyanine green; fluorescence imaging ID LASER-DOPPLER; DEPTH; LIGHT AB Background: An accurate assessment of deep dermal burns within the first week after burn is still an unresolved clinical problem, Infrared-excited fluorescence of indocyanine green was examined as a method of early determination of burn depth. Methods: Burns of varying depths were placed on the paraspinal region, flank, and abdomen of swine using a heated brass block. Fluorescence images of the burns were recorded 1, 24, 48, and 72 hours later. Results: The ratio of fluorescence in 64 burn mounds relative to adjacent normal tissue identified wounds that healed and did not heal within 21 days with an accuracy of 100%, after accounting for the age of the burn, Higher fluorescence ratios were observed in newly placed burns relative to older burns having comparable depths. Conclusion: Deep partial-thickness burns were differentiated from deep dermal full-thickness burns in a porcine skin burn model independent of body location. Diagnosis was possible between 1 and 72 hours after injury. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv Burns & Trauma, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burns Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Nishioka, NS (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, BAR703,55 Fruit St, Boston, MA 02114 USA. NR 16 TC 21 Z9 21 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD JUN PY 1999 VL 46 IS 6 BP 1085 EP 1088 DI 10.1097/00005373-199906000-00022 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 205BR UT WOS:000080801900026 PM 10372631 ER PT J AU Finlayson, SRG Birkmeyer, JD Fillinger, MF Cronenwett, JL AF Finlayson, SRG Birkmeyer, JD Fillinger, MF Cronenwett, JL TI Should endovascular surgery lower the threshold for repair of abdominal aortic aneurysms? SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 24-25, 1998 CL TORONTO, CANADA SP New England Soc Vasc Surg ID OPERATIVE MORTALITY; STENT-GRAFTS; RISK-FACTORS; MANAGEMENT; POPULATION; GROWTH; EXPERIENCE; SURVIVAL; CLASSIFICATION; COMPLICATIONS AB Purpose: Because endovascular repair of abdominal aortic aneurysms (AAAs) is less invasive, some investigators have suggested that this increasingly popular technique should broaden the indications far elective AAA repair. The purpose of this study was to calculate quality-adjusted life expectancy rates after endovascular and open AAA repair and to estimate the optimal diameter for elective AAA repair in hypothetical cohorts of patients at average risk and at high risk. Methods: A Markov decision analysis model was used in this study. Assumptions were made on the basis of published reports and included the following: (1) the annual rupture rate is a continuous function of the AAA diameter (0% for <4 cm, 1% for 4.5 cm, 11% for 5.5 cm, and 26% for 6.5 cm); (2) the operative mortality rate is 1% for endovascular repair (excluding the risk of conversion to open repair) and 3.5% for open repair at age 70 years; and (3) immediate endovascular-to-open conversion risk is 5%, and late conversion rate is 1% per year. The main outcome measure in this study was the benefit of AAA repair in quality-adjusted life years (QALYs). The optimal threshold size (the AAA diameter at which elective repair maximizes benefit) was measured in centimeters. Results: The benefit of endovascular repair is consistently greater than that of open repair, but the additional benefit is small-0.1 to 0.4 QALYs. For men in average health with gradually enlarging AAAs with initial diameters of 4 cm, endovascular surgery reduces the optimal threshold diameter by very little: from 4.6 to 4.6 cm (no change) at age 60 years, from 4.8 to 4.7 cm at age 70 years, and from 5.1 to 4.9 cm at age 80 years. for older men in poor health, endovascular surgery reduces the optimal threshold diameter substantially (8.1 to 5.7 cm at age 80 years), but the benefit of repair in this population is small (0.2 QALYs). Conclusion: For most patients, the indications for AAA repair are changed very little by the introduction of endovascular surgery. Only for older patients in poor health does endovascular surgery substantially lower the optimal threshold diameter for elective AAA repair. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Dept Vet Affairs Med Ctr, VA Outcomes Grp, White River Jct, VT 05001 USA. Dartmouth Med Sch, Dept Surg, Hanover, NH 03755 USA. Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03755 USA. Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03766 USA. RP 59 Prospect St, Sherborn, MA 01770 USA. NR 56 TC 59 Z9 59 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1999 VL 29 IS 6 BP 973 EP 984 DI 10.1016/S0741-5214(99)70238-7 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 206ER UT WOS:000080864800004 PM 10359931 ER PT J AU Cambria, RP Kaufman, JL Brewster, DC Gertler, JP LaMuraglia, GM Bazari, H Abbott, WM AF Cambria, RP Kaufman, JL Brewster, DC Gertler, JP LaMuraglia, GM Bazari, H Abbott, WM TI Surgical renal artery reconstruction without contrast arteriography: the role of clinical profiling and magnetic resonance angiography SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 24-25, 1998 CL TORONTO, CANADA SP New England Soc Vasc Surg ID MR-ANGIOGRAPHY; BREATH-HOLD; STENOSIS AB Purpose: Contrast arteriography is the accepted gold standard for diagnosis and treatment planning in patients with atherosclerotic renovascular disease (RVD). In this study, the results of a selective policy of surgical renal artery reconstruction (RAR) with magnetic resonance angiography (MRA) as the sole preoperative imaging modality are reviewed. Methods: From May 1993 to May 1998, 25 patients underwent RAR after clinical evaluation, and aortic/renal MRA performed with a gadolinium-enhanced and 3-dimensional phase contrast technique. Clinical presentations suggested severe RVD in all patients and included poorly controlled hypertension (16 patients), hospitalization for hypertensive crises and/or acute pulmonary edema (13), and deterioration of renal function within one year of operation (15). Thirteen patients had associated aortic pathologic conditions (12 aneurysms, 1 aortoiliac occlusive disease), and eight of these patients also underwent noncontrast computed tomography scans. Significant renal dysfunction (serum creatinine level, greater than or equal to 2.0 mg/dL) was present in all but 4 patients with. 14 of 25 patients having extreme (creatinine level, greater than or equal to 3.0 mg/dL) dysfunction. Results: Hemodynamically significant RVD in the main renal artery was verified at operation in 37 of 38 reconstructed main renal arteries (24/25 patients). A single accessory renal artery was missed by MRA. RAR was comprehensive (bilateral or unilateral to a single-functioning kidney) in 21 of 25 patients and consisted of hepatorenal bypass graft (3 patients), combined aortic and RAR (13 patients), isolated transaortic endarterectomy (8 patients), and aortorenal bypass graft (1 patient). Early improvement in both hypertension control and/or renal function was noted in 21 of 25 patients without operative deaths or postoperative renal failure. Sustained favorable functional results at follow-up, ranging from 5 months to 4 years, were noted in 19 of 25 patients. Conclusion: MRA is an adequate preoperative imaging modality in selected patients before RAR. This strategy is best applied in circumstances where the clinical presentation suggests hemodynamically significant bilateral RVD and/or in patients at substantial risk of complications from contrast angiography. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, 15 Parkman St WAC 458, Boston, MA 02114 USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1999 VL 29 IS 6 BP 1012 EP 1020 DI 10.1016/S0741-5214(99)70242-9 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 206ER UT WOS:000080864800012 PM 10359935 ER PT J AU Yang, OO Swanberg, SL Lu, ZJ Dziejman, M McCoy, J Luster, AD Walker, BD Herrmann, SH AF Yang, OO Swanberg, SL Lu, ZJ Dziejman, M McCoy, J Luster, AD Walker, BD Herrmann, SH TI Enhanced inhibition of human immunodeficiency virus type 1 by Met-Stromal-Derived Factor 1 beta correlates with down-modulation of CXCR4 SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; HIV-1 INFECTION; LYMPHOCYTE CHEMOATTRACTANT; GENETIC RESTRICTION; TROPIC HIV-1; T-CELLS; CCR5; RANTES; SDF-1; CLONING AB CXCR4 is a chemokine receptor used by some strains of HIV-1 as an entry coreceptor in association with cell surface CD4 on human cells. In human immunodeficiency virus type 1 (HIV-1)-infected individuals, the appearance of viral isolates with a tropism for CXCR4 (T tropic) has been correlated with late disease progression. The presumed natural ligands for CXCR4 are SDF-1 alpha and SDF-1 beta, which are proposed to play a role in blocking T-tropic HIV-1 cell entry. Here, we demonstrate that addition of an N-terminal methionine residue to SDF-1 beta (Met-SDF-1 beta) results in a dramatically enhanced functional activity compared to that of native SDF-1 beta. Equivalent concentrations of Met-SDF-1 beta are markedly more inhibitory for T-tropic HIV-1 replication than SDF-1 beta, A comparison of the biological activities of these two forms of SDF-1 beta reveals that Met-SDF-1 beta induces a more pronounced intracellular calcium flux yet binds with slightly lower affinity to CXCR4 than SDP-1 beta. Down-modulation of CXCR4 is similar after exposure of cells to either chemokine form for 2 h. However, after a 48-h incubation, the surface expression of CXCR4 is much lower for cells treated with Met-SDF-1 beta. The enhanced blocking of T-tropic HIV-1 by Met-SDF-1 beta appears to be related to prolonged CXCR4 down-modulation. C1 Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Genet Inst, Infect Dis & Mol Biol Gene Express, Cambridge, MA 02140 USA. RP Herrmann, SH (reprint author), Wyeth Cambridge, Genet Inst, Infect Dis Res, 87 Cambridge Pk Dr, Cambridge, MA 02140 USA. FU NIAID NIH HHS [AI097160-02, K08AI02524-02, R01 AI043203, R01AI43203-01, R03 AI097160] NR 55 TC 59 Z9 62 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1999 VL 73 IS 6 BP 4582 EP 4589 PG 8 WC Virology SC Virology GA 195UW UT WOS:000080271400008 PM 10233917 ER PT J AU Marshall, WL Yim, C Gustafson, E Graf, T Sage, DR Hanify, K Williams, L Fingeroth, J Finberg, RW AF Marshall, WL Yim, C Gustafson, E Graf, T Sage, DR Hanify, K Williams, L Fingeroth, J Finberg, RW TI Epstein-Barr virus encodes a novel homolog of the bcl-2 oncogene that inhibits apoptosis and associates with Bax and Bak SO JOURNAL OF VIROLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYCYSTIC KIDNEY; VIRAL HOMOLOG; DNA-SEQUENCE; B-CELLS; PROTEIN; GENE; MICE; EXPRESSION AB The sequenced gammaherpesviruses each contain a single viral bcl-2 homolog (v-bcl-2) which may encode a protein that functions in preventing the apoptotic death of virus-infected cells. Epstein-Barr virus (EBV), a gammaherpesvirus associated with several lymphoid and epithelial malignancies, encodes the v-Bcl-2 homolog BHRF1. In this report the previously uncharacterized BALF1 open reading frame in EBV is identified as having significant sequence similarity to other v-bcl-2 homologs and cellular bcl-2. Transfection of cells with a BALF1 cDNA conferred apoptosis resistance. Furthermore, a recombinant green fluorescent protein-BALF1 fusion protein suppressed apoptosis and associated with Bax and Bak These results indicate that EBV encodes a second functional v-bcl-2. C1 Dana Farber Canc Inst, Dept Adult Oncol, Div Infect Dis, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Infect Dis & Expt Med, Boston, MA 02115 USA. RP Marshall, WL (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Div Infect Dis, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [P30 CA 06516-33, P30 CA006516]; NIAID NIH HHS [AI28691-06, P30 AI028691]; NIDCR NIH HHS [R01 DE12186] NR 44 TC 109 Z9 115 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1999 VL 73 IS 6 BP 5181 EP 5185 PG 5 WC Virology SC Virology GA 195UW UT WOS:000080271400076 PM 10233985 ER PT J AU Verdolini, K Hess, MM Titze, IR Bierhals, W Gross, M AF Verdolini, K Hess, MM Titze, IR Bierhals, W Gross, M TI Investigation of vocal fold impact stress in human subjects SO JOURNAL OF VOICE LA English DT Article DE vocal fold impact stress; electroglottography; closed quotient; vocal folds ID PHONATION; PRESSURE AB The primary purpose of the study was to explore a methodology for measuring vocal fold impact stress (SI) in awake humans, and to provide information about the general magnitude of SIs that may occur at the midpoint of the membranous vocal folds during phonation. A secondary purpose was to examine the potential use of the electroglottographic closed quotient (EGG CQ) to indirectly reflect SI. Seven male and 13 female adults: were enrolled as subjects, of whom 18 had normal larynges and normal voices, 1 had nodules, and 1 had vocal fold paresis and bowing. Subjects attempted to produce 3 different voice types (pressed, normal, breathy), at 3 different pitches (low, medium, high) and 3 different loudness levels (quiet, medium, loud). For a first set of trials, only EGG data were collected, For a second set, a sensor was also introduced to the midmembranous glottis for the collection of SI data. The primary findings were that (1) endolaryngeal sensor placement was achieved during phonation trials for 17 of 20 subjects; however, grossly consistent anteroposterior positioning was accomplished, and analyzable data were obtained, for only 7 subjects; (2) SIs ranged from less than 1 kPa to about 3 kPa for those 7 subjects; and (3) no relation was detected between simultaneous CQs and SIs fur individual data, although a relation was reported in a prior canine study. One possible reason for the failure to show such a relation in the present study was subtle variations in vertical as well as anteroposterior positioning of the sensor during the trials. Future studies should focus on developing a methodology for ensuring invariant 3-dimensional sensor positioning between the membranous folds, so that the stability of both SI and simultaneous CQ data can be improved. C1 MGH, Inst Hlth Profess, Grad Program Commun Sci & Disorders, Dept Commun Sci & Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Otol & Laryngol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Voice Speech Swallowing Div, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Free Univ Berlin, Dept Audiol & Phoniatr, D-1000 Berlin, Germany. Univ Iowa, Dept Speech Pathol & Audiol, Iowa City, IA USA. Natl Ctr Voice & Speech, Iowa City, IA USA. Wilbur James Gould Voice Res Ctr, Denver, CO USA. Free Univ Berlin, Acoust Res Lab, D-1000 Berlin, Germany. RP Verdolini, K (reprint author), MGH, Inst Hlth Profess, Grad Program Commun Sci & Disorders, Dept Commun Sci & Disorders, 101 Merrimac St, Boston, MA 02114 USA. FU NIDCD NIH HHS [1 K08 DC00139-01, P60 DC00976] NR 31 TC 38 Z9 38 U1 0 U2 2 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD JUN PY 1999 VL 13 IS 2 BP 184 EP 202 DI 10.1016/S0892-1997(99)80022-8 PG 19 WC Otorhinolaryngology SC Otorhinolaryngology GA 216YR UT WOS:000081472500004 PM 10442749 ER PT J AU Endicott, J Amsterdam, J Eriksson, E Frank, E Freeman, E Hirschfeld, R Ling, F Parry, B Pearlstein, T Rosenbaum, J Rubinow, D Schmidt, P Severino, S Steiner, M Stewart, DE Thys-Jacobs, S AF Endicott, J Amsterdam, J Eriksson, E Frank, E Freeman, E Hirschfeld, R Ling, F Parry, B Pearlstein, T Rosenbaum, J Rubinow, D Schmidt, P Severino, S Steiner, M Stewart, DE Thys-Jacobs, S TI Is premenstrual dysphoric disorder a distinct clinical entity? SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; SERTRALINE TREATMENT; FLUOXETINE TREATMENT; MAJOR DEPRESSION; HORMONE AGONIST; MENSTRUAL-CYCLE; SYMPTOMS; WOMEN; CLOMIPRAMINE AB Does the evidence now available support the concept of premenstrual dysphoric disorder (PMDD) as a distinct clinical disorder such that the relative safety and efficacy of potential treatment can be evaluated? In a roundtable discussion of this question, a wealth of information was reviewed by a panel of experts. The key characteristics of PMDD, with clear onset and offset of symptoms closely linked to the menstrual cycle and the prominence of symptoms of anger, irritability, and internal tension, were contrasted with those of known mood and anxiety disorders. PMDD displays a distinct clinical picture that, in the absence of treatment, is remarkably stable from cycle to cycle and over time. Effective treatment of PMDD can be accomplished with serotinergic agents. At least 60% of patients respond to selective serotonin reuptake inhibitors (SSRIs). In comparison with other disorders, PMDD symptoms respond to low doses of SSRIs and to intermittent dosing. Normal functioning of the hypothalamic-pituitary-adrenal (HPA) axis, biologic characteristics generally related to the serotonin system, and a genetic component unrelated to major depression are further features of PMDD that separate it from other affective (mood) disorders. Based on this evidence, the consensus of the group was that PMDD is a distinct clinical entity. Potential treatments for this disorder can now be evaluated on this basis to meet the clear need for effective therapy. C1 Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Gothenburg, Gothenburg, Sweden. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Texas, Galveston, TX 77550 USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Diego, San Diego, CA 92103 USA. Butler Hosp, Providence, RI 02906 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIMH, Bethesda, MD 20892 USA. Univ New Mexico, Albuquerque, NM 87131 USA. McMaster Univ, St Josephs Hosp, Hamilton, ON L8S 4L8, Canada. Univ Toronto, Toronto Hosp, Toronto, ON, Canada. St Lukes Roosevelt Ctr, New York, NY USA. RP Endicott, J (reprint author), Columbia Univ, Coll Phys & Surg, 722 W 168th St, New York, NY 10032 USA. RI Stewart, Donna Eileen/J-2844-2016 OI Stewart, Donna Eileen/0000-0002-8157-7746 NR 81 TC 107 Z9 108 U1 1 U2 10 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD JUN PY 1999 VL 8 IS 5 BP 663 EP 679 DI 10.1089/jwh.1.1999.8.663 PG 17 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 230ZQ UT WOS:000082281900020 PM 10839653 ER PT J AU Faustman, D AF Faustman, D TI Autoimmune diseases: Why women? SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD JUN PY 1999 VL 8 IS 5 BP 703 EP 703 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 230ZQ UT WOS:000082281900055 ER PT J AU Miyamoto, MI Kim, CS Guerrero, JL Rosenzweig, A Gwathmey, JK Hajjar, RJ AF Miyamoto, MI Kim, CS Guerrero, JL Rosenzweig, A Gwathmey, JK Hajjar, RJ TI Ventricular pressure and dimension measurements in mice SO LABORATORY ANIMAL SCIENCE LA English DT Article ID HEART C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St,CNY-4,Room 4215, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL 54202, HL 50361, HL 57623] NR 8 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD JUN PY 1999 VL 49 IS 3 BP 305 EP 307 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 207QJ UT WOS:000080947300013 PM 10403446 ER PT J AU Wolf, JS Boyev, KP Manokey, BJ Mattox, DE AF Wolf, JS Boyev, KP Manokey, BJ Mattox, DE TI Success of the modified Epley maneuver in treating benign paroxysmal positional vertigo SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Southern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 15-16, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Laryngol Rhinol & Otol Soc, So Sect DE vertigo; benign paroxysmal positional vertigo (BPPV); Epley maneuver; semicircular canal ID CANALITH REPOSITIONING PROCEDURE; OCCLUSION AB Objective: Benign paroxysmal positional vertigo (BPPV) is a common condition seen by otolaryngologists. The purpose of this study is to determine the ability of the modified Epley maneuver to treat BPPV, Study Design: Retrospective review. Methods: A retrospective chart review of 107 patients diagnosed with BPPV at our institution between March of 1993 and June of 1995, Each patient was diagnosed with isolated BPPV by history and Hallpike-Dix maneuver. There were no other vestibular symptoms or electronystagmogram abnormalities. Patients diagnosed with BPPV received modified Epley maneuvers, were instructed to remain upright for 48 hours, and wore a soft collar for a week. Patients were followed up with repeat Hallpike-Dix maneuvers at 1 to 2 weeks. If symptoms persisted, the maneuver was repeated for up to a maximum of three times, at which point patients were considered to have failed treatment. Results: The average age of patients was 57.8 years old. Thirty percent were male and the right ear was affected in 54%. The posterior semicircular canal was affected in 105 ears, The average patient received 1.23 Epley maneuvers, with a success rate of 93.4%. No successfully treated patients received mastoid vibration, Seven out of 107 patients failed after three Epley maneuvers. Two failure patients had a history of temporal bone fracture. Two failure patients were treated with posterior semicircular canal block surgery. Conclusion: The modified Epley maneuver is an excellent treatment for BPPV. C1 Univ Maryland, Med Syst, Div Otolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Atlanta, GA USA. RP Wolf, JS (reprint author), Univ Maryland, Med Syst, Div Otolaryngol Head & Neck Surg, Suite 400,Frenkil Bldg,16 S Eutaw St, Baltimore, MD 21201 USA. NR 19 TC 34 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 1999 VL 109 IS 6 BP 900 EP 903 DI 10.1097/00005537-199906000-00011 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 203PW UT WOS:000080716900011 PM 10369279 ER PT J AU Webb, IJ Anderson, KC AF Webb, IJ Anderson, KC TI Risks, costs, and alternatives to platelet transfusions SO LEUKEMIA & LYMPHOMA LA English DT Review DE platelets; transfusions; complications; IL-11; thrombopoietin ID RECOMBINANT HUMAN INTERLEUKIN-11; VERSUS-HOST DISEASE; BACTERIALLY CONTAMINATED PLATELETS; ALLOGENEIC BLOOD-TRANSFUSION; CYTOMEGALO-VIRUS INFECTION; HUMAN MEGAKARYOCYTE GROWTH; PLACEBO-CONTROLLED TRIAL; CELL-REDUCTION FILTERS; ACUTE MYELOID-LEUKEMIA; PHASE-I TRIAL AB The use of platelet transfusions has increased greatly in the past decade and is likely to continue to escalate because of the risks of thrombocytopenia in patients receiving dose-intensive cancer chemotherapy, the increased use of hematopoietic progenitor cell transplantation, and the prevalence of human immunodeficiency virus infection. Despite marked advances in procedures for ensuring the safety of platelets, including intensive donor screening, infectious disease marker testing, and increased use of leukodepletion techniques, platelet transfusions carry a significant risk for immunologic disorders and transmission of bacterial, viral, and perhaps other diseases and can entail a very high cost. In addition, thrombocytopenia has the potential to interfere with delivery of chemotherapy on schedule and at the planned doses, thus potentially compromising treatment outcome. The limitations of platelet transfusions have prompted the development of agents with the potential to stimulate platelet production and thus reduce or eliminate the need for transfusions. Two such agents, interleukin-ll (IL-11) and thrombopoietin (TPO), have demonstrated promise in clinical trials. In November, 1997, IL-11 received FDA approval for the prevention of severe thrombocytopenia in high risk patients receiving myelosuppressive chemotherapy Thrombopoietic growth factors have the potential to greatly simplify and increase the safety of transfusion medicine. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Webb, IJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Dana 530, Boston, MA 02115 USA. NR 79 TC 24 Z9 26 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 1999 VL 34 IS 1-2 BP 71 EP 84 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 195LR UT WOS:000080252800007 PM 10350334 ER PT J AU Zaharchuk, G Ledden, PJ Kwong, KK Reese, TG Rosen, BR Wald, LL AF Zaharchuk, G Ledden, PJ Kwong, KK Reese, TG Rosen, BR Wald, LL TI Multislice perfusion and perfusion territory imaging in humans with separate label and image coils SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE perfusion; arterial spin labeling; perfusion territory; MRI ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; CEREBROVASCULAR-DISEASE; PARTITION-COEFFICIENT; ARTERIAL WATER; STIMULATION; INVERSION; MRI; METABOLISM; SATURATION AB An arterial spin labeling technique using separate RF labeling and imaging coils was used to obtain multislice perfusion images of the human brain at 3 T. Continuous RF irradiation at a peak power of 0.3 W was applied to the carotid arteries to adiabatically invert spins. Labeling was achieved without producing magnetization transfer effects since the B-1 field of the labeling coil did not extend into the imaging region or couple significant power into the imaging coil, Eliminating magnetization transfer allowed the acquisition of multislice perfusion images of arbitrary orientation. Combining surface coil labeling with a reduced RF duty cycle permitted significantly lower SAR than single coil approaches. The technique was also found to allow selective labeling of blood in either carotid, providing an assessment of the artery's perfusion territory. In normal subjects, these territories were well-defined and localized to the ipsilateral hemisphere, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, MIT, Sch Med, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Wald, LL (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 149 13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. RI Wald, Lawrence/D-4151-2009 FU NCI NIH HHS [5T-32CA09502-13]; NHLBI NIH HHS [2R01-HL39810-10] NR 37 TC 99 Z9 99 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUN PY 1999 VL 41 IS 6 BP 1093 EP 1098 DI 10.1002/(SICI)1522-2594(199906)41:6<1093::AID-MRM4>3.0.CO;2-0 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CG UT WOS:000081422500004 PM 10371440 ER PT J AU Ramanathan, C Ackerman, JL AF Ramanathan, C Ackerman, JL TI Quantitative solid-state NMR imaging of synthetic calcium phosphate implants SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE biomaterial; bioceramic; MRI; quantitation ID NUCLEAR MAGNETIC-RESONANCE; BONE-MINERAL DENSITY; TRABECULAR BONE; IN-VIVO; SPECTROSCOPY; INVIVO; OSTEOPOROSIS; PHASES; MODELS AB It is shown that solid-state phosphorus-31 nuclear magnetic resonance imaging can be used to measure quantitatively the mass of hydroxyapatite (HA), a synthetic calcium phosphate used as an orthopedic implant material, in the presence of bone. A three-dimensional projection reconstruction technique was used to produce solid-state images from 998 free induction decays sampled in the presence of a fixed amplitude field gradient whose direction was varied uniformly over the unit sphere. Chemical selection is achieved using T-1 contrast, as the synthetic calcium phosphate has a shorter T-1 (1.8 sec at 4.7 T) compared with the bone (approximately 15 sec at 4.7 T in vivo, 42 sec ex vivo). Experimental results demonstrating the linear relationship between image intensity and HA density in phantoms containing HA and silicon (IV) oxide, and HA and bone are shown. Chemically pure images of bone mineral and synthetic HA have been computed from images of New Zealand White rabbits acquired in vivo at two different recycle times. The technique can be used to follow noninvasively the resorption and remodeling of calcium phosphate implants in vivo. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Ackerman, JL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Rm 2301,149 13th St, Charlestown, MA 02129 USA. RI Ramanathan, Chandrasekhar/C-5207-2008; Ackerman, Jerome/E-2646-2015 OI Ramanathan, Chandrasekhar/0000-0002-7457-3608; Ackerman, Jerome/0000-0001-5176-7496 FU NIAMS NIH HHS [AR42258] NR 31 TC 12 Z9 13 U1 4 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUN PY 1999 VL 41 IS 6 BP 1214 EP 1220 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216CG UT WOS:000081422500018 PM 10371454 ER PT J AU Dohrmann, CE Belaoussoff, M Raftery, LA AF Dohrmann, CE Belaoussoff, M Raftery, LA TI Dynamic expression of TSC-22 at sites of epithelial-mesenchymal interactions during mouse development SO MECHANISMS OF DEVELOPMENT LA English DT Article DE TSC-22; mouse embryogenesis; epithelial-mesenchymal interactions; central nervous system; eye; tooth; kidney; lung; pancreas; ovary; mullerian duct; gut; ganglia; hair; skin; limb bud; cartilage ID GENE; HOMOLOG; CLONING AB The leucine zipper transcription factor TSC-22 (TGF-beta 1 Stimulated Cnone-22) was first isolated from a mouse osteoblast cell line as an immediate-early target gene of TGF-beta 1. However, work with other cell lines, as well as with a Drosophila homolog, bunched, suggests that it is an effector gene of various growth factors and potentially involved in the integration of multiple extracellular signals. Throughout mouse embryogenesis TSC-22 is expressed in a dynamic pattern. Although early TSC-22 expression is ubiquitous in 6.5 day embryos, as development proceeds TSC-22 expression is upregulated at sites of epithelial-mesenchymal interactions such as the limb bud, tooth primordiurn, hair follicle, kidney, lung, and pancreas. TSC-22 is also expressed in many neural crest-derived tissues including the mesenchyme of the branchial arches, the cranial, dorsal root, and sympathetic ganglia, as well as the facial cartilage and bone. Other areas of expression are the otic and optic vesicles, the heart, and cartilage and bone forming regions throughout the embryo. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02139 USA. Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. RP Raftery, LA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02139 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 13 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUN PY 1999 VL 84 IS 1-2 BP 147 EP 151 DI 10.1016/S0925-4773(99)00055-6 PG 5 WC Developmental Biology SC Developmental Biology GA 218PA UT WOS:000081559900015 PM 10473130 ER PT J AU Wright, SM Petersen, LA Lamkin, RP Daley, J AF Wright, SM Petersen, LA Lamkin, RP Daley, J TI Increasing use of medicare services by veterans with acute myocardial infarction SO MEDICAL CARE LA English DT Article DE AMI; veterans; Medicare; cardiac procedures; mortality; availability of cardiac technology ID NEW-YORK-STATE; CORONARY HEART-DISEASE; BYPASS GRAFT-SURGERY; UNITED-STATES; AFFAIRS; CARE; OUTCOMES; MORTALITY; CANADA; REGIONALIZATION AB OBJECTIVES. Some of the nation's 26 million veterans have two government-financed health care entitlements: Medicare and the Department of Veterans Affairs (VA). The aims of this investigation were to examine trends where Medicare-eligible VA users are initially hospitalized for acute myocardial infarction (AMI) and then to assess rates of cardiac procedure use and mortality for veterans initially admitted to each system of care. METHODS. We used VA and HCFA national databases to identify VA users (age range, greater than or equal to 65 years) who were initially admitted to a VAMC or Medicare financed hospital (Medicare hospital) with a primary diagnosis of AMI between January 1, 1992, and December 31, 1995, (n = 47,598). We examined the use of cardiac procedures (cardiac catheterization [CC] coronary artery bypass surgery [CABG], and coronary angioplasty [CA] and mortality (30-day and 1-year) by the type of initial admitting hospital within each system of care, RESULTS. Almost 70% of VA users hospitalized for AMI were initially admitted to Medicare hospitals versus VAMCs between 1992 (64%) and 1995 (72%). After adjusting for patient characteristics in logistic models, VA users initially hospitalized in Medicare hospitals were significantly more likely to undergo cardiac procedures than were VA users hospitalized in VAMCs. Differences in the odds of receiving a procedure were most significant when comparing Medicare hospitals with onsite cardiac technology to VA hospitals without on-site cardiac technology (CC: OR 4.34, 95% CI 3.98-4.73; CABG: OR 2.16, 95% CI 1.92-2.43; CA: OR 4.56, 95% CI 3.98-5.25). We found no significant differences in 30-day and 1-year adjusted mortality rates between VA users initially admitted to VAMCs or Medicare hospitals. CONCLUSIONS. Medicare-eligible VA users are increasingly hospitalized in Medicare hospitals for AMI. VA users cared for in Medicare hospitals receive more cardiac procedures but have the same survival as VA users cared for in VAMCs. These findings have policy implications for access, quality, and costs in both systems of care. C1 Harvard Univ, Sch Med, Dept Med, Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Harvard Thorndike Lab, Boston, MA USA. Harvard Univ, Sch Med,Charles A Dana Res Inst, Beth Isreal Deaconess Med Ctr, Dept Med,Div Gen Med & Primary Care, Cambridge, MA 02138 USA. RP Wright, SM (reprint author), Vet Adm Med Ctr W Roxbury, 1400 VFW Pkwy,HSR&D 151, Boston, MA 02132 USA. NR 29 TC 71 Z9 72 U1 2 U2 3 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 JUN PY 1999 VL 37 IS 6 BP 529 EP 537 DI 10.1097/00005650-199906000-00002 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 206NR UT WOS:000080886400002 PM 10386565 ER PT J AU Jospe, N Lane, A Greenlaw, J Sulkes, SB AF Jospe, N Lane, A Greenlaw, J Sulkes, SB TI Ambiguity of the external genitalia in an infant with Down syndrome: Gender assignment and ethical implications SO MENTAL RETARDATION LA English DT Editorial Material ID PLASTIC-SURGERY; CHILDREN C1 Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Med Humanities, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Div Pediat Endocrinol, Boston, MA 02114 USA. RP Jospe, N (reprint author), Univ Rochester, Sch Med & Dent, Dept Pediat, 601 Elmwood Ave,Box 777, Rochester, NY 14642 USA. NR 21 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 USA SN 0047-6765 J9 MENT RETARD JI Ment. Retard. PD JUN PY 1999 VL 37 IS 3 BP 232 EP 236 DI 10.1352/0047-6765(1999)037<0232:AOTEGI>2.0.CO;2 PG 5 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 211FE UT WOS:000081149100006 PM 10473342 ER PT J AU Pena, C Mueller, PR AF Pena, C Mueller, PR TI Metallic stents in the biliary tree SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Article DE metallic stent; biliary disease; biliary obstruction ID BILE-DUCT OBSTRUCTION; COVERED WALLSTENTS; FOLLOW-UP; ENDOPROSTHESES; COMPLICATIONS; MANAGEMENT; STRICTURES AB This paper outlines the types of metallic biliary stents available for use in malignant biliary disease. The results of various world-wide clinical trials are summarised. The future role of metallic biliary stents in malignant biliary obstruction is discussed. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ISIS MEDICAL MEDIA LTD PI OXFORD PA 59 ST ALDATES, OXFORD OX1 1ST, ENGLAND SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD JUN PY 1999 VL 8 IS 3 BP 191 EP 196 DI 10.3109/13645709909153158 PG 6 WC Surgery SC Surgery GA 214GB UT WOS:000081319300009 ER PT J AU Bloch, DB Chiche, JD Orth, D de la Monte, SM Rosenzweig, A Bloch, KD AF Bloch, DB Chiche, JD Orth, D de la Monte, SM Rosenzweig, A Bloch, KD TI Structural and functional heterogeneity of nuclear bodies SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; PROMYELOCYTIC LEUKEMIA-CELLS; PML-RAR-ALPHA; EXPRESSION; PROTEINS; GROWTH; GENE; TRANSLOCATION; DOMAINS; SP100 AB The nuclear body is a cellular structure that appears to be involved in the pathogenesis of acute promyelocytic leukemia and viral infection. In addition, the nuclear body is a target of autoantibodies in patients with the autoimmune disease primary biliary cirrhosis, Although the precise function of the nuclear body in normal cellular biology is unknown, this structure may have a role in the regulation of gene transcription. In a previous investigation, we identified a leukocyte-specific, gamma interferon (IFN-gamma)-inducible autoantigen designated Sp140. The objectives of the present study were to investigate the cellular location of Sp140 with respect to the nuclear-body components PML and Sp100 and to examine the potential role of Sp140 in the regulation of gene transcription. We used adenovirus-mediated gene transfer to express Sp140 in human cells and observed that the protein colocalized with PML and Sp100 in resting cells and associated with structures containing PML during mitosis, In cells infected with the adenovirus expressing Sp140 and incubated with IFN-gamma, the number of PML-Sp100 nuclear bodies per cell increased but immunoreactive Sp140 was not evenly distributed among the nuclear bodies. Sp140 associated with a subset of IFN-gamma-induced PML-Sp100 nuclear bodies. To examine the potential effect of Sp140 on gene transcription, a plasmid encoding Sp140 fused to the DNA-binding domain of GAL4 was cotransfected into COS cells with a chloramphenicol acetyltransferase (CAT) reporter gene containing five GAL4-binding sites and a simian virus 40 enhancer region. The GAL4-Sp140 fusion protein increased the expression of the reporter gene, In contrast, Sp100 fused to the GAL4 DNA-binding domain inhibited CAT activity in transfected mammalian cells, The results of this study demonstrate that Sp140 associates with a subset of PML-Sp100 nuclear bodies in IFN-gamma-treated cells and that Sp140 may activate gene transcription. Taken together, these observations suggest that the nuclear bodies within a cell may be heterogeneous with respect to both composition and function. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Arthritis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Bloch, DB (reprint author), Massachusetts Gen Hosp E, CNY-8,149 13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL059521, HL-54202]; NIAMS NIH HHS [AR-01866]; NIDDK NIH HHS [DK-051179] NR 36 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1999 VL 19 IS 6 BP 4423 EP 4430 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 198GX UT WOS:000080416100050 PM 10330182 ER PT J AU Dalal, SN Schweitzer, CM Gan, JM DeCaprio, JA AF Dalal, SN Schweitzer, CM Gan, JM DeCaprio, JA TI Cytoplasmic localization of human cdc25C during interphase requires an intact 14-3-3 binding site SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-DAMAGE CHECKPOINT; PHOSPHORYLATES HUMAN CDC25C; XENOPUS EGG EXTRACTS; LARGE T-ANTIGEN; PROTEIN-KINASE; CELL-CYCLE; FISSION YEAST; NUCLEAR EXPORT; MONOCLONAL-ANTIBODIES; TYROSINE PHOSPHATASE AB cdc25C induces mitosis by activating the cdc2-cyclin B complex. The intracellular localization of cyclin B1 is regulated in a cell cycle-specific manner, and its entry into the nucleus may be required for the initiation of mitosis, To determine the cellular localization of cdc25C, monoclonal antibodies specific for cdc25C were developed and used to demonstrate that in human cells, cdc25C is retained in the cytoplasm during interphase, A deletion analysis identified a 58-amino-acid region (amino acids 201 to 258) in cdc25C that was required for the cytoplasmic localization of cdc25C, This region contained a specific binding site for 14-3-3 proteins, and mutations in cdc25C that disrupted 14-3-3 binding also disrupted the cytoplasmic localization of cdc25C during interphase. cdc25C proteins that do not contain a binding site for 14-3-3 proteins showed a pancellular localization and an increased ability to induce premature chromosome condensation. The cytoplasmic localization of cdc25C was not altered by gamma irradiation or treatment with the nuclear export inhibitor leptomycin B, These results suggest that 14-3-3 proteins may negatively regulate cdc25C function by sequestering cdc25C in the cytoplasm. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA050661, CA-50661, CA-63113, R01 CA063113] NR 66 TC 221 Z9 228 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1999 VL 19 IS 6 BP 4465 EP 4479 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 198GX UT WOS:000080416100054 PM 10330186 ER PT J AU Musacchio, A Smith, CJ Roseman, AM Harrison, SC Kirchhausen, T Pearse, BMF AF Musacchio, A Smith, CJ Roseman, AM Harrison, SC Kirchhausen, T Pearse, BMF TI Functional organization of clathrin in coats: Combining electron cryomicroscopy and x-ray crystallography SO MOLECULAR CELL LA English DT Article ID RECEPTOR-MEDIATED ENDOCYTOSIS; LIGHT-CHAINS; HEAVY-CHAIN; VESICLE FORMATION; ARRESTIN/CLATHRIN INTERACTION; TERMINAL DOMAIN; G-PROTEIN; BINDING; TRIMERS; ADAPTERS AB The sorting of specific proteins into clathrin-coated pits and the mechanics of membrane invagination are determined by assembly of the clathrin lattice. Recent structures of a six-fold barrel clathrin coat at 21 Angstrom resolution by electron cryomicroscopy and of the clathrin terminal domain and linker at 2.6 Angstrom by X-ray crystallography together show how domains of clathrin interact and orient within the coat and reveal the strongly puckered shape and conformational variability of individual triskelions. The beta propeller of the terminal domain faces the membrane so that recognition segments from adaptor proteins can extend along its lateral grooves. Clathrin legs adapt to different coat environments in the barrel by flexing along a segment at the knee that is free of contacts with other molecules. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Med Lab, Boston, MA 02115 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RI Smith, Corinne/A-3170-2009 OI Smith, Corinne/0000-0003-3364-7946 FU NIGMS NIH HHS [GM36548] NR 51 TC 90 Z9 90 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JUN PY 1999 VL 3 IS 6 BP 761 EP 770 DI 10.1016/S1097-2765(01)80008-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 210UN UT WOS:000081123200008 PM 10394364 ER PT J AU Sarraf, P Mueller, E Smith, WM Wright, HM Kum, JB Aaltonen, LA de la Chapelle, A Spiegelman, BM Eng, C AF Sarraf, P Mueller, E Smith, WM Wright, HM Kum, JB Aaltonen, LA de la Chapelle, A Spiegelman, BM Eng, C TI Loss-of-function mutations in PPAR gamma associated with human colon cancer SO MOLECULAR CELL LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; GERMLINE PTEN MUTATION; HUMAN BREAST-CANCER; COWDEN-DISEASE; ADIPOCYTE DIFFERENTIATION; COLORECTAL-CANCER; OXIDIZED LDL; IN-VITRO; LIGAND; REGULATOR AB The gamma isoform of the peroxisome proliferator-activated receptor, PPAR gamma, regulates adipocyte differentiation and has recently been shown to be expressed in neoplasia of the colon and other tissues. We have found four somatic PPAR gamma mutations among 55 sporadic coln cancers: one nonsense, one frameshift, and two missense mutations. Each greatly impaired the function of the protein. c.472delA results in deletion of the entire ligand binding domain. Q286P and K319X retain a total or partial ligand binding domain but lose the ability to activate transcription through a failure to bind to ligands. R288H showed a normal response to synthetic ligands but greatly decreased transcription and binding when exposed to natural ligands. These data indicate that colon cancer in humans is associated with loss-of-function mutations in PPAR gamma. C1 Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Helsinki, Haartman Inst, Dept Med Genet, FIN-00014 Helsinki, Finland. RP Eng, C (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Dana Farber Canc Inst,Dept Canc Biol, Boston, MA 02115 USA. RI Aaltonen, Lauri/A-5375-2010 OI Aaltonen, Lauri/0000-0001-6839-4286 FU NCI NIH HHS [P30 CA16058] NR 28 TC 386 Z9 392 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JUN PY 1999 VL 3 IS 6 BP 799 EP 804 DI 10.1016/S1097-2765(01)80012-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 210UN UT WOS:000081123200012 PM 10394368 ER PT J AU Morita, Y Perez, GI Maravei, DV Tilly, KI Tilly, JL AF Morita, Y Perez, GI Maravei, DV Tilly, KI Tilly, JL TI Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RIBONUCLEIC-ACID LEVELS; CELL-DEATH; GENE FAMILY; CORPUS-LUTEUM; MEMBERS; DNA; BAX; PROTEIN; MICE; SURVIVAL AB Members of the Bcl-2 family serve as central checkpoints for cell death regulation, and overexpression of Bcl-2 is known to inhibit apoptosis in many cell types. To determine whether targeted expression of Bcl-2 could be used to protect female germ cells from apoptosis, we generated transgenic mice expressing fully functional human Bcl-2 protein only in oocytes. Transgenic mice were produced using a previously characterized 480-bp fragment of the mouse zona pellucida protein-3 (ZP3) gene 5'-flanking region to direct oocyte-specific expression of a human bcl-2 complementary DNA. Immunohistochemical analyses using a human Bcl-2-specific antibody showed that transgene expression was restricted to growing oocytes and was not observed in the surrounding ovarian somatic cells or in any other nonovarian tissues. Histomorphometric analyses revealed that ovaries collected from transgenic female mice possessed significantly fewer atretic small preantral follicles compared with wild-type sisters, resulting in a larger population of healthy maturing follicles per ovary. However, the number of oocytes ovulated in response to exogenous gonadotropin priming and the number of pups per litter were not significantly different among wild-type vs. transgenic female mice. Nonetheless, oocytes obtained from transgenic mice and cultured in vitro were found to be resistant to spontaneous and anticancer drug-induced apoptosis. We conclude that targeted expression of Bcl-2 only in oocytes can be achieved as a means to convey resistance of the female germ line to naturally occurring and chemotherapy-induced apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, VBK 137E-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226]; NIEHS NIH HHS [R01-ES-08430] NR 38 TC 106 Z9 115 U1 0 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 JUN PY 1999 VL 13 IS 6 BP 841 EP 850 DI 10.1210/me.13.6.841 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202UE UT WOS:000080669900008 PM 10379884 ER PT J AU Lavrovsky, Y Tyagi, RK Chen, S Song, CS Chatterjee, B Roy, AK AF Lavrovsky, Y Tyagi, RK Chen, S Song, CS Chatterjee, B Roy, AK TI Ribozyme-mediated cleavage of the estrogen receptor messenger RNA and inhibition of receptor function in target cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER; TRANSCRIPTIONAL ACTIVITY; HAMMERHEAD RIBOZYME; ORPHAN RECEPTOR; MCF-7; PROTEIN; GENE; BETA; LINE; ANTIESTROGENS AB Estrogen receptor (ER) functions as a ligand-activated transcription factor for estrogen-regulated genes. Because of the critical role of the ER in the proliferation of certain estrogen-dependent cancer cell types such as the mammary tumor, inhibitors of estrogen action at the level of receptor function are of major clinical interest. Here we describe developments of two ribozymes that can selectively degrade the human ER mRNA and inhibit trans-activation of an artificial promoter containing the estrogen response element. Two ribozymes, designated RZ-1 and RZ-2, cleave the human ER alpha mRNA at nucleotide positions +956 and +889, respectively. These cleavage sites lie within the coding sequence for the DNA-binding domain of the receptor protein. Both RZ-1 and RZ-2 were also effective in inhibiting the progression of quiescent MCF-7 breast cancer cells to the S phase of the cell cycle after their exposure to 17 beta-estradiol (10(-9) M). These results provide a new avenue for inhibition of estrogen action by selective mRNA degradation with its potential therapeutic application through targeted gene delivery vectors. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM roy@uthscsa.edu FU NIA NIH HHS [R37-AG-10486, T32 AG-00165]; NIDDK NIH HHS [R01-DK-14744] NR 35 TC 5 Z9 5 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1999 VL 13 IS 6 BP 925 EP 934 DI 10.1210/me.13.6.925 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202UE UT WOS:000080669900015 PM 10379891 ER PT J AU Ohh, M Kaelin, WG AF Ohh, M Kaelin, WG TI The von Hippel-Lindau tumour suppressor protein: new perspectives SO MOLECULAR MEDICINE TODAY LA English DT Review ID RENAL-CELL CARCINOMA; FACTOR MESSENGER-RNA; GENE-PRODUCT; F-BOX; GERMLINE MUTATIONS; CYCLE EXIT; VHL GENE; DISEASE; TRANSLATION; BINDING AB von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germline mutations of the VHL tumour suppressor gene. The VHL gene product, pVHL, forms multiprotein complexes that contain elongin B, elongin C and Cul-2, and negatively regulates hypoxia-inducible mRNAs, pVHL is suspected to play a role in ubiquitination given the similarity of elongin C and Cul-2 with Skp1 and Cdc53, respectively, pVHL can also interact with fibronectin and is required for the assembly of a fibronectin matrix, Finally, pVHL, at least indirectly, plays a role in the ability of cells to exit the cell cycle. Thus, pVHL is a tumour suppressor protein that regulates angiogenesis, extracellular matrix formation and the cell cycle. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ohh, M (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 45 TC 63 Z9 63 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD JUN PY 1999 VL 5 IS 6 BP 257 EP 263 DI 10.1016/S1357-4310(99)01481-1 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 219RD UT WOS:000081619900011 PM 10366821 ER PT J AU Yamamoto, H Simon, A Eriksson, U Harris, E Berson, EL Dryja, TP AF Yamamoto, H Simon, A Eriksson, U Harris, E Berson, EL Dryja, TP TI Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus SO NATURE GENETICS LA English DT Article AB The:metabolic pathways that produce Il-cis retinal are important for vision because this retinoid is the chromophore residing in rhodopsin and the tone opsins. The all-trans retinal that is generated after cone and rod photopigments absorb photons of light is recycled back to 11-cis retinal by the retinal pigment epithelium and Muller cells: of the retina. Several of the enzymes involved have:recently been purified and molecularly cloned (1-3);:here we focus on Il-cis retinol dehydrogenase (encoded by the gene RDH5; chromosome 12q13-14; ref. 4), the first cloned enzyme in this pathway. This microsomal enzyme is abundant in the retinal pigment epithelium(5), where it has been proposed to catalyse the conversion of Il-cis retinol to Il-cis retinal. We evaluated patients with hereditary retinal diseases featuring subretinal spots (retinitis punctata albescens and fundus albipunctatus) and patients with typical dominant or recessive retinitis pigmentosa for mutations in RDH5. Mutations were found only in two unrelated patients, both with fundus albipunctatus; they segregated with disease in the respective families. Recombinant mutant Il-cis retinol dehydrogenases had reduced activity compared with recombinant enzyme with wild-type sequence. Our results suggest that mutant alleles in RDH5 are a cause of fundus albipunctatus, a rare form of stationary night blindness characterized by a delay in the regeneration of cone and rod photopigments. C1 Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenat, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Ludwig Inst Canc Res, S-10401 Stockholm, Sweden. RP Dryja, TP (reprint author), Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenat, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. FU NEI NIH HHS [EY00169, EY08683] NR 16 TC 168 Z9 173 U1 1 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1999 VL 22 IS 2 BP 188 EP 191 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 202YX UT WOS:000080680900027 PM 10369264 ER PT J AU Paul, E Carroll, MC AF Paul, E Carroll, MC TI SAP-less chromatin triggers systemic lupus erythematosus SO NATURE MEDICINE LA English DT Editorial Material ID AMYLOID-P COMPONENT; CLASSICAL COMPLEMENT PATHWAY; B-CELL DELETION; TOLERANCE; CHAIN; MICE; C1Q C1 Harvard Univ, Childrens Hosp, Sch Med, Div Pediat Nephrol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Paul, E (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Div Pediat Nephrol, Boston, MA 02115 USA. NR 15 TC 32 Z9 32 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1999 VL 5 IS 6 BP 607 EP 608 DI 10.1038/9450 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 205LR UT WOS:000080823300019 PM 10371489 ER PT J AU Hare, BJ Wyss, DF Osburne, MS Kern, PS Reinherz, EL Wagner, G AF Hare, BJ Wyss, DF Osburne, MS Kern, PS Reinherz, EL Wagner, G TI Structure, specificity and CDR mobility of a class II restricted single-chain T-cell receptor SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID TOXIC LYMPHOCYTES-T; ANTIGEN RECEPTOR; NMR-SPECTROSCOPY; 3-DIMENSIONAL STRUCTURE; RELAXATION MEASUREMENTS; BACKBONE DYNAMICS; PROTEIN-STRUCTURE; THYMIC SELECTION; BINDING-SITE; PEPTIDE AB Using NMR spectroscopy, we determined the solution structure of a single-chain T-cell receptor (scTCR) derived from the major histocompatibility complex (MHC) class II-restricted D10 TCR. The conformations of complementarity-determining regions (CDRs) 3 beta and 1 alpha and surface properties of 2 alpha are different from those of related class I-restricted ICRs. We infer a conserved orientation for TCR V-alpha domains in complexes with both class I and II MHC-peptide ligands, which implies that small structural variations in V-alpha confer MHC class preference. High mobility of CDR3 residues relative to other CDR or framework residues (picosecond time scale) provides insight into immune recognition and selection mechanisms. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Procept Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Wagner, G (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 56 TC 71 Z9 72 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUN PY 1999 VL 6 IS 6 BP 574 EP 581 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 201HH UT WOS:000080589000022 PM 10360364 ER PT J AU Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB AF Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB TI Stimulus-dependent BOLD and perfusion dynamics in human V1 SO NEUROIMAGE LA English DT Article DE functional MRI; hemodynamics; visual cortex; psychophysiological habituation; contrast sensitivity; nonlinear dynamics ID CEREBRAL BLOOD-FLOW; MACAQUE STRIATE CORTEX; SENSITIVE MRI RESPONSES; HUMAN VISUAL-CORTEX; FUNCTIONAL-ANATOMY; BRAIN ACTIVATION; OXIDATIVE-METABOLISM; SENSORY STIMULATION; OXYGEN-CONSUMPTION; MODEL AB Blood oxygenation level-dependent (BOLD) fMRI signals often exhibit pronounced over- or undershoot upon changes in stimulation state. Current models postulate that this is due to the delayed onset or decay of perfusion-dependent attenuating responses such as increased cerebral blood volume or oxygen consumption, which are presumed to lag behind the rapid adjustment of blood flow rate to a new steady-state level. If this view is correct, then BOLD overshoot amplitudes in a specific tissue volume should be correlated with steady-state increases in perfusion, independent of stimulus type. To test this prediction, we simultaneously recorded BOLD and relative perfusion signals in primary visual cortex while inducing graded perfusion increases with three types of visual stimulus. Two of these, a diffuse chromatic stimulus with no luminance variation and a very high spatial frequency luminance grating, did not produce detectable BOLD overshoot (or undershoot) when an equal mean luminance baseline was used. Radial checkerboard stimuli, however, caused pronounced over/undershoot of both BOLD and perfusion signals even when temporal mean luminance was held constant and stimulus contrast was adjusted to produce the same steady-state blood flow increases evoked by the other stimuli. Transient amplitudes were relatively invariant in spite of large changes in steady-state response, demonstrating nonlinear BOLD and perfusion step responses in human V1, These findings suggest that, rather than a purely tissue-specific biomechanical or metabolic phenomenon, BOLD overshoot and undershoot represent transient features in the perfusion signal whose effects may be amplified by slowly evolving blood volume changes. (C) 1999 Academic Press. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Hoge, RD (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. RI Pike, Bruce/K-5562-2014; OI Pike, Bruce/0000-0001-8924-683X; Marrett, Sean/0000-0001-8179-6511 NR 46 TC 85 Z9 85 U1 1 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 1999 VL 9 IS 6 BP 573 EP 585 DI 10.1006/nimg.1999.0443 PN 1 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 206RE UT WOS:000080892400002 PM 10334901 ER PT J AU Bartzokis, G Beckson, M Newton, T Mandelkern, M Mintz, J Foster, JA Ling, W Bridge, TP AF Bartzokis, G Beckson, M Newton, T Mandelkern, M Mintz, J Foster, JA Ling, W Bridge, TP TI Selegiline effects on cocaine-induced changes in medial temporal lobe metabolism and subjective ratings of euphoria SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; selegiline; PET; MRI; hippocampus; amygdala; euphoria ID L-DEPRENYL SELEGILINE; CEREBRAL BLOOD-FLOW; ACETYLCHOLINE-RELEASE; HUMAN BRAIN; MAO-B; HIPPOCAMPUS; DOPAMINE; DEPENDENCE; AMYGDALA; RAT AB To test the effect of selegiline, aspecific monoamine oxidase-B (MAO-B)inhibitor, on the cerebral metabolic and euphorigenic effects of cocaine in experienced users, eight cocaine-dependent (CD) subjects were evaluated using a within-subjects design. Each subject participated in two pairs of [F-18]-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans (baseline scan followed 24 h Inter by a second scan obtained in conjunction with a 40-mg cocaine infusion) performed before and after a 1-week period of daily treatment with 10 mg selegiline administered orally. The hippocampus and amygdala were evaluated because of their hypothesized involvement in the addiction process, and the thalamus teas evaluated as a comparison region. Following 7 days of selegiline treatment, the magnitude of the subjective euphoria ("high") produced by cocaine infusion was reduced by 40% (cocaine by selegiline interaction F = 7.15, df = 1,22, p = .014). Selegiline treatment also altered glucose utilization (normalized against whole brain counts) in the two limbic regions, but not the thalamus. In the amygdala, the effects of cocaine differed, depending upon whether or not patients were being treated with selegiline (cocaine by selegiline interaction F = 4.67, df = 1,19.8, p = .043). A different effect was observed in the hippocampus, where selegiline treatment decreased metabolic activity irrespective of whether cocaine was given (main effect F = 7.70, df = 1,20, p = .012). The concomitant changes in both the subjective experience of the "high" and normalized amygdala glucose utilization after selegiline treatment, suggest that a relationship exists between cocaine-induced euphoria and limbic metabolism. The data suggest that selegiline may be a useful adjunct in the treatment of cocaine dependence. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 N Little Rock VA Med Ctr NLR, Psychiat Serv, Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. W Los Angeles Vet Affairs Med Ctr, Nucl Med Serv, Los Angeles, CA 90073 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92697 USA. NIDA, Med Dev Div, Rockville, MD 20857 USA. RP Bartzokis, G (reprint author), N Little Rock VA Med Ctr NLR, Psychiat Serv, 2200 Ft Roots Dr,Bldg 170,116A, Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013; OI newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [1YO1 DA 50038] NR 43 TC 38 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1999 VL 20 IS 6 BP 582 EP 590 DI 10.1016/S0893-133X(98)00092-X PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 191TN UT WOS:000080037800007 PM 10327427 ER PT J AU Kelley, ME Yao, JK van Kammen, DP AF Kelley, ME Yao, JK van Kammen, DP TI Plasma catecholamine metabolites as markers for psychosis and antipsychotic response in schizophrenia SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; catecholamines; homovanillic acid; psychosis ID HOMOVANILLIC-ACID LEVELS; HALOPERIDOL WITHDRAWAL; NEUROLEPTIC TREATMENT; DOPAMINE METABOLISM; TARDIVE-DYSKINESIA; CLINICAL-RESPONSE; HVA; DEBRISOQUIN; PSYCHOPATHOLOGY; NOREPINEPHRINE AB The objective of this study tons to determine Me association between the patterns of change in the dopaminergic metabolite plasma homovanillic acid (HVA), the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG), and psychosis following haloperidol withdrawal in schizophrenic patients. Weekly plasma measurements were obtained in 107 subjects with schizophrenia or schizoaffective disorder. Random regression was used to control for individual variance while modeling metabolite changes over time and relationships with psychosis. Changes in plasma MHPG were not significantly associated with relapse or psychosis, while increased plasma HVA was found to be associated with relapse. Psychosis was correlated negatively with plasma HVA levels. The current analysis, controlling for individual variance, indicates that there is evidence for pharmacological effects an plasma HVA, but not plasma MHPG. In addition, these metabolites do not appear to be direct markers of psychosis, but may be associated with a compensatory response by the system to return to the steady state. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 VA Pittsburgh Healthcare Syst, GIM 130U, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Kelley, ME (reprint author), VA Pittsburgh Healthcare Syst, GIM 130U, Univ Dr C, Pittsburgh, PA 15240 USA. FU NIMH NIH HHS [R01 MH-44841] NR 60 TC 13 Z9 14 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1999 VL 20 IS 6 BP 603 EP 611 DI 10.1016/S0893-133X(98)00094-3 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 191TN UT WOS:000080037800009 PM 10327429 ER PT J AU Rumelt, S You, TT Remulla, HD Rubin, PAD Jakobiec, FA AF Rumelt, S You, TT Remulla, HD Rubin, PAD Jakobiec, FA TI Prepartum mixed type cavernous-capillary hemangioma arising in nevus flammeus SO OPHTHALMOLOGY LA English DT Article ID PSEUDO-KAPOSIS SARCOMA; ORBITAL ARTERIOVENOUS MALFORMATION; EMBOLIZATION; PLACEMENT; PATIENT; FACE AB Objective: Capillary hemangioma may appear de novo and involute during the first decade of life, but rarely during pregnancy. This study describes the clinical and histologic findings of an eyelid mixed type cavernous-capillary hemangioma arising in a nevus flammeus and discusses the differential diagnosis of this lesion. Study Design: Clinicopathologic case report. Intervention: A reddish, protruding eyelid mass arising from a nevus flammeus at the eyelid margin in a 26-year-old woman was monitored during her pregnancy. Postpartum, the mass was excised and examined histologically. Results: The lobulated tumor recurred during the second pregnancy and partially regressed following delivery. It was composed of mixed elements of cavernous and capillary hemangioma that superficially resembled Kaposi sarcoma, set against the background of a nevus flammeus. Conclusion: The differential diagnosis of discrete prepartum vascular tumor arising in nevus flammeus includes mixed capillary-cavernous hemangioma, pseudo-Kaposi sarcoma, granuloma gravidarum, and angio-dermatitis, A common stimulus during pregnancy may be the inciting factor for the development of these tumors. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Pathol & Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ophthalm Plast & Orbit Serv, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Pathol & Oncol Unit, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1999 VL 106 IS 6 BP 1219 EP 1222 DI 10.1016/S0161-6420(99)90246-4 PG 4 WC Ophthalmology SC Ophthalmology GA 201GR UT WOS:000080587500042 PM 10366096 ER PT J AU Hayashi, N Borodic, G Karesh, JW Tolentino, MJ Remulla, HD Van Wesep, RA Grossniklaus, HE Jakobiec, FA Green, WR AF Hayashi, N Borodic, G Karesh, JW Tolentino, MJ Remulla, HD Van Wesep, RA Grossniklaus, HE Jakobiec, FA Green, WR TI Giant cell angiofibroma of the orbit and eyelid SO OPHTHALMOLOGY LA English DT Article ID SOLITARY FIBROUS TUMOR; ANTIGEN CD34; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; STROMAL TUMORS; NASAL CAVITY; ANGIOHISTIOCYTOMA; EXPRESSION; PLEURA; SARCOMA AB Purpose: To report the clinicopathologic features of a newly recognized tumor, giant cell angiofibroma, Design: Observational case series. Main Outcome Measures: Clinical and histopathologic features of giant cell angiofibroma; Methods: Light and electron microscopy and immunohistochemistry of five cases of giant cell angiofibroma, Results: A total of five patients (4 women and 1 man) are described: two presented with a painless mass in the eyelid, two with a mass in the orbit, and one presented with a conjunctival lesion. All lesions were well demarcated with no capsule and were composed of blood vessels, a patternless spindle-shaped cell proliferation with a solid and pseudovascular appearance, and multinucleated giant cells. Both spindle-shaped and giant tumor cells were intensely positive for CD34 and vimentin, Conclusion: Giant cell angiofibroma resembles solitary fibrous tumor and giant cell fibroblastoma and should;be considered in the differential diagnosis of spindle-cell tumors in the eyelid, orbit, and conjunctiva. C1 Johns Hopkins Med Inst, Wilmer Ophthalmol Inst, W Richard Green Eye Pathol Lab, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Kochi Med Sch, Dept Ophthalmol, Kochi, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Sinai Hosp, Dept Ophthalmol, Baltimore, MD 21215 USA. Sinai Hosp, Dept Pathol, Baltimore, MD 21215 USA. Emory Clin, Eye Pathol Lab, Atlanta, GA 30322 USA. RP Green, WR (reprint author), Johns Hopkins Hosp, Eye Pathol Lab Maumenee 427, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 47 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1999 VL 106 IS 6 BP 1223 EP 1229 DI 10.1016/S0161-6420(99)90270-1 PG 7 WC Ophthalmology SC Ophthalmology GA 201GR UT WOS:000080587500043 PM 10366097 ER PT J AU Eavey, RD AF Eavey, RD TI Microtia repair: Creation of a functional postauricular sulcus SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID TISSUE-ENGINEERED CARTILAGE; POLYMER-CELL CONSTRUCT; HUMAN EAR; TRANSPLANTATION; RECONSTRUCTION; GRAFTS; SHAPE AB OBJECTIVE: Auricular reconstruction for repair of severe congenital microtia can provide the patient with a realistic-looking pinna. However, an unseen functional cephaloauricular sulcus is necessary, especially for patients with eyeglasses. TECHNIQUE: (1) A skin graft is harvested, (2) The ear framework is separated substantially from the side of the head. (3) A crescent of hair-bearing scalp skin is excised. (4) The donor skin graft is divided. One part of the graft surfaces the superolateral and medial portions of the auricular framework into the sulcus depth; the remainder covers the side of the head. RESULTS: This simple technique was effective. Minor transient sequelae have included granulation tissue (2 patients), localized infection (2 patients), and adhesion (1 patient). Patients requiring glasses have worn frames soon after surgery, and no sulcus problems have resulted. CONCLUSION: Creation of this postauricular sulcus during microtia reconstruction is easily performed and offers the patient a durable and functional space, especially for eyeglass wear. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol & Laryngol, Boston, MA USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JUN PY 1999 VL 120 IS 6 BP 789 EP 793 DI 10.1016/S0194-5998(99)70315-3 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 206DU UT WOS:000080862700002 PM 10352428 ER PT J AU Bhattacharyya, N Poe, DS AF Bhattacharyya, N Poe, DS TI Otoendoscopic view of a persistent stapedial artery SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ENDOSCOPY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Sch Med, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Joint Ctr Otolaryngol, 333 Longwood Ave,3rd Floor, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JUN PY 1999 VL 120 IS 6 BP 923 EP 923 DI 10.1016/S0194-5998(99)70338-4 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 206DU UT WOS:000080862700025 PM 10352451 ER PT J AU Bruss, JB Malley, R Halperin, S Dobson, S Dhalla, M McIver, J Siber, GR AF Bruss, JB Malley, R Halperin, S Dobson, S Dhalla, M McIver, J Siber, GR TI Treatment of severe pertussis: a study of the safety and pharmacology of intravenous pertussis immunoglobulin SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pertussis; pertussis toxin; whooping cough drug therapy; pertussis immunoglobulin ID TOXIN; STANDARDIZATION; ANTIBODIES; ANTITOXIN; DIAGNOSIS; GLOBULIN; VACCINE; IGG AB Background. Pertussis in infants is often severe, resulting in complications and prolonged hospitalization. Treatment is limited to supportive care. Antibiotics do not significantly alter the course of the disease. Therapies directed at pertussis toxin, a major virulence factor of Bordetella pertussis, might be beneficial. This study examines the safety and pharmacology of intravenous pertussis immunoglobulin (P-IGIV), which has high levels of pertussis toxin antibodies. Methods. P-IGIV was prepared as a 4% IgG solution from the pooled plasma from donors immunized with inactivated pertussis toroid. The IgG pertussis toxin antibody concentration of 733 mu g/ml is >7-fold higher than contained in conventional intravenous immunoglobulin products. Children with presumptive pertussis were allocated to one of three treatment doses of P-IGIV, Results. Twenty-six of 30 enrolled children had confirmed pertussis. There were no adverse events associated with P-IGIV except one patient who had transient hypotension that responded to an infusion rate decrease. P-IGIV doses of 1500, 750 and 250 mg/kg achieved greater than or equal to 4-fold, greater than or equal to 3-fold and >2-fold rises in peak geometric mean titers of pertussis toxin IgG antibodies, respectively. P-IGIV exhibited a half-life of 38.4 days and a volume of distribution of 87.8 ml/kg. All three treatment groups showed declines in lymphocytosis (P < 0.05) and paroxysmal coughing by the third day after P-IGIV infusion compared with preinfusion values. Conclusion. P-IGIV is safe and achieves high pertussis toxin antibody titers in infants. This study provides data for a prospective, controlled trial of P-IGIV. C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Publ Hlth Biol Labs, Boston, MA USA. Dalhousie Univ, Grace Hlth Ctr, Halifax, NS B3H 3J5, Canada. British Columbia Childrens Hosp, Vancouver, BC V6H 3V4, Canada. RP Bruss, JB (reprint author), Pharmacia & Upjohn Inc, 9156-243-131,7000 Portage Rd, Kalamazoo, MI 49001 USA. NR 41 TC 32 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 1999 VL 18 IS 6 BP 505 EP 511 DI 10.1097/00006454-199906000-00006 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 205CU UT WOS:000080804400005 PM 10391179 ER PT J AU Kaban, LB Mulliken, JB Ezekowitz, RA Ebb, D Smith, PS Folkman, J AF Kaban, LB Mulliken, JB Ezekowitz, RA Ebb, D Smith, PS Folkman, J TI Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a SO PEDIATRICS LA English DT Article DE interferon alfa-2a; basic fibroblast growth factor; angiogenesis; giant cell tumor of mandible ID FIBROBLAST GROWTH-FACTOR; ALPHA-INTERFERON; HEMANGIOMAS; INFANCY; CHILDHOOD; ANGIOGENESIS; INHIBITION; LESIONS; JAWS; MICE AB We report a 5-year-old girl with a large rapidly growing giant fell tumor of the mandible that recurred 2 months after the first surgical excision and 3 months after a second resection. An angiogenic protein, (bFGF), was abnormally elevated in her urine. The patient was treated with interferon alfa-2a for 1 year because this agent inhibits angiogenesis by suppressing bFGF overexpression in infantile hemangiomas and in other human tumors. During this time the bone tumor regressed and disappeared, the urinary bFGF fell to normal levels, and the mandible regenerated. She has remained tumor-free and has been off therapy for 3 years at this writing. This first successful use of interferon alfa-2a to treat a mandibular tumor in a child demonstrates: 1) low grade tumors that overexpress bFGF may respond to interferon alfa-aa, in a manner similar to life-threatening infantile hemangiomas; 2) antiangiogenic therapy, given without interruption for 1 year, was safe and effective in this patient; and 3) treatment may be continued for 1 year without the development of drug resistance. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Rhode Isl Hosp, Div Pediat Hematol Oncol, Providence, RI USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 48 TC 149 Z9 158 U1 0 U2 1 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 JUN PY 1999 VL 103 IS 6 BP 1145 EP 1149 DI 10.1542/peds.103.6.1145 PN 1 PG 5 WC Pediatrics SC Pediatrics GA 201UF UT WOS:000080613400016 PM 10353921 ER PT J AU Thyen, U Kuhlthau, K Perrin, JM AF Thyen, U Kuhlthau, K Perrin, JM TI Employment, child care, and mental health of mothers caring for children assisted by technology SO PEDIATRICS LA English DT Article DE chronic illness; home care; technology assisted; family support; employment; quality of life; child care ID PSYCHOLOGICAL ADJUSTMENT; FAMILY; STRESS; WOMEN; WORK; DISABILITIES; FATHERS; IMPACT; PARENT AB Objective. This study examines 1) the way that children with chronic conditions are cared for at home and assisted by technology affects maternal employment and child care; 2) the social and clinical factors associated with the decision of a mother to quit employment to care for a child at home; and 3) the way in which care at home and the decision of a mother to quit a job affects maternal mental health. Design. The 6-month postdischarge status of 70 mothers of children assisted by technology (study group) was compared with the 6-month postdischarge status of 58 mothers of children (matched for age and gender) hospitalized for acute illnesses (comparison group). Between January and December 1993, we gathered information on sociodemographic status, employment status and changes in employment, severity of the child's condition, child care and nursing services at home, family support, and maternal mental health. Results. One third of mothers in the study group reported that they quit employment to take fare of a child at home with only 37.1% remaining employed outside the home, compared with 69.0% of comparison group mothers. Single caretakers were 15 times more likely to quit employment compared with mothers in two-parent families. Availability of child care had an independent effect on a mother's decision to quit a job, whereas the severity of the child's condition did not. Child care hours were significantly lower in study group families and were provided mostly by relatives compared with daycare facilities and regular babysitters in comparison families. Family support was highest among employed mothers in both the study and the comparison groups and lowest in study group mothers who were neither employed currently nor before the child's illness or who had quit employment to care for the child. Family income was significantly lower in families with a child assisted by technology. Families in the study group had 20-fold higher uncompensated health care costs than did the comparison group. Mothers caring for a child assisted by technology reported less good mental health than did comparison group mothers, and employment seems to mediate this relationship. Conclusions. Caring for a child assisted by technology seems to create barriers to maternal employment diminishing family resources at a time when financial needs actually may increase. Lack of family support and child care services increase the likelihood that mothers of children assisted by technology will stay out of the labor force. Remaining employed buffers the negative effects of care at home on maternal mental health. Health policies for children with chronic health problems should address issues of financial burdens and the labor force participation of their caretakers. C1 Univ Lubeck, Klin Padiat, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Thyen, U (reprint author), Univ Lubeck, Klin Padiat, Kahlhorststr 31-35, D-23538 Lubeck, Germany. RI Vollrath, Margarete/G-1297-2011 NR 49 TC 86 Z9 86 U1 1 U2 6 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 JUN PY 1999 VL 103 IS 6 BP 1235 EP 1242 DI 10.1542/peds.103.6.1235 PN 1 PG 8 WC Pediatrics SC Pediatrics GA 201UF UT WOS:000080613400030 PM 10353935 ER PT J AU Pontius, AA AF Pontius, AA TI Motiveless firesetting: Implicating partial limbic seizure kindling by revived memories of fires in "limbic psychotic trigger reaction" SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Academy-of-Psychiatry-and-the-Law CY OCT 21-24, 1993 CL SAN ANTONIO, TEXAS SP Amer Acad Psychiat & Law ID TEMPORAL-LOBE EPILEPSY; FRONTAL-LOBE; SYSTEM DYSFUNCTION; HOMICIDE; BEHAVIOR AB 23 unselected juvenile firesetters (M age 12.0 yr.) consisted of seven with schizophrenia, three with organic mental disorder, six with posttraumatic stress disorder, two with severe mental retardation, anti two with conduct disorders. Three previously nondestructive boys (M age 11.0 yr.), all of them loners, did not fit such traditional diagnoses. Their fleeting (c. 20 min.) symptoms included fiat affect, autonomic arousal, and delusions or hallucinations. II appeared that their motiveless, unplanned acts were each preceded by a chance encounter with an individualized stimulus which revived the three boys' repeatedly ruminated memories of intermittently experienced merely moderate stresses associated with fire, smoke, or matches. Such a sequence of events is characteristic of seizure kindling. One boy's abnormal EEG was congruent with seizures in the temporal lobe area, which includes the amygdala, i.e., that part of the limbic system particularly susceptible to seizure kindling. The three boys' consistent symptomatology was very similar to that reported for 17 men with bizarre homicidal acts implicating a kindled partial seizure called "Limbic Psychotic Trigger Reaction." In primates, too, similar partial nonconvulsive "behavioral seizures" with psychosis-like symptoms can be elicited through experiential kindling. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat APS, Boston, MA 02114 USA. RP Pontius, AA (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 49 TC 11 Z9 11 U1 0 U2 0 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 USA SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD JUN PY 1999 VL 88 IS 3 BP 970 EP 982 DI 10.2466/PMS.88.3.970-982 PN 1 PG 13 WC Psychology, Experimental SC Psychology GA 210WF UT WOS:000081127100035 PM 10407907 ER PT J AU Cohen, LG Prince, J Biederman, J Wilens, T Faraone, SV Whitt, S Mick, E Spencer, T Meyer, MC Polisner, D Flood, JG AF Cohen, LG Prince, J Biederman, J Wilens, T Faraone, SV Whitt, S Mick, E Spencer, T Meyer, MC Polisner, D Flood, JG TI Absence of effect of stimulants on the pharmacokinetics of desipramine in children SO PHARMACOTHERAPY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DRUG-INTERACTIONS; IN-VITRO; CLINICAL PHARMACOKINETICS; TRICYCLIC ANTIDEPRESSANTS; HOSPITALIZED CHILDREN; S-MEPHENYTOIN; DOUBLE-BLIND; METHYLPHENIDATE; METABOLISM AB We conducted a retrospective chart review to examine the pharmacokinetic interaction between desipramine and the stimulants methylphenidate and dexedrine using routinely monitored desipramine serum concentrations in children receiving desipramine either alone or with a stimulant. Subjects were 142 children and adolescents (age 6-17 yrs; 113 taking desipramine, 29 taking desipramine-stimulants) in whom 401 dose- and weight-normalized serum concentrations were evaluated (333 desipramine, 68 desipramine-stimulants). Desipramine pharmacokinetic parameters were similar for both groups, including mean weight-corrected dose (3.66 +/- 1.36 mg/kg, desipramine; 3.66 +/- 1.09 mg/kg, desipramine-stimulants; p=0.97), weight-and dose-normalized serum concentrations (47.26 +/- 39.26 [mu g/L]/[mg/kg], desipramine, 39.02 +/- 19.92 [mu g/L]/[mg/kg], desipramine-stimulants; p=0.09), and clearance (0.690 +/- 0.913 [L/kg]/hr, desipramine; 0.613 +/- 0.514 [L/kg]/hr, desipramine-stimulants; p=0.499). When stratified by age, gender, and type of stimulant, no difference was detected (p>0.05) between groups. Our findings indicate the absence of a clinically significant interaction between desipramine and stimulants. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Chem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cohen, LG (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 56 TC 10 Z9 10 U1 1 U2 4 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 1999 VL 19 IS 6 BP 746 EP 752 DI 10.1592/phco.19.9.746.31539 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204WD UT WOS:000080786900009 PM 10391421 ER PT J AU Chin, L AF Chin, L TI Molecular analysis of a mouse model of cutaneous melanoma. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 3S EP 4S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200011 ER PT J AU Moor, ACE Rajagopalan, K Savellano, MD Hasan, T AF Moor, ACE Rajagopalan, K Savellano, MD Hasan, T TI Photodynamic treatment of ovarian cancer cells using photosensitizer-antibody conjugates directed against the EGF-R SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 9S EP 9S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200026 ER PT J AU Kochevar, IE AF Kochevar, IE TI UVA and visible light photoaging. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 15S EP 16S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200046 ER PT J AU Zhuang, SG Lynch, MC Kochevar, IE AF Zhuang, SG Lynch, MC Kochevar, IE TI Caspase-3 is activated by caspase-8 mediated release of cytochrome c during singlet oxygen-induced apoptosis in HL-60 cells. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 39S EP 39S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200116 ER PT J AU Mulroy, L Redmond, RW Kim, J Melke, S Azar, D Kochevar, IE AF Mulroy, L Redmond, RW Kim, J Melke, S Azar, D Kochevar, IE TI Photochemical tissue bonding for corneal repair and transplants. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, 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 AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 41S EP 42S PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200124 ER PT J AU Lambert, CR Kochevar, IE Redmond, RW AF Lambert, CR Kochevar, IE Redmond, RW TI Wavelength dependence of rose bengal due to differential reactivity of upper triplet states. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Connecticut Coll, Dept Chem, New London, CT 06320 USA. Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 64S EP 64S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200192 ER PT J AU Brenneisen, P Wenk, J Redmond, R Wlaschek, M Kochevar, IE Scharffetter-Kochanek, K AF Brenneisen, P Wenk, J Redmond, R Wlaschek, M Kochevar, IE Scharffetter-Kochanek, K TI Requirement for FRAP and P70 ribosomal S6 kinase in the DNA-damage dependent signaling leading to induction of collagenase/MMP-1 and stromelysin-1/MMP-3 after UVB irradiation of dermal fibroblasts. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Univ Cologne, Dept Dermatol, D-50931 Cologne, Germany. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 88S EP 88S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200266 ER PT J AU Redmond, RW Aveline, BM AF Redmond, RW Aveline, BM TI Transient absorption spectroscopy used to study mechanisms of sensitized cellular phototoxicity. SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 1999 VL 69 SI SI BP 95S EP 95S PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220KB UT WOS:000081663200287 ER PT J AU Alcaraz, MV Pathak, MA Rius, F Kollias, N Gonzalez, S AF Alcaraz, MV Pathak, MA Rius, F Kollias, N Gonzalez, S TI An extract of Polypodium leucotomos appears to minimize certain photoaging changes in a hairless albino mouse animal model - A pilot study SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE Polypodium leucotomos; ultraviolet radiation; skin photoaging; hairless albino mouse; skin cancer ID INDUCED DERMAL DAMAGE; BIOCHEMICAL-CHANGES; ULTRAVIOLET-LIGHT; LANGERHANS CELLS; UV-RADIATION; SKIN; MICE; SUNSCREENS; ELASTOSIS; PROTECTION AB Chronic ultraviolet B (UVB) exposure of human or murine skin is known to induce cutaneous photoaging and enhanced carcinogenic risk. An extract of Polypodium leucotomos (PL), a tropical fern plant, has been known to exhibit interesting antioxidant and photoprotective properties against acute exposure to ultraviolet radiation. The objective of this preliminary (or pilot) study was to determine the photoprotective role of topically applied Polypodium leucotomos extract in the prevention or amelioration of cutaneous changes of photoaging in hairless mice. PL-treated mice showed significant reduction of skinfold thickness than those observed in PL-untreated controls. Additionally, PL-treated mice showed a significantly lower degree of histologic parameters of photoaging damage, including dermal elastosis, compared with positive control mice. Interestingly, PL treatment also showed reduction in the number of mice showing skin tumors at 8 weeks after the cessation of the UVB exposure protocol. The results of this preliminary study illustrate that PL treatment helped to ameliorate and to partially inhibit some of the histologic damage associated with photoaging of skin and appeared to contribute to a decrease in the prevalence of UVB-induced skin tumors in mice. C1 Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Massachusetts Gen Hosp, BHX 630,55 Blossom Str, Boston, MA 02114 USA. NR 28 TC 33 Z9 37 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD JUN-AUG PY 1999 VL 15 IS 3-4 BP 120 EP 126 PG 7 WC Dermatology SC Dermatology GA 205WD UT WOS:000080842800006 PM 10404722 ER PT J AU Silverman, RP Passaretti, D Huang, W Randolph, MA Yaremchuk, M AF Silverman, RP Passaretti, D Huang, W Randolph, MA Yaremchuk, M TI Injectable tissue-engineered cartilage using a fibrin glue polymer SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TRANSPLANTATION; CHONDROCYTES AB The purpose of this study was to demonstrate the feasibility of using a fibrin glue polymer to produce injectable tissue-engineered cartilage and to determine the optimal fibrinogen and chondrocyte concentrations required to produce solid, homogeneous cartilage. The most favorable fibrinogen concentration was determined by measuring the rate of degradation of fibrin glue using varying concentrations of purified porcine fibrinogen. The fibrinogen was mixed with thrombin (50 U/cc in 40 mM calcium chloride) to produce fibrin glue. Swine chondrocytes were then suspended in the fibrinogen before the addition of thrombin. The chondrocyte/polymer constructs were injected into the subcutaneous tissue of nude mice using chondrocyte concentrations of 10, 25, and 40 million chondrocytes/cc of polymer (0.4-cc injections). At 6 and 12 weeks, the neocartilage was harvested and analyzed by histology, mass, glycosaminoglycan content, DNA content, and collagen type II content. Control groups consisted of nude mice injected with fibrin glue alone (without chondrocytes) and a separate group injected with chondrocytes suspended in saline only (40 million cells/cc in saline; 0.4-cc injections). The fibrinogen concentration with the most favorable rate of degradation was SO mg/cc. Histologic analysis of the neocartilage showed solid, homogeneous cartilage when using 40 million chondrocytes/cc, both at 6 and 12 weeks. The 10 and 25 million chondrocytes/cc samples showed areas of cartilage separated by areas of remnant fibrin glue. The mass of the samples ranged from 0.07 to 0.12 g at 6 weeks and decreased only slightly by week 12. The glycosaminoglycan content ranged from 2.3 to 9.4 percent for all samples; normal cartilage controls had a content of 7.0 percent. DNA content ranged from 0.63 to 1.4 percent for all samples, with normal pig cartilage having a mean DNA content of 0.285 percent. The samples of fibrin glue alone produced no cartilage, and the chondrocytes alone produced neocartilage samples with a significantly smaller mass (0.47 g at 6 weeks and 0.46 g at 12 weeks) when compared with all samples produced from chondrocytes suspended in fibrin glue (p < 0.03). Gel electrophoreses demonstrated the presence of type II collagen in all sample groups. This study demonstrates that fibrin glue is a suitable polymer for the formation of injectable tissue-engineered cartilage in the nude mouse model. Forty million chondrocytes per cc yielded the best quality cartilage at 6 and 12 weeks when analyzed by histology and content of DNA, glycosaminoglycan, and type II collagen. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Yaremchuk, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, ACC 4,Suite 453,25 Fruit St, Boston, MA 02114 USA. NR 9 TC 143 Z9 152 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUN PY 1999 VL 103 IS 7 BP 1809 EP 1818 DI 10.1097/00006534-199906000-00001 PG 10 WC Surgery SC Surgery GA 200PU UT WOS:000080549700001 PM 10359239 ER PT J AU Brem, AS Bina, RB Fitzpatrick, C King, T Tang, SS Ingelfinger, JR AF Brem, AS Bina, RB Fitzpatrick, C King, T Tang, SS Ingelfinger, JR TI Glucocorticoid metabolism in proximal tubules modulates angiotensin II-induced electrolyte transport SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID VASCULAR SMOOTH-MUSCLE; SODIUM-TRANSPORT; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; TOAD BLADDER; RECEPTOR; EXPRESSION; SPECIFICITY; NEPHRON; KIDNEY; CELLS AB The hormonal interactions that regulate electrolyte transport in the proximal tubule are complex and incompletely understood. Since endogenous glucocorticoids and angiotensin II each can affect electrolyte transport in this renal segment, we hypothesized that local metabolism of glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) might alter the response to angiotensin II. Studies were conducted in cultured origin defective SV-40 transformed immortalized renal proximal tubule cells (IRPTC) derived from weanling Wistar rat kidney. The 11 beta-HSD contained in these cells uses NADP(+), has an apparent K-m for corticosterone of 1.6 mu M, but functions only as a dehydrogenase (corticosterone --> 11-dehydrocorticosterone), When mounted in modified Ussing chambers, IRPTC generate a transmembrane current, and angiotensin 11 (10 pM to 10 mu M) increases this sodium-dependent current. Cells incubated with corticosterone (100 nM) and the 11 beta-HSD inhibitor carbenoxolone (CBX) (1 mu M) for 24 hr and then acutely stimulated with angiotensin (10 nM) show a greater rise in current than do cells exposed to corticosterone alone and stimulated with angiotensin (corticosterone + CBX: 64.2% +/- 20.5% vs. corticosterone: 18.8% +/- 5.9%; P < 0.02 at 180 min)[mean +/- SE percentage above baseline, n = 8/group]. Cells exposed to corticosterone (100 nM) or CBX (1 mu M) alone for 24 hr and then stimulated with angiotensin 11 (10 nM) had responses similar to controls. Thus glucocorticoids can enhance angiotensin Ii-induced electrolyte transport in proximal tubule epithelial cells when local 11 beta-HSD is inhibited. C1 Rhode Isl Hosp, Div Pediat Nephrol, Providence, RI 02903 USA. Brown Univ, Sch Med, Miriam Hosp, Dept Pathol, Providence, RI 02912 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Nephrol, Boston, MA 02114 USA. RP Brem, AS (reprint author), Rhode Isl Hosp, Div Pediat Nephrol, 593 Eddy St, Providence, RI 02903 USA. FU NHLBI NIH HHS [HL43131, HL40210] NR 35 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUN PY 1999 VL 221 IS 2 BP 111 EP 117 DI 10.1046/j.1525-1373.1999.d01-63.x PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 198PW UT WOS:000080434000005 PM 10352121 ER PT J AU Fenn, DS Ganzini, L AF Fenn, DS Ganzini, L TI Attitudes of Oregon psychologists toward physician-assisted suicide and the Oregon Death With Dignity Act SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID DECISION-MAKING; EUTHANASIA; CARE; PSYCHIATRISTS; COMPETENCE AB Since the passage of the Oregon Death With Dignity Act (ODDA), psychologists have been grappling with how to fulfill their legally specified role in the process of physician-assisted suicide. We surveyed Oregon psychologists to elicit their views on assisted suicide and the process of assessing patients who request such assistance. There was a high degree of support for assisted suicide and the ODDA, but also a minority who were highly opposed. Most survey respondents raised ethical or practical concerns with their role as assessors. Many important questions about how evaluations in this complex area should be conducted remain unanswered. C1 Portland Vet Affairs Med Ctr, Psychiat Res 116AP, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. RP Fenn, DS (reprint author), Portland Vet Affairs Med Ctr, Psychiat Res 116AP, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 25 TC 24 Z9 24 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD JUN PY 1999 VL 30 IS 3 BP 235 EP 244 DI 10.1037/0735-7028.30.3.235 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 204VV UT WOS:000080786100003 PM 14626273 ER PT J AU Brawer, MK Lin, DW Williford, WO Jones, K Lepor, H AF Brawer, MK Lin, DW Williford, WO Jones, K Lepor, H TI Effect of finasteride and or terazosin on serum PSA: Results of VA cooperative study #359 SO PROSTATE LA English DT Article DE PSA; BPH; finasteride; terazosin ID PROSTATE-SPECIFIC ANTIGEN; DIGITAL RECTAL EXAMINATION; ACID-PHOSPHATASE; CANCER DETECTION; HYPERPLASIA; MEN; VARIABILITY; EFFICACY; ADENOCARCINOMA; SAFETY AB BACKGROUND. Medical management of benign prostatic hyperplasia (BPH) giving rise to lower urinary tract symptomatology (LUTS) has emerged as the mainstay for first-line therapy. Prostate-specific antigen (PSA) is the most important method of detecting prostate carcinoma. The effect of finasteride on PSA has been widely: reported. Little data exist with respect to alpha-adrenergic blocking therapy in men treated for BPH. In the present investigation we set out to evaluate the effect of these two forms of therapy. METHODS. Patients enrolled in the VA Cooperative Study #359 trial were evaluated. This study evaluated men with moderate LUTS owing to BPH in four treatment groups: placebo (P), finasteride (F), terazosin (T), and combination of finasteride plus terazosin (C). Men were recruited at 31 VA medical centers and had a baseline in 52-week PSA determination at the respective sites. RESULTS. There was no significant difference in baseline PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically significant reduction in PSA levels was observed at 52 weeks in the F and C arms (P < 0.001), whereas significant increases were observed in the T and P arms (P < 0.01). Additionally, there was no significant difference in PSA response between the T and P arms, Thirty percent of men in the C or F arms had more than 40-60% reduction of PSA. In contrast, the majority of men on T or P had less than 40% change in PSA. Only 35% of men on F or C had the expected 40-60% reduction in PSA level. CONCLUSIONS. These data demonstrate no clinically significant effect of T on PSA level. The heterogeneity of PSA response to F may make monitoring patients for the development of prostate cancer problematic. (C) 1999 Wiley-Liss, Inc. C1 Pacific NW Canc Fdn, NW Prostate Inst, Seattle, WA 98133 USA. Univ Washington, Dept Urol, Ctr Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98195 USA. Perry Point VA Med Ctr, Cooperat Studies Program Coodinating Ctr, Perry Point, MD USA. NYU Med Ctr, Dept Urol, New York, NY 10016 USA. RP Brawer, MK (reprint author), Pacific NW Canc Fdn, NW Prostate Inst, 1560 N 115th St,Suite 209, Seattle, WA 98133 USA. NR 40 TC 22 Z9 24 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 0270-4137 J9 PROSTATE JI Prostate PD JUN 1 PY 1999 VL 39 IS 4 BP 234 EP 239 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 196ZD UT WOS:000080339400003 PM 10344212 ER PT J AU Wilkins, SS Castle, S Heck, E Tanzy, K Fahey, J AF Wilkins, SS Castle, S Heck, E Tanzy, K Fahey, J TI Immune function, mood, and perceived burden among caregivers participating in a psychoeducational intervention SO PSYCHIATRIC SERVICES LA English DT Article ID DEPRESSION; STRESS C1 W Los Angeles Vet Affairs Med Ctr, Dept Vet Affairs Geriatr Res Educ & Clin Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Interdisciplinary Res Immunol & Dis, Los Angeles, CA 90024 USA. RP Wilkins, SS (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Vet Affairs Geriatr Res Educ & Clin Ctr, 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [AG-00489-01] NR 12 TC 15 Z9 15 U1 0 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 JUN PY 1999 VL 50 IS 6 BP 747 EP 749 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 202AK UT WOS:000080629800005 PM 10375143 ER PT J AU Sharkansky, EJ Brief, DJ Peirce, JM Meehan, JC Mannix, LM AF Sharkansky, EJ Brief, DJ Peirce, JM Meehan, JC Mannix, LM TI Substance abuse patients with posttraumatic stress disorder (PTSD): Identifying specific triggers of substance use and their associations with PTSD symptoms SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID ADDICTION SEVERITY INDEX; ADJUSTMENT; VETERANS; LIFE AB Although individuals with comorbid posttraumatic stress disorder (PTSD) and substance use diagnoses are at heightened risk for relapse after substance abuse treatment, little is known about the specific situations in which these individuals are likely to relapse. The present study was designed to test whether a PTSD diagnosis related to substance use in specific situations in which PTSD symptoms were likely to be present. Data were gathered from inpatients (n = 86) in a substance-abuse-treatment program, and relationships between PTSD diagnosis and frequency of substance use in high-risk situations were examined. As predicted, PTSD diagnosis was related to substance use in situations involving unpleasant emotions, physical discomfort, and interpersonal conflict, but not to substance use in other situations. C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B 3, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. VA Boston Healthcare Syst, Substance Abuse Treatment Program, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div, Boston, MA USA. RP Sharkansky, EJ (reprint author), VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div 116B 3, Jamacia Plain Campus,150 S Huntington Ave, Boston, MA 02130 USA. RI Peirce, Jessica/E-7790-2013 OI Peirce, Jessica/0000-0002-1192-3965 NR 39 TC 29 Z9 30 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 1999 VL 13 IS 2 BP 89 EP 97 DI 10.1037//0893-164X.13.2.89 PG 9 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 206PQ UT WOS:000080888600003 ER PT J AU Metzger, DS Navaline, H Woody, GE AF Metzger, DS Navaline, H Woody, GE TI Drug abuse treatment as AIDS prevention SO PUBLIC HEALTH LA English DT Article; Proceedings Paper CT Research Synthesis Symposium on the Prevention of HIV in Drug Abusers CY AUG 03-05, 1997 CL FLAGSTAFF, ARIZONA ID METHADONE-MAINTENANCE TREATMENT; HUMAN-IMMUNODEFICIENCY-VIRUS; OUT-OF-TREATMENT; NEW-YORK-CITY; HIV-INFECTION; SUBSTANCE-ABUSE; RISK-REDUCTION; UNITED-STATES; USERS; SEROCONVERSION AB Objective. As the acquired immunodeficiency syndrome (AIDS) epidemic among drug users enters its third decade in the United States, it is important to consider the role played by substance abuse treatment in the prevention of human immunodeficiency virus (HIV) infection. Methods. The authors review the research literature, examining findings from studies with behavioral and serologic measures on the association among treatment participation, HIV risk reduction, and HIV infection. Results. Numerous studies have now documented that significantly lower rates of drug use and related risk behaviors are practiced by injecting drug users (IDUs) who are in treatment. Importantly, these behavioral differences, based primarily on self-report, are consistent with studies that have examined HIV seroprevalence and seroincidence among drug users, Conclusion. The underlying mechanism of action suggested by the collective findings of the available literature is rather simple-individuals who enter and remain in treatment reduce their drug use, which leads to fewer instances of drug-related risk behavior. This lower rate of exposure results in fewer infections with HIV, The protective effects of treatment, however, can only be achieved when programs are accessible and responsive to the changing needs of drug users. Future research needs to be directed at developing a better understanding of the factors that enhance treatment entry and retention. C1 Univ Penn, Vet Adm Med Ctr, Ctr Studies Addict, Opiate & AIDS Res Div, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Subst Abuse Treatment Unit, Philadelphia, PA USA. RP Metzger, DS (reprint author), Univ Penn, Vet Adm Med Ctr, Ctr Studies Addict, Opiate & AIDS Res Div, 3900 Chestnut St, Philadelphia, PA 19104 USA. RI Metzger, David/D-9499-2012 NR 43 TC 1 Z9 1 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0033-3506 J9 PUBLIC HEALTH JI Public Health PD JUN PY 1999 VL 113 SU 1 BP 97 EP 106 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 211TJ UT WOS:000081177700011 ER PT J AU Solbiati, L Goldberg, SN Ierace, T Dellanoce, M Livraghi, T Gazelle, GS AF Solbiati, L Goldberg, SN Ierace, T Dellanoce, M Livraghi, T Gazelle, GS TI Radio-frequency ablation of hepatic metastases: Postprocedural assessment with a US microbubble contrast agent - Early experience SO RADIOLOGY LA English DT Article DE liver neoplasms, secondary; liver neoplasms, US; radiofrequency (RF) ablation; ultrasound (US), contrast media; ultrasound (US), Doppler studies; ultrasound (US), power Doppler studies ID RADIOFREQUENCY TISSUE ABLATION; HEPATOCELLULAR-CARCINOMA; MICROWAVE COAGULATION; THERMAL ABLATION; LIVER METASTASES; ULTRASOUND; TUMORS; THERAPY; MASSES AB PURPOSE: To evaluate contrast agent-enhanced ultrasonography (US) in the detection of untreated tumor after radio-frequency (RF)ablation of hepatic metastases. MATERIALS AND METHODS: Twenty patients with solitary colorectal liver metastases underwent percutaneous RF tumor ablation. Pre- and postablation imaging was performed with nonenhanced and enhanced color and power Doppler US and contrast-enhanced helical computed tomography (CT). Initial follow-up CT and US contrast-enhanced helical computed tomography (CT). Initial follow-up CT and US were performed 24 hours after ablation. The findings at US and CT were compared. RESULTS: Nonenhanced US demonstrated intratumoral signal in 15 of 20 metastases before ablation. This signal increased after contrast agent administration. Contrast-enhanced US performed 24 hours after ablation demonstrated residual foci of enhancement in three tumors, whereas no US signals were seen in any tumor on nonenhanced scans. CT demonstrated small (<3-mm) persistent foci of residual enhancement in these three tumors and in three additional lesions that were not seen at US (US sensitivity, 50%; specificity, 100%; diagnostic agreement with CT, 85%). All six patients with evidence of residual tumor underwent;repeat RF ablation. CONCLUSION: Contrast-enhanced US may depict residual tumor after RF application and thereby enable additional directed therapy. The potential reduction in treatment sessions and/or ancillary imaging procedures might increase the ease and practicality of percutaneous ablation;of focal hepatic metastases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, DATA Grp,Dept Radiol, Boston, MA 02114 USA. Osped Gen, Dept Radiol, Busto Arsizo, Italy. Osped Civile, Dept Radiol, Vimercate, MI, Italy. RP Gazelle, GS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, DATA Grp,Dept Radiol, Zero Emerson Pl,Ste 2H, Boston, MA 02114 USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 22 TC 142 Z9 151 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1999 VL 211 IS 3 BP 643 EP 649 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198VY UT WOS:000080446000009 PM 10352586 ER PT J AU Rao, PM AF Rao, PM TI Case 11: Perforated duodenal diverticulitis SO RADIOLOGY LA English DT Article DE diagnosis please; duodenum, CT; duodenum, diverticula C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Sparrow Hosp, Lansing Radiol Associates, 271 Woodland Pass,Ste 120, E Lansing, MI 48823 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1999 VL 211 IS 3 BP 711 EP 713 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198VY UT WOS:000080446000018 PM 10352595 ER PT J AU Ort, RJ Anderson, RR AF Ort, RJ Anderson, RR TI Optical hair removal SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID RUBY-LASER PULSES; FOLLICLE STEM-CELLS; SELECTIVE PHOTOTHERMOLYSIS; CYCLE; SKIN; DESTRUCTION; EPILATION; HIRSUTISM; LOCATION AB Traditional methods of hair removal have proven unsatisfactory for many individuals with excessive or unwanted hair. In the last few years, several lasers and xenon flashlamps have been developed that promise to fulfill the need for a practical, sate, and long-lasting method of hair removal. Aggressive marketing of these has contributed to their popularity among patients and physicians. However, significant controversy and confusion surrounds this held. This article provides a detailed explanation of the scientific underpinnings for optical hair removal and explores the advantages and disadvantages of the various devices currently available (Nd:YAG, ruby, alexandrite, diode losers, and xenon flashlamp). Treatment and safety guidelines are provided to assist the practitioner in the use of these devices. Although the field of optical hair removal is still in its infancy, initial reports of long-term efficacy are encouraging. Copyright (C) 1999 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ort, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. NR 41 TC 24 Z9 26 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD JUN PY 1999 VL 18 IS 2 BP 149 EP 158 DI 10.1016/S1085-5629(99)80039-X PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 202UA UT WOS:000080669500007 PM 10385283 ER PT J AU Aisenberg, AC AF Aisenberg, AC TI Primary large cell lymphoma of the mediastinum SO SEMINARS IN ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; DIFFUSE LARGE-CELL; HIGH-DOSE CHEMOTHERAPY; B-CELLS; MALIGNANT-LYMPHOMA; THYMIC LYMPHOMA; MACOP-B; SCLEROSIS; TUMOR; SUBSET C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, Boston, MA 02114 USA. RP Aisenberg, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Hematol Oncol, 75 Blossom Ct, Boston, MA 02114 USA. NR 72 TC 15 Z9 18 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 1999 VL 26 IS 3 BP 251 EP 258 PG 8 WC Oncology SC Oncology GA 205EY UT WOS:000080809400002 PM 10375082 ER PT J AU Maher, EA Fine, HA AF Maher, EA Fine, HA TI Primary CNS lymphoma SO SEMINARS IN ONCOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; HIGH-DOSE METHOTREXATE; COMBINED-MODALITY THERAPY; PRIMARY CEREBRAL LYMPHOMA; ACUTE MYELOID-LEUKEMIA; AIDS PATIENTS; IMMUNOCOMPETENT PATIENTS; DIFFERENTIAL-DIAGNOSIS; INCREASING INCIDENCE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neuro Oncol,Dept Adult Oncol, Boston, MA 02115 USA. RP Maher, EA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neuro Oncol,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 58 Z9 65 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 1999 VL 26 IS 3 BP 346 EP 356 PG 11 WC Oncology SC Oncology GA 205EY UT WOS:000080809400011 PM 10375091 ER PT J AU Brogi, E Harris, NL AF Brogi, E Harris, NL TI Lymphomas of the breast: Pathology and clinical behavior SO SEMINARS IN ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; LYMPHOCYTIC MASTOPATHY; ORAL IMMUNIZATION; BURKITTS-LYMPHOMA; CELLS; PSEUDOLYMPHOMA; MIGRATION; ANTIGENS; ANTIBODY C1 Massachusetts Gen Hosp, James Homer Wright Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, James Homer Wright Lab, Warren 2,14 Fruit St, Boston, MA 02114 USA. NR 48 TC 112 Z9 124 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 1999 VL 26 IS 3 BP 357 EP 364 PG 8 WC Oncology SC Oncology GA 205EY UT WOS:000080809400012 PM 10375092 ER PT J AU Gebhardt, MC Parekh, SG Rosenberg, AE Rosenthal, DI AF Gebhardt, MC Parekh, SG Rosenberg, AE Rosenthal, DI TI Extraskeletal myxoid chondrosarcoma of the knee SO SKELETAL RADIOLOGY LA English DT Article DE extraskeletal myxoid chondrosarcoma; metastasis; kidney; pancreas; chemotherapy; knee ID ROUGH ENDOPLASMIC-RETICULUM; SOFT-TISSUE TUMORS; CHORDOID SARCOMA; ULTRASTRUCTURE; CHROMOSOME-22 AB Extraskeletal myxoid chondrosarcoma is an uncommon neoplasm, accounting for less than 2% of all soft tissue sarcomas. It affects adult males with a median age in the fifth decade at the time of diagnosis, The tumor usually arises in the deep soft tissues, especially in the lower extremities. Patients present with a gradually enlarging mass that may or may not be associated with pain. This report describes a 25-year-old man who initially presented with a 4- to 5-year history of right knee pain and an enlarging mass in the right knee. Evaluation revealed a cartilaginous neoplasm with no evidence of metastatic disease. The tu mor was widely excised and an allograft reconstruction was performed. The patient was closely followed with an eventual above the knee amputation for recurrent myxoid chondrosarcoma. At 34 months, retroperitoneal metastases were noted on abdominal CT. The patient underwent a left radical nephrectomy, renal vein thrombectomy and enucleation of the mass in the right kidney, distal pancreatectomy, and splenectomy, The patient received postoperative chemotherapy. Forty-eight months after initial diagnosis, the patient was found to have recurrent abdominal and retroperitoneal lesions. At 64 months, the patient died from complications of extraskeletal myxoid chondrosarcoma. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Connect Tissue Oncol Ctr, Boston, MA USA. RP Gebhardt, MC (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Serv, Gray Bldg,6th Floor,55 Fruit St, Boston, MA 02114 USA. NR 40 TC 19 Z9 20 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUN PY 1999 VL 28 IS 6 BP 354 EP 358 PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 219YF UT WOS:000081635600010 PM 10450885 ER PT J AU Loechner, KJ Knox, RJ McLaughlin, JT Dunlap, K AF Loechner, KJ Knox, RJ McLaughlin, JT Dunlap, K TI Dexamethasone-mediated inhibition of calcium transients and ACTH release in a pituitary cell line (AtT-20) SO STEROIDS LA English DT Article DE dexamethasone; fura PE3/AM; omega-agatoxin IVA; dihydropyridines ID ADRENOCORTICOTROPIN RELEASE; RAT CORTICOTROPES; GLUCOCORTICOID ACTION; BRAIN SYNAPTOSOMES; GENE-EXPRESSION; PROTEIN-KINASE; TUMOR-CELLS; CURRENTS; CHANNELS; ACTIVATION AB In the corticotroph-like murine pituitary tumor cell line, AtT-20, adrenocorticotropic hormone release is triggered by corticotropin-releasing hormone and is attenuated by the synthetic adrenal steroid dexamethasone. The precise mechanisms by which dexamethasone inhibits secretion are under investigation We examined whether dexamethasone can modulate release via regulation of calcium homeostasis. More specifically, we have evaluated the effects of dexamethasone on calcium current, intracellular calcium concentration, and adrenocorticotropic hormone release. Using perforated patch-clamp and calcium imaging with fura PE3/AM, we found that dexamethasone decreases calcium current and intracellular calcium levels. The inhibition of current by dexamethasone is not, however, altered by the calcium channel antagonists nifedipine (L-type) or omega-agatoxin TVA (P/Q-type), despite the presence of these calcium channel subtypes in AtT-20 cells and the exclusive coupling of adrenocorticotropic hormone release to the L-type channel in these cells. We also evaluated the temporal relationship between dexamethasone-mediated inhibition of secretion and calcium influx. Whereas a prolonged (2 h) incubation with dexamethasone inhibits corticotropin-induced release by similar to 40%, a rapid (10 min) incubation (a time interval sufficient for dexamethasone-mediated inhibition of calcium transients) does not inhibit release. These data suggest, therefore, that dexamethasone does, indeed, modulate calcium homeostasis in AtT-20 cells, but that this effect is not responsible for its inhibition of secretion. (C) 1999 Published by Elsevier Science Inc. All rights reserved. C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA. Tufts Univ, Sch Med, Dept Pharmacol, Boston, MA 02111 USA. Harvard Med Sch, Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Loechner, KJ (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS16483] NR 41 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-128X J9 STEROIDS JI Steroids PD JUN PY 1999 VL 64 IS 6 BP 404 EP 412 DI 10.1016/S0039-128X(98)00121-4 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 218EY UT WOS:000081541300005 PM 10433177 ER PT J AU Munzenrider, JE Liebsch, NJ AF Munzenrider, JE Liebsch, NJ TI Proton therapy for tumors of the skull base SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Article DE proton therapy; skull base; chordoma; chondrosarcoma; 3D conformal radiation therapy ID RELATIVE BIOLOGICAL EFFECTIVENESS; RADIATION-THERAPY; CERVICAL-SPINE; CHORDOMAS; IRRADIATION; BEAM; CHONDROSARCOMA; RADIOTHERAPY; SURVIVAL; PHOTON AB Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Munzenrider, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA 21239] NR 46 TC 192 Z9 198 U1 0 U2 6 PU URBAN & VOGEL PI MUNICH PA LINDWURMSTRASSE 95, D-80337 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 1999 VL 175 SU 2 BP 57 EP 63 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 208MR UT WOS:000080995600019 PM 10394399 ER PT J AU Munzenrider, JE AF Munzenrider, JE TI Proton therapy for uveal melanomas and other eye lesions SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Article DE proton therapy; uveal melanoma; ocular angiomas; hemangiomas, and metastasis; age-related macular degeneration ID RELATIVE BIOLOGICAL EFFECTIVENESS; BEAM IRRADIATION; CHOROIDAL MELANOMA; RADIATION-THERAPY; CILIARY BODY; MALIGNANT-MELANOMA; SURVIVAL RATES; ENUCLEATION; RADIOTHERAPY; RETINOBLASTOMA AB Charged particle beams are ideal for treating intra-ocular lesions, since they can be made to deposit their dose in the target, while significantly limiting dose received by non-involved ocular and orbital structures. Proton beam treatment of large numbers of uveal melanoma patients consistently achieves local control rates in excess of 95%, and eye retention rates of approximately 90%. Visual preservation is related to initial visual acuity, tumor size and location, and dose received by the macula, disc, and lens. The probability of distant metastasis is increased by larger tumor diameter, more anterior tumor location, and older patient age. Proton therapy is also effective treatment for patients with ocular angiomas, hemangiomas, metastatic tumors, and retinoblastomas, and may be beneficial for patients with exudative ("wet") age-related macular degeneration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Munzenrider, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239] NR 55 TC 24 Z9 25 U1 0 U2 2 PU URBAN & VOGEL PI MUNICH PA LINDWURMSTRASSE 95, D-80337 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD JUN PY 1999 VL 175 SU 2 BP 68 EP 73 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 208MR UT WOS:000080995600022 PM 10394402 ER PT J AU Souba, WW AF Souba, WW TI How competitive forces mold strategy in academic surgery SO SURGERY LA English DT Article ID MEDICINE C1 Harvard Univ, Div Surg Oncol, Sch Med, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. RP Souba, WW (reprint author), Harvard Univ, Div Surg Oncol, Sch Med, Massachusetts Gen Hosp,Dept Surg, Cox 626,100 Blossom St, Boston, MA 02114 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 1999 VL 125 IS 6 BP 616 EP 629 DI 10.1016/S0039-6060(99)70226-6 PG 14 WC Surgery SC Surgery GA 202UN UT WOS:000080670700008 PM 10372027 ER PT J AU Abdelaziz, OS Ogilvy, CS Lev, M AF Abdelaziz, OS Ogilvy, CS Lev, M TI Is there a potential role for hyoid bone compression in pathogenesis of carotid artery stenosis? SO SURGICAL NEUROLOGY LA English DT Article DE atherosclerosis; carotid artery; carotid endarterectomy; hyoid bone ID STRESS AB BACKGROUND Blood now turbulence and increased shear stress, particularly at sites of sudden, marked arterial wall changes, are significant hemodynamic parameters in the pathogenesis of atherosclerosis. We present a case in which we found the hyoid bone protruding into the carotid vessels and may have been contributing, in part, to atherosclerotic carotid stenosis. CASE PRESENTATION An 85-year-old woman presenting with left arm and leg weakness consistent with right hemispheric transient ischemic attack. Magnetic resonance arteriography (MRA) and carotid non-invasive studies revealed a 90% stenosis of the right internal carotid artery. At surgery, the hyoid bone on the right side was projecting into the internal carotid artery, causing indentation. There was associated rotation of the internal and external carotid arteries from their normal position. Right carotid endarterectomy was performed and the lateral one-third of the hyoid bone excised to alleviate the external compression. Postoperative spiral computerized tomography (CT) scan of the carotid vessels demonstrated the extent of hyoid resection as well as rotation of the external and internal carotid arteries. CONCLUSIONS We suggest the possible contribution of hyoid bone compression to the pathogenesis of atherosclerotic carotid artery stenosis. This report also highlights the diagnostic value of CT angiography in the assessment of carotid artery occlusive disease. (C) 1999 by Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. Univ Alexandria, Fac Med, Dept Neurosurg, Alexandria, Egypt. RP Abdelaziz, OS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, 32 Fruit St,GRB 502, Boston, MA 02114 USA. NR 6 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JUN PY 1999 VL 51 IS 6 BP 650 EP 653 DI 10.1016/S0090-3019(99)00022-1 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 203HK UT WOS:000080702300023 PM 10369234 ER PT J AU Thompson, JM Ottensmeyer, MP Sheridan, TB AF Thompson, JM Ottensmeyer, MP Sheridan, TB TI Human factors in telesurgery: Effects of time delay and asynchrony in video and control feedback with local manipulative assistance SO TELEMEDICINE JOURNAL LA English DT Article AB This paper presents the results of experiments examining the performance of a telesurgeon and an assistant local to the patient performing simulated laparoscopic tasks under a variety of time-delay conditions. Of particular interest is a comparison between the surgeon provided with audio/video and force feedbck synchronously with various time delays, and the surgeon performing asynchronously, where video is delayed relative to force feedback. These conditions are relevant since current telecommunication systems have limited bandwidth, and video signals must be compressed for efficient transmission. This produces a time lag between the video camera and the surgeon's monitor, Force feedback and position commands from a surgical teleoperator require much lower bandwidth, and can be transmitted in near-real time. In the first of two series of experiments, two laparoscopic training tasks were performed under different time-delay conditions, with force and video feedback delayed by equal amounts. In the second series, using the same tasks, the force feedback was more immediate, while the video delay lagged by the time required for compression and decompression. In both experiments, there were various role assignments in terms of whether the telesurgeon or the assistant controlled the laparoscope and/or the various surgical tools required. The three most striking results are that (1) nontrivial time delays significantly degraded the performance of the surgical tasks, (2) asynchronous force feedback resulted in significantly faster task-performance than did synchronous performance when the surgeon operated the laparoscopic tools, and (3) there was no difference between synchrony and asynchrony when the remote surgeon operated the laparoscope and gave commands while the local assistant operated the surgical tools. C1 Massachusetts Gen Hosp, Clin Anes 3, Human Machine Syst Lab, Boston, MA 01890 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, JM (reprint author), Massachusetts Gen Hosp, Clin Anes 3, Human Machine Syst Lab, Fruit St, Boston, MA 01890 USA. NR 9 TC 22 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1078-3024 J9 TELEMED J JI Telemed. J. PD SUM PY 1999 VL 5 IS 2 BP 129 EP 137 DI 10.1089/107830299312096 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 239ND UT WOS:000082773500002 PM 10908425 ER PT J AU Hadlock, T Singh, S Vacanti, JP McLaughlin, BJ AF Hadlock, T Singh, S Vacanti, JP McLaughlin, BJ TI Ocular cell monolayers cultured on biodegradable substrates SO TISSUE ENGINEERING LA English DT Article ID PIGMENT EPITHELIAL-CELLS; RCS RAT; TRANSPLANTATION; POLYMERS; INVITRO; NEOVASCULARIZATION; DEGENERATION; DEGRADATION; INVIVO; RPE AB The aim of this study was to culture retinal pigment epithelial (RPE) and corneal endothelial cells on biodegradable substrates for future use in monolayer transplantation in the eye. The biodegradable polymers, poly-L-lactic (PLLA) and poly-DL-lactic-co-glycolic acid (85:15) (PLGA) (both of molecular weight 105 kd) were the biomaterials used. All materials were seeded with either pig/human retinal pigment epithelial cells or rabbit corneal endothelial cells and were maintained in tissue culture conditions. Upon confluency, the cell density was calculated and cell viability determined. All monolayers were stained with phalloidin-rhodamine for F-actin and antibodies to the tight junction (zonula occludens) protein, ZO(1), to demonstrate the presence of tight junctions. The final cell density of human RPE monolayers on PLLA films was 2950 cells/mm(2) (+/-185). The final cell density of pig RPE on PLLA and PLGA film was 2350 cells/mm(2) (+/-152 and 178, respectively). Rabbit corneal endothelial cells had a final cell density of 2650 cells/mm(2) (+/-164). F-actin staining revealed a circumferential ring of actin filaments in all of the cells grown on substrates. ZO1 immunohistochemistry demonstrated staining along the lateral cell borders of all cell types. The successful culture of retinal pigment epithelial and corneal endothelial monolayers on these substrates may have potential for transplanting cell monolayers in the eye to improve vision. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Louisville, Sch Med, Dept Ophthalmol & Visual Sci, Louisville, KY 40292 USA. FU NEI NIH HHS [EY02853] NR 28 TC 48 Z9 60 U1 1 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUN PY 1999 VL 5 IS 3 BP 187 EP 196 DI 10.1089/ten.1999.5.187 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 211UC UT WOS:000081179400001 PM 10434067 ER PT J AU DiFranza, JR Rigotti, NA AF DiFranza, JR Rigotti, NA TI Impediments to the enforcement of youth access laws SO TOBACCO CONTROL LA English DT Article DE tobacco sales; access laws; adolescents ID TOBACCO-SALES LAWS; CIGARETTE SALES; MINORS AB Objective-To recognise obstacles to the implementation of the effective enforcement of tobacco sales laws and to identify measures that could be taken to overcome these obstacles. Design-Interviews were conducted with health department officials in Massachusetts communities to determine why their efforts to prevent illegal sales of tobacco to miners had been only partially successful. Setting-Urban, suburban, and rural communities in Massachusetts, USA. Results-Organisational problems, court challenges to citations, budgetary threats, and political pressure all combined to reduce the frequency of enforcement inspections to half the intended rate. Political pressure resulted in the exclusion of older youths from compliance tests, further undermining enforcement efficacy. Conclusions-Suggestions for addressing the problems include obtaining support from the community, keeping elected and court officials informed about plans for merchant education and law enforcement, using efficient enforcement protocols, setting merchant compliance goals, and advising the public and government officials about progress towards those goals, using older youths to make purchase attempts, and testing all merchants frequently. C1 Univ Massachusetts, Med Ctr, Dept Family & Community Med, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP DiFranza, JR (reprint author), Univ Massachusetts, Med Ctr, Dept Family & Community Med, 55 Lake Ave N, Worcester, MA 01655 USA. NR 10 TC 13 Z9 13 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD SUM PY 1999 VL 8 IS 2 BP 152 EP 155 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 226ML UT WOS:000082023700013 PM 10478398 ER PT J AU Aguiar, LJ AF Aguiar, LJ TI Role of the transplant financial coordinator and its effect on recipient compliance SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT International Symposium on Transplant Recipient Compliance CY APR 03-05, 1998 CL ARLINGTON, VIRGINIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Aguiar, LJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 108, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1999 VL 31 IS 4A SU S BP 55S EP 56S DI 10.1016/S0041-1345(99)00129-3 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 205WQ UT WOS:000080843900019 PM 10372049 ER PT J AU Cosimi, AB AF Cosimi, AB TI Clinical application of tolerance induction in solid organ transplantation SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT Symposium on Present and Future Challenges in Transplantation in Honor of Felix T Rapaport and Thomas E Starzel CY JUN 01-02, 1998 CL BUENOS AIRES, ARGENTINA ID TOTAL LYMPHOID IRRADIATION; ALLOGRAFT TOLERANCE; CYNOMOLGUS MONKEYS; RENAL-ALLOGRAFTS; HEART ALLOGRAFTS; CHIMERISM; PRIMATES; REGIMEN; KIDNEY; CELLS C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. RP Cosimi, AB (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL18646]; NIAID NIH HHS [AI37692] NR 18 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1999 VL 31 IS 4 BP 1803 EP 1805 DI 10.1016/S0041-1345(99)00174-8 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 204JR UT WOS:000080761400017 PM 10371958 ER PT J AU Seebach, JD Pazmany, L Waneck, GL Minja, F Germana, S LeGuern, C Sachs, DH AF Seebach, JD Pazmany, L Waneck, GL Minja, F Germana, S LeGuern, C Sachs, DH TI HLA-G expression on porcine endothelial cells protects partially against direct human NK cytotoxicity but not against ADCC SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st International Conference on HLA-G CY JUL 06-07, 1998 CL PARIS, FRANCE ID NATURAL-KILLER-CELLS; RECEPTORS C1 Univ Zurich Hosp, Dept Internal Med, CH-8091 Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Seebach, JD (reprint author), Univ Zurich Hosp, Dept Internal Med, Ramistr 100, CH-8091 Zurich, Switzerland. NR 8 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 1999 VL 31 IS 4 BP 1864 EP 1865 DI 10.1016/S0041-1345(99)00190-6 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 204JR UT WOS:000080761400034 PM 10371975 ER PT J AU Hobert, O Ruvkun, G AF Hobert, O Ruvkun, G TI Pax genes in Caenorhabditis elegans - a new twist SO TRENDS IN GENETICS LA English DT Article ID PAIRED DOMAIN; HOMEODOMAIN; RECOGNITION C1 Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Biol Mol,Dept Genet, Boston, MA 02114 USA. RP Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA. EM or38@columbia.edu; ruvkun@frodo.mgh.harvard.edu OI Hobert, Oliver/0000-0002-7634-2854 NR 11 TC 17 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 1999 VL 15 IS 6 BP 214 EP 216 DI 10.1016/S0168-9525(99)01731-X PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 215KD UT WOS:000081380100003 PM 10354580 ER PT J AU Shekelle, PG Woolf, SH Eccles, M Grimshaw, J AF Shekelle, PG Woolf, SH Eccles, M Grimshaw, J TI Developing clinical guidelines SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID DESIGN AFFECTS OUTCOMES; CONTROLLED TRIALS; APPROPRIATENESS; BIAS; LANGUAGE; THERAPY; RATINGS; QUALITY AB The methods of guideline development should ensure that treating patients according to guidelines will achieve the outcomes that are desired. This article presents a combination of the literature about guideline: development and the results of our combined experience in guideline development in North America and Britain. It considers the 5 steps in the initial development of an evidence-based guideline. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Virginia Commonwealth Univ, Hlth Serv Res & Dev Serv, Dept Family Practice, Fairfax, VA 22033 USA. Univ Newcastle Upon Tyne, Ctr Hlth Serv Res, Newcastle Upon Tyne NE2 4AA, Tyne & Wear, England. Univ Aberdeen, Hlth Serv Res Unit, Aberdeen AB9 2ZD, Scotland. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Grimshaw, Jeremy/D-8726-2013; OI Grimshaw, Jeremy/0000-0001-8015-8243 NR 16 TC 47 Z9 48 U1 3 U2 6 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD JUN PY 1999 VL 170 IS 6 BP 348 EP 351 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 220XA UT WOS:000081692500014 PM 18751155 ER PT J AU Gribben, JG AF Gribben, JG TI Bone marrow transplant for lymphoma: where is the field going? SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Article DE non-Hodgkin's lymphoma; bone marrow transplantation; autologous; allogeneic; graft versus lymphoma; adoptive immunotherapy ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; PROGENITOR-CELL TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; HIGH-DOSE THERAPY; HUMAN FOLLICULAR LYMPHOMAS; BREAKPOINT-CLUSTER REGION; VERSUS-HOST DISEASE; CHROMOSOMAL BREAKPOINT C1 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. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAY 31 PY 1999 VL 1423 IS 3 BP C31 EP C45 DI 10.1016/S0304-419X(99)00010-4 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 205VA UT WOS:000080840200004 PM 10382538 ER PT J AU Tirnauer, JS O'Toole, E Berrueta, L Bierer, BE Pellman, D AF Tirnauer, JS O'Toole, E Berrueta, L Bierer, BE Pellman, D TI Yeast Bim1p promotes the G1-specific dynamics of microtubules SO JOURNAL OF CELL BIOLOGY LA English DT Article DE cell cycle; cell polarity; microtubule-associated proteins; microtubules; Saccharomyces cerevisiae ID CELL-CYCLE REGULATION; SACCHAROMYCES-CEREVISIAE; MITOTIC SPINDLE; BUDDING YEAST; NUCLEAR MIGRATION; BINDING PROTEIN; XENOPUS EGGS; BETA-TUBULIN; PLUS-END; KINESIN AB Microtubule dynamics vary during the cell cycle, and microtubules appear to be more dynamic in vivo than in vitro, Proteins that promote dynamic instability are therefore central to microtubule behavior in living cells. Here, we report that a yeast protein of the highly conserved EB1 family, Bim1p, promotes cytoplasmic microtubule dynamics specifically during G1. During G1, microtubules in cells lacking BIM1 showed reduced dynamicity due to a slower shrinkage rate, fewer rescues and catastrophes, and more time spent in an attenuated/paused state. Human EB1 was identified as an interacting partner for the adenomatous polyposis coli (APC) tumor suppressor protein. Like human EB1, Bim1p localizes to dots at the distal ends of cytoplasmic microtubules. This localization, together with data from electron microscopy and a synthetic interaction with the gene encoding the kinesin Kar3p, suggests that Bim1p acts at the microtubule plus end. Our in vivo data provide evidence of a cell cycle-specific microtubule-binding protein that promotes microtubule dynamicity. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Boulder Lab 3D Fine Struct, Boulder, CO 80309 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Rm M621A,44 Binney St, Boston, MA 02115 USA. OI Berrueta, Lisbeth/0000-0002-5674-6448 FU NCRR NIH HHS [P41 RR000592, RR00592]; NIDDK NIH HHS [KO8 DK02578]; NIGMS NIH HHS [GM55772] NR 59 TC 186 Z9 186 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 31 PY 1999 VL 145 IS 5 BP 993 EP 1007 DI 10.1083/jcb.145.5.993 PG 15 WC Cell Biology SC Cell Biology GA 203ZH UT WOS:000080738100008 PM 10352017 ER PT J AU Horner, MD Harvey, RT Denier, CA AF Horner, MD Harvey, RT Denier, CA TI Self-report and objective measures of cognitive deficit in patients entering substance abuse treatment SO PSYCHIATRY RESEARCH LA English DT Article DE neuropsychology; cognition; substance-related disorders; alcoholism; cocaine ID SEVERE HEAD-INJURY; NEUROPSYCHOLOGICAL PERFORMANCE; POLYDRUG USERS; COCAINE ABUSERS; ALCOHOLICS; UNAWARENESS; IMPAIRMENT; MEMORY; BRAIN AB The relationship between self-reported cognitive deficits and objectively measured cognitive performance was examined in 86 patients entering substance abuse treatment. Self-ratings of cognitive impairment were strongly correlated with indices of depression and vulnerability to stress, but not with objective cognitive performance. Confirming the lack of relationship between self-report and objective cognitive measures, cognitive performance did not differ between patients at the extremes of the cognitive-complaint distribution; and cognitively impaired patients did not differ from cognitively intact patients in their self-ratings of impairment. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Primary Care Serv, Charleston, SC 29401 USA. RP Horner, MD (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. NR 42 TC 22 Z9 22 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 31 PY 1999 VL 86 IS 2 BP 155 EP 161 DI 10.1016/S0165-1781(99)00031-1 PG 7 WC Psychiatry SC Psychiatry GA 207ZX UT WOS:000080966700007 PM 10397417 ER PT J AU Mann, DL AF Mann, DL TI Inflammatory mediators in heart failure: homogeneity through heterogeneity SO LANCET LA English DT Editorial Material ID TUMOR-NECROSIS-FACTOR; CARDIOMYOPATHY; EXPRESSION C1 Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Mann, DL (reprint author), Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 6 TC 17 Z9 17 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 MAY 29 PY 1999 VL 353 IS 9167 BP 1812 EP 1813 DI 10.1016/S0140-6736(99)90069-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 202TG UT WOS:000080667800002 PM 10359399 ER PT J AU Bradley, KA Merrill, JO AF Bradley, KA Merrill, JO TI "Doctor, is wine good for my heart?" SO LANCET LA English DT Editorial Material ID ALCOHOL-CONSUMPTION; DRINKING; WOMEN; AUDIT; RISK C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev & Primary & Specialty Med Car, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev & Primary & Specialty Med Car, Seattle, WA 98108 USA. NR 9 TC 5 Z9 5 U1 1 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 29 PY 1999 VL 353 IS 9167 BP 1815 EP 1816 DI 10.1016/S0140-6736(99)90188-5 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 202TG UT WOS:000080667800005 PM 10359402 ER PT J AU Lieberman, J Trimble, LA Friedman, RS Lisziewicz, J Lori, F Shankar, P Jessen, H AF Lieberman, J Trimble, LA Friedman, RS Lisziewicz, J Lori, F Shankar, P Jessen, H TI Expansion of CD57 and CD62L(-)CD45RA(+) CD8 T lymphocytes correlates with reduced viral plasma RNA after primary HIV infection SO AIDS LA English DT Article DE CD8 T cells; CD57; CD38; human immunodeficiency virus; primary infection ID IMMUNODEFICIENCY-VIRUS TYPE-1; HLA-DR; CELLS; ACTIVATION; ANTIGEN; AIDS; DISEASE; VIREMIA; CD38; PROGRESSION AB Objective: CD8 T cells, expressing cell surface molecules distinct from those on resting and naive T cells, are increased in HIV infection. The association of increased CD38 and human leukocyte antigen DR (HLA-DR) CD8 T cells with poor prognosis has suggested that activated CD8 T cells may aggravate HIV infection. We examined whether other immunological parameters might influence the viral setpoint. Design: Peripheral T cells from nine untreated patients, obtained after primary HIV infection when plasma HIV had stabilized, were examined for proteins expressed in activated versus resting, memory versus naive, and cytolytic versus non-cytolytic T cells. Methods: The proportion of CD8 T cells that stain for CD38 and HLA-DR, CD28 and CD57 was compared with plasma viraemia and CD4 cell count. These parameters were also compared with the proportion of CD4 and CD8 T cells that express CD62L and CD45RA, present on naive cells and down-modulated in memory cells. Internal staining for the cytotoxic protein granzyme A was also examined. Results: An increase in CD38 and CD38 HLA-DR CD8 T cells correlated with increased plasma viral RNA (P < 0.00002, P < 0.03, respectively). An increase in CD8 T cells expressing granzyme A was associated with lower CD4 cell counts (P < 0.04). However, the expansion of CD57 and CD62L(-)CD45RA(+) CD8 T cells was associated with a lower viral setpoint (P < 0.01, P < 0.02, respectively). Conclusion: Phenotypically defined activated CD8 T cells may have different functions in HIV infection. Activated CD8 T cells that are CD57 or CD62L(-)CD45RA(+) may be beneficial, because their expansion in untreated patients correlates with a reduced viral setpoint after primary infection. (C) 1999 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Georgetown Univ, Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Jessen Praxis, D-10777 Berlin, Germany. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI42519, AI45406] NR 52 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 28 PY 1999 VL 13 IS 8 BP 891 EP 899 DI 10.1097/00002030-199905280-00004 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 199VG UT WOS:000080504300004 PM 10371169 ER PT J AU Hemler, ME AF Hemler, ME TI Dystroglycan versatility SO CELL LA English DT Review ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; ALPHA-DYSTROGLYCAN; RECEPTOR; MEMBRANE; LAMININ-1; PROTEIN; AGRIN C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 17 TC 55 Z9 58 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 28 PY 1999 VL 97 IS 5 BP 543 EP 546 DI 10.1016/S0092-8674(00)80764-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 202VD UT WOS:000080672100002 PM 10367882 ER PT J AU Harkin, DP Bean, JM Miklos, D Song, YH Truong, VB Englert, C Christians, FC Ellisen, LW Maheswaran, S Oliner, JD Haber, DA AF Harkin, DP Bean, JM Miklos, D Song, YH Truong, VB Englert, C Christians, FC Ellisen, LW Maheswaran, S Oliner, JD Haber, DA TI Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1 SO CELL LA English DT Article ID INTERACT IN-VIVO; CELL-CYCLE; DNA-DAMAGE; BREAST-CANCER; TRANSCRIPTIONAL ACTIVATION; MAMMALIAN-CELLS; GENE-EXPRESSION; PROTEIN; P53; PHOSPHORYLATION AB The breast cancer susceptibility gene BRCA1 encodes a protein implicated in the cellular response to DNA damage, with postulated roles in homologous recombination as well as transcriptional regulation. To identify downstream target genes, we established cell lines with tightly regulated inducible expression of BRCA1. High-density oligonucleotide arrays were used to analyze gene expression profiles at various times following BRCA1 induction. A major BRCA1 target is the DNA damage-responsive gene GADD45. Induction of BRCA1 triggers apoptosis through activation of c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK), a signaling pathway potentially linked to GADD45 gene family members. The p53-independent induction of GADD45 by BRCA1 and its activation of JNK/SAPK suggest a pathway for BRCA1-induced apoptosis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA58596] NR 44 TC 450 Z9 461 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 28 PY 1999 VL 97 IS 5 BP 575 EP 586 DI 10.1016/S0092-8674(00)80769-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 202VD UT WOS:000080672100007 PM 10367887 ER PT J AU Osterlund, T Beussman, DJ Julenius, K Poon, PH Linse, S Shabanowitz, J Hunt, DF Schotz, MC Derewenda, ZS Holm, C AF Osterlund, T Beussman, DJ Julenius, K Poon, PH Linse, S Shabanowitz, J Hunt, DF Schotz, MC Derewenda, ZS Holm, C TI Domain identification of hormone-sensitive lipase by circular dichroism and fluorescence spectroscopy, limited proteolysis, and mass spectrometry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTROPHORESIS; SEPARATION; CHARACTER; PROTEIN AB Structure-function relationship analyses of hormone-sensitive lipase (HSL) have suggested that this metabolically important enzyme consists of several functional and at least two structural domains (Osterlund, T., Danielsson, B., Degerman, E., Contreras, J. A., Edgren, G., Davis, R. C., Schotz, M. C., and Helm, C. (1996) Bio-chem. J. 319, 411-420; Contreras, J. A., Karlsson, M., Osterlund, T., Laurell, H., Svensson, A, and Helm, C. (1996) J. Biol. Chem. 271, 31426-31430). To analyze the structural domain composition of HSL in more detail, we applied biophysical methods. Denaturation of HSL was followed by circular dichroism measurements and fluorescence spectroscopy, revealing that the unfolding of HSL is a two-step event. Using limited proteolysis in combination with mass spectrometry, several proteolytic fragments of HSL were identified, including one corresponding exactly to the proposed N-terminal domain. Major cleavage sites were found in the predicted hinge region between the two domains and in the regulatory module of the C-terminal, catalytic domain. Analyses of a hinge region cleavage mutant and calculations of the hydropathic pattern of HSL further suggest that the hinge region and regulatory module are exposed parts of HSL. Together, these data support our previous hypothesis that HSL consists of two major structural domains, encoded by exons 1-4 and 5-9, respectively, of which the latter contains an exposed regulatory module outside the catalytic alpha/beta-hydrolase fold core. C1 Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden. Univ Lund, Dept Phys Chem 2, S-22100 Lund, Sweden. Univ Virginia, Dept Chem, Charlottesville, VA 22906 USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22906 USA. Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. RP Holm, C (reprint author), Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, S-22100 Lund, Sweden. RI Hunt, Donald/I-6936-2012; OI Hunt, Donald/0000-0003-2815-6368; Linse, Sara/0000-0001-9629-7109 NR 19 TC 24 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 28 PY 1999 VL 274 IS 22 BP 15382 EP 15388 DI 10.1074/jbc.274.22.15382 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 200VE UT WOS:000080560100014 PM 10336425 ER PT J AU Silverton, SF Adebanjo, OA Moonga, BS Awumey, EM Malinski, T Zaidi, M AF Silverton, SF Adebanjo, OA Moonga, BS Awumey, EM Malinski, T Zaidi, M TI Direct microsensor measurement of nitric oxide production by the osteoclast SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXTRACELLULAR CA2+; RAT OSTEOCLASTS; IN-SITU; CELLS; SUPEROXIDE; SYNTHASES; CALCIUM; RELEASE; BONE AB Nitric oxide (NO) triggers marked osteoclast retraction which closely resembles that due to Ca2+, The effect of Ca2+ has been attributed to a stimulated release of NO. Here, we show for the first time, by direct measurement with a microsensor, that osteoclasts do indeed produce NO and that this production is enhanced by a high Ca2+. We also show that the Ca2+ ionophore, A23187, mimics the latter. Furthermore, osteoclasts on dentine produce more NO than osteoclasts on glass and NO release from dentine-plated osteoclasts is much less sensitive to stimulation by Ca2+, Finally, the microsomal Ca2+ store-depleting agent, thapsigargin, attenuates NO release only from osteoclasts on glass, suggesting that stored Ca2+ has the dominant effect in modulating NO release from non-resorbing cells. NO is a powerful inhibitor of bone resorption: a direct demonstration of its production is therefore strong evidence for a role in modulating osteoclast function. (C) 1999 Academic Press. C1 Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Dept Med, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Philadelphia, PA USA. Oakland Univ, Dept Chem, Rochester, MI 48309 USA. RP Silverton, SF (reprint author), Univ Penn, Sch Dent Med, Philadelphia, PA 19104 USA. FU NIAMS NIH HHS [R01-AR20248] NR 24 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 27 PY 1999 VL 259 IS 1 BP 73 EP 77 DI 10.1006/bbrc.1999.0703 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 201KG UT WOS:000080593500013 PM 10334918 ER PT J AU Goldmann, WH Teodoridis, JM Sharma, CP Hu, B Isenberg, G AF Goldmann, WH Teodoridis, JM Sharma, CP Hu, B Isenberg, G TI Fragments from actin binding protein (ABP-280; filamin) insert into reconstituted lipid layers SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALPHA-ACTININ; CYTOSKELETAL PROTEINS; CYTOPLASMIC DOMAINS; TALIN; IDENTIFICATION; MEMBRANES AB Previous computer analyses suggested two possible lipid binding sites, residues 49-71 and 131-155, of the primary amino acid sequence on ABP-280 (filamin), which could facilitate membrane attachment/insertion. We expressed these regions as fusion proteins with schistosomal GST and investigated their interaction with mixtures of zwitterionic (dimyristoyl-L-alpha-phosphatidylcholine, DMPC) and anionic (dimyristoyl-L-alpha-phosphatidylglycerol, DMPG) phospholipids in reconstituted lipid bilayers by differential scanning calorimetry (DSC), Using vesicles of mixed DMPC/ DMPG with increasing fusion protein concentrations, we established in calorimetric assays a decrease of the main chain transition enthalpy, Delta H, and a shift in chain melting temperature. This is indicative of the insertion of these fragments into the hydrophobic region of lipid membranes. We confirmed these findings by the film balance technique using lipid monolayers (DMPG). The binding judged from both methods was of moderate affinity, (C) 1999 Academic Press. C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Charlestown, MA USA. Tech Univ Munich, Dept Biophys E22, D-8046 Garching, Germany. RP Goldmann, WH (reprint author), Childrens Hosp, Dept Pathol, 320 Longwood Ave,Enders 10, Boston, MA 02115 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 32 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 27 PY 1999 VL 259 IS 1 BP 108 EP 112 DI 10.1006/bbrc.1999.0735 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 201KG UT WOS:000080593500019 PM 10334924 ER PT J AU Trimble, LA Xu, Z Lieberman, J AF Trimble, LA Xu, Z Lieberman, J TI Clonal expansion of antigen-specific CD8+cytotoxic T lymphocytes is regulated by late exposure to serum to prevent apoptosis SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CTL; clonal expansion; apoptosis; cytotoxicity ID ACTIVATED KILLER CELLS; FLOW-CYTOMETRY; FREE MEDIA; GENERATION; LIGAND; VIRUS; HELP; FAS; COSTIMULATION; INDIVIDUALS AB Although serum-free media have been used to expand lymphokine-activated killer cells, antigen-specific CD8 T cell cytotoxicity does not develop in vitro in the absence of serum. The immunodominant V(beta)17 response to an influenza A matrix protein epitope restricted by HLA A2.1 was used to study the serum requirement for CTL activation. Serum acts directly on T cells and not indirectly by activating APCs. In the absence of serum, the initial steps of T cell activation, including expression of CD69 and CD25, are unimpaired and some antigen-specific cytotoxicity may be generated in the first few days after stimulation. However, expression of late activation markers, such as HLA-DR and CD38, and clonal expansion of class I-restricted antigen-specific CTL does not occur if CTL are not exposed to serum within 4 days of antigen exposure. The antigen-specific CTL, but not unstimulated bystander T cells, undergo apoptosis if they are not exposed to serum within a few days of activation. Apoptosis of TCR-activated CTL does not appear to be Fas-mediated since it is not blocked by inhibiting the Fas pathway. Therefore, late exposure to an unidentified serum protein regulates the clonal expansion of TCR-activated CD8 CTL. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI36611] NR 44 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 27 PY 1999 VL 225 IS 1-2 BP 39 EP 52 DI 10.1016/S0022-1759(99)00026-5 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 199XX UT WOS:000080510300004 PM 10365780 ER PT J AU Wang, YQ He, HY Zigler, JS Iwata, T Ibaraki, N Reddy, VN Carper, D AF Wang, YQ He, HY Zigler, JS Iwata, T Ibaraki, N Reddy, VN Carper, D TI bFGF suppresses serum-deprivation-induced apoptosis in a human lens epithelial cell line SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE apoptosis; bcl-2; bFGF; lens; serum deprivation ID FIBROBLAST GROWTH-FACTOR; INTERNUCLEOSOMAL FRAGMENTATION; MOUSE LENS; BASIC FGF; C-MYC; BCL-2; EXPRESSION; DEATH; DIFFERENTIATION; DNA AB There is increasing evidence that basic fibroblast growth factor (bFGF) plays an important role in cell proliferation, differentiation, and survival in various systems. In the eye, although a truncated, dominant negative bFGF receptor in transgenic mice induced defective lens development and caused lens fiber cells to display characteristics of apoptosis, there is little direct evidence of the effect of bFGF on lens epithelial cell apoptosis. Our study examines the effects of bFGF on programmed cell death induced by serum deprivation using a human lens epithelial cell line, Cells supplemented with 20% fetal bovine serum were used as normal controls. Over a period of 7 days, the addition of 100 ng/ml bFGF effectively suppressed serum-deprived apoptosis. The expression of gamma-crystallin and major intrinsic protein, which are markers of lens cell differentiation, was not detected, Also there was no significant difference in cell proliferation between serum-deprived cells with or without bFGF. ICE (caspase-1) was expressed under both the conditions, but the level of expression between the two groups was not substantially different, bcl-2 and c-myc were upregulated only in bFGF-treated cells. Thus we speculate that the inhibitory effect of bFGF on apoptosis is through the upregulation of the inhibitor of apoptosis, instead of downregulation of the initiator. This effect appears to be independent of lens cell differentiation and proliferation, (C) 1999 Academic Press. C1 NEI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Sch Med, Kellogg Eye Ctr, Ann Arbor, MI 48105 USA. Nippon Med Sch, Dept Ophthalmol, Tokyo 113, Japan. RP Carper, D (reprint author), NEI, NIH, Bldg 6,Room 232,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 26 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 1999 VL 249 IS 1 BP 123 EP 130 DI 10.1006/excr.1999.4450 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 201LE UT WOS:000080595600013 PM 10328960 ER PT J AU Cheong, KH Zacchetti, D Schneeberger, EE Simons, K AF Cheong, KH Zacchetti, D Schneeberger, EE Simons, K TI VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; GPI-ANCHORED PROTEINS; GLYCOLIPID-ENRICHED MEMBRANES; PLASMA-MEMBRANE; EPITHELIAL-CELLS; GOLGI-NETWORK; BIOSYNTHETIC TRANSPORT; ANNEXIN XIIIB; CHOLESTEROL; VESICLES AB Apical proteins are sorted and delivered from the trans-Golgi network to the plasma membrane by a mechanism involving sphingolipid-cholesterol rafts. In this paper, we report the effects of changing the levels of VIP17/MAL, a tetraspan membrane protein localized to post-Golgi transport containers and the apical cell surface in MDCK cells, Overexpression of VIP17/MAL disturbed the morphology of the MDCK cell layers by increasing apical delivery and seemingly expanding the apical cell surface domains. On the other hand, expression of antisense RNA directed against VIP17/MAL caused accumulation in the Golgi and/or im paired apical transport of different apical protein markers, i,e,, influenza virus hemagglutinin, the secretory protein clusterin (gp80), the transmembrane protein gp114, and a glycosylphosphatidylinositol-anchored protein, However, antisense RNA expression did not affect the distribution of E-cadherin to the basolateral surface. Because VIP17/MAL associates with sphingolipid-cholesterol rafts, these data provide functional evidence that this protein is involved in apical transport and might be a component of the machinery clustering lipid rafts with apical cargo to form apical transport carriers. C1 European Mol Biol Lab, Cell Biol & Biophys Programme, D-69012 Heidelberg, Germany. Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Simons, K (reprint author), European Mol Biol Lab, Cell Biol & Biophys Programme, D-69012 Heidelberg, Germany. OI Zacchetti, Daniele/0000-0003-2724-7559 NR 54 TC 155 Z9 158 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 25 PY 1999 VL 96 IS 11 BP 6241 EP 6248 DI 10.1073/pnas.96.11.6241 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200ER UT WOS:000080527100061 PM 10339572 ER PT J AU Triggs-Raine, B Salo, TJ Zhang, H Wicklow, BA Natowicz, MR AF Triggs-Raine, B Salo, TJ Zhang, H Wicklow, BA Natowicz, MR TI Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; HUMAN SPERM; PURIFICATION; ALIGNMENT; SEQUENCE; ENZYMES; PH-20; LOCUS AB Hyaluronan (HA), a large glycosaminoglycan abundant in the extracellular matrix, is important in cell migration during embryonic development, cellular proliferation, and differentiation and has a structural role in connective tissues. The turnover of HA requires endoglycosidic breakdown by lysosomal hyaluronidase, and a congenital deficiency of hyaluronidase has been thought to be incompatible with life. However, a patient with a deficiency of serum hyaluronidase, now designated as mucopolysaccharidosis IX, was recently described. This patient had a surprisingly mild clinical phenotype, including notable periarticular soft tissue masses, mild short stature, an absence of neurological or visceral involvement, and histological and ultrastructural evidence of a lysosomal storage disease. To determine the molecular basis of mucopolysaccharidosis IX, we analyzed two candidate genes tandemly distributed on human chromosome 3p21.3 and encoding proteins with homology to a sperm protein with hyaluronidase activity. These genes, HYAL1 and HYAL2, encode two distinct lysosomal hyaluronidases with different substrate specificities. We identified two mutations in the HYAL1 alleles of the patient, a 1412G --> A mutation that introduces a nonconservative amino acid substitution (Glu268Lys) in a putative active site residue and a complex intragenic rearrangement, 1361de137ins14, that results in a premature termination codon. We further show that these two hyaluronidase genes, as well as a third recently discovered adjacent hyaluronidase gene, HYAL3, have markedly different tissue expression patterns, consistent with differing roles in HA metabolism. These data provide an explanation for the unexpectedly mild phenotype in mucopolysaccharidosis IX and predict the existence of other hyaluronidase deficiency disorders. C1 Univ Manitoba, Dept Biochem & Mol Biol, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Human Genet, Winnipeg, MB R3E 0W3, Canada. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Boston, MA 02254 USA. Massachusetts Gen Hosp, Boston, MA 02254 USA. RP Univ Manitoba, Dept Biochem & Mol Biol, 770 Bannatyne Ave, Winnipeg, MB R3E 0W3, Canada. EM traine@ms.umanitoba.ca OI Triggs-Raine, Barbara/0000-0003-4719-6779 NR 24 TC 104 Z9 106 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 25 PY 1999 VL 96 IS 11 BP 6296 EP 6300 DI 10.1073/pnas.96.11.6296 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200ER UT WOS:000080527100070 PM 10339581 ER PT J AU Kim, E Arnould, T Sellin, L Benzing, T Comella, N Kocher, O Tsiokas, L Sukhatme, VP Walz, G AF Kim, E Arnould, T Sellin, L Benzing, T Comella, N Kocher, O Tsiokas, L Sukhatme, VP Walz, G TI Interaction between RGS7 and polycystin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein-protein interaction; yeast two-hybrid system; polycystic kidney disease ID GTPASE-ACTIVATING PROTEIN; HETEROTRIMERIC G-PROTEINS; ALPHA-SUBUNITS; TRANSITION-STATE; MAMMALIAN-CELLS; FAMILY MEMBERS; KIDNEY-DISEASE; GAIP; DOMAIN; YEAST AB Regulators of G protein signaling (RGS) proteins accelerate the intrinsic GTPase activity of certain G alpha subunits and thereby modulate a number of G protein-dependent signaling cascades, Currently, little is known about the regulation of RGS proteins themselves, We identified a short-lived RGS protein, RGS7, that is rapidly degraded through the proteasome pathway. The degradation of RGS7 is inhibited by interaction with a C-terminal domain of polycystin, the protein encoded by PKD1, a gene involved in autosomal-dominant polycystic kidney disease. Furthermore, membranous expression of C-terminal polycystin relocalized RGS7. Our results indicate that rapid degradation and interaction with integral membrane proteins are potential means of regulating RGS proteins. C1 Harvard Univ, Div Renal, Beth Israel Deaconess Med Ctr, Sch Med,Dept Med, Boston, MA 02215 USA. Harvard Univ, Div Renal, Beth Israel Deaconess Med Ctr, Sch Med,Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Walz, G (reprint author), Harvard Univ, Div Renal, Beth Israel Deaconess Med Ctr, Sch Med,Dept Med, DANA 517,330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01-DK51060, R01 DK52897]; NIMH NIH HHS [MH01147] NR 46 TC 129 Z9 132 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 25 PY 1999 VL 96 IS 11 BP 6371 EP 6376 DI 10.1073/pnas.96.11.6371 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 200ER UT WOS:000080527100083 PM 10339594 ER PT J AU Wipf, JE Lipsky, BA Hirschmann, JV Boyko, EJ Takasugi, J Peugeot, RL Davis, CL AF Wipf, JE Lipsky, BA Hirschmann, JV Boyko, EJ Takasugi, J Peugeot, RL Davis, CL TI Diagnosing pneumonia by physical examination - Relevant or relic? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CLINICAL-PREDICTION; LUNG SOUNDS; CHEST; AUSCULTATION; SIGNS AB Background: The reliability of chest physical examination and the degree of agreement among examiners in diagnosing pneumonia based on these findings are largely unknown. Objectives: To determine the accuracy of various physical examination maneuvers in diagnosing pneumonia and to compare the interobserver reliability of the maneuvers among 3 examiners. Methods: Fifty-two male patients presenting to the emergency department of a university-affiliated Veterans Affairs medical center with symptoms of lower respiratory tract infection (cough and change in sputum) were prospectively examined. A comprehensive lung physical examination was performed sequentially by 3 physicians who were blind to clinical history, laboratory findings, and x-ray results. Examination findings by lung site and whether the examiner diagnosed pneumonia were recorded on a standard form. Chest x-ray films were read by a radiologist. Results: Twenty-four patients had pneumonia confirmed by chest x-ray films. Twenty-eight patients did not have pneumonia. Abnormal lung sounds were common in both groups; the most frequently detected were rales in the upright seated position and bronchial breath sounds. Relatively high agreement among examiners (kappa approximate to 0.5) occurred for rales in the lateral decubitus position and for wheezes. The 3 examiners' clinical diagnosis of pneumonia had a sensitivity of 47% to 69% and specificity of 58% to 75%. Conclusions: The degree of interobserver agreement was highly variable for different physical examination findings. The most valuable examination maneuvers in detecting pneumonia were unilateral rales and rales in the lateral decubitus position. The traditional chest physical examination is not sufficiently accurate on its own to confirm or exclude the diagnosis of pneumonia. C1 Vet Affairs Puget Sound Hlth Care Syst, Med Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Serv Radiol, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Radiol, Seattle, WA USA. RP Wipf, JE (reprint author), Univ Washington, Dept Vet Affairs, Puget Sound Hlth Care Syst, GIMC,Dept Med, 111M,1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 15 TC 114 Z9 119 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 24 PY 1999 VL 159 IS 10 BP 1082 EP 1087 DI 10.1001/archinte.159.10.1082 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 196GL UT WOS:000080300600008 PM 10335685 ER PT J AU Brown, SP Masland, RH AF Brown, SP Masland, RH TI Costratification of a population of bipolar cells with the direction-selective circuitry of the rabbit retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CD15; cholinergic amacrine cell; ganglion cell; cell adhesion molecule; inner plexiform layer; immunoreactivity; PKC ID STARBURST AMACRINE CELLS; GANGLION-CELLS; MAMMALIAN RETINA; RECEPTIVE-FIELDS; RAT RETINA; CAT RETINA; ON-CENTER; STRATIFICATION; ORGANIZATION; MORPHOLOGY AB We have stained a new population of bipolar cells in rabbit retina by using antibodies against the carbohydrate epitope, CD15. The CD15-positive bipolar cells comprise 6-8% of the total cone bipolar cells in peripheral retina. Their axonal and dendritic arbors are similar in size and range from 15 to 50 mu m in diameter. The axonal arbors are narrowly stratified in sublamina b of the inner plexiform layer. Double label experiments using an antibody against the calcium binding protein, calbindin, or an antibody against protein kinase C, demonstrate that the CD15-positive bipolar cells are a separate population from the previously identified calbindin-positive cone bipolar cells and the rod bipolar cells. Labeling the processes of starburst amacrine cells with antibodies against choline acetyltransferase showed that the CD15-positive bipolar cells stratify within and slightly more distally to the processes of the ON-starburst amacrine cells. Confocal images of retinal wholemounts showed that the axons of the CD15-positive bipolar cells follow the pattern of the ON-starburst cells' processes. Axonal varicosities of the CD15-positive bipolar cells penetrate the bundles formed by the processes of the ON-starburst cells. This finding suggests that the CD15-positive bipolar cell provides input to the ON-starburst amacrine cells and/or the ON-plexus of the ON-OFF direction-selective ganglion cells. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Brown, SP (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. RI Brown, Solange/H-1615-2012 NR 49 TC 47 Z9 47 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 24 PY 1999 VL 408 IS 1 BP 97 EP 106 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 190UK UT WOS:000079983500007 PM 10331582 ER PT J AU Sykes, M Preffer, F McAfee, S Saidman, SL Weymouth, D Andrews, DM Colby, C Sackstein, R Sachs, DH Spitzer, TR AF Sykes, M Preffer, F McAfee, S Saidman, SL Weymouth, D Andrews, DM Colby, C Sackstein, R Sachs, DH Spitzer, TR TI Mixed lymphohaemopoietic chimerism and graft-versus-lymphoma effects after non-myeloablative therapy and HLA-mismatched bone-marrow transplantation SO LANCET LA English DT Article ID TOTAL-BODY IRRADIATION; NON-HODGKINS-LYMPHOMA; HOST DISEASE; CELL TRANSPLANTATION; LEUKEMIA; AMPLIFICATION; CHEMOTHERAPY; ENGRAFTMENT; TOLERANCE; MICE AB Background. HLA-mismatched donor bone-marrow transplantation after standard myeloablative conditioning therapy for haematological malignant disorders has been limited by severe graft-versus-host disease (GVHD) and graft failure. We tested a new approach to find out whether lymphohaemopoietic graft-versus-host reactions could occur without excessive GVHD in mixed haemopoietic chimeras produced across HLA barriers with non-myeloablative conditioning. Methods. Five patients with refractory non-Hodgkin lymphoma underwent bone-marrow transplantation from haploidentical related donors sharing at least one HLA A, B, or DR allele on the mismatched haplotype. Conditioning included cyclophosphamide and thymic irradiation before transplantation, and antithymocyte globulin before and after transplantation. The only other GVHD prophylaxis was cyclosporin. Findings. Four of five patients were evaluable and showed engraftment. Mixed haemopoietic chimerism was established, with a predominance of donor lymphoid tissue and varying degrees of myeloid chimerism. Two patients were in GVHD-free states of complete and partial clinical remission at 460 and 103 days after bone-marrow transplantation. Interpretation. Mixed chimerism can be induced in adult recipients of HLA-mismatched bone-marrow transplantation by a non-myeloablative conditioning regimen. The antilymphoma responses seen in two patients suggest that allogeneic bone-marrow transplantation without myeloablative conditioning might have potent immunotherapeutic benefits. C1 Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplantat Program, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA61587] NR 23 TC 293 Z9 301 U1 1 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 22 PY 1999 VL 353 IS 9166 BP 1755 EP 1759 DI 10.1016/S0140-6736(98)11135-2 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 202TF UT WOS:000080667700014 PM 10347989 ER PT J AU Lin, AE Herring, AH Amstutz, KS Westgate, MN Lacro, RV Al-Jufan, M Ryan, L Holmes, LB AF Lin, AE Herring, AH Amstutz, KS Westgate, MN Lacro, RV Al-Jufan, M Ryan, L Holmes, LB TI Cardiovascular malformations: Changes in prevalence and birth status, 1972-1990 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Teratology-Society CY JUN 25, 1997 CL PALM BEACH, FLORIDA SP Teratol Soc DE birth defects monitoring; cardiovascular malformations; congenital heart defects; fetal echocardiography; genetic epidemiology; malformation syndromes; prenatal detection; surveillance; ultrasonography ID CONGENITAL HEART-DISEASE; FETAL ECHOCARDIOGRAPHY; PRENATAL-DIAGNOSIS; NEWBORN-INFANTS; NATURAL-HISTORY; DEFECTS; POPULATION; TRENDS; ULTRASOUND; PROGRAM AB Through an ongoing hospital-based active malformation surveillance program, we identified cardiovascular malformations (CVMs) in 3.3 per 1,000 liveborn and stillborn infants, and fetuses from pregnancies terminated electively during a 15-year period. We excluded the children of mothers who had planned delivery elsewhere, but were transferred for care of anomalies that had been detected in prenatal screening, Birth status changed markedly during the study with a significant increase in elective terminations of fetuses with a CVM from 0 to 22% (P < 0.01 based on a test for trend). The proportion of liveborn infants with CVMs decreased from 90% to 73% (P < 0.01); the frequency of stillbirths did not change, During the study period, there was a significant increase in the prevalence of CVMs in all births (P < 0.01) and elective terminations (P < 0.01), The increase in liveborn prevalence was not statistically significant (P = 0.08), Stillborn prevalence was unchanged. The number of mothers having prenatal ultrasonography (P < 0.01 for trend) and amniocentesis (P < 0.01 for trend) increased steadily. There were significant increases in the pro-portion of mothers having any ultrasound examination (P < 0.01 for trend), the number of initial ultrasound examinations occurring in the second trimester (P < 0.01 for trend), and the proportion of mothers having amniocentesis (P < 0.01 for trend), There was a significant increasing trend in the proportion of mothers who were 35 years and older (10% in 1972-1974, 26% in 1988-1990, P < 0.01), This hospital-based active surveillance program suggests that more frequent elective terminations had a significant effect on overall birth prevalence of CVMs, This trend would not have been detected by most other surveillance systems which determine prevalence of common birth defects from birth certificates and other forms of administrative reporting, and exclude elective terminations of pregnancy, Am. J, Med, Genet. 84:102-110, 1999, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lin, AE (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,35 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA48061]; NIEHS NIH HHS [5T32 ES07142] NR 38 TC 34 Z9 34 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 21 PY 1999 VL 84 IS 2 BP 102 EP 110 DI 10.1002/(SICI)1096-8628(19990521)84:2<102::AID-AJMG4>3.0.CO;2-G PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 189AZ UT WOS:000079883100004 PM 10323733 ER PT J AU Yang, H Kawakubo, K Tache, Y AF Yang, H Kawakubo, K Tache, Y TI Kainic acid into the parapyramidal region protects against gastric injury by ethanol SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE kainic acid; gastric lesion; parapyramidal region ID THYROTROPIN-RELEASING-HORMONE; RAT AB Neurons in the parapyramidal region of the ventral medulla project to the dorsal vagal complex and intermediolateral column. Kainic acid (0.5-5.0 ng) microinjected unilaterally into the parapyramidal region reduced 45% ethanol-induced gastric lesions by 50-60% in urethane anesthetized rats. Microinjections at sites nearby, but outside of the parapyramidal region, had no effect. These results provide the first evidence that the activation of parapyramidal region neurons influences gastric function and suggests a possible role of this ventral medulla region in gastric regulation. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, CURE, Digest Dis Res Ctr,Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, W Los Angeles VA Med Ctr, CURE, Digest Dis Res Ctr,Dept Med,Div Digest Dis, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-33061, DK-50255, DK-30110] NR 7 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 21 PY 1999 VL 372 IS 3 BP R1 EP R3 DI 10.1016/S0014-2999(99)00241-1 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 204KB UT WOS:000080762500017 PM 10395029 ER PT J AU Hoffmann, JA Kafatos, FC Janeway, CA Ezekowitz, RAB AF Hoffmann, JA Kafatos, FC Janeway, CA Ezekowitz, RAB TI Phylogenetic perspectives in innate immunity SO SCIENCE LA English DT Review ID DROSOPHILA HOST-DEFENSE; MANNOSE-BINDING PROTEIN; MALARIA PARASITE DEVELOPMENT; RA-REACTIVE FACTOR; ANTIMICROBIAL PEPTIDES; ANOPHELES-GAMBIAE; SERINE-PROTEASE; HUMAN BETA-DEFENSIN-1; RECEPTOR FAMILY; CYSTIC-FIBROSIS AB The concept of innate immunity refers to the first-line host defense that serves to Limit infection in the early hours after exposure to microorganisms, Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity;in mammals appears to play a key role in stimulating the subsequent, clonal response of adaptive immunity. C1 CNRS, Inst Mol & Cellular Biol, F-67084 Strasbourg, France. European Mol Biol Lab, D-69012 Heidelberg, Germany. Yale Univ, Immunobiol Sect, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Hoffmann, JA (reprint author), CNRS, Inst Mol & Cellular Biol, F-67084 Strasbourg, France. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 109 TC 1688 Z9 1777 U1 12 U2 143 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 21 PY 1999 VL 284 IS 5418 BP 1313 EP 1318 DI 10.1126/science.284.5418.1313 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198NN UT WOS:000080430600042 PM 10334979 ER PT J AU Kingston, RE AF Kingston, RE TI A shared but complex bridge SO NATURE LA English DT Article ID RNA-POLYMERASE-II; MEDIATOR C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 11 TC 21 Z9 22 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 20 PY 1999 VL 399 IS 6733 BP 199 EP 200 DI 10.1038/20302 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198MF UT WOS:000080427400025 PM 10353236 ER PT J AU Kaelin, WG AF Kaelin, WG TI Cancer - Many vessels, faulty gene SO NATURE LA English DT Editorial Material ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; LINDAU; WITHDRAWAL; PROTEIN C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. NR 14 TC 34 Z9 34 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 20 PY 1999 VL 399 IS 6733 BP 203 EP 204 DI 10.1038/20309 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198MF UT WOS:000080427400027 PM 10353237 ER PT J AU Ona, VO Li, MW Vonsattel, JPG Andrews, LJ Khan, SQ Chung, WM Frey, AS Menon, AS Li, XJ Stieg, PE Yuan, JY Penney, JB Young, AB Cha, JHJ Friedlander, RM AF Ona, VO Li, MW Vonsattel, JPG Andrews, LJ Khan, SQ Chung, WM Frey, AS Menon, AS Li, XJ Stieg, PE Yuan, JY Penney, JB Young, AB Cha, JHJ Friedlander, RM TI Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease SO NATURE LA English DT Article ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; NEURONAL INTRANUCLEAR INCLUSIONS; TROPHIC FACTOR WITHDRAWAL; TRANSGENIC MICE; IL-1-BETA-CONVERTING ENZYME; POLYGLUTAMINE TRACT; CYSTEINE PROTEASE; FAMILY PROTEASES; CELL-DEATH; GENE AB Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex(1). The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M-r 350K)(2). The length of the CAG/polyglutamine repeat is inversely correlated with the age of disease onset. The molecular pathways mediating the neuropathology of Huntington's disease are poorly understood. Transgenic mice expressing exon 1 of the human huntingtin gene with an expanded CAG/polyglutamine repeat develop a progressive syndrome with many of the characteristics of human Huntington's disease(3). Here we demonstrate evidence of caspase-1 activation in the brains of mice and humans with the disease. In this transgenic mouse model of Huntington's disease, expression of a dominant-negative caspase-1 mutant extends survival and delays the appearance of neuronal inclusions, neurotransmitter receptor alterations and onset of symptoms, indicating that caspase-1 is important in the pathogenesis of the disease. In addition, we demonstrate that intracerebroventricular administration of a caspase inhibitor delays disease progression and mortality in the mouse model of Huntington's disease. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Neurol Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Genet, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Friedlander, RM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Neurol Serv, Boston, MA 02115 USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 30 TC 456 Z9 470 U1 2 U2 21 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 20 PY 1999 VL 399 IS 6733 BP 263 EP 267 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 198MF UT WOS:000080427400057 PM 10353249 ER PT J AU Lilly, CM Mark, EJ Shepard, JO Freed, LA AF Lilly, CM Mark, EJ Shepard, JO Freed, LA TI A 77-year-old man with hemoptysis and cardiovascular disease - Dissecting aortic aneurysm, with rupture into the epicardium, interatrial septum, right ventricular outflow tract, and lungs. Acute myocardial infarction of the right ventricular outflow tract. Severe coronary artery disease. Moderate cardiac and pulmonary amyloidosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AORTOBRONCHIAL FISTULA; MASSIVE HEMOPTYSIS; TUBERCULOSIS; DIAGNOSIS; REPAIR C1 Brigham & Womens Hosp, Med Intens Care Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Med Intens Care Unit, 75 Francis St, Boston, MA 02115 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 20 PY 1999 VL 340 IS 20 BP 1571 EP 1579 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 197HG UT WOS:000080358900009 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI Catheter-based treatment of aortic dissection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 TC 8 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 20 PY 1999 VL 340 IS 20 BP 1585 EP 1586 DI 10.1056/NEJM199905203402012 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 197HG UT WOS:000080358900012 PM 10332024 ER PT J AU Wen, Y Edelman, JL Kang, T Sachs, G AF Wen, Y Edelman, JL Kang, T Sachs, G TI Lipocortin V may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TYROSINE KINASE; ANNEXIN-V; PERMEABILITY FACTOR; 2-HYBRID SYSTEM; PHOSPHORYLATION; TRANSDUCTION; CELLS; VEGF; IDENTIFICATION; BINDING AB Binding of vascular endothelial growth factor (VEGF) to its receptor, VEGFR-2 (Flk-1/KDR), induces dimerization and activation of the tyrosine kinase domain of the receptor, resulting in autophosphorylation of cytoplasmic tyrosine residues used as docking sites for signaling proteins that relay the signals for cell proliferation, migration, and permeability enhancement. We explored the VEGF/ receptor signaling pathway by performing a two-hybrid screen of a rat lung cDNA library in yeast using the intracellular domain of rat VEGFR-2 as bait. Two clones encoding lipocortin V were isolated. Subsequent studies with the yeast two-hybrid assay showed that the complete intracellular domain of VEGFR-2 was required for the interaction. Coimmunoprecipitation of translated proteins confirmed the interaction between the VEGF receptor and lipocortin V, VEGF induced a rapid tyrosine phosphorylation of lipocortin V in human umbilical vein endothelial cells (HUVEC). Pretreatment of HUVEC with antisense oligodeoxyribonucleotide (ODN) for lipocortin V significantly inhibited VEGF-induced cell proliferation, which was accompanied by a decrease in protein synthesis and tyrosine phosphorylation of lipocortin V, Our results indicate that lipocortin V may function as a signaling protein for VEGFR-2 by directly interacting with the intracellular domain of the receptor and appears to be involved in regulation of vascular endothelial cell proliferation mediated by VEGFR-2. (C) 1999 Academic Press. C1 W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. Allergan, Irvine, CA 92713 USA. RP Sachs, G (reprint author), W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Dept Med, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK46917, DK41301, DK53462] NR 51 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 19 PY 1999 VL 258 IS 3 BP 713 EP 721 DI 10.1006/bbrc.1999.0678 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 201LK UT WOS:000080596100039 PM 10329451 ER PT J AU Swearingen, B Biller, BMK Barker, FG Katznelson, L Grinspoon, S Klibanski, A Zervas, NT AF Swearingen, B Biller, BMK Barker, FG Katznelson, L Grinspoon, S Klibanski, A Zervas, NT TI Long-term mortality after transsphenoidal surgery for Cushing disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MACROADENOMAS; MICROSURGERY AB Background: Untreated Cushing disease historically has a high mortality rate, but the long-term survival of patients with Cushing disease after transsphenoidal surgery has not been reported. Objective: To determine long-term mortality rate in patients who are treated for Cushing disease with current management techniques. Design: Retrospective case series. Setting: Tertiary care center. Patients: 161 patients (32 men and 129 women; mean age, 38 years) who were treated for Cushing disease between 1978 and 1996. Intervention: Transsphenoidal adenomectomy and as-needed adjunctive therapy. Measurement: Record review with follow-up interview. Results: The cure rate for patients with microadenomas who had no previous therapy was 90% (123 of 137). No perioperative deaths occurred (0 of 193 procedures [95% CI, 0.0% to 1.9%]). Follow-up data (mean, 8.7 years) were obtained for 99% of patients (159 of 161). Six patients died. The 5- and 10-year survival rates were 99% (CI, 97% to 100%) and 93% (CI, 88% to 99%), respectively. Survival was similar to that seen in an age- and sex-matched sample that was based on U.S. population data (standardized mortality ratio, 0.98 [CI, 0.44 to 2.2]; P > 0.2). Conclusion: Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Swearingen, B (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St, Boston, MA 02114 USA. NR 18 TC 140 Z9 140 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 MAY 18 PY 1999 VL 130 IS 10 BP 821 EP 824 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 196JJ UT WOS:000080305000004 PM 10366371 ER PT J AU Luo, Y Leszyk, J Qian, YD Gergely, J Tao, T AF Luo, Y Leszyk, J Qian, YD Gergely, J Tao, T TI Residues 48 and 82 at the N-terminal hydrophobic pocket of rabbit skeletal muscle troponin-C photo-cross-link to met121 of troponin-I SO BIOCHEMISTRY LA English DT Article ID CONFORMATIONAL TRANSITION; REGULATORY DOMAIN; PROTEOLYTIC FRAGMENTS; ANGSTROM RESOLUTION; INHIBITORY REGION; CRYSTAL-STRUCTURE; CONTRACTION; COMPLEX; CALCIUM; TROPOMYOSIN AB It has been proposed [Herzberg et al. (1986) J. Biol. Chem. 261, 2638-2644], and confirmed by structural studies [Gagne et al. (1995) Not. Struct. Biol. 2, 784-789], that the binding of Ca2+ to the triggering sites in troponin-C (TnC) causes the opening of the N-terminal hydrophobic pocket bound by the B, C, and D helices. This conformational change is believed to provide an additional binding site for troponin-I (TnI) and to lead to further events in the Ca2+ regulation process. To answer the question of which part of TnI interacts with this hydrophobic patch of TnC, we constructed two TnC mutants, each with a single cysteine, one at residue 48 between helices B and C and the other at residue 82 on the D helix. Each mutant was labeled with the photoactivatable cross-linker benzophenone-4-iodoacetamide, followed by reconstitution and UV irradiation. Studies were made in the binary complex composed of TnC and TnI, the ternary complex composed of TnC, TnI, and troponin-Tr (TnT), and the synthetic thin filament composed of troponin, tropomyosin, and F-actin. TnC-TnI photo-cross-linking was observed for both mutants and for all three types of complexes. Although no Ca2+ dependence in the photo-crosslinking was observed on the binary and ternary complexes, the extent of cross-linking was reduced in the absence vs the presence of Ca2+ in the thin filament. TnI Metl21, five residues from the C-terminus of the inhibitory region, was identified as the cross-linking site for both TnC mutants using microsequencing and mass spectrometry following proteolysis. These results, obtained with intact TnC TnI complexes, indicate that the TnT segment containing Met121 is in close contact with the N-terminal hydrophobic patch of TnC, and that in the thin filament the segment containing this residue moves away slightly from the hydrophobic patch in the absence of Ca2+, possibly triggering the translocation of the actin-binding region(s) of TnI toward actin. C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. Worcester Fdn Expt Biol Inc, Microsequencing Lab, Shrewsbury, MA 01545 USA. Univ Massachusetts, Sch Med, Dept Biochem, Shrewsbury, MA 01545 USA. RP Tao, T (reprint author), Boston Biomed Res Inst, Muscle Res Grp, 20 Staniford St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL5949]; NIAMS NIH HHS [AR21673] NR 38 TC 29 Z9 29 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 18 PY 1999 VL 38 IS 20 BP 6678 EP 6688 DI 10.1021/bi9824341 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 201KJ UT WOS:000080593700035 PM 10350487 ER PT J AU Holmvang, G Fry, S Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H AF Holmvang, G Fry, S Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H TI Relation between coronary "steel" and contractile function at rest in collateral-dependent myocardium of humans with ischemic heart disease SO CIRCULATION LA English DT Article DE myocardium; blood flow; ischemia; heart diseases; collateral circulation ID BLOOD-FLOW; ARTERY DISEASE; STENOSIS; DYSFUNCTION; ARTERIOGRAPHY; HIBERNATION; CIRCULATION; ADENOSINE; EXERCISE; INSIGHTS AB Background-We tested the hypothesis that rest asynergy in collateral-dependent myocardium correlates with coronary steal. Methods and Results-PET with [N-13]ammonia measured myocardial blood flow and flow reserve in 15 patients with symptomatic chronic ischemic heart disease. Coronary angiography assessed stenosis severity and collateral blood supply. Echocardiography or contrast ventriculography evaluated regional wall motion. Collateral-dependent segments with normal flow at rest and supplied by coronary vessels having less than or equal to 50% diameter stenosis were studied. Steal was defined as a decline in myocardial blood flow with adenosine greater than or equal to 0.15 mL.min(-1).g(-1) versus rest. Blood now at rest in asynergic, collateral-dependent segments with steal (1.15+/-0.35 mL.min(-1).g(-1)) exceeded (P<0.0001) that of asynergic segments without steal (0.81+/-0.24) and those with normal contraction (0.77+/-0.18). Although the flow reserve ratio of segments with normal contraction (1.8+/-0.8) exceeded that of asynergic ones with (0.5+/-0.1) or without (1.3+/-0.4) steal, overlap was great. Correlation between basal contraction and flow reserve ratio in collateral-dependent myocardium was significant but weak (r=0.45, P<0.001). However, segments demonstrating "steal" with adenosine manifested asynergy in 22 of 23 collateral-dependent segments versus 24 of 39 nonsteal segments (chi(2)=7.10, P<0.01). Conclusions-Although myocardial flow reserve in collateral-dependent segments with normal contraction exceeded that of asynergic segments, overlap was great. However, in patients with angina or congestive heart failure, left ventricular segments demonstrating steal with adenosine almost always exhibit asynergy at rest. Thus, coronary steal may play an important role in the pathogenesis of chronic contractile impairment at rest, whereas simple reduction of flow reserve may be less important in selected patients. C1 Harvard Univ, Cardiac Unit Vincent Burnham 3, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Cardiac Unit Vincent Burnham 3, Massachusetts Gen Hosp, Sch Med,Dept Med, Boston, MA 02114 USA. NR 28 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 18 PY 1999 VL 99 IS 19 BP 2510 EP 2516 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 195VF UT WOS:000080272300004 PM 10330381 ER PT J AU Wei, CC Meng, QC Palmer, R Hageman, GR Durand, J Bradley, WE Farrell, DM Hankes, GH Oparil, S Dell'Italia, LJ AF Wei, CC Meng, QC Palmer, R Hageman, GR Durand, J Bradley, WE Farrell, DM Hankes, GH Oparil, S Dell'Italia, LJ TI Evidence for angiotensin-converting enzyme- and chymase-mediated angiotensin II formation in the interstitial fluid space of the dog heart in vivo SO CIRCULATION LA English DT Article DE angiotensin; enzymes; ventricles; hypertrophy ID SUCTION BLISTER FLUID; FORMING PATHWAYS; GENERATION; ADENOSINE; PROTEINS; SYSTEM; TISSUE AB Background-We have previously demonstrated that angiotensin II (Ang II) levels in the interstitial fluid (ISF) space of the heart are higher than in the blood plasma and do not change after systemic infusion of Ang I. In this study, we assess the enzymatic mechanisms (chymase versus ACE) by which Ang II is generated in the ISF space of the dog heart in vivo. Methods and Results-Cardiac microdialysis probes were implanted in the left ventricular (LV) myocardium (3 to 4 probes per dog) of 12 anesthetized open-chest normal dogs. ISF Ang I and II levels were measured at baseline and during ISF infusion of Ang I (15 mu mol/L, n=12), Ang I+the ACE inhibitor captopril (cap) (2.5 mmol/L, n=4), Ang I+the chymase inhibitor chymostatin (chy) (1 mmol/L, n=4), and Ang I+cap+chy (n=4). ISF infusion of Ang I increased ISF Ang II levels 100-fold (P<0.01), whereas aortic and coronary sinus plasma Ang I and II levels were unaffected and were 100-fold lower than ISF levels. Compared with ISF infusion of Ang I alone, Ang I+cap (n=4) produced a greater reduction in ISF Ang II levels than did Ang I+chy (n=4) (71% versus 43%, P<0.01), whereas Ang I+cap+chy produced a 100% decrease in ISF Ang II levels. Conclusions-This study demonstrates for the first time a very high capacity for conversion of Ang I to Ang II mediated by both ACE and chymase in the ISF space of the dog heart in vivo. C1 Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Med,Hypertens & Vasc Biol Program, Div Cardiovasc Dis,Dept Physiol & Biophys, Birmingham, AL USA. Auburn Univ, Coll Vet Med, Auburn, AL 36849 USA. RP Dell'Italia, LJ (reprint author), Univ Alabama, Dept Med, Div Cardiol, 834 MCLM,1918 Univ Blvd, Birmingham, AL 35294 USA. FU NHLBI NIH HHS [R01-HL-54816, 2T32-HL-07457] NR 28 TC 56 Z9 61 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 18 PY 1999 VL 99 IS 19 BP 2583 EP 2589 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 195VF UT WOS:000080272300015 PM 10330392 ER PT J AU Shibata, MA Liu, ML Knudson, MC Shibata, E Yoshidome, K Bandey, T Korsmeyer, SJ Green, JE AF Shibata, MA Liu, ML Knudson, MC Shibata, E Yoshidome, K Bandey, T Korsmeyer, SJ Green, JE TI Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage SO EMBO JOURNAL LA English DT Article DE apoptosis; bax; cell death; mammary gland; transgenic mice; tumor progression ID PROGRAMMED CELL-DEATH; BCL-2 HOMOLOG BAK; IN-VIVO; IMMUNOHISTOCHEMICAL ANALYSIS; SUPPRESSOR P53; E1B 19K; GENE; EXPRESSION; PROTEIN; ADENOCARCINOMA AB The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax, C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax(+/-) genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax(+/-) or bax(-/-) mice compared with bax(+/+) mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma. C1 NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. SAIC, Frederick, MD USA. RP Green, JE (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NR 29 TC 93 Z9 94 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 17 PY 1999 VL 18 IS 10 BP 2692 EP 2701 DI 10.1093/emboj/18.10.2692 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 201KK UT WOS:000080593800003 PM 10329616 ER PT J AU De Sanctis, GT MacLean, JA Hamada, K Mehta, S Scott, JA Jiao, AP Yandava, CN Kobzik, L Wolyniec, WW Fabian, AJ Venugopal, CS Grasemann, H Huang, PL Drazen, JM AF De Sanctis, GT MacLean, JA Hamada, K Mehta, S Scott, JA Jiao, AP Yandava, CN Kobzik, L Wolyniec, WW Fabian, AJ Venugopal, CS Grasemann, H Huang, PL Drazen, JM TI Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE nitric oxide; allergen; mice; asthma; nitric oxide synthase ID DEFICIENT MICE; ALLERGIC MICE; PULMONARY EOSINOPHILIA; EXHALED AIR; RAT LUNG; RESPONSES; INDUCTION; HYPERREACTIVITY; CHALLENGE; CELL AB Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was signifcantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma. C1 Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Allergy & Clin Immunol, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. Univ Western Ontario, London Hlth Sci Ctr, Div Pulm, Dept Med, London, ON N6A 4G5, Canada. Univ Western Ontario, London Hlth Sci Ctr, Dept Pharmacol, London, ON N6A 4G5, Canada. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP De Sanctis, GT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, 75 Francis St, Boston, MA 02115 USA. RI Scott, Jeremy/D-2965-2009; Drazen, Jeffrey/E-5841-2012 OI Scott, Jeremy/0000-0002-7513-6768; FU NHLBI NIH HHS [P01 HL036110, HL36110, HL56383]; NIAID NIH HHS [AI01245]; NINDS NIH HHS [R01 NS033335] NR 59 TC 167 Z9 174 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 17 PY 1999 VL 189 IS 10 BP 1621 EP 1629 DI 10.1084/jem.189.10.1621 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198TT UT WOS:000080440900011 PM 10330441 ER PT J AU Thongphasuk, J Oberley, LW Oberley, TD AF Thongphasuk, J Oberley, LW Oberley, TD TI Induction of superoxide dismutase and cytotoxicity by manganese in human breast cancer cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE manganese; MnSOD; antioxidants; 2-deoxy-D-glucose; pyruvate; tiron ID MNSOD GENE-EXPRESSION; TUMOR NECROSIS FACTOR; NF-KAPPA-B; ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; ENDOTHELIAL-CELLS; DEFICIENT MICE; MESSENGER-RNA; TNF-ALPHA; MITOCHONDRIAL AB MnCl2 induced manganese-containing superoxide dismutase (MnSOD) expression (mRNA, immunoreactive protein, and enzyme activity) in human breast cancer Hs578T cells. The induction of MnSOD immunoreactive protein in Hs578T cells was inhibited by tiron (a metal chelator and superoxide scavenger), pyruvate (a hydrogen peroxide scavenger), or 2-deoxy-D-glucose (DG, an inhibitor of glycolysis and the hexose monophosphate shunt), but not by 5,5-dimethyl-1-pyrroline-1-oxide (a superoxide scavenger), N-acetyl cysteine (a scavenger for reactive oxygen species and precursor of glutathione), diphenylene iodonium (an inhibitor of flavoproteins such as NADPH oxidase and nitric oxide synthase), or SOD (a superoxide scavenger). Northern blotting demonstrated that tiron or DG affected at the mRNA level, while pyruvate affected Mn-induced MnSOD expression at both the mRNA and protein levels. These results demonstrate that Mn can induce MnSOD expression in cultured human breast cancer cells. Mn also induced apoptosis and necrosis in these cells. Since inhibitors of Mn-induced MnSOD induction did not affect cell viability, MnSOD induction is probably not the cause of the Mn-induced cell killing, (C) 1999 Academic Press. C1 Univ Iowa, Radiat Res Lab, Med Labs B180, Iowa City, IA 52242 USA. Univ Wisconsin, Sch Med, Dept Pathol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Hosp, Lab Med Serv, Madison, WI 53705 USA. RP Thongphasuk, J (reprint author), Univ Iowa, Radiat Res Lab, Med Labs B180, Iowa City, IA 52242 USA. FU NCI NIH HHS [P01-CA66081]; NIDCR NIH HHS [P50 DE-10758] NR 64 TC 21 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 1999 VL 365 IS 2 BP 317 EP 327 DI 10.1006/abbi.1999.1179 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 201FR UT WOS:000080584800018 PM 10328827 ER PT J AU Berenson, JR Vescio, RA AF Berenson, JR Vescio, RA TI HHV-8 is present in multiple myeloma patients SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; DENDRITIC CELLS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8; INFECTION; HISTORY; LINES; BLOOD C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Div Hematol & Oncol, Sch Med, Los Angeles, CA 90024 USA. RP Berenson, JR (reprint author), W Los Angeles Vet Affairs Med Ctr, 111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 29 TC 36 Z9 40 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1999 VL 93 IS 10 BP 3157 EP 3159 PG 3 WC Hematology SC Hematology GA 194JY UT WOS:000080190100001 PM 10233867 ER PT J AU Baskin, DG Breininger, JF Bonigut, S Miller, MA AF Baskin, DG Breininger, JF Bonigut, S Miller, MA TI Leptin binding in the arcuate nucleus is increased during fasting SO BRAIN RESEARCH LA English DT Article DE hypothalamus; leptin receptor; neuropeptide Y; proopiomelanocortin; food intake ID RECEPTOR MESSENGER-RNA; OB PROTEIN; HYPOTHALAMIC NEURONS; MOUSE HYPOTHALAMUS; OB/OB MICE; LONG FORM; RAT-BRAIN; EXPRESSION; LOCALIZATION; COEXPRESSION AB The arcuate nucleus (ARC) mediates the anorexic effects of leptin and expresses the long form (Ob-Rb) of the leptin receptor. To determine whether ARC leptin binding increases when plasma leptin levels are low during fasting, [I-125]-leptin specific binding to rat brain slices was measured by quantitative autoradiography. [I-125]-leptin specific binding was dense in the ARC and increased 2-fold after a 48-h fast (P < 0.001). These findings suggest that leptin receptor binding in the ARC is upregulated during fasting and that fasting changes the sensitivity of the ARC to leptin. (C) 1999 Elsevier Science B.V. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Div Endo Metab, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98195 USA. RP Baskin, DG (reprint author), VA Puget Sound Hlth Care Syst, Div Endo Metab, Mail Stop 151,1660 So Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-17047] NR 30 TC 50 Z9 50 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 MAY 15 PY 1999 VL 828 IS 1-2 BP 154 EP 158 DI 10.1016/S0006-8993(99)01252-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 197RK UT WOS:000080379300017 PM 10320735 ER PT J AU Fuchimoto, Y Yamada, K Shimizu, A Yasumoto, A Sawada, T Huang, CH Sachs, DH AF Fuchimoto, Y Yamada, K Shimizu, A Yasumoto, A Sawada, T Huang, CH Sachs, DH TI Relationship between chimerism and tolerance in a kidney transplantation model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I-DISPARATE; MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; RENAL-ALLOGRAFTS; ORGAN-TRANSPLANTATION; MONOCLONAL-ANTIBODIES; T-CELLS; REJECTION; MICROCHIMERISM; ACCEPTANCE AB The persistence of donor leukocytes in recipients of organ allografts has been associated with long-term graft acceptance, However, it remains unclear whether this peripheral donor cell microchimerism plays an active role in graft acceptance or is simply a consequence of the maintenance of sufficient immunosuppression to avoid rejection. A model of kidney transplantation between swine leukocyte Ag (SLA)-matched miniature swine, in which tolerance can be established with or without immunosuppressive treatment, has been used to study the correlation between donor leukocyte chimerism and kidney graft acceptance. SLA-identical kidney transplants were performed from animals positive for an allelic pig leukocyte Ag to animals negative for this marker. SLA-identical kidney transplant recipients given a 12-day course of cyclosporine (CyA) (n = 3) became tolerant, shelving stable serum creatinine levels (1-2 mg/dl) after cessation of CyA treatment. Donor cell chimerism (0.2-0.7%) was present by FAGS in all three animals with peak levels detected at 3 wk, Two control animals receiving SLA-identical kidney grafts without CyA also showed stable serum creatinine levels and became tolerant. However, in neither of these animals could donor leukocytes be detected in the peripheral blood beyond 1 wk following transplantation. In one additional control animal, ureteral obstruction occurred at day 10, and was associated with additional peripheral chimerism, presumably related to inflammation rather than to immune status. These results indicate that the persistence of donor cell chimerism is not a requirement for the maintenance of tolerance to organ allografts in this model. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [5PO1 AI39755-03, 5RO1 AI37692-03] NR 36 TC 32 Z9 32 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1999 VL 162 IS 10 BP 5704 EP 5711 PG 8 WC Immunology SC Immunology GA 195FP UT WOS:000080240200009 PM 10229802 ER PT J AU Saito, NG Chang, HC Paterson, Y AF Saito, NG Chang, HC Paterson, Y TI Recognition of an MHC class I-restricted antigenic peptide can be modulated by para-substitution of its buried tyrosine residues in a TCR-specific manner SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; COMPLEX CLASS-I; INDUCED CONFORMATIONAL-CHANGES; RMA-S CELLS; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; H-2K(B) MOLECULE; HEAVY-CHAINS; HISTOCOMPATIBILITY ANTIGEN; BINDING GROOVE AB Conformational dependence of TCR contact residues of the H-2K(b) molecule on the two buried tyrosine side chains of the vesicular stomatitis virus (VSV)-8 peptide was investigated by systematic substitutions of the tyrosines with phenylalanine, p-fluorophenylalanine (pFF), or p-bromophenylalanine (pBrF), The results of peptide competition CTL assays revealed that all of the peptide variants, except for the pBrF analogues, had near-native binding to the H-2K(b) molecule. Epitope-mapped anti-H-2K(b) mAbs detected conformational differences among H-2K(b) molecules stabilized with these VSV-8 variants on RMA-S cells. Selective recognition of the VSV-8 analogues was displayed by a panel of three H-2K(b)-restricted, anti-VSV-8 TCRs, Thus, these substitutions result in an antigenically significant conformational change of the MHC molecular surface structure at both C and D pockets, and the effect of this change on cognate T cell recognition is dependent on the TCR structure. Our results confirm that the structure of buried peptide side chains can determine the surface conformation of the MHC molecule and demonstrate that even a very subtle structural nuance of the buried side chain can be incorporated into the surface conformation of the MHC molecule. The ability of buried residues to modulate this molecular surface augments the number of residues on the MHC-peptide complex that can be recognized as "foreign" by the CD8(+) T cell repertoire and allows for a higher level of antigenic discrimination. This may be an important mechanism to expand the total number of TCR specificities that can respond to a single peptide determinant. C1 Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Eldridge Reeves Johnson Fdn Molec Biophys, Philadelphia, PA 19104 USA. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. RP Paterson, Y (reprint author), Univ Penn, Sch Med, Dept Microbiol, Room 323 Jonson Pavilion, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [5-RO1-AI-39098]; NIGMS NIH HHS [5-T32-GM-07170, 5-RO1-GM-31841] NR 86 TC 7 Z9 7 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1999 VL 162 IS 10 BP 5998 EP 6008 PG 11 WC Immunology SC Immunology GA 195FP UT WOS:000080240200046 PM 10229839 ER PT J AU Marshall, WL Brinkman, BMN Ambrose, CM Pesavento, PA Uglialoro, AM Teng, E Finberg, RW Browning, JL Goldfeld, AE AF Marshall, WL Brinkman, BMN Ambrose, CM Pesavento, PA Uglialoro, AM Teng, E Finberg, RW Browning, JL Goldfeld, AE TI Signaling through the lymphotoxin-beta receptor stimulates HIV-1 replication alone and in cooperation with soluble or membrane-bound TNF-alpha SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; NF-KAPPA-B; FOLLICULAR DENDRITIC CELLS; FACTOR-DEFICIENT MICE; VIRAL LOAD; MONOCLONAL-ANTIBODIES; VERTICAL TRANSMISSION; DISEASE PROGRESSION; LYMPHOID-TISSUE AB The level of ongoing HIV-1 replication within an individual is critical to HIV-1 pathogenesis. Among host immune factors, the cytokine TNF-cu has previously been shown to increase HIV-1 replication in various monocyte and T cell model systems. Here, we demonstrate that signaling through the TNF receptor family member, the lymphotoxin-beta (LT-beta) receptor (LT-beta R), also regulates HIV-1 replication. Furthermore, HIV-1 replication is cooperatively stimulated when the distinct LT-beta R and TNF receptor systems are simultaneously engaged by their specific ligands, Moreover, in a physiological coculture cellular assay system, we show that membrane-bound TNF-alpha and LT-alpha(1)beta(2) act virtually identically to their soluble forms in the regulation of HIV-1 replication. Thus, cosignaling via the LT-beta and TNF-alpha receptors is probably involved in the modulation of HIV-1 replication and the subsequent determination of HIV-1 viral burden in monocytes, Intriguingly, surface expression of LT-alpha(1)beta(2) is up-regulated on a T cell line acutely infected with HIV-1, suggesting a positive feedback loop between HIV-1 infection, LT-alpha(1)beta(2) expression, and HIV-1 replication. Given the critical role that LT-alpha(1)beta(2) plays in lymphoid architecture, we speculate that LT-alpha(1)beta(2) may be involved in HIV-associated abnormalities of the lymphoid organs. C1 Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Biogen Inc, Cambridge, MA 02138 USA. RP Goldfeld, AE (reprint author), Dana Farber Canc Inst, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Brinkman, Brigitta/C-1100-2009; Finberg, Robert/E-3323-2010; OI Browning, Jeffrey/0000-0001-9168-5233 FU NCI NIH HHS [CA58735, P30CA06516-33]; NIAID NIH HHS [AI28691-06] NR 65 TC 14 Z9 14 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 MAY 15 PY 1999 VL 162 IS 10 BP 6016 EP 6023 PG 8 WC Immunology SC Immunology GA 195FP UT WOS:000080240200048 PM 10229841 ER PT J AU Abrahamian, G Cosimi, AB Farrell, ML Chung, R Rubin, NT Schoenfeld, D Pascual, M AF Abrahamian, G Cosimi, AB Farrell, ML Chung, R Rubin, NT Schoenfeld, D Pascual, M TI Prevalence of hepatitis C - Associated mixed cryoglobulinemia after liver transplantation SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 352 BP S630 EP S630 DI 10.1097/00007890-199905150-00376 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100371 ER PT J AU Baid, S Toth, C Tolkoff-Rubin, N Cosimi, AB Williams, W Johnson, S Farrell, ML Ko, D Delmonico, F Pascual, M AF Baid, S Toth, C Tolkoff-Rubin, N Cosimi, AB Williams, W Johnson, S Farrell, ML Ko, D Delmonico, F Pascual, M TI Significance of anticardiolipin antibodies (ACA) in renal allograft recipients SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 307 BP S619 EP S619 DI 10.1097/00007890-199905150-00331 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100326 ER PT J AU Buhler, L Awwad, M Basker, M Gojo, S Watts, A Treter, S Nash, K Chang, Q Oravec, G Thall, A Down, J Andrews, D Sackstein, R White-Scharf, ME Sachs, DH AF Buhler, L Awwad, M Basker, M Gojo, S Watts, A Treter, S Nash, K Chang, Q Oravec, G Thall, A Down, J Andrews, D Sackstein, R White-Scharf, ME Sachs, DH TI Prevention of humoral sensitization to transplanted pig hematopoietic cells in baboons SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. BioTransplant Inc, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 284 BP S613 EP S613 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100303 ER PT J AU Dicken, S Ko, C Kawai, T Sachs, DH Abrahamian, GA Mauiyyedi, S Boskovic, S Hong, HZ Wee, SL Colvin, RB Cosimi, AB AF Dicken, S Ko, C Kawai, T Sachs, DH Abrahamian, GA Mauiyyedi, S Boskovic, S Hong, HZ Wee, SL Colvin, RB Cosimi, AB TI Efficacy of mycophenolate mofetil induction in prolongation of kidney xenograft survival in a nonhuman concordant primate model SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 209 BP S595 EP S595 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100228 ER PT J AU Kaihara, S Kim, SS Vacanti, JP AF Kaihara, S Kim, SS Vacanti, JP TI Morphological characteristics of ectopically implanted hepatocytes in the portal circulation SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 412 BP S645 EP S645 DI 10.1097/00007890-199905150-00435 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100430 ER PT J AU Kaihara, S Kim, SS Kim, BS Mooney, D Vacanti, JP AF Kaihara, S Kim, SS Kim, BS Mooney, D Vacanti, JP TI Long term follow up of tissue engineered intestine after anastomosis to native small bowel SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 189 BP S590 EP S590 DI 10.1097/00007890-199905150-00213 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100208 ER PT J AU Kauffman, HM McBride, MA Delmonico, FL Penn, I AF Kauffman, HM McBride, MA Delmonico, FL Penn, I TI First report of the new international (CTTR-UNOS) transplant tumor registry: US donors with a history of cancer SO TRANSPLANTATION LA English DT Meeting Abstract C1 United Network Organ Sharing, Richmond, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 37 BP S552 EP S552 DI 10.1097/00007890-199905150-00062 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100057 ER PT J AU Kawai, T Wee, SL Boskovic, S Abrahamian, G Ko, D Hong, H Winn, H Colvin, RB Sachs, DH Cosimi, AB AF Kawai, T Wee, SL Boskovic, S Abrahamian, G Ko, D Hong, H Winn, H Colvin, RB Sachs, DH Cosimi, AB TI Association of natural killer cell depletion and induction of mixed chimerism and allograft tolerance in non-human primates SO TRANSPLANTATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 58 BP S557 EP S557 DI 10.1097/00007890-199905150-00083 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100078 ER PT J AU Mathes, DW Bourget, JL Randolph, M Sachs, DH Lee, WPA AF Mathes, DW Bourget, JL Randolph, M Sachs, DH Lee, WPA TI Recipient bone marrow engraftment in donor tissue following long-term tolerance to a hemopoietic musculoskeletal allograft SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. OI Mathes, David/0000-0003-4388-1373 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 266 BP S609 EP S609 DI 10.1097/00007890-199905150-00290 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100285 ER PT J AU Schuchert, MJ Wright, RD Colson, YL AF Schuchert, MJ Wright, RD Colson, YL TI The facilitating cell requires a functional TCR beta gene to promote allogeneic stem cell engraftment and survival. SO TRANSPLANTATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 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 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 119 BP S572 EP S572 DI 10.1097/00007890-199905150-00144 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100139 ER PT J AU Yamada, K Mawulawde, K Menard, MT Utsugi, R Shimizu, A Slisz, JK Sachs, DH Madsen, JC AF Yamada, K Mawulawde, K Menard, MT Utsugi, R Shimizu, A Slisz, JK Sachs, DH Madsen, JC TI Role of the kidney allograft in induction of tolerance and prevention of cardiac allograft vasculopathy (CAV) in combined heart kidney transplantation SO TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1999 VL 67 IS 9 MA 61 BP S558 EP S558 DI 10.1097/00007890-199905150-00086 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 201YD UT WOS:000080624100081 ER PT J AU Nam, HJ Poy, F Krueger, NX Saito, H Frederick, CA AF Nam, HJ Poy, F Krueger, NX Saito, H Frederick, CA TI Crystal structure of the tandem phosphatase domains of RPTP LAR SO CELL LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LEUKOCYTE COMMON ANTIGEN; CATALYTIC DOMAINS; MOLECULAR REPLACEMENT; ALPHA; EXPRESSION; MUTANTS; COMPLEX; ROLES; LCA AB Most receptor-like protein tyrosine phosphatases (RPTPs) contain two conserved phosphatase domains (D1 and D2) in their intracellular region. The carboxyterminal D2 domain has little or no catalytic activity. The crystal structure of the tandem D1 and D2 domains of the human RPTP LAR revealed that the tertiary structures of the LAR D1 and D2 domains are very similar to each other, with the exception of conformational differences at two amino acid positions in the D2 domain. Site-directed mutational changes at these positions (Leu-1644-to-Tyr and Glu-1779-to-Asp) conferred a robust PTPase activity to the D2 domain. The catalytic sites of both domains are accessible, in contrast to the dimeric blocked orientation model previously suggested. The relative orientation of the LAR D1 and D2 domains, constrained by a short linker, is stabilized by extensive interdomain interactions, suggesting that this orientation might be favored in solution. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Frederick, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 53415] NR 33 TC 119 Z9 123 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 14 PY 1999 VL 97 IS 4 BP 449 EP 457 DI 10.1016/S0092-8674(00)80755-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 196FV UT WOS:000080299100006 PM 10338209 ER PT J AU Greenberg, RA Chin, L Femino, A Lee, KH Gottlieb, GJ Singer, RH Greider, CW DePinho, RA AF Greenberg, RA Chin, L Femino, A Lee, KH Gottlieb, GJ Singer, RH Greider, CW DePinho, RA TI Short dysfunctional telomeres impair tumorigenesis in the INK4a(Delta 2/3) cancer-prone mouse SO CELL LA English DT Article ID ARF TUMOR-SUPPRESSOR; IMMORTAL HUMAN-CELLS; LIFE-SPAN; P53-DEPENDENT APOPTOSIS; CELLULAR SENESCENCE; LACKING TELOMERASE; HUMAN FIBROBLASTS; FISSION YEAST; INK4A LOCUS; P53 AB Maintenance of telomere length is predicted to be essential for bypass of senescence and crisis checkpoints in cancer cells. The impact of telomere dysfunction on tumorigenesis was assessed in successive generations of mice doubly null for the telomerase RNA (mTR) and the INK4a tumor suppressor genes. Significant reductions in tumor formation in vivo and oncogenic potential in vitro were observed in late generations of telomerase deficiency, coincident with severe telomere shortening and associated dysfunction. Reintroduction of mTR into cells significantly restored the oncogenic potential, indicating telomerase activation is a cooperating event in the malignant transformation of cells containing critically short telomeres. The results described here demonstrate that loss of telomere function in a cancer-prone mouse model possessing intact DNA damage responses impairs, but does not prevent, tumor formation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Struct Biol & Anat, Bronx, NY 10461 USA. Quest Diagnost Inc, Anat Pathol, Teterboro, NJ USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA16519]; NICHD NIH HHS [HD28317, HD348880] NR 57 TC 283 Z9 292 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 14 PY 1999 VL 97 IS 4 BP 515 EP 525 DI 10.1016/S0092-8674(00)80761-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 196FV UT WOS:000080299100012 PM 10338215 ER PT J AU Chin, L Artandi, SE Shen, Q Tam, A Lee, SL Gottlieb, GJ Greider, CW DePinho, RA AF Chin, L Artandi, SE Shen, Q Tam, A Lee, SL Gottlieb, GJ Greider, CW DePinho, RA TI p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis SO CELL LA English DT Article ID MOUSE CELLS LACKING; DNA-DAMAGE; LIFE-SPAN; IMMORTAL CELLS; YEAST TELOMERE; SENESCENCE; FIBROBLASTS; ARREST; GROWTH; RNA AB Maintenance of telomere length and function is critical for the efficient proliferation of eukaryotic cells. Here, we examine the interactions between telomere dysfunction and p53 in cells and organs of telomerase-deficient mice. Coincident with severe telomere shortening and associated genomic instability, p53 is activated, leading to growth arrest and/or apoptosis. Deletion of p53 significantly attenuated the adverse cellular and organismal effects of telomere dysfunction, but only during the earliest stages of genetic crisis. Correspondingly, the loss of telomere function and p53 deficiency cooperated to initiate the transformation process. Together, these studies establish a key role for p53 in the cellular response to telomere dysfunction in both normal and neoplastic cells, question the significance of crisis as a tumor suppressor mechanism, and identify a biologically relevant stage of advanced crisis, termed genetic catastrophe. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Quest Diagnost Inc, Anat Pathol, Teterboro, NJ 07608 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIAMS NIH HHS [K08AR02104-01]; NICHD NIH HHS [R01HD28317, R01HD34880] NR 44 TC 659 Z9 690 U1 3 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 14 PY 1999 VL 97 IS 4 BP 527 EP 538 DI 10.1016/S0092-8674(00)80762-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 196FV UT WOS:000080299100013 PM 10338216 ER PT J AU Gatto, C Lutsenko, S Shin, JM Sachs, G Kaplan, JH AF Gatto, C Lutsenko, S Shin, JM Sachs, G Kaplan, JH TI Stabilization of the H,K-ATPase M5M6 membrane hairpin by K+ ions - Mechanistic significance for P-2-type ATPases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA,K-ATPASE ALPHA-SUBUNIT; IN-VITRO TRANSLATION; ESCHERICHIA-COLI; CYTOPLASMIC LOOP; ATP-BINDING; IDENTIFICATION; CA2+-ATPASE; TOPOLOGY; PROTEINS; NA+,K+-ATPASE AB The integral membrane protein, the gastric H,K-ATPase, is an alpha-beta heterodimer, with 10 putative transmembrane segments in the alpha-subunit and one such segment in the beta-subunit, All transmembrane segments remain within the membrane domain following trypsinization of the intact gastric H,K-ATPase in the presence of K+ ions, identified as M1M2, M3M4, M5M6, and M7, M8, M9, and M10, Removal of K+ ions from this digested preparation results in the selective loss of the M5M6 hairpin from the membrane. The release of the M5M6 fragment is directed to the extracellular phase as evidenced by the accumulation of the released M5M6 hairpin inside the sealed inside out vesicles. The stabilization of the M5M6 hairpin in the membrane phase by the transported cation as well as loss to the aqueous phase in the absence of the transported cation has been previously observed for another P-2-type ATPase, the Na,K-ATPase (Lutsenko, S., Anderko, R., and Kaplan, J. H. (1995) Proc. Natl, Acad. Sci. U. S. A. 92, 7936-7940). Thus, the effects of the counter-transported cation on retention of the M5M6 segment in the membrane as compared with the other membrane pairs may be a general feature of P-2-ATPase ion pumps, reflecting a flexibility of this region that relates to the mechanism of transport. C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res, Los Angeles, CA 90073 USA. RP Kaplan, JH (reprint author), Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, L224,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaplan, Jack/0000-0002-7048-6574 FU NHLBI NIH HHS [HL09972, HL30315]; NIGMS NIH HHS [GM39500] NR 35 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 14 PY 1999 VL 274 IS 20 BP 13737 EP 13740 DI 10.1074/jbc.274.20.13737 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196RW UT WOS:000080322200003 PM 10318774 ER PT J AU Jonas, JC Sharma, A Hasenkamp, W Ilkova, H Patane, G Laybutt, R Bonner-Weir, S Weir, GC AF Jonas, JC Sharma, A Hasenkamp, W Ilkova, H Patane, G Laybutt, R Bonner-Weir, S Weir, GC TI Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCEROL PHOSPHATE DEHYDROGENASE; INSULIN GENE-TRANSCRIPTION; LACTATE-DEHYDROGENASE; FATTY RATS; PANCREATECTOMIZED RATS; ISOLATED ISLETS; GLUCOSE; EXPRESSION; SECRETION; GLUCOKINASE AB Differentiated pancreatic beta cells are unique in their ability to secrete insulin in response to a rise in plasma glucose. We have proposed that the unique constellation of genes they express may be lost in diabetes due to the deleterious effect of chronic hyperglycemia. To test this hypothesis, Sprague-Dawley rats were submitted to a 85-95% pancreatectomy or sham pancreatectomy. One week later, the animals developed mild to severe chronic hyperglycemia that was stable for the next 3 weeks, without significant alteration of plasma nonesterified fatty acid levels. Expression of many genes important for glucose-induced insulin release decreased progressively with increasing hyperglycemia, in parallel with a reduction of several islet transcription factors involved in beta cell development and differentiation. In contrast, genes barely expressed in sham islets (lactate dehydrogenase A and hexokinase I) were markedly increased, in parallel with an increase in the transcription factor c-Myc, a potent stimulator of cell growth. These abnormalities were accompanied by beta cell hypertrophy. Changes in gene expression were fully developed 2 weeks after pancreatectomy. Correction of blood glucose by phlorizin for the next 2 weeks normalized islet gene expression and beta cell volume without affecting plasma nonesterified fatty acid levels, strongly suggesting Chat hyperglycemia triggers these abnormalities. In conclusion, chronic hyperglycemia leads to beta cell hypertrophy and loss of beta cell differentiation that is correlated with changes in c-Myc and other key transcription factors. A similar change in beta cell differentiation could contribute to the profound derangement of insulin secretion in human diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl,Rm 535, Boston, MA 02215 USA. RI Jonas, Jean-Christophe/C-6766-2011 OI Jonas, Jean-Christophe/0000-0001-9882-5438 FU NIDDK NIH HHS [DK-35449, DK-36836, DK-44523] NR 54 TC 352 Z9 374 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 14 PY 1999 VL 274 IS 20 BP 14112 EP 14121 DI 10.1074/jbc.274.20.14112 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196RW UT WOS:000080322200057 PM 10318828 ER PT J AU Holz, GG Leech, CA Heller, RS Castonguay, M Habener, JF AF Holz, GG Leech, CA Heller, RS Castonguay, M Habener, JF TI cAMP-dependent mobilization of intracellular Ca2+ stores by activation of ryanodine receptors in pancreatic beta-cells - A Ca2+ signaling system stimulated by the insulinotropic hormone glucagon-like peptide-1-(7-37) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIC ADP-RIBOSE; INOSITOL 1,4,5-TRISPHOSPHATE; RELEASE CHANNEL; PEPTIDE-I; SARCOPLASMIC-RETICULUM; PEPTIDE-1(7-36) AMIDE; PHOSPHOLIPASE-C; CALCIUM-RELEASE; SECRETING CELLS; CARDIAC-MUSCLE AB Glucagon-like peptide-1 (GLP-1) is an intestinally derived insulinotropic hormone currently under investigation for use as a novel therapeutic agent in the treatment of type 2 diabetes mellitus, In vitro studies of pancreatic islets of Langerhans demonstrated that GLP-1 interacts with specific beta-cell G protein-coupled receptors, thereby facilitating insulin exocytosis by raising intracellular levels of cAMP and Ca2+. Here we report that the stimulatory influence of GLP-1 on Ca2+ signaling results, in part, from cAMP-dependent mobilization of ryanodine-sensitive Ca2+ stores. Studies of human, rat, and mouse beta-cells demonstrate that the binding of a fluorescent derivative of ryanodine (BODIPY FL-X ryanodine) to its receptors is specific, reversible, and of high affinity. Rat islets and BTC3 insulinoma cells are shown by reverse transcriptase polymerase chain reaction analyses to express mRNA corresponding to the type 2 isoform of ryanodine receptor-intracellular Ca2+ release channel (RYR2), Single-cell measurements of [Ca2+](i) using primary cultures of rat and human beta-cells indicate that GLP-1 facilitates Ca2+-induced Ca2+ release (CICR), whereby mobilization of Ca2+ stores is triggered by influx of Ca2+ through L-type Ca2+ channels, In these cells, GLP-1 is shown to interact with metabolism of D-glucose to produce a fast transient increase of [Ca2+](i). This effect is reproduced by 8-Br-cAMP, but is blocked by a GLP-1 receptor antagonist (exendin-(9-39)), a cAMP antagonist ((Rp)-cAMPS), an L-type Ca2+ channel antagonist (nimodipine), an antagonist of the sarco(endo)plasmic reticulum Ca2+ ATPase (thapsigargin), or by ryanodine, Characterization of the CICR mechanism by voltage clamp analysis also demonstrates a stimulation of Ca2+ release by caffeine. These findings provide new support for a model of beta-cell signal transduction whereby GLP-1 promotes CICR by sensitizing intracellular Ca2+ release channels to the stimulatory influence of cytosolic Ca2+. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Holz, GG (reprint author), NYU, Med Ctr, Dept Physiol & Neurosci, New York, NY 10016 USA. RI Heller, R.Scott/A-7279-2008; Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK-45817, DK-30834, DK-52166, R01 DK030834, R01 DK045817] NR 69 TC 157 Z9 162 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 14 PY 1999 VL 274 IS 20 BP 14147 EP 14156 DI 10.1074/jbc.274.20.14147 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196RW UT WOS:000080322200061 PM 10318832 ER PT J AU Ogris, E Du, XX Nelson, KC Mak, EK Yu, XX Lane, WS Pallas, DC AF Ogris, E Du, XX Nelson, KC Mak, EK Yu, XX Lane, WS Pallas, DC TI A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYOMAVIRUS MIDDLE-T; BACTERIAL CHEMOTAXIS; CATALYTIC SUBUNIT; BOVINE BRAIN; TYROSINE PHOSPHORYLATION; METHYL ESTERIFICATION; POLYACRYLAMIDE GELS; MUTATIONAL ANALYSIS; CELLULAR PROTEINS; OKADAIC ACID AB Carboxymethylation of proteins is a highly conserved means of regulation in eukaryotic: cells. The protein phosphatase 2A (PP2A) catalytic (C) subunit is reversibly methylated at its carboxyl terminus by specific methyltransferase and methylesterase enzymes which have been purified, but not cloned. Carboxymethylation affects PP2A activity and varies during the cell cycle. Here, we report that substitution of glutamine for either of two putative active site histidines in the PP2A C subunit results in inactivation of PP2A and formation of stable complexes between PP2A and several cellular proteins. One of these cellular proteins, herein named protein phosphatase methylesterase-1 (PME-1), was purified and microsequenced, and its cDNA was cloned. PME-1 is conserved from yeast to human and contains a motif found in lipases having a catalytic triad-activated serine as their active site nucleophile. Bacterially expressed PME-1 demethylated PP2A C subunit in vitro, and okadaic acid, a known inhibitor of the PP2A methylesterase, inhibited this reaction. To our knowledge, PME-1 represents the first mammalian protein methylesterase to be cloned. Several lines of evidence indicate that, although there appears to be a role for C subunit carboxyl-terminal amino acids in PME-1 binding, amino acids other than those at the extreme carboxyl terminus of the C subunit also play an important role in PME-1 binding to a catalytically inactive mutant. C1 Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. Harvard Univ, Biol Labs, Harvard Microchem Facil, Cambridge, MA 02138 USA. Univ Vienna, Inst Mol Biol, A-1030 Vienna, Austria. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Pallas, DC (reprint author), Emory Univ, Sch Med, Dept Biochem, 1510 Clifton Rd, Atlanta, GA 30322 USA. FU NCI NIH HHS [CA57327, R01 CA057327] NR 54 TC 111 Z9 116 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 14 PY 1999 VL 274 IS 20 BP 14382 EP 14391 DI 10.1074/jbc.274.20.14382 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 196RW UT WOS:000080322200091 PM 10318862 ER PT J AU Daws, LC Gerhardt, GA Frazer, A AF Daws, LC Gerhardt, GA Frazer, A TI 5-HT1B antagonists modulate clearance of extracellular serotonin in rat hippocampus SO NEUROSCIENCE LETTERS LA English DT Article DE 5-HT1B receptor; serotonin transporter; hippocampus; in vivo chronoamperometry; cyanopindolol; 5-HT-moduline ID IN-VIVO; RECEPTORS; TRANSPORTER; DOPAMINE; PEPTIDE AB In vivo chronoamperometry was used to determine the effects of locally applied antagonists of the serotonin-1B (5-HT1B) receptor (cyanopindolol, 5-HT-moduline and methiothepin) on the clearance of 5-HT in the CA3 region of the dorsal hippocampus and the corpus callosum (a brain region devoid of serotonin transporters and 5-HT1B receptors) of the rat. When 5-HT was pressure ejected into these regions, reproducible signals were detected. In the CA3 region, local application of 5-HT1B antagonists decreased the rate of clearance of the serotonin signal comparably to the selective 5-HT uptake inhibitor (SSRI), fluvoxamine. By contrast, in the corpus callosum, none of the drugs altered the 5-HT signal. One interpretation of these data is that 5-HT1B receptors can modulate the activity of the 5-HT transporter. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Hosp, San Antonio, TX USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol & Psychiat, Neurosci Training Program, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Rocky Mt Ctr Sensor Technol, Denver, CO USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG06434]; NIMH NIH HHS [MH57001, R01 MH057001]; NINDS NIH HHS [NS09199] NR 20 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 14 PY 1999 VL 266 IS 3 BP 165 EP 168 DI 10.1016/S0304-3940(99)00277-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 198UY UT WOS:000080443700004 PM 10465699 ER PT J AU Pestano, GA Zhou, YL Trimble, LA Daley, J Weber, GF Cantor, H AF Pestano, GA Zhou, YL Trimble, LA Daley, J Weber, GF Cantor, H TI Inactivation of misselected CD8 T cells by CD8 gene methylation and cell death SO SCIENCE LA English DT Article ID MHC CLASS-I; IMMATURE THYMOCYTES; POSITIVE SELECTION; THYMIC SELECTION; DEFICIENT MICE; LPR MICE; RECEPTOR; LYMPHOCYTES; ANTIGEN; SPECIFICITY AB Misselected CD8 cells that express T cell receptors (TCRs) that do not recognize class I major histocompatibility complex (MHC) protein can emerge from thymic selection. A postthymic quality control mechanism that purges these cells from the repertoire is defined here. The failure of mature CD8 cells to simultaneously engage their TCR and CD8 coreceptor triggers an activation process that begins with inhibition of CD8 gene expression through remethylation and concludes with up-regulation of surface Fas and pas Ligand and cellular apoptosis. Thus, inhibition of a death signal through continued TCR-CD8 coengagement of MHC molecules is a key checkpoint for the continued survival of correctly selected T cells. Molecular defects that prevent delivery of the death signal to mistakenly selected T cells underlie the expansion of double-negative T cells, which is the cellular signature of a subset of systemic autoimmune diseases. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA76176]; NIAID NIH HHS [AI 13600, AI 37833] NR 49 TC 67 Z9 68 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 MAY 14 PY 1999 VL 284 IS 5417 BP 1187 EP 1191 DI 10.1126/science.284.5417.1187 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 197HJ UT WOS:000080359100043 PM 10325233 ER PT J AU Madore, HP Estes, MK Zarley, CD Hu, B Parsons, S Digravio, D Greiner, S Smith, R Jiang, B Corsaro, B Barniak, V Crawford, S Conner, ME AF Madore, HP Estes, MK Zarley, CD Hu, B Parsons, S Digravio, D Greiner, S Smith, R Jiang, B Corsaro, B Barniak, V Crawford, S Conner, ME TI Biochemical and immunologic comparison of virus-like particles for a rotavirus subunit vaccine SO VACCINE LA English DT Article DE rotavirus; virus-like particles; QS-21 ID PROTECTIVE IMMUNITY; EXPRESSION; PROTEINS; IMMUNOGENICITY; BACULOVIRUS; MICE; VP7 AB A parenterally administered rotavirus vaccine composed of virus-like particles (VLPs) is being evaluated for human use. VLPs composed of bovine VP6 and simian VP7 (SA11, G3) proteins (6/7-VLPs) or of bovine VP2, bovine VP6, and simian VP7 (SA11, G3) proteins (2/6/7-VLPs) were synthesized and purified from Sf9 insect cells co-infected with recombinant baculoviruses. 6/7- and 2/6/7-VLP administered parenterally (i.m.) in mice had comparable immunogenicity, but the 2/6/7-VLPs were more homogeneous and stable. The inclusion of the VP2 capsid contributed to particle formation and stability. The adjuvant QS-21 significantly enhanced the immunogenicity of 2/6/7-VLPs over A10H or saline alone. Equivalent serum neutralizing antibody responses were induced over the range of 1-15 mu g/dose of 2/6/7-VLPs administered with the range of 5-20 mu g/dose of QS-21. The immunogenicity of 2/6/7-VLPs and inactivated SA11 virus were comparable. 2/6/7-VLPs are a promising candidate for a parenterally delivered rotavirus subunit vaccine. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Wyeth Lederle Vaccines & Pediat, W Henrietta, NY 14586 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. RP Madore, HP (reprint author), Wyeth Lederle Vaccines & Pediat, 211 Bailey Rd, W Henrietta, NY 14586 USA. NR 31 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 14 PY 1999 VL 17 IS 19 BP 2461 EP 2471 DI 10.1016/S0264-410X(98)00319-3 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 205BF UT WOS:000080800900017 PM 10392629 ER PT J AU Schmidt, EV AF Schmidt, EV TI The role of c-myc in cellular growth control SO ONCOGENE LA English DT Review DE translation initiation; rDNA transcription; eIF4E; translational control ID RIBOSOMAL-RNA SYNTHESIS; INITIATION-FACTOR 4E; TARGETED HOMOLOGOUS RECOMBINATION; RETINOBLASTOMA GENE-PRODUCT; POLYMERASE-I TRANSCRIPTION; FACTOR TIF-IA; TRANSLATION INITIATION; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; PROTEIN-SYNTHESIS AB Cell division is coupled to cell growth. Since some c-myc target genes are regulators of cell growth while others function in cell division pathways, c-myc is apparently poised at the interface of these processes. Cell culture systems have shown specific myc-associated growth phenotypes, Increased cell growth precedes DNA synthesis after myc activation in cells expressing myc-estrogen receptor fuson constructs and cells lacking c-myc exhibit a marked loss of protein synthesis. A number of candidate c-myc target genes regulate processes required for cell growth including rRNA transcription and processing, ribosomal protein transcription and translation, and translation initiation. These interactions all have the potential to account for the growth phenotypes in c-myc mutant cells. The ability of translation initiation factors, including eIF4E, to transform cells makes them particularly interesting targets of c-myc. Further evaluation of these target genes will provide important insights into growth control and c-myc's functions in cellular proliferation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA63117, R01-CA69069] NR 105 TC 237 Z9 245 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD MAY 13 PY 1999 VL 18 IS 19 BP 2988 EP 2996 DI 10.1038/sj.onc.1202751 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 197VZ UT WOS:000080387800008 PM 10378694 ER PT J AU Jacobs, DM Albert, SM Sano, M del Castillo-Castaneda, C Paik, MC Marder, K Bell, K Brandt, J Albert, MS Stern, Y AF Jacobs, DM Albert, SM Sano, M del Castillo-Castaneda, C Paik, MC Marder, K Bell, K Brandt, J Albert, MS Stern, Y TI Assessment of cognition in advanced AD: The test for severe impairment SO NEUROLOGY LA English DT Article AB The Test for Severe Impairment (TSI) was compared with the Mini-Mental State Examination (MMSE) and a modified MMSE (mMMSE) in a multisite, longitudinal study of AD. The TSI correlated highly with the MMSE (r = 0.83) and the mMMSE (r = 0.82), but was not redundant. There was a wide range of scores on the TSI among those scoring in the severely impaired range on the MMSE and mMMSE. The slope of cognitive change over time detected by the TSI was greater than that revealed by the MMSE or the mMMSE. Performance on the TSI was a significant predictor of survival. The TSI is a valid measure that is sensitive to cognitive change over time in severely demented patients with AD. C1 Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Sch Publ Hlth, Dept Biostat, New York, NY USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Jacobs, DM (reprint author), Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244; Albert, Steven/0000-0001-6786-9956 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370, AG08702] NR 7 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 12 PY 1999 VL 52 IS 8 BP 1689 EP 1691 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 195DJ UT WOS:000080233600033 PM 10331701 ER PT J AU Billman, GE Kang, JX Leaf, A AF Billman, GE Kang, JX Leaf, A TI Prevention of sudden cardiac death by dietary pure omega-3 polyunsaturated fatty acids in dogs SO CIRCULATION LA English DT Article DE fatty acids; death, sudden; diet ID RAT VENTRICULAR MYOCYTES; MYOCARDIAL-ISCHEMIA; LONG-CHAIN; EICOSAPENTAENOIC ACID; NA+ CHANNELS; ARRHYTHMIAS; FIBRILLATION; INFARCTION; BINDING; PHOSPHOLIPIDS AB Background-Rat diets high in fish oil have been shown to be protective against ischemia-induced fatal ventricular arrhythmias. Increasing evidence suggests that this may also apply to humans. To confirm the evidence in animals, we tested a concentrate of the free fish-oil fatty acids and found them to be antiarrhythmic. In this study, we tested the pure free fatty acids of the 2 major dietary omega-3 polyunsaturated fatty acids in fish oil: cis-5,8,11,14,17-eicosapentaenoic acid (C20:5 omega-3) and cis-4,7,10,13,16, 19-docosahexaenoic acid (C22:6 omega-3), and the parent omega-3 fatty acid in some vegetable oils, cis-9,12,15-alpha-linolenic acid (C18:3 omega-3), administered intravenously on albumin or a phospholipid emulsion. Methods and Results-The tests were performed in a dog model of cardiac sudden death. Dogs were prepared with a large anterior wall myocardial infarction produced surgically and an inflatable cuff placed around the left circumflex coronary artery. With the dogs running on a treadmill 1 month after the surgery, occlusion of the left circumflex artery regularly produced ventricular fibrillation in the control tests done 1 week before and after the test, with the omega-3 fatty acids administered intravenously as their pure free fatty acid. With infusion of the eicosapentaenoic acid, 5 of 7 dogs were protected from fatal ventricular arrhythmias (P<0.02). With docosahexaenoic acid, 6 of 8 dogs were protected, and with cy-linolenic acid, 6 of 8 dogs were also protected (P<0.004 for each). The before and after control studies performed on the same animal all resulted in fatal ventricular arrhythmias, from which they were defibrillated. Conclusions-These results indicate that purified omega-3 fatty acids can prevent ischemia-induced ventricular fibrillation in this dog model of sudden cardiac death. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Ohio State Univ, Dept Physiol, Columbus, OH 43210 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, E Bldg 149,13th St, Charlestown, MA 02129 USA. RI Billman, George/E-2758-2011 FU NIDDK NIH HHS [DK-38165] NR 39 TC 303 Z9 310 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 11 PY 1999 VL 99 IS 18 BP 2452 EP 2457 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 193NR UT WOS:000080143300018 PM 10318669 ER PT J AU McMahon, C Suthiphongchai, T DiRenzo, J Ewen, ME AF McMahon, C Suthiphongchai, T DiRenzo, J Ewen, ME TI PCAF associates with cyclin D1 and potentiates its activation of the estrogen receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA-POLYMERASE-II; NUCLEAR-RECEPTOR; TRANSCRIPTIONAL ACTIVATION; BREAST-CANCER; HISTONE ACETYLTRANSFERASES; HORMONE RECEPTORS; GENE-EXPRESSION; DNA-BINDING; COACTIVATOR; COMPLEX AB Cyclin D1 is overexpressed in a significant percentage of human breast cancers, particularly in those that also express the estrogen receptor (ER). We and others have demonstrated previously that experimentally overexpressed cyclin D1 can associate with the ER and stimulate its transcriptional functions in the absence of estrogen, This effect is separable from the established function of cyclin D1 as a regulator of cyclin-dependent kinases. Here, we demonstrate that cyclin D1 can also interact with the histone acetyltransferase, p300/CREB-binding protein-associated protein (P/CAF), thereby facilitating an association between P/CAF and the ER. Ectopic expression of P/CAF potentiates cyclin D1-stimulated ER activity in a dose-dependent manner. This effect is largely dependent on the acetyltransferase activity of P/CAF. These results suggest that cyclin D1 may trigger the activation of the ER through the recruitment of P/CAF, by providing histone acetyltransferase activity and, potentially, links to additional P/CAF-associated transcriptional coactivators. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Dana 728, Boston, MA 02115 USA. FU FIC NIH HHS [F05 TW005293]; NCI NIH HHS [R01 CA065842, CA65842] NR 53 TC 125 Z9 127 U1 1 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 MAY 11 PY 1999 VL 96 IS 10 BP 5382 EP 5387 DI 10.1073/pnas.96.10.5382 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195JG UT WOS:000080246500014 PM 10318892 ER PT J AU D'Souza, I Poorkaj, P Hong, M Nochlin, D Lee, VMY Bird, TD Schellenberg, GD AF D'Souza, I Poorkaj, P Hong, M Nochlin, D Lee, VMY Bird, TD Schellenberg, GD TI Missense and silent tau gene mutations cause frontotemporal dementia with parkinsonism-chromosome 17 type, by affecting multiple alternative RNA splicing regulatory elements SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FAMILIAL PRESENILE-DEMENTIA; PONTO-NIGRAL DEGENERATION; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; SYSTEM TAUOPATHY; SITE SELECTION; SR-PROTEINS; LINKAGE; COMPLEX; FTDP-17 AB Frontotemporal dementia with parkinsonism, chromosome 17 type (FTDP-17) is caused by mutations in the tan gene, and the signature lesions of FTDP-17 are filamentous tan inclusions, Tau mutations may be pathogenic either by altering protein function or gene regulation, Here we show that missense, silent, and intronic tau mutations can increase or decrease splicing of tau exon 10 (E10) by acting on 3 different cis-acting regulatory elements. These elements include an exon splicing enhancer that can either be strengthened (mutation (N)279(K)) or destroyed (mutation Delta 280(K)), resulting in either constitutive E10 inclusion or the exclusion of E10 from tau transcripts. E10 contains a second regulatory element that is an exon splicing silencer, the function of which is abolished by a silent FTDP-17 mutation ((L)284(L)), resulting in excess E10 inclusion. A third element inhibiting E10 splicing is contained in the intronic sequences directly flanking the 5' splice site of E10 and intronic FTDP-17 mutations in this element enhance E10 inclusion. Thus, tau mutations cause FTDP-17 by multiple pathological mechanisms, which may explain the phenotypic heterogeneity observed in FTDP-17, as exemplified by an unusual family described here with tau pathology as well as amyloid and neuritic plaques. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Neuropathol Lab, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Zachdad@U.Washington.edu FU NIA NIH HHS [R37 AG011762, AG05136, AG10210, AG11762, P50 AG005136, R01 AG011762] NR 39 TC 344 Z9 349 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 11 PY 1999 VL 96 IS 10 BP 5598 EP 5603 DI 10.1073/pnas.96.10.5598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195JG UT WOS:000080246500052 PM 10318930 ER PT J AU Levelt, CN de Jong, YP Mizoguchi, E O'Farrelly, C Bhan, AK Tonegawa, S Terhorst, C Simpson, SJ AF Levelt, CN de Jong, YP Mizoguchi, E O'Farrelly, C Bhan, AK Tonegawa, S Terhorst, C Simpson, SJ TI High- and low-affinity single-pepeide/MHC ligands have distinct effects on the development of mucosal CD8 alpha alpha and CD8 alpha beta T lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; RECEPTOR-ALPHA-BETA; CELL DEVELOPMENT; NEGATIVE SELECTION; MUTANT MICE; TRANSGENIC MICE; ANTIGEN; GUT; EXPRESSION; THYMUS AB In this study, we compared the influence of two peptides on the selection of CD8 alpha alpha and CD8 alpha beta intraepithelial lymphocytes (IELs) of the intestine, which develop by a unique and partially thymus-independent process. Mice were used in which all T cells carried one transgenic T cell antigen receptor (TCR) (F5), and in which only well defined transgenic peptides were presented by H-2D(b). The first peptide, for which the F5 TCR has a high affinity, derives from the influenza virus nucleoprotein (NP68), The second peptide, NP34, is an antagonistic variant of NP68 and is recognized by the F5 TCR with low affinity. To avoid presentation of endogenous peptides or production of T cells carrying alternative TCRs, F5 TCR transgenic mice were generated that were deficient for Tap-1 and Rag-1. In these mice, no CD3(+)CD8(+) cells were found in lymph nodes, spleen, or intestine. Introduction of transgenes encoding either NP34 or NP68 along with an endoplasmic reticulum signal sequence enabled Tap-1-independent expression of each peptide in these mice. Positive selection of F5TCR(+)CD8(+) thymocytes was not rescued by these transgenic peptides, However, the high-affinity NP68 peptide induced maturation of CD8 alpha alpha IEL, whereas the low-affinity NP34 peptide stimulated development of both CD8 alpha beta and CD8 alpha alpha IEL, but in smaller numbers. When both peptides were present, CD8 alpha beta T cells failed to develop and the number of CD8 alpha alpha IELs was lower than in mice carrying the NP68 transgene alone. These data demonstrate that single ligands with a high or low affinity for TCR are capable of inducing or inhibiting the maturation of alternative subsets of IELs. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. St Vincent Hosp, Res Labs, Educ Res Ctr, Dublin 4, Ireland. RP Simpson, SJ (reprint author), Edward Jenner Inst Vaccine Res, Newbury RG20 7NN, Berks, England. FU NCI NIH HHS [CA53874]; NIDDK NIH HHS [DK47677-01, R01 DK047677, P30DK433-51] NR 41 TC 33 Z9 33 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 11 PY 1999 VL 96 IS 10 BP 5628 EP 5633 DI 10.1073/pnas.96.10.5628 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195JG UT WOS:000080246500057 PM 10318935 ER PT J AU Liman, ER Corey, DP Dulac, C AF Liman, ER Corey, DP Dulac, C TI TRP2: A candidate transduction channel for mammalian pheromone sensory signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VOMERONASAL ORGAN; MULTIGENE FAMILY; ADENYLYL-CYCLASE; BETA-GAMMA; G-PROTEINS; DROSOPHILA; RECEPTORS; NEURONS; HOMOLOG; CALCIUM AB The vomeronasal organ (VNO) of terrestrial vertebrates plays a key role in the detection of pheromones, chemicals released by animals that elicit stereotyped sexual and aggressive behaviors among conspecifics, Sensory transduction in the VNO appears unrelated to that in the vertebrate olfactory and visual systems: the putative pheromone receptors of the VNO are evolutionarily independent from the odorant receptors and, in contrast to vertebrate visual and olfactory transduction, vomeronasal transduction is unlikely to be mediated by cyclic-nucleotide-gated channels. We hypothesized that sensory transduction in the VNO might instead involve an ion channel of the transient receptor potential (TRP) family, members of which mediate cyclic-nucleotide-independent sensory responses in Drosophila melanogaster and Caenorhabditis elegans and play unknown functions in mammals. We have isolated a cDNA (rTRP2) from rat VNO encoding a protein of 885 amino acids that is equally distant from vertebrate and invertebrate TRP channels (10-30% amino acid identity). rTRP2 mRNA is exclusively expressed in VNO neurons, and the protein is highly localized to VNO sensory microvilli, the proposed site of pheromone sensory transduction, The absence of Ca2+ stores in sensory microvilli suggests that, in contrast to a proposed mechanism of activation of mammalian TRP channels, but in accord with analysis of TRP function in Drosophila phototransduction, the gating of TRP2 is independent from the depletion of internal Ca2+ stores. Thus, TRP2 is likely to participate in vomeronasal sensory transduction, which may share additional similarities with light-induced signaling in the Drosophila eye. C1 Harvard Univ, Dept Mol & Cellular Biol, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. RP Dulac, C (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Howard Hughes Med Inst, 16 Divin Ave, Cambridge, MA 02138 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [R01 DC003903] NR 44 TC 264 Z9 279 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 11 PY 1999 VL 96 IS 10 BP 5791 EP 5796 DI 10.1073/pnas.96.10.5791 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 195JG UT WOS:000080246500085 PM 10318963 ER PT J AU Fine, MJ Stone, RA Singer, DE Coley, CM Marrie, TJ Lave, JR Hough, LJ Obrosky, DS Schulz, R Ricci, EM Rogers, JC Kapoor, WN AF Fine, MJ Stone, RA Singer, DE Coley, CM Marrie, TJ Lave, JR Hough, LJ Obrosky, DS Schulz, R Ricci, EM Rogers, JC Kapoor, WN TI Processes and outcomes of care for patients with community-acquired pneumonia - Results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID REQUIRING HOSPITALIZATION; ETIOLOGY; QUALITY; MULTICENTER AB Background: Although understanding the processes of care and medical outcomes for patients with community-acquired pneumonia is instrumental to improving the quality and cost-effectiveness of care for this illness, limited information is available on how physicians manage patients with this illness or on medical outcomes other than short-term mortality. Objectives: To describe the processes of care and to assess a broad range of medical outcomes for ambulatory and hospitalized patients with community-acquired pneumonia. Methods: This prospective, observational study was conducted at 4 hospitals and 1 health maintenance organization in Pittsburgh, Pa, Boston, Mass, and Halifax, Nova Scotia. Data were collected via patient interviews and reviews of medical records for 944 outpatients and 1343 inpatients with clinical and radiographic evidence of community-acquired pneumonia. Processes of care and medical outcomes were assessed 30 days after presentation. Results: Only 29.7% of outpatients had 1 or more microbiologic tests performed, and only 5.7% had an assigned microbiologic cause. Although 95.7% of inpatients had 1 or moro microbiologic tests performed, a cause was established in only 29.6%. Six outpatients (0.6%) died, and 3 of these deaths were pneumonia related. Of surviving outpatients, 8.0% had 1 or more medical complications. At 30 days, 88.9% (nonemployed) to 95.6% (employed) of the surviving outpatients had returned to usual activities, yet 76.0% of outpatients had 1 or more persisting pneumonia-related symptoms. Overall, 107 inpatients (8.0%) died, and 81 of these deaths were pneumonia related. Most surviving inpatients (69.0%) had 1 or more medical complications. At 30 days, 57.3% (nonemployed) to 82.0% (employed) of surviving inpatients had returned to usual activities, and 86.1% had 1 or more persisting pneumonia-related symptoms. Conclusions: In this study, conducted primarily at hospital sites with affiliated medical education training programs, virtually all outpatients and most inpatients had pneumonia of unknown cause. Although outpatients had an excellent prognosis, pneumonia-related symptoms often persisted at 30 days. Inpatients had substantial mortality, morbidity, and pneumonia-related symptoms at 30 days. C1 Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. Dalhousie Univ, Halifax, NS, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Dept Med, Halifax, NS, Canada. Queen Elizabeth 2 Hlth Sci Ctr, Dept Microbiol, Halifax, NS, Canada. RP Montefiore Univ Hosp, Room E-820,200 Lothrop St, Pittsburgh, PA 15213 USA. EM mjfl+@pitt.edu FU AHRQ HHS [R01 HS06468] NR 38 TC 182 Z9 186 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 10 PY 1999 VL 159 IS 9 BP 970 EP 980 DI 10.1001/archinte.159.9.970 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 194EH UT WOS:000080178800008 PM 10326939 ER PT J AU Giannoukos, G Williams, LJS Chilco, PJ Abou-Samra, AB AF Giannoukos, G Williams, LJS Chilco, PJ Abou-Samra, AB TI Characterization of an element within the rat parathyroid hormone parathyroid hormone-related peptide receptor gene promoter that enhances expression in osteoblastic osteosarcoma 17/2.8 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FUNCTIONAL EXPRESSION; UBIQUITOUS PROMOTERS; COMMON RECEPTOR; PTHRP RECEPTOR; PROTEIN; MOUSE; CLONING; ACIDS; CAMP AB Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) mediate their actions via a common G-protein-coupled receptor. High levels of PTH/PTHrP receptor expression have been detected in many tissues including bone and kidney. This study has demonstrated specific PTH/PTHrP receptor expression from the U3 promoter in the osteoblastic osteosarcoma ROS 17/2.8 cell line, which expresses the endogenous PTH/PTHrP receptor, compared to rat 2 fibroblasts which do not express the endogenous PTH/PTHrP receptor gene. Transient transfection studies revealed cell-specific expression of a construct containing 4391 bp of DNA upstream of exon U3 of the PTH/PTHrP receptor gene fused to a luciferase reporter gene. Deletion mapping of the 5' region of U3 revealed that a construct containing 206 bp upstream of U3 confers cell-specific expression. These data suggest that cell-specific expression in ROS 17/2.8 involves cell-specific elements within the PTH/PTHrP receptor promoter. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK45485] NR 22 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 10 PY 1999 VL 258 IS 2 BP 336 EP 340 DI 10.1006/bbrc.1999.0641 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 199VH UT WOS:000080504400020 PM 10329388 ER PT J AU Choudhury, GG Jin, DC Kim, YS Celeste, A Ghosh-Choudhury, N Abboud, HE AF Choudhury, GG Jin, DC Kim, YS Celeste, A Ghosh-Choudhury, N Abboud, HE TI Bone morphogenetic protein-2 inhibits MAPK-dependent Elk-1 transactivation and DNA synthesis induced by EGF in mesangial cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; TRANSCRIPTION FACTOR COMPLEX; FAMILY MEDIATOR SMAD1; SIGNAL-TRANSDUCTION; FACTOR RECEPTOR; BINDING-SITE; GENE-EXPRESSION; KINASE; ACTIVATION; BETA AB Bone morphogenetic protein-2 (BMP-2) is a member of the TGF beta superfamily of growth and differentiation factors. We investigated the effect of BMP-2 on epidermal growth factor (EGF)-induced mitogenic signaling in kidney glomerular mesangial cells. BMP-2 dose-dependently inhibits EGF-induced DNA synthesis. Maximum effect was obtained at a concentration of 100 ng/ml. BMP-2 had no inhibitory effect on the EGF receptor (EGFR)-associated tyrosine kinase activity indicating that inhibition of DNA synthesis is due to regulation of post-receptor signaling event(s). EGF stimulates MAPK activity in mesangial cells in a time-dependent manner. Inhibition of MAPK by the MEK inhibitor PD098059 blocks EGF-induced DNA synthesis indicating the requirement of this enzyme activity in EGF-mediated mitogenic signaling. Furthermore, we show that exposure of mesangial cells to BMP-S blocks EGF-induced MAPK activity which leads to phosphorylattion of Elk-1 transcription factor. Using a GAL-4 DNA binding-domain-Elk-1 transactivation domain fusion protein-based reporter assay, we demonstrate that BMP-2 inhibits EGF-induced Elk-1-mediated transcription. These data provide the first evidence that BMP-2 signaling in mesangial cells initiates a negative regulatory cross-talk with MAPK-based transcription to inhibit EGF-induced DNA synthesis. (C) 1999 Academic Press. C1 S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med & Pathol, San Antonio, TX 78284 USA. Inst Genet, Cambridge, MA 01810 USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDDK NIH HHS [DK-50190, DK 43988] NR 51 TC 23 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 10 PY 1999 VL 258 IS 2 BP 490 EP 496 DI 10.1006/bbrc.1999.0599 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 199VH UT WOS:000080504400046 PM 10329414 ER PT J AU Eck, MJ Kuriyan, J AF Eck, MJ Kuriyan, J TI Hot papers - Crystal structure - Three-dimensional structure of the tyrosine kinase c-Src by WQ Xu, SC Harrison, MJ Eck - Crystal structure of the Src family tyrosine kinase Hck by F. Sicheri, I. Moarefi, J. Kuriyan - Comments SO SCIENTIST LA English DT Editorial Material AB Michael J. Eck of Dana-Farber Cancer Institute and John Kuriyan of Rockefeller University discuss the Src-family kinases. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD MAY 10 PY 1999 VL 13 IS 10 BP 15 EP 15 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 194JK UT WOS:000080188900011 ER PT J AU Smith, D Buckle, GJ Hafler, DA Frank, DA Hollsberg, P AF Smith, D Buckle, GJ Hafler, DA Frank, DA Hollsberg, P TI HTLV-1-infected T cells evade the antiproliferative action of IFN-beta SO VIROLOGY LA English DT Article ID VIRUS TYPE-I; INTERFERON-ALPHA; HTLV-I; TYROSINE PHOSPHORYLATION; NEUROLOGICAL DISEASE; TARGETED DISRUPTION; MULTIPLE-SCLEROSIS; LEUKEMIA-LYMPHOMA; PERIPHERAL-BLOOD; KINASE-ACTIVITY AB Human T-cell lymphotropic virus type I (HTLV-I)-infected T-cell clones enter the S-phase of the cell cycle in the absence of exogenous IL-2. The pathway by which HTLV-I activates the host T cell may circumvent normal immunoregulatory mechanisms and thus be important for the pathogenesis of HTLV-I-induced diseases. The early control of viral infections is in part mediated by interferons (IFNs), which possess both antiviral and antiproliferative functions. In order to investigate the antiproliferative effect of IFN-beta on HTLV-l-induced T-cell activation, we generated T-cell clones from patients with HTLV-I-associated myelopathy/tropical spastic paraparesis by single-cell cloning under limiting dilution conditions. Here we demonstrate that HTLV-l-induced T-cell proliferation is resistant to the antiproliferative action of IFN-beta. Moreover, HTLV-I-infected T-cell clones continue to constitutively secrete IFN-gamma in the presence of high doses of IFN-beta. HTLV-l-infected T cells express normal levels of IFNAR1 and are able to respond to IFN-beta by phosphorylation of STAT1 on Tyr(701), although they display a relative increase in phosphorylation of the transcriptionally inactive STAT1 beta when compared with STAT1 alpha. Thus, HTLV-I promotes cell cycle progression in G(1) by a mechanism that overcomes inhibitory signals, thereby circumventing an innate immune defense mechanism. (C) 1999 Academic Press. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. RP Hollsberg, P (reprint author), Aarhus Univ, Dept Med Microbiol & Immunol, Bartholin Bldg, DK-8000 Aarhus C, Denmark. FU PHS HHS [K08] NR 49 TC 10 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 1999 VL 257 IS 2 BP 314 EP 321 DI 10.1006/viro.1999.9679 PG 8 WC Virology SC Virology GA 198ZL UT WOS:000080454600006 PM 10329542 ER PT J AU Kachnic, LA Wu, B Wunsch, H Mekeel, KL DeFrank, JS Tang, W Powell, SN AF Kachnic, LA Wu, B Wunsch, H Mekeel, KL DeFrank, JS Tang, W Powell, SN TI The ability of p53 to activate downstream genes p21(WAF1/cip1) and MDM2, and cell cycle arrest following DNA damage is delayed and attenuated in scid cells deficient in the DNA-dependent protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND BREAK REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; V(D)J RECOMBINATION; IONIZING-RADIATION; ATAXIA-TELANGIECTASIA; CHECKPOINT PATHWAY; KU-AUTOANTIGEN; G(1) ARREST; KINASE; MUTATION AB scid mouse embryonic fibroblasts are deficient in DNA-dependent protein kinase activity due to a mutation in the C-terminal domain of the catalytic subunit (DNA-PKcs). when exposed to ionizing radiation, the increase in levels of p53 was the same as in normal mouse embryonic fibroblasts. However, the rise in p21(WAF1/cip1) and mdma was found to be delayed and attenuated, which ;correlated in time with delayed onset of G(1)/S arrest by now cytometric analysis. The p53-dependent G(1) checkpoint was not eliminated: inactivation of p53 by the E6 protein in scid cells resulted in the complete loss of detectable G(1)/S arrest after DNA damage, Immunofluorescence analysis of normal cells revealed p53 to be localized predominantly within the cytoplasm prior to irradiation and then translocate to the nucleus after irradiation. In contrast, scid cells show abnormal accumulation of p53 in the nucleus independent of irradiation, which was confirmed by immunoblot analysis of nuclear lysates. Taken together, these data suggest that loss of DNA-PK activity appears to attenuate the kinetics of p53 to activate downstream genes, implying that DNA-PK plays a role in post-translational modification of p53, without affecting the increase in levels of p53 in response to DNA damage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Boston, MA 02114 USA. RP Powell, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Cox 302,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA58985] NR 66 TC 38 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 7 PY 1999 VL 274 IS 19 BP 13111 EP 13117 DI 10.1074/jbc.274.19.13111 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194NL UT WOS:000080200400026 PM 10224064 ER PT J AU Devine, JH Eubank, DW Clouthier, DE Tontonoz, P Spiegelman, BM Hammer, RE Beale, EG AF Devine, JH Eubank, DW Clouthier, DE Tontonoz, P Spiegelman, BM Hammer, RE Beale, EG TI Adipose expression of the phosphoenolpyruvate carboxykinase promoter requires peroxisome proliferator-activated receptor gamma and 9-cis-retinoic acid receptor binding to an adipocyte-specific enhancer in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SPECIFIC EXPRESSION; HUMAN GROWTH-HORMONE; GENE-EXPRESSION; TRANSGENIC MICE; PPAR-GAMMA; COUP-TF; GTP; TRANSCRIPTION; UPSTREAM; PATHWAY AB A putative adipocyte-specific enhancer has been mapped to approximately 1 kilobase pair upstream of the cytosolic phosphoenolpyruvate carboxykinase (PEPCK) gene, In the present study, we used transgenic mice to identify and characterize the 413-base pair (bp) region between -1242 and -828 bp as a bona fide adipocyte-specific enhancer in vivo. This enhancer functioned most efficiently in the context of the PEPCK promoter. The nuclear receptors peroxisome proliferator-activated receptor gamma (PPAR gamma) and g-cis-retinoic acid receptor (RXR) are required for enhancer function in vivo because: 1) a 3-bp mutation in the PPAR gamma-/RXR-binding element centered at -992 bp, PCK2, completely abolished transgene expression in adipose tissue; and 2) electrophoretic mobility supershift experiments with specific antibodies indicated that PPAR gamma and RXR are the only factors in adipocyte nuclear extracts which bind PCK2, In contrast, a second PPAR gamma/RXR-binding element centered at -446 bp, PCK1, is not involved in adipocyte specificity because inactivation of this site did not affect transgene expression, Moreover, electrophoretic mobility shift experiments indicated that, unlike PCK2, PCK1 is not selective for PPAR gamma/RXR-binding. To characterize the enhancer further, the rat and human PEPCK 5'-flanking DNA sequences were compared by computer and found to have significant similarities in the enhancer region. This high level of conservation suggests that additional transcription factors are probably involved in enhancer function. A putative human PCK2 element was identified by this sequence comparison. The human and rat PCK2 elements bound PPAR gamma/RXR with the same affinities. This work provides the first in vivo evidence that the binding of PPAR gamma to its target sequences is absolutely required for adipocyte-specific gene expression. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. Univ Texas, SW Med Ctr, Dept Biochem, Howard Hughes Med Inst, Dallas, TX 75235 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Beale, EG (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. OI Beale, Elmus/0000-0002-7758-0600 FU NIGMS NIH HHS [R01GM39895] NR 36 TC 69 Z9 74 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 MAY 7 PY 1999 VL 274 IS 19 BP 13604 EP 13612 DI 10.1074/jbc.274.19.13604 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194NL UT WOS:000080200400093 PM 10224131 ER PT J AU Lin, KI Pasinelli, P Brown, RH Hardwick, JM Ratan, RR AF Lin, KI Pasinelli, P Brown, RH Hardwick, JM Ratan, RR TI Decreased intracellular superoxide levels activate Sindbis virus-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROGRAMMED CELL-DEATH; ALPHAVIRUS-INDUCED APOPTOSIS; NF-KAPPA-B; OXIDATIVE STRESS; NEURONAL APOPTOSIS; HYDROGEN-PEROXIDE; TRANSGENIC MICE; MAMMALIAN-CELLS; INFECTED-CELLS AB Infection of many cultured cell types with Sindbis virus (SV), an alphavirus, triggers apoptosis through a commonly utilized caspase activation pathway. However, the upstream signals by which SV activates downstream apoptotic effecters, including caspases, remain unclear. Here we report that in AT-3 prostate carcinoma cells, SV infection decreases superoxide (O-radical anion) levels within minutes of infection as monitored by an aconitase activity assay. This SV-induced decrease in O-radical anion levels appears to activate or modulate cell death, as a recombinant SV expressing the O-radical anion scavenging enzyme, copper/zinc superoxide dismutase (SOD), potentiates SV-induced apoptosis. A recombinant SV expressing a mutant form of SOD, which has reduced SOD activity, has no effect. The potentiation of SV-induced apoptosis by wild type SOD is because of its ability to scavenge intracellular OX rather than its ability to promote the generation of hydrogen peroxide. Pyruvate, a peroxide scavenger, does not affect the ability of wild type SOD to potentiate cell death; and increasing the intracellular catalase activity via a recombinant SV vector has no effect on SV-induced apoptosis, Moreover, increasing intracellular O-radical anion by treatment of 3T3 cells with paraquat protects them from SV-induced death. Altogether, our results suggest that SV may activate apoptosis by reducing intracellular superoxide levels and define a novel redox signaling pathway by which viruses can trigger cell death. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Ratan, RR (reprint author), Harvard Univ, Sch Med, Dept Neurol, 77 Ave Louis Pasteur,Rm 857, Boston, MA 02115 USA. FU NINDS NIH HHS [K08 NS01951, R29 NS34943] NR 63 TC 29 Z9 29 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 7 PY 1999 VL 274 IS 19 BP 13650 EP 13655 DI 10.1074/jbc.274.19.13650 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 194NL UT WOS:000080200400099 PM 10224137 ER PT J AU Lambert, CR Kochevar, IE Redmond, RW AF Lambert, CR Kochevar, IE Redmond, RW TI Differential reactivity of upper triplet states produces wavelength-dependent two-photon photosensitization using Rose Bengal SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID LASER FLASH-PHOTOLYSIS; ROSE-BENGAL; INTENSITY; DYES; CHLORPROMAZINE; MECHANISM; PHOTOIONIZATION; EXCITATION; PROMAZINE AB Two-photon laser flash photolysis was used to investigate the wavelength dependence of upper excited state chemistry of Rose Bengal (RE) in order to rationalize differences in RE-sensitized inhibition of acetylcholinesterase (ACE) in red blood cell ghosts, observed using different irradiation modes. The absorption of the RE triplet state, generated using 532-nm irradiation, was monitored as a function of wavelength used for subsequent excitation to upper triplet levels. Triplet state bleaching, due to formation of radical species, was observed using wavelengths greater than similar to 580 nm to excite into an upper state, T-n. However, no bleaching was observed at lower wavelengths, corresponding to higher photon energies, but an increase in emission intensity from the sample, consistent with S-1 - S-0 fluorescence, was observed following the second pulse. A mechanism for this wavelength-dependent photochemistry is provided, which considers the relative positions of upper singlet and triplet states. Reverse intersystem crossing, and hence repopulation of the triplet state, are only observed when the energy of the second photon is sufficient to access a triplet state (Tn+1) of similar energy to the S-2 state. At lower photon energies (higher wavelengths), a lower energy state (T-n) state is accessed, from which radical formation and bleaching of the triplet state ensues. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Connecticut Coll, Dept Chem, New London, CT 06320 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 21 TC 21 Z9 21 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAY 6 PY 1999 VL 103 IS 18 BP 3737 EP 3741 DI 10.1021/jp983812e PG 5 WC Chemistry, Physical SC Chemistry GA 196HW UT WOS:000080303800036 ER PT J AU Present, DH Rutgeerts, P Targan, S Hanauer, SB Mayer, L van Hogezand, RA Podolsky, DK Sands, BE Braakman, T DeWoody, KL Schaible, TF van Deventer, SJH AF Present, DH Rutgeerts, P Targan, S Hanauer, SB Mayer, L van Hogezand, RA Podolsky, DK Sands, BE Braakman, T DeWoody, KL Schaible, TF van Deventer, SJH TI Infliximab for the treatment of fistulas in patients with Crohn's disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MONOCLONAL-ANTIBODY CA2; TUMOR-NECROSIS-FACTOR; INFLAMMATORY BOWEL-DISEASE; FACTOR-ALPHA; ULCERATIVE-COLITIS; ACTIVITY INDEX; METRONIDAZOLE; 6-MERCAPTOPURINE; CYCLOSPORINE; THERAPY AB Background Enterocutaneous fistulas are a serious complication of Crohn's disease and are difficult to treat. Infliximab, a chimeric monoclonal antibody to tumor necrosis factor a, has recently been developed as a treatment for Crohn's disease. We conducted a randomized, multicenter, double-blind, placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn's disease. Methods The study included 94 adult patients who had draining abdominal or perianal fistulas of at least three months' duration as a complication of Crohn's disease. Patients were randomly assigned to receive one of three treatments: placebo (31 patients), 5 mg of infliximab per kilogram of body weight (31 patients), or 10 mg of infliximab per kilogram (32 patients); all three were to be administered intravenously at weeks 0, 2, and 6. The primary end point was a reduction of 50 percent or more from base line in the number of draining fistulas observed at two or more consecutive study visits. A secondary end point was the closure of all fistulas. Results Sixty-eight percent of the patients who received 5 mg of infliximab per kilogram and 56 percent of those who received 10 mg per kilogram achieved the primary end point as compared with 26 percent of the patients in the placebo group (P=0.002 and P=0.02, respectively). In addition, 55 percent of the patients assigned to receive 5 mg of infliximab per kilogram and 38 percent of those assigned to 10 mg per kilogram had closure of all fistulas, as compared with 13 percent of the patients assigned to placebo (P=0.001 and P=0.04, respectively). The median length of time during which the fistulas remained closed was three months. More than 60 percent of patients in ail the groups had adverse events. For patients treated with infliximab, the most common were headache, abscess, upper respiratory tract infection, and fatigue. Conclusions Infliximab is an efficacious treatment for fistulas in patients with Crohn's disease. (N Engl J Med 1999;340:1398-405.) (C) 1999, Massachusetts Medical Society. C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Katholieke Univ Leuven Hosp, Louvain, Belgium. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Chicago, Chicago, IL 60637 USA. Leiden Univ, Med Ctr, Leiden, Netherlands. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Centocor, Malvern, PA USA. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. RP Present, DH (reprint author), 12 E 86th St, New York, NY 10028 USA. NR 26 TC 1607 Z9 1667 U1 8 U2 43 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 6 PY 1999 VL 340 IS 18 BP 1398 EP 1405 DI 10.1056/NEJM199905063401804 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 192QN UT WOS:000080090600004 PM 10228190 ER PT J AU Shipley, WU Thames, HD Sandler, HM Hanks, GE Zietman, AL Perez, CA Kuban, DA Hancock, SL Smith, CD AF Shipley, WU Thames, HD Sandler, HM Hanks, GE Zietman, AL Perez, CA Kuban, DA Hancock, SL Smith, CD TI Radiation therapy for clinically localized prostate cancer - A multi-institutional pooled analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; EXTERNAL-BEAM RADIATION; PSA ERA; ANTIGEN; RECURRENCE; PATTERNS; DISEASE; MEN AB Context Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrences following primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatment is limited and available mainly as single-institution reports. Objectives To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radical external beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treated since 1988, the PSA era. Design and Setting Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with external beam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years. Outcome data were analyzed using Cox regression and recursive partitioning techniques. Patients A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beam radiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher. A minimum of 2 years of subsequent follow-up was required for participation, Main Outcome Measure Actuarial estimates of freedom from biochemical failure. Results The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are 85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%), respectively, The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10 ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSA level, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patients with a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level at least 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10. The estimated rates of survival free of biochemical failure at 5 years are 81% for group 1, 69% for group 2, 47% for group 3, and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsed from the fifth to the eighth year, Conclusions Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Texas, MD Anderson Cancer Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. Eastern Virginia Med Sch, Dept Radiat Oncol, Norfolk, VA 23501 USA. Stanford Univ, Med Ctr, Dept Radiat Oncol, Palo Alto, CA 94304 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 27 TC 323 Z9 327 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1999 VL 281 IS 17 BP 1598 EP 1604 DI 10.1001/jama.281.17.1598 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 191MJ UT WOS:000080025900023 PM 10235152 ER PT J AU Wolf, GL AF Wolf, GL TI Delivery of diagnostic agents: achievements and challenges SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. RP Wolf, GL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Imaging & Pharmaceut Res, 149 13th St, Charlestown, MA 02129 USA. NR 0 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 4 PY 1999 VL 37 IS 1-3 BP 1 EP 12 DI 10.1016/S0169-409X(98)00107-0 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190RW UT WOS:000079979400001 ER PT J AU Khaw, BA AF Khaw, BA TI Antibodies as delivery systems for diagnostic functions SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE monoclonal antibodies; acute myocardial infarction; cardiomyopathies; thrombosis; athersclerotic lesions; imaging; immunoscintigraphy; charge-modified antibodies; antimyosin antibody; antifibrin antibody; anti-atherosclerotic lesion specific antibody ID EXPERIMENTAL ATHEROSCLEROTIC LESIONS; COMPLEMENTARITY-DETERMINING REGION; ACUTE MYOCARDIAL-INFARCTION; MONOCLONAL ANTIMYOSIN FAB; NEGATIVE-CHARGE; CARCINOEMBRYONIC ANTIGEN; RADIOLABELED ANTIBODIES; (FAB')2 FRAGMENTS; CARDIAC MYOSIN; SCINTIGRAPHY AB Antibodies are highly specific targeting agents. Therefore, they are invaluable for in vitro and in vivo diagnostic applications. With the advent of monoclonal antibody technology, the utilization of antibodies has increased dramatically in almost every field of biological sciences. The present review describes the utility of monoclonal antibodies primarily in the cardiovascular diseases. Monoclonal antimyosin antibodies have been developed for noninvasive scintigraphic imaging of equivocal acute myocardial infarction. They have been negative charge modified to provide quicker in vivo visualization of the targeted antibody, as well as being applied for diagnosis of other cardiomyopathies that have disruption of myocardial cell membrane as an obligatory component of the disease. The radiolabeling techniques developed initially for myocardial necrosis imaging have also been applied for imaging; of intravascular blood clots and atherosclerotic lesions. The applications of antimyosin, antifibrin and anti-atherosclerotic lesion specific monoclonal antibodies have all achieved initial clinical verification of their efficacy to target the respective lesions. However, to date, only antimyosin has been approved by the FDA for commercialization. Others must await additional studies to unequivocally verify the clinical utilities. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Ctr Drug Targeting, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Khaw, BA (reprint author), Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Ctr Drug Targeting, Rm 205,Mugar Bldg, Boston, MA 02115 USA. NR 79 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 4 PY 1999 VL 37 IS 1-3 BP 63 EP 80 DI 10.1016/S0169-409X(98)00111-2 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190RW UT WOS:000079979400005 ER PT J AU Babich, JW Fischman, AJ AF Babich, JW Fischman, AJ TI Targeted imaging of infection SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE inflammation; infection; targeting; agents ID TC-99M-LABELED CHEMOTACTIC PEPTIDES; POLYCLONAL HUMAN-IMMUNOGLOBULIN; ACUTE BACTERIAL-INFECTION; WHITE BLOOD-CELLS; FOCAL SITES; MONOCLONAL-ANTIBODIES; PHAGOCYTIC LEUKOCYTES; INFLAMMATORY LESIONS; LABELING LEUKOCYTES; RADIOACTIVE AGENTS AB The prompt identification, localization and characterization of focal sites of infection in the patients with fever is a critical step in clinical management, particularly, when localizing symptoms are not present. Although the classic signs of inflammation are suitable to localize injury at superficial sites or in the extremities, inflammation of internal structures, such as in the brain, chest and abdomen, can be difficult to localize without additional diagnostic procedures. Tissue injury, regardless of cause or anatomical site, results in a complex series of physiologic changes that we recognize as the inflammatory response. The inflammatory response is characterized by a series of biochemical events in the insulted cells and surrounding structures that results in the three major pathophysiological components: increased tissue perfusion, increased vascular permeability, and leukocytic exudation. Exploitation of the early attributes of the inflammatory process are not sufficient for the routine detection of inflammation. Currently, reagents for targeting infection represent cellular or protein components involved in the inflammatory process. Such approaches have met with some success as these agents comprise integral parts of the complex phenomena known as inflammation. This same fact also limits their utility, improved agents for targeting infection will likely be based on small molecules whose diffusion into the lesion is not hindered by molecular size constraints and which bind to molecular targets at the site of infection/inflammation. In general, the lower molecular weight should also lead to enhanced blood clearance, avoiding elevated blood pool activity which contributes to background. New agents should also obviate the need to handle blood, as this represents potential hazards to both patient and the medical personnel alike. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Babich, JW (reprint author), Biostream Inc, 160 2nd St, Cambridge, MA 02142 USA. NR 97 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 4 PY 1999 VL 37 IS 1-3 BP 237 EP 252 DI 10.1016/S0169-409X(98)00096-9 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190RW UT WOS:000079979400016 ER PT J AU Abbott, NJ Chugani, DC Zaharchuk, G Rosen, BR Lo, EH AF Abbott, NJ Chugani, DC Zaharchuk, G Rosen, BR Lo, EH TI Delivery of imaging agents into brain SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HIGH-RESOLUTION MEASUREMENT; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BENZODIAZEPINE-RECEPTOR-BINDING; 3-DIMENSIONAL FUNCTIONAL CT; CENTRAL-NERVOUS-SYSTEM; TRACER BOLUS PASSAGES; LIVING HUMAN-BRAIN; MEAN TRANSIT-TIME AB Delivery of diagnostic agents to the central nervous system (CNS) poses several challenges as a result of the special features of CNS blood vessels and tissue fluids. Diffusion barriers exist between blood and neural tissue, in the endothelium of parenchymal vessels (blood-brain barrier, BBB), and in the epithelia of the choroid plexuses and arachnoid membrane (blood-CSF barriers), which severely restrict penetration of several diagnostic imaging agents. The anatomy of large vessels can be imaged using bolus injection of X-ray contrast agents to identify sites of malformation or occlusion, and blood flow measured using MRT and CT, while new techniques permit analysis of capillary perfusion and blood volume. Absolute quantities can be derived, although relative measures in different CNS regions may be as useful in diagnosis. Local blood flow, blood volume, and their ratio (mean transit time) can be measured with high speed tomographic imaging using MRT and CT. Intravascular contrast agents for MRI are based on high magnetic susceptibility agents such as gadolinium, dysprosium and iron. Steady-state imaging using agents that cross the BBB including I-123- and Tc-99m-labelled lipophilic agents with SPECT, gives a 'snapshot' of perfusion at the time of injection. Cerebral perfusion can also be measured with PET, using (H2O)-O-15, C-11- or O-15-butanol, and F-18-fluoromethane, and cerebral blood volume measured with (CO)-O-15. Recent advances in MRI permit the non-invasive 'labelling' of endogenous water protons in flowing blood, with subsequent detection as a measure of blood flow. Imaging the BBB most commonly involves detecting disruptions of the barrier, allowing contrast agents to leak out of the vascular system. Gd-DTPA is useful in imaging leaky vessels as in some cerebral tumors, while the shortening of T-1 by MR contrast agents can be used to detect more subtle changes in BBB permeability to water as in cerebral ischemia. Techniques for imaging the dynamic activity of the brain parenchyma mainly involve PET, using a variety of radiopharmaceuticals to image glucose transport and metabolism, neurotransmitter binding and uptake, protein synthesis and DNA dynamics. PET methods permit detailed analysis of regional function by comparing resting and task-related images, important in improving understanding of both normal and pathological brain function. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ London Kings Coll, Div Biomed, London WC2R 2LS, England. Wayne State Univ, Sch Med, Childrens Hosp Michigan, PET Ctr, Detroit, MI 48201 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. RP Abbott, NJ (reprint author), Univ London Kings Coll, Div Biomed, London WC2R 2LS, England. FU Wellcome Trust NR 153 TC 35 Z9 35 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 4 PY 1999 VL 37 IS 1-3 BP 253 EP 277 DI 10.1016/S0169-409X(98)00097-0 PG 25 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190RW UT WOS:000079979400017 PM 10837739 ER PT J AU Bogdanov, AA Lewin, M Weissleder, R AF Bogdanov, AA Lewin, M Weissleder, R TI Approaches and agents for imaging the vascular system SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE imaging; contrast agent; graft co-polymer; poly(ethylene glycol; chelate; paramagnetic; gadolinium; angiogenesis; blood pool ID POOL CONTRAST AGENT; SUPERPARAMAGNETIC IRON-OXIDE; GD-DTPA-POLYLYSINE; RED-BLOOD-CELLS; HUMAN-SERUM-ALBUMIN; STERICALLY STABILIZED LIPOSOMES; COATED LIPID VESICLES; MR-ANGIOGRAPHY; GD3+-DIETHYLENETRIAMINEPENTAACETIC ACID; PARAMAGNETIC PROPERTIES AB Several classes of vascular imaging agents are described: (1) liposome-based blood cell mimetics; (2) plasma protein mimetics; (3) small molecules that bind to plasma proteins in the circulation. The characteristic features of the different agents are described and critically compared, including the advantages and potential pitfalls of each individual type. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Bogdanov, AA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Bldg 149,13th St, Boston, MA 02129 USA. NR 96 TC 39 Z9 43 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAY 4 PY 1999 VL 37 IS 1-3 BP 279 EP 293 DI 10.1016/S0169-409X(98)00098-2 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 190RW UT WOS:000079979400018 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Evans, JC Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Evans, JC Levy, D TI Heritability of heart rate variability - The Framingham Heart Study SO CIRCULATION LA English DT Article DE heart rate; genetics; epidemiology ID RESPIRATORY SINUS ARRHYTHMIA; FREQUENCY-DOMAIN; MORTALITY; DISEASE; RISK AB Background-There is evolving evidence that heart rate (HR) is genetically determined. Heart rate variability (HRV) measured by power spectral analysis provides quantitative phenotypic markers of autonomic nervous system activity. Reported determinants of HR and HRV only partially explain their variability in the population. The purpose of this study was to assess the heritability of HR and HRV and estimate the contribution of genetic factors to their variance. Methods and Results-Subjects who underwent ambulatory recordings at a routine examination were eligible; subjects with congestive heart failure, coronary artery disease, diabetes mellitus, and those taking cardioactive medications were excluded. We analyzed high-frequency power, low-frequency power, very low-frequency power, total power, low-frequency/high-frequency ratio, and the standard deviation of normal R-R intervals from 2-hour continuous ECG recordings. Heritability analysis was done by studying correlations between siblings (n = 682, in 291 sibships, 517 pairs) and between spouse pairs (n = 206 pairs) after adjusting for important covariates. Results from separate models were combined to estimate the components of variance attributable to measured covariates, additive genetic effects (heritability), and household effects. After adjusting for covariates, the correlations were consistently higher among siblings (0.21 to 0.26) compared with spouses (0.01 to 0.19). The measured covariates in general accounted for 13% to 40% of the total phenotypic variance, whereas genetic factors accounted for 13% to 23% of the variation among HR and HRV measures. Conclusions-Heritable factors may explain a substantial proportion of the variance in HR and HRV. These results highlight the contribution of genetic versus environmental factors to autonomic nervous system activity. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. Harvard Univ, Beth Israel Hosp, Sch Med, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Hosp, Sch Med, Div Clin Epidemiol, Boston, MA 02215 USA. Kansai Med Univ, Osaka, Japan. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 5 Thurber St, Framingham, MA 01702 USA. NR 24 TC 131 Z9 135 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 MAY 4 PY 1999 VL 99 IS 17 BP 2251 EP 2254 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 191CW UT WOS:000080004900006 PM 10226089 ER PT J AU Koch, M Olson, PF Albus, A Jin, W Hunter, DD Brunken, WJ Burgeson, RE Champliaud, MF AF Koch, M Olson, PF Albus, A Jin, W Hunter, DD Brunken, WJ Burgeson, RE Champliaud, MF TI Characterization and expression of the laminin gamma 3 chain: A novel, non-basement membrane-associated, laminin chain SO JOURNAL OF CELL BIOLOGY LA English DT Article DE laminin; testis; oviduct; lung; chromosome 9q31-34 ID CONGENITAL MUSCULAR-DYSTROPHY; HEPARAN-SULFATE PROTEOGLYCAN; CENTRAL-NERVOUS-SYSTEM; AMINO-ACID SEQUENCE; COLLAGEN TYPE-IV; EGF-LIKE MOTIF; S-LAMININ; CHROMOSOMAL ASSIGNMENT; NIDOGEN BINDING; CELL-ADHESION AB Laminins are heterotrimeric molecules composed of an alpha, a beta, and a gamma chain; they have broad functional roles in development and in stabilizing epithelial structures. Here, we identified a novel laminin, composed of known alpha and beta chains but containing a novel gamma chain, gamma 3. We have cloned gene encoding this chain, LAMC3, which maps to chromosome 9 at q31-34. Protein and cDNA analyses demonstrate that gamma 3 contains all the expected domains of a gamma chain, including two consensus glycosylation sites and a putative nidogen-binding site. This suggests that gamma 3-containing laminins are likely to exist in a stable matrix. Studies of the tissue distribution of gamma 3 chain show that it is broadly expressed in: skin, heart, lung, and the reproductive tracts. In skin, gamma 3 protein is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. The gamma 3 chain is also a prominent element of the apical surface of ciliated epithelial cells of: lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma 3-containing laminins on the apical surfaces of a variety of epithelial tissues is novel and suggests that they are not found within ultrastructurally defined basement membranes. It seems likely that these apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02129 USA. Tufts Univ, Dept Neurosci, Sch Med, Boston, MA 02111 USA. Tufts Univ, Dept Anat & Cell Biol, Sch Med, Boston, MA 02111 USA. Tufts Univ, Dept Ophthalmol, Sch Med, Boston, MA 02111 USA. RP Champliaud, MF (reprint author), MGH E CBRC Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [AR35689]; NINDS NIH HHS [R01 NS039502, R01 NS039502-03] NR 80 TC 172 Z9 174 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY 3 PY 1999 VL 145 IS 3 BP 605 EP 617 DI 10.1083/jcb.145.3.605 PG 13 WC Cell Biology SC Cell Biology GA 194PW UT WOS:000080203600017 PM 10225960 ER PT J AU Li, SG Ilaria, RL Million, RP Daley, GQ Van Etten, RA AF Li, SG Ilaria, RL Million, RP Daley, GQ Van Etten, RA TI The P190, P210, and P230 forms of the BCR/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Abelson virus; retroviral vector; chronic myelogenous leukemia; mouse cancer model ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCR-ABL ONCOGENE; HEMATOPOIETIC STEM-CELLS; POSITIVE ACUTE-LEUKEMIA; PHILADELPHIA-CHROMOSOME; BONE-MARROW; DISTINCT DISEASE; FUSION PROTEINS; TYROSINE KINASE AB The product of the Philadelphia chromosome (Ph) translocation, the BCR/ABL oncogene, exists in three principal forms (P190, P210, and P230 BCR/ABL) that are found in distinct forms of Ph-positive leukemia, suggesting the three proteins have different leukemogenic activity. We have directly compared the tyrosine kinase activity, in vitro transformation properties, and in vivo leukemogenic activity of the P190, P210, and P230 forms of BCR/ABL. P230 exhibited lower intrinsic tyrosine kinase activity than P210 and P190. Although all three oncogenes transformed both myeloid (32D cl3) and lymphoid (Ba/F3) interleukin (IL)3-dependent cell lines to become independent of IL-3 for survival and growth, their ability to stimulate proliferation of Ba/F3 lymphoid cells differed and correlated directly with tyrosine kinase activity. In a murine bone marrow transduction/transplantation model, the three forms of BCR/ABL were equally potent in the induction of a chronic myeloid leukemia (CML)-like myeloproliferative syndrome in recipient mice when 5-fluorouracil (5-FU)-treated donors were used. Analysis of proviral integration showed the CML-like disease to be polyclonal and to involve multiple myeloid and B lymphoid lineages, implicating a primitive multipotential target cell. Secondary transplantation revealed that only certain minor clones gave rise to day 12 spleen colonies and induced disease in secondary recipients, suggesting heterogeneity among the target cell population. In contrast, when marrow from non-5-FU-treated donors was used, a mixture of CML-like disease, B lymphoid acute leukemia, and macrophage tumors was observed in recipients. P190 BCR/ABL induced lymphoid leukemia with shorter latency than P210 or P230. The lymphoid leukemias and macrophage tumors had provirus integration patterns that were oligo- or monoclonal and limited to the tumor cells, suggesting a lineage-restricted target cell with a requirement for additional events in addition to BCR/ABL transduction for full malignant transformation. These results do not support the hypothesis that P230 BCR/ABL induces a distinct and less aggressive form of CML in humans, and suggest that the rarity of P190 BCR/ABL in human CML may reflect frequent BCR intron 1 breakpoints during the genesis of the Ph chromosome in stem cells, rather than intrinsic differences in myeloid leukemogenicity between P190 and P210. C1 Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Div Adult Oncol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57593]; NHLBI NIH HHS [HL03310] NR 60 TC 320 Z9 333 U1 2 U2 12 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 3 PY 1999 VL 189 IS 9 BP 1399 EP 1412 DI 10.1084/jem.189.9.1399 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 194NR UT WOS:000080200900005 PM 10224280 ER PT J AU Horner, MD Waid, LR Johnson, DE Latham, PK Anton, RF AF Horner, MD Waid, LR Johnson, DE Latham, PK Anton, RF TI The relationship of cognitive functioning to amount of recent and lifetime alcohol consumption in outpatient alcoholics SO ADDICTIVE BEHAVIORS LA English DT Article DE alcoholism; neuropsychology; cognition AB Previous investigations of the relationship between drinking patterns and cognitive functioning have generally studied severely alcoholic patients, in whom the neurocognitive effects of alcohol consumption can be obscured by other medical or psychosocial factors. In the present study, cognitive functioning was examined after a minimum of 4 days of abstinence in 69 mildly to moderately alcohol-dependent outpatients without comorbid psychiatric, neurologic, or systemic medical illness. Circumscribed decrements in reaction time and verbal memory were associated with higher amounts of alcohol consumption in the 90 days prior to enrollment in the study, and amount of recent consumption was correlated with scores on numerous cognitive tests. In contrast, longer drinking history was not associated with poorer performance on any neuropsychological measures. Thus, in this group of high-functioning, mildly to moderately alcohol-dependent outpatients, mild cognitive deficits were related to the amount of recent, but not lifetime, alcohol consumption. Published by Elsevier Science Ltd. C1 Ralph J Johnson DVA Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Horner, MD (reprint author), Ralph J Johnson DVA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. FU NIAAA NIH HHS [1-R01 AA09568] NR 14 TC 21 Z9 21 U1 1 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 MAY-JUN PY 1999 VL 24 IS 3 BP 449 EP 453 DI 10.1016/S0306-4603(99)00011-8 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 199UY UT WOS:000080503500015 PM 10400285 ER PT J AU Lori, F Jessen, H Lieberman, J Clerici, M Tinelli, C Lisziewicz, J AF Lori, F Jessen, H Lieberman, J Clerici, M Tinelli, C Lisziewicz, J TI Immune restoration by combination of a cytostatic drug (hydroxyurea) and anti-HIV drugs (didanosine and indinavir) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID T-CELLS; FOLLOW-UP; INFECTION; VIRUS; LYMPHOCYTES; REPLICATION; THERAPY; AIDS; HYDROXYCARBAMIDE; INDEPENDENCE AB Cell activation is essential for HIV infection. CD4(+) T lymphocyte activation allows virus replication and CD8(+) T lymphocyte activation may contribute to pathogenesis, We combined hydroxyurea, a cytostatic drug that inhibits cell activation and proliferation, with two drugs that inhibit HIV (didanosine and indinavir), to block the "cell activation-virus production-pathogenesis" cycle. HIV was strongly suppressed in treated patients, and the average CD4 count increased to 224/mm(3). Compared with a matched group of patients who had declined antiretroviral treatment, treated patients had a significantly lower proportion of activated CD8(+) T lymphocytes and a significantly higher number of naive CD8(+) and CD4(+) T lymphocytes. The proliferative responses to allogeneic and influenza virus antigens were increased in treated patients, and a defect in CD3-zeta expression, the signaling chain of the T cell receptor complex, was reversed. The use of a cytostatic drug was not detrimental to the immune system; on the contrary, the combination of antiviral and cytostatic treatment improved all of the immune parameters tested. C1 Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Jessen Praxis, D-10777 Berlin, Germany. Ctr Blood Res, Boston, MA 02115 USA. Univ Milan, Cattedra Immunol, I-20133 Milan, Italy. Policlin San Matteo, I-27100 Pavia, Italy. Res Inst Genet & Human Therapy, I-27100 Pavia, Italy. RP Lori, F (reprint author), Res Inst Genet & Human Therapy, Med Dent Bldg SW307,3900 Reservoir Rd NW, Washington, DC 20007 USA. RI Lieberman, Judy/A-2717-2015 NR 32 TC 30 Z9 30 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1999 VL 15 IS 7 BP 619 EP 624 DI 10.1089/088922299310917 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 191TF UT WOS:000080037100002 PM 10331440 ER PT J AU de la Monte, SF Ganju, N Tanaka, S Banerjee, K Karl, PJ Brown, NV Wands, JR AF de la Monte, SF Ganju, N Tanaka, S Banerjee, K Karl, PJ Brown, NV Wands, JR TI Differential effects of ethanol on insulin-signaling through the insulin receptor substrate-1 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE insulin receptor substrate type 1; ethanol; glyceraldehyde-3-phosphate dehydrogenase; proliferating cell nuclear antigen; insulin ID SELECTIVE INHIBITOR WORTMANNIN; MAP KINASE KINASE; LIVER-REGENERATION; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; RAT ADIPOCYTES; 3T3 CELLS; TYROSINE PHOSPHORYLATION; I RECEPTOR AB Insulin stimulation increases cell proliferation and energy metabolism by activating the insulin receptor substrate I (IRS-1)-signaling pathways. This downstream signaling is mediated by interactions of specific tyrosyl phosphorylated (PY) IRS-1 motifs with SH2-containing molecules such as growth-factor receptor-bound protein 2 (Grb2) and Syp. Ethanol inhibits insulin-stimulated tyrosyl phosphorylation of IRS-1 and DNA synthesis. This study explores the roles of the Grb2- and Syp-binding motifs of IRS-I in relation to the inhibitory effects of ethanol on insulin-stimulated DNA synthesis, proliferating cell nuclear antigen (PCNA) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, and activation of mitogen-activated protein kinase (MAPK), which is known to be essential for cell proliferation. NIH3T3 cells were stably transfected with wild-type IRS-1, or IRS-1 mutated at the Grb2 (IRS-1 Delta Grb2), Syp (IRS-1 Delta Syp), or Grb2 and Syp (IRS-1 Delta Grb2 Delta Syp)- binding sites. Cells transfected with IRS-1 had increased levels of DNA synthesis, PCNA, GAPDH, and activated MAPK. The IRS-1 Delta Grb2 transfectants were highly responsive to insulin stimulation, achieving levels of GAPDH, PCNA, and activated MAPK that were higher than control. In contrast, the IRS-1 Delta Syp and IRS-1 Delta Grb2 Delta Syp transfectants had reduced levels of DNA synthesis, PCNA, and activated MAPK. Ethanol exposure decreased insulin-stimulated DNA synthesis, PCNA, GAPDH, and activated MAPK levels in all clones, but the wild-type IRS-1 transfectants were relatively resistant, and the IRS-1 Delta Grb2 transfectants were extraordinarily sensitive to these inhibitory effects of ethanol. The findings suggest that insulin-stimulated DNA synthesis and PCNA expression are mediated through the Syp-binding domain, whereas GAPDH expression and MAPK activation are modulated through both the Grb2 and Syp motifs of IRS-1. In addition. ethanol exposure may preferentially inhibit downstream signaling that requires interaction between Syp and PY-IRS-1. C1 Massachusetts Gen Hosp, Dept Med, MGH E Canc Ctr, Mol Hepatol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Kyushu Univ, Med Inst Bioregulat, Beppu, Oita, Japan. Cornell Univ Med Coll, Dept Pediat, Ithaca, NY USA. RP Brown Univ, Rhode Isl Hosp, Sch Med, Dept Med, 55 Claverick St,Room 419, Providence, RI 02903 USA. EM delamonte@hotmail.com FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-10102] NR 49 TC 26 Z9 26 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 1999 VL 23 IS 5 BP 770 EP 777 DI 10.1097/00000374-199905000-00002 PG 8 WC Substance Abuse SC Substance Abuse GA 201DG UT WOS:000080579200003 PM 10371394 ER PT J AU Lieber, CS AF Lieber, CS TI Prevention and treatment of liver fibrosis based on pathogenesis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Satellite Symposium on Alcohol-Induced Hepatic Fibrosis - Mechanisms, at the Annual Meeting of the Research-Society-on-Alcoholism CY JUN, 1998 CL HILTON HEAD ISL, SOUTH CAROLINA SP Res Soc Alcoholism, NIAAA, NIH DE alcohol; cirrhosis; cytochrome P-4502E1 (CYP2E1); microsomal ethanol oxidizing system (MEOS); polyenylphosphatidylcholine ID CHRONIC ETHANOL-CONSUMPTION; SEVERE ALCOHOLIC HEPATITIS; FAT-STORING CELLS; COLLAGEN-SYNTHESIS; POLYUNSATURATED LECITHIN; PERIVENULAR FIBROSIS; CYTOCHROME P-4502E1; TRANSITIONAL CELLS; PROTEIN-SYNTHESIS; BABOON AB Multiple agents have been proposed for the prevention and treatment of fibrosis. S-adenosylmethionine was reported to oppose CCl4-induced fibrosis in the rat, to attenuate the consequences of the ethanol-induced oxidative stress, and to decrease mortality in cirrhotics. Anti-inflammatory medications and agents that interfere with collagen synthesis, such as inhibitors of prolyl-4-hydroxylase and antioxidants, are also being tested. In nonhuman primates, polyenylphosphatidylcholine (PPC), extracted from soybeans, protected against alcohol-induced fibrosis and cirrhosis and prevented the associated hepatic phosphatidylcholine (PC) depletion by increasing 18:2 containing PC species; it also attenuated the transformation of stellate cells into collagen-producing transitional cells. Furthermore, it increased collagen breakdown, as shown in cultured stellate cells enriched with PPC or pure dilinoleoyl PC, the main PC species present in the extract. Because PPC and dilinoleoyl PC promote the breakdown of collagen, there is reasonable hope that this treatment may be useful for the management of fibrosis of alcoholic, as well as nonalcoholic, etiologies and that it may affect not only the progression of the disease, but may also reverse pre-existing fibrosis, as demonstrated for CCl4-induced cirrhosis in the rat and as presently tested in an ongoing clinical trial. C1 Bronx Vet Affairs Med Ctr, Sect Liver Dis & Nutr, Ctr Alcohol Res & Treatment, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Sect Liver Dis & Nutr, Ctr Alcohol Res & Treatment, 151-2,130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA05934, AA07275, AA11115] NR 59 TC 30 Z9 33 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 1999 VL 23 IS 5 BP 944 EP 949 DI 10.1097/00000374-199905000-00028 PG 6 WC Substance Abuse SC Substance Abuse GA 201DG UT WOS:000080579200030 PM 10371420 ER PT J AU Mayer, EA Naliboff, B Lee, O Munakata, J Chang, L AF Mayer, EA Naliboff, B Lee, O Munakata, J Chang, L TI Review article: gender-related differences in functional gastrointestinal disorders SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Roundtable Meeting on Irritable Bowel Syndrome and the role of 5-ht CY MAY 15-16, 1998 CL NEW ORLEANS, LOUISIANA SP Glaxo Wellcome Res & Dev Ltd ID IRRITABLE-BOWEL-SYNDROME; INDUCED OPIOID ANALGESIA; STRESS-INDUCED ANALGESIA; SEX-DIFFERENCES; MENSTRUAL-CYCLE; CHRONIC PAIN; DEER MICE; PEROMYSCUS-MANICULATUS; POPULATION DIFFERENCES; SWIM ANALGESIA AB Many functional gastrointestinal disorders and other chronic Visceral pain disorders such as interstitial cystitis and chronic pelvic pain are more common in women than in men. In irritable bowel syndrome (IBS) there is a 2:1 female to male ratio in prevalence of symptoms in community samples, Female irritable bowel syndrome patients are more likely to be constipated, complain of abdominal distension and of certain extracolonic symptoms. While animal studies have clearly demonstrated gender-related differences in pain perception and antinociceptive mechanisms, unequivocal evidence for gender-related differences in human pain perception or modulation has only been provided recently. Gender-related differences may be related to constant differences in the physiology of pain perception, such as structural or functional differences in the visceral afferent pathways involved in pain transmission or modulation, and/or they may be related to fluctuations in female sex hormones. Preliminary evidence suggests that female irritable bowel syndrome patients show specific perceptual alterations in regards to rectosigmoid balloon distension and that they show differences in regional brain activation measured by positron emission tomography. This preliminary evidence suggests that gender-related differences in symptoms and in the perceptual responses to visceral stimuli exist in IBS patients and can be detected using specific stimulation paradigms and neuroimaging techniques. C1 Univ Calif Los Angeles, Div Digest Dis, CURE, Neuroenter Dis Program, Los Angeles, CA USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 44 TC 68 Z9 71 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD MAY PY 1999 VL 13 SU 2 BP 65 EP 69 DI 10.1046/j.1365-2036.1999.00008.x PG 5 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 211RL UT WOS:000081175000009 PM 10429743 ER PT J AU Leon, MN Harrell, LC Simosa, HF Mahdi, NA Pathan, AZ Lopez-Cuellar, J Palacios, IF AF Leon, MN Harrell, LC Simosa, HF Mahdi, NA Pathan, AZ Lopez-Cuellar, J Palacios, IF TI Comparison of immediate and long-term results of mitral balloon valvotomy with the double-balloon versus Inoue techniques SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FOLLOW-UP; COMMISSUROTOMY; VALVULOPLASTY; CATHETER; STENOSIS; COMPLICATIONS; PREDICTORS; SERIES AB There is controversy as to whether the double-balloon or Inoue technique of percutaneous mitral balloon valvotomy (PMBV) provides superior immediate and long-term results. This study compares the immediate procedural and long-term outcomes of patients undergoing PMBV using the double-balloon versus the Inoue techniques. Seven hundred thirty-four consecutive patients who underwent PMBV using the double-balloon (n = 621) or Inoue technique (n = 113) were studied. There were no statistically significant differences in baseline clinical and morphologic characteristics between the double-balloon and Inoue patients. The double-balloon technique resulted in superior immediate outcome, as reflected in a larger post-PMBV mitral valve area (1.9 +/- 0.7 vs 1.7 +/- 0.6 cm(2); p = 0.005) and a lower incidence of 3+ mitral regulation after PMBV (5.4% vs 10.6%; p = 0.05). This superior immediate outcome of the double-balloon technique was observed only in the group of patients with echocardiographic score less than or equal to 8 (post-PMBV mitral valve areas 2.1 +/- 0.7 vs 1.8 +/- 0.6; p 0.004). Despite the difference in immediate outcome, there were no significant differences in event-free survival at long-term follow-up between the 2 techniques, Our study demonstrates that compared with the Inoue technique, the double-balloon technique results in a larger mitral value area and less degree of severe mitral regurgitation after PMBV. Despite the difference in immediate outcome between both techniques, there were no significant differences in event-free survival at long-term follow-up. (C) 1999 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Dept Med, Cardiac Unit, Boston, MA 02114 USA. NR 30 TC 13 Z9 16 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 1999 VL 83 IS 9 BP 1356 EP 1363 DI 10.1016/S0002-9149(99)00100-9 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 191FA UT WOS:000080010800011 PM 10235095 ER PT J AU Sanderson, IR AF Sanderson, IR TI The physicochemical environment of the neonatal intestine SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Developmental Ecology of the Neonatal Intesting at the Experimental Biology 97 Meeting CY APR 06-09, 1997 CL NEW ORLEANS, LOUISIANA SP HJ Heinz Co Fdn, Mead Johnson Nutritionals, Nestle Food Co, Ross Prod Div, Abbott Labs, Wyeth Nurtitionals Int DE infant; peristalsis; unstirred layer; acid microclimate; nutrient regulation of gene expression; epithelial signaling; intestine ID GROWTH FACTOR-I; RAT SMALL-INTESTINE; INFLAMMATORY BOWEL-DISEASE; EPITHELIAL-CELLS; NECROTIZING ENTEROCOLITIS; GENE-EXPRESSION; DEVELOPING PIGLETS; ACID MICROCLIMATE; MESSENGER-RNA; FATTY-ACIDS AB Dietary intake, bacterial metabolites, and the secretion of factors (eg, proteins, electrolytes, lipid-soluble molecules, and water) by the body each contribute to the physicochemical environment of the gastrointestinal tract. Peristalsis regulates the changes along the length of the intestine. However, coordinated peristaltic responses develop as premature infants mature. In addition, the physicochemical environment of the center of the intestinal lumen differs from that of the epithelial surface. The area adjacent to the small intestinal epithelium is more acid than the bulk phase. Na+/H+ exchange antiporters in the epithelial cell apical membrane generate this acidity. Mucus maintains the acid microclimate by preventing free diffusion of hydrogen ions into the bulk phase. Development also affects these mechanisms. Changes in the lumenal environment may alter the synthesis of signaling molecules expressed by the intestinal epithelium. Thus, the epithelium, through changes in gene regulation, may act as an active interface that transmits information about the composition of the intestinal lumen to the mucosal immune system. Premature neonates are at risk of necrotizing enterocolitis, a disease almost exclusively associated with oral feeds. The pathogenesis of this condition may, in part, be due to the immaturity of the interactions between I-he physicochemical environment of the lumen and intestine. C1 St Bartholomews Hosp, St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, London EC1A 7BE, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Gastroenterol Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Sanderson, IR (reprint author), St Bartholomews Hosp, St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, Domin House, London EC1A 7BE, England. FU NIDDK NIH HHS [DK-47753] NR 52 TC 30 Z9 33 U1 0 U2 7 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1999 VL 69 IS 5 BP 1028S EP 1034S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 189CB UT WOS:000079885600033 PM 10232645 ER PT J AU Renshaw, AA Richie, JP Loughlin, KR Jiroutek, M Chung, A D'Amico, AV AF Renshaw, AA Richie, JP Loughlin, KR Jiroutek, M Chung, A D'Amico, AV TI Maximum diameter of prostatic carcinoma is a simple, inexpensive, and independent predictor of prostate-specific antigen failure in radical prostatectomy specimens - Validation in a cohort of 434 patients SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE prostatic neoplasms; pathology; volume; methods; prognosis ID TUMOR VOLUME; PATHOLOGICAL STAGE; CANCER; PROGNOSIS; FEATURES AB The amount of tumor in radical prostatectomy specimens can be determined with several techniques. Maximum tumor diameter correlates well with total tumor volume and can readily be obtained in incompletely submitted specimens. Initial results in a small series suggested that this measure also may predict for prostate-specific antigen (PSA)failure. We studied whether maximum tumor diameter was an independent predictor of PSA failure in a series of 434 men who underwent radical prostatectomy because of prostatic adenocarcinoma; 118 (27.2%) had PSA failure. Preoperative PSA, Gleason score, pathologic stage, margin status, and largest tumor diameter were determined, and multivariate logistic modeling was performed on the outcome of PSA failure. Maximum tumor diameter was an independent risk factor for PSA failure, along with preoperative serum PSA level, and Gleason score greater than or equal to 8. Only 15% of men with firmer with maximum diameter <1 cm had PSA failure, compared with 73% of men with tumor with maximum diameter >2. Maximum tumor diameter of prostatic carcinoma is a simple, inexpensive, and independent predictor of PSA failure that can be obtained readily from partially submitted radical prostatectomy specimens. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Renshaw, AA (reprint author), Baptist Mem Hosp, Dept Pathol, 8900 N Kendall Dr, Miami, FL 33176 USA. NR 17 TC 44 Z9 46 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1999 VL 111 IS 5 BP 641 EP 644 PG 4 WC Pathology SC Pathology GA 189RU UT WOS:000079920500008 PM 10230354 ER PT J AU Lembo, T Naliboff, B Munakata, J Fullerton, S Saba, L Tung, S Schmulson, M Mayer, EA AF Lembo, T Naliboff, B Munakata, J Fullerton, S Saba, L Tung, S Schmulson, M Mayer, EA TI Symptoms and visceral perception in patients with pain-predominant irritable bowel syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID MYOELECTRICAL ACTIVITY; PSYCHIATRIC ILLNESS; DYSFUNCTION; DISORDERS; COMMUNITY; MOTOR AB OBJECTIVE: Abdominal pain is thought to be a hallmark of the irritable bowel syndrome (IBS), although currently used symptom criteria do not differentiate between abdominal pain and discomfort. By focusing on viscerosensory symptoms, we sought to determine: 1) which type of symptoms are most commonly reported by IBS patients, and 2) whether patients who report: pain as their most bothersome symptom differ in clinical, psychological, and physiological characteristics. METHODS: A total of 443 consecutive new patient referrals to a tertiary referral center for functional gastrointestinal disorders who met symptom criteria for IBS were given validated, psychometric, health status, and bowel symptom questionnaires containing specific questions regarding the patients' predominant viscerosensory gastrointestinal symptom. Of these patients, 155 (35%) also met criteria for functional dyspepsia. A representative subset of the total IBS patient population (n = 58) underwent evaluation of perceptual responses to controlled rectal distension before and after a noxious sigmoid conditioning stimulus. RESULTS: Viscerosensory symptoms clustered into four groups: 1) abdominal pain, 2) bloating-type discomfort, 3) sensation of incomplete rectal evacuation, and 4) extra-abdominal (chest pain or pressure and nausea), A total of 66% of patients reported gas as one of their viscerosensory symptoms, whereas 60% reported abdominal pain as one of their symptoms. Only 29% rated abdominal pain as their most bothersome symptom, whereas bloating-type symptoms were Listed by 60% as most bothersome. Although pain predominance did not correlate with the severity of gastrointestinal or psychological symptoms, there was a significant correlation with the development of rectal hypersensitivity in response to the sigmoid conditioning stimulus. CONCLUSIONS: In a tertiary referral population of IBS patients: 1) abdominal pain is reported by only one third of patients as their most bothersome viscerosensory symptoms; and 2) pain-predominance correlates with development of rectal hypersensitivity after a noxious sigmoid stimulus. (C) 1999 by Am. Cell. of Gastroenterology. C1 W Los Angeles Vet Affairs Med Ctr, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, UCLA CURE Neuroenter Dis Program, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK48354] NR 31 TC 134 Z9 138 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 1999 VL 94 IS 5 BP 1320 EP 1326 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 191MY UT WOS:000080027200034 PM 10235213 ER PT J AU Rebbeck, TR Kantoff, PN Krithivas, K Neuhausen, S Blackwood, MA Godwin, AK Daly, MB Narod, SA Garber, JE Lynch, HT Weber, BL Brown, M AF Rebbeck, TR Kantoff, PN Krithivas, K Neuhausen, S Blackwood, MA Godwin, AK Daly, MB Narod, SA Garber, JE Lynch, HT Weber, BL Brown, M TI Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROSTATE-CANCER; BRCA1; MUTATIONS; TRANSACTIVATION; CARRIERS; CELLS; GENE AB Compared with the general population, women who have inherited a germline mutation in the BRCA1 gene have a greatly increased risk of developing breast cancer. However, there is also substantial interindividual variability in the occurrence of breast cancer among BRCA1 mutation carriers. We hypothesize that other genes, particularly those involved in endocrine signaling, may modify the BRCA1-associated age-specific breast cancer risk. We studied the effect of the CAG repeat-length polymorphism found in exon 1 of the androgen-receptor (AR) gene (AR-CAG). AR alleles containing longer CAG repeat lengths are associated with a decreased ability to activate androgen-responsive genes. Using a sample of women who inherited germline BRCA1 mutations, we compared AR-CAG repeat length in 165 women with and 139 women without breast cancer. We found that women were at significantly increased risk of breast cancer if they carried at least one AR allele with greater than or equal to 28 CAG repeats. Women who carried an AR-CAG allele of greater than or equal to 28, greater than or equal to 29, or greater than or equal to 30 repeats were given a diagnosis 0.8, 1.8, or 6.3 years earlier than women who did not carry at least one such allele. All 11 women in our sample who carried at least one AR-CAG allele with greater than or equal to 29 repeats had breast cancer. Our results support the hypothesis that age at breast cancer diagnosis is earlier among BRCA1 mutation carriers who carry very long AR-CAG repeats. These results suggest that pathways involving androgen signaling may affect the risk of BRCA1-associated breast cancer. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med & Genet, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, Boston, MA 02115 USA. Univ Utah, Salt Lake City, UT USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. Creighton Univ, Dept Prevent Med, Omaha, NE 68178 USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57601, CA737370]; NIEHS NIH HHS [ES97939] NR 25 TC 189 Z9 193 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 1999 VL 64 IS 5 BP 1371 EP 1377 DI 10.1086/302366 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 192RP UT WOS:000080093000015 PM 10205268 ER PT J AU Fried, L Abidi, S Bernardini, J Johnston, JR Piraino, B AF Fried, L Abidi, S Bernardini, J Johnston, JR Piraino, B TI Hospitalization in peritoneal dialysis patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE peritoneal dialysis; hospitalization; peritonitis; morbidity ID RISK-FACTORS; SURVIVAL; MEMBRANE; CAPD; EXPERIENCE AB Hospitalization rates are declining more rapidly for peritoneal dialysis (PD) than for hemodialysis patients. This has been postulated to be caused in part by lower peritonitis rates. However, the causes of admission have not been reexamined in the setting of declining rates. We prospectively examined our hospitalization rates, causes of admission, and impact of peritonitis on hospitalization in adult PD patients at a single center over a 4-year period. There were 274 admissions in 168 patient-years for a rate of 1.6 admissions and 13.0 hospital days per patient-year. Rates were greater for men (1.8 v 1.5; P = 0.013), patients with diabetes (2.2 v 1.4, P < 0.001), and those with a higher peritoneal equilibration test result. Creatinine clearance and sex were independent predictors in a multivariate analysis. The most common causes for admission were cardiac disease (14.6%) and peritonitis (13.5%), Peritonitis accounted for 0.21 admissions and 2.0 hospital days per patient-year. Thirty percent of the incident patients were admitted during the first 90 days of dialysis. Admissions for dehydration and glucose abnormalities were more common in the first 90 days. Overall admission rates, as well as admission rates for peritonitis, did not change over time, although hospital days per year decreased. Those admitted for peritonitis had higher peritonitis rates, more time on PD, and were more likely to be black. Eighty-one percent of the admissions for peritonitis were caused by Staphylococcus aureus, Streptococcus spp, or gram-negative/fungal peritonitis. Patients with peritonitis caused by Staphylococcus epidermidis were less likely to be admitted than patients with peritonitis caused by other organisms. To conclude, peritonitis remains a common cause of hospitalization, despite low peritonitis rates. To decrease admissions for peritonitis, attention should be focused on preventing peritonitis caused by organisms other than S epidermidis, (C) 1999 by the National Kidney Foundation, Inc. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Med Serv, Renal Sect, Pittsburgh, PA USA. RP Fried, L (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, 938 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. EM lff9@vms.cis.pitt.edu OI Piraino, Beth/0000-0001-5061-0841 NR 28 TC 44 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 1999 VL 33 IS 5 BP 927 EP 933 DI 10.1016/S0272-6386(99)70428-2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 189RN UT WOS:000079919900017 PM 10213651 ER PT J AU Moseley, MJ Oenning, V Melnik, G AF Moseley, MJ Oenning, V Melnik, G TI Methemoglobinemia - The only cure is intravenous methylene blue. SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Coronary Intens Care Unit, San Antonio, TX USA. RP Moseley, MJ (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Coronary Intens Care Unit, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAY PY 1999 VL 99 IS 5 BP 47 EP 47 PG 1 WC Nursing SC Nursing GA 195TR UT WOS:000080268700026 PM 10333801 ER PT J AU Uy, HS Pineda, R Shore, JW Polcharoen, W Jakobiec, FA Foster, CS AF Uy, HS Pineda, R Shore, JW Polcharoen, W Jakobiec, FA Foster, CS TI Hypertrophic discoid lupus erythematosus of the conjunctiva SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report the ophthalmic manifestations of hypertrophic discoid lupus erythematosus of the conjunctiva, METHOD: Case report and review of biopsy results, RESULTS: A 58-year-old woman with a history of chronic blepharoconjunctivitis presented with an unusual raised conjunctival lesion. Previous biopsy slides were reviewed and interpreted as diagnostic of discoid lupus erythematosus, hypertrophic or verrucous type. Both blepharoconjunctivitis and the raised conjunctival lesion resolved with hydroxychloroquine therapy, CONCLUSIONS: A raised conjunctival mass in the context of refractory blepharoconjunctivitis should elicit suspicion for discoid lupus erythrmatosus, The hypertrophic variant of this disease can affect the conjunctiva. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 3 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 1999 VL 127 IS 5 BP 604 EP 605 DI 10.1016/S0002-9394(98)00402-4 PG 2 WC Ophthalmology SC Ophthalmology GA 194DN UT WOS:000080177000018 PM 10334357 ER PT J AU Staecker, H Nadol, JB Ojeman, R McKenna, MJ AF Staecker, H Nadol, JB Ojeman, R McKenna, MJ TI Delayed intracranial abscess after acoustic neuroma surgery: A report of two cases SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE brain abscess; acoustic neuroma; intracranial complication ID BRAIN-ABSCESS; STEREOTAXIC ASPIRATION; MENINGITIS; EXPERIENCE; DIAGNOSIS AB Objective: The use of antibiotics before and after surgery has made infectious complications of neurotologic surgery rare. The neurosurgical literature cites a rate of postoperative meningitis between 1% and 2% for "clean" cases and 1.5% to 2.5% for "clean contaminated" cases, such as cerebrospinal fluid contact with the middle ear or mastoid. Reports of infections after neurotologic procedures are rare in the otologic literature. In this report, two patients with brain abscess occurring in a delayed fashion after surgery are described. Study Design: The study design was a retrospective chart review and case report. Setting: The study was conducted at a tertiary referral center. Results: Patient 1 underwent a suboccipital craniotomy for removal of an acoustic neuroma and had an uneventful postoperative recovery. Three months after surgery, he reported mild unsteadiness. Examination revealed mild ataxia, which led to repeat magnetic resonance imaging (MRI) and a diagnosis of cerebellar abscess. Patient 2 underwent translabyrinthine removal of an acoustic neuroma complicated by postoperative Pseudomonas aeruginosa meningitis, which responded promptly to intravenous antibiotics. Fifteen months after surgery, he visited a neurologist after having a seizure and was treated with anticonvulsants. After a second episode of seizure, imaging studies showed a temporal lobe abscess. Conclusions: The signs of intracranial abscess may be subtle and can occur weeks or months after surgery, requiring vigilance and a high index of suspicion for diagnosis. A change in postoperative symptoms after acoustic neuroma surgery should signal further investigation using MRI with gadolinium. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Neurotol, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol Surg, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Staecker, H (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. OI Staecker, Hinrich/0000-0002-0348-3015 NR 27 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1999 VL 20 IS 3 BP 369 EP 372 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 192QZ UT WOS:000080091600017 PM 10337980 ER PT J AU Brent, GA AF Brent, GA TI Thyroid hormone action: down novel paths - Focus on "Thyroid hormone induces activation of mitogen-activated protein kinase in cultured cells" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Editorial Material ID TRANSPORTER; EXPRESSION C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Med,Endocrinol Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Dept Med,Endocrinol Div, Los Angeles, CA 90073 USA. NR 14 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1999 VL 276 IS 5 BP C1012 EP C1013 PG 2 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 195HR UT WOS:000080245000002 PM 10329947 ER PT J AU Tian, WN Braunstein, LD Apse, K Pang, JD Rose, M Tian, XN Stanton, RC AF Tian, WN Braunstein, LD Apse, K Pang, JD Rose, M Tian, XN Stanton, RC TI Importance of glucose-6-phosphate dehydrogenase activity in cell death SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE oxidative stress; pentose phosphate pathway; apoptosis ID ACTIVATED PROTEIN-KINASE; OXIDATIVE STRESS; MEDIATED INHIBITION; SIGNAL-TRANSDUCTION; PREVENT APOPTOSIS; HYDROGEN-PEROXIDE; GROWTH; ENZYME; DEHYDROEPIANDROSTERONE; EXPRESSION AB The intracellular redox potential plays an important role in cell survival. The principal intracellular reductant NADPH is mainly produced by the pentose phosphate pathway by glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme, and by 6-phosphogluconate dehydrogenase. Considering the importance of NADPH, we hypothesized that G6PDH plays a critical role in cell death. Our results show that 1) G6PDH inhibitors potentiated H2O2-induced cell death; 2) overexpression of G6PDH increased resistance to H2O2-induced cell death; 3) serum deprivation, a stimulator of cell death, was associated with decreased G6PDH activity and resulted in elevated reactive oxygen species (ROS); 4) additions of substrates for G6PDH to serum-deprived cells almost completely abrogated the serum deprivation-induced rise in ROS; 5) consequences of G6PDH inhibition included a significant increase in apoptosis, loss of protein thiols, and degradation of G6PDH; and 6) G6PDH inhibition caused changes in mitogen-activated protein kinase phosphorylation that were similar to the changes seen with H2O2. We conclude that G6PDH plays a critical role in cell death by affecting the redox potential. C1 Beth Israel Deaconess Med Ctr, Div Renal, Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stanton, RC (reprint author), Beth Israel Deaconess Med Ctr, Div Renal, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM rstanton@bidmc.harvard.edu FU NIDDK NIH HHS [DK-09265-02] NR 43 TC 131 Z9 135 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1999 VL 276 IS 5 BP C1121 EP C1131 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 195HR UT WOS:000080245000016 PM 10329961 ER PT J AU Finegood, DT Weir, GC Bonner-Weir, S AF Finegood, DT Weir, GC Bonner-Weir, S TI Prior streptozotocin treatment does not inhibit pancreas regeneration after 90% pancreatectomy in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE islets of Langerhans; precursor cells ID TREATED NEWBORN RATS; GROWTH-FACTOR-ALPHA; BETA-CELL MASS; ENDOCRINE PANCREAS; TRANSGENIC MICE; ADULT-RATS; IN-VITRO; GLUCOSE; EXPRESSION; EXOCRINE AB The effects of residual beta-cell mass and glycemia on regeneration of endocrine pancreas after 90% pancreatectomy were investigated. Streptozotocin or buffer alone was injected into 4-wk-old male Lewis rats (day 0). On day 7, varying numbers of syngeneic islets were transplanted under the kidney capsule to achieve varying degrees of glucose normalization. On day 14, a 90% pancreatectomy or sham pancreatectomy was performed. On day 19, rats were killed and the pancreas was fixed for quantitative morphometric determination of p-cell mass. Focal areas of regenerating pancreas were observed in all animals that underwent partial pancreatectomy. The percentage of remnant pancreas classified as foci was unaffected by streptozotocin treatment or by plasma glucose. Moderate to severe hyperglycemia did not promote regeneration of the pancreatic beta-cell mass; rather the total endocrine cell mass was inversely related to the plasma glucose level (r = -0.5, P < 0.01). These data suggest that the precursor population for both endocrine and exocrine tissue is not susceptible to damage by streptozotocin and that local effects of residual beta-cell mass are not important to regeneration after a 90% pancreatectomy. C1 Simon Fraser Univ, Sch Kinesiol, Diabet Res Lab, Burnaby, BC V5A 1S6, Canada. Joslin Diabet Ctr, Elliot P Joslin Res Labs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Finegood, DT (reprint author), Simon Fraser Univ, Sch Kinesiol, Diabet Res Lab, Burnaby, BC V5A 1S6, Canada. EM finegood@sfu.ca FU NIDDK NIH HHS [DK-44523] NR 28 TC 36 Z9 36 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1999 VL 276 IS 5 BP E822 EP E827 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 194ZF UT WOS:000080224100002 PM 10329974 ER PT J AU Sherwood, DJ Dufresne, SD Markuns, JF Cheatham, B Moller, DE Aronson, D Goodyear, LJ AF Sherwood, DJ Dufresne, SD Markuns, JF Cheatham, B Moller, DE Aronson, D Goodyear, LJ TI Differential regulation of MAP kinase, p70(S6K), and Akt by contraction and insulin in rat skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE signal transduction; muscle contraction; exercise ID ACTIVATED PROTEIN-KINASE; CARDIAC MYOCYTES; SIGNAL-TRANSDUCTION; MECHANICAL-STRESS; 3T3-L1 ADIPOCYTES; GENE-EXPRESSION; GLUCOSE-UPTAKE; PHAS-I; PHOSPHORYLATION; TRANSLOCATION AB To study the effects of contractile activity on mitogen-activated protein kinase (MAP kinase), p70 S6 kinase (p70(S6K)) and Akt kinase signaling in rat skeletal muscle, hindlimb muscles were contracted by electrical stimulation of the sciatic nerve for periods of 15 s to 60 min. Contraction resulted in a rapid and transient activation of Raf-l and MAP kinase kinase 1, a rapid and more sustained activation of MAP kinase and the 90-kDa ribosomal S6 kinase 2, and a dramatic increase in c-fos mRNA expression. Contraction also resulted in an apparent increase in the association of Raf-l with p21Ras, although stimulation of MAP kinase signaling occurred independent of Shc, IRS1, and IRS2 tyrosine phosphorylation or the formation of Shc/Grb2 or LRS1/Grb2 complexes. Insulin was considerably less effective than contraction in stimulating the MAP kinase pathway. However, insulin, but not contraction, increased p70(S6K) and Akt activities in the muscle. These results demonstrate that contraction-induced activation of the MAP kinase pathway is independent of proximal steps in insulin and/or growth factor-mediated signaling, and that contraction and insulin have discordant effects with respect to the activation of the MAP kinase pathway vs, p70S6K and Akt. Of the numerous stimulators of MAP kinase in skeletal muscle, contractile activity emerges as a potent and physiologically relevant activator of MAP kinase signaling, and thus activation of this pathway is likely to be an important molecular mechanism by which skeletal muscle cells transduce mechanical and/or biochemical signals into downstream biological responses. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Merck Res Labs, Dept Mol Endocrinol, Rahway, NJ 07065 USA. RP Goodyear, LJ (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM goodyeal@joslab.harvard.edu RI Aronson, Doron/F-3390-2010 FU NIAMS NIH HHS [AR-42238] NR 41 TC 83 Z9 85 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAY PY 1999 VL 276 IS 5 BP E870 EP E878 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 194ZF UT WOS:000080224100009 PM 10329981 ER PT J AU Hall, DM Baumgardner, KR Oberley, TD Gisolfi, CV AF Hall, DM Baumgardner, KR Oberley, TD Gisolfi, CV TI Splanchnic tissues undergo hypoxic stress during whole body hyperthermia SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE heat stress; free radical; reactive oxygen species; oxidative stress; hypoxia ID H-3 MISONIDAZOLE; XANTHINE-OXIDASE; HEAT-SHOCK; INTESTINAL ISCHEMIA; BIOREDUCTIVE DRUGS; HYPOBARIC HYPOXIA; TUMOR HYPOXIA; FREE-RADICALS; NITRIC-OXIDE; CELLS AB Exposure of conscious animals to environmental heat stress increases portal venous radical content. The nature of the observed heat stress-inducible radical molecules suggests that hyperthermia produces cellular hypoxic stress in liver and intestine. To investigate this hypothesis, conscious rats bearing in-dwelling portal venous and femoral artery catheters were exposed to normothermic or hyperthermic conditions. Blood gas levels were monitored during heat stress and for 24 h following heat exposure. Hyperthermia significantly increased arterial O-2 saturation, splanchnic arterial-venous O-2 difference, and venous PCO2, while decreasing venous O-2 saturation and venous pH. One hour after heat exposure, liver glycogen levels were decreased similar to 20%. Two hours after heat exposure, the splanchnic arterial-venous O-2 difference remained elevated in heat-stressed animals despite normal T-c. A second group of rats was exposed to similar conditions while receiving intra-arterial injections of the hypoxic cell marker [H-3]misonidazole. Liver and intestine were biopsied, and [H-3]misonidazole content was quantified. Heat stress increased tissue [H-3]misonidazole retention 80% in the liver and 29% in the small intestine. Cellular [H-3]misonidazole levels were significantly elevated in intestinal epithelial cells and liver zone 2 and 3 hepatocytes and Kupffer cells. This effect was most prominent in the proximal small intestine and small liver lobi. These data provide evidence that hyperthermia produces cellular hypoxia and metabolic stress in splanchnic tissues and suggest that cellular metabolic stress may contribute to radical generation during heat stress. C1 Univ Iowa, Dept Exercise Sci, Iowa City, IA 52242 USA. Univ Iowa, Free Rad Res Inst, Iowa City, IA 52242 USA. Univ Michigan, Dept Cariol Restorat Sci & Endodont, Ann Arbor, MI 48109 USA. William S Middleton Mem Vet Hosp, Dept Pathol, Madison, WI 53705 USA. RP Hall, DM (reprint author), Univ Iowa, Dept Exercise Sci, 424 Field House, Iowa City, IA 52242 USA. EM dave-hall@uiowa.edu NR 52 TC 53 Z9 57 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1999 VL 276 IS 5 BP G1195 EP G1203 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 197BH UT WOS:000080344400016 PM 10330010 ER PT J AU Kato, K Chen, MC Nguyen, M Lehmann, FS Podolsky, DK Soll, AH AF Kato, K Chen, MC Nguyen, M Lehmann, FS Podolsky, DK Soll, AH TI Effects of growth factors and trefoil peptides on migration and replication in primary oxyntic cultures SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE gastric mucosa; thymidine incorporation; epidermal growth factor receptors; epidermal growth factor receptor antibody; peptic ulcer; cytokines ID INTESTINAL EPITHELIAL MONOLAYERS; FACTOR RECEPTOR ANTIBODIES; GASTRIC-CARCINOMA CELLS; MUCIN GENE-EXPRESSION; BREAST-CANCER-CELLS; FACTOR-I; MUCOSAL CELLS; FACTOR-ALPHA; FACTOR-BETA; ENDOTHELIAL-CELLS AB Restitution, the lateral migration of cells over an intact basement membrane, maintains mucosal integrity. We studied the regulation of migration and proliferation of enzyme-dispersed canine oxyntic mucosa cells in primary culture. Confluent monolayers were wounded and cultured in serum-free medium, and cells migrating into the wound were counted. [H-3]thymidine incorporation into DNA was studied using subconfluent cultures. Considerable migration occurred in untreated monolayers; however, epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, basic fibroblast growth factor (bFGF), insulin-like growth factor I (IGF-I), two trefoil peptides, and interleukin (IL)-1 beta further enhanced migration. The specific EGF receptor (EGFR) monoclonal antibody, MAb-528, inhibited both basal and TGF-alpha- or IL-1 beta-stimulated migration, but not the response to trefoil peptide, bFGF, or IGF-I. Exogenous TGF-beta inhibited cell proliferation but did not alter migration. Immunoneutralization with anti-TGF-beta blocked the response to exogenous TGF-beta and produced a small enhancement of basal thymidine incorporation but did not attenuate basal or TGF-alpha-stimulated migration. In conclusion, endogenous EGFR ligands regulate proliferation and migration. TGF-beta inhibits mitogenesis; it did not upregulate migration in these cultures. Although bFGF, IGF-I, and IL-1 beta enhance gastric epithelial migration, only IL-1 beta acted in a TGF-alpha-dependent fashion. C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE,Sch Med, Los Angeles, CA 90073 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Soll, AH (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE,Sch Med, Bldg 115,Rm 215 W151H, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-30444, DK-19984, DK-41557] NR 54 TC 38 Z9 41 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1999 VL 276 IS 5 BP G1105 EP G1116 PG 12 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 197BH UT WOS:000080344400006 PM 10330000 ER PT J AU McKaig, BC Makh, SS Hawkey, CJ Podolsky, DK Mahida, YR AF McKaig, BC Makh, SS Hawkey, CJ Podolsky, DK Mahida, YR TI Normal human colonic subepithelial myofibroblasts enhance epithelial migration (restitution) via TGF-beta 3 SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE transforming growth factor-beta; wound repair ID TRANSFORMING-GROWTH-FACTOR; INFLAMMATORY BOWEL-DISEASE; SMOOTH-MUSCLE CELLS; FACTOR-BETA; INVITRO MODEL; TGF-BETA; EXPRESSION; MODULATION; RECEPTOR; MUCOSA AB After injury and loss of epithelial cells, intestinal barrier function is reestablished by migration of viable epithelial cells from the wound edge (restitution). Myofibroblasts are located close to the basal surface of epithelial cells. This study aimed to investigate the role of human colonic subepithelial myofibroblasts in epithelial restitution. Primary cultures of subepithelial myofibroblasts were established. Monolayers' of the epithelial cell lines IEC-6 and T84 were "wounded" in a standard manner to create an in vitro model of restitution. Migration of epithelial cells across the wound edge was assessed following culture in myofibroblast-conditioned medium. Myofibroblast expression of transforming growth factor (TGF)-beta isoforms was examined using RT-PCR, and TGF-beta isoform bioactivity was assessed using My 1 Lu bioassay. Myofibroblast-conditioned medium, via a TGF-beta-dependent pathway, significantly enhanced migration of epithelial cells across the wound edge and significantly inhibited cell proliferation in wounded monolayers. Messenger RNA for TGF-beta 1, -beta 2, and -beta 3 was detected in the myofibroblasts, and My 1 Lu bioassay showed the presence of predominantly bioactive TGF-beta 3. This study shows that human colonic subepithelial myofibroblasts secrete predominantly bioactive TGF-beta 3 and enhance restitution in wounded epithelial monolayers via a TGF-beta-dependent pathway. C1 Univ Nottingham Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Univ Nottingham Hosp, Queens Med Ctr, Div Gastroenterol, Nottingham NG7 2UH, England. NR 46 TC 79 Z9 81 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1999 VL 276 IS 5 BP G1087 EP G1093 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 197BH UT WOS:000080344400004 PM 10329998 ER PT J AU Young, SH Ennes, HS McRoberts, JA Chaban, VV Dea, SK Mayer, EA AF Young, SH Ennes, HS McRoberts, JA Chaban, VV Dea, SK Mayer, EA TI Calcium waves in colonic myocytes produced by mechanical and receptor-mediated stimulation SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE smooth muscle; tissue culture; substance P; inositol 1,4,5-trisphosphate; ryanodine receptor; stretch-activated cation channels ID SMOOTH-MUSCLE CELLS; ION CHANNELS; RYANODINE RECEPTORS; CA2+ RELEASE; PROPAGATION; HEPATOCYTES; PATTERNS; STRETCH; SIGNAL; ENTRY AB The mechanisms underlying intracellular Ca2+ waves induced by either mechanical or receptor-mediated stimulation of myocytes isolated from the longitudinal muscle layer of the rabbit distal colon were compared using fura 2 and fluorescence videomicroscopy. Light focal mechanical deformation of the plasma membrane or focal application of substance P resulted in localized intracellular Ca2+ concentration ([Ca2+](i)) transients that propagated throughout the cell. In both cases, the Ca2+ response consisted of a transient peak response followed by a delayed-phase response. Substance P-mediated [Ca2+](i) responses involved generation of inositol 1,4,5-trisphosphate and release of Ca2+ from thapsigargin-sensitive stores, whereas mechanically induced responses were partially (29%) dependent on La3+-sensitive influx of extracellular Ca2+ and partially on release of intracellular Ca2+ from thapsigargin-insensitive stores gated by ryanodine receptors. The delayed-phase response in both cases was dependent on extracellular Ca2+. However although the response to substance P was sensitive to La3+, that after mechanical stimulation was not. In the later case, the underlying mechanism may involve capacitative Ca2+ entry channels that are activated after mechanical stimulation but not by substance P. C1 Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Neuroenter Dis Program,Dept Physiol, Los Angeles, CA 90024 USA. RP Mayer, EA (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, CURE, Neuroenter Dis Program, Bldg 115, Los Angeles, CA 90073 USA. EM emayer@ucla.edu FU NIDDK NIH HHS [DK-40919] NR 33 TC 14 Z9 15 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1999 VL 276 IS 5 BP G1204 EP G1212 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 197BH UT WOS:000080344400017 PM 10330011 ER PT J AU Gwathmey, JK Kim, CS Hajjar, RJ Khan, F DiSalvo, TG Matsumori, A Bristow, MR AF Gwathmey, JK Kim, CS Hajjar, RJ Khan, F DiSalvo, TG Matsumori, A Bristow, MR TI Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE beta-receptor antagonist; turkey; cellular mechanisms ID FURAZOLIDONE-INDUCED CARDIOMYOPATHY; IDIOPATHIC DILATED CARDIOMYOPATHY; SPONTANEOUSLY HYPERTENSIVE RATS; HUMAN VENTRICULAR MYOCARDIUM; FAILING HUMAN-HEART; SARCOPLASMIC-RETICULUM; CONGESTIVE CARDIOMYOPATHY; CONTRACTILE PERFORMANCE; ANIMAL-MODEL; ISCHEMIC CARDIOMYOPATHY AB Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta(1)-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure. C1 Boston Univ, Sch Med, Integrated Physiol Res Labs, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Univ Colorado, Div Cardiol, Denver, CO 80262 USA. Kyoto Univ, Dept Internal Med, Div 3, Kyoto 606, Japan. RP Boston Univ, Sch Med, Integrated Physiol Res Labs, 763 Bldg E Concord Ave, Cambridge, MA 02138 USA. EM gwathmey@tiac.net RI bristow, michael/G-7850-2011 FU NHLBI NIH HHS [R43-HL-55249, 2R01-HL-49574, R44-HL-55249] NR 67 TC 34 Z9 36 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1999 VL 276 IS 5 BP H1678 EP H1690 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 194ZB UT WOS:000080223700033 PM 10330254 ER PT J AU Jones, SP Girod, WG Palazzo, AJ Granger, DN Grisham, MB Jourd'heuil, D Huang, PL Lefer, DJ AF Jones, SP Girod, WG Palazzo, AJ Granger, DN Grisham, MB Jourd'heuil, D Huang, PL Lefer, DJ TI Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE mouse; neutrophils; infarction; leukocyte adhesion molecules ID REDUCES INFARCT SIZE; NF-KAPPA-B; P-SELECTIN; SMOOTH-MUSCLE; RABBIT HEART; INHIBITION; ACTIVATION; ADHESION; GENE; RAT AB Myocardial ischemia and reperfusion (MI/R) initiates a cascade of polymorphonuclear neutrophil (PMN)-mediated injury, the magnitude of which may be influenced by the bioavailability of nitric oxide (NO). We investigated the role of endothelial cell nitric oxide synthase (ecNOS) in MI/R injury by subjecting wild-type and ecNOS-deficient (-/-) mice to 20 min of coronary artery occlusion and 120 min of reperfusion. Myocardial infarct size represented 20.9 +/- 2.9% of the ischemic zone in wild-type mice, whereas the ecNOS -/- mice had significantly (P < 0.01) larger infarcts measuring 46.0 +/- 3.8% of the ischemic zone. Because P-selectin is thought to be involved with the pathogenesis of neutrophil-mediated I/R injury, we assessed the effects of MYR on P-selectin expression in the myocardium of wild-type and ecNOS -/- mice. P-selectin expression measured with a radiolabeled monoclonal antibody (MAb) technique after MI/R in wild-type mice was 0.037 +/- 0.009 mu g MAb/g tissue, whereas ecNOS -/- coronary vasculature was characterized by significantly (P < 0.05) higher P-selectin expression (0.080 +/- 0.013 mu g MAb/g tissue). Histological examination of the postischemic myocardium revealed significantly (P < 0.01) more neutrophils in the ecNOS -/- (29.5 +/- 2.5 PMN/field) compared with wild-type (5.0 +/- 0.9 PMN/field) mice. A similar trend in infarct size and neutrophil accumulation was observed when wild-type and ecNOS -/- mice were subjected to 30 min of ischemia and 120 min of reperfusion. These novel in vivo findings demonstrate a cardioprotective role for ecNOS-derived NO in the ischemic-reperfused mouse heart. C1 Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Lefer, DJ (reprint author), Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, 1501 Kings Highway, Shreveport, LA 71130 USA. RI Lefer, David/A-6372-2012; Jones, Steven/D-5092-2009 OI Jones, Steven/0000-0001-5376-8089 FU NIDDK NIH HHS [P01-DK-43785] NR 48 TC 184 Z9 188 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1999 VL 276 IS 5 BP H1567 EP H1573 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 194ZB UT WOS:000080223700019 PM 10330240 ER PT J AU Skerrett, SJ Martin, TR Chi, EY Peschon, JJ Mohler, KM Wilson, CB AF Skerrett, SJ Martin, TR Chi, EY Peschon, JJ Mohler, KM Wilson, CB TI Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE tumor necrosis factor; pneumonia; lung injury; lipopolysaccharide; cytokines; interleukin-1 ID TUMOR-NECROSIS-FACTOR; MURINE KLEBSIELLA-PNEUMONIA; FACTOR-ALPHA; NEUTROPHIL RECRUITMENT; ALVEOLAR MACROPHAGES; BACTERIAL CLEARANCE; PULMONARY INFLAMMATION; LEGIONELLA-PNEUMOPHILA; ESCHERICHIA-COLI; HOST-DEFENSE AB To determine the roles of the type 1 tumor necrosis factor (TNF) receptor (TNFR1) in lung inflammation and antibacterial defense, we exposed transgenic mice lacking TNFR1 [TNFR1(-/-)] and wild-type control mice to aerosolized lipopolysaccharide or Pseudomonas aeruginosa. After LPS, bronchoalveolar lavage fluid (BALF) from TNFR1(-/-) mice contained fewer neutrophils and less macrophage inflammatory protein-2 than BALF from control mice. TNF-alpha, interleukin-1 beta, and total protein levels in BALF as well as tissue intercellular adhesion molecule-1 expression did not differ between the two groups. In contrast, lung inflammation and bacterial clearance after infection were augmented in TNFR1(-/-) mice. BALF from infected TNFR1(-/-) mice contained more neutrophils and TNF-alpha and less interleukin-1 beta and macrophage inflammatory protein-a than that from control mice, but protein levels were similarly elevated in both groups. Lung inflammation and bacterial clearance were also augmented in mice lacking both TNF receptors. Thus TNFR1 facilitates neutrophil recruitment after inhalation of lipopolysaccharide, in part by augmenting chemokine induction. In contrast, TNFR1 attenuates lung inflammation in response to live bacteria but does not contribute to increased lung permeability and is not required for the elimination of P. aeruginosa. C1 Vet Affairs Puget Hlth Care Syst, Seattle, WA 98108 USA. Immunex Corp, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Immunol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98108 USA. RP Skerrett, SJ (reprint author), Vet Affairs Puget Hlth Care Syst, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL-30542] NR 73 TC 88 Z9 92 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAY PY 1999 VL 276 IS 5 BP L715 EP L727 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 194ZD UT WOS:000080223900005 PM 10330027 ER PT J AU Roitman, MF Patterson, TA Sakai, RR Bernstein, IL Figlewicz, DP AF Roitman, MF Patterson, TA Sakai, RR Bernstein, IL Figlewicz, DP TI Sodium depletion and aldosterone decrease dopamine transporter activity in nucleus accumbens but not striatum SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE sodium appetite; motivation; reward; rat ID SALT APPETITE; RAT-BRAIN; NEOSTRIATAL NEURONS; VENTRAL STRIATUM; MESSENGER-RNA; TRANSMISSION; RECEPTOR; BEHAVIOR; IMMUNOREACTIVITY; STIMULATION AB Motivated behaviors, including sodium (Na) appetite, are correlated with increased dopamine (DA) transmission in the nucleus accumbens (NAc). DA transporter (DAT) modulation affects DA transmission and may play a role in motivated behaviors. In vivo Na depletion, which reliably induces Na appetite, was correlated with robust decreases in DA uptake via the DAT in the rat NAc with rotating disk electrode voltammetry [1,277 +/- 162 vs. 575 +/- 89 pmol . s(-1) . g(-1); V-max of transport for control vs. Na-depleted tissue]. Plasma aldosterone (Aldo) levels increase after in vivo Na depletion and contribute to Na appetite. Decreased DAT activity in the NAc was observed after in vitro Aldo treatment (428 +/- 28 vs. 300 +/- 25 pmol . s(-1) . g(-1)). Neither treatment affected DAT activity in the striatum. These results suggest that a direct action of Aldo is one possible mechanism by which Na depletion induces a reduction in DAT activity in the NAc. Reduced DAT activity may play a role in generating increased NAc DA transmission during Na appetite, which may underlie the motivating properties of Na for the Na-depleted rat. C1 Univ Washington, Program Neurobiol & Behav, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Pfizer Inc, Cent Res, Groton, CT 06340 USA. Univ Penn, Dept Biol Anim, Philadelphia, PA 19104 USA. RP Roitman, MF (reprint author), Univ Washington, Program Neurobiol & Behav, Box 351525 Guthrie Hall, Seattle, WA 98195 USA. EM roitman@u.washington.edu FU NIDCD NIH HHS [DC-00248]; NIDDK NIH HHS [DK-40963, DK-48061] NR 41 TC 29 Z9 29 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 1999 VL 276 IS 5 BP R1339 EP R1345 PG 7 WC Physiology SC Physiology GA 194PE UT WOS:000080202100015 PM 10233025 ER PT J AU Van Dijk, G Seeley, RJ Thiele, TE Friedman, MI Ji, H Wilkinson, CW Burn, P Campfield, LA Tenenbaum, R Baskin, DG Woods, SC Schwartz, MW AF Van Dijk, G Seeley, RJ Thiele, TE Friedman, MI Ji, H Wilkinson, CW Burn, P Campfield, LA Tenenbaum, R Baskin, DG Woods, SC Schwartz, MW TI Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE OB protein; sympathetic nervous system; corticotropin-releasing hormone; proopiomelanocortin; food intake ID CORTICOTROPIN-RELEASING FACTOR; CENTRAL NEURAL NETWORKS; Y GENE-EXPRESSION; FOOD-INTAKE; OB/OB MICE; OB PROTEIN; UNCOUPLING PROTEIN-2; GLUCOSE-METABOLISM; ENERGY-EXPENDITURE; MESSENGER-RNA AB To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 mu g) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (-8%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (-15%) and gastrointestinal fill (-50%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin's anorexigenic action. C1 Univ Groningen, Dept Anim Physiol, NL-9750 AA Haren, Netherlands. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Washington, Dept Psychol, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Hoffmann La Roche Inc, Dept Metab Dis, Nutley, NJ 07110 USA. RP Van Dijk, G (reprint author), Univ Groningen, Dept Anim Physiol, POB 14, NL-9750 AA Haren, Netherlands. EM g.van.dijk@biol.rug.nl RI Jansen, Heiko/A-5770-2008; Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-53109, DK-17844]; NINDS NIH HHS [NS-32273] NR 61 TC 51 Z9 51 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAY PY 1999 VL 276 IS 5 BP R1425 EP R1433 PG 9 WC Physiology SC Physiology GA 194PE UT WOS:000080202100026 PM 10233036 ER PT J AU Chen, RH Greene, EL Collinsworth, G Grewal, JS Houghton, O Zeng, HQ Garnovskaya, M Paul, RV Raymond Jr AF Chen, RH Greene, EL Collinsworth, G Grewal, JS Houghton, O Zeng, HQ Garnovskaya, M Paul, RV Raymond, JR TI Enrichment of transiently transfected mesangial cells by cell sorting after cotransfection with GFP SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE automated cell sorting; adenovirus; lipofection; liposome ID GENE-TRANSFER; MAMMALIAN-CELLS; PROTEIN; EXPRESSION; DNA; EFFICIENT; MOUSE; VECTORS; EMBRYOS AB Early passage mesangial cells, like many other nonimmortalized cultured cells, can be difficult to transfect. We devised a simple method to improve the efficiency of transient protein expression under the transcriptional control of promoters in conventional plasmid vectors in rat mesangial cells. We used a vector encoding modified green fluorescent protein (GFP) and sterile fluorescence-activated cell sorting (FACS) to select a population consisting of >90% GFP-expressing cells from passaged nonimmortalized cultures transfected at much lower efficiency Only 10% transfection efficiency was noted with a beta-galactosidase expression vector alone, but cotransfection with GFP followed by FACS and replating of GFP(+) cells yielded greater than fivefold enrichment of cells with detectable beta-galactosidase activity. To demonstrate the expression of a properly oriented and processed membrane protein, we cotransfected GFP with a natriuretic peptide clearance receptor (NPR-C) expression vector. Plasmid-dependent cell surface NPR-C density was enhanced by 89% after FACS, though expression remained lower in selected mesangial cells than in the CHO cell line transfected with the same vector. We conclude that cotransfection of rat mesangial cells with GFP, followed by FACS, results in improvement in transient transfection efficiencies to levels that should suffice for many applications. C1 Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Raymond Jr (reprint author), Rm 829,Clin Sci Bldg,171 Ashley Ave, Charleston, SC 29425 USA. EM raymondj@musc.edu FU NHLBI NIH HHS [HL-03710]; NIDDK NIH HHS [DK-52448] NR 31 TC 8 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 1999 VL 276 IS 5 BP F777 EP F785 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 194YY UT WOS:000080223400015 PM 10330060 ER PT J AU Zhang, Z Yang, XY Cohen, DM AF Zhang, Z Yang, XY Cohen, DM TI Urea-associated oxidative stress and Gadd153/CHOP induction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE hypertonic; kidney; cell culture; mouse; Egr-1; sodium chloride ID UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR CHOP; DUCT MIMCD3 CELLS; ENDOPLASMIC-RETICULUM; TYROSINE PHOSPHORYLATION; HEMODIALYSIS-PATIENTS; HYDROGEN-PEROXIDE; GROWTH ARREST; DNA DAMAGE; ACTIVATION AB Urea treatment (100-300 mM) increased expression of the oxidative stress-responsive transcription factor, Gadd153/CHOP, at the mRNA and protein levels (at greater than or equal to 4 h) in renal medullary mIMCD3 cells in culture, whereas other solutes did not. Expression of the related protein, CCAAT/ enhancer-binding protein (C/EBP-beta), was not affected, nor was expression of the sensor of endoplasmic reticulum stress, grp78. Urea modestly increased Gadd153 transcription by reporter gene analysis but failed to influence Gadd153 mRNA stability. Importantly, upregulation of Gadd153 mRNA and protein expression by urea was antioxidant sensitive. Accordingly, urea treatment was associated with oxidative stress, as quantitated by intracellular reduced glutathione content in mIMCD3 cells. In addition, antioxidant treatment partially inhibited the ability of urea to activate transcription of an Egr-1 luciferase reporter gene. Therefore oxidative stress represents a novel solute-signaling pathway in the kidney medulla and, potentially, in other tissues. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol Hypertens & Clin Pharmacol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Mol Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Nephrol Hypertens & Clin Pharmacol, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM cohend@ohsu.edu RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362 FU NIDDK NIH HHS [DK-54924] NR 45 TC 60 Z9 60 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAY PY 1999 VL 276 IS 5 BP F786 EP F793 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 194YY UT WOS:000080223400016 PM 10330061 ER PT J AU Faraone, SV Biederman, J Weiffenbach, B Keith, T Chu, MP Weaver, A Spencer, TJ Wilens, TE Frazier, J Cleves, M Sakai, J AF Faraone, SV Biederman, J Weiffenbach, B Keith, T Chu, MP Weaver, A Spencer, TJ Wilens, TE Frazier, J Cleves, M Sakai, J TI Dopamine D-4 gene 7-repeat allele and attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NOVELTY SEEKING; RECEPTOR GENE; DRD4 GENE; ASSOCIATION; POLYMORPHISM; CHILDREN AB Objective: Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some studies have reported an association between ADHD and the dopamine D-4 (DRD4) gene. Method: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. Results: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. Conclusions: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Inst Psychiat Epidemiol & Genet, Massachusetts Mental Hlth Ctr, Boston, MA USA. Osaka Med Coll, Takatsuki, Osaka, Japan. Genome Therapuet Inc, Waltham, MA USA. Stata Corp, College Stn, TX USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-57934, MH-41314] NR 22 TC 176 Z9 183 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1999 VL 156 IS 5 BP 768 EP 770 PG 3 WC Psychiatry SC Psychiatry GA 192TM UT WOS:000080095400018 PM 10327912 ER PT J AU Quinn, DA Fogel, RB Smith, CD Laposata, M Thompson, BT Johnson, SM Waltman, AC Hales, CA AF Quinn, DA Fogel, RB Smith, CD Laposata, M Thompson, BT Johnson, SM Waltman, AC Hales, CA TI D-dimers in the diagnosis of pulmonary embolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID FIBRIN DEGRADATION PRODUCTS; PLASMA D-DIMER; VENOUS THROMBOEMBOLISM; STRATEGY; TESTS; TOOL; AID AB The aim of this study was to determine if the absence of circulating D-dimers, as determined by latex agglutination assays, can correctly exclude the presence of pulmonary embolism using pulmonary angiography as the diagnostic endpoint. Blood samples were obtained prospectively at the time of angiography for suspicion of acute pulmonary embolism. Plasma was assayed for D-dimer by five different latex agglutination assays. Angiographic evidence of pulmonary emboli was found in 34% (35/103) of patients. The latex agglutination assays had sensitivities of 97 to 100% and specificities of 19 to 29%. The negative predictive value was 94 to 100%. However, a negative D-dimer was rare in patients with recent surgery, malignancy, or total bilirubin >34 mu mol/L (>2 mg/dl). In 31 patients suspected of pulmonary emboli but without these confounding factors, the five D-dimer assays were negative in 45 to 55% of patients with normal pulmonary angiograms. The negative predictive value in these patients was 100% by all five latex agglutination assays tested. The latex agglutination assays for D-dimer, when the pulmonary angiogram is used as the diagnostic endpoint and in the absence of recent surgery, malignancy, or liver disease, appears to be a clinically useful test in the diagnosis of acute pulmonary embolism. C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Clin Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vasc Radiol Div, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Pulm Crit Care Unit, Bulfinch 1,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 09572] NR 22 TC 48 Z9 58 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY PY 1999 VL 159 IS 5 BP 1445 EP 1449 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 196GU UT WOS:000080301300014 PM 10228109 ER PT J AU Harisinghani, MG Saini, S Weissleder, R Hahn, PF Yantiss, RK Tempany, C Wood, BJ Mueller, PR AF Harisinghani, MG Saini, S Weissleder, R Hahn, PF Yantiss, RK Tempany, C Wood, BJ Mueller, PR TI MR lymphangiography using ultrasmall superparamagnetic iron oxide in patients with primary abdominal and pelvic malignancies: Radiographic-pathologic correlation SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LYMPH-NODE METASTASES; INITIAL CLINICAL-EXPERIENCE; MAGNETIC-RESONANCE; CONTRAST AGENT; HODGKIN DISEASE; NECK-CANCER; LYMPHOGRAPHY; HEAD; LYMPHADENOPATHY; PARTICLES AB OBJECTIVE, The purpose of this study was to administer ultrasmall superparamagnetic iron oxide (USPIO) and compare changes in signal intensity of lymph nodes in patients with primary abdominal and pelvic malignancies. Also, we correlated radiographic with pathologic findings. SUBJECTS AND METHODS, Nineteen patients with proven primary abdominal or pelvic cancer (prostatic [n = 10]; colonic [n = 5]; endometrial [n = 1]; Merkel cell tumor [n = 1]; lymphoma [n = 1]; seminoma [n = II) were enrolled as part of our phase II and phase III clinical trials. In these patients, 49 lymph nodes (mean size, 1.4 cm) revealed on CT or MR imaging were evaluated on T1-weighted spin-echo, T2-weighted fast spin-echo, and T2*- weighted gradient-echo MR imaging at 1.5 T 24-36 hr after IV administration of USPIO. Quantitative analyses used measurements of unenhanced and enhanced region-of-interest values in lymph nodes. Qualitative assessment used subjective evaluation and classification of changes in signal intensity. All patients underwent lymph node biopsy or surgical dissection followed by histopathologic correlation. RESULTS. Of the 49 lymph nodes that were evaluated, 20 were benign and 29 were malignant. A decrease in nodal signal intensity on enhanced T2-weighted and T2*-weighted gradient-echo images was seen in 20 benign lymph nodes and two malignant lymph nodes. No appreciable signal change was noted in 27 of the 29 malignant lymph nodes. The mean signal intensity on fast spin-echo T2-weighted images for benign lymph nodes changed from 186.48 (unenhanced) to 73.66 (enhanced). Conversely, mean signal intensity for malignant lymph nodes was relatively unchanged from 191.17 (unenhanced) to 183.18 (enhanced), CONCLUSION. USPIO appears to be a useful MR contrast agent for characterizing benign and malignant lymph nodes based on the enhancement criteria evaluated in our study. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal & Intervent Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 23 TC 110 Z9 119 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 MAY PY 1999 VL 172 IS 5 BP 1347 EP 1351 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189RM UT WOS:000079919700032 PM 10227514 ER PT J AU Chew, FS Schellingerhout, D Keel, SB AF Chew, FS Schellingerhout, D Keel, SB TI Primary lymphoma of skeletal muscle SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Wake Forest Univ, Sch Med, Dept Radiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 6 TC 11 Z9 13 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1999 VL 172 IS 5 BP 1370 EP 1370 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189RM UT WOS:000079919700037 PM 10227519 ER PT J AU Leffler, SG Chew, FS AF Leffler, SG Chew, FS TI CT-guided percutaneous biopsy of sclerotic bone lesions: Diagnostic yield and accuracy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID OSTEOSARCOMA; ASPIRATION AB OBJECTIVE, We assessed the positive predictive value of percutaneous biopsy of sclerotic lesions to determine whether the reported success rate of the percutaneous technique could be generalized to sclerotic lesions or whether our diagnostic yield was too low to justify this added step before open surgical confirmation. MATERIALS AND METHODS. We retrospectively studied all sclerotic bone lesions biopsied by the percutaneous CT-guided technique at the Massachusetts General Hospital between 1988 and 1997. The 43 lesions were categorized by location, maximum diameter, density (graded 1-4, relative to cortex), and pattern of density (geographic, vague, or geographic with sclerotic margins). Pathologic and clinical follow-up were used to determine the positive and negative predictive values. RESULTS. Of the 43 patients biopsied, neither the maximum diameter of the lesion nor its density was predictive of benignancy or malignancy. Fine-needle aspiration (FNA) complemented core biopsy results; for example, in one case, FNA showed findings indicating disease when the core biopsy showed none, and in another case the reverse occurred. No complications were reported in these 43 patients. CONCLUSION. Percutaneous CT-guided biopsy of sclerotic bone lesions is a viable alternative to open surgical biopsy. In this study, the positive predictive value of the combined FNA and bone biopsy results was 82% and the negative predictive value was 100%. No complications were reported. C1 Rhode Isl Hosp, Dept Radiol, Providence, RI 02903 USA. Brown Univ, Sch Med, Providence, RI 02903 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. RP Leffler, SG (reprint author), Rhode Isl Hosp, Dept Radiol, 593 Eddy St, Providence, RI 02903 USA. OI Chew, Felix/0000-0003-2711-2013 NR 8 TC 49 Z9 59 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1999 VL 172 IS 5 BP 1389 EP 1392 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 189RM UT WOS:000079919700040 PM 10227522 ER PT J AU McDonald, JM Moonka, R Bell, RH AF McDonald, JM Moonka, R Bell, RH TI Pathologic risk factors of occult malignancy in endoscopically unresectable colonic adenomas SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 13-14, 1998 CL TACOMA, WASHINGTON SP N Pacific Surg Assoc ID COLONOSCOPIC POLYPECTOMY; INVASIVE-CARCINOMA; COLORECTAL ADENOMA; CANCER; POLYPS; RECTUM; MODEL; SITE AB BACKGROUND: With the advent of new endoscopic and laparoscopic techniques, the likelihood of colonoscopically unresectable adenomas harboring occult malignancy influences management. While prior studies have evaluated polyp size and morphology in assessing the risk of malignancy, the relative risk of cancer based on the presence or absence of high-grade dysplasia has not been systematically studied, METHODS: For all lesions preoperatively diagnosed as adenomas without invasive cancer, multivariate logistic regression analysis was performed to elicit independent variables associated with malignancy in the resected specimen. RESULTS: One hundred patients underwent a colectomy for preoperatively diagnosed adenomatous lesions. Multivariate logistic regression analysis revealed size, degree of dysplasia, and left-sided location to be independent predictors of malignancy. CONCLUSIONS: In colonic adenomas which are not amenable to simple colonoscopic resection, the most useful predictors of the lesion harboring a malignancy are polyp size and the presence of high-grade dysplasia, and these factors can help determine management. Am J Surg. 1999;177: 384-887. (C) 1999 by Excerpta Medica, Inc. C1 Madigan Army Med Ctr, Dept Surg, Div Gen Surg, Tacoma, WA 98401 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA USA. RP McDonald, JM (reprint author), Madigan Army Med Ctr, Dept Surg, Div Gen Surg, Tacoma, WA 98401 USA. NR 22 TC 10 Z9 10 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1999 VL 177 IS 5 BP 384 EP 387 DI 10.1016/S0002-9610(99)00074-4 PG 4 WC Surgery SC Surgery GA 200RJ UT WOS:000080553600009 PM 10365875 ER PT J AU Orloff, SL Busch, AMH Olyaei, AJ Corless, CL Benner, KG Flora, KD Rosen, HR Rabkin, JM AF Orloff, SL Busch, AMH Olyaei, AJ Corless, CL Benner, KG Flora, KD Rosen, HR Rabkin, JM TI Vancomycin-resistant Enterococcus in liver transplant patients SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 13-14, 1998 CL TACOMA, WASHINGTON SP N Pacific Surg Assoc ID RISK-FACTORS; FAECIUM; INFECTION; MORTALITY; EPIDEMIOLOGY; BACTEREMIA; RECIPIENTS; EMERGENCE; PATHOGEN AB BACKGROUND: Vancomycin-resistant Enterococcus (VRE) infection is emerging in the transplant population, and there is no effective antibiotic therapy available. The aims of this retrospective review were to (1) investigate the outcome of and (2) identify common characteristics associated with VRE infection and colonization in orthotopic liver transplant (OLTx) candidates. METHODS: From October 1994 through September 1998, 126 isolates of VRE were identified in 42 of 234 OLTx recipients and 5 OLTx candidates who did not proceed to transplantation. Data were collected by patient chart review or from a computerized hospital database, RESULTS: The 1-year mortality rate with VRE infection was 82%, and with VRE colonization, 7%, This mortality rate contrasts with a 14% 1-year mortality for non-VRE transplant patients (P <0.01, infected patients and colonized patients). Characteristics of VRE colonized and infected patients included recent prior vancomycin (87%), coinfection by other microbial pathogens (74%), recent prior susceptible enterococcal infection (72%), concurrent fungal infection (62%), additional post-OLTx laparotomies (47%), and renal failure (Cr >2.5 mg/dL or need for dialysis; 43%), Biliary complications were seen in 52% of post-OLTx VRE-infected or VRE-colonized patients (versus 22% in non-VRE transplant patients, P <0.05). CONCLUSION: VRE infection is associated with a very high mortality rate after liver transplantation, The incidence of biliary complications prior to VRE isolation is very high in VRE-infected and VRE-colonized patients, The most common characteristics of VRE patients were recent prior vancomycin use, recent prior susceptible enterococcal infection, coinfection with other microbial pathogens, and concurrent fungal infection. With no proven effective antimicrobial therapy for VRE, stringent infection control measures, including strict and limited use of vancomycin, must be practiced. Am J Surg. 1999;177:418-422, (C) 1999 by Excerpta Medica, Inc. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Orloff, SL (reprint author), Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 29 TC 43 Z9 43 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1999 VL 177 IS 5 BP 418 EP 422 DI 10.1016/S0002-9610(99)00083-5 PG 5 WC Surgery SC Surgery GA 200RJ UT WOS:000080553600017 PM 10365883 ER PT J AU Rabkin, JM Olyaei, AJ Orloff, SL Geisler, SM Wahoff, DC Hering, BJ Sutherland, DER AF Rabkin, JM Olyaei, AJ Orloff, SL Geisler, SM Wahoff, DC Hering, BJ Sutherland, DER TI Distant processing of pancreas islets for autotransplantation following total pancreatectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 13-14, 1998 CL TACOMA, WASHINGTON SP N Pacific Surg Assoc ID NEAR-TOTAL PANCREATECTOMY; TRANSPLANTATION; RESECTION; PANCREATICODUODENECTOMY; ENDOCRINE; EXOCRINE; TISSUE; HEAD; DOGS AB BACKGROUND: Small duct chronic pancreatitis is associated with intractable pain and failure to thrive, usually unresponsive to conventional management approaches. Total pancreatectomy is considered after failure of medical intervention. The major morbidity following total pancreatectomy is diabetes mellitus with its associated complications. This adverse outcome can be mitigated through autotransplantation of islets recovered from the pancreatectomy specimen. This approach has been limited historically owing to the absence of an on-site islet processing facility, We present the results from 5 pancreatectomized patients whose islets were prepared 1,500 miles away. METHODS: Five patients (4 women, 1 man, average age 42 years) who failed medical therapy and were not candidates for longitudinal pancreaticojejunostomy underwent total/completion pancreatectomy (4 total, 1 completion) for intractable symptoms from idiopathic small duct chronic pancreatitis, The resected pancreata were preserved in ViaSpan solution and were transferred to an islet processing laboratory by commercial airliner and returned. The dispersed pancreatic islet tissue was infused into a portal vein tributary through an operatively placed catheter after systemic heparinization, RESULTS: All 5 patients experienced complete relief from pancreatic pain; 2 had significant residual discomfort from underlying Crohn's disease. Three of the 5 patients had minimal or no insulin requirement after autotransplantation (median follow-up of 23 months); 1 patient continued with glycemic control difficulties related to Crohn's disease. One patient died 17 months following autotransplantation from an unrelated pneumonia, CONCLUSION: Total pancreatectomy with autologous islet transplantation can offer patients with idiopathic small duct chronic pancreatitis pain relief without the sequelae of diabetes mellitus and can be performed without an on-site islet processing facility. All patients undergoing total/ completion pancreatectomy should be considered candidates for this procedure, Am J Surg. 1999;177:423-427. (C) 1999 by Excerpta Medica, Inc. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Pancreas Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Dept Surg, Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 30 TC 33 Z9 34 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1999 VL 177 IS 5 BP 423 EP 427 DI 10.1016/S0002-9610(99)00078-1 PG 5 WC Surgery SC Surgery GA 200RJ UT WOS:000080553600018 PM 10365884 ER PT J AU Latham, B Dickersin, GR Oliva, E AF Latham, B Dickersin, GR Oliva, E TI Subtypes of chromophobe cell renal carcinoma - An ultrastructural and histochemical study of 13 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE renal epithelial neoplasm; chromophobe cell renal carcinoma; cytogenetic analysis; light microscopy; ultrastructural analysis ID EPITHELIAL NEOPLASMS; TUMORS AB The Mainz classification of renal epithelial neoplasms has become accepted as a reproducable morphologic and cytogenetic classification of epithelial tumors of the kidney. Chromophobe cell renal carcinoma (CCRC) is a distinct type of renal epithelial neoplasm, first described by Thoenes et al. in 1985. Both a typical type of CCRC, composed of cells with pale reticular cytoplasm, and an eosinophilic variant (EVCCRC) have been identified. Both variants have been reported to show cytoplasmic staining with the Hale's colloidal iron method. Cytogenetic analysis has tended to confirm the Mainz classification. CCRC has been shown to have consistent chromosomal abnormalities that are not shared by other renal tumors. Ultrastructurally, CCRC is typically characterized by a cytoplasm containing scant numbers of mitochondria, which have tubulovesicular christae, and by the presence of innumerable 150- 300-mu m microvesicles scattered between the mitochondria. Erlandson et al. recently described two subtypes of EVCCRC. One subtype has sparse microvesicles and abundant mitochondria that have tubulovesicular christae, whereas the second type (described as an oncocytic EVCCRC) has no microvesicles and abundant mitochondria containing pseudovesicular or lamellar christae. This was believed to be more akin to the ultrastructural appearances of a renal oncocytoma. The authors believe that the phenotype of the EVCCRC shows a range of appearances at both the light microscopic and the ultrastructural levels, from features similar to the typical type CCRC through to a neoplasm that is phenotypically similar to renal oncocytoma. A series of 13 cases of CCRC from the files of the Massachusetts General Hospital for which ultrastructural examination was available is described. These cases include six cases of typical type CCRC and seven cases of EVCCRC. The authors confirm the findings of Erlandson et al. of two subtypes of EVCCRC and designate them as type 1 EVCCRC (with some microvesicles and mitochondria with tubulovesicular christae) and type 2 EVCCRC (with no identifiable microvesicles and mitochondria with pseudovesicular or lamellar christae). C1 Royal Perth Hosp, Dept Pathol, Perth, WA 6007, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Latham, B (reprint author), Royal Perth Hosp, Dept Pathol, Wellington St, Perth, WA 6007, Australia. NR 14 TC 35 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1999 VL 23 IS 5 BP 530 EP 535 DI 10.1097/00000478-199905000-00006 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 194EB UT WOS:000080178200006 PM 10328084 ER PT J AU Kowdley, KV Coull, BM Orwoll, ES AF Kowdley, KV Coull, BM Orwoll, ES TI Cognitive impairment and intracranial calcification in chronic hypoparathyroidism SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE hypoparathyroidism; calcification; hypocalcemia; complication; neurologic ID BASAL GANGLIA; DEMENTIA AB Background: Intracranial calcification is associated with chronic hypoparathyroidism. The relationship between intracranial calcification, neurological abnormalities and cognitive deficits in this disorder is unknown, The purpose of this study was to determine whether chronic hypoparathyroidism is associated with cognitive impairment. Methods: We studied 11 hypoparathyroid patients and compared them with a sex- age-, and education-matched control group. The hypoparathyroidism was postsurgical in nine and idiopathic in two, All patients underwent nonenhanced head computed tomography, detailed neurological examinations, and a battery of cognitive tests. These tests were performed separately and individual examiners were blinded to the results of the other components of the study. Results: The mean age of the patients was 55 years; the duration of hypoparathyroidism was at least 9 years. Neuropsychological testing revealed cognitive impairment in 65% of hypoparathyroid subjects, and the presence of significant differences between the hypoparathyroid and control groups, Computed tomography showed intracranial calcification in 6 of 10 hypoparathyroid subjects tested, and neurological (motor) examination revealed 5 of 11 with abnormal findings, There were positive correlations between the presence of cognitive deficits and cerebral calcification (r = 0.59, P = 0.07), between abnormal motor findings and cerebral calcification (r = 0.77, P < 0.01) and between abnormal motor findings and the degree of cognitive deficit (r = 0.83, P < 0.01), Conclusions: We conclude that cognitive and neurological deficits commonly occur in patients with chronic hypoparathyroidism and may be pathophysiologically related to the presence of intracranical calcification. C1 Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland VA Med Ctr, Med Serv, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland VA Med Ctr, Neuropsychol Serv, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Bone & Mineral Res Unit, Portland VA Med Ctr, Serv Neurol, Portland, OR 97201 USA. RP Kowdley, KV (reprint author), Univ Washington, Box 356174, Seattle, WA 98195 USA. EM kkowdley@u.washington.edu OI Orwoll, Eric/0000-0002-8520-7355 NR 30 TC 27 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 1999 VL 317 IS 5 BP 273 EP 277 DI 10.1097/00000441-199905000-00001 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 196EH UT WOS:000080295700001 PM 10334112 ER PT J AU Leaf, DA Kleinman, MT Hamilton, M Deitrick, RW AF Leaf, DA Kleinman, MT Hamilton, M Deitrick, RW TI The exercise-induced oxidative stress paradox: The effects of physical exercise training SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE lipid peroxidation; physical activity ID LIPID-PEROXIDATION; EXPRESSION AB Background : Although physical exercise training is highly recommended, physical exercise causes oxidative stress, which is potentially injurious, This study evaluates this 'exercise paradox' by evaluating the effect of physical exercise on exercise-induced lipid peroxidation. Methods: Measurement of lipid peroxidation (ie, expired ethane and pentane and plasma malondealdehyde) taken during cardiopulmonary exercise stress testing were compared between a group of 10 cardiac patients who underwent physical exercise training in a cardiac rehabilitation setting and a group of 10 nonexercising cardiac patients. Results: Our findings indicate that physical exercise training increased physical work capacity without a concomitant increase in expired markers of Lipid peroxidation (ethane and pentane) and decreased malondealdehyde levels, Conclusions: Because physical exercise-trained people can perform more intense physical work with less oxidative stress, we conclude that physical exercise training can reduce potential chronic health effects associated with daily activities by contributing to an overall reduction in exercise-induced free radical production. C1 W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Los Angeles, CA 90073 USA. Sch Med, Dept Med, Los Angeles, CA USA. Sch Med, Div Cardiol, Dept Med, Los Angeles, CA USA. Univ Calif Irvine, Dept Community & Environm Med, Irvine, CA 92717 USA. RP Leaf, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, Dept Med, 111G,Wilshire & Sawtelle Blvds, Los Angeles, CA 90073 USA. NR 26 TC 50 Z9 52 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 1999 VL 317 IS 5 BP 295 EP 300 DI 10.1097/00000441-199905000-00005 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 196EH UT WOS:000080295700005 PM 10334116 ER PT J AU Molenberghs, G Goetghebeur, EJT Lipsitz, SR Kenward, MG AF Molenberghs, G Goetghebeur, EJT Lipsitz, SR Kenward, MG TI Nonrandom missingness in categorical data: Strengths and limitations SO AMERICAN STATISTICIAN LA English DT Article DE contingency tables; generalized linear models; longitudinal data; maximum likelihood estimation; missing values; nonrandom missingness ID NON-IGNORABLE NONRESPONSE; NONIGNORABLE NONRESPONSE; CONTINGENCY-TABLES; REGRESSION-ANALYSIS; MAXIMUM-LIKELIHOOD; OUTCOME SUBJECT; INCOMPLETE DATA; LINEAR-MODELS; VARIABLES; EXAMPLE AB There have recently been substantial developments in the analysis of incomplete data. Modeling tools are now available for nonrandom missingness and these methods are finding their way into the broad statistical community. The computational and interpretational issues that surround such models are less well known. This article provides an exposition of several of these issues in a categorical data setting. It is argued that the use of contextual information can aid the modeler in discriminating among models that are indistinguishable purely on statistical grounds. C1 Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium. Dept Appl Math & Comp Sci, B-9000 Ghent, Belgium. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Kent, Inst Math & Sci, Canterbury CT2 7NF, Kent, England. RP Molenberghs, G (reprint author), Limburgs Univ Ctr, Univ Campus,Bldg D, B-3590 Diepenbeek, Belgium. NR 26 TC 42 Z9 43 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0003-1305 J9 AM STAT JI Am. Stat. PD MAY PY 1999 VL 53 IS 2 BP 110 EP 118 DI 10.2307/2685728 PG 9 WC Statistics & Probability SC Mathematics GA 194YV UT WOS:000080223100006 ER PT J AU Friedberg, JW Freedman, AS AF Friedberg, JW Freedman, AS TI High dose therapy and stem cell transplantation in follicular lymphoma SO ANNALS OF HEMATOLOGY LA English DT Review DE follicular lymphoma; transplantation autologous; allogeneic transplantation ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; CHRONIC MYELOGENOUS LEUKEMIA; LOW-GRADE LYMPHOMA; MYELODYSPLASTIC SYNDROME; ANTI-CD20 ANTIBODY; HISTOLOGIC TRANSFORMATION; LATE COMPLICATION; FIRST REMISSION; SINGLE-CENTER AB Indolent follicular lymphomas are diseases which are generally incurable with conventional therapy. Although patients can survive for prolonged periods, the median duration of first remissions is about 2.5 years, and subsequent remissions progressively shorten with time. High-dose therapy with hematopoietic stem cell support leads to prolonged disease free and overall survival in a subset of patients with aggressive non-Hodgkin's lymphoma. Mounting evidence suggests similar findings for selected patients with indolent follicular non-Hodgkin's lymphoma. It is still unclear as to when this approach should be used; however, inferior results have been seen in heavily pretreated patients, In contrast, encouraging results are being reported in patients undergoing such treatment early in the course of their disease. Despite these data, many patients continue to relapse, and investigations are now focused on eradication of minimal residual disease, allogeneic transplantation, novel ablative regimens, and improvements in stem cell purging. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol,Dept Med, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol,Dept Med, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA66996] NR 62 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD MAY PY 1999 VL 78 IS 5 BP 203 EP 211 DI 10.1007/s002770050503 PG 9 WC Hematology SC Hematology GA 206TN UT WOS:000080895500001 PM 10391100 ER PT J AU Vogelzang, NJ Herndon, JE Miller, A Strauss, G Clamon, G Stewart, FM Aisner, J Lyss, A Cooper, MR Suzuki, Y Green, MR AF Vogelzang, NJ Herndon, JE Miller, A Strauss, G Clamon, G Stewart, FM Aisner, J Lyss, A Cooper, MR Suzuki, Y Green, MR TI High-dose paclitaxel plus G-CSF for malignant mesothelioma: CALGB phase II study 9234 SO ANNALS OF ONCOLOGY LA English DT Article DE mesothelioma; paclitaxel ID LEUKEMIA GROUP-B; PLEURAL MESOTHELIOMA; CANCER; CISPLATIN; DIHYDRO-5-AZACYTIDINE; TRIAL AB Background: New agents with activity in mesothelioma are sorely needed. The Cancer and Leukemia Group B (CALGB) therefore performed a phase II study of high-dose paclitaxel in patients with malignant mesothelioma who had no prior chemotherapy. Patients and methods: Thirty-five patients accrued to this multi-institutional phase II study of paclitaxel given as a 24-hour infusion at 250 mg/m(2) every three weeks plus filgrastim (G-CSF) 300 mcg subcutaneously days 3-18. Results: There were three (9%) regressions of evaluable disease. The median survival was five months (95% confidence interval (95% CI): 1.9-9.6 months), the one-year survival rate was 14% and the two-year survival rate was 6%. Toxicity was tolerable with one death from pneumonia (without neutropenia) on day 18 and a 23% rate of grade 4 granulocytopenia. Conclusions: The level of activity seen with paclitaxel is similar to that seen in other CALGB trials of the single agents carboplatin, trimetrexate and 5-azacytidine. Future studies of of paclitaxel (at lower doses) in combination with synergistic agents could be considered. C1 Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Duke Univ, Med Ctr, GALGB Stat Ctr, Durham, NC USA. Univ Tennessee, Memphis, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Univ Maryland, Baltimore, MD 21201 USA. Missouri Baptist Hosp, St Louis, MO USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Mt Sinai Sch Med, New York, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Vogelzang, NJ (reprint author), Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. FU NCI NIH HHS [CA 33601, CA 41287, CA 47555] NR 13 TC 29 Z9 29 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 1999 VL 10 IS 5 BP 597 EP 600 DI 10.1023/A:1026438215309 PG 4 WC Oncology SC Oncology GA 203RC UT WOS:000080719800022 PM 10416012 ER PT J AU Busaba, NY AF Busaba, NY TI Clinical presentation and management of labyrinthine fistula caused by chronic otitis media SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Association-for-Research-in-Otolaryngology 19th Midwinter Meeting CY FEB 04-08, 1996 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol DE cholesteatoma; chronic otitis media; labyrinthine fistula ID CHOLESTEATOMA SURGERY AB To describe the clinical presentation and surgical management of patients with chronic otitis media complicated by labyrinthine fistula and to determine clinical indicators that predict postoperative hearing outcome, I performed a retrospective analysis at an academic tertiary care center. Thirty-four patients with labyrinthine fistula as a complication of chronic otitis media, documented at mastoidectomy, underwent postoperative audiometry. The median age was 50 years, and the duration of otologic symptoms ranged from 2 months to more than 40 years. On presentation, 3 patients had anacusis in the affected ear, while in the others, the pure tone average for bone conduction at the 0.5-, 1-, 2-, and 4-kHz frequencies was 34 dB hearing level. Nineteen patients (56%) complained of dizziness on presentation. The fistula test was positive in 14 of 28 patients (50%). The fistula was detected radiologically in 10 of 24 patients (42%). Cholesteatoma was present in 33 of 34 patients (97%). The lateral semicircular canal was the most common site of labyrinthine fistula. The cholesteatoma matrix was completely removed in 29 of 33 cases and exteriorized in the remaining 4. Of the 31 patients with measurable hearing preoperatively, anacusis occurred in 8 (26%). In 6 of these, the preoperative pure tone average for bone conduction was greater than 50 dB hearing level, and cholesteatoma matrix and granulation tissue invading the membranous labyrinth were found at surgery. I concluded that in chronic otitis media, labyrinthine fistulas occurred almost exclusively in the presence of a cholesteatoma. Postoperative hearing outcome correlated with the size of the fistula and the presence of granulation tissue invading the labyrinth, which could be predicted by the preoperative audiometry. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Brockton W Roxbury Vet Affairs Med Ctr, Div Otolaryngol, W Roxbury, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 12 Z9 23 U1 1 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 1999 VL 108 IS 5 BP 435 EP 439 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 197BM UT WOS:000080344800003 PM 10335702 ER PT J AU Dougherty, CM Nichol, WP Dewhurst, TA Spertus, JA AF Dougherty, CM Nichol, WP Dewhurst, TA Spertus, JA TI Patient perspectives on participation in a clinical trial of angina management SO APPLIED NURSING RESEARCH LA English DT Article C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Polyclin, Seattle, WA USA. Univ Missouri, Kansas City Sch Med, Cardiol Sect, Kansas City, MO 64110 USA. RP Dougherty, CM (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way 11B, Seattle, WA 98108 USA. NR 9 TC 3 Z9 3 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD MAY PY 1999 VL 12 IS 2 BP 107 EP 111 DI 10.1016/S0897-1897(99)80392-9 PG 5 WC Nursing SC Nursing GA 189CZ UT WOS:000079887700008 PM 10319526 ER PT J AU Taylor, CR Kwangsukstith, C Wimberly, J Kollias, N Anderson, RR AF Taylor, CR Kwangsukstith, C Wimberly, J Kollias, N Anderson, RR TI Turbo-PUVA: Dihydroxyacetone-enhanced photochemotherapy for psoriasis - A pilot study SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 12th International Conference on Photobiology CY SEP 01-06, 1996 CL VIENNA, AUSTRIA ID THERAPY; COMBINATION; PROTECTION; RADIATION AB Background: Dihydroxyacetone (DHA), a colorless sugar in "sunless" tanning lotions, binds to stratum corneum to form a UV-A-protective brown pigment. Bound DHA polymer is shed faster from hyperproliferative skin sites such as psoriatic plaques. We tested the hypothesis that selective shedding of DHA pigment during psoralen-UV-A (PUVA) treatment of psoriasis may allow higher UV-A doses, thus accelerating clearing while protecting uninvolved skin. Concurrent use of lactic acid was investigated as an aid in removing scale and residual DHA from psoriatic plaques. Observations: Thirty psoriatic patients with more than 20% body surface area involvement were recruited. The 6 PUVA study groups were (1) standard American style, (2) American style plus lactic acid, (3) DHA-PUVA or "topical ultraviolet-resisting barrier to optimize PUVA" (Turbo-PUVA), (4) Turbo-PUVA with lactic acid, (5) European style, and (6) European style plus DHA. Combinations of lactic acid and European-style treatment were not studied. Each subject received up to 30 oral PUVA treatments twice weekly 3 days apart. The DHA-PUVA groups used 15% DHA lotion twice weekly. Lactic acid groups used 7% lotion daily except on treatment days. Psoriasis area and severity index scores were recorded weekly. Turbo-PUVA allowed higher UV-A exposures with minimal burns, showed faster clearing, and required fewer treatments for 90% clearing (P<.001). Conclusions: Protection of uninvolved skin by DHA during PUVA treatment allows higher W-A exposures to be tolerated, demonstrates faster clearing, and requires fewer treatments to clear psoriasis. By reducing the total body dose received, Turbo-PUVA may also reduce long-term risks. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol,Gange Photomed Res Ctr, Boston, MA 02114 USA. Chiang Mai Univ, Dept Med, Dermatol Sect, Chiang Mai 50000, Thailand. RP Taylor, CR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Dermatol,Gange Photomed Res Ctr, Room 224,50 Blossom St, Boston, MA 02114 USA. NR 15 TC 20 Z9 20 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 MAY PY 1999 VL 135 IS 5 BP 540 EP 544 DI 10.1001/archderm.135.5.540 PG 5 WC Dermatology SC Dermatology GA 193ZE UT WOS:000080167000008 PM 10328194 ER PT J AU Harlow, BL Cohen, LS Otto, MW Spiegelman, D Cramer, DW AF Harlow, BL Cohen, LS Otto, MW Spiegelman, D Cramer, DW TI Prevalence and predictors of depressive symptoms in older premenopausal women - The Harvard Study of Mood and Cycles SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; COMMUNITY SAMPLE; UNITED-STATES; RISK-FACTORS; DISORDERS; SMOKING AB Background: The Harvard Study of Moods and Cycles is a community-based cohort study designed to evaluate the relationship between major depression and changes in menstrual and ovarian function. Methods: All women aged 36 to 44 years with a verifiable address from 7 Boston, Mass, metropolitan communities were selected from the Massachusetts Town Books. A self-administered questionnaire assessed demographic characteristics and menstrual history, depression history, and current depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) in 4161 women. Results: We observed a score of 16 or more on the CES-D in 22.4% of women surveyed, and 8.6% scored 25 or more. Widowed, divorced, or separated women were twice as likely as married women to have depression scores greater than 16 (95% confidence interval, 1.6-2.8), and smokers in the upper tertile of pack-years were 1.9 times more likely to have CES-D scores of 16 or more (95% confidence interval, 1.5-2.3). Relative to nulliparous women, those with 1 or 2 children had a 30% lower risk of historic mood disorder, and those with 3 or more children had an even greater reduction in risk (odds ratio, 0.4; 95% confidence interval, 0.3-0.6). Menstrual cycle irregularities were largely unassociated with current or past depression. However, 5 of 8 premenstrual symptoms were significantly associated with CES-D scores of 16 or more. Conclusions: These findings corroborate the prevalence of depression reported by other community-based studies, and also support a relationship between depressive symptoms and marital status, cigarette smoking, nulliparity, and premenstrual symptoms. C1 Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA USA. Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. RP Harlow, BL (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. FU NIMH NIH HHS [R01-MH-50013] NR 27 TC 104 Z9 108 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1999 VL 56 IS 5 BP 418 EP 424 DI 10.1001/archpsyc.56.5.418 PG 7 WC Psychiatry SC Psychiatry GA 193BK UT WOS:000080115400006 PM 10232296 ER PT J AU Bartzokis, G Cummings, J Perlman, S Hance, DB Mintz, J AF Bartzokis, G Cummings, J Perlman, S Hance, DB Mintz, J TI Increased basal ganglia iron levels in Huntington disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID STRIATAL EXCITOTOXIC LESIONS; BRAIN IRON; ALZHEIMERS-DISEASE; FREE-RADICALS; TRANSVERSE RELAXATION; ALPHA-TOCOPHEROL; MR EVALUATION; METAL-IONS; FERRITIN; DESFERRIOXAMINE AB Objective: To quantify in vivo brain ferritin iron levels in patients with Huntington disease (HD) and normal control subjects. Design and Subjects: A magnetic resonance imaging method that can quantify ferritin iron levels with specificity in vivo was employed to study 11 patients with HD and a matched group of 27 normal controls. Three basal ganglia structures (caudate, putamen, and globus pallidus) and 1 comparison region (frontal lobe white matter) were evaluated. Results: Basal ganglia iron levels were significantly in creased (P < .002) in patients with HD, and this increase occurred early in the disease process. This was not a generalized phenomenon, as white matter iron levels were lower in patients with HD. Conclusions: The data suggest that increased iron levels may be related to the pattern of neurotoxicity observed in HD. Reducing the oxidative stress associated with increased iron levels may offer novel ways to delay the rate of progression and possibly defer the onset of HD. C1 Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv, Little Rock, AR USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst 116A NLR, 2200 Ft Roots Dr,Bldg 170, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 NR 54 TC 106 Z9 106 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1999 VL 56 IS 5 BP 569 EP 574 DI 10.1001/archneur.56.5.569 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 193ZB UT WOS:000080166700010 PM 10328252 ER PT J AU Aarsland, D Larsen, JP Cummings, JL Laake, K AF Aarsland, D Larsen, JP Cummings, JL Laake, K TI Prevalence and clinical correlates of psychotic symptoms in Parkinson disease - A community-based study SO ARCHIVES OF NEUROLOGY LA English DT Article ID VISUAL HALLUCINATIONS; ALZHEIMERS-DISEASE; DEMENTIA; DEPRESSION AB Background: Hallucinations and delusions are frequent in patients with Parkinson disease (PD) and may have severe clinical consequences for those patients and their caregivers. However, the prevalence and clinical features of these symptoms have not been studied in a representative sample. Objective: To study the prevalence and clinical correlates of psychosis in a population-based sample of patients with PD. Method: Total ascertainment of patients with PD in a defined geographical area in Norway was attempted through a detailed community study. Clinical evaluation consisted of a neurologic examination and assessments of depression and cognition. Psychosis was assessed with the thought disorder subscale of the Unified Parkinson's Disease Rating Scale. Results: A total of 245 patients with PD were identified, 235 (95.9%) of whom participated in this study. Twenty-three patients (9.8%) had hallucinations with insight retained, and another 14 patients (6.0%) had more severe hallucinations or delusions. Psychotic symptoms were associated with age, stage and diagnostic subgroup of PD, severity of depression, and cognitive impairment. Type, duration, and dose of antiparkinson drug therapy did not differ between those patients with PD who had or did not have psychosis. In a polychotomous logistic regression analysis, severity of depression, cognitive impairment, and impairment of activities of daily living were the only significant concomitants of psychosis. Conclusions: Hallucinations and delusions are common in patients with PD. More advanced and widespread brain changes seem to increase the risk for developing psychosis in patients with PD receiving levodopa therapy. C1 Rogaland Psychiat Hosp, Sect Geriatr Psychiat, N-4004 Stavanger, Norway. Cent Hosp Rogaland, Dept Neurol, Stavanger, Norway. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Behav Neurosci Sect, Los Angeles, CA USA. Univ Oslo, Ullevaal Hosp, Dept Geriatr Med, N-0407 Oslo, Norway. RP Aarsland, D (reprint author), Rogaland Psychiat Hosp, Sect Geriatr Psychiat, POB 1163 Hillevag, N-4004 Stavanger, Norway. OI Aarsland, Dag/0000-0001-6314-216X NR 34 TC 221 Z9 224 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAY PY 1999 VL 56 IS 5 BP 595 EP 601 DI 10.1001/archneur.56.5.595 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 193ZB UT WOS:000080166700013 PM 10328255 ER PT J AU Chang, HA Krebs, DE AF Chang, HA Krebs, DE TI Dynamic balance control in elders: Gait initiation assessment as a screening tool SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article AB Objective: To determine whether measurements of center of gravity-center of pressure separation (CG-CP moment arm) during gait initiation can differentiate healthy from disabled subjects with sufficient specificity and sensitivity to be useful as a screening test for dynamic balance in elderly patients. Subjects: Three groups of elderly subjects (age, 74.97 +/- 6.56 yrs): healthy elders (HE, n = 21), disabled elders (DE, n = 20), and elders with vestibular hypofunction (VH, n = 18). Design: Cross-sectional, intact-groups research design. Peak CG-CP moment arm measures how far the subject will tolerate the whole-body CG to deviate from the ground reaction force's CP; it represents dynamic balance control. Screening test cutoff points at 16 to 18cm peak CG-CP moment arm predicted group membership. Results: The magnitude of peak CG-CP moment arm was significantly greater in HE than in DE and VH subjects (p <.01) and was not different between the DE and VH groups. The peak CG-CP moment arm occurred at the end of single stance phase in all groups. As a screening test, the peak moment arm has greater than 50% sensitivity and specificity to discriminate the HE group from the DE and VH groups with peak CG-CP moment arm cutoff points between 16 and 18cm. Conclusions: Examining dynamic balance through the use of the CG-CP moment arm during single stance in gait initiation discriminates between nondisabled and disabled older persons and warrants further investigation as a potential tool to identify people with balance dysfunction. (C) 1999 by the American Congress of rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Massachusetts Gen Hosp, Biomot Lab, Inst Hlth Profess, Grad Program Postprofess Phys Therapy, Boston, MA 02114 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, Inst Hlth Profess, Grad Program Postprofess Phys Therapy, 101 Merrimac St, Boston, MA 02114 USA. FU NIA NIH HHS [R01AG11255, R01AG12561] NR 16 TC 43 Z9 43 U1 1 U2 8 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 MAY PY 1999 VL 80 IS 5 BP 490 EP 494 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 194BF UT WOS:000080171700004 PM 10326909 ER PT J AU Burns, SP Betz, KL AF Burns, SP Betz, KL TI Seating pressures with conventional and dynamic wheelchair cushions in tetraplegia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID SPINAL-CORD INJURY; EXPERIMENTAL-MODEL; SITTING PRESSURE; RISK-FACTORS; INTERFACE; INDIVIDUALS; POSTURE; TRIALS; ULCERS AB Objective: To compare pressure relief from a dynamic wheelchair cushion to a tilt-in-space wheelchair with conventional cushions. Study Design: Repeated measures analysis. Setting and Subjects: Spinal cord injury unit; 16 tilt-in-space wheelchair users with motor-complete tetraplegia. Main Outcome Measures: Interface pressure at ischial tuberosities. Results: Mean ischial pressure with subjects seated upright on the dynamic cushion during the low ischial pressure phase was lower than tilted pressure on the gel cushion, but it was not significantly different from tilted pressure on the dry-flotation cushion (dynamic/upright, 71mmHg; gel/tilted, 86mmHg; dry-flotation/tilted, 74mmHg; p<.05 dynamic vs gel). Mean ischial pressure with subjects upright on the dynamic cushion during the high ischial pressure phase was significantly greater than the gel/upright and dry-flotation/upright conditions (dynamic/upright, 157mmHg; gel/upright, 128mmHg; dry-flotation/upright, 111mmHg;p <.01), Conclusion: The dynamic cushion produces similar pressure relief over the Ischial tuberosities during the low pressure phase to a tilt-in-space wheelchair and conventional cushions. The dynamic cushion may be an alternative to a tilt-in-space wheelchair for some individuals. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 VA Puget Sound Hlth Care Syst, Seattle Div, SCI Unit 128, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, SCI Unit 128, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 35 TC 30 Z9 32 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 1999 VL 80 IS 5 BP 566 EP 571 DI 10.1016/S0003-9993(99)90201-0 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 194BF UT WOS:000080171700018 PM 10326923 ER PT J AU Little, JW Ditunno, JF Stiens, SA Harris, RM AF Little, JW Ditunno, JF Stiens, SA Harris, RM TI Incomplete spinal cord injury: Neuronal mechanisms of motor recovery and hyperreflexia SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; DORSAL-ROOT AXONS; LOCOMOTOR RECOVERY; CHRONIC SPINALIZATION; REFLEX CHANGES; BRAIN-DAMAGE; ADULT CATS; H-REFLEX; RAT; PLASTICITY AB Objective: To understand neuronal mechanisms of motor recovery and hyperreflexia after incomplete spinal cord injury (SCI), and their role in rehabilitation. Design: Reviewed and compared clinical, neurophysiologic, and neuropathologic data from human SCI patients with behavioral, neurophysiologic, and neuroanatomic data from animals to postulate underlying neuronal mechanisms. Outcome: A postulation that two neuronal mechanisms-receptor up-regulation and synapse growth-act sequentially, to explain the gradual appearance of motor recovery after incomplete SCI, These same mechanisms may also act in spinal reflex pathways to mediate hyperreflexia cauda to SCI. Results: After incomplete SCI, walking ability and hyperreflexia often develop. Initially, cord neurons are hyperpolarized and less excitable because of loss of normal descending facilitation; this is spinal shock. Then, gradually, voluntary movement recovers and hyperreflexia develops. Early (hours to days), these changes develop simultaneously, suggesting a common postsynaptic mechanism-likely an increase in postsynaptic receptor excitability, possibly receptor up-regulation. Late (weeks to months), recovery and reflex changes occur at a slow rate, are no longer simultaneous, and are long-lasting, which suggests a presynaptic mechanism, such as local synapse growth in spared descending pathways and in reflex pathways. This presumed synapse growth is seemingly enhanced by active use of the growing pathway. Also, developing hyperreflexia appears to limit motor recovery. Conclusions: These observations suggest that rehabilitation for incomplete SCI should (1) increase activity in spared descending motor pathways, (2) initially use reflex facilitation or central nervous system stimulants to assist spared descending inputs in depolarizing cord neurons, and (3) later minimize reflex input, when spared descending inputs can depolarize cord neurons without reflex facilitation. Better understanding of neuronal mechanisms that underlie motor recovery after incomplete SCI promises better outcomes from rehabilitation. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. Thomas Jefferson Univ, Dept Rehabil Med, Philadelphia, PA 19107 USA. RP Little, JW (reprint author), Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. NR 119 TC 89 Z9 94 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAY PY 1999 VL 80 IS 5 BP 587 EP 599 DI 10.1016/S0003-9993(99)90204-6 PG 13 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 194BF UT WOS:000080171700021 PM 10326926 ER PT J AU Mangi, AA Smith, BL Gadd, MA Tanabe, KK Ott, MJ Souba, WW AF Mangi, AA Smith, BL Gadd, MA Tanabe, KK Ott, MJ Souba, WW TI Surgical management of phyllodes tumors SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the New-England-Surgical-Society CY SEP 25-27, 1998 CL TORONTO, CANADA SP New England Surg Soc ID MALIGNANT CYSTOSARCOMA-PHYLLODES; PROGNOSTIC FACTORS; PHYLLOIDES TUMOR; CLONAL ANALYSIS; BREAST; FIBROADENOMA; FEATURES; SARCOMA AB Hypothesis: Although phyllodes tumors have minimal metastatic potential, we hypothesized that they have a proclivity for local recurrence and should be excised with a wide margin. We reviewed the clinical and radiological appearance of phyllodes tumors and analyzed the role of surgical treatment in their management. Design: Medical records, imaging studies, pathology reports, and interventions were reviewed. Setting: A large tertiary care teaching hospital. Patients: Between 1980 and 1997, 40 patients with phylodes tumors were identified through the tumor registry at the Massachusetts General Hospital, Boston. Main Outcome Measures: Surgical resection margins, rates of local recurrence, incidence of distant metastases, and survival. Results: All 40 patients were female, with a mean age of 41 years. Each patient had a palpable mass or a mammographic finding that was indistinguishable from a fibroadenoma on examination. Tumor size ranged from 5 mm to 28 cm. Local recurrence correlated with excision margins (P<.05), but not with tumor grade or size. Local recurrence occurred in 5 patients, each of whom had positive margins or margins less than 1 cm after excision. After reexcision with a l-cm margin, these individuals remained free of recurrence. One patient developed metastatic disease after total mastectomy and died after chemotherapy. Conclusions: Phyllodes tumors mimic fibroadenomas and are often excised with close margins. Primary excision or reexcision with a l-cm margin is recommended. Mastectomy is indicated for patients with large lesions. Lymph node metastases are unusual and occur secondary to necrotic tumor. Chemotherapy is based on guidelines for the treatment of sarcomas, not breast adenocarcinoma. C1 Harvard Univ, Div Surg Oncol, Massachusetts Gen Hosp, Dept Surg,Sch Med, Boston, MA 02114 USA. RP Souba, WW (reprint author), Harvard Univ, Div Surg Oncol, Massachusetts Gen Hosp, Dept Surg,Sch Med, Cox 626,100 Blossom, Boston, MA 02114 USA. NR 34 TC 80 Z9 88 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 1999 VL 134 IS 5 BP 487 EP 492 DI 10.1001/archsurg.134.5.487 PG 6 WC Surgery SC Surgery GA 194BZ UT WOS:000080173400005 PM 10323420 ER PT J AU Mach, F Sauty, A Sukhova, GK Luster, AD Libby, P AF Mach, F Sauty, A Sukhova, GK Luster, AD Libby, P TI Expression of the three CXC-chemokines IP-10, MIG and I-TAC by human atheroma-associated cells in vitro and in situ: Implication for lymphocyte recruitment in atherogenesis SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1999 VL 144 SU 1 BP 86 EP 86 DI 10.1016/S0021-9150(99)80329-3 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 203BM UT WOS:000080687500330 ER PT J AU Dangas, G Konstadoulakis, MM Cohen, AM Kymionis, GD Kroubouzou, H Toutouza, MG Nanas, JN Sadaniantz, A Stefanadis, CI Chesebro, JH Toutouzas, PK AF Dangas, G Konstadoulakis, MM Cohen, AM Kymionis, GD Kroubouzou, H Toutouza, MG Nanas, JN Sadaniantz, A Stefanadis, CI Chesebro, JH Toutouzas, PK TI Myocardial injury myocardial injury markers and anticardiac auto-antibodies. A prospective evaluation of humoral autoimmunity in coronary heart disease SO ATHEROSCLEROSIS LA English DT Meeting Abstract C1 Cardiol Res Fdn, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brown Univ, Providence, RI 02912 USA. Natl Tech Univ Athens, Athens, Greece. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 1999 VL 144 SU 1 BP 118 EP 118 DI 10.1016/S0021-9150(99)80460-2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 203BM UT WOS:000080687500461 ER PT J AU Rosowski, JJ Ravicz, ME Teoh, SW Flandermeyer, D AF Rosowski, JJ Ravicz, ME Teoh, SW Flandermeyer, D TI Measurements of middle-ear function in the Mongolian gerbil, a specialized mammalian ear SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE middle-ear mechanics; comparative hearing; stapes motion ID SOUND-POWER COLLECTION; MERIONES-UNGUICULATUS; AUDITORY PERIPHERY; MECHANICS AB The middle ear of the Mongolian gerbil is thought to be specialized so that it can hear the 3,000-Hz and lower sounds produced by approaching predators. Evidence in the literature suggests several specializations: (1) an effect of the large middle-ear air spaces in the gerbil is to increase the sensitivity of this ear to sounds of 3,000 Hz and lower in frequency; (2) the combined action of the middle-ear cavity and the significant pars flaccida of the tympanic membrane in the gerbil ear reduces the sensitivity to sounds of frequencies below 500 Hz. This paper describes anatomical and functional measurements of stapes motion and suggests that the stiffness of the gerbil bil ossicular system a Iso acts to reduce sensitivity to low-frequency sounds. The primary conclusion is that the frequency dependence of the gerbil middle ear is the result of the interaction of multiple factors, thereby complicating the relationship between single structural specializations and overall function. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC000194] NR 24 TC 45 Z9 46 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PD MAY-AUG PY 1999 VL 4 IS 3-4 BP 129 EP 136 DI 10.1159/000013831 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 185HG UT WOS:000079661900003 PM 10187920 ER PT J AU Manoach, DS Press, DZ Thangaraj, V Searl, MM Goff, DC Halpern, E Saper, CB Warach, S AF Manoach, DS Press, DZ Thangaraj, V Searl, MM Goff, DC Halpern, E Saper, CB Warach, S TI Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; prefrontal cortex; working memory; functional magnetic resonance imaging; neuropsychology; functional brain mapping ID EMISSION COMPUTED-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PHYSIOLOGIC DYSFUNCTION; FRONTAL-CORTEX; BRAIN ACTIVITY; D-CYCLOSERINE; HYPOFRONTALITY; PERFORMANCE; MRI AB Background: Neuroimaging studies of schizophrenic subjects performing working memory (WM) tasks have demonstrated a relative hypoactivity of prefrontal cortex compared,with normal subjects. Methods: Using functional magnetic resonance imaging (fMRI), we compared dorsolateral prefrontal cortex (DLPFC) activation in 12 schizophrenic and 10 normal subjects during rewarded performance of a WM task. Subjects performed a modified version of the Sternberg Item Recognition Paradigm (SIRP), a continuous performance, choice reaction time (RT) task that requires WM. We compared a high WM load condition with a nonWM choice RT condition and with a low WM load condition. Results: Schizophrenic subjects performed the tasks better than chance but worse than normal subjects. They showed greater activation than normal subjects in the left DLPFC but did not differ in the right DLPFC or in the control region. In the schizophrenic group, left DLPFC activation was inversely correlated with task performance, as measured by errors. Conclusions: These findings contrast with previous studies that demonstrated task-related hypofrontality in schizophrenia. Task parameters that may contribute to this difference are discussed. We hypothesize that the performance and activation differences we observed are also manifestations of prefrontal dysfunction in schizophrenia. They reflect inefficient functioning of the neural circuitry involved in WM. (C) 1999 Society of Biological Psychiatry. C1 Beth Israel Deaconess Med Ctr, Behav Neurol Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Manoach, DS (reprint author), Beth Israel Deaconess Med Ctr, Behav Neurol Unit, 330 Brookline Ave, Boston, MA 02215 USA. NR 36 TC 269 Z9 280 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1999 VL 45 IS 9 BP 1128 EP 1137 DI 10.1016/S0006-3223(98)00318-7 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 194RT UT WOS:000080207900005 PM 10331104 ER PT J AU Bartzokis, G Beckson, M Hance, DB Lu, PH Foster, JA Mintz, J Ling, W Bridge, P AF Bartzokis, G Beckson, M Hance, DB Lu, PH Foster, JA Mintz, J Ling, W Bridge, P TI Magnetic resonance imaging evidence of "silent" cerebrovascular toxicity in cocaine dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE magnetic resonance imaging; cocaine; hyperintense lesions; aging ID MIDDLE CEREBRAL-ARTERY; POSITRON EMISSION TOMOGRAPHY; NEUROVASCULAR COMPLICATIONS; BLOOD-FLOW; ALKALOIDAL COCAINE; LACUNAR INFARCTS; CRACK COCAINE; YOUNG-ADULTS; BRAIN; STROKE AB Background: Cocaine and its metabolites can produce vasospasm. Cocaine-dependent (CD) patients are at increased risk for stroke, and a high frequency of brain perfusion defects has been observed in clinically asymptomatic CD subjects, This is the first controlled magnetic resonance imaging (MRI) study of clinically asymptomatic CD subjects. Methods: Two age-matched groups of male subjects (61 CD and 57 control) participated in the study, Subjects with a history of neurologic symptoms or major medical or neurologic illness, such as hypertension, diabetes, or significant head trauma, were excluded The severity of hyperintense lesions observed on T2-weighted MRI images were rated on a O-3-point scale by an experienced radiologist who was blind to all clinical data. Ratings of 3 were felt to be significant indicators of a possible disease process and were used in the data analysis, three regions were separately rated: the cerebral white matter, subinsular white matter, and subcortical gray matter (basal ganglia and thalamus region). Results: Despite the exclusion criteria minimizing risk factors for cerebrovascular events, 17 of the 61 (27.9%) CD subjects and 4 of 57 (7%) of the control subjects had severe hyperintense lesions suggestive of subclinical or "silent" anoxic vascular events. Significant group differences were observed in the two white matter regions but not in the subcortical gray matter region. The risk of severe white matter lesions in the CD group increased with age, reaching 50% in the oldest age quartile (46-58 years), and this increase was not related to the number of years cocaine was used. Conclusions: The data suggest that asymptomatic CD patients are a heterogeneous population with a significantly increased age-related risk of white matter neuro-vascular toxicity, Premature neurovascular damage may impact treatment outcomes and, as the CD population ages, may manifest as an increased incidence of cognitive deficits, (C) 1999 Society of Biological Psychiatry. C1 N Little Rock VA Med Ctr, Psychiat Serv, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA USA. NIDA, Med Dev Div, Rockville, MD USA. RP Bartzokis, G (reprint author), N Little Rock VA Med Ctr, Psychiat Serv, 116 NLR,2200 Fort Roots Dr Bldg,170, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 74 TC 41 Z9 41 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1999 VL 45 IS 9 BP 1203 EP 1211 DI 10.1016/S0006-3223(98)00228-5 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 194RT UT WOS:000080207900014 PM 10331113 ER PT J AU Rueda, BR Hendry, IR Tilly, JL Hamernik, DL AF Rueda, BR Hendry, IR Tilly, JL Hamernik, DL TI Accumulation of caspase-3 messenger ribonucleic acid and induction of caspase activity in the ovine corpus luteum following prostaglandin F-2 alpha treatment in vivo SO BIOLOGY OF REPRODUCTION LA English DT Article ID PROGRAMMED CELL-DEATH; DNA FRAGMENTATION; INTERLEUKIN-1-BETA-CONVERTING ENZYME; IMMUNOHISTOCHEMICAL ANALYSIS; CAENORHABDITIS-ELEGANS; ICE/CED-3 PROTEASE; FAMILY MEMBERS; BCL-2 FAMILY; GENE CED-3; IN-VIVO AB Caspase-3, a vertebrate homologue of the protein encoded by the Caenorhabditis elegans cell death gene, ced-3, induces apoptosis when overexpressed in eukaryotic cells, Since apoptosis occurs during corpus luteum (CL) regression in many species, including the ewe, these studies were conducted to 1) isolate a cDNA encoding ovine caspase-3, 2) measure steady state amounts of caspase-3 mRNA in the CL during luteolysis induced by prostaglandin F-2 alpha (PGF(2 alpha)) and during the time of maternal recognition of pregnancy, and 3) measure changes in caspase activity during PGF(2 alpha)-initiated luteal regression. Oligonucleotide primers corresponding to a human caspase-3 cDNA sequence were combined with total RNA from ovine CL in a reverse transcription-polymerase chain reaction-based procedure to amplify a 640-base pair partial cDNA with a nucleotide sequence 86% and 81% identical to the human and rat caspase-3 cDNAs, respectively. CL were collected from ewes at 0, 12, or 24 h after treatment with PGF(2 alpha) on Day 10 of the estrous cycle and from nonpregnant and pregnant ewes on Day 12 or Day 14 of the cycle. Northern blot analysis of total cellular RNA from ovine CL and a radiolabeled ovine caspase-3 cRNA probe indicated the presence of a single mRNA transcript of approximately 2.5 kilobases. Levels of caspase-3 mRNA were approximately 3-fold higher (p < 0.05) in CL at 12 h and 24 h after PGF(2 alpha) in comparison to those levels measured in matched CL from untreated ewes. There were no differences (p > 0.05) in amounts of caspase-3 mRNA in CL on Day 12 or Day 14 of the estrous cycle compared to Day 12 or Day 14 of pregnancy, respectively. Caspase activity in CL (measured by the ability of CL lysates to cleave an artificial caspase substrate) was also significantly (p < 0.05) increased in CL collected after treatment with PGF(2 alpha) compared to CL collected from nontreated ewes, We conclude that physiological cell death during PGF(2 alpha)-induced luteal regression in the ewe is mediated, at least in part, via increased expression and activity of the caspase family of pro-apoptotic proteases. C1 Womens Res Inst, Wichita, KS 67214 USA. Univ Kansas, Sch Med, Dept Obstet & Gynecol, Wichita, KS 67214 USA. Harvard Univ, Sch Med,Dept Obstet & Gynecol, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. RP Rueda, BR (reprint author), Womens Res Inst, 1010 N Kansas, Wichita, KS 67214 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 52 TC 48 Z9 50 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 1999 VL 60 IS 5 BP 1087 EP 1092 DI 10.1095/biolreprod60.5.1087 PG 6 WC Reproductive Biology SC Reproductive Biology GA 189VE UT WOS:000079926200004 PM 10208968 ER PT J AU Maheshwari, G Wells, A Griffith, LG Lauffenburger, DA AF Maheshwari, G Wells, A Griffith, LG Lauffenburger, DA TI Biophysical integration of effects of epidermal growth factor and fibronectin on fibroblast migration SO BIOPHYSICAL JOURNAL LA English DT Article ID MAMMARY ADENOCARCINOMA CELLS; SMOOTH-MUSCLE CELLS; ACTIN STRESS FIBERS; SIGNAL-TRANSDUCTION; FACTOR RECEPTOR; MAP KINASE; SUBSTRATUM ADHESION; FOCAL ADHESIONS; INTEGRIN; MOTILITY AB Cell migration is regulated simultaneously by growth factors and extracellular matrix molecules. Although information is continually increasing regarding the relevant signaling pathways, there exists little understanding concerning how these pathways integrate to produce the biophysical processes that govern locomotion. Herein, we report the effects of epidermal growth factor (EGF) and fibronectin (Fn) on multiple facets of fibroblast motility: locomotion speed, membrane extension and retraction activity, and adhesion. A surprising finding is that EGF can either decrease or increase locomotion speed depending on the surface Fn concentration, despite EGF diminishing global cell adhesion at all Fn concentrations. At the same time, the effect of EGF on membrane activity varies from negative to positive to no-effect as Fn concentration and adhesion range from low to high. Taking these effects together, we find that EGF and Fn regulate fibroblast migration speed through integration of the processes of membrane extension, attachment, and detachment, with each of these processes being rate-limiting for locomotion in sequential regimes of increasing adhesivity. Thus, distinct biophysical processes are shown to integrate for overall cell migration responses to growth factor and extracellular matrix stimuli. C1 MIT, Div Bioengn & Environm Hlth, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. RP Lauffenburger, DA (reprint author), MIT, Div Bioengn & Environm Hlth, Dept Chem Engn, 77 Massachusetts Ave,56-341, Cambridge, MA 02139 USA. OI Wells, Alan/0000-0002-1637-8150 FU NCI NIH HHS [CA69213] NR 58 TC 113 Z9 113 U1 0 U2 13 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 1999 VL 76 IS 5 BP 2814 EP 2823 PG 10 WC Biophysics SC Biophysics GA 195XZ UT WOS:000080278600047 PM 10233097 ER PT J AU Le Doux, JM Morgan, JR Yarmush, ML AF Le Doux, JM Morgan, JR Yarmush, ML TI Differential inhibition of retrovirus transduction by proteoglycans and free glycosaminoglycans SO BIOTECHNOLOGY PROGRESS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX VIRUS; SURFACE HEPARAN-SULFATE; GENE-TRANSFER; ENVELOPE GLYCOPROTEINS; MURINE LEUKEMIA; CHONDROITIN SULFATE; BINDING; CELLS; INFECTION AB We have previously shown that the efficiency of retrovirus-mediated gene transfer is limited in part due to the presence of chondroitin sulfate proteoglycans in virus stocks. In this study, we have used a model recombinant retrovirus encoding the Escherichia coli lacZ gene, bovine aorta chondroitin sulfate proteoglycan (CSPG), various free glycosaminoglycan chains (GAGs), and quantitative assays for retrovirus transduction to explore the mechanism by which proteoglycans and glycosaminoglycans inhibit retroviruses. We found that CSPG and GAGs block an early step in virus-cell interactions but do not act by inactivating viruses or by reducing the growth rate of the target cells. CSPG and most of the GAGs tested (chondroitin sulfate A, chondroitin sulfate B, heparin, heparan sulfate, and hyaluronic acid) inhibited transduction, but with widely varying degrees of activity. The chemical structure of GAGs was found to be an important determinant of their inhibitory activity, which suggests that GAGs do not inhibit transduction simply because they are highly negatively charged polymers. When GAGs were used in combination with a cationic polymer (Polybrene), however, their inhibitory activity was neutralized, and interestingly, at optimal doses of GAG and Polybrene, transduction efficiency was actually enhanced by as much as 72%. In contrast, the inhibitory activity of CSPG, due to the influence of its core protein, was not substantially reduced by Polybrene. The importance of these findings to our understanding of retrovirus-cell interactions and to the development of more efficient retrovirus gene transfer protocols is discussed. C1 Harvard Univ, Ctr Engn Med, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Surg Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Ctr Engn Med, Massachusetts Gen Hosp, Sch Med, Bigelow 1401, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [R29 AR42012]; NICHD NIH HHS [P01 HD28528]; NIGMS NIH HHS [GM-08339] NR 48 TC 27 Z9 27 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 1999 VL 15 IS 3 BP 397 EP 406 DI 10.1021/bp990049c PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 203NH UT WOS:000080713400014 PM 10356257 ER PT J AU Vyas, P Ault, K Jackson, CW Orkin, SH Shivdasani, RA AF Vyas, P Ault, K Jackson, CW Orkin, SH Shivdasani, RA TI Consequences of GATA-1 deficiency in megakaryocytes and platelets SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; GLYCOPROTEIN IB-BETA; IN-VIVO; HEMATOPOIETIC-CELLS; ERYTHROID DEVELOPMENT; BLEEDING-TIME; MICE LACKING; FACTOR NF-E2; GPIIB GENE; EXPRESSION AB In the absence of the hematopoietic transcription factor GATA-1, mice develop thrombocytopenia and an increased number of megakaryocytes characterized by marked ultrastructural abnormalities. These observations establish a critical role for GATA-1 in megakaryopoiesis and raise the question as to how GATA-1 influences megakaryocyte maturation and platelet production. To begin to address this, we have performed a more detailed examination of the megakaryocytes and platelets produced in mice that lack GATA-1 in this lineage. Our analysis demonstrates that compared with their normal counterparts, GATA-1-deficient primary megakaryocytes exhibit significant hyperproliferation in liquid culture, suggesting that the megakaryocytosis seen in animals is nonreactive. Morphologically, these mutant megakaryocytes are small and show evidence of retarded nuclear and cytoplasmic development. A significant proportion of these cells do not undergo endomitosis and express markedly lower levels of mRNA of all megakaryocyte-associated genes tested, including GPIb alpha, GPIb beta, platelet factor 4 (PF4), c-mpl, and p45 NF-EP. These results are consistent with regulation of a program of megakaryocytic differentiation by GATA-1. Bleeding times are significantly prolonged in mutant animals. GATA-1-deficient platelets show abnormal ultrastructure, reminiscent of the megakaryocytes from which they are derived, and exhibit modest but selective defects in platelet activation in response to thrombin or to the combination of adenosine diphosphate (ADP) and epinephrine, Our findings indicate that GATA-1 serves multiple functions in megakaryocyte development, influencing both cellular growth and maturation. (C) 1999 by The American Society of Hematology. C1 Childrens Hosp, Dept Hematol Oncol, Boston, MA USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol & Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Maine Med Ctr, Res Inst, S Portland, ME USA. St Jude Childrens Res Hosp, Dept Expt Hematol, Memphis, TN 38105 USA. RP Vyas, P (reprint author), Childrens Hosp, Med Ctr, 300 Longwood Ave, Boston, MA 02115 USA. NR 40 TC 237 Z9 244 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1999 VL 93 IS 9 BP 2867 EP 2875 PG 9 WC Hematology SC Hematology GA 190UZ UT WOS:000079984800014 PM 10216081 ER PT J AU Sattler, M Winkler, T Verma, S Byrne, CH Shrikhande, G Salgia, R Griffin, JD AF Sattler, M Winkler, T Verma, S Byrne, CH Shrikhande, G Salgia, R Griffin, JD TI Hematopoietic growth factors signal through the formation of reactive oxygen species SO BLOOD LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; COLONY-STIMULATING FACTOR; DNA-BINDING ACTIVITY; HYDROGEN-PEROXIDE; REDOX REGULATION; PROBE 2',7'-DICHLOROFLUORESCIN; COMPLEX-FORMATION; OXIDATIVE STRESS; FACTOR RECEPTORS; KAPPA-B AB Hematopoietic growth factors (HGFs) stimulate growth, differentiation, and prevent apoptosis of progenitor cells. Each growth factor has a specific cell surface receptor, which activates both unique and shared signal transduction pathways. We found that several HGFs, including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), steel factor (SF), and thrombopoietin (TPO) induce a rapid increase in reactive oxygen species (ROS) in quiescent cells. In an effort to understand the potential biochemical and biological consequences of increased ROS in these cells, we exposed growth factor-deprived cells to hydrogen peroxide (H2O2) at concentrations that increased intracellular ROS. H2O2 induced a dose-dependent increase in tyrosine phosphorylation, including increased tyrosine phosphorylation of the GM-CSF receptor beta chain (beta c), STATE, and other signaling proteins. H2O2 also induced expression of the early response gene c-FOS, and G1- to S-phase transition, but not S- to G2/M-phase transition of MO7e cells. The cell permeable antioxidant pyrrolidine dithiocarbamate (PDTC) decreased the intracellular levels of ROS and inhibited tyrosine phosphorylation induced by GM-CSF in MO7e cells, suggesting that ROS generation plays an important role in GM-CSF signaling. Consistent with this notion, PDTC and two other antioxidants, N-acetyl cysteine and a-mercaptoethanol, reduced growth and viability of MO7e cells. These results suggest that generation of ROS in response to HGFs may contribute to downstream signaling events, especially those involving tyrosine phosphorylation. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA01730, CA36167] NR 41 TC 193 Z9 197 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1999 VL 93 IS 9 BP 2928 EP 2935 PG 8 WC Hematology SC Hematology GA 190UZ UT WOS:000079984800020 PM 10216087 ER PT J AU Roodman, GD AF Roodman, GD TI Mechanisms of abnormal bone turnover in Paget's disease SO BONE LA English DT Article; Proceedings Paper CT 25th Anniversary Symposium of the National-Association-for-the-Relief-of-Pagets-Disease CY JUL 15-17, 1998 CL OXFORD, ENGLAND SP Natl Assoc Relief Pagets Dis ID CELLS; INTERLEUKIN-6 C1 Audie L Murphy Mem Vet Hosp, Dept Res Hematol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, Dept Res Hematol, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 10 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 1999 VL 24 IS 5 SU S BP 39S EP 40S DI 10.1016/S8756-3282(99)00045-9 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192NZ UT WOS:000080086400025 PM 10321925 ER PT J AU Krane, SM AF Krane, SM TI A marker for type I collagen degradation identified in urine from patients with Paget's disese of bone SO BONE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 1999 VL 24 IS 5 SU S BP 52S EP 52S DI 10.1016/S8756-3282(99)00054-X PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192NZ UT WOS:000080086400034 ER PT J AU Pogue, BW Momma, T Wu, HC Hasan, T AF Pogue, BW Momma, T Wu, HC Hasan, T TI Transient absorption changes in vivo during photodynamic therapy with pulsed-laser light SO BRITISH JOURNAL OF CANCER LA English DT Article DE photosensitizer; BPD-MA; pulsed-laser; optical dosimetry; tumour ID CONTINUOUS-WAVE LIGHT; RING-A BPD; PHOTOPHYSICAL PROPERTIES; BLADDER-CARCINOMA; MOUSE-TUMOR; DYE-LASER; NUDE-MICE; PHOTOSENSITIZATION; MECHANISMS; INVIVO AB High intensity pulsed-laser light can be used to excite absorbing molecules to transient states in large proportions. The laser-induced spectral changes can be characterized by transient changes in light propagation; through the tissue provided the excited states of these molecules have altered absorption spectra. Characterization of these transient changes may then be used to exploit new mechanisms in photosensitization and/or to optimize photobiological effects. In this study,transmittance and reflectance were measured as a function df laser pulse energy, from tissue-simulating media as well as in rat muscle and liver slices, both with and without the photosensitizer benzoporphyrin derivative monoacid (BPD-MA) present. There was a transient decrease in absorption from the photosensitizer at peak pulse irradiance in the range of 100-1000 W cm(-2). The depth of photodynamic treatment-induced tissue necrosis was measured in a subcutaneous prostate cancer model in Copenhagen rats. A comparison between continuous wave irradiation and pulsed irradiation with the same average incident irradiance showed no statistically significant difference in the depth of necrosis at 48 h after irradiation. These results indicate that photosensitizer population-state changes are measurable in tissues and may provide a method for measuring triplet-state properties of photosensitizer in vivo, but for BPD-MA at clinically used concentrations these changes do not significantly affect the depth of photodynamically-induced tissue damage. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. NR 45 TC 19 Z9 19 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1999 VL 80 IS 3-4 BP 344 EP 351 DI 10.1038/sj.bjc.6690361 PG 8 WC Oncology SC Oncology GA 191NR UT WOS:000080028900005 PM 10408836 ER PT J AU Gimm, O Gossling, A Marsh, DJ Dahia, PLM Mulligan, LM von Deimling, A Eng, C AF Gimm, O Gossling, A Marsh, DJ Dahia, PLM Mulligan, LM von Deimling, A Eng, C TI Mutation and deletion analysis of GFR alpha-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours SO BRITISH JOURNAL OF CANCER LA English DT Article DE GDNF; GDNFR alpha; GFR alpha-1; RET; brain tumours ID MICE LACKING GDNF; IN-SITU HYBRIDIZATION; TYROSINE KINASE RET; NEUROTROPHIC FACTOR; FAMILY RECEPTOR; GLIOBLASTOMA-MULTIFORME; FUNCTIONAL RECEPTOR; NERVOUS-SYSTEM; PTEN GENE; NEURTURIN AB Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFR alpha-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain rumours for the presence of mutations in GDNF and GFR alpha-1. No mutations were found in the coding region of GDNF. We identified six previously described GFR alpha-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 rumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFR alpha-1 are not a common aetiologic event in brain rumours. However, either deletion of GFR alpha-1 and/or nearby genes may contribute to the pathogenesis of these tumours. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Harvard Univ, Sch Med,Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Dept Med,Translat Res Lab,Dept Adult Oncol, Boston, MA 02115 USA. Univ Kliniken Bonn, Inst Neuropathol, D-53105 Bonn, Germany. Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Paediat, Kingston, ON K7L 3N6, Canada. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690C MRF, Columbus, OH 43210 USA. RI Marsh, Deborah/I-1491-2014; von Deimling, Andreas/F-7774-2013 OI Marsh, Deborah/0000-0001-5899-4931; von Deimling, Andreas/0000-0002-5863-540X NR 49 TC 6 Z9 6 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1999 VL 80 IS 3-4 BP 383 EP 386 DI 10.1038/sj.bjc.6690367 PG 4 WC Oncology SC Oncology GA 191NR UT WOS:000080028900011 PM 10408842 ER PT J AU Cenni, B Kim, HK Bubley, GJ Aebi, S Fink, D Teicher, BA Howell, S Christen, RD AF Cenni, B Kim, HK Bubley, GJ Aebi, S Fink, D Teicher, BA Howell, S Christen, RD TI Loss of DNA mismatch repair facilitates reactivation of a reporter plasmid damaged by cisplatin SO BRITISH JOURNAL OF CANCER LA English DT Article DE cisplatin; DNA mismatch repair; hMLH1; hMSH2; colon cancer; endometrial cancer ID ANTICANCER DRUG CISPLATIN; IN-VIVO; MICROSATELLITE INSTABILITY; ENHANCED REPAIR; CANCER-CELLS; TUMOR-CELLS; RESISTANCE; CIS-DIAMMINEDICHLOROPLATINUM(II); ADDUCTS; GENE AB In addition to recognizing and repairing mismatched bases in DNA, the mismatch repair (MMR) system also detects cisplatin DNA adducts and loss of MMR results in resistance to cisplatin. A comparison was made of the ability of MMR-proficient and -deficient cells to remove cisplatin adducts from their genome and to reactivate a transiently transfected plasmid that had previously been inactivated by cisplatin to express the firefly luciferase enzyme. MMR deficiency due to loss of hMLH1 function did not change the extent of platinum (Pt) accumulation or kinetics of removal from total cellular DNA. However, MMR-deficient cells, lacking either hMLH1 or hMSH2, generated twofold more luciferase activity from a cisplatin-damaged reporter plasmid than their MMR-proficient counterparts. Thus, detection of the cisplatin adducts by the MMR system reduced the efficiency of reactivation of the damaged luciferase gene compared to cells lacking this detector. The twofold reduction in reactivation efficiency was of the same order of magnitude as the difference in cisplatin sensitivity between the MMR-proficient and -deficient cells. We conclude that although MMR-proficient and -deficient cells remove Pt from their genome at equal rates, the loss of a functional MMR system facilitates the reactivation of a cisplatin-damaged reporter gene. C1 Univ Calif San Diego, Dept Med 0058, La Jolla, CA 92093 USA. Harvard Med Sch, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Christen, RD (reprint author), Univ Calif San Diego, Dept Med 0058, 9500 Gillman Dr, La Jolla, CA 92093 USA. RI Aebi, Stefan/F-2004-2010 OI Aebi, Stefan/0000-0002-3383-9449 NR 34 TC 13 Z9 15 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1999 VL 80 IS 5-6 BP 699 EP 704 DI 10.1038/sj.bjc.6690412 PG 6 WC Oncology SC Oncology GA 192CB UT WOS:000080059700009 PM 10360646 ER PT J AU Yang, C Li, YC Kuter, DJ AF Yang, C Li, YC Kuter, DJ TI The physiological response of thrombopoietin (c-Mpl ligand) to thrombocytopenia in the rat SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombocytopenia; thrombopoietin; platelets; megakaryocytes; polysome ID MEGAKARYOCYTE GROWTH; PLATELETS; MEGAPOIETIN; BUSULFAN; BINDING; RABBIT; PLOIDY; CELLS; LEVEL; MODEL AB It has been suggested that circulating levels of thrombopoietin (TPO) are determined primarily by platelet and megakaryocyte clearance of TPO and not by changes in hepatic TPO production. The experimental evidence accumulated so far to support this hypothesis is incomplete. We have therefore developed a new model of non-immune thrombocytopenia in the rat and used it to assess the relationship of TPO (c-mpl ligand) to the platelet mass. 14 d following the administration of busulphan, the platelet count reached a nadir of <2% of its initial value and remained at this level for up to 6 d. Circulating TPO was measured by two different bioassays which were sensitive enough to measure normal levels of TPO and levels rose from 106 +/- 29 pg/ml in animals with a normal platelet count to 2015 +/- 544 pg/ml in those with thrombocytopenia. These elevated levels of TPO were solely a response to the low platelet count since transfusion of a normal mass of platelets into the thrombocytopenic animals returned the TPO levels exactly to normal. The increase in TPO levels in thrombocytopenic animals was not due to increased TPO production since the thrombocytopenic animals did not show any increase in TPO mRNA in total or polysome-associated hepatic RNA. Rather, rat platelets were able to bind and stoichiometrically remove TPO from thrombocytopenic plasma via high-affinity receptors (K-d = 38 +/- 10 pM; 233 +/- 32 receptors/platelet) These results serve as a proof that the circulating level of TPO is determined not by alterations in TPO transcription or translation but by the ability of the platelet mass to bind and remove TPO from the circulation. C1 Massachusetts Gen Hosp, Hematol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Hematol Unit, Cox 640,100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 54838] NR 22 TC 38 Z9 39 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1999 VL 105 IS 2 BP 478 EP 485 DI 10.1046/j.1365-2141.1999.01359.x PG 8 WC Hematology SC Hematology GA 201XC UT WOS:000080621300026 PM 10233424 ER PT J AU Keel, SB Rosenberg, AE AF Keel, SB Rosenberg, AE TI Hemorrhagic epithelioid and spindle cell hemangioma - A newly recognized, unique vascular tumor of bone SO CANCER LA English DT Article; Proceedings Paper CT Meeting of the International-Academy-of-Pathology CY OCT 18-23, 1998 CL NICE, FRANCE SP Int Acad Pathol DE epithelioid vascular tumor of bone; epithelioid hemangioma; epithelioid hemangioendothelioma; epithelioid angiosarcoma ID LOW-GRADE ANGIOSARCOMA; HEMANGIOENDOTHELIOMA; NEOPLASM; SKIN AB BACKGROUND. Epithelioid vascular tumors of bone are uncommon and include epithelioid hemangioma, epithelioid hemangioendothelioma, and epithelioid angiosarcoma. It is important to distinguish among them because they have significantly different biologic potential and require different forms of therapy. In the current study the authors describe six cases of a distinct benign epithelioid and spindle cell vascular tumor of bone that, because of their unusual morphology, were confused with aggressive vascular neoplasms. METHODS. Cases were retrieved from the surgical pathology files of the Department of Pathology or from the consultation files of one of the authors. Hematoxylin and eosin stained slides were examined. Immunohistochemistry was performed on two cases and electron microscopy was performed on one case. RESULTS. The tumors arose in the small bones of the hands and feet and the tibia. Three patients had multifocal bone disease at the time of presentation. Histologically, all lesions were comprised of lobules of spindle cells that grew focally in a fascicular pattern and were associated with abundant hemorrhage. Plump epithelioid cells were intermixed and were present focally in the interlobular areas as well, in which they lined larger, more well developed vascular spaces, often protruding into the vascular lumen in a "tombstone" fashion. Immunohistochemically and ultrastructurally the neoplastic cells had features of endothelium. One case was treated by amputation, one by resection, three by curettage, and one by curettage plus radiation therapy. None of the lesions was locally aggressive nor did any metastasize. CONCLUSIONS. The authors believe that hemorrhagic epithelioid and spindle cell hemangioma of bone is a histologically benign bone tumor. It should be distinguished from malignant epithelioid vascular tumors of bone, which have metastatic potential and need to be treated more aggressively. (C) 1999 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rosenberg, AE (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 32 Fruit St, Boston, MA 02114 USA. NR 23 TC 21 Z9 25 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1999 VL 85 IS 9 BP 1966 EP 1972 DI 10.1002/(SICI)1097-0142(19990501)85:9<1966::AID-CNCR13>3.0.CO;2-W PG 7 WC Oncology SC Oncology GA 190AK UT WOS:000079939200013 PM 10223237 ER PT J AU Jeyarajah, AR Ind, TEJ Skates, S Oram, DH Jacobs, IJ AF Jeyarajah, AR Ind, TEJ Skates, S Oram, DH Jacobs, IJ TI Serum CA125 elevation and risk of clinical detection of cancer in asymptomatic postmenopausal women SO CANCER LA English DT Article DE CA125; cancer; ovarian carcinoma; screening ID OVARIAN-CANCER; CA-125; CARCINOMA; ANTIGEN AB BACKGROUND. This study was undertaken to assess the correlation between CA 125 elevation, a past history of cancer, and future risk of a diagnosis of cancer among asymptomatic postmenopausal women. METHODS. The subjects consisted of a study group of 771 women with elevated CA125 (greater than or equal to 30 U/mL) and a control group of 771 women with CA125 <30 U/mL. They were selected from a prospective ovarian carcinoma screening trial of 22,000 postmenopausal women followed for a mean of 2269 days. RESULTS. Subjects in the study group were more likely to have a past history of cancer than subjects in the control group (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.49-3.58). Much of the difference in cancer risk prior to CA125 testing was attributable to a past history of breast carcinoma (OR 2.53, 95% CI 1.45-4.42), but CA125 elevation did not predict recurrence of breast carcinoma. Subjects in the study group were also more likely to develop cancer in the future (OR 2.53, 95% CI 1.61-3.97). This difference was due to an increased risk of gynecologic cancer (OR 30.09, 95% CI 4.09-221.59). CA125 elevation was not associated with an increase in the future risk of developing breast carcinoma (OR 1.19, 95% CI 0.53-2.66) or nongynecologic cancer (OR 1.43, 95% CI 0.86-2.36). CONCLUSIONS. Elevated CA125 in asymptomatic postmenopausal women is not a predictor of nongynecologic cancer or recurrence of cancer, and further investigation should be limited to the detection of gynecologic cancers. (C) 1999 American Cancer Society. C1 Univ London St Bartholomews Hosp Med Coll, Gynecol Canc Res Unit, London EC1A 7BE, England. Univ London St Bartholomews Hosp Med Coll, Dept Gynecol Oncol, London EC1A 7BE, England. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacobs, IJ (reprint author), Univ London St Bartholomews Hosp Med Coll, Gynecol Canc Res Unit, London EC1A 7BE, England. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 10 TC 14 Z9 15 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1999 VL 85 IS 9 BP 2068 EP 2072 PG 5 WC Oncology SC Oncology GA 190AK UT WOS:000079939200025 PM 10223249 ER PT J AU Loeffler, JS Barker, FG Chapman, PH AF Loeffler, JS Barker, FG Chapman, PH TI Role of radiosurgery in the management of central nervous system metastases SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 14th Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium on the Challenges in Cancer Metastasis CY SEP 11-12, 1998 CL NAGOYA, JAPAN SP Bristol Myers Squibb DE radiosurgery; brain metastases; stereotaxy; radiotherapy ID SINGLE BRAIN METASTASIS; STEREOTAXIC RADIOSURGERY; LINEAR-ACCELERATOR AB Radiosurgery is being used more routinely to treat patients with inoperable, recurrent, or multiple brain metastases from systemic cancer. Results in > 2000 treated patients have been published during the past 8 years. These results indicate that permanent local control can be obtained in > 80% of treated lesions with complications in < 10% of patients. Success is independent of the histology, ie, melanoma vs adenocarcinoma, of the treated lesion or number of lesions treated. The long-term results of radiosurgery compare favorably with those seen following surgical resection. The cost-effectiveness of radiosurgery compared to surgical resection favors an expanded role for this technology in the treatment of selected patients with brain metastases. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1999 VL 43 SU S BP S11 EP S14 DI 10.1007/s002800051092 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 202DJ UT WOS:000080636600003 PM 10357553 ER PT J AU Bao, SD Chang, MS Auclair, D Sun, YP Wang, YB Wong, WK Zhang, JY Liu, Y Qian, XQ Sutherland, R Magi-Galluzi, C Weisberg, E Cheng, EYS Hao, LN Sasaki, H Campbell, MS Kraeft, SK Loda, M Lo, KM Chen, LB AF Bao, SD Chang, MS Auclair, D Sun, YP Wang, YB Wong, WK Zhang, JY Liu, Y Qian, XQ Sutherland, R Magi-Galluzi, C Weisberg, E Cheng, EYS Hao, LN Sasaki, H Campbell, MS Kraeft, SK Loda, M Lo, KM Chen, LB TI HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma SO CANCER RESEARCH LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DNA-DAMAGE AB Using the palindromic PCR-cDNA display method, we have cloned a novel gene overexpressed by human colon carcinoma relative to normal colon. Among normal tissues examined, only testis expresses it at a high level. Sequence analysis revealed its extensive homology with checkpoint genes rad17 of Schizosaccharomyces pombe and RAD24 of Saccharomyces cerevisiae. This novel gene designated as hRad17 is localized to chromosome 5q12,13.1, a region known to be deleted in a variety of human cancers. Promoter region and one pseudogene of hRad17 have been identified. Whereas the increased expression of hRad17 by human colon carcinomas may be related to the known resistance of these cells to DNA-damaging agents during therapy, the deletion of hRad17 in a variety of cancers may predispose them to increased rate of mutation and heightened sensitivity to DNA-damaging agents, including radiation and anti-cancer drugs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Boston, MA 02115 USA. Shionogi BioRes Corp, Lexington, MA 02421 USA. RP Chen, LB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA. OI CHANG, MAU-SUN/0000-0002-3703-2386 NR 20 TC 36 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1999 VL 59 IS 9 BP 2023 EP 2028 PG 6 WC Oncology SC Oncology GA 192EW UT WOS:000080066300002 PM 10232579 ER PT J AU Tai, YT Strobel, T Kufe, D Cannistra, SA AF Tai, YT Strobel, T Kufe, D Cannistra, SA TI In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene SO CANCER RESEARCH LA English DT Article ID INDUCED APOPTOSIS; IN-VIVO; DEATH; CARCINOMAS; MUTATIONS; DF3 AB The BAX proapoptotic protein is capable of inducing cell death either directly, through its effects on mitochondrial function, or indirectly, by lowering the apoptotic threshold in response to certain chemotherapy agents. In this study, we tested the hypothesis that selective expression of BAX in human ovarian cancer through adenoviral gene transfer might represent a novel approach to eradicating tumor cells in vivo. Two constructs were prepared using replication-deficient adenoviral vectors containing either the cDNA for beta-galactosidase (Ad.DF3.beta GAL) or hemagglutinin (HA)-tagged BAX (Ad.DF3.BAX) under the control of the DF3 promoter. The DF3 promoter was used to confer tumor-specific gene expression in view of its restricted pattern of expression in the majority of human ovarian cancers and its limited expression in normal peritoneal mesothelial cells. In vitro infection of up to seven different epithelial cancer cell lines with Ad.DF3.beta GAL or Ad.DF3.BAX resulted in expression of either beta-galactosidase activity or HA-BAX protein, respectively, which was highly correlated with DF3 levels. Furthermore, infection with Ad.DF3.BAX was capable of highly selective cytotoxicity of DF3-positive ovarian cancer clonogenic cells in vitro. The effect of i.p. administration of Ad.DF3.BAX was also assessed in nude mice inoculated with the DF3-positive 36M2 human ovarian cancer cell line. Expression of either beta-galactosidase activity (after Ad.DF3.beta GAL treatment) or HA-BAX transcripts (after Ad.DF3.BAX treatment) was restricted to tumor tissue in vivo. Importantly, administration of Ad.DF3.BAX on days 2 and 3 after tumor inoculation was capable of eradicating >99% of tumor implants, These results demonstrate the feasibility of tumor selective expression of a proapoptotic protein such as BAX through adenoviral gene transfer. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Pharmacol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Cannistra, SA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Hematol Oncol, E Campus,Kirstein 158,330 Brookline Ave, Boston, MA 02215 USA. NR 21 TC 79 Z9 81 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1999 VL 59 IS 9 BP 2121 EP 2126 PG 6 WC Oncology SC Oncology GA 192EW UT WOS:000080066300021 PM 10232598 ER PT J AU Woolf, CJ AF Woolf, CJ TI Neurobiology of chronic head pain. SO CEPHALALGIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 1999 VL 19 IS 4 BP 292 EP 292 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 205PC UT WOS:000080828900041 ER PT J AU Sanchez del Rio, M Bakker, D Hadjikhani, N Wu, O Cutrer, FM Sorensen, G Tootell, R Kwong, K Rosen, B Moskowitz, MA AF Sanchez del Rio, M Bakker, D Hadjikhani, N Wu, O Cutrer, FM Sorensen, G Tootell, R Kwong, K Rosen, B Moskowitz, MA TI Neurovascular cortical spreading phenomenon during spontaneous visual aura. SO CEPHALALGIA LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Stroke & Neurovasc Lab, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Neuroimaging Ctr, Charlestown, MA USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 NR 0 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD MAY PY 1999 VL 19 IS 4 BP 310 EP 310 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 205PC UT WOS:000080828900068 ER PT J AU Ay, H Ay, I Koroshetz, WJ Finklestein, SP AF Ay, H Ay, I Koroshetz, WJ Finklestein, SP TI Potential usefulness of basic fibroblast growth factor as a treatment for stroke SO CEREBROVASCULAR DISEASES LA English DT Review DE cerebral ischemia; ischemic stroke; basic fibroblast growth factor; neuroprotection; recovery ID FOCAL CEREBRAL-ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; REDUCES INFARCT SIZE; HIPPOCAMPAL-NEURONS; FUNCTIONAL MRI; MESSENGER-RNA; BRAIN INJURY; RAT-BRAIN; RECOVERY; LOCALIZATION AB Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth facto rs may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ay, H (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 41 TC 61 Z9 63 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD MAY-JUN PY 1999 VL 9 IS 3 BP 131 EP 135 DI 10.1159/000015941 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 190YY UT WOS:000079994100001 PM 10207203 ER PT J AU Evans, RH Gelder, CM Smith, AP Freedman, AR AF Evans, RH Gelder, CM Smith, AP Freedman, AR TI Pneumocystis carinii pneumonia mimicking Wegener's granulomatosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PERMEABILITY-INCREASING PROTEIN; INFLAMMATORY BOWEL-DISEASE; AUTOANTIBODIES; ANCA; BPI C1 Univ Wales Hosp, Dept Med & Infect Dis, Cardiff CF4 4XW, S Glam, Wales. Llandough Hosp, Dept Resp Med, Cardiff, S Glam, Wales. RP Evans, RH (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 5th Floor,13th St,Bldg 149, Boston, MA 02129 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1999 VL 28 IS 5 BP 1163 EP 1164 DI 10.1086/517765 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190HB UT WOS:000079955800038 PM 10452656 ER PT J AU Mankin, HJ AF Mankin, HJ TI Diversity in orthopaedics SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB There is little doubt that women, African Americans, and Hispanics, have fewer opportunities to enter, or once in, to become contributing members of orthopaedic programs in the United States. The expressed reasons for this by faculty members sometimes sound reasonable, but on analysis all are spurious. It is the responsibility of the chief of service and the faculty members to change this pattern and offer all individuals equal opportunity and treat them identically to anyone in the program or on the faculty. Some guidelines are provided. C1 Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Combined Orthopaed Residency, Boston, MA USA. Beth Israel Deaconess Hosp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, Gray 604, Boston, MA 02114 USA. NR 1 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 1999 IS 362 BP 85 EP 87 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 195AW UT WOS:000080227800015 PM 10335284 ER PT J AU Rodrigue, SW Rosenthal, DI Barton, NW Zurakowski, D Mankin, HJ AF Rodrigue, SW Rosenthal, DI Barton, NW Zurakowski, D Mankin, HJ TI Risk factors for osteonecrosis in patients with type 1 Gaucher's disease SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; ENZYME REPLACEMENT THERAPY; SKELETAL COMPLICATIONS; BONE; MARROW AB This study investigated 51 patients with Type 1 Gaucher's disease clinically and radiographically for the presence of osteonecrosis, Twenty-five female and 26 male patients with a mean age of 37 years were evaluated retrospectively for osteonecrosis of the proximal and distal femur, proximal tibia, and proximal humerus, All patients were examined before enzyme replacement therapy. Gender, age at diagnosis, prior splenectomy, hematocrit, platelet count, acid phosphatase level, radiographs of the long bones, and magnetic resonance quantitative chemical shift imaging of the spine were analyzed to see if any of these values or findings were associated with the presence of osteonecrosis, Splenectomy was an independent risk factor for the presence of osteonecrosis in three of the four major sites and was a multivariate risk factor for osteonecrosis of the proximal femur and tibia. Male gender was the other significant multivariate risk factor for osteonecrosis of the humerus and distal femur when all sites were taken into account. C1 Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Cambridge, MA 02138 USA. NIH, Inst Neurol Disorders & Stroke, Ctr Clin, Washington, DC USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. NR 34 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 1999 IS 362 BP 201 EP 207 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 195AW UT WOS:000080227800030 PM 10335299 ER PT J AU Doehring, TC Rubash, HE Dore, DE AF Doehring, TC Rubash, HE Dore, DE TI Micromotion measurements with hip center and modular neck length alterations SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FEMORAL COMPONENTS; INITIAL STABILITY; JOINT FORCES; BONE LOSS; ARTHROPLASTY; PROSTHESES; MOTION; RECONSTRUCTION; REPLACEMENT; FIXATION AB Hip center relocation often is necessary because of acetabular deformity or in revision surgery. Superolateral relocation of the acetabular component increases the hip joint reaction forces and has been associated with early femoral implant loosening. In addition, relocation can necessitate the use of extended femoral neck lengths. The purpose of this study was to compare the initial stability (micromotion) of an anatomically placed femoral component with that of a superolaterally relocated component and with a component having an extended neck length. A six-degree of freedom device was constructed to measure three-dimensional micromotion at the proximal and distal regions of the femoral component. The instrumented femur was loaded using a unique loading device that included musculature necessary to simulate stairclimbing. Results showed that superolateral relocation of the hip center (25 mm) only moderately increased femoral component micromotion (13%). However, it was found that extending the neck length 12.5 mm produced a dramatic increase in micromotion (38%), Clinically this suggests that hip center lateralization and the use of long modular neck lengths should be avoided. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Pittsburgh, Musculoskeletal Res Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. RP Rubash, HE (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,White 601, Boston, MA 02114 USA. NR 32 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 1999 IS 362 BP 230 EP 239 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 195AW UT WOS:000080227800033 PM 10335302 ER PT J AU Mankin, HJ AF Mankin, HJ TI A managed care world - Can academic activities survive? SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB As a guest speaker at the Brown University Medical School Graduation, the author described some aspects of managed care that impact on academics and more specifically teaching and research. The issues for education included the reduction in numbers of residents and fellows; the rapidity with which the patients must be treated; the reduction in monies for educational activities; and consuming and at times needless paperwork. As far as research is concerned the reduction in time and money have had a negative effect on this important aspect of academic life for physicians. Several proposals are put forth to maintain the quality of these educational and investigational pursuits, and the students soon to be residents and, hopefully academicians are advised to maintain the highest standards and appreciation for quality care, education, and research. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Serv, Boston, MA USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv Gray 604, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 1999 IS 362 BP 256 EP 260 DI 10.1097/00003086-199905000-00036 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 195AW UT WOS:000080227800036 PM 10335305 ER PT J AU Eisenfeld, L Goodman, T Bouckoms, A Burke, G Hromi, A Jellinek, M Gallant, N Block, C AF Eisenfeld, L Goodman, T Bouckoms, A Burke, G Hromi, A Jellinek, M Gallant, N Block, C TI Neonatologist attrition to general pediatrics SO CLINICAL PEDIATRICS LA English DT Article ID STRESS C1 Connecticut Childrens Med Ctr, Dept Pediat, Hartford, CT 06106 USA. Connecticut Childrens Med Ctr, Dept Psychiat, Hartford, CT 06106 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Eisenfeld, L (reprint author), Connecticut Childrens Med Ctr, Dept Pediat, 282 Washington St, Hartford, CT 06106 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD MAY PY 1999 VL 38 IS 5 BP 309 EP 311 DI 10.1177/000992289903800511 PG 3 WC Pediatrics SC Pediatrics GA 196EK UT WOS:000080295900011 PM 10349531 ER PT J AU Rao, PM Novelline, RA Zukerberg, L AF Rao, PM Novelline, RA Zukerberg, L TI Solitary caecal ulcer syndrome, a benign condition which mimics the CT appearance of caecal carcinoma SO CLINICAL RADIOLOGY LA English DT Article ID CECAL ULCER C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 1999 VL 54 IS 5 BP 331 EP 333 DI 10.1016/S0009-9260(99)90565-2 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196DK UT WOS:000080293600012 PM 10362242 ER PT J AU Akpek, EK Polcharoen, W Chan, R Foster, CS AF Akpek, EK Polcharoen, W Chan, R Foster, CS TI Ocular surface neoplasia masquerading as chronic blepharoconjunctivitis SO CORNEA LA English DT Article DE conjunctiva; masquerade syndrome; cancer ID CONJUNCTIVAL TUMORS; LESIONS; CARCINOMA; LYMPHOMA AB Purpose. To present the clinical characteristics and difficulties in the diagnosis of various ocular surface malignancies mimicking features of chronic blepharoconjunctivitis and to summarize the current therapeutic approach and prognosis of patients. Methods. Six patients with slowly evolving signs of persistent inflammation underwent a conjunctival biopsy after a prolonged course of medical treatment. The medical records of the patients were reviewed. Results. Histopathologic examination of the biopsy specimens revealed intraepithelial squamous neoplasia (one patient), invasive squamous cell carcinoma (one patient), sebaceous carcinoma (two patients), and conjunctival lymphoma (two patients). Conclusion. Although uncommon, ocular surface malignancies may involve the conjunctiva diffusely and present as chronic conjunctivitis. A high index of suspicion and an early histopathologic examination are essen tial to not delay diagnosis. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 29 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAY PY 1999 VL 18 IS 3 BP 282 EP 288 DI 10.1097/00003226-199905000-00007 PG 7 WC Ophthalmology SC Ophthalmology GA 243LY UT WOS:000083000400007 PM 10336029 ER PT J AU Zervos, G Zusman, RM Swindle, LA Alpert, NM Fischman, AJ Gewirtz, H AF Zervos, G Zusman, RM Swindle, LA Alpert, NM Fischman, AJ Gewirtz, H TI Effects of nifedipine on myocardial blood flow and systolic function in humans with ischemic heart disease SO CORONARY ARTERY DISEASE LA English DT Article DE nifedipine; myocardial blood flow; ischemic heart disease ID CORONARY-ARTERY DISEASE; DOMESTIC SWINE; CLOSED-CHEST; N-13 AMMONIA; DOUBLE-BLIND; EXERCISE; DOGS; PERFUSION; INFARCTION; QUANTIFICATION AB Objective To test the hypothesis that, in humans with ischemic heart disease, nifedipine is a primary dilator of the coronary circulation and in general exerts a net positive effect on the balance of myocardial oxygen supply and demand. Methods Positron-emission tomography with [N-13]-ammonia was used to measure myocardial blood flow in patients at rest, and during infusion of adenosine and ingestion of nifedipine (10 mg capsule, a bite-and-chew technique). Myocardial segments were defined physiologically on the basis of blood flow to adenosine as being normal or having mild, moderate, or severe impairment of dilator reserve. Myocardial systolic function was assessed under comparable physiologic conditions using gated single-photon-emission computed tomography radionuclide ventriculography. Results Our study population consisted of 13 male patients and one female patient. Ingestion of nifedipine increased heart rate (from 63 +/- 1 1 to 80 +/- 16 beats/min, P<0.001) and, as intended, lowered systolic arterial pressure (from 148 +/- 20 to 123 +/- 14 mmHg, P < 0.001) but had no effect on heart rate-pressure product (which changed from 9283 +/- 1576 to 9942 +/- 2162 mmHg/min). Myocardial blood flow in patients at rest in segments with mild, moderate, and severe reductions of dilator capacity (0.63 +/- 0.20, 0.67 +/- 0.25, and 0.58 +/- 0.27 ml/min per g, respectively) was less (P<0.01) than normal (0.91 +/- 0.29 ml/min per g). Nevertheless, flow of blood was increased versus that at rest (P< 0.01) by infusion of adenosine (to 1.78 +/- 0.13, 1.29 +/- 0.16, and 0.75 +/- 0.22 ml/min per g) and ingestion of nifedipine (to 1.17 +/-0.51, 1.06 +/- 0.36, 0.85 +/- 0.42 ml/min per g) in segments with mild, moderate, and severe reductions of dilator capacity as well as in normal segments (to 3.18 +/- 0.85 ml/min per g with adenosine and 1.68 +/- 0.65 ml/min per g with nifedipine). Global left ventricular systolic function remained unchanged versus baseline (ejection fraction 0.74 +/- 0.09) with nifedipine (0.78 +/- 0.10). Regional contraction expressed in normalized amplitude units also remained unchanged versus baseline in response to nifedipine. Conclusion Nifedipine increases myocardial blood flow in humans with ischemic heart disease in normal segments as well as in segments with mild, moderate, and severe reductions of dilator capacity, albeit to a lesser extent with increasing impairment of dilator capacity. Both global and regional left ventricular contractile function also are not adversely affected by nifedipine. These improvements in myocardial blood flow in face of no change or a decrease in myocardial demand for oxygen reflect an overall favorable effect on the balance between the supply of and demand for myocardial oxygen. Coronary Artery Dis 10:185-194 (C) 1999 Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiac Unit, Vincent Burnham 3, Boston, MA 02114 USA. NR 34 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD MAY PY 1999 VL 10 IS 3 BP 185 EP 194 DI 10.1097/00019501-199905000-00008 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 200ZQ UT WOS:000080570500008 PM 10352896 ER PT J AU Grosskreutz, CL Katowitz, WR Freeman, EE Dreyer, EB AF Grosskreutz, CL Katowitz, WR Freeman, EE Dreyer, EB TI Lidocaine toxicity to rat retinal ganglion cells SO CURRENT EYE RESEARCH LA English DT Article DE lidocaine; dizocilpine (MK801); nimodipine; retinal ganglion cells; toxicity ID SYNAPTOSOMAL PLASMA-MEMBRANE; CATARACT-SURGERY; LOCAL-ANESTHETICS; UNPRESERVED LIDOCAINE; TOPICAL ANESTHESIA; MK-801; RETROBULBAR; MODULATION; INJECTION AB Purpose. To examine the effects of the local anesthetic, lidocaine, on rat retinal ganglion cells (RGC) in vitro and in a modified in vivo assay. Methods. For in vitro experiments, RGC were dissociated from freshly harvested Long Evan's rat pup retinas. The RGC were incubated overnight with varying concentrations of lidocaine (0.5-12.0 mM). Surviving cells were assayed at 24 hours. In an in vivo assay, 7-day-old Long-Evans rat pups were anesthetized and 2 mu l of lidocaine (final intraocular concentration: 0.03-15 mM) or vehicle was injected intravitreally. Intravitreal coinjection of nimodipine or MK801 (dizocilpine) were also performed in a subset of animals. A week after injection, rat pups were sacrificed and each retina removed, dissociated and plated separately. RGC survival was immediately assessed. Living RGC were identified on the basis of morphology and counted in a masked fashion. Results. Lidocaine is toxic in a dose dependent fashion to RGC in vitro. Lower concentrations (0.5 mM and 1.0 mM) were non-toxic; 2.0, 6.0 and 12.0 mM lidocaine killed 25%, 88% and 99% of the RGC respectively. Intravitreal lidocaine was also toxic to RGC in a dose dependent fashion. Lidocaine concentrations of 3.0 mM, 7.5 mM and 15 mM killed 25%, 38% and 44% of the RGC. This effect was blocked by the simultaneous administration of either nimodipine or MK801. Conclusions. Lidocaine is toxic to RGC both in vitro and in vivo. This effect is blocked in vivo by the simultaneous administration of agents known to block glutamate mediated neuronal death, suggesting that excitotoxicity may be involved in this process. C1 Harvard Univ, Glaucoma Consultat Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Boston, MA 02114 USA. Univ Penn, Scheie Eye Inst, Dept Ophthalmol, Philadelphia, PA 19104 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Glaucoma Consultat Serv, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [K11-EY00342, R01-EY10009] NR 27 TC 8 Z9 8 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1999 VL 18 IS 5 BP 363 EP 367 PG 5 WC Ophthalmology SC Ophthalmology GA 194HM UT WOS:000080186500007 PM 10372998 ER PT J AU Housby, JN Cahill, CM Chu, BY Prevelige, R Bickford, K Stevenson, MA Calderwood, SK AF Housby, JN Cahill, CM Chu, BY Prevelige, R Bickford, K Stevenson, MA Calderwood, SK TI Non-steroidal anti-inflammatory drugs inhibit the expression of cytokines and induce HSP70 in human monocytes SO CYTOKINE LA English DT Article DE heat shock; anti-inflammatory; cytokine; transcription ID NF-KAPPA-B; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SHOCK GENE-TRANSCRIPTION; RHEUMATOID-ARTHRITIS; ADHESION MOLECULES; SODIUM-SALICYLATE; CELLS; ACTIVATION; THERAPY; PHOSPHORYLATION AB Recent studies have shown that the non-steroidal anti-inflammatory drugs (NSAIDs) activate heat shock transcription factor (HSF1) from a latent cytoplasmic form to a nuclear, DNA binding state. As HSF1 can function as both an activator of heat shock genes and a repressor of non-heat shock genes such as IL1B and c-fos, we have examined the potential role of HSF1 in the effects of NSAIDs on gene expression in a human monocytic cell line THP-1. We found that two members of the NSAIDs, sodium salicylate and sulindac repress the IL1B promoter to similar degree to heat shock or HSF1 overexpression. In addition, sodium salicylate and additional NSAIDs used at concentrations that activate HSF1 also inhibited the expression of other monocytic genes (TNF-alpha, IL-1 beta, IL-6, IL-8, IL-10, ICAM-1) activated by exposure to a pro-inflammatory stimulus (lipopolysaccharide, LPS). At least in the case of the IL1B promoter, repression did not seem to involve another factor whose activity is affected by the NSAIDs, NF kappa B as the IL1B promoter fragment used in our studies is not NF kappa B responsive and binds specifically to HSF1, Exposure to NSAIDs had a complex effect on HSP gene expression and while sulindac activated the stress responsive HSP70B promoter, sodium salicylate did not. In addition, only a subset of the NSAIDs induced HSP70 mRNA species. These findings reflect the properties of HSF1 which can be activated to at least two DNA binding forms only one of which activates heat shock promoters and suggest that individual NSAID family members may differentially induce one or other of these forms. Overall therefore, exposure to NSALDs leads to a profound switch in gene expression in monocytic cells, with suppression of genes involved in macrophage activation and induction of stress genes and HSF1 appears to play a regulatory role in these effects. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Jimmy Fund Labs 205, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA50642, CA47407, CA31303] NR 51 TC 78 Z9 83 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 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1999 VL 11 IS 5 BP 347 EP 358 DI 10.1006/cyto.1998.0437 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 196KE UT WOS:000080306900004 PM 10328874 ER PT J AU Huard, JMT Forster, CC Carter, ML Sicinski, P Ross, ME AF Huard, JMT Forster, CC Carter, ML Sicinski, P Ross, ME TI Cerebellar histogenesis is disturbed in mice lacking cyclin D2 SO DEVELOPMENT LA English DT Article DE cerebellum; cell cycle; cyclin D2; apoptosis; brain; mouse ID CELL-CYCLE; PURKINJE-CELLS; GENE-EXPRESSION; NERVOUS-SYSTEM; GENERATION; IDENTITY; DIVISION; NEURONS; LAYER; DEATH AB Formation of brain requires deftly balancing primary genesis of neurons and glia, detection of when sufficient cells of each type have been produced, shutdown of proliferation and removal of excess cells. The region and cell type-specific expression of cell cycle regulatory proteins, such as demonstrated for cyclin D2, may contribute to these processes. If so, regional brain development should be affected by alteration of cyclin expression. To test this hypothesis, the representation of specific cell types was examined in the cerebellum of animals lacking cyclin D2. The loss of this cyclin primarily affected two neuronal populations: granule cell number was reduced and stellate interneurons were nearly absent, Differences between null and wild-type siblings were obvious by the second postnatal week. Decreases in granule cell number arose from both reduction in primary neurogenesis and increase in apoptosis of cells that fail to differentiate. The dearth of stellate cells in the molecular layer indicates that emergence of this subpopulation requires cyclin D2 expression. Surprisingly, Golgi and basket interneurons, thought to originate from the same precursor pool as stellate cells, appear unaffected. These results suggest that cyclin D2 is required in cerebellum not only for proliferation of the granule cell precursors but also for proper differentiation of granule and stellate interneurons. C1 Univ Minnesota, Dept Neurol, Lab Mol Neurobiol & Dev, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ross, ME (reprint author), Univ Minnesota, Dept Neurol, Lab Mol Neurobiol & Dev, Minneapolis, MN 55455 USA. FU NINDS NIH HHS [NS31318] NR 30 TC 143 Z9 147 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1999 VL 126 IS 9 BP 1927 EP 1935 PG 9 WC Developmental Biology SC Developmental Biology GA 198WG UT WOS:000080446800013 PM 10101126 ER PT J AU Boxem, M Srinivasan, DG van den Heuvel, S AF Boxem, M Srinivasan, DG van den Heuvel, S TI The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase SO DEVELOPMENT LA English DT Article DE Caenorhabditis elegans; ncc-1; cell cycle; Cdc2; Cdk; cdk5; PCTAIRE; cell-division ID CYCLIN-DEPENDENT KINASES; PROTEIN-KINASE; C-ELEGANS; MAMMALIAN-CELLS; CHROMOSOME CONDENSATION; PHOSPHORYLATION SITES; CRYSTAL-STRUCTURE; NUCLEAR LAMINA; CDC2 KINASE; HISTONE H3 AB We have identified six protein kinases that belong to the family of cdc-related kinases in Caenorhabditis elegans, Results from RNA interference experiments indicate that at least one of these kinases is required for cell-cycle progression during meiosis and mitosis, This kinase, encoded by the nec-1 gene, is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and yeast CDC28/cdc2(+). We addressed whether nec-l acts to promote passage through a single transition or multiple transitions in the cell cycle, analogous to Cdks in vertebrates or yeasts, respectively. We isolated five recessive ncc-1 mutations in a genetic screen for mutants that resemble larval arrested ncc-1(RNAi) animals. Our results indicate that maternal ncc-1 product is sufficient for embryogenesis, and that zygotic expression is required for cell divisions during larval development. Cells that form the postembryonic lineages in wild-type animals do not enter mitosis in ncc-1 mutants, as indicated by lack of chromosome condensation and nuclear envelope breakdown. However, progression through Gr and S phase appears unaffected, as revealed by expression of ribonucleotide reductase, incorporation of BrdU and DNA quantitation. Our results indicate that C. elegans uses multiple Cdks to regulate cell-cycle transitions and that ncc-1 is the C, elegans ortholog of Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as mitotic cell cycles. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI Boxem, Mike/B-8857-2011; van den Heuvel, Sander/B-8892-2011 OI Boxem, Mike/0000-0003-3966-4173; FU NCI NIH HHS [CA09642-09] NR 73 TC 109 Z9 115 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD MAY PY 1999 VL 126 IS 10 BP 2227 EP 2239 PG 13 WC Developmental Biology SC Developmental Biology GA 203BU UT WOS:000080688100019 PM 10207147 ER PT J AU Virkamaki, A Yki-Jarvinen, H AF Virkamaki, A Yki-Jarvinen, H TI Allosteric regulation of glycogen synthase and hexokinase by glucosamine-6-phosphate during glucosamine-induced insulin resistance in skeletal muscle and heart SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IN-VIVO; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; HEXOSAMINE PATHWAY; HYPERGLYCEMIA; MECHANISMS; CELLS; QUANTITATION; TRANSPORT; RATS AB Glucosamine infusion induces insulin resistance in vivo, but the effect of glucosamine on intracellular metabolites of the hexosamine pathway, especially glucosamine-6-phosphate (GlcN6P) is unknown. Because of the structural similarity of glucose-6-phosphate (G-6-P) and GlcN6P, we hypothesized that accumulation of this metabolite might alter the activities of enzymes such as glycogen synthase and hexokinase. We infused glucosamine (30 mu mol . kg(-1) . min(-1)) to induce insulin resistance in rats during a euglycemic-hyperinsulinemic clamp. Glucosamine induced whole-body insulin resistance, which was apparent after 90 min and continued progressively for 360 min. Despite inducing severe whole-body insulin resistance and decrease in glycogen synthase fractional activity in rectus abdominis muscle (69 +/- 3 vs. 83 +/- 1%, P < 0.01) and heart (7 +/- 1 vs. 32 +/- 4%, P < 0.001), glucosamine did not change the glycogen content in rectus and even increased it in the heart (209 +/- 13 vs. 117 +/- 9 mmol/kg dry wt, P < 0.001). Glucosamine increased tissue concentrations of UDP-GlcNAc 4.4- and 4.6-fold in rectus abdominis and heart, respectively. However, GlcN6P concentrations increased 500- and 700-fold in glucosamine-infused animals in rectus abdominis (590 +/- 80 vs. 1.2 +/- 0.1 mu mol/kg wet wt, P < 0.001) and heart (7,703 +/- 993 vs. 11.2 +/- 2.3 mu mol/kg wet wt, P < 0.001). To assess the possible significance of GlcN6P accumulation, we measured the effect of GlcN6P on glycogen synthase and hexokinase activity in vitro. At the GlcN6P concentrations measured in rectus abdominis and heart in vivo, glycogen synthase was activated by 21 and 542%, while similar concentrations inhibited hexokinase activity by 5 and 46%, respectively. This study demonstrates that infusion of glucosamine during a euglycemic-hyperinsulinemic clamp results in marked accumulation of intracellular GlcN6P. The GlcN6P concentrations in the heart and rectus abdominis muscle reach levels sufficient to cause allosteric activation of glycogen synthase and inhibition of hexokinase. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ Helsinki, Div Endocrinol & Diabetol, Helsinki, Finland. RP Virkamaki, A (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 36 TC 41 Z9 41 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1999 VL 48 IS 5 BP 1101 EP 1107 DI 10.2337/diabetes.48.5.1101 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194VL UT WOS:000080214900022 PM 10331416 ER PT J AU Jiang, ZY Zhou, QL Chatterjee, A Feener, EP Myers, MG White, MF King, GL AF Jiang, ZY Zhou, QL Chatterjee, A Feener, EP Myers, MG White, MF King, GL TI Endothelin-l modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; AMINO-ACID-UPTAKE; TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-1; SERINE PHOSPHORYLATION; ESSENTIAL-HYPERTENSION; COUPLED RECEPTORS; RAT-1 FIBROBLASTS; GENE-EXPRESSION; CROSS-TALK AB Diminished insulin action in the vasculature may contribute to the development of cardiovascular diseases in diabetes. me have studied insulin's effects on the phosphatidylinositol (PI) 3-kinase pathway in arterial smooth muscle cells (SMCs) and its inhibition by endothelin (ET)-1, a potent vasoactive hormone reported to be elevated in insulin resistance and other vascular diseases. ET-1 increased the level of serine phosphorylation of insulin receptor beta subunit but increased both tyrosine and serine phosphorylation of insulin receptor substrate (IRS)-2. Pretreatment of cells with ET-1 (10 nmol/l) inhibited insulin-stimulated PI 3-kinase activity associated with IRS-2 by 50-60% and inhibited the association of p85 subunit of PI 3-kinase to IRS-2. The inhibition of insulin-stimulated PI 3-kinase activity by ET-1 was prevented by BQ-123, a selective ET, receptor antagonist, but was not affected by pertussis toxin. Treatment of cells with phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), reduced both insulin-stimulated PI 3-kinase activity by 57% and the association of IRS-2 to the p85 subunit of PI 3-kinase by 40%, whereas GF109203X, a specific inhibitor of PKC, partially prevented the inhibitory effect of ET-1 on insulin-induced PI 3-kinase activity. These results suggested that ET-1 could interfere with insulin signaling in SMCs by both PKC-dependent and -independent pathways. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesia, Boston, MA USA. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-48358, P30 DK036836, DK-53105, DK-36836] NR 65 TC 76 Z9 78 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1999 VL 48 IS 5 BP 1120 EP 1130 DI 10.2337/diabetes.48.5.1120 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194VL UT WOS:000080214900025 PM 10331419 ER PT J AU Hata, Y Rook, SL Aiello, LP AF Hata, Y Rook, SL Aiello, LP TI Basic fibroblast growth factor induces expression of VEGF receptor KDR through a protein kinase C and p44/p42 mitogen-activated protein kinase-dependent pathway SO DIABETES LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; VASCULAR-PERMEABILITY FACTOR; CAPILLARY ENDOTHELIAL-CELLS; FACTOR MESSENGER-RNA; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; CHOROIDAL NEOVASCULAR MEMBRANES; HEPARAN SULFATE COMPLEXES; BOVINE RETINAL PERICYTES; PIGMENT EPITHELIAL-CELLS; SMOOTH-MUSCLE CELLS AB Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are angiogenic molecules whose combined mitogenic activity is potently synergistic. However, the molecular mechanism underlying this synergy is incompletely understood. We examined whether VEGF and bFGF affect expression of each other or alter expression of the VEGF receptor KDR in retinal capillary endothelial cells. In addition, we investigated the intracellular signaling mechanisms involved in this response. VEGF-induced [H-3]thymidine uptake was tightly correlated with KDR mRNA and protein concentrations, suggesting that increased KDR expression might account for VEGF's synergistic activity in the presence of bFGF. bFGF (10 ng/ml) induced KDR mRNA expression within 4 h and attained a 4.0-fold increase after 24 h. KDR protein expression was increased 7.5-fold after 48 h. VEGF (=50 ng/ml) did not alter bFGF, VEGF, or KDR mRNA expression under serum-deprived conditions. In contrast, VEGF increased KDR mRNA expression 87% under growth conditions and 2.9-fold under serum-deprived conditions in the presence of bFGF. The protein kinase C (PKC) agonist phorbol myristate acetate (PMA) induced KDR mRNA expression 5.1-fold at 100 nmol/l. bFGF increased p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation within 5 min, reaching a maximum within 15 min and remaining significantly elevated for >6 h. bFGF-induced MAPK phosphorylation and KDR mRNA expression were almost completely inhibited by 5 mu mol/l GFX a non-isoform-selective PKC inhibitor. MAPK inhibitor PD98059 reduced KDR mRNA expression 72% at concentrations that inhibited bFGF-induced MAPK phosphorylation 100%, suggesting that pathways in addition to MAPK might also be involved. Inhibitors of the beta isoform of PKC (LY333531), protein kinase A (PKA) (H89), and phosphotidylinositol (PI) 3 kinase (wortmannin) had no significant effect. These data suggest that bFGF stimulates KDR expression through a PKC and p44/p42 MAPK-dependent pathway not primarily involving the beta isoform of PKC, PKA, or PI-3 kinase. Since bFGF induces VEGF expression and since increased KDR expression potentiates VEGF action, resulting in additional KDR expression and marked mitogenic activity, these data provide a novel mechanistic explanation for the angiogenic synergy between VEGF and bFGF. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY-10827]; PHS HHS [36836] NR 81 TC 80 Z9 82 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1999 VL 48 IS 5 BP 1145 EP 1155 DI 10.2337/diabetes.48.5.1145 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194VL UT WOS:000080214900028 PM 10331422 ER PT J AU Kennedy, JW Hirshman, MF Gervino, EV Ocel, JV Forse, RA Hoenig, SJ Aronson, D Goodyear, LJ Horton, ES AF Kennedy, JW Hirshman, MF Gervino, EV Ocel, JV Forse, RA Hoenig, SJ Aronson, D Goodyear, LJ Horton, ES TI Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes SO DIABETES LA English DT Article ID OBESE ZUCKER RAT; RESPONSIVE GLUCOSE TRANSPORTER; INSULIN-RESISTANCE; PLASMA-MEMBRANE; PHOTOLABELING TECHNIQUE; SMALL-INTESTINE; MORBIDLY OBESE; PROTEIN; EXPRESSION; NIDDM AB Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of Vo(2max). Skeletal muscle plasma membranes mere prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/- 20% above resting values, and for the normal subjects the increase was 71 +/- 18% above resting values. Although plasma membrane GLUT4 content was similar to 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences mere not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Metab Sect, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. Harvard Med Sch, Boston, MA USA. RP Horton, ES (reprint author), Joslin Diabet Ctr, Div Res, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. RI Aronson, Doron/F-3390-2010 FU NCRR NIH HHS [RR-01032]; NIAMS NIH HHS [AR42238]; NIDDK NIH HHS [5T32 DK07260] NR 55 TC 173 Z9 183 U1 4 U2 22 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1999 VL 48 IS 5 BP 1192 EP 1197 DI 10.2337/diabetes.48.5.1192 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 194VL UT WOS:000080214900034 PM 10331428 ER PT J AU Anderson, BJ Brackett, J Ho, J Laffel, LMB AF Anderson, BJ Brackett, J Ho, J Laffel, LMB TI An office-based intervention to maintain parent-adolescent teamwork in diabetes management - Impact on parent involvement, family conflict, and subsequent glycemic control SO DIABETES CARE LA English DT Article; Proceedings Paper CT Annual Scientific Sessions of the American-Diabetes-Association CY JUN 21-24, 1997 CL BOSTON, MASSACHUSETTS SP Amer Diabetes Assoc ID LONGITUDINAL FOLLOW-UP; METABOLIC CONTROL; MELLITUS; ADHERENCE; CHILDREN; HEALTH; MODEL; IDDM AB OBJECTIVE - To design and evaluate an office-based intervention aimed at maintaining parent-adolescent teamwork in diabetes management tasks without increasing diabetes-related family conflict. RESEARCH DESIGN AND METHODS - There were 85 patients (aged 10-15 years, mean 12.6 years) with type 1 diabetes (mean duration 5.5 years; mean HbA(1c) 8.5%) who were randomly assigned to one of three study groups-teamwork, attention control, and standard care-and followed for 24 months. At each visit, parent involvement in insulin administration and blood glucose monitoring was assessed. The teamwork and attention control interventions were integrated into routine ambulatory visits over the first 12 months (four medical visits). Measures of diabetes-related family conflict were collected at baseline and after 12 months. All patients were followed for an additional 12 months with respect to glycemic control. RESULTS - In the teamwork group, there was no major deterioration (0%) in parent involvement in insulin administration, in contrast to 16% major deterioration in the combined comparison (attention control and standard care) group (P < 0.03). Similarly, no teamwork families showed major deterioration in parent involvement with brood glucose monitoring versus 11% in the comparison group (P < 0.07). On both the Diabetes Family Conflict Scale and the Diabetes Family Behavior Checklist, teamwork families reported significantly less conflict at 12 months. An analysis of HbA(1c) over the 12- to 24-month follow-up period indicated that more adolescents in the teamwork group (68%) than in the comparison group (47%) improved their HbA(1c) (P < 0.07). CONCLUSIONS - The data demonstrate that parent involvement in diabetes management tasks can be strengthened through a low-intensity intervention integrated into routine follow-up diabetes care. Moreover, despite increased engagement between teen and parent centered around diabetes tasks, the teamwork families showed decreased diabetes-related family conflict. Within the context of a broader cultural recognition of the protective function of parent involvement in the lives of adolescents, the findings of this study reinforce the potential value of a parent-adolescent partnership in managing chronic disease. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, BJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-46887] NR 38 TC 212 Z9 212 U1 3 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1999 VL 22 IS 5 BP 713 EP 721 DI 10.2337/diacare.22.5.713 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192WP UT WOS:000080102900011 PM 10332671 ER PT J AU Glasgow, RE Fisher, EB Anderson, BJ LaGreca, A Marrero, D Johnson, SB Rubin, RR Cox, DJ AF Glasgow, RE Fisher, EB Anderson, BJ LaGreca, A Marrero, D Johnson, SB Rubin, RR Cox, DJ TI Behavioral science in diabetes - Contributions and opportunities SO DIABETES CARE LA English DT Review ID QUALITY-OF-LIFE; CHRONIC DISEASE MANAGEMENT; OFFICE-BASED INTERVENTION; DIETARY SELF-MANAGEMENT; STAGE RENAL-DISEASE; METABOLIC CONTROL; HEALTH PROMOTION; GLYCEMIC CONTROL; ENVIRONMENTAL BARRIERS; ILLNESS INTRUSIVENESS AB OBJECTIVE - To summarize the current status of behavioral research and practice in diabetes and to identify promising future directions. RESEARCH DESIGN AND METHODS - We review behavioral science contributions to diabetes in self-management and patient empowerment, interventions with children and adolescents, and special problems including blood glucose awareness training and complications such as depression. We also identify emerging areas in which behavioral science stands to make significant contributions, including quality of life, worksite and community programs, interventions using new information technologies, and translation research evaluating practical programs in representative settings. We then discuss the gap between the generally encouraging research on behavioral contributions to diabetes and the infrequent incorporation of such contributions in practice. Suggestions are made for how to close this gap, including ways to increase understanding of behavioral issues, opportunities for funding of key research and implementation questions, and how behavioral science principles can become more integrated into diabetes organizations and care. CONCLUSIONS - Changes are required on the part of behavioral scientists in how they organize and present their research and on the part of potential users of this knowledge, including other health professions, organizations, and funding agencies. Integrating behavioral science advances with other promising genetic, medical, nutritional, technology health care, and policy opportunities promises not only to broaden our understanding of diabetes but also to improve patient care, quality of life, and public health for persons with diabetes. C1 AMC Canc Res Ctr, Denver, CO 80214 USA. Washington Univ, St Louis, MO USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Miami, Miami, FL 33152 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Virginia, Charlottesville, VA USA. RP Glasgow, RE (reprint author), AMC Canc Res Ctr, 1600 Pierce St, Denver, CO 80214 USA. FU NIDDK NIH HHS [DK 20579, DK 35524] NR 164 TC 134 Z9 136 U1 4 U2 19 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1999 VL 22 IS 5 BP 832 EP 843 DI 10.2337/diacare.22.5.832 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 192WP UT WOS:000080102900031 PM 10332691 ER PT J AU Katznelson, L AF Katznelson, L TI Neuroendocrine aspects of testosterone insufficiency with aging SO ENDOCRINOLOGIST LA English DT Review ID HUMAN CHORIONIC-GONADOTROPIN; LUTEINIZING-HORMONE; ELDERLY MEN; BIOAVAILABLE TESTOSTERONE; ACQUIRED HYPOGONADISM; SEX STEROIDS; OLDER MEN; ADULT MEN; AGE; SECRETION AB As men age, there is a progressive decline in serum total testosterone: levels and a more marked reduction in free, or bioavailable, testosterone levels. Aging is associated with a progressive increase in serum gonadotropin levels, which may, in part, reflect gradual testicular dysfunction, However, multiple lines of evidence indicate that neuroendocrine control of reproduction is altered with advancing age. Aging is associated with loss of the luteinizing hormone (LH) circadian rhythm with blunted early morning LH pulses. Studies utilizing pulse analysis and responsiveness to exogenous gonadotropin-releasing hormone (GnRH) suggest that aging is associated with decreases in GnRH pulse amplitude leading to falls in LH pulse amplitude. There are age-associated alterations in LH pulse characteristics that may be due to primary changes in hypothalamic control of gonadotropin secretion or to alterations in hypothalamic-pituitary responsiveness to hypothalamic and gonadal factors, These alterations in LH pulse dynamics may lead further to diminished testicular stimulation, Age-related changes in gonadotropin secretion/regulation and testicular function may lead to a new homeostasis of testosterone metabolism that includes reductions in-serum total testosterone and free testosterone levels. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, Boston, MA 02114 USA. RP Katznelson, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, 55 Fruit St,BUL457B, Boston, MA 02114 USA. NR 41 TC 1 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAY-JUN PY 1999 VL 9 IS 3 BP 190 EP 196 DI 10.1097/00019616-199905000-00005 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 201PM UT WOS:000080604000005 ER PT J AU Lane, AH Lee, MM AF Lane, AH Lee, MM TI Clinical applications of Mullerian inhibiting substance in patients with gonadal disorders SO ENDOCRINOLOGIST LA English DT Review ID ALPHA-INHIBIN; HORMONE; SERUM; IMMUNOASSAY; CHILDREN; INVITRO; INVIVO; MARKER; TUMORS; OVARY AB Mullerian inhibiting substance (MIS) is a gonadal peptide produced uniquely by Sertoli cells of the testis and granulosa cells of the ovary. In boys, serum MIS is low at birth, increases rapidly during the first year of life, then slowly declines thereafter until puberty. In girls, MIS: is undetectable at birth, then rises minimally throughout childhood to a low pubertal peak, As a gonad-specific hormone with a sexually dimorphic pattern of expression, MIS has been recognized as having clinical applications that are relevant to the human reproductive system. Measurement of MIS in children with nonpalpable gonads and/or intersex disorders can help identify testicular tissue and assess testicular function. This is useful for the management of boys with cryptorchidism and for the diagnostic evaluation of children with intersex conditions. Moreover, the secretion of MIS by many sex-cord stromal tumors makes MIS determination beneficial for evaluating the completeness of surgical resection and for longitudinal screening of tumor recurrence in women with sex-cord tumors. MIS immunohistochemistry also may aid in the histologic diagnosis of ovarian tumors when conventional histology is ambiguous. Potential therapeutic uses of MIS that currently are; being explored are based on employing its antiproliferative properties for chemotherapy of responsive tumors. C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Lee, MM (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, BHX-410,55 Fruit St, Boston, MA 02114 USA. OI Lee, Mary/0000-0002-7204-4884 NR 25 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAY-JUN PY 1999 VL 9 IS 3 BP 208 EP 215 DI 10.1097/00019616-199905000-00007 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 201PM UT WOS:000080604000007 ER PT J AU Lee, B Jonas, JC Weir, GC Laychock, SG AF Lee, B Jonas, JC Weir, GC Laychock, SG TI Glucose regulates expression of inositol 1,4,5-trisphosphate receptor isoforms in isolated rat pancreatic islets SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; BETA-CELL LINE; INSULIN-SECRETION; GENE-EXPRESSION; MESSENGER-RNA; DOWN-REGULATION; TRISPHOSPHATE RECEPTORS; ENDOPLASMIC-RETICULUM; CALCIUM-CHANNEL; RELEASE AB Isolated rat pancreatic islets were studied to determine the dynamic regulatory effects of glucose stimulation on the expression of messenger RNA (mRNA) and protein levels for inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) isoforms I, II, and III. The relative isoform abundance was: IP3R-III > IP3R-II similar to IP3R-I. Culture of islets with glucose (G; 20 mM) or alpha-ketoisocaproic acid for 30 min increased only IP3R-III mRNA expression above control (5.5 mM glucose). 2-Deoxy-glucose was without effect. Islet culture for 2 h with G (20 mM) or alpha-ketoisocaproic acid reduced IP3R-III mRNA expression levels below control, and cycloheximide blocked the response. Culturing islets for I day or 7 days with G (11 mM) reduced the expression of IP3R-III mRNA but increased the expression of IP3R-II mRNA in a time-dependent manner. Cytosine arabinoside lowered cultured islet IP3R-II and -III mRNA levels, but glucose effects remained evident. IP3R-II mRNA levels were also significantly higher in islets from hyperglycemic 90% partial pancreatectomized rats, compared with sham animals. Islet IP3R mRNA expression also showed osmotic sensitivity. Islet IP3R-III protein levels increased after 2 h islet culture at 20 mM G, were unchanged after 1 day culture at 11 mM G, and were lower than control after 7 days culture at 11 mM G. In contrast, IP3R-II levels increased after 1 day and 7 days culture at II mM G, whereas IP3R-I protein levels remained unchanged. Thus, G stimulation rapidly increases transcription and expression of IP3R-III mRNA and protein levels in rat islets. However, chronic G stimulation up-regulates IP3R-II mRNA in cultured islets and in islets from partial pancreatectomized rats. Metabolic regulation of IP3R-II and III expression may mediate beta-cell IP3-responsive Ca2+ mobilization and insulin secretion. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. RP Laychock, SG (reprint author), SUNY Buffalo, Sch Med, 102 Farber Hall, Buffalo, NY 14214 USA. EM laychock@acsu.buffalo.edu RI Jonas, Jean-Christophe/C-6766-2011 OI Jonas, Jean-Christophe/0000-0001-9882-5438 FU NIDDK NIH HHS [DK-25705] NR 64 TC 31 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1999 VL 140 IS 5 BP 2173 EP 2182 DI 10.1210/en.140.5.2173 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187RP UT WOS:000079801200028 PM 10218969 ER PT J AU Tsaih, SW Schwartz, J Lee, MLT Amarasiriwardena, C Aro, A Sparrow, D Hu, H AF Tsaih, SW Schwartz, J Lee, MLT Amarasiriwardena, C Aro, A Sparrow, D Hu, H TI The independent contribution of bone and erythrocyte lead to urinary lead among middle-aged and elderly men: The normative aging study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood; bone; environmental exposure; K-X-ray fluorescence; lead; urine ID X-RAY-FLUORESCENCE; PRIMATE MACACA-FASCICULARIS; BLOOD LEAD; IN-VIVO; OCCUPATIONAL EXPOSURE; HOSPITAL ADMISSIONS; CIRCULATING LEAD; ISOTOPE-DILUTION; EXTERNAL SOURCES; STABLE ISOTOPE AB plasma is the component of blood from which lead is free to cross cell membranes and cause organ toxicity. Plasma lead levels, however, are extremely low and difficult to measure. Urinary lead originates from plasma lead that has been filtered at the glomerular level; thus, urinary lead adjusted for glomerular filtration rate serves as a proxy for plasma lead levels. In this investigation we examined the interrelationships of lead levels in whole blood corrected by hematocrit [i.e., erythrocyte lead (EPb)], trabecular bone (TBoPb), cortical bone (CBoPb), and urine excreted over 24 hr (UPb); all samples were obtained from 71 middle-aged and elderly men with no known occupational lead exposures. Lead was measured by graphite furnace atomic absorption spectroscopy (blood), K-X-ray fluorescence (bone), and inductively coupled plasma mass spectroscopy (urine). Lead levels were generally low, with mean EPb, TBoPb, and CBoPb values of 13.8, 31.1, and 21.7 mu g/g, respectively, and a median UPb value of 6.15 mu g/day. In generalized additive models adjusted for body weight and creatinine clearance rate, both EPb and bone lead variables remained independently and significantly associated with UPb. This finding suggests that bone influences plasma lead in a manner that is independent of the influence of erythrocytic lead on plasma lead. Thus, the superiority of bone lead over blood lead in predicting some chronic forms of toxicity may be mediated through bone's influence on plasma lead. In addition, this study suggests that measurement of urinary lead might be useful as a proxy for plasma lead levels in studies of lead toxicity. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Dept Vet Affairs, Outpatient Clin, Normat Aging Study, Boston, MA 02114 USA. RP Tsaih, SW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. OI Hu, Howard/0000-0002-3676-2707 FU NCRR NIH HHS [M01 RR02635]; NIEHS NIH HHS [P42-ES05947, R01 ES05257] NR 75 TC 26 Z9 31 U1 2 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1999 VL 107 IS 5 BP 391 EP 396 DI 10.2307/3434543 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 195BF UT WOS:000080228700023 PM 10210695 ER PT J AU Fisher, JS Turner, KJ Brown, D Sharpe, RM AF Fisher, JS Turner, KJ Brown, D Sharpe, RM TI Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE aquaporin-1; bisphenol A; diethylstilbestrol; efferent ducts; ethinyl estradiol; genistein; octylphenol; rete testis; tamoxifen ID FIBROSIS TRANSMEMBRANE REGULATOR; CYSTIC-FIBROSIS; REPRODUCTIVE-TRACT; RETE TESTIS; EFFERENTES TESTIS; RECEPTOR-ALPHA; SEMEN QUALITY; SPERM QUALITY; BISPHENOL-A; IN-VIVO AB Neonatal exposure to diethylstilbestrol (DES) can alter the structure of the testicular excurrent ducts in rats. We characterized these changes according to dose and time posttreatment and established whether potent estrogens (ethinyl estradiol), environmental estrogens (genistein, octylphenol, bisphenol A, parabens), and tamoxifen induce such changes. Rats were administered these compounds neonatally and assessed at several time points during (day 10, or day 18 for some treatments) and after (days 18, 25, 35, and 75) the treatment period to detect any changes in testis weight, distension of the rete testis and efferent ducts, epithelial cell height in the efferent ducts, and immunoexpression of the water channel aquaporin-1 (AQP-1). Treatment with DES (10, 1, or 0.1 mu g/injection; equivalent to 0.37, 0.037, or 0.0037 mg/kg/day, respectively) induced dose-dependent changes in testis weight and all parameters. These effects were most pronounced at days 18 and 25 and appeared to lessen with rime, although some persisted into adulthood. Neonatal treatment with ethinyl estradiol (10 mu g/injection; equivalent to 0.37 mg/kg/day) caused changes broadly similar to those induced by 10 pg DES. Administration of tamoxifen (2 mg/kg/day) caused changes at 18 days that were similar to those induced by 1 pg DES. Treatment with genistein (4 mg/kg/day), octylphenol (2 mg/injection; equivalent to 150 mg/kg/day), or bisphenol A (0.5 mg/injection; equivalent to 37 mg/kg/day) caused minor but significant (p<0.05) decreases in epithelial cell height of the efferent ducts at days 18 and/or 25 In animals that were followed through to 35 days and/or adulthood, these changes were no longer obvious; other parameters were either unaffected or were affected only marginally and transiently. Administration of parabens (2 mg/kg/day) had no detectable effect on any parameter at day 18. To establish whether these effects of estrogens were direct or indirect (i.e., resulting from reduced follicle-stimulating hormone/luteinizing hormone secretion), the above end points were assessed in animals in which gonadotropin secretion was suppressed neonatally by administration of a gonadotropin-releasing hormone antagonist. This treatment permanently reduced testis weight, but did not affect any of the other end points, apart from a minor transient reduction in efferent duct epithelial cell height at 18 days. This study suggests that structural and functional (expression of AQP-1) development of the excurrent ducts is susceptible to impairment by neonatal estrogen exposure, probably as a consequence of direct effects. The magnitude and duration of adverse changes induced by treatment with a range of estrogenic compounds was broadly comparable to their estrogenic potencies reported from in vitro assays. C1 MRC, Ctr Reprod Biol, Reprod Biol Unit, Edinburgh EH3 9EW, Midlothian, Scotland. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Fisher, JS (reprint author), MRC, Ctr Reprod Biol, Reprod Biol Unit, 37 Chalmers St, Edinburgh EH3 9EW, Midlothian, Scotland. RI Sharpe, Richard/D-2725-2013 OI Sharpe, Richard/0000-0003-1686-8085 NR 44 TC 90 Z9 91 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 1999 VL 107 IS 5 BP 397 EP 405 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 195BF UT WOS:000080228700024 PM 10210696 ER PT J AU Molenberghs, G Ryan, LM AF Molenberghs, G Ryan, LM TI An exponential family model for clustered multivariate binary data SO ENVIRONMETRICS LA English DT Article DE developmental toxicity; exponential family; litter effect; low birth weight; malformation; score test ID QUANTITATIVE RISK ASSESSMENT; GENERALIZED LINEAR-MODELS; DEVELOPMENTAL TOXICITY; REGRESSION-MODELS; LONGITUDINAL DATA; MIXED MODELS; RESPONSES; DISCRETE; OUTCOMES; INFERENCE AB This paper focuses on the analysis of clustered multivariate binary data that arise from developmental toxicity studies. In these studies, pregnant mice are exposed to chemicals to assess possible adverse effects on developing fetuses. Multivariate binary outcomes arise when each fetus in a litter is assessed for the presence of malformations and/or low birth weight. We analyse the data using a multivariate exponential family model which is flexible in terms of allowing response rates to depend on duster size. Maximum likelihood estimation of model parameters and the construction of score tests for dose effect are discussed. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Molenberghs, G (reprint author), Limburgs Univ Ctr, Ctr Stat, Univ Campus,Bldg D, B-3590 Diepenbeek, Belgium. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 48 TC 33 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1180-4009 J9 ENVIRONMETRICS JI Environmetrics PD MAY-JUN PY 1999 VL 10 IS 3 BP 279 EP 300 DI 10.1002/(SICI)1099-095X(199905/06)10:3<279::AID-ENV352>3.0.CO;2-X PG 22 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 215EC UT WOS:000081368100005 ER PT J AU Fujikawa, DG Shinmei, SS Cai, BY AF Fujikawa, DG Shinmei, SS Cai, BY TI Lithium-pilocarpine-induced status epilepticus produces necrotic neurons with internucleosomal DNA fragmentation in adult rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; cell death; DNA laddering; in situ DNA nick-end labelling; necrosis; seizures; TUNEL stain ID SUSTAINED ELECTRICAL-STIMULATION; APOPTOTIC CELL-DEATH; METHYL-D-ASPARTATE; KAINIC ACID; PERFORANT PATH; BRAIN-DAMAGE; NECROSIS; KAINATE; GLUTAMATE; CLEAVAGE AB Prolonged and continuous epileptic seizures [status epilepticus (SE)] produce a widespread pattern of neuronal death, primarily in limbic brain regions. Because it has been suggested that seizure-induced neuronal death may be apoptotic in nature, we tested the hypothesis that lithium-pilocarpine-induced status epilepticus (LPCSE) produces apoptotic neurons. LPCSE lasting 3 h was induced in male Wistar rats which were allowed to recover for 24 or 72 h before perfusion-fixation. Neuronal death was assessed by light microscopy with the haematoxylin-and-eosin stain (H&E), with in situ DNA nick-end labelling (TUNEL stain), by electron microscopy, and by agarose gel electrophoresis of DNA extracted from vulnerable brain regions. Ultrastructurally, acidophilic neurons identified with H&E were dark, shrunken and necrotic in appearance, exhibiting pyknotic nuclei, irregular, dispersed chromatin clumps and cytoplasmic vacuolization. No cells with apoptotic features were seen. Acidophilic neurons were found in 21 out of 23 brain regions examined, and comprised 26-45% of the total number of neurons examined. A subset of these neurons (< 10% of the total number of neurons) were TUNEL-positive at 72 h, but not 24 h, after SE. Internucleosomal DNA cleavage (DNA 'laddering') was found in the six brain regions examined ultrastructurally 24 and 72 h after SE. These results indicate that, in adult rats, LPCSE produces neuronal injury with the appearance of necrosis rather than apoptosis. The necrotic neurons show nuclear pyknosis, chromatin condensation and internucleosomal DNA fragmentation, confirming the nonspecificity of these nuclear changes. Internucleosomal DNA cleavage and other programmed cell death mechanisms can be activated by SE in neurons which become necrotic. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home 151B, Expt Neurol Lab, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home 151B, Expt Neurol Lab, Sepulveda, CA 91343 USA. NR 51 TC 80 Z9 87 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 1999 VL 11 IS 5 BP 1605 EP 1614 DI 10.1046/j.1460-9568.1999.00573.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 194CX UT WOS:000080175500013 PM 10215913 ER PT J AU Ross, RK Coetzee, GA Pearce, CL Reichardt, JKV Bretsky, P Kolonel, LN Henderson, BE Lander, E Altshuler, D Daley, G AF Ross, RK Coetzee, GA Pearce, CL Reichardt, JKV Bretsky, P Kolonel, LN Henderson, BE Lander, E Altshuler, D Daley, G TI Androgen metabolism and prostate cancer: Establishing a model of genetic susceptibility SO EUROPEAN UROLOGY LA English DT Article; Proceedings Paper CT Symposium on Strategies for the Chemoprevention of Prostate Cancer CY OCT 29-31, 1998 CL BRUSSELS, BELGIUM DE prostatic neoplasms; androgens; genetics ID RECEPTOR GENE; STEROID 5-ALPHA-REDUCTASE; CAG REPEAT; RISK; MEN; POLYMORPHISMS; DEFICIENCY; GENOME; WHITE; BLACK AB The prostate is an androgen-regulated organ, which has led to longstanding interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones. The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that genetic factors play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis, focused around a series of genes involved in androgen biosynthesis, transport and metabolism. We have begun to develop this model by utilizing sequence variants to study how polymorphic markers in two genes (SRD5A2 and AR) are related to prostate cancer risk within and between racial-ethnic groups. We are now collaborating with the Whitehead Institute/MIT, Center for Genome Research, to screen for single nucleotide polymorphisms in additional genes relevant to the androgen pathway and prostate cell growth. The model when fully developed can potentially provide a basis for targeting populations for screening interventions and for implementing primary preventive strategies. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Urol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. Univ Hawaii Manoa, Ctr Canc Res, Program Epidemiol, Honolulu, HI 96822 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. MIT, Dept Biol, Boston, MA USA. MIT, Whitehead Inst, Ctr Genome Res, Boston, MA USA. RP Henderson, BE (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Sch Med, Dept Prevent Med, 1441 Eastlake Ave,4425, Los Angeles, CA 90033 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA54281, CA17054, CA63464] NR 38 TC 19 Z9 19 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD MAY-JUN PY 1999 VL 35 IS 5-6 BP 355 EP 361 DI 10.1159/000019909 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 198BA UT WOS:000080400800004 PM 10325489 ER PT J AU Matthews, RT Klivenyi, P Mueller, G Yang, LC Wermer, M Thomas, CE Beal, MF AF Matthews, RT Klivenyi, P Mueller, G Yang, LC Wermer, M Thomas, CE Beal, MF TI Novel free radical spin traps protect against malonate and MPTP neurotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE free radicals; mitochondria; spin traps; Huntington's disease; Parkinson's disease ID TERT-BUTYL-NITRONE; NEURONAL NITRIC-OXIDE; EXCITOTOXICITY IN-VIVO; ALPHA-PHENYLNITRONE; OXIDATIVE DAMAGE; TRAPPING AGENTS; ANTIOXIDANT TREATMENT; DELAYED TREATMENT; BRAIN PROTEINS; FOCAL ISCHEMIA AB Both malonate and 1-methyl-4-phenyl-1,2,5,6 tetrahydropyridine (MPTP) are neurotoxins which cause energy depletion, secondary excitotoxicity, and free radical generation. Malonate is a reversible inhibitor of succinate dehydrogenase, while MPTP is metabolized to 1-methyl-4-phenylpyridinium, an inhibitor of mitochondrial complex I. We examined the effects of pretreatment with the cyclic nitrone free radical spin trap MDL 101,002 on malonate and MPTP neurotoxicity. MDL 101,002 produced dose-dependent neuroprotection against malonate-induced striatal lesions. MDL 101,002 produced significant protection against MPTP induced depletions of dopamine and its metabolites. MDL 101,002 also significantly attenuated MPTP-induced increases in striatal 3-nitrotyrosine concentrations. The free radical spin trap tempol also produced significant protection against MPTP neurotoxicity. These findings provide further evidence that free radical spin traps produce neuroprotective effects in vivo and suggest that they may be useful in the treatment of neurodegenerative diseases, (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Lilly Res Labs, Greenfield, IN 46140 USA. RP Matthews, RT (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, 32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS10828, NS16367, NS31579] NR 53 TC 28 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1999 VL 157 IS 1 BP 120 EP 126 DI 10.1006/exnr.1999.7045 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 195AC UT WOS:000080226100010 PM 10222114 ER PT J AU Matthews, RT Ferrante, RJ Klivenyi, P Yang, LC Klein, AM Mueller, G Kaddurah-Daouk, R Beal, MF AF Matthews, RT Ferrante, RJ Klivenyi, P Yang, LC Klein, AM Mueller, G Kaddurah-Daouk, R Beal, MF TI Creatine and cyclocreatine attenuate MPTP neurotoxicity SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Parkinson's; creatine; cyclocreatine; MPTP; free radicals; mitochondria; phosphocreatine ID NMR MAGNETIZATION-TRANSFER; PARKINSONS-DISEASE; SKELETAL-MUSCLE; HUNTINGTONS-DISEASE; ENERGY-METABOLISM; KINASE; BRAIN; RAT; PHOSPHOCREATINE; PHOSPHATE AB Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPPS), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP + in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Avicena Grp Inc, Cambridge, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. RP Matthews, RT (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. FU NINDS NIH HHS [NS31579, NS32365, NS37102] NR 40 TC 230 Z9 241 U1 5 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1999 VL 157 IS 1 BP 142 EP 149 DI 10.1006/exnr.1999.7049 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 195AC UT WOS:000080226100013 PM 10222117 ER PT J AU Zainal, TA Weindruch, R Szweda, LI Oberley, TD AF Zainal, TA Weindruch, R Szweda, LI Oberley, TD TI Localization of 4-hydroxy-2-nonenal-modified proteins in kidney following iron overload SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE aldehydes; ferric nitrilotriacetate; 4-hydroxy-2-nonenal; free radicals; immunogold; iron; lipid peroxidation; reactive oxygen species ID INDUCED LIPID-PEROXIDATION; RENAL PROXIMAL TUBULES; FERRIC NITRILOTRIACETATE; RAT-KIDNEY; WISTAR RATS; IMMUNOCHEMICAL DETECTION; OXIDATIVE STRESS; CELL CARCINOMA; DNA; NEPHROTOXICITY AB Intraperitoneal (IP) injection of ferric nitrilotriacetate (Fe-NTA) to rats and mice results in iron-induced free radical injury and cancer in kidneys. We sought to clarify the exact localization of acute oxidative damage in Fe-NTA-induced nephrotoxicity by performing immunogold light and electron microscopic (EM) techniques using an antibody against 4-hydroxy-2-nonenal (HNE)-modified proteins. Biochemical assays were done to provide complementary quantitative data. Renal accumulation of lipid peroxidation-derived aldehydes, such as malondialdehyde (MDA) and 4-hydroxy-2-alkenals (4-HDA), increased in parallel with protein carbonyl content, an indicator of protein oxidation, 30 min after administration of Fe-NTA. Immunogold light microscopy showed that HNE-modified proteins increased at 30 min with positivity localized to proximal tubular cells, Immunogold EM demonstrated that HNE-modified proteins were mainly in the mitochondria and nuclei of the proximal tubular epithelium. The intensity of labeling at both the light and EM levels increased together with levels of biochemically measured lipid peroxidation products and protein carbonyl content. Our data suggest that the mechanism of acute nephrotoxicity of Fe-NTA involves mitochondrial and nuclear oxidative damage, findings that may help to define the mechanisms of iron-induced cell injury. (C) 1999 Elsevier Science Inc. C1 Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Case Western Reserve Univ, Sch Med, Dept Phys & Biophys, Cleveland, OH USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, 2500 Overlook Terrace,Room A35, Madison, WI 53705 USA. FU NIA NIH HHS [P01 AG 11915] NR 34 TC 41 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 1999 VL 26 IS 9-10 BP 1181 EP 1193 DI 10.1016/S0891-5849(98)00312-8 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 203JR UT WOS:000080705000016 PM 10381189 ER PT J AU Guan, RJ Fu, YN Holt, PR Pardee, AB AF Guan, RJ Fu, YN Holt, PR Pardee, AB TI Association of K-ras mutations with p16 methylation in human colon cancer SO GASTROENTEROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA METHYLTRANSFERASE LEVELS; CPG ISLAND; CELL-LINES; EXPRESSION; HYPERMETHYLATION; TRANSFORMATION; TISSUE; CARCINOGENESIS; TUMORIGENESIS AB Background & Aims: K-ras mutations are early genetic changes in colon cancer, p16, a tumor-suppressor gene, is inactivated in neoplasms by mutation, deletion, or methylation. The aims of this study were to determine p16 methylation status and its possible association with K-ras mutations in human colon cancer. Methods: DNA isolated from 8 colon cancer cell lines and 41 microdissected human colon tissue samples was analyzed. p16 methylation status was determined using two analytical methods. The level of p16 expression was determined by reverse-transcription polymerase chain reaction and Northern Riot, K-ras mutations were determined by DNA sequence analysis. The DNA methyltransferase activity was determined by microassay, Parental and K-ras-transformed IEC-18 cells were used to determine the potential association between K-ras mutations and p16 methylation, Results: Methylated p16 was found in 100% of colon cancer cell lines, 55% of colon cancers, 54% of adenomas, and 25% of transitional mucosa but not in normal colonic epithelium, Forty-five percent of cancers and 38% of adenomas showed both K-ras mutations and p16 methylation. Of 11 cancers and adenomas With K-ras mutation, 10 specimens showed methylated p16. In contrast, of 13 adenomas and cancers with wild-type K-ras, only 3 specimens showed methylated p16 (P = 0.001), Stable transformation of IEC-18 cells with K-ras increased the DNA methyltransferase activity, methylated the p16 gene, and suppressed the expression of p16, Treatment with a DNA methylation inhibitor (azadeoxycytidine) resulted in reexpression of p16 in K-ras-transformed IEC-18 cells, suggesting that the expression of p16 was suppressed by DNA methylation, Conclusions: p16 methylation occurs frequently in human colonic adenomas and cancers and is closely associated with K-ras mutations. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, Div Gastroenterol, New York, NY USA. RP Guan, RJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,D602, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA61253] NR 46 TC 96 Z9 103 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1999 VL 116 IS 5 BP 1063 EP 1071 DI 10.1016/S0016-5085(99)70009-0 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190DY UT WOS:000079947900012 PM 10220498 ER PT J AU Taupin, D Podolsky, DF AF Taupin, D Podolsky, DF TI Mitogen-activated protein kinase activation regulates intestinal epithelial differentiation SO GASTROENTEROLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; CANCER CELL-LINES; TREFOIL FACTOR; HUMAN-COLON; ENTEROCYTIC DIFFERENTIATION; MONOCLONAL-ANTIBODIES; SUCRASE-ISOMALTASE; GENE-EXPRESSION; TRANSGENIC MICE; HOMEOBOX GENE AB Background & Aims: The human colon cancer-derived cell line HT29 displays a multipotent phenotype. A subclone of HT29 cells containing numerous mucous granules and termed HT29-18-N2 was studied to determine the cellular mechanisms underlying a switch to the differentiated phenotype, Methods: Northern (RNA) blotting, immunoblotting, and immunocytochemistry of HT29-N2 cells, grown under glucose-containing and glucose-free conditions with or without the use of the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor PD98059, were performed, Results: Loss of activation of the MAP kinases ERK 1 and ERK 2 in HT29-N2 cells upon a change to glucose-free growth medium preceded the change in phenotype and upregulation of the goblet cell gene product intestinal trefoil factor (ITF), Long-term pharmacological MAP kinase inhibition with the MEK inhibitor PD98059 induced expression of the terminal differentiation markers ITF, sucrase-isomaltase, and the mucin gene MUC2, This was accompanied by morphological evidence of gland formation and mucin secretion and the appearance of discrete goblet cell and enterocyte populations. Induction of ITF and sucrase-isomaltase after MEK inhibition in HT29-N2 cells did not involve loss of MAP kinase responsiveness and was not mediated by receptor tyrosine kinases, Conclusions: Regulation of ERK activation may be a key biochemical switch responsible for terminal differentiation of components of the crypt-villus unit. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Podolsky, DF (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 719,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK46906] NR 39 TC 59 Z9 62 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1999 VL 116 IS 5 BP 1072 EP 1080 DI 10.1016/S0016-5085(99)70010-7 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190DY UT WOS:000079947900013 PM 10220499 ER PT J AU Mayer, EA Marvizon, JC AF Mayer, EA Marvizon, JC TI Neurokinin 3 receptors in the gut: A new target for the treatment of visceral pain? SO GASTROENTEROLOGY LA English DT Editorial Material ID RAT SPINAL-CORD; SUBSTANCE-P; NEURONS; NK3; IMMUNOREACTIVITY; LOCALIZATION; HYPERALGESIA; TACHYKININS; ANTAGONIST C1 Univ Calif Los Angeles, Div Digest Dis, CURE Neuroenter Dis Program, Los Angeles, CA USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Neuroenter Dis Program, 11301 Wilshire Blvd,Bldg 115 CURE, Los Angeles, CA 90073 USA. NR 18 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1999 VL 116 IS 5 BP 1250 EP 1252 DI 10.1016/S0016-5085(99)70030-2 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190DY UT WOS:000079947900033 PM 10220519 ER PT J AU Lu, Y Settleman, J AF Lu, Y Settleman, J TI The Drosophila Pkn protein kinase is a Rho Rac effector target required for dorsal closure during embryogenesis SO GENES & DEVELOPMENT LA English DT Article DE Pkn; Rho GTPase; Rac GTPase; dorsal closure; signal transduction; Drosophila ID CELL-SHAPE CHANGES; SIGNAL-TRANSDUCTION PATHWAY; AMINO-TERMINAL KINASE; ACTIN STRESS FIBERS; CYTOSKELETAL ORGANIZATION; POTENTIAL EFFECTOR; SHEET MOVEMENT; MYOBLAST CITY; SMALL GTPASES; N PKN AB The PKN family of PKC-related protein kinases constitutes the major Rho GTPase-associated protein kinase activities detected in mammalian tissues. However, the biological functions of these kinases are unknown. We have identified a closely related PKN homolog in Drosophila (Pkn) that binds specifically to GTP-activated Rho1 and Rac1 GTPases through distinct binding sites on Pkn. The interaction of Pkn with either of these GTPases results in increased kinase activity, suggesting that Pkn is a shared Rho/Rac effector target. Characterization of a loss-of-function mutant of Drosophila Pkn revealed that this kinase is required specifically for the epidermal cell shape changes during the morphogenetic process of dorsal closure of the developing embryo. Moreover, Pkn, as well as the Rho1 GTPase, mediate a pathway for cell shape changes in dorsal closure that is independent of the previously reported Rac GTPase-mediated Tun amino (N)-terminal kinase (JNK) cascade that regulates gene expression required for dorsal closure. Thus, it appears that distinct but coordinated Rho- and Rac-mediated signaling pathways regulate the cell shape changes required for dorsal closure and that Pkn provides a GTPase effector function for cell shape changes in vivo, which acts together with a Rac-JNK transcriptional pathway in the morphogenesis of the Drosophila embryo. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 58 TC 99 Z9 104 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1999 VL 13 IS 9 BP 1168 EP 1180 DI 10.1101/gad.13.9.1168 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 197NW UT WOS:000080372200012 PM 10323867 ER PT J AU Haddow, JE Bradley, LA Palomaki, GE Doherty, RA Bernhardt, BA Brock, DJH Cheuvront, B Cunningham, GC Donnenfeld, AE Erickson, JL Erlich, HA Ferrie, RM FitzSimmons, SC Greene, MF Grody, WW Haddow, PK Harris, H Holmes, LB Howell, RR Katz, M Klinger, KW Kloza, EM LeFevre, ML Little, S Loeben, G McGovern, M Pyeritz, RE Rowley, PT Saiki, RK Short, MP Tabone, J Wald, NJ Wilker, NL Witt, DR AF Haddow, JE Bradley, LA Palomaki, GE Doherty, RA Bernhardt, BA Brock, DJH Cheuvront, B Cunningham, GC Donnenfeld, AE Erickson, JL Erlich, HA Ferrie, RM FitzSimmons, SC Greene, MF Grody, WW Haddow, PK Harris, H Holmes, LB Howell, RR Katz, M Klinger, KW Kloza, EM LeFevre, ML Little, S Loeben, G McGovern, M Pyeritz, RE Rowley, PT Saiki, RK Short, MP Tabone, J Wald, NJ Wilker, NL Witt, DR TI Issues in implementing prenatal screening for cystic fibrosis: Results of a working conference SO GENETICS IN MEDICINE LA English DT Article DE cystic fibrosis; screening; prenatal; genetic testing ID CONTINUING MEDICAL-EDUCATION; COST-EFFECTIVENESS; PREGNANT-WOMEN; POPULATION; CARRIERS; INFORMATION; ACCEPTABILITY; TRIAL; GENE AB Purpose: To summarize a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Methods: Participants included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Results: Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost-effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Conclusions: Once adequate facilities for patient and provider education, testing, counseling, quality control, and monitoring are in place, individual programs can begin prenatal screening for cystic fibrosis. C1 Fdn Blood Res, Scarborough, ME 04070 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Univ N Carolina, Chapel Hill, NC USA. Calif Dept Hlth, Berkeley, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. Roche Mol Syst, Alameda, CA USA. Zeneca Diagnost, Northwich, Cheshire, England. Cyst Fibrosis Fdn, Bethesda, MD USA. Vincent Mem Obstet Assoc, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Cent Manchester Hlth Care Trust, Manchester, Lancs, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Sch Med, Miami, FL USA. March Dimes Birth Defects Fdn, White Plains, NY USA. Genzyme, Framingham, MA USA. Univ Missouri, Columbia, MO USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Univ Rochester, Sch Med, Rochester, NY USA. Univ Chicago, Chicago, IL 60637 USA. Rapigene Inc, Bothell, WA USA. Wolfson Inst Prevent Med, London, England. Alliance Genet Support Grp, Washington, DC USA. Kaiser Permanente, San Jose, CA USA. RP Haddow, JE (reprint author), Fdn Blood Res, POB 190, Scarborough, ME 04070 USA. RI Pyeritz, Reed/A-1364-2010 NR 47 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 1999 VL 1 IS 4 BP 129 EP 135 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 238HH UT WOS:000082704500003 PM 11258347 ER PT J AU Jeyarajah, AR Ind, TEJ MacDonald, N Skates, S Oram, DH Jacobs, IJ AF Jeyarajah, AR Ind, TEJ MacDonald, N Skates, S Oram, DH Jacobs, IJ TI Increased mortality in postmenopausal women with serum CA125 elevation SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CA125 elevation; mortality ID OVARIAN-CANCER; CA-125; CARCINOMA; ANTIGEN; CEA AB Objectives. Serum CA125 is used in monitoring treatment and detecting recurrence in ovarian cancer (OC). We have also shown that CA125 can be used with ultrasound for the early detection of OC, However, physiological, benign, and malignant conditions are also associated with CA125 elevation. The aim of the study was to determine the prognostic implications of CA125 elevation in asymptomatic postmenopausal women. Methods. The study involved 771 volunteers in an OC screening trial of 22,000 women who had elevated serum CA125 levels (greater than or equal to 30 U/ml). The control group consisted of an equal number of volunteers with normal levels. Survival was analyzed from the first point of CA125 elevation. Univariate analyses utilized the log-rank chi(2) test. A logistic model was constructed for the multivariate analyses, Results. The mean duration of follow-up was 1614 days (SD 897 days). Eighty-four women died (elevated CA125 group-62, control group-22). Univariate analyses showed that mortality in the elevated CA125 group was significantly greater (log-rank chi(2) = 23.556, P < 0.0001, RR = 2.76), even when preexisting morbid conditions were excluded (log-rank chi(2) = 14.644, P = 0.0001, RR = 2.4), Multivariate analysis showed that CA125 elevation, age (>60 years), and a prior history of cancer were associated with a poor prognosis. Conclusions. Serum CA125 elevation is associated with a significantly increased risk of death from all causes in the next 5 years. These findings may have implications for asymptomatic postmenopausal women with CA125 elevation. (C) 1999 Academic Press. C1 Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Dept Gynecol Oncol, London EC1A 7BE, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Jeyarajah, AR (reprint author), Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med & Dent, Dept Gynecol Oncol, London EC1A 7BE, England. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 25 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 1999 VL 73 IS 2 BP 242 EP 246 DI 10.1006/gyno.1999.5350 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 196UB UT WOS:000080325000012 PM 10329041 ER PT J AU Gerson, S Belin, TR Kaufman, A Mintz, J Jarvik, L AF Gerson, S Belin, TR Kaufman, A Mintz, J Jarvik, L TI Pharmacological and psychological treatments for depressed older patients: A meta-analysis and overview of recent findings SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID SEROTONIN REUPTAKE INHIBITORS; LATE-LIFE DEPRESSION; PRETREATMENT ORTHOSTATIC HYPOTENSION; MULTICENTER DOUBLE-BLIND; GERIATRIC DEPRESSION; ELDERLY PATIENTS; MAJOR DEPRESSION; TRICYCLIC ANTIDEPRESSANTS; PRIMARY-CARE; THERAPEUTIC RESPONSE AB A meta-analysis was carried out to evaluate data published between January 1974 and February 1998 comparing rates of treatment response and tolerability of pharmacological and psychological treatments for depression in persons over age 55. Drugs (tricyclic antidepressants, selective serotonin-reuptake Inhibitors, and a mixed group of other drugs) were significantly better than placebo, with an average reduction in symptom severity of 48.0% versus 31.3% (analysis weighted by sample size; 50.6% vs. 21.4% unweighted). No single drug or group of drugs was superior in terms of efficacy, and no statistically significant differences in tolerability emerged between tricyclic antidepressants and selective serotonin-reuptake inhibitors, whether measured by total dropouts or by dropouts due to side effects. Compared to the data on pharmacological treatments, those for outcomes of psychological treatments are very limited. Existing data indicate that cognitive-behavioral, behavioral, and psychodynamic therapies are significantly better than placebo. In the current meta-analysis, response rates to these nondrug therapies did not differ significantly from those observed with tricyclic antidepressants or selective serotonin-reuptake inhibitors, but direct comparison data are insufficient for firm conclusions to be drawn about comparative efficacy. It is possible, even likely, that not only different subtypes of depression but also different patients vary in their treatment responses. However, lack of adequate data prevented the current meta-analysis from addressing these issues. Rigorously designed prospective studies on treatment outcome, taking into account the above differences, are urgently needed to provide robust data on which to base clinical recommendations for the treatment of depression in older patients. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Biostat, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Vet Affairs, Los Angeles, CA 90073 USA. RP Jarvik, L (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza, Los Angeles, CA 90024 USA. NR 245 TC 45 Z9 47 U1 2 U2 8 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 MAY-JUN PY 1999 VL 7 IS 1 BP 1 EP 28 DI 10.1093/hrp/7.1.1 PG 28 WC Psychiatry SC Psychiatry GA 200JN UT WOS:000080536500001 PM 10439302 ER PT J AU Menzel, P Gold, MR Nord, E Pinto-Prades, JL Richardson, J Ubel, P AF Menzel, P Gold, MR Nord, E Pinto-Prades, JL Richardson, J Ubel, P TI Toward a broader view of values in cost-effectiveness analysis of health SO HASTINGS CENTER REPORT LA English DT Article ID CARE; ILLNESS; OREGON; STATE C1 Pacific Lutheran Univ, Tacoma, WA 98447 USA. CUNY, Sch Med, New York, NY 10031 USA. Natl Publ Hlth Inst, Oslo, Norway. Pompeu Fabra Univ, Barcelona, Spain. Monash Univ, Hlth Econ Unit, Clayton, Vic 3168, Australia. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Menzel, P (reprint author), Pacific Lutheran Univ, Tacoma, WA 98447 USA. RI pinto prades, jose luis/B-7069-2008 OI pinto prades, jose luis/0000-0002-9684-3410 NR 36 TC 51 Z9 51 U1 3 U2 4 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAY-JUN PY 1999 VL 29 IS 3 BP 7 EP 15 DI 10.2307/3528187 PG 9 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 212TD UT WOS:000081231600008 PM 10420299 ER PT J AU Wharton, RH AF Wharton, RH TI Pedestrian vs. train SO HASTINGS CENTER REPORT LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pediat Bioeth Comm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Optimum Care Comm, Boston, MA 02114 USA. RP Wharton, RH (reprint author), Massachusetts Gen Hosp, Pediat Bioeth Comm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD MAY-JUN PY 1999 VL 29 IS 3 BP 28 EP 29 DI 10.2307/3528192 PG 2 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 212TD UT WOS:000081231600012 PM 10420303 ER PT J AU Yoshida, N Liberman, MC AF Yoshida, N Liberman, MC TI Stereociliary anomaly in the guinea pig: effects of hair bundle rotation on cochlear sensitivity SO HEARING RESEARCH LA English DT Article DE outer hair cell; congenital; stereocilia ID ACOUSTIC TRAUMA; CELLS; PROTECTION; THRESHOLD; MEMBRANE; INJURY AB Histological analysis of cochleas from 100 albino guinea pigs (Hartley strain) obtained from Charles River Laboratories revealed an apparently congenital anomaly in 24% of animals, with roughly equal prevalence in males and females. In affected animals, 15-50% of the first-row outer hair cells (OHCs) showed distinctly abnormal orientation of the W-shaped stereociliary array. These abnormal hair bundles could be rotated by up to 180 degrees from the normal quasi-radial orientation. Second- and third-row OHCs appeared normal in all cases. Cochlear sensitivity was assayed in a subset of animals via compound action potentials (CAPs): CAP thresholds in affected animals were, on average, elevated by 5-10 dB with respect to normal controls. If the contributions of individual OHCs to cochlear 'amplification' add linearly, and if the total OHC contribution corresponds to similar to 45 dB of 'gain', a quantitative correlation of the degree of stereociliary rotation and the degree of threshold shift in these ears suggests that first-row OHCs make a larger contribution to the cochlear amplifier than either of the other OHC rows. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Tohoku Univ, Sch Med, Dept Otolaryngol, Sendai, Miyagi 980, Japan. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC0188] NR 26 TC 25 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1999 VL 131 IS 1-2 BP 29 EP 38 DI 10.1016/S0378-5955(99)00008-8 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 194JG UT WOS:000080188600004 PM 10355602 ER PT J AU Arora, S Katkov, W Cooley, J Kemp, JA Johnston, DE Schapiro, RH Podolsky, D AF Arora, S Katkov, W Cooley, J Kemp, JA Johnston, DE Schapiro, RH Podolsky, D TI Methotrexate in Crohn's disease: Results of a randomized, double-blind, placebo-controlled trial SO HEPATO-GASTROENTEROLOGY LA English DT Article DE Crohn's disease; methotrexate ID INFLAMMATORY BOWEL-DISEASE; RHEUMATOID-ARTHRITIS; THERAPY; UPDATE AB BACKGROUND/AIMS: Immunosuppression with methotrexate may be useful in the treatment of Crohn's disease. We tested the efficacy of methotrexate in refractory Crohn's disease in a randomized, controlled trial. METHODOLOGY: Randomized, double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn's disease, 33% of whom had previously failed therapy with 6-mercaptopurine. Patients were given placebo or oral methotrexate 16mg/week, or adjusted up to 22.5mg/week, for up to 1 year or until treatment failure. Outcome was assessed by reduction in prednisone dosage, Crohn's Disease Activity Index, hospital admission, and laboratory parameters. RESULTS: Four patients were dropped from the study for non-compliance and one because of intercurrent illness, and 28 patients could be evaluated. Fewer methotrexate-treated patients (6/13 or 46%) had flares of Crohn's disease as compared to placebo-treated patients (12/15 or 80%), but this did not achieve statistical significance (p<0.1). There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients (3/13 or 23%) as compared to the placebo-treated patients (0/15 or 0%) (p<0.2). Laboratory indices of inflammation did not differ between the two groups. CONCLUSIONS: The methotrexate-treated group showed a trend toward fewer Crohn's disease flares, balanced by an increased number of significant side effects. C1 New England Med Ctr, Div Gastroenterol, Boston, MA 02111 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Arora, S (reprint author), Univ New Mexico, Sch Med, Div Gastroenterol, ACC-5, Albuquerque, NM 87131 USA. NR 15 TC 95 Z9 97 U1 0 U2 3 PU H G E UPDATE MEDICAL PUBL LTD. PI ATHENS PA PO BOX 17160, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD MAY-JUN PY 1999 VL 46 IS 27 BP 1724 EP 1729 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 215TH UT WOS:000081398700050 PM 10430331 ER PT J AU Perrillo, R Rakela, J Dienstag, J Levy, G Martin, P Wright, T Caldwell, S Schiff, E Gish, R Villeneuve, JP Farr, G Anschuetz, G Crowther, L Brown, N AF Perrillo, R Rakela, J Dienstag, J Levy, G Martin, P Wright, T Caldwell, S Schiff, E Gish, R Villeneuve, JP Farr, G Anschuetz, G Crowther, L Brown, N CA Lamivudine Transplant Grp TI Multicenter study of lamivudine therapy for hepatitis B after liver transplantation SO HEPATOLOGY LA English DT Article ID VIRUS-INFECTION; REINFECTION; RESISTANCE; RECIPIENTS; INTERFERON; CIRRHOSIS; TRIAL AB Hepatitis B after liver transplantation is often fatal, and no proven medical therapy exists for this condition. We chose to study the potential efficacy of lamivudine therapy for patients with chronic hepatitis B after liver transplantation. Fifty-two patients with chronic hepatitis B after liver transplantation were treated in an open label, multicenter study. Each had detectable hepatitis B virus (HBV) DNA in serum and 45 (87%) had detectable serum hepatitis B e antigen before treatment. Patients were treated for 52 weeks with lamivudine (100 mg daily). The primary endpoint was undetectability of HBV DNA; secondary endpoints included normalization of serum alanine transaminase (ALT) levels, disappearance of hepatitis B e antigen, and improvement in liver histology. After treatment, 60% of patients had undetectable HBV DNA by solution hybridization assay, 14 (31%) of the initially positive patients lost hepatitis B e antigen; hepatitis B surface antigen was undetectable in 3 (6%); and serum ALT levels normalized in 71%. Blinded histological assessments showed improvement in the histological activity index (P = .007 for periportal necrosis, .001 for lobular necrosis, and .013 for portal inflammation). YMDD variants of HBV, potentially associated with drug resistance, were detected in 14 (27%) of the patients. Repeat liver biopsies in 7 patients with the mutated virus were unchanged in 2, improved in 2, and worse in 3. We conclude that lamivudine is a potentially effective therapy for hepatitis B after liver transplantation. C1 Alton Ochsner Med Fdn & Ochsner Clin, Gastroenterol Sect, New Orleans, LA 70121 USA. Alton Ochsner Med Fdn & Ochsner Clin, Sect Pathol, New Orleans, LA 70121 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Toronto Gen Hosp, Toronto, ON, Canada. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Univ Miami, Miami, FL 33152 USA. Calif Pacific Med Ctr, San Francisco, CA USA. CHU Montreal, Montreal, PQ, Canada. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Perrillo, R (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Sect Gastroenterol & Hepatol, 1514 Jefferson Highway, New Orleans, LA 70121 USA. NR 31 TC 166 Z9 177 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 MAY PY 1999 VL 29 IS 5 BP 1581 EP 1586 DI 10.1002/hep.510290507 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 190DB UT WOS:000079945700033 PM 10216146 ER PT J AU Baskin, DG Lernmark, A AF Baskin, DG Lernmark, A TI Third Seattle Islet Symposium: Recent Advances in Signaling Mechanisms Common to the Nervous System and Islets SO HORMONE AND METABOLIC RESEARCH LA English DT Editorial Material C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Robert H Williams Lab, Dept Med, Seattle, WA USA. RP Baskin, DG (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 1999 VL 31 IS 5 BP 329 EP 329 DI 10.1055/s-2007-978747 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213NN UT WOS:000081280300008 ER PT J AU Figlewicz, DP Patterson, TA Zavosh, A Brot, MD Roitman, M Szot, P AF Figlewicz, DP Patterson, TA Zavosh, A Brot, MD Roitman, M Szot, P TI Neurotransmitter transporters: Target for endocrine regulation SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT 3rd Seattle Islet Symposium - Recent Advances in Signaling Mechanisms Common to the Nervous System and Islets CY MAY 19, 1998 CL UNIV WASHINGTON, SEATTLE, WASHINGTON SP Bayer Pharmaceut, Eli Lilly & Co, Knoll Pharmaceut, Novartis, Parke-Davis, Zymogenetics HO UNIV WASHINGTON DE insulin; glucocorticoids; aldosterone; transporters; dopamine; estrogen ID RAT DOPAMINE TRANSPORTER; BRAIN GABA TRANSPORTER; MESSENGER-RNA; SEROTONIN TRANSPORTERS; NOREPINEPHRINE UPTAKE; FUNCTIONAL REGULATION; EXPRESSION CLONING; NEURONAL CULTURES; LOCUS-CERULEUS; COCAINE AB Aminergic signaling in the CNS is terminated by clearance from the synapse via high-affinity transporter molecules in the presynaptic membrane. Relatively recent sequence identification of these molecules has now permitted the initiation of studies of regulation of transporter function at the cellular and systems levels. In vitro studies provide evidence that the transporters for dopamine, serotonin, and gamma-aminobutyric acid are substrates for regulation by protein kinase C signaling. In vivo studies provide evidence that insulin and adrenal and gonadal steroid hormones may regulate the synthesis and activity of the transporters. Future directions should permit evaluation of the role of endocrine regulation in neurotransmitter clearance, and thus in the maintenance of normal CNS aminergic signaling. C1 VA Puget Sound Hlth Care Syst, Dept Metab Endocrinol 151, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Dept Metab Endocrinol 151, 1660 So Comumbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01-DK40963] NR 58 TC 23 Z9 23 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 1999 VL 31 IS 5 BP 335 EP 339 DI 10.1055/s-2007-978749 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213NN UT WOS:000081280300010 PM 10422731 ER PT J AU Baskin, DG Hahn, TM Schwartz, MW AF Baskin, DG Hahn, TM Schwartz, MW TI Leptin sensitive neurons in the hypothalamus SO HORMONE AND METABOLIC RESEARCH LA English DT Article; Proceedings Paper CT 3rd Seattle Islet Symposium - Recent Advances in Signaling Mechanisms Common to the Nervous System and Islets CY MAY 19, 1998 CL UNIV WASHINGTON, SEATTLE, WA SP Bayer Pharmaceut, Eli Lilly & Co, Knoll Pharmaceut, Novartis, Parke-Davis, Zymogenetics HO UNIV WASHINGTON DE food intake; obesity; body weight; arcuate nucleus; NPY; POMC ID RECEPTOR MESSENGER-RNA; CORTICOTROPIN-RELEASING FACTOR; MELANIN-CONCENTRATING HORMONE; OBESE GENE-EXPRESSION; NEUROPEPTIDE-Y; OB/OB MICE; BODY-WEIGHT; FEEDING-BEHAVIOR; ARCUATE NUCLEUS; MOUSE-BRAIN AB A major paradigm in the field of obesity research is the existence of an adipose tissue-brain endocrine axis for the regulation of body weight. Leptin, the peptide mediator of this axis, is secreted by adipose cells. It lowers food intake and body weight by acting in the hypothalamus, a region expressing an abundance of leptin receptors and a variety of neuropeptides that influence food intake and energy balance. Among the most promising candidates for leptin-sensitive cells in the hypothalamus are arcuate nucleus neurons that co-express the anabolic neuropeptides, neuropeptide Y (NPY) and agouti-related peptide (AGRP), and those that express proopiomelanocortin (POMC), the precursor of the catabolic peptide, alpha MSH. These cell types contain mRNA encoding leptin receptors and show changes in neuropeptide gene expression in response to changes in food intake and circulating leptin levels. Decreased leptin signaling in the arcuate nucleus is hypothesized to increase the expression of NPY and AGRP. Levels of leptin receptor mRNA and leptin binding are increased in the arcuate nucleus during fasting, principally in NPY/AGRP neurons. These findings suggest that changes in leptin receptor expression in the arcuate nucleus are inversely associated with changes in leptin signaling, and that the arcuate nucleus is an important target of leptin action in the brain. C1 VA Puget Sound Hlth Care Syst, Med Res Serv, Div Endocrinol & Metab, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA USA. RP VA Puget Sound Hlth Care Syst, Res Serv, Mail Stop 151,1660 So Columbian Way, Seattle, WA 98108 USA. EM baskindg@u.washington.edu RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-17047, DK-52989]; NINDS NIH HHS [NS32273] NR 83 TC 114 Z9 115 U1 0 U2 4 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 EI 1439-4286 J9 HORM METAB RES JI Horm. Metab. Res. PD MAY PY 1999 VL 31 IS 5 BP 345 EP 350 DI 10.1055/s-2007-978751 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 213NN UT WOS:000081280300012 PM 10422733 ER PT J AU Mihm, MC AF Mihm, MC TI Why Wallace? Introduction SO HUMAN PATHOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mihm, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1999 VL 30 IS 5 BP 489 EP 490 DI 10.1016/S0046-8177(99)90188-0 PG 2 WC Pathology SC Pathology GA 194WZ UT WOS:000080218900001 ER PT J AU Murphy, GF Mihm, MC AF Murphy, GF Mihm, MC TI Recognition and evaluation of cytological dysplasia in acquired melanocytic nevi SO HUMAN PATHOLOGY LA English DT Article ID MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; FAMILIES; RISK; PROGRESSION; INDIVIDUALS; LESIONS C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Div Diagnost & Expt Dermatopathol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Murphy, GF (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Div Diagnost & Expt Dermatopathol, 1020 Locust St, Philadelphia, PA 19107 USA. NR 31 TC 16 Z9 16 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1999 VL 30 IS 5 BP 506 EP 512 DI 10.1016/S0046-8177(99)90192-2 PG 7 WC Pathology SC Pathology GA 194WZ UT WOS:000080218900005 PM 10333218 ER PT J AU Flotte, TJ Mihm, MC AF Flotte, TJ Mihm, MC TI Lentigo maligna and malignant melanoma in situ, lentigo maligna type SO HUMAN PATHOLOGY LA English DT Article DE lentigo maligna; melanoma in situ; pagetoid AB Some authors have considered lentigo maligna to be an atypical melanocytic proliferation, whereas others have considered it to be melanoma in situ. We reviewed 50 cases of lentigo maligna. We have identified two subsets: of lesions. The first has atypical melanocytic hyperplasia, which we postulate to be correctly designated lentigo maligna. The second subset has the following features in addition to the melanocytic hyperplasia: individual and nests of cells at varying layers of the epidermis, confluence of the melanocytes replacing the basilar region, uniformity of the cytological atypia, and nesting of uniformly atypical melanocytes. These lesions we designate as malignant melanoma in situ, lentigo maligna type. We are proposing that the lesions that have been termed lentigo maligna represent a spectrum of atypia and that the application of some of the traditional features for the diagnosis melanoma may permit the segregation of more and less aggressive lesions. HUM PATHOL 30:533-536. Copyright (C) 1999 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Flotte, TJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Warren 827,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 30 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1999 VL 30 IS 5 BP 533 EP 536 DI 10.1016/S0046-8177(99)90197-1 PG 4 WC Pathology SC Pathology GA 194WZ UT WOS:000080218900010 PM 10333223 ER PT J AU Wharton, JM Carlson, JA Mihm, MC AF Wharton, JM Carlson, JA Mihm, MC TI Desmoplastic malignant melanoma, diagnosis of early clinical lesions SO HUMAN PATHOLOGY LA English DT Article DE malignant melanoma; early spindle cell type; desmoplastic type; prognosis; histology ID NEUROTROPIC MELANOMA; VARIANT; TUMORS AB Desmoplastic malignant melanoma (DMM) is an uncommon but potentially devastating malignancy that can be cured with early recognition and surgery DMM has clinical as well as histological features that may be subtle and overlooked, or misdiagnosed as other benign or malignant lesions that would require less aggressive therapy for cure. We have reviewed the preliminary clinical diagnoses and histological features of 18 cases of desmoplastic malignant melanoma, defined as either an inapparent lesion clinically, or a papule or small nodule less than 0.7 cm, which proved histologically to be DMM. Nine of 18 cases (50%) were clinically pigmented. Histologically, early lesions were characterized by superficial tumor fascicles, and random diffuse hypercellularity in the upper dermis identified as elongated hyperchromatic pleomorphic spindle cells with stromal myxoid change. Neuroidal melanocytic structures, invasion of adventitial dermis, islands of inflammation, and epidermal lentiginous melanocytic hyperplasia were often present. The most reliable and characteristic features of an early lesion of DMM are aggregates of lymphocytes, tumor cell cytological atypia, stromal myxoid change, and poor circumscription of the dermal infiltrate. DMM is a disease best treated by complete excision at the time of initial surgery, but is also a lesion easily missed or misdiagnosed in the early stages. Features of early DMM are identified and illustrated to enable early diagnosis and cure of these lesions. HUM PATHOL 33:537-542. Copyright (C) 1999 by W.B. Saunders Company. C1 Albany Med Coll, Dept Pathol & Lab Med, Div Dermatopathol & Dermatol, Albany, NY 12208 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. RP Wharton, JM (reprint author), Albany Med Coll, Dept Pathol & Lab Med, Div Dermatopathol & Dermatol, MC-81,47 New Scotland Ave, Albany, NY 12208 USA. OI Carlson, John Andrew/0000-0002-6866-6314 NR 25 TC 32 Z9 32 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1999 VL 30 IS 5 BP 537 EP 542 DI 10.1016/S0046-8177(99)90198-3 PG 6 WC Pathology SC Pathology GA 194WZ UT WOS:000080218900011 PM 10333224 ER PT J AU Crowson, AN Magro, CM Mihm, MC AF Crowson, AN Magro, CM Mihm, MC TI Malignant melanoma with prominent pigment synthesis: "Animal type" melanoma - A clinical and histological study of six cases with a consideration of other melanocytic neoplasms with prominent pigment synthesis SO HUMAN PATHOLOGY LA English DT Article DE animal type melanoma; prominent pigment synthesis ID CELLULAR BLUE NEVUS; PILAR NEUROCRISTIC HAMARTOMA; VARIANT; SCALP AB Rare skin neoplasms in humans, comprising nodules of heavily melanized cells, mimic melanocytic neoplasms seen in horses and laboratory animals and thus are termed animal type melanomas. In part because of their rarity, behavior is unpredictable; many cases manifest a long indolent phase, and metastases are reportable. Over 6 years, the authors encountered nine skin and one lymph node biopsy specimens from six patients in whom light microscopy of formalin-fixed, paraffin-embedded tissue sections stained with hematoxylin and eosin showed melanocytic neoplasms with prominent pigment synthesis. Clinical follow-up was obtained by telephone contact with clinicians. There were three women, two men, and one boy, aged 9 to 85 years, whose lesions were described as blue-black nodules with irregular borders from 1.0 to 4.0 cm in size, located on the scalp, lower extremities, back, and sacrum. The dermatopathology com prised confluent dermal sheets of heavily melanized cells whose nuclei, where discernible, were large with irregularly thickened membranes, coarse chromatin, prominent, often spiculated nucleoli, and irregular parachromatinic clearing, Mitoses were infrequent. Four lesions had an epidermal component. One patient suffered metastases to regional lymph nodes, liver, and lung with lethal effect, one experienced regional lymph node metastases but is still alive, one had local cutaneous metastases but was lost to follow-up, and one has a chest wall mass that has not yet been investigated. This rare dermal-based melanocytic neoplasm with prominent pigment synthesis, the animal type melanoma, has a biological behavior difficult to predict on morphological grounds. We advise complete excision with a 1.0- to 2.0-cm margin of normal skin and clinical investigation for regional or distant metastases. HUM PATHOL 30:543-550. Copyright (C) 1999 by W.B. Saunders Company. C1 Misericordia Gen Hosp, Cent Med Labs, Winnipeg, MB, Canada. Misericordia Gen Hosp, Dept Labs, Winnipeg, MB, Canada. Pathol Serv Inc, Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Cambridge, MA USA. Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. RP Crowson, AN (reprint author), Reg Med Lab, 1923 S Utica St, Tulsa, OK 74104 USA. NR 35 TC 63 Z9 63 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1999 VL 30 IS 5 BP 543 EP 550 DI 10.1016/S0046-8177(99)90199-5 PG 8 WC Pathology SC Pathology GA 194WZ UT WOS:000080218900012 PM 10333225 ER PT J AU Pillai, S AF Pillai, S TI The chosen few? Positive selection and the generation of naive B lymphocytes SO IMMUNITY LA English DT Review ID LYN-DEFICIENT MICE; X-LINKED AGAMMAGLOBULINEMIA; HUMORAL IMMUNE-RESPONSE; CELL ANTIGEN RECEPTOR; SURROGATE LIGHT CHAIN; SYK TYROSINE KINASE; NF-KAPPA-B; B-1 CELLS; BONE-MARROW; T-CELL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. NR 112 TC 88 Z9 90 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1999 VL 10 IS 5 BP 493 EP 502 DI 10.1016/S1074-7613(00)80049-7 PG 10 WC Immunology SC Immunology GA 203LP UT WOS:000080709400001 PM 10367895 ER PT J AU Monroe, RJ Sleckman, BP Monroe, BC Khor, B Claypool, S Ferrini, R Davidson, L Alt, FW AF Monroe, RJ Sleckman, BP Monroe, BC Khor, B Claypool, S Ferrini, R Davidson, L Alt, FW TI Developmental regulation of TCR delta locus accessibility and expression by the TCR delta enhancer SO IMMUNITY LA English DT Article ID T-CELL DEVELOPMENT; RECEPTOR ALPHA/DELTA-LOCUS; ALPHA-BETA-LINEAGE; GAMMA-DELTA; GENE REARRANGEMENT; TRANSCRIPTIONAL ENHANCER; V(D)J RECOMBINATION; TARGETED DELETION; IG-KAPPA; C-ALPHA AB We have used gene-targeted mutation to assess the role of the T cell receptor delta (TCR delta) enhancer (E delta) in alpha beta and gamma delta T cell development. Mice lacking E delta exhibited no defects in alpha beta T cell development but had a severe reduction in thymic and peripheral gamma delta T cells and decreased VDJ delta rearrangements. Simultaneous deletion of both E delta and the TCR alpha enhancer (E alpha) demonstrated that residual TCR delta rearrangements were not driven by E alpha, implicating additional elements in TCR delta locus accessibility. Surprisingly, while deletion of E delta severely impaired germline TCR delta expression in double-negative thymocytes, absence of E delta did not affect expression of mature delta transcripts in gamma delta T cells. We conclude that E delta has an important role in TCR delta locus regulation at early, but not late, stages of gamma delta T cell development. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. FU PHS HHS [A.I.20047, A.I.01297-01] NR 57 TC 46 Z9 46 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1999 VL 10 IS 5 BP 503 EP 513 DI 10.1016/S1074-7613(00)80050-3 PG 11 WC Immunology SC Immunology GA 203LP UT WOS:000080709400002 PM 10367896 ER PT J AU Gartner, F Alt, FW Monroe, R Chu, M Sleckman, BP Davidson, L Swat, W AF Gartner, F Alt, FW Monroe, R Chu, M Sleckman, BP Davidson, L Swat, W TI Immature thymocytes employ distinct signaling pathways for allelic exclusion versus differentiation and expansion SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; CHAIN GENE REARRANGEMENT; ADAPTER PROTEIN SLP-76; ALPHA-BETA; TCR-ALPHA; IMMUNOGLOBULIN-MU; TRANSGENIC MICE; DEFICIENT MICE; TYROSINE KINASES; ANTIGEN RECEPTOR AB T cell receptor (TCR) beta chain allelic exclusion occurs at the thymocyte CD4(-)8(-) (double-negative, or DN) to CD4(+)8(+) (double-positive, or DP) transition, concurrently with differentiation and cellular expansion, and is imposed by a negative feedback loop in which a product of the first rearranged TCR allele arrests further recombination in the TCR beta locus. All of the major events associated with the development of DP cells can be induced by the introduction of TCR beta or activated Lck transgenes. Here, we present evidence that the signaling pathways that promote thymocyte differentiation and expansion of RAG-deficient DN cells but not those that suppress rearrangements of endogenous TCR beta genes in normal DN cells are engaged by activated Ras. We propose that TCR beta allelic exclusion is mediated by effector pathways downstream of Lck but independent of Ras. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-20047] NR 57 TC 94 Z9 95 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1999 VL 10 IS 5 BP 537 EP 546 DI 10.1016/S1074-7613(00)80053-9 PG 10 WC Immunology SC Immunology GA 203LP UT WOS:000080709400005 PM 10367899 ER PT J AU Beresford, PJ Xia, ZN Greenberg, AH Lieberman, J AF Beresford, PJ Xia, ZN Greenberg, AH Lieberman, J TI Granzyme A loading induces rapid cytolysis and a novel form of DNA damage independently of caspase activation SO IMMUNITY LA English DT Article ID TOXIC LYMPHOCYTE-T; CELL-MEDIATED CYTOTOXICITY; CYTOKINE RESPONSE MODIFIER; NATURAL-KILLER-CELLS; TARGET-CELLS; SERINE PROTEASES; BCR-ABL; INDUCED APOPTOSIS; MYELOID-LEUKEMIA; DEFICIENT MICE AB Cytotoxic lymphocytes trigger apoptosis by releasing perforin and granzymes (Grn). GrnB activates the caspase apoptotic pathway, but little is known about GrnA-induced cell death. Perforin was used to load recombinant GrnA and GrnB and enzymatically inactive variants into target cells. GrnA induces single-strand DNA breaks that can be labeled with Klenow polymerase and visualized on alkaline gels. GrnA-induced DNA damage but not cytolysis requires GrnA proteolysis. GrnA-induced membrane perturbation, nuclear condensation, and DNA damage are unimpaired by caspase blockade. GrnA fails to induce cleavage of caspase-3, lamin B, rho-GTPase, or PARP. GrnA-induced cytotoxicity and cleavage of PHAP II, a previously identified GrnA substrate, are unimpaired in Jurkat cells that overexpress bcl-2. Therefore, GrnA activates a novel apoptotic pathway. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 74 TC 158 Z9 161 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1999 VL 10 IS 5 BP 585 EP 594 DI 10.1016/S1074-7613(00)80058-8 PG 10 WC Immunology SC Immunology GA 203LP UT WOS:000080709400010 PM 10367904 ER PT J AU Kawashima, N Niederman, R Hynes, RO Ullmann-Cullere, M Stashenko, P AF Kawashima, N Niederman, R Hynes, RO Ullmann-Cullere, M Stashenko, P TI Infection-stimulated infraosseus inflammation and bone destruction is increased in P-/E-selectin knockout mice SO IMMUNOLOGY LA English DT Article ID METHOTREXATE-INDUCED NEUTROPENIA; LEUKOCYTE ADHESION DEFICIENCY; INDUCED PERIAPICAL LESIONS; RAT MOLARS; T-CELLS; SUSCEPTIBILITY; PATHOGENESIS; DISEASE; MAC-1; LFA-1 AB Infections of the dental pulp commonly result in infraosseus inflammation and bone destruction. However, the role of phagocytic leucocytes in the pathogenesis of pulpal infections has been uncertain. In this work we used P/E-/- selectin-deficient mice, which lack rolling adhesion of leucocytes to endothelium and mimic the human syndrome, leucocyte adhesion deficiency II (LAD-II), to test the hypothesis that phagocytic leucocytes protect against pulpal infection and subsequent periapical infraosseus bone resorption. P/E-/- mice and P/E+/+ wild-type controls were subjected to surgical pulp exposure, and both groups were infected with a mixture of pulpal pathogens including Prevotella intermedia, Fusobacterium nucleatum, Peptostreptococcus micros and Streptococcus intermedius. Animals were killed after 20 days, and the extent of infraosseus bone destruction was quantified by histomorphometry. In two separate experiments, P/E-/- mice had significantly greater bone resorption than P/E+/+ controls. The increased bone destruction correlated with a twofold decrease in polymorphonuclear (PMN) infiltration into periapical inflammatory tissues of P/E-/- mice. P/E-/- mice had higher tissue levels of the bone resorptive cytokine, interleukin (IL)-1 alpha. Tissue levels of IL-2, IL-4, IL-10, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were all higher in P/E-/- mice, but the increases were not statistically significant. Only IL-12 was higher in P/E+/+ mice, possibly reflecting a greater number of infiltrating monocytes in wild-type mice. These findings demonstrate that phagocytic leucocytes are protective in this model, and suggest that elevated expression of inflammatory cytokines is responsible for the observed bone destruction. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. MIT, Dept Biol, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA USA. RP Stashenko, P (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-41484]; NIDCR NIH HHS [DE-09018, DE-11664, R01 DE009018, R01 DE011664] NR 40 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 1999 VL 97 IS 1 BP 117 EP 123 PG 7 WC Immunology SC Immunology GA 196WT UT WOS:000080331400015 PM 10447722 ER PT J AU Borrego, F Robertson, MJ Ritz, J Pena, J Solana, R AF Borrego, F Robertson, MJ Ritz, J Pena, J Solana, R TI CD69 is a stimulatory receptor for natural killer cell and its cytotoxic effect is blocked by CD94 inhibitory receptor SO IMMUNOLOGY LA English DT Article ID ACTIVATION ANTIGEN CD69; PROTEIN-TYROSINE KINASES; HUMAN NK CELLS; GENE-COMPLEX; LYMPHOCYTE-ACTIVATION; CONFERS PROTECTION; ADHESION MOLECULES; CYTOLYTIC ACTIVITY; INDUCER MOLECULE; HLA-E AB CD69 is a differentiation antigen expressed shortly after activation on T lymphocytes and other cells of haematopoietic origin, including natural killer (NK) cells. The function of CD69 on T lymphocytes acting as a costimulatory molecule in proliferation and lymphokine secretion is well established. NK cells express CD69 after activation by different stimuli such as phorbol 12-myristate 13-acetate (PMA), interleukin (IL)-2, IL-12, interferon-alpha (IFN-alpha) or anti-CD16 monoclonal antibodies (mAbs). However, although it has been shown that CD69 triggers NK-cell-mediated cytolytic activity, its effect on other NK-cell functions has not been studied. Furthermore, the possible interaction of CD69 triggering with other C-lectin type inhibitory receptors is not known. Thus, the objective of this work is to determine whether CD69-mediated NK cytotoxicity can be regulated by CD93 inhibitory receptor and the role of CD69 on other NK-cell functions different of cytotoxicity. The results show that CD69-mediated NK cytotoxicity can be abrogated by CD93 stimulation in NK cells expressing the CD94 inhibitory form of the receptor, indicating that CD94 regulates the cytotoxic events initiated by a wide variety of NK activatory receptors. We also show that anti-CD69 mAbs, not only triggered NK cytotoxicity, but also induce NK-cell proliferation, CD25 and intracellular adhesion molecule-1 (ICAM-1) expression, TNF-alpha production and Ca2+ mobilization in preactivated NK cells. These results suggest that CD69 plays a crucial role in NK-cell function contributing to sustain NK-cell activation, as it has been previously demonstrated in T cells. C1 Univ Cordoba, Reina Sofia Univ Hosp, Fac Med, Dept Immunol, Cordoba 14004, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Haematol Malignancies, Boston, MA USA. RP Solana, R (reprint author), Univ Cordoba, Reina Sofia Univ Hosp, Fac Med, Dept Immunol, Avda Menendez Pidal S-N, Cordoba 14004, Spain. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA-01730] NR 39 TC 91 Z9 94 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAY PY 1999 VL 97 IS 1 BP 159 EP 165 PG 7 WC Immunology SC Immunology GA 196WT UT WOS:000080331400020 PM 10447727 ER PT J AU Olsen, I Solberg, CO Finegold, SH AF Olsen, I Solberg, CO Finegold, SH TI A primer on anaerobic bacteria and anaerobic infections for the uninitiated SO INFECTION LA English DT Review ID IDENTIFICATION C1 Univ Oslo, Fac Dent, Dept Oral Biol, N-0316 Oslo, Norway. Haukeland Univ Hosp, Dept Med, N-5021 Bergen, Norway. W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90024 USA. RP Olsen, I (reprint author), Univ Oslo, Fac Dent, Dept Oral Biol, PB 1052 Blindern, N-0316 Oslo, Norway. NR 15 TC 19 Z9 21 U1 0 U2 0 PU MMV MEDIEN & MEDIZIN VERLAGSGESELLSCHAFT MBH PI MUNICH PA NEUMARKTER STR 18, D-81673 MUNICH, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD MAY-JUN PY 1999 VL 27 IS 3 BP 159 EP 165 DI 10.1007/BF02561521 PG 7 WC Infectious Diseases SC Infectious Diseases GA 202RP UT WOS:000080666200002 PM 10378125 ER PT J AU Li, T Johansson, I Hay, DI Stromberg, N AF Li, T Johansson, I Hay, DI Stromberg, N TI Strains of Actinomyces naeslundii and Actinomyces viscosus exhibit structurally variant fimbrial subunit proteins and bind to different peptide motifs in salivary proteins SO INFECTION AND IMMUNITY LA English DT Article ID PROLINE-RICH PROTEINS; CALCIUM-PHOSPHATE PRECIPITATION; UROPATHOGENIC ESCHERICHIA-COLI; BETA-D-GALACTOSAMINE; APATITIC SURFACES; PORPHYROMONAS-GINGIVALIS; RECOMBINANT FIMBRILLIN; ADHESIVE PROPERTIES; TYPE-1 FIMBRIAE; STATHERIN AB Oral strains of Actinomyces spp. express type I fimbriae, which are composed of major FimP subunits, and bind preferentially to salivary acidic proline-rich proteins (,APRPs) or to statherin. We have mapped genetic differences in the fimP subunit genes and the peptide recognition motifs within the host proteins associated with these differential binding specificities. The fimP genes were amplified by PCR from Actinomyces viscosus ATCC 19246, with preferential binding to statherin, and from Actinomyces naeslundii LY7, P-I-K, and B-I-K, with preferential binding to APRPs. The fimP gene from the statherin-binding strain 19246 is novel and has about 80% nucleotide and amino acid sequence identity to the highly conserved fimP genes of the APRP-binding strains (about 98 to 99% sequence identity). The novel FimP protein contains an amino-terminal signal peptide, randomly distributed single-amino-acid substitutions, and structurally different segments and ends with a cell wall-anchoring and a membrane-spanning region. When agarose beads with CNBr-linked host determinant-specific decapeptides were used, A. viscosus 19246 bound to the Thr(42)Phe(43) terminus of statherin and A. naeslundii LY7 bound to the Pro(149)Gln(150) termini of APRPs, Furthermore, while the APRP-binding A. naeslundii strains originate from the human mouth, A. viscosus strains isolated from the oral cavity of rat and hamster hosts showed preferential binding to statherin and contained the novel fimP gene. Thus, A. viscosus and A. naeslundii display structurally variant fimP genes whose protein products are likely to interact with different peptide motifs and to determine animal host tropism. C1 Umea Univ, Dept Cariol, SE-90187 Umea, Sweden. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Johansson, I (reprint author), Umea Univ, Dept Cariol, SE-90187 Umea, Sweden. FU NIDCR NIH HHS [DE7009, DE8601] NR 60 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1999 VL 67 IS 5 BP 2053 EP 2059 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189MQ UT WOS:000079909300001 PM 10225854 ER PT J AU Cantey, JR Blake, RK Williford, JR Moseley, SL AF Cantey, JR Blake, RK Williford, JR Moseley, SL TI Characterization of the Escherichia coli AF/R1 pilus operon: Novel genes necessary for transcriptional regulation and for pilus-mediated adherence SO INFECTION AND IMMUNITY LA English DT Article ID NUCLEOTIDE-SEQUENCE; STRAIN RDEC-1; PEYERS PATCH; Y-PESTIS; PLASMID; RABBIT; DNA; EXPRESSION; ADHESIN; PROTEIN AB We isolated the genetic determinant of AF/R1 pilus production in attaching/effacing Escherichia coli RDEC-1 and identified seven genes required for pilus expression and function. DNA sequence analysis of the structural subunit gene afrA corrected an error in the published sequence and extended homology with the F18 pilus subunit of Dig edema E. coli strains. AfrB and AfrC, encoded downstream from AfrA, were required for pilus expression. AfrB was related to the usher protein PefC of Salmonella typhimurium plasmid encoded fimbriae, and AfrC was related to PefD, a chaperone protein. AfrD and AfrE, encoded downstream from AfrC, were not necessary for the expression of AF/R1 pill but were required for ileal adherence as assayed by ileal brush border aggregation. Thus, the adhesive subunit of the AF/R1 pilus is distinct from the structural subunit, as is the case for Pap pill and type I pill, AfrD was related to FedE of the F18 fimbrial operon of the E, coli strain that causes edema disease in pigs, AfrE was a novel protein. AfrR and AfrS are encoded upstream from AfrA, in the opposite orientation. AfrR is related to the AraC family of transcriptional regulators, and AfrR and AfrS interact to function in a novel mode of transcriptional activation of afrA. AF/R1 pill mediate the adherence to Peyer's patch M cells, ileal mucosa, and colonic mucosa in a rabbit model of diarrhea caused by enteropathogenic E. coli, Our observations will facilitate the further study of the phenomena of M-cell adherence. C1 Med Univ S Carolina, Div Infect Dis, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Cantey, JR (reprint author), Med Univ S Carolina, Div Infect Dis, 100 Doughty St,POB 250752, Charleston, SC 29425 USA. NR 65 TC 14 Z9 16 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1999 VL 67 IS 5 BP 2292 EP 2298 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189MQ UT WOS:000079909300033 PM 10225886 ER PT J AU Koo, SP Bayer, AS Kagan, BL Yeaman, MR AF Koo, SP Bayer, AS Kagan, BL Yeaman, MR TI Membrane permeabilization by thrombin-induced platelet microbicidal protein 1 is modulated by transmembrane voltage polarity and magnitude SO INFECTION AND IMMUNITY LA English DT Article ID STAPHYLOCIDAL ACTION; DEPENDENT DEPOLARIZATION; CYTOPLASMIC MEMBRANE; BILAYER-MEMBRANES; LIPID BILAYERS; PEPTIDE; ENDOCARDITIS; RESISTANCE; BACTERIAL; CHANNELS AB Thrombin-induced platelet microbicidal protein 1 (tPMP-1) is a small, cationic peptide generated from rabbit platelets when they are exposed to thrombin in vitro. IL has potent microbicidal activity against a broad spectrum of bacterial and fungal pathogens, including Staphylococcus aureus. Previous in vitro studies involving whole staphylococcal cells and planar lipid bilayers (as artificial bacterial membrane models) suggested that membrane permeabilization by tPMP-1 is voltage dependent (S.-P. Koo, M. R. Yeaman, and A. S. Payer, Infect. Immun. 64:3758-3764, 1996; M, R. Yeaman, A. S. Payer, S. P, Koo, W. Foss, and P, M, Sullam, J. Clin. Investig. 101:178-187, 1998), Thus, the aims of the present study were to specifically characterize the electrophysiological events associated with membrane permeabilization by tPMP-1 by using artificial planar lipid bilayer membranes. We assessed the influence of transmembrane voltage polarity and magnitude on the initiation and modulation of tPMP-1 membrane permeabilization at various concentrations of tPMP-1 (range, 1 to 100 ng/ml) added to the cis side of the membranes. The incidence of membrane permeabilization induced by tPMP-1 at all of the concentrations tested was more frequent at -90 mV than at +90 mV. It is noteworthy that membrane permeabilization due to 1-ng/ml tPMP-1 was successfully initiated at -90 mV but not at +90 mV, Further, the mean onset times of induction of tPMP-1 activity were comparable under the various conditions. Modulation of ongoing membrane permeabilization was dependent on voltage and tPMP-1 concentration. Membrane permeabilization at a low tPMP-1 concentration (1 ng/ml) was directly correlated with trans-negative voltages, while a higher tPMP-1 concentration (100 ng/ml) induced conductance which was more dependent on trans-positive voltages. Collectively, these data indicate that the mechanism of tPMP-1 microbicidal activity at the bacterial cytoplasmic membrane may involve distinct induction and propagation stages of membrane permeabilization which, in turn, are modulated by transmembrane potential, as well as peptide concentration. C1 Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Med, St Johns Cardiovasc Res Ctr,Div Infect Dis, Torrance, CA 90509 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90024 USA. RP Koo, SP (reprint author), Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Med, St Johns Cardiovasc Res Ctr,Div Infect Dis, RB-2,1000 W Carson St, Torrance, CA 90509 USA. FU NIAID NIH HHS [R01 AI039001, R01 AI039108, R29 AI039001, AI39001, AI39108]; NIMH NIH HHS [MH01174] NR 22 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1999 VL 67 IS 5 BP 2475 EP 2481 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189MQ UT WOS:000079909300057 PM 10225910 ER PT J AU Smith, DJ Heschel, RL King, WF Taubman, MA AF Smith, DJ Heschel, RL King, WF Taubman, MA TI Antibody to glucosyltransferase induced by synthetic peptides associated with catalytic regions of alpha-amylases SO INFECTION AND IMMUNITY LA English DT Article ID STREPTOCOCCUS-MUTANS GLUCOSYLTRANSFERASES; ACTIVE-SITE PEPTIDE; IMMUNOLOGICAL CHARACTERISTICS; SUBSEQUENCE PEPTIDE; NUCLEOTIDE-SEQUENCE; CHIMERIC PROTEIN; GLUCAN-BINDING; GENE; SOBRINUS; IDENTIFICATION AB We examined the immunogenicity and induction of inhibitory activity of 19-mer synthetic peptides which contained putative catalytic regions that were associated with the beta(5) (EAW) and beta(7) (HDS) strand elements of the suggested (beta,alpha)(8) catalytic barrel domain of Streptococcus mutans glucosyltransferase (GTF). Both peptides readily induced serum immunoglobulin G (IgG) and salivary IgA antipeptide activity which was reactive both with the inciting peptide and with intact S. mutans GTF. Antisera to each peptide construct also inhibited the ability of S. mutans GTF to synthesize glucan. These observations support the existence of catalytic subdomains containing glutamate and tryptophan (EAW) or aspartate and histidine (HDS) residues, each of which have been suggested to be involved with the catalytic activity of GTF. Furthermore, the epitopes defined in these sequences have significant immunogenicity and can induce immune responses which interfere with GTF-mediated glucan synthesis. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. RP Smith, DJ (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [R37 DE006153, R01 DE004733, DE-04733, DE-06153, R56 DE004733] NR 29 TC 10 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1999 VL 67 IS 5 BP 2638 EP 2642 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189MQ UT WOS:000079909300081 PM 10225934 ER PT J AU Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Arayssi, TK Gerard, HC Branigan, PJ Hudson, AP Yarboro, CH Klippel, JH Wilder, RL TI Gamma interferon and interleukin-10 gene expression in synovial tissues from patients with early stages of Chlamydia-associated arthritis and undifferentiated oligoarthritis and from healthy volunteers SO INFECTION AND IMMUNITY LA English DT Article ID REACTIVE ARTHRITIS; REITERS-SYNDROME; TRACHOMATIS; INFECTION; ANTIGEN; INHIBITION; CELLS AB Genetically determined differences in interleukin-10 (IL-10) and gamma interferon (IFN-gamma) responses in mice correlate viith clearance of Chlamydia pneumonitis infection. We measured the synovial expression of IL-10 and IFN-gamma and additional cytokine genes in patients who had recent onset Chlamydia-associated arthritis (Chl-AA). IL-IO and IFN-gamma mRNA were relatively abundant in recent-onset Chl-AA. C1 NIAMSD, ARB, NIH, Bethesda, MD 20892 USA. MCP Hahnemann Sch Med, Dept Vet Affairs Med Ctr, Philadelphia, PA USA. Med Coll Penn & Hahnemann Univ, Dept Microbiol & Immunol, Philadelphia, PA USA. Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Detroit, MI 48201 USA. RP Wilder, RL (reprint author), NIAMSD, ARB, NIH, 10 Ctr Dr,MSC 1820,Bldg 10,Rm 9N228, Bethesda, MD 20892 USA. OI Arayssi, Thurayya/0000-0003-2469-0272 FU NIAMS NIH HHS [AR-42541, R01 AR042541] NR 23 TC 27 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1999 VL 67 IS 5 BP 2682 EP 2686 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 189MQ UT WOS:000079909300090 PM 10225943 ER PT J AU Craig, WA AF Craig, WA TI The mathematics of antimicrobials SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Editorial Material ID THIGH-INFECTION; ANTIBIOTICS; MODEL C1 Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. US FDA, Antiinfect Drugs Advisory Comm, Rockville, MD 20857 USA. RP Craig, WA (reprint author), William S Middleton Mem Vet Hosp, 2500 Overlook Terrace, Madison, WI 53706 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY PY 1999 VL 8 IS 4 BP 191 EP 194 DI 10.1097/00019048-199905000-00007 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 191HK UT WOS:000080016900007 ER PT J AU Finlay, GA Brown, JS Marcus, LC Pollack, RJ AF Finlay, GA Brown, JS Marcus, LC Pollack, RJ TI Nasal myiasis - A "noso" comial infection SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID PHAENICIA-SERICATA DIPTERA; CALLIPHORIDAE; INSECT C1 New England Med Ctr, Dept Pulm & Crit Care Med, Boston, MA 02111 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Travelers Hlth & Immunizat Serv, Newton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Finlay, GA (reprint author), New England Med Ctr, Dept Pulm & Crit Care Med, 35 Kneeland St, Boston, MA 02111 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY PY 1999 VL 8 IS 4 BP 218 EP 220 DI 10.1097/00019048-199905000-00016 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 191HK UT WOS:000080016900016 ER PT J AU Mapara, MY Korner, IJ Lentzsch, S Hildebrandt, M Dorken, B AF Mapara, MY Korner, IJ Lentzsch, S Hildebrandt, M Dorken, B TI Combined positive negative selection in stem cell transplantation: Perspectives in graft engineering SO INFUSIONSTHERAPIE UND TRANSFUSIONSMEDIZIN LA English DT Review DE purging; T-cell depletion; graft engineering ID BONE-MARROW TRANSPLANTATION; BLOOD PROGENITOR CELLS; BREAST-CANCER PATIENTS; HIGH-DOSE CHEMOTHERAPY; COLONY-STIMULATING FACTOR; POLYMERASE CHAIN-REACTION; PERIPHERAL-BLOOD; T-CELL; B-CELL; SOYBEAN AGGLUTININ AB Background: Manipulation of hematopoietic stem cell grafts has become a very exciting research area due to the improved accessibility of hematopoietic progenitor cells using apheresis procedures compared to that of bone marrow harvesting. This development in graft engineering relates also the further refined approaches to eliminate contaminating tumor cells from autografts or to expand hematopoietic progenitors and postprogenitor cells ex vivo. Furthermore, manipulation of stem cell grafts in the allogeneic setting aims at the separation of graft versus leukemia(GVL)- and graft versus host(GVH)reactive cells, selection of graft-facilitating cells, and tolerance-inducing cells. This study focuses on recent advances in the field of graft engineering with respect to the combination of positive and negative cell selection. Materials and Methods: The selection procedures in use rely either on the positive selection (i.e. enrichment) of a given target cell population using either immunoaffinity approaches or density gradient centrifugation procedures. Negative selection methods (i.e. depletion of unwanted cells, e.g. tumor cells, GVH-reactive cells) also utilize immunoaffinity approaches. Furthermore, cell depletion can be achieved by pharmacological agents, cell-specific induction of apoptosis, or genetic cell manipulation. Results: Using combined positive and negative se lection, a 4 to > 6 log depletion of unwanted cells (i.e. tumor cells or T cells) from stem cell products can be achieved. Conclusion: Due to recent developments in stem cell collection and graft engineering, custom-tailored cellular therapy is becoming a reality in the setting of autologous and allogeneic stem cell transplantation. C1 Humboldt Univ, Klinikum, Med Klin Schwerpunkt Hamatol Onkol & Tumor Immuno, Robert Rossle Klin,Max Delbruck Centrum Mol Med, Berlin, Germany. RP Mapara, MY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Res Ctr, Bone Marrow Transplantat Sect,MGH, E Bldg 149-5102,13th St, Boston, MA 02129 USA. RI mapara, markus/A-2134-2013 NR 53 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-8466 J9 INFUSIONSTHERAPIE JI Infusionsther. Transfusionsmed. PD MAY PY 1999 VL 26 IS 3 BP 140 EP 145 PG 6 WC Hematology; Immunology SC Hematology; Immunology GA 208PF UT WOS:000080999700002 ER PT J AU Loeffler, JS Kooy, HM Tarbell, NJ AF Loeffler, JS Kooy, HM Tarbell, NJ TI The emergence of conformal radiotherapy: Special implications for pediatric neuro-oncology SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID FRACTIONATED STEREOTAXIC RADIOTHERAPY C1 Massachusetts Gen Hosp, Dept Radiat Oncol, NPTC, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, NPTC, 30 Fruit St, Boston, MA 02114 USA. NR 12 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1999 VL 44 IS 2 BP 237 EP 238 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 189NA UT WOS:000079910400001 PM 10928843 ER PT J AU Shulman, LN Buswell, L Riese, N Doherty, N Loeffler, JS von Roemeling, RW Coleman, CN AF Shulman, LN Buswell, L Riese, N Doherty, N Loeffler, JS von Roemeling, RW Coleman, CN TI Phase I trial of the hypoxic cell cytotoxin tirapazamine with concurrent radiation therapy in the treatment of refractory solid tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE tirapazamine; SR4233; WIN59075; bioreductive cytotoxins; phase I; hypoxic cytotoxic agents; radiation sensitizers; muscle cramping; clinical trial ID EVERY 3 WEEKS; FRACTIONATED-IRRADIATION; SR-4233 TIRAPAZAMINE; RADIOTHERAPY; ENHANCEMENT; OXYGENATION; CISPLATIN AB Purpose: Patients with refractory solid tumors were treated with the combination of fractionated radiation therapy and multiple-dose intravenous tirapazamine to determine the toxicities and maximum tolerated dose of tirapazamine when given concurrently with radiation therapy. Methods: Patients received radiation therapy in accordance with standard treatment practice in relation to fraction size and number of fractions for their particular cancer. In all cases, the course of radiation therapy exceeded the time of tirapazamine administration. Initially, tirapazamine was administered 5 days per week for 2 weeks for a total of 10 doses. After the first 8 patients, the schedule was changed to 3 times per week (Monday, Wednesday, Friday) for 4 weeks for a total of 12 doses. Between 3 and 6 patients were treated at each dose level, Results: A total of;43 patients were treated in the study between 1991 and 1995, All patients were 18 years old or older, had a Karnofsky performance status of greater than or equal to 60% and had adequate hematologic, hepatic, and renal function. Dose escalation began at 9 mg/m(2)/dose and was increased using a modified Fibonacci schema, The maximum tolerated dose was not reached and dose escalation was stopped at 260 mg/m(2) because of other data that became available suggesting 330 mg/m(2) was associated with dose-limiting toxicity (1, 2), Conclusion: Tirapazamine in doses of up to 260 mg/m(2) times 12 doses can be given safely with fractionated radiation therapy. This dose appears to result in adequate plasma exposure (2) for radiation sensitization, and this schedule is being tested in a Phase II trial by the Radiation Therapy Oncology Group to determine if tirapazamine is a radiation enhancer in the clinic, (C) 1999 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Sanofi Winthrop, Great Valley, PA USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1999 VL 44 IS 2 BP 349 EP 353 DI 10.1016/S0360-3016(99)00016-4 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 189NA UT WOS:000079910400018 PM 10760430 ER PT J AU Witte, RS Lipsitz, S Goodman, TL Asbury, RF Wilding, G Strnad, CM Smith, TJ Haller, DG AF Witte, RS Lipsitz, S Goodman, TL Asbury, RF Wilding, G Strnad, CM Smith, TJ Haller, DG TI A phase II trial of homoharringtonine and caracemide in the treatment of patients with advanced large bowel cancer SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE colon cancer; homogarringtonine caracemide ID METASTATIC COLORECTAL-CANCER; ACUTE MYELOGENOUS LEUKEMIA; FLUOROURACIL; CHEMOTHERAPY; LEUCOVORIN; IRINOTECAN; SCHEDULES; CARCINOMA; COUNCIL AB Twenty-four previously untreated, ambulatory patients with advanced colorectal carcinoma were treated with either caracemide (11 patients) or homoharringtonine (13 patients). No objective responses were observed in any of the treatment cohorts. Caracemide was well tolerated with the exception of one death due to sepsis. On the homoharringtonine arm one patient died of pulmonary sepsis, one patient experienced grade 4 leukopenia requiring more than 4 weeks of recovery, and an additional patient developed grade 4 renal failure. These severe and unexpected complications caused early termination of accrual to the homoharringtonine arm of the study. These agents have no activity in the treatment of advanced colorectal carcinoma. C1 Gundersen Lutheran, La Crosse, WI 54601 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Ellis Hosp, Schenectady, NY USA. Interlakes Oncol & Hematol, Rochester, NY USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Natalie Warren Bryant Canc Ctr, Tulsa, OK USA. Morristown Mem Hosp, Morristown, NJ USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. RP Witte, RS (reprint author), Gundersen Lutheran, 1836 South Ave, La Crosse, WI 54601 USA. FU NCI NIH HHS [CA45459, CA21076, CA23318] NR 22 TC 10 Z9 10 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD MAY PY 1999 VL 17 IS 2 BP 173 EP 177 DI 10.1023/A:1006327418043 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 256FX UT WOS:000083716200008 PM 10638488 ER PT J AU Ghiso, N Rohan, RM Amano, S Garland, R Adamis, AP AF Ghiso, N Rohan, RM Amano, S Garland, R Adamis, AP TI Suppression of hypoxia-associated vascular endothelial growth factor gene expression by nitric oxide via cGMP SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID NF-KAPPA-B; FACTOR-INDUCED ANGIOGENESIS; PERMEABILITY FACTOR; FACTOR VEGF; TUMOR ANGIOGENESIS; IN-VIVO; INDUCTION; INHIBITION; CELLS; PRIMATE AB PURPOSE. TO investigate the suppressive effect of nitric oxide (NO) on vascular endothelial growth factor (VEGF) gene expression and to elucidate its mechanism of action. METHODS. Immortalized human retinal epithelial (RPE) cells, H-ras-transfected murine capillary endothelial cells, and nuclear factor-kappa B (NF-kappa B) RelA knockout 3T3 fibroblasts had VEGF gene expression stimulated by hypoxia, TPA (phorbol eater 12-O-tetradecanoylphorbol-13 acetate), and ms-transfection. The dose response and time course of inhibition of VEGF gene expression by NO were characterized by northern blot analysis, ribonuclease protection assay, and enzyme-linked immununosorbent assay. The effects of NF-kappa B and cGMP in the NO-induced suppression of VEGF gene expression were quantitated. cGMP production was inhibited by LY 83583 (6-anilino-5,8-quinolinedione), a specific inhibitor of guanylate cyclase production, and cGMP accumulation was quantitated by immunoassay. RelA knockout 3T3 fibroblasts were used to assess the contribution of NF-KB to the downregulation of VEGF by NO. RESULTS. The NO donor sodium nitroprusside (SNP) decreased hypoxia-induced VEGF gene expression in a dose- and time-dependent manner. One hundred fifty micromolar SNP completely suppressed hypoxia-induced VEGF mRNA levels for at least 24 hours. Constitutive VEGF expression was not altered by SNP. The SNP-mediated decreases in VEGF expression were associated with increases in intracellular cGMP and were blocked by LY 83583. Sodium nitroprusside was able to decrease hypoxia-induced VEGF mRNA increases in fibroblasts deficient in the RelA subunit of NF-kappa B. Nitric oxide was also effective at suppressing increased VEGF expression secondary to mutant ras and TPA. CONCLUSIONS. These data indicate that NO decreases hypoxia-induced VEGF via a cGMP-dependent mechanism and suggest that NO may serve as an endogenous inhibitor of both hypoxia- and non-hypoxia-enhanced VEGF expression in vivo. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Adamis, AP (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 11622] NR 45 TC 53 Z9 57 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1999 VL 40 IS 6 BP 1033 EP 1039 PG 7 WC Ophthalmology SC Ophthalmology GA 192ER UT WOS:000080065900002 PM 10235536 ER PT J AU Gordon, LK Eggena, M Targan, SR Braun, J AF Gordon, LK Eggena, M Targan, SR Braun, J TI Definition of ocular antigens in ciliary body and retinal ganglion cells by the marker antibody pANCA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; INFLAMMATORY BOWEL-DISEASE; PRIMARY SCLEROSING CHOLANGITIS; ULCERATIVE-COLITIS; ANTERIOR UVEITIS; NEUTROPHIL AUTOANTIBODIES; IMMUNE CELLS; UVEAL TRACT; CLASS-II; SPONDYLOARTHROPATHY AB PURPOSE. A subset Of patients with anterior uveitis express the marker, perinuclear anti-neutrophil cytoplasmic antibody (pANCA). In this study, recombinantly isolated pANCA monoclonal antibodies were used to search for ocular cells expressing the pANCA antigen. METHODS. Paraffin sections of human ocular tissues obtained after death were analyzed by immunohistochemistry to identify cell types expressing pANCA antigen. Microdissected eye-bank ocular tissue was characterized by western blot analysis to confirm antigen expression and identify candidate protein species. RESULTS. Immunohistochemical analysis with pANCA monoclonal antibodies revealed cytoplasmic antigen expression in retinal ganglion cells and ciliary body epithelium. pANCA antigen expression was restricted to tissues bearing these cell types by western blot analysis. A common set of epitope-positive protein species was shared by the two tissues (28 kDa, 80 kDa, and 90 kDa). Comparison of ocular tissues from seven subjects revealed no heterogeneity in antigen expression. CONCLUSIONS. In this study, novel cytoplasmic antigens of the pANCA marker antibody expressed in ciliary body and retinal tissue were identified. Validation of these antigens as targets of inflammation in pANCA+ uveitis requires further biochemical and immunologic analysis. C1 Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. Cedars Sinai Med Ctr, Inflammatory Bowel Dis Res Ctr, Los Angeles, CA 90048 USA. RP Gordon, LK (reprint author), Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P01-CA12800]; NEI NIH HHS [KO8-EY00360]; NIDDK NIH HHS [P01-DK46763] NR 33 TC 11 Z9 11 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1999 VL 40 IS 6 BP 1250 EP 1255 PG 6 WC Ophthalmology SC Ophthalmology GA 192ER UT WOS:000080065900026 PM 10235560 ER PT J AU Lopez, SR Nelson, KA Snyder, KS Mintz, J AF Lopez, SR Nelson, KA Snyder, KS Mintz, J TI Attributions and affective reactions of family members and course of schizophrenia SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID EXPRESSED EMOTION; HELPING-BEHAVIOR; RELATIVES; MODEL; REPLICATION; JUDGMENTS; RELAPSE; ILLNESS AB The authors tested an attribution-affect model of schizophrenic relapse attending to the role of families' positive affect (warmth) and negative affect (criticism). Coders listened to interviews of 40 family members taken from C. E. Vaughn, K. S. Synder, S. Jones, W. B. Freeman, and I. R. Falloon (1984) and rated their attributions of controllability for the symptoms and behaviors of their relatives with schizophrenia. For family members not designated as emotionally overinvolved, perceptions that their ill relatives' symptoms and behaviors were under the patients' control were related to family members' warmth and criticism and to patients' clinical outcomes. Of the affective reactions, only criticism predicted outcome. In addition, patients' use of street drugs was related to attributions, criticism, and outcome. Together these findings suggest that families' attributions and criticism are important in understanding the relationship between family factors and course of illness. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Assoc Med Ctr, Los Angeles, CA USA. RP Lopez, SR (reprint author), Univ Calif Los Angeles, Dept Psychol, 1282A Franz Hall,Box 951563, Los Angeles, CA 90095 USA. FU FIC NIH HHS [TW0006]; NIMH NIH HHS [R03-MH53589] NR 31 TC 53 Z9 54 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1999 VL 108 IS 2 BP 307 EP 314 DI 10.1037/0021-843X.108.2.307 PG 8 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 202VV UT WOS:000080673600013 PM 10369041 ER PT J AU Adams, GB McMullen, M Turner, S Olszak, IT Scadden, DT McClure, MO Poznansky, MC AF Adams, GB McMullen, M Turner, S Olszak, IT Scadden, DT McClure, MO Poznansky, MC TI Isolation and transduction of CD34(+) cells from small quantities of peripheral blood from HIV-1-infected patients not treated with hemopoietic growth factors SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD34(+) cells; peripheral blood; HIV-1; gene therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC PROGENITOR CELLS; MEDIATED GENE-TRANSFER; COLONY-STIMULATING FACTOR; DEFECTIVE INVITRO GROWTH; BONE-MARROW; STEM-CELLS; INTRACELLULAR IMMUNIZATION; T-CELL; HIV-1 AB A proposed hemopoietic stem cell gene therapy for treatment for HIV infection would involve transduction of CD34(+) hemopoietic stem cells with vectors encoding anti-HIV constructs. Peripheral blood has proved to be a useful source of these hemopoietic stem cells and this study exploits this finding. Small quantities of peripheral blood were obtained from HIV-negative patients and HIV-positive patients who were and were not receiving hemopoietic growth factors (HGFs). CD34(+) cells were obtained from these samples using a simple technique and scored for frequency of colony type. This demonstrated that HIV-negative patients had the highest frequency of colony-forming units (CFUs). HIV-positive patients not treated with HGFs had a lower frequency of CFUs, but the same colony type distribution as HIV-negative patients. HIV-positive patients treated with HGFs had the lowest frequency of CFUs, but their colony type distribution demonstrated that they had responded to treatment. CD34+ cells selected in this way were also transduced with the murine retroviral MFG vector using a technique that demonstrated transduction efficiencies ranging from 2% to 16% (median, 11.5%). This study simplifies the experimental requirements for development of a hemopoietic stem cell gene therapy for HIV infection and offers the possibility that longitudinal studies could be performed on peripheral blood CD34(+) cells from HIV-positive or HIV-negative patients without the need for,granulocyte colony-stimulating factor mobilization. C1 Univ London Imperial Coll Sci Technol & Med, Sch Med, Dept GenitoUrinary Med & Communicable Dis, Jefferiss Res Trust Labs, London, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA USA. RP Poznansky, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, AIDS Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 32 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 1999 VL 21 IS 1 BP 1 EP 8 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 191QA UT WOS:000080032000001 PM 10235508 ER PT J AU Koek, RJ Yerevanian, BI Tachiki, KH Smith, JC Alcock, J Kopelowicz, A AF Koek, RJ Yerevanian, BI Tachiki, KH Smith, JC Alcock, J Kopelowicz, A TI Hemispheric asymmetry in depression and mania - A longitudinal QEEG study in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Review DE bipolar disorder; depression; electroencephalography; laterality; longitudinal study; mania ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; SEASONAL AFFECTIVE-DISORDER; BRAIN ELECTRICAL-ACTIVITY; MAJOR DEPRESSION; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM; MOOD DISORDERS; ELECTROENCEPHALOGRAM ASYMMETRY; QUANTITATIVE EEG AB Background: previous research has been inconclusive about the nature of hemispheric asymmetry in emotional processing. Method: 13 patients with DSM-IV bipolar disorder received repeated QEEGs over 2 years in different mood states. Z-score measures of asymmetry were assessed. Results: asymmetry in frontotemporal slow-wave activity appeared to be in opposite directions in depression compared to mania/hypomania, Conclusions: mood change in bipolar disorder is associated with change in QEEG asymmetry. Limitations: study of larger numbers of more homogenous patients under similar conditions is needed. Clinical relevance: study of mood state-dependent asymmetry changes in bipolar disorder may lead to better understanding of hemispheric processing of emotion. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Vet Adm Med Ctr, Psychiat Serv, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Anesthesiol Serv, Los Angeles, CA USA. Univ New Mexico, Med Ctr, Dept Emergency Med, Albuquerque, NM 87131 USA. San Fernando Mental Hlth Ctr, Mission Hills, CA USA. RP Koek, RJ (reprint author), Vet Adm Med Ctr, Psychiat Serv, 16111 Plummer St 116-11, Sepulveda, CA 91343 USA. OI kopelowicz, alex/0000-0002-1728-4105 NR 110 TC 22 Z9 25 U1 5 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 MAY PY 1999 VL 53 IS 2 BP 109 EP 122 DI 10.1016/S0165-0327(98)00171-2 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 199HQ UT WOS:000080475500001 PM 10360405 ER PT J AU Wechsler, H Molnar, BE Davenport, AE Baer, JS AF Wechsler, H Molnar, BE Davenport, AE Baer, JS TI College alcohol use: A full or empty glass? SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE alcohol abuse; alcohol; binge drinking; college students; substance abuse ID BINGE-DRINKING; DRUG-USE; STUDENTS; NORMS; CONSEQUENCES; CONSUMPTION; PERCEPTION; BIASES AB Data from the Harvard School of Public Health College Alcohol Study (1993) were used to describe weekly alcohol consumption and its associated problems among a representative national sample of college students. The median number of drinks consumed/week by all students, regardless of drinking status, was 1.5. When students were divided by drinking pattern, the median number of drinks/week was 0.7 for those who did not binge drink and 3.7 for those who did so infrequently. For frequent binge drinkers, the median was considerably higher: 14.5 drinks/week. Nationally, 1 in 5 five college students is a frequent binge drinker. Binge drinkers consumed 68% of all the alcohol that students reported drinking, and they accounted for the majority of alcohol-related problems. The data indicate that behavioral norms for alcohol consumption vary widely among students and across colleges. Therefore, it may not be possible to design an effective "one size fits all" approach to address college alcohol use. C1 Harvard Univ, Sch Publ Hlth, Coll Alcohol Studies, Dept Hlth & Social Behav, Boston, MA 02115 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Coll Alcohol Studies, Dept Hlth & Social Behav, 677 Huntington Ave, Boston, MA 02115 USA. NR 18 TC 74 Z9 77 U1 1 U2 8 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 MAY PY 1999 VL 47 IS 6 BP 247 EP 252 PG 6 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 197BA UT WOS:000080343700002 PM 10368558 ER PT J AU Safren, SA Heimberg, RG Horner, KJ Juster, HR Schneier, FR Liebowitz, MR AF Safren, SA Heimberg, RG Horner, KJ Juster, HR Schneier, FR Liebowitz, MR TI Factor structure of social fears: The Liebowitz Social Anxiety Scale SO JOURNAL OF ANXIETY DISORDERS LA English DT Article ID AVOIDANT PERSONALITY-DISORDER; COGNITIVE-BEHAVIORAL TREATMENT; PHOBIA SCALE; RELIABILITY; MOCLOBEMIDE; VALIDITY; SUBTYPES; VALIDATION; PHENELZINE; INTERVIEW AB In the assessment of social anxiety, investigators often differentiate between social interactional anxiety and performance anxiety. The Liebowitz Social Anxiety Scale (LSAS), a clinician-administered measure of social anxiety and avoidance, was originally developed with separate subscales for the assessment of fear and avoidance of situations involving social interaction and performance/observarion bq others. Separate confirmatory factor analyses of the LSAS fear and avoidance ratings demonstrated that this two-factor model did not provide an adequate fit to the data, suggesting the need to further investigate the underlying structure of the LSAS. Separate exploratory common factor analyses of the fear and avoidance ratings yielded four similar factors for each: (1) social interaction, (2) public speaking. (3) observation, by orllcrs, and (4) eating and di drinking in public, which demonstrated convergent and discriminant validity with other measures of social anxiety. These findings suggest that there are four global categories of social fear assessed by the LSAS, and that while social interaction anxiety appears to be unifactorial, fear of performance/observation situations may be multifactorial. (C) 1999 Elsevier Science Ltd. Ail rights reserved. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. SUNY Albany, Albany, NY 12222 USA. New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, New York, NY 10032 USA. RP Heimberg, RG (reprint author), Temple Univ, Dept Psychol, Weiss Hall,1701 N 13th St, Philadelphia, PA 19122 USA. FU NIMH NIH HHS [MH47831, MH44119, MH40121] NR 45 TC 77 Z9 80 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY-JUN PY 1999 VL 13 IS 3 BP 253 EP 270 DI 10.1016/S0887-6185(99)00003-1 PG 18 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 203XP UT WOS:000080733700002 PM 10372341 ER PT J AU Lee, FYI Montgomery, M Hazan, EJ Keel, SB Mankin, HJ Kattapuram, S AF Lee, FYI Montgomery, M Hazan, EJ Keel, SB Mankin, HJ Kattapuram, S TI Recurrent giant-cell tumor presenting as a soft-tissue mass - A report of four cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BONE; METASTASES C1 Massachusetts Gen Hosp, Orthopaed Surg Serv, Orthopaed Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lee, FYI (reprint author), Massachusetts Gen Hosp, Orthopaed Surg Serv, Orthopaed Oncol Unit, Boston, MA 02114 USA. NR 12 TC 8 Z9 8 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1999 VL 81A IS 5 BP 703 EP 707 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 198FR UT WOS:000080412800013 PM 10360699 ER PT J AU Tapanainen, JS Koivunen, R Fauser, BCJM Taylor, AE Clayton, RN Rajkowa, M White, D Franks, S Anttila, L Pettersson, KSI Huhtaniemi, IT AF Tapanainen, JS Koivunen, R Fauser, BCJM Taylor, AE Clayton, RN Rajkowa, M White, D Franks, S Anttila, L Pettersson, KSI Huhtaniemi, IT TI A new contributing factor to polycystic ovary syndrome: The genetic variant of luteinizing hormones SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LH BETA-SUBUNIT; WOMEN AB Although the etiology of polycystic ovary syndrome (PCOS) is still unclear, LH is considered to play a central role in its pathogenesis. An immunologically anomalous form of LH, with two point mutations in the LHbeta gene, has been recently described. This genetic variant of LH (v-LH), of wide geographic distribution, is functionally different from wild-type (wt) LH. To assess the role of the V-LH in PCOS, we analyzed its frequency in groups of PCOS patients from Finland, The Netherlands, the United Kingdom, and the United States. The LH status was determined by two immunofluorometric assays from a total of 1466 subjects. The carrier frequency of the V-LH allele in the whole study population was 18.5%, being highest (28.9%) in Finland and lowest (11.2%) in The Netherlands. In the individual countries, the frequency of v-LH was similar in obese and nonobese controls, but in The Netherlands and Finland, it was 5- to 7-fold lower in obese PCOS subjects compared with that in the other groups (2-4.5% us. 10.3-33.3%; P < 0.05). A similar tendency was found in the United States (5.7% vs. 11.1-25.0%), but not in the United Kingdom. The overall high prevalence of V-LH in healthy women and women with PCOS suggests that it is compatible with fertility. The similar frequency of V-LH in healthy nonobese and obese women indicates that obesity per se is not related to the variant. In contrast, the lower frequency of V-LH in obese PCOS patients suggests that v-LH somehow protects obese women from developing symptomatic PCOS. However, the regional differences in this finding between patients with apparently similar diagnostic criteria emphasizes the multifactorial nature of this syndrome, and that its pathogenesis may vary according to the genetic background. Although the definitive role of v-LH in PCOS remains to be proven, its determination may improve the prediction of risk of PCOS, especially in obese women. C1 Oulu Univ, Dept Obstet & Gynecol, Oulu 90220, Finland. Acad Hosp Rotterdam Dijkzigt, Dept Obstet & Gynecol, NL-3015 GD Rotterdam, Netherlands. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Keele Univ, Postgrad Med Sch, Dept Med, Stoke On Trent, Staffs, England. Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Reprod Sci & Med, London, England. Turku Univ, Dept Obstet & Gynecol, Turku 20520, Finland. Turku Univ, Dept Biotechnol, Turku 20520, Finland. Turku Univ, Dept Physiol, Turku 20520, Finland. RP Tapanainen, JS (reprint author), Oulu Univ Hosp, Dept Obstet & Gynecol, FIN-90220 Oulu, Finland. EM juha.tapanainen@oulu.fi NR 17 TC 63 Z9 65 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1999 VL 84 IS 5 BP 1711 EP 1715 DI 10.1210/jc.84.5.1711 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 193MZ UT WOS:000080141600041 PM 10323405 ER PT J AU D'Abronzo, FH Swearingen, B Klibanski, A Alexander, JM AF D'Abronzo, FH Swearingen, B Klibanski, A Alexander, JM TI Mutational analysis of activin/transforming growth factor-beta type I and type II receptor kinases in human pituitary tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERINE THREONINE KINASE; TGF-BETA; ACTIVIN RECEPTOR; GENE-EXPRESSION; CANCER CELLS; ADENOMAS; CLONING; INHIBIN; PROTEIN; DIFFERENTIATION AB Genetic mutation or loss of activin/transforming growth factor-p (TGF beta) receptor function has been shown in human lymphoid, breast, and colorectal tumors as well as Hep2B and Mv1Lu cell lines. Although activin stimulates FSH beta biosynthesis and secretion, a large percentage of human gonadotroph tumors have previously been demonstrated to be nonresponsive to characterized activin effects. This phenotype may be indicative of loss of functional cell surface receptors and/or intracellular signaling mediators of activin responses. Several studies examining the structure/function of type I and II receptors specific for ligands in the TGF beta superfamily have delineated the critical regions for receptor intracellular kinase function. In the case of TGF beta, inactivating mutations in these regions have been shown to render these receptors kinase deficient by a dominant negative phenotype and result in resistance to growth arrest. We therefore hypothesized that activin/TGF beta cell surface receptors may act as tumor suppressors in human pituitary tumors, and that inactivating genetic mutations in the intracellular kinase region of this gene family may release pituicytes from normal growth suppression by activin through a similar mechanism. We used single stranded conformational polymorphism analysis to examine 2 intracellular regions required for type I receptor signaling by human Alk1-5 type I receptors as well as the entire coding region of 2 activin type II receptors and the TGF beta type II receptor in 64 human pituitary tumors. A novel polymorphism was found in 45% of tumors at codon P117 of the ActRIIA gene and was used as a positive control for single stranded conformational polymorphism. One patient with a gonadotroph tumor had a confirmed A482V germline mutation in the Alk1 gene within kinase subdomains X-XI. No other mutations were detected in any tumor studied. These data suggest that somatic mutations within these intracellular kinase regions of type I/type II receptors are rare in human pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, 55 Fruit St,BUL457B, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK40947] NR 37 TC 31 Z9 32 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1999 VL 84 IS 5 BP 1716 EP 1721 DI 10.1210/jc.84.5.1716 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 193MZ UT WOS:000080141600042 PM 10323406 ER PT J AU Taupin, D Wu, DC Jeon, WK Devaney, K Wang, TC Podolsky, DK AF Taupin, D Wu, DC Jeon, WK Devaney, K Wang, TC Podolsky, DK TI The trefoil gene family are coordinately expressed immediate-early genes: EGF receptor- and MAP kinase-dependent interregulation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PANCREATIC SPASMOLYTIC POLYPEPTIDE; ACTIVATED PROTEIN-KINASE; FACTOR-BETA; CELL-PROLIFERATION; EPITHELIAL-CELLS; PEPTIDE FAMILY; MICE LACKING; MIGRATION; PS2 AB The trefoil gene family of mucus cell-secreted proteins is a critical mediator of gastrointestinal mucosal restitution. Transcription of trefoil genes is induced during mucosal repair, but the regulatory mechanisms involved are unknown. Mice deficient in the intestine-specific peptide intestinal trefoil factor (ITF), in which colonic restitution is lethally impaired, showed reduced expression of the gastric trefoil genes SP and pS2, suggesting that trefoil peptides may individually regulate transcription of the entire family. In gastric cell lines, the trefoils were shown to act in a manner suggestive of immediate-early genes capable of auto- and cross-induction through cis-acting regulatory regions. Trefoil-mediated transcriptional regulation required activation of the Ras/MEK/MAP kinase signal transduction pathway. EGF receptor (EGF-R) activation was also necessary for trefoil auto- and cross-induction, and both spasmolytic polypeptide (SP) and ITF stimulation of gastric cell lines led to phosphorylation of EGF-R. Nevertheless, ITF and ITF-thioredoxin cell surface binding at 4 degrees C colocalized not with EGF-R, but with CD71, which is found in clathrin-coated pits, suggesting that integration of trefoil peptide responses may occur after internalization. As EGF-R expression is itself strongly induced after mucosal damage, the trefoil/EGF-R relationship may be pivotal in the generation and maintenance of the mucosal repair phenotype. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ-719, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-43351, DK-41557, R01 DK041557, R37 DK041557, P30 DK043351] NR 51 TC 100 Z9 106 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1999 VL 103 IS 9 BP R31 EP R38 DI 10.1172/JCI3304 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 194PT UT WOS:000080203300020 PM 10225980 ER PT J AU Laurel, VL Meier, PA Astorga, A Dolan, D Brockett, R Rinaldi, MG AF Laurel, VL Meier, PA Astorga, A Dolan, D Brockett, R Rinaldi, MG TI Pseudoepidemic of Aspergillus niger infections traced to specimen contamination in the microbiology laboratory SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BONE-MARROW TRANSPLANT; INVASIVE ASPERGILLOSIS; HOSPITAL CONSTRUCTION; EPIDEMIOLOGY AB We report a pseudo-outbreak of Aspergillus niger that followed building construction in our clinical microbiology laboratory, Because outbreaks of invasive aspergillosis have been linked to hospital construction, strategies to minimize dust in patient care areas are common practise. We illustrate that the impact of false-positive cultures on patient care should compel laboratories to prevent specimen contamination during construction. C1 Wilford Hall USAF Med Ctr, Div Infect Dis, Dept Med, San Antonio, TX 78236 USA. Wilford Hall USAF Med Ctr, Dept Microbiol, San Antonio, TX 78236 USA. Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX 78284 USA. RP Laurel, VL (reprint author), Wilford Hall USAF Med Ctr, MMII, 2200 Bergquist Dr,Suite 1, Lackland AFB, TX 78236 USA. NR 16 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1999 VL 37 IS 5 BP 1612 EP 1616 PG 5 WC Microbiology SC Microbiology GA 187NG UT WOS:000079792400076 PM 10203538 ER PT J AU Frei, E AF Frei, E TI In memoriam - C. Gordon Zubrod, MD SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Biographical-Item C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1331 EP 1333 PG 3 WC Oncology SC Oncology GA 195TH UT WOS:000080267900001 ER PT J AU Harrington, DP AF Harrington, DP TI The tea leaves of small trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Harrington, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1336 EP 1338 PG 3 WC Oncology SC Oncology GA 195TH UT WOS:000080267900003 PM 10334516 ER PT J AU Costanza, ME Weiss, RB Henderson, IC Norton, L Berry, DA Cirrincione, C Winer, E Wood, WC Frei, E McIntyre, OR Schilsky, RL AF Costanza, ME Weiss, RB Henderson, IC Norton, L Berry, DA Cirrincione, C Winer, E Wood, WC Frei, E McIntyre, OR Schilsky, RL CA Canc Leukemia Grp B TI Safety and efficacy of using a single agent or a phase II agent before instituting standard combination chemotherapy in previously untreated metastatic breast cancer patients: Report of a randomized study - Cancer and leukemia group B 8642 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACETYLATOR PHENOTYPE; AMONAFIDE; TRIMETREXATE; THERAPY; TRIAL; DRUG; CARBOPLATIN; PHARMACOKINETICS; INFUSION; ACID AB Purpose: We undertook a prospective, randomized phase III trial to evaluate the safety and efficacy of using a phase II agent before initiating therapy with standard combination chemotherapy in metastatic breast cancer patients. Patients and Methods: A total of 365 women with measurable metastatic breast cancer, previously untreated with chemotherapy for their metastatic disease, were randomized to receive either immediate chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or up to four cycles of one of five sequential cohorts of single-agent drugs: trimetrexate, melphalan, amonafide, carboplatin, or elsamitrucin, followed by CAF, Results: The toxicity of each single agent followed by CAF was comparable to that of CAF alone. The cumulative response rates for the single agent followed by CAF were not statistically different from those of CAF alone (44% v 52%; P = 24) However. in the multivariate analysis, patients with visceral disease had a trend toward lower response rates on the phase II agent plus CAF arm (P =.078). Although survival and response duration also were not statistically significantly different between the two study arms (P =.074 and P =.069, respectively), there was a suggestion of benefit for the CAF-only arm. Conclusion: The brief use of a phase II agent, regardless of its efficacy, followed by CAF resulted in response rates, toxicities, durations of response, and survival statistically equivalent to those seen with the use of CAF alone. These findings support the use of a new paradigm for the evaluation of phase II agents in the treatment of patients with metastatic breast cancer. J Clin Oncol 17:1397-1406. (C) 1999 by American Society of Clinical Oncology. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Sch Med, Atlanta, GA USA. Dartmouth Med Sch, Norris Cotton Canc Ctr, Lebanon, NH USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Costanza, ME (reprint author), Univ Massachusetts, Med Ctr, Dept Med, Div Hematol Oncol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NCI NIH HHS [CA60138, CA26506, CA37135] NR 51 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1397 EP 1406 PG 10 WC Oncology SC Oncology GA 195TH UT WOS:000080267900011 PM 10334524 ER PT J AU Shapiro, CL Ervin, T Welles, L Azarnia, N Keating, J Hayes, DF AF Shapiro, CL Ervin, T Welles, L Azarnia, N Keating, J Hayes, DF CA TLC D-99 Study Grp TI Phase II trial of high-dose liposome-encapsulated doxorubicin with granulocyte colony-stimulating factor in metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol ID PROSPECTIVE RANDOMIZED TRIAL; CONGESTIVE HEART-FAILURE; RADIONUCLIDE ANGIOCARDIOGRAPHY; ENDOMYOCARDIAL BIOPSY; RESPONSE RELATIONSHIP; CARDIOTOXICITY; EPIRUBICIN; INTENSITY; CHEMOTHERAPY; ADRIAMYCIN AB Purpose: To estimate the toxicity and response rate of high-dose liposome-encapsulated doxorubicin (TLC D-99, Evacet, The Liposome Company Inc, Princeton, NJ) in patients with advanced breast cancer. Patients and Methods: Fifty-two breast cancer patients with bidimensionally measurable metastatic disease and no prior chemotherapy for metastatic disease received a 135 mg/m(2) intravenous (IV) bolus of TLC D-99 with 5 mu g/kg of granulocyte colony-stimulating factor via subcutaneous injection every 21 days. Results: The median number of treatment cycles of TLC D-99 was three (range, one to 10 cycles), and the median total cumulative dose of TLC D-99 was 405 mg/m2 (range, 135 to 1,065 mg/m(2)). Grade IV neutropenia, thrombocytopenia, and mucositis were experienced by 48 (92%), 46 (88%), and 10 (19%) patients, respectively. Twenty (38%) of patients experienced cardiac toxicity: four (8%) experienced a decrease of 20% or more in left ventricular ejection fraction (LVEF) to a final value greater than or equal to 50%, nine (17%) experienced a decrease of 10% or more in LVEF to a final value less than 50%, and seven (13%) developed symptomatic congestive heart failure (CHF), including one patient who died of cardiomyopathy after receiving a total dose of 1,035 mg/m(2), In a stepwise logistic regression model, the significant risk factors for the development of CHF were the cumulative dose of prior adjuvant doxorubicin (P =.007) and the total cumulative dose of TLC D-99 (P =.032). The overall response rate was 46% (95% confidence interval [CI], 32% to 61%) on an intent-to-treat basis. The median duration of response was 7.4 months (95% CI, 6.1 to 19.6 months) and the median progression-free survival was 6.1 months (95% CI, 5.4 to 7.5 months), Conclusion: There was no added therapeutic benefit to the dose escalation of TLC D-99 in this study. A high rate of cardiotoxicity was also observed, especially among patients who had received prior adjuvant doxorubicin. This was probably attributable to the dose and schedule of TLC D-99 used in this trial, as well as the patient's lifetime cumulative doxorubicin dose. Administration of high-dose TLC D-99 at 135 mg/m(2) every 3 weeks by IV bolus infusion does not warrant further investigation. J Clin Oncol 17:1435-1441, (C) 1999 by American Society of Clinical Oncology. C1 Ohio State Univ, Arthur James Canc Hosp & Res Inst, Columbus, OH 43210 USA. Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA USA. Maine Ctr Canc Med, Portland, ME USA. Liposome Co Inc, Princeton, NJ USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. RP Shapiro, CL (reprint author), Ohio State Univ, Arthur James Canc Hosp & Res Inst, Starling-Loving Hall,320 W 10th St, Columbus, OH 43210 USA. NR 39 TC 48 Z9 49 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1435 EP 1441 PG 7 WC Oncology SC Oncology GA 195TH UT WOS:000080267900015 PM 10334528 ER PT J AU Parmigiani, G Berry, DA Winer, EP Tebaldi, C Iglehart, JD Prosnitz, LR AF Parmigiani, G Berry, DA Winer, EP Tebaldi, C Iglehart, JD Prosnitz, LR TI Is axillary lymph node dissection indicated for early-stage breast cancer? A decision analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSERVATIVE TREATMENT; ADJUVANT CHEMOTHERAPY; ROUTINE MANAGEMENT; RADICAL-MASTECTOMY; FOLLOW-UP; CARCINOMA; SURVIVAL; THERAPY; IRRADIATION; TRIAL AB Purpose: Axillary lymph node dissection (ALND) has been a standard procedure in the management of breast cancer. In a patient with a clinically negative axilla, ALND is performed primarily for staging purposes, to guide adjuvant treatment. Recently, the routine use of ALND has been questioned because the results of the procedure may not change the choice of adjuvant systemic therapy and/or the survival benefit of a change in adjuvant therapy would be small. We constructed a decision model to quantify the benefits of ALND for patients eligible for breast-conserving therapy. Methods: Patients were grouped by age, tumor size, and estrogen receptor (ER) status. The model uses the Oxford overviews and three combined Cancer and Leukemia Group B studies. We assumed that patients who did not undergo ALND received axillary radiation therapy and that the two procedures are equally effective. All chemotherapy combinations were assumed to be equally efficacious. Results: The largest benefits from ALND are seen in ER-positive women with small primary tumors who might not be candidates for adjuvant chemotherapy if their lymph nodes test negative. Virtually no benefit results in ER-negative women, almost all of whom would receive adjuvant chemotherapy. When adjusted for quality of life (QOL), ALND may have an overall negative impact. In general, the benefits of ALND increase with the expected severity of adjuvant therapy on QOL. Conclusion: Our model quantifies the benefits of ALND and assists decision making by patients and physicians. The results suggest that the routine use of ALND in breast cancer patients should be reassessed and may not be necessary in many patients. J Clin Oncol 17:1465-1473. (C) 1999 by American Society of Clinical Oncology. C1 Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. Duke Univ, Ctr Clin Hlth Policy Res, Durham, NC 27708 USA. Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Ctr Atmospher Res, Boulder, CO 80307 USA. RP Parmigiani, G (reprint author), Duke Univ, Inst Stat & Decis Sci, Box 90251, Durham, NC 27708 USA. RI tebaldi, claudia/E-3089-2013 FU NCI NIH HHS [R21-CA68438-01, P50 CA68438] NR 35 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1465 EP 1473 PG 9 WC Oncology SC Oncology GA 195TH UT WOS:000080267900019 PM 10334532 ER PT J AU Cortazar, P Johnson, BE AF Cortazar, P Johnson, BE TI Review of the efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing for patients with cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CELL LUNG-CANCER; PROSPECTIVE CLINICAL-TRIAL; METASTATIC BREAST-CANCER; SUBRENAL CAPSULE ASSAY; TUMOR STEM-CELLS; PHASE-II TRIAL; OVARIAN-CANCER; ANTHRACYCLINE-RESISTANT; COLORIMETRIC ASSAY; MTT ASSAY AB Purpose: The purpose of this study is to review the potential efficacy of individualized chemotherapy selected by in vitro drug sensitivity testing (DST) compared with empiric regimens for patients with cancer. Methods: MEDLINE and CANCERLIT were searched for articles published tin English) about prospective clinical trials in which patients were treated with chemotherapy that was selected with the use of in vitro DST. Results: We identified 12 prospective studies that examined the benefit of chemotherapy selected by DST. Five hundred six patients (33%) were treated with chemotherapy that was selected with the use of in vitro DST. The mean response rate for patients treated with in vitro-selected therapy was 27% (range, 10% to 100%; 12 studies) compared with 18% (range, 0% to 100%; n = 7 studies) for patients treated with empiric therapy Five studies (only one randomized) evaluated the impact of chemotherapy selected by in vitro DST on patient survival. Three studies showed that survival was 1 to 4 months longer for the 238 patients treated with empiric chemotherapy compared with that of the 65 patients treated with chemotherapy that wets selected by in vitro testing. Two nonrandomized studies showed that survival wets 4 or 19 months longer for 27 patients treated with chemotherapy selected by in vitro testing compared with that of 80 patients who were treated with empiric chemotherapy. Conclusion: Only one third of patients entered in prospective trials of in vitro DST were actually treated with an in vitro best regimen. The response rates seem to be better with in vitro selected chemotherapy regimens than with empiric regimens, but the impact on survival has not been adequately addressed. J Clin Oncol 17:1625-1631. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Lung Canc Biol Sect, Med Branch, USN,Div Clin Sci, Bethesda, MD 20892 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. NR 41 TC 71 Z9 72 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1999 VL 17 IS 5 BP 1625 EP 1631 PG 7 WC Oncology SC Oncology GA 195TH UT WOS:000080267900039 PM 10334552 ER PT J AU Blais, MA Hilsenroth, MJ Fowler, JC Conboy, CA AF Blais, MA Hilsenroth, MJ Fowler, JC Conboy, CA TI A rorschach exploration of the DSM-IV Borderline Personality Disorder SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID OBJECT RELATIONS; CRITERIA; STYLE AB Rorschach data has been useful in identifying the DSM Borderline Personality Disorder (BPD) and has potential for improving our understanding of this disorder. Recently. the DSM-IV BPD has been shown to be composed of 3 primary or core factors: Factor I-unstable self-other images, Factor II-deficits in affect and thought modulation, and Factor III-impulsive self-damaging actions. In a sample or outpatients with personality disorders. we explored the relationships among 6 psychoanalytically derived Rorschach scales (primitive aggression, oral dependency, self-other differentiation, splitting, devaluation, and projective identification),, and the core BPD features. Significant correlations were found between 5 of the Rorschach variables and BPD total scores. Correlations between these 5 variables and the BPD core features showed that oral dependency needs were negatively associated with all 3 BPD core features. whereas the defenses of devaluation and splitting were positively associated with these core features. The clinical implications of these findings are reviewed. (C) 1999 John Wiley & Sons. Inc. C1 Harvard Univ, Inpatient Psychiat Serv, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Arkansas, Fayetteville, AR 72701 USA. RP Blais, MA (reprint author), Harvard Univ, Inpatient Psychiat Serv, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 17 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 1999 VL 55 IS 5 BP 563 EP 572 DI 10.1002/(SICI)1097-4679(199905)55:5<563::AID-JCLP4>3.0.CO;2-7 PG 10 WC Psychology, Clinical SC Psychology GA 190JN UT WOS:000079959500004 PM 10392787 ER PT J AU Sugarman, PB Bigby, M AF Sugarman, PB Bigby, M TI Lichen planus lesional T cells lyse lesional keratinocytes in vitro. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1999 VL 78 IS 5 BP 951 EP 951 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 196PK UT WOS:000080316600220 ER PT J AU Mattos-Graner, RO King, WF Mayer, MPA Smith, DJ AF Mattos-Graner, RO King, WF Mayer, MPA Smith, DJ TI Association of mutans streptococcal and their glucosyltransferase activity with caries incidence. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 USP, BR-09500900 Sao Paulo, Brazil. Forsyth Dent Ctr, Boston, MA 02115 USA. RI Mattos-Graner, Renata/C-9410-2012; Mayer, Marcia/D-4645-2012 OI Mattos-Graner, Renata/0000-0001-8309-8135; Mayer, Marcia/0000-0002-5910-8433 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1999 VL 78 IS 5 BP 969 EP 969 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 196PK UT WOS:000080316600302 ER PT J AU Goncalves, C Ximenes, LA Haffajee, A Socransky, SS AF Goncalves, C Ximenes, LA Haffajee, A Socransky, SS TI DNA probes from subgingival bacteria on the analysis of supragingival plaque. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 UFRJ, Sch Dent, Rio De Janeiro, Brazil. Forsyth Dent Ctr, Boston, MA USA. RI Koga-Ito, Cristiane /D-7999-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1999 VL 78 IS 5 BP 1006 EP 1006 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 196PK UT WOS:000080316600580 ER PT J AU Taubman, MA AF Taubman, MA TI Current perspectives of dental caries vaccine research SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1999 VL 78 IS 5 BP 1114 EP 1114 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 196PK UT WOS:000080316601284 ER PT J AU Mehta, A Dreyer, K Thrall, J AF Mehta, A Dreyer, K Thrall, J TI Enhancing availability of the electronic image record for patients and caregivers during follow-up care SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT 16th Symposium for Computer Applications in Radiology on PACS - Performance Improvement in Radiology (SCAR 99), at the Annual Meeting of SCAR CY MAY 06-09, 1999 CL HOUSTON, TEXAS SP Soc Comp Applicat Radiol AB Purpose: To develop a personal computer (PC)-based software package that allows portability of the electronic imaging record. To create custom software that enhances the transfer of images in two fashions. Firstly, to an end user, whether physician or patient, provide a browser capable of viewing digital images on a conventional personal computer. Second, to provide the ability to transfer the archived Digital Imaging and Communications in Medicine (DICOM) images to other institutional picture archiving and communications systems (PACS) through a transfer engine. Method/materials: Radiologic studies are provided on a CD-ROM. This CD-ROM contains a copy of the browser to view images, a DICOM-based engine to transfer images to the receiving institutional PACS, and copies of all pertinent imaging studies for the particular patient. The host computer system in an Intel based Pentium 90 MHz PC with Microsoft Windows 95 software (Microsoft Inc, Seattle, WA). The system has 48 MB of random access memory, a 3.0 GB hard disk, and a Smart and Friendly CD-R 2006 CD-ROM recorder (Smart and Friendly Inc, Chatsworth, CA). Results: Each CD-ROM disc can hold 640 MB of data. In our experience, this houses anywhere from, based on Table 1, 12 to 30 computed tomography (CT) examinations, 24 to 80 magnetic resonance (MR) examinations, 60 to 128 ultrasound examinations, 32 to 64 computed radiographic examinations, 80 digitized x-rays, or five digitized mammography examinations. We have been able to successfully transfer DICOM images from one DICOM-based PACS to another DICOM-based PACS. This is accomplished by inserting the created CD-ROM onto a CD drive attached to the receiving PACS and running the transfer engine application. Conclusions: Providing copies of radiologic studies performed to the patient is a necessity in every radiology department. Conventionally, film libraries have provided copies to the patient generating issues of cost of loss of film, as well as mailing costs. This software package saves costs and loss of studies, as well as improving patient care by enabling the patient to maintain an archive of their electronic imaging record. Copyright (C) 1999 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Mehta, A (reprint author), 8 Whittier Pl,Suite 19D, Boston, MA 02114 USA. NR 3 TC 6 Z9 6 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAY PY 1999 VL 12 IS 2 SU 1 BP 78 EP 80 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197GB UT WOS:000080356100022 PM 10342173 ER PT J AU Horak, MJ Nadel, ES Brown, DFM Mycyk, M Juang, P Legome, E Wolfe, RE Dart, R AF Horak, MJ Nadel, ES Brown, DFM Mycyk, M Juang, P Legome, E Wolfe, RE Dart, R TI Dyspnea in pregnancy SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MASSIVE PULMONARY-EMBOLISM; TISSUE-PLASMINOGEN-ACTIVATOR; RIGHT-VENTRICULAR DYSFUNCTION; THROMBOLYTIC THERAPY; MULTICENTER REGISTRY; VALVE PROSTHESIS; RT-PA; ECHOCARDIOGRAPHY; FRAGMENTATION; STREPTOKINASE C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 33 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY-JUN PY 1999 VL 17 IS 3 BP 507 EP 511 PG 5 WC Emergency Medicine SC Emergency Medicine GA 229EB UT WOS:000082179600021 PM 10338247 ER PT J AU Yang, HT Wu, SV Pichuantes, S Song, M Wang, J Zhou, DY Xu, ZM Quan, S Polito, A Walsh, JH AF Yang, HT Wu, SV Pichuantes, S Song, M Wang, J Zhou, DY Xu, ZM Quan, S Polito, A Walsh, JH TI High prevalence of cagA-positive strains in Helicobacter pylori-infected, healthy, young Chinese adults SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE cagA; gastritis; Helicobacter pylori; pathogenesis; peptic ulcer disease ID VACUOLATING-CYTOTOXIN ACTIVITY; PEPTIC-ULCER DISEASE; VIRULENCE FACTORS; GENE; EXPRESSION; GASTRITIS; ANTIGEN; PROTEIN AB Background: Cytotoxin-associated gene A (cagA) has been implicated as a potential pathogenic marker for Helicobacter pylori-induced severe gastroduodenal diseases. Although the prevalence of cagA-positive strains has been reported in patient populations from developed countries, only limited information from developing countries is available. Methods: Polymerase chain reaction (PCR) in combination with immunoblot analysis was used to determine the prevalence of cagA and its adjacent cagE genes and to evaluate the expression of CagA protein in 55 H. pylori clinical isolates from China. Results: The expected PCR products derived from H. pylori cagA and cagE genes were identified in all Chinese H. pylori clinical isolates. Similarly, the CagA protein was detected in all 40 isolates tested. Conclusions: These results demonstrated that the presence of the cagA gene correlated well with expression of the CagA protein in all surveyed Chinese H. pylori isolates and that infection with cagA-positive H. pylori strains is highly common in China and independent of clinical presentation. (C) 1999 Blackwell Science Asia Pty Ltd. C1 W Los Angeles Vet Affairs Med Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Dept Med,Sch Med, Los Angeles, CA 90024 USA. Chiron Corp, Emeryville, CA 94608 USA. Nanfang Hosp, Inst Digest Dis, Guangzhou, Peoples R China. RP Wu, SV (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, Bldg 115,Room 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-17294, DK-40301] NR 24 TC 9 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAY PY 1999 VL 14 IS 5 BP 476 EP 480 DI 10.1046/j.1440-1746.1999.01892.x PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208FP UT WOS:000080980500014 PM 10355513 ER PT J AU Pechan, PA Herrlinger, U Aghi, M Jacobs, A Breakefield, XO AF Pechan, PA Herrlinger, U Aghi, M Jacobs, A Breakefield, XO TI Combined HSV-1 recombinant and amplicon piggyback vectors: Replication-competent and defective forms, and therapeutic efficacy for experimental gliomas SO JOURNAL OF GENE MEDICINE LA English DT Article DE gene therapy; virus vectors; herpes simplex virus; cancer; brain tumors; amplicons ID HERPES-SIMPLEX VIRUS; MALIGNANT GLIOMAS; THYMIDINE KINASE; DELETION MUTANTS; BRAIN-TUMORS; VIRAL MUTANT; GENE-THERAPY; TYPE-1; SYSTEM; ICP27 AB Background The versatility of HSV-1 vectors includes large transgene capacity, selective replication of mutants in dividing cells, and availability of recombinant virus (RV) and plasmid-derived (amplicon) vectors, which can be propagated in a co-dependent, 'piggyback', manner. Methods A replication-defective piggyback vector system was generated in which the amplicon carries either of two genes essential for virus replication, IE2 (ICP27) or IE3 (ICP4), as well as lacZ; the RV is deleted in both these genes, and vector stocks are propagated in cells transfected with one of the complementary genes. In the replication-competent system, the amplicon carries the IE2 and lacZ; the RV had a large deletion in the IE2; and stocks are propagated in untransfected cells. Titers over successive passages, recombination between amplicon and RV, and the structural integrity of vector genomes were evaluated. The replication-competent system was tested for therapeutic efficacy in subcutaneous 9L gliosarcoma tumors in nude mice with activation of ganciclovir via the viral HSV-thymidine kinase gene. Results Both systems generated high titer amplicon vectors (about 10(7) tu/ml) and amplicon:RV ratios (0.6-3.0). No replication-competent RV was generated in either system. The replication-defective system showed low toxicity and increased packaging efficiency of amplicon vectors, as compared to single mutant RV helper virus. The replication-competent system allowed co-propagation of amplicon and RV; injection into tumors followed by ganciclovir treatment inhibited tumor growth without systemic toxicity. Conclusion New replication-defective and replication-competent piggyback HSV, vector systems allow gene delivery via amplicon vectors with reduced toxicity and co-propagation of both RV and amplicon vectors in target cells, with effective tumor therapy via focal virus replication and pro-drug activation. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp E, Neurosci Program, Boston, MA 02129 USA. Harvard Med Sch, Dept Neurosurg, Massachusetts Gen Hosp E, Neurosci Program, Boston, MA 02129 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS24279] NR 37 TC 12 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAY-JUN PY 1999 VL 1 IS 3 BP 176 EP 185 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 252JB UT WOS:000083497400003 PM 10738566 ER PT J AU Chin, KR Jupiter, JB AF Chin, KR Jupiter, JB TI Wire-loop fixation of volar displaced osteochondral fractures of the distal radius SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal radius; lunate facet; wire; fracture AB We describe the technique of wire-loop fixation to treat 4 young men with a unique variant of Melone's type 4 articular fracture of the volar lunate facet, characterized by a displaced rotated articular fragment supported by a limited amount of subchondral bone. This is an unusual injury that threatens the integrity of both the radiocarpal and distal radioulnar joints. It is the result of a compressive force to the wrist and may require trispiral computed tomography for delineation. Open reduction and internal fixation is recommended to maintain stability and articular congruity. The displaced volar-articular fragment, however, may be relatively small; therefore, direct manipulation could lead to soft tissue stripping and osteonecrosis. We have found the technique of wire-loop fixation to be a simple, reproducible, and effective alternative method of internal fixation for these difficult fractures. Malunion, nonunion, loss of fixation, tendon rupture, infection, arthrosis, or pain caused by hardware has not occurred. Use of this technique is not recommended in patients with osteoporotic bone. Copyright (C) 1999 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, WACC 527, Boston, MA 02114 USA. NR 15 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 1999 VL 24A IS 3 BP 525 EP 533 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 197AU UT WOS:000080343100013 PM 10357531 ER PT J AU He, SQ Lemmon, JD Weston, MW Jensen, MOJ Levine, RA Yoganathan, AP AF He, SQ Lemmon, JD Weston, MW Jensen, MOJ Levine, RA Yoganathan, AP TI Mitral valve compensation for annular dilatation: In vitro study into the mechanisms of functional mitral regurgitation with an adjustable annulus model SO JOURNAL OF HEART VALVE DISEASE LA English DT Article ID LEFT-VENTRICULAR SHAPE; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; DILATED CARDIOMYOPATHY; IN-VITRO; ECHOCARDIOGRAPHY; SURVIVAL; DETERMINANT; DISEASE; FLOW AB Background and aim of the study: Mitral annulus dilatation has been identified as an important factor in functional mitral regurgitation (FMR). However, the pathophysiologic interaction of annular dilatation and papillary muscle (PM) displacement in FMR, which occurs clinically in left ventricular (LV) dilatation, is still not well understood. It is difficult to separate these competing factors in vivo, leading to confusion in identifying the real role of the annular dilatation in FMR and its interaction with PM displacement. Methods: To better understand the competing factors, an in vitro model was developed with a D-shaped adjustable mitral annulus that could be changed from 5.5 cm(2) to 13.0 cm2 during experiments, independent of varying PM positions. Six excised normal porcine mitral valves were mounted in a left ventricular model with the adjustable annulus device and tested in a physiologic pulsatile flow system under normal cardiac output and left ventricular pressure (5.0 l/min, 120 mmHg). Papillary muscles were placed in normal and then displaced to an apical posterolateral position, to simulate pathological conditions seen clinically. Regurgitation was measured directly by a flow probe and the mitral valve geometry and leaflet coaptation were recorded by video camera through the model's atrium window. In addition, 2D echocardiography was used to evaluate leaflet coaptation and color Doppler flow mapping to detect the regurgitant flow field. Results: The results showed that in normal PM position, the mitral regurgitant was consistently at low level until the annulus was enlarged to 1.75 times the normal size, at which time it increased sharply. Papillary muscle apical posterolateral displacement, which simulates a dilated LV, caused regurgitation to occur earlier (1.5 times the normal annulus size), and had an increased regurgitant volume (p <0.05). The leaflet gaps were first observed at the commissural areas of the valves, consistent with the location of regurgitant jets detected by color Doppler flow mapping. Asymmetric PM displacement created more regurgitation than both the symmetric PM tethering (p = 0.063) and normal PM position (p <0.01). The regurgitant jets were observed at the same commissural side as the PM displacement, even without significant enlargement of the annulus. Conclusions: This in vitro study provides insight into the interaction between annular dilatation and PM displacement on FMR. The resulting effects and their overall similarity to clinical observation could help further understand the mechanism of FMR and provide additional information to improve future therapeutic strategies. C1 Georgia Inst Technol, Sch Biomed Engn, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Yoganathan, AP (reprint author), Georgia Inst Technol, Sch Biomed Engn, 654 Cherry St, Atlanta, GA 30332 USA. NR 36 TC 56 Z9 56 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAY PY 1999 VL 8 IS 3 BP 294 EP 302 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 200ZC UT WOS:000080569300010 PM 10399664 ER PT J AU Rosowsky, A Papoulis, AT Queener, SE AF Rosowsky, A Papoulis, AT Queener, SE TI One-step synthesis of novel 2,4-diaminopyrimidine antifolates from bridged alicyclic ketones and cyanoguanidine SO JOURNAL OF HETEROCYCLIC CHEMISTRY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; GONDII DIHYDROFOLATE-REDUCTASE; TOXOPLASMA-GONDII; OPPORTUNISTIC INFECTIONS; ANTITUMOR AGENTS; INHIBITORS; TRIMETHOPRIM; PIRITREXIM; ANALOGS AB A convenient one-step reaction with cyanoguanidine was used to convert alicyclic ketones to previously undescribed 2,4-diamino-5,6,7,8-tetrahydroquinazolines with a one-, two-, or three-carbon bridge in the carbocyclic ring. Although the yields of the desired products were modest, the principal advantage of this one-step process was that it provided easy access to a variety of novel bridged heterocyclic ring systems whose synthesis from sterically hindered ketones by other methods would have required multiple steps with an even lower overall yield. The products were tested as inhibitors of dihydrofolate reductases from Pneumocystis carinii, Toxaplasma gondii, and rat liver with a view to examining the effect of a space-filling bridge on binding. The most potent and selective compound in the group was 4,6-diamino-3,5-diazatricyclo[7.2.1.0(2,7)] dodeca-2,4,6-triene (13), whose potency and selectivity approached those of trimethoprim, a drug commonly used to treat P. carnii and T. gondii infection. 3,5-Diamino-4,6-diazatricyclo[6.2.1.0(2,7)]-undeca-2,4,6-triene (14), the analog of 13 with a one-carbon rather than a two-carbon bridge showed similar potency and selectivity against the T. gondii enzyme, but was a weak and nonselective inhibitor of P. carinii dihydrofolate reductase. The other compounds tested were likewise weak and nonselective. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 14 Z9 14 U1 1 U2 1 PU HETERO CORPORATION PI ODESSA PA PO BOX 993, ODESSA, FL 33556-0993 USA SN 0022-152X J9 J HETEROCYCLIC CHEM JI J. Heterocycl. Chem. PD MAY-JUN PY 1999 VL 36 IS 3 BP 723 EP 728 PG 6 WC Chemistry, Organic SC Chemistry GA 215HR UT WOS:000081376600024 ER PT J AU Friedman, T Shimizu, A Smith, RN Colvin, RB Seebach, JD Sachs, DH Iacomini, J AF Friedman, T Shimizu, A Smith, RN Colvin, RB Seebach, JD Sachs, DH Iacomini, J TI Human CD4(+) T cells mediate rejection of porcine xenografts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; IMMUNODEFICIENT MOUSE; DIRECT RECOGNITION; MINIATURE SWINE; PIG; TRANSPLANTATION; CYTOTOXICITY; SKIN; COSTIMULATION AB It has previously been demonstrated that xenograft rejection in rodents is dependent on CD4(+) T cells. However, because of the lack of an appropriate in vivo model, Little is known about the cellular basis of human T cell-mediated rejection of xenografts, In this study, we have evaluated the ability of human T cells to mediate rejection of porcine skin grafts in a novel in vivo experimental system using immunodeficient mice as recipients, Recombinase-activating gene-1-deficient mice (R-) lacking mature B and T cells were grafted with porcine skin and received human lymphocytes stimulated in vitro crith irradiated porcine PBMC. Skin grafts on mice given either unseparated, activated human lymphocytes . or NK cell-depicted lymphocyte populations were rejected within 18 days after adoptive cell transfer, In contrast, skin grafts on mice given T cell-depleted human lymphocytes or saline showed no gross or histologic evidence of rejection up to 100 days after adoptive transfer. Purified CD4(+) T cells were also able to mediate rejection of porcine skin grafts. These data suggest that human CD4(+) T cells are sufficient to induce rejection of porcine xenografts. Thus, strategies directed toward CD4(+) T cells ma effectively prevent cellular rejection of porcine xenografts in humans. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI41081, 5 F32 AI09882-02] NR 38 TC 51 Z9 53 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1999 VL 162 IS 9 BP 5256 EP 5262 PG 7 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600034 PM 10228000 ER PT J AU Biancone, L Stamenkovic, I Cantaluppi, V Boccellino, M De Martino, A Bussolino, F Camussi, G AF Biancone, L Stamenkovic, I Cantaluppi, V Boccellino, M De Martino, A Bussolino, F Camussi, G TI Expression of L-selectin ligands by transformed endothelial cells enhances T cell-mediated rejection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEFICIENT MICE; P-SELECTIN; IN-VIVO; ADHESION; ANTIGEN; GROWTH; RECRUITMENT; DETERMINES; MIGRATION; ONCOGENE AB Recent immunohistochemical studies have suggested that L-selectin Ligands may be implicated in the infiltration of tumors and rejected transplants by lymphocytes. In the present study, polyoma-middle T Ag-transformed endothelial cells (H,end), which typically form in vivo immunogenic vascular tumors resembling Kaposi's sarcoma, were engineered to express L-selectin ligands by stable transfection with a cDNA encoding alpha(1,3/4)-fucosyltransferase (H.endft). The ability of these cells to form tumors in the s.c. tissues of normal and immunocompromised mice was then compared with that of H,end cells transfected with the hygromycin-resistance vector only (H.endhygro). H,endhygro cells rapidly formed local and metastatic tumors in normal syngeneic mice, leading to death within 2-3 mo postinjection, By contrast, tumors derived from H.endft cells displayed a slower rate of growth, an absence of metastasis, and marked lymphocyte infiltration, Animals bearing these tumors survived for a significantly longer duration than animals injected with H.endhygro cells. Alternatively, H.endft and H.endhygro cells formed tumors with comparable aggressiveness in immunocompromised mice, resulting in animal death within 3 wk of injection. H.endft but not H.endhygro cells supported L-selectin-dependent adhesion and cytolytic T cell activity in vitro. Taken together, our observations indicate that the in situ expression of fucosyltransferase may significantly influence the cellular immune response in endothelioma tumors. These results may be relevant in understanding the development of vascular opportunistic tumors such as Kaposi's sarcoma. C1 Univ Turin, Chair Nephrol, Dept Internal Med, Turin, Italy. Harvard Med Sch, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Inst Canc Res & Treatment, Candiolo, Italy. Univ Turin, Dept Genet Biol & Biochem, I-10124 Turin, Italy. RP Camussi, G (reprint author), Lab Immunopatol Renale, Corso Dogliotti 14, I-10126 Turin, Italy. RI Camussi, Giovanni/J-7624-2016; Bussolino, Federico/K-2500-2016 OI Camussi, Giovanni/0000-0003-2795-232X; Bussolino, Federico/0000-0002-5348-1341 FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM48614] NR 26 TC 8 Z9 8 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 MAY 1 PY 1999 VL 162 IS 9 BP 5263 EP 5269 PG 7 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600035 PM 10228001 ER PT J AU Awane, M Andres, PG Li, DJ Reinecker, HC AF Awane, M Andres, PG Li, DJ Reinecker, HC TI NF-kappa B-inducing kinase is a common mediator of IL-17-, TNF-alpha-, and IL-1 beta-induced chemokine promoter activation in intestinal epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED NEUTROPHIL CHEMOATTRACTANT; INFLAMMATORY BOWEL-DISEASE; C-X-C; PROINFLAMMATORY CYTOKINES; INTERLEUKIN-8 FAMILY; PROTEIN-1 GENE; RAT CINC; T-CELL; SIGNAL AB IL-17 expression is restricted to activated T cells, whereas the IL-17R is expressed in a variety of cell types including intestinal epithelial cells. However, the functional responses of intestinal epithelial cells to stimulation with IL-17 are unknown. Moreover, the signal transduction pathways activated by the IL-17R have not been characterized. IL-17 induced NF-kappa B protein-DNA complexes consisting of p65/p50 heterodimers in the rat intestinal epithelial cell Line IEC-6, The induction of NF-kappa B correlated with the induction of CXC and CC chemokine mRNA expression in IEC-6 cells, IL-17 acted in a synergistic fashion with IL-1 beta to induce the NF-kappa B site-dependent CINC promoter. Induction of the CINC promoter by IL-17 in IEC-6 cells was TNF receptor-associated factor-6 (TRAF6), but not TRAF2, dependent. Furthermore, IL-17 induction of the CINC promoter could be inhibited by kinase-negative mutants of NF-kappa B-inducing kinase and I kappa B kinase-alpha. In addition to activation of the NF-kappa B, IL-17 regulated the activities of extracellular regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases in IEC-6 cells. Whereas the IL-17-mediated activation of extracellular regulated kinase mitogen-activated protein kinases was mediated through ras, c-Jun N-terminal kinase activation was dependent on functional TRAF6, These data suggest that NF-kappa B-inducing kinase serves as the common mediator in the NF-kappa B signaling cascades triggered by IL-17, TNF-alpha, and IL-1 beta in intestinal epithelial cells. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Ctr Study Inflammatory Bowel Dis, Jackson Bldg R711,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK51003] NR 47 TC 204 Z9 212 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1999 VL 162 IS 9 BP 5337 EP 5344 PG 8 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600043 PM 10228009 ER PT J AU Hausmann, S Biddison, WE Smith, KJ Ding, YH Garboczi, DN Utz, U Wiley, DC Wucherpfennig, KW AF Hausmann, S Biddison, WE Smith, KJ Ding, YH Garboczi, DN Utz, U Wiley, DC Wucherpfennig, KW TI Peptide recognition by two HLA-A2/Tax(11-19)-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOTROPIC VIRUS; RECEPTOR; ANTIGEN; TCR; BINDING; MOLECULES; COMPLEX; DISEASE; LIGANDS; HLA-A2 AB The crystal structures of two human TCRs specific for a HTLV-I Tax peptide bound to HLA-A2 were recently determined, for the first time allowing a functional comparison of TCRs for which the MHC/peptide/TCR structures are known. Extensive amino acid substitutions show that the native Tax residues are optimal at each peptide position. A prominent feature of the TCR contact surface is a deep pocket that accommodates a tyrosine at position 5 of the peptide, For one of these TCRs, this pocket is highly specific for aromatic residues, In the other TCR structure, this pocket is larger, allowing many different residues to be accommodated. The CTL clones also show major differences in the specificity for several other peptide residues, including side chains that are not directly contacted by the TCR Despite the specificity of these clones, peptides that are distinct at five or six positions from Tax(11-19) induce CTL activity, indicating that substantial changes of the peptide surface are tolerated. Human peptides with limited sequence homology to Tax(11-19) represent partial TCR agonists for these CTL clones. The distinct functional properties of these CTL clones highlight structural features that determine TCR specificity and cross-reactivity for MHC-bound peptides. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NIAID, Struct Biol Sect, NIH, Rockville, MD 20852 USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI42316]; NICHD NIH HHS [HD-17461] NR 30 TC 64 Z9 64 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 MAY 1 PY 1999 VL 162 IS 9 BP 5389 EP 5397 PG 9 WC Immunology SC Immunology GA 189EZ UT WOS:000079892600050 PM 10228016 ER PT J AU Ruprecht, RM Baba, TW Liska, V Ray, NB Martin, LN Murphey-Corb, M Rizvi, TA Bernacky, BJ Keeling, ME McClure, HM Andersen, J AF Ruprecht, RM Baba, TW Liska, V Ray, NB Martin, LN Murphey-Corb, M Rizvi, TA Bernacky, BJ Keeling, ME McClure, HM Andersen, J TI Oral transmission of primate lentiviruses SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on HIV-1 Infection, Mucosal Immunity, and Pathogenesis CY SEP 11-13, 1997 CL BETHESDA, MARYLAND ID HUMAN-IMMUNODEFICIENCY-VIRUS; FRANCISCO MENS HEALTH; HOMOSEXUAL BISEXUAL MEN; CELL-FREE SIV; RHESUS-MONKEYS; MUCOSAL INFECTION; ATTENUATED SIV; MACAQUES; AIDS; VACCINE AB Oral transmission of human immunodeficiency virus type 1 (HIV-1) is well documented in children who become infected postnatally through breast milk. In contrast, epidemiologic surveys have yielded conflicting data regarding oral HIV-1 transmission among adults, even though case reports have described seroconversion and the development of AIDS in adults whose only risk was oral-genital contact. To study oral virus transmission in primate models, we exposed rhesus macaques of various ages to cell-free simian immunodeficiency virus (SIV), including uncloned and molecularly cloned viruses. In neonates, viremia and AIDS developed after nontraumatic oral exposure to several SIV strains. Furthermore, chimeric simian human immunodeficiency viruses containing the HIV-1 envelope can also cross intact upper gastrointestinal mucosal surfaces in neonates. In adult macaques, infection and AIDS have resulted from well-controlled, nontraumatic, experimental oral exposure to different strains of SIV. These findings have implications for the risks of HIV-1 transmission during oral-genital contact. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Tulane Reg Primate Res Ctr, Covington, LA USA. Univ Texas, MD Anderson Canc Ctr, Dept Vet Sci, Bastrop, TX USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-24845, AI-32330, AI-34266] NR 26 TC 29 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1999 VL 179 SU 3 BP S408 EP S412 DI 10.1086/314794 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 190PP UT WOS:000079973300006 PM 10099108 ER PT J AU Means, RT AF Means, RT TI Commentary: An anemia of chronic disease, after all? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material ID PATHOGENESIS C1 Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Div Hematol Oncol, Charleston, SC USA. RP Means, RT (reprint author), Med Univ S Carolina, Div Hematol Oncol, 903 CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 NR 10 TC 6 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAY PY 1999 VL 47 IS 5 BP 203 EP 203 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 199PY UT WOS:000080491900003 PM 10361378 ER PT J AU Watson, FL Porcionatto, MA Bhattacharyya, A Stiles, CD Segal, RA AF Watson, FL Porcionatto, MA Bhattacharyya, A Stiles, CD Segal, RA TI TrkA glycosylation regulates receptor localization and activity SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE neurotrophins; Trks; glycosylation; receptor tyrosine kinases ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; INSULIN-RECEPTOR; NEUROTROPHIC FACTOR; BIOCHEMICAL-CHARACTERIZATION; NEURONAL DIFFERENTIATION; DEPENDENT ACQUISITION; BINDING-ACTIVITY; PLC-GAMMA; FAMILY AB The human nerve growth factor receptor (TrkA) contains four potential N-glycosylation sites that are highly conserved within the Trk family of neurotrophin receptors, and nine additional sites that are less well conserved. Using a microscale deglycosylation assay, we show here that both conserved and variable N-glycosylation sites are used during maturation of TrkA. Glycosylation at these sites serves two distinct functions, First, glycosylation is necessary to prevent Ligand-independent activation of TrkA, Unglycosylated TrkA core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules Shc and PLC-gamma. Second, glycosylation is required to localize TrkA to the cell surface, where it can trigger the Ras/Raf/MAP kinase cascade. Using confocal microscopy, we show that unglycosylated active Trk receptors are trapped intracellularly. Furthermore, the unglycosylated active TrkA receptors are unable to activate kinases in the Ras-MAP kinase pathway, MEK and Erk. Consistent Kith these biochemical observations, unglycosylated TrkA core protein does not promote neuronal differentiation in Trk PC12 cells even at high levels of constitutive catalytic activity, (C) 1999 John Wiley & Sons, Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. UNIFESP, EPM, Dept Bioquim, Disciplina Biol Mol, Sao Paulo, Brazil. RP Watson, FL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana Bldg,Rm 620,44 Binney St, Boston, MA 02115 USA. RI Porcionatto, Marimelia/C-3322-2012 OI Porcionatto, Marimelia/0000-0001-6287-916X FU NICHD NIH HHS [HD 18655]; NINDS NIH HHS [NS35148] NR 48 TC 86 Z9 86 U1 1 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAY PY 1999 VL 39 IS 2 BP 323 EP 336 DI 10.1002/(SICI)1097-4695(199905)39:2<323::AID-NEU15>3.0.CO;2-4 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 187WL UT WOS:000079811200015 PM 10235685 ER PT J AU White, AR Bush, AI Beyreuther, K Masters, CL Cappai, R AF White, AR Bush, AI Beyreuther, K Masters, CL Cappai, R TI Exacerbation of copper toxicity in primary neuronal cultures depleted of cellular glutathione SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyloid-beta; neurodegeneration; Alzheimer's disease; buthionine sulfoximine; neurons; toxicity ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PRECURSOR PROTEIN; CU,ZN-SUPEROXIDE DISMUTASE MUTANT; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; IN-VITRO; NEURODEGENERATIVE DISORDERS; SUPEROXIDE-DISMUTASE; RADICAL FORMATION AB Perturbations to glutathione (GSH) metabolism may play an important role in neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases. A primary function of GSH is to prevent the toxic interaction between free radicals and reactive transition metals such as copper (Cu), Due to the potential role of Cu in neurodegeneration, we examined the effect of GSH depletion on Cu toxicity in murine primary neuronal cultures. Depletion of cellular GSH with L-buthionine-[S,R]sulfoximine resulted in a dramatic potentiation of Cu toxicity in neurons without effect on iron (Fe) toxicity. Similarly, inhibition of glutathione reductase (GR) activity with 1,3-bis(2-chloroethyl)-1-nitrosurea also increased Cu toxicity in neurons. To determine if the Alzheimer's amyloid-P (A beta) peptide can affect neuronal resistance to transition metal toxicity, we exposed cultures to nontoxic concentrations of A beta 25-35 in the presence or absence of Cu or Fe. A beta 25-35 pretreatment was found to deplete neuronal GSH and increase GR activity, confirming the ability of A beta to perturb neuronal GSH homeostasis, A beta 25-35 pretreatment potently increased Cu toxicity but had no effect on Fe toxicity. These studies demonstrate an important role for neuronal GSH homeostasis in selective protection against Cu toxicity, a finding with widespread implications for neurodegenerative disorders. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst, Melbourne, Vic, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA USA. Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany. RP White, AR (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016 OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891 NR 48 TC 67 Z9 68 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1999 VL 72 IS 5 BP 2092 EP 2098 DI 10.1046/j.1471-4159.1999.0722092.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186WJ UT WOS:000079753400036 PM 10217289 ER PT J AU De Girolami, UL Louis, DN Schoene, WC Vonsattel, JPG Hedley-Whyte, ET AF De Girolami, UL Louis, DN Schoene, WC Vonsattel, JPG Hedley-Whyte, ET TI Edward Peirson Richardson, Jr. 1918-1998 - In Memoriam SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Biographical-Item C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Neuropathol Lab,Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP De Girolami, UL (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Neuropathol Lab,Childrens Hosp, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 BP 506 EP 507 DI 10.1097/00005072-199905000-00011 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700010 ER PT J AU de la Monte, SM Ganju, N Luong, T Janssens, S Bloch, KD Feroz, N Wands, JR AF de la Monte, SM Ganju, N Luong, T Janssens, S Bloch, KD Feroz, N Wands, JR TI Over-expression of nitric oxide synthase-3 (NOS-3) and free-radical injury cause apoptosis and phospho-tau accumulation in neuronal cells. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 12 BP 512 EP 512 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700023 ER PT J AU Louis, DN Zlatescu, MC Ino, Y Cairncross, JG AF Louis, DN Zlatescu, MC Ino, Y Cairncross, JG TI Long survivals and therapeutic responses in high-grade gliomas with chromosome 1p loss that are not classic anaplastic oligodendrogliomas. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 14 BP 512 EP 512 DI 10.1097/00005072-199905000-00025 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700025 ER PT J AU Primavera, J Lu, BX Iulian, M de la Monte, SM AF Primavera, J Lu, BX Iulian, M de la Monte, SM TI Unusual cerebral amyloidosis in amyotrophic lateral sclerosis: Case report and analysis of other neurodegenerative diseases. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 157 BP 548 EP 548 DI 10.1097/00005072-199905000-00168 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700168 ER PT J AU Karluk, D Myers, RH DiFiglia, M Gusella, JF MacDonald, ME Penney, JB Young, AB Hobbs, W Lenzi, S Srinidhi, S Hedley-Whyte, ET Vonsattel, JP AF Karluk, D Myers, RH DiFiglia, M Gusella, JF MacDonald, ME Penney, JB Young, AB Hobbs, W Lenzi, S Srinidhi, S Hedley-Whyte, ET Vonsattel, JP TI Nonagenarians with Huntington disease (HD) have low CAG repeats. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1999 VL 58 IS 5 MA 159 BP 549 EP 549 DI 10.1097/00005072-199905000-00170 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 194PA UT WOS:000080201700170 ER EF