FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hadigan, C Rabe, J Grinspoon, S AF Hadigan, C Rabe, J Grinspoon, S TI Sustained benefits of metformin therapy on markers of cardiovascular risk in human immunodeficiency virus-infected patients with fat redistribution and insulin resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; DIABETES-MELLITUS; LIPODYSTROPHY; HYPERLIPIDEMIA; DISEASE AB The purpose of this study was to evaluate the metabolic and cardiovascular benefits of continued metformin therapy for HIV-infected patients with lipodystrophy. Eligible subjects who participated in the 3-month randomized study received an additional 6-month open label metformin treatment extension. Nineteen of the 25 potential subjects were eligible to receive open label metformin based on preestablished safety and efficacy criteria. Insulin and glucose response to oral glucose challenge, cardiovascular disease risk markers (e.g. tissue plasminogen activator), weight, and anthropometric measurements were the primary outcome measures. Continued treatment with metformin resulted in further significant reductions in tissue plasminogen activator antigen levels (P = 0.02) and body mass index (P = 0.03). Reductions in insulin levels were sustained during the 6-month treatment extension. In addition, waist circumference decreased significantly in subjects continuing metformin treatment (P = 0.01). Metformin was well tolerated and no one discontinued treatment due to side effects. These data demonstrate a sustained benefit of metformin treatment to reduce hyperinsulinemia and certain markers of cardiovascular disease risk in patients with HIV infection and lipodystrophy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Hadigan, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. EM chadigan@partners.org FU NCRR NIH HHS [M01-RR-300088]; NIDDK NIH HHS [R01-DK-59535, T32-DK-07703, K23-DK-02844] NR 13 TC 54 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 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2002 VL 87 IS 10 BP 4611 EP 4615 DI 10.1210/jc.2002-020709 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 604YZ UT WOS:000178649800034 PM 12364443 ER PT J AU Danila, DC Zhang, X Zhou, YL Haidar, JNS Klibanski, A AF Danila, DC Zhang, X Zhou, YL Haidar, JNS Klibanski, A TI Overexpression of wild-type activin receptor Alk4-1 restores activin antiproliferative effects in human pituitary tumor cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-BETA; RIBONUCLEIC-ACID LEVELS; EXPRESSION; FOLLISTATIN; APOPTOSIS; SUBUNIT; CANCER; LINE; PHEOCHROMOCYTOMAS; PROLIFERATION AB Activin is a member of the TGFbeta family of cytokines involved in the control of cell proliferation. We have previously shown that the majority of clinically nonfunctioning pituitary tumors do not respond to activin-induced growth suppression. Human pituitary tumors specifically express alternatively spliced activin type I receptor Alk4 mRNAs, producing C-terminus truncated isoforms designated Alk4-2, 4-3, and 4-4. However, it is not known whether these truncated activin receptors suppress activin effects on cell proliferation in human pituitary cells. Therefore, we investigated activin signaling in a human pituitary tumor cell line, HP75, derived from a clinically nonfunctioning pituitary tumor. HP75 cells express activin A mRNA and secrete activin A, as measured by ELISA and a functional bioassay. TGFbeta administration decreases the proliferation of HP75 cells, suggesting that the signaling pathway shared by TGFbeta and activin is functional in this cell line. However, activin neither inhibits cell proliferation nor stimulates reporter gene expression in HP75 cells, indicating that activin signaling is specifically blocked at the receptor level. HP75 cells express all truncated activin type I receptor Alk4 isoforms, as determined by RT-PCR. Because truncated Alk4 receptor isoforms inhibit activin signaling by competing with the wild-type receptor for binding to activin type II receptors, we hypothesized that overexpression of wild-type activin type I receptor will restore activin signaling. In HP75 cells, cotransfection of the wild-type activin type I receptor Alk4-1 expression vector increases activin-responsive reporter activity. Furthermore, transfection with wildtype activin receptor type I results in activin-mediated suppression of cell proliferation. These data indicate that truncated Alk4 isoforms interfere with activin signaling pathways and thereby may contribute to uncontrolled cell growth. Overexpression of the wild-type Alk4-1 receptor restores responsiveness to activin in human pituitary tumor-derived cells. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01-DK-40947] NR 31 TC 12 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2002 VL 87 IS 10 BP 4741 EP 4746 DI 10.1210/jc.2002-020527 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 604YZ UT WOS:000178649800055 PM 12364468 ER PT J AU Long, JA Ickovics, JR Gill, TM Horwitz, RI AF Long, JA Ickovics, JR Gill, TM Horwitz, RI TI Social class and mortality in older women SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE social class; mortality; clinical covariates; women; occupations ID SOCIOECONOMIC-STATUS; RISK-FACTORS; CARDIOVASCULAR-DISEASE; CIVIL-SERVANTS; FOLLOW-UP; HEALTH; INEQUALITIES; PREDICTORS; INCOME; EMPLOYMENT AB In middle-aged people, social class is one of the strongest predictors of mortality. However. to date, research prospectively evaluating the relationship between social class and mortality in the older persons has produced conflicting results. This may be due to the lack of clinical covariates in many analyses. The objective of this study was to determine the relationship between social class markers-education, income, husband's work history, and personal work history-and mortality in a cohort of older women, after adjusting for clinical and behavioral factors. The participants were 737 ambulatory, community-living women, age 72 and older, followed from 1989 to 1993. In addition to education attained, present income, husband's work history, and personal work history, proportional hazard models adjusted for age, race, marital status, number of chronic conditions, number of medications used, Activities of Daily Living status, Mini-Mental State Exam score, physical activity, and alcohol use. In multivariable models personal work history was the only social class marker that remained significantly associated with mortality. Compared with managers and professionals, women who never worked outside the home had a 3.5 greater risk of death (95% CI, 1.6-7.5), while women who had worked in partly/unskilled or skilled professions were over two and a half times more likely to die; the adjusted hazard ratios were 2.7 (95% CI, 1.2-6.4) and 2.7 (95% CI, 1.3-5.7), respectively. In this population of older women, personal work history was the only social class marker predictive of mortality. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Ctr Hlth Equ Res & Promot, Philadelphia Vet Adm, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. RP Long, JA (reprint author), Ctr Hlth Equ Res & Promot, Philadelphia Vet Adm, 1201 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NIA NIH HHS [R01 AG 07449, K32 AG 00759] NR 45 TC 4 Z9 4 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2002 VL 55 IS 10 BP 952 EP 958 AR PII S0895-4356(02)00464-X DI 10.1016/S0895-4356(02)00464-X PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 615JE UT WOS:000179241400001 PM 12464370 ER PT J AU Cooper, GS Dooley, MA Treadwell, EL Clair, EWS Gilkeson, GS AF Cooper, GS Dooley, MA Treadwell, EL Clair, EWS Gilkeson, GS TI Risk factors for development of systemic lupus erythematosus: Allergies, infections, and family history SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE systemic lupus erythematosus; autoimmune disease; sulfa drug; herpes zoster; infections ID BARR-VIRUS INFECTION; AUTOIMMUNE-DISEASES; MULTIPLE-SCLEROSIS; REVISED CRITERIA; UNITED-STATES; HERPES-ZOSTER; EPIDEMIOLOGY; ENGLAND; CLASSIFICATION; ANTIBODIES AB We examined risk factors for systemic lupus erythematosus (SLE) in 265 recently diagnosed patients in North Carolina and South Carolina and 355 control subjects identified through driver's license records and frequency matched to patients by age, sex, and state. Analyses were limited to exposures before diagnosis (cases) or reference year (control subjects). SLE patients were more likely than control subjects to report a history of allergy to medications (odds ratio [OR] 3.1, 95% confidence interval [CI], 2.1-4.5), particularly to antibiotics. SLE risk increased with history of shingles (OR 2.5, 95 % CI 1.1-5.9) and with frequent (more than once per year) cold sores in the 3 years before diagnosis (OR 2.8, 95 % CI 1.4-5.4). There was little association with history of mononucleosis, a marker of late infection with Epstein-Barr virus, implanted medical devices, or hepatitis B vaccination. History of lupus in parents or siblings was associated with an increased risk (OR 3.3, 95% CI 1.2-8.6). Further research is needed to clarify whether medication allergies and specific infectious agents are involved in the etiology of SLE. Published by Elsevier Science Inc. C1 NIEHS, Epidemiol Branch, Durham, NC 27709 USA. Univ N Carolina, Div Rheumatol, Chapel Hill, NC USA. E Carolina Univ, Sch Med, Div Rheumatol, Greenville, NC USA. Duke Univ, Med Ctr, Div Rheumatol Allergy & Clin Immunol, Durham, NC USA. Ralph H Johnson Vet Adm Med Ctr, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, A3-05,POB 12233, Durham, NC 27709 USA. NR 35 TC 50 Z9 52 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2002 VL 55 IS 10 BP 982 EP 989 AR PII S0895-4356(02)00429-8 DI 10.1016/S0895-4356(02)00429-8 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 615JE UT WOS:000179241400005 PM 12464374 ER PT J AU Panigrahy, D Singer, S Shen, LQ Butterfield, CE Freedman, DA Chen, EJ Moses, MA Kilroy, S Duensing, S Fletcher, C Fletcher, JA Hlatky, L Hahnfeldt, P Folkman, J Kaipainen, A AF Panigrahy, D Singer, S Shen, LQ Butterfield, CE Freedman, DA Chen, EJ Moses, MA Kilroy, S Duensing, S Fletcher, C Fletcher, JA Hlatky, L Hahnfeldt, P Folkman, J Kaipainen, A TI PPAR gamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; HUMAN PROSTATE-CANCER; HUMAN BREAST-CANCER; IN-VITRO; INDUCE APOPTOSIS; CELLS; DIFFERENTIATION; NEOVASCULARIZATION; EXPRESSION; VIVO AB Several drugs approved for a variety of indications have been shown to exhibit antiangiogenic effects. Our study focuses on the PPARgamma ligand rosiglitazone, a compound widely used in the treatment of type 2 diabetes. We demonstrate, for the first time to our knowledge, that PPARgamma is highly expressed in tumor endothelium and is activated by rosiglitazone in cultured endothelial cells. Furthermore, we show that rosiglitazone suppresses primary tumor growth and metastasis by both direct and indirect antiangiogenic effects. Rosiglitazone inhibits bovine capillary endothelial cell but not tumor cell proliferation at low doses in vitro and decreases VEGF production by tumor cells. In our in vivo studies, rosiglitazone suppresses angiogenesis in the chick chorioallantoic membrane, in the avascular cornea, and in a variety of primary tumors. These results suggest that PPARgamma ligands may be useful in treating angiogenic diseases such as cancer by inhibiting angiogenesis. C1 Harvard Univ, Childrens Hosp, Surg Res Lab, Sch Med,Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Ctr Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Kaipainen, A (reprint author), 320 Longwood Ave,Enders 1050, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009535, T32CA09535] NR 48 TC 264 Z9 283 U1 4 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2002 VL 110 IS 7 BP 923 EP 932 DI 10.1172/JCI200215634 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 601VW UT WOS:000178470200009 PM 12370270 ER PT J AU Xuan, SH Kitamura, T Nakae, J Politi, K Kido, Y Fisher, PE Morroni, M Cinti, S White, MF Herrera, PL Accili, D Efstratiadis, A AF Xuan, SH Kitamura, T Nakae, J Politi, K Kido, Y Fisher, PE Morroni, M Cinti, S White, MF Herrera, PL Accili, D Efstratiadis, A TI Defective insulin secretion in pancreatic beta cells lacking type 1 IGF receptor SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-II; ADULT-RAT ISLETS; TRANSGENIC MICE; NEONATAL RAT; TARGETED EXPRESSION; PIMA-INDIANS; GLUCOSE; RESISTANCE; ENDOCRINE; RELEASE AB Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase of beta cell mass and impaired glucose-dependent insulin release. beta cell proliferation and secretion are thought to be regulated by signaling through receptor tyrosine kinases. In this regard, we sought to examine the potential proliferative and/or antiapoptotic role of IGFs in beta cells by tissue-specific conditional mutagenesis ablating type 1 IGF receptor (IGF1R) signaling. Unexpectedly, lack of functional IGF1R did not affect beta cell mass, but resulted in age-dependent impairment of glucose tolerance, associated with a decrease of glucose- and arginine-dependent insulin release. These observations reveal a requirement of IGF1R-mediated signaling for insulin secretion. C1 Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. Univ Ancona, Sch Med, Dept Anat, Ancona, Italy. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Geneva, Dept Morphol, Geneva, Switzerland. RP Accili, D (reprint author), Berrie Res Pavil,1150 St Nicholas Ave,Room 238, New York, NY 10032 USA. NR 70 TC 123 Z9 127 U1 1 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2002 VL 110 IS 7 BP 1011 EP 1019 DI 10.1172/JCI200215276 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 601VW UT WOS:000178470200018 PM 12370279 ER PT J AU Singer, EJ Aronow, HA Lee, SY Hinkin, CH Lazarus, T AF Singer, EJ Aronow, HA Lee, SY Hinkin, CH Lazarus, T TI Stability of human immunodeficiency virus type 1 RNA in cerebrospinal fluid determined with the AMPLICOR HIV-1 MONITOR test, version 1.5 (Ultrasensitive) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRAL LOAD; PLASMA; QUANTITATION; ASSAY; DEMENTIA; DISEASE; PCR AB We evaluated the effects of time, temperature, freezing, and thawing on the cerebrospinal fluid viral load by using the Roche AMPLICOR HIV-1 MONITOR test, version 1.5 (ultrasensitive). While a statistically significant decrease from the baseline was observed at 24 h, but not at 6 or 12 h, and with one freeze-thaw cycle, all changes were within the range of intra-assay variability. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Dept Neurol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, AIDS Healthcare Fdn, Dept Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Consolidated Lab, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Psychol Serv, Los Angeles, CA USA. New York Med Coll, Dept Internal Med, New York, NY USA. Roche Diagnost Corp, Indianapolis, IN USA. RP Singer, EJ (reprint author), 11645 Wilshire Blvd,Suite 770, Los Angeles, CA 90025 USA. FU NINDS NIH HHS [NS-38841, R24 NS038841] NR 16 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2002 VL 40 IS 10 BP 3863 EP 3864 DI 10.1128/JCM.40.10.3863-3864.2002 PG 2 WC Microbiology SC Microbiology GA 600MP UT WOS:000178394800058 PM 12354902 ER PT J AU Levine, M LaPolla, S Owen, WL Socransky, SS AF Levine, M LaPolla, S Owen, WL Socransky, SS TI Antibody-based diagnostic for 'refractory' periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE actinomyces; antibodies; D-alanyl glycerol lipoteichoic acid; logistic regression; lysine decarboxylase; periodontitis; refractory ID EXPERIMENTAL GINGIVITIS; LIPOTEICHOIC ACID; PLAQUE; SUPRAGINGIVAL; PARAMETERS; DISEASES AB Objective: About 10-15% of US adults are 'refractory' to therapy for chronic periodontitis. Recently, studies suggest that these patients have elevated lysine decarboxylase activity in the sulcular microbiota. The aim of this study was to determine whether an elevated IgG antibody response to lysine decarboxylase, alone or with antibody to other bacterial antigens and baseline clinical measurements, would predict 'refractory' patients with high accuracy. Methods: Chronic periodontitis patients were treated using scaling and root planing (SRP) followed by maintenance SRP and 3-monthly re-examinations. If there was a loss of mean full mouth attachment or more than three sites appeared with >2.5 mm new loss within a year, the subjects were re-treated (modified Widman flap surgery and systemically administered tetracycline). If attachment loss as above recurred, the subjects were 'refractory'. Baseline clinical measurements and specific antibody responses were used in a logistic regression model to predict 'refractory' subjects. Results: Antibody to a peptide portion of lysine decarboxylase (HKL-Ab) and baseline bleeding on probing (BOP) prevalence measurements predicted attachment loss 3 months after initial therapy [pIAL=loss (0) or gain (1)]. IgG antibody contents to a purified antigen from Actinomyces spp. (A-Ab) and streptococcal D-alanyl glycerol lipoteichoic acid (S-Ab) were related in 'refractory' patients (R-2=0.37, p<0.01). From the regression equation, the relationship between the antibodies was defined as linear (pLA/S-Ab=0) or non-linear pLA/S-Ab=1). Using pLA/S-Ab, pIAL and age, a logistic regression equation was derived from 48 of the patients. Of 59 subjects, 37 had 2-4 mm attachment loss and were assigned as 'refractory' or successfully treated with 86% accuracy. Conclusion: HKL-Ab facilitated an accurate prediction of therapeutic outcome in subjects with moderate periodontitis. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. BioMed Serv Inc, Austin, TX USA. Forsyth Inst, Dept Biostat, Boston, MA USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Levine, M (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, 940 Stanton L Young Blvd, Oklahoma City, OK 73104 USA. FU NIDCR NIH HHS [R41 DE012556-01, 01R41DE12556-01] NR 34 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2002 VL 29 IS 10 BP 935 EP 943 DI 10.1034/j.1600-051X.2002.291009.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 621CF UT WOS:000179570400009 PM 12445226 ER PT J AU Wirshing, DA Boyd, JA Meng, LR Ballon, JS Marder, SR Wirshing, WC AF Wirshing, DA Boyd, JA Meng, LR Ballon, JS Marder, SR Wirshing, WC TI The effects of novel antipsychotics on glucose and lipid levels SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SERUM TRIGLYCERIDE LEVELS; ONSET DIABETES-MELLITUS; WEIGHT-GAIN; CLOZAPINE TREATMENT; OLANZAPINE TREATMENT; PSYCHOTROPIC-DRUGS; PLASMA-LEVELS; KETOACIDOSIS; HYPERGLYCEMIA; RISPERIDONE AB Background. The novel antipsychotics are extensively used based on their favorable extrapyramidal side effect profiles. However, accumulating evidence suggests that these agents, particularly clozapine and olanzapine, have serious side effects of their own, including weight gain and elevated glucose and triglyceride levels. The goal of this study is to compare the effects of novel antipsychotics clozapine, olanzapine, risperidone, and quetiapine and typical antipsychotics haloperidol and fluphenazine on glucose and lipid levels. Method: The charts of 590 patients were retrospectively reviewed. Of those, 215 patients had adequate laboratory data for inclusion. Glucose and lipid level data from 2 1/2 years before and after initiation of the target antipsychotic were included. Covariates, including patients' age, the duration of antipsychotic treatment, other medications that may affect glucose or lipid levels, and the initial laboratory values, were controlled for in the analyses. Results: Glucose levels were increased from baseline for patients treated with clozapine, olanzapine, and haloperidol. There were statistically and clinically significant differences among the medications' effects on lipid profiles (p < .05). Those receiving clozapine and olanzapine demonstrated statistically significant increases in triglyceride levels compared with the other groups. Over one third of patients treated with any of the novel antipsychotics had clinically meaningful triglyceride elevations. Conclusion: It has been shown that novel antipsychotics are associated with weight gain. This risk factor along with others, such as elevated glucose and triglyceride levels, compounds the risk for coronary artery disease. Routine monitoring of glucose and lipid levels during treatment with novel antipsychotics should be advocated. 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. Mental Illness Res Educ & Clin Ctr, MIRECC, VA VISN 22, Los Angeles, CA USA. RP Wirshing, DA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, 11301 Wilshire Blvd,B151-H, Los Angeles, CA 90073 USA. OI Ballon, Jacob/0000-0002-6157-4847 NR 61 TC 217 Z9 228 U1 2 U2 7 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 OCT PY 2002 VL 63 IS 10 BP 856 EP 865 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 608VA UT WOS:000178866700002 PM 12416594 ER PT J AU Joo, JH Lenze, EJ Mulsant, BH Begley, AE Weber, EM Stack, JA Mazumdar, S Reynolds, CF Pollock, BG AF Joo, JH Lenze, EJ Mulsant, BH Begley, AE Weber, EM Stack, JA Mazumdar, S Reynolds, CF Pollock, BG TI Risk factors for falls during treatment of late-life depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID OLDER-PEOPLE; ANTIDEPRESSANTS; FRACTURES AB Background. Prior studies have found that antidepressant medications are associated with an increased risk of falling in elderly persons. However, little is known about the prevention of falls during treatment for depression in elderly persons. This study evaluated the time course and potential risk factors for falls in a treatment protocol for late-life depression to identify specific at-risk periods and risk factors for falls in this population. Method: One hundred four subjects aged 69 years and over were treated in a protocolized manner using paroxetine and interpersonal psychotherapy. Those who did not respond received augmentation therapy with bupropion, nortriptyline, or lithium. Subjects were assessed at baseline and weekly during treatment; demographic and clinical characteristics of those who experienced a fall during treatment were compared with those who did not fall. Cox proportional hazards models were used to define risk factors for falls in univariate and multivariate models. Results: During a mean of 21 weeks of treatment, 40 subjects (38%) fell. About half (53%) of the subjects fell during the first 6 weeks of treatment. In the multivariate model, memory impairment and orthostatic changes in blood pressure during treatment were risk factors for failing. Additionally, augmentation with bupropion appeared to be a risk factor for falls in univariate analysis, but this result is preliminary due to the small number of subjects who took bupropion. Conclusion: Increased monitoring for falls is warranted during the acute treatment of late-life depression. When treating such patients, clinicians should be especially watchful of those with memory impairments or those who develop orthostatic blood pressure changes; orthostatic blood pressure should be measured throughout acute treatment. Additionally, augmenting paroxetine with bupropion may also increase the risk of falls, and this medication combination should be used with caution in elderly patients. C1 Univ Pittsburgh, Sch Med, Intervent Res Ctr Late Life Mood Disorders, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, GRECC, Pittsburgh, PA USA. RP Lenze, EJ (reprint author), Western Psychiat Inst & Clin, Room E1124,3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [K05 MH00295, R37 MH43832, R01 MH37869, K01 MH01613, K02 MH01509, P30 MH 52247, K23 MH64196, T32 MH19986] NR 25 TC 28 Z9 28 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2002 VL 63 IS 10 BP 936 EP 941 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 608VA UT WOS:000178866700012 PM 12416604 ER PT J AU Faraone, SV Biederman, J Roe, C AF Faraone, SV Biederman, J Roe, C TI Comparative efficacy of Adderall and methylphenidate in attention-deficit/hyperactivity disorder: A meta-analysis SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; RESPONSE CURVE; DRUG-PLACEBO; CHILDREN AB Because methylphenidate is currently the most widely prescribed medication for attention-deficit/hyperactivity disorder, several studies have used it as the active comparator medication for evaluating the efficacy of a newer stimulant, Adderall. These prior studies show Adderall to be superior to placebo and suggest it is at least as effective as the standard-release form of methylphenidate and has a longer duration of action. Although these initial studies provide useful information for clinicians treating children with attention-deficit/hyperactivity disorder, they are difficult to interpret because findings vary among studies and among the different types of measures used within each study. To provide a clearer picture of what conclusions can be drawn from these studies, we performed a meta-analysis. Data from the four available studies suggest that Adderall has a small but statistically significant advantage over the standard-release form of methylphenidate. This advantage was observed for both symptom measures and global ratings but was strongest for global ratings. The effect of Adderall was significant for clinician and parent ratings but not for teacher ratings and was significant for both fixed-dose and best-dose designs. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. RP Faraone, SV (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 NR 12 TC 40 Z9 40 U1 2 U2 10 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 OCT PY 2002 VL 22 IS 5 BP 468 EP 473 DI 10.1097/01.jcp.0000033401.43191.26 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 597EW UT WOS:000178210100005 PM 12352269 ER PT J AU Perlis, RH Nierenberg, AA Alpert, JE Pava, J Matthews, JD Buchin, J Sickinger, AH Fava, M AF Perlis, RH Nierenberg, AA Alpert, JE Pava, J Matthews, JD Buchin, J Sickinger, AH Fava, M TI Effects of adding cognitive therapy to fluoxetine dose increase on risk of relapse and residual depressive symptoms in continuation treatment of major depressive disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID RECURRENT DEPRESSION; BEHAVIORAL TREATMENT; PHARMACOTHERAPY; PREVENTION; EFFICACY; TRIAL AB Patients with major depressive disorder remain at risk for relapse following remission and often continue to experience subthreshold symptoms. This study compared the rate of relapse of major depressive disorder and the prevalence of residual depressive symptoms during the continuation phase for patients treated with fluoxetine dose increase alone or in combination with cognitive therapy. A total of 132 outpatients with major depressive disorder who achieved remission with 8 weeks of treatment with fluoxetine 20 mg had the dose increased to 40 mg. They were randomized to receive cognitive therapy or medication management alone and were followed for up to 28 weeks for depressive relapse and change in depressive symptoms. A total of 47 (35.6%) out of 132 patients did not complete the 28-week continuation phase. Rates of discontinuation or relapse did not differ significantly between the groups. Change in residual symptoms or wellbeing as measured by Hamilton Depression Scale score or Symptom Questionnaire self-report also did not differ between groups. In this sample of outpatients in continuation phase treatment for major depressive disorder, the combination of cognitive therapy and fluoxetine 40 mg failed to yield any significant benefit in symptoms or relapse rates over fluoxetine 40 mg alone during 28 weeks of follow-up. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 parkman St,WACC812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 36 TC 45 Z9 47 U1 5 U2 11 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 OCT PY 2002 VL 22 IS 5 BP 474 EP 480 DI 10.1097/01.jcp.0000033402.43191.fd PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 597EW UT WOS:000178210100006 PM 12352270 ER PT J AU Solai, LK Pollock, BG Mulsant, BH Frye, RF Miller, MD Sweet, RA Kirshner, M Sorisio, D Begley, A Reynolds, CF AF Solai, LK Pollock, BG Mulsant, BH Frye, RF Miller, MD Sweet, RA Kirshner, M Sorisio, D Begley, A Reynolds, CF TI Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DEXTROMETHORPHAN IN-VITRO; EXTENSIVE METABOLIZERS; DEBRISOQUINE OXIDATION; SPARTEINE OXIDATION; RATING-SCALE; RISK-FACTORS; HUMAN-LIVER; SERTRALINE; INHIBITION AB This study was performed in elderly patients (1) to assess in vivo the degree to which CYP2D6-mediated metabolism of debrisoquine at baseline determines plasma concentration to dose quotients for nortriptyline or paroxetine after 4 weeks of treatment, and (2) to compare the effects of nortriptyline and paroxetine on debrisoquine metabolism after 6 weeks of treatment. CYP2D6 activity was estimated in 66 subjects (71.4 +/- 7.2 years) before initiating treatment and again after 6 weeks of treatment with either nortriptyline or paroxetine under randomized, double-blind conditions according to a standard protocol. CYP2D6 activity was estimated by the debrisoquine recovery ratio in a 6- to 8-hour urine sample collected after oral administration of 10 mg debrisoquine sulfate. Nortriptyline and paroxetine plasma concentrations were obtained weekly. Baseline debrisoquine recovery ratio values were significantly correlated with the plasma concentration to dose quotient at 4 weeks for both nortriptyline (r = -0.75, p = 0.0001, N = 29) and paroxetine (r = -0.50,p = 0.003, N = 33). Treatment with either nortriptyline or paroxetine was associated with a significant decrease in the median debrisoquine recovery ratio, reflecting inhibition of CYP2D6 metabolism. The percent decrease associated with nortriptyline was significantly smaller than that with paroxetine (p < 0.0001). None of the patients treated with nortriptyline but 19 of the 32 extensive metabolizers treated with paroxetine were converted to phenotypic poor metabolic status. Our observations of CYP2D6 inhibition are consistent with in vitro data and results obtained in younger healthy volunteers. The significant correlations between baseline debrisoquine recovery ratio and the plasma concentrations to dose quotients at 4 weeks for both nortriptyline and paroxetine are consistent with CYP2D6 playing a major role in the metabolism of both drugs. CYP2D6 inhibition by paroxetine, which effectively converted 59% of patients to phenotypic PMs, may be especially relevant for elderly patients given their generally higher concentration of paroxetine. C1 Univ Pittsburgh, Sch Med, Mental Hlth Intervent Res Ctr Study Late Life Moo, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. RP Solai, LK (reprint author), Western Psychiat Inst & Clin, Beaver Valley Mental Hlth Serv, 176 Virginia Ave, Rochester, PA 15074 USA. OI Frye, Reginald/0000-0002-1841-1401 FU NIMH NIH HHS [MH64173, MH 00295, MH 65416, MH 01613, MH 52247, MH 43832, MH 37869, MH59666] NR 31 TC 14 Z9 14 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 OCT PY 2002 VL 22 IS 5 BP 481 EP 486 DI 10.1097/01.jcp.0000033398.43191.6a PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 597EW UT WOS:000178210100007 PM 12352271 ER PT J AU Huang, GT Rosowski, JJ Ravicz, ME Peake, WT AF Huang, GT Rosowski, JJ Ravicz, ME Peake, WT TI Mammalian ear specializations in arid habitats: structural and functional evidence from sand cat (Felis margarita) SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE adaptation; comparative hearing; sand cat; sensory ecology ID MIDDLE-EAR; SOUND LOCALIZATION; TYMPANIC MEMBRANE; EXTERNAL-EAR; EVOLUTION; IMPEDANCE; HEARING; ABSORPTION; CARNIVORA; MERIONES AB To test whether structural specializations of sand-cat ears are adaptations to their desert habitats we measured structural and acoustic features of their ears. The area of the external ear's pinna flange is similar to that of domestic cat. The dimensions of the ear canal are about twice domestic cat's, as is the volume of the middle-ear air space. The magnitude of the acoustic input-admittance at the tympanic membrane is about five times larger than that of domestic cat; both the middle-ear cavities and the ossicular chain contribute to the increase. Structure-based models suggest the acoustic admittance looking outward through the external ear is generally larger for sand cat than for domestic cat; the radiation power-efficiency is also larger in sand cat for frequencies below 2 kHz. Hearing sensitivity (estimated from measurements and model calculations) in sand cat is predicted to be about 8 dB greater than in domestic cat for frequencies below 2 kHz. Analysis of attenuation of sound in deserts implies that the increased sensitivity extends sand cat's hearing, range beyond domestic cat by 0.4 km at 0.5 kHz. Thus, the structural specializations may provide habitat-specific survival value. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, 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 89 TC 18 Z9 21 U1 1 U2 14 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD OCT PY 2002 VL 188 IS 9 BP 663 EP 681 DI 10.1007/s00359-002-0332-8 PG 19 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 619ZV UT WOS:000179508800001 PM 12397438 ER PT J AU Young, CS Terada, S Vacanti, JP Honda, M Bartlett, JD Yelick, PC AF Young, CS Terada, S Vacanti, JP Honda, M Bartlett, JD Yelick, PC TI Tissue engineering of complex tooth structures on biodegradable polymer scaffolds SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE tissue engineering; polymer scaffold; enamel; dentin ID EPITHELIAL ROOT SHEATH; ORGAN-CULTURE; DENTAL-PULP; ATTACHMENT PROTEIN; IN-VITRO; CEMENTUM; DIFFERENTIATION; SIALOPROTEIN; MORPHOGENESIS; EXPRESSION AB Tooth loss due to periodontal disease, dental caries, trauma, or a variety of genetic disorders continues to affect most adults adversely at some time in their lives. A biological tooth substitute that could replace lost teeth would provide a vital alternative to currently available clinical treatments. To pursue this goal, we dissociated porcine third molar tooth buds into single-cell suspensions and seeded them onto biodegradable polymers. After growing in rat hosts for 20 to 30 weeks, recognizable tooth structures formed that contained dentin, odontoblasts, a well-defined pulp chamber, putative Hertwig's root sheath epithelia, putative cementoblasts, and a morphologically correct enamel organ containing fully formed enamel. Our results demonstrate the first successful generation of tooth crowns from dissociated tooth tissues that contain both dentin and enamel, and suggest the presence of epithelial and mesenchymal dental stem cells in porcine third molar tissues. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Forsyth Inst, Forsyth Dept Oral Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Nagoya Univ, Sch Med, Dept Oral & Maxillofacial Surg, Nagoya, Aichi 466, Japan. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE014084] NR 32 TC 214 Z9 262 U1 5 U2 28 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2002 VL 81 IS 10 BP 695 EP 700 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 599FP UT WOS:000178323700008 PM 12351668 ER PT J AU Jellinek, MS Belluck, J AF Jellinek, MS Belluck, J TI Children of victims of September 11th: A perspective on the emotional and developmental challenges they face and how to help meet them - Introduction SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, 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 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2002 VL 23 IS 5 BP 377 EP 377 PG 1 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 604CL UT WOS:000178598000011 ER PT J AU Swick, SD Dechant, E Jellinek, MS AF Swick, SD Dechant, E Jellinek, MS TI Children of victims of September 11th: A perspective on the emotional and developmental challenges they face and how to help meet them SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article ID PARENTALLY BEREAVED CHILDREN; CHILDHOOD BEREAVEMENT; STRESS-DISORDER; DEATH; DEPRESSION C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, 55 Fruit St,Bulfinch Rm 351, Boston, MA 02114 USA. NR 22 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2002 VL 23 IS 5 BP 378 EP 384 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 604CL UT WOS:000178598000012 PM 12394527 ER PT J AU Binder, WD Brown, DFM Nadel, ES AF Binder, WD Brown, DFM Nadel, ES TI Blurred vision, epistaxis, and fever in a young man SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; HYPERLEUKOCYTOSIS; LEUKOSTASIS; LEUKAPHERESIS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2002 VL 23 IS 3 BP 275 EP 278 AR PII S0736-4679(02)00536-X DI 10.1016/S0736-4679(02)00536-X PG 4 WC Emergency Medicine SC Emergency Medicine GA 612TU UT WOS:000179092200009 PM 12426019 ER PT J AU Struyk, AF Cannon, SC AF Struyk, AF Cannon, SC TI Slow inactivation does not block the aqueous accessibility to the outer pore of voltage-gated Na channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE gating; cysteine-scanning mutagenesis; methanthiosulfonate; NaV1.4 ID SODIUM-CHANNELS; PERIODIC PARALYSIS; CYSTEINE MUTAGENESIS; K+ CHANNEL; MUTATION; REARRANGEMENT AB Slow inactivation of voltage-gated Na channels is kinetically and structurally distinct from fast inactivation. Whereas structures that participate in fast inactivation are well described and include the cytoplasmic III-IV linker, the nature and location of the slow inactivation gating mechanism remains poorly understood. Several lines of evidence suggest that the pore regions (P-regions) are important contributors to slow inactivation gating. This has led to the proposal that a collapse of the pore impedes Na current during slow inactivation. We sought to determine whether such a slow inactivation-coupled conformational change could be detected in the outer pore. To accomplish this, we used a rapid perfusion technique to measure reaction rates between cysteine-substituted side chains lining the aqueous pore and the charged sulfhydryl-modifying reagent MTS-ET. A pattern of incrementally slower reaction rates was observed at substituted sites at increasing depth in the pore. We found no state-dependent change in modification rates of P-region residues located in all four domains, and thus no change in aqueous accessibility, between slow- and nonslow-inactivated states. In domains I and IV, it was possible to measure modification rates at residues adjacent to the narrow DEKA selectivity filter (Y401C and G1530C), and yet no change was observed in accessibility in either slow- or nonslow-inactivated states. We interpret these results as evidence that the outer mouth of the Na pore remains open while the channel is slow inactivated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. RP Cannon, SC (reprint author), Univ Texas, SW Med Ctr, Dept Neurol, F2-318,5323 Harry Hines Blvd, Dallas, TX 75390 USA. FU NIAMS NIH HHS [AR42703, R37 AR042703, R01 AR042703]; NINDS NIH HHS [K08-NS02137, K08 NS002137] NR 27 TC 30 Z9 31 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD OCT PY 2002 VL 120 IS 4 BP 509 EP 516 DI 10.1085/jgp.20028672 PG 8 WC Physiology SC Physiology GA 602XF UT WOS:000178529200008 PM 12356853 ER PT J AU Scadden, DT AF Scadden, DT TI Toward cellular-based therapies for HIV infection SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC STEM-CELLS; CD8(+) T-CELLS; ANTIRETROVIRAL THERAPY; BONE-MARROW; LYMPHOID-TISSUES; CD34(+) CELLS; CD4(+); TYPE-1; GENE AB Infection with HIV-1 progressively erodes immune function, leading ultimately to multiple hematopoietic cytopenias. In advanced HIV disease, anemia, neutropenia, and thrombocytopenia occur in a large fraction of patients and are reflective of a striking inability of the bone marrow to accomplish a compensatory increase in production. No failure of compensatory production is greater than that of the T lymphoid system, where despite apparently effective control of HIV replication, restoration of anti-HIV immunity does not occur. Recent technical developments have provided considerable insight into hematopoietic dysfunction in HIV disease and, in particular, in vivo T cell generation. This article will review some of the mechanisms participating in immune regeneration, the stakes involved in effectively accomplishing full reconstitution, and potential approaches to enhance the limited endogenous regenerative process. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. NR 34 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2002 VL 11 IS 5 BP 759 EP 764 DI 10.1089/152581602760404568 PG 6 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 608ML UT WOS:000178850000003 PM 12427282 ER PT J AU Bunting, RW Selig, MK AF Bunting, RW Selig, MK TI Localization of DNA in ultrascopic nuclear appendages of polymorphonuclear white blood cells from patients with low serum B-12 SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE cobalamin; vitamin B-12; nuclear appendages; DNA ID HOMOCYSTEINE STATUS; PERIPHERAL-BLOOD; BONE-MARROW; FOLATE; MICRONUCLEI; COBALAMIN; URACIL; DAMAGE; LYMPHOCYTES; VITAMIN-B12 AB Polymorphonuclear white blood cells from patients with low serum vitamin B-12 (cobalamin) have ultrascopic, appendages that project from their nuclear membranes. These appendages Are most often found in the shape of blebs and stalks. Cytoplasmic rings that may be separated from the nucleus have also been seen. There is no known function for these appendages. Blood from 11 patients with low serum B-12 was processed for electron microscopic examination. In situ end-labeling of DNA and subsequent electron microscopic examination were performed. DNA was localized in all of the visualized appendages and rings. Treatment with DNases I and II decreased the labeling of these appendages by 63%. These DNA-laden appendages are a unique ultrastructural finding and may function to transfer fragmented DNA, which occurs in vitamin B-12 deficiency, from the nucleus into the cytoplasm. C1 Spaulding Rehabil Hosp, Dept Hematol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Bunting, RW (reprint author), Spaulding Rehabil Hosp, Dept Hematol, 125 Nashua St, Boston, MA 02114 USA. NR 27 TC 2 Z9 2 U1 0 U2 1 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 OCT PY 2002 VL 50 IS 10 BP 1381 EP 1388 PG 8 WC Cell Biology SC Cell Biology GA 605GY UT WOS:000178670700011 PM 12364571 ER PT J AU Cameron, TO Norris, PJ Patel, A Moulon, C Rosenberg, ES Mellins, ED Wedderburn, LR Stern, LJ AF Cameron, TO Norris, PJ Patel, A Moulon, C Rosenberg, ES Mellins, ED Wedderburn, LR Stern, LJ TI Labeling antigen-specific CD4(+) T cells with class II MHC oligomers SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE MHC tetramers; helper T cell; T lymphocyte; avidity; receptor-ligand interactions; multi-valent binding; flow cytometry; binding assay; HLA-DR ID HISTOCOMPATIBILITY COMPLEX PROTEINS; MYELIN BASIC-PROTEIN; ESCHERICHIA-COLI; PEPTIDE COMPLEXES; INFLUENZA HEMAGGLUTININ; IMMUNODOMINANT PEPTIDE; VIRAL-ANTIGEN; TCR AVIDITY; IN-VITRO; HLA-DR AB Class I MHC-peptide oligomers (MHC tetramers) have become popular reagents for the detection and characterization of antigen-specific CD8(+) T cells. Class II MHC proteins can be produced by expression in Escherichia coli followed by in vitro folding, or by native expression in insect cells; biotin can be introduced by site-specific chemical modification of cysteine, or by enzymatic modification of a peptide tag; and a variety of fluorescent streptavidin preparations can be used for oligomerization. Here we review methodologies for production of fluorescent oligomers of soluble class II MHC proteins and discuss their use in analysis of antigen-specific CD4(+) T cells. We explore the experimental conditions necessary for efficient staining of CD4(+) T cells using oligomers of class II MHC proteins, and we establish a standard protocol. Finally, we consider complications and challenges associated with these reagents, discuss the interpretation of staining results, and suggest future. directions for investigation, in particular the use of MHC oligomers for the study of T cell avidity modulation. (C) 2002 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. UCL, Inst Child Hlth, Rheumatol Unit, London WC1N 1EH, England. Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. RP Stern, LJ (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM stern@mit.edu FU NIAID NIH HHS [K08 AI001698, AI 40873, AI 01698-01, AI 95361, K08 AI001698-01A1]; NIGMS NIH HHS [T32 GM08334] NR 57 TC 37 Z9 37 U1 0 U2 2 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 OCT 1 PY 2002 VL 268 IS 1 BP 51 EP 69 AR PII S0022-1759(02)00200-4 DI 10.1016/S0022-1759(02)00200-4 PG 19 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 599FR UT WOS:000178323900008 PM 12213343 ER PT J AU Schneider, H Mandelbrot, DA Greenwald, RJ Ng, F Lechler, R Sharpe, AH Rudd, CE AF Schneider, H Mandelbrot, DA Greenwald, RJ Ng, F Lechler, R Sharpe, AH Rudd, CE TI Cutting edge: CTLA-4 (CD152) differentially regulates mitogen-activated protein kinases (extracellular signal-regulated kinase and c-Jun N-terminal kinase) in CD4(+) T cells from receptor/ligand-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-ASSOCIATED ANTIGEN-4; PHOSPHATIDYLINOSITOL 3-KINASE; CTLA-4-DEFICIENT MICE; MAP KINASES; JNK GROUP; CD28; B7-1; ERK; COSTIMULATION; TRANSDUCTION AB Although CTLA-4 (CD152) has potent inhibitory effects,on T cell function, the signaling events affected by this coreceptor remain to be fully defined. Mitogen-activated protein kinases (MAPK) extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) act as crucial regulators of multiple aspects of cell function. Ab ligation studies have reported an inhibitory effect of CTLA-4 on TCR-induced ERK and JNK activation. In this study, we have re-examined the specificity of CTLA-4 inhibition of MAPKs by using natural ligand with ex vivo-purified CD4(+) T cells deficient in CD80 and CD86 (double knockout), or CTLA-4, CD80, and CD86 (triple knockout). Under these conditions, CTLA-4 ligation was found to up-regulate and sustain JNK activation, while inhibiting ERK activity. At the same time, JNK activation could not account for CTLA-4 induction of TGF-beta production. Our findings demonstrate that CTLA-4 cosignaling is more complex than previously appreciated, with an ability to differentially regulate members of the MAPK family in T cells. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Hematol, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Immunol, London W12 0NN, England. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Rudd, CE (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Hematol, London W12 0NN, England. NR 39 TC 33 Z9 34 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2002 VL 169 IS 7 BP 3475 EP 3479 PG 5 WC Immunology SC Immunology GA 598QV UT WOS:000178288800001 PM 12244135 ER PT J AU Haller, GW Lima, B Kunisaki, SM Germana, S Leguern, C Huang, CA Sachs, DH AF Haller, GW Lima, B Kunisaki, SM Germana, S Leguern, C Huang, CA Sachs, DH TI MHC alloantigens elicit secondary, but not primary, indirect in vitro proliferative responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN-PRESENTING CELLS; LYMPHOCYTE PRECURSOR FREQUENCIES; T-CELLS; MINIATURE SWINE; INDIRECT RECOGNITION; INTERLEUKIN-2 PRODUCTION; KIDNEY ALLOGRAFTS; REJECTION; TRANSPLANTATION AB The relative contributions of direct and indirect pathways of allorecognition to graft rejection remain controversial. Recent reports suggest that the indirect pathway may play a prominent role in both acute and chronic allograft rejection. Such studies suggest that MHC-derived allopeptides are more immunogenic than those derived from minor histocompatibility or other nominal Ags. The aim of this study was to characterize the immunogenicity of MHC alloantigens in MHC-defined miniature swine via primary and secondary MLR culture assays. APCs were selectively depleted from either responder or stimulator cell populations to specifically analyze direct and indirect proliferative responses, respectively. Radio-resistant cytokine secretion and subsequent backstimulation of responder cells was eliminated by using stimulators that were either lysed or unresponsive to the responder MHC haplotypes. When the effect of backstimulation was eliminated from MLR culture assays, indirect proliferative responses were not observed among naive responders. Only after in vivo priming of responder animals could indirect proliferation be detected. These data do not refute the potential importance of indirect allorecognition in graft rejection. However, they suggest that MHC-derived alloantigens behave similarly in vitro to minor histocompatibility Ags, with comparable immunogenicity. These data also suggest that the MLR culture assay does not accurately reflect the importance of indirect mechanisms that have previously been reported in experimental models of graft rejection. A greater understanding of the indirect pathway and the associated immunogenicity of MHC allopeptides has the potential benefit of enabling the development of therapeutic interventions to prevent or halt allograft rejection. 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 NCI NIH HHS [1R01 CA79988-01A1]; NHLBI NIH HHS [5R01 HL63430-02] NR 29 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 OCT 1 PY 2002 VL 169 IS 7 BP 3613 EP 3621 PG 9 WC Immunology SC Immunology GA 598QV UT WOS:000178288800018 PM 12244152 ER PT J AU Tian, CR Bagley, J Iacomini, J AF Tian, CR Bagley, J Iacomini, J TI Expression of antigen on mature lymphocytes is required to induce T cell tolerance by gene therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; MIXED CHIMERISM; STEM-CELLS; ALLOGRAFTS; MICE AB Expression of a retrovirally encoded allogeneic MHC class I gene in bone marrow-derived cells can be used to induce tolerance to the product of the retrovirally transduced gene. In this work we examined whether expression of a retrovirally transduced allogeneic MHC class I gene in bone marrow-derived cells from recombinase-activating gene-1 (RAG-1)-deficient mice was sufficient to induce tolerance when transplanted into conditioned hosts together with bone marrow from MHC-matched wild-type mice. Reconstitution of mice with either MHC-matched RAG-1-deficient or wild-type bone marrow transduced with the allogeneic MHC class I gene H-2K(b) led to long-term expression of K-b on the surface of bone marrow-derived hematopoietic lineages. T cells from mice reconstituted with H-2K(b)-transduced wild-type bone marrow were tolerant to K-b. In contrast, expression of K-b in the periphery of mice reconstituted with a mixture of retrovirally transduced RAG-1-deficient bone marrow and mock-transduced wild-type bone marrow fell below detectable levels by 4 wk after transplantation. T cells that developed in these mice appeared to be hyporesponsive to K-b, demonstrating that expression of K-b on bone marrow-derived APCs was not sufficient to induce tolerance. Our data suggest that induction of tolerance in molecular chimeras requires expression of the retrovirally transduced allogeneic MHC Ag on the surface of mature lymphocytes that populate the host thymus. C1 Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI43619, T32 AI07529] NR 23 TC 24 Z9 26 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 OCT 1 PY 2002 VL 169 IS 7 BP 3771 EP 3776 PG 6 WC Immunology SC Immunology GA 598QV UT WOS:000178288800037 PM 12244171 ER PT J AU Henneke, P Takeuchi, O Malley, R Lien, E Ingalls, RR Freeman, MW Mayadas, T Nizet, V Akira, S Kasper, DL Golenbock, DT AF Henneke, P Takeuchi, O Malley, R Lien, E Ingalls, RR Freeman, MW Mayadas, T Nizet, V Akira, S Kasper, DL Golenbock, DT TI Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; CUTTING EDGE; MURINE MACROPHAGES; GENE-EXPRESSION; NITRIC-OXIDE; MYD88-DEFICIENT MICE; BINDING PROTEINS; WALL COMPONENTS; LIPOPOLYSACCHARIDE AB Group B streptococci (GBS) vigorously activate inflammatory responses. We reported previously that a secreted GBS "factor" activates phagocytes via Toll-like receptor (TLR)2 and TLR6, but that GBS cell walls activate cells independently of these receptors. We hypothesized that the phagocytic immune functions in response to GBS, such as inflammation, uptake, and elimination of bacteria, occur through a coordinated engagement of TLRs, along with the coreceptors CD14 and CD11b/CD18. Using various knockout mice we show that GBS-induced activation of p38 and NF-kappaB depends upon the expression of the cytoplasmic TLR adapter protein, myeloid differentiation factor 88 (MyD88), but not TLR2 and/or TLR4. Macrophages with deletions of CD14 and complement receptor 3 had a normal cytokine response to whole bacteria, although the response to GBS factor was abrogated in CD14-null cells. The intracellular formation of bactericidal oxygen species proved to be MyD88 dependent; however, uptake of GBS, a prerequisite for intracellular killing by O-2 radicals, occurred independently of MyD88. While deletion of complement receptor 3 greatly diminished the uptake of opsonized GBS, it did not affect the formation of bactericidal O-2 radicals or inflammatory signaling intermediates. We conclude that the inflammatory, bactericidal, and phagocytic responses to GBS occur via parallel but independent processes. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. Free Univ Berlin, Dept Pediat, D-1000 Berlin, Germany. Osaka Univ, Res Inst Microbial Dis, Osaka, Japan. Harvard Univ, Sch Med, Channing Lab, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Genet, Boston, MA 02115 USA. Boston Univ, Sch Med, Evans Biomed Res Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. RP Golenbock, DT (reprint author), Univ Massachusetts, Sch Med, Dept Med, Lazare Res Bldg,Room 309,364 Plantat St, Worcester, MA 01605 USA. RI Akira, Shizuo/C-3134-2009; Takeuchi, Osamu/D-6007-2011 FU NCRR NIH HHS [RR14466]; NHLBI NIH HHS [HL36028]; NIAID NIH HHS [AI46613, AI23339, AI38515, AI52455]; NIDDK NIH HHS [DK50305]; NIGMS NIH HHS [GM54060] NR 61 TC 96 Z9 99 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2002 VL 169 IS 7 BP 3970 EP 3977 PG 8 WC Immunology SC Immunology GA 598QV UT WOS:000178288800064 PM 12244198 ER PT J AU Weber, GF Zawaideh, S Hikita, S Kumar, VA Cantor, H Ashkar, S AF Weber, GF Zawaideh, S Hikita, S Kumar, VA Cantor, H Ashkar, S TI Phosphorylation-dependent interaction of osteopontin with its receptors regulates macrophage migration and activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE integrins; delayed-type hypersensitivity; CD44; metalloproteases ID EXTRACELLULAR-MATRIX PROTEINS; CULTURED CHICKEN OSTEOBLASTS; GLYCINE-ASPARTIC ACID; MUSCLE CELL-MIGRATION; IN-VITRO; BONE SIALOPROTEIN; ESCHERICHIA-COLI; SECRETED PHOSPHOPROTEIN; THROMBIN-CLEAVAGE; ADHESION AB Neutrophil-independent macrophage responses are a prominent part of delayed-type immune and healing processes and depend on T cell-secreted cytokines. An important mediator in this setting is the phosphoprotein osteopontin, whose secretion by activated T cells confers resistance to infection by several intracellular pathogens through recruitment and activation of macrophages. Here, we analyze the structural basis of this activity following cleavage of the phosphoprotein by thrombin into two fragments. An interaction between the C-terminal domain of osteopontin and the receptor CD44 induces macrophage chemotaxis, and engagement of beta(3)-integrin receptors by a nonoverlapping N-terminal osteopontin domain induces cell spreading and subsequent activation. Serine phosphorylation of the osteopontin molecule on specific sites is required for functional interaction with integrin but not CD44 receptors. Thus, in addition to regulation of intracellular enzymes and substrates, phosphorylation also regulates the biological activity of secreted cytokines. These data, taken as a whole, indicate that the activities of distinct osteopontin domains are required to coordinate macrophage migration and activation and may bear on incompletely understood mechanisms of delayed-type hypersensitivity, wound healing, and granulomatous disease. C1 Harvard Univ, Childrens Hosp, Sch Med,Dept Orthoped Surg, Lab Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weber, GF (reprint author), Tufts Univ New England Med Ctr, Dept Radiat & Canc Biol, NEMC 824,750 Washington St, Boston, MA 02111 USA. FU NCI NIH HHS [CA76176]; NIAID NIH HHS [AI12184] NR 53 TC 160 Z9 169 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 2002 VL 72 IS 4 BP 752 EP 761 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 602NV UT WOS:000178512100018 PM 12377945 ER PT J AU Dresselhaus, TR Luck, J Peabody, JW AF Dresselhaus, TR Luck, J Peabody, JW TI The ethical problem of false positives: a prospective evaluation of physician reporting in the medical record SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID STANDARDIZED PATIENTS; CHART ABSTRACTION; QUALITY; RESIDENTS; DECEPTION; CARE; WELL AB Objective: To determine if the medical record might overestimate the quality of care through false, and potentially unethical, documentation by physicians. Design: Prospective trial comparing two methods for measuring the quality of care for four common outpatient conditions: (1) structured reports by standardised patients (SPs) who presented unannounced to the physicians' clinics, and (2) abstraction of the medical records generated during these visits. Setting: The general medicine clinics of two veterans affairs medical centres. Participants: Twenty randomly selected physicians (10 at each site) from among eligible second and third year internal medicine residents and attending physicians. Main measurements: Explicit criteria were used to score the medical records of physicians and the reports of SPs generated during 160 visits (8 cases x 20 physicians). Individual scoring items were categorised into four domains of clinical performance: history, physical examination, treatment, and diagnosis. To determine the false positive rate, physician entries were classified as false positive (documented in the record but not reported by the SP), false negative, true positive, and true negative. Results: False positives were identified in the medical record for 6.4% of measured items. The false positive rate was higher for physical examination (0.330) and diagnosis (0.304) than for history (0.166) and treatment (0.082). For individual physician subjects, the false positive rate ranged from 0.098 to 0.397. Conclusions: These data indicate that the medical record falsely overestimates the quality of important dimensions of care such as the physical examination. Though it is doubtful that most subjects in our study participated in regular, intentional falsification, we cannot exclude the possibility that false positives were in some instances intentional, and therefore fraudulent, misrepresentations. Further research is needed to explore the questions raised but incompletely answered by this research. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, San Francisco, CA 94105 USA. Univ Calif San Diego, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, 74 New Montgomery St,Ste 508, San Francisco, CA 94105 USA. NR 24 TC 1 Z9 1 U1 0 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD OCT PY 2002 VL 28 IS 5 BP 293 EP 296 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 603BC UT WOS:000178538100007 ER PT J AU Wang, F Trial, J Diwan, A Gao, F Birdsall, HH Entman, ML Hornsby, PJ Sivasubramaniam, N Mann, DL AF Wang, F Trial, J Diwan, A Gao, F Birdsall, HH Entman, ML Hornsby, PJ Sivasubramaniam, N Mann, DL TI Regulation of cardiac fibroblast cellular function by leukemia inhibitory factor SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE cytokine; leukemia inhibitory factor; cardiac fibroblast; proliferation; differentiation; collagen content; MMP activity ID SMOOTH MUSCLE ACTIN; GENE-EXPRESSION; DIFFERENTIATION; MYOFIBROBLASTS; COLLAGEN; PROLIFERATION; MYOBLAST; MYOCYTES; GP130; CELLS AB Background: Previous studies have shown that leukemia inhibitory factor (LIF) provokes hypertrophic and cytoprotective effects in cardiac myocytes. However, the effects of LIF in cardiac fibroblasts are not known. Given that the cardiac fibroblast is the most abundant cell type in the heart, we sought to examine the functional effects of LIF on cardiac fibroblasts in vitro. Results: Short-term LIF stimulation (24 h) had no effect on fibroblast proliferation and/or cell differentiation. However. longer-term LIT stimulation (48-72 h) increased fibroblast proliferation, and significantly inhibited cardiac fibroblast differentiation into myofibroblasts. Moreover, 72 It of LIF stimulation significantly reduced collagen content in cardiac fibroblasts cultures, as well as decreased MMP activity in fibroblast culture supernatants. Conclusion: The results of this study suggest that LIF stimulation down-regulates several key components of the remodeling process, including collagen content and matrix metalloproteinase (MMP) activation, and thus suggest that LIF may play an important autocrine/paracrine role in preventing excessive extracellular matrix remodeling following acute myocardial injury. (C) 2002 Published by Elsevier Science Ltd. C1 Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, Houston VAMC, Huffington Ctr Aging, Houston, TX 77030 USA. Baylor Coll Med, Houston VAMC, Dept Otorhinolaryngol, Houston, TX 77030 USA. Baylor Coll Med, Houston VAMC, Dept Med, Houston, TX 77030 USA. Methodist Hosp, DeBakey Heart Ctr, Program Cardiovasc Sci, Houston, TX 77030 USA. RP Mann, DL (reprint author), Winters Ctr Heart Failure Res, MS 524 6565 Fannin St, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL 61543-01, R01 HL 58081-01, HL 42250-10/10] NR 28 TC 32 Z9 33 U1 0 U2 2 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 OCT PY 2002 VL 34 IS 10 BP 1309 EP 1316 DI 10.1006/jmcc.2002.2059 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 613HE UT WOS:000179126200012 PM 12392991 ER PT J AU He, B Tong, TK Hiou-Tim, FFT Al-Akad, B Kronenberg, HM Karaplis, AC AF He, B Tong, TK Hiou-Tim, FFT Al-Akad, B Kronenberg, HM Karaplis, AC TI The murine gene encoding parathyroid hormone: genomic organization, nucleotide sequence and transcriptional regulation SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; CARBOXYL-TERMINAL REGION; PREPROPARATHYROID HORMONE; PROPARATHYROID HORMONE; RESPONSE ELEMENT; RECEPTOR; PEPTIDE; PROTEIN; CELLS; RAT AB The type 1 parathyroid hormone receptor (PTHR1) binds, with equal affinity, two ligands with distinct biological functions: PTH, the major peptide hormone controlling calcium homeostasis, and the paracrine factor, PTH-related peptide (PTHrP), a local regulator of cellular proliferation and differentiation. To clarify the complexity of possible interactions between two distinct ligands, PTH and PTHrP, and their common receptor in the intact organism, and to identify as yet unrecognized roles for PTH in normal physiology, we have cloned and characterized the structural organization, nucleotide sequence and transcriptional regulation of the murine gene encoding PTH. One recombinant clone isolated from a mouse genomic library contained 14 kb of DNA, encompassing the entire Pth gene. The transcriptional unit spans 3.2 kb of genomic DNA and, analogous to the human PTH gene, it is interrupted by two introns. The deduced mRNA encodes the 115-amino acid precursor, preproPTH. Comparison of the murine preproPTH sequence with other mammalian forms of the protein shows it to be highly conserved and to share limited structural similarity to PTHrP at the amino-terminal region, a domain critical for binding and activation of their common receptor. Putative binding motifs for the transcription factors sex-determining region Y gene product, transcriptional repressor CDP, hepatic nuclear factor 3beta, GATA-binding factor 1, glucocorticoid receptor, SRY-related high mobility group box protein 5 and CAMP response element binding protein were identified in the 5' flanking region of the Pth gene. When placed upstream of a reporter gene, these sequences failed to confer transcriptional regulation in response to 1,25(OH)(2) vitamin D-3, but responded positively to the addition of isoproterenol and forskolin. Mutational analysis identified a cAMP-response element in the Pth promoter. C1 McGill Univ, Lady Davis Inst Med Res, SMBD Jewish Gen Hosp, Dept Med,Div Endocrinol, Montreal, PQ H3T 1E2, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Karaplis, AC (reprint author), McGill Univ, Lady Davis Inst Med Res, SMBD Jewish Gen Hosp, Dept Med,Div Endocrinol, 3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 39 TC 14 Z9 14 U1 0 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD OCT PY 2002 VL 29 IS 2 BP 193 EP 203 DI 10.1677/jme.0.0290193 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 607XN UT WOS:000178816200002 PM 12370121 ER PT J AU Shoelson, S AF Shoelson, S TI JMM - Past and Present - Invited comment on W. Ebstein: On the therapy of diabetes mellitus, in particular on the application of sodium salicylate SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Editorial Material ID KAPPA-B; ASPIRIN; BETA C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 4 TC 10 Z9 12 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 2002 VL 80 IS 10 BP 618 EP 619 DI 10.1007/s00109-002-0383-x PG 2 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 618YW UT WOS:000179446600002 ER PT J AU Dagnaes-Hansen, F Holst, HU Sondergaard, M Vorup-Jensen, T Flyvbjerg, A Jensen, UB Jensen, TG AF Dagnaes-Hansen, F Holst, HU Sondergaard, M Vorup-Jensen, T Flyvbjerg, A Jensen, UB Jensen, TG TI Physiological effects of human growth hormone produced after hydrodynamic gene transfer of a plasmid vector containing the human ubiquitin promotor SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE human growth hormone; nonviral gene therapy; hydrodynamic gene transfer; ubiquitin promoter ID LONG-TERM EXPRESSION; IN-VIVO; TRANSGENE EXPRESSION; FACTOR-IX; DNA; INSULIN; LIVER; MICE; LEVEL AB Human growth hormone (hGH) deficiency causes retarded growth and abnormalities in body fat distribution and abundance, muscle growth, and bone mineralization. While injection of recombinant hGH may reverse or ameliorate symptoms of deficiency. therapy aiming, at in vivo synthesis of hGH is still of considerable clinical interest. Hydrodynamic injection of a simple plasmid vector containing a human ubiquitin promotor and the hGH gene were found to result in high and prolonged expression, Synthesis of hGH was achieved both in NOD/SCID mice and in three different inbred strains of immune competent mice. Although hGH antibodies were produced in immunocompetent mice., physiological effects of the protein were documented by increase in body weight, increased serum levels of insulin-like growth factor I and relative increased weight of the internal organs. Nonviral gene therapy may be regarded as a potential future way of reconstituting hGH expression in deficient individuals. C1 Aarhus Univ, Dept Human Genet, DK-8000 Aarhus C, Denmark. Aarhus Univ, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Aarhus Univ Hosp, Med Res Lab, DK-8000 Aarhus C, Denmark. RP Jensen, TG (reprint author), Aarhus Univ, Dept Human Genet, DK-8000 Aarhus C, Denmark. OI Vorup-Jensen, Thomas/0000-0002-4140-6563 NR 18 TC 22 Z9 22 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD OCT PY 2002 VL 80 IS 10 BP 665 EP 670 DI 10.1007/s00109-002-0371-1 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 618YW UT WOS:000179446600008 PM 12395151 ER PT J AU Eskandar, EN Assad, JA AF Eskandar, EN Assad, JA TI Distinct nature of directional signals among parietal cortical areas during visual guidance SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; PURSUIT EYE-MOVEMENTS; EXTRASTRIATE CORTEX; NEURONAL-ACTIVITY; MONKEY; MST; MACAQUE; MT; INTENTION; MOTION AB We examined neuronal signals in the monkey medial superior temporal area (MST), the medial intraparietal area (MIP), and the lateral intraparietal area (LIP) during visually guided hand movements. Two animals were trained to use a joystick to guide a spot to a target. Many neurons responded in a direction-selective manner in this guidance task. We tested whether the direction selectivity depended on the direction of the stimulus spot or the direction of the hand movement. First, in some trials, the moving spot disappeared transiently. Second, the mapping between the hand direction and the spot direction was reversed on alternate blocks of trials. Third, we recorded the spot's movement while the animals moved the joystick and then played back that movement while the animals fixated without moving the joystick. Neurons in the three parietal areas conveyed distinct directional information. MST neurons were active and directional only on visible trials in both joystick-movement mode and playback mode and were not affected by the direction of hand movement. MIP neurons were mainly directional with respect to the hand movement, although some MIP neurons were also selective for stimulus direction. MIP neurons were much less active in playback mode. LIP neurons were active and directional in both joystick-movement mode and playback mode. Directional signals in LIP were unrelated to planning saccades. The selectivity of LIP neurons also became evident hundreds of milliseconds before the start of movement. Since the direction of movement was consistent throughout a block of trials, these signals could provide a prediction of the upcoming direction of motion. We tested this by alternating blocks of trials in which the direction was consistent or randomized. The direction selectivity developed earlier on trials in which the upcoming direction could be predicted. These results suggest that LIP neurons combine "bottom-up" visual motion signals with extraretinal, predictive signals about stimulus motion. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Assad, JA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY-12106] NR 33 TC 35 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2002 VL 88 IS 4 BP 1777 EP 1790 DI 10.1152/jn.00095.2002 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 600BF UT WOS:000178370200019 PM 12364506 ER PT J AU Scheller, M Forman, SA AF Scheller, M Forman, SA TI Coupled and uncoupled gating and desensitization effects by pore domain mutations in GABA(A) receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA receptor; acetylcholine receptor; ion channel; gating; desensitization; pore; electrophysiology ID AMINOBUTYRIC ACID(A) RECEPTORS; NICOTINIC ACETYLCHOLINE-RECEPTORS; CONSERVED M2 LEUCINE; ALPHA-SUBUNIT; XENOPUS-OOCYTES; BETA-SUBUNIT; A RECEPTORS; OPEN STATE; CHANNEL; SEGMENT AB GABA(A) receptors are allosteric ligand-gated ion channels. Agonist-induced gating and desensitization have been proposed to be coupled via pore domain structures. Mutations at two alpha(1) subunit pore-domain (transmembrane domain 2) residues enhance GABA sensitivity, leucine-to-threonine at position 264 (9'), and serine-to-isoleucine at position 270 (15'). We investigated the role of these residues in gating, desensitization, and deactivation of alpha(1)beta(2)gamma(2L) GABA(A) receptors using rapid GABA concentration jumps and patch-clamp electrophysiology. GABA EC50 values for alpha(1)(L264T)beta(2)gamma(2L) and alpha(1)(S270I)beta(2)gamma(2L) currents were, respectively, similar to80-fold and 13-fold lower than the wild-type EC50. Unlike wild type, both mutant receptors displayed significant picrotoxin-sensitive currents in the absence of GABA, indicating that they enhance gating efficacy. Both mutants displayed current activation rates that matched wild type at 1 muM GABA and above. Desensitization of wild-type and alpha(1)(S270I)beta(2)gamma(2L) currents displayed indistinguishable rates and amplitudes, whereas alpha(1)(L264T)beta(2)gamma(2L) currents desensitized extremely slowly. Deactivation of wild-type currents displayed two rates and slowed after partial desensitization, whereas currents from both mutants deactivated slowly with single rate constants that were unaffected by desensitization. These results indicate that both alpha(1)(L264T) and alpha(1)(S270I) mutations increase the gating efficacy of receptors by slowing channel closing, which accounts for nearly all of the similar changes that they produce in macrocurrent dynamics. Because the alpha(1)(S270I) mutation uncouples its gating effects from those on rapid desensitization, these two processes are necessarily associated with movements of distinct receptor structures (gates). The effects of the alpha(1)(L264T) mutation suggest that the conserved leucines may play a role in gating-desensitization coupling. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, Boston, MA 02114 USA. Tech Univ Munich, Klinikum Rechts Isar, Anasthesiol Klin, D-81675 Munich, Germany. RP Forman, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, 55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [P01-GM58448] NR 59 TC 55 Z9 55 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 2002 VL 22 IS 19 BP 8411 EP 8421 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 597XL UT WOS:000178246000009 PM 12351715 ER PT J AU Richardson-Burns, SM Kominsky, DJ Tyler, KL AF Richardson-Burns, SM Kominsky, DJ Tyler, KL TI Reovirus-induced neuronal apoptosis is mediated by caspase 3 and is associated with the activation of death receptors SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE apoptosis; caspases; CNS; neuroblastoma; neuronal cultures; virus ID CENTRAL-NERVOUS-SYSTEM; ENCEPHALITIS-VIRUS INFECTION; NECROSIS-FACTOR-ALPHA; CELL-DEATH; DNA FRAGMENTATION; BRAIN INJURY; EXPRESSION; INHIBITION; RAT; ISCHEMIA AB Reovirus infection of the central nervous system (CNS) is an important experimental system for understanding the pathogenesis of neurotropic viral infection. Infection of neonatal mice with T3 reoviruses causes lethal encephalitis in which injury results from virus-induced apoptosis. We now show that this apoptosis in vivo is associated with activation of caspase 3, and use neuroblastoma and primary neuronal cultures to identify the cellular pathways involved. Reovirus-induced apoptosis in neuronal cultures is initiated by activation of the tumor necrosis factor (TNF) receptor superfamily death receptors and is inhibited by treatment with soluble death receptors (DRs). The DR-associated initiator caspase, caspase 8, is activated following infection, this activation is inhibited by a cell-permeable peptide inhibitor (IETD-CHO). In contrast to our previous findings in non-neuronal cell lines, reovirus-induced neuronal apoptosis is not accompanied by significant release of cytochrome c from the mitochondria or with caspase 9 activation following infection. This suggests that in neuronal cells, unlike their non-neuronal counterparts, the mitochondria-mediated apoptotic pathway associated with cytochrome c release and caspase 9 activation does not play a significant role in augmenting reovirus-induced apoptosis. Consistent with these results, peptide caspase inhibitors show a hierarchy of efficacy in inhibiting reovirus-induced apoptosis, with inhibitors of caspase 3 > caspase 8 >>> caspase 9. These studies provide a comprehensive profile of the pattern of virus-induced apoptotic pathway activation in neuronal culture. C1 Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1R01AG14071] NR 65 TC 42 Z9 42 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 2002 VL 8 IS 5 BP 365 EP 380 DI 10.1080/13550280290100806 PG 16 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 626FL UT WOS:000179861500002 PM 12402163 ER PT J AU Kaban, LB Troulis, MJ Ebb, D August, M Hornicek, FJ Dodson, TB AF Kaban, LB Troulis, MJ Ebb, D August, M Hornicek, FJ Dodson, TB TI Antiangiogenic therapy with interferon alpha for giant cell lesions of the jaws SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT Combined Meeting of the American-Association-of-Oral-and-Maxillofacial Surgeons/British-Society-of-Oral-and-Maxillofacial-Surgeons CY JUN, 2002 CL KILLARNEY, IRELAND SP Amer Assoc Oral Maxillofacial Surg, British Assoc Oral Maxillofacial Surg ID LIFE-THREATENING HEMANGIOMAS; ENDOTHELIAL GROWTH-FACTOR; ALFA-2A THERAPY; TUMOR; INFANCY; BONE; ANGIOGENESIS; INHIBITION; GRANULOMAS; EXPRESSION AB Purpose: Giant cell tumors are classified and treated based on their biologic behavior. We hypothesize that they are proliferative vascular lesions and would be expected to respond to antiangiogenic therapy. The purpose of this report is to present a treatment protocol consisting of enucleation, with preservation of vital structures, followed by subcutaneous interferon alpha. Materials and Methods: Patients with a biopsy-confirmed giant cell lesion satisfying criteria for "aggressive giant cell tumor" were included. Instead of wide en bloc resection, lesions were enucleated and the patients started on interferon alpha-2 or beta (3,000,000 units/m(2)) 48 to 72 hours postoperatively. The subjects were followed by clinical examination and radiography, immediately after surgery and every 3 months until the bone cavity completely healed. Thereafter, follow-up was every 6 months. Results: Eight patients (7 females), with a mean age of 18.7 +/- 11.1 years, have been enrolled. Six tumors were in the posterior mandible, and 2 were in the anterior maxilla. The mean size was 29.0 mm (range, 15 to 70 mm). All patients underwent enucleation. There were no postoperative complications, and all patients tolerated interferon. There was no evidence of tumor growth during treatment. Seven of 8 patients have completed interferon therapy, and there have been no recurrences during 1 to 6 years of follow-up. The other patient continues on treatment with no evidence of disease. Conclusion: Antiangiogenic therapy, in combination with curettage, is a promising strategy for treatment of aggressive giant cell tumors. Combined treatment results in a high rate of tumor control with decreased operative morbidity compared with conventional treatment. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept OMS, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept OMS, Warren bldg 1201,55 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [K-23 DE14070-02, K-24-DE 00448-02] NR 51 TC 86 Z9 93 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2002 VL 60 IS 10 BP 1103 EP 1111 DI 10.1053/joms.2002.34975 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 600LN UT WOS:000178392000002 PM 12378481 ER PT J AU Manne, S DuHamel, K Nereo, N Ostroff, J Parsons, S Martini, R Williams, S Mee, L Sexson, S Wu, L Difede, J Redd, WH AF Manne, S DuHamel, K Nereo, N Ostroff, J Parsons, S Martini, R Williams, S Mee, L Sexson, S Wu, L Difede, J Redd, WH TI Predictors of PTSD in mothers of children undergoing bone marrow transplantation: The role of cognitive and social processes SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE posttraumatic stress disorder; pediatric bone marrow transplantation; mothers; psychological distress ID POSTTRAUMATIC-STRESS-DISORDER; PEDIATRIC CANCER SURVIVORS; PSYCHOMETRIC PROPERTIES; SCREENING INSTRUMENT; SYMPTOMATOLOGY; INVENTORY; SYMPTOMS; SUPPORT; DEPRESSION; DIAGNOSIS AB Objective: To investigate the role of cognitive and social processing in posttraumatic stress symptoms and disorder (PTSD) among mothers of children undergoing bone marrow and hematopoietic stem-cell transplantation (BMT/SCT). Method: Questionnaires assessing emotional distress, BMT-related fears, and negative responses of family and friends were completed by 90 mothers at the time of the BMT infusion and 3 and 6 months post-BMT. PTSD symptoms were measured 6 months post-BMT by both paper-and-pencil and structured interview methods. Results: Emotional distress, BMT-related fears, and negative responses of family and friends assessed at the time of BMT hospitalization were predictive of later PTSD symptoms. None of these variables prospectively predicted a PTSD diagnosis as measured by the structured interview. Conclusions: Higher levels of general psychological distress, cognitive interpretations of the threat of the BMT for the child's future functioning, and negative responses of family and friends may place mothers at risk for post-BMT posttraumatic stress symptomatology. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Mt Sinai Sch Med, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Med Ctr, Evanston, IL 60208 USA. Stanford Univ, Med Ctr, Packard Childrens Hosp, Stanford, CA 94305 USA. Emory Univ, Med Ctr, Atlanta, GA 30322 USA. RP Manne, S (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 7701 Burholme Ave,CPP Suite 1100, Philadelphia, PA 19111 USA. FU NIMH NIH HHS [MH57738] NR 34 TC 60 Z9 60 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD OCT PY 2002 VL 27 IS 7 BP 607 EP 617 DI 10.1093/jpepsy/27.7.607 PG 11 WC Psychology, Developmental SC Psychology GA 593NP UT WOS:000177998600006 PM 12228332 ER PT J AU Cassano, P Fava, M AF Cassano, P Fava, M TI Depression and public health - An overview SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE comorbidity; depression; management; medical illnesses; primary care; public health ID PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; RANDOMIZED TRIAL; GLOBAL BURDEN; SUSTAINED-RELEASE; SMOKING CESSATION; COMMUNITY SAMPLE; EUROPEAN-SOCIETY; MEDICAL OUTCOMES; HIGH UTILIZERS AB Depressive disorders are a significant public health issue. They are prevalent, disabling, often chronic illnesses, which cause a high economic burden for society, related to both direct and indirect costs. Depressive disorders also influence significantly the outcome of comorbid medical illnesses such as cardiac diseases, diabetes, and cancer. In primary care, underrecognition and undertreatment of depressive disorders are common, despite their relatively high prevalence, which accounts typically for more than 10% of patients. Primary care physicians should be aware of the common risk factors for depressive disorders such as gender, neuroticism, life events and adverse childhood experiences, and they should be familiar with associated features such as a positive psychiatric family history and prior depressive episodes. In primary care settings, depressive disorders should be considered with patients with multiple medical problems, unexplained physical symptoms, chronic pain or use of medical services that is more frequent than expected. Management of depressive disorders in primary care should include treatment with the newer antidepressant agents (given the fact they are typically well tolerated and safe) and focus on concomitant unhealthy behaviors as well as treatment adherence, which may both affect patient outcome. Programs aimed at improving patient follow-up and the coordination of the primary care intervention with that of specialists have been found to improve patient outcomes and to be cost effective. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkham St,ACC 812, Boston, MA 02114 USA. RI Cassano, Paolo/I-6959-2012 NR 95 TC 201 Z9 210 U1 12 U2 39 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 OCT PY 2002 VL 53 IS 4 BP 849 EP 857 AR PII S0022-3999(02)00304-5 DI 10.1016/S0022-3999(02)00304-5 PG 9 WC Psychiatry SC Psychiatry GA 606ME UT WOS:000178737100004 PM 12377293 ER PT J AU Wagner, KD Weller, EB Carlson, GA Sachs, G Biederman, J Frazier, JA Wozniak, P Tracy, K Weller, RA Bowden, C AF Wagner, KD Weller, EB Carlson, GA Sachs, G Biederman, J Frazier, JA Wozniak, P Tracy, K Weller, RA Bowden, C TI An open-label trial of divalproex in children and adolescents with bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; divalproex; children; adolescents ID ONSET MANIA; LITHIUM; PHENOTYPE; ATTENTION; EFFICACY; RECOVERY; PLACEBO; RELAPSE; SODIUM AB Objective: This study evaluated the safety and effectiveness of divalproex sodium (Depakote(R)) in the treatment of youths with bipolar disorder. Method: Forty bipolar disorder patients aged 7 to 19 years, with a manic. hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks). Results: Twenty-two subjects (61%) showed greater than or equal to 50% a improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant (p < .001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis. Conclusion: This study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths. C1 Univ Texas, Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA. Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Bipolar Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Abbott Labs, N Chicago, IL 60064 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Wagner, KD (reprint author), Univ Texas, Med Branch, Dept Psychiat & Behav Sci, 301 Univ Blvd, Galveston, TX 77555 USA. NR 27 TC 85 Z9 88 U1 0 U2 2 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 OCT PY 2002 VL 41 IS 10 BP 1224 EP 1230 DI 10.1097/01.CHI.0000020278.43550.E6 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 597CC UT WOS:000178203700012 PM 12364844 ER PT J AU Yun, PL Tachihara, R Anderson, RR AF Yun, PL Tachihara, R Anderson, RR TI Efficacy of erbium: yttrium-aluminum-garnet laser-assisted delivery of topical anesthetic SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ER-YAG LASER; EMLA CREAM; EUTECTIC MIXTURE; PRILOCAINE EMLA; LIDOCAINE; STIMULATION; ANALGESIA; DEPTH; PAIN; SKIN AB Background: Penetration through the stratum corneum limits effectiveness of topical anesthetics. Objective: Our aim was to evaluate the effectiveness of 5% lidocaine (ELA-Max) cream applied after erbium:yttrium-aluminum-garnet (Er:YAG) laser ablation of the stratum corneum. Methods: Randomized, controlled, split-face comparison of anesthesia was performed on 12 volunteers. The stratum corneum was painlessly ablated with a low-fluence Er:YAG laser on half of the face, then the whole face was covered with ELA-Max cream for 60 minutes. Full-face laser resurfacing was performed, and visual analog pain scores (0 to 10) were recorded during each of 2 passes. Results: Laser-assisted topical anesthesia demonstrated significantly lower mean pain scores than topical anesthesia alone. This was more pronounced during the more painful second pass. Resurfacing after laser-assisted topical anesthesia was well tolerated by 72% of subjects in pass 1 and 58% in pass 2. Conclusion: Laser-assisted topical anesthesia is fast, painless, and substantially more effective than conventional topical anesthesia but does not provide adequate anesthesia for full-face resurfacing in all subjects. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dermatol Laser Ctr, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett Hall Extens 630,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 34 Z9 34 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2002 VL 47 IS 4 BP 542 EP 547 DI 10.1067/mjd.2002.124819 PG 6 WC Dermatology SC Dermatology GA 600MZ UT WOS:000178395900012 PM 12271298 ER PT J AU Balcom, JH Keck, T Warshaw, AL Graeme-Cook, F Fernandez-del Castillo, C AF Balcom, JH Keck, T Warshaw, AL Graeme-Cook, F Fernandez-del Castillo, C TI Prevention of pancreatic fistula with a new synthetic, absorbable sealant: Evaluation in a dog model SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 20-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract ID DISTAL PANCREATECTOMY; HEAD RESECTION; AIR LEAKS; PANCREATICODUODENECTOMY; COMPLICATIONS; OCTREOTIDE; GLUE; SURGERY; TRIAL; PANCREATICOJEJUNOSTOMY AB BACKGROUND: Pancreatic fistula complicates up to 15% to 25% of pancreatic resections, especially with soft, normal pancreas, and is most common after distal pancreatectomy. A new synthetic, absorbable hydrogel sealant has recently been developed and tested for sealing of human aorta, bronchi, and dura; it is FDA approved as a lung sealant in humans. Our objective was to test the efficacy of the sealant in preventing pancreatic leaks in a dog model of distal pancreatectomy. STUDY DESIGN: Ten dogs underwent bilateral distal pancreatectomy under general anesthesia. Animals were randomized to receive application of the sealant to the pancreatic stumps (n = 5) or no treatment (n = 5). The transected pancreatic duct was not ligated, and the end of the pancreas was neither oversewn nor stapled; closed-suction drains were placed in proximity to the pancreatic stumps before abdominal closure. All animals received normal chow starting on the second postoperative day. Drainage was collected for volume and amylase determination twice daily for 14 days, after which the animals were sacrificed. Pancreatic tissue was collected from the area of transection and was formalin fixed for histopathology. RESULTS: There was no perloperative mortality. Fluid recovered from closed-suction drains in all animals was uniformly amylase-rich. Over the 14-day study period, daily volume of pancreatic drainage was significantly different between control animals and animals treated with sealant (p < 0.001). By postoperative day 6, the total mean pancreatic drainage in dogs treated with sealant was 25 +/- 5 mL/drain (versus 91 +/- 26 mL/drain in untreated dogs; p < 0.05). This is the point at which we remove the drains in our clinical practice. Examination at 14 days revealed intact sealant at the pancreatic stumps in the treatment group, and histopathology showed a characteristic benign histiocyte reaction to the sealant but no other qualitative differences in the degree of inflammation between control and treatment animals. There were no undrained collections or abscesses. CONCLUSIONS: A new synthetic hydrogel sealant prevents the formation of significant pancreatic fistulae after distal pancreatectomy in the dog and may be suitable for clinical application. (C) 2002 by the American College of Surgeons. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,55 Fruit St, Boston, MA 02114 USA. NR 31 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD OCT PY 2002 VL 195 IS 4 BP 490 EP 496 DI 10.1016/S1072-7515(02)01313-3 PG 7 WC Surgery SC Surgery GA 600GC UT WOS:000178381400009 PM 12375754 ER PT J AU Amory, JK Chansky, HA Chansky, KL Camuso, MR Hoey, CT Anawalt, BD Matsumoto, AM Bremner, WJ AF Amory, JK Chansky, HA Chansky, KL Camuso, MR Hoey, CT Anawalt, BD Matsumoto, AM Bremner, WJ TI Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE arthritis; arthroplasty; FIM; rehabilitation ID RANDOMIZED CONTROLLED TRIAL; TOTAL HIP; ELECTIVE HIP; ARTHROPLASTY; FRACTURE AB Objectives: Older patients undergoing knee replacement surgery can recover more slowly than younger patients and require extended rehabilitation. Because administration of supraphysiological testosterone (T) dramatically increases strength, we hypothesized that preoperative T therapy would improve functional recovery and reduce hospital stay in older men undergoing knee replacement surgery. Design: Double-blinded, placebo-controlled pilot trial. Setting: A Veterans Affairs orthopedics clinic and inpatient postoperative unit. Participants: Twenty-five men, mean age 70, undergoing elective knee replacement. Intervention: Preoperative, supraphysiological T administration (600 mg T enanthate intramuscularly weekly for 4 weeks) or sesame oil placebo. Measurements: Length of hospital stay and functional ability by Functional Independence Measure (FIM) score. Results: Mean length of hospital stay +/- standard deviation was nonsignificantly reduced in the T group (5.9+/-2.4 days vs 6.8+/-2.5 days; P=.15). At postoperative Day 3, there was a significant improvement in ability to stand (mean FIM score 5.2+/-1.0 vs 4.0+/-1.1; P=.04) and trends towards improvements in walking and stair climbing in the T group. There were no complications attributable to T therapy. Conclusions: In older men undergoing knee replacement surgery, preoperative supraphysiological T administration may confer some clinical benefit. Future studies using longer courses of preoperative T administration in larger numbers of older men undergoing knee replacement surgery are warranted. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Orthoped, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Pharm, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Geriatr Clin Res Ctr, Seattle, WA USA. RP Amory, JK (reprint author), Univ Washington, Dept Med, Box 356429,1959 NE Pacific St, Seattle, WA 98195 USA. NR 16 TC 42 Z9 43 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2002 VL 50 IS 10 BP 1698 EP 1701 DI 10.1046/j.1532-5415.2002.50462.x PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 602AP UT WOS:000178482800011 PM 12366624 ER PT J AU Sanicola, SM Arnold, TB Osher, L AF Sanicola, SM Arnold, TB Osher, L TI Is the radiographic appearance of the hallucal tarsometatarsal joint representative of its true anatomical structure? SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID AUSTRALOPITHECUS-AFARENSIS; EVOLVING FOOT AB The medial cuneiforms and first metatarsals were identified in 515 randomly selected specimens at the Hamman-Todd osteology collection in the Cleveland Museum of Natural History in Cleveland, Ohio, and the transverse plane angulation of the hallucal tarsometatarsal joint was determined by direct measurement of the selected bones. Medial cuneiforms were subsequently separated into three categories corresponding to the amount of measured obliquity. The first tarsometatarsal joint was reassembled, and the paired medial cuneiforms and first metatarsals were radiographed at different declination angles in inverted, everted, and rectus positions. Radiographic evaluation revealed discordance between the appearance of atavism and true atavism in the cuneiform. Specifically, it was determined that the position of the hallucal tarsometatarsal joint significantly influenced the appearance of atavism in the cuneiform. It is concluded that the position of the first ray in an anteroposterior radiograph can produce the appearance of an increased obliquity angle of the medial cuneiform, resulting in an inaccurate representation of the hallucal tarsometatarsal joint. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Sanicola, SM (reprint author), Denver Vet Affairs Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. NR 35 TC 4 Z9 4 U1 0 U2 0 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD OCT PY 2002 VL 92 IS 9 BP 491 EP 498 PG 8 WC Orthopedics SC Orthopedics GA 607PZ UT WOS:000178801100003 PM 12381798 ER PT J AU Scherrer-Crosbie, M Glysing-Jensen, T Fry, SJ Vancon, AC Gadiraju, S Picard, MH Russell, ME AF Scherrer-Crosbie, M Glysing-Jensen, T Fry, SJ Vancon, AC Gadiraju, S Picard, MH Russell, ME TI Echocardiography improves detection of rejection after heterotopic mouse cardiac transplantation SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR MASS; HEART-TRANSPLANTATION; KNOCKOUT MICE; IN-VIVO; ARTERIOSCLEROSIS; HYPERTROPHY; ALLOGRAFTS; MODELS AB Background: Current assessments of cardiac rejection in murine transplant models rely on subjective estimates of the force of the palpable heart beat that have limited sensitivity and precision. Methods: We used 2-dimensional echocardiography to evaluate changes in left ventricular posterior wall thickness (PWT) in a heterotopic cardiac mouse transplant model of rejection. Nine allografts and 6 isografts were imaged daily for 6 days and harvested. Thirteen allografts were imaged daily and harvested at day 3. Results: Intraobserver variability on PWT was 0.003 +/- 0.09 mm, interobserver variability 0.09 +/- 0.11 mm. Allograft PWT increased after transplantation (0.74 +/- 0.02 mm to 1.28 +/- 0.05 mm at day 5, P < .0001). For isografts, PWT remained constant (0.73 +/- 0.03 mm to 0.85 +/- 0.01 mm) after an initial increase at day 1. Palpation failed to identify rejection at day 3 whereas PWT was already increased (1.15 +/- 0.02 mm in the allografts at day 3 vs 0.85 +/- 0.02 mm in the isografts, P < .0001). There was a relation between histologic score and PWT (P < .0001). Conclusion: Two-dimensional echocardiography allows the noninvasive detection and follow-up of cardiac rejection after transplantation. It eliminates the subjectivity of palpation and provides quantitative and reliable indices of rejection. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 22 TC 9 Z9 9 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD OCT PY 2002 VL 15 IS 10 BP 1315 EP 1320 DI 10.1067/mje.2002.124644 PN 2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 605FL UT WOS:000178666700031 PM 12411923 ER PT J AU Rhea, JT AF Rhea, JT TI Lumbar fractures in adult blunt trauma: Axial and single-slice helical abdominal and pelvic computed tomographic scans versus portable plain films - Editorial comment SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Emergency Radiol Div, Boston, MA 02114 USA. RP Rhea, JT (reprint author), Massachusetts Gen Hosp, Emergency Radiol Div, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD OCT PY 2002 VL 53 IS 4 BP 667 EP 667 PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 604JZ UT WOS:000178618400011 ER PT J AU Ruscio, AM Weathers, FW King, LA King, DW AF Ruscio, AM Weathers, FW King, LA King, DW TI Male war-zone veterans' perceived relationships with their children: The importance of emotional numbing SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the International-Society-of-Traumatic-Stress-Studies CY NOV 20-23, 1998 CL WASHINGTON, D.C. SP Int Soc Traumat Stress Studies DE posttraumatic stress disorder; emotional numbing; parent-child relationship; interpersonal problems ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM COMBAT VETERANS; ADMINISTERED PTSD SCALE; ADJUSTMENT; FAMILY AB Despite growing recognition of substantial interpersonal impairment among many war-zone veterans with posttraumatic stress disorder (PTSD), little is known about the association between PTSD symptomatology and veterans' relationships with their children. This study examined the differential pattern of associations between the symptom clusters of PTSD and the perceived father-child relationships of 66 male Vietnam veterans. Analyses revealed that only the emotional numbing cluster was significantly related to perceived quality of all relationship domains. The association between emotional numbing and perceived relationship quality remained significant in regression analyses even after controlling for fathers' family-of-origin stressors, combat exposure, depression, and substance abuse. Findings suggest that emotional numbing may be the component of PTSD most closely linked to interpersonal impairment in war-zone veterans. C1 Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA. Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Ruscio, AM (reprint author), Penn State Univ, Dept Psychol, 429 Bruce V,Moore Bldg, University Pk, PA 16802 USA. FU NIMH NIH HHS [MH12675] NR 29 TC 135 Z9 135 U1 5 U2 17 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2002 VL 15 IS 5 BP 351 EP 357 AR UNSP 0894-9867/02/1000-0351/1 DI 10.1023/A:1020125006371 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 593AK UT WOS:000177968900002 PM 12392222 ER PT J AU Bromley, B Lieberman, E Shipp, TD Benacerraf, BR AF Bromley, B Lieberman, E Shipp, TD Benacerraf, BR TI The genetic sonogram - A method of risk assessment for Down syndrome in the second trimester SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE aneuploidy risk assessment; fetal Down syndrome markers; genetic sonogram; prenatal sonography; trisomy 21 ID 2ND-TRIMESTER ULTRASOUND MARKERS; ECHOGENIC INTRACARDIAC FOCUS; SCORING INDEX; 2ND TRIMESTER; MATERNAL AGE; NUCHAL FOLD; ULTRASONOGRAPHIC MARKERS; AUTOSOMAL TRISOMY; FETUSES; AMNIOCENTESIS AB To determine the risk of Down syndrome in fetuses with sonographic markers using the Bayes theorem and likelihood ratios. Methods. We prospectively evaluated the midtrimester sonographic features of fetuses with Down syndrome and compared them with euploid fetuses. Patients were referred for an increased risk of aneuploidy and evaluated for the presence of structural defects, a nuchal fold, short long bones, pyelectasis, an echogenic intracardiac focus, and hyperechoic bowel. All fetuses underwent amniocentesis at the time of sonographic assessment. The sensitivity, specificity, and likelihood ratios for markers were calculated both as nonisolated and isolated findings. Results. There were 164 fetuses with Down syndrome and 656 euploid fetuses. The presence of any marker resulted in sensitivity for the detection of Down syndrome of 80.5% with a false-positive rate of 12.4%. The absence of any markers conferred a likelihood ratio of 0.2, decreasing the risk of Down syndrome by 80%. As an isolated marker, the nuchal fold had an "infinite" likelihood ratio for Down syndrome; a short humerus had a likelihood ratio of 5.8, whereas structural anomalies had a likelihood ratio of 3.3. Other isolated markers had low likelihood ratios because of the higher prevalence in the unaffected population. The likelihood ratios for the presence of 1, 2, and 3 of any of the markers were 1.9, 6.2, and 80, respectively. Conclusions. Although an isolated marker with a low likelihood ratio may not increase a patient's risk of Down syndrome, the presence of such a marker precludes reducing the risk of aneuploidy. Clusters of markers appear to confer a higher risk. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 42 TC 102 Z9 108 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD OCT PY 2002 VL 21 IS 10 BP 1087 EP 1096 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 599DR UT WOS:000178319300004 PM 12369663 ER PT J AU Xiang, SH Kwong, PD Gupta, R Rizzuto, CD Casper, DJ Wyatt, R Wang, LP Hendrickson, WA Doyle, ML Sodroski, J AF Xiang, SH Kwong, PD Gupta, R Rizzuto, CD Casper, DJ Wyatt, R Wang, LP Hendrickson, WA Doyle, ML Sodroski, J TI Mutagenic stabilization and/or disruption of a CD4-bound state reveals distinct conformations of the human immunodeficiency virus type 1 gp120 envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Review ID CAVITY-CREATING MUTATIONS; HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID CHANGES; T-CELL-LINE; RECEPTOR-BINDING; HUMAN CD4; CHEMOKINE RECEPTORS; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; HYDROPHOBIC CORE AB The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein is conformationally flexible. Upon binding to the host cell receptor CD4, gp120 assumes a conformation that is recognized by the second receptor, CCR5 and/or CXCR4, and by the CD4-induced (CD4i) antibodies. Guided by the X-ray crystal structure of a gp120-CD4-CD4i antibody complex, we introduced changes into gp120 that were designed to stabilize or disrupt this conformation. One mutant, 375 S/W, in which the tryptophan indole group is predicted to occupy the Phe 43 cavity in the gp120 interior, apparently favors a gp120 conformation closer to that of the CD4-bound state. The 375 S/W mutant was recognized, as well as or better than wild-type gp120 by CD4 and CD4i antibodies, and the large decrease in entropy observed when wild-type gp120 bound CD4 was reduced for the 375 S/W mutant. The recognition of the 375 S/W mutant by CD4BS antibodies, which are directed against the CD4-binding region of gp120, was markedly reduced compared with that of the wild-type gp120. Compared with the wild-type virus, viruses with the 375 S/W envelope glycoproteins were resistant to neutralization by IgG1b12, a CD4BS antibody, were slightly more sensitive to soluble CD4 neutralization and were neutralized more efficiently by the 2G12 antibody. Another mutant, 423 I/P, in which the gp120 bridging sheet was disrupted, did not bind CD4, CCR5, or CD4i antibodies, even though recognition by CD4BS antibodies was efficient. These results indicate that CD4BS antibodies recognize conformations of gp120 different from that recognized by CD4 and CD4i antibodies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. GlaxoSmithKline Pharmaceut, Dept Biol Struct, King Of Prussia, PA 19406 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI41815, AI24030, AI24755, AI31783, AI42848, P30 AI042848, R01 AI024030, R01 AI031783, R01 AI041851, R37 AI024755] NR 102 TC 138 Z9 140 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2002 VL 76 IS 19 BP 9888 EP 9899 DI 10.1128/JVI.76.19.9888-9899.2002 PG 12 WC Virology SC Virology GA 590XE UT WOS:000177849100031 PM 12208966 ER PT J AU Allen, TM Jing, PC Calore, B Horton, H O'Connor, DH Hanke, T Piekarczyk, M Ruddersdorf, R Mothe, BR Emerson, C Wilson, N Lifson, JD Belyakov, IM Berzofsky, JA Wang, CX Allison, DB Montefiori, DC Desrosiers, RC Wolinsky, S Kunstman, KJ Altman, JD Sette, A McMichael, AJ Watkins, DI AF Allen, TM Jing, PC Calore, B Horton, H O'Connor, DH Hanke, T Piekarczyk, M Ruddersdorf, R Mothe, BR Emerson, C Wilson, N Lifson, JD Belyakov, IM Berzofsky, JA Wang, CX Allison, DB Montefiori, DC Desrosiers, RC Wolinsky, S Kunstman, KJ Altman, JD Sette, A McMichael, AJ Watkins, DI TI Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; VIRAL REPLICATION; HIV-1 INFECTION; PATHOGENIC SIV; VACCINE; AIDS; PROTECTION; INDUCTION; MACAQUES; VIREMIA AB Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication. C1 Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. John Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England. NCI, Retroviral Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Alabama, Sect Stat Genet, Dept Biostat, Birmingham, AL 35294 USA. Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Epimmune Inc, San Diego, CA 92121 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53706 USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Wolinsky, Steven/B-2893-2012; Allen, Todd/F-5473-2011; OI Wolinsky, Steven/0000-0002-9625-6697; o'connor, david/0000-0003-2139-470X; Allison, David/0000-0003-3566-9399 FU NCI NIH HHS [CA 79458, N01 CO 56000]; NCRR NIH HHS [P51 RR000167, RR 00167]; NIAID NIH HHS [AI 46366, AI 38081, AI 49120, R01 AI046366, R01 AI049120, R56 AI049120] NR 41 TC 54 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2002 VL 76 IS 20 BP 10507 EP 10511 DI 10.1128/JVI.76.20.10507-10511.2002 PG 5 WC Virology SC Virology GA 599DV UT WOS:000178319600046 PM 12239328 ER PT J AU Simmons, SF Babineau, S Garcia, E Schnelle, JF AF Simmons, SF Babineau, S Garcia, E Schnelle, JF TI Quality assessment in nursing homes by systematic direct observation: Feeding assistance SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LONG-TERM-CARE; WEIGHT-LOSS; RESIDENTS; DIFFICULTIES; MEALTIME; STAFF AB Background. Direct observation of care is an important data source for nursing home (NH) quality assessment, especially in light of evidence that chart information is inaccurate or incomplete for many daily care areas. The purpose of this study was to describe a standardized feeding assistance observational protocol that is designed for routine use by external (survey teams) and internal (licensed NH staff) quality assurance personnel to (i) maximize the amount Of useful information gained from relatively brief observational periods; (ii) provide specific rules of measurement, which allow for replication and valid comparisons between NHs; and (iii) provide specific scoring rules that allow defensible categorical statements to be made about feeding assistance care quality within the NH. Methods. Four feeding assistance care quality indicators (QIs) were defined and operationalized in this study for 302 long-term residents in 10 skilled NHs: (i) Staff ability to accurately identify residents with clinically significant low oral food and fluid intake during mealtime; (ii) Staff ability to provide feeding assistance to at-risk residents during mealtime; (iii) Staff ability to provide feeding assistance to residents identified by the Minimum Data Set as requiring staff assistance to eat; and (iv) Staff ability to provide a verbal prompt to residents who receive physical assistance at mealtimes. Results. There were significant differences between facilities for three of the four QIs. The proportion of participants in each facility where staff "failed" the QIs ranged as follows: (Quality Indicator i) 42% to 91%; (ii) 25% to 73%; (iii) 11% to 82%; and (iv) 0% to 100%. Conclusions. A standardized observational protocol can be used to accurately measure the quality of feeding assistance care in NHs. This protocol is replicable and shows significant differences between facilities with respect to accuracy of oral intake documentation and the adequacy and quality of feeding assistance during mealtimes. C1 Univ Calif Los Angeles, Borun Ctr Gerontol Res, Sch Med, Dept Geriatr, Los Angeles, CA USA. Jewish Home Aging, Reseda, CA USA. Brown Univ, Sch Med, Providence, RI USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Sepulveda Geriatr Res, Educ & Clin Ctr, Sepulveda, CA USA. RP Simmons, SF (reprint author), Univ Calif Los Angeles, Borun Ctr Gerontol Res, Jewish Home Aging, 7150 Tampa Ave, Reseda, CA 91335 USA. NR 26 TC 52 Z9 53 U1 1 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2002 VL 57 IS 10 BP M665 EP M671 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 598TB UT WOS:000178291600013 PM 12242322 ER PT J AU Berfield, AK Andress, DL Abrass, CK AF Berfield, AK Andress, DL Abrass, CK TI IGF-1-induced lipid accumulation impairs mesangial cell migration and contractile function SO KIDNEY INTERNATIONAL LA English DT Article DE mesangial cell; IGF-1; IGFBP-5; contraction; migration; atherosclerosis; lipids; glomerulosclerosis ID LOW-DENSITY-LIPOPROTEIN; GROWTH-FACTOR-I; MONOCYTE CHEMOATTRACTANT PROTEIN-1; EXTRACELLULAR-MATRIX; GLOMERULAR INJURY; ANGIOTENSIN-II; MESSENGER-RNA; INSULIN; GLOMERULOSCLEROSIS; EXPRESSION AB Background. Chronic treatment of mesangial cells with insulin-like growth factor-1 (IGF-1) results in intracellular lipid accumulation. These mesangial cells resemble foam cells. Methods. To determine whether this phenotype affects cell function, lipid-laden mesangial cells were tested for their ability to migrate in response to IGF-binding protein-5 (IGFBP-5) and to contract in response to angiotensin II (Ang II). IGFBP-5 binding and subsequent activation of the signal transduction cascade for migration were examined. To confirm that lipid accumulation was responsible for impaired contractility, lipid was removed from lipid-laden mesangial cells and the cells were re-tested for contractile response to Ang II. Results. In comparison to control mesangial cells, lipid-laden cells failed to migrate in response to IGFBP-5. Although cellular binding of IGFBP-5 was not altered by lipid accumulation, IGFBP-5 failed to activate cdc42, a Rho GTPase required for IGFBP-5-mediated mesangial cell migration. These data indicate that lipid accumulation within the mesangial cell interferes with the signal transduction response to IGFBP-5. In addition, mesangial cells treated with IGF-1 had reduced contraction to Ang II. When lipid accumulation was exaggerated by adding cholesteryl esters to the culture medium, mesangial cells failed to contract in response to Ang II. Following removal of excess lipid from these mesangial cells, the contractile response to Ang II was restored. Conclusions. IGF-1 induces lipid accumulation in mesangial cells, which impairs their ability to respond to specific migratory and contractile stimuli. These observations are relevant to understanding functional abnormalities in diseases where mesangial foam cells occur, such as focal and segmental glomerulosclerosis and diabetic nephropathy. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. RP Abrass, CK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Nephrol, 111A,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAMS NIH HHS [R01 AR-44911]; NIDDK NIH HHS [R01 DK-49771] NR 45 TC 24 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 2002 VL 62 IS 4 BP 1229 EP 1237 DI 10.1046/j.1523-1755.2002.00578.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 594GV UT WOS:000178042000013 PM 12234293 ER PT J AU Metson, R Samaha, M AF Metson, R Samaha, M TI Reduction of diplopia following endoscopic orbital decompression: The orbital sling technique SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern-Section of the Triological-Society CY JAN 25-27, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Triol Soc DE orbital decompression; diplopia; endoscopic orbital decompression; Graves disease ID OPHTHALMOPATHY; STRUT AB Objective: Although endoscopic orbital decompression has become the surgical treatment of choice for patients with proptosis from Graves disease, postoperative diplopia requiring corrective eye muscle surgery can occur in up to 63% of patients. The purpose of the study was to evaluate a new technique intended to reduce the incidence of diplopia following endoscopic orbital decompression. Study Design: Case-control. Methods: Endoscopic orbital decompression was performed on 58 orbits in 37 patients with proptosis from Graves disease. The orbital sling technique, which makes use of a horizontal strip of periorbital fascia to prevent prolapse of the medial rectus muscle, was used on 20 orbits in 13 patients. Conventional endoscopic decompression was performed in 24 control subjects. The mean duration of follow-up was 3.3 +/- 1.3 years (range, 1.7-5.1 y). Results: The incidence of new-onset or worsened diplopia following endoscopic decompression was significantly lower for the orbital sling group compared with control subjects (0% vs. 29.2%, respectively [P = .038]). No patients in the orbital sling group developed new-onset diplopia following surgery. Of the eight patients with pre-existing diplopia from the orbitopathy, double vision improved in four patients (50%) and was unchanged in the remaining four patients (50%). The mean reduction in proptosis was comparable for the orbital sling and control groups (5.1 +/- 1.1 mm vs. 5.0 +/- 1.9 mm, respectively [P = .98]). Conclusions: The preservation of a fascial sling overlying the medial rectus muscle during endoscopic orbital decompression appears to reduce the incidence of postoperative diplopia, while still allowing for a satisfactory reduction in proptosis. This modification of the standard decompression technique should he considered for the treatment of patients with proptosis. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 13 TC 34 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2002 VL 112 IS 10 BP 1753 EP 1757 DI 10.1097/00005537-200210000-00008 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 603ZE UT WOS:000178590500008 PM 12368609 ER PT J AU Stripecke, R Levine, AM Pullarkat, V Cardoso, AA AF Stripecke, R Levine, AM Pullarkat, V Cardoso, AA TI Immunotherapy with acute leukemia cells modified into antigen-presenting cells: ex vivo culture and gene transfer methods SO LEUKEMIA LA English DT Review DE AML; ALL; CD40L; GM-CSF; CD80; immunotherapy; gene therapy; lentivirus ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; HUMAN HEMATOPOIETIC-CELLS; T-LYMPHOCYTE ACTIVATION; MHC CLASS-I; IMMUNE-RESPONSE AB Adult patients with acute leukemia have, in general, a poor prognosis, with long-term, disease-free survival achieved in only approximately one-third of cases. One of the proposed mechanisms for this poor overall response is the inability of the immune system to detect and eliminate residual malignant leukemia cells, which subsequently serve as a source of leukemic relapse. This review discusses the rationale of immunotherapy for acute leukemia and presents in vitro and in vivo model systems that were devised for pre-B acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML). New advances in the ex vivo manipulation of acute leukemia cells are presented, which attempt to modify these cells into functional antigen-presenting cells. These cells can then be used as autologous vaccines at the time of minimal residual disease after standard chemotherapy, to stimulate host immune responses against their own leukemia cells. The various approaches toward this aim include incubation of leukemia cells with cytokines or growth factors and gene manipulation of these cells. In particular, ex vivo culture of ALL cells with CD40 ligand, incubation of AML cells with granulocyte-macrophage colony-stimulating factor and interleukin-4 (GM-CSF/IL-4) and lentiviral transduction of ALL and AML cells for expression of immunomodulators (CD80 and GM-CSF) are current approaches under investigation for the development of autologous acute leukemia cell vaccines. C1 Univ So Calif, Inst Med Genet, Los Angeles, CA 90033 USA. Univ So Calif, Div Hematol, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Los Angeles, CA 90033 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stripecke, R (reprint author), Univ So Calif, Inst Med Genet, 2250 Alcazar St CSC-240, Los Angeles, CA 90033 USA. FU NCI NIH HHS [K01-CA87864-01, P01 CA6848] NR 90 TC 41 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2002 VL 16 IS 10 BP 1974 EP 1983 DI 10.1038/sj.leu.2402701 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 603YV UT WOS:000178589600009 PM 12357348 ER PT J AU Tuch, DS Reese, TG Wiegell, MR Makris, N Belliveau, JW Wedeen, VJ AF Tuch, DS Reese, TG Wiegell, MR Makris, N Belliveau, JW Wedeen, VJ TI High angular resolution diffusion imaging reveals intravoxel white matter fiber heterogeneity SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion; diffusion-weighted MRI (DWI); diffusion tensor imaging (DTI); white matter; tractography ID MAGNETIC-RESONANCE; IN-VIVO; HUMAN BRAIN; TENSOR MRI; TOPOGRAPHIC PARCELLATION; AXONAL PROJECTIONS; WATER DIFFUSION; ARCHITECTURE; TRACKING; PATHWAYS AB Magnetic resonance (MR) diffusion tensor imaging (DTI) can resolve the white matter fiber orientation within a voxel provided that the fibers are strongly aligned. However, a given voxel may contain a distribution of fiber orientations due to, for example, intravoxel fiber crossing. The present study sought to test whether a geodesic, high b-value diffusion gradient sampling scheme could resolve multiple fiber orientations within a single voxel. In regions of fiber crossing the diffusion signal exhibited multiple local maxima/minima as a function of diffusion gradient orientation, indicating the presence of multiple intravoxel fiber orientations. The multimodality of the observed diffusion signal precluded the standard tensor reconstruction, so instead the diffusion signal was modeled as arising from a discrete mixture of Gaussian diffusion processes in slow exchange, and the underlying mixture of tensors was solved for using a gradient descent scheme. The multitensor reconstruction resolved multiple intravoxel fiber populations corresponding to known fiber anatomy. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA. RP Wedeen, VJ (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. NR 27 TC 745 Z9 756 U1 0 U2 42 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD OCT PY 2002 VL 48 IS 4 BP 577 EP 582 DI 10.1002/mrm.10268 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 599XT UT WOS:000178361000001 PM 12353272 ER PT J AU Becchetti, FD Sisterson, JM AF Becchetti, FD Sisterson, JM TI High energy electron beams shaped with applied magnetic fields could provide a competitive and cost-effective alternative to proton and heavy-ion radiotherapy SO MEDICAL PHYSICS LA English DT Editorial Material ID PHOTON C1 Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Becchetti, FD (reprint author), Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2002 VL 29 IS 10 BP 2435 EP 2437 DI 10.1118/1.1510453 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 604XR UT WOS:000178646800028 PM 12408319 ER PT J AU Rosen, HR AF Rosen, HR TI Hepatitis C in the liver transplant recipient: current understanding and treatment SO MICROBES AND INFECTION LA English DT Article DE liver transplantation; immunosuppression; recurrent disease; outcomes; rejection ID INTERFERON-ALPHA; RECURRENCE; CIRRHOSIS; IMMUNOSUPPRESSION; CYCLOSPORINE; TACROLIMUS; REJECTION; RIBAVIRIN; INFECTION; OKT3 AB Hepatitis C virus (HCV)-related liver disease is the leading indication for orthotopic liver transplantation worldwide. Recurrent HCV infection as defined by viremia after transplantation is nearly universal, with histologic evidence of recurrent hepatitis present in the majority. Although short-term survival appears to be similar to that in other causes of liver failure, it has recently been demonstrated that approximately 20-30% of HCV-positive patients develop allograft cirrhosis by 5 years. Therefore, it is possible to define disease outcomes within a relatively short period of follow-up. Identification of patients who are likely to develop progressive HCV-related allograft injury is important to optimize results of current antiviral therapy. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Liver Transplantat Program, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, POB 1034,P3-G1,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD OCT PY 2002 VL 4 IS 12 BP 1253 EP 1258 AR PII S1286-4579(02)01653-2 DI 10.1016/S1286-4579(02)01653-2 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 618GL UT WOS:000179410300008 PM 12467767 ER PT J AU Rheinwald, JG Hahn, WC Ramsey, MR Wu, JY Guo, ZY Tsao, H De Luca, M Catricala, C O'Toole, KM AF Rheinwald, JG Hahn, WC Ramsey, MR Wu, JY Guo, ZY Tsao, H De Luca, M Catricala, C O'Toole, KM TI A two-stage, p16(INK4A)- and p53-dependent keratinocyte senescence mechanism that limits replicative potential independent of telomere status (vol 22, pg 5157, 2002) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction 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. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Ist Dermatopat Immacolata, Lab Tissue Engn, Rome, Italy. San Gallicano Hosp, Rome, Italy. RP Rheinwald, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI De Luca, Michele/N-5883-2014 OI De Luca, Michele/0000-0002-0850-8445 NR 1 TC 1 Z9 1 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2002 VL 22 IS 19 BP 6930 EP 6930 DI 10.1128/MCB.22.19.6930.2002 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 592XJ UT WOS:000177961900028 ER PT J AU Taki, K Kogai, T Kanamoto, Y Hershman, JM Brent, GA AF Taki, K Kogai, T Kanamoto, Y Hershman, JM Brent, GA TI A thyroid-specific far-upstream enhancer in the human sodium/iodide symporter gene requires Pax-8 binding and cyclic adenosine 3 ',5 '-monophosphate response element-like sequence binding proteins for full activity and is differentially regulated in normal and thyroid cancer cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID SODIUM-IODIDE SYMPORTER; TRANSCRIPTION FACTOR-I; TISSUE-SPECIFIC EXPRESSION; THYROTROPIN RECEPTOR GENE; POLYMERASE-CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; NA+/I SYMPORTER; KINASE-A; FRTL-5 CELLS; THYROGLOBULIN PROMOTER AB The sodium/iodide symporter (NIS) gene is highly expressed in the thyroid gland and is important for the diagnosis and radioiodide therapy of differentiated thyroid cancers. We investigated a human NIS (hNIS) gene 5'-far-upstream enhancer (hNUE) (-9847 to -8968). The hNUE is TSH responsive in both FRTL-5 cells and primary normal thyroid cells, but not in human papillary thyroid cancer cells (BHP cells). The hNUE enhanced expression of the basal hNIS promoter 15-fold and required both a Pax-8 binding site and a cAMP response element (CRE)-like sequence for full activity. The hNUE activated transcription in a thyroid-selective and cAMP-dependent manner, mediated by both protein kinase A (PKA)-dependent and PKA-independent pathways. Pax-8 and two CRE-like sequence binding proteins bind to the hNUE. Supershift binding assay indicated that one of the CRE-like sequence binding protein(s) was CRE-binding protein-1, activation transcription factor-1, and/or CRE modulator, and the other was an unknown factor(s) that is absent in BHP 2-7 cells. A far-upstream enhancer is important for hNIS regulation in the thyroid. Deficient CRE-like sequence binding protein(s) that bind to the hNUE in normal thyroid cells may be responsible for reduced NIS gene expression in some thyroid carcinomas. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Div Endocrinol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Div Endocrinol, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA-89364] NR 66 TC 65 Z9 67 U1 0 U2 0 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 OCT PY 2002 VL 16 IS 10 BP 2266 EP 2282 DI 10.1210/me.2002-0109 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 598GC UT WOS:000178266700008 PM 12351692 ER PT J AU Ling, LJ Wang, JH Cui, Y Li, W Chen, RS AF Ling, LJ Wang, JH Cui, Y Li, W Chen, RS TI Proteome-wide analysis of protein function composition reveals the clustering and phylogenetic properties of organisms SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID GENOME SEQUENCE; GENE CONTENT; ARCHAEA; TREES AB A 17-dimensional vector named the proteome vector is defined to represent an organism. The components of the vector reflect the relative contents of protein-encoding genes of the 17 cluster of orthologous groups of proteins (COGs) classes in the whole genome of the relevant organism. Based on the definition of this proteome vector, the fuzzy clustering of 36 completely sequenced organisms (8 archaea, 24 bacteria, and 4 eukarya) was performed and a proteome tree was constructed. Our results show that (1) the 36 organisms can be 100% correctly classified into three clusters corresponding to the three primary kingdoms, (2) our proteome tree is remarkably similar to that derived from 16S rRNA, and (3) the chromosomes and/or plasmids belonging to the same organism have very similar gene composition. Based on these results, we argue that the 17-dimensional proteome vector could be a good criterion for clustering approaches and to a large extent reveals the phylogenetic properties of organisms; the Three Primary Kingdoms Hypothesis is trustworthy although the existence of lateral gene transfer (LGT) brings controversy to the construction of the "universal tree of life." (C) 2002 Elsevier Science (USA). All rights reserved. C1 Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China. Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ling, LJ (reprint author), Chinese Acad Sci, Inst Biophys, 15 Datun Rd,Chaoyang Dist, Beijing 100101, Peoples R China. RI Li, Wei/A-8544-2009 NR 20 TC 5 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD OCT PY 2002 VL 25 IS 1 BP 101 EP 111 AR PII S1055-7903(02)00354-8 DI 10.1016/S1055-7903(02)00354-8 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 611QC UT WOS:000179028400009 PM 12383754 ER PT J AU Bond, J Roberts, E Mochida, GH Hampshire, DJ Scott, S Askham, JM Springell, K Mahadevan, M Crow, YJ Markham, AF Walsh, CA Woods, CG AF Bond, J Roberts, E Mochida, GH Hampshire, DJ Scott, S Askham, JM Springell, K Mahadevan, M Crow, YJ Markham, AF Walsh, CA Woods, CG TI ASPM is a major determinant of cerebral cortical size SO NATURE GENETICS LA English DT Article ID RECESSIVE MICROCEPHALY MAPS; NEURONAL MIGRATION; MOLECULAR-GENETICS; ABNORMAL SPINDLE; DROSOPHILA; LOCUS; ADULT; NEUROGENESIS; CENTROSOMES; MUTATIONS AB One of the most notable trends in mammalian evolution is the massive increase in size of the cerebral cortex, especially in primates. Humans with autosomal recessive primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex associated with mild to moderate mental retardation(1-4). Genes linked to this condition offer potential insights into the development and evolution of the cerebral cortex. Here we show that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp)(5), which is essential for normal mitotic spindle function in embryonic neuroblasts(6). The mouse gene Aspm is expressed specifically in the primary sites of prenatal cerebral cortical neurogenesis. Notably, the predicted ASPM proteins encode systematically larger numbers of repeated 'IQ' domains between flies, mice and humans, with the predominant difference between Aspm and ASPM being a single large insertion coding for IQ domains. Our results and evolutionary considerations suggest that brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells. C1 Univ Leeds, St Jamess Univ Hosp, Mol Med Unit, Leeds LS9 7TF, W Yorkshire, England. Univ Leeds, St Jamess Univ Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurol,Div Neurogenet,Harvard Inst Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. RP Woods, CG (reprint author), Univ Leeds, St Jamess Univ Hosp, Mol Med Unit, Beckett St, Leeds LS9 7TF, W Yorkshire, England. RI woods, christopher/A-1361-2010; Crow, Yanick/N-6120-2014; OI Crow, Yanick/0000-0001-7211-7564 NR 30 TC 301 Z9 318 U1 8 U2 19 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 OCT PY 2002 VL 32 IS 2 BP 316 EP 320 DI 10.1038/ng995 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 599AP UT WOS:000178311100024 PM 12355089 ER PT J AU Kavanagh, DG Bhardwaj, N AF Kavanagh, DG Bhardwaj, N TI A division of labor: DC subsets and HIV receptor diversity SO NATURE IMMUNOLOGY LA English DT Editorial Material ID T-CELLS; INFECTION; SIGN AB DCs from different anatomical sites express distinct arrays of alternative HIV receptors. Some of these subsets could represent good gatekeepers, whereas others may be "Trojan horses" that carry HIV into the lymph node. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rockefeller Univ, New York, NY 10021 USA. NYU, Sch Med, New York, NY 10016 USA. RP Kavanagh, DG (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 12 TC 15 Z9 17 U1 2 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2002 VL 3 IS 10 BP 891 EP 893 DI 10.1038/ni1002-891 PG 3 WC Immunology SC Immunology GA 597VU UT WOS:000178242100004 PM 12352961 ER PT J AU Lang, HLE Jacobsen, H Ikemizu, S Andersson, C Harlos, K Madsen, L Hjorth, P Sondergaard, L Svejgaard, A Wucherpfennig, K Stuart, DI Bell, JI Jones, EY Fugger, L AF Lang, HLE Jacobsen, H Ikemizu, S Andersson, C Harlos, K Madsen, L Hjorth, P Sondergaard, L Svejgaard, A Wucherpfennig, K Stuart, DI Bell, JI Jones, EY Fugger, L TI A functional and structural basis for TCR cross-reactivity in multiple sclerosis SO NATURE IMMUNOLOGY LA English DT Article ID T-CELL-RECEPTOR; ELECTRON-DENSITY MAPS; MOLECULAR MIMICRY; CRYSTAL-STRUCTURE; IMMUNODOMINANT PEPTIDE; AUTOIMMUNE-DISEASE; PROTEIN; MYELIN; HLA-DR2; COMPLEX AB The multiple sclerosis (MS)-associated HLA major histocompatibility complex (MHC) class II alleles DRB1*1501, DRB5*0101 and DQB1*0602 are in strong linkage disequilibrium, making it difficult to determine which is the principal MS risk gene. Here we show that together the DRB1 and DRB5 loci may influence susceptibility to MS. We demonstrate that a T cell receptor (TCR) from an MS patient recognized both a DRB1*1501-restricted myelin basic protein (MBP) and DRB5*0101-restricted Epstein-Barr virus (EBV) peptide. Crystal structure determination of the DRB5*0101-EBV peptide complex revealed a marked degree of structural equivalence to the DRB1*1501-MBP peptide complex at the surface presented for TCR recognition. This provides structural evidence for molecular mimicry involving HLA molecules. The structural details suggest an explanation for the preponderance of MHC class II associations in HLA-associated diseases. C1 Univ Oxford, Div Struct Biol, Oxford OX3 7BN, England. John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8200 Aarhus N, Denmark. Rigshosp, Dept Clin Immunol, DK-2200 Copenhagen N, Denmark. Aarhus Univ, Inst Mol & Struct Biol, DK-8000 Aarhus C, Denmark. Univ Copenhagen, Inst Mol Biol, DK-1353 Copenhagen K, Denmark. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Jones, EY (reprint author), Univ Oxford, Div Struct Biol, Henry Wellcome Bldg Genom Med,Roosevelt Dr, Oxford OX3 7BN, England. EM yvonne@strubi.ox.ac.uk; fugger@inet.uni2.dk RI Jones, Yvonne/J-2293-2016; OI Jones, Yvonne/0000-0002-3834-1893; Lang, Heather/0000-0002-9710-0627 NR 36 TC 316 Z9 333 U1 0 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2002 VL 3 IS 10 BP 940 EP 943 DI 10.1038/ni835 PG 4 WC Immunology SC Immunology GA 597VU UT WOS:000178242100014 PM 12244309 ER PT J AU Watanabe, T Nanez, JE Koyama, S Mukai, I Liederman, J Sasaki, Y AF Watanabe, T Nanez, JE Koyama, S Mukai, I Liederman, J Sasaki, Y TI Greater plasticity in lower-level than higher-level visual motion processing in a passive perceptual learning task SO NATURE NEUROSCIENCE LA English DT Article ID DISCRIMINATION TASK; CEREBRAL-CORTEX; V1 NEURONS; ORIENTATION; DIRECTION; SPECIFICITY; ATTENTION; IMPROVEMENT; INTEGRATION; DISPLAYS AB Simple exposure is sufficient to sensitize the human visual system to a particular direction of motion, but the underlying mechanisms of this process are unclear. Here, in a passive perceptual learning task, we found that exposure to task-irrelevant motion improved sensitivity to the local motion directions within the stimulus, which are processed at low levels of the visual system. In contrast, task-irrelevant motion had no effect on sensitivity to the global motion direction, which is processed at higher levels. The improvement persisted for at least several months. These results indicate that when attentional influence is limited, lower-level motion processing is more receptive to long-term modification than higher-level motion processing in the visual cortex. C1 Boston Univ, Dept Psychol, Boston, MA 02215 USA. Arizona State Univ W, Dept Social & Behav Sci, Phoenix, AZ 85069 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Watanabe, T (reprint author), Boston Univ, Dept Psychol, 64 Cummington St, Boston, MA 02215 USA. OI Koyama, Shinichi/0000-0001-6280-5750 NR 50 TC 125 Z9 125 U1 0 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2002 VL 5 IS 10 BP 1003 EP 1009 DI 10.1038/nn915 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 597VV UT WOS:000178242200020 PM 12219093 ER PT J AU Goodman, WG Salusky, IB Juppner, H AF Goodman, WG Salusky, IB Juppner, H TI New lessons from old assays: parathyroid its receptors, and the potential biological hormone (PTH), relevance of PTH fragments SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material DE C-terminal; N-terminal; parathyroid hormone; parathyroid hormone receptors; radioimmunoassay ID CARBOXYL-TERMINAL REGION; IONIZED CALCIUM-CONCENTRATION; PHOTOAFFINITY CROSS-LINKING; CHRONIC-RENAL-FAILURE; IMMUNORADIOMETRIC ASSAY; PEPTIDE RECEPTOR; BONE-DISEASE; PEDIATRIC-PATIENTS; INTACT; BINDING C1 Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Med,Div Nephrol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Div Pediat Nephrol, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Goodman, WG (reprint author), Univ Calif Los Angeles, Med Ctr, Sch Med, Dept Med,Div Nephrol, 7-155 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-50708, DK-35423, DK-52905, DK-60107, DK-4618] NR 56 TC 25 Z9 25 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD OCT PY 2002 VL 17 IS 10 BP 1731 EP 1736 DI 10.1093/ndt/17.10.1731 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 601XZ UT WOS:000178475700004 PM 12270977 ER PT J AU Namura, S Hirt, L Wheeler, VC McGinnis, KM Hilditch-Maguire, P Moskowitz, MA MacDonald, ME Persichetti, F AF Namura, S Hirt, L Wheeler, VC McGinnis, KM Hilditch-Maguire, P Moskowitz, MA MacDonald, ME Persichetti, F TI The HD mutation does not alter neuronal death in the striatum of Hdh(Q92) knock-in mice after mild focal ischemia SO NEUROBIOLOGY OF DISEASE LA English DT Article ID HUNTINGTONS-DISEASE GENE; POLYGLUTAMINE TRACT; CASPASE CLEAVAGE; APOPTOSIS; ACTIVATION; BRAIN; DEGENERATION; EXPANSION; PROTEASE; TOXICITY AB Huntington's disease, with its dominant loss of striatal neurons, is triggered by an expanded glutamine tract in huntingtin. To investigate a proposed role for increased activation of the apoptotic cascade in mutant huntingtin's trigger mechanism, we examined huntingtin cleavage and lesion severity after mild ischemic injury in Hdh(Q92) mice. We found activation of calpain and caspase proteases and proteolysis of huntingtin in lesioned striatum. However, huntingtin fragments resembled products of calpain 1, not caspase-3, cleavage and turnover was accompanied by augmented levels of full-length normal and mutant protein. By contrast, the number of apoptotic cells, total and striatal infarct size, and degree of neurologic deficit were similar in Hdh(Q92) and wild-type mice, indicating that the disease process neither strongly protected nor sensitized striatal neurons to apoptotic death. Thus, our findings do not support a role for increased apoptosis or caspase-3 cleavage in the mechanism by which mutant huntingtin triggers disease. However, they suggest that calpain activation and huntingtin regulation merit investigation as modifiers of disease progression in neurons injured by the harmful consequences of full-length mutant huntingtin. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Persichetti, F (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Hirt, Lorenz/G-3553-2010 OI Hirt, Lorenz/0000-0002-2921-5000 FU NINDS NIH HHS [NS10828, NS16367, NS32765] NR 32 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2002 VL 11 IS 1 BP 147 EP 154 DI 10.1006/nbdi.2002.0532 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 616QH UT WOS:000179314100013 PM 12460554 ER PT J AU Strangman, G Culver, JP Thompson, JH Boas, DA AF Strangman, G Culver, JP Thompson, JH Boas, DA TI A quantitative comparison of simultaneous BOLD fMRI and NIRS recordings during functional brain activation SO NEUROIMAGE LA English DT Article DE near-infrared spectroscopy; functional magnetic resonance imaging; oxyhemoglobin; deoxyhemoglobin; T-2* ID NEAR-INFRARED SPECTROSCOPY; BLOOD OXYGENATION CHANGES; CEREBRAL BLOOD; WAVELENGTH DEPENDENCE; IMAGING SPECTROSCOPY; SENSORY STIMULATION; OPTICAL PATHLENGTH; ABSORPTION-SPECTRA; INTRINSIC SIGNALS; NEURAL ACTIVITY AB Near-infrared spectroscopy (NIRS) has been used to noninvasively monitor adult human brain function in a wide variety of tasks. While rough spatial correspondences with maps generated from functional magnetic resonance imaging (fMRI) have been found in such experiments, the amplitude correspondences between the two recording modalities have not been fully characterized. To do so, we simultaneously acquired LAIRS and blood-oxygenation level-dependent (BOLD) fMRI data and compared Delta(1BOLD) (approximate toR(2)*) to changes in oxyhemoglobin, deoxyhemoglobin, and total hemoglobin concentrations derived from the LAIRS data from subjects performing a simple motor task. We expected the correlation with deoxyhemoglobin to be strongest, due to the causal relation between changes in deoxyhemoglobin concentrations and BOLD signal. Instead we found highly variable correlations, suggesting the need to account for individual subject differences in our NIBS calculations. We argue that the variability resulted from systematic errors associated with each of the signals, including: (1) partial volume errors due to focal concentration changes, (2) wavelength dependence of this partial volume effect, (3) tissue model errors, and (4) possible spatial incongruence between oxy- and deoxyhemoglobin concentration changes. After such effects were accounted for, strong correlations were found between fMRI changes and all optical measures, with oxyhemoglobin providing the strongest correlation. Importantly, this finding held even when including scalp, skull, and inactive brain tissue in the average BOLD signal. This may reflect, at least in part, the superior contrast-to-noise ratio for oxyhemoglobin relative to deoxyhemoglobin (from optical measurements), rather than physiology related to BOLD signal interpretation. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Charlestown, MA 02129 USA. RP Strangman, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [F32-NS10567-01, R29-NS38842] NR 70 TC 449 Z9 459 U1 4 U2 38 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT PY 2002 VL 17 IS 2 BP 719 EP 731 DI 10.1006/nimg.2002.1227 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 604VP UT WOS:000178642000017 PM 12377147 ER PT J AU Street, VA Meekins, G Lipe, HP Seltzer, WK Carter, GT Kraft, GH Bird, TD AF Street, VA Meekins, G Lipe, HP Seltzer, WK Carter, GT Kraft, GH Bird, TD TI Charcot-Marie-Tooth neuropathy: clinical phenotypes of four novel mutations in the MPZ and Cx 32 genes SO NEUROMUSCULAR DISORDERS LA English DT Article DE neuropathy; Charcot-Marie-Tooth; myelin pzero; comnexin 32 ID MYELIN PROTEIN ZERO; UNUSUAL ELECTROPHYSIOLOGICAL FINDINGS; DISEASE TYPE-1A; FAMILY; P-0; IDENTIFICATION; POLYNEUROPATHY; DUPLICATION; RECOGNITION; ASSOCIATION AB Charcot-Marie-Tooth Hereditary Neuropathy is a heterogeneous syndrome associated with mutations in several different genes including peripheral myelin protein 22, myelin P0, connexin 32, and early growth response 2. There is considerable variability in the phenotypic expression of this syndrome and the relationship of this variability to mutation genotypes requires extensive analysis. Here we describe the phenotypes and genotypes of four new mutations underlying the Charcot-Marie-Tooth syndrome and document segregation with disease. Four families with Charcot-Marie-Tooth were ascertained, examined, and evaluated electrophysiologically. Each family had peripheral blood DNA screened for mutations in myelin protein 22, myelin P0, and connexin 32. Two families were found with new mutations in the myelin P0 gene: S140T in the extracellular domain and K236del in the cytoplasmic domain. All families showed segregation of the mutations with the Charcot-Marie-Tooth phenotype as did a new family with the rare G163R mutation in the membrane domain. A 49-year-old man with the S140T mutation demonstrated conduction block on electrophysiological testing. A family with a novel S49P mutation in the connexin 32 gene had a neuropathy with very slow nerve conduction. These new mutations in the myelin P0 and connexin 32 genes help to clarify the pathophysiology of the clinical Charcot-Marie-Tooth syndrome. The S140T mutation in myelin P0 can be associated with conduction block and Charcot-Marie-Tooth should be part of the differential diagnosis of that phenomenon. Mutations in the cytoplasmic domain of myelin P0 can cause clinical neuropathy. The S49P mutation in the connexin 32 gene can produce aspects of a demyelinating type of X-linked hereditary neuropathy. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Bloedel Hearing Ctr, Seattle, WA 98195 USA. VA Med Ctr, GRECC S 182, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Athena Diagnost Inc, Worcester, MA 01605 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Bird, TD (reprint author), Univ Washington, Dept Neurol, Seattle, WA 98195 USA. NR 34 TC 22 Z9 24 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD OCT PY 2002 VL 12 IS 7-8 BP 643 EP 650 AR PII S0960-8966(02)00021-4 DI 10.1016/S0960-8966(02)00021-4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 602HA UT WOS:000178498800005 PM 12207932 ER PT J AU Bartzokis, G AF Bartzokis, G TI Schizophrenia: Breakdown in the well-regulated lifelong development and SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE schizophrenia; brain; development; myelin; white matter; connectivity; neural networks; frontal; temporal; association regions ID MAGNETIC-RESONANCE SPECTROSCOPY; AGE-RELATED-CHANGES; CHILDHOOD-ONSET SCHIZOPHRENIA; FIRST-EPISODE SCHIZOPHRENIA; 22Q11 DELETION SYNDROME; PREFRONTAL GRAY-MATTER; HUMAN CEREBRAL-CORTEX; WHITE-MATTER; APOLIPOPROTEIN-D; IN-VIVO AB Recent evidence suggests that the temporal extent of brain development/maturation can be expanded into middle age when maximal white matter volume and myelination are reached in frontal lobes and association areas. This temporally expanded view of brain development underlies a more comprehensive conceptual model of schizophrenia that incorporates both the reduction of gray matter volume and the complementary expansion of white matter volume occurring from adolescence until middle age. The model posits that the brain is in a constant state of well-regulated structural and functional change roughly defined as periods of development continuing into middle age followed by degeneration. Multiple genetic and environmental factors can interfere with the developmental processes resulting in a dysregulation of the complementary changes occurring in gray and white matter. This dysregulation in development results in an insufficient capacity to maintain temporal synchrony of widely distributed neural networks and is manifested in the heterogeneity of symptoms and cognitive impairments of schizophrenia. The model highlights the contributory role of myelination to synchronous brain function, provides explanations for inconsistencies in the existing literature, and suggests testable hypotheses and novel approaches for intervention efforts. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Cent Arkansas Vet Hlthcare Syst, Little Rock, AR USA. Greater Los Angeles VA Hlthcare Syst, Los Angeles, CA USA. RP Bartzokis, G (reprint author), 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 FU NIMH NIH HHS [MH-51928] NR 144 TC 120 Z9 121 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2002 VL 27 IS 4 BP 672 EP 683 AR PII S0893-133X(02)00364-0 DI 10.1016/S0893-133X(02)00364-0 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 593GY UT WOS:000177983700017 PM 12377404 ER PT J AU Bacskai, BJ Hyman, BT AF Bacskai, BJ Hyman, BT TI Alzheimer's disease: What multiphoton microscopy teaches us SO NEUROSCIENTIST LA English DT Article DE multiphoton; Alzheimer's; senile plaque; amyloid-beta; imaging; microscopy ID 2-PHOTON FLUORESCENCE MICROSCOPY; AMYLOID PRECURSOR PROTEIN; DIAGNOSTIC-CRITERIA; TRANSGENIC MICE; LIVING CELLS; RECEPTOR; GENETICS; PLAQUES AB A definitive diagnosis of Alzheimer's disease depends on postmortem analysis of brain tissue bearing the pathological hallmarks of the disease: plaques and tangles. Imaging techniques that allow visualization and characterization of these lesions in living animals permit a better understanding of the pathogenesis of the disease as well as paradigms for preventing or reversing the deposits. Multiphoton microscopy uses near infrared light that is benign to living tissue and penetrates more deeply than visible or UV light, permitting high-resolution imaging of these microscopic structures deep within the cortex of living transgenic mice over time. This in vivo imaging approach allows direct examination of the natural history of plaques and evaluation of antiplaque therapeutics in mouse models of the disease. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02139 USA. FU NIA NIH HHS [AG08487] NR 21 TC 10 Z9 10 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2002 VL 8 IS 5 BP 386 EP 390 DI 10.1177/107385802236963 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 598CA UT WOS:000178256500010 PM 12374422 ER PT J AU Takagi, Y Ishikawa, M Nozaki, K Yoshimura, S Hashimoto, N AF Takagi, Y Ishikawa, M Nozaki, K Yoshimura, S Hashimoto, N TI Increased expression of phosphorylated c-Jun amino-terminal kinase and phosphorylated c-Jun in human cerebral aneurysms: Role of the c-Jun amino-terminal kinase/c-Jun pathway in apoptosis of vascular walls SO NEUROSURGERY LA English DT Article DE apoptosis; cerebral aneurysm; c-Jun; c-Jun amino-terminal kinase; deoxyribonucleic acid fragmentation; vascular remodeling ID SMOOTH-MUSCLE CELLS; ACTIVATED PROTEIN-KINASES; ABDOMINAL AORTIC-ANEURYSMS; TRANSIENT FOREBRAIN ISCHEMIA; NF-KAPPA-B; CARDIOVASCULAR-DISEASE; MATRIX; RATS; STIMULATION; MECHANISMS AB OBJECTIVE: Vascular remodeling via apoptotic mechanisms is an important factor in vascular disease, c-Jun amino-terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and initiates apoptosis mainly via phosphorylation of the c-Jun transcription factor. We performed this study to clarify the roles of the JNK/c-Jun pathway and apoptosis in the pathogenesis of cerebral aneurysms. METHODS: Cerebral aneurysms from 12 patients and control vessels form 5 patients were studied. We analyzed the expression of phosphorylated JNK and phosphorylated c-Jun in cerebral aneurysms by using immunohistochemical methods. RESULTS: Immunoreactivity for phosphorylated JNK and phosphorylated c-Jun was increased in aneurysmal tissue, compared with control vessels, and was colocalized with that for phosphorylated JNK and phosphorylated c-Jun in smooth muscle cells. CONCLUSION: These observations may lead to better understanding of the role of JNK/c-Jun pathway in the development of cerebral aneurysms and to new strategies for treatment. C1 Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto 6068507, Japan. Kitano Hosp, Inst Med Res, Dept Neurosurg, Osaka, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Neurosurg, Boston, MA USA. RP Takagi, Y (reprint author), Kyoto Univ, Grad Sch Med, Dept Neurosurg, 54 Kawahara Cho, Kyoto 6068507, Japan. NR 32 TC 36 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2002 VL 51 IS 4 BP 997 EP 1002 DI 10.1227/01.NEU.0000027766.04146.C4 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 598ZV UT WOS:000178308500043 PM 12234410 ER PT J AU Sanchez-Pernaute, R Brownell, A Isacson, O AF Sanchez-Pernaute, R Brownell, A Isacson, O TI Functional imaging of the dopamine system: In vivo evaluation of dopamine deficiency and restoration SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 19th International Neurotoxicology Conference CY AUG 25-28, 2001 CL COLORADO SPRINGS, COLORADO DE dopamine; Parkinson's disease; PET ID POSITRON-EMISSION-TOMOGRAPHY; EARLY PARKINSONS-DISEASE; MPTP-INDUCED PARKINSONISM; C-11 WIN 35,428; IN-VIVO; BASAL GANGLIA; PRIMATE MODEL; UP-REGULATION; D2 RECEPTORS; SUBTHALAMIC NUCLEUS AB Dopamine deficiency causes a severe impairment in motorfunction in patients with Parkinson's disease (PD) and in experimental animal models. Recent developments in neuroimaging techniques provide a means to assess in vivo the state of the dopamine system. From a functional perspective, four levels need to be operative and integrated in the system: the dopamine cell (pre-synaptic), the striatal dopamine receptors (post-synaptic), adequate release of dopamine (intra-synaptic), and the cortico-subcortical motor projections. Neuroimaging functional methods can be used to estimate, at these four levels, dopamine cell degeneration, adaptive responses to injury and, importantly, the effect of therapeutic interventions. In this respect, data from functional imaging studies at clinical and pre-clinical stages, support the idea that cell replacement therapy might achieve a more physiological restoration of the dopamine motor system than other therapies (such as ablative surgery, administration of precursor deep brain stimulation) that currently are equally or more effective in relieving motor symptoms. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, McLean Hosp, Sch Med,Neuroregenerat Lab, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med,Neuroregenerat Lab, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. FU NINDS NIH HHS [NS-41263, P50 NS39793] NR 84 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD OCT PY 2002 VL 23 IS 4-5 BP 469 EP 478 AR PII S0161-813X(02)00064-5 DI 10.1016/S0161-813X(02)00064-5 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 610WT UT WOS:000178985400006 PM 12428719 ER PT J AU Porte, D Baskin, DG Schwartz, MW AF Porte, D Baskin, DG Schwartz, MW TI Leptin and insulin action in the central nervous system SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT 19th Marabou Symposium Leptin - A Key Regulator in Nutrition CY JUN 15-17, 2001 CL SUNDBYBERG, SWEDEN SP 4 DE adiposity; insulin; leptin; ventral hypothalamus; anabolic; catabolic signaling; satiety system ID PROOPIOMELANOCORTIN MESSENGER-RNA; MELANIN-CONCENTRATING-HORMONE; REDUCES FOOD-INTAKE; BODY-WEIGHT; GENE-EXPRESSION; ARCUATE NUCLEUS; BRAIN INSULIN; OB/OB MICE; MELANOCORTIN RECEPTORS; HYPOTHALAMIC NEURONS AB Body adiposity is known to be carefully regulated and to remain relatively stable for long periods of time in most mammalian species. This review summarizes old and recent data implicating insulin and leptin as key circulating signals to the central nervous system, particularly the ventral hypothalamus, in communicating the size and the distribution of body fat stores. This input ultimately alters food intake and energy expenditure to maintain constancy of the adipose depot The key primary neurons in the arcuate nucleus containing NPY/AgRP and POMC/CART appear be critical constituents of the CNS regulating system, and are shown to contribute to anabolic and catabolic signaling systems to complete the feedback loop. New data to indicate shared intracellular signaling from leptin and insulin is provided. The satiety system for meals, consisting of neural afferents to the hind-brain from the gastrointestinal tract, is described and its effectiveness is shown to vary with the strength of the insulin and leptin signals. This provides an efferent mechanism that plays a key role in a complex feedback system that allows intermittent meals to vary from day to day, but provides appropriate long-term adjustment to need. Recently described contributions of this system to obesity are described and potential therapeutic implications are discussed. C1 Univ Calif San Diego, Div Metab Diabet & Endocrinol, San Diego, CA 92161 USA. VA San Diego Healthcare Syst, San Diego, CA 92161 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Div Endocrine, Seattle, WA 98104 USA. RP Porte, D (reprint author), Univ Calif San Diego, Div Metab Diabet & Endocrinol, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK 52989, DK12829]; NINDS NIH HHS [NS 32273] NR 93 TC 105 Z9 108 U1 2 U2 12 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD OCT PY 2002 VL 60 IS 10 BP S20 EP S29 PN 2 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 602VB UT WOS:000178524200003 PM 12403080 ER PT J AU Spigel, DR Burstein, HJ AF Spigel, DR Burstein, HJ TI HER2 testing and correlation with efficacy of trastuzumab therapy - The Fornier et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BREAST-CANCER C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Med Oncol,Breast Oncol Ctr, Boston, MA 02115 USA. RP Spigel, DR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Dept Med,Div Med Oncol,Breast Oncol Ctr, Boston, MA 02115 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 2002 VL 16 IS 10 BP 1352 EP + PG 3 WC Oncology SC Oncology GA 613DU UT WOS:000179117200009 ER PT J AU Miserocchi, E Modorati, G Foster, CS Brancato, R AF Miserocchi, E Modorati, G Foster, CS Brancato, R TI Ocular and extracutaneous involvement in pyoderma gangrenosum SO OPHTHALMOLOGY LA English DT Article AB Purpose: To report an unusual presentation of pyoderma gangrenosum with ocular and extracutaneous involvement. Design: A single, interventional case report. Methods: A 28-year-old female presented with nodular scleritis in the right eye and left orbital inflammation lasting 1 year. The patient initially responded to systemic steroids, but then ocular inflammation became more severe, associated with onset of fever, myalgias, and elevation of the erythrocyte sedimentation rate, accompanied by formation of multiple cutaneous abscesses. Main Outcome Measures: Ocular and systemic disease control. Results: The diagnosis of pyoderma gangrenosum was made 1 year after the occurrence of ocular symptomatology, when the patient presented with ocular and skin lesions and abscesses in the spleen and liver. Conclusions: Pyoderma gangrenosum is a rare, necrotizing, noninfectious ulcerating skin disease. Ocular and extracutaneous involvement rarely occur, but the disease should be included in the differential diagnosis of scleritis and orbital inflammation. (C) 2002 by the American Academy of Ophthalmology. C1 Univ Hosp San Raffaele, Dept Ophthalmol & Visual Sci, I-20132 Milan, Italy. Harvard Univ, Sch Med,Massachusetts Eye & Ear Infirmary, Dept Ophthalmol, Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Brancato, R (reprint author), Univ Hosp San Raffaele, Dept Ophthalmol & Visual Sci, Via Olgettina 60, I-20132 Milan, Italy. NR 11 TC 19 Z9 19 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2002 VL 109 IS 10 BP 1941 EP 1943 AR PII S0161-6420(02)01165-X DI 10.1016/S0161-6420(02)01165-X PG 3 WC Ophthalmology SC Ophthalmology GA 601AW UT WOS:000178424800035 PM 12359619 ER PT J AU Roberts, A Matthews, JB Socransky, SS Freestone, PPE Williams, PH Chapple, ILC AF Roberts, A Matthews, JB Socransky, SS Freestone, PPE Williams, PH Chapple, ILC TI Stress and the periodontal diseases: effects of catecholamines on the growth of periodontal bacteria in vitro SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE catecholamines; pathogenesis; periodontal bacteria; periodontal disease ID GRAM-NEGATIVE BACTERIA; INFECTIOUS-DISEASE; ESCHERICHIA-COLI; SUBGINGIVAL PLAQUE; RISK INDICATORS; ATTACHMENT LOSS; EXPRESSION; HEALTH AB Microorganisms possess the ability to recognize hormones within the host and utilize them to adapt to their surroundings. Noradrenaline and adrenaline, which are released during human stress responses, may act as environmental cues to alter the growth of individual organisms within subgingival biofilms. The aims of this study were to modify, for anaerobic culture, existing methodology used in determining microorganism catecholamine responses and to investigate the growth responses to noradrenaline and adrenaline of 43 microorganisms found within subgingival microbial complexes. We established initial inocula for each strain using anaerobic culture, re-inoculated into a minimal serum-based medium and grown anaerobically at 35degreesC. We assessed organism growth by optical density (OD600nm ) readings, with test and control cultures performed in triplicate. Test cultures were supplemented with 50 mum noradrenaline or 100 mum adrenaline. We observed significant growth effects for supplementation with noradrenaline (20 species responding positively) and adrenaline (27 species responding positively), with differences in growth response observed within bacterial species and within and between microbial complexes. The most pronounced positive growth effects of noradrenaline were demonstrated in Actinomyces naeslundii (+ 49.4%), Actinomyces gerenscseriae (+ 57.2%), Eikenella corrodens (+ 143.3%) and Campylobacter gracilis (+ 79.9%). We also observed inhibitory effects of noradrenaline supplementation for Porphyromonas gingivalis (- 11.9%) and Bacteroides forsythus (- 22.2%). Responses to adrenaline tended to mirror the responses seen with noradrenaline. Individual organisms from different microbial complexes vary in their in vitro growth responses to noradrenaline and adrenaline. Such variation may influence the in vivo composition of the subgingival biofilm in response to stress-induced changes in local catecholamine levels and play a significant role in the aetiology and pathogenesis of the periodontal diseases. C1 Birmingham Sch Dent, Unit Periodontol, Birmingham B4 6NN, W Midlands, England. Birmingham Sch Dent, Unit Oral Biol & Pathol, Birmingham B4 6NN, W Midlands, England. Forsyth Inst, Dept Periodontol, Boston, MA USA. Univ Leicester, Dept Microbiol & Immunol, Leicester, Leics, England. RP Chapple, ILC (reprint author), Birmingham Sch Dent, Unit Periodontol, St Chads Queensway, Birmingham B4 6NN, W Midlands, England. NR 28 TC 57 Z9 58 U1 1 U2 12 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 2002 VL 17 IS 5 BP 296 EP 303 DI 10.1034/j.1399-302X.2002.170506.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 598CT UT WOS:000178258200006 PM 12354211 ER PT J AU Friedlander, AH Norman, DC AF Friedlander, AH Norman, DC TI Late-life depression: Psychopathology, medical interventions, and dental implications SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; BURNING MOUTH SYNDROME; NURSING-HOME RESIDENTS; ELECTROCONVULSIVE-THERAPY; GERIATRIC DEPRESSION; MAJOR DEPRESSION; OLDER ADULTS; TRICYCLIC ANTIDEPRESSANTS; PSYCHOLOGICAL-ASPECTS; DRUG-INTERACTIONS AB Background. Late-life depression (LLD) initially occurs after age 65 years and is a major public health concern because the elderly who are at high risk constitute an ever-expanding segment of the population. LLD is a mental illness in which mood, thought content, and behavioral patterns are impaired, causing the individual distress, compromising social function; and impairing self-maintenance skills (eg, bathing, dressing, hygiene). LLD characterized by marked sadness or a loss of interest or pleasure in daily activities and maybe accompanied by weight change, sleep disturbance, fatigue, difficulty in concentration, and a high suicide rate. Diagnosis of LLD is sometimes complicated by a denial of mood change and an inability to distinguish symptoms of a concurrent physical illness from those of a depressive etiology. The disorder is most frequently treated with antidepressant medications, and although older individuals have a recovery rate that is comparable with younger adults, they often take longer to recover, have more frequent relapses, and are more sensitive to the side effects of the drugs. Clinical implications. Individuals undergoing treatment for LLD and those whose illness has not been diagnosed or treated often are seen with significant oral disease by the dentist. Dentists need to be cognizant of how to safely and compassionately provide care to those already receiving mental health services. They must also be familiar with the psychiatric symptoms of the disorder to effectuate a timely referral to a physician of those with occult or relapsing disease. LLD is frequently associated with a disinterest in oral hygiene, a cariogenic diet, diminished salivary flow, rampant dental decay, advanced periodontal disease, and oral dysesthesias. Many medications used to treat the disease magnify the xerostomia and increase the incidence of dental disease. Appropriate dental management necessitates a vigorous preventive dental education program, the use of artificial salivary products, antiseptic mouthwash, daily fluoride mouth rinse, and special precautions in administration of local anesthetics with vasoconstrictors and prescription of analgesics. Conclusion. Dentists who invoke appropriate precautions can usually provide a full range of services to individuals with LLD, thereby enhancing patient self-esteem and contributing to the psychotherapeutic aspect of management. C1 VA Greater Los Angeles Healthcare Syst 14, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Med, Hosp Dent Serv, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst 14, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 96 TC 21 Z9 23 U1 0 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD OCT PY 2002 VL 94 IS 4 BP 404 EP 412 DI 10.1067/moe.2002.122434 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 602KF UT WOS:000178503900004 PM 12374911 ER PT J AU Gill, TJ Steadman, JR AF Gill, TJ Steadman, JR TI Anterior cruciate ligament reconstruction - The two-incision technique SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID TIBIAL TUNNEL PLACEMENT; ENDOSCOPIC ACL RECONSTRUCTION; 2-INCISION TECHNIQUES; GRAFT FIXATION; STRENGTH; SINGLE; LENGTH AB Historically, the two-incision technique for anterior cruciate ligament (ACL) reconstruction was the standard of practice. It allows predictable, near-Anatomic placement of the femoral tunnel and provides highly reproducible results with few complications. There are several major advantages of the two-incision technique over endoscopic methods. These include consistent femoral tunnel placement, elimination of concern for "blowing out the back wall," elimination of the problem of graft-tunnel mismatch, elimination of the problem of screw divergence, and ease of use for revision ACL reconstruction procedures. The angle of the ACL graft is also more anatomic, matching the angle of the native ACL. In this chapter we present our technique for reconstruction of the ACL using the two-incision approach. Indications for its use are discussed. Advantages and disadvantages of the two-incision method compared with the all-endoscopic approach are reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ambulatory Care Ctr,Dept Orthoped Surg, Boston, MA 02114 USA. Steadman Hawkins Clin, Vail, CO USA. SW Med Sch, Dallas, TX USA. RP Gill, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ambulatory Care Ctr,Dept Orthoped Surg, 15 Parkman St, Boston, MA 02114 USA. NR 42 TC 23 Z9 24 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 2002 VL 33 IS 4 BP 727 EP + AR PII S0030-5898(02)00030-5 DI 10.1016/S0030-5898(02)00030-5 PG 10 WC Orthopedics SC Orthopedics GA 617CX UT WOS:000179343600012 PM 12528914 ER PT J AU Kim, YJ Glazer, PA AF Kim, YJ Glazer, PA TI Delayed esophageal perforation and abscess formation after cervical vertebrectomy and fusion SO ORTHOPEDICS LA English DT Article ID SPINE; TRAUMA; INJURY C1 Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Boston, MA 02114 USA. RP Glazer, PA (reprint author), Boston Orthoped Grp, 1269 Beacon St, Brookline, MA 02446 USA. NR 11 TC 11 Z9 11 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD OCT PY 2002 VL 25 IS 10 BP 1091 EP 1093 PG 3 WC Orthopedics SC Orthopedics GA 603FG UT WOS:000178547700018 PM 12401019 ER PT J AU D'Avila, A Gutierrez, P Scanavacca, M Reddy, V Lustgarten, DL Sosa, E Ramires, JAF AF D'Avila, A Gutierrez, P Scanavacca, M Reddy, V Lustgarten, DL Sosa, E Ramires, JAF TI Effects of radiofrequency pulses delivered in the vicinity of the coronary arteries: Implications for nonsurgical transthoracic epicardial catheter ablation to treat ventricular tachycardia SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; coronary artery; arrhythmia; epicardium; ventricular tachycardia ID MYOCARDIAL-INFARCTION; COAGULATION NECROSIS; IRRIGATED-TIP; DISEASE; HEART AB This study evaluates the effects of epicardial RF ablation on the coronary vessels in a canine model. Nonsurgical epicardial catheter ablation is a minimally invasive procedure that has proven to be efficacious for the treatment of VT. This approach is limited by concern regarding the potential adverse effects of RF ablation on the epicardial coronary arteries. After lateral thoracotomy, a multipolar linear ablation catheter was sewn adjacent to or crossing the LAD in nine mongrel dogs. Five of these dogs also had a standard 4-mm tip ablation catheter sewn adjacent to the LAD. RF pulses were delivered using temperature control. Animals were sacrificed 14 days after ablation for histological analyses. Using the 4-mm tip catheter, 22 consecutive single lesions of 2.67 +/- 0.35 mm depth were studied. The only coronary arterial change seen was replacement of the media with extracellular matrix. Using the linear ablation catheter, 117 pulses were applied to generate 24 linear lesions (3.8 +/- 1 mm depth). Replacement of the coronary arterial media with extracellular matrix proliferation was commonly seen, and severe hyperplasia occurred in one artery. Intravascular thrombosis occurred in six arteries. The internal Perimeter of the vessel (0.78 +/- 0.49 mm vs 1.79 +/- 0.83 mm) was the only variable associated with severe arterial damage. The effects of RF ablation delivered adjacent to the LAD were limited to the media but when delivered above the artery, severe intimal hyperplasia and intravascular thrombosis may occur. Susceptibility to damage is inversely proportional to the vessel size. C1 Univ Sao Paulo, Unidade Clin Arritmia, Inst Coracao, Sch Med,Heart Inst, BR-05403000 Sao Paulo, Brazil. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Oklahoma, Ctr Hlth, Cardiac Arrhythmia Res Inst, Oklahoma City, OK USA. RP D'Avila, A (reprint author), Univ Sao Paulo, Unidade Clin Arritmia, Inst Coracao, Sch Med,Heart Inst, Av Eneas Carvalho Aguiar 44, BR-05403000 Sao Paulo, Brazil. RI d'Avila, Andre/A-7693-2009; Gutierrez, Paulo/E-6783-2012; d'Avila, Andre Luiz/F-8009-2010 OI Gutierrez, Paulo/0000-0002-9544-2359; d'Avila, Andre Luiz/0000-0001-8769-1411 NR 27 TC 66 Z9 66 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD OCT PY 2002 VL 25 IS 10 BP 1488 EP 1495 DI 10.1046/j.1460-9592.2002.01488.x PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 609AR UT WOS:000178880900013 PM 12418747 ER PT J AU Yang, H Tache, Y Ohning, G Go, VLW AF Yang, H Tache, Y Ohning, G Go, VLW TI Activation of raphe pallidus neurons increases insulin through medullary thyrotropin-releasing hormone (TRH)-vagal pathways SO PANCREAS LA English DT Article DE dorsal motor nucleus (DMN); kainic acid; pancreas; serum insulin levels; TRH antibody; vagus ID DORSAL VAGAL COMPLEX; GASTRIC-ACID SECRETION; WISTAR FATTY RATS; OBESE FA/FA RATS; VAGUS NERVE; MOTOR NUCLEUS; SUBSTANCE-P; PREGANGLIONIC NEURONS; ENDOCRINE PANCREAS; GENE-EXPRESSION AB Introduction: Pancreatic insulin secretion is regulated by the vagus nerve. Medullary thyrotropin-releasing hormone (TRH) containing projections from the raphe pallidus (Rpa) neurons innervate vagal preganglionic motor neurons in the dorsal vagal complex (DVC) and are involved in vagal regulation of gastric functions, Aim: To investigate whether chemical stimulation of Rpa neurons influences circulating insulin levels through brain medullary TRH-vagal pathways. Methodology: In fasted, pentobarbital-anesthetized rats, kainic acid (10 ng/50 nL) was microinjected into the Rpa, and serum insulin levels were measured. Gastric acid secretion was monitored as a control of vagally mediated visceral response. Results: Chemical stimulation of Rpa neuronal cell bodies significantly increased serum insulin levels. Values before and at 30, 60, and 90 minutes after the microinjection of kainic acid were 0.34 +/- 0.02, 0.54 +/- 0.06, 0.60 +/- 0.06, and 0.99 +/- 0.13 ng/mL, respectively. In the same rats, gastric acid secretion was stimulated (basal, 2.3 +/- 0.6, versus 26.1 +/- 8.6 mumol/15 min at 30 minutes). Microinjections outside of the Rpa had no effect. The Rpa stimulation-induced increase in serum insulin could be mimicked by DVC microinjection of TRH analog, completely prevented by bilateral cervical vagotomy, and significantly reduced by bilateral microinjection of TRH antibody into the DVC. Conclusion: Chemical activation of Rpa neurons increases pancreatic insulin release through medullary TRH and vagal-mediated pathways. C1 Univ Calif Los Angeles, CURE,Digest Dis Res Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA USA. Brain Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA USA. RP Yang, H (reprint author), W Los Angeles VA Med Ctr, DDRC, CURE, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-50255, DK-30110, DK-41301] NR 50 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD OCT PY 2002 VL 25 IS 3 BP 301 EP 307 DI 10.1097/01.MPA.0000016985.11229.48 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598DE UT WOS:000178259400014 PM 12370543 ER PT J AU Wolfe, J Friebert, S Hilden, J AF Wolfe, J Friebert, S Hilden, J TI Caring for children with advanced cancer integrating palliative care SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID OF-LIFE CARE; SPINAL-CORD COMPRESSION; TERMINALLY ILL CHILDREN; FAR-ADVANCED CANCER; PHASE-I TRIALS; ORAL ETOPOSIDE; CLINICAL-TRIAL; RECURRENT MEDULLOBLASTOMA; INTESTINAL-OBSTRUCTION; MEGESTROL-ACETATE AB Palliative care is defined as the total active total care of patients and families, including control of pain, other symptoms, and psychological, social and spiritual concerns. Optimal care of children with advanced cancer includes early integration of palliative care with continued efforts to treat the underlying illness. This chapter reviews empiric data suggesting, however, that children with advanced cancer experience significant suffering at the end of life and that communication is not optimal. Barriers to optimal care are reviewed including lack of formal education, reimbursement issues and the emotional burden of caring for a child who may die and caring for their family. The chapter also focuses on strategies to optimize communication, symptom management and meaningfulness in this patient population. C1 Childrens Hosp, Cleveland Clin, Dept Pediat Hematol Oncol, Cleveland, OH 44195 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Med Ctr Akron, Dept Pediat Hematol Oncol, Akron, OH 44308 USA. RP Hilden, J (reprint author), Childrens Hosp, Cleveland Clin, Dept Pediat Hematol Oncol, 9500 Euclid Ave,Desk S20, Cleveland, OH 44195 USA. NR 116 TC 26 Z9 27 U1 6 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD OCT PY 2002 VL 49 IS 5 BP 1043 EP + AR PII S0031-3955(02)00034-2 DI 10.1016/S0031-3955(02)00034-2 PG 22 WC Pediatrics SC Pediatrics GA 610GK UT WOS:000178952200010 PM 12430625 ER PT J AU Monks, NR Ferraz, A Bordignon, S Machado, KR Lima, MFS da Rocha, AB Schwartsmann, G AF Monks, NR Ferraz, A Bordignon, S Machado, KR Lima, MFS da Rocha, AB Schwartsmann, G TI In vitro cytotoxicity of extracts from Brazilian Asteraceae SO PHARMACEUTICAL BIOLOGY LA English DT Article DE in vitro screening; cytotoxic activity; Asteraceae; Rio Grande do Sul; Brazil ID BACCHARIS-CORIDIFOLIA; ANTITUMOR AGENTS; NATURAL SOURCES; CANCER; ANTIOXIDANT; DISCOVERY; DC AB Aqueous and organic extracts of Asteraceae (Compositae) collected from the State of Rio Grande do Sul, Brazil, have been tested in vitro for cytotoxic activity against human solid tumour cell lines. Twenty-five species, 125 extracts in total, were screened against HT29 human colon adenocarcinoma cells and NCI-H460 human non-small cell lung cancer cells. Twenty-five extracts from 11 species demonstrated cytotoxicity at 100 mug/ml against one or both of the cell lines tested. Further analysis was performed on the active extracts using three cell lines HT29, NCI-H460, and U373 human glioblastoma cells, to determine the IC50 and the degree of tumour cell line selectivity. Extracts from Baccharis coridifolia, Baccharis ochracea, Eupatorium macrocephalum, Eupatorium pedunculosum and Stenachaenium riedelii all produced IC50 values below 5 mug/ml. Comparison of the IC50 results between cell lines identified that Baccharis coridifolia, Baccharis ochracea, Eupatorium laevigatum and Pluchea sagittalis extracts produced differential sensitivity across the panel of three cell lines. These species are currently under further investigation with the ultimate objective of isolation and identification of the active principles responsible for the anti-proliferative activity. C1 ULBRA, CINCAN, Canoas, RS, Brazil. Hosp Clin Porto Alegre, SOAD, Porto Alegre, RS, Brazil. RP Monks, NR (reprint author), Dana Farber Canc Inst, Smith Bldg Rm 934,44 Binney St, Boston, MA 02115 USA. RI Monks, Noel/B-5886-2013; Schwartsmann, Gilberto/G-4256-2016 OI Monks, Noel/0000-0001-6587-9827; Schwartsmann, Gilberto/0000-0002-7850-1644 NR 46 TC 19 Z9 19 U1 0 U2 6 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PD OCT PY 2002 VL 40 IS 7 BP 494 EP 500 PG 7 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 632MB UT WOS:000180226100004 ER PT J AU Belperio, PS Glassman, PA Simon, B Lanto, A AF Belperio, PS Glassman, PA Simon, B Lanto, A TI Role of pharmacists in improving provider recognition of drug interactions. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 20-23, 2002 CL ALBUQUERQUE, NEW MEXICO SP Amer Coll Clin Pharmacy C1 VA HSR&D Ctr Excellence Study Healthcare Provider, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2002 VL 22 IS 10 MA 10 BP 1325 EP 1325 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 601GN UT WOS:000178438300021 ER PT J AU Hamm, JW Washington, DM Cobb, TH Herndon, KC AF Hamm, JW Washington, DM Cobb, TH Herndon, KC TI Evaluation of a proton pump inhibitor step-down initiative in a Veterans Affairs medical center. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 20-23, 2002 CL ALBUQUERQUE, NEW MEXICO SP Amer Coll Clin Pharmacy C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Pfizer Inc, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2002 VL 22 IS 10 MA 92 BP 1339 EP 1339 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 601GN UT WOS:000178438300088 ER PT J AU Eladoumikdachi, F Valkov, PL Thomas, J Netscher, DT AF Eladoumikdachi, F Valkov, PL Thomas, J Netscher, DT TI Anatomy of the intrinsic hand muscles revisited: Part I. Interossei SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB In this article, the anatomic variations in interosseous muscle insertions are described based on a review of the literature and 14 fresh cadaver hand dissections. The findings are correlated and compared with those of a number of other investigators, and the clinical implications are discussed (i.e., in the correction of ulnar deviation in arthritis patients and in the treatment of congenital anomalies of the hand). It is concluded that descriptions of insertion sites of the intrinsic muscles have been oversimplified by previous researchers, and a number of variations are identified through the cadaver dissections. The differing and confusing nomenclature used by other investigators is discussed and simplified. The results of this study indicate that not only are there important distal insertions onto bone and the extensor apparatus, but there is also an additional insertion onto the volar plate ("assemblage nucleus"), as Zancolli reported. It was found that the palmar interossei, generally thought to insert only onto the extensor apparatus, could also insert onto bone and onto the volar plate. Classic teaching is that all dorsal interossei (except the third) have two heads and that all palmar interossei have only one head. In this study, however, 38 percent of the palmar interossei and 75 percent of the dorsal interossei had more than one head. The complexity of the interossei is apparent when as many as three different muscle heads are present, each with a different distal destination. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 11 TC 14 Z9 16 U1 1 U2 2 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 OCT PY 2002 VL 110 IS 5 BP 1211 EP 1224 DI 10.1097/01.PRS.0000024442.72140.56 PG 14 WC Surgery SC Surgery GA 596WJ UT WOS:000178189200001 PM 12360058 ER PT J AU Eladoumikdachi, F Valkov, PL Thomas, J Netscher, DT AF Eladoumikdachi, F Valkov, PL Thomas, J Netscher, DT TI Anatomy of the intrinsic hand muscles revisited: Part II. Lumbricals SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB The authors discuss the anatomic variations and the precise origins and insertions of the lumbrical muscles, after dissecting 14 fresh cadavers (56 lumbrical muscles) and reviewing the scant published literature. They compare the findings with those of other investigators, and they describe the lumbrical muscle insertions discovered during the dissections. The authors conclude that descriptions of the origins and insertions of the lumbrical muscles have been oversimplified or not investigated at all, that lumbricals originate variably from the flexor digitorum profundus tendon and may even be bipinnate, and that three different major destinations exist for distal insertion of these intrinsic muscles: bone, volar plate, and extensor apparatus. Previous descriptions have focused only on the lumbrical continuation to the lateral band of the extensor mechanism. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 9 TC 21 Z9 23 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 2002 VL 110 IS 5 BP 1225 EP 1231 DI 10.1097/01.PRS.0000024443.27141.1D PG 7 WC Surgery SC Surgery GA 596WJ UT WOS:000178189200002 PM 12360059 ER PT J AU Chang, S DePinho, RA AF Chang, S DePinho, RA TI Telomerase extracurricular activities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN-DIPLOID FIBROBLASTS; MAMMARY EPITHELIAL-CELLS; LARGE T-ANTIGEN; CATALYTIC SUBUNIT; LIFE-SPAN; IMMORTAL CELLS; TUMOR-CELLS; MAINTENANCE; LENGTH; TUMORIGENESIS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIA NIH HHS [K08 AG001019] NR 35 TC 49 Z9 52 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 OCT 1 PY 2002 VL 99 IS 20 BP 12520 EP 12522 DI 10.1073/pnas.212514699 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 600LK UT WOS:000178391700007 PM 12271146 ER PT J AU Stewart, SA Hahn, WC O'Connor, BF Banner, EN Lundberg, AS Modha, P Mizuno, H Brooks, MW Fleming, M Zimonjic, DB Popescu, NC Weinberg, RA AF Stewart, SA Hahn, WC O'Connor, BF Banner, EN Lundberg, AS Modha, P Mizuno, H Brooks, MW Fleming, M Zimonjic, DB Popescu, NC Weinberg, RA TI Telomerase contributes to turnorigenesis by a telomere length-independent mechanism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMORTAL HUMAN-CELLS; HUMAN TUMOR-CELLS; CATALYTIC SUBUNIT; LIFE-SPAN; CANCER-CELLS; MAINTENANCE; RECOMBINATION; APOPTOSIS; PATHWAY; RECONSTITUTION AB Once immortalized, human cells are susceptible to transformation by introduction of an oncogene such as ras. Several lines of evidence now suggest that the maintenance of telomere length is a major determinant of replicative lifespan in human cells and thus of the immortalized state. The majority of human tumor cells acquire immortality through expression of the catalytic subunit of telomerase (hTERT), whereas others activate an alternative mechanism of telomere maintenance (ALT) that does not depend on the actions of telomerase. We have examined whether ALT could substitute for telomerase in the processes of transformation in vitro and tumorigenesis in vivo. Expression of oncogenic H-Ras in the immortal ALT cell line GM847 did not result in their transformation. However, subsequent ectopic expression of hTERT in these cells imparted a tumorigenic phenotype. Indeed, this outcome was also observed after introduction of a mutant hTERT that retained catalytic activity but was incapable of maintaining telomere length. These studies indicate that hTERT confers an additional function that is required for tumorigenesis but does not depend on its ability to maintain telomeres. C1 NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 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. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Genzyme Inc, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Weinberg, RA (reprint author), NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RI Stewart, Sheila/C-5213-2012 FU NCI NIH HHS [K01 CA094223, R01 CA078461, R01 CA78461] NR 51 TC 319 Z9 336 U1 1 U2 10 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 OCT 1 PY 2002 VL 99 IS 20 BP 12606 EP 12611 DI 10.1073/pnas.182407599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 600LK UT WOS:000178391700023 PM 12193655 ER PT J AU Humphreys, D Eggan, K Akutsu, H Friedman, A Hochedlinger, K Yanagimachi, R Lander, ES Golub, TR Jaenisch, R AF Humphreys, D Eggan, K Akutsu, H Friedman, A Hochedlinger, K Yanagimachi, R Lander, ES Golub, TR Jaenisch, R TI Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FETAL OVERGROWTH; IMPRINTED GENES; ES CELLS; CLONING; MOUSE; FETUSES; CULTURE; TRANSCRIPTION; METHYLATION; PATTERNS AB To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear transfer (NT) from both cultured embryonic stem cells and freshly isolated cumulus cells. Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types approximate to4% of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally expressed genes were common to both types of clones. Importantly, however, the expression of a smaller set of genes differed between the embryonic stem cell- and cumulus cell-derived clones. The livers of the cloned mice also showed abnormal gene expression, although to a lesser extent, and with a different set of affected genes, than seen in the placentas. Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Univ Hawaii, John A Burns Sch Med, Dept Anat & Reprod Biol, Honolulu, HI 96822 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Jaenisch, R (reprint author), MIT, Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [R01 CA084198, R01-CA84198, 5-R35-CA44339] NR 37 TC 290 Z9 317 U1 0 U2 15 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 OCT 1 PY 2002 VL 99 IS 20 BP 12889 EP 12894 DI 10.1073/pnas.192433399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 600LK UT WOS:000178391700071 PM 12235366 ER PT J AU Garb, HN Wood, JM Lilienfeld, SO Nezworski, MT AF Garb, HN Wood, JM Lilienfeld, SO Nezworski, MT TI Effective use of projective techniques in clinical practice: Let the data help with selection and interpretation SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID COMPREHENSIVE SYSTEM; PERSONALITY-DISORDER; DEPRESSION INDEXES; RORSCHACH; VALIDITY; NORMS; CHILDREN; DRAWINGS; MMPI-2; TAT AB By learning about the validity of individual test scores, psychologists can avoid using scores that are invalid and making judgments that are potentially harmful to their clients. This is important not only for improving clinical and forensic practice but also for avoiding lawsuits. In this article, the effective use of projective techniques is described, with attention to the overperception of psychopathology, diagnosis and the description of symptoms, and the detection of child abuse. Guidelines are offered for using the Rorschach, Thematic Apperception Test, human figure drawings, and the Washington University Sentence Completion Test. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Texas, El Paso, TX 79968 USA. Univ Texas, Dallas, TX 75230 USA. RP Garb, HN (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 79 TC 24 Z9 25 U1 8 U2 20 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 OCT PY 2002 VL 33 IS 5 BP 454 EP 463 DI 10.1037//0735-7028.33.5.454 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 596VT UT WOS:000178187700004 ER PT J AU Guille, C Sachs, G AF Guille, C Sachs, G TI Clinical outcome of adjunctive topiramate treatment in a sample of refractory bipolar patients with comorbid conditions SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE bipolar disorder; comorbid psychiatric conditions; refractory; topiramate ID DISORDERS; MANIA; SCALE AB Topiramate, a novel antiepileptic agent, has shown promise in the treatment of bipolar disorder. Patients attending a bipolar specialty clinic and treated with topiramate were identified by chart review, and data were harvested from systematic prospective assessments used routinely in the clinic. Fourteen patients who received topiramate for an average of 22.4 weeks were identified. All but one of these patients were considered to be highly refractory to standard treatment and 13 met the criteria for at least one comorbid psychiatric condition. Nine of these patients (64%) experienced an increased level of functioning and decrease in symptom severity during treatment with adjunctive topiramate. Eleven patients remained on treatment for longer than 2 weeks. Eight of these patients (73%) experienced a significant improvement in their comorbid conditions. Patients with a body mass index (BMI) of greater than or equal to 28 (n = 4) experienced a mean weight loss of 29.7 lb while on topiramate. Topiramate appears to be a promising agent for the treatment of bipolar disorder associated kith comorbid psychiatric conditions and obesity. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, Boston, MA 02114 USA. RP Sachs, G (reprint author), 50 Staniford St,Floor 5, Boston, MA 02114 USA. NR 21 TC 26 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT PY 2002 VL 26 IS 6 BP 1035 EP 1039 AR PII S0278-5846(01)00278-0 DI 10.1016/S0278-5846(01)00278-0 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 608LA UT WOS:000178846700003 PM 12452523 ER PT J AU Smith, JJ Maida, A Henderson, JA AF Smith, JJ Maida, A Henderson, JA TI Hospital outpatient prospective payment under Medicare: Understanding the system and its implications SO RADIOLOGY LA English DT Review DE radiology and radiologists, departmental management; radiology and radiologists, socioeconomic issues; review AB The newly implemented Medicare hospital outpatient prospective payment system provides fixed prospectively determined reimbursement for technical and other nonphysician services provided to beneficiaries in the hospital outpatient setting. AS such, it represents the latest attempt by the federal government to control health care costs through prospective bundled payment systems such as the well-known Medicare diagnosis-related group system for hospital inpatients. The new system is complex, however, with several. discrete reimbursement mechanisms possible for the same service. This complexity in concert with the major change in outpatient reimbursement that the system represents, creates considerable uncertainty for radiologists and:for medicine in general. It is incumbent on the radiology community to understand and assess the hospital outpatient prospective payment system and to work with the Centers for Medicare and Medicaid Services to minimize any potential negative effects on the profession and on patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Ctr Integrat Med & Innovat Technol, Regulatory Affairs Program, Boston, MA USA. RP Smith, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2002 VL 225 IS 1 BP 13 EP 19 DI 10.1148/radiol.2251011304 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598FE UT WOS:000178264300005 PM 12354977 ER PT J AU Moy, L Slanetz, PJ Moore, R Satija, S Yeh, ED McCarthy, KA Hall, D Staffa, M Rafferty, EA Halpern, E Kopans, DB AF Moy, L Slanetz, PJ Moore, R Satija, S Yeh, ED McCarthy, KA Hall, D Staffa, M Rafferty, EA Halpern, E Kopans, DB TI Specificity of mammography anal US in the evaluation of a palpable abnormality: Retrospective review SO RADIOLOGY LA English DT Review DE breast neoplasms, diagnosis; breast neoplasms, radiography; breast neoplasms, US ID DETECTION DEMONSTRATION PROJECT; BREAST-CANCER; SONOGRAPHY; WOMEN AB PURPOSE: To determine the number of patients who received a diagnosis of breast cancer after having an area of clinical concern at presentation and combined negative mammographic and ultrasonographic (US) findings. MATERIALS AND METHODS: During a 4-year period, 829 patients with a palpable abnormality at presentation and combined negative mammographic and US findings were identified. The number of women who went on to receive a diagnosis of breast cancer was determined retrospectively. The authors searched the breast imaging database and the pathology database, sent a contact letter to the referring physicians, and linked their data to the State Cancer Registry. They also analyzed the breast parenchymal density among all patients who had more than 2 years of follow-up. RESULTS: Of the 829 women, 374 had follow-up information. Two-hundred thirty-three patients had negative imaging findings with more than 2 years of follow-up. The other 141 women were presumed to be cancer free, as they were not identified by the State Cancer Registry. Six (2.6%) of the 233 women had a diagnosis of breast cancer in the area of the palpable abnormality. The six cancers were diagnosed among the 156 women who had radiographically dense breast tissue (Breast Imaging Reporting and Data System category 3 or 4). Among the 77 women with predominantly fatty tissues, no cancers were diagnosed. CONCLUSION: A negative mammographic and US finding of a palpable abnormality does not exclude breast cancer, but the likelihood of breast cancer is low, approximately 2.6%-2.7%. It may be higher if the breast tissues are dense and lower if they are predominantly fatty. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Breast Imaging, Boston, MA 02114 USA. RP Moy, L (reprint author), NYU, Sch Med, Breast Imaging Ctr, 530 1st Ave,FPT Suite 8N, New York, NY 10016 USA. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 14 TC 48 Z9 57 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2002 VL 225 IS 1 BP 176 EP 181 DI 10.1148/radiol.2251010999 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598FE UT WOS:000178264300027 PM 12355002 ER PT J AU Ng, EWM Costa, R Samiy, N Ruoff, KL Connolly, E Cousins, FV D'amico, DJ AF Ng, EWM Costa, R Samiy, N Ruoff, KL Connolly, E Cousins, FV D'amico, DJ TI Contribution of pneumolysin and autolysin to the pathogenesis of experimental pneumococcal endophthalmitis SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID STAPHYLOCOCCUS-AUREUS VIRULENCE; STREPTOCOCCUS-PNEUMONIAE; OCULAR INFECTIONS; HEMOLYSIN BL; MODEL; GENE AB Purpose: To determine the contribution of pneumolysin and autolysin, two putative pneumococcal virulence proteins, to the pathogenesis of Streptococcus pneumoniae endophthalmitis. Methods: Endophthalmitis was established in Lewis rats by intravitreal injection of pneumococcal strains at an inoculum of 101 organisms. The virulence of three closely related type 2 S. pneumoniae strains were compared: a pneumolysin-deficient derivative (PLN-A), an autolysin-deficient derivative (AL-6), and their isogenic wild-type parent (D39). Clinical and histologic inflammation scores were compared 24 hours and 48 hours after inoculation. Results: Eyes infected with PLN-A and AL-6 strains showed less anterior segment inflammation clinically at 24 hours than did eyes infected with the wild-type strain. Histologic examination at 24 hours showed significantly less corneal infiltration and vitritis and more relative preservation of retinal tissue in eyes infected with PLN-A and AL-6 strains than in eyes infected with the wild-type strain. At 48 hours, no observable differences between PLN-A and wild-type strains were present clinically or histologically. Histologically, however, the AL-6 strain caused less retinal damage than did the wild-type strain. Conclusions: Intraocular infection with pneumolysin-deficient S, pneumoniae results in less severe tissue damage in the first 24 hours of disease compared with infection with pneumolysin-producing S. pneumoniae. Autolysin-deficient S. pneumoniae shows a similar degree of attenuated virulence. Pneumolysin and autolysin may contribute to the early pathogenesis of pneumococcal endophthalmitis. C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Wilmer Ophthalmol Inst, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Ctr Brasileiro Cirurg Olhos, Retina Serv, Goiania, Go, Brazil. Univ Fed Goias, Goiania, Go, Brazil. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP D'amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD OCT PY 2002 VL 22 IS 5 BP 622 EP 632 DI 10.1097/00006982-200210000-00014 PG 11 WC Ophthalmology SC Ophthalmology GA 604LC UT WOS:000178621400014 PM 12441729 ER PT J AU McClain, MT Scofield, RH Kurien, BT Gross, TF James, JA AF McClain, MT Scofield, RH Kurien, BT Gross, TF James, JA TI Selective small antigenic structures are capable of inducing widespread autoimmunity which closely mimics the humoral fine specificity of human SLE SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNE-RESPONSE; 60-KDA RO; SM B/B'; IMMUNIZATION; PEPTIDES; ANTIBODIES; DISEASE; PROTEIN; MICE AB Recent data have suggested that autoantibodies in lupus can progress from simple immunity against a few antigenic structures to a complex response against multiple autoantigens. Our aim was to determine whether these diverse epitope patterns can indeed be generated by antigenic challenge with a single, small structure. Rabbits were immunized with either a 60 kDa Ro peptide commonly antigenic in human system lupus erythematosus (SLE) (Ro 274-289) or one which is rarely a humoral target (Ro 500-515). Rabbits immunized with the antigenic peptide (Ro 287-289) not only developed antibodies to multiple epitopes of 60 kDa Ro and La, as has been described, but also produced non-cross-reactive antibodies to the common spliceosomal proteins Sm B' and D1, and nRNP A and C. Rabbits immunized with the Ro 274-289 peptide also mount a progressive, diversified immune response to the sequential antigenic regions of these proteins (60 kDa Ro, Sm B' and D1, nRNP A and C), which is nearly identical to that seen in human SLE. Animals immunized with the nonantigenic peptide Ro 500-515 develop antibodies only to 60 kDa Ro. These results demonstrate that loss of tolerance to select single, small antigenic structures can begin a cascade which virtually recreates, at the epitope level, the humoral autoimmune specificity seen in human SLE. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73114 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73114 USA. RI Kurien, Biji/C-2392-2008 FU NIAID NIH HHS [AI31584]; NIAMS NIH HHS [AR01981, AR45084, AR45451] NR 33 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD OCT PY 2002 VL 56 IS 4 BP 399 EP 407 DI 10.1046/j.1365-3083.2002.01141.x PG 9 WC Immunology SC Immunology GA 594HP UT WOS:000178044100008 PM 12234261 ER PT J AU Mazarati, AM Sofia, RD Wasterlain, CG AF Mazarati, AM Sofia, RD Wasterlain, CG TI Anticonvulsant and antiepileptogenic effects of fluorofelbamate in experimental status epilepticus SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE fluorofelbamate; self-sustaining status epilepticus; spontaneous seizures; rat; hippocampus; antiepileptic drugs ID METHYL-D-ASPARTATE; SUSTAINING STATUS EPILEPTICUS; TEMPORAL-LOBE EPILEPSY; IN-VITRO REACTIVITY; RAT MODEL; FELBAMATE; RECEPTORS; SEIZURES; METABOLITE; MECHANISM AB Purpose: To examine the seizure-protective properties of fluorofelbamate, a felbamate analog, on acute and chronic seizures in an experimental model of self-sustaining status epilepticus (SSSE). Methods: SSSE was induced by stimulation of the perforant path for 30 min (PPS) through chronically implanted electrodes in free-running adult male Wistar rats. Fluorofelbamate was injected intravenously (i.v.) either 10 min, or 40 min after SSSE induction. Seizure and spike profiles were analyzed off-line. Results: Fluorofelbamate injected during the early stages of SSSE (10 min after the end of PPS), shortened the duration of seizures in a dose-dependent manner. While a dose of 50 mg kg(-1) was ineffective, 100 and 200 mg kg(-1) reduced cumulative seizure time from 393 +/- 10 min to 15 +/- 8 min and 2.4 +/- 0.5 min respectively. Administration of fluorofelbamate (200 and 300 mg kg-1) at a late stage of SSSE, which is refractory to treatment with conventional anticonvulsants, also significantly attenuated seizures. Acute fluorofelbamate treatment (200 mg kg-1 10 min after PPS) significantly decreased the frequency of spontaneous seizures which follow SSSE after a 'latent' interval. Moreover, in contrast to control animals, fluorofelbamate-treated rats showed regression of spontaneous seizures, and an apparent remission of epilepsy within 2 months after SSSE. Conclusions: Acute treatment of SSSE with fluorofelbamate showed strong anticonvulsant effects even during the late stages of SSSE. In this model, it also displayed antiepileptogenic properties: it reduced the severity of chronic epilepsy after SSSE and lead to apparent remissions of that epilepsy. (C) 2002 BEA Trading Ltd. Published by Elsevier Science Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Wallace Pharmaceut, Cranbury, NJ USA. RP Wasterlain, CG (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. FU NINDS NIH HHS [NS13515] NR 32 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD OCT PY 2002 VL 11 IS 7 BP 423 EP 430 DI 10.1053/seiz.2002.0677 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 609BF UT WOS:000178882200003 PM 12237067 ER PT J AU Xia, F Powell, SN AF Xia, F Powell, SN TI The molecular basis of radio sensitivity and chemosensitivity in the treatment of breast cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID POTENTIALLY LETHAL DAMAGE; TUMOR-SUPPRESSOR GENES; DOUBLE-STRAND BREAKS; FACTOR-I RECEPTOR; CELL-LINES; ATAXIA-TELANGIECTASIA; CYCLIN D1; MONOCLONAL-ANTIBODY; DNA-REPAIR; HOMOLOGOUS RECOMBINATION C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Med Sch, Boston, MA 02114 USA. RP Powell, SN (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Med Sch, Cox Bldg,Room 302,100 Blossom St, Boston, MA 02114 USA. RI Xia, Fen/G-3708-2013 NR 80 TC 37 Z9 39 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2002 VL 12 IS 4 BP 296 EP 304 DI 10.1053/srao.2002.35250 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 610BN UT WOS:000178941000003 PM 12382188 ER PT J AU Fan, CM Santilli, JG AF Fan, CM Santilli, JG TI Endovascular repair of abdominal aortic aneurysms SO SEMINARS IN ROENTGENOLOGY LA English DT Article ID ENDOLUMINAL AAA REPAIR; STENT-GRAFT TREATMENT; FOLLOW-UP; RISK-FACTORS; ENDOLEAKS; EMBOLIZATION; ARTERY; TERM; CLASSIFICATION; EXPERIENCE C1 Massachusetts Gen Hosp, Div Vasc Radiol, Boston, MA 02114 USA. RP Fan, CM (reprint author), Massachusetts Gen Hosp, Div Vasc Radiol, GRB 290,55 Fruit St, Boston, MA 02114 USA. NR 39 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD OCT PY 2002 VL 37 IS 4 BP 282 EP 292 DI 10.1053/sroe.2002.37128 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 614NR UT WOS:000179196700005 PM 12455126 ER PT J AU Ramnath, RR Rosenthal, DI Cates, J Gebhardt, M Quinn, RH AF Ramnath, RR Rosenthal, DI Cates, J Gebhardt, M Quinn, RH TI Intracortical chondroma simulating osteoid osteoma treated by radiofrequency SO SKELETAL RADIOLOGY LA English DT Article DE intracortical chondroma; osteoid osteoma, radiofrequency ablation periosteal chondroma, radiofrequency ablation; radiographs; CT ID PERIOSTEAL CHONDROMA AB Two children presented with painful lytic lesions in the lower extremity. The lesions were located within cortical bone, and surrounded by sclerosis of the medullary bone and periosteal new bone formation. The lesions were painful, and nonsteroidal anti-inflammatory agents relieved the pain. CT-guided core biopsies were performed followed by radiofrequency treatment. Pathologic evaluation of the specimens revealed features consistent with benign intracortical chondroma. In one case radiofrequency treatment appears to have cured the tumor. The other patient required operative intervention. C1 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. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Orthopaed Associates Hartford, Hartford, CT 06106 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. OI Cates, Justin/0000-0002-7336-5196 NR 14 TC 20 Z9 20 U1 0 U2 1 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 OCT PY 2002 VL 31 IS 10 BP 597 EP 602 DI 10.1007/s00256-002-0501-4 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 607CG UT WOS:000178773000007 PM 12324830 ER PT J AU Claus, F Mijnheer, B Rasch, C Bortfeld, T Fraass, B De Gersem, W Wirtz, H Hoinkis, C Cho, BC Kwong, LWD Bae, H Muller, K De Neve, W AF Claus, F Mijnheer, B Rasch, C Bortfeld, T Fraass, B De Gersem, W Wirtz, H Hoinkis, C Cho, BC Kwong, LWD Bae, H Muller, K De Neve, W TI Report of a study on IMRT planning strategies for ethmoid sinus cancer SO STRAHLENTHERAPIE UND ONKOLOGIE LA English DT Article DE radiotherapy planning; IMRT; ethmoid sinus cancer ID CONFORMAL RADIATION-THERAPY; EXTERNAL-BEAM IRRADIATION; OPTIC NEUROPATHY; PARANASAL SINUS; TUMORS; RADIOTHERAPY; VERIFICATION; HEAD AB Aim: This communication reviews the planning strategies and dose statistics of nine IMRT plans generated for a complex head and neck case. Patient and Method: An ethmoid sinus cancer case was sent as an IMRT planning task to all participants of the ESTRO course on "IMRT and Other Conformal Techniques in Practice", held in Amsterdam in June 2001. Results: Nine IMRT plans were generated for the case, the majority of the plans generated with commercial planning systems. The number of beam incidences ranged between four and eleven, white five of the nine beam setups were coplanar. The planning target volume dose homogeneity was inversely correlated with the degree of sparing of the surrounding organs at risk. Conclusion: IMRT strategies for complex head and neck cases, such as ethmoid sinus cancer, can be strikingly different in various aspects, such as beam setup, total number of segments, PTV dose coverage and dose statistics for organs at risks. C1 State Univ Ghent Hosp, Div Radiotherapy P7, B-9000 Ghent, Belgium. Netherlands Canc Inst, NL-1066 EC Amsterdam, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Hosp Dresden, Dept Radiotherapy, Dresden, Germany. Hallym Univ Hosp, Dept Radiat Oncol, Seoul, South Korea. Queen Mary Hosp, Dept Radiotherapy, Hong Kong, Hong Kong, Peoples R China. Erasmus Med Ctr, Dept Radiotherapy, Rotterdam, Netherlands. RP Claus, F (reprint author), State Univ Ghent Hosp, Div Radiotherapy P7, De Pintelaan 185, B-9000 Ghent, Belgium. NR 17 TC 23 Z9 23 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD OCT PY 2002 VL 178 IS 10 BP 572 EP 576 DI 10.1007/s00066-002-0999-3 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 605ZM UT WOS:000178707000007 PM 12386789 ER PT J AU Jing, H Takagi, J Liu, JH Lindgren, S Zhang, RG Joachimiak, A Wang, JH Springer, TA AF Jing, H Takagi, J Liu, JH Lindgren, S Zhang, RG Joachimiak, A Wang, JH Springer, TA TI Archaeal surface layer proteins contain beta propeller, PKD, and beta helix domains and are related to metazoan cell surface proteins SO STRUCTURE LA English DT Article DE surface layer protein; beta propeller; PKD; beta helix; domain architecture; Methanosarcina ID METHANOSARCINA-MAZEI S-6; POLYCYSTIC KIDNEY-DISEASE; CRYSTAL-STRUCTURE; SEQUENCE ALIGNMENT; BINDING; PROFILE; SYSTEM; GENES; CRYSTALLOGRAPHY; SUPERFAMILY AB The surface layer of archaeobacteria protects cells from extreme environments and, in Methanosarcina, may regulate cell adhesion. We identify three domain types that account for the complete architecture of numerous Methanosarcina surface layer proteins (SLPs). We solve the crystal structure for two of these domains, which correspond to the two N-terminal domains of an M. mazei SLP. One domain displays a unique, highly symmetrical, seven-bladed beta propeller fold, and the other belongs to the polycystic kidney disease (PKD) superfamily fold. The third domain is predicted to adopt a beta helix fold. These domains have homologs in metazoan cell surface proteins, suggesting remarkable relationships between domains in archaeal SLPs and metazoan cell surface proteins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Argonne Natl Lab, Struct Biol Ctr, Biosci Div, Chicago, IL USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL48675] NR 54 TC 80 Z9 81 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD OCT PY 2002 VL 10 IS 10 BP 1453 EP 1464 AR PII S0969-2126(02)00840-7 DI 10.1016/S0969-2126(02)00840-7 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 601XX UT WOS:000178475400018 PM 12377130 ER PT J AU Spangenberg, KM Peretti, GM Trahan, CA Randolph, MA Bonassar, LJ AF Spangenberg, KM Peretti, GM Trahan, CA Randolph, MA Bonassar, LJ TI Histomorphometric analysis of a cell-based model of cartilage repair SO TISSUE ENGINEERING LA English DT Article ID ARTICULAR-CARTILAGE; DEPENDENT CONTROL; ADHESION; CHONDROCYTES; ACTIVATION; STRENGTH AB This study examined the morphology of chondrocytes in an established model of articular cartilage repair. Articular cartilage was harvested from young sheep and seeded onto pieces of devitalized sheep cartilage. The seeded pieces were stacked in pairs and wrapped in fibrin glue, and then implanted subcutaneously in the dorsum of athymic mice. Samples were harvested after 6 weeks and examined by transmission electron microscopy (TEM) or by light microscopy. TEM revealed that the cells in direct apposition to the devitalized cartilage were elongated, with an enlarged cytoplasm, and a ruffled border. TEM of cells far from the interface with scaffold tissue revealed rounded cells with large nuclei that appeared similar to normal chondrocytes. Quantitative morphometry of histologic specimens revealed that cell area, relative amount of cytoplasm, cell aspect ratio, and relative nuclear displacement were all higher in cells near the interface with the scaffold tissue, and decreased with distance from the interface. These indices of cell morphology are all consistent with an active remodeling of the scaffold at the cell-scaffold interface. C1 Univ Massachusetts, Sch Med, Ctr Tissue Engn, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bonassar, LJ (reprint author), Univ Massachusetts, Sch Med, Ctr Tissue Engn, Biotech 1,Suite 190,55 Lake Ave N, Worcester, MA 01655 USA. RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 30 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2002 VL 8 IS 5 BP 839 EP 846 DI 10.1089/10763270260424196 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 610AH UT WOS:000178938200011 PM 12459062 ER PT J AU Ballen, KK Hicks, J Dharan, B Ambruso, D Anderson, K Bianco, C Bemiller, L Dickey, W Lottenberg, R O'Neil, M Popovsky, M Skerrett, D Sniecinski, I Wingard, JR AF Ballen, KK Hicks, J Dharan, B Ambruso, D Anderson, K Bianco, C Bemiller, L Dickey, W Lottenberg, R O'Neil, M Popovsky, M Skerrett, D Sniecinski, I Wingard, JR TI Racial and ethnic composition of volunteer cord blood donors: comparison with volunteer unrelated marrow donors SO TRANSFUSION LA English DT Article ID PLACENTAL-BLOOD; ORGAN DONATION; TRANSPLANTATION; RECONSTITUTION; RECIPIENTS; LEUKEMIA; BANKING; LONDON; SYSTEM; UNITS AB BACKGROUND: Umbilical cord blood is an alternative peripheral blood progenitor cell source for patients who need transplantation. A presumed advantage of cord blood is the ability to increase minority recruitment. STUDY DESIGN AND METHODS: The racial composition of five member cord blood banks of the National Marrow Donor Program (NMDP) was compared, representing 9020 cord blood donors with NMDP marrow donors from comparable geographic areas, representing 417,676 donors. Cord blood and marrow donors self-reported racial designations on questionnaires. Donor statistics were compared with baseline racial data of deliveries from participating hospitals for cord blood donors and with geographic census data for marrow donors. RESULTS: The California, Florida, and Massachusetts cord blood banks recruited a lower percentage of minorities than the corresponding marrow donor centers. In New York and Colorado, minority recruitment was equivalent. In California, Florida, Massachusetts, and New York, the cord blood banks recruited a lower percentage of minorities than those delivering at the respective hospitals. The cord blood banks in California, Colorado, Florida, and Massachusetts recruited a lower percentage of minorities compared with delivery data than the corresponding marrow donor centers compared with census population (p < 0.001). In New York, the percentages were similar. CONCLUSION: The problem of insufficient minority recruitment of cord blood has not yet been solved. Better strategies are needed to recruit minority donors. C1 Univ Massachusetts Mem Hlth Care, Amer Red Cross Cord Blood Program, Worcester, MA USA. Dana Farber Canc Inst, New England Marrow Donor Program, Boston, MA 02115 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Mt Sinai Hosp, Cord Blood Program, New York Blood Ctr, New York, NY 10029 USA. Univ Florida, Coll Med, Lifecord Cord Blood Bank, Gainesville, FL USA. Lifesouth Community Blood Ctr, Gainesville, FL USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. San Diego Blood Bank, Ashley Ross Cord Blood Program, Duarte, CA USA. Univ Colorado, Sch Med, Colorado Marrow Donor Program, Bonfils Cord Blood Serv,Bonfils Blood Ctr, Denver, CO USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 29 TC 34 Z9 36 U1 1 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2002 VL 42 IS 10 BP 1279 EP 1284 DI 10.1046/j.1537-2995.2002.00191.x PG 6 WC Hematology SC Hematology GA 601TX UT WOS:000178465200008 PM 12423511 ER PT J AU Alper, CA Kevy, SV Konugres, AA AF Alper, CA Kevy, SV Konugres, AA TI Louis K. Diamond - Obituary SO TRANSFUSION LA English DT Biographical-Item C1 Ctr Blood Res, Boston, MA 02115 USA. RP Alper, CA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2002 VL 42 IS 10 BP 1381 EP 1382 DI 10.1046/j.1537-2995.2002.00262.x PG 2 WC Hematology SC Hematology GA 601TX UT WOS:000178465200021 PM 12449155 ER PT J AU Berzins, SP Uldrich, AP Sutherland, JS Gill, J Miller, JFAP Godfrey, DI Boyd, RL AF Berzins, SP Uldrich, AP Sutherland, JS Gill, J Miller, JFAP Godfrey, DI Boyd, RL TI Thymic regeneration: teaching an old immune system new tricks SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID T-CELL-RECEPTOR; BONE-MARROW TRANSPLANTATION; HIV-1 INFECTION; EMIGRANTS; INDIVIDUALS; LYMPHOCYTES; POOL; MICE; RECONSTITUTION; THYMOCYTES AB Recent studies in mice and humans show that the importance of the thymus extends well beyond the initial seeding of the peripheral T-cell pool. Although peripheral homeostasis can maintain T-cell numbers, the thymus is the major, if not the exclusive, source of new T-cell specificities. With age,thymus atrophy dramatically reduces the export of new T cells and predisposes an individual to impaired T-cell function, reduced T-cell immunity, and increased autoimmunity. Thymus atrophy is also the primary obstacle to restoration of the T-cell pool in the aftermath of HIV treatment or lymphoablative therapies. Here, we review thymus T-cell production, with particular attention to the factors that influence thymocyte export, and examine the impact that recent thymic emigrants have on the peripheral pool. In the future, thymic regeneration might become a feasible and potentially powerful approach to rejuvenating a depleted peripheral T-cell pool. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Monash Univ, Sch Med, Dept Pathol & Immunol, Prahran, Vic 3181, Australia. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RP Berzins, SP (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. OI Sutherland, Jayne/0000-0002-7083-4997 FU Medical Research Council [MC_U190071468] NR 53 TC 75 Z9 78 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD OCT PY 2002 VL 8 IS 10 BP 469 EP 476 DI 10.1016/S1471-4914(02)02415-2 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 599VP UT WOS:000178356100004 PM 12383769 ER PT J AU Collins, MM Barry, MJ Zietman, A Albertsen, PC Talcott, JA Corkery, EW Elliott, DB Fowler, FJ AF Collins, MM Barry, MJ Zietman, A Albertsen, PC Talcott, JA Corkery, EW Elliott, DB Fowler, FJ TI United States radiation oncologists' and urologists' opinions about screening and treatment of prostate cancer vary by region SO UROLOGY LA English DT Article ID MEDICAL-CARE; SERVICES AB Objectives. To examine whether physicians' views on prostate cancer screening and treatment vary by geographic region in the United States. Methods. A mail survey was sent in 1998 to a random sample of physicians in the United States who were listed as radiation oncologists (response rate 76%, n = 559) and urologists (response rate 64%, n = 504) in the American Medical Association Registry of Physicians and practicing at least 20 hr/wk. Results. Radiation oncologists and urologists in Florida were more likely to report recommending routine prostate-specific antigen testing for men aged 75 years and older than were their colleagues in other regions of the United States. The Florida physicians were more likely to report treating at least 20% of their patients with brachytherapy and to report believing that brachytherapy has survival value for men with a less than 10-year life expectancy. No regional differences were found in the radiation oncologists' and urologists' beliefs about the survival value of radical prostatectomy; however, for men with a less than 10-year life expectancy, Florida urologists had more confidence in the survival benefit of external beam radiotherapy than urologists in other regions (P = 0.04). Radiation oncologists in Florida reported higher rates of recommending early androgen deprivation for a rising PSA after both radiotherapy and surgery (P = 0.008 and P = 0.001, respectively) than did their colleagues in other regions. Conclusions. Florida radiation oncologists and urologists reported beliefs and practices that differed from their colleagues in other regions of the United States. Whether the distinctive style of prostate cancer diagnosis and treatment in Florida results in improved outcomes has yet to be proved. (C) 2002, Elsevier Science Inc. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Outcomes Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Dept Radiat Oncol, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 19 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD OCT PY 2002 VL 60 IS 4 BP 628 EP 633 AR PII S0090-4295(02)01832-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 603UK UT WOS:000178578700018 ER PT J AU Freedland, SJ Amling, CL Dorey, F Kane, CJ Presti, JC Terris, MK Aronson, WJ AF Freedland, SJ Amling, CL Dorey, F Kane, CJ Presti, JC Terris, MK Aronson, WJ CA Search Database Study Grp TI Race as an outcome predictor after radical prostatectomy: Results from the shared equal access regional cancer hospital (search) database SO UROLOGY LA English DT Article ID SEXTANT BIOPSIES; INDEPENDENT PREDICTOR; DISEASE RECURRENCE; SURVIVAL; IMPACT; RISK; MEN AB Objectives. Whether race is an independent predictor of prostate-specific antigen (PSA) recurrence after RP is controversial. To compare racial differences in clinical and pathologic features and biochemical recurrence in men undergoing radical prostatectomy (RP), we used a newly established multicenter database of patients from four equal-access healthcare centers in California, the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Methods. A retrospective survey of 1547 patients treated with RP at four different equal-access medical centers in California between 1988 and 2001 was undertaken. Race was categorized as white (n = 10 14), black (n = 338), or nonwhite-nonblack (n = 195). Patients were analyzed for racial differences in preoperative variables (age at surgery, clinical stage, PSA, and biopsy Gleason score) and surgical variables (pathologic stage, surgical Gleason score, incidence of seminal vesicle invasion, positive surgical margins, capsular penetration, and pelvic lymph node involvement). Patients were followed up for PSA recurrence. Multivariate analysis was used to determine whether race was an independent predictor of biochemical failure. Results. Significant differences were found among the races in the preoperative factors of clinical stage, age, serum PSA, and biopsy Gleason score, although the absolute differences were small. No differences were found among the races in the pathologic features of the RP specimens, including Gleason score, pathologic stage, and incidence of positive surgical margins, capsular penetration, seminal vesicle invasion, or lymph node involvement. In both univariate and multivariate analyses, only serum PSA (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of time to biochemical recurrence. Conclusions. In a large multicenter cohort of patients from four equal-access medical care facilities in California, although racial differences were found in clinical stage, age, biopsy Gleason score, and serum PSA level at diagnosis, we found race was not an independent predictor of biochemical recurrence after RP. Race should not be used in models or nomograms predicting PSA failure after RP. The current study represents the largest series of black patients and the first large series of nonwhite-nonblack patients treated with RP reported to date. The Shared Equal Access Regional Cancer Hospital database is a valuable resource for studying patients treated with RP. (C) 2002, Elsevier Science Inc. C1 Univ Calif Los Angeles, Dept Urol, Sch Med, Los Angeles, CA 90095 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Univ Calif Los Angeles, Dept Biostat, Sch Med, Los Angeles, CA USA. Vet Affairs Med Ctr, Dept Surg, Urol Sect, San Francisco, CA 94121 USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. Palo Alto Vet Affairs Med Ctr, Dept Surg, Palo Alto, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Dept Urol, Sch Med, Box 951738, Los Angeles, CA 90095 USA. NR 16 TC 84 Z9 87 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD OCT PY 2002 VL 60 IS 4 BP 670 EP 674 AR PII S0090-4295(02)01847-2 DI 10.1016/S0090-4295(02)01847-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 603UK UT WOS:000178578700026 PM 12385931 ER PT J AU Kazarov, AR Yang, XW Stipp, CS Sehgal, B Hemler, ME AF Kazarov, AR Yang, XW Stipp, CS Sehgal, B Hemler, ME TI An extracellular site on tetraspanin CD151 determines alpha 3 and alpha 6 integrin-dependent cellular morphology SO JOURNAL OF CELL BIOLOGY LA English DT Article DE integrins; Matrigel; tetraspanin proteins; CD151 antigen; laminin ID TRANSMEMBRANE-4 SUPERFAMILY; BASEMENT-MEMBRANE; TM4SF PROTEINS; MIGRATION; COMPLEXES; ASSOCIATION; DISTINCT; MATRIX; CELLS; ALPHA(3)BETA(1) AB he alpha3beta1 integrin shows strong, stoichiometric, direct lateral association with the tetraspanin CD151. As shown here, an extracellular CD151 site (QRD(194-196)) is required for strong (i.e., Triton X-100-resistant) alpha3beta1 association and for maintenance of a key CD151 epitope (defined by monoclonal antibody TS151r) that is blocked upon alpha3 integrin association. Strong CD151 association with integrin alpha6beta1 also required the QRD(194-196) site and masked the TS151r epitope. For both alpha3 and alpha6 integrins, strong QRD/TS151r-dependent CD151 association occurred early in biosynthesis and involved alpha subunit precursor forms. In contrast, weaker associations of CD151 with itself, integrins, or other tetraspanins (Triton X-100-sensitive but Brij 96-resistant) were independent of the QRD/TS151r site, occurred late in biosynthesis, and involved mature integrin subunits. Presence of the CD151-QRD(194-196)-->INF mutant disrupted alpha3 and alpha6 integrin-dependent formation of a network of cellular cables by Cos7 or NIH3T3 cells on basement membrane Matrigel and markedly altered cell spreading. These results provide definitive evidence that strong lateral CD151-integrin association is functionally important, identify CD151 as a key player during 0 and a6 integrin-dependent matrix remodeling and cell spreading, and support a model of CD151 as a transmembrane linker between extracellular integrin domains and intracellular cytoskeleton/signaling molecules. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Rm D1430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA086712, CA42368, CA86712, R01 CA042368] NR 60 TC 109 Z9 129 U1 1 U2 6 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 SEP 30 PY 2002 VL 158 IS 7 BP 1299 EP 1309 DI 10.1083/jcb.200204056 PG 11 WC Cell Biology SC Cell Biology GA 600TL UT WOS:000178407500015 PM 12356873 ER PT J AU Luck, J Peabody, JW AF Luck, J Peabody, JW TI Using standardised patients to measure physicians' practice: validation study using audio recordings SO BRITISH MEDICAL JOURNAL LA English DT Article ID SIMULATED PATIENTS; CHART ABSTRACTION; PERFORMANCE; QUALITY; SKILLS AB Objective To assess the validity of standardised patients to measure the quality of physicians' practice. Design Validation study of standardised patients' assessments. Physicians saw unannounced standardised patients presenting with common outpatient conditions. The standardised patients covertly tape recorded their visit and completed a checklist of quality criteria immediately afterwards. Their assessments were compared against independent assessments of the recordings by a trained medical records abstractor. Setting Four general internal medicine primary care clinics in California. Participants 144 randomly selected consenting physicians. Main outcome measures Rates of agreement between the patients' assessments and independent assessment. Results 40 visits, one per standardised patient, were recorded. The overall rate of agreement between the standardised patients' checklists and the independent assessment of the audio transcripts was 91% (K=0.81). Disaggregating the data by medical condition, site, level of physicians' training, and domain (stage of the consultation) gave similar rates of agreement. Sensitivity of the standardised patients' assessments was 95%, and specificity was 85%. The area under the receiver operator characteristic curve was 90%. Conclusions Standardised patients' assessments seem to be a valid measure of the quality of physicians' care for a variety of common medical conditions in actual outpatient settings. Properly trained standardised. patients compare well with independent assessment of recordings of the consultations and may justify their use as a "gold standard" in comparing the quality of care across sites or evaluating data obtained from other sources, such as medical records and clinical vignettes. C1 Inst Global Hlth, San Francisco, CA 94105 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Peabody, JW (reprint author), Inst Global Hlth, 74 New Montgomery St, San Francisco, CA 94105 USA. NR 30 TC 90 Z9 91 U1 1 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD SEP 28 PY 2002 VL 325 IS 7366 BP 679 EP + DI 10.1136/bmj.325.7366.679 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 600JV UT WOS:000178387600018 PM 12351358 ER PT J AU Chung, RT Evans, SR Yang, YJ Theodore, D Valdez, H Clark, R Shikuma, C Nevin, T Sherman, KE AF Chung, RT Evans, SR Yang, YJ Theodore, D Valdez, H Clark, R Shikuma, C Nevin, T Sherman, KE CA AIDS Clin Trials Grp 383 Study Tea TI Immune recovery is associated with persistent rise in hepatitis C virus RNA, infrequent liver test flares, and is not impaired by hepatitis C virus in co-infected subjects SO AIDS LA English DT Article DE HAART; HCV; hepatotoxicity; HIV; immune recovery ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; COINFECTED PATIENTS; HEMOPHILIC MEN; HIV; DISEASE; REPLICATION; INTERFERON-ALPHA-2B; PROGRESSION; COMBINATION AB Objectives: The impact of highly active antiretroviral therapy (HAART) on hepatitis C virus (HCV) is unknown. We analysed changes in HCV RNA and the frequency of hepatotoxicity in co-infected patient enrolling in AIDS Clinical Trials Group trials, and determined whether HCV impairs successful immune reconstitution in these populations. Design/methods: In a prospective analysis of co-infected patients completing at least 16 weeks of HAART in four trials, and co-infected patients with available stored plasma from two other completed HAART trials, HCV RNA was measured at baseline and to week 48. A retrospective analysis of immune recovery in 40 HCV-RNA-positive and 129 HCV-RNA-negative patients from a single trial was performed. Results: Prospective analysis: 60 patients completed at least 16 weeks of HAART. The mean HCV-RNA level increased 0.35 log(10) IU/ml at week 16 and 0.43 log(10) IU/ml at week 48. When stratified by baseline CD4 cell count, subjects' HCV-RNA levels increased 0.43 and 0.59 log(10) IU/ml at weeks 16 and 48 for entry CD4 cell counts < 350 cells/mm(3), but only 0.26 and 0.1 log(10) IU/ml at weeks 16 and 48 for entry CD4 cell counts > 350 cells/mm(3). Severe alanine aminotransferase elevations occurred in only 3.3%. Retrospective analysis: HCV co-infection had no effect on the overall mean CD4 cell increase at weeks 16 or 48 compared with uninfected controls. Conclusion: In HCV-co-infected patients undergoing HAART, immune recovery is associated with a persistent increase in HCV RNA, especially with baseline CD4 cell counts < 350 cells/mm(3). HCV co-infection did not antagonize the CD4 cell response to HAART. (C) 2002 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Tulane Univ, New Orleans, LA 70118 USA. Univ Hawaii, Honolulu, HI 96822 USA. ACTG Operat Ctr, Rockville, MD USA. Univ Cincinnati, Cincinnati, OH USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. NR 24 TC 117 Z9 119 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 SEP 27 PY 2002 VL 16 IS 14 BP 1915 EP 1923 DI 10.1097/00002030-200209270-00008 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 611WE UT WOS:000179040100008 PM 12351951 ER PT J AU Chen, JF Steyn, S Staal, R Petzer, JP Xu, K Van der Schyf, CJ Castagnoli, K Sonsalla, PK Castagnoli, N Schwarzschild, MA AF Chen, JF Steyn, S Staal, R Petzer, JP Xu, K Van der Schyf, CJ Castagnoli, K Sonsalla, PK Castagnoli, N Schwarzschild, MA TI 8-(3-chlorostyryl)caffeine may attenuate MPTP neurotoxicity through dual actions of monoamine oxidase inhibition and A(2A) receptor antagonism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARKINSONS-DISEASE; HUMAN-PLACENTA; CAFFEINE; BRAIN; MICE; MODELS; RISK AB Caffeine and more specific antagonists of the adenosine A(2A) receptor recently have been found to be neuroprotective in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease. Here we show that 8-(3-chlorostyryl)caffeine (CSC), a specific A(2A) antagonist closely related to caffeine, also attenuates MPTP-induced neurotoxicity. Because the neurotoxicity of MPTP relies on its oxidative metabolism to the mitochondrial toxin MPP+, we investigated the actions of CSC on striatal MPTP metabolism in vivo. CSC elevated striatal levels of MPTP but lowered levels of the oxidative intermediate MPDP+ and of MPP+, suggesting that CSC blocks the conversion of MPTP to MPDP+ in vivo. In assessing the direct effects of CSC and A(2A) receptors on monoamine oxidase (MAO) activity, we found that CSC potently and specifically inhibited mouse brain mitochondrial MAO-B activity in vitro with a K-i value of 100 nm, whereas caffeine and another relatively specific A(2A) antagonist produced little or no inhibition. The A(2A) receptor independence of MAO-B inhibition by CSC was further supported by the similarity of brain MAO activities derived from A(2A) receptor knockout and wild-type mice and was confirmed by demonstrating potent inhibition of A(2A) receptor knockout-derived MAO-B by CSC. Together, these data indicate that CSC possesses dual actions of MAO-B inhibition and A(2A) receptor antagonism, a unique combination suggesting a new class of compounds with the potential for enhanced neuroprotective properties. C1 Massachusetts Gen Hosp, Mol Neurobiol Lab, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Virginia Tech, Dept Chem, Harvey W Peters Ctr, Blacksburg, VA 24061 USA. Univ Med & Dent New Jersey, Dept Neurol, Piscataway, NJ 08854 USA. RP Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM chenjf@bu.edu; michaels@helix.mgh.harvard.edu OI Petzer, Jacobus/0000-0002-7114-8120 FU NIA NIH HHS [AG08479, AG18167]; NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS37403, NS41083] NR 28 TC 52 Z9 54 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 27 PY 2002 VL 277 IS 39 BP 36040 EP 36044 DI 10.1074/jbc.M206830200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 598KN UT WOS:000178275100036 PM 12130655 ER PT J AU Benn, SC Perrelet, D Kato, AC Scholz, J Decosterd, I Mannion, RJ Bakowska, JC Woolf, CJ AF Benn, SC Perrelet, D Kato, AC Scholz, J Decosterd, I Mannion, RJ Bakowska, JC Woolf, CJ TI Hsp27 upregulation and phosphorylation is required for injured sensory and motor neuron survival SO NEURON LA English DT Article ID BACTERIAL ARTIFICIAL CHROMOSOME; PERIPHERAL-NERVE INJURY; C-DEPENDENT ACTIVATION; PROGRAMMED CELL-DEATH; HEAT-SHOCK PROTEINS; IAP FAMILY PROTEINS; CYTOCHROME-C; DEVELOPING MOTONEURONS; SCIATIC-NERVE; IN-VIVO AB Peripheral nerve transection results in the rapid death by apoptosis of neonatal but not adult sensory and motor neurons. We show that this is due to induction and phosphorylation in all adult axotomized neurons of the small heat shock protein Hsp27 and the failure of such induction in most neonatal neurons. In vivo delivery of human Hsp27 but not a nonphosphorylatable mutant prevents neonatal rat motor neurons from nerve injury-induced death, while knockdown in vitro and in vivo of Hsp27 in adult injured sensory neurons results in apoptosis. Hsp27's neuroprotective action is downstream of cytochrome c release from mitochondria and upstream of caspase-3 activation. Transcriptional and posttranslational regulation of Hsp27 is necessary for sensory and motor neuron survival following peripheral nerve injury. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. CHU Vaudois, Dept Anesthesiol, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Expt Surg, CH-1011 Lausanne, Switzerland. Ctr Med Univ Geneva, Fac Med, Dept Anesthesiol Pharmacol & Surg Intens Care, CH-1211 Geneva 4, Switzerland. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD38533]; NINDS NIH HHS [NS38253] NR 62 TC 174 Z9 182 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 26 PY 2002 VL 36 IS 1 BP 45 EP 56 DI 10.1016/S0896-6273(02)00941-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 598UP UT WOS:000178295100006 PM 12367505 ER PT J AU Ji, RR Samad, TA Jin, SX Schmoll, R Woolf, CJ AF Ji, RR Samad, TA Jin, SX Schmoll, R Woolf, CJ TI p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia SO NEURON LA English DT Article ID NERVE GROWTH-FACTOR; ROOT GANGLION NEURONS; SIGNAL-REGULATED KINASE; PROTEIN-KINASE; CAPSAICIN RECEPTOR; PAIN HYPERSENSITIVITY; VANILLOID RECEPTOR-1; MESSENGER-RNA; IMMUNOCYTOCHEMICAL LOCALIZATION; PERIPHERAL INFLAMMATION AB Peripheral inflammation induces p38 MAPK activation in the soma of C fiber nociceptors in the dorsal root ganglion [DRG) after 24 hr. Inflammation also increases protein, but not mRNA levels, of the heat-gated ion channel TRPV1 (VR1) in these cells, which is then transported to peripheral but not central C fiber terminals. Inhibiting p38 activation in the DRG reduces the increase in TRPV1 in the DRG and inflamed skin and diminishes inflammation-induced heat hypersensitivity without affecting inflammatory swelling or basal pain sensitivity. p38 activation in the DRG is secondary to peripheral production of NGF during inflammation and is required for NGF-induced increases in TRPV1. The activation of p38 in the DRG following retrograde NGF transport, by increasing TRPV1 levels in nociceptor peripheral terminals in a transcription-independent fashion, contributes to the maintenance of inflammatory heat hypersensitivity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Ji, RR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [R 01 NS39518, R01 NS040698, R01 NS40698] NR 64 TC 722 Z9 762 U1 8 U2 30 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 26 PY 2002 VL 36 IS 1 BP 57 EP 68 DI 10.1016/S0896-6273(02)00908-X PG 12 WC Neurosciences SC Neurosciences & Neurology GA 598UP UT WOS:000178295100007 PM 12367506 ER PT J AU Kronenberg, HM AF Kronenberg, HM TI NPT2a - The key to phosphate homeostasis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GENE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 28 Z9 29 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 2002 VL 347 IS 13 BP 1022 EP 1024 DI 10.1056/NEJMe020098 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 596RD UT WOS:000178178400010 PM 12324560 ER PT J AU Warren, HS Suffredini, AF Eichacker, PQ Munford, RS AF Warren, HS Suffredini, AF Eichacker, PQ Munford, RS TI Risks and benefits of activated protein C treatment for severe sepsis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID APACHE-II; VARIABILITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIAID NIH HHS [AI18188]; NIGMS NIH HHS [R01-GM59694-02] NR 14 TC 161 Z9 167 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 26 PY 2002 VL 347 IS 13 BP 1027 EP 1030 DI 10.1056/NEJMsb020574 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 596RD UT WOS:000178178400012 PM 12324562 ER PT J AU Horwitz, SM Kelleher, K Boyce, T Jensen, P Murphy, M Perrin, E Stein, REK Weitzman, M AF Horwitz, SM Kelleher, K Boyce, T Jensen, P Murphy, M Perrin, E Stein, REK Weitzman, M TI Barriers to health care research for children and youth with psychosocial problems SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies CY APR 29-MAY 13, 2001 CL BALTIMORE, MARYLAND SP Pediatr Acad Soci ID PEDIATRIC PRIMARY CARE; IDENTIFICATION; PREVALENCE; DISORDERS AB Context The 1999 surgeon general's report on mental health concluded that insufficient attention to mental health disorders is being paid in children's primary medical care services. This lack of attention has occurred despite considerable attention to this issue in the planning documents of many federal agencies. Objective To assess the extent to which federal agencies' portfolios of funded research grants were consistent with the directives for primary care-based mental health services for children and adolescents featured in their planning documents. Data Source A cross-sectional review of the 66749 abstracts listed in the April 2001 Computer Retrieval of information on Scientific Projects (CRISP) database of currently funded research grants supported by the US Department of Health and Human Services. Abstracts were rated by whether they targeted primary care, examined behavioral or emotional issues, and examined or modified a facet of primary care. Data Synthesis Of the 45022 research abstracts in the CRISP database, 2720 (6%) contained the words children, adolescents, or youth. Sixty-three abstracts contained work on children, adolescents, or youth in primary care (0.14% of the portfolio). Of these 63 abstracts, only 21 (0.05% of the portfolio) addressed behavioral or emotional issues. Of the 21 projects, only 11 examined aspects of the primary care process. When the distribution of child and adult studies on the treatment of depression within primary care settings was examined, it was found that adults received 15 times the research attention compared with children. Conclusion Even though the importance of primary care as a system for identifying and treating behavioral and emotional problems in children has been recognized for more than 20 years, little attention is being paid to this topic in the research portfolios of the National Institutes of Health and other federal agencies that support research. C1 Yale Univ, Sch Med, Ctr Child Study, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Ohio State Univ, Childrens Res Inst, Columbus, OH 43210 USA. Univ Calif Berkeley, Sch Publ Hlth, Inst Human Dev, Berkeley, CA 94720 USA. Columbia Univ, Ctr Advancement Childrens Mental Hlth, New York, NY USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Dept Pediat, Boston, MA 02111 USA. Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA. Amer Acad Pediat Ctr Child Hlth Res, Rochester, NY USA. Univ Rochester, Sch Med & Dent, Strong Childrens Res Ctr, Rochester, NY USA. RP Horwitz, SM (reprint author), Yale Univ, Sch Med, Ctr Child Study, Dept Epidemiol & Publ Hlth, 60 Coll St,Box 208034, New Haven, CT 06520 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 15 TC 27 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 25 PY 2002 VL 288 IS 12 BP 1508 EP 1512 DI 10.1001/jama.288.12.1508 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 596AT UT WOS:000178142000022 PM 12243638 ER PT J AU Inglessis, L Pomerantsev, E Bloch, KD Hales, C Palacios, IF Semigran, MJ AF Inglessis, L Pomerantsev, E Bloch, KD Hales, C Palacios, IF Semigran, MJ TI Nonuniformity of pulmonary arterial thickening in patients with chronic pulmonary hypertension: An intravascular ultrasound study. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 14th Annual Symposium on Transcatheter Cardiovascular Therapeutics CY SEP 24, 2002 CL WASHINGTON, D.C. SP Cardiovasc Res Fdn, Lenoz Hill Heart, Vasc Inst New York C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 24 PY 2002 VL 90 IS 6A SU S MA TCT325 BP 127H EP 127H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594XH UT WOS:000178077400322 ER PT J AU Marshik, B Tan, H Tang, J Zuluaga, A Moreno, PR Purushothaman, KR O'Connor, W Tearney, G AF Marshik, B Tan, H Tang, J Zuluaga, A Moreno, PR Purushothaman, KR O'Connor, W Tearney, G TI Discrimination of lipid-rich plaques in human aorta specimens with NIR spectroscopy through whole blood. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 14th Annual Symposium on Transcatheter Cardiovascular Therapeutics CY SEP 24, 2002 CL WASHINGTON, D.C. SP Cardiovasc Res Fdn, Lenoz Hill Heart, Vasc Inst New York C1 InfraReDx Inc, Cambridge, MA USA. Univ Kentucky, Lexington, KY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 24 PY 2002 VL 90 IS 6A SU S MA TCT330 BP 129H EP 129H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594XH UT WOS:000178077400327 ER PT J AU Cannon, CP AF Cannon, CP TI Evidence-based risk stratification to target therapies in acute coronary syndromes SO CIRCULATION LA English DT Editorial Material DE editorials; angina; myocardial infarction; catheterization; anticoagulants ID ELEVATION MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; TROPONIN-T; UNSTABLE ANGINA; ARTERY DISEASE; THROMBOLYTIC THERAPY; BENEFIT; MORTALITY; TIROFIBAN; OUTCOMES C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 41 TC 40 Z9 43 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 24 PY 2002 VL 106 IS 13 BP 1588 EP 1591 DI 10.1161/01.CIR.0000030416.80014.F4 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 599AQ UT WOS:000178311500010 PM 12270844 ER PT J AU Yabushita, H Bourna, BE Houser, SL Aretz, T Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Kang, DH Halpern, EF Tearney, GJ AF Yabushita, H Bourna, BE Houser, SL Aretz, T Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Kang, DH Halpern, EF Tearney, GJ TI Characterization of human atherosclerosis by optical coherence tomography SO CIRCULATION LA English DT Article DE atherosclerosis; catheters; imaging; tomography; plaque ID HUMAN CORONARY-ARTERIES; INTRAVASCULAR ULTRASOUND; IN-VIVO; PLAQUES; TISSUE; VITRO; CLASSIFICATION; SPECTROSCOPY; CHOLESTEROL; VALIDATION AB Background-High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 mum. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. Methods and Results-OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96%, and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). Conclusions-Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality mid will provide a basis for the interpretation of intracoronary OCT images obtained from patients. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kinki Univ, Sch Med, Dept Internal Med 1, Osakasayama, Osaka, Japan. RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 40 Blossom St,BAR 703, Boston, MA 02114 USA. NR 34 TC 587 Z9 621 U1 1 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 24 PY 2002 VL 106 IS 13 BP 1640 EP 1645 DI 10.1161/01.CIR.0000029927.92825.F6 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 599AQ UT WOS:000178311500022 PM 12270856 ER PT J AU Zandi, PP Anthony, JC Hayden, KM Mehta, K Mayer, L Breitner, JCS AF Zandi, PP Anthony, JC Hayden, KM Mehta, K Mayer, L Breitner, JCS CA Cache County Study Investigators TI Reduced incidence of AD with NSAID but not H-2 receptor antagonists - The Cache County Study SO NEUROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HISTAMINE-H2 BLOCKING-DRUGS; ALZHEIMERS-DISEASE; RHEUMATOID-ARTHRITIS; COGNITIVE DECLINE; CONTROLLED TRIAL; DOUBLE-BLIND; DEMENTIA; RISK; INFLAMMATION AB Background: Previous analyses from the Cache County (UT) Study showed inverse associations between the prevalence of AD and the use of nonsteroidal anti-inflammatory drugs (NSAID), aspirin compounds, or histamine H, receptor antagonists (H,RA). The authors re-examined these associations using data on incident AD. Methods: In 1995 to 1996, elderly (aged 65+) county residents were assessed for dementia, with current and former use of NSAID, aspirin, and H,RA as well as three other "control" medication classes also noted. Three years later, interval medication histories were obtained and 104 participants with incident AD were identified among 3,227 living participants. Discrete time survival analyses estimated the risk of incident AD in relation to medication use. Results: AD incidence was marginally reduced in those reporting NSAID use at any time. Increased duration of use was associated with greater risk reduction, and the estimated hazard ratio was 0.45 with greater than or equal to2 years of exposure. Users of NSAID at baseline showed little reduction in AD incidence, regardless of use thereafter. By contrast, former NSAID users showed substantially reduced incidence (estimated hazard ratio = 0.42), with a trend toward greatest risk reduction among those with extended exposure. Similar patterns appeared with aspirin but not with any other medicines examined. Conclusions: Long-term NSAID use may reduce the risk of AD, provided such use occurs well before the onset of dementia. More recent exposure seems to offer little protection. Recently initiated randomized trials of NSAID for primary prevention of AD are therefore unlikely to show effects with treatment until participants have been followed for several years. C1 VA Puget Sound Hlth Care Syst, GRECC S182, Seattle, WA 98108 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Banner Hlth Syst, Phoenix, AZ USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [AG-11380]; NIMH NIH HHS [MH-14592] NR 48 TC 218 Z9 224 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 24 PY 2002 VL 59 IS 6 BP 880 EP 886 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 596JH UT WOS:000178161100015 PM 12297571 ER PT J AU Clegg, LX Li, FP Hankey, BG Chu, K Edwards, BK AF Clegg, LX Li, FP Hankey, BG Chu, K Edwards, BK TI Cancer survival among US whites and minorities - A SEER (Surveillance, Epidemiology, and End Results) program population-based study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID FECAL-OCCULT-BLOOD; LOCALIZED PROSTATE-CANCER; BREAST-CANCER; COLORECTAL-CANCER; RACIAL-DIFFERENCES; DECISION-ANALYSIS; BLACK-WOMEN; LUNG-CANCER; RACE; STAGE AB Background: Available cancer statistics pertain primarily to white and African American populations. This study describes racial or ethnic patterns of cancer-specific survival and relative risks (RRs) of cancer death for all cancers combined and for cancers of the colon and rectum, lung and bronchus, prostate, and female breast for the 6 major US racial or ethnic groups. Methods: Cancer-specific survival rates were analyzed for more than 1.78 million patients who resided in the 9 SEER (Surveillance, Epidemiology, and End Results) Program geographic areas and were diagnosed between 1975 and 1997 as having an incident invasive cancer, by 6 racial or ethnic groups (non-Hispanic whites, Hispanic whites, African Americans, Asian Americans, Hawaiian natives, and American Indians and Alaskan natives). Results: Survival rates improved between 1988 to 1997 for virtually all racial or ethnic groups. However, racial or ethnic differences in RRs of cancer death persisted after controlling for age for all cancers combined and for age and stage for specific cancer sites (P<.01). African American, American Indian and Alaskan native, and Hawaiian native patients tended to have higher RRs of cancer death than the other groups. American Indians and Alaskan natives generally exhibited the highest RRs of cancer death, except for colorectal cancer in males. Conclusions: Survival rates in patients with cancer have improved in recent years, but racial or ethnic differences in survival rates and in RRs of cancer death persist. Additional studies are needed to clarify the socioeconomic, medical, biological, cultural, and other determinants of these findings. C1 NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. NCI, Ctr Reduce Canc Hlth Dispar, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Clegg, LX (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,MSC 8316,Suite 504, Bethesda, MD 20892 USA. FU NCI NIH HHS [U01CA86322] NR 52 TC 325 Z9 329 U1 1 U2 7 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 SEP 23 PY 2002 VL 162 IS 17 BP 1985 EP 1993 DI 10.1001/archinte.162.17.1985 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 594TM UT WOS:000178067100009 PM 12230422 ER PT J AU Crackower, MA Oudit, GY Kozieradzki, I Sarao, R Sun, H Sasaki, T Hirsch, E Suzuki, A Shioi, T Irie-Sasaki, J Sah, R Cheng, HYM Rybin, VO Lembo, G Fratta, L Oliveira-dos-Santos, AJ Benovic, JL Kahn, CR Izumo, S Steinberg, SF Wymann, MP Backx, PH Penninger, JM AF Crackower, MA Oudit, GY Kozieradzki, I Sarao, R Sun, H Sasaki, T Hirsch, E Suzuki, A Shioi, T Irie-Sasaki, J Sah, R Cheng, HYM Rybin, VO Lembo, G Fratta, L Oliveira-dos-Santos, AJ Benovic, JL Kahn, CR Izumo, S Steinberg, SF Wymann, MP Backx, PH Penninger, JM TI Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways SO CELL LA English DT Article ID PROTEIN-COUPLED RECEPTORS; TUMOR-SUPPRESSOR GENE; PHOSPHOINOSITIDE 3-KINASE; CARDIAC-HYPERTROPHY; PTEN; ACTIVATION; KINASE; PHOSPHOLAMBAN; PI3K-GAMMA; HEART AB The PTEN/PI3K signaling pathway regulates a vast array of fundamental cellular responses. We show that cardiomyocyte-specific inactivation of tumor suppressor PTEN results in hypertrophy, and unexpectedly, a dramatic decrease in cardiac contractility. Analysis of double-mutant mice revealed that the cardiac hypertrophy and the contractility defects could be genetically uncoupled. PI3Kalpha mediates the alteration in cell size while PI3Kgamma acts as a negative regulator of cardiac contractility. Mechanistically, PI3Kgamma inhibits cAMP production and hypercontractility can be reverted by blocking cAMP function. These data show that PTEN has an important in vivo role in cardiomyocyte hypertrophy and GPCR signaling and identify a function for the PTEN-PI3Kgamma pathway in the modulation of heart muscle contractility. C1 Austrian Acad Sci, Inst Mol Biotechnol, IMBA, A-1030 Vienna, Austria. Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 2C1, Canada. Univ Toronto, Ontario Canc Inst, Dept Immunol, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Physiol, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Univ Hlth Network Richard Lewar Heart & Stroke Ct, Toronto, ON, Canada. Tokyo Metropolitan Inst Med Sci, Dept Pharmacol, Tokyo 113, Japan. JST, PRESTO, Tokyo, Japan. Univ Turin, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy. Akita Univ, Dept Biochem, Sch Med, Akita 0108543, Japan. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Columbia Univ, Dept Pharmacol, New York, NY 10032 USA. Columbia Univ, Dept Med, New York, NY 10032 USA. Neuromed Inst, Dept Neurocardiol, Pozzilli, Italy. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Immunol, Philadelphia, PA 19107 USA. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Fribourg, Dept Med, Div Biochem, CH-1700 Fribourg, Switzerland. RP Penninger, JM (reprint author), Austrian Acad Sci, Inst Mol Biotechnol, IMBA, Dr Bohr Gasse 7, A-1030 Vienna, Austria. RI Wymann, Matthias/C-3227-2008; Hirsch, Emilio/F-4848-2013; Penninger, Josef/I-6860-2013; OI Hirsch, Emilio/0000-0002-9073-6024; Penninger, Josef/0000-0002-8194-3777; Lembo, Giuseppe/0000-0002-3510-223X FU NHLBI NIH HHS [HL28958, HL65742] NR 47 TC 386 Z9 422 U1 2 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 20 PY 2002 VL 110 IS 6 BP 737 EP 749 DI 10.1016/S0092-8674(02)00969-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 596TV UT WOS:000178182800009 PM 12297047 ER PT J AU Wojtowicz, WM Farzan, M Joyal, JL Carter, K Babcock, GJ Israel, DI Sodroski, J Mirzabekov, T AF Wojtowicz, WM Farzan, M Joyal, JL Carter, K Babcock, GJ Israel, DI Sodroski, J Mirzabekov, T TI Stimulation of enveloped virus infection by beta-amyloid fibrils SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; NEUTRALIZATION SENSITIVITY; HIV-INFECTION; TYPE-1 RNA; CELL-LINE; DEMENTIA; CCR5; RECEPTOR AB Alzheimer's disease is characterized by deposition of beta-amyloid peptide (Abeta) into plaques in the brain, leading to neuronal toxicity and dementia. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system can also cause a dementia, and amyloid deposition in the central nervous system is significantly higher in HIV-1-infected individuals compared with uninfected controls. Here we report that Abeta fibrils stimulated, by 5-20-fold, infection of target cells expressing CD4 and an appropriate coreceptor by multiple HIV-1 isolates but did not permit infection of cells lacking these receptors. Abeta enhanced infection at the stage of virus attachment or entry into the cell. Abeta fibrils also stimulated infection by amphotrophic Moloney leukemia virus, herpes simplex virus, and viruses pseudotyped with the envelope glycoprotein of vesicular stomatitis virus. Other synthetic fibril-forming peptides similarly enhanced viral infection and may be useful in gene delivery applications utilizing retroviral vectors. These data suggest that Abeta deposition may increase the vulnerability of the central nervous system to enveloped viral infection and that amyloidogenic peptides could be useful in enhancing gene transfer by enveloped viral vectors. C1 Praecis Pharmaceut Inc, Waltham, MA 02451 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Mirzabekov, T (reprint author), Praecis Pharmaceut Inc, 830 Winter St, Waltham, MA 02451 USA. FU NIAID NIH HHS [AI42848, AI31783, AI41851, AI46725] NR 50 TC 42 Z9 43 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 SEP 20 PY 2002 VL 277 IS 38 BP 35019 EP 35024 DI 10.1074/jbc.M203518200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 595PB UT WOS:000178117000047 PM 12119288 ER PT J AU Johnson, KR Becker, KP Facchinetti, MM Hannun, YA Obeid, LM AF Johnson, KR Becker, KP Facchinetti, MM Hannun, YA Obeid, LM TI PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane - Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 2ND MESSENGER; CELL-GROWTH; 1-PHOSPHATE; CERAMIDASE; EXPRESSION; STRESS; SPHINGOMYELINASE; DIFFERENTIATION; PROLIFERATION; SURVIVAL AB Sphingosine-1-phosphate (S1P) is a highly bioactive sphingolipid involved in diverse biological processes leading to changes in cell growth, differentiation, motility, and survival. S1P generation is regulated via sphingosine kinase (SK), and many of its effects are mediated through extracelluar action on G-protein-coupled receptors. In this study, we have investigated the mechanisms regulating SK, where this occurs in the cell, and whether this leads to release of S1P extracellularly. The protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), induced early activation of SK in HEK 293 cells, and this activation was more specific to the membrane-associated SK. Therefore, we next investigated whether PMA induced translocation of SK to the plasma membrane. PMA induced translocation of both endogenous and green fluorescent protein (GFP)-tagged human SKI (hSK1) to the plasma membrane. PMA also induced phosphorylation of GFP-hSK1. The PMA-induced translocation was abrogated by preincubation with known PKC inhibitors (bisindoylmaleimide and calphostin-c) as well as by the indirect inhibitor of PKC, C-6-ceramide, supporting a role for PKC in mediating translocation of SK to the plasma membrane. SK activity was not necessary for translocation, because a dominant negative G82D mutation also translocated in response to PMA. Importantly, PKC regulation of SK was accompanied by a 4-fold increase in S1P in the media. These results demonstrate a novel mechanism by which PKC regulates SK and increases secretion of S1P, allowing for autocrine/paracrine signaling. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Dept Vet Affairs, Ralph H Johnson Vet Affairs Med Ctr, Div Gen Internal Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Univ Buenos Aires, Fac Farm & Bioquim, Dept Biol Sci, RA-1113 Buenos Aires, DF, Argentina. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NHLBI NIH HHS [HL43707, HL07260]; NIGMS NIH HHS [GM62887] NR 30 TC 202 Z9 209 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 20 PY 2002 VL 277 IS 38 BP 35257 EP 35262 DI 10.1074/jbc.M203033200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 595PB UT WOS:000178117000077 PM 12124383 ER PT J AU Jatana, M Giri, S Singh, AK AF Jatana, M Giri, S Singh, AK TI Apoptotic positive cells in Krabbe brain and induction of apoptosis in rat C6 glial cells by psychosine SO NEUROSCIENCE LETTERS LA English DT Article DE Krabbe brain; terminal dUTP nick-end labeling; apoptosis; psychosine; C6 glial cells; annexin-V ID MURINE MODEL; OLIGODENDROCYTES; LEUKODYSTROPHY; LOCALIZATION; ACCUMULATION; METABOLITE; TWITCHER; DISEASE; DEATH AB Globoid cell leukodystrophy (GILD) is an autosomal recessive disorder of infants, caused by deficient activity of cerebroside-beta-galactosidase resulting in loss of myelin accompanied by loss of oligodendrocytes. The loss of oligodendrocyte population is accompanied by accumulation of psychosine, which is considered as the molecule responsible for the observed pathophysiology of GLD. We were able to detect apoptotic cells by terminal dUTP nick-end labeling assay and nuclear localization of p53 in postmortem brain tissue of Krabbe's disease patients, which were not detected in the control brain. To study the role of psychosine in cell death, we investigated the effect of psychosine on C6 glial cell survival by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Similar to ceramide (43.8% loss) the galactopsychosine and glucopsychosine treatment killed up to 46.3 and 48.75% of cells, respectively. On the other hand, sphingosine had no effect. DNA laddering assay confirmed these results. Moreover, psychosine-induced detection of annexin-V positive cells supports a role for psychosine in C6 glial cell death via the apoptotic pathway. These results indicate that psychosine may play a role in apoptotic cell loss observed in GILD brain. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Pathol & Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Pediat, 316 Clin Sci Bldg,POB 250160, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-37766] NR 20 TC 54 Z9 55 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 SEP 20 PY 2002 VL 330 IS 2 BP 183 EP 187 AR PII S0304-3940(02)00655-9 DI 10.1016/S0304-3940(02)00655-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 606GC UT WOS:000178725400015 PM 12231442 ER PT J AU Liberman, MC Gao, JG He, DZZ Wu, XD Jia, SP Zuo, J AF Liberman, MC Gao, JG He, DZZ Wu, XD Jia, SP Zuo, J TI Prestin is required for electromotility of the outer hair cell and for the cochlear amplifier SO NATURE LA English DT Article ID BASILAR-MEMBRANE; MOTOR PROTEIN; RESPONSES; ADAPTATION AB Hearing sensitivity in mammals is enhanced by more than 40 dB (that is, 100-fold) by mechanical amplification thought to be generated by one class of cochlear sensory cells, the outer hair cells(1-4). In addition to the mechano-electrical transduction required for auditory sensation, mammalian outer hair cells also perform electromechanical transduction, whereby transmembrane voltage drives cellular length changes at audio frequencies in vitro(5-7). This electromotility is thought to arise through voltage-gated conformational changes in a membrane protein 8,9, and prestin has been proposed as this molecular motor(10-12). Here we show that targeted deletion of prestin in mice results in loss of outer hair cell electromotility in vitro and a 40-60 dB loss of cochlear sensitivity in vivo, without disruption of mechano-electrical transduction in outer hair cells. In heterozygotes, electromotility is halved and there is a twofold (about 6 dB) increase in cochlear thresholds. These results suggest that prestin is indeed the motor protein, that there is a simple and direct coupling between electromotility and cochlear amplification, and that there is no need to invoke additional active processes to explain cochlear sensitivity in the mammalian ear. C1 St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN 38163 USA. RP Zuo, J (reprint author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM jian.zuo@stjude.org NR 29 TC 452 Z9 480 U1 7 U2 42 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 19 PY 2002 VL 419 IS 6904 BP 300 EP 304 DI 10.1038/nature01059 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 594NH UT WOS:000178056300046 PM 12239568 ER PT J AU Tawakol, A Forgione, MA Steuhlinger, M Alpert, NM Cooke, JP Loscalzo, J Fischman, AJ Creager, MA Gewirtz, H AF Tawakol, A Forgione, MA Steuhlinger, M Alpert, NM Cooke, JP Loscalzo, J Fischman, AJ Creager, MA Gewirtz, H TI Homocysteine impairs coronary microvascular dilator function in humans SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MYOCARDIAL BLOOD-FLOW; ENDOTHELIUM-DEPENDENT VASODILATION; POSITRON-EMISSION-TOMOGRAPHY; NITRIC-OXIDE SYNTHASE; PLASMA HOMOCYSTEINE; ARTERY DISEASE; VASCULAR-DISEASE; RISK FACTOR; HYPERHOMOCYST(E)INEMIA; HYPERHOMOCYSTEINEMIA AB OBJECTIVES We sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function. BACKGROUND Hyperhomocysteinemia is associated with abnormal endothetium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known. METHODS Eighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist N-G-monomethyl-L-arginine (L-NMMA) (0.3 mg/kg/min intravenously). RESULTS Hyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 +/- 1.00 ml/min/g vs. 0.58 +/- 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 +/- 2.6% vs. 2.6 +/- 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of L-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of L-NMMA (2.08 +/- 1.34 ml/min/g vs. 1.48 +/- 1.32 ml/min/g, placebo VS. L-NMMA, p < 0.05). CONCLUSIONS The data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability. C1 Massachusetts Gen Hosp, Cardiac Unit Vincent Burnham 3, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Med, Boston, MA 02215 USA. Stanford Univ, Med Ctr, Dept Med, Stanford, CA 94305 USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac Unit Vincent Burnham 3, Dept Med, Boston, MA 02114 USA. OI Cooke, John/0000-0003-0033-9138 FU NHLBI NIH HHS [HL55993, HL10107, HL48743, HL58638, HL58976, HL61795] NR 33 TC 57 Z9 62 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 18 PY 2002 VL 40 IS 6 BP 1051 EP 1058 AR PII S0735-1097(02)02069-7 DI 10.1016/S0735-1097(02)02069-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 593TQ UT WOS:000178009900005 PM 12354427 ER PT J AU Ratcliffe, MB AF Ratcliffe, MB TI Non-ischemic infarct extension - A new type of infarct enlargement and a potential therapeutic target SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID LEFT-VENTRICULAR ANEURYSM; ACUTE MYOCARDIAL-INFARCTION; MATRIX-METALLOPROTEINASE; MECHANICAL DYSFUNCTION; VOLUME REDUCTION; PATCH REPAIR; BORDER ZONE; CELL-DEATH; MODEL; MYOCYTES C1 San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Surg, Div Cardiothorac Surg, San Francisco, CA 94143 USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, 4150 Clement St, San Francisco, CA 94121 USA. NR 31 TC 33 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 18 PY 2002 VL 40 IS 6 BP 1168 EP 1171 AR PII S0735-1097(02)02113-7 DI 10.1016/S0735-1097(02)02113-7 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 593TQ UT WOS:000178009900023 ER PT J AU Berg, AO Allan, JD Frame, PS Homer, CJ Johnson, MS Klein, JD Lieu, TA Mulrow, CD Orleans, CT Peipert, JF Pender, NJ Siu, AL Teutsch, SM Westhoff, C Woolf, SH AF Berg, AO Allan, JD Frame, PS Homer, CJ Johnson, MS Klein, JD Lieu, TA Mulrow, CD Orleans, CT Peipert, JF Pender, NJ Siu, AL Teutsch, SM Westhoff, C Woolf, SH CA US Preventive Serv Task Force TI Screening for osteoporosis in postmenopausal women: Recommendations and rationale SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BONE DENSITOMETRY AB This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendations on screening for osteoporosis and the supporting scientific evidence and updates the 1996 USPSTF recommendations on this topic. The complete USPSTF recommendation and rationale statement on this topic, which includes a brief review of the supporting evidence, is available through the USPSTF Web site (www.preventiveservices.ahrq.gov), the National Guideline Clearinghouse (www.guideline.gov), and in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (telephone, 800-358-9295; e-mail, ahrqpubs@ahrq.gov). The complete information on which this statement is based, including evidence tables and references, is available in the accompanying article in this issue and in the summary of the evidence and the systematic evidence review on the Web sites already mentioned. C1 Univ Washington, Seattle, WA 98195 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Rochester, Rochester, NY 14627 USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Rochester, Sch Med, Rochester, NY 14642 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Brown Univ, Women & Infants Hosp, Providence, RI 02905 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Mt Sinai Sch Med, New York, NY USA. Merck & Co Inc, W Point, PA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Virginia Commonwealth Univ, Fairfax, VA USA. RP Berg, AO (reprint author), Univ Washington, Seattle, WA 98195 USA. NR 5 TC 216 Z9 220 U1 1 U2 5 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 SEP 17 PY 2002 VL 137 IS 6 BP 526 EP 528 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 594UJ UT WOS:000178069100008 ER PT J AU Stevaux, O Dimova, D Frolov, MV Taylor-Harding, B Morris, E Dyson, N AF Stevaux, O Dimova, D Frolov, MV Taylor-Harding, B Morris, E Dyson, N TI Distinct mechanisms of E2F regulation by Drosophila RBF1 and RBF2 SO EMBO JOURNAL LA English DT Article DE cell cycle; Drosophila; E2F; RBF; Retinoblastoma ID RETINOBLASTOMA PROTEIN; S-PHASE; ECTOPIC EXPRESSION; DNA-REPLICATION; FAMILY MEMBERS; RB/E2F PATHWAY; G(1) CONTROL; CELL-CYCLE; GENE; PRB AB RBF1, a Drosophila pRB family homolog, is required for cell cycle arrest and the regulation of E2F-dependent transcription. Here, we describe the properties of RBF2, a second family member. RBF2 represses E2F transcription and is present at E2F-regulated promoters. Analysis of in vivo protein complexes reveals that RBF1 and RBF2 interact with different subsets of E2F proteins. dE2F1, a potent transcriptional activator, is regulated specifically by RBF1. In contrast, RBF2 binds exclusively to dE2F2, a form of E2F that functions as a transcriptional repressor. We find that RBF2-mediated repression requires dE2F2. More over, RBF2 and dE2F2 act synergistically to antagonize dE2F1-mediated activation, and they co-operate to block S phase progression in transgenic animals. The network of interactions between RBF1 or RBF2 and dE2F1 or dE2F2 reveals how the activities of these proteins are integrated. These results suggest that there is a remarkable degree of symmetry in the arrangement of E2F and RB family members in mammalian cells and in Drosophila. C1 Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. FU NCI NIH HHS [F32 CA88474, F32 CA93045]; NIGMS NIH HHS [GM53203, R01 GM053203] NR 44 TC 77 Z9 78 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 16 PY 2002 VL 21 IS 18 BP 4927 EP 4937 DI 10.1093/emboj/cdf501 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 595RT UT WOS:000178123100018 PM 12234932 ER PT J AU Widlund, HR Horstmann, MA Price, ER Cui, JI Lessnick, SL Wu, M He, X Fisher, DE AF Widlund, HR Horstmann, MA Price, ER Cui, JI Lessnick, SL Wu, M He, X Fisher, DE TI beta-Catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Wnt-signaling; beta-catenin; MITF; survival; melanoma ID NEURAL CREST; MALIGNANT-MELANOMA; REGULATES EXPRESSION; WAARDENBURG SYNDROME; COLON-CARCINOMA; GENE-PRODUCT; CELL FATE; CYCLIN D1; C-MYC; WNT AB The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of beta-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that beta-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF Moreover, suppression of melanoma clonogenic growth by disruption of beta-catenin-T-cell transcription factor/ LEF is rescued by constitutive MITF This rescue occurs largely through a prosurvival mechanism. Thus, beta-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 630,44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 07574-20, T32 HL007574]; NIAMS NIH HHS [AR 43369, R01 AR043369] NR 41 TC 144 Z9 147 U1 0 U2 6 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 SEP 16 PY 2002 VL 158 IS 6 BP 1079 EP 1087 DI 10.1083/jcb.200202049 PG 9 WC Cell Biology SC Cell Biology GA 596WP UT WOS:000178189700011 PM 12235125 ER PT J AU Detmar, M Hirakawa, S AF Detmar, M Hirakawa, S TI The formation of lymphatic vessels and its importance in the setting of malignancy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; BREAST-CANCER METASTASIS; CC-CHEMOKINE RECEPTOR-7; TUMOR LYMPHANGIOGENESIS; HEREDITARY LYMPHEDEMA; ANGIOGENESIS; PROMOTES; EXPRESSION; LYVE-1; SYSTEM C1 Massachusetts Gen Hosp, CBRC, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, CBRC, Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 52 TC 39 Z9 39 U1 1 U2 3 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 SEP 16 PY 2002 VL 196 IS 6 BP 713 EP 718 DI 10.1084/jem.20021346 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 596BD UT WOS:000178143100001 PM 12235205 ER PT J AU Pasparakis, M Schmidt-Supprian, M Rajewsky, K AF Pasparakis, M Schmidt-Supprian, M Rajewsky, K TI I kappa B kinase signaling is essential for maintenance of mature B cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE NF-kappa B; IKK; CD19-Cre; B cell subsets; maintenance ID SEVERE LIVER DEGENERATION; GAMMA-DEFICIENT MICE; TRANSCRIPTION FACTORS; INCONTINENTIA PIGMENTI; IKK-BETA; MARGINAL ZONE; ACTIVATION; LYMPHOCYTES; RECEPTOR; GENE AB Nuclear factor (NF)-kappaB proteins play crucial roles in immune responses and cellular survival. Activation of NF-kappaB is mediated by the IkappaB kinase (IKK) complex, which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-kappaB essential modulator (NEMO). IKK2- and NEMO-deficient mice die at early embryonic stages. We therefore used conditional gene targeting to evaluate the role of these proteins in B cells in adult mice. B lineage-specific disruption of either IKK signaling by deletion of NEMO, or of IKK2-specific signals by ablation of IKK2 activity leads to the disappearance of mature B lymphocytes. We conclude that maintenance of mature B cells depends on IKK-mediated activation of NF-kappaB. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Cologne, Inst Genet, D-50931 Cologne, Germany. EMBL Mouse Biol Programme, I-00016 Monterotondo, Italy. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Pasparakis, Manolis/0000-0002-9870-0966 NR 47 TC 138 Z9 145 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 16 PY 2002 VL 196 IS 6 BP 743 EP 752 DI 10.1084/jem.20020907 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 596BD UT WOS:000178143100004 PM 12235208 ER PT J AU Okamura, H Shibahara-Maruyama, I Sugai, N Adams, JC AF Okamura, H Shibahara-Maruyama, I Sugai, N Adams, JC TI Innervation of supporting cells in the guinea pig cochlea detected in bloc-surface preparations SO NEUROREPORT LA English DT Article DE bloc-surface preparation; cochlea; innervation; supporting cells ID OSMIUM-TETROXIDE; INTENSIFICATION; ENHANCEMENT; PEROXIDASE; MICROSCOPY AB We immunohistochemically examined the distribution of nerve fibers among supporting cells of the cochlea by using the bloc-surface preparation. The existence of these nerve fibers was not very clear in the standard avidin-biotin complex (ABC) method. However, the standard ABC method complemented with silver intensification procedure provided very fine details of the nerve fibers. The nerves started to appear at low density about 55% of the distance from the apex, and their density gradually increased toward the upper turn. In each portion, the nerve fibers increased in thickness and length as well as the number of synapses made with the nuclei. Moreover, the distribution of these nerves in the fetal cochlea was similar to that in the adult. However, the functional significance and importance of these nerves remains to be determined. Our study also indicates that the silver intensification procedure combined with the standard ABC method is useful for the detailed observation of stereoscopic innervation in thick tissue preparations like such as the cochlea. C1 Tokyo Med & Dent Univ, Dept Audiovestibular Neurosci, Bunkyo Ku, Tokyo 1138519, Japan. Fukushima Med Univ, Dept Anat & Histol, Fukushima 9601295, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Okamura, H (reprint author), Tokyo Med & Dent Univ, Dept Audiovestibular Neurosci, Bunkyo Ku, 1-5-45 Yushima, Tokyo 1138519, Japan. NR 13 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 16 PY 2002 VL 13 IS 13 BP 1585 EP 1588 DI 10.1097/00001756-200209160-00002 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 602JM UT WOS:000178502200004 PM 12352606 ER PT J AU Mukamal, KJ Muller, JE Walkoff, DS Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Muller, JE Walkoff, DS Maclure, M Sherwood, JB Mittleman, MA TI Comparison of courses of patients with acute myocardial infarction with chest pain appearing during exertion versus those with chest pain not occurring during exertion SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PHYSICAL EXERTION; Q-WAVE; EXERCISE; ACTIVATION; MEN AB To better determine the clinical course of acute myocardial infarction (AMI) that begins during exertion and how habitual exertion alters that course, we studied patients enrolled in the Determinants of Myocardial Infarction Onset study, for whom information about recent and habitual exertion was available. 1,2 The Onset study was an observational study of early survivors of AMI that incorporated chart reviews and face-to-face interviews with each patient. We hypothesized that habitual exertion would attenuate risks associated with an exertion-associated onset of symptoms. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Social Behav, Boston, MA 02115 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL41016]; NIAAA NIH HHS [K23AA00299] NR 16 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2002 VL 90 IS 6 BP 642 EP + AR PII S0002-9149(02)02573-0 DI 10.1016/S0002-9149(02)02573-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594UD UT WOS:000178068600017 PM 12231095 ER PT J AU Lepore, JJ Maroo, A Pereira, NL Ginns, LC Dec, GW Zapol, WM Bloch, KD Semigran, MJ AF Lepore, JJ Maroo, A Pereira, NL Ginns, LC Dec, GW Zapol, WM Bloch, KD Semigran, MJ TI Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEMODYNAMICS AB Breathing low concentrations of nitric oxide (NO) produces selective pulmonary vasodilatation and increases exercise capacity in patients with pulmonary hypertension of various etiologies,(1,2) and an acute pulmonary vasodilator response to NO inhalation has been used as a predictor of response to oral vasodilators.(3) Continuous or intermittent NO inhalation has been proposed as chronic pulmonary vasodilator therapy;(4) however, many patients with pulmonary hypertension do not have a pulmonary vasodilator response to inhaled NO, and in patients who do respond, the duration of vasodilatation after cessation of NO inhalation is brief. Inhaled NO exerts its pulmonary vasodilator effects by diffusing into pulmonary vascular smooth muscle cells and stimulating the production of cyclic guanosine 3'-5' monophosphate, a mediator of vasodilatation.(5) One approach to augment and prolong the pulmonary vasodilator effects of inhaled NO is the concomitant administration of an inhibitor of cyclic guanosine 3'-5' monophosphate metabolism. Sildenafil is a selective inhibitor of type 5 phosphodiesterase, a phosphodiesterase isoenzyme that metabolizes cyclic guanosine 3'-5' monophosphate specifically and is present in pulmonary vascular smooth muscle cells.(6) Our laboratory has recently reported that sildenafil is a selective pulmonary vasodilator in lambs with experimental pulmonary hypertension.(7) Several case reports have suggested that sildenafil has pulmonary vasodilator effects in humans,(8-10) that it can augment the pulmonary vasodilator effects of inhaled NO,(11) and that it can prevent rebound pulmonary hypertension after cessation of NO inhalation.(12,13) In this report, we describe hemodynamic effects of sildenafil administered alone and in combination with inhaled NO in a series of adult patients with primary pulmonary hypertension. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiol Div, Pulm & Crit Care Unit,Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 646,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-04021, HL-42397, HL-57172] NR 17 TC 92 Z9 102 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 2002 VL 90 IS 6 BP 677 EP + AR PII S0002-9149(02)02586-9 DI 10.1016/S0002-9149(02)02586-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 594UD UT WOS:000178068600030 PM 12231108 ER PT J AU Ly, J Percy, L Dhanani, S AF Ly, J Percy, L Dhanani, S TI Use of dietary supplements and their interactions with prescription drugs in the elderly SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 10, 2001 CL CHICAGO, ILLINOIS SP Amer Geriatr Soc ID ALTERNATIVE MEDICINE USE; GINKGO-BILOBA; CLINICAL CONSIDERATIONS; HERBAL MEDICINALS; SAFETY ISSUES; INGESTION; THERAPIES AB The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited. C1 Vet Affairs Greater Los Angeles Healthcare Syst, GRECC 11 G, Los Angeles, CA 90073 USA. San Gabriel Med Ctr, San Gabriel, CA USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. Univ Pacific, Stockton, CA 95211 USA. Western Univ Hlth Sci, Pomona, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Evaluat & Management Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med Geriatr Med, Los Angeles, CA USA. RP Dhanani, S (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, GRECC 11 G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 33 TC 11 Z9 11 U1 2 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD SEP 15 PY 2002 VL 59 IS 18 BP 1759 EP 1762 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 597PY UT WOS:000178231000014 PM 12298114 ER PT J AU Lewinsohn, DA Lines, RA Lewinsohn, DM AF Lewinsohn, DA Lines, RA Lewinsohn, DM TI Human dendritic cells presenting adenovirally expressed antigen elicit Mycobacterium tuberculosis-specific CD8(+) T cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE CD8-positive T lymphocytes; dendritic cells; tuberculosis ID PULMONARY TUBERCULOSIS; IMMUNE-RESPONSES; INFECTION; MICE; VACCINATION; CD4(+); LYMPHOCYTES; PROTEINS; EPITOPE; MODELS AB Previous studies in murine and human models have suggested an important role for CD8(+) T cells in host defense to Mycobacterium tuberculosis (Mtb). Consequently, a successful tuberculosis vaccine may require the elicitation of sustained CD4(+) and CD8(+) T cell responses. We tested the hypothesis that the potent CD4(+) T cell antigen Mtb39 is also a CD8(+) T cell antigen. A recombinant adenovirus-expressing Mtb39 (adenoMtb39) was used to infect monocyte-derived dendritic cells. Using interferon-gamma enzyme-linked immunospot, Mtb39-specific CD8(+) T lymphocytes were detected in three healthy individuals with latent tuberculosis infection who also had strong anti-Mtb39-specific CD4(+) T cell responses. An Mtb39-specific CD8(+) T cell line was generated using Mtb39-expressing dendritic cells. Mtb39-specific T cell clones were obtained by limiting dilution cloning. All seven T cell clones obtained were HLA-B44 restricted. Using a panel of synthetic overlapping peptides representative of Mtb39, the peptide epitope was identified for two clones. Furthermore, all T cell clones recognized Mtb-infected dendritic cells and were cytolytic. We conclude that infection of dendritic cells with adenoviral vectors expressing Mtb proteins allows for measurement of antigen-specific CD8(+) T cell responses from peripheral blood mononuclear cells. The technique will be useful in defining CD8(+) T cell antigens and in measuring immunogenicity of tuberculosis vaccines. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Pediat Infect Dis, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97201 USA. RP Lewinsohn, DM (reprint author), Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Pediat Infect Dis, Dept Mol Microbiol & Immunol, 3710 SW US Vet Rd,R&D 11, Portland, OR 97201 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIAID NIH HHS [1K08AI01644, 1KO8AI01645-03]; NICHD NIH HHS [HD33703] NR 32 TC 25 Z9 26 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 15 PY 2002 VL 166 IS 6 BP 843 EP 848 DI 10.1164/rccm.2110094 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 594AU UT WOS:000178027300014 PM 12231495 ER PT J AU Davidson, RJ Lewis, DA Alloy, LB Amaral, DG Bush, G Cohen, JD Drevets, WC Farah, MJ Kagan, J McClelland, JL Nolen-Hoeksema, S Peterson, BS AF Davidson, RJ Lewis, DA Alloy, LB Amaral, DG Bush, G Cohen, JD Drevets, WC Farah, MJ Kagan, J McClelland, JL Nolen-Hoeksema, S Peterson, BS TI Neural and Behavioral substrates of mood and mood regulation SO BIOLOGICAL PSYCHIATRY LA English DT Review DE mood; mood disorders; behavior; neurobiology ID CEREBRAL-BLOOD-FLOW; ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; NATIONAL-COMORBIDITY-SURVEY; RECURRENT MAJOR DEPRESSION; EEG ALPHA ASYMMETRY; LONG-TERM-MEMORY AB A review of behavioral and neurobiological data on mood and mood regulation as they pertain to an understanding of mood disorders is presented. Four approaches are considered: 1) behavioral and cognitive; 2) neurobiological; 3) computational; and 4) developmental. Within each of these four sections, we summarize the current status of the field and present our vision for the future, including particular challenges and opportunities. We conclude with a series of specific recommendations for National Institute of Mental Health priorities. Recommendations arc presented for the behavioral domain, the neural domain, the domain of behavioral-neural interaction, for training, and for dissemination. It is in the domain of behavioral-neural interaction, in particular, that new research is required that brings together traditions that have developed relatively independently. Training interdisciplinary clinical scientists who meaningfully draw upon both behavioral and neuroscientific literatures and methods is critically required for the realization of these goals. C1 Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. Univ Pittsburgh, Pittsburgh, PA USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Calif Davis, Davis, CA 95616 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Princeton Univ, Princeton, NJ 08544 USA. NIMH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Davidson, RJ (reprint author), Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA. RI McClelland, James/F-6004-2011; Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 NR 213 TC 204 Z9 218 U1 7 U2 37 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 SEP 15 PY 2002 VL 52 IS 6 BP 478 EP 502 AR PII S0006-3223(02)01458-0 DI 10.1016/S0006-3223(02)01458-0 PG 25 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 598VK UT WOS:000178297000003 PM 12361665 ER PT J AU Costello, EJ Pine, DS Hammen, C March, JS Plotsky, PM Weissman, MA Biederman, J Goldsmith, HH Kaufman, J Lewinsohn, PM Hellander, M Hoagwood, K Koretz, DS Nelson, CA Leckman, JF AF Costello, EJ Pine, DS Hammen, C March, JS Plotsky, PM Weissman, MA Biederman, J Goldsmith, HH Kaufman, J Lewinsohn, PM Hellander, M Hoagwood, K Koretz, DS Nelson, CA Leckman, JF TI Development and natural history of mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Review DE depession; bipolar disorder; evidence-based treatments; prevention; research training ID BIPOLAR AFFECTIVE-DISORDER; MAJOR DEPRESSIVE DISORDER; DEFICIT HYPERACTIVITY DISORDER; GROUP COGNITIVE INTERVENTION; SUICIDE-PREVENTION PROGRAMS; NATIONAL COMORBIDITY SURVEY; RANDOMIZED CLINICAL-TRIAL; ADOLESCENT DEPRESSION; ANXIETY DISORDERS; GENERAL-POPULATION AB To expand and accelerate research on mood disorders, the National Institute of Mental Health (NIMH) developed a project to formulate a strategic research plan for mood disorder research. One of the areas selected for review concerns the development and natural history of these disorders. The NIMH convened a multidisciplinary Workgroup of scientists to review the field and the NIMH portfolio and to generate specific recommendations. To encourage a balanced and creative set of proposals, experts were included within and outside this area of research, as well as public stakeholders. The Workgroup identified the need for expanded knowledge of mood disorders in children and adolescents, noting important gaps in understanding the onset, course, and recurrence of early-onset unipolar and bipolar disorder. Recommendations included the need for a multidisciplinary research initiative on the pathogenesis of unipolar depression encompassing genetic and environmental risk and protective factors. Specifically, we encourage the NIMH to convene a panel of experts and advocates to review the findings concerning children at high risk for unipolar depression. Joint analyses of existing data sets should examine specific risk factors to refine models of pathogenesis in preparation for the next era of multidisciplinary research. Other priority areas include the need to assess the long-term impact of successful treatment of juvenile depression and known precursors of depression, in particular, childhood anxiety disorders. Expanded knowledge of pediatric-onset bipolar disorder was identified as a particularly pressing issue because of the severity of the disorder, the controversies surrounding its diagnosis and treatment, and the possibility that widespread use of psychotropic medications in vulnerable children may precipitate the condition. The Workgroup recommends that the NIMH establish a collaborative multisite multidisciplinary Network of Research Programs on PediatricOnset Bipolar Disorder to achieve a better understanding of its causes, course, treatment, and prevention. The NIMH should develop a capacity-building plan to ensure the availability of trained investigators in the child and adolescent field. Mood disorders are among the most prevalent, recurrent, and disabling of all illnesses. They are often disorders of early onset. Although the NIMH has made important strides in mood disorders research, more data, beginning with at-risk infants, children, and adolescents, are needed concerning the etiology and developmental course of these disorders. A diverse program of multidisciplinary research is recommended to reduce the burden on children and families affected with these conditions. C1 Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. NIMH, Extramural Res Program, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Clin & Genet Epidemiol, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Psychol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Oregon Res Inst, Eugene, OR 97403 USA. Child & Adolescent Bipolar Fdn, Wilmette, IL USA. Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. RP Leckman, JF (reprint author), Yale Univ, Sch Med, Ctr Child Study, 230 S Frontage Rd,Rm I-269 SHM, New Haven, CT 06520 USA. OI Weissman, Myrna/0000-0003-3490-3075 NR 130 TC 220 Z9 223 U1 10 U2 52 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 SEP 15 PY 2002 VL 52 IS 6 BP 529 EP 542 AR PII S0006-3223(02)01372-0 DI 10.1016/S0006-3223(02)01372-0 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 598VK UT WOS:000178297000005 PM 12361667 ER PT J AU Tamminga, CA Nemeroff, CB Blakely, RD Brady, L Carter, CS Davis, KL Dingledine, R Gorman, JM Grigoriadis, DE Henderson, DC Innis, RB Killen, J Laughren, TP McDonald, WM Murphy, GM Paul, SM Rudorfer, MV Sausville, E Schatzberg, AF Scolnick, EM Suppes, T AF Tamminga, CA Nemeroff, CB Blakely, RD Brady, L Carter, CS Davis, KL Dingledine, R Gorman, JM Grigoriadis, DE Henderson, DC Innis, RB Killen, J Laughren, TP McDonald, WM Murphy, GM Paul, SM Rudorfer, MV Sausville, E Schatzberg, AF Scolnick, EM Suppes, T TI Developing novel treatments for mood disorders: Accelerating discovery SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression bipolar disorder research resources; government/industry collaboration ID SEROTONIN TRANSPORTER GENE; ANTIDEPRESSANT-INDUCED MANIA; ELECTROCONVULSIVE-THERAPY; ELECTRODE PLACEMENT; MAJOR DEPRESSION; PHARMACOLOGICAL PROFILE; ENDOGENOUS-DEPRESSION; REFRACTORY DEPRESSION; PSYCHOTIC DEPRESSION; REUPTAKE INHIBITORS AB This review was generated from discussions by the Pharmacologic and Somatic Treatments Section of the National Institute of Mental Health Strategic Plan for Mood Disorders Committee on advancing novel pharmacologic and somatic treatments for mood disorders. The opening section of the article summarizes in broad strokes, current pharmacologic treatments, and new directions in the field. Thereafter the topics focus on specific research initiatives that could advance the current therapeutics for mood disorders including new basic and clinical research in vivo human imaging procedures, somatic therapeutics, and the vast new area of pharmacogenetics. New scientific and technical opportunities exist today based on advances in basic neuroscience, opportunities in clinical testing, industry interest in advancing central nervous system therapeutics, and on active consumer advocacy groups. The question of how to bring all of these positive forces together to accelerate discovery in mood disorder therapeutics is the topic of this article. C1 Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. NIMH, Neuropharmacol Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Drug Discovery Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Clin Therapeut Program, Mol & Cellular Neurosci Res Branch, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY USA. Neurocrine Biosci Inc, San Diego, CA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Rockville, MD USA. Merck Res Labs, W Point, PA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. RP Tamminga, CA (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. RI dingledine, Ray/F-5173-2011 NR 83 TC 52 Z9 55 U1 3 U2 10 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 SEP 15 PY 2002 VL 52 IS 6 BP 589 EP 609 AR PII S0006-3223(02)01470-1 DI 10.1016/S0006-3223(02)01470-1 PG 21 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 598VK UT WOS:000178297000008 PM 12361670 ER PT J AU Ng, AK Bernardo, MVP Weller, E Backstrand, K Silver, B Marcus, KC Tarbell, NJ Stevenson, MA Friedberg, JW Mauch, PM AF Ng, AK Bernardo, MVP Weller, E Backstrand, K Silver, B Marcus, KC Tarbell, NJ Stevenson, MA Friedberg, JW Mauch, PM TI Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: long-term risks and risk factors SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; 2ND PRIMARY CANCERS; BREAST-CANCER; LUNG-CANCER; ALKYLATING-AGENTS; SOLID TUMORS; FOLLOW-UP; RADIOTHERAPY; IRRADIATION; EXPERIENCE AB The excess risk of second malignancy after Hodgkin disease is an increasing problem. In light of the long-term data, guidelines for follow-up of survivors of Hodgkin disease need to be redefined. In this study we attempt to analyze the long-term risks and temporal trends, identity patient- and treatment-related risk factors, and determine the prognosis of patients who develop a second malignancy after radiation treatment with or without chemotherapy for Hodgkin disease. Among 1319 patients with clinical stage I-IV Hodgkin disease, 181 second malignancies and 18 third malignancies were observed. With a median follow-up of 12 years, the relative risk (RR) and absolute excess risk of second malignancy were 4.6 and 89.3/10 000 person-years. The RR was significantly higher with combined chemotherapy and radiation therapy (6.1) than with radiation therapy alone (4.0, P = .015). The risk increased with increasing radiation field size (P = .03) in patients who received combined modality therapy, and with time after Hodgkin disease. After 15 and 20 years, there was a 2.3% and 4.0% excess risk of second malignancy per person per year. The 5-year survival after development of a second malignancy was 38.1%, with the worst prognosis seen after acute leukemia and lung cancer. The excess risk of second malignancy after Hodgkin disease continues to be increased after 15 to 20 years, and there does not appear to be a plateau. Our analysis suggests that the risk may be reduced with smaller radiation fields, as are used in current trials of abbreviated chemotherapy and limited-field radiation therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mauch, PM (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA. NR 55 TC 243 Z9 250 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2002 VL 100 IS 6 BP 1989 EP 1996 DI 10.1182/blood-2002-02-0634 PG 8 WC Hematology SC Hematology GA 591MT UT WOS:000177884800008 PM 12200357 ER PT J AU Yu, CN Niakan, KK Matsushita, M Stamatoyannopoulos, G Orkin, SH Raskind, WH AF Yu, CN Niakan, KK Matsushita, M Stamatoyannopoulos, G Orkin, SH Raskind, WH TI X-linked thrombocytopenia with thalassemia from a mutation in the amino finger of GATA-1 affecting DNA binding rather than FOG-1 interaction SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; TERMINAL ZINC-FINGER; COFACTOR FOG; STEM-CELLS; DIFFERENTIATION; HEMATOPOIESIS; ERYTHROPOIESIS; EXPRESSION; PROTEIN; LACKING AB Transcription factor GATA-1 is essential for the development of erythroid cells and megakaryocytes. Each of its 2 zinc fingers is critical for normal function. The C-terminal finger is necessary for DNA binding. The N finger mediates interaction with FOG-1, a cofactor for GATA-1, and also modulates DNA-binding affinity, notably at complex or palindromic GATA sites. Residues of the N finger-mediating interaction with FOG-1 lie on the surface of the N finger facing away from DNA. Strong sequence conservation of residues facing DNA suggests that this other surface may also have an important role. We report here that a syndrome of X-linked thrombocytopenia with thalassemia in humans is caused by a missense mutation (Arg216Gln) in the GATA-1 N finger. To investigate the functional consequences of this substitution, we used site-directed mutagenesis to alter the corresponding residue in GATA-1. Compared with wild-type GATA-1, Arg216Gln GATA-1 shows comparable affinity to single GATA sites but decreased affinity to palindromic sites. Arg216Gln GATA-1 interacts with FOG-1 similarly with wild-type GATA-1. Arg216Gln GATA-1 supports erythroid maturation of GATA-1 erythroid cells, albeit at reduced efficiency compared with wild-type GATA-1. Together, these findings suggest that residues of the N finger of GATA-1-facing DNA contribute to GATA-1 function apart from interaction with the cofactor FOG-1. This is also the first example of beta-thalassemia in humans caused by a mutation in an erythroid transcription factor. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. RP Orkin, SH (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL020899-23, R01 HL020899]; NIDDK NIH HHS [R01 DK045365-06S1, R01 DK045365] NR 29 TC 112 Z9 116 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2002 VL 100 IS 6 BP 2040 EP 2045 DI 10.1182/blood-2002-02-0387 PG 6 WC Hematology SC Hematology GA 591MT UT WOS:000177884800015 PM 12200364 ER PT J AU Krackhardt, AM Witzens, M Harig, S Hodi, FS Zauls, AJ Chessia, M Barrett, P Gribben, JG AF Krackhardt, AM Witzens, M Harig, S Hodi, FS Zauls, AJ Chessia, M Barrett, P Gribben, JG TI Identification of tumor-associated antigens in chronic lymphocytic leukemia by SEREX SO BLOOD LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; RENAL-CELL CARCINOMA; BREAST-CANCER; TRANSCRIPTION FACTOR; ANTIBODY-RESPONSES; CONTAINING PROTEIN; HER-2/NEU PROTEIN; PRESENTING CELLS; MYELOID-LEUKEMIA; BINDING PROTEINS AB Chronic lymphocytic leukemia (CLL) is associated with a variety of immunologic disturbances. Hypogammaglobulinemia and autoimmune phenomena are both often present in this disease. In contrast, humoral or cellular antitumor responses are rarely observed. It has been previously shown that antigens detected in patients with malignant diseases can provide information regarding intracellular molecules engaged in the transformation process and can identify tumor antigens that may be useful for development of immunotherapeutic strategies. Serologic identification by recombinant expression cloning (SEREX) has been demonstrated to be a useful method to detect tumor and tumor-associated antigens in a variety of malignancies. Although this approach is complicated in CLL, we used a modified SEREX approach and identified 14 antigens (KW-1 to KW-14) using this methodology. Several clones showed a restricted expression pattern in normal tissues. Moreover, distinctive expression of splice variants and aberrant gene expression in malignant tissue were detected. In this study, 6 antigens were detected exclusively in patients with CLL. Eight antigens were detected also in lymphoma patients. Healthy donors showed antibody responses against only 3 of the identified antigens. T cells with specific cytotoxicity against peptides derived from the 2 antigens tested could be generated from healthy donors. These findings demonstrate that humoral and cellular immune responses against CLL-associated antigens can be detected. Ongoing experiments investigate their potential for the development of immunotherapeutic strategies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ Klinikum Benjamin Franklin, Med Klin 3, Berlin, Germany. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA 81534] NR 60 TC 94 Z9 106 U1 2 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2002 VL 100 IS 6 BP 2123 EP 2131 DI 10.1182/blood-2002-02-0513 PG 9 WC Hematology SC Hematology GA 591MT UT WOS:000177884800027 PM 12200376 ER PT J AU Chauhan, D Catley, L Hideshima, T Li, GL Leblanc, R Gupta, D Sattler, M Richardson, P Schlossman, RL Podar, K Weller, E Munshi, N Anderson, KC AF Chauhan, D Catley, L Hideshima, T Li, GL Leblanc, R Gupta, D Sattler, M Richardson, P Schlossman, RL Podar, K Weller, E Munshi, N Anderson, KC TI 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells SO BLOOD LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; INHIBITS TUBULIN POLYMERIZATION; ENDOTHELIAL GROWTH-FACTOR; CYTOCHROME-C; TUMOR-GROWTH; CANCER-CELLS; POLY(ADP-RIBOSE) POLYMERASE; ESTROGEN-RECEPTORS; INDUCED APOPTOSIS; INTERLEUKIN-6 AB 2-Methoxyestradiol (2ME2) an estrogen derivative, induces growth arrest and apoptosis in leukemic cells and is also antiangiogenic. In this study, we demonstrate that 2ME2 inhibits growth and induces apoptosis in multiple myeloma (MM) cell lines and patient cells. Significantly, 2ME2 also inhibits growth and induces apoptosis in MM cells resistant to conventional therapies including melphalan (LR-5), doxorubicin (Dox-40 and Dox-6), and dexamethasone (MM.1R). In contrast to its effects on MM cells, 2ME2 does not reduce the survival of normal peripheral blood lymphocytes. Moreover, 2ME2 enhances Dex-induced apoptosis, and its effect is not blocked by interleukin-6 (IL-6). We next examined the effect of 2ME2 on MM cells in the bone marrow (BM) milieu. 2ME2 decreases survival of BM stromal cells (BMSCs), as well as secretion of vascular endothelial growth factor (VEGF), and IL-6 triggered by the adhesion of MM cells to BMSCs. We show that apoptosis induced by 2ME2 is mediated by the release of mitochondrial cytochrome-c (cyto-c) and Smac, followed by the activation of caspases-8, -9, and -3. Finally, 2ME2 inhibits MM cell growth, prolongs survival, and decreases angiogenesis in a murine model. These studies, therefore, demonstrate that 2ME2 mediates anti-MM activity directly on MM cells and in the BM microenvironment. They provide a framework for the use of 2ME2, either alone or in combination with Dex, to overcome drug resistance and to improve outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P01 78378, R01 50947] NR 46 TC 91 Z9 96 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2002 VL 100 IS 6 BP 2187 EP 2194 DI 10.1182/blood-2002-02-0376 PG 8 WC Hematology SC Hematology GA 591MT UT WOS:000177884800035 PM 12200384 ER PT J AU Gilles, FH Leviton, A Tavare, CJ Adelman, L Rorke, LB Sobel, EL Hedley-Whyte, ET Davis, RL AF Gilles, FH Leviton, A Tavare, CJ Adelman, L Rorke, LB Sobel, EL Hedley-Whyte, ET Davis, RL CA Childhood Brain Tumor Consortium TI Clinical and survival covariates of eight classes of childhood supratentorial neuroglial tumors SO CANCER LA English DT Article DE brain tumor; child; supratentorial; survival ID PHASE-II; GLIOBLASTOMA-MULTIFORME; RADIATION-THERAPY; VINCRISTINE; GLIOMAS; BROMODEOXYURIDINE; PROCARBAZINE; CHEMOTHERAPY; LIMITATIONS; LOMUSTINE AB BACKGROUND. in the current study, the authors investigated clinical, surgical, and histologic characteristics (covariates) and their interactions in eight previously identified classes of childhood supratentorial neuroglial tumors. The classes resulted from 5 factor score profiles on 703 supratentorial. neuroglial tumors in the Childhood Brain Tumor Consortium database. METHODS. The Cox proportional models were used to identify class survival covariates. RESULTS. Age was found to be a survival covariate only in Class 1, in which older age increased the 5-year survival rate 73% from the first year (0.49) to the tenth year (0.85). A greater amount of tumor removed improved survival in Classes 2 and 4 only. Rosenthal fibers improved survival in Class 2 and overrode the negative effects of high Proliferative factor scores and pleomorphic nuclei. Survival for Class 3 children with high Proliferative factor scores improved from 0.60 to 0.95 as the Spongy factor scores increased. Survival in Class 4 increased from 0.17 to 0.39 with total tumor removal. Irregular nuclei and glomeruloid capillaries improved survival in Class 5 patients. Class 6 survival improved with low cell density. Macrocysts in tumors in Classes 1 and 5 were found to improve survival. CONCLUSIONS. As a result of the current study, the authors conclude that survival covariates differ with tumor class and may modify prognosis considerably. (C) 2002 American Cancer Society. C1 Childrens Hosp Los Angeles, Div Neuropathol, Dept Pathol & Lab Med, Los Angeles, CA 90027 USA. Univ So Calif, Sch Med, Los Angeles, CA 90089 USA. Childrens Hosp, Div Neuroepidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Neuropathol Lab, Boston, MA 02111 USA. Tufts Univ, Boston, MA 02111 USA. Childrens Hosp Philadelphia, Div Neuropathol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ So Calif, Sch Med, Dept Prevent Med, Div Biostat, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Med, Dept Pathol, San Francisco, CA 94143 USA. RP Gilles, FH (reprint author), Childrens Hosp Los Angeles, Div Neuropathol, Dept Pathol & Lab Med, 4650 Sunset Blvd,MS 43, Los Angeles, CA 90027 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2002 VL 95 IS 6 BP 1302 EP 1310 DI 10.1002/cncr.10813 PG 9 WC Oncology SC Oncology GA 592NE UT WOS:000177943100017 PM 12216099 ER PT J AU Hawkins, DS Felgenhauer, J Park, J Kreissman, S Thomson, B Douglas, J Rowley, SD Gooley, T Sanders, JE Pendergrass, TW AF Hawkins, DS Felgenhauer, J Park, J Kreissman, S Thomson, B Douglas, J Rowley, SD Gooley, T Sanders, JE Pendergrass, TW TI Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic sarcomas SO CANCER LA English DT Article DE pediatric; sarcoma; metastatic; dose intensity; chemotherapy; peripheral blood stem cells; granulocyte-colony stimulating factor ID SOFT-TISSUE SARCOMAS; BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; POLYMERASE CHAIN-REACTION; SHORT-TERM CHEMOTHERAPY; TOTAL-BODY IRRADIATION; BREAST-CANCER PATIENTS; RISK EWINGS-SARCOMA; INTERGROUP RHABDOMYOSARCOMA; PROGENITOR CELLS AB BACKGROUND. To increase the dose intensity (131) of chemotherapy for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC). METHODS. Twenty-three children and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate (mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5 mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4, mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8. RESULTS. PBSC collections were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year event free survival (EFS) rate of 39% (95% confidence interval, 19, 59%). Hematopoietic toxicity was severe and cumulative, although it was less than that seen previously without PBSC support. CONCLUSIONS. PBSC-supported multicycle chemotherapy is a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens. (C) 2002 American Cancer Society. C1 Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA 98105 USA. Deaconess Med Ctr, Spokane, WA USA. Duke Univ, Med Ctr, Durham, NC USA. Childrens Hosp & Med Ctr, Div Pediat Hematol Oncol, Cincinnati, OH USA. Univ Washington, Med Ctr, Dept Radiat Oncol, Seattle, WA 98195 USA. Hackensack Univ, Med Ctr, Dept Hematol & Oncol, Hackensack, NJ USA. Fred Hutchinson Canc Res Div, Div Clin Res, Seattle, WA USA. RP Hawkins, DS (reprint author), Childrens Hosp & Reg Med Ctr, Dept Pediat, MS CH-29,4800 Sand Point Way, Seattle, WA 98105 USA. NR 67 TC 23 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 2002 VL 95 IS 6 BP 1354 EP 1365 DI 10.1002/cncr.10801 PG 12 WC Oncology SC Oncology GA 592NE UT WOS:000177943100023 PM 12216105 ER PT J AU Janne, PA Taffaro, ML Salgia, R Johnson, BE AF Janne, PA Taffaro, ML Salgia, R Johnson, BE TI Inhibition of epidermal growth factor receptor signaling in malignant pleural mesothelioma SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; FACTOR-ALPHA; PHASE-II; G(1) ARREST; MONOCLONAL-ANTIBODY; EXPRESSION; CARCINOMA; SURVIVAL; HEAD AB Malignant pleural mesothelioma (MPM) is a rare malignancy with no known curative modality. Approximately 70% of MPMs have high levels of expression of the epidermal growth factor receptor (EGFR), and a subset of cell lines derived from MPM patients express both EGFR and transforming growth factor a, suggesting an autocrine role for EGFR in MPM. We have determined the effects of EGFR inhibition in MPM cell lines in vitro, using four MPM cell lines derived from previously untreated patients with epithelial (H2461 and H2591), sarcomatoid (H2373), and biphasic (MSTO-211H) MPM. All four cell lines expressed EGFR at levels comparable with the non-small cell lung carcinoma (NSCLC) cell line A549, as shown by Western blot analysis. ZD1839 significantly inhibited epidermal growth factor-dependent cell signaling including phosphorylation of AKT and extracellular signal-regulated kinases 1 and 2 in all MPM cell lines. Furthermore, treatment with ZD1839 led to a significant dose-dependent reduction of colony formation (41-89% at 10 muM) when MPM cells were grown in soft agarose. MSTO-211H, H2461, and H2373 were more sensitive to the growth-inhibitory effects of ZD1839 than was the NSCLC cell line A549, whereas H2591 had similar sensitivity to A549. This variability in growth-inhibitory effects is not related to the amount of EGFR present on MPM cells or to the degree of inhibition of EGFR phosphorylation by ZD1839. We show that H2373 MPM cells, which show 89% growth inhibition at 10 muM ZD1839, undergo a dose-dependent arrest at the G(1)-S phase of the cell cycle and a corresponding increase in p27 levels. However, H2591 cell lines, which show 41% growth inhibition at 10 muM ZD1839, undergo no significant cell cycle changes or changes in p27 levels. Our findings demonstrate that in vitro, ZD1839 is as effective or more effective against MPM cell lines as it is against the NSCLC cell line A549 and suggest that ZD1839 may be an effective therapeutic option for patients with MPM. C1 Dana Farber Canc Inst, Low Ctr Thorac 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 Janne, PA (reprint author), Dana Farber Canc Inst, Low Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. NR 45 TC 100 Z9 101 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 2002 VL 62 IS 18 BP 5242 EP 5247 PG 6 WC Oncology SC Oncology GA 594TE UT WOS:000178066400021 PM 12234991 ER PT J AU Demou, ZN McIntire, LV AF Demou, ZN McIntire, LV TI Fully automated three-dimensional tracking of cancer cells in collagen gels: Determination of motility phenotypes at the cellular level SO CANCER RESEARCH LA English DT Article ID IN-VITRO; TUMOR-CELLS; INVASION; MIGRATION; LINES; MATRIX; LOCOMOTION; MEMBRANE; RECEPTOR; ABILITY AB We developed a fully automated three-dimensional cell tracking system that quantified the effect of extracellular matrix components on the infiltration and migration of tumor cells. The three-dimensional trajectories of two highly invasive cell lines, the human HT-1080 fibrosarcoma and the human MDA-MB-231 adenocarcinoma, were determined for long-term infiltration in plain or Matrigel-containing collagen type I gels. We modeled the trajectories with a novel formulation of the continuous Markov chain model that can distinguish between the tendencies for infiltration or lateral motion. Parameters such as the speed of sub-populations, the persistence of motion in certain directions, the turning frequency of the cells, the ultimate direction of motion, and the cell distribution with the infiltration depth were obtained to quantify the migration and infiltration at the cellular level. Distinct migratory and infiltration phenotypes were identified for the two cell types that were significantly dependent on gel composition. The HT-1080 cell, line expressed a high motility phenotype on the plain collagen gel surface. The Matrigel-containing gel significantly enhanced the infiltration and the turning frequency of the HT-1080 cells. This study shows that tumor cell infiltration and migration are dynamic processes that depend significantly on the cell type and the microenvironment. C1 Rice Univ, Inst Biosci & Bioengn, Cox Lab Biomed Engn, Houston, TX 77005 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Steele Lab Tumor Biol, Boston, MA 02114 USA. RP McIntire, LV (reprint author), Rice Univ, Inst Biosci & Bioengn, Cox Lab Biomed Engn, MS-144,6100 Main St, Houston, TX 77005 USA. FU NHLBI NIH HHS [HL 18670] NR 24 TC 36 Z9 38 U1 0 U2 3 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 SEP 15 PY 2002 VL 62 IS 18 BP 5301 EP 5307 PG 7 WC Oncology SC Oncology GA 594TE UT WOS:000178066400030 PM 12235000 ER PT J AU Mandell, LA Peterson, LR Wise, R Hooper, D Low, DE Schaad, UB Klugman, KP Courvalin, P AF Mandell, LA Peterson, LR Wise, R Hooper, D Low, DE Schaad, UB Klugman, KP Courvalin, P TI The battle against emerging antibiotic resistance: Should fluoroquinolones be used to treat children? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; SOFT-TISSUE INFECTIONS; STREPTOCOCCUS-PNEUMONIAE; ORAL CIPROFLOXACIN; ANTIMICROBIAL AGENTS; NASOPHARYNGEAL CARRIAGE; PNEUMOCOCCAL PNEUMONIA; MOLECULAR EPIDEMIOLOGY; HORIZONTAL TRANSFER; CYSTIC-FIBROSIS AB Inappropriate use of antibiotic drugs in humans and animals has led to widespread resistance among microbial pathogens. Resistance is the phenotypic expression corresponding to genetic changes caused by either mutation or acquisition of new genetic information. In some cases, multidrug resistance occurs. Streptococcus pneumoniae is one of the most important respiratory pathogens, playing a major role in both upper and lower respiratory tract infections. Pneumococcal resistance to antimicrobials may be acquired by means of horizontal transfer followed by homologous recombination of genetic material from the normal flora of the human oral cavity or by means of mutation. Resistance to penicillins and macrolides has been increasing for some time, but, recently, fluoroquinolone resistance has become an issue as well. We are concerned that, if fluoroquinolones are approved for use in children, their widespread use will result in rapid emergence of pneumococcal resistance, because children are more often colonized in the nasopharynx with high-density populations of pneumococci than are adults. C1 Inst Pasteur, Unite Agents Antibacteriens, F-75724 Paris 15, France. McMaster Univ, Sch Med, Div Infect Dis, Hamilton, ON L8S 4L8, Canada. Univ Toronto, Div Microbiol & Med, Toronto, ON, Canada. Northwestern Univ, Dept Med, Evanston, IL USA. Northwestern Univ, Dept Pathol, Evanston, IL USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Int Hlth, Atlanta, GA 30322 USA. City Hosp, Dept Med Microbiol, Birmingham, W Midlands, England. Univ Childrens Hosp, Dept Pediat, Basel, Switzerland. Pneumococcal Dis Res Unit, Johannesburg, South Africa. RP Courvalin, P (reprint author), Inst Pasteur, Unite Agents Antibacteriens, 28 Rue Dr Roux, F-75724 Paris 15, France. RI Low, Donald/B-1726-2012 NR 90 TC 51 Z9 52 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2002 VL 35 IS 6 BP 721 EP 727 DI 10.1086/341900 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 589MQ UT WOS:000177763200012 PM 12203170 ER PT J AU Butt, AA AF Butt, AA TI Hepatitis C information on the World Wide Web SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; INITIAL TREATMENT; VIRUS-INFECTION; NON-A; INTERFERON-ALPHA-2B; TRIAL AB World Wide Web sites about hepatitis C vary from simple Web sites that provide basic information to the layperson to regularly updated medical-information portals. Medical professionals can use these Web sites to obtain up-to-date information on the epidemiological characteristics of hepatitis C and treatment of and information materials for their patients. For researchers in this field, there are Web sites that provide bibliographies, conference summaries and updates, and continuing medical education credits. This review provides an overview of selected Web sites for health care providers and researchers, sites of professional societies, sites created by patients, and sites created by the pharmaceutical industry. C1 Univ Pittsburgh, Div Infect Dis, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Butt, AA (reprint author), Univ Pittsburgh, Div Infect Dis, VA Pittsburgh Healthcare Syst, 3601 5th Ave,Ste 3A,Falk Med Bldg, Pittsburgh, PA 15213 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 15 PY 2002 VL 35 IS 6 BP 754 EP 759 DI 10.1086/342204 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 589MQ UT WOS:000177763200017 PM 12203174 ER PT J AU Shivdasani, RA AF Shivdasani, RA TI Molecular regulation of vertebrate early endoderm development SO DEVELOPMENTAL BIOLOGY LA English DT Review ID NODAL-RELATED SIGNALS; BOX TRANSCRIPTION FACTOR; MATERNAL MESSENGER-RNA; GERM-LAYER FORMATION; MESODERM FORMATION; XENOPUS-LAEVIS; MOUSE EMBRYO; VISCERAL ENDODERM; PRIMITIVE STREAK; GUT ENDODERM AB Detailed study of the ectoderm and mesoderm has led to increasingly refined understanding of molecular mechanisms that operate early in development to generate cellular diversity. More recently, a number of powerful studies have begun to characterize the molecular determinants of the endoderm, a germ layer previously neglected in developmental biology. Work in diverse model systems has converged on an integrated transcriptional and signaling pathway that serves to establish the vertebrate endoderm. A T-box transcription factor identified in Xenopus embryos, VegT, appears to function near the top of an endoderm-specifying transcriptional hierarchy. VegT activates and reinforces Nodal-related TGFbeta signaling and also induces expression of essential downstream transcriptional regulators, Mix-like paired-homeodomain and GATA factors. These proteins cooperate to regulate expression of a relay of HMG-box Sox-family transcription factors culminating with Sox 17, which may be an obligate mediator of vertebrate endoderm development. This review synthesizes findings in three vertebrate model organisms and discusses these genetic interactions in the context of the progressive acquisition of endodermal identity early in vertebrate development. (C) 2002 Elsevier Science (USA). C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 110 TC 60 Z9 60 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 2002 VL 249 IS 2 BP 191 EP 203 DI 10.1006/dbio.2002.0765 PG 13 WC Developmental Biology SC Developmental Biology GA 595XF UT WOS:000178133300001 PM 12221001 ER PT J AU Fossale, E Wheeler, VC Vrbanac, V Lebel, LA Teed, A Mysore, JS Gusella, JF MacDonald, ME Persichetti, F AF Fossale, E Wheeler, VC Vrbanac, V Lebel, LA Teed, A Mysore, JS Gusella, JF MacDonald, ME Persichetti, F TI Identification of a presymptomatic molecular phenotype in Hdh CAG knock-in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE GENE-PRODUCT; CREB-BINDING PROTEIN; HUNTINGTONS-DISEASE; TRINUCLEOTIDE REPEAT; MOUSE MODEL; MUTANT HUNTINGTIN; TRANSGENIC MICE; CELL-DEATH; EXPANDED POLYGLUTAMINE; MEDIATED TRANSCRIPTION AB The hallmark striatal neurodegeneration of Huntington's disease (HD) is first triggered by a dominant property of the expanded glutamine tract in mutant huntingtin that increases in severity with glutamine size. Indeed 111-glutamine murine huntingtin leads to a dominant cascade of phenotypes in Hdh(Q111) mice, although these abnormalities are not manifest in Hdh(Q50) mice, with 50-glutamine mutant protein. Therefore, to identify phenotypes that might reflect events closer to the fundamental trigger mechanism, and that can be measured as a consequence of adult-onset HD mutant huntingtin, we have screened for altered expression of genes conserved in evolution, which are likely to encode essential proteins. Probes generated from Hdh(Q111) homozygote and wild-type striatal RNAs were hybridized to human gene segments on filter arrays, disclosing a mutant-specific increase in hybridization to Rrs1, encoding a ribosomal protein. Subsequent, quantitative RT-PCR assays demonstrated increased Rrs1 mRNA from 3 weeks of age in homozygous and heterozygous Hdh(Q111) striatum and increased Rrs1 mRNA expression with a single copy's worth of 50-glutamine mutant huntingtin in Hdh(Q50) striatum. Moreover, quantitative RT-PCR assays for the human homologue demonstrated elevated Rrs1 mRNA in HD compared with control postmortem brain. These findings, therefore, support a chronic impact of mutant huntingtin on an essential ribosomal regulatory gene to be investigated for its role very early in HD pathogenesis. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Persichetti, F (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS32765, NS16367] NR 59 TC 39 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 15 PY 2002 VL 11 IS 19 BP 2233 EP 2241 DI 10.1093/hmg/11.19.2233 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 593NV UT WOS:000177999200004 PM 12217951 ER PT J AU DiGianni, LM Garber, JE Winer, EP AF DiGianni, LM Garber, JE Winer, EP TI Complementary and alternative medicine use among women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID UNITED-STATES; THERAPY USE; INTERVENTION; PREVALENCE; RECURRENCE; SURVIVAL; SUPPORT; TRENDS; CARE AB Complementary and alternative medicine (CAM) use has increased in recent years, with at least 42% of individuals in the United States using some form of CAM in 1997. CAM includes a variety of modalities, ranging from nutritionally based interventions to behavioral techniques. This article reviews the status of CAM use among women with breast cancer. Patients are increasingly incorporating CAM into cancer prevention and treatment regimens. The prevalence of CAM use by breast cancer patients varies; however, it is typically higher than among individuals in the general population. Commonly used CAMs among women with breast cancer include nutritional/dietary supplements, relaxation strategies, and various types of social support groups. Apart from psychosocial interventions, little scientific evidence exists regarding the efficacy of CAM use for breast cancer patients. A common theme seen in many studies is that CAM use in women with breast cancer is highly correlated with increased psychosocial distress. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP DiGianni, LM (reprint author), Dana Farber Canc Inst, 44 Binney St SM204, Boston, MA 02115 USA. NR 43 TC 63 Z9 65 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 15 PY 2002 VL 20 IS 18 SU S BP 34S EP 38S DI 10.1200/JCO.2002.07.176 PG 5 WC Oncology SC Oncology GA 597HH UT WOS:000178215800004 PM 12235222 ER PT J AU Eder, JP Supko, JG Clark, JW Puchalski, TA Garcia-Carbonero, R Ryan, DP Shulman, LN Proper, J Kirvan, M Rattner, B Connors, S Keogan, MT Janicek, MJ Fogler, WE Schnipper, L Kinchla, N Sidor, C Phillips, E Folkman, J Kufe, DW AF Eder, JP Supko, JG Clark, JW Puchalski, TA Garcia-Carbonero, R Ryan, DP Shulman, LN Proper, J Kirvan, M Rattner, B Connors, S Keogan, MT Janicek, MJ Fogler, WE Schnipper, L Kinchla, N Sidor, C Phillips, E Folkman, J Kufe, DW TI Phase I clinical trial of recombinant human endostatin administered as a short intravenous infusion repeated daily SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol ID ANGIOGENESIS INHIBITOR ENDOSTATIN; TUMOR ANGIOGENESIS; PHARMACOKINETIC PARAMETERS; ANTIANGIOGENIC THERAPY; LIVER METASTASES; CANCER-PATIENTS; GROWTH-FACTOR; SOLID TUMORS; ANGIOSTATIN; CARCINOMA AB Purpose: To perform a phase I trial of recombinant human endostatin (rhEndostatin; EntreMed, Rockville, MD) given as a daily 20-minute intravenous (IV) injection in adult patients with refractory solid tumors. Patients and Methods: The daily dose was increased from 15 to 240 mg/m(2) by a factor of 100% in cohorts of three patients. In the absence of dose-limiting toxicity, uninterrupted treatment was continued until the tumor burden increased by more than 50% from baseline. Correlative studies included dynamic contrast-enhanced magnetic resonance imaging of tumor blood flow, urinary vascular endothelial growth factor and basic fibroblast growth factor levels, rhEndostatin serum pharmacokinetics, and monitoring of circulating antibodies to rhEndostatin. Results: There were no notable treatment related toxicities among 15 patients receiving a total of 50 monthly cycles of rhEndostatin. One patient with a pancreatic neuroendocrine tumor had a minor response and two patients showed disease stabilization. Linearity in the pharmacokinetics of rhEndostatin was indicated by dose-proportionate increases in the area under the curve for the first dose and the peak serum concentration at steady state. Daily systemic exposure to rhEndostatin in patients receiving 240 mg/m(2)/d was approximately 50% lower than that provided by the therapeutically optimal dose in preclinical studies. Conclusion: rhEndostatin administered as a 20-minute daily IV injection at doses up to 240 mg/m(2) showed no significant toxicities. Evidence of clinical benefit was observed in three patients. Due to high variability between the peak and trough serum concentrations associated with the repeated short IV infusion schedule, daily serum drug levels only briefly exceeded concentrations necessary for in vitro antiangiogenic effects. (C) 2002 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Med, Div Oncol, Boston, MA 02114 USA. Beth Israel Med Ctr, Dept Surg, Childrens Hosp, New York, NY 10003 USA. Harvard Univ, Ctr Canc, Sch Med, Cambridge, MA 02138 USA. EntreMed, Rockville, MD USA. RP Eder, JP (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St,Rm M1B34, Boston, MA 02115 USA. FU NCI NIH HHS [2 P30 CA0516, U01-CA-62490] NR 56 TC 196 Z9 226 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 15 PY 2002 VL 20 IS 18 BP 3772 EP 3784 DI 10.1200/JCO.2002.02.082 PG 13 WC Oncology SC Oncology GA 597HF UT WOS:000178215600005 PM 12228197 ER PT J AU Singer, S Rubin, BP Lux, ML Chen, CJ Demetri, GD Fletcher, CDM Fletcher, JA AF Singer, S Rubin, BP Lux, ML Chen, CJ Demetri, GD Fletcher, CDM Fletcher, JA TI Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COPY NUMBER CHANGES; INTERSTITIAL-CELLS; C-KIT; DNA-PLOIDY; CAJAL; FUSION; IMMUNOPHENOTYPE; PROLIFERATION; DETERMINANT; SARCOMA AB Purpose: Previous studies have reported clinical correlates for KIT mutations in GISTs, but in most of those studies the KIT mutations were found in less than 50% of the GISTs. The aim of this study was to evaluate the prognostic relevance for KIT mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing. Patients and Methods: A comprehensive clinical and pathologic analysis of 48 patients with GISTs who had snap-frozen tissue was performed. The median tumor size was 10 cm (range, 2 to 30 cm). Median follow-up for disease-free patients was 48 months. KIT genomic and cDNA was sequenced by using nucleic acid templates isolated from frozen tumors. Results: The overall 5-year recurrence-free survival was 41% +/- 6%. Five-year recurrence-free survival for patients with tumors that had mitotic counts of three mitoses or fewer per 30 high-power fields (HPF), more than three to less than or equal to 15 mitoses per 30 HPF, and more than 15 mitoses per 30 HPF were 89% +/- 7%, 49% +/- 12%, and 16% +/- 6%, respectively (P = .0001). The 32 patients with spindle-cell histology had a 49% 7% 5-year recurrence-free survival; in contrast, the 16 patients with epithelioid or mixed histology had a 23% +/- 11% 5-year recurrence-free survival (P = .01). Five-year recurrence-free survival for patients with tumors less than 5 cm, 5 to 10 cm, and more than 10 cm were 82% +/- 12%, 45% +/- 9%, and 27% +/- 8%, respectively (P = .03). Prognostic associations were found with particular KIT mutation types, and patients with missense exon 11 mutations had a 5-year recurrence-free survival of 89% +/- 11% compared with 40% +/- 8% for GISTs with other mutation types (P = .03). The independent predictors for disease-free survival were the presence of deletion/insertion exon 11 mutations (hazard ratio [HR] 4; P = .006), more than 15 mitoses per 30 HPF (HR 18; P = .0001), mixed histology (HR = 21; P = .0001), and male sex (HR = 3; P = .05). Conclusion: In this series of KIT-expressing GISTs, tumor mitotic activity and histologic subtype were the most important prognostic features. The majority of GISTs contain KIT-activating mutations with the type/location of mutation serving as an independent predictor for disease-free survival. These results suggest that KIT mutation and activation are important in GIST pathogenesis and also may provide important prognostic information. (C) 2002 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Singer, S (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. NR 37 TC 277 Z9 313 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 15 PY 2002 VL 20 IS 18 BP 3898 EP 3905 DI 10.1200/JCO.2002.03.095 PG 8 WC Oncology SC Oncology GA 597HF UT WOS:000178215600019 PM 12228211 ER PT J AU Parhami-Seren, B Krudysz, J Tsantili, P AF Parhami-Seren, B Krudysz, J Tsantili, P TI Affinity panning of peptide libraries using anti-streptokinase monoclonal antibodies: selection of an inhibitor of plasmin(ogen) active site SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE streptokinase; murine anti-streptokinase monoclonal antibodies neutralizing human anti-SK Abs; SK-plasminogen activator complex; phage-displayed peptide libraries; epitope mapping ID PLASMINOGEN ACTIVATION; FUNCTIONAL-ANALYSIS; SYNTHETIC PEPTIDES; CRYSTAL-STRUCTURE; COMPLEX; BINDING; REGION; DOMAIN; PHAGE; DEGRADATION AB To select sequences complementary to their binding sites, two anti-streptokinase (SK) monoclonal antibodies (mAbs), A4.5 and A5.5, were used in biopanning of 15-mer and hexamer phage-displayed peptide libraries, respectively. mAb A4.5 inhibits the catalytic activity of streptokinase-plasminogen activator complex (SKPAC, the binding of plasminogen to SK and the binding of human anti-SK polyclonal Abs to SK. All clones selected from the 15-mer peptide library by mAb A4.5 had identical nucleotide and amino acid sequences, RSVYRCSPFVGCWFG. An 11-mer peptide (peptide A4.5, YRCSPFVGCWF) derived from this sequence inhibited the binding of mAb A4.5 and human anti-SK polyclonal Abs to SK as well as the catalytic activity of both SKPAC and plasmin. The binding of the second mAb (mAb A5.5) to SK is lost upon interaction of SK with plasminogen, suggesting that sequences selected by this mAb are likely associated with the C-terminal cleavage site of SK. Biopanning of a hexamer peptide library with mAb A5.5 selected the sequence RYLQDY that is homologous to residues 324-328, adjacent to one possible terminal cleavage site in SK. A 10-mer synthetic peptide (LDFRDLYDPR) corresponding to residues 321-330 in SK specifically inhibited the binding of mAb A5.5 to SK. The selection and characterization of these two peptides enhances our understanding of SK structure, maps an antigenic epitope, and identifies a peptide inhibitor of plasminogen activation, (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Parhami-Seren, B (reprint author), Univ Vermont, Coll Med, Dept Biochem, Given Bldg,Rm C444,89 Beaumont Ave, Burlington, VT 05405 USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL52282]; NIAID NIH HHS [AI33175] NR 41 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 15 PY 2002 VL 267 IS 2 BP 185 EP 198 AR PII S0022-1759(02)00183-7 DI 10.1016/S0022-1759(02)00183-7 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 590UP UT WOS:000177842300010 PM 12165440 ER PT J AU Bashir, MEH Andersen, P Fuss, IJ Shi, HN Nagler-Anderson, C AF Bashir, MEH Andersen, P Fuss, IJ Shi, HN Nagler-Anderson, C TI An enteric helminth infection protects against an allergic response to dietary antigen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL; TH2 RESPONSES; IL-10; ATOPY; MICE; NONRESPONSIVENESS; SENSITIZATION; ANAPHYLAXIS; INHIBITION; REACTIVITY AB Although helminths induce a polarized Th2 response they have been shown, in clinical studies, to confer protection against allergies. To elucidate the basis for this paradox, we have examined the influence of an enteric helminth infection on a model of food allergy. Upon Ag challenge, mice fed peanut (PN) extract plus the mucosal adjuvant cholera toxin (CT) produced PN-specific IgE that correlated with systemic anaphylactic symptoms and elevated plasma histamine. PN-specific IgE was not induced in helminth-infected mice fed PN without CT. Moreover, when PN plus CT was fed to helminth-infected mice, both PN-specific IgE and anaphylactic symptoms were greatly diminished. The down-regulation of PN-specific IgE was associated with a marked reduction in the secretion of IL-13 by PN-specific T cells. When helminth-infected PN plus CT-sensitized mice were treated with neutralizing Abs to IL-10, the PN-specific IgE response and anaphylactic symptoms were similar to, or greater than, those seen in mice that receive PN and CT alone. Taken together, these results suggest that helminth-dependent protection against allergic disease involves immunoregulatory mechanisms that block production of allergen-specific IgE. C1 Massachusetts Gen Hosp East, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Nagler-Anderson, C (reprint author), Massachusetts Gen Hosp East, Mucosal Immunol Lab, Bldg 114,16th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 40561, DK43551, T32-DK07471, DK 55678] NR 36 TC 163 Z9 174 U1 1 U2 8 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2002 VL 169 IS 6 BP 3284 EP 3292 PG 9 WC Immunology SC Immunology GA 592VU UT WOS:000177958200060 PM 12218148 ER PT J AU Wellington, CL Ellerby, LM Gutekunst, CA Rogers, D Warby, S Graham, RK Loubser, O van Raamsdonk, J Singaraja, R Yang, YZ Gafni, J Bredesen, D Hersch, SM Leavitt, BR Roy, S Nicholson, DW Hayden, MR AF Wellington, CL Ellerby, LM Gutekunst, CA Rogers, D Warby, S Graham, RK Loubser, O van Raamsdonk, J Singaraja, R Yang, YZ Gafni, J Bredesen, D Hersch, SM Leavitt, BR Roy, S Nicholson, DW Hayden, MR TI Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; huntingtin; caspase cleavage; in vivo; corticostriatal pathway; neurodegeneration ID N-TERMINAL FRAGMENTS; CELL-DEATH; POLYGLUTAMINE TRACT; STRIATAL NEURONS; TRANSGENIC MICE; WILD-TYPE; MOUSE MODEL; CAG REPEAT; TOXICITY; BRAIN AB Huntington's disease (HD) results from polyglutamine expansion in huntingtin (htt), a protein with several consensus caspase cleavage sites. Despite the identification of htt fragments in the brain, it has not been shown conclusively that htt is cleaved by caspases in vivo. Furthermore, no study has addressed when htt cleavage occurs with respect to the onset of neurodegeneration. Using antibodies that detect only caspase-cleaved htt, we demonstrate that htt is cleaved in vivo specifically at the caspase consensus site at amino acid 552. We detect caspase-cleaved htt in control human brain as well as in HD brains with early grade neuropathology, including one homozygote. Cleaved htt is also seen in wild-type and HD transgenic mouse brains before the onset of neurodegeneration. These results suggest that caspase cleavage of htt may be a normal physiological event. However, in HD, cleavage of mutant htt would release N-terminal fragments with the potential for increased toxicity and accumulation caused by the presence of the expanded polyglutamine tract. Furthermore, htt fragments were detected most abundantly in cortical projection neurons, suggesting that accumulation of expanded htt fragments in these neurons may lead to corticostriatal dysfunction as an early event in the pathogenesis of HD. C1 British Columbia Childrens & Womens Hosp, Ctr Mol Med & Therapeut, Vancouver, BC V5Z 4H4, Canada. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Buck Inst Res Aging, Novato, CA 94945 USA. Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada. RP Hayden, MR (reprint author), Ctr Mol Med & Therapeut, 980 W 28th Ave, Vancouver, BC V5Z 4H4, Canada. RI Leavitt, Blair/G-1934-2012; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU NCCIH NIH HHS [AT00613]; NINDS NIH HHS [NS35255, NS40251] NR 50 TC 218 Z9 226 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2002 VL 22 IS 18 BP 7862 EP 7872 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 592BC UT WOS:000177916000006 PM 12223539 ER PT J AU Bacskai, BJ Kajdasz, ST McLellan, ME Games, D Seubert, P Schenk, D Hyman, BT AF Bacskai, BJ Kajdasz, ST McLellan, ME Games, D Seubert, P Schenk, D Hyman, BT TI Non-Fc-mediated mechanisms are involved in clearance of amyloid-beta in vivo by immunotherapy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid; transgenic; Alzheimer; multiphoton; imaging; senile plaque; microglia; immunotherapy; antibody ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; PRECURSOR PROTEIN; MOUSE MODEL; PEPTIDE; PLAQUES; IMMUNIZATION; ANTIBODIES; MICROSCOPY; PATHOLOGY AB Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP) develop senile plaques similar to those found in Alzheimer's disease in an age-dependent manner. Recent reports demonstrated that immunotherapy is effective at preventing or removing amyloid-beta deposits in the mouse models. To characterize the mechanisms involved in clearance, we used antibodies of either IgG1 (10d5) or IgG2b (3d6) applied directly to the brains of 18-month-old Tg2576 or 20-month-old PDAPP mice. Both 10d5 and 3d6 led to clearance of 50% of diffuse amyloid deposits in both animal models within 3 d. Fc receptor-mediated clearance has been shown to be important in an ex vivo assay showing antibody-mediated clearance of plaques by microglia. We now show, using in vivo multiphoton microscopy, that FITC-labeled F( ab')(2) fragments of 3d6 (which lack the Fc region of the antibody) also led to clearance of 45% of the deposits within 3 d, similar to the results obtained with full-length 3d6 antibody. This result suggests that direct disruption of plaques, in addition to Fc-dependent phagocytosis, is involved in the antibody-mediated clearance of amyloid-beta deposits in vivo. Dense-core deposits that were not cleared were reduced in size by similar to30% with full-length antibodies and F( ab')(2) fragments 3 d after a topical treatment. Together, these results indicate that clearance of amyloid deposits in vivo may involve, in addition to Fc-dependent clearance, a non-Fc-mediated disruption of plaque structure. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Elan Pharmaceut, San Francisco, CA 94080 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Alzheimers Dis Res Lab, Charlestown Navy Yard 2450,114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08487, P01 AG15453]; NIGMS NIH HHS [T32GM07753, T32 GM007753] NR 24 TC 253 Z9 266 U1 3 U2 22 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2002 VL 22 IS 18 BP 7873 EP 7878 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 592BC UT WOS:000177916000007 PM 12223540 ER PT J AU Dhavan, R Greer, PL Morabito, MA Orlando, LR Tsai, LH AF Dhavan, R Greer, PL Morabito, MA Orlando, LR Tsai, LH TI The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Cdk5; p35; p39; CaMKII; actinin; synapses; calcium; yeast two-hybrid; NMDA ID BRAIN-SPECIFIC ACTIVATOR; D-ASPARTATE RECEPTOR; HIPPOCAMPAL-NEURONS; NMDA RECEPTOR; GLUTAMATE RECEPTORS; POSTSYNAPTIC DENSITY; CYTOPLASMIC DYNEIN; DENDRITIC SPINES; REVERSE 2-HYBRID; NR2B SUBUNIT AB Cyclin-dependent kinase 5 (Cdk5) is a critical regulator of neuronal migration in the developing CNS, and recent studies have revealed a role for Cdk5 in synaptogenesis and regulation of synaptic transmission. Deregulation of Cdk5 has been linked to the pathology of neurodegenerative diseases such as Alzheimer's disease. Activation of Cdk5 requires its association with a regulatory subunit, and two Cdk5 activators, p35 and p39, have been identified. To gain further insight into the functions of Cdk5, we identified proteins that interact with p39 in a yeast two-hybrid screen. In this study we report that alpha-actinin-1 and the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II (CaMKIIalpha), two proteins localized at the postsynaptic density, interact with Cdk5 via their association with p35 and p39. CaMKIIalpha and alpha-actinin-1 bind to distinct regions of p35 and p39 and also can interact with each other. The association of CaMKIIalpha and alpha-actinin-1 to the Cdk5 activators, as well as to each other, is stimulated by calcium. Further, the activation of glutamate receptors increases the association of p35 and p39 with CaMKIIalpha, and the inhibition of CaMKII activation diminishes this effect. The glutamate-mediated increase in association of p35 and CaMKIIalpha is mediated in large part by NMDA receptors, suggesting that cross talk between the Cdk5 and CaMKII signal transduction pathways may be a component of the complex molecular mechanisms contributing to synaptic plasticity, memory, and learning. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Dept Pathol, Armenise Bldg,Room 342,200 Longwood Ave, Boston, MA 02115 USA. NR 61 TC 90 Z9 96 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2002 VL 22 IS 18 BP 7879 EP 7891 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 592BC UT WOS:000177916000008 PM 12223541 ER PT J AU DaSilva, AFM Becerra, L Makris, N Strassman, AM Gonzalez, RG Geatrakis, N Borsook, D AF DaSilva, AFM Becerra, L Makris, N Strassman, AM Gonzalez, RG Geatrakis, N Borsook, D TI Somatotopic activation in the human trigeminal pain pathway SO JOURNAL OF NEUROSCIENCE LA English DT Article DE pain; functional magnetic resonance imaging; trigeminal system; trigeminal nucleus; noxious heat; spinal nucleus of V; somatotopy; ventrobasal complex; somatosensory cortex ID MEDULLARY DORSAL HORN; HUMAN SOMATOSENSORY CORTEX; FOS-LIKE IMMUNOREACTIVITY; SURFACE-BASED ANALYSIS; THALAMIC VPM NUCLEUS; NOXIOUS HEAT STIMULI; NOCICEPTIVE NEURONS; FUNCTIONAL MRI; HUMAN BRAIN; AREA 3B AB Functional magnetic resonance imaging was used to image pain-associated activity in three levels of the neuraxis: the medullary dorsal horn, thalamus, and primary somatosensory cortex. In nine subjects, noxious thermal stimuli (46degreesC) were applied to the facial skin at sites within the three divisions of the trigeminal nerve (V1, V2, and V3) and also to the ipsilateral thumb. Anatomical and functional data were acquired to capture activation across the spinothalamocortical pathway in each individual. Significant activation was observed in the ipsilateral spinal trigeminal nucleus within the medulla and lower pons in response to at least one of the three facial stimuli in all applicable data sets. Activation from the three facial stimulation sites exhibited a somatotopic organization along the longitudinal (rostrocaudal) axis of the brain stem that was consistent with the classically described "onion skin" pattern of sensory deficits observed in patients after trigeminal tractotomy. In the thalamus, activation was observed in the contralateral side involving the ventroposteromedial and dorsomedial nuclei after stimulation of the face and in the ventroposterolateral and dorsomedial nuclei after stimulation of the thumb. Activation in the primary somatosensory cortex displayed a laminar sequence that resembled the trigeminal nucleus, with V2 more rostral, V1 caudal, and V3 medial, abutting the region of cortical activation observed for the thumb. These results represent the first simultaneous imaging of pain-associated activation at three levels of the neuraxis in individual subjects. This approach will be useful for exploring central correlates of plasticity in models of experimental and clinical pain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain Funct Neuroimaging & Therapy Res, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal,Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Pain Funct Neuroimaging & Therapy Res, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 76 TC 112 Z9 114 U1 2 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2002 VL 22 IS 18 BP 8183 EP 8192 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 592BC UT WOS:000177916000039 PM 12223572 ER PT J AU Mao, JR Sung, BK Ji, RR Lim, G AF Mao, JR Sung, BK Ji, RR Lim, G TI Chronic morphine induces downregulation of spinal glutamate transporters: Implications in morphine tolerance and abnormal pain sensitivity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE tolerance; opioid; glutamate transporter; NMDA; hyperalgesia; riluzole; PDC ID PROTEIN-KINASE-C; OPIOID RECEPTOR EXPRESSION; OXIDE SYNTHASE INHIBITOR; RAT-BRAIN; MESSENGER-RNA; IN-VIVO; ANTINOCICEPTIVE TOLERANCE; PRECIPITATED WITHDRAWAL; NEUROPATHIC PAIN; KAPPA-OPIOIDS AB Tolerance to the analgesic effects of an opioid occurs after its chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we examined the role of spinal glutamate transporters (GTs) in the development of both morphine tolerance and associated thermal hyperalgesia. Chronic morphine administered through either intrathecal boluses or continuous infusion induced a dose-dependent downregulation of GTs (EAAC1 and GLAST) in the rat's superficial spinal cord dorsal horn. This GT downregulation was mediated through opioid receptors because naloxone blocked such GT changes. Morphine-induced GT downregulation reduced the ability to maintain in vivo glutamate homeostasis at the spinal level, because the hyperalgesic response to exogenous glutamate was enhanced, including an increased magnitude and a prolonged time course, in morphine-treated rats with reduced spinal GTs. Moreover, the downregulation of spinal GTs exhibited a temporal correlation with the development of morphine tolerance and thermal hyperalgesia. Consistently, the GT inhibitor L-trans-pyrrolidine-2-4-dicarboxylate (PDC) potentiated, whereas the positive GT regulator riluzole reduced, the development of both morphine tolerance and thermal hyperalgesia. The effects from regulating spinal GT activity by PDC were at least in part mediated through activation of the NMDA receptor (NMDAR), because the noncompetitive NMDAR antagonist MK-801 blocked both morphine tolerance and thermal hyperalgesia that were potentiated by PDC. These results indicate that spinal GTs may contribute to the neural mechanisms of morphine tolerance and associated abnormal pain sensitivity by means of regulating regional glutamate homeostasis. C1 Harvard Univ, Sch Med, MGH Pain Ctr, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp,Neural Plastic Res Grp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, MGH Pain Ctr, Massachusetts Gen Hosp, Suite WACC 324,15 Parkman St, Boston, MA 02114 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NIDA NIH HHS [DA08835]; NINDS NIH HHS [R01 NS040698] NR 84 TC 245 Z9 263 U1 2 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2002 VL 22 IS 18 BP 8312 EP 8323 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 592BC UT WOS:000177916000053 PM 12223586 ER PT J AU Goto, T Takahashi, T Miyama, S Nowakowski, RS Bhide, PG Caviness, VS AF Goto, T Takahashi, T Miyama, S Nowakowski, RS Bhide, PG Caviness, VS TI Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis: Implications for a hypothesis relating to mitogen-antimitogen opposition SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cell cycle; FGF; gap junction; neuronogenesis; neuronal differentiation ID MURINE CEREBRAL WALL; PSEUDOSTRATIFIED VENTRICULAR EPITHELIUM; INTERKINETIC NUCLEAR MIGRATION; CORTICAL PROGENITOR CELLS; NEURAL STEM-CELLS; NERVOUS-SYSTEM; G1 PHASE; PROLIFERATIVE EPITHELIUM; DEVELOPING NEOCORTEX; CYCLE PARAMETERS AB Neocortical neurons arise from a pseudostratified ventricular epithelium (PVE) that lies within the ventricular zone (VZ) at the margins of the embryonic cerebral ventricles. We examined the effects of fibroblast growth factor-2 (FGF-2) and 1-octanol on cell output behavior of the PVE in explants of the embryonic mouse cerebral wall. FGF-2 is mitogenic and 1-octanol antimitogenic in the PVE. Whereas all postmitotic cells migrate out of the VZ in vivo, in the explants some postmitotic cells remain within the VZ. We refer to these cells as the indeterminate or / fraction, because they neither exit from the VZ nor reenter S phase as part of the proliferative (P) fraction. They are considered to be either in an extremely prolonged G, phase, unable to pass the G(1)/S transition, or in the G. state. The I fate choice is modulated by both FGF-2 and 1-octanol. FGF-2 decreased the I fraction and increased the P fraction. In contrast, 1-octanol increased the I fraction and nearly eliminated the P fraction. The effects of FGF-2 and 1-octanol were developmentally regulated, in that they were observed in the developmentally advanced lateral region of the cerebral wall but not in the medial region. (C) 2002 Wiley-Liss, Inc. C1 Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, Tokyo 1608582, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Goto, T (reprint author), Keio Univ, Sch Med, Dept Pediat, Shinjuku Ku, 35 Shinano Machi, Tokyo 1608582, Japan. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NICHD NIH HHS [HD05515]; NINDS NIH HHS [NS12005, NS33433] NR 44 TC 12 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 15 PY 2002 VL 69 IS 6 BP 714 EP 722 DI 10.1002/jnr.10361 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 589ZR UT WOS:000177792600004 PM 12205664 ER PT J AU Cai, L Hayes, NL Takahashi, T Caviness, VS Nowakowski, RS AF Cai, L Hayes, NL Takahashi, T Caviness, VS Nowakowski, RS TI Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE ventricular zone; asymmetric cell divisions; symmetric cell divisions ID DEVELOPING CEREBRAL-CORTEX; CLONALLY RELATED CELLS; NEURONAL CLONES; PROLIFERATIVE EPITHELIUM; ASYMMETRIC INHERITANCE; RECOMBINANT RETROVIRUS; TANGENTIAL MIGRATION; VENTRICULAR ZONE; CORTICAL-NEURONS; NERVOUS-SYSTEM AB Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neuronogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types. (C) 2002 Wiley-Liss, Inc. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Rutgers State Univ, Physiol & Neurobiol Grad Program, Piscataway, NJ USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. RP Nowakowski, RS (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, 675 Hoes Lane, Piscataway, NJ 08854 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NIMH NIH HHS [MH63957]; NINDS NIH HHS [NS12005] NR 59 TC 44 Z9 46 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD SEP 15 PY 2002 VL 69 IS 6 BP 731 EP 744 DI 10.1002/jnr.10398 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 589ZR UT WOS:000177792600006 PM 12205666 ER PT J AU Iacomini, J AF Iacomini, J TI Rejection of alpha Gal mismatched skin grafts: a model of acute vascular rejection? SO TRANSPLANTATION LA English DT Editorial Material ID ANTIBODIES; MICE C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 7 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 SEP 15 PY 2002 VL 74 IS 5 BP 599 EP 600 DI 10.1097/00007890-200209150-00002 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 595UR UT WOS:000178127600002 PM 12357986 ER PT J AU Perez, A Grikscheit, TC Blumberg, RS Ashley, SW Vacanti, JP Whang, EE AF Perez, A Grikscheit, TC Blumberg, RS Ashley, SW Vacanti, JP Whang, EE TI Tissue-engineered small intestine - Ontogeny of the immune system SO TRANSPLANTATION LA English DT Article ID SHORT-BOWEL SYNDROME; DOSE GROWTH-HORMONE; BODY-COMPOSITION; DOUBLE-BLIND; GLUTAMINE; TRANSPLANTATION; ABSORPTION; CROSSOVER; DIET AB Background. Using tissue-engineering techniques, we have developed a neointestine that regenerates structural and transporter properties of native jejunum. The purpose of this study was to characterize the mucosal immune system of the engineered neointestine. We hypothesized that the neointestinal mucosa is capable of developing a mature immunocyte population and that exposure to luminal stimuli is critical to this development. Methods. Neointestinal cysts were engineered by implanting polymer-organoid constructs into syngeneic adult recipients. Neointestine (cysts left nonanastomosed [NA] and cysts anastomosed to native bowel [AN] and native jejunum were harvested serially (3-56 weeks postoperatively). Immune cell subsets were characterized by the immunohistochemical detection of cell-specific antigens (T cells [CD3], B cells [CD32], NK cells [CD56], anD macrophages [CD68]) combined with computer-based morphometry. Results. Intraepithelial and lamina propria immunocyte population densities and subset distributions were identical in AN cysts harvested 20 weeks postoperatively and in native jejunum. Mucosal immunocyte population densities were lower in AN cysts harvested 10 weeks postoperatively and only rudimentary in NA cysts, even those harvested 20 weeks postoperatively. Conclusions. These results suggest that tissue-engineered intestine has the capacity to develop a mucosal immune system with an immunocyte population similar to that of native small intestine. The development of this immune system is a function of both exposure to luminal stimuli and the duration of this exposure. Tissue-engineered intestine offers promise as a new therapeutic approach for patients who have intestinal insufficiency. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Whang, EE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL60424]; NIDDK NIH HHS [DK02786, DK47326] NR 20 TC 37 Z9 39 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 SEP 15 PY 2002 VL 74 IS 5 BP 619 EP 623 DI 10.1097/01.TP.0000026662.89071.A8 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 595UR UT WOS:000178127600006 PM 12352876 ER PT J AU Ren, J Datta, R Shioya, H Li, YQ Oki, EJ Biedermann, V Bharti, A Kufe, D AF Ren, J Datta, R Shioya, H Li, YQ Oki, EJ Biedermann, V Bharti, A Kufe, D TI p73 beta is regulated by protein kinase C delta catalytic fragment generated in the apoptotic response to DNA damage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ABL TYROSINE KINASE; TUMOR-NECROSIS-FACTOR; PROTEOLYTIC ACTIVATION; IONIZING-RADIATION; INDUCE APOPTOSIS; P53 HOMOLOG; P73; CELLS; CLEAVAGE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE AB Protein kinase C (PKC) delta is cleaved by caspase-3 to a kinase-active catalytic fragment (PKCdeltaCF) in the apoptotic response of cells to DNA damage. Expression of PKCdeltaCF contributes to the induction of apoptosis by mechanisms that are presently unknown. Here we demonstrate that PKCdeltaCF associates with p73beta, a structural and functional homologue of the p53 tumor suppressor. The results show that PKCdeltaCF phosphorylates the p73beta transactivation and DNA-binding domains. One PKCdeltaCF-phosphorylation site has been mapped to Ser-289 in the p73beta DNA-binding domain. PKCdeltaCF-mediated phosphorylation of p73beta is associated with accumulation of p73beta and induction of p73beta-mediated transactivation. By contrast, PKCdeltaCF-induced activation of p73beta is attenuated by mutating Ser-289 to Ala (S289A). The results also demonstrate that PKCdeltaCF stimulates p73beta-mediated apoptosis and that this response is attenuated with the p73beta(S289A) mutant. These findings demonstrate that cleavage of PKCdelta to PKCdeltaCF induces apoptosis by a mechanism in part dependent on PKCdeltaCF-mediated phosphorylation of the p73beta Ser-289 site. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 55241]; NIGMS NIH HHS [GM 58200] NR 41 TC 92 Z9 93 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 13 PY 2002 VL 277 IS 37 BP 33758 EP 33765 DI 10.1074/jbc.M110667200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 592WD UT WOS:000177959100032 PM 12097319 ER PT J AU Litovchick, L Friedmann, E Shaltiel, S AF Litovchick, L Friedmann, E Shaltiel, S TI A selective interaction between OS-9 and the carboxyl-terminal tail of meprin beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPLITTING MEMBRANAL PROTEINASE; ENDOPLASMIC-RETICULUM; C-2-DOMAIN PROTEINS; CATALYTIC SUBUNIT; CARGO SELECTION; BINDING PROTEIN; KINASE-A; N-COPINE; GENE; EXPRESSION AB OS-9, a protein previously uncharacterized, was shown to interact specifically with the intracellular region of the membrane proteinase meprin beta found in brush border membranes of kidney and small intestine. We have shown previously that this cytoplasmic region is indispensable for the maturation of meprin beta, which included an endoplasmic reticulum. (ER)-to-Golgi translocation. We characterized OS-9 and found that it is associated with ER membranes and that it is exposed to the cytoplasm. Consistent with the kinetics of maturation of meprin beta, OS-9 associates with meprin beta only transiently, coinciding with ER-to-Golgi transport of meprin beta. The OS-9-binding site in the cytoplasmic domain of meprin beta overlaps the region essential for this transport. We characterized alternatively spliced forms of rat and mouse OS-9, and we found that only the non-spliced form of OS-9 binds to meprin beta, implicating the spliced out segment in the binding, and suggesting the possible mechanism of the regulation of OS-9 function. Taken together, our results indicated that OS-9 may be involved in the ER-to-Golgi transport of meprin beta. Ubiquitous expression of OS-9 raises the possibility that it may interact with other membrane proteins that possess the cytoplasmic moiety homologous to that of meprin beta during their ER-to-Golgi transition. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. RP Litovchick, L (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Mayer Bldg 444, Boston, MA 02115 USA. NR 40 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 13 PY 2002 VL 277 IS 37 BP 34413 EP 34423 DI 10.1074/jbc.M203986200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 592WD UT WOS:000177959100114 PM 12093806 ER PT J AU DiLorenzo, L Kobierski, L Moore, KA Borsook, D AF DiLorenzo, L Kobierski, L Moore, KA Borsook, D TI A water-soluble synthetic spicamycin derivative (SAN-Gly) decreases mechanical allodynia in a rodent model of neuropathic pain SO NEUROSCIENCE LETTERS LA English DT Article DE SAN-Gly; spicamycin; neuropathic pain; allodynia; rats; spared nerve injury model ID NERVE; RATS AB The goal of this study was to examine the effects of synthetic spicamycin derivative, SAN-Gly, on mechanical allodynia in a spared nerve injury animal model of neuropathic pain. Adult male rats underwent surgical ligation and cutting of the common peroneal and tibial nerves, which produced a mechanical allodynia within 2-4 days. One week after the surgery, SAN-Gly was administered via intravenous injection. Mechanical allodynia was measured using von-Frey hairs. Spicamycin produced a significant reduction in mechanical allodynia for up to 6 weeks. This study demonstrates that SAN-Gly may be of potential use in treating patients with neuropathic pain. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Radiol, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Neurol, Charlestown, MA 02129 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Radiol, NMR Ctr, Rm 2316,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD SEP 13 PY 2002 VL 330 IS 1 BP 37 EP 40 AR PII S0304-3940(02)00724-3 DI 10.1016/S0304-3940(02)00724-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 600HQ UT WOS:000178384900010 PM 12213629 ER PT J AU Bardeesy, N Sinha, M Hezel, AF Signoretti, S Hathaway, NA Sharpless, NE Loda, M Carrasco, DR DePinho, RA AF Bardeesy, N Sinha, M Hezel, AF Signoretti, S Hathaway, NA Sharpless, NE Loda, M Carrasco, DR DePinho, RA TI Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation SO NATURE LA English DT Article ID PEUTZ-JEGHERS-SYNDROME; SOMATIC MUTATIONS; G(1) CONTROL; INK4A LOCUS; GROWTH; EXPRESSION; MICE; IMMORTALIZATION; ACTIVATION; SENESCENCE AB Germline mutations in LKB1 (also known as STK11) are associated with Peutz-Jeghers syndrome (PJS), a disorder with predisposition to gastrointestinal polyposis and cancer(1). PJS polyps are unusual neoplasms characterized by marked epithelial and stromal overgrowth but have limited malignant potential(2). Here we show that Lkb1(+/-) mice develop intestinal polyps identical to those seen in individuals affected with PJS. Consistent with this in vivo tumour suppressor function, Lkb1 deficiency prevents culture-induced senescence without loss of Ink4a/Arf or p53. Despite compromised mortality, Lkb1(-/-) mouse embryonic fibroblasts show resistance to transformation by activated Ha-Ras either alone or with immortalizing oncogenes. This phenotype is in agreement with the paucity of mutations in Ras seen in PJS polyps(3,4) and suggests that loss of Lkb1 function as an early neoplastic event renders cells resistant to subsequent oncogene-induced transformation. In addition, the Lkb1 transcriptome shows modulation of factors linked to angiogenesis, extracellular matrix remodelling, cell adhesion and inhibition of Ras transformation. Together, our data rationalize several features of PJS polyposis-notably its peculiar histopathological presentation and limited malignant potential-and place Lkb1 in a distinct class of tumour suppressors. 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. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 271 Z9 279 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 12 PY 2002 VL 419 IS 6903 BP 162 EP 167 DI 10.1038/nature01045 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 592HK UT WOS:000177931200040 PM 12226664 ER PT J AU Sasaki, Y Murakami, I Cavanagh, P Tootell, RHB AF Sasaki, Y Murakami, I Cavanagh, P Tootell, RHB TI Human brain activity during illusory visual jitter as revealed by functional magnetic resonance imaging SO NEURON LA English DT Article ID RAT FOREPAW STIMULATION; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; AREA MT; EYE-MOVEMENTS; MACAQUE MONKEY; BLOOD-FLOW; MOTION; V1; ACTIVATION AB One central problem in vision is how to compensate for retinal slip. A novel illusion (visual jitter) suggests the compensation mechanism is based solely on retinal motion. Adaptation to visual noise attenuates the motion signals used by the compensation stage, producing illusory jitter due to the undercompensation of retinal slip. Here, we investigated the neural substrate of retinal slip compensation during this illusion using high-field fMRI and retinotopic mapping in flattened cortical format. When jitter perception occurred, MR signal decreased in lower stages of the visual system but increased prominently in area MT+. In conclusion, visual areas as early as V1 are responsible for the adaptation stage, and MT+ is involved in the compensation stage. The present finding suggests the pathway from V1 to MT+ has an important role in stabilizing the visual world. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. NTT Corp, NTT Commun Sci Labs, Human & Informat Sci Lab, Kanagawa 2430198, Japan. Harvard Univ, Dept Psychol, Vis Sci Lab, Cambridge, MA 02138 USA. RP Sasaki, Y (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. FU NEI NIH HHS [EY07980] NR 62 TC 22 Z9 22 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP 12 PY 2002 VL 35 IS 6 BP 1147 EP 1156 DI 10.1016/S0896-6273(02)00899-1 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 594GC UT WOS:000178040000014 PM 12354403 ER PT J AU Vasan, RS Benjamin, EJ Larson, MG Leip, EP Wang, TJ Wilson, PWF Levy, D AF Vasan, RS Benjamin, EJ Larson, MG Leip, EP Wang, TJ Wilson, PWF Levy, D TI Plasma natriuretic peptides for community screening for left ventricular hypertrophy and systolic dysfunction - The Framingham Heart study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MYOCARDIAL-INFARCTION; DIAGNOSTIC-TEST; PRIMARY-CARE; ECHOCARDIOGRAPHY; POPULATION; ACCURACY; FAILURE; MARKER; MORTALITY; SURVIVAL AB Context Several reports have suggested the usefulness of plasma brain natriuretic peptide (BNP) as a screening test for left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD). Prior studies were limited by small sample sizes and selection bias and none compared the diagnostic performance of these peptides in men and women. Objectives To examine the usefulness of natriuretic peptides for screening for elevated LV mass and LVSD in the community. Design, Setting, and Participants Community-based prospective cohort study of 3177 participants (1707 women) from the Framingham Study who attended a routine examination in 1995-1998. Main Outcome Measures Receiver operating characteristic (ROC) curves, test sensitivity, specificity, positive and negative predictive values, and likelihood ratios for identifying elevated LV mass (sex-specific 90th percentile or higher of LV mass/[height](2)), LVSD (ejection fraction less than or equal to 50% and/or fractional shortening <29%), and moderate to severe LVSD (ejection fraction less than or equal to40% and/or fractional shortening <22%) at different discrimination limits of plasma BNP and N-terminal proatrial natriuretic peptide (NT-ANP), with echocardiography as the criterion standard. Results The areas under the ROC curves for elevated LV mass or LVSD were at or below 0.75 for both peptides, were higher for men compared with women, and were similar for BNP and NT-ANP. The diagnostic performance of natriuretic peptides for LVSD improved in women but not in men when select high-risk subgroups were targeted. Discrimination limits based on high specificity (0.95) yielded better positive predictive values and likelihood ratios compared with age- and sex-specific reference limits yet only identified less than one third of participants who had elevated LV mass or LVSD. Conclusion In our large community-based sample, the performance of BNP and NT-ANP for detection of elevated LV mass and LVSD was suboptimal, suggesting limited usefulness of natriuretic peptides as mass screening tools. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Div Endocrinol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01HL67288-01, K24 HL 04334-01A1, N01-HC-25195] NR 42 TC 299 Z9 313 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 2002 VL 288 IS 10 BP 1252 EP 1259 DI 10.1001/jama.288.10.1252 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 592BW UT WOS:000177917700024 PM 12215132 ER PT J AU Sutton, MS Weyman, AE AF Sutton, MS Weyman, AE TI Mitral valve prolapse prevalence and complications an ongoing dialogue SO CIRCULATION LA English DT Editorial Material DE editorials; mitral valve; complications ID TERM FOLLOW-UP; REQUIRING SURGERY; SUDDEN-DEATH; RISK; REGURGITATION; ASSOCIATION; MANAGEMENT; DIAGNOSIS; LEAFLET C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. RP Weyman, AE (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. NR 20 TC 19 Z9 20 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 SEP 10 PY 2002 VL 106 IS 11 BP 1305 EP 1307 DI 10.1161/01.CIR.0000031759.92250.F3 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593LN UT WOS:000177993100009 ER PT J AU Neagoe, C Kulke, M del Monte, F Gwathmey, JK de Tombe, PP Hajjar, RJ Linke, WA AF Neagoe, C Kulke, M del Monte, F Gwathmey, JK de Tombe, PP Hajjar, RJ Linke, WA TI Titin isoform switch in ischemic human heart disease SO CIRCULATION LA English DT Article DE preload; connectin; ischemia; diastole; coronary artery disease ID TROPONIN-I DEGRADATION; FAILING HUMAN HEART; CARDIAC MYOFIBRILS; MYOCARDIUM; FAILURE; FILAMENTS; MUSCLE; SARCOMERE; TENSION; PROTEIN AB Background-Ischemia-induced cardiomyopathy usually is accompanied by elevated left ventricular end-diastolic pressure, which follows from increased myocardial stiffness resulting from upregulated collagen expression. In addition to collagen, a main determinant of stiffness is titin, whose role in ischemia-induced left ventricular stiffening was studied here. Human heart sarcomeres coexpress 2 principal titin isoforms, a more compliant N2BA isoform and a stiffer N2B isoform. In comparison, normal rat hearts express almost no N2BA titin. Methods and Results-Gel electrophoresis and immunoblotting were used to determine the N2BA-to-N2B titin isoform ratio in nonischemic human hearts and nonnecrotic left ventricle of coronary artery disease (CAD) patients. The average N2BA-to-N2B ratio was 47:53 in severely diseased CAD transplanted hearts and 32:68 in nonischemic transplants. In normal donor hearts and donor hearts with CAD background, relative N2BA titin content was approximate to30%. The titin isoform shift in CAD transplant hearts coincided with a high degree of modifications of cardiac troponin 1, probably indicating increased preload. Immunofluorescence microscopy on CAD transplant specimens showed a regular cross-striated arrangement of titin and increased expression of collagen and desmin. Force measurements on isolated myofibrils revealed reduced passive-tension levels in sarcomeres of CAD hearts with high left ventricular end-diastolic pressure compared with sarcomeres of normal hearts. In a rat model of ischemia-induced myocardial infarction (left anterior descending coronary artery ligature), 43% of animals, but only 14% of sham-operated animals, showed a distinct N2BA titin band on gels. Conclusions-A titin isoform switch was observed in chronically ischemic human hearts showing extensive remodeling, which necessitated cardiac transplantation. The shift, also confirmed in rat hearts, caused reduced titin-derived myofibrillar stiffness. Titin modifications in long-term ischemic myocardium could impair the ability of the heart to use the Frank-Starling mechanism. C1 Univ Heidelberg, Inst Physiol & Pathophysiol, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. RP Linke, WA (reprint author), Univ Heidelberg, Inst Physiol & Pathophysiol, Neuenheimer Feld 326, D-69120 Heidelberg, Germany. RI Neagoe, Ciprian/B-5863-2011; Linke, Wolfgang/E-8662-2012 OI Neagoe, Ciprian/0000-0002-7328-1654; FU NHLBI NIH HHS [P01-HL-62426, R01-HL-52322] NR 23 TC 192 Z9 197 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 10 PY 2002 VL 106 IS 11 BP 1333 EP 1341 DI 10.1161/01.CIR.0000029803.93022.93 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593LN UT WOS:000177993100016 PM 12221049 ER PT J AU Cai, JM Hastukami, TS Ferguson, MS Small, R Polissar, NL Yuan, C AF Cai, JM Hastukami, TS Ferguson, MS Small, R Polissar, NL Yuan, C TI Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging SO CIRCULATION LA English DT Article DE magnetic resonance imaging; atherosclerosis; carotid arteries ID HIGH-RESOLUTION MRI; ARTERY STENOSIS; IN-VIVO; PLAQUE; HEMORRHAGE; THROMBOSIS; ACCURACY; RUPTURE AB Background-Recent studies demonstrated that in vivo and ex vivo MRI can characterize the components of the carotid atherosclerotic plaque, such as fibrous tissue, lipid/necrotic core, calcium, hemorrhage, and thrombus. The purpose of this study was to determine whether in vivo high-resolution multicontrast MRI could accurately classify human carotid atherosclerotic plaque according to the American Heart Association classification. Methods and Results-Sixty consecutive patients (mean age 70 years; 54 males) scheduled for carotid endarterectomy were imaged with a 1.5-T scanner after informed consent was obtained. A standardized protocol was used to obtain 4 different contrast-weighted images (time of flight and T1-, PD-, and T2-weighted) of the carotid arteries. Best voxel size was 0.25 x 0.25 x 1 mm(3). Carotid plaques were removed intact and processed for histological examination. Both MR images and histological sections were independently reviewed, categorized, and compared. Overall, the classification obtained by MRI and the American Heart Association classifications showed good agreement, with Cohen's kappa (95% CI) of 0.74 (0.67 to 0.82) and weighted kappa of 0.79. The sensitivity and specificity, respectively, of MRI classification were as follows: type I-II lesions, 67% and 100%; type III lesions, 81% and 98%; type IV-V lesions, 84% and 90%; type VI lesions, 82% and 91%; type VII lesions, 80% and 94%; and type VIII lesions, 56% and 100%. Conclusions-In vivo high-resolution multicontrast MRI is capable of classifying intermediate to advanced atherosclerotic lesions in the human carotid artery and is also capable of distinguishing advanced lesions from early and intermediate atherosclerotic plaque. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Peoples Liberat Army Gen Hosp, Dept Radiol, Beijing, Peoples R China. Mt Whisper Light Stat Consulting, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Yuan, C (reprint author), Univ Washington, Dept Radiol, Box 357115, Seattle, WA 98195 USA. FU NHLBI NIH HHS [R01 HL56874, R01 HL60213] NR 23 TC 373 Z9 415 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 10 PY 2002 VL 106 IS 11 BP 1368 EP 1373 DI 10.1161/01.CIR.0000028591.44554.F9 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593LN UT WOS:000177993100021 PM 12221054 ER PT J AU Montgomery, RB AF Montgomery, RB TI Antagonistic and agonistic effects of quinazoline tyrosine kinase inhibitors on mutant EGF receptor function SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE EGFR; dimerization; quinazoline; tyrphostin; mutant; tyrosine kinase ID EPIDERMAL GROWTH-FACTOR; CONFERS ENHANCED TUMORIGENICITY; HUMAN GLIOBLASTOMA CELLS; SIGNAL-TRANSDUCTION; DNA-SYNTHESIS; TYRPHOSTINS; PATHWAY; PHOSPHORYLATION; PROLIFERATION; DIMERIZATION AB A mutated form of the EGF receptor (EGFRvIII), resulting from deletion of exons 2-7, is an oncogenic protein that is expressed in multiple human tumors. This mutation induces ligand-independent activation of the EGFR tyrosine kinase and thereby can initiate unregulated cell growth and tumorigenesis. Thus, inhibition of the kinase activity of EGFRvIII is a potential means of suppressing its oncogenic properties. Certain tyrosine kinase inhibitors (tyrphostins) specifically inhibit the wild-type EGFR and thereby inhibit tumor growth both in vitro and in vivo. We demonstrate that the quinazoline tyrphostins AG 1478 and AG 15 17 can suppress morphologic transformation of cell lines by EGFRvIII. Quinazolines were found to inhibit receptor autophosphorylation and signaling through MAP kinase, but had minimal effects on association of EGFRvIII with Grb2/SOS. Low concentrations of quinazoline also increased receptor dimerization and phosphotyrosine content. This was associated with increases in colony formation in soft agar and increased invasion through matrigel for AG 1478. Thus, both AG 1478 and AG 15 17 can inhibit multiple EGFRvIII signaling pathways, but at low concentrations AG 1478 can enhance colony formation, presumably related to augmented homodimerization of the receptor and activation of downstream signaling. (C) 2002 Wiley-Liss, Inc. C1 VA Puget Sound HCS, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Oncol, Seattle, WA 98195 USA. RP Montgomery, RB (reprint author), VA Puget Sound HCS, 111ONC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NCI NIH HHS [CA60782] NR 36 TC 18 Z9 19 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 10 PY 2002 VL 101 IS 2 BP 111 EP 117 DI 10.1002/ijc.10560 PG 7 WC Oncology SC Oncology GA 587CH UT WOS:000177622600002 PM 12209987 ER PT J AU Goldstein, IB Bartzokis, G Guthrie, D Shapiro, D AF Goldstein, IB Bartzokis, G Guthrie, D Shapiro, D TI Ambulatory blood pressure and brain atrophy in the healthy elderly SO NEUROLOGY LA English DT Article ID CARDIOVASCULAR HEALTH; HYPERTENSION; PEOPLE; DISEASE; VOLUMES; MATTER; MRI; AGE AB Background: Brain lesions and atrophy increase with age and hypertension. Objective: To evaluate the relationship of age and ambulatory blood pressure (BP) to brain atrophy in healthy elderly individuals. Methods: MRI volume measurements (normalized to intracranial volume) were taken of total brain and lateral and third ventricles in 155 healthy men and women who went through extensive medical examinations. Younger (56 to 66 years old) and older (67 to 80 years old) subgroups were compared on casual and 24-hour ambulatory BP values and MRI volume measurements. Results: Older subjects had smaller brain volumes and larger lateral and third ventricles. Compared with women, men had larger lateral and third ventricles. With age controlled for, greater sleep systolic BP (SBP) variability was associated with smaller brain volumes; greater waking and sleep SBP variability were associated with larger lateral and third ventricles. Subjects with higher casual and waking SBP and waking diastolic BP had larger lateral ventricles. Among older subjects, only those with elevated SBP had smaller brain volumes and larger lateral ventricles. Conclusions: These results indicate that if BP levels are within the upper normal range, even healthy individuals with no prior diagnosis of hypertension are more likely to have brain atrophy than those with lower BP. Moreover, not only do BP level and variability relate to brain atrophy, but the combination of high level and greater variability shows an even stronger relationship to brain atrophy than either one of these variables alone. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA 90095 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Goldstein, IB (reprint author), Univ Calif Los Angeles, Dept Psychiat, 760 Westwood Plaza, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG-11595] NR 30 TC 38 Z9 39 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 10 PY 2002 VL 59 IS 5 BP 713 EP 719 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 591TU UT WOS:000177897000012 PM 12221162 ER PT J AU Cudkowicz, ME Pastusza, KA Sapp, PC Mathews, RK Leahy, J Pasinelli, P Francis, JW Jiang, D Andersen, JK Brown, RH AF Cudkowicz, ME Pastusza, KA Sapp, PC Mathews, RK Leahy, J Pasinelli, P Francis, JW Jiang, D Andersen, JK Brown, RH TI Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE MUTATION; MOTOR-NEURON DISEASE; HYDROGEN-PEROXIDE; OXIDATIVE DAMAGE; MOUSE MODEL; RADICAL PRODUCTION; NITRIC-OXIDE; VITAMIN-E; IN-VIVO AB Objective: Transgenic mice that overexpress a human gene encoding mutant cytosolic superoxide dismutase (SOD1) develop a progressive motor neuron loss that resembles human ALS. Why mutant SOD1 initiates motor neuron death is unknown. One hypothesis proposes that the mutant molecule has enhanced peroxidase activity, reducing hydrogen peroxide (H2O2) to form toxic hydroxyl adducts on critical targets. To test this hypothesis, the authors generated transgenic ALS mice with altered levels of glutathione peroxidase (GSHPx), the major soluble enzyme that detoxifies H2O2. Methods: SOD1(G93A) ALS mice were bred with mice bearing a murine GSHPx transgene that have a four-fold elevation in brain GSHPx levels and with mice having targeted inactivation of the GSHPx gene and reduced brain GSHPx activity. Results: Survival was not prolonged in ALS mice with elevated brain GSHPx activity (p = 0.09). ALS mice with decreased GSHPx brain activity (20% of normal) showed no acceleration of the disease course (p = 0.89). The age at disease onset in the ALS mice was unaffected by brain GSHPx activity. Conclusion: The level of GSHPx activity in the CNS of transgenic ALS mice does not play a critical role in the development of motor neuron disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Day Neuromuscular Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Div Neurogerontol, Los Angeles, CA 90089 USA. Univ So Calif, Program Neurobiol, Los Angeles, CA 90089 USA. Buck Inst Age Res, Novato, CA USA. RP Cudkowicz, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, 15 Parkman St,ACC 836, Boston, MA 02115 USA. FU NIA NIH HHS [AG12990-07]; NINDS NIH HHS [5R01NS36640, R01NS37912] NR 47 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 10 PY 2002 VL 59 IS 5 BP 729 EP 734 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 591TU UT WOS:000177897000015 PM 12221165 ER PT J AU Bolay, H Moskowitz, MA AF Bolay, H Moskowitz, MA TI Mechanisms of pain modulation in chronic syndromes SO NEUROLOGY LA English DT Article ID INFLAMMATORY PAIN; MIGRAINE AB Transmission of pain from the periphery to the cortex depends on integration and signal processing within the spinal cord, brainstem, and forebrain. Sensitization, a component of persistent or chronic pain, may develop either through peripheral mechanisms or as a consequence of altered physiology in the spinal cord or forebrain. Several molecular and biophysical mechanisms contribute to the phenomenon of sensitization and persistent pain, including upregulation of sensory neuron-specific sodium channels and vanilloid receptors, phenotypic switching of large myelinated axons, sprouting within the dorsal horn, and loss of inhibitory neurons due to apoptotic cell death. Recently, forebrain structures have been implicated in the pathophysiology of persistent pain. Although a number of treatment options are used, unfortunately pharmacotherapy for neuropathic pain is often ineffective. Unraveling the mysteries of chronic pain may lead to better treatment options, such as drugs that act specifically on sensory neuron-specific sodium channels or as NR2B-subunit-selective N-methyl-D-aspartate receptor antagonists. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 16 TC 74 Z9 79 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 10 PY 2002 VL 59 IS 5 SU 2 BP S2 EP S7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 593BE UT WOS:000177970700002 PM 12221149 ER PT J AU Moskowitz, MA AF Moskowitz, MA TI Advances in understanding chronic pain - Mechanisms of pain modulation and relationship to treatment SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. NR 0 TC 3 Z9 4 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 SEP 10 PY 2002 VL 59 IS 5 SU 2 BP S1 EP S1 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 593BE UT WOS:000177970700001 ER PT J AU Wang, TJ Mort, EA Nordberg, P Chang, YC Cadigan, ME Mylott, L Ananian, LV Thompson, BT Fessler, M Warren, W Wheeler, A Jordan, M Fifer, MA AF Wang, TJ Mort, EA Nordberg, P Chang, YC Cadigan, ME Mylott, L Ananian, LV Thompson, BT Fessler, M Warren, W Wheeler, A Jordan, M Fifer, MA TI A utilization management intervention to reduce unnecessary testing in the coronary care unit SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHEST X-RAYS; LABORATORY TESTS; DIAGNOSTIC-TESTS; RADIOGRAPHS; BEHAVIOR; EFFICACY; COSTS AB Background: There have been no studies of interventions to reduce test utilization in the coronary care U it. Objective: To determine whether a 3-part intervention in a coronary care unit could decrease utilization without affecting clinical outcomes. Methods: Practice guidelines for routine laboratory and chest radiographic testing were developed by a multidisciplinary team, using evidence-based recommendations when possible and expert opinion otherwise. These guidelines were incorporated into the computer admission orders for the coronary care unit at a large teaching hospital, and educational efforts were targeted at the house staff and nurses. Utilization during the 3-month intervention period was compared with utilization during the same 3 months in the prior year. The hospital's medical intensive care unit, which did not receive the specific intervention, provided control data. Results: During the intervention period, there were significant reductions in utilization of all chemistry tests (from 7% to 40%). Reductions in ordering of complete blood counts, arterial blood gas tests, and chest radiographs were not statistically significant. After controlling for trends in the control intensive care unit, however, the reductions in arterial blood gas tests (P=.04) and chest radiographs (P<.001) became significant. The reductions in potassium, glucose, calcium, magnesium, and phosphorus testing, but not other chemistries, remained significant. The estimated reduction in expenditures for "routine" blood tests and chest radiographs was 17% (P<001). There were no significant changes in length of stay, readmission to intensive care, hospital mortality, or ventilator days. Conclusion: The utilization management intervention was associated with significant reductions in test ordering without a measurable change in clinical outcomes. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 478, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Care Management Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 478, Dept Med, 15 Parkman St, Boston, MA 02114 USA. NR 16 TC 63 Z9 65 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 9 PY 2002 VL 162 IS 16 BP 1885 EP 1890 DI 10.1001/archinte.162.16.1885 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 593DT UT WOS:000177976500012 PM 12196088 ER PT J AU Olson, DP Scadden, DT D'Aquila, RT De Pasquale, MP AF Olson, DP Scadden, DT D'Aquila, RT De Pasquale, MP TI The protease inhibitor ritonavir inhibits the functional activity of the multidrug resistance related-protein 1 (MRP-1) SO AIDS LA English DT Article DE efflux pump; multidrug resistance; HIV-1 protease inhibitors; MRP-1 ID P-GLYCOPROTEIN; ANTIVIRAL EFFICACY; GENE-PRODUCT; CELL-LINES; TRANSPORTER; HIV-1; BLOOD; MDR1; BARRIER; EXPRESSION AB Background: Efflux pumps situated on the plasma membrane, such as P-glycoprotein (Pgp) and the multidrug resistance related-protein 1 (MRP-1), have been shown to extrude HIV protease inhibitors from the cell. MRP-1 is present on many barrier sites throughout the body, such as the blood-brain and blood-testis interfaces and could reduce the concentration of protease inhibitors in these sanctuary sites for HIV-1 replication. Factors that modulate efflux pump function in vivo are poorly defined. Objective: To analyze the inhibitory potential of the anti-retroviral drugs indinavir, amprenavir, ritonavir, lamivudine or zidovudine to modulate MRP-1 function. Methods: Effect of anti-HIV drugs on the efflux pump activity of MRP-1 was evaluated in the presence of increasing concentrations of human plasma, using UMCC-1/VP cells which stably over-express MRP-1. MRP-1 activity was abrogated by probenecid. The potential of blocking MRP-1 function for an extended (3 day) time period, was also examined in MRP-1 over-expressing cells cultured with either probenecid or the anti-retroviral drugs and a cytotoxic compound (etoposide) that is transported by MRP-1. Results: Ritonavir inhibited the functional activity of MRP-1 similarly to probenecid, as demonstrated by re-sensitization of MRP-1 over-expressing cells to cytotoxic effects of etoposide. Inhibition by ritonavir was inversely related to the concentration of human plasma added to the cells (r(2)=0.89). Other anti-HIV drugs didn't affect the MRP-1 mediated efflux of etoposide. Conclusions: These data may be exploitable to further improve sanctuary site concentrations of anti-HIV or anti-cancer drugs by using ritonavir as a lead compound to develop more potent MRP-1 inhibitors. (C) 2002 Lippincott Williams Wilkins. C1 Vanderbilt Univ, Med Ctr, Div Infect Dis, Med Ctr N A 4120, Nashville, TN 37232 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA USA. RP De Pasquale, MP (reprint author), Vanderbilt Univ, Med Ctr, Div Infect Dis, Med Ctr N A 4120, 1161 21st Ave S, Nashville, TN 37232 USA. NR 22 TC 66 Z9 66 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 SEP 6 PY 2002 VL 16 IS 13 BP 1743 EP 1747 DI 10.1097/00002030-200209060-00005 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 594AZ UT WOS:000178027800004 PM 12218384 ER PT J AU Takagi, J Petre, BM Walz, T Springer, TA AF Takagi, J Petre, BM Walz, T Springer, TA TI Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling SO CELL LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; AFFINITY MODULATION; RECEPTOR ACTIVATION; ELECTRON-MICROSCOPY; CRYSTAL-STRUCTURE; GPIIB-IIIA; LIGAND; ANTAGONISTS; ALPHA-V-BETA-3; MECHANISM AB How ligand binding alters integrin conformation in outside-in signaling, and how inside-out signals alter integrin affinity for ligand, have been mysterious. We address this with electron microscopy, physicochemical measurements, mutational introduction of disulfides, and ligand binding to alphaVbeta3 and alphaIIbbeta3 integrins. We show that a highly bent integrin conformation is physiological and has low affinity for biological ligands. Addition of a high affinity ligand mimetic peptide or Mn2+ results in a switch blade-like opening to an extended structure. An outward swing of the hybrid domain at its junction with the I-like domain shows conformational change within the headpiece that is linked to ligand binding. Breakage of a C-terminal clasp between the alpha and beta subunits enhances Mn2+ induced unbending and ligand binding. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. EM springeroffice@cbr.med.harvard.edu FU NHLBI NIH HHS [HL48675]; NIGMS NIH HHS [GM62580] NR 45 TC 687 Z9 703 U1 2 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 6 PY 2002 VL 110 IS 5 BP 599 EP 611 DI 10.1016/S0092-8674(02)00935-2 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 592NL UT WOS:000177943700007 PM 12230977 ER PT J AU Assil-Kishawi, I Abou-Samra, AB AF Assil-Kishawi, I Abou-Samra, AB TI Sauvagine cross-links to the second extracellular loop of the corticotropin-releasing factor type 1 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND INTERACTION; HORMONE-RECEPTOR; PROTEIN-RECEPTOR; AGONIST-BINDING; AMINO-TERMINUS; XENOPUS-LAEVIS; HIGH-AFFINITY; PEPTIDE; CLONING; DOMAINS AB Contact sites between the corticotropin-releasing factor receptor type 1 (CRFR1), the sauvagine (SVG) radio-ligands [Tyr(0),Gln(1)]SVG (I-125-YQS) and [Tyr(0),Gln(1), Leu(17)] SVG (I-125-YQLS) were examined. I-125-YQLS or I-125-YQS was cross-linked to CRFR1 using the chemical cross-linker, disuccinimidyl. suberate (DSS), which cross-links the epsilon amino groups of lysine residues that have a molecular distance of 11.4 Angstrom. DSS specifically and efficiently cross-linked I-125-YQLS and I-125-YQS to CRFR1. CRFR1 contains 5 putative extracellular lysine residues (Lys(110), Lys(111), Lys(113), Lys(257), and Lys(262)) that can cross-link to the 4 lysine residues (Lys(16), Lys(22), Lys(25), and Lys(27)) of the radioligands. Identification of the CNBr-cleaved fragments of CRFR1 cross-linked to I-125-YQLS or I-125-YQS established that the second extracellular loop of CRFR1 cross-links to Lys(16) of YQS. Additionally, site-directed mutagenesis (changing Lys to Arg in CRFR1 individually and in combination) revealed that Lys(257) in the second extracellular loop of CRFR1 is an important cross-linking site. In conclusion, it was shown that in SVG-bound CRFR1, Lys(257) of CRFR1 lies in close proximity (11.4 Angstrom) to Lys(16) of SVG. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK45020] NR 26 TC 27 Z9 27 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 SEP 6 PY 2002 VL 277 IS 36 BP 32558 EP 32561 DI 10.1074/jbc.M204964200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 591BC UT WOS:000177859000023 PM 12029097 ER PT J AU Martemyanov, KA Arshavsky, VY AF Martemyanov, KA Arshavsky, VY TI Noncatalytic domains of RGS9-1 center dot G beta 5L play a decisive role in establishing its substrate specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-EFFECTOR COMPLEX; RGS PROTEINS; GTPASE ACCELERATION; BETA-SUBUNIT; TRANSDUCIN; PHOTORECEPTORS; REGULATORS; PURIFICATION; PHOSPHODIESTERASE; PHOTOTRANSDUCTION AB The complex between the photoreceptor-specific regulator of G protein signaling (RGS) protein, RGS9-1, and type 5 G protein beta-subunit, Gbeta5L, regulates the duration of the cellular response to light by stimulating the GTPase activity of G protein, transducin. An important property of RGS9-1.Gbeta5L is that it interacts specifically with transducin bound to its effector, cGMP phosphodiesterase, rather than with transducin alone. The minimal structure within the RGS9-1.Gbeta5L complex capable of activating transducin GTPase is the catalytic domain of RGS9. This domain itself is also able to discriminate between free and effector-bound transducin but to a lesser degree than RGS9-1.Gbeta5L. The goal of this study was to determine whether other, noncatalytic domains of RGS9-1.Gbeta5L enhance the intrinsic specificity of the catalytic domain or whether they set the specificity of RGS9-1-G/35L regardless of the specificity of its catalytic domain. We found that a double L353E/R360P amino acid substitution reversed the specificity of the recombinant catalytic domain but did not reverse the specificity of RGS9-1.Gbeta5L. However, the degree of discrimination between free and effector-bound transducin was reduced. Therefore, noncatalytic domains of RGS91.Gbeta5L play a decisive role in establishing its substrate specificity, yet the high degree of this specificity ob. served under physiological conditions requires an additional contribution from the catalytic domain. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs,MEEI, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Howe Labs,MEEI, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY-12859] NR 31 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 6 PY 2002 VL 277 IS 36 BP 32843 EP 32848 DI 10.1074/jbc.M205170200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 591BC UT WOS:000177859000059 PM 12093815 ER PT J AU Wilcox-Adelman, SA Denhez, F Goetinck, PF AF Wilcox-Adelman, SA Denhez, F Goetinck, PF TI Syndecan-4 modulates focal adhesion kinase phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; ACTIN STRESS FIBERS; SWISS 3T3 CELLS; HEPARAN-SULFATE PROTEOGLYCANS; TYROSINE PHOSPHORYLATION; CYTOPLASMIC DOMAIN; EXTRACELLULAR-MATRIX; SIGNAL-TRANSDUCTION; RHO-FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE AB The cell-surface heparan sulfate proteoglycan syndecan-4 acts in conjunction with the alpha(5)beta(1) integrin to promote the formation of actin stress fibers and focal adhesions in fibronectin (FN)-adherent cells. Fibroblasts seeded onto the cell-binding domain (CBD) fragment of FN attach but do not fully spread or form focal adhesions. Activation of Rho, with lysophosphatidic acid (LPA), or protein kinase C, using the phorbol ester phorbol 12-myristate 13-acetate, or clustering of syndecan-4 with antibodies directed against its extracellular domain will stimulate formation of focal adhesions and stress fibers in CBD-adherent fibroblasts. The distinct morphological differences between the cells adherent to the CBD and to full-length FN suggest that syndecan-4 may influence the organization of the focal adhesion or the activation state of the proteins that comprise it. FN-null fibroblasts (which express syndecan-4) exhibit reduced phosphorylation of focal adhesion kinase (FAK) tyrosine 397 (Tyr(397)) when adherent to CBD compared with FN-adherent cells. Treating the CBD-adherent fibroblasts with LPA, to activate Rho, or the tyrosine phosphatase inhibitor sodium vanadate increased the level of phosphorylation of Tyr(397) to match that of cells plated on FN. Treatment of the fibroblasts with PMA did not elicit such an effect. To confirm that this regulatory pathway includes syndecan-4 specifically, we examined fibroblasts derived from syndecan-4-null mice. The phosphorylation levels of FAK Tyr(397) were lower in FN-adherent syndecan-4-null fibroblasts compared with syndecan-4-wild type and these levels were rescued by the addition of LPA or re-expression of syndecan-4. These data indicate that syndecan-4 ligation regulates the phosphorylation of FAK Tyr(397) and that this mechanism is dependent on Rho but not protein kinase C activation. In addition, the data suggest that this pathway includes the negative regulation of a protein-tyrosine phosphatase. Our results implicate syndecan-4 activation in a direct role in focal adhesion regulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Goetinck, PF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [HD-37490, F32 HD41235] NR 96 TC 91 Z9 92 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 6 PY 2002 VL 277 IS 36 BP 32970 EP 32977 DI 10.1074/jbc.M201283200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 591BC UT WOS:000177859000076 PM 12087088 ER PT J AU Turner, RB Liu, L Sazonova, IY Reed, GL AF Turner, RB Liu, L Sazonova, IY Reed, GL TI Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; ACTIVATOR; STREPTOKINASE; ALPHA-2-ANTIPLASMIN; STAPHYLOKINASE; COMPLEX; INHIBITOR; KINETICS; PROGRAM; POTENT AB There is remarkable homology between the core structures of plasmin, a fibrin clot-degrading enzyme, and factor D, a complement-activating enzyme, despite markedly different biological functions. We postulated that sequence divergence in the loop structures between these two enzymes mediated the unique substrate and inhibitor interactions of plasmin. Recombinant microplasminogens chimerized with factor D sequences at loops 3, 5, and 7 were cleaved by the plasminogen activator urokinase and developed titratable active sites. Chimerization abolished functional interactions with the plasminogen activator streptokinase but did not block complex formation. The microplasmin chimeras showed enhanced resistance (k(i) decreased up to two to three times) to inactivation of microplasmin by alpha(2)-antiplasmin. Microplasmin chimerization had minimal (similar to2 fold) effects on the catalytic efficiency for cleavage of small substrates and did not alter the cleavage of fibrin. However, microplasmin and the microplasmin chimeras showed enhanced abilities to degrade fibrin in plasma clots suspended in human plasma. These studies indicate that loop regions of the protease domain of plasmin are important for interactions with substrates, regulatory molecules, and inhibitors. Because modification of these regions affected substrate and inhibitor interactions, loop chimerization may hold promise for improving the clot dissolving properties of this enzyme. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, II-127,677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-58946] NR 23 TC 10 Z9 10 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 SEP 6 PY 2002 VL 277 IS 36 BP 33068 EP 33074 DI 10.1074/jbc.M203782200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 591BC UT WOS:000177859000087 PM 12080056 ER PT J AU Fitzgerald, ML Morris, AL Rhee, JS Andersson, LP Mendez, AJ Freeman, MW AF Fitzgerald, ML Morris, AL Rhee, JS Andersson, LP Mendez, AJ Freeman, MW TI Naturally occurring mutations in the largest extracellular loops of ABCA1 can disrupt its direct interaction with apolipoprotein A-I SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN DEFICIENCY; BINDING CASSETTE TRANSPORTER-1; CORONARY HEART-DISEASE; HDL PARTICLE UPTAKE; TANGIER-DISEASE; CHOLESTEROL EFFLUX; CELLULAR CHOLESTEROL; PLASMA-MEMBRANE; LIPID EFFLUX; GENE AB The ABCA1 transporter contains two large domains into which many of the genetic mutations in individuals with Tangier disease fall. To investigate the structural requirements for the cellular cholesterol efflux mediated by ABCA1, we have determined the topology of these two domains and generated transporters harboring five naturally occurring missense mutations in them. These mutants, unlike wild type ABCA1, produced little or no apoA-I-stimulated cholesterol efflux when transfected into 293 cells, establishing their causality in Tangier disease. Because all five mutant proteins were well expressed and detectable on the plasma membrane, their interaction with the ABCA1 ligand, apolipoprotein (apo) A-I, was measured using bifunctional cross-linking agents. Four of five mutants had a marked decline in cross-linking to apoA-I, whereas one (W590S) retained full cross-linking activity. Cross-linking of apoA-I was temperature-dependent, rapid in onset, and detectable with both lipid-and water-soluble cross-linking agents. These results suggest that apoA-I-stimulated cholesterol efflux cannot occur without a direct interaction between the apoprotein and critical residues in two extracellular loops of ABCAI. The behavior of the W590S mutant indicates that although binding of apoA-I by ABCA1 may be necessary, it is not sufficient for stimulation of cholesterol efflux. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Miami, Sch Med, Diabet Res Inst, Miami, FL 33101 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL10398, HL45098, HL68988] NR 36 TC 135 Z9 144 U1 1 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 SEP 6 PY 2002 VL 277 IS 36 BP 33178 EP 33187 DI 10.1074/jbc.M204996200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 591BC UT WOS:000177859000101 PM 12084722 ER PT J AU Lee, DM Friend, DS Gurish, MF Benoist, C Mathis, D Brenner, MB AF Lee, DM Friend, DS Gurish, MF Benoist, C Mathis, D Brenner, MB TI Mast cells: A cellular link between autoantibodies and inflammatory arthritis SO SCIENCE LA English DT Article ID FC-GAMMA-RIII; C-KIT LIGAND; RHEUMATOID-ARTHRITIS; DIFFERENTIAL EXPRESSION; ARTHUS REACTION; TNF-ALPHA; T-CELL; RECEPTOR; MOUSE; DISEASE AB Previous studies have revealed that autoantibodies, complement components, and Fc receptors each participate in the pathogenesis of erosive arthritis in K/BxN mice. However, it is not known which cellular populations are responsive to these inflammatory signals. We find that two strains of mice deficient in mast cells, W/W-v and Sl/Sl(d) were resistant to development of joint inflammation and that susceptibility was restored in the W/W-v strain by mast cell engraftment. Thus, mast cells may function as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Brenner, MB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. FU NIAMS NIH HHS [1R01 AR/AI46580-01] NR 34 TC 545 Z9 567 U1 0 U2 13 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 SEP 6 PY 2002 VL 297 IS 5587 BP 1689 EP 1692 DI 10.1126/science.1073176 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590JE UT WOS:000177819100046 PM 12215644 ER PT J AU Goulder, PJR Walker, BD AF Goulder, PJR Walker, BD TI HIV-1 superinfection - A word of caution SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SIMIAN IMMUNODEFICIENCY VIRUS; VIRAL DIVERSITY; IMMUNE CONTROL; INFECTION; AIDS; VIREMIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goulder, PJR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 29 Z9 30 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 5 PY 2002 VL 347 IS 10 BP 756 EP 758 DI 10.1056/NEJMe020091 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 589NH UT WOS:000177765800011 PM 12213949 ER PT J AU Wong, M Staszewsky, L Latini, R Barlera, S Volpi, A Chiang, YT Benza, RL Gottlieb, SO Kleemann, TD Rosconi, F Vandervoort, PM Cohn, JN AF Wong, M Staszewsky, L Latini, R Barlera, S Volpi, A Chiang, YT Benza, RL Gottlieb, SO Kleemann, TD Rosconi, F Vandervoort, PM Cohn, JN CA Val-HeFT Heart Failure Trial Inves TI Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DYSFUNCTION; HYPERTROPHY; CARVEDILOL; MORTALITY; ENALAPRIL; BLOCKADE; THERAPY; ENZYME; TRIAL AB OBJECTIVES The objective of the study was to evaluate the effect of an angiotensin receptor blocker on left ventricular (LV) structure and function when added to prescribed heart failure therapy. BACKGROUND The clinical benefit derived from heart failure therapy is attributed to the regression of LV remodeling. METHODS At 302 multinational sites, 5,010 patients in New York Heart Association (NYHA) classification II to IV heart failure taking angiotensin-converting enzyme inhibitor (ACEI) and/or beta-blocker (BB) were randomized into valsartan and placebo groups and followed for a mean of 22.4 months. Serial echocardiographic measurements of left ventricular internal diastolic diameter (LVIDd) and ejection fraction (EF) were recorded. Total study reproducibility calculated to 90% power at 5% significance defined detectable differences of 0.09 cm for LVIDd and 0.86% for EF. RESULTS Baseline LVIDd and EF for valsartan and placebo groups were similar: 3.6 +/- 0.5 versus 3.7 +/- 0.5 (cm/m(2)) and 26.6 +/- 7.3 versus 26.9 +/- 7.0 (%). Mean group changes from baseline over time were compared. Significant decrease in LVIDd and increase in EF began by four months, reached plateau by one year, and persisted to two years in valsartan compared with placebo patients, irrespective of age, gender, race, etiology, NYHA classification, and co-treatment therapy. Changes at 18 months were -0.12 +/- 0.4 versus -0.05 +/- 0.4 (cm/m(2)), p < 0.00001 for LVIDd, and +4.5 +/- 8.9 versus +3.2 +/- 8.6 (%), p < 0.00001 for EF. The exception occurred in patients taking both ACEI and BB as co-treatment, in whom the decrease in LVIDd and increase in EF were no different between valsartan and placebo groups. CONCLUSIONS The Val-HeFT echocardiographic substudy of 5,010 patients with moderate heart failure demonstrated that valsartan therapy taken with either ACEI or BB reversed LV remodeling. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Ist Mario Negri, Milan, Italy. C Borella Hosp, Milan, Italy. Novartis Pharmaceut, E Orange, NJ USA. Univ Alabama, Birmingham, AL USA. Mid Atlantic Cardiovasc Associates, Baltimore, MD USA. Herzzentrum Ludwigshafen, Ludwigshafen, Germany. Osped Passirana Rho, Milan, Italy. Hartctr Limburg, Genk, Belgium. Univ Minnesota, Minneapolis, MN USA. RP Wong, M (reprint author), VA Greater Los Angeles Healthcare Syst, 00QM,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 22 TC 114 Z9 128 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP 4 PY 2002 VL 40 IS 5 BP 970 EP 975 AR PII S0735-1097(02)02063-6 DI 10.1016/S0735-1097(02)02063-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 589ND UT WOS:000177765200020 PM 12225725 ER PT J AU Michaud, DS Liu, SM Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Michaud, DS Liu, SM Giovannucci, E Willett, WC Colditz, GA Fuchs, CS TI Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CORONARY HEART-DISEASE; NATIONAL DEATH INDEX; MIXED MEALS; CLINICAL IMPLICATIONS; INSULIN RESPONSES; DIRECT INTERVIEWS; NUTRIENT INTAKE; GLUCOSE; WOMEN AB Background: Evidence from both animal and human studies suggests that abnormal glucose metabolism plays an important role in pancreatic carcinogenesis. We investigated whether diets high in foods that increase postprandial glucose levels are associated with an increased risk of pancreatic cancer. Methods: In a cohort of U.S. women (n = 88 802) participating in the Nurses' Health Study, 180 case subjects with pancreatic cancer were diagnosed during 18 years of follow-up. We used frequency of intake of individual foods as reported on a food-frequency questionnaire in 1980 to calculate sucrose, fructose, and carbohydrate intakes; glycemic index (postprandial blood glucose response as compared with a reference food); and glycemic load (glycemic index multiplied by carbohydrate content). Analyses of relative risk (RR) were performed by using multivariable Cox proportional hazards models to adjust for potential confounders. All statistical tests were two-sided. Results: Carbohydrate and sucrose intake were not associated with overall pancreatic cancer risk in this cohort. A statistically nonsignificant 53% increase in risk of pancreatic cancer (RR = 1.53, 95% confidence interval [CI] = 0.96 to 2.45) was observed among women with a high glycemic load intake, and a similar association was observed for fructose intake (RR = 1.57, 95% CI = 0.95 to 2.57). The associations of glycemic load and fructose intakes with pancreatic cancer risk were most apparent among women with elevated body mass index (greater than or equal to25 kg/m(2)) or with low physical activity. Among women who were both overweight and sedentary, a high glycemic load was associated with an RR of 2.67 (95% CI = 1.02 to 6.99; highest versus lowest quartile of intake; P for trend = .03), and high fructose was associated with an RR of 3.17 (95% CI = 1.13 to 8.91; P for trend = .04). Conclusion: Our data support other findings that impaired glucose metabolism may play a role in pancreatic cancer etiology. A diet high in glycemic load may increase the risk of pancreatic cancer in women who already have an underlying degree of insulin resistance. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Michaud, DS (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Rm 3032, Rockville, MD 20852 USA. RI Liu, Simin/I-3689-2014; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Liu, Simin/0000-0003-2098-3844; Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA86102, CA87969]; NIDDK NIH HHS [DK02767] NR 47 TC 127 Z9 130 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 4 PY 2002 VL 94 IS 17 BP 1293 EP 1300 PG 8 WC Oncology SC Oncology GA 588ZJ UT WOS:000177732100009 PM 12208894 ER PT J AU Humphrey, LL Helfand, M Chan, BKS Woolf, SH AF Humphrey, LL Helfand, M Chan, BKS Woolf, SH TI Breast cancer screening: A summary of the evidence for the US Preventive Services Task Force SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; POSITIVE PREDICTIVE VALUE; SWEDISH 2-COUNTY TRIAL; FAMILY HISTORY; FOLLOW-UP; REPLACEMENT THERAPY; SELF-EXAMINATION; SOJOURN TIME; RISK-FACTORS; DEATH RATES AB Purpose: To synthesize new data on breast cancer screening for the U.S. Preventive Services Task Force. Data Sources: MEDLINE; the Cochrane Controlled Trials Registry; and reference lists of reviews, editorials, and original studies. Study Selection: Eight randomized, controlled trials of mammography and 2 trials evaluating breast self-examination were included. One hundred fifty-four publications of the results of these trials, as well as selected articles about the test characteristics and harms associated with screening, were examined. Data Extraction: Predefined criteria were used to assess the quality of each study. Meta-analyses using a Bayesian random-effects model were conducted to provide summary relative risk estimates and credible intervals (CrIs) for the effectiveness of screening with mammography in reducing death from breast cancer. Data Synthesis: For studies of fair quality or better, the summary relative risk was 0.84 (95% CrI, 0.77 to 0.91) and the number needed to screen to prevent one death from breast cancer after approximately 14 years of observation was 1224 (CrI, 665 to 2564). Among women younger than 50 years of age, the summary relative risk associated with mammography was 0.85 (CrI, 0.73 to 0.99) and the number needed to screen to prevent one death from breast cancer after 14 years of observation was 1792 (CrI, 764 to 10 540). For clinical breast examination and breast self-examination, evidence from randomized trials is inconclusive. Conclusions: in the randomized, controlled trials, mammography reduced breast cancer mortality rates among women 40 to 74 years of age. Greater absolute risk reduction was seen among older women. Because these results incorporate several rounds of screening, the actual number of mammograms needed to prevent one death from breast cancer is higher. In addition, each screening has associated risks and costs. C1 Oregon Hlth & Sci Univ, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Virginia Commonwealth Univ, Med Coll Virginia, Fairfax, VA USA. RP Humphrey, LL (reprint author), Agcy Healthcare Res & Qual, Publicat Clearinghouse, Rockville, MD 20852 USA. FU PHS HHS [290-97-0018] NR 99 TC 662 Z9 686 U1 5 U2 34 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 SEP 3 PY 2002 VL 137 IS 5 BP 347 EP 360 PN 1 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 591DZ UT WOS:000177865600007 PM 12204020 ER PT J AU Wang, TJ Larson, MG Levy, D Benjamin, EJ Kupka, MJ Manning, WJ Clouse, ME D'Agostino, RB Wilson, PWF O'Donnell, CJ AF Wang, TJ Larson, MG Levy, D Benjamin, EJ Kupka, MJ Manning, WJ Clouse, ME D'Agostino, RB Wilson, PWF O'Donnell, CJ TI C-reactive protein is associated with subclinical epicardial coronary calcification in men and women - The Framingham heart study SO CIRCULATION LA English DT Article DE coronary disease; inflammation; imaging ID BEAM COMPUTED-TOMOGRAPHY; BODY-MASS INDEX; ARTERY CALCIUM; RISK FACTOR; DISEASE; ADULTS; ATHEROSCLEROSIS; PREDICTION AB Background-High C-reactive protein (CRP) levels are associated with an increased risk of cardiovascular events, even in apparently healthy individuals. It has not been established whether elevated CRP reflects an increased burden of subclinical coronary atherosclerosis. Methods and Results-We studied a stratified random sample of 321 men and women (mean age 60 years) from the Framingham Heart Study who were free of clinically apparent cardiovascular disease. Subjects underwent electron-beam computed tomography to assess the number of coronary calcifications and the coronary artery calcification (CAC) Agatston score. Spearman correlation coefficients between CRP and CAC score were calculated and adjusted for age, age plus individual risk factors, and age plus the Framingham coronary heart disease risk score. For both sexes, CRP was significantly correlated with the Agatston score (age-adjusted Spearman correlation: 0.25 for men, 0.26 for women; both P < 0.01). After adjustment for age and Framingham risk score, the correlation remained significant (P = 0.01) for both sexes. Further adjustment for body mass index attenuated the correlation coefficient for women (0.14, P = 0.09) but not for men (0.19, P < 0.05). Conclusions-High CRP levels are associated with increased coronary calcification. Among individuals with elevated CRP, subclinical atherosclerosis may contribute to an increased risk for future cardiovascular events. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Radiol, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01-HL64753, N01-HC-25195] NR 17 TC 128 Z9 137 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 3 PY 2002 VL 106 IS 10 BP 1189 EP 1191 DI 10.1161/01.CIR.000032135.98011.C4 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 593AG UT WOS:000177968600004 PM 12208790 ER PT J AU Long, XM Spycher, C Han, ZS Rose, AM Muller, F Avruch, J AF Long, XM Spycher, C Han, ZS Rose, AM Muller, F Avruch, J TI TOR deficiency in C-elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation SO CURRENT BIOLOGY LA English DT Article ID PROTEIN PHOSPHATASE 2A; AGE-1 PI3 KINASE; CAENORHABDITIS-ELEGANS; CELL-GROWTH; CATALYTIC SUBUNIT; SIGNALING PATHWAY; PHOSPHATIDYLINOSITOL 3-KINASE; S6 KINASE; IN-VIVO; RAPAMYCIN AB Background: TOR is a phosphatidylinositol kinase (PIK)-related kinase that controls cell growth and proliferation in response to nutritional cues. We describe a C. elegans TOR homolog (CeTOR) and phenotypes associated with CeTOR deficiency. These phenotypes are compared with the response to starvation and the inactivation of a variety of putative TOR targets. Results: Whether caused by mutation or RNA interference, TOR deficiency results in developmental arrest at mid-to-late L3, which is accompanied by marked gonadal degeneration and a pronounced intestinal cell phenotype. A population of refractile, autofluorescent intestinal vesicles, which take up the lysosomal dye Neutral Red, increases dramatically in size, while the number of normal intestinal vesicles and the intestinal cytoplasmic volume decrease progressively. This is accompanied by an increase in the gut lumen size and a compromise in the intestine's ability to digest and absorb nutrients. CeTOR-deficient larvae exhibit no significant dauer characteristics, but share some features with starved L3 larvae. Notably, however, starved larvae do not have severe intestinal atrophy. Inactivation of C. elegans p70S6K or TAP42 homologs does not reproduce CeTOR deficiency phenotypes, nor does inactivation of C. elegans TIP41, a putative negative regulator of CeTOR function, rescue CeTOR deficiency. In contrast, inactivating the C. elegans eIF-4G homolog and eIF-2 subunits results in developmental arrest accompanied by the appearance of large, refractile intestinal vesicles and severe intestinal atrophy resembling that of CeTOR deficiency. Conclusions: The developmental arrest and intestinal phenotypes of CeTOR deficiency are due to an inhibition of global mRNA translation. Thus, TOR is a major up-stream regulator of overall mRNA translation in C. elegans, as in yeast. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Univ Fribourg, Inst Zool, CH-1700 Fribourg, Switzerland. Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z3, Canada. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NCI NIH HHS [CA73818] NR 65 TC 153 Z9 159 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 3 PY 2002 VL 12 IS 17 BP 1448 EP 1461 AR PII S0960-9822(02)01091-6 DI 10.1016/S0960-9822(02)01091-6 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 590PP UT WOS:000177831500013 PM 12225660 ER PT J AU Davis, JH Szostak, JW AF Davis, JH Szostak, JW TI Isolation of high-affinity GTP aptamers from partially structured RNA libraries SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IN-VITRO SELECTION; INVITRO SELECTION; POLYMERASE; MOLECULES; LIGANDS AB Aptamers, RNA sequences that bind to target ligands, are typically isolated by in vitro selection from RNA libraries containing completely random sequences. To see whether higher-affinity aptamers can be isolated from partially structured RNA libraries, we selected for aptamers that bind GTP, starting from a mixture of fully random and partially structured libraries. Because stem-loops are common motifs in previously characterized aptamers, we designed the partially structured library to contain a centrally located stable stem-loop. We used an off-rate selection protocol designed to maximize the enrichment of high-affinity aptamers. The selection produced a surprisingly large number of distinct sequence motifs and secondary structures, including seven different aptamers with K(d)s ranging from 500 to 25 nanomolar. The engineered stem-loop was present in the three highest affinity aptamers, and in 12 of 13 independent isolates with a single consensus sequence, suggesting that its inclusion increased the abundance of high-affinity aptamers in the starting pool. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM53036, F32 GM017438, GM17438] NR 18 TC 78 Z9 81 U1 1 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 SEP 3 PY 2002 VL 99 IS 18 BP 11616 EP 11621 DI 10.1073/pnas.182095699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100018 PM 12185247 ER PT J AU Kelly, JA Thompson, K Kilpatrick, J Lam, T Nath, SK Gray-McGuire, C Reid, J Namjou, B Aston, CE Bruner, GR Scofield, RH Harley, JB AF Kelly, JA Thompson, K Kilpatrick, J Lam, T Nath, SK Gray-McGuire, C Reid, J Namjou, B Aston, CE Bruner, GR Scofield, RH Harley, JB TI Evidence for a susceptibility gene (SLEH1) on chromosome 11q14 for systemic lupus erythematosus (SLE) families with hemolytic anemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIB-PAIR FAMILIES; AUTOIMMUNE-DISEASE; REVISED CRITERIA; UNITED-STATES; GENOME SCAN; BXSB MICE; LINKAGE; NEPHRITIS; LOCUS; PREVALENCE AB Hemolytic anemia is a forme fruste of systemic lupus erythematosus (SLE), being observed months or even years before the onset of other clinical manifestations in some patients. We hypothesized that hemolytic anemia in those SLE-affected patients would identify a group of SLE pedigrees that share a high degree of genetic homogeneity. From 160 multiplex SLE pedigrees, we sought evidence for linkage in 35 (16 African-American, 17 European-American, and 2 Hispanic) who had at least one SLE-affected patient with hemolytic anemia. Significant linkage was present at 11q14 in the 16 African-American pedigrees, yielding a maximum two-point logarithm of odds (LOD) score of 4.5 at D11S2002. The segregation pattern of SLE in these African-American pedigrees suggested a dominant mode of inheritance and, when maximized across penetrance and disease allele frequencies, produced a multipoint LOD of 4.7. Multipoint analysis yielded a multipoint heterogeneity LOD score of 3.6 (alpha = 0.63), again with maximum LOD at D11S2002. Finally, markerstyped 7 centimorgans to either side of D11S2002 achieved LOD scores of 3 or better by using the maximized model, supporting linkage to 11q14. Clearly, pedigree ascertainment based on select clinical manifestations is an important tool, capable of revealing otherwise cryptic genetic linkages in complex genetic diseases. Thus, we show strong evidence for an SLE susceptibility gene, SLEH1, near D11S2002 in African-American pedigrees multiplex for SLE that have at least one SLE-affected patient with hemolytic anemia. C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK 73104 USA. RP Harley, JB (reprint author), 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NCRR NIH HHS [RR15577, P20 RR015577, P41 RR003655, 1 P41 RR03655]; NIAID NIH HHS [AI31584, AI24717, R01 AI031584, R37 AI024717, R01 AI024717]; NIAMS NIH HHS [AR42460, N01AR12253, R01 AR042460] NR 62 TC 29 Z9 30 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 SEP 3 PY 2002 VL 99 IS 18 BP 11766 EP 11771 DI 10.1073/pnas.182162399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100043 PM 12192084 ER PT J AU Manz, MG Miyamoto, T Akashi, K Weissman, IL AF Manz, MG Miyamoto, T Akashi, K Weissman, IL TI Prospective isolation of human clonogenic common myeloid progenitors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN BONE-MARROW; HEMATOPOIETIC STEM-CELLS; DENDRITIC CELLS; CORD-BLOOD; RECEPTOR EXPRESSION; NATURAL-KILLER; FETAL LIVER; IN-VITRO; DIFFERENTIATION; LEUKEMIA AB The hierarchical development from hematopoietic stem cells to mature cells of the hematolymphoid system involves progressive loss of self-renewal capacity, proliferation ability, and lineage potentials. Here we show the prospective isolation of early developmental intermediates, the human clonogenic common myeloid progenitors and their downstream progeny, the granulocyte/macrophage and megakaryocyte/erythrocyte progenitors. All three populations reside in the lineage-negative (lin(-)) CD34(+)CD38(+) fraction of adult bone marrow as well as in cord blood. They are distinguishable by the expression of the IL-3Ralpha chain, the receptor of an early-acting hematopoietic cytokine, and CD45RA, an isoform of a phosphotyrosine phosphatase involved in negative regulation of cytokine signaling. Multipotent progenitors, early lymphoid progenitors, and the here-defined myeloid progenitors express distinct profiles of hematopoiesis-affiliated genes. The isolation of highly purified hematopoietic intermediates provides tools to better understand developmental programs underlying normal and leukemic hernatopoiesis. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Manz, MG (reprint author), Stanford Univ, Sch Med, Dept Pathol, B257 Beckman Ctr, Stanford, CA 94305 USA. RI Manz, Markus/C-7588-2011 FU NCI NIH HHS [R01 CA086017, CA86017] NR 38 TC 248 Z9 257 U1 0 U2 5 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 SEP 3 PY 2002 VL 99 IS 18 BP 11872 EP 11877 DI 10.1073/pnas.172384399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100061 PM 12193648 ER PT J AU Cowan, S Hatziioannou, T Cunningham, T Muesing, MA Gottlinger, HG Bieniasz, PD AF Cowan, S Hatziioannou, T Cunningham, T Muesing, MA Gottlinger, HG Bieniasz, PD TI Cellular inhibitors with Fv1-like activity restrict human and simian immunodeficiency virus tropism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MURINE LEUKEMIA VIRUSES; RETROVIRUS RESTRICTION; PERSISTENT INFECTION; TYPE-1 REPLICATION; HOST-RANGE; CELLS; HIV-1; GENE; MACAQUES; LYMPHOCYTES AB Many nonhuman primate cells are unable to support the replication of HIV-1, whereas others are nonpermissive for infection by simian immunodeficiency virus from macaques (SIVmac). Here, we show that restricted HIV-1 and SIVmac infection of primate cell lines shares some salient features with Fv1 and Ref1-mediated restriction of murine retrovirus infection. In particular, the nonpermissive phenotype is most evident at low multiplicities of infection, results in reduced accumulation of reverse transcription products, and is dominant in heterokaryons generated by fusion of permissive and nonpermissive target cells. Moreover, in nonpermissive primate cells, HIV-1 and SIVmac infection is cooperative, and enveloped HIV-1 virus-like particles, minimally containing Gag and protease, abrogate restriction. In African green monkey cells, HIV-1 virus-like particles ablate restrictions to HIV-1 and SIVmac, suggesting that both are restricted by the same factor. Finally, a virus that contains an HIV-1 capsid-p2 domain in an SIVmac background exhibits a tropism for primate cells that is HIV-1-like rather than SIVmac-like. These data indicate the existence of one or more saturable inhibitors that are polymorphic in primates and prevent HIV and SIV infection by targeting the capsid of the incoming lentivirus particle. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Harvard Univ, Dana Faber Inst, Boston, MA 02115 USA. RP Bieniasz, PD (reprint author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1St Ave, New York, NY 10016 USA. FU NIAID NIH HHS [R01AI50111, R01AI47054, R01 AI050111, R01 AI047054] NR 40 TC 229 Z9 230 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 2002 VL 99 IS 18 BP 11914 EP 11919 DI 10.1073/pnas.162299499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 590UW UT WOS:000177843100068 PM 12154227 ER PT J AU Israel, JA Lee, K AF Israel, JA Lee, K TI Amphetamine usage and genital self-mutilation SO ADDICTION LA English DT Article DE amphetamine; self-mutilation; self-injurious; substance abuse ID INJURIOUS-BEHAVIOR; RATS; AMPUTATION AB Amphetamine usage has been associated with addiction, psychosis and self-injurious behavior. We report on two patients who severely and repeatedly mutilated their own genitalia while intoxicated on amphetamines and consider possible diagnostic etiologies. C1 Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, Consultat Liason Psychiat Serv, San Francisco, CA 94121 USA. RP Israel, JA (reprint author), Vet Affairs Med Ctr, Acute Psychiat Serv, 4150 Clement St 116N, San Francisco, CA 94121 USA. NR 27 TC 13 Z9 13 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD SEP PY 2002 VL 97 IS 9 BP 1215 EP 1218 DI 10.1046/j.1360-0443.2002.00230.x PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 593GB UT WOS:000177981700019 PM 12199837 ER PT J AU Teichner, G Horner, MD Roitzsch, JC Herron, J Thevos, A AF Teichner, G Horner, MD Roitzsch, JC Herron, J Thevos, A TI Substance abuse treatment outcomes for cognitively impaired and intact outpatients SO ADDICTIVE BEHAVIORS LA English DT Article DE cognitive impairment; treatment outcome; substance abuse; treatment dropouts ID MEN ALCOHOLICS; COCAINE; RELAPSE; ACQUISITION; PERSONALITY; PREDICTION; LENGTH; MEMORY; STAY AB The purpose of this research was to examine the effects of cognitive impairment on the efficacy of substance abuse treatment outcome. Alcohol, drug, medical, legal, psychological, employment, and family functioning related treatment outcomes were examined for 26 cognitively impaired and 68 cognitively intact abusing outpatients. Subjects were enrolled in an intensive, 3-week, outpatient program for the treatment of their substance abuse. Subjects were administered a battery of neuropsychological tests prior to treatment onset, and outcome data were obtained at 1, 3, 6, and 12 months posttreatment entry. No significant between-group differences were found on any of the outcome measures, and significant treatment gains were observed across all problem domains in both groups. Subjects' largest improvements were made in the first month of treatment for alcohol, drug, legal, family, and psychological problems. Improvements for employment and medical problems were not observed until 6 months posttreatment. Success across domains was maintained through 12 months follow-up, with the exception of psychological problems; 12-month data indicated a return to the level observed at 30 days posttreatment for psychological problems, a level that reflected significant improvement from baseline functioning. A greater proportion of treatment dropouts (i.e., no follow-up data obtained after 30 days) were cognitively impaired as compared to treatment completers. These results suggest that this method of intensive substance abuse outpatient treatment is effective for cognitively impaired patients, an important finding given that research evaluating the efficacy of interventions for such patients is limited. Additionally, neuropsychological evaluation may be important in reducing treatment dropouts, as the present findings indicated that greater cognitive impairment was related to an increased likelihood of treatment dropout. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Teichner, G (reprint author), Med Univ S Carolina, Dept Neurol, 96 Jonathan Lucas St,CSB 3,POB 280606, Charleston, SC 29425 USA. NR 42 TC 60 Z9 60 U1 0 U2 1 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 SEP-OCT PY 2002 VL 27 IS 5 BP 751 EP 763 AR PII S0306-4603(01)00207-6 DI 10.1016/S0306-4603(01)00207-6 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 584WZ UT WOS:000177492900008 PM 12201382 ER PT J AU Ferry, JA AF Ferry, JA TI Angioimmunoblastic T-cell lymphoma SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE T-cell lymphoma; angioimmunoblastic; lymphadenopathy; immunophenotype; follicular dendritic cells ID ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; DENDRITIC CELLS; DYSPROTEINEMIA; DISEASE; IMMUNOPHENOTYPE; APPEARANCE; PATTERNS AB Angioimmunoblastic T-cell lymphoma (AIL-TCL) is a rare subtype of lymphoma, making up only 1% to 2% of nonHodgkin's lymphomas; however, it accounts for a major subset of peripheral T-cell lymphomas. Angioimmunoblastic T-cell lymphoma has clinical and pathologic features that set it apart from other B- and T-cell lymphomas. More recent studies have delineated the immunophenotypic and genetic features of this unusual lymphoma, and have tentatively identified the cell of origin of this neoplasm. 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 Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 31 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2002 VL 9 IS 5 BP 273 EP 279 DI 10.1097/00125480-200209000-00001 PG 7 WC Pathology SC Pathology GA 585GQ UT WOS:000177517400001 PM 12195216 ER PT J AU Hong, SJ Wong, JT Bloch, KJ AF Hong, SJ Wong, JT Bloch, KJ TI Reactions to radiocontrast media SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID RADIOGRAPHIC CONTRAST-MEDIA; HIGH-RISK PATIENTS; ADVERSE REACTIONS; ANAPHYLACTOID REACTIONS; PREMEDICATION; PRETREATMENT; ANTAGONISTS; HISTAMINE; SAFETY; ANGIOGRAPHY AB Adverse reactions to radiocontrast media (RCM) occur unexpectedly and may be life-threatening. This article describes an anaphylactoid reaction (AR) in one patient. The term AR refers to a syndrome clinically similar to anaphylaxis, but these reactions are independent of immunoglobulin E antibody-mediated mast cell or basophil degranulation. This article briefly reviews the literature regarding RCMs and types of reactions to RCM. The risk factors for AR to RCM infusions will be discussed along with current concepts of the pathogenesis of RCM-induced ARs. This article also describes the therapeutic management of patients who have had a previous adverse reaction to RCM and provides an approach to patients who have breakthrough reactions despite adequate premedication, but require additional radiographic studies. C1 Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Clin Immunol Unit, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Allergy Unit, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hong, SJ (reprint author), 15 Parkman,WACC 626, Boston, MA 02114 USA. NR 34 TC 10 Z9 10 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 2002 VL 23 IS 5 BP 347 EP 351 PG 5 WC Allergy SC Allergy GA 612AR UT WOS:000179051600010 PM 12476546 ER PT J AU Every, N Hallstrom, A McDonald, KM Parsons, L Thom, D Weaver, D Hlatky, MA AF Every, N Hallstrom, A McDonald, KM Parsons, L Thom, D Weaver, D Hlatky, MA TI Risk of sudden versus nonsudden cardiac death in patients with coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEART-RATE-VARIABILITY; STRATIFICATION; METAANALYSIS; ANGIOPLASTY; SURVIVORS; SURGERY; ARREST AB Background Patients at high risk of sudden cardiac death, yet at low risk of nonsudden death, might be ideal candidates for antiarrhythmic drugs or devices. Most previous studies of prognostic markers for sudden cardiac death have ignored the competitive risk of nonsudden cardiac death. The goal of the present study was to evaluate the ability of clinical factors to distinguish the risks of sudden and nonsudden cardiac death. Methods We identified all deaths during a 3.3-year follow-up of 30,680 patients discharged alive after admission to the cardiac care unit of a Seattle hospital. Detailed chart reviews were conducted on 1093 subsequent out-of-hospital sudden deaths, 973 nonsudden cardiac deaths, and 442 randomly selected control patients. Results Patients who died in follow-up (suddenly or nonsuddenly) were significantly different for many clinical factors from control patients. In contrast, patients with sudden cardiac death were insignificantly different for most clinical characteristics from patients with nonsudden cardiac death. The mode of death was 20% to 30% less likely to be sudden in women, patients who had angioplasty or bypass surgery, and patients prescribed beta-blockers. The mode of death was 20% to 30% more likely to be sudden in patients with heart failure, frequent ventricular ectopy, or a discharge diagnosis of acute myocardial infarction. A multivariable model had only modest predictive capacity for mode of death (c-index of 0.62). Conclusion Standard clinical evaluation is much better at predicting overall risk of death than at predicting the mode of death as sudden or nonsudden. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. Univ Washington, VA Puget Sound Healthcare Syst, NW Hlth Serv Res & Dev Ctr Excellence, Dept Biostat, Seattle, WA 98195 USA. Henry Ford Healthcare, Div Cardiol, Detroit, MI USA. RP Hlatky, MA (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, HRP Redwood Bldg,Room 150, Stanford, CA 94305 USA. FU AHRQ HHS [HS08362] NR 23 TC 23 Z9 28 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2002 VL 144 IS 3 BP 390 EP 396 DI 10.1067/mhj.2002.125495 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 595BK UT WOS:000178086800005 PM 12228774 ER PT J AU Wilbur, DC Parker, EM Foti, JA AF Wilbur, DC Parker, EM Foti, JA TI Location-guided screening of liquid-based cervical cytology specimens - A potential improvement in accuracy and productivity is demonstrated in a preclinical feasibility trial SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United States and Canadian Academy of Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE cervical cytology; Papanicolaou smear; automation; computerization; AutoPap ID AUTOPAP SYSTEM; SMEARS; SENSITIVITY AB A 2-armed, masked study was performed on 1,275 AutoCyte PREP (TriPath, Burlington, NC) slides. Manual screening (current practice [CP]) was compared with automated screening with location-guided screening (LGS) using the AutoPap system with the SlideWizard 2 automated review microscopy station (TriPath). Cytologic adjudication determined "truth" for each slide. LGS identified more abnormal cases at all interpretive levels and classified abnormalities more specifically. For high-grade squamous intraepithelial lesions and above, the overall sensitivity of appropriate triage to pathologist review was 98.4% for LGS and 91.1% for CP The appropriate triage for all abnormal cases was 92.1% for LGS and 87.9% for CP The potential exists for more accurate and productive cytologic interpretation using this system, which requires no manual screening of a portion of slides and only limited review of another portion of "predotted" slides. C1 ViaHlth, Cytopathol Unit, New Rochelle, NY USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Cytopathol Unit, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD SEP PY 2002 VL 118 IS 3 BP 399 EP 407 PG 9 WC Pathology SC Pathology GA 588CP UT WOS:000177683400010 PM 12219782 ER PT J AU Oei, TT Dulai, GS Gralnek, IM Chang, D Kilbourne, AM Sale, GA AF Oei, TT Dulai, GS Gralnek, IM Chang, D Kilbourne, AM Sale, GA TI Hospital care for low-risk patients with acute, nonvariceal upper GI hemorrhage: A comparison of neighboring community and tertiary care centers SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-College-of-Gastroenterology CY OCT 16-18, 2000 CL NEW YORK, NEW YORK SP Amer Coll Gastroenterol ID UPPER GASTROINTESTINAL HEMORRHAGE; PEPTIC-ULCER HEMORRHAGE; OUTPATIENT MANAGEMENT; TRACT HEMORRHAGE; EARLY DISCHARGE; SCORING SYSTEM; MORTALITY; ENDOSCOPY; COST; ANTAGONISTS AB Objectives: The proportion of patients admitted to the hospital with acute upper GI hemorrhage (UGIH) who are at low risk for adverse outcomes may be substantial. The process of care for this low risk population likely varies across practice settings but has not been extensively studied. Use of the Rockall Risk score, a simple validated scoring index that predicts outcomes in UGIH, may help to identify these low risk patients. Methods: We evaluated and compared the incidence of low risk UGIH admissions, adverse outcomes, and level of healthcare resource use in a community hospital (SMH) and a neighboring tertiary care university hospital (CHS). Cases of UGIH were identified from administrative databases during 1997 and 1998. Medical record data were abstracted in a standardized manner. Cases were defined as low risk on the basis of Rockall risk scores of less than or equal to2. Results: The low risk study groups consisted of 49 of 187 (26%) SMH cases and 53/175 (30%) CHS cases (p=0.40). Rebleeding was uncommon (6% at SMH; 4% at CHS) (p=0.64). No deaths occurred; 71% at SMH versus 49% at CHS were admitted to a monitored bed (p=0.04); and 92% at SMH versus 57% at CHS were prescribed i.v. H2 blockers for the acute bleeding event (p<0.001). Low risk patients had a mean hospital length of stay of 3.3+2.4 days at SMH versus 2.6+2.1 days at CHS (p=0.15). Conclusions: In this study, the proportion of acute, low risk, nonvariceal, upper GI hemorrhage admissions to neighboring community and tertiary care medical centers was high, whereas adverse clinical outcomes in this group of patients was low. Use of healthcare resources seemed to be greater in the community hospital. This observed variation in the process of care for populations with similar disease severity and outcomes suggests an opportunity for evidence-based interventions aimed at improving the efficiency of care. C1 VA Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ctr Hlth Serv Res, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Harbor UCLA Med Ctr, Los Angeles, CA USA. RP Gralnek, IM (reprint author), VA Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res Ctr, Ctr Study Digest Healthcare Qual & Outcomes, Bldg 115,Room 215B,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 45 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 BP 2271 EP 2278 AR PII S0002-9270(02)04338-1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PJ UT WOS:000178229700020 PM 12358244 ER PT J AU Bounds, BC Pitman, MB Brugge, WR AF Bounds, BC Pitman, MB Brugge, WR TI Endoscopic ultrasound guided fine needle aspiration (EUSFNA): Interpretation of cytology results SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 221 BP S73 EP S73 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400222 ER PT J AU Bounds, BC Kelsey, PB AF Bounds, BC Kelsey, PB TI Duodenoscope assisted cholangiopancreatoscopy without fluoroscopy: An alternative to ERCP in selected patients SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 222 BP S73 EP S74 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400223 ER PT J AU El-Serag, HB Garewel, H Sampliner, RE AF El-Serag, HB Garewel, H Sampliner, RE TI Where did the long Barrett's esophagus go? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 So Arizona VA Healthcare Syst, Tucson, AZ USA. Univ Arizona, Tucson, AZ 85724 USA. Houston VA Med Ctr, Gastroenterol & Hlth Serv Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 18 BP S6 EP S6 DI 10.1016/S0002-9270(02)04451-9 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400019 ER PT J AU Gralnek, IM Dulai, GS Coulter, ID Maida, CA AF Gralnek, IM Dulai, GS Coulter, ID Maida, CA TI What constitutes exemplary care for "low-risk" patients with acute, non-variceal upper gastrointestinal hemorrhage (NVUGIH)? A stakeholder analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RAND Corp, Hlth Sci Program, Los Angeles, CA USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 705 BP S231 EP S231 DI 10.1016/S0002-9270(02)05187-0 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400706 ER PT J AU Lichtenstein, GR Feagan, BG Yan, SK Bala, M Hartman, P Sands, B AF Lichtenstein, GR Feagan, BG Yan, SK Bala, M Hartman, P Sands, B TI Maintenance treatment with infliximab reduces hospitalizations and surgeries/procedures in patients with fistulizing Crohn's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Hosp Univ Penn, Philadelphia, PA 19104 USA. Univ Western Ontario, London, ON, Canada. Centocor Inc, Malvern, PA 19355 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Feagan, Brian/M-4283-2015 NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 805 BP S264 EP S265 DI 10.1016/S0002-9270(02)05288-7 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400805 ER PT J AU Littner, MR Leung, FW Ballard, ED Huang, BD Samra, NK AF Littner, MR Leung, FW Ballard, ED Huang, BD Samra, NK TI Lansoprazole for 24 weeks reduces asthma exacerbations and improves quality of life in subjects with symptoms of acid reflux - A multicenter, randomized, double-blind, placebo controlled trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. TAP Pharmaceut Inc, Lake Forest, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 39 BP S13 EP S13 DI 10.1016/S0002-9270(02)04472-6 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400040 ER PT J AU Malaty, HM Wilsey, MJ Abudayyeh, S Graham, DY Wristers, K Rabeneck, LR AF Malaty, HM Wilsey, MJ Abudayyeh, S Graham, DY Wristers, K Rabeneck, LR TI Soda (severity of dyspepsia assessment) in children: A new outcome measure in relation to Helicobacter pylori infection in children with recurrent abdominal SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Digest Dis Sect, Houston, TX 77030 USA. Texas Childrens Hosp, Digest Dis Sect, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 695 BP S227 EP S228 DI 10.1016/S0002-9270(02)05177-8 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400696 ER PT J AU Mamula, P Cohen, SA Ferry, GD Kirschner, BS Winter, HS Patel, J Baldassano, RN AF Mamula, P Cohen, SA Ferry, GD Kirschner, BS Winter, HS Patel, J Baldassano, RN TI CDP571, a novel humanized anti-TNF alpha antibody, in pediatric patients with Crohn's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Celltech Res & Dev, Slough, Berks, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Childrens Hosp, Chicago, IL 60637 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Childrens Ctr Digest Healthcare, Atlanta, GA USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 842 BP S276 EP S277 DI 10.1016/S0002-9270(02)05325-X PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400842 ER PT J AU Nieto, JM Ashook, M Farrell, JJ AF Nieto, JM Ashook, M Farrell, JJ TI Intraductal papillary mucinous tumor: A new extraintestinal manifestation of Peutz-Jegher syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 551 BP S181 EP S181 DI 10.1016/S0002-9270(02)05033-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400552 ER PT J AU Nieto, JM DeRosa, VP DeGuzman, LJ AF Nieto, JM DeRosa, VP DeGuzman, LJ TI Vulvular Crohns antedating gastrointestinal involvment: Case report and review of the literature SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Arrowhead Reg Med Ctr, Colton, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 542 BP S178 EP S179 DI 10.1016/S0002-9270(02)05024-4 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400543 ER PT J AU Qureshi, WA Heiser, M Abudayyeh, S Anand, BS AF Qureshi, WA Heiser, M Abudayyeh, S Anand, BS TI Selecting the right patient for PEG/PEJ placement: Do clinical and laboratory parameters help? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 712 BP S233 EP S233 DI 10.1016/S0002-9270(02)05194-8 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400713 ER PT J AU Sands, B Van Deventer, S Blank, M Marsters, P Travers, SA AF Sands, B Van Deventer, S Blank, M Marsters, P Travers, SA CA Accent II Trial TI Maintenance infliximab is safe and effective in fistulizing Crohn's disease(CD); Results from the ACCENT II trial SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Afdeling Gastroenterol Acad Med Ctr, Amsterdam, Netherlands. Centocor Inc, Malvern, PA 19355 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 787 BP S258 EP S258 DI 10.1016/S0002-9270(02)05270-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400787 ER PT J AU Stoffel, E Spigel, D Grace, N AF Stoffel, E Spigel, D Grace, N TI Waldenstrom's macroglobulinemia presenting as new-onset ascites SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Faulkner Hosp, Div Gastroenterol, Boston, MA USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 524 BP S172 EP S173 DI 10.1016/S0002-9270(02)05006-2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400525 ER PT J AU Syngal, S Chung, D Willett, C Schoetz, D Schroy, P Stoffel, E Jagadeesh, D Morel, K Ross, M AF Syngal, S Chung, D Willett, C Schoetz, D Schroy, P Stoffel, E Jagadeesh, D Morel, K Ross, M TI Stool DNA analysis for the detection and follow-up of colorectal cancer (CRC) and advanced adenomas (AA): Sensitivity in a prospective series SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Boston Med Ctr, Boston, MA USA. Exact Sci Corp, Maynard, MA USA. NR 0 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 332 BP S109 EP S109 DI 10.1016/S0002-9270(02)04804-9 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400333 ER PT J AU Yamaguchi, DJ Tachiki, K Germano, P Oh, D Pisegna, JR AF Yamaguchi, DJ Tachiki, K Germano, P Oh, D Pisegna, JR TI Description of a technique to isolate and purify ECL cells by FACS analysis: Investigations of the expression and proliferative effects of the PAC1 receptor expressed on isolated ECL cells SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, CURE, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 2002 VL 97 IS 9 SU S MA 163 BP S54 EP S54 DI 10.1016/S0002-9270(02)04635-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 597PR UT WOS:000178230400164 ER PT J AU Natarajan, S Clyburn, EB Brown, RT AF Natarajan, S Clyburn, EB Brown, RT TI Association of exercise stages of change with glycemic control in individuals with type 2 diabetes SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article ID PHYSICAL-ACTIVITY; BEHAVIOR-CHANGE; POPULATION; PATTERNS; DISEASE; SMOKING C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Hlth Profess, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. RP Natarajan, S (reprint author), 135 Cannon St,Suite 403,PO 250837, Charleston, SC 29425 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER J HEALTH PROMOTION INC PI KEEGO HARBOR PA 1660 CASS LAKE RD, STE 104, KEEGO HARBOR, MI 48320 USA SN 0890-1171 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 2002 VL 17 IS 1 BP 72 EP 75 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 593ZD UT WOS:000178023600004 PM 12271755 ER PT J AU Meigs, JB AF Meigs, JB TI Epidemiology of the metabolic syndrome, 2002 SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID CORONARY HEART-DISEASE; INSULIN-RESISTANCE SYNDROME; MIDDLE-AGED MEN; CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; SYNDROME PREDICTS; HELSINKI POLICEMEN; GENERAL-POPULATION; PROVISIONAL REPORT AB Background: The close association of type 2 diabetes and atherosclerotic cardiovascular disease (CVD) suggests that they share a common physiologic antecedent, postulated to be tissue resistance to insulin. Insulin resistance is associated with a cluster of risk factors recognized as the metabolic syndrome. Objective: To describe the epidemiology of the insulin resistance syndrome, also known as the metabolic syndrome. Methods: Overall obesity, central obesity, dyslipidemia characterized by elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol, hyperglycemia, and hypertension are common traits that, when they occur together, constitute the metabolic syndrome. The World Health Organization and the National Cholesterol Education Program Adult Treatment Panel III have proposed working definitions for the syndrome based on these traits. Cross-sectional and longitudinal epidemiologic studies provide an emerging picture of the prevalence and outcomes of the syndrome. Results: National survey data suggest the metabolic syndrome is very common, affecting about 24% of US adults who are 20 to 70 years of age and older. The syndrome is more common in older people and in Mexican Americans. People with the syndrome are about twice as likely to develop CVD and over 4 times as likely to develop type 2 diabetes compared with subjects who do not have metabolic syndrome. While this syndrome may have a genetic basis, environmental factors are important modifiable risk factors for the condition. Conclusions: The metabolic syndrome is very common and will become even more common as populations age and become more obese. Treatment for component traits is known to reduce the risk for type 2 diabetes and CVD; whether risk is reduced by treatment of the syndrome, specifically, remains uncertain. Primary care physicians must recognize that the co-occurrence of risk factors for type 2 diabetes and CVD represents an extremely adverse metabolic state warranting aggressive risk factor intervention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA. RP Meigs, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02115 USA. NR 64 TC 91 Z9 102 U1 0 U2 3 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD SEP PY 2002 VL 8 IS 11 SU S BP S283 EP S292 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 597HA UT WOS:000178215100001 PM 12240700 ER PT J AU Ioannou, GN Rockey, DC Bryson, CL Weiss, NS AF Ioannou, GN Rockey, DC Bryson, CL Weiss, NS TI Iron deficiency and gastrointestinal malignancy: a population-based cohort study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PREMENOPAUSAL WOMEN; ANEMIA; TRACT; CANCER AB PURPOSE: We investigated whether iron deficiency, with or without anemia, is associated with an increased likelihood of gastrointestinal malignancy. SUBJECTS AND METHODS: Data were obtained from the first National Health and Nutrition Examination Survey and Epidemiologic Followup Study, a nationally representative, prospective cohort study that measured hemoglobin levels and iron saturation and recorded follow-up diagnoses. We included persons 25 to 74 years of age with no previous gastrointestinal malignancy. Anemia was defined as a hemoglobin value below the fifth percentile for each age group and sex. Iron deficiency was defined as an iron saturation below 15%. RESULTS: Eighteen (0.2%) gastrointestinal malignancies were identified among the 9024 participants during the first 2 years of follow-up. None of the 442 premenopausal women with iron deficiency (92 with anemia and 350 without anemia) were diagnosed with gastrointestinal malignancy. Among men and postmenopausal women, the proportion diagnosed with gastrointestinal malignancy was 31 times greater (95% confidence interval [CI]: 9 to 107) in those with iron deficiency anemia (3/51 [6%]) and five times greater (95% Cl: 1 to 21) in those with iron deficiency without anemia (2/223 [1%]), compared with those with normal hemoglobin levels and iron saturation (11/5733 [0.2%]). CONCLUSION: Gastrointestinal malignancy is uncommon in iron-deficient premenopausal women with or without anemia, Among men and postmenopausal Women, gastrointestinal malignancy is significantly more common in those with iron deficiency than in persons with normal serum iron saturation and hemoglobin levels. C1 Univ Washington, Ctr Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Ctr Med, Div Gastroenterol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Duke Univ, Ctr Med, Div Gastroenterol, Dept Med, Durham, NC USA. Duke Univ, Ctr Med, Duke Liver Ctr, Durham, NC USA. RP Ioannou, GN (reprint author), Vet Adm Med Ctr, Hlth Serv Res & Dev, 1660 S Columbian Way,MS 152,Bldg 1,Room 422, Seattle, WA 98108 USA. NR 21 TC 52 Z9 57 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2002 VL 113 IS 4 BP 276 EP 280 DI 10.1016/S0002-9343(02)01214-7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 599DU UT WOS:000178319500002 PM 12361812 ER PT J AU Metchick, LN Petit, WA Inzucchi, SE AF Metchick, LN Petit, WA Inzucchi, SE TI Inpatient management of diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; INSULIN-GLUCOSE INFUSION; WOUND-INFECTION; SLIDING-SCALE; RISK; MECHANISMS; MORTALITY; COHORT; DIGAMI; STATE AB There is now widespread appreciation of the importance of maintaining glucose levels as close to the normal range as possible among outpatients with diabetes. However, the importance of tight glucose control in inpatients is less well established. During the past several years, it has become apparent that hyperglycemia in hospitalized patients, especially those in the postoperative setting, is associated with poorer outcomes. In addition, two randomized trials have shown improved outcomes with intensive glucose management in acutely ill patients. Based on these studies and our own experience, we propose guidelines and a framework for improving the glycemic control of hospitalized patients. C1 Yale Univ, Sch Med, Endocrinol Sect, Dept Med, New Haven, CT 06520 USA. Univ Connecticut, Sch Med, Dept Med, Farmington, CT USA. Joslin Diabet Ctr, New Britain, CT USA. RP Inzucchi, SE (reprint author), Yale Univ, Sch Med, Endocrinol Sect, Dept Med, TMP 534 Endocrinol,333 Cedar St, New Haven, CT 06520 USA. NR 39 TC 33 Z9 36 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2002 VL 113 IS 4 BP 317 EP 323 DI 10.1016/S0002-9343(02)01213-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 599DU UT WOS:000178319500008 PM 12361818 ER PT J AU Nathan, DM AF Nathan, DM TI Small steps, large problems: Advances in the management of diabetes mellitus SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID BEDTIME NPH INSULIN; FASTING GLUCOSE; HYPOGLYCEMIA; THERAPY C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 2002 VL 113 IS 4 BP 339 EP 340 AR PII S0002-9343(02)01219-6 DI 10.1016/S0002-9343(02)01219-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 599DU UT WOS:000178319500013 PM 12361823 ER PT J AU Meisenhelder, JB AF Meisenhelder, JB TI Anniversary responses to terrorism SO AMERICAN JOURNAL OF NURSING LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; LIFE EVENTS; PTSD; SURVIVORS C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Meisenhelder, JB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD SEP PY 2002 VL 102 IS 9 BP 24AA EP + PG 3 WC Nursing SC Nursing GA 594UF UT WOS:000178068800021 ER PT J AU Stehman-Breen, CO Levine, RJ Qian, C Morris, CD Catalano, PM Curet, LB Sibai, BM AF Stehman-Breen, CO Levine, RJ Qian, C Morris, CD Catalano, PM Curet, LB Sibai, BM TI Increased risk of preeclampsia among nulliparous pregnant women with idiopathic hematuria SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preeclampsia; gestational hypertension; pregnancy; hematuria ID RENAL-DISEASE; HYPERTENSION; CALCIUM; TRIAL AB OBJECTIVE: Our purpose was to determine the risk of preeclampsia and gestational hypertension among nulliparous pregnant women with idiopathic hematuria. STUDY DESIGN: We conducted a prospective cohort study using data from the trial of Calcium for Preeclampsia Prevention (CPEP). Participants were followed up from screening and enrollment (gestational weeks 11-21) throughout pregnancy. Our analysis was limited to women who had been followed up to at least 20 weeks' gestation, had outcome information available, and were not suspected to have had urolithiasis. Surveillance for hematuria was conducted with dipsticks on clean-catch urine specimens obtained at research clinic visits. Idiopathic hematuria was defined as hematuria identified at regularly scheduled clinic visits in the absence of urinary tract infection and before the onset of labor. Logistic regression was used to estimate the risk of preeclampsia among women with hematuria compared with women without hematuria. RESULTS: Among the 4307 women available for analysis, 132 (3%) had idiopathic hematuria during pregnancy. Idiopathic hematuria was associated with an almost 2-fold increased odds for development of preeclampsia (adjusted odds ratio [aOR] = 1.89, 95% Cl 1.12-3.18) but not with increased odds of gestational hypertension (aOR = 0.78, 95% Cl 0.46-1.32). CONCLUSIONS: Idiopathic hematuria identified during pregnancy is associated with greater risk of preeclampsia but not gestational hypertension. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Oregon Hlth Sci Univ, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. RP Stehman-Breen, CO (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Nephrol, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. FU NICHD NIH HHS [N01-HD-1-3122, N01-HD-1-3125, N01-HD-1-3121, N01-HD-2-3154, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3126, N01-HD-5-3246] NR 23 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 2002 VL 187 IS 3 BP 703 EP 708 DI 10.1067/mob.2002.125768 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 598BZ UT WOS:000178256400031 PM 12237651 ER PT J AU Zhu, WH MacIntyre, A Nicosia, RF AF Zhu, WH MacIntyre, A Nicosia, RF TI Regulation of angiogenesis by vascular endothelial growth factor and angiopoietin-1 in the rat aorta model - Distinct temporal patterns of intracellular signaling correlate with induction of angiogenic sprouting SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; RECEPTOR TYROSINE KINASE; CELL-SURVIVAL; TRANSDUCTION PATHWAY; TIE2 RECEPTOR; ACTIN REORGANIZATION; BLOOD-VESSEL; AKT; MIGRATION; GENE AB Vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) promote the spontaneous angiogenic response of freshly cut rat aortic rings. When VEGF and Ang-1 were tested in cultures of 14-day-old rings, which are quiescent and unable to spontaneously produce neovessels, only VEGF was capable of inducing an angiogenic response. Ang-1 failed to initiate angiogenesis in this system, but significantly potentiated VEGF-induced neovessel sprouting. Potential differences in cell signaling triggered by VEGF and Ang-1 were evaluated in cultures of quiescent rings. VEGF induced biphasic and prolonged (15 minutes and 4 to 24 hours) phosphorylation of p44/42 MAPK and Akt, while the effect of Ang-1 was transient and monophasic (15 minutes). Both VEGF and Ang-1 induced rapid, monophasic (15 minutes) phosphorylation of p38 MAPK. When VEGF and Ang-1 were administered together, the second peak of VEGF-induced p44/42 MAPK phosphorylation was markedly reduced. The effect of the VEGF/Ang-1 combination on AKT phosphorylation was, instead, additive over time, and sustained over a 24-hour period. The VEGF/ Ang-1 combination caused an additive effect also on p38 MAPK phosphorylation at 1 hour. Confocal microscopy of VEGF-, Ang-1, or VEGF/Ang-1-stimulated aortic rings double stained at time points of maximal phosphorylation for cell markers and signal transduction proteins demonstrated phosphorylated p44/42 MAPK, p38 MAPK, and Akt predominantly in endothelial cells. Experiments with specific inhibitors demonstrated that p44/42 MAPK and Akt, but not p38 MAPK, are necessary for neovessel sprouting. These results identify p44/42 MAPK and Akt as critical intracellular mediators of angiogenesis, whose transient phosphorylation is, however, not sufficient for the initiation of this process. The observation that sustained phosphorylation of these signaling pathways, particularly of Akt, correlates with induction of angiogenesis suggests that the duration of phosphorylation signals influences critical cellular events required for the induction of angiogenic sprouting. C1 VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, S113 Lab, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Philadelphia Coll Osteopath Med, Dept Pathol Microbiol & Immunol, Philadelphia, PA USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, S113 Lab, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL52585, R01 HL052585] NR 42 TC 72 Z9 74 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 2002 VL 161 IS 3 BP 823 EP 830 DI 10.1016/S0002-9440(10)64242-3 PG 8 WC Pathology SC Pathology GA 591BJ UT WOS:000177859600011 PM 12213710 ER PT J AU Bradley, RL Mansfield, JPR Maratos-Flier, E Cheatham, B AF Bradley, RL Mansfield, JPR Maratos-Flier, E Cheatham, B TI Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE melanin-concentrating hormone receptor; adipose tissue; leptin promoter ID PROTEIN-COUPLED RECEPTOR; MCH RECEPTOR; RAT-BRAIN; S6 KINASE; INSULIN-RESISTANCE; ADIPOSE-TISSUE; MESSENGER-RNA; LEPTIN ACTION; BODY-WEIGHT; IDENTIFICATION AB Energy homeostasis is regulated by peripheral signals, such as leptin, and by several orexigenic and anorectic neuropeptides. Recently, we reported that the orexigenic neuropeptide melanin-concentrating hormone (MCH) stimulates leptin production by rat adipocytes and that the MCH receptor (MCH-R1) is present on these cells. Here, we show that MCH-R1 is present on murine 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with 1 muM MCH for up to 2 h acutely downregulated MCH-R1, indicating a mechanism of ligand-induced receptor downregulation. Potential signaling pathways mediating MCH-R1 action in adipocytes were investigated. Treatment of 3T3-L1 adipocytes with 1 muM MCH rapidly induced a threefold and a fivefold increase in p44/42 MAPK and pp70 S6 kinase activities, respectively. In addition, 3T3-L1 adipocytes transiently transfected with a murine leptin-luciferase promoter construct showed a fourfold and a sixfold increase in leptin promoter-reporter gene expression at 1 h and 4 h, respectively, in response to MCH. Activity decreased to basal levels at 8 h. Furthermore, MCH-stimulated leptin promoter-driven luciferase activity was diminished in the presence of the MAP/ERK kinase inhibitor PD-98059 and in the presence of rapamycin, an inhibitor of pp70 S6 kinase activation. These results provide further evidence for a functional MCH signaling pathway in adipocytes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Maratos-Flier, E (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK-51668, R01-DK53978, DK-09745] NR 52 TC 47 Z9 48 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2002 VL 283 IS 3 BP E584 EP E592 DI 10.1152/ajpendo.00161.2001 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 582LT UT WOS:000177353000022 PM 12169453 ER PT J AU White, MF AF White, MF TI IRS proteins and the common path to diabetes SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE insulin receptor substrate ID INSULIN-RECEPTOR SUBSTRATE-1; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-I; PLECKSTRIN HOMOLOGY DOMAINS; MICE LACKING; POSTNATAL-GROWTH; BETA-CELLS; TARGETED DISRUPTION; INTERACTING PROTEIN; GENE-EXPRESSION AB Although a full understanding of insulin/insulin-like growth factor (IGF) action is evolving, the discovery of insulin receptor substrate (IRS) proteins and their role to link cell surface receptors to the intracellular signaling cascades provided an important step forward. Moreover, Insulin/IGF receptors use common signaling pathways to accomplish many tasks, the IRS proteins add a unique layer of specificity and control. Importantly, the IRS-2 branch of the insulin/IGF-signaling pathway is a common element in peripheral insulin response and pancreatic beta-cell growth and function. Failure of IRS-2 signaling might explain the eventual loss of compensatory hyperinsulinemia during prolonged periods of peripheral insulin resistance. Moreover, short-term inhibition of IRS protein functions by serine phosphorylation, or sustained inhibition by ubiquitin-targeted proteosome-mediated degradation suggests a common molecular mechanism for insulin resistance during acute injury or infection, or the sensitivity of beta-cells to autoimmune destruction. The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 95 TC 375 Z9 393 U1 3 U2 26 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 SEP PY 2002 VL 283 IS 3 BP E413 EP E422 DI 10.1152/ajpendo.00514.2001 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 582LT UT WOS:000177353000002 PM 12169433 ER PT J AU Yuan, PQ Yang, H AF Yuan, PQ Yang, H TI Neuronal activation of brain vagal-regulatory pathways and upper gut enteric plexuses by insulin hypoglycemia SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE dorsal motor nucleus of the vagus; nucleus tractus solitarii; glucose; vagus; stomach ID NITRIC-OXIDE SYNTHASE; NUCLEUS-TRACTUS-SOLITARII; GASTRIC MYENTERIC NEURONS; DORSAL MOTOR NUCLEUS; PORTAL-VEIN AREA; FOS EXPRESSION; NERVOUS-SYSTEM; VAGUS NERVE; GUINEA-PIG; HYPOTHALAMIC NEURONS AB Neuronal activation of brain vagal-regulatory nuclei and gastric/duodenal enteric plexuses in response to insulin (2 U/kg, 2 h) hypoglycemia was studied in rats. Insulin hypoglycemia significantly induced Fos expression in the paraventricular nucleus of the hypothalamus, locus coeruleus, dorsal motor nucleus of the vagus (DMN), and nucleus tractus solitarii (NTS), as well as in the gastric/duodenal myenteric/ submucosal plexuses. A substantial number of insulin hypoglycemia-activated DMN and NTS neurons were choline acetyltransferase and tyrosine hydroxylase positive, respectively, whereas the activated enteric neurons included NADPH- and vasoactive intestinal peptide neurons. The numbers of Fos-positive cells in each above-named brain nucleus or in the gastric/duodenal myenteric plexus of insulin-treated rats were negatively correlated with serum glucose levels and significantly increased when glucose levels were lower than 80 mg/dl. Acute bilateral cervical vagotomy did not influence insulin hypoglycemia-induced Fos induction in the brain vagal-regulatory nuclei but completely and partially prevented this response in the gastric and duodenal enteric plexuses, respectively. These results revealed that brain-gut neurons regulating vagal outflow to the stomach/duodenum are sensitively responsive to insulin hypoglycemia. C1 VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Yang, H (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, 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-50255, DK-41301] NR 77 TC 27 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 2002 VL 283 IS 3 BP E436 EP E448 DI 10.1152/ajpendo.00538.2001 PG 13 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 582LT UT WOS:000177353000005 PM 12169436 ER PT J AU Simon, FR Fortune, J Iwahashi, M Sutherland, E AF Simon, FR Fortune, J Iwahashi, M Sutherland, E TI Sexual dimorphic expression of ADH in rat liver: importance of the hypothalamic-pituitary-liver axis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE growth hormone; thyroxine; hypophysectomy; estrogen; testosterone ID GROWTH-HORMONE SECRETION; ALCOHOL-DEHYDROGENASE ACTIVITY; GENE-EXPRESSION; HYPOPHYSECTOMIZED RATS; HEPATOCYTE CULTURE; TESTOSTERONE; METABOLISM; ESTRADIOL; TURNOVER; ENZYMES AB Hepatic alcohol dehydrogenase (ADH) activity is higher in female than in male rats. Although sex steroids, thyroid, and growth hormone (GH) have been shown to regulate hepatic ADH, the mechanism(s) for sexual dimorphic expression is unclear. We tested the possibility that the GH secretory pattern determined differential expression of ADH. Gonadectomized and hypophysectomized male and female rats were examined. Hepatic ADH activity was 2.1-fold greater in females. Because protein and mRNA content were also 1.7- and 2.4-fold greater, results indicated that activity differences were due to pretranslational mechanisms. Estradiol increased ADH selectively in males, and testosterone selectively decreased activity and mRNA levels in females. Effect of sex steroids on ADH was lost after hypophysectomy; infusion of GH in males increased ADH to basal female levels, supporting a role of the pituitary-liver axis. However, GH and L-thyroxine (T-4) replacements alone in hypophysectomized rats did not restore dimorphic differences for either ADH activity or mRNA levels. On the other hand, T-4 in combination with intermittent administration of GH reduced ADH activity and mRNA to basal male values, whereas T-4 plus GH infusion replicated female levels. These results indicate that the intermittent male pattern of GH secretion combined with T-4 is the principal determinant of low ADH activity in male liver. C1 Univ Colorado, Hlth Sci Ctr, Dept Cellular & Struct Biol, Denver Vet Affairs Hosp, Denver, CO 80262 USA. RP Simon, FR (reprint author), Univ Colorado, Sch Med, Dept Med B145, Hepatobiliary Res Ctr, 4200 E 9th Ave, Denver, CO 80262 USA. FU NIDDK NIH HHS [R01-DK-15851] NR 63 TC 18 Z9 19 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 SEP PY 2002 VL 283 IS 3 BP G646 EP G655 DI 10.1152/ajpgi.00438.2001 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 585AY UT WOS:000177502000019 PM 12181179 ER PT J AU Kaprielian, R Sah, R Nguyen, T Wickenden, AD Backx, PH AF Kaprielian, R Sah, R Nguyen, T Wickenden, AD Backx, PH TI Myocardial infarction in rat eliminates regional heterogeneity of AP profiles, I-to K+ currents, and [Ca2+](i) transients SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE right ventricle; septum; heart disease; contraction ID HYPERTROPHIED VENTRICULAR MYOCYTES; SPONTANEOUSLY HYPERTENSIVE RAT; OUTWARD CURRENT; HEART-FAILURE; GENE-EXPRESSION; CURRENT-DENSITY; DOWN-REGULATION; EPICARDIAL DIFFERENCES; POTASSIUM CURRENTS; CARDIAC MYOCYTES AB Transient outward K+ current density (I-to) has been shown to vary between different regions of the normal myocardium and to be reduced in heart disease. In this study, we measured regional changes in action potential duration (APD), I-to, and intracellular Ca2+ concentration ([Ca2+](i)) transients of ventricular myocytes derived from the right ventricular free wall (RVW) and interventricular septum (SEP) 8 wk after myocardial infarction (MI). At + mV, I-to density in sham-operated hearts was significantly higher (P<0.01) in the RVW (15.0&PLUSMN;0.8 pA/pF, n=47) compared with the SEP (7.0&PLUSMN;1.1 pA/pF, n=18). After MI, I-to density was not reduced in SEP myocytes but was reduced (P<0.01) in RVW myocytes (8.7+/-1.0 pA/pF, n=26) to levels indistinguishable from post-MI SEP myocytes. These changes in I-to density correlated with Kv4.2 (but not Kv4.3) protein expression. By contrast, Kv1.4 expression was significantly higher in the RVW compared with the SEP and increased significantly after MI in RVW. APD measured at 50% or 90% repolarization was prolonged, whereas peak [Ca2+](i) transients amplitude was higher in the SEP compared with the RVW in sham myocytes. These regional differences in APD and [Ca2+](i) transients were eliminated by MI. Our results demonstrate that the significant regional differences in I-to density, APD, and [Ca2+](i) between RVW and SEP are linked to a variation in Kv4.2 expression, which largely disappears after MI. C1 Univ Toronto, Heart & Stroke Richard Lewar Ctr, Toronto, ON M5G 2C4, Canada. Univ Toronto, Dept Physiol, Toronto, ON M5G 2C4, Canada. Univ Toronto, Dept Med, Toronto, ON M5G 2C4, Canada. Univ Hlth Network, Div Cardiol, Toronto, ON M5G 2C4, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Backx, PH (reprint author), Univ Toronto, Heart & Stroke Richard Lewar Ctr, Rm 68,Fitzgerald Bldg,150 Coll St, Toronto, ON M5G 2C4, Canada. NR 61 TC 42 Z9 45 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2002 VL 283 IS 3 BP H1157 EP H1168 DI 10.1152/ajpheart.00518.2001 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 585BA UT WOS:000177502200038 PM 12181147 ER PT J AU Frossard, JL Saluja, AK Mach, N Lee, HS Bhagat, L Hadenque, A Rubbia-Brandt, L Dranoff, G Steer, ML AF Frossard, JL Saluja, AK Mach, N Lee, HS Bhagat, L Hadenque, A Rubbia-Brandt, L Dranoff, G Steer, ML TI In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE granulocyte-macrophage colony-stimulating factor; caerulein; inflammation; adult respiratory distress syndrome; adhesion molecules; neutrophils ID COLONY-STIMULATING FACTOR; EXPRESSION; RATS; PATHOGENESIS; GENERATION; EOSINOPHIL; CYTOKINES; RECEPTOR; MODEL; CELLS AB Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GMCSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GMCSF knockout mice (GM-CSF -/-). Pancreatitis was induced by hourly (12x) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF -/- mice. Lung injury, quantitated by measuring lung myeloperoxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF -/- than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF -/- mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Hosp Geneva, Div Gastroenterol, CH-1211 Geneva, Switzerland. Univ Hosp Geneva, Div Oncol, CH-1211 Geneva 14, Switzerland. Univ Hosp Geneva, Div Clin Pathol, CH-1211 Geneva 14, Switzerland. RP Steer, ML (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. NR 36 TC 19 Z9 19 U1 0 U2 0 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 SEP PY 2002 VL 283 IS 3 BP L541 EP L548 DI 10.1152/ajplung.00413.2001 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 582LU UT WOS:000177353100007 PM 12169573 ER PT J AU Tian, W Cohen, DM AF Tian, W Cohen, DM TI Urea stress is more akin to EGF exposure than to hypertonic stress in renal medullary cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE expression array; tonicity enhancer binding protein; hypertonicity; cytoprotection; activating transcription factor 3; mIMCD3 cells; epidermal growth factor ID DUCT MIMCD3 CELLS; EPITHELIAL-CELLS; CYCLOOXYGENASE-2 EXPRESSION; RESPONSE ELEMENT; KIDNEY-CELLS; MDCK CELLS; C-FOS; ACTIVATION; PROTEIN; GENE AB Although urea is considered to be a cell stressor even in renal medullary cells perpetually exposed to this solute in vivo by virtue of the renal concentrating mechanism, aspects of urea signaling resemble that of a peptide mitogen. Urea was compared with epidermal growth factor and hypertonic NaCl or hypertonic mannitol using a large-scale expression array-based approach. The expression profile in response to urea stress more closely resembled that of EGF treatment than hypertonic stress, as determined by hierarchical cluster analysis; the effect of urea+NaCl was equidistant from that of either solute applied individually. Among the most highly urea- and hypertonicity-responsive transcripts were genes that had previously been shown to be responsive to these solutes, validating this approach. Increased expression of the activating transcription factor 3 by urea was newly detected via expression array and confirmed via immunoblot analysis. Earlier, we noted an abrogation of tonicity-dependent gene regulation by urea, primarily in a transient transfection-based model (Tian W and Cohen DM. Am J Physiol Renal Physiol 280: F904-F912, 2001). Here we applied K-means cluster analysis to demonstrate that the genes most profoundly up- or downregulated by hypertonic stress were partially restored toward basal levels in the presence of urea pretreatment. These global expression data are consistent with our earlier biochemical studies suggesting that urea affords cytoprotection in this context. In the aggregate, these data strongly support the hypothesis that the urea effect in renal medullary cells resembles that of a peptide mitogen in terms of the adaptive program of gene expression and in terms of cytoprotection from hypertonicity. C1 Oregon Hlth Sci Univ, Dept Med, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Cell & Dev Biol, 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, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM cohend@ohsu.edu FU NCI NIH HHS [5P30 CA69533-04]; NIDDK NIH HHS [DK-52494] NR 41 TC 15 Z9 15 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 SEP PY 2002 VL 283 IS 3 BP F388 EP F398 DI 10.1152/ajprenal.00031.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 581VV UT WOS:000177315600003 PM 12167588 ER PT J AU Silverman, DHS Small, GW AF Silverman, DHS Small, GW TI Prompt identification of Alzheimer's disease with brain PET imaging of a woman with multiple previous diagnoses of other neuropsychiatric conditions SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; DIFFERENTIAL-DIAGNOSIS; LEWY BODIES; FDG PET; DEMENTIA; PATTERNS; RISK C1 Univ Calif Los Angeles, Sch Med, Ahmanson Biol Imaging Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Silverman, DHS (reprint author), Univ Calif Los Angeles, Sch Med, Ahmanson Biol Imaging Ctr, Dept Mol & Med Pharmacol, CHS AR-144,MC694215, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG-13308, AG-10123]; NIMH NIH HHS [MH-52453] NR 28 TC 3 Z9 3 U1 1 U2 1 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 SEP PY 2002 VL 159 IS 9 BP 1482 EP 1488 DI 10.1176/appi.ajp.159.9.1482 PG 7 WC Psychiatry SC Psychiatry GA 591EQ UT WOS:000177867100004 PM 12202266 ER PT J AU Weiss, AP Dodson, CS Goff, DC Schacter, DL Heckers, S AF Weiss, AP Dodson, CS Goff, DC Schacter, DL Heckers, S TI Intact suppression of increased false recognition in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th Biennial Mt Sinai Conference on Cognition in Schizophrenia CY APR 27, 2001 CL WHISTLER, CANADA ID WORKING-MEMORY IMPAIRMENT; AGE-RELATED DEFICITS; CONSCIOUS RECOLLECTION; OLDER ADULTS; DISCRIMINATION ACCURACY; OPPOSITION PROCEDURE; MONITORING DEFICITS; COGNITION; YOUNGER; METAANALYSIS AB Objective: Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. Method: The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. Results: Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding, Conclusions: Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Univ Virginia, Dept Psychol, Charlottesville, VA 22903 USA. RP Weiss, AP (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang ACC812, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG-08441]; NIMH NIH HHS [MH-01763] NR 59 TC 32 Z9 32 U1 2 U2 3 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2002 VL 159 IS 9 BP 1506 EP 1513 DI 10.1176/appi.ajp.159.9.1506 PG 8 WC Psychiatry SC Psychiatry GA 591EQ UT WOS:000177867100008 PM 12202270 ER PT J AU Dickey, CC McCarley, RW Voglmaier, MM Frumin, M Niznikiewicz, MA Hirayasu, Y Fraone, S Seidman, LJ Shenton, ME AF Dickey, CC McCarley, RW Voglmaier, MM Frumin, M Niznikiewicz, MA Hirayasu, Y Fraone, S Seidman, LJ Shenton, ME TI Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUPERIOR TEMPORAL GYRUS; HUMAN AUDITORY-CORTEX; PLANUM TEMPORALE; SCHIZOPHRENIA SPECTRUM; VENTRICULAR VOLUME; COGNITIVE FUNCTION; GRAY-MATTER; HALLUCINATIONS; LOBE; MRI AB Objective: Individuals with schizophrenia spectrum disorders evince similar genetic, neurotransmitter, neuropsychological, electrophysiological, and structural abnormalities. Magnetic resonance imaging (MRI) studies have shown smaller gray matter volume in patients with schizotypal personality disorder than in matched comparison subjects in the left superior temporal gyrus, an area important for language processing. In a further exploration, the authors studied two components of the superior temporal gyrus: Heschl's gyrus and the planum temporale. Method: MRI scans were acquired from 21 male, neuroleptic-naive subjects recruited from the community who met DSM-IV criteria for schizotypal personality disorder and 22 male comparison subjects similar in age. Eighteen of the 21 subjects with schizotypal personality disorder had additional comorbid, nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on coronal images with subsequent identification of Heschl's gyrus and the planum temporale, Exploratory correlations between region of interest volumes and neuropsychological measures were also performed. Results: Left Heschl's gyrus gray matter volume was 21% smaller in the schizotypal personality disorder subjects than in the comparison subjects, a difference that was not associated with the presence of comorbid axis I disorders. There were no between-group volume differences in right Heschl's gyrus or in the right or left planum temporale, Exploratory analyses also showed a correlation between poor logical memory and smaller left Heschl's gyrus volume. Conclusions: Smaller left Heschl's gyrus gray matter volume in subjects with schizotypal personality disorder may help to explain the previously reported abnormality in the left superior temporal gyrus and may be a vulnerability marker for schizophrenia spectrum disorders. C1 VA Boston Healthcare Syst, Brigham & Womens Hosp, Surg Planning Lab, MRI Div,Dept Radiol, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Clin Neurosci Div, Lab Neurosci,Dept Psychiatr, Cambridge, MA 02138 USA. RP McCarley, RW (reprint author), VA Boston Healthcare Syst, Brigham & Womens Hosp, Surg Planning Lab, MRI Div,Dept Radiol, 940 Belmont St, Brockton, MA 02401 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH-01110, MH-40799, MH-50740, MH-52807, R01 MH040799, R01 MH050740, R01 MH050740-14, R01 MH052807] NR 54 TC 43 Z9 44 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2002 VL 159 IS 9 BP 1521 EP 1527 DI 10.1176/appi.ajp.159.9.1521 PG 7 WC Psychiatry SC Psychiatry GA 591EQ UT WOS:000177867100010 PM 12202272 ER PT J AU Biederman, J Faraone, SV Monuteaux, MC AF Biederman, J Faraone, SV Monuteaux, MC TI Differential effect of environmental adversity by gender: Rutter's index of adversity in a group of boys and girls with and without ADHD SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT HYPERACTIVITY; DISORDER; FAMILY AB Objective: This study examined the effect of gender in mediating the association between environmental adversity and the risk of attention deficit hyperactivity disorder (ADHD) and associated impairments. Method: The authors studied 280 ADHD and 242 healthy comparison probands of both genders who were between the ages of 6 and 17 years. They tested the association between Rutter's indicators of adversity (including family conflict, social class, family size, maternal psychopathology, and paternal criminality) and ADHD, comorbidity, and functioning. Results: Greater levels of environmental adversity were associated with a greater risk for ADHD and other comorbidity in both genders in a dose-dependent fashion. However, learning disability and global functioning were modified by gender, with more detrimental effects observed in boys than in girls, Low social class, maternal psychopathology, and family conflict were significantly associated with psychopathology and functional impairment in the probands, with control for gender, parental ADHD, proband ADHD status, and maternal smoking during pregnancy. Conclusions: Psychosocial adversity in general and low social class, maternal psychopathology, and family conflict in particular increased the risk for ADHD and associated morbidity independently of gender and other risk factors, but gender modified the risk for adverse cognitive and interpersonal outcomes; boys were more vulnerable to the disorder than girls. Because of the difficulties in separating the effects of genetics from environment, these results must be interpreted as provisional until confirmation from twin and adoption studies. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit ACC725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit ACC725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314] NR 29 TC 123 Z9 131 U1 0 U2 17 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 2002 VL 159 IS 9 BP 1556 EP 1562 DI 10.1176/appi.ajp.159.9.1556 PG 7 WC Psychiatry SC Psychiatry GA 591EQ UT WOS:000177867100015 PM 12202277 ER PT J AU Mulsant, BH Kastango, KB Rosen, J Stone, RA Mazumdar, S Pollock, BG AF Mulsant, BH Kastango, KB Rosen, J Stone, RA Mazumdar, S Pollock, BG TI Interrater reliability in clinical trials of depressive disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: The goal of this study was to review the reported methods of rater training, assessment of interrater reliability, and rater drift in clinical trials of treatments for depressive disorders. Method: Two psychiatrists independently identified all original reports of clinical trials relevant to depressive disorders published between 1996 and 2000 in the American Journal of Psychiatry and the Archives of General Psychiatry, Reported methods of rater training, assessment of interrater reliability, and rater drift were systematically summarized. Results: Sixty-three original papers met criteria for inclusion. Only 11 (17%) of the studies reported the number of raters. Only two (9%) of the 22 multicenter and four (10%) of the 41 single-center trials documented rater training. Only nine (22%) of the single-center trials and three (14%) of the multicenter trials reported interrater reliability, despite a median number of five raters (range=2-20). Only three (5%) of the 63 articles reported rater drift. Conclusions: Few published reports of clinical trials of treatments for depressive disorders document adequately the number of raters, rater training, assessment of interrater reliability, and rater drift. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Intervent Res Ctr Study Late Life Mood Disorders, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Mulsant, BH (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Intervent Res Ctr Study Late Life Mood Disorders, 3811 Ohara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-52247, MH-59566, MH-01613, MH-65416, MH-61639] NR 6 TC 23 Z9 23 U1 0 U2 1 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 SEP PY 2002 VL 159 IS 9 BP 1598 EP 1600 DI 10.1176/appi.ajp.159.9.1598 PG 3 WC Psychiatry SC Psychiatry GA 591EQ UT WOS:000177867100023 PM 12202285 ER PT J AU Angus, DC Marrie, TJ Obrosky, DS Clermont, G Dremsizov, TT Coley, C Fine, MJ Singer, DE Kapoor, WN AF Angus, DC Marrie, TJ Obrosky, DS Clermont, G Dremsizov, TT Coley, C Fine, MJ Singer, DE Kapoor, WN TI Severe community-acquired pneumonia - Use of intensive care services and evaluation of American and British Thoracic Society diagnostic criteria SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE artificial ventilation; community-acquired infections; intensive care; outcomes assessment; pneumonia ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL THERAPY; PROGNOSTIC FACTORS; MEDICAL OUTCOMES; HOSPITAL STAY; GUIDELINES; ADULTS; OUTPATIENTS; PREDICTION; MANAGEMENT AB Despite careful evaluation of changes in hospital care for community-acquired pneumonia (CAP), little is known about intensive care unit (ICU) use in the treatment of this disease. There are criteria that define CAP as "severe," but evaluation of their predictive value is limited. We compared characteristics, course, and outcome of inpatients who did (n = 170) and did not (n = 1,169) receive ICU care in the Pneumonia Patient Outcomes Research Team prospective cohort. We also assessed the predictive characteristics of four prediction rules (the original and revised American Thoracic Society criteria, the British Thoracic Society criteria, and the Pneumonia Severity Index [PSI]) for ICU admission, mechanical ventilation, medical complications, and death (as proxies for severe CAP). ICU patients were more likely to be admitted from home and had more comorbid conditions. Reasons for ICU admission included respiratory failure (57%), hemodynamic monitoring (32%), and shock (16%). ICU patients incurred longer hospital stays (23.2 vs. 9.1 days, p < 0.001), higher hospital costs ($21,144 vs. $5,785, p < 0.001), more nonpulmonary organ dysfunction, and higher hospital mortality (18.2 vs. 5.0%, p < 0.001). Although ICU patients were sic er 27% were of low risk (PSI Risk Classes I-III). Severity-adjusted ICU admission rates varied across institutions, but mechanical ventilation rates did not. The revised American Thoracic Society criteria rule was the best discriminator of ICU admission and mechanical ventilation (area under the receiver operating characteristic curve, 0.68 and 0.74, respectively) but none of the prediction rules were particularly good. The PSI was the best predictor of medical complications and death (area under the receiver operating characteristic curve, 0.65 and 0.75, respectively), but again, none of the prediction rules were particularly good. In conclusion, ICU use for CAP is common and expensive but admission rates are variable. Clinical prediction rules for severe CAP do not appear adequately robust to guide clinical care at the current time. C1 Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Illness Lab, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Div Hlth Policy & Management, Pittsburgh, PA 15260 USA. Univ Alberta, Dept Med, Edmonton, AB, Canada. Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. RP Angus, DC (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Illness Lab, Room 604,Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. RI Angus, Derek/E-9671-2012 FU AHRQ HHS [R01 HSO 6468]; NIGMS NIH HHS [R01 GM61992-01] NR 41 TC 191 Z9 206 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP 1 PY 2002 VL 166 IS 5 BP 717 EP 723 DI 10.1164/rccm.2102084 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 588ZZ UT WOS:000177734100019 PM 12204871 ER PT J AU Titton, RL Lucey, BC Gervais, DA Boland, GW Mueller, PR AF Titton, RL Lucey, BC Gervais, DA Boland, GW Mueller, PR TI Interventional radiology case conferences Massachusetts General Hospital - Celiac plexus block: A palliative tool underused by radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID REGIONAL ANATOMIC DISTORTIONS; PAIN RELIEF; PANCREATIC-CANCER; ANTERIOR APPROACH; GANGLIA BLOCK; NEUROLYSIS C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 13 Z9 16 U1 0 U2 4 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 SEP PY 2002 VL 179 IS 3 AR UNSP 0361-803X/02/1793-633 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 586FU UT WOS:000177574600014 PM 12185033 ER PT J AU Jiang, Z Wu, CL Woda, BA Dresser, K Xu, JC Fanger, GR Yang, XMJ AF Jiang, Z Wu, CL Woda, BA Dresser, K Xu, JC Fanger, GR Yang, XMJ TI P504S/alpha-methylacyl-CoA racemase - A useful marker for diagnosis of small foci of prostatic carcinoma on needle biopsy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE P504S; alpha-methylacyl-CoA racemase; limited prostate carcinoma ID CANCER; TISSUES AB Establishing a definitive diagnosis of malignancy in prostate needle biopsies with very small foci of adenocarcinoma is a major diagnostic challenge for surgical pathologists. A positive diagnostic marker specific for prostatic adenocarcinoma may enhance our ability to detect limited prostate cancer and reduce errors in diagnosis. P504S, also known as alpha-methylacyl-CoA racemase, recently identified by cDNA subtraction and microarray technology, might serve as such a specific marker because it has been demonstrated to be highly expressed in prostatic adenocarcinoma, but not in benign prostatic glands. However, whether small foci of carcinoma can be reliably detected by this marker is a crucial question for its clinical application. The aim of this study was to assess the utility of P504S immunohistochemistry in detecting small amounts of prostate cancer in prostate needle biopsies. A total of 142 prostate needle biopsies, including 73 cases with a small focus of prostatic adenocarcinoma (<1 mm) and 69 benign prostates, were examined by using immunohistochemistry for P504S and high molecular weight cytokeratin (34betaE12). P504S immunoreactivity was found in 69 of 73 cases (94.5%) of carcinoma but not in any benign prostates (0 of 69) or benign glands adjacent to malignant glands. The 34betaE12 immunostaining confirmed the absence of basal cells in the focus of carcinoma in all 73 cases. The high specificity and sensitivity of P504S in the detection of minimal prostatic adenocarcinoma indicated its potential diagnostic value in clinical practice. Using a combination of P504S and 34betaE12 can help the diagnosis of limited prostatic adenocarcinoma on needle biopsy. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Corixa Corp, Seattle, WA USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Dept Urol Surg, Chicago, IL 60637 USA. RP Jiang, Z (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave, Worcester, MA 01655 USA. NR 18 TC 126 Z9 145 U1 2 U2 5 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 SEP PY 2002 VL 26 IS 9 BP 1169 EP 1174 DI 10.1097/01.PAS.0000024997.88486.83 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 588ZW UT WOS:000177733700007 PM 12218573 ER PT J AU Rosengard, BR Feng, S Alfrey, EJ Zaroff, JG Emond, JC Henry, ML Garrity, ER Roberts, JP Wynn, JJ Metzger, RA Freeman, RB Port, FK Merion, RM Love, RB Busuttil, RW Delmonico, FL AF Rosengard, BR Feng, S Alfrey, EJ Zaroff, JG Emond, JC Henry, ML Garrity, ER Roberts, JP Wynn, JJ Metzger, RA Freeman, RB Port, FK Merion, RM Love, RB Busuttil, RW Delmonico, FL TI Report of the crystal city meeting to maximize the use of organs recovered from the cadaver donor SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 173 Z9 182 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2002 VL 2 IS 8 BP 701 EP 711 DI 10.1034/j.1600-6143.2002.20804.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 594BY UT WOS:000178029900004 PM 12243491 ER PT J AU Rosendale, JD Chabalewski, FL McBride, MA Garrity, ER Rosengard, BR Delmonico, FL Kauffman, HM AF Rosendale, JD Chabalewski, FL McBride, MA Garrity, ER Rosengard, BR Delmonico, FL Kauffman, HM TI Increased transplanted organs from the use of a standardized donor management protocol SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE critical pathway; donor management ID UNITED NETWORK; PROCUREMENT AB The organ shortage has resulted in increasing recipient waiting lists and waiting-list deaths. The increased use of expanded donors has been associated with increased discarding of procured organs because of poor organ function. A structured donor management algorithm or critical pathway was tested to determine its effect on the donor management and procurement process. A pilot study examined donors from 88 critical care units in 10 organ procurement organizations managed under the critical pathway and compared them to retrospective data collected at those same pilot sites. The total number of organs both procured and transplanted per 100 donors was significantly greater (p <0.01) in the critical pathway group when compared to the control group. There was no significant difference in 1-year graft survival for any of the organs recovered, and no significant difference in the rate of delayed graft function in the kidneys transplanted. Use of a structured donor management algorithm results in significant increases in organs procured and organs transplanted without any reduction in the quality of the organs being transplanted. C1 United Network Organ Sharing, Dept Res, Richmond, VA USA. United Network Organ Sharing, Profess Serv Dept, Richmond, VA USA. Loyola Univ, Dept Med, Chicago, IL 60611 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosendale, JD (reprint author), United Network Organ Sharing, Dept Res, Richmond, VA USA. NR 23 TC 91 Z9 99 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD SEP PY 2002 VL 2 IS 8 BP 761 EP 768 DI 10.1034/j.1600-6143.2002.20810.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 594BY UT WOS:000178029900010 PM 12243497 ER PT J AU Raines, DE Claycomb, RJ Forman, SA AF Raines, DE Claycomb, RJ Forman, SA TI Nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes inhibit alpha(4)beta(2) neuronal nicotinic acetylcholine receptors SO ANESTHESIA AND ANALGESIA LA English DT Article ID HALOGENATED COMPOUNDS; GENERAL-ANESTHESIA; MECHANISMS; CHANNELS; DISOBEY AB The nonhalogenated anesthetic alkanes, cyclopropane and butane, do not enhance gamma-aminobutyric acid-elicited GABAergic currents, suggesting that these agents produce anesthesia via interactions with other molecular targets. Perhalogenated nonimmobilizing alkanes, such as 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane, also fail to enhance GABAergic currents, but display specific behavioral effects that are distinct from those of structurally similar anesthetics. At concentrations predicted to be anesthetic, 1,2-dichlorohexafluorocyclobutane and 2,3-dichlorooctafluorobutane produce amnesia but fail to produce immobility. Neuronal nicotinic acetylcholine (nACh) receptors are sensitive to many anesthetics and are thought to have an important role in learning and memory. We, postulated that neuronal nACh receptors might mediate the common amnestic action of nonhalogenated and perhalogenated alkanes. To test the hypothesis that neuronal nACh receptors have a role in mediating the behavioral effects of general anesthetics and nonimmobilizers, we quantified the inhibitory potencies of nonhalogenated anesthetic alkanes and perhalogenated nonimmobilizing alkanes on currents mediated by alpha(4)beta(2) neuronal nACh receptors. Our studies reveal that anesthetics and nonimmobilizers significantly inhibit alpha(4)beta(2) neuronal nACh receptors at concentrations that suppress learning and with potencies that correlate with their hydrophobicities. These results support the hypothesis that alpha(4)beta(2) neuronal nACh receptors mediate the amnestic actions of alkanes but not their immobilizing actions. C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM 61927] NR 18 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2002 VL 95 IS 3 BP 573 EP 577 AR UNSP 0003-2999/02 DI 10.1097/00000539-200209000-00015 PG 5 WC Anesthesiology SC Anesthesiology GA 589DW UT WOS:000177743900015 PM 12198040 ER PT J AU Desjardins, PJ Shu, VS Recker, DP Verburg, KM Woolf, CJ AF Desjardins, PJ Shu, VS Recker, DP Verburg, KM Woolf, CJ TI A single preoperative oral dose of valdecoxib, a new cyclooxygenase-2 specific inhibitor, relieves post-oral surgery or bunionectomy pain SO ANESTHESIOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; POSTOPERATIVE ANALGESIA; AMBULATORY SURGERY; DENTAL PAIN; EFFICACY; TONSILLECTOMY; PARACETAMOL; METAANALYSIS; COMBINATION; CELECOXIB AB Background: The trend toward day-case surgery, with discharge on oral medication, has highlighted the need for effective and safe analgesics that facilitate a rapid recovery and discharge time. This study evaluated the analgesic efficacy, dose dependency, duration of action, and safety of the cyclooxygenase-2 specific inhibitor, valdecoxib, administered before oral or orthopedic surgery. Methods: Eligible healthy adult patients were scheduled to undergo either extraction of two impacted third molar teeth (n = 284) or bunionectomy surgery (n = 223) with local anesthesia in two randomized, double-blind, placebo-controlled studies conducted at three centers in the United States. Patients received a single, preoperatively administered oral dose of placebo or 10 (oral surgery only), 20, 40, or 80 mg valdecoxib. Analgesic efficacy was assessed postoperatively, over a 24-h treatment period, or until the patient required rescue medication. Efficacy measures included time to rescue medication, proportion of patients requiring such rescue, pain intensity, and the Patient's Global Evaluation of Study Medication. Results: In both studies, all doses of valdecoxib, produced analgesia with a duration (time to rescue analgesia) and magnitude (Pain Intensity, Patient's Global Evaluation) significantly greater than placebo. A dose-dependent effect was observed up to 40 mg valdecoxib, with an 80-mg dose providing no additional analgesic benefit. In both models, all doses of valdecoxib were well tolerated, with no clinically significant treatment-related gastrointestinal, renal, or platelet-derived adverse events, and no evidence of a dose-related increase in adverse events. Conclusions: Preoperative orally administered valdecoxib provides well-tolerated and effective analgesia for mild to moderate postoperative pain. C1 SCIREX Corp, Clin Site Adm, Analgesia Dept, Austin, TX USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4310, Charlestown, MA 02129 USA. NR 35 TC 76 Z9 79 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2002 VL 97 IS 3 BP 565 EP 573 DI 10.1097/00000542-200209000-00008 PG 9 WC Anesthesiology SC Anesthesiology GA 589NL UT WOS:000177766100007 PM 12218521 ER PT J AU Melo, MFV Harris, RS Layfield, D Musch, G Venegas, JG AF Melo, MFV Harris, RS Layfield, D Musch, G Venegas, JG TI Changes in regional ventilation after autologous blood clot pulmonary embolism SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 13-17, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Soc Anesthesiologists ID LUNG-MECHANICS; HYPOXEMIA; PET; HETEROGENEITY; PERFUSION; HUMANS; ALPHA AB Background: Previous studies have suggested that pulmonary embolism (PE) and pulmonary artery occlusion result in a shift in alveolar ventilation away from unperfused regions. This study aimed to directly assess changes in regional specific ventilation (s(V)over dot(A)) due to autologous; blood clot PE using positron emission tomography. Methods: Pulmonary embolism was created in six anesthetized, paralyzed, and mechanically ventilated sheep by injecting cylindrical clots of autologous blood (7 mm in diameter and height). Clots were progressively infused into a central vein until a stable mean pulmonary artery pressure between 30 and 40 mmHg was achieved. A multislice positron emission tomography camera was used to image 15 contiguous, 6.5-mm-thick transverse cross-sections of the chest beginning just above the diaphragm. s(V)over dot(A) from perfused regions (s(V)over dot(A,p)) was assessed as the ventilatory turnover rate of the tracer (NN)-N-13 after central venous injection of (NN)-N-13-labeled saline. Results: Pulmonary embolism obstructed flow to 64% of imaged areas. Before PE, s(V)over dot(A,p) was equivalent in areas that would remain perfused and those that would become embolized after PE (0.021 +/- 0.007 vs. 0.021 +/- 0.006 s(-1); P = nonsignificant). After PE, s TA,p of areas remaining perfused increased to 0.033 +/- 0.011 s(-1) (P < 0.005). This effect on regional s(V)over dot(A,p) could have been caused by active redistribution of s(V)over dot(A,p) or by a reduction in tracer concentration of perfused areas due to the dead space common to perfused and embolized regions. Model simulations indicated that the common dead-space effect could only explain a small part of the s(V)over dot(A,p) increase Conclusions: An increase in s(V)over dot(A) of perfused regions occurs following PE with 7-mm autologous blood clots. This increase is most likely caused by a shift in ventilation away from embolized areas mediated by hypocapnic pneumoconstriction. C1 Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 24 TC 43 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2002 VL 97 IS 3 BP 671 EP 681 PG 11 WC Anesthesiology SC Anesthesiology GA 589NL UT WOS:000177766100021 PM 12218535 ER PT J AU Takeuchi, M Goddon, S Dolhnikoff, M Shimaoka, M Hess, D Amato, MBP Kacmarek, RM AF Takeuchi, M Goddon, S Dolhnikoff, M Shimaoka, M Hess, D Amato, MBP Kacmarek, RM TI Set positive end-expiratory pressure during protective ventilation affects lung injury SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 96th International Conference of the American-Thoracic-Society CY MAY 05-10, 2000 CL TORONTO, CANADA SP Amer Thorac Soc ID RESPIRATORY-DISTRESS SYNDROME; TIDAL VOLUME VENTILATION; FREQUENCY OSCILLATORY VENTILATION; MEAN AIRWAY PRESSURE; MECHANICAL VENTILATION; RECRUITMENT MANEUVERS; GAS-EXCHANGE; MATHEMATICAL-MODEL; FAILURE; CURVE AB Background. The most appropriate method of determining positive end-expiratory pressure (PEEP) level during a lung protective ventilatory strategy has not been established. Methods: In a lavage-injured sheep acute respiratory distress syndrome model, the authors compared the effects of three approaches to determining PEEP level after a recruitment maneuver: (1) 2 cm H2O above the lower inflection point on the inflation pressure-volume curve, (2) at the point of maximum curvature on the deflation pressure-volume curve, and (3) at the PEEP level that maintained target arterial oxygen partial pressure at a fraction of inspired oxygen of 0.5. Results: Positive end-expiratory pressure set 2 cm H2O above the lower inflection point resulted in the least injury over the course of the study. PEEP based on adequate arterial oxygen partial pressure/fraction of inspired oxygen ratios had to be increased over time and resulted in higher mRNA levels for interleukin-8 and interleukin-1beta and greater tissue inflammation when compared with the other approaches. PEEP at the point of maximum curvature could not maintain eucapneia even at an increased ventilatory rate. Conclusion: Although generating higher plateau pressures PEEP levels based on pressure-volume curve analysis were more effective in maintaining gas exchange and minimizing injury than PEEP based on adequate oxygenation. PEEP at 2 cm H2O above the lower inflection point was most effective. C1 Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Ctr Blood Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Univ Sao Paulo, Dept Pathol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Dept Med, BR-05508 Sao Paulo, Brazil. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Resp Care, Ctr Blood Res, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 43 TC 50 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2002 VL 97 IS 3 BP 682 EP 692 DI 10.1097/00000542-200209000-00023 PG 11 WC Anesthesiology SC Anesthesiology GA 589NL UT WOS:000177766100022 PM 12218536 ER PT J AU Delahanty, LM Hayden, D Ammerman, A Nathan, DM AF Delahanty, LM Hayden, D Ammerman, A Nathan, DM TI Medical nutrition therapy for hypercholesterolemia positively affects patient satisfaction and quality of life outcomes SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID CONTROLLED-TRIAL; CARDIOVASCULAR-DISEASE; CHOLESTEROL; DIET; INTERVENTION; PROGRAM; EDUCATION; MEN; EXERCISE; HEALTH AB Following a heart-healthy diet to lower cholesterol levels is often assumed to be difficult, to be burdensome, and to have a negative impact on quality of life (QOL). The purpose of this study was to evaluate the impact of medical nutrition therapy (MNT) versus usual care (UC) for hypercholesterolemia on patient satisfaction and QOL. Ninety ambulatory care patients (60 men and 30 women), age 28 to 66, were randomly assigned to receive either MNT from dietitians using a National Cholesterol Education Program-based protocol or UC from their physicians. Patients who received MNT reported no difference in QOL related to the taste or enjoyment of food compared with UC patients. However the MNT group reported initial improvements in QOL related to the convenience and cost of following a low-fat diet when compared with the UC group. The MNT group also reported significant and lasting improvements in perceived QOL related to self-care compared with the UC group. MNT patients were more satisfied with the interaction at visits, knowledge and ability to manage their cholesterol, eating habits, appearance, time spent exercising, and life in general. Moreover MNT patients did not report any negative impact related to following a low-fat diet in regard to feeling restricted by diet; interference with lifestyle activities; or difficulty planning, purchasing, or preparing meals or eating away from home. Contrary to popular belief, there is no apparent reduction but rather an improvement in some measures of QOL and patient satisfaction with MNT for hypercholesterolemia. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM Ldelahanty@partners.org FU NCRR NIH HHS [M01RR01066] NR 29 TC 10 Z9 11 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 EI 1532-4796 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FAL PY 2002 VL 24 IS 4 BP 269 EP 278 DI 10.1207/S15324796ABM2404_03 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 613DQ UT WOS:000179116900003 PM 12434938 ER PT J AU Lum, G AF Lum, G TI Utilization and cost effectiveness of standardized testing for screening and confirmation of drugs of abuse in urine SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE drugs of abuse in urine; assay standardization; confirmation; utilization; cost analysis ID AMPHETAMINE METHAMPHETAMINE ASSAY; SUBSTANCE USE; SERVICE AB Screening and confirmation testing for drugs of abuse in urine (DAU) represent areas for potential reduction of laboratory workload and attendant cost savings. Following a careful review of the clinical needs of the underlying veteran patient population served by 7 medical facilities in the Boston area, DAU test ordering frequencies, positive rates for several screening panels and the associated confirmation tests, DAU panel standardization, and confirmation testing only by request were introduced. These changes were all reviewed and approved by the clinician users of DAU testing at each institution before the changes were implemented. Before standardization of DAU screening panels, 59,835 DAU screening requests were done at a cost of $216,005; following standardization, there was 47% decrease in DAU screening utilization (27,876) and costs ($100,633). Before implementation of a DAU confirmation by request only policy, 5,331 confirmation tests were done at a cost of $111,502; after institution of the confirmation policy, there was 95% decrease in confirmation tests (5,080) and costs ($105,826). DAU panel standardization and DAU confirmation by request only have resulted in substantial reductions of laboratory workload and costs in a veterans population and may serve as a model for other patient populations with perhaps similar outcomes. (received 9 March 2002; accepted 20 May 2002). C1 VA Boston Healthcare Syst, Lab Med Serv, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Lab Med Serv, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD FAL PY 2002 VL 32 IS 4 BP 387 EP 392 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 615QZ UT WOS:000179259300007 PM 12458891 ER PT J AU Keahey, L Bulloch, B Becker, AB Pollack, CV Clark, S Camargo, CA AF Keahey, L Bulloch, B Becker, AB Pollack, CV Clark, S Camargo, CA TI Initial oxygen saturation as a predictor of admission in children presenting to the emergency department with acute asthma SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ACUTE BRONCHIAL-ASTHMA; PULSE OXIMETRY; DIAGNOSTIC-TEST; HOSPITALIZATION; RELAPSE; INDEX; PREDNISONE; CHILDHOOD; NEED AB Background: Previous studies have looked at the relationship between initial oxygen saturation (SaO(2)) and the need for admission in children presenting with an acute asthma exacerbation. If initial SaO(2) value is indeed predictive of admission, then the admission process could be initiated sooner, and time spent in the emergency department could be potentially lessened. Study objective: The objective of the current study was to examine whether initial room air SaO(2) in children presenting to the ED with acute asthma is a reliable predictor of hospital admission. Methods: This was a prospective multicenter study during 1997 and 1998 at 44 North American EDs as part of the Multicenter Airway Research Collaboration. Inclusion criteria were physician diagnosis of acute asthma and age between 2 and 17 years. The association between hospital admission and SaO(2) was examined by using logistic regression. Likelihood ratios were used to assess the diagnostic value of SaO(2). Results: Of the 1,184 children enrolled in the current study, 1,040 (88%) had a documented initial SaO(2) value on room air. The mean age of the cohort was 8 4 years, with a mean initial SaO(2) of 95%+/-4%. Overall, 241 (23%) children were admitted to the hospital. The mean SaO(2) value of children admitted to the hospital was 93%+/-5% versus 96%+/-3% for those not admitted (P<.001). The admission rate decreased with increasing SaO(2); 73% (30/41) of children with an Sa value of 88% or less were admitted versus 8% (7/88) with an SaO(2) value of 100%. In the logistic regression model, children with an SaO(2) value of 88% or less were 32 (95% confidence interval 11 to 89) times more likely to be admitted than those with an SaO(2) value of 100%. The likelihood ratio for admission was 12 for children with an Sa value of 88% or less (42/1,040) but decreased to 4.6 for children with an SaO(2) value of 91% or less (130/1,040) and 2.7 for children with an SaO(2) value of 94% or less (333/1,040). Conclusion: This large, clinical multicenter study does not support earlier findings that SaO(2) alone is a clinically useful predictor of hospital admission in children who present to the ED with acute asthma. C1 Winnipeg Childrens Hosp, Pediat Emergency Serv, Allergy & Clin Immunol Sect, Winnipeg, MB R3M 3V7, Canada. Winnipeg Childrens Hosp, Dept Pediat Emergency Med, Winnipeg, MB R3M 3V7, Canada. Maricopa Cty Gen Hosp, Dept Emergency Med, Phoenix, AZ USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Keahey, L (reprint author), Winnipeg Childrens Hosp, Pediat Emergency Serv, Allergy & Clin Immunol Sect, 840 Sherbrook St, Winnipeg, MB R3M 3V7, Canada. FU NHLBI NIH HHS [HL-03533, HL-63253] NR 22 TC 22 Z9 23 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2002 VL 40 IS 3 BP 300 EP 307 DI 10.1067/mem.2002.126813 PG 8 WC Emergency Medicine SC Emergency Medicine GA 589EM UT WOS:000177745700006 PM 12192354 ER PT J AU Fink, AS Campbell, DA Mentzer, RM Henderson, WG Daley, J Bannister, J Hur, K Khuri, SF AF Fink, AS Campbell, DA Mentzer, RM Henderson, WG Daley, J Bannister, J Hur, K Khuri, SF TI The National Surgical Quality Improvement Program in non-veterans administration hospitals - Initial demonstration of feasibility SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Surgical-Association CY APR 24-27, 2002 CL HOT SPRINGS, VIRGINIA SP Amer Surg Assoc ID CORONARY-ARTERY BYPASS; RISK ADJUSTMENT; CARE; OUTCOMES; SURGERY; MORTALITY; MORBIDITY; COORDINATION; SERVICES; LESSONS AB Objective To assess the feasibility of implementing the National Surgical Quality Improvement Program (NSQIP) methodology in non-VA hospitals. Summary Background Data Using data adjusted for patient preoperative risk, the NSQIP compares the performance of all VA hospitals performing major surgery and anonymously compares these hospitals using the ratio of observed to expected adverse events. These results are provided to each hospital and used to identify areas for improvement. Since the NSQIP's inception in 1994, the VA has reported consistent improvements in all surgery performance measures. Given the success of the NSQIP within the VA, as well as the lack of a comparable system in non-VA hospitals, this pilot study was undertaken to test the applicability of the NSQIP models and methodology in the nonfederal sector. Methods Beginning in 1999, three academic medical centers (Emory University, Atlanta, GA; University of Michigan, Ann Arbor, MI; University of Kentucky, Lexington, KY) volunteered the time of a dedicated surgical nurse reviewer who was trained in NSQIP methodology. At each academic center, these nurse reviewers used NSQIP protocols to abstract clinical data from general surgery and vascular surgery patients. Data were manually collected and then transmitted via the Internet to a secure web site developed by the NSQIP. These data were compared to the data for general and vascular surgery patients collected during a concurrent time period (10/99 to 9/00) within the VA by the NSQIP. Logistic regression models were developed for both non-VA and VA hospital data. To assess the models' predictive values, C-indices (0.5 = no prediction; 1.0 = perfect prediction) were calculated after applying the models to the non-VA as well as the VA databases. Results Data from 2,747 (general surgery 2,251; vascular surgery 496) non-VA hospital cases were compared to data from 41,360 (general surgery 31,393; vascular surgery 9,967) VA cases. The bivariate relationships between individual risk factors and 30-day mortality or morbidity were similar in the non-VA and VA patient populations for over 66% of the risk variables. C-indices of 0.942 (general surgery), 0.915 (vascular surgery), and 0.934 (general plus vascular surgery) were obtained following application of the VA NSQIP mortality model to the non-VA patient data. Lower C-indices (0.778, general surgery; 0.638, vascular surgery; 0.760, general plus vascular surgery) were obtained following application of the VA NSQIP morbidity model to the non-VA patient data. Although the non-VA sample size was smaller than the VA, preliminary analysis suggested no differences in risk-adjusted mortality between the non-VA and VA cohorts. Conclusions With some adjustments, the NSQIP methodology can be implemented and generates reasonable predictive models within non-VA hospitals. C1 Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Atlanta VAMC, Dept Surg, Atlanta, GA USA. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Ctr Hlth, Ann Arbor, MI USA. Univ Kentucky, Med Ctr, Lexington, KY 40506 USA. Lexington VAMC, Lexington, KY USA. Hines VAMC, CSPCC, Hines, IL USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MGH Partners HCS, Ctr Hlth Syst Design & Evaluat, Inst Hlth Policy, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. RP Fink, AS (reprint author), Atlanta VAMC, Surg Serv, 112,1670 Clairmont Rd, Decatur, GA 30033 USA. NR 28 TC 307 Z9 308 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 2002 VL 236 IS 3 BP 344 EP 354 DI 10.1097/01.SLA.0000027082.79556.55 PG 11 WC Surgery SC Surgery GA 589CY UT WOS:000177741500011 PM 12192321 ER PT J AU Gojo, S Yamamoto, S Patience, C LeGuern, C Cooper, DKC AF Gojo, S Yamamoto, S Patience, C LeGuern, C Cooper, DKC TI Gene therapy - its potential in surgery SO ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND LA English DT Review DE gene therapy; surgery; cancer; cardiovascular disease; transplantation ID CLINICAL-TRIAL; PHASE-I; INTERLEUKIN-2; IMMUNOTHERAPY; TRANSFECTION; PHVEGF(165); EXPRESSION; ISCHEMIA; MELANOMA; TUMORS AB Advances in techniques have resulted in practical applications for gene therapy, which is becoming applicable for the treatment of human disease. This review outlines the advantages and disadvantages of the techniques available. Examples of research efforts in the treatment of diseases of relevance to the surgeon (cardiovascular diseases, cancer, wound healing, fracture repair, and in organ transplantation) are presented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 24 TC 4 Z9 4 U1 0 U2 0 PU ROYAL COLL SURGEONS ENGLAND PI LONDON PA 35-43 LINCOLN'S INN FIELDS, LONDON WC2A 3PN, ENGLAND SN 0035-8843 J9 ANN ROY COLL SURG JI Ann. R. Coll. Surg. Engl. PD SEP PY 2002 VL 84 IS 5 BP 297 EP 301 DI 10.1308/003588402760452367 PG 5 WC Surgery SC Surgery GA 601DE UT WOS:000178430600001 PM 12398117 ER PT J AU Khuri, SF AF Khuri, SF TI Quality, advocacy, healthcare policy, and the surgeon SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID AFFAIRS SURGICAL RISK; IMPROVEMENT-PROGRAM; CARE; ADJUSTMENT; OPERATIONS; VOLUME C1 VA Boston Healthcare Syst, Dept Cardiovasc Surg, Boston, MA 02132 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Dept Cardiovasc Surg, 1400 Vet Foreign Wars Pkwy, Boston, MA 02132 USA. NR 9 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2002 VL 74 IS 3 BP 641 EP 649 AR PII S0003-4975(02)03795-5 DI 10.1016/S0003-4975(02)03795-5 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 591MH UT WOS:000177883900001 PM 12238818 ER PT J AU Perea, S Gonzalez, G Fothergill, AW Kirkpatrick, WR Rinaldi, MG Patterson, TF AF Perea, S Gonzalez, G Fothergill, AW Kirkpatrick, WR Rinaldi, MG Patterson, TF TI In vitro interaction of caspofungin acetate with voriconazole against clinical isolates of Aspergillus spp. SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL MK-0991 L-743,872; DIMORPHIC FUNGI; CANDIDIASIS; TERBINAFINE; FUSARIUM; LY303366 AB The interaction between caspofungin acetate and voriconazole was studied in vitro by using 48 clinical Aspergillus spp. isolates obtained from patients with invasive aspergillosis. MICs were determined by the NCCLS broth microdilution method. Synergy, defined as a fractional inhibitory concentration (FIC) index of < 1, was detected in 87.5% of the interactions; an additive effect, defined as an FIC index of 1.0, was observed in 4.2% of the interactions; and a subadditive effect, defined as an FIC index of 1.0 to 2.0, was found in 8.3% of the interactions. No antagonism was observed. Animal models are required to validate the in vivo significance of these in vitro data presented for the combination of caspofungin and voriconazole. C1 Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Audie Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Perea, S (reprint author), Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Med, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. FU NCRR NIH HHS [M01 RR001346, M01-RR-01346]; NIDCR NIH HHS [R01 DE011381, 5 R01 DE11381] NR 17 TC 132 Z9 137 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2002 VL 46 IS 9 BP 3039 EP 3041 DI 10.1128/AAC.46.9.3039-3041.2002 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 585FQ UT WOS:000177515000045 PM 12183266 ER PT J AU Hadigan, C Chung, R Murray, G Purkis, D Grinspoon, S AF Hadigan, C Chung, R Murray, G Purkis, D Grinspoon, S TI Hepatitis B and C co-infection and alanine aminotransferase are associated with increased insulin resistance and diabetes in patients with fat redistribution SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD SEP PY 2002 VL 7 IS 3 MA 34 BP L24 EP L25 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 619WY UT WOS:000179501500044 ER PT J AU Justice, AC McGinnis, KA Skanderson, M Conigliaro, J Kilbourne, A Good, C Fultz, SL Rabenenck, L Rodriguez-Barradas, M Weissman, S AF Justice, AC McGinnis, KA Skanderson, M Conigliaro, J Kilbourne, A Good, C Fultz, SL Rabenenck, L Rodriguez-Barradas, M Weissman, S CA VACS 3 Project Team TI Comorbid disease is a major determinant of patient outcomes in HIV infection SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International HIV Workshop on Management of Treatment-Experienced Patients CY SEP 26-27, 2002 CL SAN DIEGO, CALIFORNIA C1 VA Pittsburgh Healthcare Syst, Vet Aging Cohort Study Ctr, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Sch Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Excellence VA Med Ctr, VA Hlth Serv Res & Dev Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD SEP PY 2002 VL 7 IS 3 MA 108 BP L69 EP L70 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 619WY UT WOS:000179501500118 ER PT J AU Rhew, D Kim, M Bernal, M Aguilar, D Iloeje, U Goetz, MB AF Rhew, D Kim, M Bernal, M Aguilar, D Iloeje, U Goetz, MB TI Association between protease inhibitors and increased cardiovascular risk: a systematic review SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA C1 Zynx Hlth, Beverly Hills, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD SEP PY 2002 VL 7 IS 3 MA 56 BP L38 EP L38 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 619WY UT WOS:000179501500066 ER PT J AU Tong, Q Sankale, JL Hadigan, CM Tan, G Rosenberg, ES Kanki, PJ Grinspoon, SK Hotamisligil, GS AF Tong, Q Sankale, JL Hadigan, CM Tan, G Rosenberg, ES Kanki, PJ Grinspoon, SK Hotamisligil, GS TI Direct regulation of adiponectin by HIV and its link to lipodystrophy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Publ Hlth, Div Biol Sci, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Program Nutr Metab, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD SEP PY 2002 VL 7 IS 3 MA 32 BP L23 EP L23 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 619WY UT WOS:000179501500042 ER PT J AU Lee, CU Shenton, ME Salisbury, DF Kasai, K Onitsuka, T Dickey, CC Yurgelun-Todd, D Kikinis, R Jolesz, FA McCarley, RW AF Lee, CU Shenton, ME Salisbury, DF Kasai, K Onitsuka, T Dickey, CC Yurgelun-Todd, D Kikinis, R Jolesz, FA McCarley, RW TI Fusiform gyrus volume reduction in first-episode schizophrenia - A magnetic resonance imaging study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; LEFT TEMPORAL-LOBE; PLANUM TEMPORALE; FACE RECOGNITION; GRAY-MATTER; MRI; DISORDER; AREA; MISIDENTIFICATION; POSTMORTEM AB Background: The fusiform gyrus (occipitotemporal gyrus) is thought to be critical for face recognition and may possibly be associated with impaired facial recognition and interpretation of facial expression in schizophrenia. Results of postmortem studies have suggested that fusiform gyrus volume is reduced in schizophrenia, but there have been no in vivo structural studies of the fusiform gyrus in schizophrenia using magnetic resonance imaging. Methods: High-spatial resolution magnetic resonance images were used to measure the gray matter volume of the fusiform gyrus in 22 patients with first-episode schizophrenia (first hospitalization), 20 with first-episode affective psychosis (mainly manic), and 24 control subjects. Results: Patients with first-episode schizophrenia had overall smaller relative volumes (absolute volume/intracranial contents) of fusiform gyrus gray matter compared with controls (9%) and patients with affective psychosis (7%). For the left fusiform gyrus, patients with schizophrenia showed an 11% reduction compared with controls and patients with affective psychosis. Right fusiform gyrus volume differed in patients with schizophrenia only compared with controls (8%). Conclusion: Schizophrenia is associated with a bilateral reduction in fusiform gyrus gray matter volume that is evident at the time of first hospitalization and is different from the presentation of affective psychosis. C1 Harvard Univ, Sch Med,Lab Neurosci, VA Boston Healthcare Syst,Clin Neurosci Div, Dept Psychiat 116A,Brockton Div, Brockton, MA 02301 USA. McLean Hosp, Cognit Neurosci Lab, Belmont, MA 02178 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol,Surg Planning Lab,MRI Div, Boston, MA USA. RP Shenton, ME (reprint author), Harvard Univ, Sch Med,Lab Neurosci, VA Boston Healthcare Syst,Clin Neurosci Div, Dept Psychiat 116A,Brockton Div, 940 Belmont St, Brockton, MA 02301 USA. EM martha_shenton@hms.harvard.edu; robert_mccarley@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCIRD CDC HHS [IP1PR13218]; NCRR NIH HHS [R01RR11747, P41 RR013218, R01 RR011747]; NIMH NIH HHS [K02 MH 01110, K02 MH001110, R01 MH 40799, R01 MH 50747, R01 MH040799, R01 MH050740] NR 45 TC 78 Z9 80 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD SEP PY 2002 VL 59 IS 9 BP 775 EP 781 DI 10.1001/archpsyc.59.9.775 PG 7 WC Psychiatry SC Psychiatry GA 592JV UT WOS:000177935300001 PM 12215076 ER PT J AU Seidman, LJ Faraone, SV Goldstein, JM Kremen, WS Horton, NJ Makris, N Toomey, R Kennedy, D Caviness, VS Tsuang, MT AF Seidman, LJ Faraone, SV Goldstein, JM Kremen, WS Horton, NJ Makris, N Toomey, R Kennedy, D Caviness, VS Tsuang, MT TI Left hippocampal volume as a vulnerability indicator for schizophrenia - A magnetic resonance imaging morphometric study of nonpsychotic first-degree relatives SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 11-13, 2000 CL CHICAGO, ILLINOIS SP Soc Biol Psychiat ID LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; TEMPORAL-LOBE; RISK-FACTORS; TOPOGRAPHIC PARCELLATION; OBSTETRIC COMPLICATIONS; BRAIN VOLUMES; WHITE-MATTER; MRI; MEMORY AB Background: Clues to the causes of schizophrenia can be derived from studying first-degree relatives because they are genetically related to an ill family member. Abnormalities observed in nonpsychotic relatives are indicators of possible genetic vulnerability to illness, independent of psychosis. We tested 4 hypotheses: (1) that hippocampal volume is smaller in nonpsychotic relatives than in controls, particularly in the left hemisphere; (2) that hippocampi will be smaller in multiplex relatives as compared with simplex relatives, and both will be smaller than in controls; (3) that hippocampal volumes and verbal declarative memory function will be positively correlated; and (4) that hippocampi will be smaller in patients with schizophrenia than in their nonpsychotic relatives or in controls. Methods: Subjects were 45 nonpsychotic adult firstdegree relatives from families with either 2 people ("multiplex," n=17) or 1 person ("simplex," n=28) diagnosed with schizophrenia, 18 schizophrenic relatives, and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3-dimensional magnetic resonance images of the brain were acquired on a 1.5-T magnet. Volumes of the total cerebrum and the hippocampus were measured. Results: Compared with controls, relatives, particularly from multiplex families, had significantly smaller left hippocampi. Verbal memory and left hippocampal volumes were significantly and positively correlated. Within families, hippocampal volumes did not differ between schizophrenic patients and their nonpsychotic relatives. Conclusions: Results support the hypothesis that the vulnerability to schizophrenia includes smaller left hippocampi and verbal memory deficits. Findings suggest that smaller left hippocampi and verbal memory deficits are an expression of early neurodevelopmental compromise, reflecting the degree of genetic liability to schizophrenia. C1 Massachusetts Mental Hlth Ctr, Neuropsychol Lab, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Dept Psychiat, Brockton, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Cambridge, MA 02138 USA. Univ Calif Davis, Davis Sch Med, Davis Napa Psychiat Res Ctr, Dept Psychiat, Sacramento, CA 95817 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Serv Radiol, Boston, MA USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Serv Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Seidman, LJ (reprint author), Massachusetts Mental Hlth Ctr, Neuropsychol Lab, 74 Fenwood Rd, Boston, MA 02115 USA. RI Horton, Nicholas/A-2493-2008; Kennedy, David/H-3627-2012; OI Horton, Nicholas/0000-0003-3332-4311; Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [SDA K21 MH 00976]; NIMH NIH HHS [MH 46318, MH 56956, MH43518] NR 92 TC 184 Z9 186 U1 1 U2 8 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 SEP PY 2002 VL 59 IS 9 BP 839 EP 849 DI 10.1001/archpsyc.59.9.839 PG 11 WC Psychiatry SC Psychiatry GA 592JV UT WOS:000177935300009 PM 12215084 ER PT J AU Fukumoto, H Cheung, BS Hyman, BT Irizarry, MC AF Fukumoto, H Cheung, BS Hyman, BT Irizarry, MC TI beta-secretase protein and activity are increased in the neocortex in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; CLEAVING ENZYME; BACE; SITE; CLEAVAGE; BRAIN; MICE; IDENTIFICATION; EXPRESSION; MATURATION AB Context: Amyloid plaques, a major pathological feature of Alzheimer disease (AD), are composed of an internal fragment of amyloid precursor protein (APP): the 4-kd amyloid-beta protein (Abeta). The metabolic processing of APP that results in Abeta formation requires 2 enzymatic cleavage events, a gamma-secretase cleavage dependent on presenilin, and a beta-secretase cleavage by the aspartyl protease beta-site APP-cleaving enzyme (BACE). Objective: To test the hypothesis that BACE protein and activity are increased in regions of the brain that develop amyloid plaques in AD. Methods: We developed an antibody capture system to measure BACE protein level and BACE-specific beta-secretase activity in frontal, temporal, and cerebellar brain homogenates from 61 brains with AD and 33 control brains. Results: In the brains with AD, BACE activity and protein were significantly increased (P<001). Enzymatic activity increased by 63% in the temporal neocortex (P=.007) and 13% in the frontal neocortex (P=.003) in brains with AD, but not in the cerebellar cortex. Activity in the temporal neocortex increased with the duration of AD (P=.008) but did not correlate with enzyme-linked immunosorbent assay measures of insoluble Aβ in brains with AD. Protein level was increased by 14% in the frontal cortex of brains with AD (P=.004), with a trend toward a 15% increase in BACE protein in the temporal cortex (P=.07) and no difference in the cerebellar cortex. Immunohistochemical analysis demonstrated that BACE immunoreactivity in the brain was predominantly neuronal and was found in tangle-bearing neurons in AD. Conclusions: The BACE protein and activity levels are increased in brain regions affected by amyloid deposition and remain increased despite significant neuronal and synaptic loss in AD. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Unit, Charlestown, MA USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Ctr Aging Genet & Neurodegenerat, Alzheimer Dis Res Unit, Bldg 114,Room 2010,114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134, AG00793]; NIMH NIH HHS [MH/NS 31862] NR 38 TC 424 Z9 433 U1 1 U2 14 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 SEP PY 2002 VL 59 IS 9 BP 1381 EP 1389 DI 10.1001/archneur.59.9.1381 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 593JM UT WOS:000177987800004 PM 12223024 ER PT J AU Zarbo, RJ Jones, BA Friedberg, RC Valenstein, PN Renner, SW Schifman, RB Walsh, MK Howanitz, PJ AF Zarbo, RJ Jones, BA Friedberg, RC Valenstein, PN Renner, SW Schifman, RB Walsh, MK Howanitz, PJ CA Coll Amer Pathologists TI Q-Tracks - A College of American Pathologists program of continuous laboratory monitoring and longitudinal performance tracking SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID BLOOD CULTURE CONTAMINATION; FROZEN-SECTION CONSULTATION; Q-PROBES; DIAGNOSTIC REPRODUCIBILITY; SPECIMEN ACCEPTABILITY; QUALITY IMPROVEMENT; SMALL HOSPITALS; INSTITUTIONS; CYTOLOGY; IDENTIFICATION AB Context.-Continuous monitoring of key laboratory indicators of quality by hundreds of laboratories in a standardized measurement program affords an opportunity to document the influence of longitudinal tracking on performance improvement by participants focused on that outcome. Objective.-To describe the results of the first 2 years of participation in a unique continuous performance assessment program for pathology and laboratory medicine. Design.-Participants in any of 6 modules in the 1999 and 2000 College of American Pathologists (CAP) Q-Tracks program collected data according to defined methods and sampling intervals on standardized input forms. Data were submitted quarterly to CAP for statistical analysis. Inter-institutional comparison reports returned in 6 weeks provided each laboratory with its performance profile of key indicators and its percentile ranking compared with all participants in that quarter. This also included longitudinal comparisons of performance during previous cumulative quarters. Control charts graphically displayed data with flags identifying performance points that were out of statistical control. Setting.-Hospital-based laboratories in the United States (98%), Canada, and Australia. Participants.-Voluntary subscriber laboratories in the CAP Q-Tracks performance measurement program: roughly 70% from hospitals of 300 occupied beds or fewer, 65% from private, nonprofit institutions, slightly more than half located in cities, one third from teaching hospitals, and 20% with pathology residency training programs. Main Outcome Measures.-Each module measured several major and additional minor quality indicators and unbenchmarked individualized data for internal use. Results.-Participants in 4 of 6 Q-Tracks continuous monitors demonstrated statistically significant performance improvement trends in 1999 and 2000, which were most marked for laboratories that continued participation throughout both years. These monitors were wristband patient identification, laboratory specimen acceptability, blood product wastage, and intraoperative frozen section consultation. Conclusions.-Key continuous indicators chosen on the basis of a decade's experience in the CAP Q-Probes quality improvement program are useful measurement and benchmarking tools for laboratories to improve performance. In general, measures in which there is a broad range of demonstrable performance initially are most optimal for subsequent improvement using continuous monitoring. These studies have shown that quality is not static, but rather is a moving benchmark of performance as seen in the redefinition of benchmarks over time by participants in the first 2 years of the CAP Q-Tracks program. C1 Henry Ford Hosp, Dept Pathol, Detroit, MI 48202 USA. St John Hosp & Med Ctr, Dept Pathol, Detroit, MI USA. Baystate Med Ctr, Dept Pathol, Springfield, MA USA. St Joseph Mercy Hlth Syst, Dept Pathol, Ann Arbor, MI USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. Vet Adm Med Ctr, Dept Diagnost, Tucson, AZ 85723 USA. Coll Amer Pathologists, Northfield, IL USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. RP Renner, SW (reprint author), Henry Ford Hosp, Dept Pathol, 2799 W Grand Blvd, Detroit, MI 48202 USA. NR 29 TC 65 Z9 73 U1 1 U2 5 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD SEP PY 2002 VL 126 IS 9 BP 1036 EP 1044 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 594UA UT WOS:000178068300006 PM 12204052 ER PT J AU Pollack, CV Pollack, ES Baren, JM Smith, SR Woodruff, PG Clark, S Camargo, CA AF Pollack, CV Pollack, ES Baren, JM Smith, SR Woodruff, PG Clark, S Camargo, CA CA Multictr Airway Res Collaboration TI A prospective multicenter study of patient factors associated with hospital admission from the emergency department among children with acute asthma SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID CHILDHOOD ASTHMA; MANAGEMENT; POPULATION; RISK; CARE; READMISSION; GUIDELINES; WEATHER; HEALTH; INDEX AB Background: Recent studies show that objective measures such as peak flow rates are strongly associated with asthma admission among adults. Objective: To identify factors associated with admission among children. Methods: We performed a prospective cohort study as part of the Multicenter Airway Research Collaboration. Patients aged 2 to 17 years who presented to the emergency department (ED) with acute asthma underwent a structured interview in the ED and another by telephone 2 weeks later. The study was performed at 44 EDs in 18 US states and 4 Canadian provinces. The decision to admit was made at the discretion of the treating physician. Univariate analysis of risk factors for admission was followed by multivariate logistic regression. Results: Of the 1178 eligible subjects, 275 (23%; 95% confidence interval, 21%-26%) were admitted or placed into ED observation units. A multivariate model that included 12 characteristics measured at presentation and during the ED stay was associated with an area under the receiver operating characteristic curve of 0.91. Demographic factors were not independently associated with admission. Severity of symptoms (odds ratio, 13) and intensity of therapy both before and during ED visit correlated with the likelihood of admission. Previous admission for asthma (P = .02) and recent use of inhaled corticosteroids (P = .04) also were associated with admission. Peak flows were associated with admission but were infrequently (23% overall) measured. Conclusion: Hospitalization for asthma exacerbation in children is primarily associated with clinical indicators in the ED and with historical factors such as previous asthma admission or intubation, recent use of corticosteroids, and comorbidity. C1 Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. Washington Univ, Sch Med, Childrens Hosp, St Louis, MO 63110 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pollack, CV (reprint author), Penn Hosp, Dept Emergency Med, 800 Spruce St, Philadelphia, PA 19107 USA. FU NHLBI NIH HHS [HL-63253, HL-03533, HL-07427] NR 39 TC 43 Z9 44 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 2002 VL 156 IS 9 BP 934 EP 940 PG 7 WC Pediatrics SC Pediatrics GA 591BG UT WOS:000177859400017 PM 12197803 ER PT J AU da Cunha, IT Lim, PA Qureshy, H Henson, H Monga, T Protas, EJ AF da Cunha, IT Lim, PA Qureshy, H Henson, H Monga, T Protas, EJ TI Gait outcomes after acute stroke rehabilitation with supported treadmill ambulation training: A randomized controlled pilot study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE ambulation; cerebrovascular accident; gait; rehabilitation; treadmill test ID BODY-WEIGHT SUPPORT; NONAMBULATORY HEMIPARETIC PATIENTS; MENTAL-STATE-EXAMINATION; ENERGY-EXPENDITURE; RECOVERY; WALKING; RELIABILITY; LOCOMOTION; THERAPY; SCALE AB Objective: To investigate gait outcomes with supported treadmill ambulation training (STAT) associated with regular rehabilitation in acute stroke survivors. Design: Randomized controlled trial, pilot study. Setting: Rehabilitation medicine service at a Veterans Affairs medical center. Participants: Seven acute stroke survivors assigned to regular intervention group and 6 patients assigned to STAT intervention. Interventions: Regular intervention consisted of 3 hours daily of physical therapy, kinesiotherapy, and occupational therapy. STAT group received regular rehabilitation with STAT substituted for usual gait training. Participants were tested at baseline, treated for an average of 3 weeks, and retested on discharge. The analysis of covariance procedure was used to test for differences between the 2 approaches. Main Outcome Measures: Functional Ambulation Category Scale, gait speed, walking distance, gait energy expenditure, and gait energy cost. Results: The small sample size did not generate enough power to detect significant differences in any variable. However, medium to large effect sizes of 0.7 and 1.16 standard deviation units were observed for gait energy cost and walk distance, respectively. Conclusions: This pilot study indicated that STAT is a safe, feasible, and promising intervention for acute stroke survivors. A larger trial is warranted for statistical relevance. C1 Texas Womans Univ, Sch Phys Therapy, Houston, TX USA. Houston Vet Affairs Med Ctr, Dept Phys Med & Rehabil, Houston, TX USA. Houston Vet Affairs Med Ctr, Rehabil Res & Dev Ctr Excellenve Healthy Aging &, Houston, TX USA. Singapore Gen Hosp, Singapore 0316, Singapore. RP Protas, EJ (reprint author), 1130 John Freeman Blvd, Houston, TX 77030 USA. NR 45 TC 85 Z9 89 U1 1 U2 17 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 SEP PY 2002 VL 83 IS 9 BP 1258 EP 1265 DI 10.1053/apmr.2002.34267 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 591AE UT WOS:000177856500011 PM 12235606 ER PT J AU Morales, TI AF Morales, TI TI The insulin-like growth factor binding proteins in uncultured human cartilage - Increases in insulin-like growth factor binding protein 3 during osteoarthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BOVINE ARTICULAR-CARTILAGE; FACTOR-I; IGF-I; INCREASED EXPRESSION; RECEPTOR; CHONDROCYTES; BINDING-PROTEIN-3; DISRUPTION; EXPLANTS; IGFBP-3 AB Objective. To assess changes in the insulin-like growth factor binding proteins (IGFBPs) in uncultured cartilage during stages of osteoarthritis (OA), and to determine if OA cartilage is capable of autocrine secretion of IGFBPs. Methods. Articular cartilage was dissected from fibrillated and nonfibrillated sites of 11 human femoral heads, and extracted in buffer containing 8M urea. IGFBPs were identified by immunoprecipitation and subsequent analysis by I-125-IGF-2 Western ligand blotting (WLB), radioimmunoassay, or 2-site immunoradiometric assay (IRMA). IGFBPs were assessed in cartilage extracts by WLB. IGFBP-3 content was determined by IRMA and synthesis by metabolic labeling with S-35-cysteine in organ cultures. Results. Sample grouping into 3 distinct OA strata was supported by gross pathology of the femoral heads, histologic grading of cartilage slices, and biochemical analysis of the glycosaminoglycan and protein content of the extracts. Group I was normal/mild OA, group II was intermediate OA, and group III was severe OA. IGFBP-2 was present in all samples, IGFBP-4 in sporadic samples, and BP-3 in group II-III samples. By IRMA, group I had a mean +/- SD of 6.26 +/- 2.6 ng IGFBP-3/mg soluble protein (IGFBP-3) (n = 6), group II had a mean +/- SD 14 +/- 7.5 IGFBP-3 (n = 10), and group III had a mean +/- SD 17.03 +/- 8.94 IGFBP-3 (n = 6). Analysis of variance showed group differences (F[3,19] = 3.84, P = 0.04), and post hoc tests revealed that IGFBP-3 levels were higher for group III versus group I (P = 0.04). OA cartilage synthesized IGFBP-3. Conclusion. Increases in net cartilage content of IGFBP-3 occurred in intact OA cartilage, reaching statistically significant elevation in severe disease. There was autocrine IGFBP-3 production in OA cartilage. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Jackson 1223,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R03-AG-16390] NR 27 TC 31 Z9 32 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 BP 2358 EP 2367 DI 10.1002/art.10482 PG 10 WC Rheumatology SC Rheumatology GA 600ZK UT WOS:000178421500011 PM 12355483 ER PT J AU Ibrahim, SA Siminoff, LA Burant, CJ Kwoh, CK AF Ibrahim, SA Siminoff, LA Burant, CJ Kwoh, CK TI Differences in expectations of outcome mediate African American/white patient differences in "willingness" to consider joint replacement SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TOTAL HIP-ARTHROPLASTY; RACIAL-DIFFERENCES; OSTEOARTHRITIS; PREFERENCES; KNEE; VALIDATION; DEPRESSION; POPULATION; ARTHRITIS; HEALTH AB Objective. Joint replacement therapy is an effective treatment option for end-stage osteoarthritis (OA) of the knee and/or hip. There are marked racial/ethnic disparities in the utilization of this procedure. The reasons for these disparities are not known. We sought to determine whether African American patients differ from white patients in their "willingness" to consider joint replacement and to determine the factors that influence this relationship. Methods. We performed a cross-sectional survey of 596 elderly, male, African American or white patients with moderate-to-severe symptomatic knee or hip OA who were receiving primary care at the Department of Veterans Affairs outpatient clinics. Results. The groups were similar with respect to age, severity of arthritis measured by the Lequesne Scale and the Western Ontario and McMaster Universities Osteoarthritis-Index, and scores on the Charlson Comorbidity Index and Geriatric Depression Scale. Compared with whites, African Americans were less likely to be employed or married or to have attained a high school education, but were more likely to report a median annual household income of <$10,000. They were also less likely than whites to be familiar with joint replacement and more likely to expect a longer duration of hospital course, pain, and functional disability following replacement surgery. African American patients were less "willing" than white patients to consider joint replacement (odds ratio 0.50, 95% confidence interval 0.30-0.84). However, this difference was explained by the between-group differences in expectations. Conclusion. African American patients were less likely than white patients to express "willingness" to consider joint replacement if the procedure was needed and recommended. This difference was explained by differences between the groups in their expectations of hospital course, pain, and function following replacement surgery. C1 VA Pittsburgh HealthCare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh HealthCare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11-E,130 A-U, Pittsburgh, PA 15240 USA. RI Siminoff, Laura /H-6277-2012 NR 34 TC 110 Z9 110 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 BP 2429 EP 2435 DI 10.1002/art.10494 PG 7 WC Rheumatology SC Rheumatology GA 600ZK UT WOS:000178421500019 PM 12355491 ER PT J AU Amante, EJB Choi, HK AF Amante, EJB Choi, HK TI Cause-specific mortality in rheumatoid arthritis: A meta-analysis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Hyon K Choi Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S457 EP S457 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801237 ER PT J AU Byrne, M O'Malley, K Suarez-Almazor, ME AF Byrne, M O'Malley, K Suarez-Almazor, ME TI Ethnic differences in arthritis health preferences: Analysis using willingness-to-pay. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Pittsburgh, Pittsburgh, PA USA. Baylor Coll Med, Houston VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S73 EP S73 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800122 ER PT J AU Choi, HK Atkinson, K Karlson, EW Curhan, G AF Choi, HK Atkinson, K Karlson, EW Curhan, G TI Weight gain, obesity, and incident gout in a large, long-term, prospective cohort study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S592 EP S592 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801623 ER PT J AU Choi, HK Michaud, K Wolfe, F AF Choi, HK Michaud, K Wolfe, F TI Utility measures in rheumatic disorders. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Arthrit Res Ctr Fdn, Wichita, KS USA. NR 0 TC 7 Z9 7 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S76 EP S76 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800129 ER PT J AU Costenbader, KH Liang, MH Karlson, EW AF Costenbader, KH Liang, MH Karlson, EW TI Cardiovascular risk factor awareness and management in systemic lupus erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S56 EP S56 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800070 ER PT J AU Hitchon, CA van Venrooij, W Mathis, D Matsumoto, I Benoist, C El-Gabalawy, HS AF Hitchon, CA van Venrooij, W Mathis, D Matsumoto, I Benoist, C El-Gabalawy, HS TI Native American Indians with early rheumatoid arthritis have a higher prevalence of autoantibodies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S542 EP S542 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801479 ER PT J AU Karlson, EW McAlindon, TE Massarotti, EM Fitzgerald, LM Drake-Saucer, B Jajoo, R Husni, E Costenbader, KH Atkinson, KV Amante, E Ang, HT Fraser, PA AF Karlson, EW McAlindon, TE Massarotti, EM Fitzgerald, LM Drake-Saucer, B Jajoo, R Husni, E Costenbader, KH Atkinson, KV Amante, E Ang, HT Fraser, PA TI A stud of a potential epidemiologic cluster of SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Brigham & Womens Hosp, RBB Arthritis & Musculoskeletal Dis Clin Res Ctr, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Women Courage, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S264 EP S265 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800675 ER PT J AU Messer, J Michaud, K Choi, HK Wolfe, F AF Messer, J Michaud, K Choi, HK Wolfe, F TI Lifetime direct medical costs of rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Wichita State Univ, Wichita, KS USA. Natl Data Bank Rheumat Dis, Wichita, KS USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S581 EP S581 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801592 ER PT J AU Michaud, K Messer, J Choi, HK Wolfe, F AF Michaud, K Messer, J Choi, HK Wolfe, F TI The economic consequences of changes in disease activity, functional status, and utility measure in patients with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Natl Data Bank Rheumat Dis, Wichita, KS USA. Wichita State Univ, Wichita, KS USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S581 EP S581 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801591 ER PT J AU Namjou, B Kilpatrick, J Kelly, JA Aberle, T Lam, T Reid, J Wilson, J Kimberly, RP Provost, TT James, JA Harley, JB AF Namjou, B Kilpatrick, J Kelly, JA Aberle, T Lam, T Reid, J Wilson, J Kimberly, RP Provost, TT James, JA Harley, JB TI Biopsy-proven vasculitis is related to genetic linkages at 1p36 and 3p14-12 in systemic lupus erythematosus (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Mississippi, US Dept Vet Affairs, Jackson, MS 39216 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, US Dept Vet Affairs Med Ctr, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S37 EP S37 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800016 ER PT J AU Ohmura, K Benoist, C Mathis, D AF Ohmura, K Benoist, C Mathis, D TI Development of Th1-directed but IL4-dependent arthritis in K/BxN mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S565 EP S565 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801546 ER PT J AU Singh, J Pando, J Tomaszewski, J Schumacher, R AF Singh, J Pando, J Tomaszewski, J Schumacher, R TI Quantitative immunobistochemistry of synovium in very early rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Minneapolis VA Med Ctr, Minneapolis, MN USA. None, Rehoboth Beach, DE USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S102 EP S102 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800203 ER PT J AU Tylaska, LA Boring, L Charo, IF Rollins, BJ Gladue, RP AF Tylaska, LA Boring, L Charo, IF Rollins, BJ Gladue, RP TI CCR2 regulates T cell activity and modulates the level of MCP-1/CCL2 at inflammatory sites. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Pfizer Global Res & Dev, Groton, CT USA. Gladstone Inst, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S387 EP S387 PG 1 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421801034 ER PT J AU Wong, AL Mittman, BS Aiso, J Beardmore, TD Louie, JS Kitridou, RC Harker, JO Paulus, HE AF Wong, AL Mittman, BS Aiso, J Beardmore, TD Louie, JS Kitridou, RC Harker, JO Paulus, HE TI A data driven approach to pharmacy policy for management of RA in a county healthcare system. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 66th Annual Scientific Meeting of the American-College-of-Rheumatology/37th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 24-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol, Assoc Rheumatol Hlth Profess C1 Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ So Calif, Sch Pharm, Los Angeles, CA USA. Rancho Los Amigos Natl Rehabil Ctr, Downey, CA USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. LAC, Los Angeles, CA USA. USC, Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2002 VL 46 IS 9 SU S BP S88 EP S89 PG 2 WC Rheumatology SC Rheumatology GA 600ZN UT WOS:000178421800169 ER PT J AU Quarterman, RL Moonly, S Wallace, AW Guccione, J Ratcliffe, MB AF Quarterman, RL Moonly, S Wallace, AW Guccione, J Ratcliffe, MB TI A finite element model of left ventricular cellular transplantation in dilated cardiomyopathy SO ASAIO JOURNAL LA English DT Article ID VOLUME REDUCTION SURGERY; IMPROVED HEART FUNCTION; STRESS; MECHANICS; MUSCLE; CARDIOMYOCYTES; MYOCARDIUM; ANEURYSM; GRAFTS; TISSUE AB Surgical therapies for heart failure that reduce left ventricular (LV) size have failed to improve LV function. Recent reports describe the direct injection of myocytes into the LV wall and suggest that myocyte transplantation improves regional contractile ability and improves LV function. Using a previously described finite element model, we simulated myocyte transplantation in the failing LV and tested the hypothesis that myocyte transplantation improves LV function (Starling relationship). An elastance model for active fiber stress was incorporated in an axisymmetric geometric model of the dilated, poorly contractile LV (dilated cardiomyopathy [DCM]). The nonlinear stress-strain relationship for the diastolic myocardium was anisotropic with respect to the local muscle fiber direction. Systolic material properties were depressed by assigning a peak intracellular calcium concentration (Ca2+) of 1.8 mumoL (normal value: 4.2 mumoL). Six different simulations of myocyte transplantation were performed in which transplanted areas were assigned a peak intracellular calcium concentration (Ca2+) of 4.2 mumoL. The pattern of myocyte engraftment was varied (transmural versus subepicardial; confluent versus heterogeneous), as was the amount of the LV free wall that was transplanted (17% vs 33%). Models were created and loaded with a range of physiologic LV pressures. Simulated myocyte transplantation increased the slope of the end-systolic elastance curve, improved the Starling relationship, and improved stroke volume and ejection fraction compared with DCM. This study demonstrated an improvement in LV function after myocyte transplantation. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Div Cardiothorac Surg, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, San Francisco, CA 94143 USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, 112D,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01-HL-58759, R01-HL-63348] NR 36 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD SEP-OCT PY 2002 VL 48 IS 5 BP 508 EP 513 DI 10.1097/01.MAT.0000026353.66193.6B PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 594GG UT WOS:000178040500012 PM 12296571 ER PT J AU Hegel, MT Barrett, JE Cornell, JE Oxman, TE AF Hegel, MT Barrett, JE Cornell, JE Oxman, TE TI Predictors of response to problem-solving treatment of depression in primary care SO BEHAVIOR THERAPY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; COGNITIVE-BEHAVIORAL-THERAPY; MINOR DEPRESSION; EMOTIONAL DISORDERS; HOMEWORK COMPLIANCE; MAJOR DEPRESSION; OLDER ADULTS; PSYCHOTHERAPY; DYSTHYMIA; IMPACT AB Problem-solving treatment of depression is a brief intervention specifically designed for primary care (PST-PC). To date, predictors of an optimal response to PST-PC have not been studied. In primary care, knowing such factors is essential for proper triage decisions. Patient, therapist, and process variables were evaluated for their ability to predict remission of minor depression or dysthymia in patients treated with PST PC. The most salient predictors of remission were the ability to understand the PST-PC rationale and to apply the PST-PC procedure in early treatment sessions, having a cognitive-behavioral therapist, and, for dysthymia, having a lower depression severity level at baseline. These results provide preliminary evidence of some factors associated with an optimal response to PST-PC and also present challenges for the ability to broadly disseminate the intervention. Modifications to the existing PST PC training program and directions for future research are discussed. C1 Dartmouth Coll Sch Med, Lebanon, NH 03756 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Affairs Hlth Care Syst, San Antonio, TX 78284 USA. RP Hegel, MT (reprint author), Dartmouth Hitchcock Med Ctr, Dept Psychiat, 1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 53 TC 25 Z9 25 U1 2 U2 4 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 0005-7894 J9 BEHAV THER JI Behav. Therapy PD FAL PY 2002 VL 33 IS 4 BP 511 EP 527 DI 10.1016/S0005-7894(02)80014-4 PG 17 WC Psychology, Clinical SC Psychology GA 607CZ UT WOS:000178774900003 ER PT J AU Seow, KT Xiong, JP Arnaout, MA Welge, J Rippmann, F Goodman, SL AF Seow, KT Xiong, JP Arnaout, MA Welge, J Rippmann, F Goodman, SL TI Divalent cations and the relationship between alpha A and beta A domains in integrins SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Meeting on Cell Signaling Transcription and Translation as Therapeutic Targets CY JAN 30-FEB 02, 2002 CL LUXEMBOURG, GERMANY DE integrin; alpha upsilon beta 3; alpha A domain; beta A domain; crystal structure ID FUNCTION-ASSOCIATED ANTIGEN-1; LIGAND-BINDING SITE; I-DOMAIN; CRYSTAL-STRUCTURE; DEPENDENT ADHESION; HIGH-AFFINITY; ACTIVATION; COLLAGEN; SUBUNIT; IDENTIFICATION AB Integrins contain either one or two von Willebrand factor A-like domains, which are primary ligand and cation binding regions in the molecules. Here we examine the first structure of an A domain of a beta subunit, in alphavbeta3 and compare it to known A domain structures of alpha subunits. Ligand binding to immobilized alphavbeta3 domain is stimulated by Ca2+ rather than inhibited by it. Biochemical, cell biological and structural evidence suggests that the A domain is a major site of ligand interaction in alphavbeta3. The Arg-Gly-Asp based inhibitor cilengitide (EMD 121974) inhibites ligand interaction with transmembrane-truncated alphavbeta3 in the presence of either Ca2+ or Mn2+ ions, and does so with similar kinetics. The alphavbeta3 structure reveals that both the alphaA and betaA domains share common structural cores. But, in contrast to alphaA, the betaA domain has three cation binding sites, that are involved either directly or indirectly in ligand binding. Structural alignment of alphaA and betaA domains reveals additional loops unique only to the betaA domain and much evidence support that that these loops are important for ligand binding specificity and for the interaction between alpha and beta subunits. Since the position of these loops are evolutionary conserved but their primary sequence varies between the various betaA domains, they represents potential targets for dissecting functional diversity among integrins. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Dept Preclin Res Oncol, D-64271 Darmstadt, Germany. Merck KGAA, Dept Bio & Chemoinformat, D-64271 Darmstadt, Germany. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Goodman, SL (reprint author), Dept Preclin Res Oncol, Frankfurterstr 250, D-64271 Darmstadt, Germany. NR 38 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD SEP PY 2002 VL 64 IS 5-6 BP 805 EP 812 AR PII S0006-2952(02)01142-5 DI 10.1016/S0006-2952(02)01142-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 599XU UT WOS:000178361100008 PM 12213573 ER PT J AU Suri, R Stowe, ZN Hendrick, V Hostetter, A Widawski, M Altshuler, LL AF Suri, R Stowe, ZN Hendrick, V Hostetter, A Widawski, M Altshuler, LL TI Estimates of nursing infant daily dose of fluoxetine through breast milk SO BIOLOGICAL PSYCHIATRY LA English DT Article DE breastfeeding; postpartum; depression; fluoxetine; collection; infant ID POSTNATAL DEPRESSION; POSTPARTUM DEPRESSION; EXCRETION; DESMETHYLSERTRALINE; NORFLUOXETINE; SERTRALINE; PAROXETINE; CITALOPRAM AB Background: This study compared three methods of estimating the daily dose of fluoxetine to nursing infants and the relationship between these estimates and infant serum concentrations. Methods: Breast milk and infant serum concentrations of fluoxetine and norfluoxetine were obtained from 10 nursing mother-infant pairs. Quantification of daily infant dose was determined by three methods: 1) collection of the total volume of breast milk over 24 hours and determination of the average breast milk concentration (Baby's Total Daily Dose); 2) determination of the maximum and minimum breast milk concentrations during 24 hours and an estimated milk consumption of 150 mL/kg/day (Atkinson Model); and 3) determination of the gradient of excretion of medication into breast milk at a specified time after the maternal dose, applying this gradient to each nursing collection and summing the values over 24 hours (Mathematical Model). The relationship between the 24-hour medication dose, obtained from each method, and the infant serum concentrations was examined. Results: A total of 177 breast milk and 10 infant serum samples were collected. An estimate of the infant daily medication dose obtained by the Mathematical Model was the best predictor of total infant serum concentration. Conclusions: Breast milk analysis may allow one to determine whether medication concentrations will be detectable in an infant, eliminating the need for an infant serum concentration. Although the Mathematical Model seems to reflect infant serum concentration most accurately, all three methods suggest that the maximum dose that a nursing child receives over the course of a year equals as much as 120 mg, or 160 +/- 47% of the maternal daily dose. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90095 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Suri, R (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, 300 UCLA Med Plaza,Suite 2339, Los Angeles, CA 90095 USA. NR 18 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2002 VL 52 IS 5 BP 446 EP 451 AR PII S0006-3223(02)01368-9 DI 10.1016/S0006-3223(02)01368-9 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 593HN UT WOS:000177985100009 PM 12242061 ER PT J AU Lipsitz, SR Fitzmaurice, GM Ibrahim, JG Gelber, R Lipshultz, S AF Lipsitz, SR Fitzmaurice, GM Ibrahim, JG Gelber, R Lipshultz, S TI Parameter estimation in longitudinal studies with outcome-dependent follow-up SO BIOMETRICS LA English DT Article DE estimating equations; follow-up time process; maximum likelihood; multivariate normal distribution ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DOXORUBICIN THERAPY; CHILDHOOD; MODELS; CANCER AB In many observational studies, individuals are measured repeatedly over time, although not necessarily at a set. of prespecified occasions. Instead, individuals may be measured at irregular intervals, with those having a history of poorer health outcomes being measured with somewhat greater frequency and regularity: i.e., those individuals with poorer health outcomes may have more frequent follow-up measurements and the intervals between their repeated measurements may be shorter. In this article, we consider estimation of regression parameters in models for longitudinal data where the follow-up times are not fixed by design but can depend on previous outcomes. In particular, we focus on general linear models for longitudinal data where the repeated measures are assumed to have a multivariate Gaussian distribution. We consider assumptions regarding the follow-up time process that result in the likelihood function separating into two components: one for the follow-up time process, the other for the outcome process. The practical implication of this separation is that the former process can be ignored when making likelihood-based inferences about the latter; i.e., maximum likelihood (ML) estimation of the regression parameters relating the mean of the longitudinal outcomes to covariates does not require that a model for the distribution of follow-up times he specified. As a result, standard statistical software, e.g., SAS PROC MIXED (Littell et al.. 1996; SAS System for Mixed Models), can be used to analyze the data. However, we also demonstrate that misspecification of the model for the covariance among the repeated measures will, in general, result in regression parameter estimates that are biased. Furthermore, results of a simulation study indicate that the potential bias due to misspecification of the covariance can be quite considerable in this setting. Finally, we illustrate these results using data from a longitudinal observational study (Lipshultz et al., 1995, New England Journal of Medicine 332, 1738-1743) that explored the cardiotoxic effects of doxorubicin chemotherapy for the treatment of acute lymphoblastic leukemia in children. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Harvard Sch Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. RP Lipsitz, SR (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, 135 Rutledge Ave, Charleston, SC 29425 USA. FU NCI NIH HHS [CA 70101, CA 55576, CA 74015, CA-68484]; NIGMS NIH HHS [GM 29745]; NIMH NIH HHS [MH 17119] NR 12 TC 48 Z9 49 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2002 VL 58 IS 3 BP 621 EP 630 DI 10.1111/j.0006-341X.2002.00621.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 680KF UT WOS:000182975800016 PM 12229997 ER PT J AU Ramanujan, S Pluen, A McKee, TD Brown, EB Boucher, Y Jain, RK AF Ramanujan, S Pluen, A McKee, TD Brown, EB Boucher, Y Jain, RK TI Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium SO BIOPHYSICAL JOURNAL LA English DT Article ID EXTRACELLULAR-SPACE; SOLID TUMORS; HYALURONIC-ACID; AGAROSE GELS; IN-VITRO; MACROMOLECULES; TORTUOSITY; MOLECULES; DELIVERY; CELLS AB Diffusion coefficients of tracer molecules in collagen type I gels prepared from 0-4.5% w/v solutions were measured by fluorescence recovery after photobleaching. When adjusted to account for in vivo tortuosity, diffusion coefficients in gels matched previous measurements in four human tumor xenografts with equivalent collagen concentrations. In contrast, hyaluronan solutions hindered diffusion to a lesser extent when prepared at concentrations equivalent to those reported in these tumors. Collagen permeability, determined from flow through gels under hydrostatic pressure, was compared with predictions obtained from application of the Brinkman effective medium model to diffusion data. Permeability predictions matched experimental results at low concentrations, but underestimated measured values at high concentrations. Permeability measurements in gels did not match previous measurements in tumors. Visualization of gels by transmission electron microscopy and light microscopy revealed networks of long collagen fibers at lower concentrations along with shorter fibers at high concentrations. Negligible assembly was detected in collagen solutions pregelation. However, diffusion was similarly hindered in pre and postgelation samples. Comparison of diffusion and convection data in these gels and tumors suggests that collagen may obstruct diffusion more than convection in tumors. These findings have significant implications for drug delivery in tumors and for tissue engineering applications. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, EL Steele Lab Tumor Biol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu RI Kipke, Daryl/A-2167-2009; Pluen, Alain/F-5300-2015; OI Pluen, Alain/0000-0002-5953-8011; McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [F32-CA83248, F32CA88490, P01-CA-80124, R53-CA56591]; NIGMS NIH HHS [5 T32 GM08334] NR 42 TC 239 Z9 242 U1 2 U2 56 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 2002 VL 83 IS 3 BP 1650 EP 1660 PG 11 WC Biophysics SC Biophysics GA 589RQ UT WOS:000177774500038 PM 12202388 ER PT J AU Hu, P Zelen, M AF Hu, P Zelen, M TI Experimental design issues for the early detection of disease: novel designs SO BIOSTATISTICS LA English DT Article ID CANCER-SCREENING PROGRAMS; BREAST-CANCER; DEATH RATES; FOLLOW-UP; MORTALITY; MAMMOGRAPHY; TRIAL AB This paper investigates two experimental designs which have been used to evaluate the benefit of the early detection of breast cancer. They have some advantages over a classical design (the screening program versus usual medical care) in that subjects in a control group may benefit by participating in the study. We refer to the two experimental designs as the up-front (UFD) and close-out (COD) designs. The UFD consists of offering an initial exam to all participants. Then they can be randomized to a usual care group or a screening group receiving one or more special examinations. If the outcome of the initial examination is included in the analysis, then the study can answer the question of the benefit of an additional screening program after an initial examination. If the analysis excludes all the cases diagnosed at the initial examination, then the analysis evaluates the benefit of a screening program after elimination of the prevalent cases. These prevalent cases are most likely to be affected by length bias sampling and consequently will tend to have less aggressive disease and live longer. As a result, the UFD can answer two scientific questions. The COD consists of randomizing subjects to a usual care group and a screened group. However, the usual care group receives an examination which coincides at the time of the last exam in the study group. In this paper the power of these two designs have been evaluated. In both cases the power is severely reduced compared to the usual control group receiving no special exams. The power is a function of the sensitivity of the exam, the number and spacings of the exams given to the screened group as well as the sample size, disease incidence of the population and the survival distribution. The theoretical results on power are applied to the Canadian National Breast Cancer Study (ages 40-49) which used an UFD and the Stockholm Mammography Breast Cancer Screening Trial which utilized a COD. C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hu, P (reprint author), NCI, Biometry Res Grp, Bethesda, MD 20892 USA. NR 38 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD SEP PY 2002 VL 3 IS 3 BP 299 EP 313 DI 10.1093/biostatistics/3.3.299 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 678YQ UT WOS:000182894600001 PM 12933599 ER PT J AU Herring, AH Ibrahim, JG AF Herring, AH Ibrahim, JG TI Maximum likelihood estimation in random effects cure rate models with nonignorable missing covariates SO BIOSTATISTICS LA English DT Article DE cure rate model; Gibbs sampling; missing covariates; Monte Carlo EM algorithm; nonignorable missing data; random effects; survival analysis ID PROPORTIONAL HAZARDS REGRESSION; MIXTURE-MODELS; SURVIVAL-DATA; MONTE-CARLO; EM ALGORITHM; RISK; FRACTION; MELANOMA; TESTS; RANK AB We introduce a method of parameter estimation for a random effects cure rate model. We also propose a methodology that allows us to account for nonignorable missing covariates in this class of models. The proposed method corrects for possible bias introduced by complete case analysis when missing data are not missing completely at random and is motivated by data from a pair of melanoma studies conducted by the Eastern Cooperative Oncology Group in which clustering by cohort or time of study entry was suspected. In addition, these models allow estimation of cure rates, which is desirable when we do not wish to assume that all subjects remain at risk of death or relapse from disease after sufficient follow-up. We develop an EM algorithm for the model and provide an efficient Gibbs sampling scheme for carrying out the E-step of the algorithm. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Herring, AH (reprint author), Univ N Carolina, Dept Biostat, Campus Box 7420, Chapel Hill, NC 27599 USA. NR 37 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD SEP PY 2002 VL 3 IS 3 BP 387 EP 405 DI 10.1093/biostatistics/3.3.387 PG 19 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 678YQ UT WOS:000182894600007 PM 12933605 ER PT J AU Gilliland, DG Griffin, JD AF Gilliland, DG Griffin, JD TI The roles of FLT3 in hematopoiesis and leukemia SO BLOOD LA English DT Review ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; RECEPTOR TYROSINE KINASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL FACTOR; EXPRESSING DIFFERENT LEVELS; GROWTH-FACTOR RECEPTOR; COLONY-FORMING CELLS; PROGENITOR CELLS; MURINE FLT3 AB FLT3 is a receptor tyrosine kinase expressed by immature hematopoietic cells and is important for the normal development of stem cells and the immune system. The ligand for FLT3 is expressed by marrow stromal cells and other cells and synergizes with other growth factors to stimulate proliferation of stem cells, progenitor cells, dendritic cells, and natural killer cells. Mutations of FLT3 have been detected in about 30% of patients with acute myelogenous leukemia and a small number of patients with acute lymphocytic leukemia or myelodysplastic syndrome. Patients with FLT3 mutations tend to have a poor prognosis. The mutations most often involve small tandem duplications of amino acids within the juxtamembrane domain of the receptor and result in constitutive tyrosine kinase activity. Expression of a mutant FLT3 receptor in murine marrow cells results in a lethal myeloproliferative syndrome and preliminary studies suggest that mutant FLT3 cooperates with other leukemia oncogenes to confer a more aggressive phenotype. Taken together, these results suggest that FLT3 is an attractive therapeutic target for kinase inhibitors or other approaches for patients with mutations of this gene. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, 4 Blackfan Circle,Room 418, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA66996]; NIDDK NIH HHS [P01 DK5654] NR 151 TC 724 Z9 760 U1 8 U2 48 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1532 EP 1542 DI 10.1182/blood-2002-02-0492 PG 11 WC Hematology SC Hematology GA 587WU UT WOS:000177667700006 PM 12176867 ER PT J AU Sparano, JA Weller, E Nazeer, T Habermann, T Traynor, AE Manalo, J Cassileth, P AF Sparano, JA Weller, E Nazeer, T Habermann, T Traynor, AE Manalo, J Cassileth, P TI Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma: an Eastern Cooperative Oncology Group trial (E3493) SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; HIGHLY-ACTIVE REGIMEN; B-CELL LYMPHOMA; CHEMOTHERAPY REGIMENS; CHOP CHEMOTHERAPY; RANDOMIZED TRIAL; TOXICITY; SCHEDULE; IDEC-C2B8; REMISSION AB Preclinical and clinical evidence suggest a potential advantage for infusional therapy In lymphoma. Sixty-two analyzable patients with predominantly Intermediate-grade non-Hodgkin lymphoma received cyclophosphamide (200 mg/m(2) per day), doxorubicin (12.5 mg/m(2) per day), and etoposide (60 mg/m(2) per day) (CDE) by continuous intravenous Infusion for 4 days (96 hours) every 3 weeks for a maximum of 8 cycles. By the age-adjusted International Prognostic Index (IPI), 42% were at high risk and 58% were at high-intermediate risk. Complete response (CR) occurred In 30 (48%) patients (95% confidence Interval [CI], 35%, 64%), and partial response occurred in 16 (26%) patients, yielding an overall response rate of 74% (95% CI, 62%, 84%). Failure-free survival (FFS) rates at 1 and 2 years were 55% (95% CI, 43%, 67%) and 50% (95% CI, 38%, 62%), respectively. When comparing the outcome for 62 patients receiving infusional CDE with historical data derived from 927 IPI-matched lymphoma patients using a Cox proportional hazards model, there was a nonsignificant trend favoring CDE in FFS (P = .12) and overall survival (P = .09). Severe or life-threatening toxicity included neutropenia (68%), anemia (57%), thrombocytopenia (44%), and infection (24%). Two patients (3%) died of treatment-related Infectious complications. The primary end point of improving 1-year FFS from 55% to 70% was not achieved with infusional CDE given as initial therapy in patients with poor-risk Intermediate-grade lymphoma. It Is unlikely that infusional therapy as used In this study produces a 25% or greater relative improvement In FFS compared with standard therapy. (C) 2002 by The American Society of Hematology. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Oncol, Montefiore Med Ctr, Bronx, NY 10461 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. Albany Med Coll, Albany, NY 12208 USA. Mayo Clin, Rochester, MN USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. Univ Miami, Sylvester Canc Ctr, Miami, FL 33152 USA. RP Sparano, JA (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Oncol, Montefiore Med Ctr, 2 South,Rm 47,1825 Eastchester Rd, Bronx, NY 10461 USA. FU NCI NIH HHS [CA13650, CA06594, CA14958, CA17145, CA21115, CA23318, CA66636] NR 45 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1634 EP 1640 PG 7 WC Hematology SC Hematology GA 587WU UT WOS:000177667700021 PM 12176882 ER PT J AU Mapara, MY Kim, YM Wang, SP Bronson, R Sachs, DH Sykes, M AF Mapara, MY Kim, YM Wang, SP Bronson, R Sachs, DH Sykes, M TI Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELLS; ADOPTIVE IMMUNOTHERAPY; DELAYED INFUSION; DISEASE; THERAPY; TRANSFUSIONS; RESPONSES; PRESERVES AB In mice, donor leukocyte infusion (DLI) given to established mixed allogeneic chimeras can mediate powerful graft-versus-host (GVH) reactions confined to the lymphohematopoietic system without inducing graft-versus-host disease (GVHD). In a clinical trial attempting to capture this approach to achieve graft-versus-leukemia/lymphoma (GVL) effects without GVHD, we have observed surprisingly powerful antitumor effects of DLI in patients achieving mixed chimerism after nonmyeloablative bone marrow transplantation. This observation led us to hypothesize that host antigen-presenting cells in mixed chimeras might be required to optimally present recipient antigens to the donor lymphocytes, leading to maximal graft-versus-tumor effects. To test this hypothesis, we established mixed and fully allogeneic hematopoietic chimeras in B6 mice and evaluated the effect of DLI on EL4 T-cell lymphoma. DLI administration to mixed chimeras produced dramatically improved leukemia-free survival compared to administration of DLI to full donor chimeras. DLI also converted mixed chimeras to full chimeras without causing GVHD. The magnitude of the GVL effect was dependent on the level of major histocompatibility complex class I expression on recipient hematopoietic cells in mixed chimeras. Thus, the induction of mixed chimerism followed by delayed DLI provides an approach to inhibiting GVHD that optimizes GVL effects. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E Bldg 149-5102, Boston, MA 02129 USA. RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01 CA 79989] NR 26 TC 169 Z9 172 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1903 EP 1909 DI 10.1182/blood-2002-01-0023 PG 7 WC Hematology SC Hematology GA 587WU UT WOS:000177667700054 PM 12176915 ER PT J AU Deng, HY Chu, JT Rettig, MB Martinez-Maza, O Sun, R AF Deng, HY Chu, JT Rettig, MB Martinez-Maza, O Sun, R TI Rta of the human herpesvirus 8/Kaposi sarcoma-associated herpesvirus up-regulates human interleukin-6 gene expression SO BLOOD LA English DT Article ID MULTICENTRIC CASTLEMANS-DISEASE; PRIMARY EFFUSION LYMPHOMA; NF-KAPPA-B; EPSTEIN-BARR-VIRUS; KAPOSIS-SARCOMA; VIRAL INTERLEUKIN-6; DNA-SEQUENCES; CELLS; LYMPHOCYTES; ACTIVATION AB Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus (KSHV) is linked to a number of malignancies thought to be driven by cytokines, including interieukin-6 (IL-6). Rta, a transcriptional activator encoded by HHV-8/KSHV, activates the viral lytic cycle leading to the expression of several viral genes implicated in viral pathogenesis. However, the effect of HHV-8/KSHV Rta on cellular genes has not been reported. We present.. evidence that the human IL-6 (hIL-6) gene is up-regulated by Rta. Rta potently activated (up to 164-fold) the hIL-6 promoter in a dose-dependent manner in a transient transfection reporter system. Rta also induced expression of the endogenous hIL-6 gene, as shown by enzyme-linked immunosorbent assays. Activation of the hIL-6 gene by HHV-8/KSHV supports the role of hIL-6 in the development of these malignancies. (C) 2002 by The American Society of Hematology. C1 Univ Calif Los Angeles, Dent Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP Sun, R (reprint author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RI Martinez-Maza, Otoniel/B-2667-2009 OI Martinez-Maza, Otoniel/0000-0003-1364-0675 FU NCI NIH HHS [CA83525, CA57152, CA91791]; NIDCR NIH HHS [DE14153] NR 25 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2002 VL 100 IS 5 BP 1919 EP 1921 DI 10.1182/blood-2002-01-0015 PG 3 WC Hematology SC Hematology GA 587WU UT WOS:000177667700058 PM 12176919 ER PT J AU Ryoo, JJ Cole, CE Anderson, KC AF Ryoo, JJ Cole, CE Anderson, KC TI Novel therapies, for multiple myeloma SO BLOOD REVIEWS LA English DT Review DE multiple myeloma; proteasome inhibitors; thalidomide; immunomodulatory drugs; arsenic trioxide; angiogenesis; cytokines ID NF-KAPPA-B; BONE-MARROW ANGIOGENESIS; ENDOTHELIAL GROWTH-FACTOR; PROTEASOME INHIBITOR PS-341; INDUCED CELL-DEATH; ARSENIC TRIOXIDE; INDUCED APOPTOSIS; DRUG-RESISTANCE; INTERLEUKIN-6 SECRETION; CYTOKINE PRODUCTION AB Multiple myeloma (MM) continues to evade cure by conventional therapies, increasing the urgency for new, biologically based treatments. Reviewed in this discussion are novel chemotherapies under clinical trial that capitalize upon greater comprehension of tumor pathophysiology. In targeting tumor biology, these therapies serve. as a model of treatment with great potential for improving outcomes in patients with MM. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Ryoo, JJ (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 97 TC 5 Z9 5 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 0268-960X J9 BLOOD REV JI Blood Rev. PD SEP PY 2002 VL 16 IS 3 BP 167 EP 174 DI 10.1016/S0268-960X(02)00009-7 PG 8 WC Hematology SC Hematology GA 595MT UT WOS:000178113900002 PM 12163002 ER PT J AU Restrepo, A Devore, P Encarnacion, CE Wholey, MH Schneider, D Callander, NS Ferral, H Postoak, D Anderson, JE Walsh, T Padayao, G Gokmen, E Ehsan, A Ochoa, L Neumon, B West, G Restrepo, MI Przykucki, J Patterson, J Freytes, CO AF Restrepo, A Devore, P Encarnacion, CE Wholey, MH Schneider, D Callander, NS Ferral, H Postoak, D Anderson, JE Walsh, T Padayao, G Gokmen, E Ehsan, A Ochoa, L Neumon, B West, G Restrepo, MI Przykucki, J Patterson, J Freytes, CO TI Performance of a hybrid central venous catheter utilized for both peripheral blood stem cell harvest and transplant support of patients undergoing autologous peripheral blood stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE catheters; indwelling; infection; hematopoietic stem cell transplantation ID PROGENITOR CELLS; CANCER-PATIENTS; RISK-FACTORS; COMPLICATIONS; INFECTIONS; MARROW; CHEMOTHERAPY; COLLECTION; HICKMAN; DEVICES AB Patients undergoing autologous peripheral blood stem cell transplantation (PBSC) frequently require the sequential insertion of two central venous catheters, one for leukapheresis and one for transplant support. Hybrid catheters suitable for leukapheresis and long-term use have been increasingly used, but there is limited information regarding their performance and complication rate. The purpose of this study was to determine the performance of the Pheres-Flow hybrid catheter when utilized for both leukapheresis and transplant support, with particular emphasis on the incidence of infectious and occlusive complications. We prospectively analyzed the performance of 92 catheters in 82 consecutive patients who underwent autologous peripheral blood stem cell (PBSC) transplantation. Occlusion was the most frequent complication of this catheter with 29% of the patients experiencing difficulty drawing blood or infusing fluids. Infection was another frequent complication. Twenty-two percent of patients developed catheter-related bloodstream infections and 15 catheters had to be removed because of proven or suspected infection that did not respond to antibiotic therapy. Nevertheless, 77% of patients were able to complete leukapheresis and transplant support with only one catheter. We conclude that the utilization of the Pheres-Flow catheter for both leukapheresis and transplant support is feasible, but that new strategies need to be developed to decrease the incidence of occlusive and infectious complications of hybrid catheters. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Freytes, CO (reprint author), Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD SEP PY 2002 VL 30 IS 6 BP 389 EP 395 DI 10.1038/sj.bmt.1703647 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 603EK UT WOS:000178545700009 PM 12235524 ER PT J AU Jones, DS AF Jones, DS TI Tobacco use by Native North Americans: Sacred smoke and silent SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jones, DS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD FAL PY 2002 VL 76 IS 3 BP 611 EP 612 DI 10.1353/bhm.2002.0130 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 592CM UT WOS:000177919200022 ER PT J AU Dasgupta, RA Schulz, JT Lee, RC Ryan, CM AF Dasgupta, RA Schulz, JT Lee, RC Ryan, CM TI Severe hypokalemia as a cause of acute transient paraplegia following electrical shock SO BURNS LA English DT Article DE electrical burn; acute flaccid paralysis; paraplegia; hypokalemia; periodic paralysis; metabolic acidosis ID PERIODIC PARALYZES; BURNS; MEMBRANE; INJURIES; TRAUMA AB Transient lower extremity paralysis has been previously reported following high voltage electrical injury. The following case report describes an unusual presentation of transient acute flaccid lower extremity paralysis following a high voltage electrical injury associated with profound hypokalemia and acid/base abnormalities similar to the periodic paralysis syndrome. The patient's symptoms resolved with correction of severe hypokalemia. Potential mechanisms for a metabolic neuromuscular disorder induced by electrical injury are proposed. (C) 2002 Elsevier Science Ltd and ISBI. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Sumner Redstone Burn Ctr, Boston, MA 02114 USA. RP Ryan, CM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv,Sumner Redstone Burn Ctr, Bigelow 1302, Boston, MA 02114 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD SEP PY 2002 VL 28 IS 6 BP 609 EP 611 AR PII S0305-4179(02)00063-3 DI 10.1016/S0305-4179(02)00063-3 PG 3 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 602TK UT WOS:000178520400015 PM 12220923 ER PT J AU Morrow, M Strom, EA Bassett, LW Dershaw, DD Fowble, B Harris, JR O'Malley, F Schnitt, SJ Singletary, SE Winchester, DP AF Morrow, M Strom, EA Bassett, LW Dershaw, DD Fowble, B Harris, JR O'Malley, F Schnitt, SJ Singletary, SE Winchester, DP TI Standard for the management of ductal carcinoma in situ of the breast (DCIS) SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID SURGICAL ADJUVANT BREAST; RANDOMIZED CLINICAL-TRIAL; IN-SITU; INTRADUCTAL CARCINOMA; RADIATION-THERAPY; FOLLOW-UP; CONSERVING SURGERY; LOCAL RECURRENCE; CONSERVATIVE SURGERY; DEFINITIVE IRRADIATION AB The multidisciplinary guidelines for management of ductal carcinoma in situ of the breast from the American College of Radiology, the American College of Surgeons, the College of American Pathology, and the Society of Surgical Oncology have been updated to take into account continuing advances in the diagnosis and treatment of this disease. The continued growth in mammographic evaluation and technology has resulted in an increase in the diagnosis of ductal carcinoma in situ of the breast (DCIS). The resulting guidelines provide a framework for clinical decision-making for patients with DCIS based on review of relevant literature, and includes information on patient selection and evaluation, technical aspects of surgical treatment, techniques of irradiation, and follow-up care. C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Lynn Sage Breast Ctr, Chicago, IL USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Univ Calif Los Angeles, Sch Med,Med Ctr, Iris Cantor Ctr Breast Imaging, Dept Radiol Sci,Jonsson Comprehens Canc Ctr, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Northwestern Univ, Feinberg Sch Med, Evanston, IL USA. Evanston NW Hlth Care, Dept Surg, Evanston, IL USA. RP Morrow, M (reprint author), Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 119 TC 81 Z9 84 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 2002 VL 52 IS 5 BP 256 EP 276 PG 21 WC Oncology SC Oncology GA 601VK UT WOS:000178469100002 PM 12363325 ER PT J AU Morrow, M Strom, EA Bassett, LW Dershaw, DD Fowble, B Giuliano, A Harris, JR O'Malley, F Schnitt, SJ Singletary, SE Winchester, DP AF Morrow, M Strom, EA Bassett, LW Dershaw, DD Fowble, B Giuliano, A Harris, JR O'Malley, F Schnitt, SJ Singletary, SE Winchester, DP TI Standard for breast conservation therapy in the management of invasive breast carcinoma SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; SURGICAL ADJUVANT BREAST; COMPARING TOTAL MASTECTOMY; NEGATIVE LYMPH-NODES; RADIATION-THERAPY; CONSERVING SURGERY; STAGE-I; CANCER PATIENTS; AXILLARY DISSECTION; MARGIN STATUS AB Multidisciplinary guidelines for management of invasive breast carcinoma from the American College of Radiology, the American College of Surgeons, the College of American Pathology, and the Society of Surgical Oncology have been updated to reflect the continuing advances in the diagnosis and treatment of invasive breast cancer. The guidelines provide a framework for clinical decision-making for patients with invasive breast carcinoma based on review of relevant literature and include information on patient selection and evaluation, technical aspects of surgical treatment, techniques of irradiation, and follow-up care. C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Lynn Sage Breast Ctr, Chicago, IL USA. MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA. Univ Calif Los Angeles, Iris Cantor Ctr Breast Imaging, Dept Radiol Sci,Sch Med, Med Ctr,Jonssson Comprehens Canc Ctr, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Calif Los Angeles, Joyce Eisenberg Keefer Breast Ctr, Med Ctr, Los Angeles, CA 90024 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Lab Med & Pathol, Toronto, ON, Canada. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Evanston NW Hlth Care, Feinberg Sch Med, Evanston, IL USA. Evanston NW Hlth Care, Dept Surg, Evanston, IL USA. RP Morrow, M (reprint author), Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 99 TC 143 Z9 160 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD SEP-OCT PY 2002 VL 52 IS 5 BP 277 EP 300 PG 24 WC Oncology SC Oncology GA 601VK UT WOS:000178469100003 PM 12363326 ER PT J AU Kornblith, AB Kemeny, M Peterson, BL Wheeler, J Crawford, J Bartlett, N Fleming, G Graziano, S Muss, H Cohen, HJ AF Kornblith, AB Kemeny, M Peterson, BL Wheeler, J Crawford, J Bartlett, N Fleming, G Graziano, S Muss, H Cohen, HJ CA Canc Leukemia Group B TI Survey of oncologists' perceptions of barriers to accrual of older patients with breast carcinoma to clinical trials SO CANCER LA English DT Article DE accrual; clinical trials; breast carcinoma; elderly patients; physician perspective ID CANCER-TREATMENT TRIALS; ELDERLY-PATIENTS; REPRESENTATION AB BACKGROUND. Prior research has documented the under-representation in clinical trials of older patients with cancer. In part of a larger study to test the magnitude of these barriers to entering eligible older patients with carcinoma of the breast into clinical trials (Cancer and Leukemia Group B [CALGB] trial 9670), barriers to accruing eligible older patients to clinical trials were obtained from the physician's perspective. METHODS. One hundred fifty-six physicians (85% oncologists) who treated patients with breast carcinoma at 10 CALGB institutions completed a questionnaire concerning what they perceived as barriers to enrolling older patients with breast carcinoma on clinical trials and possible interventions that may improve accrual. RESULTS. Physicians' perceptions of the most important barriers to accrual of older patients were: 1) elderly patients have significant comorbid conditions that are not excluded by the protocol but that may affect how they would respond to treatment (16%); elderly patients have difficulty understanding what is required in a complicated treatment trial, resulting in poor compliance (16%); treatment toxicity (14%); and elderly patients often do not meet the eligibility criteria (15%). Oncologists most frequently suggested that the most effective interventions for improving the accrual of elderly patients to trials included making personnel available in the clinic to explain clinical trials to older patients and their families (25%) and providing physicians with educational materials concerning treatment toxicity in the elderly (18%). CONCLUSIONS. Physicians viewed barriers to accruing older patients with breast carcinoma to clinical trials as multidimensional, with the most important involving protocol requirements, treatment specific issues, and older patients' medical and cognitive characteristics. Thus, a variety of interventions would be needed to improve accrual of older patients to clinical trials, including increasing physicians' knowledge concerning treatment toxicity in the elderly, simplifying protocol requirements, and reducing treatment toxicity. C1 Dana Farber Canc Inst, Womens Canc Program, Boston, MA 02115 USA. Queens Med Ctr, Queens, NY USA. Duke Univ, Med Ctr, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Duke Univ, Med Ctr, Data Management Ctr, Canc & Leukemia Grp B, Durham, NC USA. Vet Adm Med Ctr, Durham, NC USA. Washington Univ, Med Ctr, St Louis, MO USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. SUNY Upstate Med Univ, Syracuse, NY USA. Vermont Reg Canc Ctr, Burlington, VT USA. RP Kornblith, AB (reprint author), Dana Farber Canc Inst, Womens Canc Program, Room D1210,44 Binney St, Boston, MA 02115 USA. EM alice_kornblith@dfci.harvard.edu FU NCI NIH HHS [CA31946] NR 15 TC 102 Z9 102 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 1 PY 2002 VL 95 IS 5 BP 989 EP 996 DI 10.1002/cncr.10792 PG 8 WC Oncology SC Oncology GA 586VF UT WOS:000177606000006 PM 12209681 ER PT J AU Vaughn, DJ Manola, J Dreicer, R See, W Levitt, R Wilding, G AF Vaughn, DJ Manola, J Dreicer, R See, W Levitt, R Wilding, G TI Phase II study of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction (E2896) - A trial of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 19-23, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Oncol DE bladder carcinoma; renal dysfunction; chemotherapy; paclitaxel; carboplatin ID TRANSITIONAL-CELL CARCINOMA; SURVIVAL; THERAPY; REGIMEN; CANCER AB BACKGROUND. Chemotherapy options for the patients with advanced urothelial carcinoma and renal dysfunction are limited. The authors performed a Phase II trial of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium and renal dysfunction. METHODS. Forty-two patients were accrued; 37 eligible patients were treated. Patients received paclitaxel 225 mg/m(2) over three hours followed by carboplatin targeted area under the concentration-time curve = 6 mg/mL . minute every three weeks for up to six cycles. RESULTS. The median number of cycles received was four (range, one to six). The objective response rate was 24.3% (95% confidence interval, 11.9-41.7%). The median progression free survival was 3 months and the median overall survival was 7.1 months. The number of poor prognostic risk factors (Eastern Cooperative Oncology Group performance status >1 or lung, liver, or bone metastases) significantly predicted for survival. The most common greater than or equal to1 Grade 3 toxicities included granulocytopenia (60%) and neurotoxicity (35%). CONCLUSIONS. Paclitaxel/carboplatin is a chemotherapy option for patients with advanced urothelial carcinoma and renal dysfunction. Future trials in chemotherapy development for this patient population are warranted. C1 Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Roger Marris Canc Ctr, Fargo, ND USA. Univ Wisconsin, Madison, WI USA. RP Vaughn, DJ (reprint author), Univ Penn, Abramson Canc Ctr, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA15488, CA21115, CA13650, CA21076, CA23318, CA66636] NR 14 TC 55 Z9 55 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2002 VL 95 IS 5 BP 1022 EP 1027 DI 10.1002/cncr.10782 PG 6 WC Oncology SC Oncology GA 586VF UT WOS:000177606000011 PM 12209686 ER PT J AU Pawlik, TM Nakamura, H Mullen, JT Kasuya, H Yoon, SS Chandrasekhar, S Chiocca, EA Tanabe, KK AF Pawlik, TM Nakamura, H Mullen, JT Kasuya, H Yoon, SS Chandrasekhar, S Chiocca, EA Tanabe, KK TI Prodrug bioactivation and oncolysis of diffuse liver metastases by a herpes simplex virus 1 mutant that expresses the CYP2B1 transgene SO CANCER LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the Society-of-Surgical-Oncology CY MAR 16-19, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Surg Oncol DE colorectal carcinoma; liver metastases; cyclophosphamide; cytochrome p450; herpes simplex virus 1; oncolysis; prodrug bioactivation ID THYMIDINE KINASE GENE; RIBONUCLEOTIDE REDUCTASE; REPLICATION-COMPETENT; COLON-CARCINOMA; DELETION MUTANT; VIRAL THERAPY; SUICIDE GENE; CANCER-CELLS; TUMOR-CELLS; IN-VIVO AB BACKGROUND. Herpes simplex virus 1 (HSV-1) infection of cancer cells results in viral replication with cell destruction and liberation of progeny virion that infect adjacent tumor cells. rRp450 is a novel replication-conditional HSV-1 mutant that expresses both the endogenous herpes viral thymidine kinase gene and the rat p450 CYP2B1 transgene; p450 bioactivates such cancer prodrugs as cyclophosphamide. METHODS. Viral cytotoxicity and replication assays were performed in colon carcinoma cells as well as primary human hepatocytes. For in vivo studies, diffuse liver metastases were generated by inoculating MC26 cells into the portal system of BALB/c mice. Mice were treated with control media, rRp450, or rRp450 plus cyclophosphamide. RESULTS. Cytopathic effects induced by rRp450 replication in colon carcinoma cells were equivalent to those induced by wild type HSV-1 in vitro. Assays developed to separate cytotoxicity mediated by viral replication from cytotoxicity mediated by chemotherapy confirmed that HSV-1 thymidine kinase bioactivates ganciclovir and CYP2B1 bioactivates cyclophosphamide in rRp450-infected cells. rRp450 mediated cytotoxicity in the presence of cyclophosphamide was increased by 21% to 30% above that achieved by viral replication alone. Cyclophosphamide bioactivation produced bystander killing of colon carcinoma cells but not hepatocytes. In contrast to these effects of cyclophosphamide, rRp450 mediated cytotoxicity was reduced in the presence of ganciclovir. These findings are explained by further experiments showing that bioactivation of cyclophosphamide only minimally affected HSV-1 replication in colon carcinoma cells, whereas bioactivation of ganciclovir markedly attenuated HSV-1 replication. In vivo studies revealed a substantial decrease in hepatic tumor burden in all rRp450-treated animals compared to controls. The addition of cyclophosphamide augmented rRp450's in vivo anti-neoplastic effect. CONCLUSIONS. The rRp450 mutant HSV-1 is highly oncolytic against colon carcinoma cells both in vitro and in vivo. rRp450 displays preferential replication in colon carcinoma cells compared to normal hepatocytes. Activation of cyclophosphamide by the p450 transgene augmented the anti-neoplastic effects of rRp450 without simultaneously decreasing viral replication. Oncolysis induced by HSV-1 replication combined with cyclophosphamide prodrug activation warrants further investigation as a potential therapy for colon carcinoma liver metastases. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Cox Bldg 626,100 Blossom St, Boston, MA 02114 USA. RI Kasuya, hideki/I-7278-2014 FU NCI NIH HHS [CA69246, CA64454, CA76183, CA71345]; NIDDK NIH HHS [DK43352]; NIGMS NIH HHS [GM07035] NR 51 TC 49 Z9 54 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2002 VL 95 IS 5 BP 1171 EP 1181 DI 10.1002/cncr.10776 PG 11 WC Oncology SC Oncology GA 586VF UT WOS:000177606000030 PM 12209705 ER PT J AU Letai, A Bassik, MC Walensky, LD Sorcinelli, MD Weiler, S Korsmeyer, SJ AF Letai, A Bassik, MC Walensky, LD Sorcinelli, MD Weiler, S Korsmeyer, SJ TI Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics SO CANCER CELL LA English DT Article ID CYTOCHROME-C RELEASE; BCL-X-L; INDUCE APOPTOSIS; CELL-DEATH; BAX; PROTEIN; FAMILY; MEMBRANE; SURVIVAL; PEPTIDES AB The "BH3-only" proteins of the BCL-2 family require "multidomain" proapoptotic members BAX and BAK to release cytochrome c from mitochondria and kill cells. We find short peptides representing the alpha-helical BH3 domains of BID or BIM are capable of inducing oligomerization of BAK and BAX to release cytochrome c. Another subset characterized by the BH3 peptides from BAD and BIK cannot directly activate BAX, BAK but instead binds antiapoptotic BCL-2, resulting in the displacement of BID-like BH3 domains that initiate mitochondrial dysfunction. Transduced BAD-like and BID-like BH3 peptides also displayed synergy in killing leukemic cells. These data support a two-class model for BH3 domains: BID-like domains that "activate" BAX, BAK and BAD-like domains that "sensitize" by occupying the pocket of antiapoptotic members. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 92625] NR 37 TC 991 Z9 1033 U1 8 U2 46 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD SEP PY 2002 VL 2 IS 3 BP 183 EP 192 DI 10.1016/S1535-6108(02)00127-7 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599UF UT WOS:000178353000007 PM 12242151 ER PT J AU Abraham, JL AF Abraham, JL TI Care without chemotherapy: The role of the palliative care team SO CANCER JOURNAL LA English DT Article ID OF-LIFE CARE; CANCER-PATIENTS; DRIVING ABILITY; TERMINALLY ILL; RESUSCITATION; MANAGEMENT; DEPRESSION; EDUCATION; RESIDENTS; SUPPORT C1 Dana Farber Canc Inst, Pain & Palliat Care Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Abraham, JL (reprint author), Dana Farber Canc Inst, Pain & Palliat Care Program, SW 312,44 Binney St, Boston, MA 02115 USA. NR 55 TC 1 Z9 1 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2002 VL 8 IS 5 BP 357 EP 363 DI 10.1097/00130404-200209000-00003 PG 7 WC Oncology SC Oncology GA 609FZ UT WOS:000178894100002 PM 12416890 ER PT J AU Kulke, MH Demetri, GD Sharpless, NE Ryan, DP Shivdasani, R Clark, JS Speigelman, BM Kim, H Mayer, RJ Fuchs, CS AF Kulke, MH Demetri, GD Sharpless, NE Ryan, DP Shivdasani, R Clark, JS Speigelman, BM Kim, H Mayer, RJ Fuchs, CS TI A phase II study of troglitazone, an activator of the PPAR gamma receptor, in patients with chemotherapy-resistant metastatic colorectal cancer SO CANCER JOURNAL LA English DT Article DE differentiation; thiazolidinedione; peroxisome proliferator-activated receptor-gamma ID TERMINAL DIFFERENTIATION; TISSUE DISTRIBUTION; ADIPOSE-TISSUE; X-RECEPTOR; LIPOSARCOMA; EXPRESSION; REGULATOR; LIGANDS; ALPHA; OBESE AB PURPOSE Troglitazone, a potent activator of the peroxisome proliferator-activated receptor-gamma, induces tumor differentiation in human liposarcomas and causes regression of tumors that are derived from human colon cancer cells in nude mice. We therefore assessed the efficacy of troglitazone in the treatment of metastatic colon cancer in humans. METHODS Twenty-five patients with metastatic colorectal cancer were treated with oral troglitazone. Patients were followed up for evidence of toxicity, tumor response, and survival. RESULTS The treatment was well tolerated: no grade 3/4 treatment-related toxicities were observed. However, no objective tumor responses were noted, and all 25 patients had progressive disease as their best response to therapy. The median progression-free survival time was only 1.6 months, and the median survival time was 3.9 months. DISCUSSION Troglitazone is not an active agent for the treatment of metastatic colorectal cancer. C1 Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Ctr Gastrointestinal Oncol, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 103 Z9 107 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD SEP-OCT PY 2002 VL 8 IS 5 BP 395 EP 399 DI 10.1097/00130404-200209000-00010 PG 5 WC Oncology SC Oncology GA 609FZ UT WOS:000178894100009 PM 12416897 ER PT J AU Gordon, GJ Jensen, RV Hsiao, LL Gullans, SR Blumenstock, JE Ramaswamy, S Richards, WG Sugarbaker, DJ Bueno, R AF Gordon, GJ Jensen, RV Hsiao, LL Gullans, SR Blumenstock, JE Ramaswamy, S Richards, WG Sugarbaker, DJ Bueno, R TI Translation of Microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma SO CANCER RESEARCH LA English DT Article ID DIFFERENTIAL-DIAGNOSIS; OVARIAN-CANCER; IMMUNOCYTOCHEMISTRY; CLASSIFICATION; ADENOCARCINOMA; CARCINOMAS; ANTIBODIES AB The pathological distinction between malignant pleural mesothelioma (MPM) and adenocarcinoma (ADCA) of the lung can be cumbersome using established methods. We propose that a simple technique, based on the expression levels of a small number of genes, can be useful in the early and accurate diagnosis of MPM and lung cancer. This method is designed to accurately distinguish between genetically disparate tissues using gene expression ratios and rationally chosen thresholds. Here we have tested the fidelity of ratio-based diagnosis in differentiating between MPM and lung cancer in 181 tissue samples (31 MPM and 150 ADCA). A training set of 32 samples (16 MPM and 16 ADCA) was used to identify pairs of genes with highly significant, inversely correlated expression levels to form a total of 15 diagnostic ratios using expression profiling data. Any single ratio of the 15 examined was at least 90% accurate in predicting diagnosis for the remaining 149 samples (e.g., test set). We then examined (in the test set) the accuracy of multiple ratios combined to form a simple diagnostic tool. Using two and three expression ratios, we found that the differential diagnoses of MPM and lung ADCA were 95% and 99% accurate, respectively. We propose that using gene expression ratios is an accurate and inexpensive technique with direct clinical applicability for distinguishing between MPM and lung cancer, Furthermore, we provide evidence suggesting that this technique can be equally accurate in other clinical scenarios. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, Boston, MA 02115 USA. Wesleyan Univ, Dept Phys, Middletown, CT 06457 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. RP Bueno, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK58849] NR 20 TC 421 Z9 437 U1 1 U2 8 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 SEP 1 PY 2002 VL 62 IS 17 BP 4963 EP 4967 PG 5 WC Oncology SC Oncology GA 591TW UT WOS:000177897200020 PM 12208747 ER PT J AU LeBlanc, R Catley, LP Hideshima, T Lentzsch, S Mitsiades, CS Mitsiades, N Neuberg, D Goloubeva, O Pien, CS Adams, J Gupta, D Richardson, PG Munshi, NC Anderson, KC AF LeBlanc, R Catley, LP Hideshima, T Lentzsch, S Mitsiades, CS Mitsiades, N Neuberg, D Goloubeva, O Pien, CS Adams, J Gupta, D Richardson, PG Munshi, NC Anderson, KC TI Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model SO CANCER RESEARCH LA English DT Article ID FACTOR-KAPPA-B; TUMOR-GROWTH; ANGIOGENESIS; APOPTOSIS; PATHWAY; CARCINOMA; AGENTS AB The proteasome is a ubiquitous and essential intracellular enzyme that degrades many proteins regulating cell cycle, apoptosis, transcription, cell adhesion, angiogenesis, and antigen presentation. We have shown recently that the proteasome inhibitor PS-341 inhibits growth, induces apoptosis. and overcomes drug resistance in human myeloma cells in vitro. In this study, we examined the efficacy, toxicity, and in vivo mechanism of action of PS-341 using a human plasmacytoma xenograft mouse model. One hundred immunodeficient (beige-nude-xid) mice were used in two independent experiments. The mice were injected s.c. with 3x10(7) RPMI-8226 myeloma cells. When tumors became measurable (9.2 days; range, 6-13 days after tumor injection), mice were assigned to treatment groups receiving PS-341 0.05 mg/kg (n=13), 0.1 mg/kg (n=15), 0.5 mg/kg (n=14),or 1.0 mg/kg (n=14) twice weekly via tail rein, or to control groups (n=13) receiving the vehicle only. Significant inhibition of tumor growth, even with some complete tumor regression, was observed in PS-341-treated mice. The median overall survival was also significantly prolonged compared with controls (30 and 34 days for high dose-treated mice versus 14 days for controls; P<0.0001). PS-341 was well tolerated up to 0.5 mg/kg, but some mice treated at 1.0 mg/kg became moribund and lost weight. Analysis of tumors harvested from treated animals showed that PS-341 induced apoptosis and decreased angiogenesis in vivo. These studies therefore demonstrate that PS-341 has significant in vivo antimyeloma activity at doses that are well tolerated in a murine model, confirming our in vitro data and further supporting the early clinical promise of PS-341 to overcome drug resistance and improve patient outcome. C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P01 78378, R01 50947] NR 28 TC 337 Z9 353 U1 0 U2 10 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 SEP 1 PY 2002 VL 62 IS 17 BP 4996 EP 5000 PG 5 WC Oncology SC Oncology GA 591TW UT WOS:000177897200025 PM 12208752 ER PT J AU Lin, B Podar, K Gupta, D Tai, YT Li, SG Weller, E Hideshima, T Lentzsch, S Davies, F Li, C Weisberg, E Schlossman, RL Richardson, PG Griffin, JD Wood, J Munshi, NC Anderson, KC AF Lin, B Podar, K Gupta, D Tai, YT Li, SG Weller, E Hideshima, T Lentzsch, S Davies, F Li, C Weisberg, E Schlossman, RL Richardson, PG Griffin, JD Wood, J Munshi, NC Anderson, KC TI The vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584 inhibits growth and migration of multiple myeloma cells in the bone marrow microenvironment SO CANCER RESEARCH LA English DT Article ID DRUG-RESISTANCE; ARSENIC TRIOXIDE; POTENT INHIBITOR; STROMAL CELLS; KAPPA-B; INTERLEUKIN-6; APOPTOSIS; TUMOR; ADHESION; LINES AB Our prior studies show that multiple myeloma (MM) cell lines and patient cells express high-affinity vascular endothelial growth factor (VEGF) receptor (VEGFR) Flt-1 but not Flk-1/KDR. Moreover, these studies have shown that VEGF induces proliferation and migration of MM cells, and we have begun to delineate the signaling cascades mediating those sequelae. In this study, we examined the activity of PTK787/ZK 222584 (PTK787), a molecule designed to bind specifically to the tyrosine kinase domain of VEGFR and inhibit angiogenesis. We show that PTK787 acts both directly on MM cells and in the bone marrow microenvironment. Specifically, PTK787 (1-5 muM) inhibits proliferation of MM cells by 50%, as assayed by [H-3]thymidine uptake. This effect of PTK787 is dose dependent in both MM cell lines and patient cells that are both sensitive and resistant to conventional therapy. PTK787 enhances the inhibitory effect of dexamethasone on growth of MM cells and can overcome the protective effect of interleukin 6 (IL-6) against dexamethasone-induced apoptosis. PTK787 (1 muM) also blocks VEGF-induced migration of MM cells across an extracellular matrix. Importantly, PTK787 also inhibits the increased MM cell proliferation and increased IL-6 and VEGF secretion in cultures of MM cells adherent to bone marrow stem cells. These findings therefore demonstrate that PTK787 both acts directly on MM cells and inhibits paracrine IL-6-mediated MM cell growth in the bone marrow milieu. The demonstrated anti-MM activity of PTK787, coupled with its antiangiogenic effects, provides the framework for clinical trials of this agent to overcome drug resistance and improve outcome in MM. C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Novartis Pharma AG, Dept Oncol Res, CH-4002 Basel, Switzerland. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378, R0-1 50947] NR 37 TC 133 Z9 144 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 5019 EP 5026 PG 8 WC Oncology SC Oncology GA 591TW UT WOS:000177897200029 PM 12208756 ER PT J AU Shi, YJ Gera, J Hu, LP Hsu, JH Bookstein, R Li, WQ Lichtenstein, A AF Shi, YJ Gera, J Hu, LP Hsu, JH Bookstein, R Li, WQ Lichtenstein, A TI Enhanced sensitivity of multiple myeloma cells containing PTEN mutations to CCI-779 SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; PLASMA-CELLS; AKT KINASE; RAPAMYCIN; EXPRESSION; ACTIVATION; SURVIVAL; P70(S6K); PATHWAY AB Recent work identifies the AKT kinase as a potential mediator of tumor expansion in multiple myeloma. The finding of PTEN mutations in several myeloma cell lines suggests that loss of PTEN function may be one mechanism by which AKT activity is increased in this disease. Because PTEN-deficient myeloma cells may have up-regulated activity of the mammalian target of rapamycin (mTOR), downstream of AKT. they may, be particularly sensitive to mTOR inhibition. To test this hypothesis, we challenged myeloma cell lines with CCI-779, a newly developed analogue of rapamycin and an efficient inhibitor of mTOR. Three of four PTEN-deficient cell lines with constitutively active AKT were remarkably sensitive to cytoreduction and G(1) arrest induced by CCI-779 with ID50 concentrations of <1 nM. In contrast, myeloma cells expressing wild-type PTEN were >1000-fold more resistant. Acute expression of a constitutively active AKT gene in CCI-779-resistant myeloma cells containing wild-type PTEN and quiescent AKT did not convert them to the CCI-779-sensitive phenotype. Conversely, expression of wild-type PTEN in CCI-779-sensitive, PTEN-deficient myeloma cells did not induce resistance. Differential sensitivity did not appear to be due to differences in the ability of CCI-779 to inhibit mTOR and induce dephosphorylation of p70S6kinase or 4E-BP1. However, CCI-779 inhibited expression of c-myc in CCI-sensitive PTEN-null myeloma cells but had no effect on expression in CCI-resistant cells. In contrast, cyclin D1 expression was not altered in either sensitive or resistant cells. These results indicate that PTEN-deficient myeloma cells are remarkably sensitive to mTOR inhibition. Although the results of transfection studies suggest that the level of PTEN and AKT function per se does not regulate sensitivity, PTEN/AKT status may be a good predictive marker of sensitivity. C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Canji Inc, San Diego, CA 92121 USA. RP Lichtenstein, A (reprint author), VA W Los Angeles Hosp, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 96920-01] NR 29 TC 205 Z9 216 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2002 VL 62 IS 17 BP 5027 EP 5034 PG 8 WC Oncology SC Oncology GA 591TW UT WOS:000177897200030 PM 12208757 ER PT J AU Kominsky, DJ Bickel, RJ Tyler, KL AF Kominsky, DJ Bickel, RJ Tyler, KL TI Reovirus-induced apoptosis requires both death receptor- and mitochondrial-mediated caspase-dependent pathways of cell death SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; reovirus; caspase; death receptor; mitochondria ID CYTOCHROME-C RELEASE; PROTEIN; ACTIVATION; FAMILY; BCL-2; INHIBITION; INFECTION; COMPLEX; SPECIFICITIES; MODULATION AB Apoptosis plays an important role in the pathogenesis of many viral infections. Despite this fact, the apoptotic pathways triggered during viral infections are incompletely understood. We now provide the first detailed characterization of the pattern of caspase activation following infection with a cytoplasmically replicating RNA virus. Reovirus infection of HEK293 cells results in the activation of caspase-8 followed by cleavage of the pro-apoptotic protein Bid. This initiates the activation of the mitochondrial apoptotic pathway leading to release of cytochrome c and activation of caspase-9. Combined activation of death receptor and mitochondrial pathways results in downstream activation of effector caspases including caspase-3 and caspase-7 and cleavage of cellular substrates including PARP. Apoptosis is initiated by death receptor pathways but requires mitochondrial amplification producing a biphasic pattern of caspase-8, Bid, and caspase-3 activation. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave,B-182, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1R01AG14071] NR 40 TC 62 Z9 65 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD SEP PY 2002 VL 9 IS 9 BP 926 EP 933 DI 10.1038/sj.cdd.4401045 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 586KN UT WOS:000177583300008 PM 12181743 ER PT J AU Heckers, S Weiss, AP Alpert, NM Schacter, DL AF Heckers, S Weiss, AP Alpert, NM Schacter, DL TI Hippocampal and brain stem activation during word retrieval after repeated and semantic encoding SO CEREBRAL CORTEX LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CONSCIOUS RECOLLECTION; RECOGNITION MEMORY; PREFRONTAL CORTEX; EPISODIC MEMORY; FMRI; PET; DOPAMINE; COGNITION; AMYGDALA AB Repeated word presentation during learning and the use of a semantic encoding task both increase the accuracy of subsequent word retrieval. Previous neuroimaging studies have shown that successful word retrieval depends on the recruitment of the hippocampus, whereas the effort of retrieval is linked to activation of prefrontal cortex modules. We studied the effects of repetition (4x versus 1x presentation) and encoding task (semantic versus perceptual) on hippocampal and prefrontal cortex activation during word-stem cued recall using positron emission tomography. Repeated and semantic encoding resulted in increased recall accuracy, with word repetition showing a greater effect when using a semantic encoding task. The more successful retrieval of words presented repeatedly compared with words presented once was associated with activation of the left anterior hippocampus. The more successful retrieval of words encoded using a semantic compared with a perceptual task was associated with activation of the right posterior and, less significantly, the left anterior hippocampus. The greater benefit of repeated learning when using the semantic task was linked to activation of the right brainstem, in the region of the ventral tegmentum. Our results suggest that word repetition and semantic encoding increase recall accuracy during subsequent word retrieval via distinct hippocampal mechanisms and that ventral tegmentum activation is relevant for word retrieval after semantic encoding. These findings confirm the importance of hippocampal recruitment during word retrieval and provide novel evidence for a role of brainstem neurons in word retrieval after semantic encoding. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Cambridge, MA USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [MH01763-02, MH60941] NR 34 TC 25 Z9 26 U1 2 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD SEP PY 2002 VL 12 IS 9 BP 900 EP 907 DI 10.1093/cercor/12.9.900 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 585CF UT WOS:000177505000002 PM 12183389 ER PT J AU Hirshfeld-Becker, DR Biederman, J AF Hirshfeld-Becker, DR Biederman, J TI Rationale and principles for early intervention with young children at risk for anxiety disorders SO CLINICAL CHILD AND FAMILY PSYCHOLOGY REVIEW LA English DT Review DE anxiety disorders; children; parents; prevention; cognitive-behavioral therapy ID RANDOMIZED CLINICAL-TRIAL; DSM-III DISORDERS; PANIC DISORDER; BEHAVIORAL-INHIBITION; CHILDHOOD ANXIETY; SOCIAL PHOBIA; FOLLOW-UP; EXPRESSED EMOTION; MAJOR DEPRESSION; PARENTAL ANXIETY AB Anxiety disorders are one of the most prevalent categories of disorder among adults and children. Children of parents with anxiety disorders are known to be at higher risk for anxiety disorders themselves, with manifestations of this risk often appearing in toddlerhood or early childhood. Yet because affected parents are often unskilled in anxiety management, they often have difficulty in helping their young children learn to manage anxiety. Literature on the course of anxiety disorders through childhood and on effective cognitive-behavioral interventions suggests that preventive interventions even with very young children could potentially be of benefit in mitigating the course of these often debilitating disorders. This paper outlines the rationale for offering early or preventive interventions to preschool-age children at risk and their parents and discusses means of identifying children to target for intervention and the importance of parental involvement. Drawing upon the literature on parental factors in childhood anxiety disorders as well as on effective intervention strategies with preschool-age children, it delineates principles for intervention with parents and effective components of intervention with youngsters in this age range. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, 185 Alewife Brook Pkwy,Suite 2100, Cambridge, MA 02138 USA. FU NIMH NIH HHS [MH-01538-04] NR 112 TC 73 Z9 73 U1 0 U2 21 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1096-4037 J9 CLIN CHILD FAM PSYCH JI Clin. Child Fam. Psychol. Rev. PD SEP PY 2002 VL 5 IS 3 BP 161 EP 172 AR UNSP 1096-4037/02/0900-0161/0 DI 10.1023/A:1019687531040 PG 12 WC Psychology, Clinical SC Psychology GA 582HN UT WOS:000177344900001 PM 12240705 ER PT J AU Fairfield, WP Sesmilo, G Katznelson, L Pulaski, K Freda, PU Stavrou, S Kleinberg, D Klibanski, A AF Fairfield, WP Sesmilo, G Katznelson, L Pulaski, K Freda, PU Stavrou, S Kleinberg, D Klibanski, A TI Effects of a growth hormone receptor antagonist on bone markers in acromegaly SO CLINICAL ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; BIOCHEMICAL MARKERS; BODY-COMPOSITION; MINERAL DENSITY; GLA PROTEIN; FACTOR-I; DEFICIENCY; OSTEOCALCIN; METABOLISM; TURNOVER AB OBJECTIVE Excess GH secretion, as occurs in acromegaly, is associated with abnormalities in bone turnover markers and bone mineral density (BMD). GH administration in GH deficient patients causes an increase in bone turnover. IGF-I mediates many of the metabolic actions of GH, although GH may have direct effects upon bone. In patients with acromegaly who are treated with a GH receptor antagonist, selective blockade of the GH receptor results in a decrease in circulating IGF-I levels in the majority of cases. We hypothesized that, in acromegaly, antagonism of GH receptors would result in a decrease in serum markers of bone turnover, including serum procollagen I carboxy-terminal propeptide (PICP), osteocalcin and N-telopeptide (NTx). DESIGN AND SUBJECTS Twenty-seven patients with acromegaly were enrolled as part of a multicentre 12-week trial of a GH receptor antagonist and were randomized to placebo (n = 7) or 10, 15 or 20 mg of pegvisomant (n = 20). MEASUREMENTS Serum markers of bone turnover were determined at baseline and 12 weeks. RESULTS Baseline bone turnover markers were above the upper limit of normal in 23%, 19% and 32% of subjects for osteocalcin, PICP and NTx, respectively. During the 12-week placebo-controlled period, there were significant decreases in serum markers of bone formation, osteocalcin (-2.2 +/- 0.44 vs. placebo +0.01 +/- 0.39 nmol/l, P = 0.009) and PICP (-23.6 +/- 9.6 vs. placebo +18.1 +/- 12.8 mug/l, P = 0.022) and a serum marker of bone resorption, NTx (-4.4 +/- 1.4, placebo +1.0 +/- 0.3 nm, P = 0.024). CONCLUSIONS Using a specific GH receptor antagonist, we found that normalization of IGF-I is associated with rapid reductions in markers of both bone formation and resorption, and that these processes remain coupled. These data confirm the highly significant effects of GH and IGF-I in modulating bone turnover. The independent contributions of GH and IGF-I to these effects and the long-term effects on BMD in this population remain to be determined. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Clin Barcelona, Serv Endocrinol, Barcelona, Spain. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Univ Med Ctr, New York, NY USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066] NR 23 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2002 VL 57 IS 3 BP 385 EP 390 DI 10.1046/j.1365-2265.2002.01624.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 589FF UT WOS:000177747500012 PM 12201832 ER PT J AU Vielma, S Virella, G Gorod, AJ Lopes-Virella, MF AF Vielma, S Virella, G Gorod, AJ Lopes-Virella, MF TI Chlamydophila pneumoniae infection of human aortic endothelial cells induces the expression of FC gamma receptor II (Fc gamma RII) SO CLINICAL IMMUNOLOGY LA English DT Article DE Chlamydophila pneumoniae; Fc gamma receptors; atherosclerosis; endothelial dysfunction ID CORONARY HEART-DISEASE; CIRCULATING IMMUNE-COMPLEXES; ACUTE MYOCARDIAL-INFARCTION; CHLAMYDIA-PNEUMONIAE; ATHEROSCLEROTIC PLAQUES; RESPIRATORY-TRACT; ARTERY DISEASE; RISK-FACTORS; IN-VITRO; T-CELLS AB Chronic endothelial infection is believed to be one of the factors able to cause endothelial cell damage and trigger the onset of human atherosclerosis. Chlamydophila pneumoniae infects endothelial cells and has received special attention because of both epidemiological and experimental evidence supporting its role as a risk factor for atherosclerosis. It is also possible that otherwise independent risk factors for atherosclerosis may have synergistic effects. Immune phenomena, such as the formation of circulating immune complexes (IC) containing modified LDL and corresponding antibodies, have been linked to the development of coronary artery disease. The antibodies involved in the immune response to modified lipoproteins are predominantly of the pro-inflammatory IgG1 and IgG3 subclasses. However, it is difficult to understand how circulating IC could cause endothelial damage and initiate the atherosclerotic process, unless they were formed in the subendothelial space or immobilized by endothelial cells. The last hypothesis would be possible if endothelial cells expressed Fcgamma receptors. Healthy endothelial cells do not express Fcgamma receptors, but endothelial cells infected by a variety of infectious agents do. Thus we decided to investigate whether infection of endothelial cells with C. pneumoniae is also able to cause the expression of Fcgamma receptors. The expression of Fcgamma receptors (CD64, 32, and 16) on human aortic endothelial cells infected with C. pneumoniae for 4, 24, 36, and 48 h was studied by flow cytometry. Twenty-four hours after infection 30-40% of the endothelial cells had detectable inclusion bodies, 8-9% of the total number of cells (approximately 25% of the infected cells) expressed FcgammaRII, and about 1.5-2% (5% of infected cells) expressed FcgammaRI and FcgammaRIII. Double-staining studies confirmed that the expression of FcgammaRII was limited to C. pneumoniae-infected endothelial cells. We conclude that C. pneumoniae infection induces primarily the expression of FcgammaRII by endothelial cells and this may be a significant link between two proposed pathogenic mechanisms involved in the pathogenesis of human atherosclerosis. (C) 2002 Elsevier Science (USA). C1 Med Univ S Carolina, Dept Med, Div Endocrinol Metab Nutr, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Vielma, S (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Metab Nutr, Charleston, SC 29425 USA. NR 48 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD SEP PY 2002 VL 104 IS 3 BP 265 EP 273 DI 10.1006/clim.2002.5237 PG 9 WC Immunology SC Immunology GA 603FW UT WOS:000178549100010 PM 12217337 ER PT J AU Walensky, RP Paltiel, AD Freedberg, KA AF Walensky, RP Paltiel, AD Freedberg, KA TI AIDS Drug Assistance Programs: Highlighting inequities in human immunodeficiency virus-infection health care in the United States SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; MEDICAL-CARE; HIV THERAPY; ADULTS; NEEDS; RECOMMENDATIONS; IMPACT; PANEL AB The AIDS Drug Assistance Programs (ADAPs) were founded in 1987 to pay for human immunodeficiency virus (HIV)-related medications in the United States and to help provide prescriptions for HIV-infected patients ineligible for Medicaid who have no private health insurance. As HIV care has shifted from the inpatient to the outpatient arena and as patients live longer because of more-effective antiretroviral therapy, medication costs have increased, and ADAPs have increasingly been operating under emergency measures, with coverage limitations and eligibility restrictions. Because these programs operate at the state level, inequalities in resource distribution to those in need are manifest and appear to contribute to differences in disease outcomes that are based solely on patients' place of residence. Cost-effectiveness analysis would offer a more informed basis for distribution of ADAP resources in an efficient and equitable manner, leading to a standardized national structure. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Yale Sch Med, New Haven, CT USA. RP Walensky, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. FU AHRQ HHS [5T32HS00020]; NIAID NIH HHS [1K23AI01794, P30 AI042851, K23 AI001794, R01AI42006, R01 AI042006, P30AI42851]; NIDA NIH HHS [DA 09531-01 A2]; ODCDC CDC HHS [U64/CCU119525, U64/CCU114927] NR 29 TC 12 Z9 12 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2002 VL 35 IS 5 BP 606 EP 610 DI 10.1086/341903 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 583VJ UT WOS:000177431000017 PM 12173137 ER PT J AU Finegold, SM Molitoris, D Song, YL Liu, CX Vaisanen, ML Bolte, E McTeague, M Sandler, R Wexler, H Marlowe, EM Collins, MD Lawson, PA Summanen, P Baysallar, M Tomzynski, TJ Read, E Johnson, E Rolfe, R Nasir, P Shah, H Haake, DA Manning, P Kaul, A AF Finegold, SM Molitoris, D Song, YL Liu, CX Vaisanen, ML Bolte, E McTeague, M Sandler, R Wexler, H Marlowe, EM Collins, MD Lawson, PA Summanen, P Baysallar, M Tomzynski, TJ Read, E Johnson, E Rolfe, R Nasir, P Shah, H Haake, DA Manning, P Kaul, A TI Gastrointestinal microflora studies in late-onset autism SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Anaerobe Odyssey Symposium held in honor of Sydney M Finegolds 80th Birthday CY AUG 12, 2001 CL UNIV CALIF LOS ANGELES, FAC CLUB, LOS ANGELES, CALIFORNIA HO UNIV CALIF LOS ANGELES, FAC CLUB ID MYELIN BASIC-PROTEIN; AMINO-ACIDS; CHILDREN; BACTERIA; DEGRADATION; ANTIBODIES; INTESTINE; PRODUCTS; DISORDER; STRAINS AB Some cases of late-onset (regressive) autism may involve abnormal flora because oral vancomycin, which is poorly absorbed, may lead to significant improvement in these children. Fecal flora of children with regressive autism was compared with that of control children, and clostridial counts were higher. The number of clostridial species found in the stools of children with autism was greater than in the stools of control children. Children with autism had 9 species of Clostridium not found in controls, whereas controls yielded only 3 species not found in children with autism. In all, there were 25 different clostridial species found. In gastric and duodenal specimens, the most striking finding was total absence of non-spore-forming anaerobes and microaerophilic bacteria from control children and significant numbers of such bacteria from children with autism. These studies demonstrate significant alterations in the upper and lower intestinal flora of children with late-onset autism and may provide insights into the nature of this disorder. C1 W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111 F, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Clin Microbiol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Rush Childrens Hosp, Chicago, IL USA. Univ Wisconsin, Dept Food Microbiol & Toxicol & Bacteriol, Madison, WI USA. Texas Tech Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Lubbock, TX 79430 USA. Childrens Hosp, Med Ctr, Div Pediat Gastroenterol & Nutr, Cincinnati, OH 45229 USA. Univ Reading, Sch Food Biosci, Dept Microbiol, Reading, Berks, England. Cent Publ Hlth Lab, Publ Hlth Lab Serv, Identificat Serv Unit, London NW9 5HT, England. RP Finegold, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111 F, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Lawson, Paul/E-3760-2012 NR 47 TC 193 Z9 211 U1 3 U2 38 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2002 VL 35 SU 1 BP S6 EP S16 DI 10.1086/341914 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 585PH UT WOS:000177533400002 PM 12173102 ER PT J AU Wexler, HM AF Wexler, HM TI Outer-membrane pore-forming proteins in gram-negative anaerobic bacteria SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Anaerobe Odyssey Symposium held in honor of Sydney M Finegolds 80th Birthday CY AUG 12, 2001 CL UNIV CALIF LOS ANGELES, FAC CLUB, LOS ANGELES, CALIFORNIA HO UNIV CALIF LOS ANGELES, FAC CLUB ID PORPHYROMONAS-GINGIVALIS W50; ESCHERICHIA-COLI K-12; BACTEROIDES-FRAGILIS; FUSOBACTERIUM-NUCLEATUM; PSEUDOMONAS-AERUGINOSA; ACTIVE EFFLUX; CELL-SURFACE; IDENTIFICATION; PORINS; GENE AB The outer-membrane proteins (OMPs) of bacteria function as the dynamic interface between the bacterium and its surroundings and are involved in maintenance of cell structure, binding a variety of substances, adhesion to other cells, and regulation of transport of both nutrients and bactericidal agents. There is a vast amount of information about aerobic OMPs and their roles in immunogenicity, virulence, and antimicrobial resistance. Knowledge about OMPs in anaerobic bacteria is much sparser. Genetic data present in data banks regarding aerobic porins are not readily helpful in identifying or analyzing anaerobic porins because of the large phylogenetic distance between the aerobic and anaerobic organisms. We recently identified and sequenced the genes for both a porin protein complex and an OmpA protein in Bacteroides fragilis, and the data are summarized here. Also, recent information is presented about similar OMPs found in other gram-negative anaerobic bacteria, including Bacteroides thetaiotaomicron, Bacteroides distasonis, Porphyromonas, and Fusobacterium. C1 VA Greater Los Angeles Healthcare Syst, Microbial Dis Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Wexler, HM (reprint author), VA Greater Los Angeles Healthcare Syst, Microbial Dis Res Lab, Bldg 304,Rm E3-224,691-151J, Los Angeles, CA 90073 USA. NR 43 TC 16 Z9 17 U1 2 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2002 VL 35 SU 1 BP S65 EP S71 DI 10.1086/341923 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 585PH UT WOS:000177533400011 PM 12173111 ER PT J AU Otto, MW AF Otto, MW TI The dose and delivery of psychotherapy: A commentary on Hansen et al. SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Article DE psychotherapy outcome; dose-response; cognitive-behavior therapy; treatment engagement; effectiveness research ID COGNITIVE-BEHAVIOR THERAPY; PANIC DISORDER AB Hansen et al. provide important data on the dose of psychotherapy received in clinical practice. For their sample of over 6,000 patients, they found the median number of sessions of psychotherapy received was three, with a recovery rate of 6.5%. In contrast, data from controlled clinical trials reviewed by Hansen et al. indicated patients received an average of 13 sessions of treatment, with half the sample achieving remission. In this commentary, potential reasons for this rift between research and clinical practice are discussed, with attention to factors associated with engagement in treatment. In particular, every controlled trial reviewed by Hansen et al. involved cognitive-behavioral interventions, whereas application of these programs of treatment is relatively rare in clinical practice. Elements of the treatment and treatment context are identified that may be useful for enhancing the dose of psychotherapy. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, WACC-812,15 Parkman St, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 1 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 FAL PY 2002 VL 9 IS 3 BP 348 EP 349 DI 10.1093/clipsy/9.3.348 PG 2 WC Psychology, Clinical SC Psychology GA 584MT UT WOS:000177470900012 ER PT J AU Litz, BT Gray, MJ AF Litz, BT Gray, MJ TI Early intervention for mass violence: What is the evidence? What should be done? SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MALE VIETNAM VETERANS; ACCIDENT VICTIMS; SOCIAL SUPPORT; FOLLOW-UP; TRAUMA; FEMALE; SYMPTOMS; SOLDIERS AB Incidents of mass violence, such as the September 11, 2001, terrorist attacks on the World Trade Center and the Pentagon, have the capacity to produce profound emotional distress in thousands of people. Such distress is a normal human emotional response in the wake of such devastation, and in the vast majority of cases this distress remits in the weeks following the traumatic event. Despite the fact that only a small percentage of individuals fail to adjust positively following trauma, the magnitude and scope of incidents of mass violence dictate that a large number of individuals may develop enduring psychopathology as a result of such events. This article reviews the empirical literature bearing on early interventions for trauma victims that have been developed to date. Promising cognitive-behavioral interventions that appear to overcome significant limitations of traditional early intervention approaches are delineated and discussed. Although early interventions for trauma remain underdeveloped and understudied, practice guidelines gleaned from preliminary but promising treatment approaches are offered. Attention to PTSD risk factors is paramount in order to facilitate the identification of individuals most likely to benefit from early posttraumatic treatment. These risk factors are presented and discussed in order to facilitate assessment and treatment planning. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Arts & Sci, Boston, MA 02118 USA. Boston Vet Hlth Care Syst, Boston, MA USA. Univ Wyoming, Laramie, WY 82071 USA. RP Litz, BT (reprint author), Boston VA, Natl Ctr PTSD, 116B-5,150 S Huntington Ave, Boston, MA 02130 USA. EM Brett.Litz@Med.Va.Gov NR 41 TC 10 Z9 10 U1 5 U2 10 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD FAL PY 2002 VL 9 IS 4 BP 266 EP 272 DI 10.1016/S1077-7229(02)80019-0 PG 7 WC Psychology, Clinical SC Psychology GA 918NT UT WOS:000228550500003 ER PT J AU Tedlow, J Smith, M Neault, N Polania, L Alpert, J Nierenberg, A Fava, M AF Tedlow, J Smith, M Neault, N Polania, L Alpert, J Nierenberg, A Fava, M TI Melancholia and axis II comorbidity SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID PERSONALITY-DISORDER; MAJOR DEPRESSION; DSM-III; SUBTYPES; VALIDITY; SAMPLE AB This study assessed whether the rates of comorbid personality disorders differed between DSM-IV melancholic and nonmelancholic major depressive disorder. We evaluated 260 consecutive depressed outpatients (140 women [53.8%]; mean age, 39.01 +/- 10.4 years) with DSM-III-R major depressive disorder (MDD). MDD was diagnosed with the use of the Structured Clinical Interview for DSM-III-R-Patient Edition (SCID-P); enrolled patients were required to have a score greater than or equal to 16 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The presence of the melancholic subtype of major depression was determined with the use of a DSM-IV checklist, while the presence of personality disorders was assessed using the Structured Clinical Interview for DSM-III-R-Personality Disorders (SCID-II). Of the 102 (39.2%) patients who met criteria for melancholic depression and the 158 (60.7%) who did not, there were no significant differences in age, gender, or rates of personality disorder diagnoses. We observed no significant difference in rates of individual personality disorder clusters between melancholic and nonmelancholic depressed patients. Our findings of comparable rates of comorbid personality disorders between melancholic and nonmelancholic depression are consistent with the decision made by the DSM-IV task force to drop the DSM-III-R melancholic feature criterion of "no significant personality disturbance before first major depressive episode" as they challenge the usefulness of trying to establish such absence of premorbid personality features in acutely depressed patients. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Tedlow, J (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 16 TC 13 Z9 13 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD SEP-OCT PY 2002 VL 43 IS 5 BP 331 EP 335 DI 10.1053/comp.2002.34631 PG 5 WC Psychiatry SC Psychiatry GA 592NW UT WOS:000177944600001 PM 12216007 ER PT J AU Hartwig, W Carter, EA Jimenez, RE Jones, R Fischman, AJ Fernandez-del Castillo, C Warshaw, AL AF Hartwig, W Carter, EA Jimenez, RE Jones, R Fischman, AJ Fernandez-del Castillo, C Warshaw, AL TI Neutrophil metabolic activity but not neutrophil sequestration reflects the development of pancreatitis-associated lung injury SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the International-Association-of-Pancreatology/American-Pancreatic-Associati on CY NOV 01-05, 2000 CL CHICAGO, ILLINOIS SP Int Assoc Pancreatol, Amer Pancreat Assoc DE [F-18]fluorodeoxyglucose; glucose metabolism; leukocytes; inflammation ID RESPIRATORY-DISTRESS SYNDROME; CEREBRAL GLUCOSE-UTILIZATION; CHEMOTACTIC PEPTIDE ANALOGS; IMAGING FOCAL SITES; BACTERIAL-INFECTION; LEUKOCYTES; ACTIVATION; TISSUE; RAT; ACCUMULATION AB Objective: Activated neutrophils are presumed to injure pulmonary endothelium by releasing oxygen radicals, proteases, and proinflammatory cytokines. Standard counting methods do not distinguish between leukocytosis, neutrophil sequestration, and activation. We used leukocyte uptake of the glucose analog [F-18]fluorodeoxyglucose ((18)FDG), which indicates postmigrational neutrophil activity, to identify and quantify the relationship between acute respiratory distress syndrome and neutrophil activation in experimental pancreatitis in rats. Design: Prospective, experimental study. Setting: Research laboratory at a university hospital. Subjects: Mild and severe pancreatitis models in the rat. Interventions: Pulmonary (with muscle as control) leukocyte accumulation was assessed by uptake of technetium-99m-labeled chemotactic peptide (fMLFK) and confirmed by measurement Of myeloperoxidase activity. Neutrophil activity was assessed by (18)FDG uptake. Tissue-to-blood ratios for fMLFK (18)FDG, and leukocytes were calculated to control for background. Neutrophils were counted in histologic sections of saline-perfused lungs. Bronchoalveolar lavage fluid was assessed for neutrophil migration and autoradiographed for intracellular (18)FDG localization. Measurements and Main Results: Lung myeloperoxidase activity, (18)FDG, and peripheral white blood cells all significantly increased in both mild and severe pancreatitis, but lung fMLFK only increased in severe pancreatitis. After correction for blood background, only (18)FDG in lung (but not muscle) was significantly increased in pancreatitis (severe > mild > normal, p <.001). Histologic analysis showed significant increase in extravascular (migrated) neutrophils only in severe pancreatitis. Autoradiography of bronchoalveolar lavage fluid confirmed the (18)FDG within intra-alveolar neutrophils. Conclusions: In this pancreatitis model of acute respiratory distress syndrome, there was nonspecific and noninjurious increase of neutrophils in the lung, attributable in part to background leukocytosis and to intravascular sequestration. However, (18)FDG uptake uniquely showed that interstitial and intra-alveolar neutrophil migration and activation occurred in severe but not in mild pancreatitis, consistent with clinical correlations between acute respiratory distress syndrome and severity of underlying systemic disease. (18)FDG uptake, which is also accessible by positron emission tomography scanning, better quantitates the contribution of activated neutrophils to tissue injury than other measurements of neutrophil accumulation or sequestration. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, WHT 506,55 Fruit St, Boston, MA 02114 USA. NR 38 TC 27 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2002 VL 30 IS 9 BP 2075 EP 2082 DI 10.1097/01.CCM.0000020985.14851.06 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 599XC UT WOS:000178359600020 PM 12352044 ER PT J AU Hess, DR AF Hess, DR TI Liberation from mechanical ventilation: Weaning the patient or weaning old-fashioned ideas? SO CRITICAL CARE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 2002 VL 30 IS 9 BP 2154 EP 2155 DI 10.1097/01.CCM.0000025911.91700.D5 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 599XC UT WOS:000178359600039 PM 12352063 ER PT J AU Stoffel, EM Syngal, S AF Stoffel, EM Syngal, S TI Colon cancer screening strategies SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; CONVENTIONAL COLONOSCOPY; COST-EFFECTIVENESS; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; CT COLONOGRAPHY; POPULATION; CARE; RECOMMENDATIONS; PREVENTION AB Screening has been shown to reduce morbidity and mortality related to colorectal cancer. However, the optimal strategy for population screening for colorectal cancer has been a topic of heated debate. Recent studies have challenged the efficacy and cost-effectiveness of current population screening practices. Novel approaches to improve the assessment of an individual's colorectal cancer risk and advances in technology are changing our approach to colorectal screening. This review covers current guidelines for screening for colorectal cancer, recent advances in cancer risk assessment, and the role of endoscopy, virtual colonoscopy, and fecal DNA testing in colorectal cancer screening. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Smith 209, Boston, MA 02115 USA. NR 39 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD SEP PY 2002 VL 18 IS 5 BP 595 EP 601 DI 10.1097/01.MOG.0000025742.54502.E3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 584ZN UT WOS:000177498800012 PM 17033339 ER PT J AU Marshansky, V Ausiello, DA Brown, D AF Marshansky, V Ausiello, DA Brown, D TI Physiological importance of endosomal acidification: potential role in proximal tubulopathies SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE CLC-5; cubilin; endosomal acidification; Fanconi syndrome; kidney proximal tubule; megalin; protein reabsorption; receptor-mediated endocytosis; V-ATPase ID MOLECULAR-WEIGHT PROTEINURIA; CADMIUM-INTOXICATED RATS; RENAL BRUSH-BORDER; INTESTINAL COBALAMIN MALABSORPTION; LINKED HEREDITARY NEPHROLITHIASIS; RECEPTOR-MEDIATED ENDOCYTOSIS; EXCHANGER ISOFORM NHE3; CHLORIDE CHANNEL GENE; DENTS-DISEASE; TUBULE CELLS AB Purpose of review In recent years, there have been significant advances in our understanding of the molecular mechanisms relating proximal tubule abnormalities to the pathogenesis of renal Fanconi syndrome. This review focuses on the role of intra-endosomal acidification-machinery proteins (V-ATPase, CLC-5, NHE-3), as well as apical receptors (megalin and cubilin), in the receptor-mediated endocytosis pathway and in the pathogenesis of proximal tubulopathies. Recent findings Animal models, including CLC-5 and megalin knockout mice, cubilin-deficient dogs and cadmium-toxicity studies in rats, have shed light on defects leading to low-molecular-weight proteinuria. In particular, the important contribution of defective endosomal acidification and membrane-protein recycling to the pathogenesis of the Fanconi syndrome has emerged from these studies. These observations, together with recent findings in patients with Dent's disease, Lowe's syndrome, autosoma dominant idiopathic Fanconi syndrome and Imerslund-Grasbeck disease, show that the proteinuria of the Fanconi syndrome is more generalized than previously suspected. High concentrations of polypeptides, including hormones, vitamin-binding proteins and chemokines in urine from these patients and animals may play an important role in the progressive renal failure that is associated with the syndrome. Summary The molecular mechanism of proximal tubule protein reabsorption, which is defective in renal Fanconi syndrome, includes a crucial role for endosomal acidification-machinery proteins, in particular the V-ATPase and CLC-5 chloride channels, in the trafficking and acidification-dependent recycling of apical membrane proteins, including the endocytotic receptors megalin and cubilin. An increased understanding of the roles of V-ATPase and CLC-5 in proximal tubule endosomal acidification, in the regulation of the megalin/cubilin-mediated endocytosis pathway and finally in the pathogenesis of human Fanconi syndrome will help in the devising of appropriate strategies for therapeutic intervention for this disorder. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Program Membrane Biol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA USA. RP Marshansky, V (reprint author), Massachusetts Gen Hosp E, Program Membrane Biol, 149 13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [R01DK42956, P01DK38452, 1P30DK57521] NR 103 TC 72 Z9 73 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD SEP PY 2002 VL 11 IS 5 BP 527 EP 537 DI 10.1097/00041552-200209000-00009 PG 11 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 595RC UT WOS:000178121700009 PM 12187318 ER PT J AU Bauer, KA Eriksson, BI Lassen, MR Turpie, AGG AF Bauer, KA Eriksson, BI Lassen, MR Turpie, AGG TI Factor Xa inhibition in the prevention of venous thromboembolism and treatment of patients with venous thromboembolism SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article ID COAGULATION-FACTOR-XA; DEEP-VEIN THROMBOSIS; CAROTID-ARTERY THROMBOSIS; LEECH HIRUDO-MEDICINALIS; SALIVARY-GLANDS; ANTICOAGULANT PEPTIDE; ANTITHROMBOTIC EFFICACY; SYNTHETIC INHIBITOR; RABBIT MODEL; TICK AB Venous thromboembolism (VTE) is a life-threatening complication following orthopedic surgery. Selective factor Xa inhibition is a new antithrombotic approach designed to avoid difficulties associated with heparins and other current anticoagulants. Several antifactor Xa compounds are in early investigation, but fondaparinux (Arixtra; NV Organon, Oss, The Netherlands; Sanofi-Synthelabo, Paris, France) is the first and most advanced compound in the development of a new class of synthetic antithrombotic agents-the selective factor Xa inhibitors. Fondaparinux has a highly favorable pharmacokinetic profile; four large phase 3 trials comparing subcutaneous fondaparinux 2.5 mg once daily with the low molecular weight heparin (LMWH) enoxaparin in doses approved by regulatory bodies showed that fondaparinux reduced the overall risk of VTE in major orthopedic surgery by > 50% without increasing clinically relevant bleeding. Fondaparinux also appears to be a very promising candidate for the treatment of patients with existing VTE. (C) 2002 Lippincott Williams Wilkins, Inc. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Sahlgrens Univ Hosp, Dept Orthoped, Gothenburg, Sweden. Hoersholm Hosp, Dept Spinal Surg, Horsholm, Denmark. Hoersholm Hosp, Dept Clin Sci, Horsholm, Denmark. Hamilton Hlth Sci Corp, Gen Div, Hamilton, ON, Canada. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. NR 58 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD SEP PY 2002 VL 8 IS 5 BP 398 EP 404 DI 10.1097/01.MCP.0000026996.50462.21 PG 7 WC Respiratory System SC Respiratory System GA 606HL UT WOS:000178728500010 PM 12172443 ER PT J AU Gribben, JG AF Gribben, JG TI Immunotherapy in the B-cell lymphomas SO CYTOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; FOLLICULAR LYMPHOMAS; VACCINATION; TUMOR; CHEMOTHERAPY; IMMUNIZATION; MALIGNANCIES; RESPONSES; INDUCTION; ANTIBODY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PD SEP 1 PY 2002 VL 4 IS 5 BP 439 EP 440 DI 10.1080/146532402320776107 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 612LQ UT WOS:000179077500013 PM 12473217 ER PT J AU Li, WX Agaisse, H Mathey-Prevot, B Perrimon, N AF Li, WX Agaisse, H Mathey-Prevot, B Perrimon, N TI Differential requirement for STAT by gain-of-function and wild-type receptor tyrosine kinase Torso in Drosophila SO DEVELOPMENT LA English DT Article DE Drosophila; receptor tyrosine kinase (RTK); Torso; STAT ID GROWTH-FACTOR RECEPTOR; CELL-CYCLE ARREST; EMBRYONIC TERMINI; TARGETED DISRUPTION; TAILLESS EXPRESSION; GENE TAILLESS; ACTIVATION; RAF; PATHWAY; TRANSCRIPTION AB Malignant transformation frequently involves aberrant signaling from receptor tyrosine kinases (RTKs). These receptors commonly activate Ras/Raf/MEK/MAPK signaling but when overactivated can also induce the JAK/STAT pathway, originally identified as the signaling cascade downstream of cytokine receptors. Inappropriate activation of STAT has been found in many human cancers. However, the contribution of the JAK/STAT pathway in RTK signaling remains unclear. We have investigated the requirement of the JAK/STAT pathway for signaling by wild-type and mutant forms of the RTK Torso (Tor) using a genetic approach in Drosophila. Our results indicate that the JAK/STAT pathway plays little or no role in signaling by wild-type Tor. In contrast, we find that STAT, encoded by marelle (mrl; DSW92E), is essential for the gain-of-function mutant Tor (Tor(GOF)) to activate ectopic gene expression. Our findings indicate that the Ras/Raf/MEK/MAPK signaling pathway is sufficient to mediate the normal functions of wild-type RTK, whereas the effects of gain-of-function mutant RTK additionally require STAT activation. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Dept Biomed Genet, Rochester, NY 14642 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Li, WX (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. RI Perrimon, Norbert/F-9766-2011 FU NHLBI NIH HHS [R01 HL62434]; NIGMS NIH HHS [R01 GM065774, R01 GM065774-01, R01 GM65774-01] NR 43 TC 13 Z9 13 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 SEP PY 2002 VL 129 IS 18 BP 4241 EP 4248 PG 8 WC Developmental Biology SC Developmental Biology GA 602WT UT WOS:000178528000007 PM 12183376 ER PT J AU Guha, U Gomes, WA Kobayashi, T Pestell, RG Kessler, JA AF Guha, U Gomes, WA Kobayashi, T Pestell, RG Kessler, JA TI In vivo evidence that BMP signaling is necessary for apoptosis in the mouse limb SO DEVELOPMENTAL BIOLOGY LA English DT Article DE BMP; noggin; limb development; apoptosis; Msx; Hox; FGF8; keratin 14 ID PROGRAMMED CELL-DEATH; BONE MORPHOGENETIC PROTEINS; APICAL ECTODERMAL RIDGE; TRANSGENIC MICE; VERTEBRATE LIMB; RETINOIC ACID; FEEDBACK LOOP; CHICK LIMB; INTERDIGITAL APOPTOSIS; ECTOPIC EXPRESSION AB To determine the role of Bone morphogenetic protein (BMP) signaling in murine limb development in vivo, the keratin 14 promoter was used to drive expression of the BMP antagonist Noggin in transgenic mice. Phosphorylation and nuclear translocation of Smad1/5 were dramatically reduced in limbs of the transgenic animals, confirming the inhibition of BMP signaling. These mice developed extensive limb soft tissue syndactyly and postaxial polydactyly. Apoptosis in the developing limb necrotic zones was reduced with incomplete regression of the interdigital tissue. The postaxial extra digit is also consistent with a role for BMPs in regulating apoptosis. Furthermore, there was persistent expression of Fgf8, suggesting a delay in the regression of the AER. However, Msx1 and Msx2 expression was unchanged in these transgenic mice, implying that induction of these genes is not essential for mediating BMP-induced interdigital apoptosis in mice. These abnormalities were rescued by coexpressing BMP4 under the same promoter in double transgenic mice, suggesting that the limb abnormalities are a direct effect of inhibiting BMP signaling. (C) 2002 Elsevier Science (USA). C1 Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Med, Albert Einstein Canc Ctr, Div Hormone Dependant Tumor Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. RP Guha, U (reprint author), Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. FU NCI NIH HHS [R01 CA86072, R01CA70896, R01CA75503]; NINDS NIH HHS [R01 NS20013, R01 NS20778] NR 62 TC 105 Z9 107 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2002 VL 249 IS 1 BP 108 EP 120 DI 10.1006/dbio.2002.0752 PG 13 WC Developmental Biology SC Developmental Biology GA 592EW UT WOS:000177924600009 PM 12217322 ER PT J AU Way, KJ Isshiki, K Suzuma, K Yokota, T Zvagelsky, D Schoen, FJ Sandusky, GE Pechous, PA Vlahos, CJ Wakasaki, H King, GL AF Way, KJ Isshiki, K Suzuma, K Yokota, T Zvagelsky, D Schoen, FJ Sandusky, GE Pechous, PA Vlahos, CJ Wakasaki, H King, GL TI Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta 2 activation and diabetes SO DIABETES LA English DT Article ID FAILING HUMAN HEART; EXTRACELLULAR-MATRIX; MESANGIAL CELLS; HIGH GLUCOSE; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; POTENTIAL ROLE; TGF-BETA; RATS; MELLITUS AB Protein kinase C (PKC) beta isoform activity is increased in myocardium of diabetic rodents and heart failure patients. Transgenic mice overexpressing PKCbeta2 (PKCbeta2Tg) in the myocardium exhibit cardiomyopathy and cardiac fibrosis. In this study, we characterized the expression of connective tissue growth factor (CTGF) and transforming growth factor beta (TGFbeta) with the development of fibrosis in heart from PKCbeta2Tg mice at 4-16 weeks of age. Heart-to-body weight ratios of transgenic mice increased at 8 and 12 weeks, indicating hypertrophy, and ratios did not differ at 16 weeks. Collagen VI and fibronectin mRNA expression increased hi PKCbeta2Tg hearts at 4-12 weeks. Histological examination revealed myocyte hypertrophy and fibrosis in 4 to 16-week PKCbeta2Tg hearts. CTGF expression increased in PKCbeta2Tg hearts at all ages, whereas TGFbeta increased only at 8 and 12 weeks. In 8-week diabetic mouse heart, CTGF and TGFbeta expression increased two- and fourfold, respectively. Similarly, CTGF expression increased in rat hearts at 2-8 weeks of diabetes. This is the first report of increased CTGF expression in myocardium of diabetic rodents suggesting that cardiac injury associated with PKCbeta2 activation, diabetes, or heart failure is marked by increased CTGF expression. CTGF could act independently or together with other cytokines to induce cardiac fibrosis and dysfunction. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Lilly Res Labs, Indianapolis, IN USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY5110]; NIDDK NIH HHS [DK59725-01] NR 50 TC 120 Z9 132 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 SEP PY 2002 VL 51 IS 9 BP 2709 EP 2718 DI 10.2337/diabetes.51.9.2709 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600007 PM 12196463 ER PT J AU Hiramatsu, Y Sekiguchi, N Hayashi, M Isshiki, K Yokota, T King, GL Loeken, MR AF Hiramatsu, Y Sekiguchi, N Hayashi, M Isshiki, K Yokota, T King, GL Loeken, MR TI Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy SO DIABETES LA English DT Article ID NEURAL-TUBE DEFECTS; SMOOTH-MUSCLE CELLS; RAT EMBRYOS; VITAMIN-E; HIGH GLUCOSE; DIFFERENTIAL EXPRESSION; DEVELOPMENTAL DAMAGE; GLYCEMIC CONTROL; GENE-EXPRESSION; HUMAN PLACENTA AB Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade by excess glucose has been implicated in vascular complications of diabetes. Its involvement in diabetic embryopathy has not been established. We examined DAG production and PKC activities in embryos and decidua of streptozotocin (STZ)-diabetic or transiently hyperglycemic mice during neural tube formation. STZ diabetes significantly increased DAG and total PKC activity in decidua (1.5- and 1.4-fold, respectively) and embryos (1.7- and 1.3-fold, respectively) on day 9.5. Membrane-associated PKC alpha, betaII, delta, and zeta were increased in decidua by 1.25- to 2.8-fold. Maternal hyperglycemia induced by glucose injection on day 7.5, the day before the onset of neural tube formation, also increased DAG, PKC activity, and PKC isoforms (1.1-, 1.6-, and 1.5-fold, respectively) in the embryo on day 9.5. Notably, membrane-associated PKC activity was increased 24-fold in embryos of diabetic mice with structural defects. These data indicate that hyperglycemia just before organogenesis activates the DAG-PKC cascade and is correlated with congenital defects. C1 Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Vasc Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Okayama Univ, Dept Obstet & Gynecol, Grad Sch Med & Dent, Okayama, Japan. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [R01-EY5110]; NIDDK NIH HHS [R01-DK52865] NR 49 TC 42 Z9 43 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 SEP PY 2002 VL 51 IS 9 BP 2804 EP 2810 DI 10.2337/diabetes.51.9.2804 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600018 PM 12196474 ER PT J AU Chan, BWH Chan, KS Koide, T Yeung, SM Leung, MBW Copp, AJ Loeken, MR Shiroishi, T Shum, ASW AF Chan, BWH Chan, KS Koide, T Yeung, SM Leung, MBW Copp, AJ Loeken, MR Shiroishi, T Shum, ASW TI Maternal diabetes increases the risk of caudal regression caused by retinoic acid SO DIABETES LA English DT Article ID NEURAL-TUBE; SACRAL AGENESIS; MOUSE EMBRYO; TAIL BUD; WNT-3A; MALFORMATIONS; MORPHOGENESIS; DEFECTS; MICE; RECEPTORS AB Maternal diabetes increases the risk of congenital malformations in the offspring of affected pregnancies. This increase arises from the teratogenic effect of the maternal diabetic milieu on the developing embryo, although the mechanism of this action is poorly understood. In the present study, we examined whether the vitamin A metabolite retinoic acid (RA), a common drug with well-known teratogenic properties, may interact with maternal diabetes to alter the incidence of congenital malformations in mice. Our results show that when treated with RA, embryos of diabetic mice are significantly more prone than embryos of nondiabetic mice to develop caudal regression, a defect that is highly associated with diabetic pregnancy in humans. By studying the vestigial tail (Wnt-3a(vt)) mutant, we provide evidence that Wnt-3a, a gene that controls the development of the caudal region, is directly involved in the pathogenic pathway of RA-induced caudal regression. We further show that the molecular basis of the increased susceptibility of embryos of diabetic mice to RA involves enhanced downregulation of Wnt-3a expression. This positive interaction between RA and maternal diabetes may have implications for humans in suggesting increased susceptibility to environmental teratogens during diabetic pregnancy. C1 Chinese Univ Hong Kong, Dept Anat, Shatin, Hong Kong, Peoples R China. Natl Inst Genet, Mammalian Genet Lab, Mishima, Shizuoka 411, Japan. UCL, Neural Dev Unit, Inst Child Hlth, London, England. Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shum, ASW (reprint author), Chinese Univ Hong Kong, Dept Anat, Shatin, Hong Kong, Peoples R China. EM alisa-shum@cukh.edu.hk RI Copp, Andrew/C-4174-2008 OI Copp, Andrew/0000-0002-2544-9117 FU NIDDK NIH HHS [DK52865] NR 32 TC 37 Z9 38 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2002 VL 51 IS 9 BP 2811 EP 2816 DI 10.2337/diabetes.51.9.2811 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600019 PM 12196475 ER PT J AU Pani, L Horal, M Loeken, MR AF Pani, L Horal, M Loeken, MR TI Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy SO DIABETES LA English DT Article ID INDUCED EMBRYONIC MALFORMATIONS; CONGENITAL-MALFORMATIONS; GENE-EXPRESSION; PAX-3 GENE; VITAMIN-E; MOUSE; RATS; OVEREXPRESSION; PROTECTION; PREVENTION AB Previously, we demonstrated that neural tube defects (NTDs) are significantly increased in a mouse model of diabetic pregnancy. In addition, expression of Pax-3, a gene encoding a transcription factor required for neural tube development, is significantly decreased. This suggests that diabetic embryopathy results from impaired expression of genes regulating essential morphogenetic processes. Here, we report that in one mouse strain, C57B1/6J, embryos are resistant to the effects of maternal diabetes on NTDs and Pax-3 expression, in contrast to a susceptible strain, FVB, in which maternal diabetes significantly increases NTDs (P = 0.02) and inhibits Pax-3 expression (P = 0.01). Resistance to NTDs caused by diabetic pregnancy is a dominant trait, as demonstrated by heterozygous embryos of diabetic or nondiabetic mothers of either strain. There was no significant difference between strains in expression of genes that regulate free radical scavenging pathways, suggesting that susceptibility to oxidative stress does not account for the genetic differences. Understanding the genetic bases for differential susceptibility to altered gene expression and NTDs in diabetic mice may be important in delineating the mechanisms by which maternal hyperglycemia interferes with embryo gene expression. Moreover, if susceptibility to diabetic embryopathy is variable in humans as well as in mice, it may be possible to screen individuals at increased risk for this complication of diabetes. C1 Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Cellular & Mol Physiol, 1 Joslin Pl, Boston, MA 02215 USA. NR 23 TC 38 Z9 38 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2002 VL 51 IS 9 BP 2871 EP 2874 DI 10.2337/diabetes.51.9.2871 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 588KX UT WOS:000177701600028 PM 12196484 ER PT J AU Liao, D Asberry, PJ Shofer, JB Callahan, H Matthys, C Boyko, EJ Leonetti, D Kahn, SE Austin, M Newell, L Schwartz, RS Fujimoto, WY AF Liao, D Asberry, PJ Shofer, JB Callahan, H Matthys, C Boyko, EJ Leonetti, D Kahn, SE Austin, M Newell, L Schwartz, RS Fujimoto, WY TI Improvement of BMI, body composition, and body fat distribution with lifestyle modification in Japanese Americans with impaired glucose tolerance SO DIABETES CARE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; FASTING PLASMA-INSULIN; CORONARY-HEART-DISEASE; VISCERAL ADIPOSITY; RISK-FACTORS; WEIGHT-LOSS; FOLLOW-UP; MEN; PREVENTION; NIDDM AB OBJECTIVE- To determine whether diet and endurance exercise improved adiposity-related measurements in Japanese Americans with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS- This study compared the effects of an American Heart Association (AHA) step 2 diet (< 30% of total calories as fat, < 7% saturated fat, 55% carbohydrate, and < 200 mg cholesterol daily) plus endurance exercise for I h three times a week (treatment group) with an AHA step I diet (30% of total calories as fat, 10% saturated fat, 50% carbohydrate, and < 300 mg cholesterol) plus stretching exercise three times a week (control group) on BMI, body composition (% fat), and body fat distribution at 6 and 24 months of follow-up in 64 Japanese American men and women with IGT, 58 of whom completed the study. RESULTS- At 6 months, the treatment group showed significantly greater reduction in percent, body fat (-1.4 +/- 0.4 vs. -0.3 +/- 0.3%); BMI (-1.1 +/- 0.2 vs. -0.4 +/- 0.1 kg/m(2)); subcutaneous fat by computed tomography at the abdomen (-29.3 +/- 4.2 vs. -5.7 +/- 5.9 cm(2)), thigh (-13.2 +/- 3.6 vs. -3.6 +/- 3.0 cm(2)), and thorax (-19.6 +/- 3.6 vs. -8.9 +/- 2.6 cm(2)); and skinfold thickness at the bicep (-2.0 +/- 0.6 vs. 1.1 +/- 0.6 mm) and tricep (-3.7 +/- 0.8 vs. -0.9 +/- 0.6 MITI), which continued despite moving to home-based exercise for the last 18 months. CONCLUSIONS- Diet and endurance exercise improved BMI, body composition, and body fat distribution and, thus, may delay or prevent type 2 diabetes in Japanese Americans with IGT. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Gen Clin Res Ctr, Seattle, WA 98195 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Liao, D (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Box 356426, Seattle, WA 98195 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-00037]; NIDDK NIH HHS [DK-02654, DK-1707, DK-35816, DK-48152] NR 32 TC 47 Z9 49 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2002 VL 25 IS 9 BP 1504 EP 1510 DI 10.2337/diacare.25.9.1504 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UE UT WOS:000185504400002 PM 12196418 ER PT J AU Franceschi, F Genta, RM Gasbarrini, A Silveri, NG Gasbarrini, G Sepulveda, AR AF Franceschi, F Genta, RM Gasbarrini, A Silveri, NG Gasbarrini, G Sepulveda, AR TI Helicobacter pylori infection and expression of the angiogenic factor platelet-derived endothelial cell growth factor by pre-neoplastic gastric mucosal lesions and gastric carcinoma SO DIGESTIVE AND LIVER DISEASE LA English DT Article DE angiogenic factors; gastric cancer; Helicobacter pylori; platelet-derived endothelial cell growth factor ID THYMIDINE PHOSPHORYLASE; PROGNOSTIC-SIGNIFICANCE; CANCER; LECTURE AB Background. Expression of the angiogenic factor platelet-derived endothelial cell growth factor is induced in some gastric carcinomas. Whether angiogenesis is induced early in the development of gastric pre-neoplastic lesions and whether Helicobacter pylori infection affects platelet-derived endothelial cell growth factor expression is not known. Aim. To assess whether chronic gastritis, intestinal metaplasia, gastric dysplasia and gastric carcinomas express platelet-derived endothelial cell growth factor and whether Helicobacter pylori infection might affect the expression of platelet-derived endothelial cell growth factor in these lesions. Patients and Methods. Patients with gastric carcinomas, atrophic gastritis with associated intestinal metaplasia, dysplasia and controls without infection or carcinoma were studied. Results. Platelet-derived endothelial cell growth factor was detected by immunohistochemistry in 9 out 19 gastric carcinomas (459,D). Only focal immunostaining was detected in intestinal metaplasia adjacent to dysplasia and in dysplastic cells. Of the tumours, 90% contained platelet-derived endothelial cell growth factor-positive interstitial cells. A significant correlation was found between active Helicobacter pylori infection and a larger number of platelet-derived endothelial cell growth factor-positive interstitial cells in areas of intestinal metaplasia (p<0.05). Conclusion. Helicobacter pylori infection does not influence the expression of platelet-derived endothelial cell growth factor once gastric cancer has developed. However Helicobacter pylori infection may increase the extension of expression of platelet-derived endothelial cell growth factor by infiltrating interstitial cells in premalignant lesions, such as intestinal metaplasia, which may help create a favourable environment for tumour development. This may possibly be due to nonspecific increase in recruitment of inflammatory cells caused by Heli cobacter pylori infection. Further studies, with a larger number of samples, are now needed in order to confirm this finding. C1 Univ Sacred Heart, Policlin Gemelli, Dept Internal Med, I-00168 Rome, Italy. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. RP Gasbarrini, G (reprint author), Univ Sacred Heart, Policlin Gemelli, Dept Internal Med, Largo A Gemelli 8, I-00168 Rome, Italy. NR 25 TC 9 Z9 10 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD SEP PY 2002 VL 34 IS 9 BP 621 EP 625 DI 10.1016/S1590-8658(02)80203-1 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600KE UT WOS:000178388500004 PM 12405247 ER PT J AU O'Connor, DH Allen, TM Watkins, DI AF O'Connor, DH Allen, TM Watkins, DI TI Cytotoxic T-lymphocyte escape monitoring in simian immunodeficiency virus vaccine challenge studies SO DNA AND CELL BIOLOGY LA English DT Article ID MHC CLASS-I; HIGH-AVIDITY; RHESUS-MONKEYS; HIV-INFECTION; VIRAL LOAD; AIDS; PLASMA; INDUCTION; MACAQUES; VIREMIA AB Several vaccine studies have ameliorated disease progression in simian-human immunodeficiency virus (SHIV) infections. The successes of these vaccines have been largely attributed to protective effects of cytotoxic T-lymphocyte (CTL) responses, although the precise correlates of immune protection remain poorly defined. It is now well established that vigorous CTL and antibody responses can rapidly select for viral escape variants after HIV and SIV infection. Here we suggest that viral variation analyses should be performed on viruses derived from vaccinated, SIV-, or SHIV-challenged animals as a routine component of vaccine evaluation to determine the contribution of immune responses to the success (or failure) of the vaccine regimen. To illustrate the importance of escape analysis, we show that rapid emergence of escape variants postchallenge contributed to the failure of a DNA prime/MVA boost vaccine regimen encoding SIV Tat. C1 Univ Wisconsin, Dept Pathol, Madison, WI 53709 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP O'Connor, DH (reprint author), Univ Wisconsin, Dept Pathol, 1300 Univ Ave, Madison, WI 53709 USA. RI Allen, Todd/F-5473-2011; OI o'connor, david/0000-0003-2139-470X NR 27 TC 17 Z9 17 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 659 EP 664 DI 10.1089/104454902760330192 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500008 PM 12396608 ER PT J AU Addo, MM Yu, XG Rosenberg, ES Walker, BD Altfeld, M AF Addo, MM Yu, XG Rosenberg, ES Walker, BD Altfeld, M TI Cytotoxic T-lymphocyte (CTL) responses directed against regulatory and accessory proteins in HIV-1 infection SO DNA AND CELL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CELLULAR IMMUNE-RESPONSES; ESCAPE VARIANTS; VIREMIA; CELLS; AIDS; EPITOPES; VACCINE; CD4(+); TAT AB The HIV-1 regulatory proteins Tat and Rev and the accessory proteins Vpr, Vpu, and Vif are essential for viral replication, and their cytoplasmic production suggests that they should be processed for recognition by cytotoxic T lymphocytes. However, only limited data is available evaluating to which extent these proteins are targeted in natural infection and optimal cytotoxic T lymphocyte (CTL) epitopes within these proteins have not been defined. In this study, CTL responses against HIV-1 Tat, Rev, Vpr, Vpu, and Vif were analyzed in 70 HIV-1 infected individuals and 10 HIV-1 negative controls using overlapping peptides spanning the entire proteins. Peptide-specific interferon-gamma (IFN-gamma) production was measured by Elispot assay and flow-based intracellular cytokine quantification. HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8+ T-cell lines. All regulatory and accessory proteins served as targets for HIV-1-specific CTL and multiple CTL epitopes were identified in functionally important regions of these proteins. In certain individuals HIV-1-specific CD8+ T-cell responses to these accessory and regulatory proteins contributed up to a third to the magnitude of the total HIV-1-specific CTL response. These data indicate that despite the small size of these proteins regulatory and accessory proteins are targeted by CTL in natural HIV-1 infection, and contribute importantly to the total HIV-1-specific CD8+ T-cell responses. These findings are relevant for the evaluation of the specificity and breadth of immune responses during acute and chronic infection, and will be useful for the design and testing of candidate human immunodeficiency virus (HIV) vaccines. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. RP Addo, MM (reprint author), MGH E, CNY 5246, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI 50429] NR 41 TC 47 Z9 50 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 2002 VL 21 IS 9 BP 671 EP 678 DI 10.1089/104454902760330219 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 598JA UT WOS:000178271500010 PM 12396610 ER PT J AU Puglielli, L AF Puglielli, L TI Is ACAT a novel pharmacological target for the treatment of Alzheimer's disease? SO DRUGS OF THE FUTURE LA English DT Review ID ACYL-COENZYME-A; COA-CHOLESTEROL ACYLTRANSFERASE; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; TRANSGENIC MOUSE MODEL; DENSITY-LIPOPROTEIN; BETA-PEPTIDE; ESTERIFICATION; PRESENILINS; EXPRESSION AB Several independent epidemiological studies have suggested a role for cholesterol in the pathogenesis of Alzheimer's disease (Abeta). Consistent with this role, elevated cholesterol, levels have been reported to increase the biogenesis/deposition of amyloid beta-peptide (AD) in the brains of AD transgenic mouse models. Both cellular and biochemical studies have now confirmed the potential role of cholesterol metabolism and distribution in the regulation of the very first step of AD pathogenesis: the biogenesis of Abeta. Although the molecular mechanisms involved in the sterol-dependent regulation of AD generation have not yet been completely,, revealed, recent reports seem to implicate AcylCoA:cholesterol acyltransferase (ACAT), a key enzyme in the regulation of intracellular cholesterol distribution. C1 Massachusetts Gen Hosp, CAGN, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Puglielli, L (reprint author), Massachusetts Gen Hosp, CAGN, Genet & Aging Res Unit, Bldg 114,16th St,C3009, Charlestown, MA 02129 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD SEP PY 2002 VL 27 IS 9 BP 863 EP 868 DI 10.1358/dof.2002.027.09.856986 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 620FK UT WOS:000179523200006 ER PT J AU Schlozman, SC AF Schlozman, SC TI When illness strikes SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Grad Sch Educ, Boston, MA USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD SEP PY 2002 VL 60 IS 1 BP 82 EP 83 PG 2 WC Education & Educational Research SC Education & Educational Research GA 592LE UT WOS:000177938500018 ER PT J AU Laurich, VM Trbovich, AM O'Neill, FH Houk, CP Sluss, PM Payne, AH Donahoe, PK Teixeira, J AF Laurich, VM Trbovich, AM O'Neill, FH Houk, CP Sluss, PM Payne, AH Donahoe, PK Teixeira, J TI Mullerian inhibiting substance blocks the protein kinase Alpha-induced expression of cytochrome P450 17 alpha-hydroxylase/C17-20 lyase mRNA in a mouse Leydig cell line independent of cAMP responsive element binding protein phosphorylation SO ENDOCRINOLOGY LA English DT Article ID STEROIDOGENIC FACTOR-I; EPIDERMAL GROWTH-FACTOR; REGULATORY STAR GENE; BOVINE CYP17; TRANSCRIPTIONAL REGULATION; TUMOR-CELLS; CYCLIC-AMP; SEXUAL DEVELOPMENT; HORMONE-RECEPTOR; TRANSGENIC MICE AB Mullerian inhibiting substance (MIS) is produced by fetal Sertoli cells and causes regression of the Mullerian duct in male fetuses shortly after commitment of the bipotential embry. onic gonad to testes differentiation. MIS is also produced by the Sertoli cells and granulosa cells of the adult gonads where it plays an important role in regulating steroidogenesis. We have previously shown that MIS can dramatically reduce testosterone synthesis in Leydig cells by inhibiting the expression of cytochrome P450 17alpha-hydroxylase/C17-20 lyase (Cyp17) mRNA in vitro and in vivo. To characterize the signal trans. duction pathway used by MIS to control expression of endogenous Cyp17 in a mouse Leydig cell line, we demonstrate that MIS inhibits both LH- and cAMP-induced expression of Cyp17 at concentrations as low as 3.5 nm and for as long as 18 h. The induction of steroidogenic acute regulatory protein (SCAR) mRNA by cAMP, however, was slightly increased by addition of MIS. Protein kinase A (PKA) inhibition with H-89 blocked Cyp17 mRNA induction, suggesting that MIS interferes with the PKA signal transduction pathway. Inhibition of Cyp17 induction was not seen with added U0126, and wortmannin inhibited the induction incompletely. In addition, phosphorylation of the cAMP responsive element binding protein (CREB) was not detected following 50 muM cAMP exposure, a concentration sufficient for Cyp17 mRNA induction. Moreover, CREB phosphorylation, which was observed with addition of 500 pm cAMP, was not inhibited by coincubation with MIS. Taken together, these results suggest that cAMP induces expression of Cyp17 by a PKA-mediated mechanism and that this induction, which is inhibited by MIS signal transduction, does not require CREB activity, and is distinct from that used to induce steroidogenic acute regulatory protein expression. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Stanford Univ, Div Reprod Biol, Dept Obstet Gynecol, Palo Alto, CA 94305 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, WRN1024,32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R01-CA-17393, R29 CA079459, R29 CA079459-03, R29-CA79459]; NICHD NIH HHS [U54-HD-28138, U54-HD-31398] NR 65 TC 32 Z9 35 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3351 EP 3360 DI 10.1210/en.2001-211352 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800018 PM 12193547 ER PT J AU Sooy, K Demay, MB AF Sooy, K Demay, MB TI Transcriptional repression of the rat osteocalcin gene by delta EF1 SO ENDOCRINOLOGY LA English DT Article ID BINDING PROTEIN DELTA-EF1; LENS-SPECIFIC ACTIVITY; PROMOTER ACTIVITY; ZINC-FINGER; ELEMENT; BONE; SILENCER; ENHANCER; DELTA-1-CRYSTALLIN; DIFFERENTIATION AB Intron I of the rat osteocalcin gene contains silencer elements that suppress osteocalcin-reporter fusion gene transcription. The consensus sequence for the transcription factor deltaEF1 is homologous to two pyrimidine-rich repeats in intron 1 that contribute to silencing of osteocalcin-reporter fusion genes. To assess if overexpression of deltaEF1 augments transcriptional repression by these sequences, the intron 1 sequences (wtS) were placed upstream to the native rat osteocalcin promoter fused to a luciferase reporter gene (-306-OCluc). Coexpression of the wtS-(-306-OCluc) fusion gene with deltaEF1 decreased luciferase activity 30% relative to cotransfection with empty vector. Repression was abolished by point mutations in the putative deltaEF1 motifs, mS-(-306-OCluc). To determine whether deltaEF1 binds to these DNA sequences, gel retardation assays were performed using oligonucleotides containing the putative osteocalcin deltaEF1 motifs and a classical deltaEF1 motif, as radiolabeled probes. A comigrating DNA-protein complex generated by these probes was recognized by an antibody directed against deltaEF1 and competed for by excess unlabeled wild-type oligonucleotides. Oligonucleotides with mutations in the osteocalcin sequences, which abolish suppression, and in the deltaEF1 consensus site, that abolishes binding to deltaEF1, were unable to compete for the formation of this complex. Overexpression of deltaEF1 in ROS 17/2.8 cells led to an 84% decrease in osteocalcin mRNA levels relative to cells transfected with empty vector, confirming that deltaEF1 suppresses expression of the endogenous osteocalcin gene. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [F32 DK-10136-02, DK-36597] NR 28 TC 16 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3370 EP 3375 DI 10.1210/en.2001-211441 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800020 PM 12193549 ER PT J AU Cavicchio, VA Pru, JK Davis, BS Davis, JS Rueda, BR Townson, DH AF Cavicchio, VA Pru, JK Davis, BS Davis, JS Rueda, BR Townson, DH TI Secretion of monocyte chemoattractant protein-1 by endothelial cells of the bovine corpus luteum: Regulation by cytokines but not prostaglandin F2 alpha SO ENDOCRINOLOGY LA English DT Article ID RIBONUCLEIC-ACID EXPRESSION; INTERFERON-TAU; CELLULAR COMPOSITION; MESSENGER-RNA; LUTEOLYSIS; KINASE; PREGNANCY; INDUCTION; RAT; MACROPHAGES AB Information regarding the regulation of monocyte chemoattractant protein-1 (MCP-1) in regression of the corpus luteum (CL) is limited. This study tested the hypothesis that endothelial cells derived from bovine CL are a source of MCP-1, and that proinflammatory cytokines, prostaglandin F2alpha (PGF2alpha), and progesterone regulate MCP-1 expression. Endothelial cells were treated without (Control) or with PGF2alpha (1 muM), TNFalpha (100 ng/ml), interferon-gamma (IFNgamma, 200 IU/ml), and TNFalpha + IFNgamma for 24 and 48 h in the absence or presence of progesterone (P4, 250 ng/ml). Increases in MCP-1 mRNA and protein were observed in response to TNFalpha within 24 and 48 h of culture, respectively (P < 0.05). Interferon-gamma stimulated (P < 0.05) both MCP-1 mRNA and protein after 24 h of culture, and this effect was also sustained through 48 h of culture (P 0.05). Cotreatment of cultures with TNFalpha + IFNgamma lead to further increases (P < 0.05) in MCP-1 in both 24- and 48-h cultures. Surprisingly, neither PGF2alpha nor P4 affected MCP-1 production. Subsequent experiments revealed that the endothelial cells lacked prostaglandin F2alpha receptor mRNA, and the MAPK pathway, although present and responsive to growth factor stimulation, was unresponsive to PGF2alpha stimulation. In summary, endothelial cells derived from bovine CL respond to TNFalpha and IFNgamma stimulation with an increase in MCP-1 secretion. In contrast, neither PGF2alpha nor P4 directly influenced endothelial expression of MCP-1. These results suggest that cytokines stimulate the synthesis of MCP-1 observed during PGF2alpha-induced luteal regression. C1 Univ New Hampshire, Dept Anim & Nutr Sci, Durham, NH 03824 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Kansas, Sch Med, Vet Affairs Med Ctr, Womens Res Inst, Wichita, KS 67214 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Olson Ctr Womens Hlth, Omaha, NE 68198 USA. RP Townson, DH (reprint author), Univ New Hampshire, Dept Anim & Nutr Sci, 128 Main St, Durham, NH 03824 USA. FU NICHD NIH HHS [R01-HD-35934] NR 46 TC 24 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3582 EP 3589 DI 10.1210/en.2002-220388 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800045 PM 12193574 ER PT J AU Donohue, MM Demay, MB AF Donohue, MM Demay, MB TI Rickets in VDR null mice is secondary to decreased apoptosis of hypertrophic chondrocytes SO ENDOCRINOLOGY LA English DT Article ID VITAMIN-D-RECEPTOR; MINERAL ION HOMEOSTASIS; PHOSPHATE IONS; SKELETAL PHENOTYPE; ABLATED MICE; CARTILAGE; CELLS; BONE; OSSIFICATION; MECHANISM AB Both vitamin D deficiency and the absence of a functional vitamin D receptor (VDR) lead to a growth plate abnormality known as rickets. Prevention of abnormal mineral ion homeostasis by early institution of dietary therapy in VDR null mice prevents rickets, demonstrating that the VDR is not required for normal growth plate maturation. We, therefore, hypothesized that rickets, in the absence of a functional VDR, is due to impaired mineral ion homeostasis. Analyses of growth plate morphology in VDR null mice demonstrated normal resting and proliferating chondrocyte layers; however an expansion of the hypertrophic chondrocyte layer was present by 24 days of age. Because extracellular calcium has been shown to play a role in chondrocyte maturation, we addressed the hypothesis that hypocalcemia led to impaired chondrocyte differentiation. However, in situ hybridization analyses revealed normal expression of hypertrophic chondrocyte markers in the tibias growth plate of 24 day old VDR null mice, suggesting that the increase in the hypertrophic chondrocyte layer was not secondary to impaired differentiation. We then addressed whether expansion of the hypertrophic chondrocyte layer was secondary to increased proliferation or decreased apoptosis. BrdU labeling failed to demonstrate an increase in chondrocyte proliferation in the VDR null mice; however, apoptosis was markedly diminished in the late hypertrophic chondroctyes of the VDR null mice, suggesting that impairment in programmed cell death of these cells leads to the characteristic findings of rickets. C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK46974, R01 DK046974] NR 22 TC 53 Z9 55 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2002 VL 143 IS 9 BP 3691 EP 3694 DI 10.1210/en.2002-220454 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586CY UT WOS:000177567800056 PM 12193585 ER PT J AU Magari, SR Schwartz, J Williams, PL Hauser, R Smith, TJ Christiani, DC AF Magari, SR Schwartz, J Williams, PL Hauser, R Smith, TJ Christiani, DC TI The association of particulate air metal concentrations with heart rate variability SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cardiac autonomic function; heart rate variability; metal exposure; occupational exposures; particulate matter ID TRANSITION-METALS; EPITHELIAL-CELLS; US CITIES; POLLUTION; MORTALITY; MATTER; WORKERS; INJURY; OIL; HYPERREACTIVITY AB Numerous studies show an association between particulate air pollution and adverse health effects. Particulate matter is a complex mixture of elemental carbon, ammonium, sulfates, nitrates, organic components, and metals. The mechanisms of action of particulate matter less than or equal to 2.5 mum in mean aerodynamic diameter (PM2.5), as well as the constituents responsible for the observed cardiopulmonary health effects, have not been identified. In this study we focused on the association between the metallic component of PM2.5 and cardiac autonomic function based on standard heart rate variability (HRV) measures in an epidemiologic study of boilermakers. Thirty-nine male boilermakers were monitored throughout a work shift. Each subject wore an ambulatory electrocardiogram (Holter) monitor and a personal monitor to measure PM2.5. We used mixed-effects models to regress heart rate and SDNN index (standard deviation of the normal-to-normal) on PM2.5 and six metals (vanadium, nickel, chromium, lead, copper, and manganese). There were statistically significant mean increases in the SDNN index of 11.30 msec and 3.98 msec for every 1 mug/m(3) increase in the lead and vanadium concentrations, respectively, after adjusting for mean heart rate, age, and smoking status. Small changes in mean heart rate were seen with all exposure metrics. The results of this study suggest an association between exposure to airborne metals and significant alterations in cardiac autonomic function. These results extend our understanding of the adverse health effects of the metals component of ambient PM2.5. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Epidemiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1402,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES00002, ES09860, T32 ES07069] NR 29 TC 89 Z9 96 U1 1 U2 13 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 2002 VL 110 IS 9 BP 875 EP 880 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 591RJ UT WOS:000177893800028 PM 12204821 ER PT J AU Takeoka, M Riviello, JJ Pfeifer, H Thiele, EA AF Takeoka, M Riviello, JJ Pfeifer, H Thiele, EA TI Concomitant treatment with topiramate and ketogenic diet in pediatric epilepsy SO EPILEPSIA LA English DT Article DE topiramate; ketogenic diet; cotreatment; bicarbonate; metabollic acidosis ID METABOLIC-ACIDOSIS; 150 CHILDREN; SEIZURES; EFFICACY AB Purpose: Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD. Methods: Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control. Results: Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained oil cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis. Conclusions: Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels Should lie monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic. C1 Childrens Hosp, Div Epilepsy & Clin Neurophysiol, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Takeoka, M (reprint author), Keio Univ, Sch Med, Dept Pediat, Child Neurol Serv,Shijuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. NR 16 TC 32 Z9 33 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2002 VL 43 IS 9 BP 1072 EP 1075 DI 10.1046/j.1528-1157.2002.00602.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 592CB UT WOS:000177918200015 PM 12199733 ER PT J AU Licht, EA Fujikawa, DG AF Licht, EA Fujikawa, DG TI Nonconvulsive status epilepticus with frontal features: quantitating severity of subclinical epileptiform discharges provides a marker for treatment efficacy, recurrence and outcome SO EPILEPSY RESEARCH LA English DT Article DE nonconvulsive status epilepticus; subclinical epileptiform discharges; subclinical seizures; frontal lobe seizures; cognitive deficits ID CONVULSIVE STATUS EPILEPTICUS; CONFUSION; SEIZURES AB Nonconvulsive status epilepticus (NCSE) is difficult to diagnose but is an important cause of cognitive impairment. Electroencephalogram (EEG) monitoring is required for diagnosis and treatment. Little is known regarding the stability of subclinical epileptiform discharges (SEDs) preceding NCSE nor what strategies may optimize patient outcomes. We report extended follow-up of patients with recurrent frontal SEDs, integrating EEG and cognitive findings before and following treatment of NCSE, and show that quantitating SED severity provides an objective marker of treatment efficacy and recurrence. (C) 2002 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Dept Neurol, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. Nursing Home Care Unit, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90024 USA. RP Licht, EA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, Sepulveda Ambulatory Care Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD SEP PY 2002 VL 51 IS 1-2 BP 13 EP 21 AR PII S0920-1211(02)00107-9 DI 10.1016/S0920-1211(02)00107-9 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 605VE UT WOS:000178697100003 PM 12350380 ER PT J AU Demetri, GD AF Demetri, GD TI Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (ST1571) SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT Symposium on the Treatment of Gastrointestinal Stromal Tumors (GISTs) CY SEP 07-08, 2001 CL HELSINKI, FINLAND DE gastrointestinal stromal tumor; signal transduction; targeted therapy; imatinib mesylate; receptor protein-tyrosine kinase; enzyme inhibitor; oncogene; c-kit ID GASTROINTESTINAL STROMAL TUMORS; C-KIT; BCR-ABL; DIFFERENTIAL-DIAGNOSIS; INTERSTITIAL-CELLS; MUTATIONS; EFFICACY; GROWTH; SAFETY; STI571 AB Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The concept of GIST and the definition of GIST pathology have evolved greatly over the past 5 years. GIST has been shown to share immunohistochemical, ultrastructural and histogenic similarities with the interstitial cells of Cajal. Both GIST and the interstitial cells of Cajal express KIT, the receptor tyrosine kinase that is the protein product of the c-kit proto-oncogene. KIT is universally phosphorylated in GISTs. Sequencing of c-kit complementary DNA from human GIST cells has demonstrated a high frequency of mutations that lead to constitutive activation of the KIT tyrosine kinase in the absence of stimulation by its physiologic ligand (stem cell factor). This, in turn, causes uncontrolled stimulation of downstream signaling cascades with aberrant cellular proliferation and resistance to apoptosis. Historically, malignant GIST has been highly refractory to conventional cytotoxic therapy. Signal transduction inhibition as cancer therapy was first tested successfully with imatinib mesylate (formerly known as STI571), a selective small-molecule tyrosine kinase inhibitor, with the initial target being blockade of Bcr-Abl, the oncogene with tyrosine kinase activity responsible for the pathogenesis of chronic myelogenous leukemia (CML). Imatinib was subsequently shown to block activity of the KIT tyrosine kinase as well, and in laboratory studies this led to apoptotic death of GIST cells. The first GIST patient to receive imatinib exhibited dramatic benefit despite far-advanced metastatic disease that was previously refractory to all chemotherapy. Subsequently, multicenter clinical trials have been performed to assess the safety, efficacy and biologic activity of imatinib in patients with advanced GIST. The results from these studies have established imatinib as an effective new therapeutic alternative for the majority of patients with advanced GIST, a solid tumor for which no prior chemotherapy has ever shown antitumor efficacy. This work provides proof of concept to the hypothesis that selective inhibition of aberrant signal transduction can provide important anticancer activity, if the proper signaling pathways are identified and blocked. (C) 2002,Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. NR 29 TC 75 Z9 80 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2002 VL 38 SU 5 BP S52 EP S59 DI 10.1016/S0959-8049(02)80603-7 PG 8 WC Oncology SC Oncology GA 614QJ UT WOS:000179200600009 PM 12528773 ER PT J AU Van den Abbeele, AD Badawi, RD AF Van den Abbeele, AD Badawi, RD TI Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs) SO EUROPEAN JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT Symposium on the Treatment of Gastrointestinal Stromal Tumors (GISTs) CY SEP 07-08, 2001 CL HELSINKI, FINLAND DE Positron emission tomography (PET); F-18-fluoro-2-deoxy-D-glucose (FDG); Gastrointestinal stromal tumor (GIST) ID CELL LUNG-CANCER; FDG-PET SCAN; BREAST-CANCER; C-KIT; NECK-CANCER; CHEMOTHERAPY; HEAD; SARCOMA; RAT; RADIOTHERAPY AB The reliability of established anatomical imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), is compromised in following response to certain types of treatment if metabolic improvement occurs before morphologic change is apparent. Thus, traditional imaging techniques cannot discriminate early tumor response because they are based on purely visual structural assessments. Recently, the use of positron emission tomography (PET), most commonly employing the radiotracer F-18-fluoro-2-deoxy-D-glucose (FDG), has been shown to improve the assessment of tumor behavior by highlighting early functional changes in tumor glucose metabolism that appear to correlate closely with metabolic tumor response to imatinib mesylate. Like CT and MRI, PET can identify an abnormal mass; its improvement over these techniques lies in its ability to differentiate active tumor from necrosing tissue, malignant from benign tissue, and recurrent tumor from scar tissue. Understanding and using this tool should improve our ability to accurately follow response in GIST patients treated with imatinib mesylate, and permit this new therapeutic approach to be used optimally with accurate follow-up assessments and informed therapeutic decision-making. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Van den Abbeele, AD (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. NR 50 TC 150 Z9 151 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 2002 VL 38 SU 5 BP S60 EP S65 DI 10.1016/S0959-8049(02)80604-9 PG 6 WC Oncology SC Oncology GA 614QJ UT WOS:000179200600010 PM 12528774 ER PT J AU Chatzistamou, I Schally, AV Pafiti, A Kiaris, H Koutselini, H AF Chatzistamou, I Schally, AV Pafiti, A Kiaris, H Koutselini, H TI Expression of growth hormone-releasing hormone in human primary endometrial carcinomas SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; PEPTIDE PRODUCT; CELL; CANCERS; RECEPTOR; TUMOR; GHRH; PROLIFERATION; LOCALIZATION; ANTAGONISTS AB Background: Hypothalamic GH-releasing hormone (GHRH) regulates GH release from the pituitary, but an ectopic production of GHRH has been detected in various non-hypothalamic tissues, especially cancers. Objective: To investigate whether endometrial tumors produce GHRH. Methods: Twenty-four endometrioid, three serous papillary (SP), three mixed type endometrioid/serous papillary adenocarcinomas and one malignant mixed Milllerian tumor (MMMT) were assessed for GHRH inummoreactivity by the polyclonal anti-rabbit antibody SV95 and for the expression of GHRH mRNA by in situ hybridization using an oligonucleotide probe. Results: Increased GHRH immunoreactivity was detected in 15 out of 24 (63%) of the endometrioid tumors, including two out of three (66%) of the mixed type endometrioid/scrous adenocarcinomas but not in the three SP or the MMMT tumor. Cytoplasmic staining was detected in all positive cases, while in three of them strong nuclear localization of GHRH was also revealed. In situ hybridization indicated the presence of GHRH mRNA in six cases, all characterized as positive for GHRH inummoreactivity. Conclusion: GHRH is expressed in a subset of endometrial tumors, of the endometrioid type in particular. A paracrine/autocrine role for GHRH in the development of the disease should be considered. C1 Univ Athens, Sch Med, Aretaie Univ Hosp, Dept Pathol, Athens, Greece. Univ Athens, Sch Med, Aretaie Univ Hosp, Dept Cytopathol, Athens, Greece. Tulane Univ, Sch Med, Dept Med, Sect Expt Med, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Koutselini, H (reprint author), Univ Athens, Sch Med, Aretaie Univ Hosp, Dept Pathol, Vassilisis Sofias 76, Athens, Greece. OI Schally, Andrew/0000-0003-1273-6747 NR 32 TC 21 Z9 21 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 2002 VL 147 IS 3 BP 381 EP 386 DI 10.1530/eje.0.1470381 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606QD UT WOS:000178743900014 PM 12213676 ER PT J AU Paul, E Pozdnyakova, OO Mitchell, E Carroll, MC AF Paul, E Pozdnyakova, OO Mitchell, E Carroll, MC TI Anti-DNA autoreactivity in C4-deficient mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE complement; B lymphocyte; anti-DNA antibody; lupus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CLASSICAL PATHWAY COMPLEMENT; AUTOIMMUNE-DISEASE; ASSOCIATION; ALLELES; C4; GLOMERULONEPHRITIS; SUSCEPTIBILITY; IMMUNOLOGY; DEFICIENCY AB Mice lacking the classical complement component C4 (C4(-/-)) were evaluated for autoreactivity because classical complement deficiencies are major risk factors for human systemic lupus erythematosus (SLE). Naive, 6-month-old C4(-/-) mice have significantly more IgM anti-double-strand DNA antibodies than C4(+/+) controls. By 9 months, IgG anti-dsDNA antibodies are increased and this spontaneous autoreactivity is evident across a mixture of genetic backgrounds. C4(+/-) heterozygous mice also develop autoantibodies, reminiscent of the high incidence of partial C4 deficiency observed in human SLE. Kidneys of C4(-/-) mice have glomerular immune complexes, but progressive renal disease is not apparent in unmanipulated animals. Nonetheless, splenic B cells from C4(-/-) and not C4(+/+) mice as young as 3 months can be triggered to secrete IgM anti-dsDNA antibodies in vitro, before autoantibody titers are significantly elevated in vivo. These findings suggest that C4 normally helps prevent early stages of autoimmune disease and that C4 deficiency predisposes to abnormal regulation of autoreactive B cells. C1 Ctr Blood Res, Carroll Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. RP Paul, E (reprint author), Ctr Blood Res, Carroll Lab, 200 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [K08-AI01841]; NICHD NIH HHS [R01-HD38749] NR 22 TC 46 Z9 50 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2002 VL 32 IS 9 BP 2672 EP 2679 DI 10.1002/1521-4141(200209)32:9<2672::AID-IMMU2672>3.0.CO;2-X PG 8 WC Immunology SC Immunology GA 596BX UT WOS:000178144900031 PM 12207352 ER PT J AU Dickinson, KA Wright, DL Veiga, C McLellan, ST Toth, TL Chen, ZY AF Dickinson, KA Wright, DL Veiga, C McLellan, ST Toth, TL Chen, ZY TI Prediction of in vitro fertilization success rates using post-preparation sperm parameters. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA P419 BP S255 EP S255 DI 10.1016/S0015-0282(02)04075-X PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400707 ER PT J AU Gross, GL Chen, ZY AF Gross, GL Chen, ZY TI Natural cycle oocyte retrieval/intravaginal fertilization (NORIF) a simplified form of IVF embryo transfer, is a reliable approach for restoration of fertility to couples with previous tubal ligation. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 New England Fertil & Endocrinol Assoc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA P364 BP S236 EP S236 DI 10.1016/S0015-0282(02)04171-7 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400653 ER PT J AU Wright, DL Veiga, C Mclellan, S Dickinson, K Toth, TL AF Wright, DL Veiga, C Mclellan, S Dickinson, K Toth, TL TI Failure to conceive in an IVF cycle with blastocyst transfer is not correlated with pregnancy outcome in a subsequent cycle. SO FERTILITY AND STERILITY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 12-17, 2002 CL SEATTLE, WASHINGTON SP Amer Soc Reproduct Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2002 VL 78 IS 3 SU 1 MA P378 BP S240 EP S241 DI 10.1016/S0015-0282(02)04180-8 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 597UP UT WOS:000178239400666 ER PT J AU Davis, JS Rueda, BR AF Davis, JS Rueda, BR TI The corpus luteum: An ovarian structure with maternal instincts and suicidal tendencies SO FRONTIERS IN BIOSCIENCE LA English DT Review DE cytokines; Fas ligand; TNF alpha; corpus luteum; prostaglandin F2 alpha; luteolysis; review ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; MESSENGER-RIBONUCLEIC-ACID; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MICROVASCULAR ENDOTHELIAL-CELLS; HUMAN GRANULOSA-CELLS; NF-KAPPA-B; GONADOTROPIN-RELEASING-HORMONE; ACUTE REGULATORY PROTEIN; BOVINE CORPORA-LUTEA AB The corpus luteum is a unique hormone-regulated, transient reproductive gland that produces progesterone, a required product for the establishment and maintenance of early pregnancy. In the absence of pregnancy the corpus luteum will cease to produce progesterone and the structure itself will regress in size over time. Although the process of luteal regression has been studied for several decades, many of the regulatory mechanisms involved in loss of function and involution of the structure are incompletely understood. More importantly, we are far from understanding how these complex mechanisms function in unison. The factor or factors responsible for initiating and mediating luteolysis are no doubt more complex than originally envisioned. Further, efforts to elucidate the mechanisms responsible for luteolysis have been complicated by different interpretations of what is 'luteolysis', discrepancies between in vitro and in vivo studies, and subsequent biases which are associated with the different methods of analyses. Moreover, the complexity of the mechanisms which regulate the life span of the corpus luteum are compounded by the presence of a heterogeneous population of cells which often respond differentially to the same ligand or stimuli. Attempts to isolate specific luteal cell types for the intention of defining intracellular signaling mechanisms have yielded valuable information. However, studies of a specific cell type taken out of context are often subject to criticism. The most obvious being that the cells are no environment. Evaluation of the corpus luteum in vivo, is not without its criticisms either. A subtle change evoked within a subpopulation of cells can be overlooked if measured in whole tissue or in mixed cell preparations. Furthermore, treatment in vivo with a single agent/ligand (i.e., prostaglandin F2 alpha) may induce a secondary ligand that is ultimately responsible for the biological response. All arguments are valid and cannot be ignored. There are secondary levels of complexity in the corpus luteum brought about by the pleiotropic actions of specific ligands. For example, one ligand can be luteotropic to a steroid producing cell and cytotoxic to a luteal endothelial cell. Furthermore, a specific cell type within the corpus luteum may respond differentially depending on the developmental stage of the luteal phase (i.e., early, mid, or late luteal phase) suggesting that the intracellular signaling pathways are key to defining ligand-induced biological responses. The purpose of this review is to culminate what is known regarding signal transduction pathways activated by initiator(s) and/or mediators of luteolysis. We recognize that an all-inclusive review describing the molecular mechanisms involved in the development, maintenance and regression of the corpus luteum would be impossible within the context of this review. There are a number of recent reviews that discuss luteal development, luteal maintenance and luteolysis with emphasis on neuroendocrine events (13). Consequently, we have focused our review primarily on potential intracellular signaling events of proposed regulators and mediators of luteal regression. Where possible we have attempted to incorporate references that represent rodents, domestic farm animals and primates. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Olson Ctr Womens Hlth, Omaha, NE 68198 USA. Vet Affairs Med Ctr, Res Serv, Omaha, NE 68105 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, 55 Fruit St,VBK137E-GYN, Boston, MA 02114 USA. NR 427 TC 45 Z9 45 U1 0 U2 10 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2002 VL 7 BP D1949 EP D1978 DI 10.2741/davis1 PG 30 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 581PX UT WOS:000177303000008 PM 12161347 ER PT J AU Harisinghani, MG Hahn, PF AF Harisinghani, MG Hahn, PF TI Computed tomography and magnetic resonance imaging evaluation of liver cancer SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID OPERATING CHARACTERISTIC ANALYSIS; SUPERPARAMAGNETIC IRON-OXIDE; NON-HODGKINS-LYMPHOMA; CONTRAST-ENHANCED CT; HEPATOCELLULAR-CARCINOMA; HEPATIC METASTASES; HELICAL CT; MR-IMAGES; PATHOLOGICAL CORRELATION; DIFFERENTIAL-DIAGNOSIS AB Focal liver lesions occur commonly and with varying histology, each requiring radically different management. There are a multitude of imaging modalities currently being used for detecting and characterizing focal liver neoplasms. The primary modalities include ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), and rarely, angiography. CT and MRI have benefited from rapid technologic advances, and MRI, in particular, from the advent of new contrast agents. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. NR 43 TC 8 Z9 8 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD SEP PY 2002 VL 31 IS 3 BP 759 EP + AR PII S0889-8553(02)00028-6 DI 10.1016/S0889-8553(02)00028-6 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 623EZ UT WOS:000179691500006 PM 12481730 ER PT J AU Farrell, JJ Brugge, WR AF Farrell, JJ Brugge, WR TI EUS-guided fine-needle aspiration of a renal mass: an alternative method for diagnosis of malignancy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CELL CARCINOMA; ENDOSCOPIC ULTRASONOGRAPHY; PANCREATIC METASTASES; BIOPSY; ACCURACY; ENDOSONOGRAPHY; CYTODIAGNOSIS; FEATURES; SURVIVAL; CANCER C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Blake 4,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 11 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD SEP PY 2002 VL 56 IS 3 BP 450 EP 452 DI 10.1067/mge.2002.126834 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 589TE UT WOS:000177775800030 PM 12196796 ER PT J AU Ritchie, KJ Malakhov, MP Hetherington, CJ Zhou, LM Little, MT Malakhova, OA Sipe, JC Orkin, SH Zhang, DE AF Ritchie, KJ Malakhov, MP Hetherington, CJ Zhou, LM Little, MT Malakhova, OA Sipe, JC Orkin, SH Zhang, DE TI Dysregulation of protein modification by ISG15 results in brain cell injury SO GENES & DEVELOPMENT LA English DT Article DE interferon; ubiquitin; knockout ID UBIQUITIN-SPECIFIC PROTEASE; NEURAL STEM-CELL; DEUBIQUITINATING ENZYMES; COP9 SIGNALOSOME; VIRUS-INFECTION; INTERFERON; HYDROCEPHALUS; SYSTEM; PATHOGENESIS; CONJUGATION AB UBP43 (USP18) is a protease that removes the ubiquitin-like modifier ISG15 from conjugated proteins. Here we present the first report of dysregulation of protein ISG15 modification by the generation of UBP43 knockout mice. In the absence of UBP43, brain tissue showed an elevated level of ISG15 conjugates, and cellular necrosis was evident in the ependyma. Such disruption of the blood-brain barrier resulted in severe neurologic disorders. These results demonstrate that UBP43 plays a critical role in maintaining the homeostatic balance of ISG15-conjugated protein, and that regulation of cellular levels of ISG15 protein modification is essential for brain cell function. C1 Scripps Res Inst, Dept Mol & Expt Med, MEM L51, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Zhang, DE (reprint author), Scripps Res Inst, Dept Mol & Expt Med, MEM L51, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM dzhang@scripps.edu FU NCI NIH HHS [CA79849, R01 CA079849] NR 40 TC 102 Z9 103 U1 0 U2 2 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 SEP 1 PY 2002 VL 16 IS 17 BP 2207 EP 2212 DI 10.1101/gad.1010202 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 592VF UT WOS:000177957000003 PM 12208842 ER PT J AU Talora, C Sgroi, DC Crum, CP Dotto, GP AF Talora, C Sgroi, DC Crum, CP Dotto, GP TI Specific down-modulation of Notch1 signaling in cervical cancer cells is required for sustained HPV-E6/E7 expression and late steps of malignant transformation SO GENES & DEVELOPMENT LA English DT Article DE Notch; p21(WAF1/Cip1); Fra-1; c-Fos; keratinocyte transformation ID HUMAN PAPILLOMAVIRUS TYPE-16; FOS-RELATED ANTIGEN; CARCINOMA CELLS; NEOPLASTIC LESIONS; MAMMALIAN NOTCH; E7 ONCOPROTEIN; GENE-PRODUCT; MOUSE NOTCH1; E2 PROTEIN; AP1 SITES AB The Notch family of cell surface receptors plays a key role in cell-fate determination and differentiation, functioning in a cell- and context-specific manner. In mammalian cells, Notch activation is generally thought to maintain stem cell potential and inhibit differentiation, thereby promoting carcinogenesis. However, in other contexts such as primary epithelial cells (keratinocytes), increased Notch activity causes exit from the cell cycle and/or commitment to differentiation. We now report that expression of the endogenous Notch1 gene is markedly reduced in a panel of cervical carcinoma cells whereas expression of Notch2 remains elevated, and Notch1 expression is similarly reduced or absent in invasive cervical cancers. Conversely, expression of activated Notch1 causes strong growth inhibition of HPV-positive, but not HPV-negative, cervical carcinoma cells, but exerts no such effects on other epithelial tumor cells. Increased Notch1 signaling, but not Notch2, causes a dramatic down-modulation of HPV-driven transcription of the E6/E7 viral genes, through suppression of AP-1 activity by up-regulation of the Fra-1 family member and decreased c-Fos expression. Thus, Notch1 exerts specific protective effects against HPV-induced transformation through suppression of E6/E7 expression, and down-modulation of Notch1 expression is likely to play an important role in late stages of HPV-induced carcinogenesis. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA16038, CA73796, P01 CA016038, R01 CA073796]; NIAMS NIH HHS [AR39190, R01 AR039190] NR 44 TC 173 Z9 189 U1 0 U2 8 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 SEP 1 PY 2002 VL 16 IS 17 BP 2252 EP 2263 DI 10.1101/gad.988902 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 592VF UT WOS:000177957000009 PM 12208848 ER PT J AU Tseng, ASK Hariharan, IK AF Tseng, ASK Hariharan, IK TI An overexpression screen in Drosophila for genes that restrict growth or cell-cycle progression in the developing eye SO GENETICS LA English DT Article ID CENTROMERE PROTEIN INCENP; DEPENDENT KINASE INHIBITOR; OF-FUNCTION SCREEN; INNER CENTROMERE; CHROMOSOME SEGREGATION; MISEXPRESSION SCREEN; RNA INTERFERENCE; CLEAVAGE FURROW; MELANOGASTER; EXPRESSION AB We screened for genes that, when overexpressed in the proliferating cells of the eye imaginal disc, result in a reduction in the size of the adult eye. After crossing the collection of 2296 EP lines to the ey-GAL4 driver, we identified 46 lines, corresponding to insertions in 32 different loci, that elicited a small eye phenotype. These lines were classified further by testing for an effect in postmitotic cells using the sev-GAL4 driver, by testing for an effect in the wing using en-GAL4, and by testing for the ability of overexpression of cycE to rescue the small eye phenotype. EP lines identified in the screen encompass known regulators of eye development including hh and dpp, known genes that have not been studied previously with respect to eye development, as well as 19 novel ORFs. Lines with insertions near INCENP, elB, and CG11518 were characterized in more detail with respect to changes in growth, cell-cycle phasing, and doubling times that were elicited by overexpression. RNAi-induced phenotypes were also analyzed in SL2 cells. Thus overexpression screens can be combined with RNAi experiments to identify and characterize new regulators of growth and cell proliferation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,16th St, Charlestown, MA 02129 USA. FU NEI NIH HHS [EY11632] NR 62 TC 53 Z9 54 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2002 VL 162 IS 1 BP 229 EP 243 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 599YT UT WOS:000178363400019 PM 12242236 ER PT J AU Baker, SE Lorenzen, JA Miller, SW Bunch, TA Jannuzi, AL Ginsberg, MH Perkins, LA Brower, DL AF Baker, SE Lorenzen, JA Miller, SW Bunch, TA Jannuzi, AL Ginsberg, MH Perkins, LA Brower, DL TI Genetic interaction between integrins and moleskin, a gene encoding a Drosophila homolog of importin-7 SO GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; WING VEIN DEVELOPMENT; PS INTEGRINS; EGF RECEPTOR; NUCLEAR IMPORT; MEDIATED ADHESION; IMAGINAL DISKS; FOCAL ADHESION; CELL-ADHESION; SHP-2 AB The Drosophila PSI and PS2 integrins are required to maintain the connection between the dorsal and ventral wing epithelia. If alphaPS subunits are inappropriately expressed during early pupariation, the epithelia separate, causing a wing blister. Two lines of evidence indicate that this apparent loss-of-function phenotype is not a dominant negative effect, but is due to inappropriate expression of functional integrins: wing blisters are not generated efficiently by misexpression of loss-of-function alphaPS2 subunits with mutations that inhibit ligand binding, and gain-of-function, hyperactivated mutant alphaPS2 proteins cause blistering at expression levels well below those required by wild-type proteins. A genetic screen for dominant suppressors of wing blisters generated null alleles of a gene named moleskin, which encodes the protein DIM-7. DIM-7, a Drosophila homolog of vertebrate importin-7, has recently been shown to bind the SHP-2 tyrosine phosphatase homolog Corkscrew and to be important in the nuclear translocation of activated D-ERK. Consistent with this latter finding, homozygous mutant clones of moleskin fail to grow in the wing. Genetic tests suggest that the moleskin suppression of wing blisters is not directly related to inhibition of D-ERK nuclear import. These data are discussed with respect to the possible regulation of integrin function by cytoplasmic ERK. C1 Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85721 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Charlestown, MA 02129 USA. Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA. RP Brower, DL (reprint author), Univ Arizona, Dept Mol & Cellular Biol, Life S Bldg,1007 E Lowell St, Tucson, AZ 85721 USA. FU NHLBI NIH HHS [HL48728]; NIGMS NIH HHS [5F32GM19149, R01GM42474, 5F32GM17901, R01GM61707] NR 79 TC 23 Z9 23 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2002 VL 162 IS 1 BP 285 EP 296 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 599YT UT WOS:000178363400023 PM 12242240 ER PT J AU Lehmann, LS Weeks, JC Klar, N Garber, JE AF Lehmann, LS Weeks, JC Klar, N Garber, JE TI A population-based study of Ashkenazi Jewish women's attitudes toward genetic discrimination and BRCA1/2 testing SO GENETICS IN MEDICINE LA English DT Article DE genetic testing; BRCA1/2; genetic discrimination; Ashkenazi Jews ID BREAST-CANCER PATIENTS; OVARIAN-CANCER; COLORECTAL-CANCER; MUTATIONS; COMMUNITIES; GUIDELINES; DATABASE; DISEASE; JEWS; NEED AB Purpose: The Human Genome Project continues to produce an increasing number of genetic susceptibility tests. Some of these genetic tests target social or ethnic groups who are at increased risk of developing a disease. The Ashkenazi Jewish community is one ethnic group that is an ongoing subject of genetic investigation. We assessed the attitudes of a population-based sample of Ashkenazi Jewish women toward breast-ovarian cancer susceptibility testing (BRCA1/2). In particular, we assessed concerns about group discrimination, perceptions of the advantages and disadvantages of BRCA1/2 testing, and the relationship between concerns about discrimination and the potential benefits of genetic testing. Methods: A telephone survey of a population-based sample of 200 Jewish women. Results: A minority of women (17%) in this study expressed concern or discomfort with Jews being offered BRCA1/2 testing. Most women believed there were scientific reasons for testing Jews (71%), and only 5% of women felt that research that focused on Jews was bad for Jews as a group. Increased concern about genetic discrimination was associated with women who were highly educated (odds ratio 2.68). Forty percent of women surveyed were interested in BRCA1/2 testing, 40% were not interested, and 20% were uncertain about whether they would obtain BRCA1/2 testing. Increased interest in genetic testing was associated with a desire to obtain information about children's risk of disease and valuing information for its own sake. Conclusions: The majority of a population-based sample of Jewish women did not express concerns about group discrimination resulting from genetic testing. Women who are highly educated are more concerned about genetic discrimination. There is significant variation among Jewish women's interest in breast cancer susceptibility testing. C1 Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Lehmann, LS (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. FU BHP HRSA HHS [5 T32 PE11001] NR 40 TC 28 Z9 28 U1 0 U2 1 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 SEP-OCT PY 2002 VL 4 IS 5 BP 346 EP 352 DI 10.1097/01.GIM.0000029069.64884.66 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 642GZ UT WOS:000180797000005 PM 12394347 ER PT J AU Rowan, AJ AF Rowan, AJ TI Seizure - Fundamentals of drug management of epilepsy in the older patient SO GERIATRICS LA English DT Article AB Although commonly perceived as a condition of the young, epilepsy has a significant presence in the geriatric population. The most common seizure types in older persons are complex partial, simple partial, and secondarily generalized tonic clonic. Patient assessment and management objectives include determining the seizure type, calculating the risk of seizure recurrence, and determining whether to initiate anticonvulsant therapy. These objectives are pursued using clinical, electroencephalographic (EEG), and neuroimaging findings. Treatment can reduce the risk of recurrence and prevent injuries likely to occur among older persons experiencing seizures. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Neurol, Bronx, NY USA. RP Rowan, AJ (reprint author), CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD SEP PY 2002 VL 57 IS 9 BP 33 EP 37 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 595VP UT WOS:000178129500009 PM 12271827 ER PT J AU Rice, CA Kapur, R AF Rice, CA Kapur, R TI The impact of the "troubles" on therapy groups in Northern Ireland SO GROUP LA English DT Article DE group therapy; trauma; civil strife and chronic trauma; intergroup conflict; civil strife and group therapy; group therapists and trauma AB Since September 11, 2001, terrorism has become familiar to us. The word itself rolls readily off our lips and we wonder about, and struggle with, the lasting consequences of that late summer day. In this paper we speak about thirty-four years of civil strife and terrorism in Northern Ireland. We examine the traumatic impact of that chronic strife on the therapy groups in Northern Ireland. Specifically we examine its impact on therapy groups-as-a-whole, on therapy group members and their interactions with each other, and on the group therapists who lead those groups. A brief review of the history of the strife and its impact on the citizenry precedes these central discussions. We conclude with suggestions about how we may use specially designed groups to enable therapists to address those effects in their groups. Some of these suggestions are already underway. C1 Boston Inst Psychotherapies Inc, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston Inst Psychotherapy, Cambridge, MA 02138 USA. RP Rice, CA (reprint author), 23 Briarwood Circle, Needham, MA 02494 USA. NR 19 TC 2 Z9 2 U1 0 U2 2 PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0362-4021 J9 GROUP JI Group PD SEP PY 2002 VL 26 IS 3 BP 247 EP 264 DI 10.1023/A:1021065211860 PG 18 WC Psychology, Clinical SC Psychology GA 625VE UT WOS:000179835600006 ER PT J AU Franceschi, F Sepulveda, AR Penland, R Fukui, H Osato, M Gasbarrini, A Gasbarrini, G Graham, DY Genta, RM AF Franceschi, F Sepulveda, AR Penland, R Fukui, H Osato, M Gasbarrini, A Gasbarrini, G Graham, DY Genta, RM TI Pathological changes in the gastric mucosa of Mongolian gerbils infected by different strains of Helicobacter pylori SO GUT LA English DT Meeting Abstract CT 15th International Workshop on Gastrointestinal Pathology and Helicobacter CY SEP 11-14, 2002 CL ATHENS, GREECE C1 Univ Sacred Heart, I-00168 Rome, Italy. Univ Pittsburgh, Pittsburgh, PA USA. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 SU 2 MA 813 BP A49 EP A50 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 599PJ UT WOS:000178344100176 ER PT J AU Franceschi, F Penland, R Fukui, H Osato, M Gasbarrini, A Gasbarrini, G Graham, DY Sepulveda, AR Genta, RM AF Franceschi, F Penland, R Fukui, H Osato, M Gasbarrini, A Gasbarrini, G Graham, DY Sepulveda, AR Genta, RM TI Helicobacter pylori infection affects growth rate in Mongolian gerbils SO GUT LA English DT Meeting Abstract CT 15th International Workshop on Gastrointestinal Pathology and Helicobacter CY SEP 11-14, 2002 CL ATHENS, GREECE C1 Univ Sacred Heart, I-00168 Rome, Italy. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 SU 2 MA 810 BP A49 EP A49 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 599PJ UT WOS:000178344100173 ER PT J AU Kwon, DH Dore, MP Kim, JJ Lee, M Kato, M Graham, DY AF Kwon, DH Dore, MP Kim, JJ Lee, M Kato, M Graham, DY TI Mechanism of acquired-multidrug resistance in Helicobacter pylori: Alterations of outer membrane proteins and lipopolysaccharide SO GUT LA English DT Meeting Abstract CT 15th International Workshop on Gastrointestinal Pathology and Helicobacter CY SEP 11-14, 2002 CL ATHENS, GREECE C1 VA Med Ctr, Houston, TX USA. Univ Sassari, Dept Med, I-07100 Sassari, Italy. Sungkyunkwan Univ, Dept Med, Samsung Med Ctr, Seoul, South Korea. Ewha Womans Univ, Dept Clin Pathol, Seoul, South Korea. Hokkaido Univ, Sch Med, Dept Endoscopy, Sapporo, Hokkaido 060, Japan. RI Kato, Mototsugu/A-6736-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 SU 2 MA 107 BP A2 EP A2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 599PJ UT WOS:000178344100009 ER PT J AU Taylor, NS Ge, Z Dewhirst, FE Fox, JG AF Taylor, NS Ge, Z Dewhirst, FE Fox, JG TI Cytolethal distending toxin in Helicobacter cinaedi SO GUT LA English DT Meeting Abstract CT 15th International Workshop on Gastrointestinal Pathology and Helicobacter CY SEP 11-14, 2002 CL ATHENS, GREECE C1 MIT, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 SU 2 MA 304 BP A13 EP A14 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 599PJ UT WOS:000178344100052 ER PT J AU Vakil, N Kovacs, T Ignatowitz, W Hahne, W Barth, J AF Vakil, N Kovacs, T Ignatowitz, W Hahne, W Barth, J TI Presence or absence of peptic ulcer disease does not affect H-pylori eradication rates with rabeprazole-based triple therapy SO GUT LA English DT Meeting Abstract CT 15th International Workshop on Gastrointestinal Pathology and Helicobacter CY SEP 11-14, 2002 CL ATHENS, GREECE C1 Univ Wisconsin, Sch Med, Milwaukee, WI 53201 USA. Univ Calif Los Angeles, W Los Angeles VAMC, CURE Clin, Los Angeles, CA USA. Pharma Trials Inc, Brooklyn, NY USA. Eisai Inc, Teaneck, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD SEP PY 2002 VL 51 SU 2 MA 1509 BP A93 EP A93 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 599PJ UT WOS:000178344100321 ER PT J AU Seiden, MV Swenerton, KD Matulonis, U Campos, S Rose, P Batist, G Ette, E Garg, V Fuller, A Harding, MW Charpentier, D AF Seiden, MV Swenerton, KD Matulonis, U Campos, S Rose, P Batist, G Ette, E Garg, V Fuller, A Harding, MW Charpentier, D TI A phase II study of the MDR inhibitor biricodar (INCEL, VX-710) and paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy SO GYNECOLOGIC ONCOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE GENE; TUBULIN ISOTYPE EXPRESSION; PROTEIN MRP GENE; P-GLYCOPROTEIN; PROGNOSTIC FACTORS; CELL-DEATH; CARCINOMA; TUMORS; CHEMOTHERAPY; APOPTOSIS AB Purpose. Incel (biricodar, VX-710) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug-resistance-associated protein (MRP1) expressing cells. This phase II study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with advanced ovarian cancer refractory to prior paclitaxel therapy. Experimental design. Eligible patients had paclitaxel-refractory disease defined as progressive disease after a minimum of two cycles of paclitaxel (weekly or 3-week schedule) or relapsed disease within 4 months of prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h starting 4 h after initiation of a 24-h continuous intravenous infusion of 120 mg/m(2)/h VX-710. Cycles were repeated every 3 weeks. Results. Fifty patients received treatment and 45 were evaluable for response. VX-710 + paclitaxel therapy was generally well tolerated. Myelosuppression was the principal toxicity, with a median Cycle I nadir absolute neutrophil count of 0.27 X 10(9) cells/L and a 47% overall incidence of Grade 4 neutropenia. Mild to moderate peripheral neuritis or neuropathy was the primary nonhematologic toxicity, affecting 62% of patients. Other nonhematologic toxicities were generally mild to moderate and reversible. Paclitaxel area under the concentration-versus-time curve (AUC) (16 +/- 5.3 mug X h/mL) during the first treatment cycle was comparable to standard 175 mg/m(2) paclitaxel administered over 3 h. Of the 3 patients who achieved partial responses, 2 had progressed during prior paclitaxel therapy. Twelve patients maintained stable disease and 14/45 (31%) of patients had CA-125 reductions of 50-90% for up to 24 weeks. The median time-to-disease progression was 10 weeks for the intent-to-treat population and 20.7 weeks for the CA-125 responders. Conclusions. The results suggest that VX-710 with paclitaxel has modest activity in paclitaxel-resistant ovarian cancer. Further research is warranted in less heavily treated patients. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Case Western Reserve Univ, MacDonald Womens Hosp, Cleveland, OH 44109 USA. Jewish Gen Hosp, Montreal, PQ, Canada. Vertex Pharmaceut Inc, Cambridge, MA 02139 USA. CHUM, Montreal, PQ H2L 4M1, Canada. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 55 TC 58 Z9 66 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD SEP PY 2002 VL 86 IS 3 BP 302 EP 310 DI 10.1006/gyno.2002.6762 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 592YT UT WOS:000177965000012 PM 12217752 ER PT J AU Heckers, S AF Heckers, S TI How many bipolar mixed states are there? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material C1 McLean Hosp, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Heckers, S (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 10 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2002 VL 10 IS 5 BP 276 EP 279 DI 10.1093/hrp/10.5.276 PG 4 WC Psychiatry SC Psychiatry GA 597QW UT WOS:000178233100002 PM 12202453 ER PT J AU Bernstein, ME Reich, DB Zanarini, MC Siever, LJ AF Bernstein, ME Reich, DB Zanarini, MC Siever, LJ TI "Late-onset" borderline personality disorder: A life unraveling SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID SELF-INJURIOUS-BEHAVIOR; OPEN-LABEL TRIAL; NALTREXONE C1 McLean Hosp, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Bernstein, ME (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. NR 17 TC 3 Z9 3 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 2002 VL 10 IS 5 BP 292 EP 301 DI 10.1093/hrp/10.5.292 PG 10 WC Psychiatry SC Psychiatry GA 597QW UT WOS:000178233100004 PM 12202455 ER PT J AU Young, RH Clement, PB AF Young, RH Clement, PB TI Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis SO HISTOPATHOLOGY LA English DT Review DE uterine cervix; adenocarcinoma; usual type; villoglandular papillary; mucinous; endometrioid; clear cell; serous; mesonephric; adenosquamous; other variants ID MINIMAL-DEVIATION ADENOCARCINOMA; ADENOID CYSTIC CARCINOMA; UTERINE CERVIX; GLANDULAR HYPERPLASIA; ENDOMETRIOID ADENOCARCINOMA; MICROGLANDULAR HYPERPLASIA; BASAL CARCINOMA; TUNNEL CLUSTERS; CELL-CARCINOMA; MALIGNUM AB Adenocarcinoma of the uterine cervix and its variants account for a much greater number of cases in routine practice of histopathology than they did several decades ago. The varied morphology of these tumours results in diverse problems in differential diagnosis. The overall area of glandular pathology of the cervix, of which invasive adenocarcinoma is only one subset, is further complicated by the fact that there are many benign glandular proliferations of the cervix that can potentially be misinterpreted as adenocarcinoma. In this review the histopathology of endocervical adenocarcinoma and its variants is presented with the emphasis on evaluation of routinely stained sections, still the bedrock of routine practice, relatively little aid being provided by immunohistochemistry or other new techniques, contrary to what is sometimes implied in the literature. Description of the appearance of each subtype of adenocarcinoma or variant thereof is followed by a section on their differential diagnosis. Eighty percent of endocervical carcinomas are of the so-called usual type being characterized by cells with eosinophilic cytoplasm and generally brisk mitotic activity. It is sometimes stated that endocervical adenocarcinomas are mucinous but the usual form just noted often has little or no mucin. Pure or almost pure mucinous adenocarcinoma do occur, however, and have an important subtype, the so-called adenoma malignum (minimal deviation adenocarcinoma). Although treacherous because of its bland cytological features and sometimes deceptive pattern, a cone biopsy or hysterectomy specimen showing this neoplasm typically has easily recognizable features that indicate the presence of an infiltrative adenocarcinoma. An important variant of usual endocervical adenocarcinoma is the well differentiated villoglandular papillary adenocarcinoma, a designation that should be reserved for tumours with grade 1 cytologic features as usual endocervical adenocarcinoma, which is typically grade 2, may have papillae. In our opinion all other variants of pure adenocarcinoma, including endometrioid, are rare and include in addition to the latter clear cell, serous and mesonephric neoplasms. Tumours witha glandular and nonglandular component are also reviewed: adenosquamous carcinoma, glassy cell carcinoma, adenoid basal carcinoma, 'adenoid cystic' carcinoma and adenocarcinoma admixed with a neuroendocrine tumour. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Univ British Columbia, Vancouver Gen Hosp, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, 55 Fruit St,WTN215, Boston, MA 02114 USA. NR 67 TC 97 Z9 109 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD SEP PY 2002 VL 41 IS 3 BP 185 EP 207 DI 10.1046/j.1365-2559.2002.01462.x PG 23 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 589YT UT WOS:000177789700001 PM 12207781 ER PT J AU Madry, H Padera, R Seidel, J Langer, R Freed, LE Trippel, SB Vunjak-Novakovic, G AF Madry, H Padera, R Seidel, J Langer, R Freed, LE Trippel, SB Vunjak-Novakovic, G TI Gene transfer of a human insulin-like growth factor I cDNA enhances tissue engineering of cartilage SO HUMAN GENE THERAPY LA English DT Article ID ARTICULAR-CARTILAGE; POLYMER SCAFFOLDS; IGF-I; CHONDROCYTES; VIVO; TRANSPLANTATION; EXPLANTS; COLLAGEN; CULTIVATION; MODULATE AB The repair of articular cartilage lesions remains a clinical problem. Two novel approaches to cartilage formation, gene transfer and tissue engineering, have been limited by short-term transgene expression in transplanted chondrocytes and inability to deliver regulatory signals to engineered tissues according to specific temporal and spatial patterns. We tested the hypothesis that the transfer of a cDNA encoding the human insulin-like growth factor I (IGF-I) can provide sustained gene expression in cell-polymer constructs in vitro and in vivo and enhance the structural and functional properties of tissue-engineered cartilage. Bovine articular chondrocytes genetically modified to overexpress human IGF-I were seeded into polymer scaffolds, cultured in bioreactors in serum-free medium, and implanted subcutaneously in nude mice; constructs based on nontransfected or lacZ-transfected chondrocytes served as controls. Transgene expression was maintained throughout the duration of the study, more than 4 weeks in vitro followed by an additional 10 days either in vitro or in vivo. Chondrogenesis progressed toward the formation of cartilaginous tissue that was characterized by the presence of glycosaminoglycans, aggrecan, and type II collagen, and the absence of type I collagen. IGF-I constructs contained increased amounts of glycosaminoglycans and collagen and confined-compression equilibrium moduli as compared with controls; all groups had subnormal cellularity. The amounts of glycosaminoglycans and collagen per unit DNA in IGF-I constructs were markedly higher than in constructs cultured in serum-supplemented medium or native cartilage. This enhancement of chondrogenesis by spatially defined overexpression of human IGF-I suggests that cartilage tissue engineering based on genetically modified chondrocytes may be advantageous as compared with either gene transfer or tissue engineering alone. C1 MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02142 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthoped Res Labs,Dept Orthoped Surg, Boston, MA 02114 USA. Univ Saarland, Lab Expt Orthoped, Dept Orthoped Surg, D-66421 Homburg, Germany. RP Vunjak-Novakovic, G (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, MIT E25-330,45 Carleton St, Cambridge, MA 02142 USA. EM gordana@mit.edu OI Vunjak-Novakovic, Gordana/0000-0002-9382-1574 FU NIAMS NIH HHS [AR 31068, AR 45749] NR 45 TC 62 Z9 68 U1 1 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2002 VL 13 IS 13 BP 1621 EP 1630 DI 10.1089/10430340260201716 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 588YX UT WOS:000177730800009 PM 12228017 ER PT J AU Reche, PA Glutting, JP Reinherz, EL AF Reche, PA Glutting, JP Reinherz, EL TI Prediction of MHC class I binding peptides using profile motifs SO HUMAN IMMUNOLOGY LA English DT Article DE PSSM; profile; epitopes; MHC; prediction ID SEQUENCE WEIGHTS; MOLECULES; PROTEIN; DATABASE; COMPLEXES; PRINCIPLES; LIBRARIES; MATRICES; SEARCHES; BLOCKS AB Peptides that bind to a given major histocompatibility complex (MHC) molecule share sequence similarity. Therefore, a position specific scoring matrix (PSSM) or profile derived from a set of peptides known to bind to a specific MHC molecule would be a suitable predictor of whether other peptides might bind, thus anticipating possible T-cell epitopes within a protein. In this approach, the binding potential of any peptide sequence (query) to a given MHC molecule is linked to its similarity to a group of aligned peptides known to bind to that MHC, and can be obtained by comparing the query to the PSSM. This article describes the derivation of alignments and profiles from a collection of peptides known to bind a specific MHC, compatible with the structural and molecular basis of the peptide-MHC class I (MHCI) interaction. Moreover, in order to apply these profiles to the prediction of peptide-MHCI binding, we have developed a new search algorithm (RANKPEP) that ranks all possible peptides from an input protein using the PSSM coefficients. The predictive power of the method was evaluated by running RANKPEP on proteins known to bear MHCI K-b- and D-b-restricted T-cell epitopes. Analysis of the results indicates that > 80% of. these epitopes are among the top 2% of scoring peptides. Prediction of peptide-MHC binding using a variety of MHCI-specific PSSMs is available on line at our RANKPEP web server (www.mifoundation.org/Tools/rankpep.html). In addition, the RANKPEP server also allows the user to enter additional profiles, making the server a powerful and versatile computational biology benchmark for the prediction of peptide-MHC binding. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med, 44 Binney St, Boston, MA 02115 USA. RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI50900] NR 42 TC 185 Z9 196 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP PY 2002 VL 63 IS 9 BP 701 EP 709 AR PII S0198-8859(02)00432-9 DI 10.1016/S0198-8859(02)00432-9 PG 9 WC Immunology SC Immunology GA 590DZ UT WOS:000177804200001 PM 12175724 ER PT J AU Rajsbaum, R Fici, D Boggs, DA Fraser, PA Flores-Villanueva, PO Awdeh, ZL AF Rajsbaum, R Fici, D Boggs, DA Fraser, PA Flores-Villanueva, PO Awdeh, ZL TI Linkage disequilibrium between HLA-DPB1 alleles and retinoid X receptor beta haplotypes SO HUMAN IMMUNOLOGY LA English DT Article DE HLA-DPB1; linkage disequilibrium; polymorphism; retinoid X receptor; SNP ID DIABETES-MELLITUS; ACID; H-2RIIBP; GENES; IDDM AB The human retinoid X receptor beta (RXRB) gene maps to the major histocompatibility complex (MHC) region, between KE4 and COL11A2, approximately 130-kb centromeric to HLA-DPB1. We have recently reported a new polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to detect the G to T single nucleotide polymorphism (SNP) located seven nucleotides after the tenth exon of the RXRB gene, or 3' end+7 position according to existing nomenclature. We also reported strong linkage disequilibrium between the HLA-DPB1*0401 and RXRB+7*T alleles. In the present study, we describe two PCR-RFLP methods to detect additional SNPs in the RXRB gene, T to A, at exon10+378 and A to T at 3'end+140. This new methodology permitted the unambiguous assignment of three distinct SNPs at RXRB exon10+378, 3'end+7 and 3'end+140 to form an "RXRB haplotype." The data generated from this study were used to determine linkage disequilibrium between several MHC markers and the RXRB alleles and haplotypes. Family studies revealed significant linkage disequilibrium between the RXRB alleles and a number of HLA-DPB1 alleles. (C) American Society for Histocompatibility and Immunogenetics, 2002. Published by Elsevier Science Inc. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Awdeh, ZL (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Rajsbaum, Ricardo/F-2046-2014 FU NHLBI NIH HHS [HL-29583] NR 22 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD SEP PY 2002 VL 63 IS 9 BP 771 EP 778 AR PII S0198-8859(02)00427-5 DI 10.1016/S0198-8859(02)00427-5 PG 8 WC Immunology SC Immunology GA 590DZ UT WOS:000177804200009 PM 12175732 ER PT J AU Sharma, R Bhatti, S Gomez, M Clark, RM Murray, C Ashizawa, T Bidichandani, SI AF Sharma, R Bhatti, S Gomez, M Clark, RM Murray, C Ashizawa, T Bidichandani, SI TI The GAA triplet-repeat sequence in Friedreich ataxia shows a high level of somatic instability in vivo, with a significant predilection for large contractions SO HUMAN MOLECULAR GENETICS LA English DT Article ID LYMPHOBLASTOID CELL-LINES; SMALL POOL PCR; REPLICATION PROTEIN-A; SINGLE SPERM ANALYSIS; DOT-TTC REPEATS; MYOTONIC-DYSTROPHY; TRINUCLEOTIDE REPEATS; INTERGENERATIONAL INSTABILITY; DIAGNOSTIC-CRITERIA; CLINICAL-FEATURES AB Friedreich ataxia is commonly caused by large expansions of a GAA triplet-repeat (GAA-TR) sequence in the first intron of the FRDA gene. We used small-pool PCR to analyze somatic variability among 7190 individual FRDA molecules from peripheral blood DNA of subjects carrying 12 different expanded alleles, ranging in size from 241 to 1105 triplets. Expanded alleles showed a length-dependent increase in somatic variability, with mutation loads ranging from 47% to 78%. We noted a strong contraction bias among long alleles (>500 triplets), which showed a 4-fold higher frequency of large contractions versus expansions. Some contractions were very large; of all somatic mutations scored, similar to5% involved contractions of >50% of the original allele length, and 0.29% involved complete reversion to the normal/premutation length (less than or equal to60 triplets). These observations contrast sharply with the strong expansion bias seen in expanded CTG triplet repeats in myotonic dystrophy. No somatic variability was detected in >6000 individual FRDA molecules analyzed from 15 normal alleles (8-25 triplets). A premutation allele with 44 uninterrupted GAA repeats was found to be unstable, ranging in size from 6 to 113 triplets, thus establishing the threshold for somatic instability between 26 and 44 GAA triplets. Analysis of an additional 7850 FRDA molecules from serially passaged lymphoblastoid cell lines carrying nine expanded alleles (132-933 triplets) showed very low mutation loads, ranging from 0% to 6.2%. Our data indicate that expanded GAA-TR alleles in Friedreich ataxia are highly mutable and have a natural tendency to contract in vivo, and that these properties depend on multiple factors, including DNA sequence, triplet-repeat length and unknown cell-type-specific factors. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73104 USA. Univ Cent Oklahoma, Dept Math & Stat, Edmond, OK USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Bidichandani, SI (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, 975 NE,10th,BRC458, Oklahoma City, OK 73104 USA. NR 62 TC 43 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2002 VL 11 IS 18 BP 2175 EP 2187 DI 10.1093/hmg/11.18.2175 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 586NU UT WOS:000177590700011 PM 12189170 ER PT J AU Eslami, P Nyby, MD Corry, D Eggena, P Tuck, ML AF Eslami, P Nyby, MD Corry, D Eggena, P Tuck, ML TI Angiotensin II AT1 receptor blocker decreases insulin-stimulated intracellular angiotensin II in vascular smooth muscle cells SO HYPERTENSION LA English DT Meeting Abstract CT 56th Annual Fall Conference and Scientific Sessions of the Council-for-High-Blood-Pressure-Research in Associaton with the Council-on-Kidney-in-Cardiovascular-Disease CY SEP 25-28, 2002 CL ORLANDO, FLORIDA SP Council High Blood Pressure, Council Kidney Cardiovas Dis, Council Nutrition Phys Activ & Metab C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif, Sepulveda, CA USA. Sepulveda VA Med Ctr, Sepulveda, CA 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2002 VL 40 IS 3 MA P19 BP 398 EP 398 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 594LY UT WOS:000178052900132 ER PT J AU Jabara, HH Laouini, D Tsitsikov, E Mizoguchi, E Bhan, AK Castigli, E Dedeoglu, F Pivniouk, V Brodeur, SR Geha, RS AF Jabara, HH Laouini, D Tsitsikov, E Mizoguchi, E Bhan, AK Castigli, E Dedeoglu, F Pivniouk, V Brodeur, SR Geha, RS TI The binding site for TRAF2 and TRAF3 but not for TRAF6 is essential for CD40-mediated immunoglobulin class switching SO IMMUNITY LA English DT Article ID NF-KAPPA-B; RECEPTOR-ASSOCIATED FACTORS; TERMINAL KINASE; IMMUNE-RESPONSES; CD40 LIGAND; DEFECTIVE INTERLEUKIN-1; ECTODERMAL DYSPLASIA; CD40-DEFICIENT MICE; TARGETED DISRUPTION; GENE-EXPRESSION AB To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40DeltaTRAF6), TRAF2 and TRAF3 (CD40DeltaTRAF2/3), or both (CD40DeltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch defect in CD40(-/-) mice was fully corrected by WT and CD40Delta TRAF6, partially by CD40DeltaTRAF2/3, and not at all by CD40DeltaTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFkappaB in B cells were normal in WT and CD40DeltaTRAF6 mice, severely impaired in CD40DeltaTRAF2/3, and absent in CD40DeltaTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells. C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02115 USA. RP Geha, RS (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31136] NR 51 TC 88 Z9 91 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2002 VL 17 IS 3 BP 265 EP 276 DI 10.1016/S1074-7613(02)00394-1 PG 12 WC Immunology SC Immunology GA 596KB UT WOS:000178163100004 PM 12354380 ER PT J AU Ghiran, I Tyagi, SR Klickstein, LB Weller, AN AF Ghiran, I Tyagi, SR Klickstein, LB Weller, AN TI Expression and function of C1q receptors and C1q binding proteins at the cell surface SO IMMUNOBIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Early Phases of Complement Activation and Innate Immunity CY 2001 CL SEEHEIM JUGENHEIM, NAMIBIA ID SYSTEMIC LUPUS-ERYTHEMATOSUS; HUMAN C3B/C4B RECEPTOR; C-REACTIVE PROTEIN; NEUTROPHIL SUPEROXIDE PRODUCTION; C3B C4B RECEPTOR; COMPLEMENT ACTIVATION; APOPTOTIC CELLS; POLYMORPHONUCLEAR LEUKOCYTE; SARCOPLASMIC-RETICULUM; ENDOTHELIAL-CELLS AB C1q is the recognition unit of the first component of complement that binds not only IgG and IgM containing immune complexes, but also recognizes foreign structures such as the lipid A of endotoxin, and molecules expressed at the surface of apoptotic cells. In this review, the plasma membrane receptors and binding proteins for C1q are discussed and new data are presented on calreticulin expression on human peripheral blood cells. Although much is known about C1q receptors and binding molecules there are still many questions regarding their role in vivo. C1 Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Allergy, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Inflammat & Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. RP Weller, AN (reprint author), BIDMC, Dana 617,330 Brookline Ave, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL73368]; NIAID NIH HHS [AI42987]; NIAMS NIH HHS [AR47243] NR 79 TC 21 Z9 21 U1 0 U2 4 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD SEP PY 2002 VL 205 IS 4-5 BP 407 EP 420 DI 10.1078/0171-2985-00142 PG 14 WC Immunology SC Immunology GA 601EE UT WOS:000178432900007 PM 12396003 ER PT J AU Haake, DA Matsunaga, J AF Haake, DA Matsunaga, J TI Characterization of the leptospiral outer membrane and description of three novel leptospiral membrane proteins SO INFECTION AND IMMUNITY LA English DT Article ID TWO-DIMENSIONAL ELECTROPHORESIS; IMMOBILIZED PH GRADIENTS; TREPONEMA-PALLIDUM; PATHOGENIC LEPTOSPIRA; BORRELIA-BURGDORFERI; ESCHERICHIA-COLI; MAMMALIAN INFECTION; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; SIGNAL PEPTIDES AB The outer membrane (OM) of the mammalian pathogen Leptospira kirschneri was isolated in the form of membrane vesicles by alkaline plasmolysis and separated from the protoplasmic cylinder by sucrose density gradient ultracentrifugation. All four components of the alkaline plasmolysis buffer, including 1.0 M NaCl, 27% sucrose (wt/vol), 2 mM EDTA, and 10 mM Tris (pH 9), were required for efficient OM release, as judged by recovery of leptospiral lipopolysaccharide. Two populations of OM vesicles (OMVs) were recovered, with peak concentrations found in the sucrose gradient at densities of 1.16 and 1.18 g/ml. Transmission electron microscopy revealed that the more buoyant OMV population was smaller (<0.1 μm,m in diameter) than the denser OMV population (0.2 to 0.3 μm in diameter). The densities of both populations of OMVs were distinct from that of the protoplasmic-cylinder material, which was found in the sucrose gradient at a density of 1.20 g/ml. The OMV fractions were free of protoplasmic-cylinder material, as judged by immunoblotting with antibodies to the endoflagellar sheath protein, heat shock protein GroEL, and two novel cytoplasmic membrane proteins, lipoprotein LipL31 and transmembrane protein ImpL63. The protein components of the OMVs were characterized by one- and two-dimensional immunoblotting and found to include previously described OM proteins (OMPs), including the porin OmpL1; the lipoproteins LipL32, LipL36, and LipL41; and the peripheral membrane protein P31(LipL45). A number of less well-characterized OMPs were also identified, including those with molecular masses of 16, 21, 21.5, 22, 31, 36, 44, 48, 90, and 116 kDa. The 48-kDa OMP was identified as a novel OM lipoprotein designated LipL48. The use of membrane-specific markers in OM isolation techniques facilitates an accurate description of the leptospiral OM and its components. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Haake, DA (reprint author), VA Greater LA Healthcare Syst, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. FU NIAID NIH HHS [R29 AI034431, R01 AI034431-06A2, R01 AI034431, AI-34431, R21 AI034431] NR 45 TC 71 Z9 85 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2002 VL 70 IS 9 BP 4936 EP 4945 DI 10.1128/IAI.70.9.4936-4945.2002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 584WE UT WOS:000177491100024 PM 12183539 ER PT J AU Weber, JM Sheridan, RL Schulz, JT Tompkins, RG Ryan, CM AF Weber, JM Sheridan, RL Schulz, JT Tompkins, RG Ryan, CM TI Effectiveness of bacteria-controlled nursing units in preventing cross-colonization with resistant bacteria in severely burned children SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INFECTION; ENTEROCOCCI; TRANSMISSION; EXPERIENCE AB Bacteria-controlled nursing units (BCNUs) are laminar airflow patient isolation units. The rate of cross-colonization with resistant organisms in 66 critically ill pediatric burn patients with massive open wounds and ventilators housed in BCNUs during 5 years was examined and found to be extremely low (3.2 cases per 1,000 patient-days). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burn Hosp, Sumner Redstone Burn Ctr, Boston, MA USA. RP Ryan, CM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Bigelow 1302, Boston, MA 02114 USA. NR 8 TC 16 Z9 16 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 2002 VL 23 IS 9 BP 549 EP 551 DI 10.1086/502106 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 593MA UT WOS:000177994200016 PM 12269456 ER PT J AU Giallourakis, C AF Giallourakis, C TI Lowering the stress of inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Whitehead Inst, Ctr Genome Res, Inflammatory Dis Res Grp, Cambridge, MA 02142 USA. RP Giallourakis, C (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2002 VL 8 IS 5 BP 370 EP 371 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 592ZU UT WOS:000177967400011 PM 12479654 ER PT J AU Hodin, R Abedrapo, M AF Hodin, R Abedrapo, M TI Perhaps we can, but should we? SO INFLAMMATORY BOWEL DISEASES LA English DT Article C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, R (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD SEP PY 2002 VL 8 IS 5 BP 372 EP 373 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 592ZU UT WOS:000177967400013 PM 12479656 ER PT J AU Puyana, JC Sims, C Menconi, M Shim, I Ochoa, C Van Bastelaar, J Clavijo, JA AF Puyana, JC Sims, C Menconi, M Shim, I Ochoa, C Van Bastelaar, J Clavijo, JA TI Skeletal muscle and subcutaneous multiparameter monitoring correlate in a model of hemorrhagic shock SO INTENSIVE CARE MEDICINE LA English DT Meeting Abstract CT 15th Annual Congress on European-Society-of-Internsive-Care-Medicine CY SEP 29-OCT 02, 2002 CL BARCELONA, SPAIN SP European Soc Interns Care Med C1 Univ Pittsburgh, Med Ctr, Dept Trauma & CCM, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD SEP PY 2002 VL 28 SU 1 MA 200 BP S55 EP S55 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 599QD UT WOS:000178345900201 ER PT J AU Lowe, HC Burkoff, D Khachigian, LM MacNeill, BD Hayase, M Oesterle, SN AF Lowe, HC Burkoff, D Khachigian, LM MacNeill, BD Hayase, M Oesterle, SN TI Beyond angioplasty: novel developments in interventional cardiology SO INTERNAL MEDICINE JOURNAL LA English DT Review DE coating; gene; myocardial; revascularization stent ID MYOCARDIAL REVASCULARIZATION; INTRAVASCULAR ULTRASOUND; THERAPEUTIC ANGIOGENESIS; NEOINTIMAL PROLIFERATION; CORONARY-ARTERIES; LASER; RESTENOSIS; STENTS AB Two specific areas in interventional cardiology have, until recently, remained problematic. First is the emerging issue of the so-called 'no option' patient, considered untreatable by conventional percutaneous coronary intervention (PCI) or surgery. Second is the long-standing dilemma of restenosis following PCI. Strategies addressing these two critical areas have been the subject of intense research efforts recently. Several important breakthroughs are being made in the important areas of novel revascularization techniques, antirestenotic agents and stent-based delivery methods. It is conceivable that these novel developments will soon mean that a broader range of patients can be treated, and that the issue of restenosis will now be seriously challenged. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA 02144 USA. Columbia Univ, New York, NY USA. Univ New S Wales, Sydney, NSW, Australia. RP Oesterle, SN (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bullfinch 105, Boston, MA 02144 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1444-0903 J9 INTERN MED J JI Intern. Med. J. PD SEP-OCT PY 2002 VL 32 IS 9-10 BP 470 EP 474 DI 10.1046/j.1445-5994.2002.00261.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 589FQ UT WOS:000177748400009 PM 12380701 ER PT J AU Harsh, GR Thornton, AF Chapman, PH Bussiere, MR Rabinov, JD Loeffler, JS AF Harsh, GR Thornton, AF Chapman, PH Bussiere, MR Rabinov, JD Loeffler, JS TI Proton beam stereotactic radiosurgery of vestibular schwannomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE vestibular schwannoma; radiosurgery; proton beam; acoustic neuroma ID LINEAR-ACCELERATOR RADIOSURGERY; ACOUSTIC NEUROMA RADIOSURGERY; GAMMA-KNIFE; HEARING PRESERVATION; BRAIN-STEM; RADIOTHERAPY; VOLUME; COMPLICATIONS; EXPERIENCE; NEURINOMAS AB Purpose: The proton beam's Bragg peak permits highly conformal radiation of skull base tumors. This study, prompted by reports of transient (30% each) and permanent (10% each) facial and trigeminal neuropathy after stereotactic radiosurgery of vestibular schwannomas with marginal doses of 16-20 Gy, assessed whether proton beam radiosurgery using a marginal dose of only 12 Gy could control vestibular schwannomas while causing less neuropathy. Methods and Materials: Sixty-eight patients (mean age 67 years) were treated between 1992 and 1998. The mean tumor volume was 2.49 cm(3). The dose to the tumor margin (70% isodose line) was 12 Gy. The prospectively specified follow-up consisted of neurologic evaluation and MRI at 6, 12, 24, and 36 months. Results: After a mean clinical follow-up of 44 months and imaging follow-up of 34 months in 64 patients, 35 tumors (54.7%) were smaller and 25 (39.1%) were unchanged (tumor control rate 94%; actuarial control rate 94% at 2 years and 84% at 5 years). Three tumors enlarged: one shrank after repeated radiosurgery, one remained enlarged at the time of unrelated death, and one had not been imaged for 4 years in a patient who remained asymptomatic at last follow-up. Intratumoral hemorrhage into one stable tumor required craniotomy that proved successful. Thus, 97% of tumors required no additional treatment. Three patients (4.7%) underwent shunting for hydrocephalus evident as increased ataxia. Of 6 patients with functional hearing ipsilaterally, 1 improved, 1 was unchanged, and 4 progressively lost hearing. Cranial neuropathies were infrequent: persistent facial hypesthesia (2 new, 1 exacerbated; 4.7%); intermittent facial paresthesias (5 new, 1 exacerbated; 9.4%); persistent facial weakness (2 new, 1 exacerbated; 4.7%) requiring oculoplasty; transient partial facial weakness (5 new, 1 exacerbated; 9.4%), and synkinesis (5 new, 1 exacerbated; 9.4%). Conclusion: Proton beam stereotactic radiosurgery of vestibular schwannomas at the doses used in this study controls tumor growth with relatively few complications. (C) 2002 Elsevier Science Inc. C1 Stanford Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Radiat Oncol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Radiol, Boston, MA 02114 USA. RP Harsh, GR (reprint author), Stanford Med Ctr, Dept Neurosurg, 300 Pasteur Dr,R227, Stanford, CA 94305 USA. NR 42 TC 28 Z9 30 U1 0 U2 2 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 SEP 1 PY 2002 VL 54 IS 1 BP 35 EP 44 AR PII S0360-3016(02)02910-3 DI 10.1016/S0360-3016(02)02910-3 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 589VH UT WOS:000177780900005 PM 12182972 ER PT J AU Coleman, CN Kelly, L Daly, NR Beard, C Kaplan, I Lamb, C Propert, K Manola, J AF Coleman, CN Kelly, L Daly, NR Beard, C Kaplan, I Lamb, C Propert, K Manola, J TI Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE nonsteroidal anti-inflammatory agents; cyclooxygenase inhibitors; ibuprofen; prostate cancer; radiation toxicity ID PROSTATE-CANCER CELLS; NF-KAPPA-B; CYCLOOXYGENASE-2 INHIBITOR; GAMMA-RADIATION; RADIOSENSITIVITY; ANGIOGENESIS; RADIOTHERAPY; ENHANCEMENT; PREVENTION; ACTIVATION AB Purpose: On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score. Methods and Materials: Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week. Results: Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation. Conclusion: The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non-cyclooxygenase mechanisms. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Coleman, CN (reprint author), NIH, Radiat Oncol Branch, Bldg 10,B3-B69, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA-42391] NR 24 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2002 VL 54 IS 1 BP 191 EP 194 AR PII S0360-3016(02)02907-3 DI 10.1016/S0360-3016(02)02907-3 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 589VH UT WOS:000177780900024 PM 12182991 ER PT J AU Moore, JE McMullen, TCB Campbell, IL Rohan, R Kaji, Y Afshari, NA Usui, T Archer, DB Adamis, AP AF Moore, JE McMullen, TCB Campbell, IL Rohan, R Kaji, Y Afshari, NA Usui, T Archer, DB Adamis, AP TI The inflammatory milieu associated with conjunctivalized cornea and its alteration with IL-1 RA gene therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LIMBAL STEM-CELLS; ADHESION MOLECULES; EXPRESSION; EPITHELIUM; CYTOKINE AB PURPOSE. This study was designed to gain an insight into the inflammatory milieu into which a donor limbal graft is routinely introduced. The objective of this study was to modulate this environment by gene therapy with the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1 RA). METHODS. In a mouse model, the ocular surface cytokine environment associated with a conjunctivalized cornea was assessed 4 weeks after injury. Total corneal epithelial and limbal debridement was performed with a combination of alkali and scrape injury. The cytokines and adhesion molecules measured included IL-1a, IL-10, IL-6, VEGF, intercellular adhesion molecule (ICAM)-1, and vascular adhesion molecule (VCAM)-1, by real-time PCR or ELISA. Injured corneas were transfected with IL-1 RA by injection of naked plasmid vector pIRES-EGFP-IL-1 RA immediately after injury. Corneas transfected with pIRES-EGFP served as the control. Expression of corneal IL-1 RA after transfection with pIRES-EGFP-IL1-RA was assessed over a 2-week period by real-time PCR and Western blot analysis. In addition, limbal stem cell grafts transfected with IL-1 RA were assessed for leukocyte influx. RESULTS. Conjunctivalized corneas showed increased expression of IL-1alpha, IL-1beta, IL-1 RA, IL-6, VEGF, ICAM-1, and VCAM-1, compared with normal cornea. Transfection-efficiency experiments indicated that corneal expression Of IL-1 RA peaked between 12 and 24 hours and lasted up to 2 weeks after the initial transfection. IL-1 RA corneal gene therapy resulted in a downregulation of IL-10 and VCAM-1 expression at 4 weeks after injury, whereas downregulation of IL-6 was evident only at 1 week after injury. Corneal neovascularization was also reduced. In addition, corneal limbal stem cell grafts transfected with IL-1 RA showed a decreased leukocyte influx compared with control grafts. CONCLUSIONS. Transfection of a cornea with IL-1 RA immediately after epithelial injury selectively altered the cytokine profile of the resultant conjunctivalized cornea and suppressed corneal neovascularization. Transfection of corneal limbal donor tissue with IL-1 RA before engraftment can reduce leukocyte influx into the graft. The findings demonstrate the feasibility of using transient cytokine gene expression, either in donor or recipient corneal tissue, to alter the ocular surface environment beneficially. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Queens Univ Belfast, Royal Victoria Hosp, Dept Ophthalmol, Belfast, Antrim, North Ireland. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02114 USA. Univ Ulster, Sch Biomed Sci, Coleraine BT52 1SA, Londonderry, North Ireland. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA USA. Duke Univ, Ctr Eye, Durham, NC USA. RP Adamis, AP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. OI Moore, Tara/0000-0002-7659-9326; Moore, Johnny/0000-0001-8451-9421 FU NEI NIH HHS [EY11627, EY12611] NR 20 TC 38 Z9 41 U1 0 U2 0 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 SEP PY 2002 VL 43 IS 9 BP 2905 EP 2915 PG 11 WC Ophthalmology SC Ophthalmology GA 589FN UT WOS:000177748200014 PM 12202509 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Role of enhanced expression of m-CSF in conjunctiva affected by cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COLONY-STIMULATING FACTOR; LOCAL MACROPHAGE PROLIFERATION; COLLAGEN-BINDING HEAT-SHOCK-PROTEIN-47; NECROSIS-FACTOR-ALPHA; PERIPHERAL-BLOOD MONOCYTES; PROGRESSIVE RENAL INJURY; NF-KAPPA-B; GROWTH-FACTORS; FACTOR-I; RAT AB PURPOSE. Local proliferation of macrophages has been reported to augment the inflammatory response in various human and experimental diseases. Macrophage accumulation in the submucosa is also an important feature in the pathogenesis of ocular cicatricial pemphigoid (OCP). In the present study, the role of local proliferation of macrophages in conjunctiva affected by OCP and the relationship between local proliferation of macrophages and expression of macrophage-colony-stimulating factor (m-CSF) in such conjunctiva were examined. METHODS. Biopsy specimens from the conjunctiva of 10 untreated patients with active OCP and from 5 normal subjects were studied for the expression of m-CSF, macrophages, and proliferating cell nuclear antigen (PCNA), a cell cycle protein, by immunohistochemistry. Dual staining for CD68 (a cell surface marker for macrophages) and PCNA was also performed to identify proliferating macrophages. In addition, fibroblasts isolated from conjunctiva of normal individuals and from patients with OCP were studied for the expression of m-CSF by immunostaining and real-time PCR. To identify the factors that induce m-CSF in conjunctival fibroblasts, the fibroblasts were incubated with different concentrations of interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha, and the levels of m-CSF mRNA were determined by real-time PCR and the amount of m-CSF produced was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS. Normal conjunctiva showed weak expression of mCSF in the conjunctival epithelial cells and stroma. Conjunctival expression of m-CSF protein was significantly (P < 0.0001) increased in conjunctival biopsy specimens from patients with OCP. m-CSF was detected in the infiltrating macrophages, stromal cells (presumably fibroblasts), and conjunctival epithelial cells. Compared with normal control conjunctival tissue, a 1.2-fold increase in the expression of mRNA for m-CSF was detected by real-time PCR in the conjunctival tissue obtained from patients with OCP. Increased expression of m-CSF correlated significantly (P < 0.0004) with an increased stromal accumulation of macrophages in conjunctival biopsy specimens of patients with OCP. A number of these accumulated macrophages (CD68-positive) Were found to be proliferating (PCNA-positive). In addition, fibroblasts isolated and cultured from conjunctiva of patients with OCP showed significantly increased (1.7-fold) expression of m-CSF compared with normal conjunctival fibroblasts. When conjunctival fibroblasts were treated with IL-1alpha or TNF-alpha, real-time PCR and ELISA detected an increased level of m-CSF. CONCLUSIONS. An increased expression of m-CSF was observed in conjunctiva from patients with active OCP. There was a positive correlation between expression of m-CSF and accumulation of macrophages in conjunctival biopsy sections obtained from patients with OCP. Increased expression of m-CSF, mainly by conjunctival fibroblasts and infiltrating inflammatory cells, may play an important role in the regulation of local proliferation of macrophages in OCP. In the conjunctiva of patients with OCP, this process could augment or enhance the local inflammatory response and tissue injury consequent to it. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [R01EY08379] NR 41 TC 26 Z9 27 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 SEP PY 2002 VL 43 IS 9 BP 2977 EP 2983 PG 7 WC Ophthalmology SC Ophthalmology GA 589FN UT WOS:000177748200023 PM 12202518 ER PT J AU Berson, EL Rosner, B Weigel-DiFranco, C Dryja, TP Sandberg, MA AF Berson, EL Rosner, B Weigel-DiFranco, C Dryja, TP Sandberg, MA TI Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VISUAL-FIELD LOSS; TRANSGENIC MICE; OCULAR FINDINGS; OUTER SEGMENT; VITAMIN-A; GENE; PROTEIN; MODEL; SUPPLEMENTATION; RATES AB PURPOSE. To measure the rate of progression of retinal degeneration in patients with retinitis pigmentosa due to dominant rhodopsin mutations and to determine whether the rate of progression correlates with the location of the altered amino acid in the rhodopsin molecule. METHODS. Change in ocular function was observed for an average of 8.7 years in 140 patients. After censoring data to eliminate "ceiling" and "floor" effects, longitudinal rates of change were compared, after weighting by follow-up time and number of visits, with rates inferred from cross-sectional analyses of the data from baseline visits. Mean rates of change were compared among groups of patients with mutations affecting the globule, plug, or C-terminal region of the protein after adjusting for age, gender, and baseline function. RESULTS. Mean annual exponential rates of decline were 1.8% for visual acuity, 2.6% for visual field area, and 8.7% for ERG amplitude. The rates of visual acuity and ERG amplitude decline were significantly faster, and the rate of visual field area decline was significantly slower, than those inferred from baseline visits. Rates of acuity loss did not vary significantly with the region affected by the mutation. In contrast, the mean annual rate of field loss in the C terminus group (7.4%) was significantly faster than that in the globule (1.7%) or plug (1.1%) group. The mean annual rate of ERG decline was also significantly faster in the C terminus group (13.5%) than in the globule (8.5%) or plug (3.7%) groups and significantly faster in the globule group than in the plug group. CONCLUSIONS. Rates of decline in visual function for groups of patients with rhodopsin mutations cannot be accurately inferred from cross-sectional analyses of baseline visits. Average rates of decline of visual field area and ERG amplitude are fastest in patients with mutations affecting the C-terminal region. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Berson, EL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Berman Gund Lab, Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY08683, EY00169] NR 27 TC 69 Z9 70 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 SEP PY 2002 VL 43 IS 9 BP 3027 EP 3036 PG 10 WC Ophthalmology SC Ophthalmology GA 589FN UT WOS:000177748200031 PM 12202526 ER PT J AU Walensky, RP Goldie, SJ Sax, PE Weinstein, MC Paltiel, AD Kimmel, AD Seage, GR Losina, E Zhang, H Islam, R Freedberg, KA AF Walensky, RP Goldie, SJ Sax, PE Weinstein, MC Paltiel, AD Kimmel, AD Seage, GR Losina, E Zhang, H Islam, R Freedberg, KA TI Treatment for primary HIV infection: Projecting outcomes of immediate, interrupted, or delayed therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE primary HIV infection; structured treatment interruption; Markov model ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; PNEUMOCYSTIS-CARINII PNEUMONIA; COST-EFFECTIVENESS; VIRAL LOAD; OPPORTUNISTIC INFECTIONS; CONTROLLED TRIAL; PLUS INDINAVIR; DISCONTINUATION; PROPHYLAXIS AB With limited data available on the optimal treatment of primary HIV infection, disease modeling can be used to project clinical outcomes and inform decision makers. The authors developed a simulation model to evaluate the clinical outcomes and life expectancy projections for three primary HIV infection treatment strategies: 1) continuous antiretroviral therapy (ART) initiated at CD4 count <350 cells/mm(3); 2) continuous ART initiated immediately on diagnosis of primary HIV infection; and 3) ART initiated on diagnosis followed by structured treatment interruption. Projected life expectancies for the three strategies were 23.92, 24.46, and 26.07 years, respectively. The impact of key variables was assessed in sensitivity analysis, with the structured treatment interruption strategy remaining the most effective over a broad range of inputs. The immunologic benefit associated with immediate therapy and the potential for antiretroviral resistance due to structured treatment interruption have the most important impact on the optimal strategy. Based on current data, immediate treatment on diagnosis of primary HIV infection followed by structured treatment interruption will likely yield the best outcome. These results can assist decision makers and those planning clinical trials in defining evidence-based performance measures for primary HIV infection treatment and future trials. C1 Harvard Univ, Sch Med, Div Gen Med, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Infect Dis, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Dept Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Walensky, RP (reprint author), Harvard Univ, Sch Med, Div Gen Med, Dept Med,Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [5T32HS00020]; NIAID NIH HHS [K23-AI01794, K23 AI001794, P30 AI042851, P30-AI42851, R01 AI042006, R01-AI42006]; ODCDC CDC HHS [U64/CCU114927, U64/CCU119525] NR 63 TC 30 Z9 31 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD SEP 1 PY 2002 VL 31 IS 1 BP 27 EP 37 DI 10.1097/01.QAI.0000026905.47530.70 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 609AH UT WOS:000178880100004 PM 12352147 ER PT J AU Wang, Y Hirose, K Liberman, MC AF Wang, Y Hirose, K Liberman, MC TI Dynamics of noise-induced cellular injury and repair in the mouse cochlea SO JARO LA English DT Article DE acoustic trauma; permanent threshold shift; temporary threshold shift; histopathology ID INDUCED HEARING-LOSS; GUINEA-PIG COCHLEA; KAINIC ACID EXCITOTOXICITY; PERMANENT THRESHOLD SHIFT; INTENSE SOUND EXPOSURE; ACOUSTIC INJURY; TUNING CURVES; HAIR-CELLS; MICE; STEREOCILIA AB To assess the dynamics of noise-induced tissue injury and repair, groups of CBA/CaJ mice were exposed to an octave-band noise for 2 hours at levels of 94, 100, 106, 112, or 116 dB SPL and evaluated at survival times of 0, 12, 24 hours or 1, 2, or 8 weeks. Functional change, assessed via auditory brainstem response (ABR), ranged from a reversible threshold shift (at 94 dB) to a profound permanent loss (at 116 dB). Light microscopic histopathology was assessed in serial thick plastic sections and involved quantitative evaluation of most major cell types within the cochlear duct, including hair cells (and their stereocilia), supporting cells, ganglion cells, spiral ligament fibrocytes, spiral limbus fibrocytes, and the stria vascularis. Morphometry allowed patterns of damage to be systematically assessed as functions of (1) cochlear location, (2) exposure level, and (3) postexposure survival. Insights into mechanisms of acute and chronic noise-induced cellular damage are discussed. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC0188] NR 46 TC 243 Z9 247 U1 3 U2 31 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2002 VL 3 IS 3 BP 248 EP 268 DI 10.1007/s101620020028 PG 21 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 600NR UT WOS:000178397700003 PM 12382101 ER PT J AU Thiers, FA Burgess, BJ Nadol, JB AF Thiers, FA Burgess, BJ Nadol, JB TI Reciprocal innervation of outer hair cells in a human infant SO JARO LA English DT Article DE reciprocal synapse; outer hair cells; efferent; type II spiral ganglion cell; outer spiral bundle; neural network ID SPIRAL GANGLION NEURONS; GUINEA-PIG COCHLEA; OLFACTORY-BULB; HUMAN ORGAN; ULTRASTRUCTURAL ANALYSIS; HORSERADISH-PEROXIDASE; JAPANESE MACAQUE; AFFERENT-FIBERS; CAROTID-BODY; ADULT CATS AB Reciprocal synapses are characterized by the presence of both afferent and efferent types of synaptic specializations between two cells. They have been described at the neural poles of outer hair cells (OHCs) in humans with advanced age and two monkey species. Our objective was to study the innervation of the OHCs and determine if reciprocal synapses were present in a young (8-month-old infant) human subject. We studied the synaptic and cytoplasmic morphology of 162 nerve terminals innervating 29 OHCs using serial section transmission electron microscopy. Seventy-six percent of all OHCs were innervated by terminals with reciprocal synapses. This prevalence increased from the first toward the third row (p < 0.001), and 100% of OHCs in the third row demonstrated at least one reciprocal synapse. The prevalence of terminals with reciprocal synapses was higher in the human infant than in older human subjects and was very similar to what has been reported for the chimpanzee. Reciprocal synapses occur in sufficient numbers to be physiologically significant in primates. The nerve terminals were found to segregate into two groups on the basis of their cytoplasmic morphological characteristics: (1) vesicle-rich/neurofilament-poor (VR/NP) and (2) vesicle-poor/neurofilament-rich (VP/NR). All afferent and reciprocal terminals were of the VP/NR variety. The majority of the efferent terminals originated from VR/NP nerve fibers (classical olivocochlear morphology), but 23.5% of the efferent terminals were VP/NR. The hypothesis that peripheral processes of type II spiral ganglion cells form classical afferent, reciprocal, and a number of purely presynaptic terminals on OHCs is discussed. The presence of different types of synaptic specializations on OHCs formed by nerve fibers of the same type (VP/NR) suggests the existence of reciprocal neuronal circuits between OHCs sharing the dendritic arborization of a type 11 spiral ganglion cell. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01-DC00152-20] NR 60 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2002 VL 3 IS 3 BP 269 EP 278 DI 10.1007/s101620020024 PG 10 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 600NR UT WOS:000178397700004 PM 12382102 ER PT J AU Boyev, KP Liberman, MC Brown, MC AF Boyev, KP Liberman, MC Brown, MC TI Effects of anesthesia on efferent-mediated adaptation of the DPOAE SO JARO LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Association-for-Research-in-Otolaryngology CY FEB 20-24, 2000 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolarynol DE olivocochlear reflex; otoacoustic emission; sodium pentobarbital; superior olivary complex; cochlea ID PRODUCT OTOACOUSTIC EMISSION; SINGLE OLIVOCOCHLEAR NEURONS; COCHLEAR MICROMECHANICAL PROPERTIES; COMPOUND ACTION-POTENTIALS; GUINEA-PIG COCHLEA; 2 DISCRETE SOURCES; INFERIOR COLLICULUS; CONTRALATERAL SOUND; RESPONSE PROPERTIES; ACOUSTIC STIMULATION AB Distortion product otoacoustic emissions (DPOAE) adapt after primary tone onset, with an similar to100 ms time constant, due to feedback effects of medial olivo-cochlear (MOC) activity elicited by the primary tones. We tracked DPOAE postonset adaptation as a metric of MOC reflex strength, before during and after induction of anesthesia in guinea pigs. Reflex strength was significantly diminished by the barbiturate/neuroleptic anesthesia most commonly used in this species. The MOC reflex recovered more slowly than toe-pinch or startle reflexes, correlating better with recovery of general mobility. When individual anesthetic agents were assessed, the barbiturate (pentobarbital) significantly diminished MOC reflex strength, whereas fentanyl. or droperidol did not. These results suggest that previous studies using anesthetized preparations may have underestimated the magnitude of sound-evoked responses in the OC pathway. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, T32 DC00020, 5 R01 DC00188, R01 DC01089] NR 55 TC 38 Z9 41 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2002 VL 3 IS 3 BP 362 EP 373 DI 10.1007/s101620020044 PG 12 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 600NR UT WOS:000178397700011 PM 12382109 ER PT J AU He, CF Young, AJ West, CA Su, M Konerding, MA Mentzer, SJ AF He, CF Young, AJ West, CA Su, M Konerding, MA Mentzer, SJ TI Stimulation of regional lymphatic and blood flow by epicutaneous oxazolone SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE microcirculation; lymph; skin; microscopy ID LASER-DOPPLER FLOWMETRY; MICROVASCULAR ARCHITECTURE; REFLECTANCE SPECTROSCOPY; SKIN COLOR; ERYTHEMA; INVIVO; ULTRASTRUCTURE; MICROCIRCULATION; ORGANIZATION AB The application of the epicutaneous antigen oxazolone results in persistent induration and erythema; however, the relative changes in lymph and blood flow in the inflammatory skin are largely unknown. To define the contribution of lymph and blood flow to the clinical appearance of cutaneous inflammation, we studied the sheep ear after the application of oxazolone. As a model for the study of these changes, the sheep ear had several experimental advantages: 1) a simplified superficial vascular network, 2) defined lymphatic drainage, and 3) an avascular and alymphatic cartilaginous barrier. Lymph flow was continuously monitored by cannulation of the prescapular efferent lymph duct. Blood flow, as reflected by cutaneous erythema, was noninvasively measured by use of a visible-spectrum spectrophotometer. The application of the epicutaneous oxazolone resulted in increased ear thickness for >7 days. The lymph flow from the oxazolone-stimulated ear peaked between 24 and 48 h after oxazolone stimulation. Spectrophotometric evaluation indicated that the cutaneous erythema peaked 72-96 h after application of oxazolone. Corrosion casting and scanning electron microscopy of the microcirculation at 96 h after antigen stimulation demonstrated significant dilatation of the superficial vascular network. These results suggest a biphasic response to oxazolone stimulation: 1) an early increase in vascular permeability associated with increased lymph flow and 2) a subsequent increase in relative blood flow associated with a dilated inflammatory microcirculation. C1 Brigham & Womens Hosp, Dept Surg, Dana Farber Canc Inst, Div Thorac Surg,Lab Immunophysiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Mainz, Dept Anat, D-55099 Mainz, Germany. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Dept Surg, Dana Farber Canc Inst, Div Thorac Surg,Lab Immunophysiol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-47078] NR 45 TC 16 Z9 17 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2002 VL 93 IS 3 BP 966 EP 973 DI 10.1152/japplphysiol.00212.2002 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 586FF UT WOS:000177573400021 PM 12183492 ER PT J AU Galletti, GG Venegas, JG AF Galletti, GG Venegas, JG TI Tracer kinetic model of regional pulmonary function using positron emission tomography SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE modeling; perfusion; ventilation ID PET; HETEROGENEITY AB To determine the spatial distributions of pulmonary perfusion, shunt, and ventilation, we developed a compartmental model of regional N-13-labeled molecular nitrogen ((NN)-N-13) kinetics measured from positron emission tomography (PET) images. The model features a compartment for right heart and pulmonary vasculature and two compartments for each region of interest: 1) aerated alveolar units and 2) alveolar units with no gas content (shunting). The model was tested on PET data from normal animals (dogs and sheep) and from animals with experimentally injured lungs simulating acute respiratory distress syndrome. The analysis yielded estimates of regional perfusion, shunt fraction, and specific ventilation with excellent goodness-of-fit to the data (R-2 > 0.99). Model parameters were estimated to within 10% accuracy in the presence of exaggerated levels of experimental noise by using a Monte Carlo sensitivity analysis. Main advantages of the present model are that 1) it separates intraregional blood flow to aerated alveolar units from that shunting across nonaerated units and 2) it accounts and corrects for intraregional tracer removal by shunting blood when estimating ventilation from subsequent washout of tracer. The model was thus found to provide estimates of regional parameters of pulmonary function in sizes of lung regions that could potentially approach the intrinsic resolution for PET images of (NN)-N-13 in lung (similar to7.0 mm for a multiring PET camera). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Clin 237F, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 14 TC 30 Z9 30 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2002 VL 93 IS 3 BP 1104 EP 1114 DI 10.1152/japplphysiol.00910.2001 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 586FF UT WOS:000177573400037 PM 12183508 ER PT J AU Willey-Courand, DB Harris, RS Galletti, GG Hales, CA Fischman, A Venegas, JG AF Willey-Courand, DB Harris, RS Galletti, GG Hales, CA Fischman, A Venegas, JG TI Alterations in regional ventilation, perfusion, and shunt after smoke inhalation measured by PET SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE positron emission tomography ID ACUTE LUNG INJURY; PULMONARY-FUNCTION; MODEL AB Regional changes in ventilation and perfusion occurring in the early hours after smoke inhalation injury were evaluated through the use of positron emission tomography. Five lambs were imaged before and 1, 2, and 4 h after receiving 100 breaths of cotton smoke. Utilizing a recently developed model of N-13 tracer kinetics (3), we evaluated changes in ventilation, perfusion, shunt, and regional gas content in nondependent, middle, and dependent lung zones. The data demonstrated a progressive development of regional shunt in dependent (dorsal) regions in which perfusion remained the highest throughout the study. These findings, together with decreasing regional ventilation and fractional gas content in the dependent regions, correlated with decreasing arterial Pa-O2 values over the course of the study. A negative correlation between regional shunt fraction and regional gas content in dependent and middle regions suggests that shunt was caused by progressive alveolar derecruitment or flooding. C1 Massachusetts Gen Hosp, Dept Anesthesia, Clin 2, Shriners Burn Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Div Pulm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Clin 2, Shriners Burn Inst, Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267F] NR 26 TC 17 Z9 17 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2002 VL 93 IS 3 BP 1115 EP 1122 DI 10.1152/japplphysiol.00911.2001 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 586FF UT WOS:000177573400038 PM 12183509 ER PT J AU Cotton, A Farley, M Baron, R AF Cotton, A Farley, M Baron, R TI Attitudes toward prostitution and acceptance of rape myths SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID COLLEGE-STUDENTS; VIOLENCE; RAPISTS; WOMEN AB Rape myths and prostitution myths are a component of culturally supported attitudes that normalize violence against women. Prostitution myths justify the existence of prostitution, promote misinformation about prostitution, and contribute to a social climate that exploits and harms not only prostituted women, but all women. This study investigated the relationship between prostitution myth acceptance and rape myth acceptance in a sample of university undergraduates. Rape myth acceptance was positively correlated with prostitution myth acceptance among 783 university undergraduates from California, Iowa, Oregon, and Texas. College men were significantly more accepting of prostitution myths than were college women. Results suggest that acceptance of prostitution myths are a component of attitudes that justify violence against women. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Prostitut Res & Educ, San Francisco, CA USA. Univ Iowa, Iowa City, IA USA. RP Farley, M (reprint author), Box 16254, San Francisco, CA 94116 USA. NR 21 TC 18 Z9 19 U1 2 U2 15 PU V H WINSTON & SON INC PI PALM BEACH PA 360 SOUTH OCEAN BLVD, PH-B, PALM BEACH, FL 33480 USA SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD SEP PY 2002 VL 32 IS 9 BP 1790 EP 1796 DI 10.1111/j.1559-1816.2002.tb00259.x PG 7 WC Psychology, Social SC Psychology GA 636RV UT WOS:000180471400002 ER PT J AU Jupiter, JB Ring, D AF Jupiter, JB Ring, D TI Treatment of unreduced elbow dislocations with hinged external fixation SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID RECONSTRUCTION AB Background: The results of operative treatment of an unreduced elbow dislocation have been regarded with pessimism. Suggested procedures have included tendon-lengthening, tendon transfer, or reconstruction of ligament or bone. Methods: Three women and two men (average age, forty-nine years) with an unreduced dislocation of the elbow without associated fractures were treated with open relocation of the joint and hinged external fixation at an average of eleven weeks (range, six to thirty weeks) after the initial injury. The lateral soft tissues, including the origin of the lateral collateral ligament complex, were reattached to the lateral epicondyle in three patients, but no attempt was made to reconstruct the ligaments, tendons, or bone. A passive worm gear incorporated into a hinged external fixator was used to mobilize the elbow initially, and active mobilization was gradually introduced. The hinge was removed at an average of five weeks after the procedure. Results: At an average of thirty-eight months (range, twelve to ninety-eight months), a stable, concentric reduction had been maintained in all five patients, with radiographic signs of mild arthrosis in four. The average arc of flexion was 123degrees, and all patients had full forearm rotation. The average score on the Mayo Elbow Performance Index was 89 points, with two excellent and three good results. The average scores on the Disabilities of the Arm, Shoulder and Hand (DASH) and American Shoulder and Elbow Surgeons outcome instruments (13 and 92 points, respectively) reflected mild residual pain and disability. Conclusions: Treatment of unreduced elbow dislocations with open reduction and hinged external fixation as much as thirty weeks after the injury can restore a stable, mobile joint without the need for tendon-lengthening or transfer, ligament reconstruction, or deepening of the trochlear notch of the ulna. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 31 TC 63 Z9 73 U1 2 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2002 VL 84A IS 9 BP 1630 EP 1635 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 593VY UT WOS:000178016100017 PM 12208921 ER PT J AU Warner, JJP Venegas, AA Lehtinen, JT Macy, JJ AF Warner, JJP Venegas, AA Lehtinen, JT Macy, JJ TI Management of capsular deficiency of the shoulder - A report of three cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article C1 Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA. Univ Hosp, Bogota, Colombia. Univ Hosp, Tampere, Finland. RP Warner, JJP (reprint author), Harvard Univ, Dept Orthopaed Surg, Massachusetts Gen Hosp, Shoulder Serv, Profess Off Bldg,Suite 403,275 Cambridge St, Boston, MA 02114 USA. NR 25 TC 12 Z9 12 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 SEP PY 2002 VL 84A IS 9 BP 1668 EP 1671 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 593VY UT WOS:000178016100023 PM 12208927 ER PT J AU Kondo, H Guo, J Bringhurst, FR AF Kondo, H Guo, J Bringhurst, FR TI Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE parathyroid hormone; parathyroid hormone/parathyroid hormone-related protein receptor; stromal cell; osteoclastogenesis; RANKL ID INDUCED BONE-RESORPTION; C ACTIVATION DOMAIN; INHIBITORY FACTOR; PHOSPHOLIPASE-C; MOUSE BONE; IN-VITRO; DIFFERENTIATION FACTOR; HUMORAL HYPERCALCEMIA; PTH/PTHRP RECEPTOR; ADENYLATE-CYCLASE AB Parathyroid hormone (PTH) is a major regulator of osteoclast formation and activation, effects that are associated with reciprocal up- and down-regulation of RANKL and osteoprotegerin (OPG), respectively. The roles of specific downstream signals generated by the activated PTH/PTH-related protein (PTHrP) receptor (PTH1R), such as cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) and phospholipase C/protein kinase C (PLC/PKC), in controlling RANKL and OPG expression and osteoclastogenesis remain uncertain. In MS1 conditionally transformed clonal murine marrow stromal cells, which support PTH-induced osteoclast formation from cocultured normal spleen cells, PTH(1-34) increased RANKL and macrophage colony-stimulating factor (M-CSF) mRNA expression and decreased that of OPG when present continuously for 7-20 days at 37degreesC in the presence of dexamethasone (Dex). In cells precultured for 7 days and then treated with PTH(1-34), similar reciprocal regulation of RANKL and OPG occurred, maximally at 6-24 h, that was of greater amplitude than the changes induced by chronic (7-10 days) PTH exposure. These acute effects of PTH(1-34) were mimicked by PKA stimulators (8-bromoadenosine [8Br]-cAMP or forskolin [FSK]), blocked by the PKA inhibitor Rp-cAMPs but unaffected by the PKC inhibitor GF109203X. Amino-truncated PTH(1-34) analogs PTH(5-34) and PTH(7-34) neither increased cAMP production in MS1 cells nor regulated RANKL or OPG mRNA. Reciprocal RANKL/OPG mRNA regulation was induced in MS1 cells by PTH(3-34) but only at high concentrations that also increased cAMP. The highly PKA-selective PTH analog [Gly(1),Arg(19)]human PTH(1-28) exerted effects similar to PTH(1-34) on RANKL and OPG mRNAs and on osteoclast formation, both in MS1/spleen cell cocultures and in normal murine bone marrow cultures. The direct PKC stimulator 12-O-tetradecanoylphorbol-13-acetate (PMA) did not induce RANKL mRNA in MS1 cells, but it did up-regulate OPG mRNA and also antagonized osteoclast formation induced by PTH(1-34) in both MS1/spleen cocultures and normal bone marrow cultures. Thus, cAMP/PKA signaling via the PTH1R is the primary mechanism for controlling RANKL-dependent osteoclastogenesis, although direct PKC activation may negatively regulate this effect of PTH by inducing expression of OPG. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kondo, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 79 TC 84 Z9 88 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 IS 9 BP 1667 EP 1679 DI 10.1359/jbmr.2002.17.9.1667 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586ZN UT WOS:000177616200014 PM 12211438 ER PT J AU Lopez, I Aguilera-Tejero, E Felsenfeld, AJ Estepa, JC Rodriguez, M AF Lopez, I Aguilera-Tejero, E Felsenfeld, AJ Estepa, JC Rodriguez, M TI Direct effect of acute metabolic and respiratory acidosis on parathyroid hormone secretion in the dog SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE acidosis; calcium; metabolic acidosis; parathyroid hormone; respiratory acidosis ID CHRONIC-RENAL-FAILURE; PTH-CALCIUM CURVE; IONIZED CALCIUM; HYPOCALCEMIA; PHOSPHATE; MAGNESIUM; DISEASE; HUMANS; CELLS; RAT AB Because both metabolic (Met Acid) and respiratory acidosis (Resp Acid) have diverse effects on mineral metabolism, it has been difficult to establish whether acidosis directly affects parathyroid hormone (PTH) secretion. Our goal was to determine whether acute Met Acid and Resp Acid directly affected PTH secretion. Three groups of dogs were studied: control, acute Met Acid induced by HCl infusion, and acute Resp Acid induced by hypoventilation. EDTA was infused to prevent acidosis-induced increases in ionized calcium, but more EDTA was needed in Met Acid than in Resp Acid. The PTH response to EDTA-induced hypocalcemia was evaluated also. Magnesium needed to be infused in groups receiving EDTA to prevent hypomagnesemia. The half-life of intact PTH (iPTH) was determined during hypocalcemia when PTH was measured after parathyroidectomy. During normocalcemia, PTH values were greater (p < 0.05) in Met Acid (92 +/- 19 pg/ml) and Resp Acid (77 h 22 pg/ml) than in controls (27 +/- 5 pg/ml); the respective pH values were 7.23 +/- 0.01, 7.24 +/- 0.01, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was greater (p < 0.05) in Met Acid (443 54 pg/ml) than in Resp Acid (267 +/- 37 pg/ml) and controls (262 +/- 48 pg/ml). The half-life of PTH was greater (p < 0.05) in Met Acid than in controls, but the PTH secretion rate also was greater (p < 0.05) in Met Acid than in the other two groups. In conclusion, (1) both acute Met Acid and Resp Acid increase PTH secretion when the ionized calcium concentration is normal; (2) acute Met Acid may increase the bone efflux of calcium more than Resp Acid; (3) acute Met Acid acts as a secretogogue for PTH secretion because it enhances the maximal PTH response to hypocalcemia. C1 Hosp Univ Reina Sofia, Unidad Invest, Cordoba 14004, Spain. Hosp Univ Reina Sofia, Dept Nefrol, Cordoba 14004, Spain. Univ Cordoba, Dept Med & Cirugia Anim, E-14071 Cordoba, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Rodriguez, M (reprint author), Hosp Univ Reina Sofia, Unidad Invest, Avda Menendez Pidal SN, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011 NR 52 TC 22 Z9 22 U1 0 U2 4 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 IS 9 BP 1691 EP 1700 DI 10.1359/jbmr.2002.17.9.1691 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 586ZN UT WOS:000177616200016 PM 12211440 ER PT J AU Abboud, SL Woodruff, K Ghosh-Choudhury, N AF Abboud, SL Woodruff, K Ghosh-Choudhury, N TI Rescue of the osteopetrotic defect in op/op mice by osteoblast-specific targeting of membrane-bound CSF-1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1122 BP S154 EP S154 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800123 ER PT J AU Ammerman, DQ Desphande, AM Pathmanathan, D Bhatia, P Unni, KK Seton, M Leach, RJ Hansen, MF AF Ammerman, DQ Desphande, AM Pathmanathan, D Bhatia, P Unni, KK Seton, M Leach, RJ Hansen, MF TI Elevated expression of RANK in osteoblasts from Pagetic lesions SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Connecticut, Ctr Hlth, Farmington, CT USA. Mayo Clin, Rochester, MN USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F412 BP S212 EP S212 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800373 ER PT J AU Bastepe, M Weinstein, L Kronenberg, HM Juppner, H Chung, U AF Bastepe, M Weinstein, L Kronenberg, HM Juppner, H Chung, U TI In vivo role of stimulatory G protein (Gs) in cartilage development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 NIDDK, NIH, Bethesda, MD USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1065 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800066 ER PT J AU Bischoff, DS Zhu, JH Makhijani, NS Yamaguchi, DT AF Bischoff, DS Zhu, JH Makhijani, NS Yamaguchi, DT TI TGF-beta 3 regulation of KC chemokine expression in mouse mesenchymal C3H10T1/2 and pre-osteoblast MC3T3-E1 cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M153 BP S430 EP S430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801327 ER PT J AU Calvi, LM Adams, GB Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Kronenberg, HM Scadden, DT AF Calvi, LM Adams, GB Olson, DP Knight, MC Bringhurst, FR Schipani, E Divieti, P Kronenberg, HM Scadden, DT TI Expression of a constitutively active PTH/PTHrP receptor in bone marrow stromal cells leads to expansion of hematopoietic stem cells in vivo and in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1053 BP S138 EP S138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800054 ER PT J AU Choudhury, I Williams, S Raggatt, LJ Byrne, MH Krane, SM Partridge, NC AF Choudhury, I Williams, S Raggatt, LJ Byrne, MH Krane, SM Partridge, NC TI Characterization of collagenase-3 binding to the collagenase-3 specific receptor and LRP1. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. RI Raggatt, Liza-Jane/A-5297-2011; Raggatt, Liza-Jane/S-4530-2016 OI Raggatt, Liza-Jane/0000-0002-7920-6225 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1198 BP S171 EP S171 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800199 ER PT J AU Chung, U Stover, M Kalajzic, I Rowe, DW Lichtler, AC AF Chung, U Stover, M Kalajzic, I Rowe, DW Lichtler, AC TI Use of a Col1a1-GFP retroviral marker system to monitor in vitro differentiation of ES cells into osteoblastic cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1186 BP S168 EP S169 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800187 ER PT J AU Colbert, MC Qian, J Stuart, WD Witte, D Gruenstein, E Osinska, H Lanske, B Kronenberg, HM Clemens, TL AF Colbert, MC Qian, J Stuart, WD Witte, D Gruenstein, E Osinska, H Lanske, B Kronenberg, HM Clemens, TL TI Genetic rescue of cardiac defects in mice lacking the PTH/PTHrP receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. Univ Cincinnati, Dept Med, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Mol Genet, Cincinnati, OH 45221 USA. Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Forsythe Hosp, Dept Oral Pathol, Boston, MA USA. Harvard Univ, Sch Dent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F446 BP S215 EP S215 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800385 ER PT J AU D'Ippolito, G Divieti, P Howard, GA Bringhurst, FR Schiller, PC AF D'Ippolito, G Divieti, P Howard, GA Bringhurst, FR Schiller, PC TI Regulation of gap-functional communication in bone-derived cells by PTH fragments with different C termini. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 VAMC, CRECC Res, Miami, FL USA. Univ Miami, Sch Med, Miami, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU444 BP S392 EP S393 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801158 ER PT J AU Divieti, P Lotz, O Geller, A Juppner, H Bringhurst, FR AF Divieti, P Lotz, O Geller, A Juppner, H Bringhurst, FR TI Inhibition of osteoclast formation by human PTH(7-84) involves direct actions on hematopoietic cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1178 BP S167 EP S167 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800179 ER PT J AU Donohue, MM Demay, MB AF Donohue, MM Demay, MB TI Rickets in VDR null mice is secondary to decreased apoptosis of hypertrophic chondrocytes. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1030 BP S132 EP S132 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800031 ER PT J AU Finkelstein, JS Hayes, A Rao, A Neer, RM AF Finkelstein, JS Hayes, A Rao, A Neer, RM TI Effects of parathyroid hormone, alendronate, or both on bone density in osteoporotic men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 2 Z9 4 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1007 BP S127 EP S127 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800008 ER PT J AU Gensure, RC Shimizu, N Tsang, JC Juppner, H Gardella, TJ AF Gensure, RC Shimizu, N Tsang, JC Juppner, H Gardella, TJ TI Evidence that Bpa19-modified parathyroid hormone-related peptide (PTHrP) agonist and antagonist analogs crosslink to distinct sites in transmembrane domain 2 of the PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SA448 BP S286 EP S287 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800685 ER PT J AU Ghosh-Choudhury, N Abboud, SL Choudhury, GG AF Ghosh-Choudhury, N Abboud, SL Choudhury, GG TI BMP-2-induced phosphatidylinositol 3 kinase (PI 3-K) regulates GATA-4 and MEF2 ttranscription factors during cardiomyocyte differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU45 BP S303 EP S303 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800758 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI Temporospatial expression of BIG-3 during endochondral and intramembranous ossification. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F38 BP S181 EP S181 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800239 ER PT J AU Guo, J Chung, U Bringhurst, RF Kronenberg, HM AF Guo, J Chung, U Bringhurst, RF Kronenberg, HM TI Distinct roles of individual signaling pathways activated by the PTH/PTHrP receptor in endochondral development ex-vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1066 BP S141 EP S141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800067 ER PT J AU Inada, M Wang, Y Byrne, MH Miyaura, C Krane, SM AF Inada, M Wang, Y Byrne, MH Miyaura, C Krane, SM TI Loss of function of matrix metalloproteinase-13 (MMP-13) affects collagen accumulation and bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Tokyo Univ Pharm & Life Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1197 BP S171 EP S171 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800198 ER PT J AU Jonsson, KB Zahradnik, R Larsson, T White, KE Hampson, G Miyauchi, A Ljunggren, O Koshiyama, H Sugimoto, T Oba, K Yamamoto, T Imanishi, Y Econs, M Lavigne, J Jueppner, H AF Jonsson, KB Zahradnik, R Larsson, T White, KE Hampson, G Miyauchi, A Ljunggren, O Koshiyama, H Sugimoto, T Oba, K Yamamoto, T Imanishi, Y Econs, M Lavigne, J Jueppner, H TI FGF-23 is a circulating factor that is elevated in oncogenic osteomalacia and X-linked hypophosphatemic rickets. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Uppsala, Dept Med Sci, S-75105 Uppsala, Sweden. Immutopics Inc, San Clemente, CA USA. Indiana Univ, Sch Med, Indianapolis, IN 46223 USA. St Thomas Hosp, London SE1 7EH, England. Kobe Univ, Grad Sch Med, Kobe, Hyogo 657, Japan. Amagasaki Hosp, Amagasaki, Hyogo, Japan. Kyushu Univ, Fukuoka 812, Japan. Osaka Univ, Osaka, Japan. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1139 BP S158 EP S158 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800140 ER PT J AU Kammerer, CM Mitchell, BD Schneider, JL Cole, SA Hixson, JE Perez, R Bauer, RL AF Kammerer, CM Mitchell, BD Schneider, JL Cole, SA Hixson, JE Perez, R Bauer, RL TI Quantitative trait loci for spine bone mineral density are linked to chromosome 19q in men and women and to 21q in women less than 50 years old. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1079 BP S144 EP S144 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800080 ER PT J AU Karasik, Q Hannan, MT Kiel, DP Bouxsein, ML Cupples, LA AF Karasik, Q Hannan, MT Kiel, DP Bouxsein, ML Cupples, LA TI Is a factor score combining dual X-ray absorptiometry and ultrasound a better phenotype for genetic studies? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, Hebrew Rehab Ctr, Divis Aging, Boston, MA 02115 USA. BIDMC, Orthoped Biomech Lab, Boston, MA USA. Boston Uni, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SA125 BP S236 EP S236 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800475 ER PT J AU Kondo, H Guo, J Chung, U Kasugai, S Kronenberg, HM Bringhurst, FR AF Kondo, H Guo, J Chung, U Kasugai, S Kronenberg, HM Bringhurst, FR TI Effects of PTH/PTHrP receptor-generated signals on RANKL/RANK-induced osteoclastogenesis: Analyses in vitro, in vivo and ex vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Tokyo Med & Dent Univ, Tokyo 1138549, Japan. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1177 BP S166 EP S167 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800178 ER PT J AU Larsson, T Zahradnik, R Marsell, R Ljunggren, O Lavigne, J Jueppner, H Jonsson, K AF Larsson, T Zahradnik, R Marsell, R Ljunggren, O Lavigne, J Jueppner, H Jonsson, K TI Immunohistochemical detection of FGF-23 protein in tumors that cause oncogenic osteomalacia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Hosp, Dept Med Sci, Uppsala, Sweden. Immutop Inc, San Clemente, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SA396 BP S279 EP S279 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800652 ER PT J AU Li, YP Deng, W Shimizu, K Chen, W AF Li, YP Deng, W Shimizu, K Chen, W TI A novel osteoclast-specific cis-acting element controls expression of a mouse cathepsin K gene SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU266 BP S351 EP S351 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800980 ER PT J AU Liu, B Wang, J Yu, H Chung, P Bringhurst, F AF Liu, B Wang, J Yu, H Chung, P Bringhurst, F TI Estrogen inhibits PTH-stimulated osteoclastogenesis through prevention of PTH-induced osteoprotegerin downregulation in mouse marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Natl Taiwan Univ, Natl Taiwan Univ Hosp, Taipei 10764, Taiwan. Natl Taiwan Univ, Sch Dent, Taipei 10764, Taiwan. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU254 BP S348 EP S349 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800968 ER PT J AU MacLean, HE Paller, CJ Kronenberg, HM AF MacLean, HE Paller, CJ Kronenberg, HM TI Role of cell cycle factors in regulating chondrocyte proliferation, and mediating PTHrP action, in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M436 BP S493 EP S493 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801610 ER PT J AU Mahon, MJ Segre, GV AF Mahon, MJ Segre, GV TI Parathyroid hormone-mediated activation of MAPK is dependent upon NHERF2 in PS120 cells SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F449 BP S215 EP S215 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800386 ER PT J AU Makhijani, NS Bischoff, DS Yamaguchi, DT AF Makhijani, NS Bischoff, DS Yamaguchi, DT TI TGF-beta isoforms stimulate chemotaxis but not cell proliferation in the pluripotent mesenchymal stem cell line C3H10T1/2. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M154 BP S430 EP S430 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801328 ER PT J AU Mulder, JE Sklar, CA Klibanski, A Bilezikian, JP AF Mulder, JE Sklar, CA Klibanski, A Bilezikian, JP TI Estrogen in the establishment of peak bone mass. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M384 BP S481 EP S481 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801558 ER PT J AU Nazarian, A von Stechow, D Cordio, MS Mueller, R Snyder, BD AF Nazarian, A von Stechow, D Cordio, MS Mueller, R Snyder, BD TI Analytic model to predict mechanical behavior of skeletal metastasis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, BIDMC, Orthopaed Biomech Lab, Boston, MA 02115 USA. Swiss Fed Inst Technol, Zurich, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M91 BP S416 EP S416 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801266 ER PT J AU Neer, R Hayes, A Rao, A Finkelstein, J AF Neer, R Hayes, A Rao, A Finkelstein, J TI Effects of parathyroid hormone, alendronate, or both on bone density in osteoporotic postmenopausal women. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1039 BP S135 EP S135 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800040 ER PT J AU Ogata, N Roth, SI Kawaguchi, H Segre, GV AF Ogata, N Roth, SI Kawaguchi, H Segre, GV TI Activation of PKC by G alpha q results in osteopenia by blocking osteoblast differentiation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Univ Tokyo, Tokyo, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1051 BP S138 EP S138 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800052 ER PT J AU Piserchio, A Shimizu, N Gardella, TJ Mierke, DF AF Piserchio, A Shimizu, N Gardella, TJ Mierke, DF TI Residue 19 of parathyroid hormone: Structural insight into the role in binding and activation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Brown Univ, Dept Chem & Mol Pharmacol, Providence, RI 02912 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU440 BP S392 EP S392 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801154 ER PT J AU Schipani, E Chiusaroli, R Maier, A Knight, MC Byrne, M Inada, M Calvi, L Wang, Y Baron, R Krane, SM AF Schipani, E Chiusaroli, R Maier, A Knight, MC Byrne, M Inada, M Calvi, L Wang, Y Baron, R Krane, SM TI In vivo impairment of collagenase activity does not affect bone formation in transgenic mice expressing constitutively active PTH/PTHrP receptors in osteoblastic cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Yale Univ, New Haven, CT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ciid, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU66 BP S308 EP S308 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800779 ER PT J AU Schipani, E Kobayashi, T MacLean, HE Knight, MC Johnson, RS Haase, V AF Schipani, E Kobayashi, T MacLean, HE Knight, MC Johnson, RS Haase, V TI The tumor suppressor gene VHL is a critical modulator of cell proliferation and cell growth in the mammalian growth plate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Calif San Diego, Mol Biol Sect, Div Biol, San Diego, CA 92103 USA. Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. RI Haase, Volker Hans/A-6758-2013 OI Haase, Volker Hans/0000-0002-7051-8994 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1152 BP S160 EP S161 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800153 ER PT J AU Schulten, M Kaban, LB Perrott, D Glowacki, J AF Schulten, M Kaban, LB Perrott, D Glowacki, J TI Effect of nicotine on distraction osteogenesis of the rat mandible. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SA167 BP S243 EP S243 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800504 ER PT J AU Shimizu, N Tsang, JC Potts, JT Piserchio, A Mierke, DF Gardella, TJ AF Shimizu, N Tsang, JC Potts, JT Piserchio, A Mierke, DF Gardella, TJ TI Role of residue 19 in PTH(1-20) analogs: Functional evidence for modulation of N-terminal alpha-helical structure. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Brown Univ, Dept Chem & Mol Pharmacol, Providence, RI 02912 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU427 BP S389 EP S389 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801141 ER PT J AU Shimizu, N Gardella, TJ AF Shimizu, N Gardella, TJ TI Structurally varied conformationally constrained amino acids substitutions at positions 1 and 3 of PTH(1-14) preserve or enhance P1R binding affinity and cAMP-signaling potency. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU426 BP S389 EP S389 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801140 ER PT J AU Solomon, DH Finkelstein, J Mogun, H Avorn, J AF Solomon, DH Finkelstein, J Mogun, H Avorn, J TI Has treatment for osteoporosis improved? SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU378 BP S378 EP S378 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801092 ER PT J AU Sooy, K Demay, MB AF Sooy, K Demay, MB TI Analyses of osteoblasts lacking the vitamin D receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M217 BP S444 EP S444 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801391 ER PT J AU Tawfeek, HA Abou-Samra, AB AF Tawfeek, HA Abou-Samra, AB TI PTH stimulation of mitogen-activated protein kinases does not require PTH/PTHrP receptor phosphorylation and internalization or phospholipase C activation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU442 BP S392 EP S392 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801156 ER PT J AU Vallarta-Ast, N Krueger, D Binkley, N AF Vallarta-Ast, N Krueger, D Binkley, N TI Clinical utility of combining calcaneal bone mass measurement with central DXA in men. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M78 BP S413 EP S413 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801253 ER PT J AU Valverde, P Kawai, T Taubman, MA AF Valverde, P Kawai, T Taubman, MA TI Kaliotoxin decreases receptor activator of NF kappa B ligand (RANKL) expression in activated T cells in vitro and ameliorates local inflammatory bone resorption in experimental periodontal disease SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Forsyth Inst, Boston, MA USA. RI Valverde, Paloma/A-9897-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F422 BP S213 EP S213 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800377 ER PT J AU von Stechow, D Quibria, N Fish, S Alexander, JM AF von Stechow, D Quibria, N Fish, S Alexander, JM TI Evidence that estrogen receptor AF-1 activity prevents bone loss: Results from selective estrogen receptor modulator (SEAM) therapy in OVX mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, BIDMC, Bone & Mineral Metab Unit, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Orthoped Biomech Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA M385 BP S481 EP S481 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801559 ER PT J AU Wise, LM Grynpas, MD Jurisicova, A Korsmeyer, SJ Perez, GI Tilly, JL AF Wise, LM Grynpas, MD Jurisicova, A Korsmeyer, SJ Perez, GI Tilly, JL TI Age-dependent effect of Bax deficiency on bone quality in mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA 1219 BP S176 EP S177 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800220 ER PT J AU Wittelsberger, A Corich, M Barazza, A Yacobi, R Lee, BK Rosenblatt, M Alexander, JM Chorev, M AF Wittelsberger, A Corich, M Barazza, A Yacobi, R Lee, BK Rosenblatt, M Alexander, JM Chorev, M TI Identification of novel contact points between residues in the mid-region of PTH(1-34) and the PTH1-receptor: Refinement of the model of the PTH--PTH1-receptor complex. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, Sch Med, Dept Bone & Mineral Metab, BIDMC, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA SU443 BP S392 EP S392 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952801157 ER PT J AU Wittelsberger, A Yahalom, D Mierke, DF Rosenblatt, M Alexander, JM Chorev, M AF Wittelsberger, A Yahalom, D Mierke, DF Rosenblatt, M Alexander, JM Chorev, M TI Identification of the RGD-binding site in the human osteoclast alphaVbeta3 integrin receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res C1 Harvard Univ, BIDMC, Sch Med, Dept Bone & Mineral Metab, Boston, MA 02115 USA. Brown Univ, Div Biol & Med, Dept Chem, Providence, RI 02912 USA. Brown Univ, Div Biol & Med, Dept Mol Pharmacol, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2002 VL 17 SU 1 MA F227 BP S197 EP S197 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 592TK UT WOS:000177952800306 ER PT J AU Ryan, CM Schoenfeld, DA Malloy, M Schulz, JT Sheridan, RL Tompkins, RG AF Ryan, CM Schoenfeld, DA Malloy, M Schulz, JT Sheridan, RL Tompkins, RG TI Use of Integra artificial skin is associated with decreased length of stay for severely injured adult burn survivors SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article AB Mortality and length of stay (LOS) of survivors was examined retrospectively in 270 adults with acute burns greater than or equal to20% of body surface area to determine the effect of Integra((R)) Dermal Regeneration Template treatment on outcome. No difference in mortality was found between patients who received Integra((R)) (30%; n = 43) and patients who did not (30%; n = 227). Surviving Integra((R)) patients (n = 30) stayed longer, but they were more extensively injured than survivors who did not receive Integra((R)) (n = 158), and therefore longer hospitalizations were expected. In a subgroup analysis, mean LOS of Integra((R)) patients with two or more mortality risk factors (age > 60 years, burn size >40% body surface area, or inhalation injury; n = 15) was 63 days compared with 107 days in patients with two or more risk factors (n = 29) who did not receive Integra((R)) (P = 014). Integra((R)) use in severely injured burned adults was associated with a marked decrease in LOS. C1 Massachusetts Gen Hosp, Bigelow Surg Serv 1302, Sumner Redstone Ctr, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Shriners Burns Hosp Children, Boston Burns Unit, Boston, MA USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Bigelow Surg Serv 1302, Sumner Redstone Ctr, Dept Surg, Boston, MA 02114 USA. NR 7 TC 40 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD SEP-OCT PY 2002 VL 23 IS 5 BP 311 EP 317 DI 10.1097/01.BCR.0000028566.85892.54 PG 7 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 606ZJ UT WOS:000178765700002 PM 12352131 ER PT J AU Carter, J Park, ER Moadel, A Cleary, SD Morgan, C AF Carter, J Park, ER Moadel, A Cleary, SD Morgan, C TI Cancer knowledge, attitudes, beliefs, and practices (KABP) of disadvantaged women in the south Bronx SO JOURNAL OF CANCER EDUCATION LA English DT Article ID BREAST-CANCER; CERVICAL-CANCER; PAP SMEAR; PREVENTION; ETHNICITY; BEHAVIOR; AGE AB Background. This study assessed cancer knowledge, attitudes, beliefs, and practices (KABP) among 1,280 African American and Hispanic women. Methods. A written self-report KABP survey was administered. Results. Most women reported using breast self-examination (BSE), clinical breast examination (CBE), and mammography, but only 66% had had Pap tests in the preceding year. Group comparisons revealed significant differences for cancer and disease beliefs between the Black and the Hispanic women. Less knowledge about screening significantly predicted underutilization of Pap testing (OR = 2.71, CI 2.02, 3.63), BSE (OR = 1.63, CI 1.63, 2.13), and CBE (OR = 1.66, CI 1.27, 2.18). Conclusions. KABP surveys were important in developing cancer interventions. C1 Mem Sloan Kettering Canc Ctr, Dept Psychiat, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Inst Hlth Policy, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA. George Washington Univ, Dept Epidemiol & Biostat, Washington, DC 20052 USA. RP Carter, J (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat, 1242 2nd Ave, New York, NY 10021 USA. FU NCI NIH HHS [R25 CA57806] NR 43 TC 21 Z9 21 U1 1 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD FAL PY 2002 VL 17 IS 3 BP 142 EP 149 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 594WK UT WOS:000178074600007 PM 12243219 ER PT J AU Chen, CC Izadshenas, A Rana, AA Azar, DT AF Chen, CC Izadshenas, A Rana, AA Azar, DT TI Corneal asphericity after hyperopic laser in situ keratomileusis SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID EXCIMER-LASER; PHOTOREFRACTIVE KERATECTOMY; TOPOGRAPHY; MYOPIA; SURGERY AB Purpose: To analyze corneal asphericity after hyperopic laser in situ keratomileusis (LASIK) and its relationship to the clinical outcomes. Setting: Corneal and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. Methods: In a retrospective case series, 23 patients (33 eyes) with hyperopia or hyperopic astigmatism who had LASIK were evaluated. A computer program (Holladay Diagnostic Summary, EyeSys Laboratories) was used to analyze corneal asphericity (Q) before and after LASIK. Corneal asphericity was evaluated to determine the association with the postoperative refractive error, best spectacle-corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA), achieved refractive correction, mean corneal power (K), refractive yield (achieved/attempted correction), and keratometric yield (change in keratometry/attempted correction). Results: After hyperopic LASIK, all corneas exhibited increased negative central Q. The postoperative corneal radius of curvature, BSCVA, and refractive and keratometric yields were not significantly correlated with the preoperative Q values. The asphericity change, DeltaQ, was highly correlated with the achieved correction (r = 0.747, P < .0001). The postoperative Q value correlated well with the preoperative value (r = 0.534, P < .05) and the achieved correction (r = 0.601, P < .05) but not with the &UDelta;Q. Neither the postoperative Q nor the &UDelta;Q was correlated with the spherical equivalent, K, BSCVA, or UCVA. Conclusions: Asphericity may be a useful quantitative descriptor of the corneal optical contour after hyperopic LASIK. Negative central Q increased after hyperopic LASIK, especially when greater degrees of refractive correction were attempted. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 41 Z9 44 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2002 VL 28 IS 9 BP 1539 EP 1545 AR PII S0886-3350(02)01541-9 DI 10.1016/S0886-3350(02)01541-9 PG 7 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 595GA UT WOS:000178099100013 PM 12231307 ER PT J AU Prisant, O Thanh, HX Proano, G Hernandez, E Awad, S Azar, DT AF Prisant, O Thanh, HX Proano, G Hernandez, E Awad, S Azar, DT TI Vector summation of anterior and posterior corneal topographical astigmatism SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; SURFACE TORICITY; BED THICKNESS; CURVATURE; SYSTEM; RADIUS; POWER; KERATOMETRY; PACHYMETRY; SURGERY AB Purpose: To determine whether vector addition of posterior corneal astigmatism improves the correlation between topographical and refractive astigmatism. Setting: Massachusetts Eye and Ear Infirmary and Harvard Medical School, Boston, Massachusetts, USA. Methods: Orbscan topographical maps of 40 eyes (31 patients) showing 1.0 to 6.0 diopters (D) of astigmatism were analyzed. Topographical anterior and posterior corneal surface astigmatism was determined. Refractive astigmatism was compared to topographical astigmatism using 3 methods: anterior topographical astigmatism, overall topographical astigmatism obtained by vector summation of anterior and posterior topographical astigmatism, and simulated keratometry (SimK). Results: Refractive astigmatism ranged from 0.25 to 5.00 D. The mean error in magnitude between topographical and refractive astigmatism was significantly smaller with the overall topographical method (1.06 D +/- 0.92 [SD]) than the anterior topographical method (1.37 +/- 1.04 D) (P < .0001). The mean error in axis between topographical and refractive astigmatism was smaller with the overall topographical method (10.4 &PLUSMN; 13 degrees) than with the anterior topographical method (15.5 &PLUSMN; 30.6 degrees) and with SimK (13.3 &PLUSMN; 15.1 degrees), but these differences were not statistically significant. Conclusion: Consideration of the Orbscan measurement of posterior corneal surface toricity may improve the prediction of the magnitude of refractive astigmatism. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Services, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Fdn Ophtalmol Adolphe Rothschild, Paris, France. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Services, 243 Charles St, Boston, MA 02114 USA. NR 30 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD SEP PY 2002 VL 28 IS 9 BP 1636 EP 1643 AR PII S0886-3350(01)01258-5 DI 10.1016/S0886-3350(01)01258-5 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 595GA UT WOS:000178099100031 PM 12231325 ER PT J AU Bacskai, BJ Klunk, WE Mathis, CA Hyman, BT AF Bacskai, BJ Klunk, WE Mathis, CA Hyman, BT TI Imaging amyloid-beta deposits in vivo SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review DE Alzheimer; amyloid-beta; SPECT; PET ID MILD ALZHEIMERS-DISEASE; HIGH-RESOLUTION SPECT; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; ENTORHINAL CORTEX; MULTIPHOTON MICROSCOPY; HIPPOCAMPAL-FORMATION; SENILE PLAQUES; BRAIN; MRI AB Alzheimer disease (AD) is an illness that can only be diagnosed With certainty with postmortem examination of brain tissue. Tissue samples from afflicted patients show neuronal loss, neurofibrillary tangles (NFTs), and amyloid-beta plaques. An imaging technique that permitted in vivo detection of NFTs or amyloid-beta plaques would be extremely valuable. For example, chronic imaging of senile plaques would provide a readout of the efficacy of experimental therapeutics aimed at removing these neuropathologic lesions. This review discusses the available techniques for imaging amyloid-beta deposits in the intact brain, including magnetic resonance imaging, positron emission tomography, single photon emission computed tomography, and multiphoton microscopy. A variety of agents that target amyloid-beta deposits specifically have been developed using one or several of these imaging modalities. The difficulty in developing these tools lies in the need for the agents to cross the blood-brain barrier while recognizing amyloid-beta with high sensitivity and specificity. This review describes the progress in developing reagents suitable for in vivo imaging of senile plaques. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Unit, CNY 2450, Charlestown, MA 02129 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Lab Mol Neuropharmacol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Radiol, PET Facil, Pittsburgh, PA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Unit, CNY 2450, 114 16th St, Charlestown, MA 02129 USA. RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [AG18402, AG202226, NIH-AG01039, NIH-AG08487] NR 49 TC 70 Z9 76 U1 2 U2 11 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 SEP PY 2002 VL 22 IS 9 BP 1035 EP 1041 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 592CP UT WOS:000177919400001 PM 12218409 ER PT J AU Pollock, RA Carter, AS Avenevoli, S Dierker, LC Chazan-Cohen, R Merikangas, KR AF Pollock, RA Carter, AS Avenevoli, S Dierker, LC Chazan-Cohen, R Merikangas, KR TI Anxiety sensitivity in adolescents at risk for psychopathology SO JOURNAL OF CLINICAL CHILD AND ADOLESCENT PSYCHOLOGY LA English DT Article ID PANIC DISORDER; DIAGNOSTIC INTERVIEW; MAJOR DEPRESSION; CHILDREN; CHILDHOOD; COMORBIDITY; PARENTS; ATTACKS; INDEX; SCHIZOPHRENIA AB Examined the associations of adolescents' self-reported anxiety sensitivity with semi-structured, interview-based anxiety and depressive symptoms and anxiety disorders. The sample included 121 adolescents and their parents who participated in a larger epidemiological, high-risk family study of substance abuse and anxiety disorders (Merikangas, Dierker, & Szatmari, 1998). A series of hierarchical multiple regressions revealed the incremental validity of anxiety sensitivity, beyond the contribution of self-rated anxiety, to anxiety symptoms and comorbid anxiety disorders. Furthermore, familial risk for anxiety moderated the association between anxiety sensitivity and number of anxiety symptoms as well as number of comorbid anxiety disorders. Analyses of high- and low-risk groups demonstrated that the association between anxiety sensitivity and anxiety symptoms and disorders was evident in high-risk adolescents only. Although self-reported anxiety was associated with depressive symptoms, anxiety sensitivity was not. Results from this investigation further support the utility of assessing anxiety sensitivity in an adolescent population and suggest it as a trait marker of anxiety among at-risk individuals. C1 Massachusetts Gen Hosp, Dept Psychiat, Unit Psychiat & Neurodev Genet, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, VA New England Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Cambridge, MA 02138 USA. Univ Massachusetts, Boston, MA 02125 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. Adm Children Youth & Families, Commissioners Off Res & Evaluat, Washington, DC USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth Psychol, New Haven, CT 06520 USA. RP Pollock, RA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Unit Psychiat & Neurodev Genet, CNY Bldg 149,13th St,10th Floor, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA 00293] NR 50 TC 16 Z9 16 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1537-4416 J9 J CLIN CHILD ADOLESC JI J. Clin. Child Adolesc. Psychol. PD SEP PY 2002 VL 31 IS 3 BP 343 EP 353 DI 10.1207/S15374424JCCP3103_06 PG 11 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 574VQ UT WOS:000176910600005 PM 12149972 ER PT J AU Pitteloud, N Hayes, FJ Dwyer, A Boepple, PA Lee, H Crowley, WF AF Pitteloud, N Hayes, FJ Dwyer, A Boepple, PA Lee, H Crowley, WF TI Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; FOLLICLE-STIMULATING-HORMONE; HUMAN MENOPAUSAL GONADOTROPIN; CLINICAL RESEARCH-CENTER; GERM-CELL MATURATION; INHIBIN-B; SERTOLI-CELL; LUTEINIZING-HORMONE; TESTICULAR GROWTH AB GnRH treatment is successful in inducing virilization and spermatogenesis in men with idiopathic hypogonadotropic hypogonadism (IHH). However, a small subset of IHH men, poorly characterized to date, fail to reach a normal testicular volume (TV) and produce sperm on this therapy. To determine predictors of outcome in terms of TV and sperm count, we studied 76 IHH men (38% with anosmia) undergoing GnRH therapy for 12-24 months. The population was stratified according to the baseline degree of prior pubertal development: absent (group 1, n = 52), partial (group 2, n = 18), or complete (adult onset HH; group 3, n = 6). Cryptorchidism was recorded in 40% of group 1, 5% of group 2, and none in group 3. Pulsatile GnRH therapy was initiated at 5-25 ng/kg per pulse sc and titrated to attain normal adult male testosterone (T) levels. LH, FSH, T, and inhibin B (I(B)) levels were measured serially, and maximum sperm count was recorded. A longitudinal mixed effects model was used to determine predictors of final TV. LH (97%) and T (93%) levels were normalized in the majority of IHH men. Groups 2 and 3 achieved a normal adult testicular size (92%), FSH (96%), I(B) levels (93%), and sperm in their ejaculate (100%). However, given their prior complete puberty and thus primed gonadotropes and testes, group 3 responded faster, normalizing androgen production by 2 months and completing spermatogenesis by 6 months. In contrast, group 1 failed to normalize TV (11 +/- 0.4 ml) and I(B) levels (92 +/- 6 pg/ml) by 24 months, despite normalization of their FSH levels (11 +/- 2 IU/liter). Similarly, sperm counts of group 1 plateaued well below the normal range (median of 3 x 10(6)/ml) with 18% remaining azoospermic. The independent predictors of outcome of long-term GnRH therapy were: 1) the presence of some prior pubertal development (positive predictor; group effect (13) = 4.3; P = 0.003); 2) a baseline I(B) less than 60 pg/ml (negative predictor; beta = -3.7; P = 0.009); and 3) prior cryptorchidism (negative predictor; beta = -1.8; P = 0.05). Notably, anosmia was not an independent predictor of outcome when adjusted for other baseline variables. Our conclusions are: 1) pulsatile GnRH therapy in IHH men is very successful in inducing androgen production and spermatogenesis; 2) normalization of the LH-Leydig cell-T axis is achieved more uniformly than the FSH-Sertoli cell-I(B), axis during GnRH therapy; and 3) favorable predictors for achieving an adult testicular size and consequently optimizing spermatogenesis are prior history of sexual maturation, a baseline I(B) greater than 60 pg/ml, and absence of cryptorchidism. C1 Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Chem, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Chem, Reprod Endocrine Unit, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [P30 HD028138, R01 HD015788, R01 HD15788, U54 HD028138, U54 HD029164, U54-HD-28138]; NIDDK NIH HHS [U54DK07028-24] NR 78 TC 75 Z9 86 U1 2 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2002 VL 87 IS 9 BP 4128 EP 4136 DI 10.1210/jc.2002-020518 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 597BB UT WOS:000178201200019 PM 12213860 ER PT J AU Soyka, LA Misra, M Frenchman, A Miller, KK Grinspoon, S Schoenfeld, DA Klibanski, A AF Soyka, LA Misra, M Frenchman, A Miller, KK Grinspoon, S Schoenfeld, DA Klibanski, A TI Abnormal bone mineral accrual in adolescent girls with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; X-RAY ABSORPTIOMETRY; SOFT-TISSUE COMPOSITION; CALCIUM SUPPLEMENTATION; BIOCHEMICAL MARKERS; FEMALE ADOLESCENTS; HEALTHY-CHILDREN; BODY-COMPOSITION; DENSITY; TURNOVER AB Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean SEM, 15.4 +/- 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); p = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 +/- 0.001 g/cm(2.)month vs. 0.000 +/- 0.001 g/cm(2.)month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 mug/liter-month, vs. control, -1.1 +/- 0.4 mug/liter-month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter-month, vs. control, -1.5 +/- 0.4 U/liter-month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol creatinine (cr) (.)month, vs. control, -0.4 +/- 0.1 nmol/mmol cr-month; P = 0.005], and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066] NR 37 TC 158 Z9 161 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2002 VL 87 IS 9 BP 4177 EP 4185 DI 10.1210/jc.2001-011889 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 597BB UT WOS:000178201200028 PM 12213868 ER PT J AU Ma, XW Warram, JH Trischitta, V Doria, A AF Ma, XW Warram, JH Trischitta, V Doria, A TI Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID INSULIN-RESISTANCE; EXPRESSION; OBESITY; MELLITUS; FAMILY; CALPAIN-10; RECEPTOR; MUSCLE; HUMANS; LEVEL AB Resistin is a newly identified hormone secreted by adipocytes that inhibits insulin action on peripheral tissues. The aim of our study was to investigate whether genetic variability at this locus is associated with the risk of type 2 diabetes. By sequencing 32 subjects with type 2 diabetes, we identified 8 single nucleotide polymorphisms (SNPs) in the 5'-flanking region and introns of the resistin gene. Allele and genotype distributions were determined for all 8 SNPs in 312 cases with type 2 diabetes and 303 nondiabetic controls, all of Caucasian origin. No significant association with type 2 diabetes was found at any of the polymorphic loci. However, an interactive effect of genotype at SNP 6 (IVS2 + 181G-->A) and obesity was a significant determinant of type 2 diabetes risk in this population. The relative risk of diabetes for the A/A genotype was 4.8 (95% confidence interval, 1.1-21.0) in individuals above the median for body weight, but only 0.7 (95% confidence interval, 0.2-2.1) in those below the median. This difference between relative risks was significant (chi(2) = 4.5; P = 0.03). A similar, but much weaker, interaction with obesity was observed for SNPs in linkage disequilibrium with SNP6. In conclusion, resistin does not appear to be a major gene for type 2 diabetes. However, our data suggest a synergistic effect of sequence differences at the resistin locus and obesity on risk of type 2 diabetes. Further studies are needed to confirm this finding in other populations. C1 Joslin Diabet Ctr, Sect Genet Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Osped Casa Sollievo Sofferenza, I-71013 San Giovanni Rotondo, Italy. Univ Roma La Sapienza, Dept Clin Sci, I-00161 Rome, Italy. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu RI Trischitta, Vincenzo/K-1487-2016 OI Trischitta, Vincenzo/0000-0003-1174-127X FU NIDDK NIH HHS [DK-36836, R01-DK-47475, R01-DK-55523] NR 19 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 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2002 VL 87 IS 9 BP 4407 EP 4410 DI 10.1210/jc.2002-020109 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 597BB UT WOS:000178201200063 PM 12213908 ER PT J AU Lotti, B Wendland, T Furrer, H Yawalkar, N Greyerz, SV Schnyder, K Brandes, M Vernazza, P Wagner, R Nguyen, T Rosenberg, E Pichler, WJ Brander, C AF Lotti, B Wendland, T Furrer, H Yawalkar, N Greyerz, SV Schnyder, K Brandes, M Vernazza, P Wagner, R Nguyen, T Rosenberg, E Pichler, WJ Brander, C TI Cytotoxic HIV-1 p55(gag)-specific CD4(+) T cells produce HIV-inhibitory cytokines and chemokines. SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE CD4 T cell; HIV; chemokines; cytotoxic; antiviral activity ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIGEN-PRESENTING CELLS; MEDIATED CYTOTOXICITY; ANTIRETROVIRAL THERAPY; RESPONSES; RECEPTOR; CLONES; LYMPHOCYTES; DISEASE; CD8(+) AB CD4(+) T-helper cells appear to be essential in sustaining immune responses in chronic viral infections, as the maintenance of CD8(+) cytotoxic T-lymphocyte responses and the control of viremia were demonstrated to depend on CD4(+) T cell help. In order to investigate the function of HIV-specific CD4(+) T cells in chronic HIV-1-infection, 49 chronically HIV-infected patients were analyzed before and 3 and 6 months after initiation of antiviral treatment. Ten patients showed a substantial, although weak, proliferative response to HIV-1-p55(g)ag protein for which no improvement was observed upon initiation of HAART. From one individual, HIV-1-p55(g)ag-specific CD4-positive T-cell clones were generated that were heterogeneous in their TCR Vbeta gene usage and HLA-DRB1*13 and DRB1*03 restricted, respectively. In addition, some CD4(+) TCC produced substantial amounts of IFN-gamma and MIP-1alpha/beta, were perforin-positive, and showed cytotoxic activity. These diverse functional features of HIV-specific CD4(+) T cells suggest that they may exert direct antiviral activity. C1 Univ Hosp Bern, Clin Rheumatol & Clin Immunol Allergol, Div Allegol, CH-3010 Bern, Switzerland. Univ Hosp Bern, Div Infect Dis, Bern, Switzerland. Univ Bern, Theodor Kocher Inst, Bern, Switzerland. Kantonsspital St Gallen, St Gallen, Switzerland. Univ Regensburg, Inst Med Microbiol & Hyg, D-8400 Regensburg, Germany. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. RP Brander, C (reprint author), AIDS Res Ctr, MGH E 5214,149 13th St, Charlestown, MA 02129 USA. RI Furrer, Hansjakob/G-6768-2013 OI Furrer, Hansjakob/0000-0002-1375-3146 NR 47 TC 12 Z9 12 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD SEP PY 2002 VL 22 IS 5 BP 253 EP 262 AR UNSP 0271-9142/02/0900/0253/0 DI 10.1023/A:1020066404226 PG 10 WC Immunology SC Immunology GA 587FB UT WOS:000177628900001 PM 12405158 ER PT J AU Inada, M Krane, SM AF Inada, M Krane, SM TI Targeting rheumatoid inflammation and joint destruction in the mouse SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID PROSTAGLANDIN E-2; BONE-RESORPTION; MICE LACKING; RECEPTOR; ARTHRITIS; EP4 C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krane, SM (reprint author), Massachusetts Gen Hosp, Dept Med, 149 13th St, Boston, MA 02129 USA. RI inada, masaki/D-1581-2013 OI inada, masaki/0000-0002-5066-8506 NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 5 BP 611 EP 612 DI 10.1172/JCI200216549 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590LF UT WOS:000177823800006 PM 12208860 ER PT J AU Signoretti, S Di Marcotullio, L Richardson, A Ramaswamy, S Isaac, B Rue, M Monti, F Loda, M Pagano, M AF Signoretti, S Di Marcotullio, L Richardson, A Ramaswamy, S Isaac, B Rue, M Monti, F Loda, M Pagano, M TI Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID KINASE INHIBITOR P27; F-BOX PROTEIN; PROTEASOME-DEPENDENT DEGRADATION; CELL-CYCLE REGULATORS; S-PHASE KINASE; DIFFERENTIAL EXPRESSION; COLORECTAL CARCINOMAS; P27(KIP1); PROGRESSION; PROLIFERATION AB Estrogen receptor (ER) expression and Her-2 amplification define specific subsets of breast tumors for which specific therapies exist. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis and immunohistochemistry, we determined that higher levels of Skp2 are present more frequently in ER-negative tumors than in ER-positive cases. Interestingly, the subset of ER-negative breast carcinomas overexpressing Skp2 are also characterized by high tumor grade, negativity for Her-2, basal-like phenotype, high expression of certain cell cycle regulatory genes, and low levels of p27 protein. We also found that Skp2 expression is cell adhesion-dependent in normal human mammary epithelial cells but not in breast cancer cells and that an inhibition of Skp2 induces a decrease of adhesion-independent growth in both ER-positive and ER-negative cancer cells. Finally, forced expression of Skp2 abolished effects of antiestrogens, suggesting that deregulated Skp2 expression might play a role in the development of resistance to antiestrogens. We conclude that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2 inhibitors may represent a valid therapeutic option. C1 NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Inst Canc, New York, NY 10016 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Whitehead Inst MIT Ctr Genom Res, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Sanitaria Locale Rimini, Dept Oncol, Azienda Unita, Rimini, Italy. Ist Oncol Romagnolo, Rimini, Italy. RP Pagano, M (reprint author), NYU, Sch Med, Dept Pathol, 550 1st Ave,MSB 599, New York, NY 10016 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA89393, CA84995, P50 CA089393, R01 CA076584, R01-CA76584, R01-CA81755, U01 CA084995]; NIGMS NIH HHS [R01 GM057587, R01-GM57587] NR 39 TC 221 Z9 252 U1 1 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 5 BP 633 EP 641 DI 10.1172/JCI200215795 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 590LF UT WOS:000177823800010 PM 12208864 ER PT J AU Pai, SY Ho, IC AF Pai, SY Ho, IC TI c-Rel delivers a one-two punch in Th1 cell differentiation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID NF-KAPPA-B; CYTOKINE; EXPRESSION C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Ho, IC (reprint author), Smith Bldg,Room 526D,1 Jimmy Fund Way, Boston, MA 02115 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 741 EP 742 DI 10.1172/JCI200216552 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300005 PM 12235102 ER PT J AU Opitz, OG Harada, H Suliman, Y Rhoades, B Sharpless, NE Kent, R Kopelovich, L Nakagawa, H Rustgi, AK AF Opitz, OG Harada, H Suliman, Y Rhoades, B Sharpless, NE Kent, R Kopelovich, L Nakagawa, H Rustgi, AK TI A mouse model of human oral-esophageal cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; CYCLIN D1 OVEREXPRESSION; CIS-REGULATORY ELEMENT; SKIN TUMOR-DEVELOPMENT; TRANSGENIC MICE; TELOMERE DYSFUNCTION; HAPLO-INSUFFICIENT; P53; EXPRESSION; PROMOTER AB Squamous cancers of the oral cavity and esophagus are common worldwide, but no good genetically based animal model exists. A number of environmental factors as well as genetic alterations have been identified in these cancers, yet the specific combination of genetic events required for cancer progression remains unknown. The Epstein-Barr virus ED-L2 promoter (L2) can be used to target genes in a specific fashion to the oral-esophageal squamous epithelium. To that end, we generated L2-cyclin D 1 (L2D1(+)) mice and crossbred these with p53-deficient mice. Whereas L2D1(+) mice exhibit a histologic phenotype of oral-esophageal dysplasia, the combination of cyclin D1 expression and p53 deficiency results in invasive oral-esophageal cancer. The development of the precancerous lesions was significantly reversed by the application of sulindac in the drinking water of the L2D1(+)/p53(+/-) mice. Furthermore, cell lines derived from oral epithelia of L2D1(+)/p53(+/-) and L2D1(+)/p53(-/-) mice, but not control mice, formed tumors in athymic nude mice. These data demonstrate that L2D1(+)/p53(+/-) mice provide a well-defined, novel, and faithful model of oral-esophageal cancer, which allows for the testing of novel chemopreventive, diagnostic, and therapeutic approaches. C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Ctr Res Inst, Philadelphia, PA 19104 USA. Univ Freiburg, Dept Med, D-7800 Freiburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, 415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [N01-CN-95031-72]; NIDCR NIH HHS [P01 DE-12467, P01 DE012467]; NIDDK NIH HHS [P30 DK-50306, P30 DK050306] NR 44 TC 64 Z9 67 U1 1 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2002 VL 110 IS 6 BP 761 EP 769 DI 10.1172/JCI200215324 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 594VX UT WOS:000178073300010 PM 12235107 ER PT J AU Raja, R Salunga, R Taylor, T Bennett, A Firouzi, A Mikulowska-Mennis, A Ma, XJ Sgroi, D Erlander, M Kunitake, S AF Raja, R Salunga, R Taylor, T Bennett, A Firouzi, A Mikulowska-Mennis, A Ma, XJ Sgroi, D Erlander, M Kunitake, S TI A microgenomics platform for high-throughput gene expression analysis of pure cell populations SO JOURNAL OF CLINICAL LIGAND ASSAY LA English DT Article DE microarrays; linear amplification; pure cells; laser capture microdissection; LCM; gene expression; expression profiling; fidelity; RNA; functional genomics ID LASER-CAPTURE MICRODISSECTION; MOLECULAR ANALYSIS; RNA AMPLIFICATION; MICROARRAY; PATTERNS; GENOME; CDNA AB Differential expression of thousands of genes can be monitored in parallel using microarrays. Microarrays provide a valuable tool for studying variations in gene expression that contribute to diseases and aid in disease diagnoses and drug discovery. However, whole tissue biopsies are typically used for such studies because micrograms of RNA are required for microarray analysis. Hence, molecular signal measurements are averaged over several dissimilar cell types, resulting in decreased assay sensitivity or misleading results leading to erroneous conclusions. We have developed a novel platform that attains improved sensitivity at three stages: 1) capturing pure cell populations through laser-capture microdissection (LCM) while maintaining integrity of cellular RNA; 2) efficiently recovering RNA from small samples through an optimized RNA isolation system; and 3) linearly amplifying messages from total cellular RNA to provide adequate amounts of amplified antisense RNA for microarray analysis. Using this platform, considerably higher sensitivity and specificity in quantifying differential gene expression is attained over traditional approaches. Moreover, the system is capable of revealing signatures not resolved when whole tissues are assayed. Using as few as 250 LCM cells, molecular signatures for different breast cancer stages have been identified, suggesting direct application to clinical analyses. C1 Arcturus, Mountain View, CA 94043 USA. Arcturus Appl Genom, Carlsbad, CA USA. Harvard Univ, Sch Med, Dept Pathol, Mol Pathol Res Unit,Massachusetts Gen Hosp, Boston, MA USA. RP Raja, R (reprint author), Arcturus, 400 Logue Ave, Mountain View, CA 94043 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU CLINICAL LIGAND ASSAY SOC PI WAYNE PA 3139 S WAYNE RD, WAYNE, MI 48184 USA SN 1081-1672 J9 J CLIN LIGAND ASSAY JI J. Clin. Ligand Assay PD FAL PY 2002 VL 25 IS 3 BP 253 EP 259 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 697NL UT WOS:000183949500003 ER PT J AU Martinez, M Lopez-Ribot, JL Kirkpatrick, WR Coco, BJ Bachmann, SP Patterson, TF AF Martinez, M Lopez-Ribot, JL Kirkpatrick, WR Coco, BJ Bachmann, SP Patterson, TF TI Replacement of Candida albicans with C-dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-VITRO; ANTIFUNGAL AGENTS; CHROMOGENIC AGAR; UNITED-STATES; IDENTIFICATION; SUSCEPTIBILITY; INDIVIDUALS; RESISTANCE; RADIATION AB Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human Immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed fluconazole resistance (fluconazole MIC, greater than or equal to64 mug/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 mug/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 mug/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 mug/ml and those for the other two were 32 and 64 mug/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species. C1 Univ Texas, Hlth Sci Ctr San antonio, S Texas Ctr Biol Med, Dept Med,Div Infect Dis, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RP Lopez-Ribot, JL (reprint author), Univ Texas, Hlth Sci Ctr San antonio, S Texas Ctr Biol Med, Dept Med,Div Infect Dis, 15355 Lambda Dr, San Antonio, TX 78245 USA. RI Lopez-Ribot, Jose/D-2048-2010 FU NCRR NIH HHS [M01-RR-01346, M01 RR001346]; NIAID NIH HHS [R29 AI42401]; NIDCR NIH HHS [5 R01 DE11381-04A2, R01 DE011381] NR 35 TC 63 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3135 EP 3139 DI 10.1128/JCM.40.9.3135-3139.2002 PG 5 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900004 PM 12202543 ER PT J AU Smole, SC McAleese, F Ngampasutadol, J von Reyn, CF Arbeit, RD AF Smole, SC McAleese, F Ngampasutadol, J von Reyn, CF Arbeit, RD TI Clinical and epidemiological correlates of genotypes within the Mycobacterium avium complex defined by restriction and sequence analysis of hsp65 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HEAT-SHOCK-PROTEIN; ENZYME ANALYSIS; NONTUBERCULOUS MYCOBACTERIA; GENETIC DIVERSITY; GROWING MYCOBACTERIA; SPECIES ASSIGNMENT; DNA PROBES; IDENTIFICATION; STRAINS; INFECTION AB Species identification of isolates of the Mycobacterium avium complex (MAC) remains a difficult task. Although M. avium and Mycobacterium intracellulare can be identified with expensive, commercially available probes, many MAC isolates remain unresolved, including those representing Mycobacterium lentiflavum as well as other potentially undefined species. PCR restriction analysis (PRA) of the hsp6.5 gene has been proposed as a rapid and inexpensive approach. We applied PRA to 278 MAC isolates, including 126 from blood of human immunodeficiency virus (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary isolates from a different study. A total of 15 different PRA patterns were observed. For 27 representative isolates, a 441-bp fragment of the hsp65 gene was sequenced; based on 54 polymorphic sites, 18 different alleles were defined, including 12 alleles not previously reported. Species and phylogenetic relationships were more accurately defined by sequencing than by PRA or commercial probe. The distribution of PRA types and, by implication, phylogenetic lineages among blood isolates was significantly different from that for pulmonary and environmental isolates, suggesting that particular lineages have appreciably greater virulence and invasive potential. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02130 USA. VA Boston Healthcare Syst, Med Serv, Infect Dis Sect, Boston, MA 02130 USA. Dartmouth Coll, Hitchcock Med Ctr, Dept Med, Hanover, NH 03756 USA. Dartmouth Coll Sch Med, Hanover, NH 03756 USA. RP Arbeit, RD (reprint author), Cubist Pharmaceut Inc, 65 Hayden Dr, Lexington, MA 02420 USA. NR 29 TC 35 Z9 37 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3374 EP 3380 DI 10.1128/JCM.40.9.3374-3380.2002 PG 7 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900042 PM 12202581 ER PT J AU Chen, HI Hulten, K Clarridge, JE AF Chen, HI Hulten, K Clarridge, JE TI Taxonomic subgroups of Pasteurella multocida correlate with clinical presentation SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PNEUMONIA; CAT AB Pasteurella multocida is a small nonmotile gram-negative coccobacillus that is found in the nasopharynx and gastrointestinal tract of many wild and domesticated animals. In humans it most commonly causes cellulitis and localized superficial skin abscesses following an animal bite or scratch. The respiratory tract is the second most common site of infection for Pasteurella. Of the more than 17 species of Pasteurella known, Pasteurella multocida subsp. multocida and Pasteurella multocida subsp. septica are among the most common pathogens in humans. With the use of molecular techniques, distinction between different subspecies of P. multocida can be made more easily and accurately. We used the sequence of the 16S ribosomal DNA (rDNA) and repetitive extragenic palindromic sequence-PCR (REP-PCR) to characterize 20 strains (14 of P. multocida subsp. multocida and 6 of P. multocida subsp. septica; the 16S rDNA is identical for P. multocida subsp. multocida and Pasteurella multocida subsp. gallicida but differs from that of P. multocida subsp. septica) isolated from various anatomic sites. We found excellent correlation between the 16S rDNA sequence (a marker for a small conserved region of the genome), REP-PCR (a marker for a large portion of the genome), and biochemical tests (trehalose and sorbitol). We also found a correlation between the clinical presentation and the taxonomic group, with P. multocida subsp. septica more often associated with wounds than with respiratory infections (67 versus 17%, respectively) (P < 0.05, Z test) and P. multocida subsp. multocida more often associated with respiratory infections than with wounds (71 versus 14%, respectively) (P < 0.05, Z test). C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Vet Affairs Med Ctr, Pathol & Lab Med Serv, Houston, TX 77030 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98102 USA. OI Hulten, Kristina/0000-0001-7446-157X NR 12 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3438 EP 3441 DI 10.1128/JCM.40.9.3438-3441.2002 PG 4 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900051 PM 12202590 ER PT J AU Clarridge, JE Zhang, Q AF Clarridge, JE Zhang, Q TI Genotypic diversity of clinical Actinomyces species: Phenotype, source, and disease correlation among genospecies SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID DNA RESTRICTION ANALYSIS; RAPID ANA-II; SP-NOV; IDENTIFICATION; SPECIMENS; TURICENSIS; EUROPAEUS; RADINGAE; SYSTEMS AB We determined the frequency distribution of Actinomyces spp. recovered in a routine clinical laboratory and investigated the clinical significance of accurate identification to the species level. We identified 92 clinical strains of Actinomyces, including 13 strains in the related Arcanobacterium-Actinobaculum taxon, by 16S rRNA gene sequence analysis and recorded their biotypes, sources, and disease associations. The clinical isolates clustered into 21 genogroups. Twelve genogroups (74 strains) correlated with a known species, and nine genogroups (17 strains) did not. The individual species had source and disease correlates. Actinomyces turicensis was the most frequently isolated species and was associated with genitourinary tract specimens, often with other organisms and rarely with inflammatory cells. Actinomyces radingae was most often associated with serious, chronic soft tissue abscesses of the breast, chest, and back. Actinomyces curopaeus was associated with skin abscesses of the neck and genital areas. Actinomyces lingnae, Actinomyces gravenitzii, Actinomyces odontolyticus, and Actinomyces meyeri were isolated from respiratory specimens, while A. odontolyticus-like strains were isolated from diverse sources. Several of the species were commonly eoisolated with a particular bacterium:Actinomyces israelii was the only Actinomyces spp. coisolated with Actinobacillus (Haemophilus) actinomycetemcomitans; Actinomyces meyeri was coisolated with Peptostreptococcus micros and was the only species other than A. israelii associated with sulfur granules in histological specimens. Most genogroups had consistent biotypes (as determined with the RapID ANA II system); however, strains were misidentified, and many codes were not in the database. One biotype was common to several genogroups, with all of these isolates being identified as A. meyeri. Despite the recent description of new Actinomyces spp., 19% of the isolates recovered in our routine laboratory belonged to novel genospecies. One novel group with three strains, Actinomyces houstonensis sp. nov., was phenotypically similar to A. meyeri and A. turicensis but was genotypically closest to Actinomyces neuii. A. houstonensis sp. nov. was associated with abscesses. Our data documented consistent site and disease associations for 21 genogroups of Actinomyces spp. that provide greater insights into appropriate treatments. However, we also demonstrated a complexity within the Actinomyces genus that compromises the biochemical identification of Actinomyces that can be performed in most clinical laboratories. It is our hope that this large group of well-defined strains will be used to find a simple and accurate biochemical test for differentiation of the species in routine laboratories. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Vet Affairs Med Ctr, Pathol & Lab Med Serv, Houston, TX 77030 USA. RP Clarridge, JE (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA 98102 USA. NR 14 TC 50 Z9 51 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2002 VL 40 IS 9 BP 3442 EP 3448 DI 10.1128/JCM.40.9.3442-3448.2002 PG 7 WC Microbiology SC Microbiology GA 590NX UT WOS:000177829900052 PM 12202591 ER PT J AU Bunnell, CA Winer, EP AF Bunnell, CA Winer, EP TI Lumping versus splitting: The splitters take this round SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; THERAPY C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bunnell, CA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2002 VL 20 IS 17 BP 3576 EP 3577 DI 10.1200/JCO.2002.06.157 PG 2 WC Oncology SC Oncology GA 596RB UT WOS:000178178100006 PM 12202656 ER PT J AU He, YL Connors, PM Rosow, DE Rosow, CE AF He, YL Connors, PM Rosow, DE Rosow, CE TI Dose-dependent bioavailability of intranasal butorphanol in surgical patients. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 73 BP 1067 EP 1067 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000077 ER PT J AU Matzke, GR Palevsky, PM Frye, RF AF Matzke, GR Palevsky, PM Frye, RF TI In-vitro assessment of influence of molecular weight on drug clearance by conventional and synthetic dialyzers. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Pharm & Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2002 VL 42 IS 9 MA 85 BP 1070 EP 1070 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 586HR UT WOS:000177579000088 ER PT J AU Altshuler, LL Gitlin, MJ Mintz, J Leight, KL Frye, MA AF Altshuler, LL Gitlin, MJ Mintz, J Leight, KL Frye, MA TI Subsyndromal depression is associated with functional impairment in patients with bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; MAJOR DEPRESSION; MEDICAL OUTCOMES; MANIA; SYMPTOMS; ILLNESS; DISABILITY; VALIDITY; LITHIUM; SCALE AB Background: The purpose of this study was to assess whether a relationship exists between mild depressive symptoms and overall functioning in subjects with bipolar disorder. Method: Twenty-five male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined using, the Structured Clinical Interview for DSM-III-R, were evaluated for degree of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis V). Results: GAF scores were significantly negatively correlated with HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a HAM-D score high enough to be considered clinically depressed. Conclusion: The results of this study support a relationship between subsyndromal depressive symptoms and functional impairment in bipolar subjects, despite their not meeting threshold criteria for a major depressive episode. These findings raise the possibility that in some patients with bipolar disorder subsyndromal depressive symptoms might contribute to ongoing functional impairment. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Altshuler, LL (reprint author), Vet Adm Med Ctr, B116AA,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 137 Z9 139 U1 0 U2 3 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 SEP PY 2002 VL 63 IS 9 BP 807 EP 811 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 599PP UT WOS:000178344600010 PM 12363122 ER PT J AU Kalra, MK Maher, MM Sahani, DV Digmurthy, S Saini, S AF Kalra, MK Maher, MM Sahani, DV Digmurthy, S Saini, S TI Current status of imaging in pancreatic diseases SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE pancreatic diseases; imaging features; CT; MR ID PAPILLARY MUCINOUS TUMOR; PHASE HELICAL CT; MR CHOLANGIOPANCREATOGRAPHY; PATHOLOGICAL CORRELATION; AUTOIMMUNE PANCREATITIS; NEUROENDOCRINE TUMORS; GADOLINIUM CHELATE; SEROUS CYSTADENOMA; CYSTIC NEOPLASMS; MANGANESE-DPDP AB Recent technological developments in multidetector CT allow pancreatic imaging in a single breath-hold, which is especially valuable in obtaining isotropic three-dimensional reformations that improve our ability to provide accurate preoperative vascular mapping. Advanced MR technology allows faster imaging of pancreas, thus facilitating MR cholangiopancreatography. Use of tissue-specific MR contrast agents, endoscopic ultrasound, and positron emission tomography (PET) in pancreatic imaging has evolved considerably. This review article discusses the roles of CT, MR, endoscopic ultrasound, and PET imaging in the pancreas. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 64 TC 26 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2002 VL 26 IS 5 BP 661 EP 675 DI 10.1097/00004728-200209000-00001 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 619LV UT WOS:000179478200001 PM 12439296 ER PT J AU Prasad, SR Saini, S Stewart, S Hahn, PF Halpern, EF AF Prasad, SR Saini, S Stewart, S Hahn, PF Halpern, EF TI CT characterization of "indeterminate" renal masses: Targeted or comprehensive scanning? SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE kidney; computed tomography; ultrasound; indeterminate mass ID MANAGEMENT; LESIONS; CARE AB Purpose: A comprehensive renal mass evaluation CT protocol is usually performed for simultaneous characterization and staging of incidentally discovered renal masses considered indeterminate on ultrasound (US). The purpose of the study was to determine if a comprehensive examination is appropriate in these patients. Materials and Methods: The authors performed a retrospective review of 100 patients (mean age, 61 years) with 102 sonographically indeterminate renal masses and who were referred to undergo CT for lesion characterization. Lesions were classified according to surgical histology or imaging follow-up evaluation. Statistical analysis was performed. Results: Thirteen lesions (12.7%) in 11 (11%) patients (mean age, 59 years) were malignant. Eighty-seven lesions (85.3%) in 87 patients (87%; mean age, 62 years) were benign. Two lesions (1.96%) in two patients (2%) remained indeterminate. Conclusion: Although comprehensive renal mass evaluation protocol provides a more thorough patient evaluation, only a small fraction of indeterminate renal masses seen on US are malignant. The authors' results suggest a targeted renal CT imaging protocol for evaluation of indeterminate renal masses incidentally discovered on US. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ellison 234,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2002 VL 26 IS 5 BP 725 EP 727 DI 10.1097/00004728-200209000-00010 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 619LV UT WOS:000179478200010 PM 12439305 ER PT J AU Wicky, S Rosol, M Hamberg, LM Hoffmann, U Enzweiler, C Graziano, M Brady, T AF Wicky, S Rosol, M Hamberg, LM Hoffmann, U Enzweiler, C Graziano, M Brady, T TI Evaluation of retrospective multisector and half scan ECG-gated multidetector cardiac CT protocols with moving phantoms SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography (CT), technology; computed tomography, thin section; coronary vessels, CT; heart, CT ID CORONARY AB Purpose: We evaluated independently retrospective half scan and multisector mode manufacturer's protocols and compared them with modified acquisition protocols to determine optimal imaging parameters for cardiac scanning. Materials and Methods: Data were acquired using two fabricated gated moving phantoms. In half scan mode, the manufacturer's recommended pitch values were compared with adjacent values at different motion rates. In multisector mode, the manufacturer's protocols were compared with ones with different gantry speeds and pitch values at the same motion rates. Weighted CT dose indexes (CTDI) were obtained for all protocols. Gated and reformatted reconstructed images of the moving phantoms were evaluated. Results: In half scan mode, slightly better image quality was observed by lowering the pitch value, but with an increase of 6.3% of the weighted CTDI. Better results were obtained in multisector mode by lowering the pitch value, up to 0.2, but with an increase of 14.3% of the weighted CTDI. Optimal images were obtained with the lowest temporal resolution. Conclusions: Gated moving phantom studies offer the advantage of testing acquisition protocols of complex motions and of helping to establish appropriate protocols. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Wicky, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 3 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2002 VL 26 IS 5 BP 768 EP 776 DI 10.1097/00004728-200209000-00018 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 619LV UT WOS:000179478200018 PM 12439313 ER PT J AU Torriani, M Dertkigil, SS Etchebehere, M Amstalden, EMI AF Torriani, M Dertkigil, SS Etchebehere, M Amstalden, EMI TI Magnetic resonance imaging of tibial classic adamantinoma at 2 Tesla SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE adamantinoma; MR imaging; bone; neoplasms ID LONG BONES; OSTEOFIBROUS DYSPLASIA AB Adamantinoma is a rare malignant neoplasm arising most often in the tibia and is locally aggressive. Conservative surgical treatment frequently is followed by recurrence and magnetic resonance (MR) imaging plays an important role in preoperative planning. Magnetic resonance features of this tumor have not been described in detail. We report three cases of classic tibial adamantinoma examined at 2 Tesla. High-resolution images with findings that may influence management are discussed. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. UNICAMP, Dept Radiol, Campinas, Brazil. UNICAMP, Dept Orthoped, Campinas, Brazil. UNICAMP, Dept Pathol, Campinas, Brazil. UNICAMP, Fac Ciencias Med, Campinas, Brazil. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St, Boston, MA 02114 USA. RI San Juan Dertkigil, Sergio/F-6745-2013; Etchebehere, Mauricio/C-6785-2013 OI Etchebehere, Mauricio/0000-0002-5176-2369 NR 13 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2002 VL 26 IS 5 BP 855 EP 859 DI 10.1097/00004728-200209000-00033 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 619LV UT WOS:000179478200033 PM 12439328 ER PT J AU Datto, C Rai, AK Ilivicky, HJ Caroff, SN AF Datto, C Rai, AK Ilivicky, HJ Caroff, SN TI Augmentation of seizure induction in electroconvulsive therapy: A clinical reappraisal SO JOURNAL OF ECT LA English DT Review DE electroconvulsive therapy; proconvulsant agents; caffeine; theophylline; etomidate; ketamine; hyperventilation; seizures ID ELECTRICALLY INDUCED SEIZURES; ECT-SEIZURE; STIMULUS-INTENSITY; CAFFEINE AUGMENTATION; INTRAVENOUS CAFFEINE; COMBINED CLOZAPINE; STATUS EPILEPTICUS; PROLONGED SEIZURE; ANESTHETIC AGENTS; DURATION AB Objective: Missed or abortive seizures during electroconvulsive therapy (ECT) may preclude completion of an effective course of treatment in some cases. Seizure augmentation, using proconvulsant agents, has been used to overcome resistance to the induction and continuation of seizure activity. In this review, we analyze published clinical data on the effects and safety of seizure augmentation techniques. Method: Clinical studies and case reports were obtained through a MEDLINE literature search from 1966 to 2001, cross-referencing ECT and proconvulsant agents. Article references were also scanned for relevant studies. Results and Conclusions: Data from clinical trials indicate that augmentation facilitates seizure induction when maximal electrical stimuli fail. Anesthetic modifications, including hyperventilation and substitution with etomidate, ketamine, or other agents, often are successful in overcoming seizure resistance and compare favorably with the use of caffeine. In a few studies, augmentation enabled the use of lower stimulus intensities and fewer treatments without loss of efficacy, even in patients not resistant to seizure induction. However, effects of proconvulsants must be reconciled with increasing evidence of the importance of stimulus dosing relative to seizure threshold and other parameters, now considered key to the efficacy of ECT. Further investigations of pharmacologic augmentation could facilitate the administration of ECT and could provide further insights concerning parameters of seizure efficacy and the mechanism of action underlying convulsive therapies. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. New Hope Penn Inc, Wyoming, PA USA. St Charles Psychiat Associates, St Charles, MO USA. RP Caroff, SN (reprint author), Dept Vet Affairs Med Ctr, 116A,Univ Ave, Philadelphia, PA 19104 USA. NR 105 TC 30 Z9 30 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD SEP PY 2002 VL 18 IS 3 BP 118 EP 125 DI 10.1097/00124509-200209000-00002 PG 8 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 605KX UT WOS:000178678000002 PM 12394529 ER PT J AU Yeo, CJ Adsay, NV del-Castillo, CF Traverso, LW AF Yeo, CJ Adsay, NV del-Castillo, CF Traverso, LW TI "How I do it" session: Intraductal papillary mucinous neoplasms of the pancreas - The year 2002 SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Harper Univ Hosp, Detroit, MI 48201 USA. Karmanos Canc Ctr, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. RP Yeo, CJ (reprint author), Harper Univ Hosp, Detroit, MI 48201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 2002 VL 6 IS 5 BP 655 EP 655 AR PII S1091-255X(02)00056-2 PG 1 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627ER UT WOS:000179920700001 ER PT J AU Fernandez-del Castillo, C AF Fernandez-del Castillo, C TI Surgical treatment of intraductal papillary mucinous neoplasms of the pancreas: The conservative approach SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material ID TUMORS; FEATURES C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 2002 VL 6 IS 5 BP 660 EP 661 AR PII S1091-255X(02)00058-6 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627ER UT WOS:000179920700003 PM 12399052 ER PT J AU Holmes, WC Pace, JL AF Holmes, WC Pace, JL TI HIV-seropositive individuals' optimistic beliefs about prognosis and relation to medication and safe sex adherence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV; AIDS; prognosis; patient compliance; sex behavior ID TRIPLE-DRUG THERAPY; ANTIRETROVIRAL THERAPY; UNITED-STATES; INFECTION; DISEASE; CARE; AIDS; ZIDOVUDINE; ADULTS; MEN AB OBJECTIVE: The study objective was to characterize respondents' prognostic perceptions of HIV infection and to explore how perceptions might affect medication and safe sex nonadherence. METHODS: Surveys were mailed to 295 clients of an HIV-specific case management organization. Participants were asked to describe experience with HIV/AIDS right after serostatus knowledge and currently, using provided word lists, after which they were asked to assess current life expectancy. Self-reported information on antiretroviral medication and safe sex nonadherence was obtained. RESULTS: A total of 220 (75%) clients (66% nonwhite, 73% male, 63% gay/bisexual, 50% educated >12 years, and 53% with incomes <$10,000/year) returned surveys. Negative descriptors from word lists were significantly less common and positive descriptors significantly more common now compared to right after serostatus knowledge. Current perceptions about life expectancy indicated that most respondents thought they would live many years, many believing they would live well into old age. Whites (odds ratio [OR], 0.34; P = .01) were less likely and those with >12 years education (OR, 2.76; P = .02) and with CD4 cell counts >200 (OR, 2.70; P = .01) were more likely to have optimistic prognostic beliefs. The optimistic subgroup, when compared with the pessimistic subgroup, was more likely to report medication (26% vs 13%, P = .04) and safe sex (57% vs 29%, P = .004) nonadherence. CONCLUSIONS: Seropositive individuals, including persons of color (adjusted) as well as women and drug users (unadjusted), self-reported optimistic beliefs about their prognosis. Those with more optimism about their prognosis were significantly more likely to report medication and safe sex nonadherence. A better understanding of seropositive patients' prognostic beliefs and the factors determining them is warranted. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [AI01482] NR 29 TC 21 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2002 VL 17 IS 9 BP 677 EP 683 DI 10.1046/j.1525-1497.2002.00746.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 594AF UT WOS:000178026100003 PM 12220363 ER PT J AU Halpern, SD Ubel, PA Berlin, JA Townsend, RR Asch, DA AF Halpern, SD Ubel, PA Berlin, JA Townsend, RR Asch, DA TI Physicians' preferences for active-controlled versus placebo-controlled trials of new anti hypertensive drugs SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE clinical trials; placebo-controlled trials; antihypertensive drugs; physicians' preferences; ethics ID RANDOMIZED CLINICAL-TRIALS; BLOOD-PRESSURE; BREAST-CANCER; PARTICIPATION; ISSUES; MORBIDITY; MORTALITY AB OBJECTIVE: To evaluate physicians' preferences for referring patients to, and using information from, active-controlled trials (ACTs) versus placebo-controlled trials (PCTs) of new antihypertensive drugs. DESIGN AND SETTING: Nationwide mailed survey, with telephone contact of nonresponders to assess nonresponse bias. PARTICIPANTS: One thousand two hundred primary care physicians randomly selected from the American Medical Association's Master File. Of 1, 154 physicians eligible to respond, 651 (56.4%) returned completed questionnaires. MEASUREMENTS AND MAIN RESULTS: We measured physicians' stated willingness to encourage hypertensive patients to enroll in ACTs and PCTs of new antihypertensive drugs, their views of the relative merits of ACTs versus PCTs, their stated willingness to prescribe new drugs tested in ACTs or PCTs, and their views regarding the overall justifiability of the 2 designs. Physicians were significantly more likely to indicate they would encourage their patients to enroll in ACTs than in PCTs (P < .0001). Physicians thought ACTs provided more valuable information for their practices, were more likely to lead to a public health benefit, offered enrolled patients greater opportunity for personal benefit, and were less likely to expose enrolled patients to unnecessary risks (all P < .0001). Physicians were more likely to prescribe new drugs that had been compared in ACTs (P < .0001). and viewed ACTs as a more justifiable method for testing new antihypertensive drugs (P < .0001). There was no evidence of nonresponse bias for these main results. CONCLUSIONS: Although PCTs remain the standard method for testing new antihypertensive drugs, physicians strongly prefer ACTs. Using ACTs to test new antihypertensive drugs may enhance the efficiency of patient recruitment and more strongly influence physicians' prescribing practices. C1 Univ Penn, Leonard Davis Inst Hlth Econ, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. Univ Michigan, Sch Med, Div Gen Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Med, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. RP Halpern, SD (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, Sch Med, 3641 Locust Walk, Philadelphia, PA 19104 USA. NR 38 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2002 VL 17 IS 9 BP 689 EP 695 DI 10.1046/j.1525-1497.2002.11024.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 594AF UT WOS:000178026100005 PM 12220365 ER PT J AU Nelson, K Geiger, AM Mangione, CM AF Nelson, K Geiger, AM Mangione, CM TI Effect of health beliefs on delays in care for abnormal cervical cytology in a multiethnic population SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Gen Internal Med DE Papanicolaou smear; health beliefs; patient adherence ID FOLLOW-UP RECOMMENDATIONS; INCOME MINORITY WOMEN; PAPANICOLAOU SMEARS; PAP SMEARS; RACIAL-DIFFERENCES; AMERICAN WOMEN; ANGLO WOMEN; CANCER; BREAST; KNOWLEDGE AB CONTEXT. Women from racial and ethnic minorities in the United States have higher rates of cervical cancer and present with later stage disease compared to whites. Delays in care for abnormal Papanicolaou (Pap) smears can lead to missed cases of cervical cancer or late-stage presentation and may be one explanation for these differences. about cancer, but not race and ethnicity, were independently associated with delays in care. OBJECTIVE: To determine if race and ethnicity, health beliefs, and cancer knowledge are associated with delays in care for abnormal Pap smears. DESIGN, PARTICIPANTS, AND SETTING: We conducted a mailed survey with telephone follow-up of all women with an abnormal Pap smear who received care at Kaiser Permanente Los Angeles Medical Center between October 1998 and October 1999 (n = 1,049). MEASUREMENTS AND MAIN RESULTS: A delay in care was defined as not attending the first scheduled clinic visit to follow up on an abnormal Pap smear, or requiring multiple contact attempts, including a certified letter, to schedule a follow-up visit. Our response rate was 70% (n = 733) and the sample was 51% Latina. Spanish-speaking Latinas and women of Asian descent were more likely to endorse fatalistic beliefs and misconceptions about cancer. Thirteen percent of the sample delayed follow-up on their abnormal Pap smear. Women who delayed care were more fatalistic and endorsed more misconceptions about cervical cancer. Delays in care were not independently associated with race and ethnicity. CONCLUSIONS: Health beliefs and cancer knowledge differed by race and ethnicity among women in a large managed care organization. Fatalistic health beliefs and misconceptions about cancer, but not race and ethnicity, were independently associated with delays in care. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. So Calif Permanente Med Grp, Dept Res & Evaluat, Pasadena, CA USA. Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA USA. RP Nelson, K (reprint author), VA Puget Sound Med Ctr, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NCI NIH HHS [F32 CA088495, 1F32 CA 88495-01] NR 54 TC 43 Z9 43 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2002 VL 17 IS 9 BP 709 EP 716 DI 10.1046/j.1525-1497.2002.11231.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 594AF UT WOS:000178026100008 PM 12220368 ER PT J AU Datto, CJ Oslin, DW Streim, JE Scheinthal, SM DiFilippo, S Katz, IR AF Datto, CJ Oslin, DW Streim, JE Scheinthal, SM DiFilippo, S Katz, IR TI Pharmacologic treatment of depression in nursing home residents: A mental health services perspective SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID LATE-LIFE DEPRESSION; CLINICAL-TRIAL; SERTRALINE; CARE AB Over the past 10 to 15 years, there has been marked progress in clinical research on depression in nursing home residents. There have also been significant changes in federal regulations designed to improve the quality of care. In 1987, only 10% of nursing home residents diagnosed with depression were receiving treatment, but by 1999, 25% of all residents were receiving antidepressants. We report on two studies: one demonstrating that treatment for depression has a substantial, ecologically relevant impact in the nursing home and another demonstrating that profound changes have occurred in the clinical epidemiology of depression and its treatment in the nursing home. Although the numbers of nursing home residents receiving antidepressants have increased dramatically, there are now second-generation problems that must be addressed to ensure the delivery of effective treatment. Developing models to ensure quality of care will require focused mental health services research. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Med & Dent New Jersey, Sch Osteopath Med, Stratford, NJ 08084 USA. RP Oslin, DW (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Rm 3055, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [P30-MH52129, R37-MH51247] NR 25 TC 27 Z9 27 U1 0 U2 2 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 2002 VL 15 IS 3 BP 141 EP 146 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 592XA UT WOS:000177961100005 PM 12230084 ER PT J AU Re, FB Belyanskaya, SL Riese, RJ Cipriani, B Fischer, FR Granucci, F Ricciardi-Castagnoli, P Brosman, C Stern, LJ Strominger, JL Santambrogio, L AF Re, FB Belyanskaya, SL Riese, RJ Cipriani, B Fischer, FR Granucci, F Ricciardi-Castagnoli, P Brosman, C Stern, LJ Strominger, JL Santambrogio, L TI Granulocyte-macrophage colony-stimulating factor induces an expression program in neonatal microglia that primes them for antigen presentation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAT-STABLE ANTIGEN; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CLASS-II INDUCIBILITY; MYELIN BASIC-PROTEIN; GM-CSF RECEPTOR; NERVOUS-SYSTEM; DENDRITIC CELLS; CULTURED ASTROCYTES; NITRIC-OXIDE; CATHEPSIN-S AB Neonatal microglial cells respond to GM-CSF and M-CSF by acquiring different morphologies and phenotypes. To investigate the extent and consequences of this process, a global gene expression analysis was performed, with significant changes in transcript levels confirmed by biochemical analyses. Primary murine microglial cells underwent substantial expression reprogramming after treatment with GM-CSF or M-CSF with many differentially expressed transcripts important in innate and adaptive immunity. In particular, many gene products involved in Ag presentation were induced by GM-CSF, but not M-CSF, thus potentially priming relatively quiescent microglia cells for Ag presentation. This function of GM-CSF is distinct from its primary function in cell proliferation and survival. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Univ Milano Bicocca, Dept Biosci & Biotechnol, I-20126 Milan, Italy. Univ Giessen, Dept Neurol, Giessen, Germany. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Santambrogio, L (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Laura_Santambrogio@dfci.harvard.edu RI Castagnoli, Paola/E-8288-2010 FU NCI NIH HHS [R35-CA47554]; NIAID NIH HHS [R01-AI-48832, R01-AI48833] NR 56 TC 67 Z9 70 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2002 VL 169 IS 5 BP 2264 EP 2273 PG 10 WC Immunology SC Immunology GA 586PV UT WOS:000177594100006 PM 12193691 ER PT J AU Werth, VP Callen, JP Ang, G Sullivan, KE AF Werth, VP Callen, JP Ang, G Sullivan, KE TI Associations of tumor necrosis factor alpha and HLA polymorphisms with adult dermatomyositis: Implications for a unique pathogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ultraviolet light ID CUTANEOUS LUPUS-ERYTHEMATOSUS; TNF-ALPHA; PROMOTER POLYMORPHISM; JUVENILE DERMATOMYOSITIS; KERATINOCYTE APOPTOSIS; TNF-ALPHA-308A ALLELE; GENE POLYMORPHISM; SUSCEPTIBILITY; CELLS; TRANSCRIPTION AB We recently reported that the -308A tumor necrosis factor alpha promoter polymorphism is associated with the photosensitive disorder subacute cutaneous lupus erythematosus and mediates an exaggerated tumor necrosis factor alpha response to ultraviolet B. We now sought to examine the association of this polymorphism with adult dermatomyositis, a photosensitive disease that exhibits some features in common with subacute cutaneous lupus erythematosus. Fifty adult patients with dermatomyositis and 239 healthy, race-matched controls were examined for the -308A tumor necrosis factor alpha polymorphism and the more common -308G allele. The frequency of the -308A allele was 0.27 in the entire dermatomyositis group, versus 0.14 in the controls (p = 0.003, chi(2) 2 x 2 table). Caucasians were the only racial/ethnic group in our study large enough to allow separate statistical analysis (47 dermatomyositis, 223 controls). The frequency of the -308A allele was 0.26 for dermatomyositis and 0.14 for controls (p = 0.014). Caucasians are known to exhibit a linkage disequilibrium between -308A and HLA-DR3, which we previously found to be significantly enhanced in subacute cutaneous lupus erythematosus patients. In contrast, we now found no increase in the association of -308A and HLA-DR3 in Caucasians with dermatomyositis compared to controls. Consistent with this observation, the association of these two genes in dermatomyositis was significantly less than we previously reported in Caucasians with subacute cutaneous lupus erythematosus (p = 0.016). We conclude that the tumor necrosis factor -308A polymorphism is associated with dermatomyositis, which suggests a pathophysiologic contribution from ultraviolet-induced production of tumor necrosis factor alpha, similar to subacute cutaneous lupus erythematosus. The differences in linkage with HLA-DR3, as well as several divergent clinical features, indicate that there are also fundamental mechanistic differences between dermatomyositis and subacute cutaneous lupus erythematosus. C1 Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Louisville, Dept Dermatol, Louisville, KY 40292 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Dept Dermatol, 2 Rhoads Pavil,36th & Spruce St, Philadelphia, PA 19104 USA. FU NIAMS NIH HHS [1K24AR002207-01] NR 37 TC 52 Z9 57 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2002 VL 119 IS 3 BP 617 EP 620 DI 10.1046/j.1523-1747.2002.01869.x PG 4 WC Dermatology SC Dermatology GA 592RV UT WOS:000177951400011 PM 12230503 ER PT J AU Stokvis, E Rosing, H Lopez-Lazaro, L Rodriguez, I Jimeno, JM Supko, JG Schellens, JHM Beijnen, JH AF Stokvis, E Rosing, H Lopez-Lazaro, L Rodriguez, I Jimeno, JM Supko, JG Schellens, JHM Beijnen, JH TI Quantitative analysis of the novel depsipeptide anticancer drug Kahalalide F in human plasma by high-performance liquid chromatography under basic conditions coupled to electrospray ionization tandem mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE Kahalalide F; bioanalysis; liquid chromatography mass spectrometry; peptide; trifluoroacetic acid ID SOLID-PHASE EXTRACTION; ECTEINASCIDIN-743; SAMPLES; AGENT; ACID; ION AB Kahalalide F (KF) is a novel cyclic depsipeptide anticancer drug, which has shown anticancer activity both in vitro and in vivo especially against human prostate cancer cell lines. To characterize the pharmacokinetics of KF during a phase I clinical trial in patients with androgen refractory prostate cancer, a method was developed and validated for the quantitative analysis of KF in human plasma using high-performance liquid chromatography (HPLC) coupled to positive electrospray ionization tandem mass spectrometry (ESI-MS/MS). Microbore reversed-phase liquid chromatography (LC) performed with mobile phases containing trifluoroacetic acid, an additive commonly used for separating peptides, resulted in substantial suppression of the signal for KF on ESI-MS/MS. An alternative approach employing a basic mobile phase provided an excellent response for KF when detected in the positive ion mode. Plasma samples were prepared for LC MS/MS by solid-phase extraction on C-18 cartridges. The LC separation was performed on a Zorbax Extend C-18 column (150 x 2.1 mm i.d., particle size 5 mum) with acetonitrile -10 mm aqueous ammonia (85:15, v/v) as the mobile phase, at a flow-rate of 0.20 ml min(-1). A butyric acid analogue of KF was used as the internal standard. The lower limit of quantitation (LLQ) using a 500 mul sample volume was 1 ng ml(-1) and the linear dynamic range extended to 1000 ng ml(-1). The inter-assay accuracy of the assay was -15.1% at the LLQ and between -2.68 and -9.05% for quality control solutions ranging in concentration from 2.24 to 715 ng ml(-1). The inter-assay precision was 9.91% or better at these concentrations. The analyte was stable in plasma under all relevant conditions evaluated and for a period of 16 h after reconstituting plasma extracts for LC analysis at ambient temperature. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Slotervaart Hosp, Dept Pharm & Pharmacol, Netherlands Canc Inst, NL-1066 EC Amsterdam, Netherlands. Pharma Mar SA, Res & Dev, Madrid 28760, Spain. Massachusetts Gen Hosp, Div Hematol & Oncol, Clin Pharmacol Lab, Boston, MA 02114 USA. Netherlands Canc Inst, Antoni van Leeuwenhoek Hosp, NL-1066 CX Amsterdam, Netherlands. Univ Utrecht, Fac Pharm, Dept Biomed Anal, Div Drug Toxicol, NL-3508 TB Utrecht, Netherlands. RP Stokvis, E (reprint author), Slotervaart Hosp, Dept Pharm & Pharmacol, Netherlands Canc Inst, Louwesweg 6, NL-1066 EC Amsterdam, Netherlands. NR 28 TC 36 Z9 39 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD SEP PY 2002 VL 37 IS 9 BP 992 EP 1000 DI 10.1002/jms.362 PG 9 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 601CB UT WOS:000178427600012 PM 12271442 ER PT J AU Mann, DL AF Mann, DL TI Endothelin antagonism and the failing heart: An unfilled promise, an unmet need, or an unanswered question? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Editorial Material ID MYOCARDIAL ENDOTHELIN; RECEPTORS; FAILURE; EXPRESSION; SYSTEM C1 Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Med Serv Care Line, Houston, TX 77030 USA. RP Mann, DL (reprint author), Baylor Coll Med, Winters Ctr Heart Failure Res, Dept Med, MS 524,6565 Fannin, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 NR 13 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 2002 VL 34 IS 9 BP 1131 EP 1133 DI 10.1006/jmcc.2002.2054 PG 3 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 604LL UT WOS:000178622500008 PM 12392886 ER PT J AU Ge, YL Wang, XY Chen, ZH Landman, N Lo, EH Kang, JX AF Ge, YL Wang, XY Chen, ZH Landman, N Lo, EH Kang, JX TI Gene transfer of the Caenorhabditis elegans n-3 fatty acid desaturase inhibits neuronal apoptosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE apoptosis; fat-1; n-3 fatty acids; n-6 fatty acids; neurons; polyunsaturated fatty acids ID CYTOSOLIC PHOSPHOLIPASE A(2); TUMOR-NECROSIS-FACTOR; DOCOSAHEXAENOIC ACID; RETINAL PHOTORECEPTORS; IN-VITRO; BRAIN; RAT; PROSTAGLANDIN; MICE; DEFICIENCY AB Previous studies have shown that n-3 polyunsaturated fatty acids (PUFAs) can exert an antiapoptotic effect on neurons. The present study was designed to investigate whether the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase (an enzyme that converts n-6 PUFAs to corresponding n-3 PUFAs) can be expressed functionally in rat cortical neurons and whether its expression can change the ratio of n-6 : n-3 fatty acids in the cell membrane and exert an effect on neuronal apoptosis. Infection of primary rat cortical cultures with Ad-fat-1 resulted in high expression of the fat-1 gene. Lipid analysis indicated a decrease in the ratio of n-6 : n-3 PUFAs from 5.9 : 1 in control cells, to 1.45 : 1 in cells expressing the n-3 fatty acid desaturase. Accordingly, the levels of prostaglandin E-2, an eicosanoid derived from n-6 PUFA, were significantly lower in cells infected with Ad-fat-1 when compared with control cells. Finally, there was a significant inhibition of growth factor withdrawal-induced apoptotic cell death in neurons expressing the fat-1 gene. These results demonstrate that expression of the fat-1 gene can inhibit apoptotic cell death in neurons and suggest that the change in the n-6 : n-3 fatty acid ratio may play a key role in this protective effect. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-79553]; NIDDK NIH HHS [P30 DK40561] NR 40 TC 21 Z9 28 U1 1 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2002 VL 82 IS 6 BP 1360 EP 1366 DI 10.1046/j.1471-4159.2002.01077.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 589YW UT WOS:000177790000005 PM 12354283 ER PT J AU Yohrling, GJ Jiang, GCT DeJohn, MM Robertson, DJ Vrana, KE Cha, JHJ AF Yohrling, GJ Jiang, GCT DeJohn, MM Robertson, DJ Vrana, KE Cha, JHJ TI Inhibition of tryptophan hydroxylase activity and decreased 5-HT1A receptor binding in a mouse model of Huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brainstem; GST pull-down; Huntington's disease; receptor binding; serotonin; tryptophan hydroxylase ID TRANSGENIC MOUSE; 5-HYDROXYINDOLEACETIC ACID; TYROSINE-HYDROXYLASE; MOVEMENT-DISORDERS; MICE; SEROTONIN; BRAIN; EXPRESSION; GENE; PROTEIN AB The pathogenic mechanisms of the mutant huntingtin protein that cause Huntington's disease (HD) are unknown. Previous studies have reported significant decreases in the levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brains of the R6/2 transgenic mouse model of HD. In an attempt to elucidate the cause of these neurochemical perturbations in HD, the protein levels and enzymatic activity of tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, were determined. Enzyme activity was measured in brainstem homogenates from 4-, 8-, and 12-week-old R6/2 mice and compared with aged-matched wild-type control mice. We observed a 62% decrease in brainstem TPH activity (p = 0.009) in 4-week-old R6/2 mice, well before the onset of behavioral symptoms. In addition, significant decreases in TPH activity were also observed at 8 and 12 weeks of age (61%, p = 0.02 and 86%, p = 0.005, respectively). In the 12-week-old-mice, no change in immunoreactive TPH was observed. In vitro binding showed that TPH does not bind to exon 1 of huntingtin in a polyglutamine-dependent manner. Specifically, glutathione-S -transferase huntingtin exon 1 proteins with 20, 32 or 53 polyglutamines did not interact with radiolabeled tryptophan hydroxylase. Therefore, the inhibition of TPH activity does not appear to result from a direct huntingtin/TPH interaction. Receptor binding analyses for the 5-HT1A receptor in 12-week-old R6/2 mice revealed significant reductions in 8-OH-[H-3]DPAT binding in several hippocampal and cortical regions. These results demonstrate that the serotonergic system in the R6/2 mice is severely disrupted in both presymptomatic and symptomatic mice. The presymptomatic inhibition of TPH activity in the R6/2 mice may help explain the functional consequences of HD and provide insights into new targets for pharmacotherapy. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27103 USA. Wake Forest Univ, Bowman Gray Sch Med, Mol Genet Program, Winston Salem, NC 27103 USA. RP Yohrling, GJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St,B114-2250, Charlestown, MA 02129 USA. OI Vrana, Kent/0000-0003-4902-7733 FU NIGMS NIH HHS [R01 GM-38931]; NINDS NIH HHS [R01 NS-38106] NR 54 TC 20 Z9 20 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2002 VL 82 IS 6 BP 1416 EP 1423 DI 10.1046/j.1471-4159.2002.01084.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 589YW UT WOS:000177790000011 PM 12354289 ER PT J AU Offner, H Zamora, A Drought, H Matejuk, A Auci, DL Morgan, EE Vandenbark, AA Reading, CL AF Offner, H Zamora, A Drought, H Matejuk, A Auci, DL Morgan, EE Vandenbark, AA Reading, CL TI A synthetic androstene derivative and a natural androstene metabolite inhibit relapsing-remitting EAE SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE EAE; MS; androstene; DHEA; cytokines ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; NECROSIS-FACTOR-ALPHA; MULTIPLE-SCLEROSIS; IN-VITRO; CYTOKINE PRODUCTION; TNF-ALPHA; IMMUNE-RESPONSE; T-LYMPHOCYTES; DEHYDROEPIANDROSTERONE AB Experimental allergic encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system (CNS), shares many pathological and clinical similarities with multiple sclerosis (MS), and thus represents an attractive animal model for this disease. The goal of this study was to evaluate the suppressive effects of fluasterone (HE2500), a synthetic androstene derivative, and androstenetriol (HE2200), a natural androstene hormone on EAE. SJL mice were immunized with proteolipid protein (PLP) 139-151 peptide/CFA to induce EAE. Starting on day -7, animals were given daily injections (s.c.) of derivatives (3.0 mg) in vehicle, or vehicle alone for 33 days. Both HE2500 and HE2200 significantly delayed the onset, reduced the peak clinical score and cumulative disease index of EAE, and prevented or significantly attenuated relapses. Lower doses or other routes of administration were less effective. Moreover, T cells from treated mice had significantly reduced PLP 139-151-specific T cell proliferation responses and reduced numbers of TNF-alpha- and IFN-gamma-producing cells in the CNS. Daily treatment of B10.PL mice with HE2500, starting on day 0, completely prevented the development of disease in these animals. Finally, SJL mice treated with HE2500 at EAE onset showed significantly reduced mean clinical scores. Thus, these compounds, which have been reported to have a few androgenic or estrogenic side effects, appear to have a potent inhibitory activity in EAE. These observations suggest that HE2500, and/or HE2200 limit the production of autoimmune Th1 associated cytokines, and ultimately may be beneficial for patients with MS or other autoimmune diseases. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Vet Affairs Med Ctr, Portland, OR 97201 USA. Hollis Eden Pharmaceut Inc, San Diego, CA 92121 USA. Polish Acad Sci, L Hirszfeld lnst Immunol & Expt Therapy, Wroclaw, Poland. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23444] NR 51 TC 35 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 2002 VL 130 IS 1-2 BP 128 EP 139 AR PII S0165-5728(02)00214-X DI 10.1016/S0165-5728(02)00214-X PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 599HX UT WOS:000178329200013 PM 12225895 ER PT J AU Tang, W Duke-Cohan, JS AF Tang, W Duke-Cohan, JS TI Human secreted attractin disrupts neurite formation in differentiating cortical neural cells in vitro SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE attractin; cerebrospinal fluid; neurite; neurodegeneration ID CENTRAL-NERVOUS-SYSTEM; IMMUNE-SYSTEM; CUB-FAMILY; IV CD26; DPPT-L; MAHOGANY; PROTEINS; MUTATIONS; OBESITY; SERUM AB Mutations at the Atrn locus that encodes a transmembrane protein with a large ectodomain are responsible for a juvenile-onset neurodegeneration manifest as hypomyelination and cerebral vacuole development in several rodent species. In addition to a membrane isoform, the human Atrn locus generates by alternative splicing a secreted form corresponding to the entire ectodomain that then circulates at high concentration in the periphery, released in part by activated T lymphocytes. We report here that the secreted form mRNA is downregulated throughout representative discrete regions of the human brain while membrane attractin mRNA is well represented, resulting in the apparent absence of secreted attractin protein in cerebrospinal fluid (CSF). Transcription of attractin secreted form mRNA is strongly downregulated upon differentiation of a human cortical neuron-derived cell line (HCN-1A) to a mature neuron phenotype in response to nerve growth factor. Recombinant secreted attractin disrupts neurite formation by differentiated HCN-1A cells, resulting in higher levels of branching with shorter processes. This effect is duplicated by anti-attractin and by human serum but not by human serum depleted of attractin or by CSF We propose that inappropriate expression of secreted attractin in the CNS blocks membrane attractin function and that its presence, either by leakage from the periphery, aberrant transcription, or release from inflammatory foci may affect neuron extracellular interactions leading to neurodegeneration in the human. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Duke-Cohan, JS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, D1526,44 Binney St, Boston, MA 02115 USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIAID NIH HHS [AI012069] NR 42 TC 9 Z9 10 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2002 VL 61 IS 9 BP 767 EP 777 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 592VA UT WOS:000177956500003 PM 12230323 ER PT J AU Klunk, WE Bacskai, BJ Mathis, CA Kajdasz, ST McLellan, ME Frosch, MP Debnath, ML Holt, DP Wang, YM Hyman, BT AF Klunk, WE Bacskai, BJ Mathis, CA Kajdasz, ST McLellan, ME Frosch, MP Debnath, ML Holt, DP Wang, YM Hyman, BT TI Imaging A beta plaques in living transgenic mice with multiphoton microscopy and methoxy-X04, a systemically administered Congo red derivative SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; amyloid; chrysamine-G; imaging; multiphoton microscopy; positron emission tomography; transgenic mice ID POSITRON-EMISSION-TOMOGRAPHY; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; MOUSE MODEL; PRESENILIN-1 TRANSGENES; MUTANT PRESENILIN-1; GAMMA-SECRETASE; BRAIN; PEPTIDE; BINDING AB The identification of amyloid deposits in living Alzheimer disease (AD) patients is important for both early. diagnosis and for monitoring the efficacy of newly developed anti-amyloid therapies. Methoxy-X04 is a derivative of Congo red and Chrysamine-G that contains no acid groups and is therefore smaller and much more lipophilic than Congo red or Chrysamine-G. Methoxy-X04 retains in vitro binding affinity for amyloid beta (Abeta) fibrils (K-i = 26.8 nM) very similar to that of Chrysamine-G (K-i = 25.3 nM). Methoxy-X04 is fluorescent and stains plaques, tangles, and cerebrovascular amyloid in postmortem sections of AD brain with good specificity. Using multiphoton microscopy to obtain high-resolution (1 mum) fluorescent images from the brains of living PS1/APP mice, individual plaques could be distinguished within 30 to 60 min after a single i.v. injection of 5 to 10 mg/kg methoxy-X04. A single i.p. injection of 10 mg/kg methoxy-X04 also produced high contrast images of plaques and cerebrovascular amyloid in PS1/APP mouse brain. Complementary quantitative studies using tracer doses of carbon-11-labeled methoxy-X04 show that it enters rat brain in amounts that suggest it is a viable candidate as a positron emission tomography (PET) amyloid-imaging agent for in vivo human studies. C1 Univ Pittsburgh, Sch Med, Lab Mol Neuropharmacol, Dept Psychiat, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA USA. Univ Pittsburgh, Sch Med, Dept Radiol, PET Facil, Pittsburgh, PA USA. Brigham & Womens Hosp, Dept Pathol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klunk, WE (reprint author), Univ Pittsburgh, Sch Med, Lab Mol Neuropharmacol, Dept Psychiat, 705 Parran Hall GSPH,130 DeSoto St, Pittsburgh, PA 15213 USA. RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [5P01 AG15379, AG20226, NIH-AG01039, NIH-AG08487] NR 52 TC 195 Z9 204 U1 3 U2 14 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 SEP PY 2002 VL 61 IS 9 BP 797 EP 805 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 592VA UT WOS:000177956500006 PM 12230326 ER PT J AU Harms, MP Melcher, JR AF Harms, MP Melcher, JR TI Sound repetition rate in the human auditory pathway: Representations in the waveshape and amplitude of fMRI activation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID CEREBRAL BLOOD-FLOW; PRIMARY VISUAL-CORTEX; STIMULUS-PRESENTATION RATE; MEDIAN NERVE-STIMULATION; SINGLE-UNIT ACTIVITY; HUMAN BRAIN-STEM; FUNCTIONAL MRI; INFERIOR COLLICULUS; SYNAPTIC ACTIVITY; BOLD RESPONSE AB Sound repetition rate plays an important role in stream segregation, temporal pattern recognition, and the perception of successive sounds as either distinct or fused. This study was aimed at elucidating the neural coding of repetition rate and its perceptual correlates. We investigated the representations of rate in the auditory pathway of human listeners using functional magnetic resonance imaging (fMRI), an indicator of population neural activity. Stimuli were trains of noise bursts presented at rates ranging from low (1-2/s; each burst is perceptually distinct) to high (35/s; individual bursts are not distinguishable). There was a systematic change in the form of fMRI response rate-dependencies from midbrain to thalamus to cortex. In the inferior colliculus, response amplitude increased with increasing rate while response waveshape remained unchanged and sustained. In the medial geniculate body, increasing rate produced an increase in amplitude and a moderate change in waveshape at higher rates (from sustained to one showing a moderate peak just after train onset). In auditory cortex (Heschl's gyrus and the superior temporal gyrus), amplitude changed somewhat with rate, but a far more striking change occurred in response waveshape-low rates elicited a sustained response, whereas high rates elicited an unusual phasic response that included prominent peaks just after train onset and offset. The shift in cortical response waveshape from sustained to phasic with increasing rate corresponds to a perceptual shift from individually resolved bursts to fused bursts forming a continuous (but modulated) percept. Thus at high rates, a train forms a single perceptual "event," the onset and offset of which are delimited by the on and off peaks of phasic cortical responses. While auditory cortex showed a clear, qualitative correlation between perception and response waveshape, the medial geniculate body showed less correlation (since there was less change in waveshape with rate), and the inferior colliculus showed no correlation at all. Overall, our results suggest a population neural representation of the beginning and the end of distinct perceptual events that is weak or absent in the inferior colliculus, begins to emerge in the medial geniculate body, and is robust in auditory cortex. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Harms, MP (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. OI Harms, Michael/0000-0001-7945-036X FU NIDCD NIH HHS [P01 DC000119-24, P01DC-00119, R03DC-03122, T32 DC000038-12, T32DC-00038] NR 139 TC 113 Z9 114 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2002 VL 88 IS 3 BP 1433 EP 1450 DI 10.1152/jn.00156.2002 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 589MX UT WOS:000177764100035 PM 12205164 ER PT J AU Mendez, MF Perryman, KM AF Mendez, MF Perryman, KM TI Neuropsychiatric features of frontotemporal dementia: Evaluation of consensus criteria and review SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID CLINICAL DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; PICKS-DISEASE; LOBAR DEGENERATION; BEHAVIOR; DIFFERENTIATION; NEUROPATHOLOGY; NOSOLOGY; SYMPTOMS AB Neuropsychiatric features characterize frontotemporal dementia (FTD). The authors evaluated the neuropsychiatric features of 53 FTD patients and retrospectively applied the Consensus Criteria for this disorder. Only one-third of the patients met Consensus Criteria for FTD on presentation. Most had early disengagement with poor insight; however, more than half retained socially appropriate interpersonal conduct and emotional expression. Supportive features, including compulsive-like acts and speech changes, were common presenting features, and 20% developed the Kluver-Bucy syndrome on 2-year follow-up. Consensus Criteria for FTD offer guidelines for diagnosis, but further refinement is needed, particularly for patients who lack early changes in social interpersonal conduct. C1 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. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 68 Z9 73 U1 1 U2 2 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 FAL PY 2002 VL 14 IS 4 BP 424 EP 429 DI 10.1176/appi.neuropsych.14.4.424 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 611ZB UT WOS:000179047300005 PM 12426410 ER PT J AU Mao, JR Sung, BK Ji, RR Lim, G AF Mao, JR Sung, BK Ji, RR Lim, G TI Neuronal apoptosis associated with morphine tolerance: Evidence for an opioid-induced neurotoxic mechanism SO JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; opioid tolerance; analgesia; NMDA; glutamate transporter; caspase-3; Bax; Bcl-2 ID PROTEIN-KINASE-C; PAINFUL PERIPHERAL MONONEUROPATHY; ASPARTATE-INDUCED APOPTOSIS; SUPERFICIAL DORSAL HORN; AMINO-ACID RECEPTORS; LUNG-CANCER CELLS; RAT SPINAL-CORD; NEUROPATHIC PAIN; GLUTAMATE UPTAKE; NUCLEUS-ACCUMBENS AB Tolerance to the analgesic effect of an opioid is a pharmacological phenomenon that occurs after its prolonged administration. Activation of the NMDA receptor (NMDAR) has been implicated in the cellular mechanisms of opioid tolerance. However, activation of NMDARs can lead to neurotoxicity under many circumstances. Here we demonstrate that spinal neuronal apoptosis was induced in rats made tolerant to morphine administered through intrathecal boluses or continuous infusion. The apoptotic cells were predominantly located in the superficial spinal cord dorsal horn, and most apoptotic cells also expressed glutamic acid decarboxylase, a key enzyme for the synthesis of the inhibitory neurotransmitter GABA. Consistently, increased nociceptive sensitivity to heat stimulation was observed in these same rats. Mechanistically, the spinal glutamatergic activity modulated morphine-induced neuronal apoptosis, because pharmacological perturbation of the spinal glutamate transporter activity or coadministration of morphine with the NMDAR antagonist (+)- 5- methyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5,10-imine maleate affected both morphine tolerance and neuronal apoptosis. At the intracellular level, prolonged morphine administration resulted in an upregulation of the proapoptotic caspase-3 and Bax proteins but a downregulation of the antiapoptotic Bcl-2 protein in the spinal cord dorsal horn. Furthermore, coadministration with morphine of N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (a pan-caspase inhibitor) or acetyl-aspartyl-glutamyl-valyl-aspart-1-aldehyde (a relatively selective caspase-3 inhibitor) blocked morphine-induced neuronal apoptosis. Blockade of the spinal caspase-like activity also partially prevented morphine tolerance and the associated increase in nociceptive sensitivity. These results indicate an opioid-induced neurotoxic consequence regulated by the NMDAR-caspase pathway, a mechanism that may have clinical implications in opioid therapy and substance abuse. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Neural Plast Res Grp, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Pain Ctr, Suite WACC 324,15 Parkman St, Boston, MA 02114 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [R01 NS040698] NR 93 TC 162 Z9 175 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2002 VL 22 IS 17 BP 7650 EP 7661 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 587CK UT WOS:000177622800037 PM 12196588 ER PT J AU Gewirtz, H Tawakol, A Bacharach, SL AF Gewirtz, H Tawakol, A Bacharach, SL TI Heterogeneity of myocardial blood flow and metabolism: Review of physiologic principles and implications for radionuclide imaging of the heart SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SPATIAL HETEROGENEITY; PERFUSION-PRESSURE; CORONARY STENOSIS; PET/SPECT IMAGES; DOMESTIC SWINE; LEFT-VENTRICLE; CLOSED-CHEST; GATED SPECT; DOG HEARTS C1 Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. NIH, Ctr Clin, Div Nucl Med, Bethesda, MD 20892 USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Vincent Burnham 3,32 Blossom St, Boston, MA 02114 USA. NR 50 TC 7 Z9 7 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD SEP-OCT PY 2002 VL 9 IS 5 BP 534 EP 541 DI 10.1067/mnc.2002.125916 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 602JN UT WOS:000178502300012 PM 12360134 ER PT J AU Soteriades, ES Kales, SN Liarokapis, D Christoudias, SG Tucker, SA Christiani, DC AF Soteriades, ES Kales, SN Liarokapis, D Christoudias, SG Tucker, SA Christiani, DC TI Lipid profile of firefighters over time: Opportunities for prevention SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; RISK-FACTORS; MORTALITY; COHORT AB Heart disease is the primary cause of on-duty deaths in firefighters, but little is known about their lipid profile. We evaluated the lipid profile in relation to other cardiovascular disease risk factors in 321 firefighters at a baseline examination. Prospective comparisons were performed for 285 firefighters, who were enrolled in a statewide medical surveillance program, and had complete follow-up data for 4 years. The average cholesterol level in firefighters declined from 224 mg/dL at baseline (1996-1997) to 214 mg/dL at the follow-up examination (P < 0.0001). Conversely, both obesity (body mass index greater than or equal to 30; 34% versus 40%, P = 0.008) and triglycerides (200 mg/dL; 27% versus 35%, P = 0.047) increased over time. The proportion of firefighters taking lipid-lowering medications increased from 3% at baseline to 12% at follow-up (P < 0.0001). Cholesterol levels declined significantly, and treatment rates for elevated cholesterol increased over time. Despite repeated examinations, a considerable number of firefighters had persistently elevated cholesterol, and only a minority were receiving adequate treatment. C1 Cambridge Hosp, Dept Med Occupat & Environm Hlth, Harvard Med Sch, Cambridge, MA 02139 USA. Univ Massachusetts, Boston, MA 02125 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Crit Care Unit, Boston, MA USA. Olympus Specialty & Rehabil Hosp, Ctr Occupat & Environm Med, Braintree, MA USA. RP Kales, SN (reprint author), Cambridge Hosp, Dept Med Occupat & Environm Hlth, Harvard Med Sch, 1493 Cambridge St, Cambridge, MA 02139 USA. FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [OH03729] NR 34 TC 14 Z9 14 U1 1 U2 2 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 SEP PY 2002 VL 44 IS 9 BP 840 EP 846 DI 10.1097/01.jom.0000026643.83602.e7 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 591KX UT WOS:000177880000006 PM 12227676 ER PT J AU Thurmuller, P Troulis, M O'Neill, MJ Kaban, LB AF Thurmuller, P Troulis, M O'Neill, MJ Kaban, LB TI Use of ultrasound to assess healing of a mandibular distraction wound SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID BONE-FORMATION; COMPUTED-TOMOGRAPHY; OSTEOGENESIS; OSTEODISTRACTION; LATENCY; MODEL AB Purpose: A standardized, noninvasive technique to assess healing of the mandibular distraction wound is not available. Current methods include clinical examination, plain radiography, and computed tomography. These imaging techniques are expensive and obligate the patient to serial radiation exposure. In addition, anatomic overlap and metal artifacts may obscure the distraction gap. In contrast, ultrasound has been shown to be a noninvasive, efficient, and inexpensive way to evaluate bone healing. The purpose of this study was to test the feasibility of ultrasound to evaluate an experimental mandibular distraction osteogenesis wound. Materials and Methods: Distraction devices were placed via a submandibular incision into 24 minipigs. The protocol consisted of 0-day latency and distraction rates of 1, 2, or 4 mm/d for a 12-mm. gap. The wounds were assessed in vivo after 0, 8, 16, and 24 days of neutral fixation. Ex vivo radiographs were used to estimate bone fill using a semiquantitative score. A semiquantitative ultrasound score was assigned, and the beam penetration depth was measured in millimeters. Results: In all groups, clinical stability of the distraction wound increased with the duration of fixation. Plain radiographs, taken during neutral fixation, showed that the desired distraction gap was achieved and maintained. The ultrasound score increased with fixation time, whereas beam penetration depth decreased as expected. Ex vivo radiographs showed increasing bone fill score with time and paralleled the ultrasound score. Conclusions: The results of this feasibility study indicate that ultrasound is potentially useful for the assessment of bone formation in distraction osteogenesis wounds. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Oral & Maxillofacial Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Oral & Maxillofacial Surg Serv, Fruit St,Warren Bldg 1201, Boston, MA 02114 USA. NR 30 TC 28 Z9 28 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2002 VL 60 IS 9 BP 1038 EP 1044 DI 10.1053/joms.2002.34417 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 589NF UT WOS:000177765500017 PM 12215991 ER EF