FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Davids, E Zhang, KH Tarazi, FI Baldessarini, RJ AF Davids, E Zhang, KH Tarazi, FI Baldessarini, RJ TI Animal models of attention-deficit hyperactivity disorder SO BRAIN RESEARCH REVIEWS LA English DT Review DE attention deficit-hyperactivity disorder; behavior; dopamine; hyperactivity; norepinephrine; serotonin; stimulants ID SPONTANEOUSLY HYPERTENSIVE-RAT; DOPAMINE TRANSPORTER GENE; NEONATAL 6-HYDROXYDOPAMINE LESIONS; STIMULANT DRUG-ACTION; POLYCHLORINATED BIPHENYL CONGENERS; H-3 RECEPTOR ANTAGONISTS; PREFRONTAL CORTEX SLICES; FRONTAL-LOBE DYSFUNCTION; NAPLES HIGH-EXCITABILITY; DEPLETING BRAIN-LESIONS AB Attention-deficit hyperactivity disorder (ADHD) involves clinically heterogeneous dysfunctions of sustained attention, with behavioral overactivity and impulsivity, of juvenile onset. Experimental models, in addition to mimicking syndromal features, should resemble the clinical condition in pathophysiology, and predict potential new treatments. One of the most extensively evaluated animal models of ADHD is the spontaneously hypertensive rat. Other models include additional genetic variants (dopamine transporter gene knock-out mouse, coloboma mouse, Naples hyperexcitable rat, acallosal mouse, hyposexual rat, and population-extreme rodents), neonatal lesioning of dopamine neurons with 6-hydroxydopamine, and exposure to other neurotoxins or hippocampal irradiation. None is fully comparable to clinical ADHD. The pathophysiology involved varies, including both deficient and excessive dopaminergic functioning, and probable involvement of other monoamine neurotransmitters. Improved models as well as further testing of their ability to predict treatment responses are required. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Neurosci Program, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Mailman Res Ctr, McLean Div, Belmont, MA 02178 USA. Univ Essen Gesamthsch, Dept Psychiat & Psychotherapy, Essen, Germany. RP Baldessarini, RJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mclean.org FU NIMH NIH HHS [MH-34006, MH-47370] NR 308 TC 133 Z9 139 U1 6 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD APR PY 2003 VL 42 IS 1 BP 1 EP 21 DI 10.1016/S0165-0173(02)00274-6 PG 21 WC Neurosciences SC Neurosciences & Neurology GA 672ND UT WOS:000182526300001 PM 12668288 ER PT J AU Irwin, MS Kondo, K Marin, MC Cheng, LS Hahn, WC Kaelin, WG AF Irwin, MS Kondo, K Marin, MC Cheng, LS Hahn, WC Kaelin, WG TI Chemosensitivity linked to p73 function SO CANCER CELL LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; KINASE C-ABL; DNA-DAMAGE; MUTANT P53; APOPTOTIC RESPONSE; RNA INTERFERENCE; MAMMALIAN-CELLS; CANCER; EXPRESSION; GENE AB Most chemotherapeutic agents induce DNA damage, leading to p53 accumulation and apoptosis. The factors that determine chemosensitivity in p53-defective tumor cells are poorly understood. We found that the p53 family member p73 is induced by a wide variety of chemotherapeutic drugs. Blocking p73 function with a dominant-negative mutant, siRNA, or homologous recombination led to chemoresistance of human tumor cells and engineered transformed cells, irrespective of p53 status. Mutant p53 can inactivate p73 and downregulation of mutant p53 enhanced chemosensitivity. These findings indicate that p73 is a determinant of chemotherapeutic efficacy in humans. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Univ Toronto, Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 41 TC 322 Z9 330 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2003 VL 3 IS 4 BP 403 EP 410 DI 10.1016/S1535-6108(03)00078-3 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 671TQ UT WOS:000182480500012 PM 12726865 ER PT J AU DiGianni, LM Kim, HT Emmons, K Gelman, R Kalkbrenner, KJ Garber, JE AF DiGianni, LM Kim, HT Emmons, K Gelman, R Kalkbrenner, KJ Garber, JE TI Complementary medicine use among women enrolled in a genetic testing program SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER PATIENTS; UNITED-STATES; ALTERNATIVE MEDICINE; OVARIAN-CANCER; LONG-TERM; NATIONAL SURVEY; DIETARY-FAT; RISK; THERAPIES; PERCEPTIONS AB The purpose of this study is to explore complementary and alternative medicine (CAM) use and factors influencing CAM use by women enrolled in a genetic testing program for predisposition to breast/ovarian cancer. A cohort of 236 high-risk women completed baseline questionnaires at enrollment into BRCA1/2 testing program. CANT use and correlates of use were assessed using logistic regression models. CAM was used by 53% of the overall cohort. Cancer survivors reported significantly more use of complementary treatments than did unaffected women (61 versus 42%; P < 0.05). Participants had good overall health behaviors. daily fruit/vegetable consumption was significantly related to CAM use. Increased depression level, knowledge of cancer genetics, and frequency of breast self-examination were significantly associated with using CAM for cancer survivors. Among unaffected women only, cancer risk perception and sunscreen use were significantly correlated with CAM use. Recognition of heightened breast cancer risk is correlated with increased complementary therapy use by unaffected women undergoing genetic testing for cancer predisposition but not to the extent that cancer survivors use these strategies. Any potential effects of the genetic information itself on CAM use, and any possible relationship of CAM use to other risk reduction behaviors, require further research. 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. FU NHGRI NIH HHS [R01 HG012044] NR 37 TC 23 Z9 23 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2003 VL 12 IS 4 BP 321 EP 326 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 667WR UT WOS:000182258000005 PM 12692106 ER PT J AU Zhou, W Liu, G Miller, DP Thurston, SW Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC AF Zhou, W Liu, G Miller, DP Thurston, SW Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC TI Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CUMULATIVE CIGARETTE-SMOKING; MICROSOMAL EPOXIDE HYDROLASE; NUCLEOTIDE EXCISION-REPAIR; XPD POLYMORPHISMS; ADDUCTS; SUSCEPTIBILITY; CAPACITY; DAMAGE; SAMPLE; CELLS AB XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (greater than or equal to55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Thorac Surg Unit,Dept Surg, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU FIC NIH HHS [TW00828]; NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES00002, ES/CA 06409]; PHS HHS [T3206709] NR 37 TC 154 Z9 162 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2003 VL 12 IS 4 BP 359 EP 365 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 667WR UT WOS:000182258000010 PM 12692111 ER PT J AU Weiss, WA Burns, MJ Hackett, C Aldape, K Hill, JR Kuriyama, H Kuriyama, N Milshteyn, N Roberts, T Wendland, MF DePinho, R Israel, MA AF Weiss, WA Burns, MJ Hackett, C Aldape, K Hill, JR Kuriyama, H Kuriyama, N Milshteyn, N Roberts, T Wendland, MF DePinho, R Israel, MA TI Genetic determinants of malignancy in a mouse model for oligodendroglioma SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-BRAIN-TUMORS; ADULT-RAT-BRAIN; TRANSGENIC MICE; CHROMOSOME 1P; IN-VIVO; EXPRESSION; SURVIVAL; GLIOMAS; ASTROCYTOMAS AB Oligodendrogliomas of all grades overexpress epidermal growth factor receptor (EGFR), whereas deletion of ink4a/arf is found only in high-grade tumors. We used the S100beta promoter to generate transgenic mice expressing v-erbB, a transforming allele of EGFR. These mice developed low-grade oligodendroglioma. Transgenic animals heterozygous for ink4a/arf orp53 developed high-grade tumors. Comparative genomic hybridization revealed loss of distal mouse chromosome 4, a region orthologous with human chromosome 1p, which is commonly lost in oligodendroglioma. Our results demonstrate that overexpression of EGFR, an epigenetic observation of uncertain significance in human oligodendroglioma, can initiate oligodendroglioma in the mouse. Furthermore, p53 pathway mutations can mediate the transition from low to high grade. These models hold promise for studying tumor lineage, identifying contributing genetic alterations and evaluating preclinical therapies in this important neoplasm. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Toronto, Toronto, ON M5S 1A1, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. RP Weiss, WA (reprint author), Univ Calif San Francisco, Dept Neurol, 521 Parnassus Ave, Room C-215, San Francisco, CA 94143 USA. FU NCI NIH HHS [U01 CA84290] NR 43 TC 113 Z9 120 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2003 VL 63 IS 7 BP 1589 EP 1595 PG 7 WC Oncology SC Oncology GA 661NP UT WOS:000181896900024 PM 12670909 ER PT J AU Nutt, CL Mani, DR Betensky, RA Tamayo, P Cairncross, JG Ladd, C Pohl, U Hartmann, C McLaughlin, ME Batchelor, TT Black, PM von Deimling, A Pomeroy, SL Golub, TR Louis, DN AF Nutt, CL Mani, DR Betensky, RA Tamayo, P Cairncross, JG Ladd, C Pohl, U Hartmann, C McLaughlin, ME Batchelor, TT Black, PM von Deimling, A Pomeroy, SL Golub, TR Louis, DN TI Gene expression-based classification of malignant gliomas correlates better with survival than histological classification SO CANCER RESEARCH LA English DT Article ID MOLECULAR MARKERS; RHO GTPASES; OLIGODENDROGLIOMAS; PREDICTION; DIAGNOSIS; CANCER AB In modern clinical neuro-oncology, histopathological diagnosis affects therapeutic decisions and prognostic estimation more than any other variable. Among high-grade gliomas, histologically classic glioblastomas and anaplastic oligodendrogliomas follow markedly different clinical courses. Unfortunately, many malignant gliomas are diagnostically challenging; these nonclassic lesions are difficult to classify by histological features, generating considerable interobserver variability and limited diagnostic reproducibility. The resulting tentative pathological diagnoses create significant clinical confusion. We investigated whether gene expression profiling, coupled with class prediction methodology, could be used to classify high-grade gliomas in a manner more objective, explicit, and consistent than standard pathology. Microarray analysis was used to determine the expression of similar to12,000 genes in a set of 50 gliomas, 28 glioblastomas and 22 anaplastic oligodendrogliomas. Supervised learning approaches were used to build a two-class prediction model based on a subset of 14 glioblastomas and 7 anaplastic oligodendrogliomas with classic histology. A 20-feature k-nearest neighbor model correctly classified 18 of the 21 classic cases in leave-one-out cross-validation when compared with pathological diagnoses. This model was then used to predict the classification of clinically common, histologically nonclassic samples. When tumors were classified according to pathology, the survival of patients with nonclassic glioblastoma and nonclassic anaplastic oligodendroglioma was not significantly different (P = 0.19). However, class distinctions according to the model were significantly associated with survival outcome (P = 0.05). This class prediction model was capable of classifying high-grade, nonclassic glial tumors objectively and reproducibly. Moreover, the model provided a more accurate predictor of prognosis in these nonclassic lesions than did pathological classification. These data suggest that class prediction models, based on defined molecular profiles, classify diagnostically challenging malignant gliomas in a manner that better correlates with clinical outcome than does standard pathology. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol & Neurosurg Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Western Ontario, Dept Oncol & Clin Neurol Sci, London, ON N6A 4L6, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Humboldt Univ, Charite Hosp, Dept Neuropathol, Berlin, Germany. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Lab, CNY7,149 13th St, Charlestown, MA 02129 USA. RI Nutt, Catherine/K-8794-2012; von Deimling, Andreas/F-7774-2013; Hartmann, Christian/D-1882-2010 OI von Deimling, Andreas/0000-0002-5863-540X; FU NCI NIH HHS [CA57683]; NINDS NIH HHS [NS35701] NR 19 TC 556 Z9 572 U1 1 U2 16 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 APR 1 PY 2003 VL 63 IS 7 BP 1602 EP 1607 PG 6 WC Oncology SC Oncology GA 661NP UT WOS:000181896900026 PM 12670911 ER PT J AU Goel, A Arnold, CN Niedzwiecki, D Chang, DK Ricciardiello, L Carethers, JM Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR AF Goel, A Arnold, CN Niedzwiecki, D Chang, DK Ricciardiello, L Carethers, JM Dowell, JM Wasserman, L Compton, C Mayer, RJ Bertagnolli, MM Boland, CR TI Characterization of sporadic colon cancer by patterns of genomic instability SO CANCER RESEARCH LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; LEVEL MICROSATELLITE INSTABILITY; DNA MISMATCH REPAIR; II RECEPTOR GENE; REPLICATION ERRORS; HMLH1 PROMOTER; MUTATIONS; HYPERMETHYLATION; CARCINOMA; PROGRESSION AB Colorectal cancer (CRC) can progress through two pathways of genomic instability: chromosomal (CIN) and microsatellite instability (NISI). We hypothesized that these two pathways are not always independent and that some tumorstherefore show a significant degree of overlap between these two mechanisms. We classified 209 high-risk stage II and stage III sporadic CRCs based on their MSI status, using a National Cancer Institute-recommended panel of microsatellite markers, and also identified MSI-associated mutations of CRC target genes such as TGFbetaRII. Evidence for CIN was gathered by identifying loss of heterozygosity (LOH) events on chromosomal arms 1p, 2p, 3p, 5q, 17p, and 18q, which are regions harboring mismatch-repair and tumor-suppressor genes that are significant in CRC development. Results of all molecular markers tested were correlated with clinicopathological variables of the cohort, including treatment outcome. Of the 209 cases, 65% cancers were microsatellite stable, 21% were MSI-low, and 14% were MSI-high (MSI-H). Overall, 51% of the tumors had at least one LOH event, with most frequent chromosomal losses observed on 18q (72.5%), followed by 5q (22%), 17p (21%), and 3p (14%). Interestingly, we observed a significant degree of overlap between MSI and CIN pathways. Of 107 cancers with LOH events, 7 (6.5%) were also MSI-H, and of 30 cancers that were MSI-H, 7 (23.3%) also had one or more LOH events. We also found that 37.8% of microsatellite-stable cancers had no LOH events identified, thus comprising a subgroup of tumors that were not representative of either of these two pathways of genomic instability. Our data suggest that molecular mechanisms of genomic instability are not necessarily independent and may not be fully defined by either the MSI or CIN pathways. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Duke Univ, CALGB Stat Ctr, Durham, NC USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. McGill Univ, Dept Pathol, Montreal, PQ, Canada. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. OI RICCIARDIELLO, LUIGI/0000-0003-2568-6208 FU NCI NIH HHS [CA31946, R01 CA090231, R01 CA090231-03, R01-CA72851]; NIDDK NIH HHS [K08 DK002433, K08 DK002433-05] NR 45 TC 203 Z9 213 U1 0 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 APR 1 PY 2003 VL 63 IS 7 BP 1608 EP 1614 PG 7 WC Oncology SC Oncology GA 661NP UT WOS:000181896900027 PM 12670912 ER PT J AU Kandasamy, K Srinivasula, SM Alnemri, ES Thompson, CB Korsmeyer, SJ Bryant, JL Srivastava, RK AF Kandasamy, K Srinivasula, SM Alnemri, ES Thompson, CB Korsmeyer, SJ Bryant, JL Srivastava, RK TI Involvement of proapoptotic molecules Bax and Bak in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced mitochondrial disruption and apoptosis: Differential regulation of cytochrome c and Smac/DIABLO release SO CANCER RESEARCH LA English DT Article ID TRAIL-INDUCED APOPTOSIS; DEPENDENT ANION CHANNEL; PROGRAMMED CELL-DEATH; IN-VIVO; MUTATIONAL INACTIVATION; OLIGOMERIZES BAK; LEUKEMIC-CELLS; DEFICIENT MICE; BCL-2; MEMBRANE AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L induces apoptosis in a wide variety of cancer and transformed cells. Activation of BID, a "BH3-domain-only" Bcl-2 family member, triggers the oligomerization of proapoptotic family members Bak or Bax, resulting in the release of mitochondrial proteins to cytosol. In this study, we have shown the importance of Bax and Bak in TRAIL-induced apoptosis by studying in murine embryonic fibroblasts (MEFs) from Bax(-/-) and Bak(-/-) animals. TRAIL induced cytochrome c release and apoptosis in wild-type, Bid(-/-), Bax(-/-), or Bak(-/-) MEFs, but not in Bax(-/-) Bak(-/-) double knockout (DKO) MEFs. Bid, which functions upstream of cytochrome c release, was cleaved in all of the knockout cells except in Bid(-/-) MEFs. The release of cytochrome c was correlated with caspase-9 activity. TRAIL increased caspase-3 activity in all of the cells except in DKO cells. TRAIL-induced drop in mitochondrial membrane potential was not observed in DKO MEFs. Unlike cytochrome c release, TRAIL-induced Smac/DIABLO release was blocked in Bid(-/-), Bax(-/-), Bak(-/-), or DKO MEFs, suggesting the differential regulation of these mitochondrial proteins during apoptosis. The apoptotic events downstream of mitochondria were intact in DKO MEFs, because microinjection of cytochrome c, or ectopic expression of mature Smac/DIABLO or pretreatment of Smac N7 peptide completely restored TRAIL sensitivity. In conclusion, the data suggest that Bax and Bak differentially regulate the release of cytochrome c and Smac/DIABLO from mitochondria, and Smac/DIABLO can be used to sensitize cells that are deficient in Bax and Bak genes, or resistant to TRAIL. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Greene Canc Ctr, Baltimore, MD 21201 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Ctr Apoptosis, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. 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. Univ Maryland, Inst Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. RP Srivastava, RK (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Greene Canc Ctr, 20 N Pine St, Baltimore, MD 21201 USA. NR 77 TC 144 Z9 153 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 APR 1 PY 2003 VL 63 IS 7 BP 1712 EP 1721 PG 10 WC Oncology SC Oncology GA 661NP UT WOS:000181896900041 PM 12670926 ER PT J AU Walters, DL Sanchez, PL Rodriguez-Alemparte, M Colon-Hernandez, PJ Hourigan, LA Palacios, IF AF Walters, DL Sanchez, PL Rodriguez-Alemparte, M Colon-Hernandez, PJ Hourigan, LA Palacios, IF TI Transthoracic left ventricular puncture for the assessment of patients with aortic and mitral valve prostheses: The Massachusetts General Hospital experience, 1989-2000 SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE hemodynamic; prosthetic valve dysfunction; double valve replacement ID LEFT-HEART CATHETERIZATION; DOPPLER-ECHOCARDIOGRAPHY; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; ANATOMIC CORRELATIONS; CLINICAL-APPLICATIONS; IMAGE ORIENTATION; REOPERATION; POSITION; TIME AB Accurate assessment of suspected prosthetic valve dysfunction is critically important as reoperation carries high risk. Noninvasive methods of hemodynamic assessment of patients with both aortic and mitral mechanical valves continue to be frustrated by the interference created by prosthetic material and direct left ventricular puncture may be required for definitive hemodynamic assessment. We report the hemodynamic and angiographic results and outcomes of 38 consecutive patients with double valve replacement who underwent left ventricular puncture as part of evaluation of possible prosthetic dysfunction. These results were compared with those obtained by noninvasive testing. We found noninvasive assessment alone to be unsatisfactory as measurements of regurgitation and stenosis correlated poorly with those obtained by direct left ventricular puncture. Important information that altered patient management was obtained from invasive assessment in 68% of cases with an acceptable rate of complications. Therefore, hemodynamic and angiographic assessment using transthoracic left ventricular puncture should be entertained in patients with mitral and aortic valve replacement presenting with congestive heart failure and suspected prosthesis dysfunction. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Dept,Cardiol Div,Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Dept,Cardiol Div,Cardiac Catheterizat Lab, Boston, MA 02114 USA. RI Walters, Darren/A-7069-2011; OI Sanchez, Pedro L/0000-0002-4288-345X NR 36 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD APR PY 2003 VL 58 IS 4 BP 539 EP 544 DI 10.1002/ccd.10473 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 677NR UT WOS:000182814900022 PM 12652508 ER PT J AU Barreto, A Gonzalez, JM Kabingu, E Asea, A Fiorentino, S AF Barreto, A Gonzalez, JM Kabingu, E Asea, A Fiorentino, S TI Stress-induced release of HSC70 from human tumors SO CELLULAR IMMUNOLOGY LA English DT Article DE chaperokine; heat shock proteins; interferon-gamma; proteasome ID HEAT-SHOCK-PROTEIN; INTERFERON-GAMMA; CELLS; HSP70; INTERLEUKIN-10; CYTOKINES; PATHWAY AB In this study, we demonstrate that the pro-inflammatory cytokine interferon-gamma (IFN-gamma) induces the active release of the constitutive form of the 70-kDa heat shock protein (HSC70) from K562 erythroleukemic cells. Treatment of K562 cells with IFN-gamma induced the upregulation of the inducible form of the 70-kDa heat shock protein (HSP70), but not the constitutive form of HSC70 within the cytosol, in a proteasome-dependent manner. In addition, IFN-gamma induced the downregulation of surface-bound HSC70, but did not significantly alter surface-bound HSP70 expression. These findings indicate that HSC70 can be actively released from tumor cells and is indicative of a previously unknown mechanism by which immune modulators stimulate the release of intracellular HSC70. This mechanism may account for the potent chaperokine activity of heat shock proteins recently observed during heat shock protein-based immunotherapy against a variety of cancers. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Pontificia Univ Javeriana, Fac Ciencias, Grp Immunobiol, Bogota, Colombia. Pontificia Univ Javeriana, Fac Ciencias, Dept Microbiol, Bogota, Colombia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fiorentino, S (reprint author), Pontificia Univ Javeriana, Fac Ciencias, Grp Immunobiol, Bogota, Colombia. RI Asea, Alexzander/I-4112-2013; OI Asea, Alexzander/0000-0003-3592-3481; Gonzalez, John M./0000-0001-6925-0620; FIORENTINO, SUSANA/0000-0002-4664-0682 FU NCI NIH HHS [R01 CA091889-02] NR 21 TC 83 Z9 91 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR PY 2003 VL 222 IS 2 BP 97 EP 104 DI 10.1016/S0008-8749(03)00115-1 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 698JN UT WOS:000183995600002 PM 12826079 ER PT J AU Seiffert, AE Somers, DC Dale, AM Tootell, RBH AF Seiffert, AE Somers, DC Dale, AM Tootell, RBH TI Functional MRI studies of human visual motion perception: Texture, luminance, attention and after-effects SO CEREBRAL CORTEX LA English DT Article ID CONTRAST-MODULATED GRATINGS; 2ND-ORDER MOTION; FIRST-ORDER; AREA MT; COMPUTATIONAL MODEL; WAVE RECTIFICATION; SPATIAL ATTENTION; PERIPHERAL-VISION; CORTICAL AREAS; MACAQUE MONKEY AB Motion of an object is thought to be perceived independently of the object's surface properties. However, theoretical, neuropsychological and psychophysical observations have suggested that motion of textures, called 'second-order motion', may be processed by a separate system from luminance-based, or 'first-order', motion. Functional magnetic resonance imaging (fMRI) responses during passive viewing, attentional modulation and post-adaptation motion after-effects (MAE) of these stimuli were measured in seven retinotopic visual areas (labeled V1, V2, V3, VP V4v, V3A and LO) and the motion-sensitive area MT/MST (V5). In all visual areas, responses were strikingly similar to motion of first- and second-order stimuli. These results differ from a prior investigation, because here the motion-specific responses were isolated. Directing attention towards and away from the motion elicited equivalent response modulation for the two types. Dramatic post-adaptation (MAE) differences in perception of the two stimuli were observed and fMRI activation mimicked perceptual changes, but did not reveal the processing differences. In fact, no visual area was found to respond selectively to the motion of second-order stimuli, suggesting that motion perception arises from a unified motion detection system. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Seiffert, AE (reprint author), Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. RI Somers, David/G-5802-2010; Dale, Anders/A-5180-2010; OI Somers, David/0000-0002-4169-5895 FU NEI NIH HHS [EY-11005, EY-07980] NR 72 TC 75 Z9 78 U1 4 U2 12 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 APR PY 2003 VL 13 IS 4 BP 340 EP 349 DI 10.1093/cercor/13.4.340 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 660KK UT WOS:000181832200002 PM 12631563 ER PT J AU Chapel, H Geha, R Rosen, F AF Chapel, H Geha, R Rosen, F CA IUIS PID Classification Comm TI Primary immunodeficiency diseases: an update SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article C1 John Radcliffe Hosp, Dept Immunol, Nuffield Dept Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Chapel, H (reprint author), John Radcliffe Hosp, Dept Immunol, Nuffield Dept Med, Headley Way, Oxford OX3 9DU, England. EM helen.chapel@ndm.ox.ac.uk NR 2 TC 81 Z9 89 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD APR PY 2003 VL 132 IS 1 BP 9 EP 15 DI 10.1046/j.1365-2249.2003.02110.x PG 7 WC Immunology SC Immunology GA 659QX UT WOS:000181789900002 PM 12653830 ER PT J AU Keeton, EK Brown, M AF Keeton, EK Brown, M TI Coregulator expression and breast cancer: Improving the predictive power of estrogen receptor alpha SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID TAMOXIFEN; TRANSCRIPTION C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 12 TC 5 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 2003 VL 9 IS 4 BP 1229 EP 1230 PG 2 WC Oncology SC Oncology GA 664NP UT WOS:000182067400001 PM 12684386 ER PT J AU Ridker, PM AF Ridker, PM TI Connecting the role of C-reactive protein and statins in cardiovascular disease SO CLINICAL CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Reaching Goal - Conquering the Treatment Gaps in Dyslipidemia Management CY MAR, 2002 CL ATLANTA, GEORGIA DE biomarkers; C-reactive protein; high-density lipoprotein cholesterol; 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition; hyperlipidemia; low-density lipoprotein cholesterol; myocardial infarction; statin ID CORONARY HEART-DISEASE; APPARENTLY HEALTHY-MEN; FUTURE MYOCARDIAL-INFARCTION; AVERAGE CHOLESTEROL LEVELS; PLASMA-CONCENTRATION; PRIMARY PREVENTION; RISK-FACTORS; EVENTS; INFLAMMATION; INTERLEUKIN-6 AB The observation that almost half of all myocardial infarctions and strokes occur in persons without elevated levels of low-density lipoprotein cholesterol has prompted the study of factors other than hyperlipidemia that contribute to the development of atherosclerosis. A growing body of evidence indicates that inflammation plays a substantial role in plaque progression and rupture. Research interest has increasingly focused on biomarkers of inflammation as a means of predicting more accurately which patients are at high risk for cardiovascular disease (CVD). Clinical studies indicate that C-reactive protein (CRP), a marker of systemic inflammation, independently predicts cardiovascular risk in healthy persons as well as in persons with established CVD and those with acute ischemia. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, have been shown to reduce levels of CRP through mechanisms independent of their effects on lipid levels. Initial clinical studies also suggest that CRP levels may have utility in the targeting of statin therapy, particularly in primary prevention. These results need direct testing in large, prospective clinical trials to determine whether statin therapy will benefit persons without overt hyperlipidemia but with evidence of systemic inflammation. Confirmation of these preliminary findings, if incorporated into evidence-based guidelines, may profoundly change the approach to diagnosis and treatment of CVD. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. RP Ridker, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Cardiovasc Dis Prevent, 75 Francis St,Bldg Tower 3C, Boston, MA 02115 USA. NR 38 TC 24 Z9 24 U1 0 U2 3 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2003 VL 26 IS 4 SU 3 BP 39 EP 44 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 663DW UT WOS:000181991800007 ER PT J AU Lichterfeld, M Nischalke, HD van Lunzen, J Sohne, J Schmeisser, N Woitas, R Sauerbruch, T Rockstroh, JK Spengler, U AF Lichterfeld, M Nischalke, HD van Lunzen, J Sohne, J Schmeisser, N Woitas, R Sauerbruch, T Rockstroh, JK Spengler, U TI The tandem-repeat polymorphism of the DC-SIGNR gene does not affect the susceptibility to HIV infection and the progression to AIDS SO CLINICAL IMMUNOLOGY LA English DT Article DE HIV-1; DC-SIGNR; CD209L; genetic polymorphisms; transreceptor ID DISEASE PROGRESSION; ENDOTHELIAL-CELLS; TRANSMISSION; EXPRESSION; ALLELE AB DC-SIGNR is a C-type lectin that functions as a transreceptor for HIV-1. The exon 4 of the DC-SIGNR gene comprises a variable number of 69-bp tandem repeats, encoding for parts of the extracellular protein domain. Here, we analyzed the relevance of this gene polymorphism for the interindividual transmission of HIV-1 and the progression to AIDS. A cross-sectional comparison between HIV-1-infected patients (n = 391) and healthy volunteers (n = 134) did not reveal significant differences with regard to the DG-SIGNR allele distribution. Moreover, DC-SIGNR allele frequencies were similar in slowly progressing HIV patients (n = 31) and patients who rapidly progressed to AIDS (n = 46). Additionally, in a cohort of 149 newly HIV-infected patients, no relationship was found between HIV set point viremia and DC-SIGNR genotypes. Thus, the DC-SIGNR tandem-repeat polymorphism in exon 4 does not have a significant impact on the host's susceptibility to HIV and the clinical progression to AIDS. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Bonn, Dept Gen Internal Med, D-5300 Bonn, Germany. Univ Klinikum Eppendorf, Zentrum Innere Med, Med Klin 1, Hamburg, Germany. RP Lichterfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Room 5246, Boston, MA 02129 USA. NR 13 TC 27 Z9 29 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 APR PY 2003 VL 107 IS 1 BP 55 EP 59 DI 10.1016/S1521-6616(02)00050-5 PG 5 WC Immunology SC Immunology GA 680DA UT WOS:000182960000007 PM 12738250 ER PT J AU Hadigan, C Meigs, JB Wilson, PWF D'Agostino, RB Davis, B Basgoz, N Sax, PE Grinspoon, S AF Hadigan, C Meigs, JB Wilson, PWF D'Agostino, RB Davis, B Basgoz, N Sax, PE Grinspoon, S TI Prediction of coronary heart disease risk in HIV-infected patients with fat redistribution SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; INSULIN-RESISTANCE; METABOLIC COMPLICATIONS; CARDIOVASCULAR-DISEASE; GLUCOSE-TOLERANCE; LIPODYSTROPHY; ABNORMALITIES; THERAPY; MEN; PREVALENCE AB A metabolic syndrome has been described among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy; the syndrome is characterized by fat redistribution, insulin resistance, and dyslipidemia. We compared the 10-year coronary heart disease (CHD) risk estimates for 91 HIV-infected men and women with fat redistribution with the risk estimates for 273 age-, sex-, and body mass index (BMI)-matched subjects enrolled in the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were also compared with 90 age- and BMI-matched control subjects. The 10-year CHD risk estimate was significantly elevated among HIV-infected patients with fat redistribution, particularly among men; however, when they were matched with control subjects by waist-to-hip ratio, the 10-year CHD risk estimate did not significantly differ between groups. HIV-infected patients without fat redistribution did not have a greater CHD risk estimate than did control subjects. In addition, the CHD risk estimate was greatest in HIV-infected patients who had primary lipoatrophy, compared with those who had either lipohypertrophy or mixed fat redistribution. Therefore, although CHD risk is increased in HIV-infected patients with fat redistribution, the pattern of fat distribution and sex are potential important components in determining the risk in this population. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Infect Dis Unit, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Boston, MA USA. RP Hadigan, C (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, L0N 207,55 Fruit St, Boston, MA 02114 USA. EM chadigan@partners.org FU NCRR NIH HHS [M01-RR300088]; NHLBI NIH HHS [N01-HC-38083]; NIDDK NIH HHS [F32-DK09218, K23-DK02844, R01-DK 54167, R01-DK59535] NR 29 TC 84 Z9 88 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2003 VL 36 IS 7 BP 909 EP 916 DI 10.1086/368185 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 659DF UT WOS:000181761700013 PM 12652392 ER PT J AU Grinspoon, S Mulligan, K AF Grinspoon, S Mulligan, K CA Dept Hlth Human Serv Working Grp P TI Weight loss and wasting in patients infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PLACEBO-CONTROLLED TRIAL; HUMAN GROWTH-HORMONE; ACTIVE ANTIRETROVIRAL THERAPY; RESTING ENERGY-EXPENDITURE; TOTAL PARENTERAL-NUTRITION; LOW TESTOSTERONE LEVELS; BODY CELL MASS; RESISTANCE EXERCISE; HIV-INFECTION; DOUBLE-BLIND AB Weight loss and muscle wasting remain significant clinical problems, even in the era of potent antiretroviral therapy. In patients infected with human immunodeficiency virus (HIV), wasting, particularly loss of metabolically active lean tissue, has been associated with increased mortality, accelerated disease progression, loss of muscle protein mass, and impairment of strength and functional status. Factors that may contribute to wasting include inadequate intake, malabsorptive disorders, metabolic alterations, hypogonadism, and excessive cytokine production. Evidence now demonstrates that nutritional counseling and support, appetite stimulants, progressive resistance training, and anabolic hormones can reverse weight loss and increase lean body mass in HIV-infected patients. Despite a growing body of evidence on the importance of nutritional intervention to prevent wasting in adults, maintain growth velocity in children, and promote restoration of weight and lean body mass in stable, low-weight patients, no therapeutic guidelines currently exist for the management of weight loss and wasting in HIV-infected patients. Principles and guidelines for assessment and management of weight loss and wasting in patients with HIV/AIDS are presented. C1 Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIDDK NIH HHS [DK 54167, DK 54615] NR 104 TC 87 Z9 88 U1 2 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 1 PY 2003 VL 36 SU 2 BP S69 EP S78 DI 10.1086/367561 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 659KH UT WOS:000181775500004 PM 12652374 ER PT J AU Wright, K Popli, S Gandhi, VC Lentino, JR Reyes, CV Leehey, DJ AF Wright, K Popli, S Gandhi, VC Lentino, JR Reyes, CV Leehey, DJ TI Paecilomyces peritonitis: case report and review of the literature SO CLINICAL NEPHROLOGY LA English DT Review DE paecilomyces; fungal peritonitis; peritoneal dialysis ID VARIOTII PERITONITIS; DIALYSIS; PATIENT AB While filamentous fungi are a rare cause of peritonitis in peritoneal dialysis patients, there is increasing recognition of Paecilomyces species as pathogens in such patients. We herein report a case of fungal peritonitis secondary to the filamentous Paecilomyces variotii species. The patient had a long and ultimately fatal course of illness despite catheter removal, discontinuation of peritoneal dialysis, recurrent intra-abdominal abscess drainage, and prolonged courses of antifungal therapy. Our experience with this case and a review of the literature suggests that infection with this fungus can cause substantial morbidity and is probably best treated with prompt catheter removal, aggressive antifungal therapy and vigilant observation for complications. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Leehey, DJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, 111-L,Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 14 TC 11 Z9 13 U1 2 U2 3 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD APR PY 2003 VL 59 IS 4 BP 305 EP 310 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 661EL UT WOS:000181878200011 PM 12708573 ER PT J AU Chin, KR Nagarkatti, DG Miranda, MA Santoro, VM Baumgaertner, MR Jupiter, JB AF Chin, KR Nagarkatti, DG Miranda, MA Santoro, VM Baumgaertner, MR Jupiter, JB TI Salvage of distal tibia metaphyseal nonunions with the 90 degrees cannulated blade plate SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ANKLE ARTHRODESIS; MANAGEMENT; DEFORMITY; FRACTURES; FIXATION; FUSION AB Nonunion of distal tibia metaphyseal fractures after trauma is a major problem. Treating these nonunions is made more challenging by the presence of symptomatic ipsilateral tibiotalar arthrosis. The current study examined the use of the 90degrees cannulated blade plate as an alternative method of stable internal fixation for 13 distal tibia metaphyseal nonunions and simultaneous fusion of three arthritic tibiotalar joints in 13 patients (seven males and six females) with an average age of 42.4 years (range, 21-73 years). Each patient had an average of three prior procedures (range, 2-6). Patients were followed up for an average of 34.2 months (range, 24-55 months). All 13 patients achieved radiographic and clinical union an average of 15.6 weeks (range, 12-20 weeks) from the date of the definitive procedure. There were two broken screws, but no secondary procedures were required to obtain fusion. All patients were ambulatory without support at the last followup. The implant proved effective for stable internal fixation of distal tibia metaphyseal nonunions alone or with simultaneous fusion of the tibiotalar joint. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Connecticut, Sch Med, Dept Orthoped, Farmington, CT USA. Univ Connecticut, Sch Med, Hartford, CT 06112 USA. Orthopaed Associates Hartford PC, Hartford, CT USA. Yale Univ, Sch Med, Dept Orthopaed, New Haven, CT 06520 USA. RP Chin, KR (reprint author), 338 Pearl St, Cambridge, MA 02139 USA. NR 26 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2003 IS 409 BP 241 EP 249 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 666KY UT WOS:000182177500032 PM 12671508 ER PT J AU Ring, D Jupiter, JB Gulotta, L AF Ring, D Jupiter, JB Gulotta, L TI Atrophic nonunions of the proximal ulna SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Ten consecutive patients were treated by one surgeon for an atrophic nonunion of the proximal ulna. There were six men and four women with an average age of 47 years. Nine of the initial injuries were fracture-dislocations (seven posterior Monteggia lesions and two transolecranon fracture-dislocations) and one was a fracture of the proximal ulnar and radial diaphysis. The nonunion was associated with failed operative fixation in nine patients and occurred after treatment in cast in one patient. Three patients had synovial pseudarthroses and eight had bony defects. Debridement of the nonunion, autogenous cancellous bone grafting, and contoured limited-contact plate fixation were done at an average of 36 months after the original injury. The patients were followed up for an average of 39 months. Union was achieved in all 10 patients. The average arc of ulnohumeral motion was 105degrees and the average arc of forearm rotation was 130degrees. According to the system of Broberg and Morrey five patients had an excellent result, four had a good result, and one had a fair result. The fair result was attributable to proximal radioulnar synostosis and severe ulnohumeral arthrosis. Atrophic nonunion of fractures of the proximal ulna usually follow a complex injury treated with inadequate fixation. Stable plate fixation and autogenous bone graft predictably lead to union, but the functional result may be limited by associated problems. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hand Surg Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA. NR 17 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2003 IS 409 BP 268 EP 274 DI 10.1097/01.blo.0000052936.71325.eb PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 666KY UT WOS:000182177500035 PM 12671511 ER PT J AU Murata, M Trahan, C Hirahashi, J Mankin, HJ Towle, CA AF Murata, M Trahan, C Hirahashi, J Mankin, HJ Towle, CA TI Intracellular interleukin-1 receptor antagonist in osteoarthritis chondrocytes SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID ARTICULAR-CARTILAGE; PROSTAGLANDIN E-2; IL-1; EXPRESSION; IL-1-ALPHA; IL-1-BETA; GENE; INVOLVEMENT; SYNTHESIZES; AUTOCRINE AB The objective of the current study was to determine whether the balance of interleukin-1 and intracellular interleukin-1 receptor antagonist in chondrocytes in osteoarthritic human joints favors agonist action. Chondrocytes were isolated from cartilage specimens taken at the time of joint arthroplasty. Interleukin-1alpha, interleukin-1beta, and intracellular interleukin-1 receptor antagonist messenger ribonucleic acids were assessed by reverse transcriptase-polymerase chain reaction, and chondrocyte lysates were analyzed by enzyme-linked immunosorbent assay for the respective proteins. Type I intracellular interleukin receptor antagonist transcripts were the only intracellular variant detected in osteoarthritis chondrocytes. In cartilage graded as advanced osteoarthritis both interleukin proteins in chondrocyte lysates decreased, correlating with decreased interleukin-1alpha and beta messenger ribonucleic acids. Interieukin-1 receptor antagonist exceeded interleukin-lalpha in chondrocyte lysates by one order of magnitude except that in moderate osteoarthritis, antagonist was only two- to fourfold in excess. Interleukin-1alpha and interleukin-1beta proteins were correlated closely in individual lysates, with interleukin-1beta exceeding interleukin-1beta by one order of magnitude. In moderately degenerated cartilage, intracellular antagonist may not be sufficiently abundant to block postulated intracellular functions of precursor interleukin-1alpha. Furthermore, if stored interleukin-1alpha, interleukin-1beta, and interleukin receptor antagonist are released from chondrocytes, the localized antagonist would be insufficient to prevent signaling through cell surface receptors. Chondrocyte-derived interleukin-1alpha and interleukin-1beta may locally overwhelm inhibition by interleukin receptor antagonist to promote the early degenerative changes in osteoarthritis. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Towle, CA (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, Dept Orthopaed Surg, GRJ 1124,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [1R03AG16885]; PHS HHS [2 R01 16265] NR 44 TC 11 Z9 11 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 2003 IS 409 BP 285 EP 295 DI 10.1097/01.blo.0000059582.08469.ac PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 666KY UT WOS:000182177500038 PM 12671514 ER PT J AU O'Malley, ME Hahn, PF Yoder, IC Gazelle, GS McGovern, FJ Mueller, PR AF O'Malley, ME Hahn, PF Yoder, IC Gazelle, GS McGovern, FJ Mueller, PR TI Comparison of exeretory phase, helical computed tomography with intravenous urography in patients with painless haematuria SO CLINICAL RADIOLOGY LA English DT Article DE CT; urography; genito-urinary system ID ASYMPTOMATIC MICROSCOPIC HEMATURIA; CT; DIAGNOSIS AB AIM: To compare excretory phase, helical computed tomography (CT) with intravenous (IV) urography for evaluation of the urinary tract in patients with painless haematuria. MATERIALS AND METHODS: Ninety-one out-patients had IV urography followed by helical CT limited to the urinary tract. Both IV urograms and CT images were evaluated for abnormalities of the urinary tract in a blinded, prospective manner. The clinical significance of abnormalities was scored subjectively and receiver operator characteristic curve analysis was performed. RESULTS: In 69 of 91 patients (76%), no cause of haematuria was identified. In 22 of 91 patients (24%), the cause of haematuria was identified as follows: transitional cell cancer of the bladder (n = 15). urinary tract stones (n = 3), cystitis (n = 2), haemorrhagic pyelitis (n = 1) and benign ureteral stricture (n = 1). With IV urography, there were 15 true-positive, seven false-negative and three false-positive interpretations. With CT, there were 18 true-positive, four false-negative and two false-positive interpretations. There was no significant difference between IV and CT urography for the significance of the positive interpretations (n = 0.47). CONCLUSION: Excretory phase CT urography was comparable with IV urography for evaluation of the urinary tract in patients with painless haematuria. However, the study population did not include any upper tract cancers. (C) 2003 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP O'Malley, ME (reprint author), Toronto Gen Hosp, Dept Med Imaging, ESI-401A,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. NR 19 TC 31 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2003 VL 58 IS 4 BP 294 EP 300 DI 10.1016/S0009-9260(02)00464-6 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 669JC UT WOS:000182347300005 PM 12662950 ER PT J AU Harisinghani, MG Wittenberg, J Blake, MA Chen, S Jhaveri, K Mueller, PR AF Harisinghani, MG Wittenberg, J Blake, MA Chen, S Jhaveri, K Mueller, PR TI Halo sign: Useful CT sign for differentiating benign from malignant colonic disease SO CLINICAL RADIOLOGY LA English DT Article DE computed tomography; halo sign; colonic disease ID COMPUTED-TOMOGRAPHY; CROHNS-DISEASE; BOWEL WALL; COLITIS; CANCER; CARCINOMA; DIAGNOSIS; FEATURES; TRACT AB AIM: To evaluate the halo sign for accurately distinguishing benign from malignant colonic wall thickening. MATERIALS AND METHODS: Computed tomography (CT) examinations of 92 patients (70 men; 22 women; mean age 57 years) with pathologically proven colonic wall thickening (51 benign and 41 malignant) were retrospectively reviewed in a blinded fashion. The affected segment was assessed for presence of the halo sign, degree and uniformity of thickness and density of the intramural stratum. RESULTS: The halo sign was present in 74.5% (38/51) patients with benign and 7.3% (3/41) patients with malignant bowel disease. The presence of the halo sign was 75.4% sensitive and 92.5% specific for benign bowel wall thickening. All 38 benign halos showed uniform, continuous stratification; only one of three malignant halos met the strict criteria for benign halo. CONCLUSION: The halo sign is a moderately sensitive and highly specific sign for distinguishing benign from malignant bowel wall thickening. However, it is not pathognomonic for benign disease. Detailed analysis of halo characteristics is necessary to improve the usefulness of this finding. (C) 2003 The Royal College of Radiologists. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2003 VL 58 IS 4 BP 306 EP 310 DI 10.1016/S0009-9260(02)00520-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 669JC UT WOS:000182347300007 PM 12662952 ER PT J AU Belton, AL Saini, S Liebermann, K Boland, GW Halpern, EF AF Belton, AL Saini, S Liebermann, K Boland, GW Halpern, EF TI Tumour size measurement in an oncology clinical trial: Comparison between off-site and on-site measurements SO CLINICAL RADIOLOGY LA English DT Article DE diagnostic radiology; observer performance; images; interpretation; efficacy study ID CANCER; CAPECITABINE; ERROR AB AIM: To evaluate the degree of variability between lesion measurements obtained by a single observer compared with multiple observers, and in selected cases evaluate which of the two measurements more accurately represented the lesion size. MATERIALS AND METHODS: In this study we compared the performance of a single off-site observer to multiple on-site observers during measurement of 300 abdominal and thoracic lesions. Lesion measurements that were larger than 1 cm(2), differed by more than 50%, but by less than 100%, were compared by a single adjudicator, who was blinded to the measurement source (n = 46) RESULTS: Measurements of the 300 lesions differed by an average of 109% (SD 251%). Of 266 lesions larger than 1 cm(2), results of the single observer compared with multiple observers differed by more than 10% for 249 lesions, more than 30% for 169 lesions, more than 50% for 126 lesions, and more than 100% for 66 lesions. Forty-six lesions were compared by the adjudicator. The adjudicator selected the measurement of the single observer for 37 lesions (80.4%), and the measurement determined by one of the multiple observers for nine lesions (19.6%; p = 0.00002). CONCLUSION: Measurement of lesion size by a single observer compared with multiple observers reveals a high degree of variability. An adjudicator selected the measurement of the single observer more frequently than that of multiple observers, with statistical significance. These findings suggest that studies designed to quantify imaging features should limit the number of observers. (C) 2003 Published by Elsevier Science Ltd on behalf of The Royal College of Radiologists. C1 Radiol Associates Wausau, Wausau, WI 54401 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. WorldCare Inc, Cambridge, MA USA. RP Belton, AL (reprint author), Radiol Associates Wausau, Suite 106,2800 Westhill Dr, Wausau, WI 54401 USA. NR 10 TC 28 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2003 VL 58 IS 4 BP 311 EP 314 DI 10.1016/S0009-9260(02)00577-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 669JC UT WOS:000182347300008 PM 12662953 ER PT J AU Shulman, DG Amdahl, L Washington, C Graves, A AF Shulman, DG Amdahl, L Washington, C Graves, A TI A combined analysis of two studies assessing the ocular comfort of antiallergy ophthalmic agents SO CLINICAL THERAPEUTICS LA English DT Article DE seasonal allergic conjunctivitis; pemirolast; cromolyn; ketorolac; nedocromil; comfort ID SEASONAL ALLERGIC CONJUNCTIVITIS; PEMIROLAST; TILAVIST; EFFICACY; SAFETY; SODIUM AB Background: Many topical agents with similar efficacies are available for the treatment of ocular allergies. In addition to efficacy, comfort is an important criterion because it affects overall patient satisfaction, compliance, and in turn efficacy. Objective: The goal of this study was to compare the comfort profiles of pemirolast, ketorolac, cromolyn, and nedocromil ophthalmic solutions using combined results from 2 separate clinical trials. Methods: Two clinical trials were conducted. Adults with asymptomatic eyes were included in the first study. In this single-center, 7-day, prospective, double-blind, single-dose, crossover, parallel-group study, subjects were randomized to be bilaterally dosed with pemirolast, cromolyn, or ketorolac at each of 3 visits. Study 2 was a single-center, I-day, prospective, randomized, double-blind, single-dose, contralateral, active-control study in which subjects received pemirolast in I eye and nedocromil in the contralateral eye. In both studies, subjects completed a pre- and postinstillation ocular comfort questionnaire: the primary variable was overall ocular discomfort, measured on a 4-point scale original to these studies (0 = absent, I = mild, 2 = moderate, 3 = severe). Half-increments were permitted. Secondary variables included burning/stinging, foreign-body sensation, tearing, and photophobia. Results: Forty-five subjects (29 women, 16 men; mean [SD] age, 35.9 [12.6] years) were enrolled in study 1; 48 subjects (30 women, 18 men; mean [SD] age, 33.6 [10.2] years) were enrolled in study 2. In study 1, overall discomfort was significantly lower with pemirolast than with cromolyn (P = 0.001) or ketorolac (P < 0.001). In terms of overall discomfort, the number of subjects with a clinically significant increase (greater than or equal to1 unit) in score was significantly lower with pemirolast compared with ketorolac (P = 0.021). Burning/stinging and tearing were also significantly lower with pemirolast than with cromolyn (P < 0. 00 1 and P = 0. 0 14, respectively). Mean changes in score compared with preinstillation were consistently lower with pemirolast than with cromolyn for both burning/stinging (P < 0.001) and tearing (P = 0.014). In study 2, overall discomfort was significantly lower with pemirolast than with nedocromil (P < 0.001). The number of subjects with a clinically significant increase in overall discomfort score was significantly lower with pemirolast than with nedocromil (P = 0.007). No changes in ocular tolerability parameters were reported in either study Conclusion: In these single-dose studies, pemirolast was found to be significantly more comfortable than cromolyn, ketorolac, or nedocromil. Copyright (C) 2003 Excerpta Medica, Inc. C1 Univ Texas, Hlth Sci Ctr, Audie Murphy Vet Adm Hosp, San Antonio, TX USA. Santen Inc, Napa, CA USA. RP Shulman, DG (reprint author), 999 E Basse Rd,Suite 127, San Antonio, TX 78209 USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD APR PY 2003 VL 25 IS 4 BP 1096 EP 1106 DI 10.1016/S0149-2918(03)80069-3 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 674GC UT WOS:000182628200004 PM 12809959 ER PT J AU Laposata, M Johnson, SM AF Laposata, M Johnson, SM TI Assessment of the stability of dalteparin sodium in prepared syringes for up to thirty days: an in vitro study SO CLINICAL THERAPEUTICS LA English DT Article DE low-molecular-weight heparin; anticoagulants; dalteparin; stability; deep-vein thrombosis; anti-factor Xa; storage; syringes ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARINS; UNFRACTIONATED HEPARIN; OUTPATIENT TREATMENT; VENOUS THROMBOSIS; HOME; ENOXAPARIN AB Background: If a low-molecular-weight heparin (LMWH) injectable formulation maintains its stability for up to 30 days, substantial cost reductions in hospital stay could be achieved with its use on an outpatient basis in patients who might otherwise be treated with IV heparin as inpatients. Objective: This study was designed to assess the stability for up to 30 days of injectable solutions of the LMWH dalteparin sodium when repackaged in plastic syringes. Methods: In the first part of the study, 1-mL and 3-mL plastic syringes were filled with the contents of a 10,000-IU/mL dalteparin ampule or a 25,000-IU/mL dalteparin multidose vial. In a separate part of the study, 1-mL and 3-mL syringes were filled with doses of 7500 IU and 10,000 IU, respectively, from a 10,000-IU/mL multidose vial. After the syringes were brought to room temperature or 4degreesC, the stability of dalteparin was assessed over 30 days by measuring anti-factor Xa levels. Results: No significant loss of dalteparin activity was found for up to 30 days in the syringes after storage at room temperature or 4degreesC. The solutions retained antifactor Xa activity at room temperature and under refrigeration. Conclusion: Dalteparin is stable for up to 30 days when stored at room temperature or 4degreesC. The findings suggest that preparation of a postdischarge supply of dalteparin is feasible, contributing to more convenient and effective management of outpatients at risk for thrombotic complications. Copyright (C) 2003 Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Room 235,Gray Bldg,Fruit ST, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD APR PY 2003 VL 25 IS 4 BP 1219 EP 1225 DI 10.1016/S0149-2918(03)80078-4 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 674GC UT WOS:000182628200013 PM 12809968 ER PT J AU Geller, DA Coffey, B Faraone, S Hagermoser, L Zaman, NK Farrell, CL Mullin, B Biederman, J AF Geller, DA Coffey, B Faraone, S Hagermoser, L Zaman, NK Farrell, CL Mullin, B Biederman, J TI Does comorbid attention-deficit/hyperactivity disorder impact the clinical expression of pediatric obsessive-compulsive disorder? SO CNS SPECTRUMS LA English DT Article ID CHILDREN; ADOLESCENTS; SCALE; PHENOMENOLOGY; RELIABILITY; VALIDITY; ADULTS; ONSET AB What is the impact of attention-deficit/hyperactivity disorder (ADHD) on the phenotypic expression of pediatric obsessive-compulsive disorder (OCD). We examined phenotypic features, and functional and clinical correlates in youths with OCD, with and without comorbid ADHD, from a large sample of consecutively referred pediatric psychiatry patients. Although comorbid ADHD had no meaningful impact on the phenotypic expression or clinical correlates of OCD, it was associated with higher rates Of compromised educational functioning compared with other OCD youths. Our findings suggest that the OCD phenotype runs true and is not impacted by comorbid ADHD in youths diagnosed with both OCD and ADHD. In such affected youths, both disorders contribute to morbid dysfunction and require treatment. More work is needed to determine whether OCD plus ADHD represents a developmentally and etiologically distinct form of the OCD syndrome. C1 Massachusetts Gen Hosp, Obsess Compuls Disorders Clin Res Program, Boston, MA 02114 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol Res Off, Boston, MA 02114 USA. McLean Hosp, Joint Program Pediat Psychopharmacol Res Off, Belmont, MA 02178 USA. McLean Hosp, Pediat Tourettes Syndrome Clin, Belmont, MA 02178 USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Obsess Compuls Disorders Clin Res Program, 15 Pkman St,WACC 725, Boston, MA 02114 USA. EM geller@mclean.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K08-MH01481] NR 26 TC 36 Z9 37 U1 6 U2 6 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD APR PY 2003 VL 8 IS 4 BP 259 EP 264 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 710MH UT WOS:000184683600009 PM 12679741 ER PT J AU Ganis, G Kutas, M AF Ganis, G Kutas, M TI An electrophysiological study of scene effects on object identification SO COGNITIVE BRAIN RESEARCH LA English DT Article DE object identification; event-related potentials; visual scenes; context effects; N400 ID EVENT-RELATED POTENTIALS; MEDIAL TEMPORAL-LOBE; VISUAL-EVOKED POTENTIALS; SELECTIVE ATTENTION; BRAIN POTENTIALS; INFEROTEMPORAL CORTEX; SCALP DISTRIBUTIONS; BOOTSTRAP METHOD; MACAQUE MONKEY; WORD TYPE AB The meaning of a visual scene influences the identification of visual objects embedded in it. We investigated the nature and time course of scene effects on object identification by recording event-related brain potentials (ERPs) and response times (RTs). In three experiments, participants identified objects within a scene that were either semantically congruous (e.g., a pot in a kitchen) or incongruous (e.g., a desk in a river). As expected. RTs were faster for congruous than incongruous objects. The earliest sign of reliable scene congruity effects in the ERPs (greater positivity for congruous pictures between 300 and 500 ms) was around 300 ms. Both the morphology and time course of the N390 scene congruity effect are reminiscent of the N400 sentence congruity effect typically observed in sentence context paradigms, suggesting a functional similarity of the neural processes involved. Overall, these results support theories postulating that visual scenes do not appreciably affect object identification processes before associated semantic information is activated. We speculate that the N390 scene congruity effect reflects the action of visual scene schemata stored in the anterior temporal lobe. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02139 USA. Univ Calif San Diego, Dept Cognit Sci & Neurosci, La Jolla, CA 92093 USA. RP Ganis, G (reprint author), Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. OI Ganis, Giorgio/0000-0001-6175-2618 NR 79 TC 93 Z9 94 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD APR PY 2003 VL 16 IS 2 BP 123 EP 144 DI 10.1016/S0926-6410(02)00244-6 PG 22 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 697ZC UT WOS:000183972300001 ER PT J AU Martin, TR Nakamura, M Matute-Bello, G AF Martin, TR Nakamura, M Matute-Bello, G TI The role of apoptosis in acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Margaux Conference on Critical Illness CY NOV 13-17, 2002 CL SINTRA, PORTUGAL DE acute lung injury; acute respiratory distress syndrome; apoptosis; Fas ligand; inflammation; neutrophils ID RESPIRATORY-DISTRESS SYNDROME; EPITHELIAL-CELL APOPTOSIS; FAS LIGAND; NEUTROPHIL APOPTOSIS; PULMONARY FIBROSIS; II PNEUMOCYTES; SOLUBLE FORM; TGF-BETA; IN-VIVO; INFLAMMATION AB Objective: To discuss current aspects of our understanding of the role of apoptosis in lung injury. Data Sources: Review of English language literature. Data Summary: Apoptosis is a process that produces timely death in senescent cells. Apoptosis is important in developmental biology and in remodeling of tissues during repair. Many apoptosis pathways converge in intracellular protease cascades that lead to DNA cleavage and cell death. Apoptosis pathways can be triggered by surface receptors, which interact with soluble proteins or membrane-bound proteins, such as Fas ligand. Fas ligand accumulates in soluble form at sites of tissue inflammation and has the potential to initiate apoptosis of leukocytes, epithelial cells, and other parenchymal cells. Dysregulation of apoptosis pathways could contribute to the epithelial injury that is characteristic of acute lung injury in humans. The effects of Fas ligand are modulated by factors in lung fluids, such as cytokines (e.g., transforming growth factor-beta, surfactant protein A, and angiotensin II) and a specific Fas ligand decoy receptor (DcR3). Conclusion. Strategies to block apoptosis pathways could be useful in limiting some forms of acute lung injury in humans. C1 VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Martin, TR (reprint author), VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL70840, HL30542, HL65892] NR 55 TC 100 Z9 112 U1 1 U2 8 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 APR PY 2003 VL 31 IS 4 SU S BP S184 EP S188 DI 10.1097/01.CCM.0000057841.33876.B1 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 672HG UT WOS:000182514700002 PM 12682438 ER PT J AU Thompson, BT AF Thompson, BT TI Glucocorticoids and acute lung injury SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Margaux Conference on Critical Illness CY NOV 13-17, 2002 CL SINTRA, PORTUGAL DE adrenal; cortisol; cytokines; glucocorticoid; hypothalamic-pituitary-adrenal axis ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE ADRENAL INSUFFICIENCY; HIGH-DOSE CORTICOSTEROIDS; SEPTIC SHOCK; CORTISOL RESPONSE; ADRENOCORTICAL RESPONSIVENESS; HYDROCORTISONE; MORTALITY; FAILURE; THERAPY AB Objectives: To describe hypothalamic-pituitary-adrenal (HPA) activation and the role of glucocorticoids in immune modulation during critical illness, and to review clinical trials of pharmacologic and "replacement"' doses of glucocorticoids in early and late acute respiratory distress syndrome (ARDS) and sepsis. Data Extraction and Synthesis: Selected review of published literature (1963 to present), clinical trials, and meta-analyses. Data Summary: HPA axis activation is an important component of the compensatory anti-inflammatory response to critical illness. Cortisol supports vascular tone and endothelial integrity, modulates a large number of proinflammatory cytokines, and suppresses phospholipase A(2), cyclo-oxygenase, and nitric oxide synthase. Cortisol has putative antifibrotic activities, including inhibition of fibroblast growth and collagen deposition and stimulation of T-cell and monocyte apoptosis. During critical illness, neurohumoral factors, cytokines, endothelin, and atrial natriuretic peptide all may participate in HPA axis activation, resulting in elevated plasma cortisol production and plasma concentrations. In general, cortisol concentrations correlate with severity of illness, and higher plasma concentrations are associated with a poorer outcome. Failure of adrenocorticotropic hormone to augment plasma cortisol appears to be a poor prognostic finding in vasopressor-dependent sepsis and may indicate "relative adrenal insufficiency." Replacement glucocorticoid/mineralocorticoid therapy over 7 days appears to be beneficial in such individuals. However, a meta-analysis of high-dose, short-course glucocorticoid treatment involving 1,297 patients with sepsis enrolled in nine trials showed a trend toward harm, and four trials in patients with, or at risk for, ARDS showed no benefit or a greater likelihood of progression to ARDS. In contrast, observational studies and one small randomized controlled trial suggest that lower pharmacologic doses of glucocorticoids given late (>1 wk) in the course of ARDS may be beneficial. The National Heart, Lung, and Blood Institute's ARDS Network currently is testing the use of methylprednisolone in late ARDS. This study was reviewed by an independent data safety monitoring board for safety and efficacy after enrolling 60 and 120 patients and is currently ongoing. Conclusion: Current evidence indicates that short-duration, high-dose glucocorticoid therapy is not effective for early ARDS or severe sepsis. One small randomized, controlled trial suggests that moderate doses of glucocorticoids may be beneficial for patients with late ARDS; a much larger randomized controlled trial is ongoing. Some patients with pressor-dependent severe sepsis appear to have relative adrenal insufficiency and benefit from replacement glucocorticoid/mineralocorticoid therapy. The accuracy of the diagnostic criteria for, and the prevalence of, relative adrenal insufficiency in patients with acute lung injury/ARDS is unknown. It is also unclear whether such a response, if present, predisposes patients to ongoing lung inflammation and the development of late fibroproliferative ARDS, or if it is predictive of a beneficial response to steroids. Studies of HPA axis activation and the role of relative adrenal insufficiency on the outcome of patients with acute lung injury are needed. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 46 TC 61 Z9 75 U1 1 U2 5 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 APR PY 2003 VL 31 IS 4 SU S BP S253 EP S257 DI 10.1097/01.CCM.0000057900.19201.55 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 672HG UT WOS:000182514700013 PM 12682449 ER PT J AU Schapira, L AF Schapira, L TI Communication skills training in clinical oncology: the ASCO position reviewed and an optimistic personal perspective SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE communication; psycho-oncology; American Society of Clinical Oncology; ethics ID BREAKING BAD-NEWS; PSYCHO-ONCOLOGY; ILLNESS; CANCER AB As a result of the emergence of patient-centered care and a considerable body of data in psycho-oncology, cancer specialists are now beginning to recognize the value of improving their communication skills. Training models involving residential workshops are briefly reviewed. A historical perspective of educational programs offered by the American Society of Clinical Oncology is included to emphasize the growing acceptance by this professional society of the need to provide training for cancer specialists at all levels of professional experience. The author's personal account serves to highlight the integration of philosophy, ethics' and psychology in the daily practice of medicine. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 28 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD APR PY 2003 VL 46 IS 1 BP 25 EP 31 DI 10.1016/S1040-8428(03)00003-9 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 668GZ UT WOS:000182283100004 PM 12672516 ER PT J AU Eroglu, A Lawitts, JA Toner, M Toth, TL AF Eroglu, A Lawitts, JA Toner, M Toth, TL TI Quantitative microinjection of trehalose into mouse oocytes and zygotes, and its effect on development SO CRYOBIOLOGY LA English DT Article DE quantitative microinjection; mouse oocyte; egg; trehalose; toxicity; development; hypertonic medium ID INTRACELLULAR TREHALOSE; DESICCATION TOLERANCE; MAMMALIAN-CELLS; ORGANIC OSMOLYTES; EMBRYOS; CRYOPRESERVATION; ANHYDROBIOSIS; ACCUMULATION; OSMOLARITY; PREGNANCY AB Sugars such as trehalose are effectively used by various organisms as protective agents to undergo anhydrobiosis and cryobiosis. The objective of this study was first to establish a method for quantitative delivery of trehalose as a model sugar into oocytes, and then to evaluate its effect on development of mouse zygotes. To this end, a quantitative microinjection technique was developed using volumetric response of microdroplets suspended in dimethylpolysilaxene. To verify accuracy of this technique, both microdroplets and oocytes were microinjected with fluorophore-labeled dextran. Thereafter, injection volumes were calculated from fluorescence intensity, and volumetric responses of both microdroplets and oocytes. Comparison of calculated injection volumes revealed that this technique reflects microinjection into oocytes with pL-accuracy. The next series of experiments focused on toxicity of injection buffers (i.e., 10 mM Tris and 15 mM Hepes) and trehalose. Microinjection of Hepes and Tris buffer in the presence of 0.1 M trehalose resulted in blastocyst rates of 86 and 72%, respectively, without a significant difference when compared to controls (86%). In subsequent experiments, Hepes was used as the injection buffer, and embryonic development of zygotes was studied as a function of intracellular trehalose concentrations. Microinjection of trehalose up to 0.15 M resulted in development to blastocyst stage similar to controls (85 and 87%, respectively) while the blastocyst rate was significantly decreased (43%) in the presence of 0.20 M intracellular trehalose. When transferred to foster mothers, trehalose-injected zygotes (0.1 M) implanted and developed to day 16 fetuses similar to controls, healthy pups were born. The findings of this study suggest that trehalose at effective intracellular concentrations does not impair development of mouse zygotes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burn Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Toth, TL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 38 TC 40 Z9 49 U1 3 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD APR PY 2003 VL 46 IS 2 BP 121 EP 134 DI 10.1016/S0011-2240(03)00018-X PG 14 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 671DD UT WOS:000182449300002 PM 12686202 ER PT J AU Walsh, SR Bhardwaj, N Gandhi, RT AF Walsh, SR Bhardwaj, N Gandhi, RT TI Dendritic cells and the promise of therapeutic vaccines for human immunodeficiency virus (HIV)-1 SO CURRENT HIV RESEARCH LA English DT Review DE therapeutic vaccine; immunotherapy; human immunodeficiency virus; dendritic cell ID CYTOTOXIC T-LYMPHOCYTES; ACTIVE ANTIRETROVIRAL THERAPY; PERIPHERAL LYMPHOID ORGANS; RESPONSES IN-VITRO; C-TYPE LECTIN; MHC CLASS-II; IMMUNE-RESPONSES; DC-SIGN; CANCER-IMMUNOTHERAPY; PROSTATE-CANCER AB Treatment of human immunodeficiency virus (HIV)-1 infection with potent antiretroviral medications has provided considerable clinical benefit. However because of the limitations of current therapy, innovative approaches are needed to better control HIV-1 infection. Several studies have suggested that robust CD4+ T helper and CD8+ T cell responses may contribute to the immunologic control of HIV-1 infection in certain individuals. Most chronically infected patients, however, cannot control the infection and may benefit from stimulation of cellular immunity with immunotherapy. Dendritic cells (DCs) are potent professional antigen-presenting cells (APCs) and have a central role in directing the adaptive immune response to pathogens. The ability of DCs to stimulate naive T cells has long been thought to be crucial in initiating an effective immune response. As DCs are uniquely situated at the interface between the innate and adaptive immune systems, they are currently under intense scrutiny as potential adjuvants for vaccines in many clinical settings. Studies in healthy volunteers and patients with cancer have shown that antigen-pulsed DCs can boost both CD8+ and CD4+ T cell responses in vivo. Based on these promising findings, ex vivo antigen-pulsed DCs are being actively investigated in studies aimed at developing a therapeutic vaccine for individuals with HIV-1 infection. C1 Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. Partners AIDS Res Ctr, Boston, MA USA. NYU, Sch Med, New York, NY USA. RP Walsh, SR (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM swalsh@partners.org FU NIAID NIH HHS [AI-44628, AI-01443-04, AI-39516, AI-007387-12] NR 159 TC 8 Z9 9 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD APR PY 2003 VL 1 IS 2 BP 205 EP 216 DI 10.2174/1570162033485285 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 761VD UT WOS:000187935400005 PM 15043203 ER PT J AU Streams, BN Williams, JM Moschella, SM AF Streams, BN Williams, JM Moschella, SM TI Mid-dermal elastolysis SO CUTIS LA English DT Article; Proceedings Paper CT Meeting of the New-England-Dermatological-Society CY FEB 09, 2002 CL BOSTON, MASSACHUSETTS SP New England Dermatolog Soc AB Mid-dermal elastolysis (MDE), which presents as fine wrinkling of the skin or perifollicular papules, is extremely rare. This entity is distinguished from other elastolytic disorders by its characteristic bandlike loss of elastic fibers limited to the mid dermis. We report a case of MDE that developed gradually in an otherwise healthy woman without prior cutaneous disease. The current theories on the pathogenesis of MDE also are discussed. C1 Harvard Univ, Sch Med, Lahey Clin, Dept Dermatol, Burlington, MA USA. RP Streams, BN (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett Hall 6R, Boston, MA 02114 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD APR PY 2003 VL 71 IS 4 BP 312 EP 314 PG 3 WC Dermatology SC Dermatology GA 667FQ UT WOS:000182220900010 PM 12729097 ER PT J AU Chen, W Liang, YQ Deng, WJ Shimizu, K Ashique, AM Li, E Li, YP AF Chen, W Liang, YQ Deng, WJ Shimizu, K Ashique, AM Li, E Li, YP TI The zinc-finger protein CNBP is required for forebrain formation in the mouse SO DEVELOPMENT LA English DT Article DE CNBP; retroviral insertional mutagenesis; forebrain patterning; AVE; ADE; ANE; cell proliferation defects; Myc expression ID ACID-BINDING-PROTEIN; ANTERIOR NEURAL PLATE; GERM LAYER FORMATION; C-MYC; VISCERAL ENDODERM; DEFINITIVE ENDODERM; EMBRYONIC LETHALITY; PRIMITIVE STREAK; GENE-EXPRESSION; XENOPUS-LAEVIS AB Mouse mutants have allowed us to gain significant insight into axis development. However, much remains to be learned about the cellular and molecular basis of early forebrain patterning. We describe a lethal mutation mouse strain generated using promoter-trap mutagenesis. The mutants exhibit severe forebrain truncation in homozygous mouse embryos and various craniofacial defects in heterozygotes. We show that the defects are caused by disruption of the gene encoding cellular nucleic acid binding protein (CNBP); Cnbp transgenic mice were able to rescue fully the mutant phenotype. Cnbp is first expressed in the anterior visceral endoderm (AVE) and, subsequently, in the anterior definitive endoderm (ADE), anterior neuroectoderm (ANE), anterior mesendoderm (AME), headfolds and forebrain. In Cnbp(-/-) embryos, the visceral endoderm remains in the distal tip of the conceptus and the ADE fails to form, whereas the node and notochord form normally. A substantial reduction in cell proliferation was observed in the anterior regions of Cnbp(-/-) embryos at gastrulation and neural-fold stages. In these regions, Myc expression was absent, indicating CNBP targets Myc in rostral head formation. Our findings demonstrate that Cnbp is essential for the forebrain induction and specification. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR44741, AR-48133-01] NR 57 TC 40 Z9 42 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 2003 VL 130 IS 7 BP 1367 EP 1379 DI 10.1242/dev.00349 PG 13 WC Developmental Biology SC Developmental Biology GA 663GX UT WOS:000181998800014 PM 12588852 ER PT J AU Grandbarbe, L Bouissac, J Rand, M de Angelis, MH Artavanis-Tsakonas, S Mohier, E AF Grandbarbe, L Bouissac, J Rand, M de Angelis, MH Artavanis-Tsakonas, S Mohier, E TI Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process SO DEVELOPMENT LA English DT Article DE neural stem cells; Notch-delta signaling; cell fate specification; neurospheres; mouse ID CENTRAL-NERVOUS-SYSTEM; PROGENITOR CELLS; OLIGODENDROCYTE DIFFERENTIATION; DROSOPHILA-MELANOGASTER; GLIAL DIFFERENTIATION; NEUROGENESIS; LIGAND; FATE; MAINTENANCE; EGF AB We examined the role of Notch signaling on the generation of neurons and glia from neural stem cells by using neurospheres that are clonally derived from neural stem cells. Neurospheres prepared from Dll1(lacZ/lacZ) mutant embryos segregate more neurons at the expense of both oligodendrocytes and astrocytes. This mutant phenotype could be rescued when Dll1(lacZ/lacZ) spheres were grown and/or differentiated in the presence of conditioned medium from wild-type neurospheres. Temporal modulation of Notch by soluble forms of ligands indicates that Notch signaling acts in two steps. Initially, it inhibits the neuronal fate while promoting the glial cell fate. In a second step, Notch promotes the differentiation of astrocytes, while inhibiting the differentiation of both neurons and oligodendrocytes. C1 CNRS, Lab Neurobiol Dev & Regenerat, F-67000 Strasbourg, France. Univ Vermont, Coll Med, Dept Anat & Neurobiol, Burlington, VT 05405 USA. GSF, Inst Mammalian Genet, D-85764 Neuherberg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Cell Biol, Charlestown, MA 02129 USA. Coll France, Lab Embryol Cellulaire & Mol, F-94736 Nogent Sur Marne, France. RP Mohier, E (reprint author), CNRS, Lab Neurobiol Dev & Regenerat, 5 Rue Blaise Pascal, F-67000 Strasbourg, France. RI Hrabe de Angelis, Martin/F-5531-2012 OI Hrabe de Angelis, Martin/0000-0002-7898-2353 NR 36 TC 164 Z9 178 U1 1 U2 8 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 APR PY 2003 VL 130 IS 7 BP 1391 EP 1402 DI 10.1242/dev.00374 PG 12 WC Developmental Biology SC Developmental Biology GA 663GX UT WOS:000181998800016 PM 12588854 ER PT J AU Houghton, L Freeman, A Morgan, BA AF Houghton, L Freeman, A Morgan, BA TI Expression and regulation of groucho-related genes in the embryonic chicken feather bud SO DEVELOPMENTAL DYNAMICS LA English DT Article DE groucho-related gene; grg; chicken; embryo; feather bud; beta-catenin; BMP ID TRANSCRIPTIONAL REPRESSORS; DIFFERENTIATION; WNT; INTERACT; ENHANCER; SIGNALS; NOTCH; FATE; SKIN; BMPS AB The groucho-related gene (Grg) products modulate the transcriptional response to several extracellular signals, including the Writs. In an effort to define the roles of Grgs in the morphogenesis of the feather bud, cDNAs encoding members of the Grg family were cloned from embryonic chick skin. In situ hybridization was used to localize transcripts for cGrg2, Grg3, Grg4, and Grg5 in embryos from day 6 through day 9. Expression of cGrg2, 3, and 5 is detected throughout the initial epidermal placode. As the buds mature, expression becomes limited to the posterior halves and eventually to the distal tip of the outgrowing bud. This pattern and the effects of forced activation of the bone morphogenetic protein and beta-catenin signal transduction pathways on Grg gene expression suggest that these genes act downstream of the early activation of the beta-catenin pathway that initiates placode formation. Induction of Grg genes by beta-catenin may serve as a negative feedback to modulate pathway activation while also altering the activity of other transduction pathways involved in bud patterning. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NICHD NIH HHS [1 R01 HD38465 A 01] NR 25 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 2003 VL 226 IS 4 BP 587 EP 595 DI 10.1002/DVDY.10268 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 663GW UT WOS:000181998700002 PM 12666196 ER PT J AU Penson, DF Latini, DM Lubeck, DP Wallace, KL Henning, JM Lue, TF AF Penson, DF Latini, DM Lubeck, DP Wallace, KL Henning, JM Lue, TF TI Do impotent men with diabetes have more severe erectile dysfunction and worse quality of life than the general population of impotent patients? Results from the Exploratory Comprehensive Evaluation of Erectile Dysfunction (ExCEED) database SO DIABETES CARE LA English DT Article ID SILDENAFIL; TYPE-1 AB Objective-Little is known regarding how diabetic men with erectile dysfunction (ED) differ from the general population of impotent men. The primary objective of this study was to compare disease-specific health-related quality of life (HRQOL) and severity of ED in impotent men with and without diabetes. Research Design and Methods-Validated functional and HRQOL questionnaires (including the International Index of Erectile Function, the Sexual Self-Efficacy Scale, and the Psychological Impact of Erectile Dysfunction scales) were administered to patients in an ED disease registry. Men with ED and a history of diabetes (n=20) were compared with men with ED and no history of diabetes (n=90) at baseline and at the 12-month follow-up. Results-Diabetic impotent men reported worse erectile function and intercourse satisfaction at baseline, and ED had a greater impact on their emotional life-Diabetic men with ED had significantly different trends over time in the Erectile Function (P<0.001.), Intercourse Satisfaction (P<0.013), Sexual Desire (P<0.016), Overall Satisfaction (P<0.023), and the. Sexual Experience-Psychological Impact domains (P<0.002). In addition, there was a trend toward a difference over time in the Emotional Life-Psychological impact domain (P<0.0067). Conclusions-impotent men with diabetes present with worse ED than nondiabetic men with ED, resulting in worse disease-specific HRQOL in the diabetic men. Although diabetic patients initially respond well to ED treatment, responses do not appear to be durable over time. Therefore, clinicians must provide longer-term follow-up when treating ED in diabetic patients. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Penson, DF (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Urol Sect, 112-UR,1660 S Columbian Way, Seattle, WA 98108 USA. OI Latini, David/0000-0002-6161-4861 NR 16 TC 94 Z9 104 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2003 VL 26 IS 4 BP 1093 EP 1099 DI 10.2337/diacare.26.4.1093 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UP UT WOS:000185505300021 PM 12663579 ER PT J AU Malecki, MT Klupa, T Wolkow, P Bochenski, J Wanic, K Sieradzki, J AF Malecki, MT Klupa, T Wolkow, P Bochenski, J Wanic, K Sieradzki, J TI Association study of the vitamin D: 1alpha-hydroxylase (CYP1alpha) gene and type 2 diabetes mellitus in a Polish population SO DIABETES & METABOLISM LA English DT Article DE vitamin D 1alpha-hydroxylase; gene; polymorphism; type 2 diabetes ID D-DEFICIENCY RICKETS; INSULIN-SECRETION; ADIPOSE DIFFERENTIATION; GLUCOSE-TOLERANCE; MUTATIONS; POLYMORPHISMS; OBESITY; SUSCEPTIBILITY; NEPHROPATHY; CALCITRIOL AB Objectives: Type 2 diabetes mellitus (T2DM) is a complex disease. Genetic and environmental factors cooperate together to form its clinical picture. Polymorphisms in genes involved in the metabolism of vitamin D may influence susceptibility to T2DM. One of them is the vitamin D 1alpha-hydroxylase (CYP1alpha) gene. In this study we searched for the association of two markers, one in its intron 6 and the another one located upstream from the 5' end of CYP1alpha gene, with T2DM in a Polish population. Methods: Overall 522 individuals were included in this study: 291 T2DM patients and 231 controls. The sequences, which contain both examined variants, were amplified by polymerase chain reaction (PCR). The T --> C polymorphism in intron 6 was assessed by the dot-blotting method using P-32. Genotyping of the other variant in the 5' end of CYP1alpha gene was carried out by restriction fragment length polymorphism (RFLP) method. Since variants of both SNPs were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. The distribution of alleles, genotypes, haplotypes and haplotype combinations was compared between the groups by chi(2) test. Results: The frequency of T/C alleles of the 5' end variant was 81.7%/18.3% in T2DM patients and 82.8%/17.2% in the controls (chi(2) = 0.2, 1.d.f., p = 0.65). For a T --> C polymorphism in intron 6 the frequency of alleles was 65.1%/34.9% and 67.5%/32.5% in T2DM patients and controls, respectively (chi(2) = 0.413, 1.d.f., .p = 0.669). Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In stratified analysis, we observed that the T-C/T-T heterozygous haplotype combination was more prevalent in the subgroup of obese T2DM patients (BMI greater than or equal to 30) than in the controls (41.5% vs 28.6%, p = 0.01). Conclusions: Vitamin D 1alpha-hydroxylase is not a major gene for T2DM in a Polish population. However, this gene may be associated with T2DM in subjects with obesity. Thus, to definitely determine the role of this gene in T2DM further studies are necessary in other populations using larger sample size. C1 Jagiellonian Univ, Coll Med, Dept Metab Dis, PL-31501 Krakow, Poland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Malecki, MT (reprint author), Jagiellonian Univ, Coll Med, Dept Metab Dis, 15 Kopernika St, PL-31501 Krakow, Poland. FU FIC NIH HHS [1 R03 TW01351-01] NR 38 TC 12 Z9 12 U1 0 U2 1 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD APR PY 2003 VL 29 IS 2 BP 119 EP 124 DI 10.1016/S1262-3636(07)70017-4 PN 1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 683AK UT WOS:000183124400003 PM 12746631 ER PT J AU Chang, TI Horal, M Jain, SK Wang, F Patel, R Loeken, MR AF Chang, TI Horal, M Jain, SK Wang, F Patel, R Loeken, MR TI Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects SO DIABETOLOGIA LA English DT Article DE embryogenesis; diabetic pregnancy; oxidative stress; free radicals; neural tube defects; Pax-3; cell death; gene expression ID OXIDATIVE STRESS; VITAMIN-E; CONGENITAL-ANOMALIES; LIPID-PEROXIDATION; REDOX REGULATION; GLYCEMIC CONTROL; MOUSE EMBRYOS; CELL-DEATH; KAPPA-B; MALFORMATIONS AB Aims/hypothesis. Maternal diabetes increases oxidative stress in embryos. Maternal diabetes also inhibits expression of embryonic genes, most notably, Pax-3, which is required for neural tube closure. Here we tested the hypothesis that oxidative stress inhibits expression of Pax-3, thereby providing a molecular basis for neural tube defects induced by diabetic pregnancy. Methods. Maternal diabetes-induced oxidative stress was blocked with cc-tocopherol (vitamin E), and oxidative stress was induced with the complex III electron transport inhibitor, antimycin A, using pregnant diabetic or non-diabetic mice, primary cultures of neurulating mouse embryo tissues, or differentiating P19 embryonal carcinoma cells. Pax-3 expression was assayed by quantitative RT-PCR, and neural tube defects were scored by visual inspection. Oxidation-induced DNA fragmentation in P19 cells was assayed by electrophoretic analysis. Results. Maternal diabetes inhibited Pax-3 expression and increased neural tube defects, and (x-tocopherol blocked these effects. In addition, induction of oxidative stress with antimycin A inhibited Pax-3 expression and increased neural tube defects. In cultured embryo tissues, high glucose-inhibited Pax-3 expression, and this effect was blocked by alpha-tocopherol and GSH-ethyl ester, and Pax-3 expression was inhibited by culture with antimycin A. In differentiating P19 cells, antimycin A inhibited Pax-3 induction but did not induce DNA strand breaks. Conclusion/interpretation. Oxidative stress inhibits expression of Pax-3, a gene that is essential for neural tube closure. Impaired expression of essential developmental control genes could be the central mechanism by which neural tube defects occur during diabetic pregnancy, as well as other sources of oxidative stress. C1 Joslin Diabet Ctr, Sect Mol Biol & Complicat, Boston, MA 02215 USA. Louisiana State Univ, Med Ctr, Dept Pediat, Shreveport, LA USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Mol Biol & Complicat, 1 Joslin Pl, Boston, MA 02215 USA. OI Patel, Rakesh/0000-0002-1526-4303 FU NIDDK NIH HHS [DK52865, DK58300] NR 62 TC 97 Z9 103 U1 1 U2 13 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2003 VL 46 IS 4 BP 538 EP 545 DI 10.1007/s00125-003-1063-2 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 684HD UT WOS:000183198600015 PM 12739027 ER PT J AU Panhuysen, CIM Cupples, LA Wilson, PWF Herbert, AG Myers, RH Meigs, JB AF Panhuysen, CIM Cupples, LA Wilson, PWF Herbert, AG Myers, RH Meigs, JB TI A genome scan for loci linked to quantitative insulin traits in persons without diabetes: the Framingham Offspring Study SO DIABETOLOGIA LA English DT Article DE insulin; insulin resistance; diabetes mellitus; non-insulin-dependent; chromosome mapping; chromosomes; human; pair 9; chromosomes; human; pair 11; chromosomes; human; pair 17 ID HOMEOSTASIS MODEL ASSESSMENT; MELLITUS GENETICS FUSION; BODY-MASS INDEX; PIMA-INDIANS; GLUCOSE-TOLERANCE; OBESITY; RESISTANCE; GENES; RISK; SECRETION AB Aims/hypothesis. Hyperinsulinaemia and insulin resistance usually precede clinical hyperglycaemia and Type 2 diabetes. Thus, plasma insulin concentrations and insulin resistance are important quantitative traits associated with risk of Type 2 diabetes, and represent key measures for genetic analysis of the syndrome. Methods. We carried out a genome-wide search for loci related to plasma insulin concentrations and insulin resistance in 330 extended, community-based pedigrees from the Framingham Heart Study. Normalized deviates of the standardized residuals of plasma insulin concentrations in the fasting state, 2 h after oral glucose challenge and as a measure of insulin resistance were used in linkage analysis with the variance components model implemented in the computer program SOLAR. Results. The results suggest susceptibility loci influencing plasma concentrations of fasting insulin and insulin resistance on chromosomes 11 (LOD 2.43 at 85 cM close to D11S2002) and 17 (LOD 1.8 at 60 cM, close to D17S784); and susceptibility loci influencing 2-h plasma insulin concentrations on chromosomes 9 (LOD 2.8 at 80 cM, close to D9S922) and 19 (LOD 1.8 at 66 cM, close to D19S245). The results of the analysis of 1000 simulations of the trait and an unlinked marker suggest that in a genome scan of 401 markers fewer than one LOD score over 1 would be due to Type I error, and be a false positive. Conclusion/interpretation. We conclude that these suggestive regions for quantitative pre-diabetic insulin traits could contain major loci in the pathogenesis of Type 2 diabetes. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Gen Internal Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, Gen Internal Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083, P01-HL41484] NR 43 TC 39 Z9 39 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD APR PY 2003 VL 46 IS 4 BP 579 EP 587 DI 10.1007/s001250-003-1066-z PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 684HD UT WOS:000183198600020 PM 12739029 ER PT J AU Moriarty, AT Wilbur, D AF Moriarty, AT Wilbur, D TI Those gland problems in cervical cytology: Faith or fact? Observations from the Bethesda 2001 Terminology Conference SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Editorial Material ID NORMAL ENDOMETRIAL CELLS; POSTMENOPAUSAL WOMEN; ADENOCARCINOMA; SMEARS C1 AmeriPath Indiana, Indianapolis, IN 46219 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Cytopathol, Boston, MA 02114 USA. RP Moriarty, AT (reprint author), AmeriPath Indiana, 2560 N Shadeland Ave,Suite A, Indianapolis, IN 46219 USA. NR 12 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD APR PY 2003 VL 28 IS 4 BP 171 EP 174 DI 10.1002/dc.00000 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 662AN UT WOS:000181923300001 PM 12672090 ER PT J AU Chen, JF Schwarzschild, MA AF Chen, JF Schwarzschild, MA TI Gene knockout approach to adenosine A(2A) receptors in Parkinson's disease SO DRUG DEVELOPMENT RESEARCH LA English DT Article; Proceedings Paper CT 7th International Symposium on Adenosine and Adenine Nucleotides CY MAY 26-31, 2002 CL GOLD COAST, AUSTRALIA DE adenosine A(2A) receptor; Parkinson's disease; gene knockout; caffeine; adenosine A(2A) antagonist; dopamine D-2 receptor ID RAT STRIATAL MEMBRANES; C-FOS EXPRESSION; GABAERGIC SYNAPTIC-TRANSMISSION; CENTRAL-NERVOUS-SYSTEM; AGONIST H-3 CGS-21680; MPTP-TREATED MONKEYS; 6-HYDROXYDOPAMINE-LESIONED RATS; L-DOPA; CEREBRAL-ISCHEMIA; BASAL GANGLIA AB Recently, the adenosine A(2A) receptor (A(2A)R) has emerged as an attractive target for Parkinson's disease (PD) treatment by virtue of its coexpression with the dopamine D-2 receptor (D2R) in the striatum and its modulation of dopamine receptor-mediated functions. Moreover, the adenosine antagonist, caffeine, has recently been linked to,a reduced risk of developing PD in large prospective epidemiological studies, raising the possibility that caffeine and more specific adenosine antagonists may protect against dopaminergic neuron death. Recently, we and others have developed a series of A(2A)R and D2R knockout (KO) mouse models. These mutant mouse models with complete, specific genetic inactivation of A(2A)Rs and D(2)Rs overcome some of the intrinsic limitations of A(2A) antagonists and provide an opportunity to investigate A(2A)R's role in the development and treatment of PD. First, we used D-2 as well as A(2A)R KO mice to dissect the molecular mechanism of the A(2A)R's action by determining the dependence of A(2A)R function on D-2 receptors. The A(2A) antagonist (CSC) and the nonspecific antagonist caffeine induced motor stimulation in naive and reserpinized mice deficient in D-2 receptor. These results suggest that A(2A)R antagonists enhance motor function at least partially independent of D-2 receptors. Second, we explored the role of A(2A)Rs in the development of L-clopa-induced behavioral sensitization in unilaterally 6-hydroxydopamine-lesioned mice, an animal model of the behavioral and neurochemical features of dyskinesia in PD. Genetic inactivation of A(2A)Rs markedly attenuated the development and persistence of L-dopa-induced rotational behavioral sensitization and attenuated induction of dynorphin mRNA in the striatum. The results suggest that A(2A)R plays a critical role in the development of persistent maladaptive dyskinetic responses to chronic L-dopa treatment in PD. Finally, we showed that genetic inactivation of A(2A)Rs attenuates MPTP-induced depletion of dopamine and dopamine transporter (DAT) in the striatum and loss of dopaminergic neurons in the substantia nigra. Together, these results obtained with genetic approaches demonstrate that A(2A)R inactivation may have multiple therapeutic benefits for PD: motor enhancement through a partial D-2-independent mechanism, prevention of L-dopa-induced behavioral sensitization, and attenuation of dopaminergic neurodegeneration. The generation of tissue-specific and inducible A(2A) KO mouse models will further refine our understanding of the A(2A) receptor's role in the development and treatment of PD. (C) 2003 Wiley-Liss, Inc. C1 Boston Univ, Sch Med, Dept Neurol, Mol Neuropharmacol Lab, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Chen, JF (reprint author), Boston Univ, Sch Med, Dept Neurol, Mol Neuropharmacol Lab, 715 Albany St,C314, Boston, MA 02118 USA. EM chenjf@bu.edu NR 128 TC 5 Z9 7 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD APR PY 2003 VL 58 IS 4 BP 354 EP 367 DI 10.1002/ddr.10215 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 686XQ UT WOS:000183346600009 ER PT J AU Schlozman, SC AF Schlozman, SC TI The prescription challenge SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2003 VL 60 IS 7 BP 91 EP 93 PG 3 WC Education & Educational Research SC Education & Educational Research GA 665CP UT WOS:000182102300020 ER PT J AU Li, N Sioutas, C Cho, A Schmitz, D Misra, C Sempf, J Wang, MY Oberley, T Froines, J Nel, A AF Li, N Sioutas, C Cho, A Schmitz, D Misra, C Sempf, J Wang, MY Oberley, T Froines, J Nel, A TI Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE concentrated ambient particles; dithiothreitol assay; heme oxygenase-1; mitochondrial damage; oxidative stress; polycyclic aromatic hydrocarbon; ultrafine particles ID DIESEL EXHAUST PARTICLES; BRONCHIAL EPITHELIAL-CELLS; HEME OXYGENASE-1; AIR-POLLUTION; CYTOCHROME-P450 1A1; URBAN AIR; INFLAMMATION; EXPRESSION; MACROPHAGES; CHEMICALS AB The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 mum), fire (<2.5 μm), and ultrafine (<0.1 mum) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPS. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondrial where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. So Calif Particle Ctr & Supersite, Los Angeles, CA USA. Univ So Calif, Dept Civil & Environm Engn, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. William S Middleton Mem Vet Adm Med Ctr, Pathol Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. Univ Calif Los Angeles, Ctr Environm & Occupat Hlth, Los Angeles, CA USA. RP Nel, A (reprint author), Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RI Nel, Andre/J-2808-2012 FU NIEHS NIH HHS [R01-ES10553] NR 37 TC 969 Z9 1015 U1 51 U2 284 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 APR PY 2003 VL 111 IS 4 BP 455 EP 460 DI 10.1289/ehp.6000 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 665WM UT WOS:000182144300030 PM 12676598 ER PT J AU Hussein, MR Haemel, AK Wood, GS AF Hussein, MR Haemel, AK Wood, GS TI p53-related pathways and the molecular pathogenesis of melanoma SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Review DE cutaneous malignant melanoma; p53; ultraviolet radiation; UV ID TUMOR-SUPPRESSOR GENE; CUTANEOUS MALIGNANT-MELANOMA; CELL NUCLEAR ANTIGEN; DNA MISMATCH REPAIR; P53 GENE; PROTEIN EXPRESSION; MICROSATELLITE INSTABILITY; P53-MEDIATED APOPTOSIS; FAMILY PROTEINS; DYSPLASTIC NEVI AB Cutaneous malignant melanoma (CMM) is a life-threatening cancer that can have a poor prognosis with high metastatic potential. Its incidence is rapidly increasing worldwide. Its molecular alterations involve multiple pathways, including those related to p53. Since 1981, more than 380 papers containing the terms 'p53 and melanoma' as key words in the Abstract have been published in the literature. However, in spite of these extensive investigations, a review of p53 and associated genes in CMM is still lacking. To remedy this issue, this review seeks to provide a brief overview of p53 and discuss the genes targeted along its related pathways. (C) 2003 Lippincott Williams Wilkins. C1 Dept Dermatol, Madison, WI 53705 USA. Assiut Univ, Fac Med, Dept Pathol, Assiut, Egypt. Univ Wisconsin, William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Wood, GS (reprint author), Dept Dermatol, Madison, WI 53705 USA. FU NIAMS NIH HHS [AR02136] NR 108 TC 48 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD APR PY 2003 VL 12 IS 2 BP 93 EP 100 DI 10.1097/01.cej.0000062797.86004.35 PG 8 WC Oncology SC Oncology GA 677DW UT WOS:000182792500002 PM 12671532 ER PT J AU McGibbon, CA AF McGibbon, CA TI Toward a better understanding of gait changes with age and disablement: Neuromuscular adaptation SO EXERCISE AND SPORT SCIENCES REVIEWS LA English DT Review DE hip; knee; ankle; power and energy; compensation; neuromuscular; strength impairment; arthritis ID ENERGY-TRANSFER; COORDINATION; WALKING; SPEED AB Gait changes in the elderly, such as reduced step length and walking speed, are well documented but not well understood. This review explores the hypothesis that neuromuscular adaptations are a response to age-related impairments and play a key role in causing gait changes in the elderly, and that different neuromuscular adaptations may exist depending on the impairment and presence of comorbidities, such as knee arthritis. C1 Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Grad Program Phys Therapy, Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Inst Hlth Profess, RSL 010,40 Parkman St, Boston, MA 02114 USA. NR 14 TC 73 Z9 74 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-6331 J9 EXERC SPORT SCI REV JI Exerc. Sport Sci. Rev. PD APR PY 2003 VL 31 IS 2 BP 102 EP 108 DI 10.1097/00003677-200304000-00009 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 667UT UT WOS:000182253000009 PM 12715975 ER PT J AU Greenstein, S Krett, NL Kurosawa, Y Ma, CU Chauhan, D Hideshima, T Anderson, KC Rosen, ST AF Greenstein, S Krett, NL Kurosawa, Y Ma, CU Chauhan, D Hideshima, T Anderson, KC Rosen, ST TI Characterization of the MM.1 human multiple myeloma (MM) cell lines: A model system to elucidate the characteristics, behavior, and signaling of steroid-sensitive and -resistant MM cells SO EXPERIMENTAL HEMATOLOGY LA English DT Review ID FOCAL TYROSINE KINASE; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; GLUCOCORTICOID-INDUCED APOPTOSIS; OVERCOMES DRUG-RESISTANCE; GROWTH-FACTOR RECEPTOR-3; MESSENGER-RNA; PHOSPHOTYROSINE PHOSPHATASE; LYMPHOBLASTIC-LEUKEMIA; HEMATOPOIETIC-CELLS AB Multiple myeloma (MM) is a clonal B-lymphocyte malignancy, which is characterized by the accumulation of terminally differentiated antibody-producing cells in the bone marrow. Because current treatments offer only a median survival of 3 years, investigators continue to search for novel therapeutic strategies to combat the disease. Rational drug design is enhanced by understanding MM cell proliferation and key signaling pathways employed. In addition, a model system for preclinical evaluation of novel therapeutics is critical. Our laboratory has developed MM cell lines to study drug action and resistance, cell proliferation, and apoptosis. These cell lines are widely used in MM research. From a single MM patient, three separate cell lines were established that parallel the progression of the disease. These three cell lines, designated MM1S, MM1.R-E, and MM1.R-L, can be distinguished on the basis of their sensitivity to steroid hormones such as glucocorticoids (GCs). Utilization of these cell lines to study the etiology of MM, effects of chemotherapeutic agents, and development of clinical resistance, will provide us with vital information for the evolution of new and more efficacious therapeutics. The aim of this review is to summarize the morphological, biochemical, and growth characteristics of these cells, and to review the results from investigations of the MMA signaling pathways. This information will enhance the study, treatment, and eventual eradication of MM. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol,Dept Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Krett, NL (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol,Dept Med, 303 E Chicago Ave,8340 Olson Pavil, Chicago, IL 60611 USA. FU NCI NIH HHS [T32 CA70085]; PHS HHS [P0-1 78378, R0-1 50947, R0-1 85915] NR 90 TC 73 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD APR PY 2003 VL 31 IS 4 BP 271 EP 282 DI 10.1016/S0301-472X(03)00023-7 PG 12 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 667HC UT WOS:000182224400001 PM 12691914 ER PT J AU Letai, A AF Letai, A TI BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE apoptosis; BAD; BCL-2; BH3; BID; cancer; peptide ID REFRACTORY PROSTATE-CANCER; SMALL-MOLECULE INHIBITORS; CYTOCHROME-C RELEASE; B-CELL LYMPHOMA; PROTEIN EXPRESSION; MALIGNANT-MELANOMA; ANTISENSE THERAPY; TUMOR-CELLS; IN-VIVO; MITOCHONDRIAL DYSFUNCTION AB It is likely that most, if not all, cancer cells possess a mechanism for opposing programmed cell death, or apoptosis. One mechanism often used by cancer cells to escape apoptosis is the overexpression of B cell leukaemia/lymphoma-2 protein (BCL-2) or related antiapoptotic proteins. Inhibiting BCL-2, therefore, is an anticancer strategy worthy of attention. BCL-2 homology 3 (BH3) domains are a-helical segments found in BCL-2 family member proteins. In pro-apoptotic members, the BH3 domain is necessary for pro-apoptotic function. It has been shown that short peptides derived from the BH3 region possess intrinsic pro-death activity. Furthermore, certain peptides of this group exert their pro-death function by specifically binding BCL-2 and opposing BCL-2's antideath function. Therefore, BH3 domains are prototype BCL-2 inhibitors. Mimetics of BH3 domains, whether derived from peptides or small molecules, have promise as cancer therapeutics. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Smith 758,1 Jimmy FoundWay, Boston, MA 02115 USA. NR 97 TC 16 Z9 16 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD APR PY 2003 VL 3 IS 2 BP 293 EP 304 DI 10.1517/14712598.3.2.293 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 670DR UT WOS:000182392600009 PM 12662143 ER PT J AU O'Kane, FW McGibbon, CA Krebs, DE AF O'Kane, FW McGibbon, CA Krebs, DE TI Kinetic analysis of planned gait termination in healthy subjects and patients with balance disorders SO GAIT & POSTURE LA English DT Article DE gait termination; vestibular hypofunction; cerebellar disease; balance impairments; whole body energetics; center of mass kinematics and kinetics ID ENERGY-EXPENDITURE PROBLEM; MECHANICAL ENERGY; FRACTIONS APPROACH; DYNAMIC STABILITY; LINK SYSTEM; TOTAL WORK; POWER; MODEL; KINEMATICS; TRANSFERS AB We examined the stability and strategies used by balance impaired (vestibular hypofunction, VH : n = 25; cerebellar damage, CB: n = 20) patients and healthy (HE: n = 52) controls during planned gait termination. Upper body strategies (during final stride and final step) were investigated using peak positive kinetic power (KP(+): kinetic energy increasing), and peak negative kinetic power (KP(-): kinetic energy decreasing) of the head-arms-trunk segment. Compared to HE controls (P < 0.05): CB patients' medio-lateral KP(+) and KP(-) and were 53 and 71% higher during final stride, respectively; VH patients medio-lateral KP(+) and KP(-) was 78 and 57% higher during final step, respectively, and; during the final, standing stage VH patients were 32% less stable (from phase plane analysis) in the frontal plane. The excessive energy transfers in final stride for CB patients was likely due to poor eccentric muscle control when preparing for the stop. VH patients had difficulty controlling lateral stability during final step and once they had stopped walking, probably due to the lack of vestibular feedback regarding forward velocity changes. A better understanding of these abnormal movement patterns or compensatory strategies may assist in rehabilitation of patients with balance dysfunction. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. MGH, Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, RSH 01040 Parkman St, Boston, MA 02114 USA. EM cincgibbon@partners.org FU NCCIH NIH HHS [RZ1 AT00553]; NIA NIH HHS [R01 AG11255] NR 52 TC 16 Z9 17 U1 1 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD APR PY 2003 VL 17 IS 2 BP 170 EP 179 AR PII S0966-6362(02)00104-2 DI 10.1016/S0966-6362(02)00104-2 PG 10 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 658RP UT WOS:000181734500011 PM 12633778 ER PT J AU Hisamatsu, T Suzuki, M Reinecker, HC Nadeau, WJ McCormick, BA Podolsky, DK AF Hisamatsu, T Suzuki, M Reinecker, HC Nadeau, WJ McCormick, BA Podolsky, DK TI CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; CROHNS-DISEASE; ESCHERICHIA-COLI; FAMILY MEMBER; SUSCEPTIBILITY; BACTERIAL; NOD2; TOMATO; LOCUS AB Background & Aims: Mutations in the CARD15/NOD2 gene, a putative intracellular pattern recognition receptor, have been linked to the risk for Crohn's disease. Because intestinal epithelial cells play a role as the barrier to luminal microorganisms, we investigated the expression and function of CARD15/NOD2 in intestinal epithelial cells. Methods: Expression of CARD15/NOD2 messenger RNA (mRNA) in intestinal epithelial cell lines and primary intestinal epithelial cells was assessed by reverse-transcription polymerase chain reaction (RT-PCR). Regulation of expression of CARD15/NOD2 by cytokines was determined by Northern blot using the SW480 cell line. Active CARD15/ NOD2 protein in SW480 cells was assessed by the combination of immunoprecipitation and immunoblotting using anti-CARD15/NOD2 antisera. To identify the functional role of CARD15/NOD2 in intestinal epithelial cells, gentamicin protection assays of Salmonella typhimurium were performed using Caco2 cells stably transfected with either wild-type CARD15/NOD2 or the 3020insC mutant associated with Crohn's disease. Results. CARD15/NOD2 mRNA was expressed in both intestinal epithelial cell lines and primary intestinal epithelial cells. CARD15/NOD2 mRNA and protein were up-regulated by tumor necrosis factor et (TNFalpha) in SW480 cells. The number of viable internalized S. typhimurium in Caco2 cells stably transfected with CARD15/NOD2 expression plasmid was lower than untransfected Caco2 cells or MOCK transfectant. In contrast, expression of a variant associated with Crohn's disease was unable to constrain bacteria[ survival. Conclusions: CARD15/NOD2 is expressed in intestinal epithelial cells and may serve as a key component of innate mucosal responses to luminal bacteria as an antibacterial factor. Failure in this activity may contribute to the development of Crohn's disease. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Dept Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK33506, DK43351, DK56754, DK60049, R01 DK060049] NR 24 TC 439 Z9 454 U1 3 U2 17 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2003 VL 124 IS 4 BP 993 EP 1000 DI 10.1053/gast.2003.50153 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663JP UT WOS:000182002700020 PM 12671896 ER PT J AU Kanwal, F Dulai, G Jensen, DM Gralnek, IM Kovacs, TOG Machicado, GA Jutabha, R AF Kanwal, F Dulai, G Jensen, DM Gralnek, IM Kovacs, TOG Machicado, GA Jutabha, R TI Major stigmata of recent hemorrhage on rectal ulcers in patients with severe hematochezia: endoscopic diagnosis, treatment, and outcomes SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy CY MAY 20-23, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Gastrointestinal Endoscopy ID MASSIVE HEMORRHAGE; URGENT COLONOSCOPY; STERCORAL ULCER; DISEASE; THERAPY AB Background. Endoscopic diagnosis and treatment of hematochezia caused by rectal ulcers is poorly described. Methods: Consecutive patients hospitalized with severe hematochezia underwent urgent colonoscopy after purge. Those with rectal ulcers were divided into 2 groups based on the absence or presence of major stigmata of recent hemorrhage: active bleeding, visible vessel, or adherent clot. Major stigmata were treated with epinephrine injection and coagulation with a bipolar probe. The primary outcome endpoint was recurrent bleeding within 4 weeks of diagnosis. Results: Rectal ulcers were identified in 23 of 285 (8%) patients. Twelve of 23 patients had major stigmata; these patients had an arithmetically greater decrease in hematocrit and required more blood transfusions than patients without major stigmata. Initial hemostasis was achieved in all, but bleeding recurred in 5 with stigmata. Four patients died of comorbid conditions. There was no recurrent bleeding or death in those without stigmata. Conclusions: Patients with rectal ulcers harboring major stigmata are at high risk for severe bleeding, recurrent bleeding, and death. For ulcers with major stigmata, endoscopic hemostasis is feasible but rates of recurrent bleeding are high. C1 VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [1K23 RR16188]; NIDDK NIH HHS [1K24 DK02650, DK41301] NR 19 TC 18 Z9 18 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 APR PY 2003 VL 57 IS 4 BP 462 EP 468 DI 10.1067/mge.2003.147 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663KH UT WOS:000182004400005 PM 12665754 ER PT J AU Hunt, GC Rader, AE Faigel, DO AF Hunt, GC Rader, AE Faigel, DO TI A comparison of EUS features between CD-117 positive GI stromal tumors and CD-117 negative GI spindle cell tumors SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/Annual Meeting of the American-Gastroenterology-Association CY MAY 19-23, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Gastroenterol Assoc ID FINE-NEEDLE ASPIRATION; C-KIT; SUBMUCOSAL TUMORS; DIFFERENTIAL-DIAGNOSIS; INTERSTITIAL-CELLS; LEIOMYOSARCOMAS; LEIOMYOMAS; MUTATIONS; BENIGN; TRACT AB Background. GI stromal tumors are spindle cell tumors that stain positive for immunohistochemical CD-117 (c-kit). Prognostic factors for malignancy include size ( A cm), mitotic index (5 mitotic figures/50 high-powered fields), and ulcerated, cystic, or necrotic areas within the tumor. The purpose of this study was to compare these features in c-kit positive vs. c-kit negative tumors. Methods: All patients referred for EUS of submucosal lesions were identified, and histopathology, including immunohistochemical staining, was reviewed to determine all diagnoses of GI stromal tumors. Size, echo pattern, and presence, of cystic spaces and ulceration were recorded as diagnosed by EUS. Histopathologic diagnoses were made by FNA or endoscopic submucosal-mucosal resection. If surgical resection followed, the surgical diagnosis, staining pattern, mitotic index, and presence of ulceration, necrosis, and nuclear atypia were recorded. Results: Forty patients (21 men, 19 women; 38 white, 2 African American; mean age 58 +/- 2.6 years) had 46 EUS procedures performed for evaluation of spindle cell tumors. Seventeen stained positive for c-kit (mean age, 59 +/- 3.6 years; range 19 to 80 years) and 12 negative (mean age, 57 +/- 3.8 years; range 31 to 76 years); 11 were not stained for c-kit (excluded from analysis). On EUS, 7 were ulcerated, 3 cystic, and 6 were larger than 4 cm. This group of findings was observed in 12 patients, 11 of whom had c-kit positive tumors (11/17 vs. 1/12; p = 0.006). Tumors positive for c-kit were larger (42.4 +/- 5.5 mm vs. 19.0 +/- 5.9 mm; p = 0.005). There were 13 c-kit positive tumors in the stomach, 2 in the duodenum, and 1 each in the esophagus and at the gastroesophageal junction. Of the 12 c-kit negative tumors, 8 were located in the esophagus and 1 at the gastroesophageal junction (9/12 vs. 2/17; p < 0.01). Surgical resection was performed on 13 patients, 12 of whom had c-kit positive tumors, and 3 of these 12 tumors had greater than 5 mitoses per 50 high-powered field. Conclusions: If a GI stromal tumor is suspected, EUS-FNA with immunohistochemical staining should be performed for CD-117 (c-kit). C-kit tumors are more likely to have malignant features and should be resected or subjected to close clinical follow-up. C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Pathol, Portland, OR 97201 USA. RP Faigel, DO (reprint author), Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Dept Med, P3GI, Portland, OR 97201 USA. NR 27 TC 40 Z9 42 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 APR PY 2003 VL 57 IS 4 BP 469 EP 474 DI 10.1067/mge.2003.146 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663KH UT WOS:000182004400006 PM 12665755 ER PT J AU Bagley, J Iacomini, J AF Bagley, J Iacomini, J TI Gene Therapy Progress and Prospects: Gene therapy in organ transplantation SO GENE THERAPY LA English DT Review DE transplantation; gene transfer; tolerance ID MYELOID DENDRITIC CELLS; DONOR-SPECIFIC HYPORESPONSIVENESS; ISCHEMIA-REPERFUSION INJURY; BONE-MARROW CELLS; T-CELL; ALLOGRAFT SURVIVAL; IN-VIVO; LIVER-TRANSPLANTATION; CARDIAC ALLOGRAFTS; PROLONGS SURVIVAL AB One major complication facing organ transplant recipients is the requirement for life-long systemic immunosuppression to prevent rejection, which is associated with an increased incidence of malignancy and susceptibility to opportunistic infections. Gene therapy has the potential to eliminate problems associated with immunosuppression by allowing the production of immunomodulatory proteins in the donor grafts resulting in local rather than systemic immunosuppression. Alternatively, gene therapy approaches could eliminate the requirement for general immunosuppression by allowing the induction of donor-specific tolerance. Gene therapy interventions may also be able to prevent graft damage owing to nonimmune-mediated graft loss or injury and prevent chronic rejection. This review will focus on recent progress in preventing transplant rejection by gene therapy. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [T32 AI07529, R01 AI43619, R01 AI44268] NR 47 TC 28 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2003 VL 10 IS 8 BP 605 EP 611 DI 10.1038/sj.gt.3302020 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 667KP UT WOS:000182231000001 PM 12692588 ER PT J AU Li, WQ Kennedy, SG Ruvkun, G AF Li, WQ Kennedy, SG Ruvkun, G TI daf-28 encodes a C-elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway SO GENES & DEVELOPMENT LA English DT Article DE insulin signaling; TGF beta signaling; Caenorhabditis elegans; dauer; pheromone; furin ID NEMATODE CAENORHABDITIS-ELEGANS; CONTROLLING DAUER FORMATION; NUCLEOTIDE-GATED CHANNEL; GUANYLYL CYCLASE DAF-11; DOUBLE-STRANDED-RNA; AGE-1 PI3 KINASE; LARVAL DEVELOPMENT; LIFE-SPAN; GENE-EXPRESSION; CHEMOSENSORY NEURONS AB In Caenorhabditis elegans, the decision to enter a developmentally arrested dauer larval stage is triggered by a combination of signals from sensory neurons in response to environmental cues, which include a dauer pheromone. These sensory inputs are coupled to the parallel DAF-2/insulin receptor-like and DAF-7/TGFbeta-like signaling pathways. Although sensory inputs have been shown to physiologically regulate DAF-7/TGFbeta expression, no such regulation of insulin-like ligands in the DAF-2 pathway has been reported. We show here that daf-28 encodes an insulin-like protein, which when mutated causes dauer arrest and down-regulation of DAF-2/IR signaling. A daf-28:: GFP fusion gene is expressed in ASI and ASJ, two sensory neurons that regulate dauer arrest. daf-28:: GFP expression in ASI and ASJ is down-regulated under dauer-inducing conditions and in mutants of DAF-11/guanylyl cyclase, a predicted component of the dauer-pheromone-sensing pathway. Thus, daf-28 expression in sensory neurons is regulated by the environmental cues that normally trigger dauer arrest. Among the 38 C. elegans insulin genes, daf-28 is so far the only insulin mutant to affect dauer arrest. daf-28 was revealed from this functional redundancy by a dominant-negative allele that disrupts a probable proteolytic processing site required for insulin maturation. This DAF-28 mutant is likely to be poisonous to wild-type DAF-28 and other insulins. C1 Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIA NIH HHS [R01 AG014161, R01 AG 16636, R01 AG 14161, R01 AG016636] NR 80 TC 196 Z9 221 U1 1 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2003 VL 17 IS 7 BP 844 EP 858 DI 10.1101/gad.1066503 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 664CT UT WOS:000182044700006 PM 12654727 ER PT J AU Grobet, L Pirottin, D Farnir, F Poncelet, D Royo, LJ Brouwers, B Christians, E Desmecht, D Coignoul, F Kahn, R Georges, M AF Grobet, L Pirottin, D Farnir, F Poncelet, D Royo, LJ Brouwers, B Christians, E Desmecht, D Coignoul, F Kahn, R Georges, M TI Modulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene SO GENESIS LA English DT Article DE myostatin; conditional knockout; cre-lox; muscular hypertrophy ID BETA SUPERFAMILY MEMBER; TRANSGENIC MICE; BELGIAN BLUE; CATTLE; RECOMBINATION; MUTATIONS; GROWTH; EXPRESSION; KNOCKOUT; DELETION AB By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGFbeta family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. (C) 2003 Wiley-Liss, Inc. C1 Univ Liege, Fac Vet Med, Dept Genet, B-4000 Liege, Belgium. Univ Liege, Fac Vet Med, Dept Histol Embryol, B-4000 Liege, Belgium. Univ Liege, Fac Vet Med, Dept Pathol, B-4000 Liege, Belgium. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02115 USA. RP Georges, M (reprint author), Univ Liege, Fac Vet Med, Dept Genet, B43,20 Blvd Colonster, B-4000 Liege, Belgium. RI Royo, Luis /B-4024-2012 OI Royo, Luis /0000-0002-5939-3000 NR 28 TC 114 Z9 126 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD APR PY 2003 VL 35 IS 4 BP 227 EP 238 DI 10.1002/gene.10188 PG 12 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 673PM UT WOS:000182589400005 PM 12717734 ER PT J AU Miller, JW AF Miller, JW TI Photodynamic therapy for choroidal neovascularization - The Jules Gonin Lecture, Montreux, Switzerland, 1 September 2002 SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Conference on Photodynamic Therapy for Choroidal Neovascularization CY SEP 01, 2002 CL MONTREUX, SWITZERLAND ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; MACULAR DEGENERATION; BENZOPORPHYRIN; VERTEPORFIN; MODEL; PHASE-1; VESSELS C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophtalmol,Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophtalmol,Retina Serv,Laser Lab, Boston, MA USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophtalmol,Retina Serv,Angiogenesis Lab, Boston, MA 02114 USA. NR 30 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD APR PY 2003 VL 241 IS 4 BP 258 EP 262 DI 10.1007/s00417-003-0623-y PG 5 WC Ophthalmology SC Ophthalmology GA 682ZH UT WOS:000183121900002 PM 12719985 ER PT J AU Steidl, SM Hirose, T AF Steidl, SM Hirose, T TI Subretinal organization in stage 5 retinopathy of prematurity SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID PIGMENT EPITHELIAL-CELLS; MASSIVE PERIRETINAL PROLIFERATION; GROWTH-FACTOR-BETA; MORPHOLOGIC CHARACTERISTICS AB Background: The subretinal organization (SRO) seen in patients who undergo vitrectomy for stage 5 retinopathy of prematurity has not previously been characterized. We report our observations of SRO and correlate its development with previous laser and cryotreatment for neovascular disease. Methods: We surveyed data from 426 eyes in a retrospective chart review of 263 patients that underwent open-sky vitrectomy for stage 5 retinopathy of prematurity. Results: Of 426 eyes evaluated, 130 eyes received laser, cryo, or a combination of both treatments. In 44 eyes (10.3%), SRO was observed and considered the cause of incomplete retinal attachment. Three forms of SRO were identified: subretinal bands (63.6%), subretinal plaques (15.9%), and diffuse SRO (18.2%). One patient had both a band and a plaque. SRO developed in 24 eyes after cryotreatment, 3 after laser, and 2 after combination cryo and laser treatment. Fewer untreated eyes than cryotreatment eyes developed SRO (15 of 296 eyes, 5.1%; (P=0.0001). Eyes without laser or cryotreatment had a 5.1% frequency of developing SRO. Conclusion: Subretinal organization, a previously uncharacterized entity in retinopathy of prematurity, was most frequently identified in the form of subretinal band formation. SRO was identified in 10.3% of all stage 5 eyes evaluated, and was associated with incomplete retinal reattachment in all cases. C1 Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. Schepens Retina Associates, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Steidl, SM (reprint author), Univ Maryland, Sch Med, Dept Ophthalmol, Suite 420,419 W Redwood St, Baltimore, MD 21201 USA. NR 16 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD APR PY 2003 VL 241 IS 4 BP 263 EP 268 DI 10.1007/s00417-003-0632-x PG 6 WC Ophthalmology SC Ophthalmology GA 682ZH UT WOS:000183121900003 PM 12719986 ER PT J AU Willert, RP Hobson, AR Woolf, Q Thompson, DG Aziz, Q AF Willert, RP Hobson, AR Woolf, Q Thompson, DG Aziz, Q TI Ketamine, an NMDA receptor antagonist prevents the induction of central sensitisation in a human model of visceral pain hypersensitivity SO GUT LA English DT Meeting Abstract CT Annual meeting of the British-Society-of-Gastroenterology CY MAR 23-26, 2003 CL BIRMINGHAM, ENGLAND SP British Soc Gastroenterol C1 Univ Manchester, Hope Hosp, Manchester M13 9PL, Lancs, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 APR PY 2003 VL 52 SU 1 MA 55 BP A15 EP A15 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660HY UT WOS:000181828800056 ER PT J AU Batorfi, J Fulop, V Kim, JH Genest, DR Doszpod, J Mok, SC Berkowitz, RS AF Batorfi, J Fulop, V Kim, JH Genest, DR Doszpod, J Mok, SC Berkowitz, RS TI Osteopontin is down-regulated in hydatidiform mole SO GYNECOLOGIC ONCOLOGY LA English DT Article DE osteopontin; OPN; hydatidiform mole; placenta; laser capture microdissection; LCM; real-time PCR; immunohistochemstry ID GESTATIONAL TROPHOBLASTIC DISEASES; INDUCED BONE-RESORPTION; NORMAL PLACENTA; MATRIX-METALLOPROTEINASE; CANCER PROGRESSION; EXPRESSION; PROGESTERONE; CELLS; RECEPTOR; INTEGRIN AB Objective. Osteopontin (OPN) is a glycoprotein of the extracellular matrix that can bind to different types of receptors including integrins and CD44 receptors. Multiple binding affinity enables OPN to play a role in many physiological and pathological processes. OPN contributes to tumorigenesis in several types of cancers. OPN is also expressed by the endometrium and by trophoblast cells of the chorionic villus in human placenta, where OPN may regulate implantation and placentation in early pregnancies by promoting cell-cell interactions, adhesion, spreading, and migration of trophoblast. Our purpose was to determine the expression of OPN mRNA and protein in hydatidiform mole and in normal placenta of comparable gestational age. Methods. A total of 13 fresh tissues from complete hydatidiform moles, 2 from partial hydatidiform moles, and 9 from normal placentas were analyzed by performing quantitative real-time PCR on microdissected trophoblast cells and immunohistochemistry on frozen sections of tissue. Results. Our results showed significantly lower expression of OPN mRNA and protein in hydatidiform mole, and in particular complete mole (P = 0.001 by real-time PCR and P < 0.001 by immunohistochemistry) as compared to nermal placenta. Conclusion. Although precise molecular mechanisms of gestational trophoblastic diseases have not yet been determined, down-regulation of osteopontin may play an important role in the pathogenesis of molar pregnancy. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol,Dana Farber Canc Inst, Trophoblast Tumor Registry,Med Sch, Boston, MA 02115 USA. Natl Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. St Vincent Hosp, Dept Obstet & Gynecol, Suwon, South Korea. Catholic Univ Korea, Suwon, South Korea. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 16 Z9 19 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 2003 VL 89 IS 1 BP 134 EP 139 DI 10.1016/S0090-8258(03)00067-2 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 669PE UT WOS:000182359000022 PM 12694667 ER PT J AU McBride, CM Emmons, KM Lipkus, IM AF McBride, CM Emmons, KM Lipkus, IM TI Understanding the potential of teachable moments: the case of smoking cessation SO HEALTH EDUCATION RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; ENVIRONMENTAL TOBACCO-SMOKE; NECK-CANCER PATIENTS; POSITIVE AFFECT; HOSPITALIZED-PATIENTS; ASTHMATIC-CHILDREN; LUNG-CANCER; FOLLOW-UP; MATERNAL SMOKING; PASSIVE SMOKING AB The label 'teachable moment' (TM) has been used to describe naturally occurring health events thought to motivate individuals to spontaneously adopt risk-reducing health behaviors. This manuscript summarizes the evidence of TMs for smoking cessation, and makes recommendations for conceptual and methodological refinements to improve the next generation of related research. TM studies were identified for the following event categories: office visits, notification of abnormal test results, pregnancy, hospitalization and disease diagnosis. Cessation rates associated with pregnancy, hospitalization and disease diagnosis were high (10-60 and 15-78%, respectively), whereas rates for clinic visits and abnormal test results were consistently lower (2-10 and 7-21%, respectively). Drawing from accepted conceptual models, a TM heuristic is outlined that suggests three domains underlie whether a cueing event is significant enough to be a TM for smoking cessation: the extent to which the event (1) increases perceptions of personal risk and outcome expectancies, (2) prompts strong affective or emotional responses, and (3) redefines self-concept or social role. Research in TMs could be improved by giving greater attention to assessment of conceptually grounded cognitive and emotional variables, appropriately timed assessment and intervention, and inclusion of appropriate target and comparison samples. C1 Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP McBride, CM (reprint author), Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. FU NCI NIH HHS [CA 89009, CA 72099, CA 74000, CA 76945, CA 80262]; NIMH NIH HHS [MH 56846] NR 118 TC 435 Z9 436 U1 7 U2 38 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD APR PY 2003 VL 18 IS 2 BP 156 EP 170 DI 10.1093/her/18.2.156 PG 15 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 670DP UT WOS:000182392400003 PM 12729175 ER PT J AU Volpp, KGM Williams, SV Waldfogel, J Silber, JH Schwartz, JS Pauly, MV AF Volpp, KGM Williams, SV Waldfogel, J Silber, JH Schwartz, JS Pauly, MV TI Market reform in New Jersey and the effect on mortality from acute myocardial infarction SO HEALTH SERVICES RESEARCH LA English DT Article DE quality of health care; health care reform; economics; financing; economics/hospital ID NEW-YORK-STATE; HOSPITAL COMPETITION; CARE; OUTCOMES; SURGERY; COST; CALIFORNIA; DISEASE; PROGRAM; LENGTH AB Objective. To determine whether mortality rates for patients with acute myocardial infarction (AMI) changed in New Jersey after implementation of the Health Care Reform Act, which reduced subsidies for hospital care for the uninsured and changed hospital payment to price competition from a rate-setting system based on hospital cost. Data Sources/Study Setting. Patient discharge data from hospitals in New Jersey and New York from 1990 through 1996 and the Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample (NIS). Study Design. A comparison between states over time of unadjusted and risk-adjusted mortality and cardiac procedure rates. Data Collection. Discharge data were obtained for 286,640 patients with the primary diagnosis of AMI admitted to hospitals in NewJersey or New York from 1990 through 1996. Records of 364,273 NIS patients were used to corroborate time trends. Principal Findings. There were no significant differences in AMI mortality among insured patients in New Jersey relative to New York or the NIS. However, there was a relative increase in mortality of 41 to 57 percent among uninsured NewJersey patients post-reform, and their rates of expensive cardiac procedures decreased concomitantly. Conclusions. The introduction of hospital price competition and reductions in subsidies for hospital care of the uninsured were associated with an increased mortality rate among uninsured NewJersey AMI patients. A relative decrease in the use of cardiac procedures in NewJersey may partly explain this finding. Additional studies should be done to identify whether other market reforms have been associated with changes in the quality of care. C1 Univ Penn, Sch Med, Wharton Sch, Philadelphia, PA 19104 USA. Philadelphia Vet Hosp, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Gen Internal Med Sect, Philadelphia, PA 19104 USA. Natl Bur Econ Res, Cambridge, MA 02138 USA. Univ Penn, Sch Med, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. RP Volpp, KGM (reprint author), Univ Penn, Sch Med, Wharton Sch, 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Waldfogel, Joel/A-1047-2007; Waldfogel, Joel/A-4916-2015 OI Waldfogel, Joel/0000-0002-8040-7227 FU AHRQ HHS [R03 HS09325-01]; NIGMS NIH HHS [5-T32-GM-07170, T32 GM007170] NR 32 TC 43 Z9 43 U1 2 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2003 VL 38 IS 2 BP 515 EP 533 DI 10.1111/1475-6773.00131 PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 677EF UT WOS:000182793400004 PM 12785559 ER PT J AU Hadley, J Mandelblatt, JS Mitchell, JM Weeks, JC Guadagnoli, E Hwang, YT AF Hadley, J Mandelblatt, JS Mitchell, JM Weeks, JC Guadagnoli, E Hwang, YT CA OPTIONS Res Team TI Medicare breast surgery fees and treatment received by older women with localized breast cancer SO HEALTH SERVICES RESEARCH LA English DT Article DE breast cancer; breast surgery fees; older women; economics; Medicare ID CONSERVING SURGERY; GEOGRAPHIC-VARIATION; COMMUNITY HOSPITALS; RADIATION-THERAPY; STAGE-I; PATIENT; CARE; PATTERNS; PHYSICIANS; CARCINOMA AB Objective. To determine whether area-level Medicare physician fees for mastectomy and breast conserving surgery Were associated with treatment received by Medicare beneficiaries with localized breast cancer and to compare these results with an earlier analysis conducted using small areas (three-digit zip codes) as the unit of observation. Data Source. Medicare claims and physician survey data for a national sample of elderly (aged 67 or older) Medicare beneficiaries with localized breast cancer treated in 1994 (unweighted n = 1,787). Study Design. Multinomial logistic regression analysis was used to estimate a model of. treatment received as a function of Medicare fees, controlling for other area economic factors, patient demographic and clinical characteristics, physician experience, and region. Principal Findings. In 1994, average Medicare fees (adjusted for the effects of modifiers and procedure mix) for mastectomy (MST) and breast conserving surgery (BCS) were $904 and $305, respectively. Holding other fees and factors fixed, a 10 percent increase in the BCS fee increased the odds of breast conserving surgery with radiation therapy relative to mastectomy to 1.34 (p = 0.02), while a 10 percent decrease in the MST fee increased the odds of breast conserving surgery with radiation therapy to 1.86 (p<0.01). Conclusions. Among older women with localized breast cancer, financial incentives appear to influence the use of mastectomy and breast conserving surgery with radiation therapy. This finding is consistent with the hypothesis that physicians are responsive to financial incentives when the alternative procedures have clinically equivalent outcomes and the patient's clinical condition does not dominate the treatment choice. We also find that the fee effects derived from this analysis of individual data with more precise measurement of both diagnosis and treatment are qualitatively similar to the results of the small-area analysis. This suggests that the earlier study was not severely affected by ecological bias or other data limitations inherent in Medicare claims data. C1 Urban Inst, Washington, DC 20037 USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Human Oncol, Washington, DC USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Med, Washington, DC USA. Georgetown Univ, Publ Policy Inst, Washington, DC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Natl Taipei Univ, Dept Stat, Taipei, Taiwan. RP Hadley, J (reprint author), Urban Inst, 2100 M St NW, Washington, DC 20037 USA. FU AHRQ HHS [HS08395, R01 HS008395] NR 33 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2003 VL 38 IS 2 BP 553 EP 573 DI 10.1111/1475-6773.00133 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 677EF UT WOS:000182793400006 PM 12785561 ER PT J AU Stafford, RS Davidson, SM Davidson, H Miracle-McMahill, H Crawford, SL Blumenthal, D AF Stafford, RS Davidson, SM Davidson, H Miracle-McMahill, H Crawford, SL Blumenthal, D TI Chronic disease medication use in managed care and indemnity insurance plans SO HEALTH SERVICES RESEARCH LA English DT Article DE managed care; physician practice patterns; medication prescribing; chronic disease ID CONGESTIVE-HEART-FAILURE; PERFORMANCE; GUIDELINES; HMO; QUALITY; UPDATE AB Objective. To evaluate the impact of managed care on the use of chronic disease, medications. Data Source. Claims data from 1997 from two indemnity and three independent practice association (IPA) model managed care insurance plans. Research Design. Cross-sectional analysis of claims data. Data Collection. Adult patients with diabetes mellitus (DM, n = 26,444), congestive heart failure (CHF, n = 7,978), and asthma (n =9,850) were identified by ICD-9 codes. Chronic disease medication use was defined through pharmacy claims for patients receiving one or more prescriptions for drugs used in treating these conditions. Using multiple logistic regression we adjusted for patient case mix and the number of primary care visits. Principal Findings. With few exceptions, managed care patients were more likely to use chronic disease medications than indemnity patients. In DM, managed care patients were more likely to use sulfonylureas (43 percent versus 39 percent for indemnity), metformin (26 percent versus 18 percent), and troglitazone (8.8 percent versus 6.4 percent), but not insulin. For CHF patients, managed care patients were more likely to -use loop diuretics (45 percent versus 41 percent), ACE inhibitors or angiotensin receptor blockers (50 percent versus 41 percent), and beta-blockers (23 percent versus 16 percent); but we found no differences in digoxin use. In asthma, managed care patients were more likely to use inhaled cortlcosteroids (34 percent versus 30 percent), systemic corticosteroids (18 percent versus 16 percent), short-acting beta-agonists (42 percent versus 33 percent), long-acting beta-agonists (9.9 percent versus 8.6 percent), and leukotriene modifiers (5.4 percent versus 4.1 percent); but not cromolyn or methylxanthines. Statistically significant differences remained after multivariate analysis that controlled for age, gender, and severity. Conclusions. Chronic disease patients in these managed care plans are more likely to receive both inexpensive and expensive medications. Exceptions included older medications partly supplanted by newer therapies. Differences may be explained by the fact that patients in indemnity plans face higher out-of-pocket costs and managed care plans promote more aggressive medication use. The relatively low likelihood of condition-specific medications in both plan types is a matter of concern, however. C1 Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94306 USA. Boston Univ, Sch Management, Boston, MA 02215 USA. John Snow Inc, Boston, MA USA. Beth Israel Deaconess Hosp, Boston, MA USA. New England Res Inst, Watertown, MA 02172 USA. Univ Massachusetts, Med Ctr, Dept Prevent & Behav Med, Worcester, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners Inst Hlth Policy, Boston, MA USA. RP Stafford, RS (reprint author), Stanford Univ, Stanford Ctr Res Dis Prevent, 1000 Welch Rd, Palo Alto, CA 94306 USA. RI Miracle, Maria /G-3482-2016 NR 22 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2003 VL 38 IS 2 BP 595 EP 612 DI 10.1111/1475-6773.00135 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 677EF UT WOS:000182793400008 PM 12785563 ER PT J AU Dienstag, JL Cianciara, J Karayalcin, S Kowdley, KV Willems, B Plisek, S Woessner, M Gardner, S Schiff, E AF Dienstag, JL Cianciara, J Karayalcin, S Kowdley, KV Willems, B Plisek, S Woessner, M Gardner, S Schiff, E TI Durability of serologic response after lamivudine treatment of chronic hepatitis B SO HEPATOLOGY LA English DT Article ID TERM FOLLOW-UP; E-ANTIGEN SEROCONVERSION; INTERFERON-ALFA; HBEAG SEROCONVERSION; THERAPY; TRIAL AB Forty subjects with chronic hepatitis B and hepatitis B c antigen (HBeAg) seroconversion following lamivudine therapy in previous trials were monitored after treatment to assess the durability of serologic responses. Patient follow-up began a median of 4.3 months after completion of therapy in previous trials. At months 2, 4, 6, 9, and 12 of year 1, and every 6 months thereafter, we tested for HBeAg and hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) DNA, and alanine aminotransferase (ALT). After a median (range) of 36.6 (4.8-45.6) months of follow-up monitoring, HBeAg seroconversion was demonstrated at the last visit by 77% (30 of 39) of patients. In a post hoc analysis of a slightly different population of all 65 patients with HBeAg seroconversion in previous trials, the 3-year durability of HBeAg seroconversion measured from the time immediately after discontinuing lamivudine therapy was 64%. Nine (9 of 40, 23%) patients were HBsAg negative at the last assessment. Seventy-four percent (17 of 23) of patients with baseline undetectable HBV DNA and normal ALT maintained these responses at the last visit. Eight patients (8 of 40, 20%) initiated retreatment for reappearance of HBV markers, and 7 showed biochemical and/or virologic improvement (including regained HBeAg seroconversion in 2). No safety issues of concern emerged. In conclusion, most HBeAg responses achieved during lamivudine therapy were durable, and most responders experienced prolonged clinical benefit after HBeAg seroconversion and subsequent discontinuation of lamivudine. Lamivudine retreatment for reappearance of hepatitis B markers can achieve resumption of viral suppression. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Med Acad Warsaw, Warsaw, Poland. Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. Univ Washington, Seattle, WA 98195 USA. CHU Montreal, Hosp St Luc, Montreal, PQ, Canada. Infekeni Klin, Hradec Kralove, Czech Republic. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Miami, Miami, FL 33152 USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. NR 22 TC 171 Z9 182 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2003 VL 37 IS 4 BP 748 EP 755 DI 10.1053/jhep.2003.50117 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663KK UT WOS:000182004600006 PM 12668966 ER PT J AU Ioannou, GN Dominitz, JA Weiss, NS Heagerty, PJ Kowdley, KV AF Ioannou, GN Dominitz, JA Weiss, NS Heagerty, PJ Kowdley, KV TI Racial differences in the relationship between hepatitis C infection and iron stores SO HEPATOLOGY LA English DT Article ID CHRONIC VIRAL-HEPATITIS; INTERFERON THERAPY; CONTROLLED TRIAL; UNITED-STATES; LIPID-PEROXIDATION; AFRICAN-AMERICANS; ALPHA-INTERFERON; VIRUS-INFECTION; PLUS RIBAVIRIN; CIRRHOSIS AB Black race and increased hepatic iron stores predict poor response to interferon treatment for chronic hepatitis C virus (HCV) infection. We tested the hypothesis that these 2 observations are linked by investigating whether HCV-infected African-Americans have increased iron stores relative to uninfected persons. Using data from the third National Health and Nutrition Examination Survey (NHANES III), we determined the risk of having increased iron stores, defined as elevation of both serum ferritin and transferrin-iron saturation (TS), in HCV-RNA-positive blacks (n = 100) and nonblacks (n = 126) relative to HCV-RNA-negative blacks (n = 4,002) and nonblacks (n = 10,943). HCV-positive blacks were 5.4 times (95% CI, 1.2 to 24) more likely to have increased iron stores than HCV-positive nonblacks. The proportion of HCV-positive blacks who had increased iron stores was 16.4% among those with abnormal liver enzymes and 2.8% among those with normal liver enzymes, compared with only 0.6% among HCV-negative blacks. After adjustment for age, alcohol intake, gender, menopausal status, education, body mass index, and poverty index, HCV-positive blacks with abnormal liver enzymes had an elevated risk of having increased iron stores (odds ratio, 17.8; 95% CI, 5.1 to 63). In contrast, among persons of other races, there was a much smaller difference in the proportion of persons with increased iron stores between HCV-positive persons with (3.4%) or without (1.4%) abnormal liver enzymes and HCV-negative persons (0.9%). In conclusion, a greater proportion of blacks than persons of other races respond to HCV infection with an increase in iron stores. This finding may partly explain the reduced response of HCV-positive African-Americans to antiviral treatment. C1 Univ Washington, Med Ctr, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, NW Hepatitis C Resouce Ctr, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Kowdley, KV (reprint author), Univ Washington, Med Ctr, Div Gastroenterol, Dept Med, Box 356174,1959 NE Pacific St, Seattle, WA 98195 USA. OI Dominitz, Jason/0000-0002-8070-7086 FU NIDDK NIH HHS [K24DK02957-01] NR 50 TC 37 Z9 37 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2003 VL 37 IS 4 BP 795 EP 801 DI 10.1053/jhep.2003.50147 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663KK UT WOS:000182004600012 PM 12668972 ER PT J AU Carretero, J Vazquez, G Rubio, M Blanco, E Juanes, JA Perez, E Burks, D Vazquez, R AF Carretero, J Vazquez, G Rubio, M Blanco, E Juanes, JA Perez, E Burks, D Vazquez, R TI Postnatal differentiation of the immunohistochemical expression of aromatase P450 in the rat pituitary gland SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE rat; pituitary gland; postnatal differentiation; aromatase ID FOLLICLE-STIMULATING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; LUTEINIZING-HORMONE; BRAIN AROMATASE; AGING MEN; REPRODUCTIVE HORMONES; FEMALE RATS; ANDROGEN; TESTOSTERONE; AGE AB At our laboratory, we have recently demonstrated the immunohistochemical expression of aromatase P450 in the pituitary glands of adult rats; this expression was seen to be sex-dependent. In order to determine whether the changes in the expression of the enzyme are related to changes in the gonadal sphere and whether the expression of the enzyme is related to the postnatal differentiation of hypophyseal cytology, in the present work we performed an immunohistochemical study in the rat pituitary gland from birth to old age. The immunohistochemical reaction to aromatase was evident and very generalized at 7 days after birth, with no large differences between the male and female animals. At 14 days the immunohistochemical reaction was decreased in the females, with no changes in the males. At 17 days, aromatase immunoreactivity in the pituitary glands of female rats was very weak whereas the males showed large numbers of reactive cells. These observations were further pronounced at 21 days and 2 months of life. At 24 months, the immunoreactivity found in the pituitary glands of the male rats had almost completely disappeared. Our results show that a postnatal differentiation in the immunohistochemical expression of aromatase occurs; this is tightly linked to sexual activity and is lost in old age. This suggests that hypophyseal aromatase would be related to the mechanisms of action of gonadal steroids on hypophyseal differentiation and secretion. C1 Univ Salamanca, Inst Neurosci Castilla & Leon, Neuroendocrinol Lab, E-37007 Salamanca, Spain. Harvard Univ, Joslin Diabet Ctr, Cambridge, MA 02138 USA. Univ Salamanca, Fac Med, Dept Surg, E-37007 Salamanca, Spain. Univ Salamanca, Fac Med, Dept Human Anat & Histol, E-37007 Salamanca, Spain. RP Carretero, J (reprint author), Univ Salamanca, Inst Neurosci Castilla & Leon, Neuroendocrinol Lab, Avda Alfonso X el Sabio S-N, E-37007 Salamanca, Spain. RI Carretero, Jose/L-6930-2014; Blanco, Enrique/B-2243-2017 OI Carretero, Jose/0000-0003-3143-6512; Blanco, Enrique/0000-0002-5332-4282 NR 34 TC 17 Z9 17 U1 0 U2 2 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD APR PY 2003 VL 18 IS 2 BP 419 EP 423 PG 5 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 655WP UT WOS:000181575900011 PM 12647792 ER PT J AU Chen, W Hahn, WC AF Chen, W Hahn, WC TI SV40 early region oncoproteins and human cell transformation SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Review DE SV40 Early Region; small t antigen; large T antigen; human cell transformation; tumor suppressor genes ID SMALL-T-ANTIGEN; PROTEIN PHOSPHATASE 2A; SIMIAN-VIRUS-40 LARGE-T; SMALL TUMOR-ANTIGEN; MOUSE EMBRYO FIBROBLASTS; RETINOBLASTOMA SUSCEPTIBILITY GENE; HUMAN-PAPILLOMAVIRUS TYPE-16; AMINO-TERMINAL DOMAIN; SIMIAN VIRUS-40; LIFE-SPAN AB We now understand neoplastic transformation to be the consequence of multiple acquired genetic alterations. The combination of these acquired changes confer the various phenotypes that constitute the clinical features of cancer. Although only rare human cancers derive from a viral etiology, the study of DNA tumor viruses that transform rodent and human cells has led to a greater understanding of the molecular events that program the malignant state. In particular, investigation of the viral oncoproteins specified by the Simian Virus 40 Early Region (SV40 ER) has revealed critical host cell pathways, whose perturbation play an essential role in the experimental transformation of mammalian cells. Recent work has reinvestigated the roles of two SV40 ER oncoproteins, the large T antigen (LT) and the small t antigen (ST), in human cell transformation. Co-expression of these two oncoproteins, together with the telomerase catalytic subunit, hTERT, and an oncogenic version of the H-Ras oncoprotein, suffices to transform human cells. LT inactivates two key tumor suppressor pathways by binding to the retinoblastoma protein (pRB) and p53. The ability of ST to transform human cells requires interactions with PP2A, an abundant family of serine-threonine phosphatases. Here we review recent developments in our understanding of how these two viral oncoproteins facilitate human cell transformation. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [K01 CA94223] NR 113 TC 30 Z9 39 U1 0 U2 0 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD APR PY 2003 VL 18 IS 2 BP 541 EP 550 PG 10 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 655WP UT WOS:000181575900024 PM 12647805 ER PT J AU McLean, DC Spruill, I Gevao, S Morrison, EYS Bernard, OS Argyropoulos, G Garvey, WT AF McLean, DC Spruill, I Gevao, S Morrison, EYS Bernard, OS Argyropoulos, G Garvey, WT TI Three novel mtDNA restriction site polymorphisms allow exploration of population affinities of African Americans SO HUMAN BIOLOGY LA English DT Article DE mitochondrial DNA; Gullah African American; restriction site polymorphism; admixture; population affinities ID HUMAN MITOCHONDRIAL GENOME; DNA; EVOLUTION; ADMIXTURE; SEQUENCE; PROPORTIONS AB To develop informative tools for the study of population affinities in African Americans, we sequenced the hypervariable segments I and 11 (HVS I and HVS II) of mitochondrial DNA (mtDNA) from 96 Sierra Leoneans; European Americans; rural, Gullah-speaking African Americans; urban African Americans living in Charleston, South Carolina; and Jamaicans. We identified single nucleotide polymorphisms (SNPs) exhibiting ethnic affinities, and developed restriction endonuclease tools to screen these SNPs. Here we show that three HVS restriction site polymorphisms (RSPs), EcoRV, FokI, and MfeI, exhibit appreciable differences in frequency (average delta = 0.4165) between putative African American parental populations (i.e., extant Africans living in Sierra Leone and European Americans). Estimates of European American mtDNA admixture, calculated from haplotypes composed of these three novel RSPs, show a cline of increasing admixture from Gullah-speaking African American (m = 0.0300) to urban Charleston African American (m = 0.0689) to West Coast African American (m = 0.1769) populations. This haplotype admixture in the Gullahs is the lowest recorded to date among African Americans, consistent with previous studies using autosomal markers. These RSPs may become valuable new tools in the study of ancestral affinities and admixture dynamics of African Americans. C1 Med Univ S Carolina, Sea Isl Families Project, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Project Sugar, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Univ Sierra Leone, Coll Med & Allied Hlth Sci, Freetown, Sierra Leone. Univ W Indies, Dept Basic Med Sci, Biochem Sect, Kingston 7, Jamaica. Univ W Indies, Ctr Biotechnol, Kingston 7, Jamaica. Diabet Assoc Jamaica, Kingston, Jamaica. RP McLean, DC (reprint author), Med Univ S Carolina, Sea Isl Families Project, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. FU NIDDK NIH HHS [DK-47461] NR 31 TC 22 Z9 23 U1 1 U2 4 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD APR PY 2003 VL 75 IS 2 BP 147 EP 161 DI 10.1353/hub.2003.0035 PG 15 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 681XE UT WOS:000183060200001 PM 12943155 ER PT J AU Appleman, LJ Boussiotis, VA AF Appleman, LJ Boussiotis, VA TI T cell anergy and costimulation SO IMMUNOLOGICAL REVIEWS LA English DT Review ID GLYCOGEN-SYNTHASE KINASE-3; MULTIORGAN TISSUE DESTRUCTION; STAPHYLOCOCCAL ENTEROTOXIN-B; ANTIGEN-PRESENTING CELLS; PROTEIN-TYROSINE KINASE; TUMOR-BEARING MICE; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; IN-VIVO; SIGNAL-TRANSDUCTION AB T lymphocytes play a key role in immunity by distinguishing self from nonself peptide antigens and regulating both the cellular and humoral arms of the immune system. Acquired, antigen-specific unresponsiveness is an important mechanism by which T cell responses to antigen are regulated in vivo . Clonal anergy is the term that describes T cell unresponsiveness at the cellular level. Anergic T cells do not proliferate or secrete interleukin (IL)-2 in response to appropriate antigenic stimulation. However, anergic T cells express the IL-2 receptor, and anergy can be broken by exogenous IL-2. Anergy can be induced by submitogenic exposure to peptide antigen in the absence of a costimulatory signal provided by soluble cytokines or by interactions between costimulatory receptors on T cells and counter-receptors on antigen-presenting cells. The molecular events that mediate the induction and maintenance of T cell anergy are the focus of this review. The molecular consequences of CD28-B7 interaction are discussed as a model for the costimulatory signal that leads to T cell activation rather than the induction of anergy. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst,Dept Med, Dept Med Oncol,Div Med Oncol, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Mayer 547,44 Binney St, Boston, MA 02115 USA. OI Appleman, Leonard/0000-0003-4951-7388 FU NIAID NIH HHS [AI 46548, AI 43552] NR 221 TC 158 Z9 165 U1 0 U2 6 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2003 VL 192 IS 1 BP 161 EP 180 DI 10.1034/j.1600-065X.2003.00009.x PG 20 WC Immunology SC Immunology GA 663MG UT WOS:000182008900014 PM 12670403 ER PT J AU Sifri, CD Begun, J Ausubel, FM Calderwood, SB AF Sifri, CD Begun, J Ausubel, FM Calderwood, SB TI Caenorhabditis elegans as a model host for Staphylococcus aureus pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID VIRULENCE DETERMINANT PRODUCTION; GREEN FLUORESCENT PROTEIN; ACCESSORY REGULATOR SAR; SIGMA-FACTOR SIGMA(B); GENE REGULATOR; ALPHA-TOXIN; PSEUDOMONAS-AERUGINOSA; ENTEROCOCCUS-FAECALIS; LOCUS SAR; DIMINISHED VIRULENCE AB Staphylococcus aureus, an important pathogen of humans and other warm-blooded animals, is also capable of killing the nematode Caenorhabditis elegans. Here, we show that C. elegans organisms that are fed S. aureus die over the course of several days in a process that is correlated with the accumulation of bacteria within the nematode digestive tract. Several S. aureus virulence determinants known or speculated to be important in rnammalian pathogenesis, including the quorum-sensing global virulence regulatory system agr and the global virulence regulator sarA, the alternative sigma factor sigma(B), alpha-hemolysin, and V8 serine protease, are required for full pathogenicity in nematodes. In addition, several defined C. elegans mutants were examined for susceptibility to S. aureus infection. Enhanced susceptibility to S. aureus killing was observed with loss-of-function mutations in the C. elegans genes esp-2/sek-1 and esp-8/nsy-1, which encode components of a conserved p38 MAP kinase signaling pathway involved in nematode defense against multiple pathogens. These results suggest that key aspects of S. aureus pathogenesis have been conserved, irrespective of the host, and that specific C. elegans host factors can alter susceptibility to this gram-positive human pathogen. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. RI Begun, Jakob/J-6793-2014 OI Begun, Jakob/0000-0001-5256-7672 NR 85 TC 169 Z9 176 U1 2 U2 20 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 APR PY 2003 VL 71 IS 4 BP 2208 EP 2217 DI 10.1128/IAI.71.4.2208-2217.2003 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 662BQ UT WOS:000181926200072 PM 12654843 ER PT J AU Mintzer, JE Kershaw, P AF Mintzer, JE Kershaw, P TI The efficacy of galantamine in the treatment of Alzheimer's disease: comparison of patients previously treated with acetylcholinesterase inhibitors to patients with no prior exposure SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE galantamine; efficacy; acetylcholinesterase inhibitors; Alzheimer's disease ID PLACEBO-CONTROLLED TRIAL; AD AB Background Acetylcholinesterase inhibitors (AChEIs) can provide benefits at the cognitive, behavioral, and functional levels to patients with Alzheimer's disease (AD). With more AChEIs now available, treatment considerations may include whether the patient has had prior exposure to an AChEI. Objective To compare the effects of galantamine in patients with AD who were previously exposed to AChEIs with its effects in patients with AD who had no previous exposure, using a post hoc analysis. Results Patients in groups treated with galantamine 16 mg/day and 24 mg/day achieved statistically significant improvements in ADAS-cog/11 scores in comparison with those who received placebo (naive: p = 0.003 and 0.005, respectively; prior exposure: p < 0.001 and 0.001. respectively). Similarly, a greater number of patients treated with galamainine 16 mg/day and 24 mg/day exhibited no change or improvement in their CIBIC-plus scores compared to patients who received placebo (naive: p < 0.001 and p = 0.077, respectively: prior exposure: p = 0.005 and p = 0.001, respectively). There were no significant differences in adverse events between naive patients and those with prior exposure to AChEIs. Conclusions Galantamine is effective and safe in patients with AD, regardless of previous exposure to AChEIs, Copyright (C) 2003 John Wiley Sons, Ltd. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, N Charleston, SC USA. Janssen Pharmaceut Prod LP, Titusville, NJ USA. RP Mintzer, JE (reprint author), Alzeimers Res & Clin Programs, 5900 Core Rd,Suite 203, Charleston, SC 29406 USA. NR 11 TC 19 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD APR PY 2003 VL 18 IS 4 BP 292 EP 297 DI 10.1002/gps.826 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 669LW UT WOS:000182353600005 PM 12673604 ER PT J AU Baker, PM Young, RH AF Baker, PM Young, RH TI Brenner tumor of the ovary with striking microcystic change SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; neoplasm; Brenner tumor; microcysts AB An ovarian Brenner tumor from a 39-year-old woman exhibited striking microcystic change that was so extensive it largely obscured the nature of the tumor, causing initial diagnostic difficulty. The patient presented with symptoms related to a pelvic mass and had a unilateral, 24 cm in maximal dimension, stage I tumor that was solid and cystic. Microscopic examination revealed extensive microcystic change within the epithelial nests in large areas of the tumor such that transitional-type epithelium was only recognized very focally. The tumor had minor areas (<5%) that showed marked cytological atypia and mitotic activity, interpreted as microscopic foci of intraepithelial carcinoma, but was predominantly benign. The presence of characteristic fibromatous stroma. and mucinous metaplasia within the epithelial nests provided important clues to the correct diagnosis. C1 Univ Manitoba, Ctr Hlth Sci, Dept Pathol, Winnipeg, MB R3A 1R9, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Baker, PM (reprint author), Univ Manitoba, Ctr Hlth Sci, Dept Pathol, Winnipeg, MB R3A 1R9, Canada. NR 9 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 2003 VL 22 IS 2 BP 185 EP 188 DI 10.1097/01.PGP.0000055051.78118.FC PG 4 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 658NF UT WOS:000181726500012 PM 12649675 ER PT J AU Marcus, KJ Dutton, SC Barnes, P Coleman, CN Pomeroy, SL Goumnerova, L Billett, AL Kieran, M Tarbell, NJ AF Marcus, KJ Dutton, SC Barnes, P Coleman, CN Pomeroy, SL Goumnerova, L Billett, AL Kieran, M Tarbell, NJ TI A phase I trial of etanidazole and hyperfractionated radiotherapy in children with diffuse brainstem glioma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE etanidazole; hyperfractionated radiotherapy ID PEDIATRIC-ONCOLOGY-GROUP; RADIATION-THERAPY; STEM GLIOMAS; CANCER-GROUP; MALIGNANT GLIOMA; I/II TRIAL; SR 2508; TUMORS; SR-2508; RADIOSENSITIZATION AB Purpose: To determine the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brainstem glioma. Methods and Materials: Eighteen patients with brainstem glioma were treated with etanidazole and HRT on a dose escalation protocol (Phase I trial) between 1990 and 1996. All patients had MRI confirmation of diffuse pontine glioma and signs/symptoms of cranial nerve deficit, ataxia, or long tract signs of <6 months' duration. Cervicomedullary tumors were excluded. Patients (median age: 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2-cm margin with parallel-opposed 6-15-MV photons. The total dose was 66 Gy in 44 fractions (1.5 Gy b.i.d., with at least 6 h between fractions) for the first 3 patients and 63 Gy in 42 fractions for the subsequent 15 patients. Etanidazole was administered as a rapid i.v. infusion 30 min before the morning fraction of HRT. Planned doses of etanidazole were 1.8 g/m(2) x 17 doses (30.6 g/m(2)) at Step 1 to a maximum of 2.4 g/m(2) x 21 doses (50.4 g/m(2)) at Step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Results: Three patients were treated at each dose level except Level 2, on which only I patient was treated. The highest dose level achieved was Level 7, which delivered a total etanidazole dose of 46.2 g/m(2). Two patients were treated at this level, and both patients experienced Grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 g/m(2) (dose Level 6) without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 23 cases of Grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 weight loss, 3 others), 11 cases of Grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, I arthralgia, 1 urinary retention, 1 hematologic), and 4 Grade 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral neuropathy was not seen at any dose level. The median survival from the start of treatment was 8.5 months (range: 3-58 months). Conclusion: The MTD of etanidazole in children receiving HRT for brainstem glioma is 42 g/m2, with cutaneous rash as the dose-limiting toxicity. This is in contrast to the adult experience, which demonstrates a 24% lower MTD of 34 g/m(2) limited by peripheral neuropathy. (C) 2003 Elsevier Science Inc. C1 Childrens Hosp, Dept Med, Div Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Marcus, KJ (reprint author), Childrens Hosp, Dept Med, Div Radiat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM KMARCUS@LROC.Harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 24 TC 23 Z9 26 U1 0 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 APR 1 PY 2003 VL 55 IS 5 BP 1182 EP 1185 DI 10.1016/S0360-3016(02)04391-2 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 659XJ UT WOS:000181803500007 PM 12654425 ER PT J AU Powell, SN Taghian, AG Kachnic, LA Coen, JJ Assaad, SI AF Powell, SN Taghian, AG Kachnic, LA Coen, JJ Assaad, SI TI Risk of lymphedema after regional nodal irradiation with breast conservation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; breast cancer; lymphedema; axillary surgery ID SENTINEL LYMPHADENECTOMY; ADJUVANT CHEMOTHERAPY; AXILLARY DISSECTION; PREMENOPAUSAL WOMEN; RADIATION-THERAPY; ARM EDEMA; CANCER; CARCINOMA; RADIOTHERAPY; MORBIDITY AB Purpose: To evaluate the risk factors for lymphedema in patients receiving breast conservation therapy for early-stage breast cancer. Methods and Materials: Between 1982 and 1995, 727 Stage I-II breast cancer patients were treated with breast conservation therapy at Massachusetts General Hospital. A retrospective analysis of the development of persistent arm edema was performed. Lymphedema was defined as a >2-cm difference in forearm circumference compared with the untreated side. The median follow-up was 72 months. Breast and regional nodal irradiation (BRNI) was administered in 32% of the cases and breast irradiation alone in 68%. Results: Persistent arm lymphedema was documented in 21 patients. The 10-year actuarial incidence was 4.1%. The median time to edema was 39 months. The only significant risk factor for lymphedema was BRNI. The 10-year risk was 1.8% for breast irradiation alone vs. 8.9% for BRNI (p = 0.001). The extent I of axillary dissection did not predict for lymphedema even within the subgroups of patients defined by the extent of irradiation. Most patients underwent Level I or II dissection. In this subgroup, the lymphedema risk At 10 years was 10.7% for BRNI vs. 1.0% for breast irradiation alone (p = 0.0003). Conclusion: Nodal irradiation was the only significant risk factor for arm lymphedema in patients receiving breast conservation therapy for early-stage breast cancer. Our data suggest that this risk is low with Level I/II dissection and breast irradiation. However, even after the addition of radiotherapy to the axilla and supraclavicular fossa, the development of lymphedema was only 1 in 10, lower than generally recognized. (C) 2003 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Powell, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM snpowell@partners.org NR 27 TC 102 Z9 106 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 APR 1 PY 2003 VL 55 IS 5 BP 1209 EP 1215 DI 10.1016/S0360-3016(02)04273-6 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 659XJ UT WOS:000181803500011 ER PT J AU Razzaque, MS Foster, CS Ahmed, AR AF Razzaque, MS Foster, CS Ahmed, AR TI Role of collagen-binding heat shock protein 47 and transforming growth factor-beta 1 in conjunctival scarring in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID F9 TERATOCARCINOMA CELLS; STRESS PROTEIN; TGF-BETA; MESSENGER-RNA; EXTRACELLULAR-MATRIX; MOLECULAR CHAPERONE; FISCHER-344 RAT; HSP47 GENE; EXPRESSION; HEAT-SHOCK-PROTEIN-47 AB PURPOSE. Submucosal fibrosis due to excessive accumulation of collagens is an important histologic feature in the pathogenesis of ocular cicatricial pemphigoid (OCP). Heat shock protein 47 (HSP47), a collagen-binding protein, plays an important role in the biosynthesis of procollagens. In the present study, we examined the role of HSP47 in conjunctival scarring in patients with OCP. METHODS. Biopsy specimens of the conjunctiva of 15 patients with OCP and 5 normal subjects were studied for the expression of HSP47, transforming growth factor (FGF)-beta1, type I collagen, and type III collagen. The-role of TGF-beta1 on the induction of HSP47 and type I collagen by conjunctival fibroblasts was studied by immunostaining, Western blot analysis, and quantitative real-time PCR. RESULTS. Compared with the control, increased accumulations of type I and type III collagens were detected by immunohistochemistry in fibrotic conjunctiva of patients with OCP. Weak and sparse expression of HSP47 was detected in the epithelial cells and stromal fibroblasts in control conjunctival tissues. In contrast to the control, the expression of HSP47 was markedly increased in the stromal fibroblasts in conjunctival tissues obtained from patients with OCP, as detected by immunohistochemistry. By quantitative real-time PCR, compared with control conjunctival tissues, a 3.4-fold increase in the expression of HSP47 was noted in the conjunctival tissues obtained from patients with OCP. Similar to conjunctival tissues, fibroblasts isolated from conjunctiva of patients with OCP exhibited 4.8-fold increase in the expression of HSP47, compared with control fibroblasts. When conjunctival fibroblasts were treated with various concentration of TGF-beta1, upregulation in the expression of HSP47 and type I collagen was detected. CONCLUSIONS. This study demonstrated increased expression of HSP47 and TGF-beta1 by conjunctival fibroblasts in biopsy specimens obtained from patients with OCP. TGF-beta1 induced the expression of HSP47 and type I collagen by conjunctival fibroblasts. Increased levels of TGF-beta1 and HSP47 may regulate increased synthesis, assembly, and production of collagens and thereby could significantly contribute to the process of conjunctival scarring in patients with OCP. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Razzaque, MS (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. NR 45 TC 40 Z9 42 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 APR PY 2003 VL 44 IS 4 BP 1616 EP 1621 DI 10.1167/iovs.02-0644 PG 6 WC Ophthalmology SC Ophthalmology GA 660TG UT WOS:000181848900033 PM 12657600 ER PT J AU Yildiz, A Sachs, GS AF Yildiz, A Sachs, GS TI Age onset of psychotic versus non-psychotic bipolar illness in men and in women SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar illness; psychosis; age of onset; gender ID GENDER DIFFERENCES; SCHIZOAFFECTIVE DISORDER; SCHIZOPHRENIA; ADOLESCENT; MANIA; HYPERINTENSITIES AB Objective: To investigate the relationship between psychotic symptoms and age at onset of bipolar illness. Method: The charts of bipolar patients treated at the Massachusetts General Hospital Bipolar Clinic were reviewed for age of first affective episode, demographics and history of psychotic symptoms. Results: Data was obtained for 328 bipolar patients (56.7% females) of whom 42% had psychotic symptoms sometime through the course of their illness. Overall, there was no significant difference in age of onset between the psychotic and non-psychotic groups. Additional analysis carried out separately by gender found significant difference for males but not for females. Age at onset for psychotic males was significantly lower than non-psychotic males. Psychosis was less common in males than females. The mean age of onset for psychotic males was significantly lower than psychotic females. Conclusion: This result implies that developmental physiology underlying psychosis in bipolar illness may differ for men and women. The different proportions of males and females in the study samples may account for conflicting results reported in the literature for age of onset of psychotic bipolar illness. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Clin, Boston, MA USA. RP Yildiz, A (reprint author), Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. NR 21 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD APR PY 2003 VL 74 IS 2 BP 197 EP 201 DI 10.1016/S0165-0327(02)00003-4 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 676JX UT WOS:000182749100011 PM 12706522 ER PT J AU Stafford, RS Ma, J Finkelstein, SN Haver, K Cockburn, I AF Stafford, RS Ma, J Finkelstein, SN Haver, K Cockburn, I TI National trends in asthma visits and asthma pharmacotherapy, 1978-2002 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma visits; asthma pharmacotherapy; inhaled corticosteroids; bronchodilators; controller-to-reliever ratio; evidence-based guidelines ID GENERAL-PRACTICE; INHALED STEROIDS; UNITED-STATES; DRUG-THERAPY; MANAGEMENT; GUIDELINES; CARE; BRONCHODILATOR; MORBIDITY; MORTALITY AB Background: Research is limited on physicians' compliance with recent clinical guidelines for asthma treatment. Objective: Our purpose was to investigate the relationships among clinical guidelines, asthma pharmacotherapy, and office-based visits through use of nationally representative data. Methods: Nationally representative data on prescribing patterns by office-based US physicians were extracted from the National Disease and Therapeutic Index. We tracked 19782002 trends in the frequency of asthma visits and patterns of asthma pharmacotherapy, focusing on the use of controller and reliever medications. Results: The estimated annual number of asthma visits in the United States increased continuously from 1978 through 1990 (18 million visits); since 1990, it has remained relatively stable. Controller medication use increased 8-fold between 1978 and 2002, inhaled corticosteroids manifesting the biggest increases. The use of reliever medications, particularly short-acting oral beta(2)-agonists, decreased modestly over this period. The aggregate use of controllers (83% of visits) superseded that of relievers (80%) for the first time in 2001. Improved appropriateness of asthma pharmacotherapy was also suggested by an increase in the controller-to-reliever ratio, which reached 92% in 2002. Xanthines, which once dominated asthma therapy (63% of visits in 1978), were used in only 2% of visits in 2002. More recent drug entrants have been adopted rapidly, single-entity long-acting inhaled beta(2)-agonists being used in 9% of visits and leukotriene modifiers in 24% of visits in 2002. Conclusion: Asthma pharmacotherapy has changed extensively in the past 25 years. Practices over the last decade are increasingly consistent with evidence-based guidelines. These changes in medication use might have contributed to the lack of a recent increase in asthma visits. C1 Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. MIT, Program Pharmaceut Ind, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pediat, Pulm Unit, Boston, MA 02114 USA. Boston Univ, Sch Management, Boston, MA 02215 USA. RP Stafford, RS (reprint author), Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. RI Cockburn, Iain/G-9524-2013 OI Cockburn, Iain/0000-0003-2034-0187 FU AHRQ HHS [R01-HS013405] NR 31 TC 56 Z9 56 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2003 VL 111 IS 4 BP 729 EP 735 DI 10.1067/mai.2003.177 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 667WW UT WOS:000182258500009 PM 12704350 ER PT J AU Metlay, JP Strom, BL Asch, DA AF Metlay, JP Strom, BL Asch, DA TI Prior antimicrobial drug exposure: a risk factor for trimethoprim-sulfamethoxazole-resistant urinary tract infections SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-11, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID ACUTE UNCOMPLICATED CYSTITIS; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; ANTIBIOTIC-RESISTANCE; INCREASING PREVALENCE; UNITED-STATES; BETA-LACTAM; CONSUMPTION; PENICILLIN; ERYTHROMYCIN AB Objectives: Antimicrobial drug use is believed to be an important risk factor for the emerging problem of antimicrobial drug resistance, yet strong evidence for the causal relationship in community settings has been limited. Detailed analysis of this risk factor at the level of the individual patient has been hampered by limited availability of drug exposure data among patients with outpatient infections. We used a novel data system to identify patterns of individual antimicrobial drug exposures associated with trimethoprim-sulfamethoxazole-resistant urinary tract infections (UTIs). Materials and methods: This was a retrospective case-control study. Subjects were veterans with Gram-negative UTIs seen at the Philadelphia VA Medical Center from 1 July 1996 to 31 December 1999. Subjects were linked to a national VA outpatient pharmacy database. Cases and controls were identified based on the results of trimethoprim-sulfamethoxazole susceptibility testing. Results: Three hundred and ninety-three veterans with UTIs could be linked to electronic pharmacy records. The overall rate of trimethoprim-sulfamethoxazole drug resistance was 13%, without significant annual variation. Antimicrobial drug exposure within 6 months was strongly associated with the probability of a trimethoprim-sulfamethoxazole-resistant infection (OR = 4.1,95% Cl 2.2-7.5). This association extended to exposure to other antimicrobial drugs in addition to trimethoprim-sulfamethoxazole and the overall association displayed a dose-response relationship in terms of the number of prior drug exposures. Conclusions: Prior antimicrobial drug exposure is a strong risk factor for infection with trimethoprim-sulfamethoxazole-resistant Gram-negative bacteria among patients with UTIs. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 31 TC 30 Z9 31 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD APR PY 2003 VL 51 IS 4 BP 963 EP 970 DI 10.1093/jac/dkg146 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 670DV UT WOS:000182392900024 PM 12654756 ER PT J AU Li, G DeFrate, L Suggs, J Gill, T AF Li, G DeFrate, L Suggs, J Gill, T TI Determination of optimal graft lengths for posterior cruciate ligament reconstruction - A theoretical analysis SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID PATELLAR TENDON; BIOMECHANICAL ANALYSIS; KNEE-JOINT; IN-VITRO; FIXATION; MODEL; PLACEMENT; STRENGTH; CONTACT; COMPLEX AB Various graft materials have been used in posterior cruciate ligament (PCL) reconstruction. However it is unclear if these grafts can reproduce the structural behavior of the PCL. This paper analyzed the effect of graft length on the structural behavior of the graft using a minimal deformation energy method. An analytical solution was obtained to determine the optimal effective graft length that can best reproduce the structural behavior of the PCL. This optimal graft length was determined as a function of the axial rigidity of the graft. Two typical grafts, bone-patella tendon-bone (BPTB) and Achilles tendon, were analyzed. The data demonstrated that in order to reproduce the PCL behavior the effective length of a BPTB graft (10 nun width) should be 34 mm, while the Achilles tendon graft (with a cross sectional area of 55 nun 2) needs to be 48 nun in length. Longer grafts result in less resistance and shorter graft increased the graft resistance. An initial graft tension cannot help recreate the overall structural behavior of the PCL. These results suggest that graft length is an important surgical variable in PCL reconstruction. An optimal reconstruction of the PCL should reproduce the structural properties of the PCL by using a graft with an optimal length. C1 BIDMC, MGH, Orthopaed Biomech Lab, Boston, MA 02214 USA. Harvard Univ, Sch Med, Boston, MA 02214 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. BIDMC, MGH, Orthopaed Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Li, G (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02214 USA. NR 33 TC 7 Z9 8 U1 0 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD APR PY 2003 VL 125 IS 2 BP 295 EP 299 DI 10.1115/1.1554409 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 675YV UT WOS:000182725900017 PM 12751293 ER PT J AU Iftimia, N Bouma, BE Tearney, GJ AF Iftimia, N Bouma, BE Tearney, GJ TI Speckle reduction in optical coherence tomography by "path length encoded" angular compounding SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE speckle reduction; optical coherence tomography; catheters; endoscopes ID CATHETER; INTERFEROMETER AB Speckle, the dominant factor reducing image quality in optical coherence tomography (OCT), limits the ability to identify cellular structures that are essential for diagnosis of a variety of diseases. We describe a new high-speed method for implementing angular compounding by path length encoding (ACPE) for reducing speckle in OCT images. By averaging images obtained at different incident angles, with each image encoded by path length, ACPE maintains high-speed image acquisition and requires minimal modifications to OCT probe optics. ACPE images obtained from tissue phantoms and human skin in vivo demonstrate a qualitative improvement over traditional OCT and an increased SNR that correlates well with theory. (C) 2003 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Pathol, Boston, MA 02114 USA. RP Iftimia, N (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 703, Boston, MA 02114 USA. NR 11 TC 85 Z9 85 U1 1 U2 6 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2003 VL 8 IS 2 BP 260 EP 263 DI 10.1117/1.1559060 PG 4 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 669XE UT WOS:000182375200012 PM 12683852 ER PT J AU Payne, BP Venugopalan, V Mikic, BB Nishioka, NS AF Payne, BP Venugopalan, V Mikic, BB Nishioka, NS TI Optoacoustic determination of optical attenuation depth using interferometric detection SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photoacoustic; thermoelastic; optical diagnostics; optical properties ID TIME-RESOLVED REFLECTANCE; BIOLOGICAL TISSUE; INFRARED-SPECTROSCOPY; DIFFUSE-REFLECTANCE; LASER-ABLATION; ABSORPTION; TRANSDUCER; SCATTERING; TRANSMITTANCE; COEFFICIENTS AB We use a modified Mach-Zehnder interferometer to measure surface displacement resulting from the thermoelastic response of a target to the absorption of a short laser pulse with axial and temporal resolutions of 0.1 nm and 3 ns, respectively. These measurements are used in conjunction with a solution to the thermoelastic wave equation and a nonlinear optimization algorithm to extract optical attenuation depth. We demonstrate the ability to determine the effective optical attenuation depth of homogeneous targets with either diffuse or specular reflecting surfaces with a precision of less than or equal to4% for attenuation depths spanning 0.1 to 2 mm. (C) 2003 Society of Photo-Optical instrumentation. C1 Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. Beckman Laser Inst & Med Clin, Laser Microbeam & Med Program, Irvine, CA 92697 USA. RP Venugopalan, V (reprint author), Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. EM vvenugop@uci.edu FU NCRR NIH HHS [NCRR-01192] NR 33 TC 19 Z9 19 U1 1 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2003 VL 8 IS 2 BP 264 EP 272 DI 10.1117/1.1559731 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 669XE UT WOS:000182375200013 PM 12683853 ER PT J AU Payne, BP Venugopalan, V Mikic, BB Nishioka, NS AF Payne, BP Venugopalan, V Mikic, BB Nishioka, NS TI Optoacoustic tomography interferometric detection using time-resolved of surface displacement SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE photoacoustic; thermoelastic; optical diagnostics; optical imaging ID OPTICAL COHERENCE TOMOGRAPHY; IN-VIVO; IMAGE-RECONSTRUCTION; BLOOD-VESSELS; TISSUE; ULTRASOUND; TRANSDUCER; SKIN; DISTRIBUTIONS; MICROSCOPY AB We introduce a minimally invasive technique for optoacoustic imaging of turbid media using optical interferometric detection of surface displacement produced by thermoelastic stress transients. The technique exploits endogenous or exogenous optical contrast of heterogeneous tissues and the low attenuation of stress wave propagation to localize and image subsurface absorbers in optically turbid media. We present a system that utilizes a time-resolved high-resolution interferometer capable of angstrom-level displacement resolution and nanosecond temporal resolution to detect subsurface blood vessels within model tissue phantoms and a human forearm in vivo. (C) 2003 Society of Photo-Optical Instrumentation Engineers. C1 Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. Beckman Laser Inst & Med Clin, Laser Microbeam & Med Program, Irvine, CA 92697 USA. RP Venugopalan, V (reprint author), Univ Calif Irvine, Dept Chem Engn & Mat Sci, Irvine, CA 92697 USA. EM vvenugop@uci.edu FU NCRR NIH HHS [P41-RR-01192] NR 40 TC 47 Z9 48 U1 0 U2 5 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD APR PY 2003 VL 8 IS 2 BP 273 EP 280 DI 10.1117/1.1559727 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 669XE UT WOS:000182375200014 PM 12683854 ER PT J AU Weber, KL Gebhardt, MC AF Weber, KL Gebhardt, MC TI What's new in musculoskeletal oncology SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OSTEOLYTIC BONE METASTASES; RENAL-CELL CARCINOMA; BREAST-CANCER CELLS; PROSTATE-CANCER; MULTIPLE-MYELOMA; SKELETAL COMPLICATIONS; OSSEOUS METASTASES; SURGICAL-TREATMENT; GENE-EXPRESSION; IN-VIVO C1 Univ Texas, MD Anderson Canc Ctr, Sect Orthopaed Oncol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Weber, KL (reprint author), Univ Texas, MD Anderson Canc Ctr, Sect Orthopaed Oncol, Box 444,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 60 TC 4 Z9 4 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 APR PY 2003 VL 85A IS 4 BP 761 EP 767 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 664MV UT WOS:000182065600029 PM 12672857 ER PT J AU Hindman, HB Marty-Roix, R Tang, JB Jupiter, JB Simmons, BP Spector, M AF Hindman, HB Marty-Roix, R Tang, JB Jupiter, JB Simmons, BP Spector, M TI Regulation of expression of alpha-smooth muscle actin in cells of Dupuytren's contracture SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID GROWTH FACTOR-BETA; GRANULATION-TISSUE; GAMMA-INTERFERON; FIBROBLASTS; DISEASE; DIFFERENTIATION; MYOFIBROBLASTS; STIMULATION; QUIESCENT; INDUCTION AB Our aims were to describe the distribution of alpha-smooth muscle actin (SMA)-containing cells in Dupuytren's tissue in vivo and to determine the effects of selected agents in regulating the expression of SMA in Dupuytren's cells in vitro. In selected hypercellular zones of Dupuytren's nodules up to 40% of the cells contained SMA, as shown by immunohistochemistry. A lower percentage (20%) of SMA-containing cells was found in regions of lower cellularity. A notable finding was that treatment in vitro of Dupuytren's cells with platelet-derived growth factor significantly reduced the content of SMA. Cells from the same patients showed a significant increase in expression of SMA in response to treatment with transforming growth factor, which confirmed recent findings. In addition, interferon-gamma, which has been previously used as a treatment for Dupuytren's disease in a clinical study, had no reproducible effect on the expression of this actin isoform. Our findings are of significance for the conservative management of contractures. C1 VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spector, M (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. NR 30 TC 18 Z9 19 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD APR PY 2003 VL 85B IS 3 BP 448 EP 455 DI 10.1302/0301-620X.85B3.13219 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 669XW UT WOS:000182377200028 PM 12729127 ER PT J AU Havranek, EP Masoudi, FA Rumsfeld, JS Steiner, JF AF Havranek, EP Masoudi, FA Rumsfeld, JS Steiner, JF TI A broader paradigm for understanding and treating heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE chronic illness model; heart failure; health-related quality of life; heart failure epidemiology ID QUALITY-OF-LIFE; IMPROVING PRIMARY-CARE; HEALTH-STATUS; CLINICAL-TRIALS; CHRONIC ILLNESS; MORTALITY; SURVIVAL; HOSPITALIZATIONS; DEPRESSION; PREDICTOR AB Several recent clinical trials in heart failure have failed to demonstrate improvements in survival, suggesting that new approaches must be adopted if there are to be further improvements in heart failure treatment. We propose a broader paradigm for heart failure care based on a chronic rather than an acute illness model. This approach recognizes a broader range of outcomes including patient-perceived health status, expanded populations of interest that more closely reflect the changing epidemiology of heart failure, and a wider scope of interventions that address co-morbidity and health behavior. This approach will require a rationally designed health care delivery system that applies the best available evidence to the care of individual patients with heart failure. C1 Denver Hlth Med Ctr, Div Cardiol, Dept Med, Denver, CO 80204 USA. Colorodo Hlth Sci Ctr, Div Cardiol, Dept Med, Denver, CO USA. Univ Colorado, Ctr Hlth Sci, Colorado Hlth Outcomes Program, Denver, CO USA. Denver Vet Affairs Med Ctr, Cardiol & Hlth Serv Res, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO USA. RP Havranek, EP (reprint author), Denver Hlth Med Ctr, Div Cardiol, Dept Med, 777 Bannock St, Denver, CO 80204 USA. NR 41 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD APR PY 2003 VL 9 IS 2 BP 147 EP 152 DI 10.1054/jcaf.2003.21 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 669BW UT WOS:000182332900011 PM 12751136 ER PT J AU D'Avila, A Scanavacca, M Sosa, E Ruskin, JN Reddy, VY AF D'Avila, A Scanavacca, M Sosa, E Ruskin, JN Reddy, VY TI Pericardial anatomy for the interventional electrophysiologist SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE pericardium; catheter ablation; sinuses ID RECURRENT VENTRICULAR-TACHYCARDIA; EPICARDIAL CATHETER ABLATION; ATRIAL-FIBRILLATION; ATRIOVENTRICULAR NODES; VAGAL INNERVATION; CANINE HEART; RECESSES; CT; INFARCTION; SINUSES AB Pericardial Anatomy for the Interventional Electrophysiologist. investigators are beginning to exploit the pericardial space for a number of cardiovascular applications, including catheter ablation of cardiac arrhythmias, cardiovascular drug therapy, and cardiac pacing. This review explores the anatomy of the pericardial space and the anatomic variants that may be encountered in this novel approach to the heart. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, Inst Heart,InCor, Unidade Clin Arritmia, Sao Paulo, Brazil. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. RI d'Avila, Andre/A-7693-2009; Scanavacca, Mauricio Ibrahim/F-7693-2012; d'Avila, Andre Luiz/F-8009-2010 OI Scanavacca, Mauricio Ibrahim/0000-0001-7327-2275; d'Avila, Andre Luiz/0000-0001-8769-1411 FU NHLBI NIH HHS [K23 HL68064-01A1] NR 43 TC 37 Z9 38 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD APR PY 2003 VL 14 IS 4 BP 422 EP 430 DI 10.1046/j.1540-8167.2003.02487.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 674HU UT WOS:000182632000018 PM 12741718 ER PT J AU Kijima, T Maulik, G Ma, PC Madhiwala, P Schaefer, E Salgia, R AF Kijima, T Maulik, G Ma, PC Madhiwala, P Schaefer, E Salgia, R TI Fibronectin enhances viability and alters cytoskeletal functions (with effects on the phosphatidylinositol 3-kinase pathway) in small cell lung cancer SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE PI3-K; cell motility; cytoskeletal protein; extracellular matrix; small cell lung cancer ID SIGNAL-TRANSDUCTION; C-MET; ONCOGENESIS; ADHESION; GROWTH; PROLIFERATION; INHIBITION; MODULATION; MIGRATION; PROTEINS AB Small cell lung cancer (SCLC) is a rapidly progressive disease with ultimate poor outcome. SCLC has been shown to interact closely with the stromal and extracellular matrix (ECM) components of the diseased host. ECM consists of type I/IV collagen, laminin, vitronectin, and fibronectin (FN) among others. Herein, we investigated the behavior of a SCLC cell line (NCI-H446) on FN-coated surface. Over a course of 72 h, FN (10 mug/ml) caused both increased survival and proliferation of NCI-H446 cells. Survival under serum-starved conditions increased 1.44-fold and proliferation in the presence of fetal calf serum increased by 1.30-fold. The phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002 reduced both survival and proliferation of NCI-H446 cells (0.48- and 0.27-fold, respectively), even on FN-coated surface. We next determined the effects of FN on cytoskeletal function such as cell motility/morphology and adhesion. Over a course of 24 h, FN reduced aggregation of NCI-H446 cells and induced flattened cellular morphology with neurite-like projections after I h, however, in the presence of LY294002, the cells rounded up. Adhesion of NCI-H446 cells also increased with FN (4.47-fold) which was abrogated with LY294002 treatment. This correlated with phosphorylation of the cytoskeletal protein p125FAK, on Tyr397, Tyr861 and Ser843 residues with IN. Even in the presence of LY294002, these serine/tyrosine residues were still phosphorylated on FN-coated surface. In contrast, the focal adhesion protein paxillin was not phosphorylated at Tyr31 with FN. In summary, IN stimulation of SCLC cells leads to enhancement of viability and changes in cytoskeletal function that are partially mediated through the PI3-K pathway. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Dept Hematol & Oncol, Boston, MA 02111 USA. Biosource Int, Hopkinton, MA USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1234B,44 Binney St, Boston, MA 02115 USA. NR 20 TC 26 Z9 26 U1 0 U2 0 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD APR-JUN PY 2003 VL 7 IS 2 BP 157 EP 164 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 707TT UT WOS:000184526500009 PM 12927054 ER PT J AU Morley, SC Sun, GP Bierer, BE AF Morley, SC Sun, GP Bierer, BE TI Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE apoptosis; Cytochalasin D; actin; cytokine-withdrawal ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; RECEPTOR ZETA-CHAIN; T-CELL ACTIVATION; CYTOCHALASIN-D; FLOW-CYTOMETRY; LYMPHOCYTES; CYTOSKELETON; CLEAVAGE; MECHANISM; FAMILY AB We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259-4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, awe I I-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-x(L), but, unlike jasplakinolide, cytochalasin D modestly affected the "execution" stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway. Published 2003 Wiley-Liss, Inc.(dagger). C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. Div Med Sci, Comm Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Bierer, BE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 810,44 Binney St, Boston, MA 02115 USA. NR 52 TC 41 Z9 43 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 1 PY 2003 VL 88 IS 5 BP 1066 EP 1076 DI 10.1002/jcb.10449 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 656HC UT WOS:000181601700019 ER PT J AU Randolph, JF Sowers, M Gold, EB Mohr, BA Luborsky, J Santoro, N McConnell, DS Finkelstein, JS Korenman, SG Matthews, KA Sternfeld, B Lasley, BL AF Randolph, JF Sowers, M Gold, EB Mohr, BA Luborsky, J Santoro, N McConnell, DS Finkelstein, JS Korenman, SG Matthews, KA Sternfeld, B Lasley, BL TI Reproductive hormones in the early menopausal transition: Relationship to ethnicity, body size, and menopausal status SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; DEHYDROEPIANDROSTERONE-SULFATE; SERUM TESTOSTERONE; PHYSICAL-ACTIVITY; BINDING GLOBULIN; OVARIAN RESERVE; WOMEN; POPULATION; ESTRADIOL; AGE AB We measured serum reproductive hormone concentrations in a community-based, multiethnic population of premenopausal and early perimenopausal women to determine whether there are ethnic differences in hormones that can be explained by host factors. We studied 2930 participants in the Study of Women's Health Across the Nation who were aged 42-52 yr and self-identified as African-American (27.6%), Caucasian (47.1%), Chinese (7.4%), Hispanic (8.8%), or Japanese (9.0%) at 7 clinical sites. Outcome measures from this baseline assessment of a longitudinal study were serum estradiol (E2), FSH, testosterone (T), dehydroepiandrosterone sulfate, and SHBG concentrations and calculated estimates of free steroid availability, free testosterone index, and free E2 index from serum collected primarily in the early follicular phase of a spontaneous menstrual cycle. The primary explanatory variables were race/ethnicity, menopausal status, age, body mass index, day of the cycle, smoking, alcohol use, and physical activity. Chinese women had lower unadjusted E2 and SHBG levels, and Hispanic women had lower unadjusted T levels than other ethnic groups. Unadjusted serum FSH levels did not differ by race/ethnicity. E2 levels adjusted for host characteristics, particularly body size, did not differ by race/ethnicity. Adjusted FSH levels were higher, and adjusted T levels were lower in African-American and Hispanic women. Serum E2 and FSH concentrations were highly variable. Serum FSH levels, but no other hormone concentrations, were positively correlated with menopausal status. Serum dehydroepiandrosterone sulfate levels were negatively correlated with age, but not menopausal status. All hormone concentrations were significantly correlated with body mass index. We conclude that serum sex steroid, FSH, and SHBG levels vary by ethnicity, but are highly confounded by ethnic disparities in body size. C1 Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Univ, Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Pittsburgh, Pittsburgh, PA 15213 USA. Med Res Labs, Highland Hts, KY 41076 USA. New England Res Inst, Watertown, MA 02172 USA. RP Randolph, JF (reprint author), Univ Michigan Hlth Syst, Womens Hosp L4228, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [K24-DK-02759] NR 39 TC 189 Z9 193 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2003 VL 88 IS 4 BP 1516 EP 1522 DI 10.1210/jc.2002-020777 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667BM UT WOS:000182211000017 PM 12679432 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 Regulation of adiponectin in human immunodeficiency virus-infected patients: Relationship to body composition and metabolic indices SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE SYNDROME; COMPLEMENT-RELATED PROTEIN; ADIPOSE-SPECIFIC PROTEIN; ANTIRETROVIRAL THERAPY; PREADIPOCYTE DIFFERENTIATION; POTENTIAL MECHANISM; PLASMA-PROTEIN; LEPTIN LEVELS; OBESITY; FAT AB HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidemia, and insulin resistance. Adiponectin is an adipose-derived peptide thought to act as a systemic regulator of glucose and lipid metabolism. We investigated adiponectin concentrations in 10 HIV-infected patients during acute HIV infection (viral load, 2.0 x 10(6) +/- 1.0 x 10(6) copies/ml) and then 6-8 months later, as well as cross-sectionally in 41 HIV-infected patients (21 with evidence of fat redistribution and 20 without evidence of fat redistribution) in comparison with 20 age- and body mass index-matched healthy control subjects. Circulating adiponectin concentrations did not change with treatment of acute HIV infection (5.8 +/- 0.4 vs. 5.9 +/- 0.7 mug/ml, P = 0.96) but were reduced in patients with chronic HIV infection and fat redistribution (7.8 +/- 0.9 mug/ml), compared with age- and body mass index-matched HIV-infected patients without fat redistribution (12.7 +/- 1.7 mug/ml) and healthy control subjects (11.9 +/- 1.7 mug/ml, P < 0.05 vs. HIV-infected patients without fat redistribution and vs. control subjects). Adiponectin concentrations correlated with body composition [ correlation coefficient (r) = -0.47, P = 0.002 vs. trunk fat: total fat; r = 0.51, P < 0.001 vs. extremity fat: total fat], insulin response to glucose challenge (r = -0.36, P = 0.03), triglyceride (r = -0.39, P = 0.01), and high-density lipoprotein (r = 0.37, P = 0.02) among the HIV-infected patients. Adiponectin remained a significant correlate of insulin response to GTT, controlling for medication use and body composition changes in HIV-infected patients. These data suggest a strong relationship between adiponectin and body composition in HIV-infected patients. Changes in adiponectin may contribute to the metabolic dysregulation in this group of patients. C1 Harvard Univ, Sch Publ Hlth, Div Biol Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Harvard Univ, Sch Publ Hlth, Div Biol Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM sgrinspoon@partners.org; ghotamis@hsph.harvard.edu FU NIAID NIH HHS [AI-43879, AI-467274]; NIDDK NIH HHS [R01-DK-59535] NR 50 TC 68 Z9 70 U1 1 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 APR PY 2003 VL 88 IS 4 BP 1559 EP 1564 DI 10.1210/jc.2002-021600 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667BM UT WOS:000182211000024 PM 12679439 ER PT J AU Weigle, DS Cummings, DE Newby, PD Breen, PA Frayo, RS Matthys, CC Callahan, HS Purnell, JQ AF Weigle, DS Cummings, DE Newby, PD Breen, PA Frayo, RS Matthys, CC Callahan, HS Purnell, JQ TI Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOOD-INTAKE; INSULIN-RESISTANCE; PLASMA LEPTIN; ACYLATED PEPTIDE; INDUCED OBESITY; HUMANS; ADIPOSITY; WOMEN; APPETITE; RATS AB Loss of body fat by caloric restriction is accompanied by decreased circulating leptin levels, increased ghrelin levels, and increased appetite. In contrast, dietary fat restriction often decreases adiposity without increasing appetite. Substitution of dietary carbohydrate for fat has been shown to increase the area under the plasma leptin vs. time curve (AUC) over the course of 24 h. This effect, if sustained, could explain the absence of a compensatory increase in appetite on a low fat diet. To clarify the effect of dietary fat restriction on leptin and ghrelin, we measured AUC for these hormones in human subjects after each of the following sequential diets: 2 wk on a weight-maintaining 35% fat (F), 45% carbohydrate (C), 20% protein (P) diet (n = 18); 2 wk on an isocaloric 15% F, 65% C, 20% P diet (n = 18); and 12 wk on an ad libitum 15% F, 65% C, 20% P diet (n = 16). AUC for leptin was similar on the isocaloric 15% F and 35% F diets (555 +/- 57 vs. 580 +/- 56 ng/ ml.24 h; P = NS). Body weight decreased from 74.6 +/- 2.4 to 70.8 +/- 2.7 kg on the ad libitum 15% F diet (P < 0.001) without compensatory increases in food consumption or AUC for ghrelin. Proportional amplitude of the 24-h leptin profile was increased after 12 wk on the 15% fat diet. We conclude that weight loss early in the course of dietary fat restriction occurs independently of increased plasma leptin levels, but that a later increase in amplitude of the 24-h leptin signal may contribute to ongoing weight loss. Fat restriction avoids the increase in ghrelin levels caused by dietary energy restriction. C1 Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Weigle, DS (reprint author), Univ Washington, Harborview Med Ctr, Box 359757,325 9th Ave, Seattle, WA 98104 USA. EM weigle@u.washington.edu FU NCRR NIH HHS [RR-00037]; NIDDK NIH HHS [DK-35816, DK-17047, DK-02689, DK-02860, DK-55460] NR 43 TC 129 Z9 136 U1 0 U2 4 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 APR PY 2003 VL 88 IS 4 BP 1577 EP 1586 DI 10.1210/jc.2002-021262 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667BM UT WOS:000182211000027 PM 12679442 ER PT J AU Welt, CK Pagan, YL Smith, PC Rado, KB Hall, JE AF Welt, CK Pagan, YL Smith, PC Rado, KB Hall, JE TI Control of follicle-stimulating hormone by estradiol and the inhibins: Critical role of estradiol at the hypothalamus during the luteal-follicular transition SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FREE ALPHA-SUBUNIT; POSTMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; DIMERIC INHIBIN; PULSE FREQUENCY; ACTIVIN-A; PLASMA GONADOTROPINS; PREMENOPAUSAL WOMEN AB To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free alpha-subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 +/- 3.1 vs. 13.2 +/- 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 +/- 0.7 vs. 7.3 +/- 0.6 IU/liter; P < 0.01). In normal women, free alpha-subunit pulse frequency increased (7.3 +/- 0.4 vs. 4.8 +/- 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 +/- 1.6 vs. 12.5 +/- 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Med, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 511,Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [K24-HD-01290, U54-HD-29164] NR 48 TC 48 Z9 49 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 APR PY 2003 VL 88 IS 4 BP 1766 EP 1771 DI 10.1210/jc.2002-021516 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667BM UT WOS:000182211000056 PM 12679471 ER PT J AU Vahl, TP Paty, BW Fuller, BD Prigeon, RL D'Alessio, DA AF Vahl, TP Paty, BW Fuller, BD Prigeon, RL D'Alessio, DA TI Effects of GLP-1-(7-36)NH(2), GLP-1-(7-37), and GLP-1-(9-36)NH(2) on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; GASTRIC-INHIBITORY POLYPEPTIDE; DIABETIC-PATIENTS; 7-36 AMIDE; IN-VIVO; PHYSIOLOGICAL INCRETIN; RECEPTOR; IV; DEGRADATION; METABOLITE AB Glucagon-like peptide 1 (GLP-1) is an insulin secretagogue synthesized in the intestine and released in response to meal ingestion. It is secreted primarily in two forms, GLP1-(7-37) and GLP-1-(7-36)NH(2), both of which bind to a specific GLP-1 receptor (GLP-1r) on the pancreatic beta-cell and augment glucose-stimulated insulin secretion. Once secreted, GLP-1-(7-36)NH(2) is rapidly metabolized to GLP-1-(9-36)NH(2), which is the predominant form of GLP-1 in postprandial plasma because of its relatively slower clearance. Although no clear biological role for GLP-1-(9-36)NH(2) in humans has been identified, recent studies in animals suggest two potential effects: to antagonize the effects of intact GLP-1 and to promote glucose disappearance in peripheral tissues. In the studies reported here we compared the independent effects of GLP-1-(7-36)NH(2), GLP-1-(7-37), and GLP-1-(9-36)NH(2) on parameters of iv glucose tolerance and determined whether GLP-1-(9-36) NH(2) inhibits the insulinotropic actions of GLP-1. Ten healthy subjects underwent 4 separate frequently sampled iv glucose tolerance tests during infusions of GLP-1-(7-37), GLP-1-(7-36)NH(2), GLP-1-(9-36)NH, or saline. Results from the iv glucose tolerance test were used to obtain indexes of beta-cell function (acute insulin response to glucose) and iv glucose tolerance (glucose disappearance constant), and the minimal model of glucose kinetics was used to obtain indexes of glucose effectiveness and insulin sensitivity. Compared with control studies, both GLP-1-(7-36)NH(2) and GLP-1-(7-37) significantly increased acute insulin response to glucose, glucose disappearance constant, glucose effectiveness, and glucose effectiveness at zero insulin, but did not change the insulin sensitivity index. In contrast, none of the parameters of glucose tolerance was measurably affected by GLP-1-(9-36) amide. In a second set of experiments, 10 healthy subjects had glucose-stimulated insulin secretion measured during an infusion of GLP-1-(7-36)NH(2) alone or with a simultaneous infusion of GLP-1-(9-36)NH(2) that increased plasma levels approximately 10-fold over those produced by unmetabolized GLP-1. Augmentation of glucose-stimulated insulin secretion by GLP-1-(7-36)NH(2) was not altered by the coadministration of GLP-1-(9-36)NH(2). Based on these results we conclude that GLP-1-(9-36)NH(2) does not regulate insulin release or glucose metabolism in healthy humans. C1 Univ Cincinnati, Div Endocrinol, Cincinnati, OH 45267 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP D'Alessio, DA (reprint author), Univ Cincinnati, Div Endocrinol, ML-0547, Cincinnati, OH 45267 USA. EM david.d'alessio@uc.edu FU NCRR NIH HHS [M01-RR-08084]; NIDDK NIH HHS [R01-DK-54263] NR 37 TC 94 Z9 102 U1 0 U2 9 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 APR PY 2003 VL 88 IS 4 BP 1772 EP 1779 DI 10.1210/jc.2002-021479 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667BM UT WOS:000182211000057 PM 12679472 ER PT J AU Yang, CL Angell, J Mitchell, R Ellison, DH AF Yang, CL Angell, J Mitchell, R Ellison, DH TI WNK kinases regulate thiazide-sensitive Na-Cl cotransport SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FUNCTIONAL EXPRESSION; GITELMANS-SYNDROME; DISTAL NEPHRON; MUTATIONS; HYPERTENSION; DIURETICS; DENSITY; TUBULE; KIDNEY; GENE AB Pseudohypoaldosteronism type II (PHAII) is an autosomal dominant disorder of hyperkalemia and hypertension. Mutations in two members of the WNK kinase family, WNK1 and WNK4, cause the disease. WNK1 mutations are believed to increase WNK1 expression; the effect of WNK4 mutations remains unknown. The clinical phenotype of PHAII is opposite to Gitelman syndrome, a disease caused by dysfunction of the thiazide-sensitive Na-Cl cotransporter. We tested the hypothesis that WNK kinases regulate the mammalian thiazide-sensitive Na-Cl cotransporter (NCC). Mouse WNK4 was cloned and expressed in Xenopus oocytes with or without NCC. Coexpression with WNK4 suppressed NCC activity by more than 85%. This effect did not result from defects in NCC synthesis or processing, but was associated with an 85% reduction in NCC abundance at the plasma membrane. Unlike WNK4, WNK1 did not affect NCC activity directly. WNK1, however, completely prevented WNK4 inhibition of NCC. Some WNK4 mutations that cause PHAII retained NCC-inhibiting activity, but the Q562E WNK4 demonstrated diminished activity, suggesting that some PHAII mutations lead to loss of NCC inhibition. Gain-of-function WNK1 mutations would be expected to inhibit WNK4 activity, thereby activating NCC, contributing to the PHAII phenotype. Together, these results identify WNK kinases as a previously unrecognized sodium regulatory pathway of the distal nephron. This pathway likely contributes to normal and pathological blood pressure homeostasis. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Ellison, DH (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [R01 DK-51496, R01 DK051496] NR 25 TC 302 Z9 310 U1 1 U2 9 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 APR PY 2003 VL 111 IS 7 BP 1039 EP 1045 DI 10.1172/JCI200317443 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 662VY UT WOS:000181970600015 PM 12671053 ER PT J AU Soberman, RJ Christmas, P AF Soberman, RJ Christmas, P TI The organization and consequences of eicosanoid signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); LEUKOTRIENE C-4 SYNTHASE; PROSTAGLANDIN E-2 BIOSYNTHESIS; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); CYCLOPENTENONE PROSTAGLANDINS; PHOSPHORYLATION SITES; RECEPTOR ANTAGONIST; HUMAN EOSINOPHILS; NUCLEAR-ENVELOPE; HUMAN-LEUKOCYTES C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Soberman, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, 149 Navy Yard, Charlestown, MA 02129 USA. EM Soberman@helix.mgh.harvard.edu FU NIDDK NIH HHS [K01 DK 59991]; NIGMS NIH HHS [R01 GM 061823, R01 GM061823] NR 98 TC 92 Z9 99 U1 2 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2003 VL 111 IS 8 BP 1107 EP 1113 DI 10.1172/JCI200318338 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 668GE UT WOS:000182281300002 PM 12697726 ER PT J AU Dranoff, G AF Dranoff, G TI Coordinated tumor immunity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CANCER; VACCINATION; CARCINOGENESIS; LYMPHOCYTES; MICE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 66996, R01 CA074886, CA 39542, CA 74886, P01 CA066996, P01 CA039542] NR 15 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2003 VL 111 IS 8 BP 1116 EP 1118 DI 10.1172/JCI200318359 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 668GE UT WOS:000182281300004 PM 12697728 ER PT J AU Teramoto, T Qu, JH Plumier, JC Moskowitz, MA AF Teramoto, T Qu, JH Plumier, JC Moskowitz, MA TI EGF amplifies the replacement of parvalbumin-expressing striatal interneurons after ischemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; ADULT SUBVENTRICULAR ZONE; FOCAL CEREBRAL-ISCHEMIA; NEUROGENESIS IN-VITRO; RAT-BRAIN; GABAERGIC INTERNEURONS; FACTOR RECEPTOR; STIMULATES NEUROGENESIS; HUNTINGTONS-DISEASE AB EGF promotes proliferation and migration of stem/progenitor cells in the normal adult brain. The effect of epidermal growth factor on neurogenesis in ischemic brain is unknown, however. Here we show that intraventricular administration of EGF and albumin augments 100-fold neuronal replacement in the injured adult mouse striatum after cerebral ischemia. Newly born immature neurons migrate into the ischemic lesion and differentiate into mature parvalbumin-expressing neurons, replacing more than 20% of the interneurons lost by 13 weeks after ischemia and representing 2% of the total BrdU-Iabeled cells. These data suggest that administration of EGF and albumin could be used to manipulate endogenous neurogenesis in the injured brain and to promote brain self-repair. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Ctr,Radiol Dept, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Univ Liege, Dept Sci Vie, Serv Physiol Anim, B-4000 Sart Tilman Par Liege, Belgium. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Neurosci, Bldg 149,13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [5P50 NS 10828, P50 NS010828] NR 52 TC 152 Z9 171 U1 1 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2003 VL 111 IS 8 BP 1125 EP 1132 DI 10.1172/JCI200317170 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 668GE UT WOS:000182281300008 PM 12697732 ER PT J AU DePinho, RA Wong, KK AF DePinho, RA Wong, KK TI The age of cancer: telomeres, checkpoints, and longevity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; MOUSE TELOMERASE; DYSKERATOSIS-CONGENITA; NEOPLASTIC PHENOTYPE; TUMOR MAINTENANCE; HUMAN FIBROBLASTS; IMMORTAL CELLS; LIVER-DISEASES; INK4A LOCUS; MICE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St,M413, Boston, MA 02115 USA. NR 76 TC 26 Z9 26 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2003 VL 111 IS 7 BP S9 EP S14 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 662VY UT WOS:000181970600023 PM 12688272 ER PT J AU Song, YL Liu, CX McTeague, M Finegold, SM AF Song, YL Liu, CX McTeague, M Finegold, SM TI 16S ribosomal DNA sequence-based analysis of clinically significant gram-positive anaerobic cocci SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SP-NOV; GENUS PEPTOSTREPTOCOCCUS; RNA GENE; IDENTIFICATION; SPECIMENS; BACTERIA; PROPOSAL; SYSTEMS; HUMANS AB Sequence analysis of the 16S rRNA gene represents a highly accurate and versatile method for bacterial classification and identification, even when the species in question is notoriously difficult to identify by phenotypic means. However, its use for identification based on public sequence databases is not without limitation due to the presence of ambiguous data in the databases. In this study, we evaluated the utility of 16S ribosomal DNA sequencing as a means of identifying clinically important gram-positive anaerobic cocci (GPAC) by sequencing 13 type strains of established GPAC species and 156 clinical isolates that had been studied only by phenotypic tests. Among the 13 type strains of GPAC species we tested, only 4 gave a "perfect" match with their corresponding sequences in GenBank, whereas the other 9 had lower sequence similarities (<98%). This indicates that data in the public database may be inaccurate at times. Based on the sequences of the 13 type strains obtained in this study, 84% (131 of 156) of the clinical isolates were accurately identified to species level, with the remaining 25 clinical strains revealing nine unique sequences that may represent eight novel species. This finding is in contrast to the phenotypic identification results, by which only 56% of isolates were correctly identified to species level. C1 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. W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90073 USA. RP Song, YL (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd,Rm E3-237,Bldg 304, Los Angeles, CA 90073 USA. NR 39 TC 51 Z9 54 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 APR PY 2003 VL 41 IS 4 BP 1363 EP 1369 DI 10.1128/JCM.41.4.1363-1369.2003 PG 7 WC Microbiology SC Microbiology GA 666LZ UT WOS:000182179900003 PM 12682115 ER PT J AU Wallgren, A Bonetti, M Gelber, RD Goldhirsch, A Castiglione-Gertsch, M Holmberg, SB Lindtner, J Thurlimann, B Fey, M Werner, ID Forbes, JF Price, K Coates, AS Collins, J AF Wallgren, A Bonetti, M Gelber, RD Goldhirsch, A Castiglione-Gertsch, M Holmberg, SB Lindtner, J Thurlimann, B Fey, M Werner, ID Forbes, JF Price, K Coates, AS Collins, J TI Risk factors for locoregional recurrence among breast cancer patients: Results from international breast cancer study group trials I through VII SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPH-NODE METASTASIS; POSTOPERATIVE RADIOTHERAPY; PROGNOSTIC-SIGNIFICANCE; ADJUVANT CHEMOTHERAPY; PREMENOPAUSAL WOMEN; CLINICAL-TRIALS; COMPETING RISK; THERAPY; MASTECTOMY; TAMOXIFEN AB Purpose: To explore prognostic factors for locoregional failures (LRF) among women treated for invasive breast cancer within clinical trials of adjuvant therapies. Patients and Methods: The study population consisted of 5,352 women who were treated with a modified radical mastectomy and enrolled in one of seven International Breast Cancer Study Group randomized trials. A total of 1,275 women with node-negative disease received either no adjuvant therapy or a single cycle of perioperative chemotherapy, and 4,077 women with node-positive disease received adjuvant chemotherapy of at least 3 months' duration and/or tamoxifen. Median follow-up is 12 to 15.5 years. Results: In women with node-negative disease, factors associated with increased risk of LRF were vascular invasion (VI) and tumor size greater than 2 cm for premenopausal and VI for postmenopausal patients. Of the 1,275 patients, 345 (27%) met criteria for the highest risk groups, and the 10-year cumulative incidences of LRF with or without distant metastases were 16% for premenopausal and 19% for postmenopausal women. For the node-positive cohort, number of nodes and tumor grade were factors for both menopausal groups, with additional prediction provided by VI for premenopausal and tumor size for postmenopausal patients. Of the 4,077 patients, 815 (20%) met criteria for the highest risk groups, and 10-year cumulative incidences were 35% for premenopausal and 34% for postmenopausal women. Conclusion: LRFs are a significant problem after mastectomy alone even for some patients with node-negative breast cancer, as well as after mastectomy and adjuvant treatment for some subgroups of patients with node-positive disease. In addition to number of positive lymph nodes, predictors of LRF include tumor-related factors, such as vascular invasion, higher grade, and larger size. (C) 2003 by American Society of Clinical Oncology. C1 Gothenburg Univ, Sahlgrens Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. Int Breast Canc Study Grp, Ctr Stat, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. European Inst Oncol, Milan, Italy. Oncol Inst So Switzerland, Bellinzona, Switzerland. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Inselspital Bern, Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. SU Moelndal Hosp, Dept Surg, Molndal, Sweden. Inst Oncol, Ljubljana, Slovenia. Groote Shuur Hosp, Cape Town, South Africa. Univ Cape Town, ZA-7700 Rondebosch, South Africa. Australian New Zealand Breast Canc Trials Grp, Newcastle, NSW, Australia. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. RP Wallgren, A (reprint author), Gothenburg Univ, Sahlgrens Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. OI Bonetti, Marco/0000-0003-2304-4180 NR 35 TC 151 Z9 158 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1205 EP 1213 DI 10.1200/JCO.2003.03.130 PG 9 WC Oncology SC Oncology GA 662XB UT WOS:000181973400003 PM 12663706 ER PT J AU Messing, EM Manola, J Wilding, G Propert, K Fleischmann, J Crawford, ED Pontes, JE Hahn, R Trump, D AF Messing, EM Manola, J Wilding, G Propert, K Fleischmann, J Crawford, ED Pontes, JE Hahn, R Trump, D TI Phase III study of interferon Alfa-NL as adjuvant treatment for resectable renal cell carcinoma: An eastern cooperative oncology group/intergroup trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; PROGNOSTIC FACTORS; ALPHA-INTERFERON; RANDOMIZED TRIAL; INTERLEUKIN-2; CANCER; SURVIVAL; THERAPY; GAMMA; MULTICENTER AB Purpose: To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma. Patients and Methods: A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate. Results: At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v NO, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P = .009) and shorter time to recurrence (P < .0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment. Conclusion: Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients. (C) 2003 by American Society of Clinical Oncology. C1 Univ Rochester, Sch Med & Dent, Rochester, NY 14642 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Einstein & New York Westchester Sq, Bronx, NY USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Mayo Clin, Rochester, MN USA. RP Messing, EM (reprint author), Univ Rochester, Sch Med & Dent, 601 Elmwood Ave,Box 656, Rochester, NY 14642 USA. FU NCI NIH HHS [CA-23318] NR 46 TC 142 Z9 155 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1214 EP 1222 DI 10.1200/JCO.2003.02.005 PG 9 WC Oncology SC Oncology GA 662XB UT WOS:000181973400004 PM 12663707 ER PT J AU Halabi, S Small, EJ Kantoff, PW Kattan, MW Kaplan, EB Dawson, NA Levine, EG Blumenstein, BA Vogelzang, NJ AF Halabi, S Small, EJ Kantoff, PW Kattan, MW Kaplan, EB Dawson, NA Levine, EG Blumenstein, BA Vogelzang, NJ TI Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LEUKEMIA GROUP-B; ENDOTHELIAL GROWTH-FACTOR; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; CLINICAL-TRIAL; GLEASON SCORE; PHASE-II; ANTIGEN; CARCINOMA; THERAPY AB Purpose: To develop and validate a model that can be used to predict the overall survival probability among metastatic hormone-refractory prostate cancer patients (HRPC). Patients and Methods: Data from six Cancer and Leukemia Group B protocols that enrolled 1,101 patients with metastatic hormone-refractory adenocarcinoma of the prostate during the study period from 1991 to 2001 were pooled. The proportional hazards model was used to develop a multivariable model on the basis of pretreatment factors and to construct a prognostic model. The area under the receiver operating characteristic curve (ROC) was calculated as a measure of predictive discrimination. Calibration of the model predictions was assessed by comparing the predicted probability with the actual survival probability. An independent data set was used to validate the fitted model. Results: The final model included the following factors: lactate dehydrogenase, prostate-specific antigen, alkaline phosphatase, Gleason sum, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease. The area under the ROC curve was 0.68. Patients were classified into one of four risk groups. We observed a good agreement between the observed and predicted survival probabilities for the four risk groups. The observed median survival durations were 7.5 (95% confidence interval [CI], 6.2 to 10.9), 13.4 (95% CI, 9.7 to 26.3), 18.9 (95% CI, 16.2 to 26.3), and 27.2 (95% CI, 21.9 to 42.8) months for the first, second, third, and fourth risk groups, respectively. The corresponding median predicted survival times were 8.8,13.4,17.4, and 22.80 for the four risk groups. Conclusion: This model could be used to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials. (C) 2003 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Duke Univ, Med Ctr, CALGB Stat Ctr, Durham, NC 27710 USA. Univ Calif San Francisco, Urol Oncol Program, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Chicago, Med Ctr, Dept Med, Sect Hematol & Oncol, Chicago, IL 60637 USA. RP Halabi, S (reprint author), Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Box 3958, Durham, NC 27710 USA. FU NCI NIH HHS [CA31946, CA36601] NR 41 TC 418 Z9 422 U1 3 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1232 EP 1237 DI 10.1200/JCO.2003.06.100 PG 6 WC Oncology SC Oncology GA 662XB UT WOS:000181973400006 PM 12663709 ER PT J AU Pollack, A Grignon, DJ Heydon, KH Hammond, EH Lawton, CA Mesic, JB Fu, KK Porter, AT Abrams, RA Shipley, WU AF Pollack, A Grignon, DJ Heydon, KH Hammond, EH Lawton, CA Mesic, JB Fu, KK Porter, AT Abrams, RA Shipley, WU TI Prostate cancer DNA ploidy and response to salvage hormone therapy after radiotherapy with or without short-term total androgen blockade: An analysis of RTOG 8610 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID S-PHASE FRACTION; DEOXYRIBONUCLEIC-ACID PLOIDY; CYTOMETRIC PROLIFERATION INDEX; RADICAL PROSTATECTOMY; RADIATION-THERAPY; FLOW-CYTOMETRY; PATHOLOGICAL STAGE; LOW-GRADE; CARCINOMA; ADENOCARCINOMA AB Purpose: DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus shortcourse (similar to4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB). Patients and Methods: The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival. Results: DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation. Conclusions: Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB. (C) 2003 by American Society of Clinical Oncology. C1 Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Radiat Therapy Oncol Grp, Philadelphia, PA USA. Karmanos CA Inst, Dept Pathol, Detroit, MI USA. Wayne State Univ, Dept Radiat Oncol, Detroit, MI USA. LDS Hosp, Dept Pathol, Salt Lake City, UT USA. Med Coll Wisconsin, Dept Radiat Oncol, Milwaukee, WI 53226 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Johns Hopkins Univ Hosp, Div Radiat Oncol, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Pollack, A (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 46 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1238 EP 1248 DI 10.1200/JCO.2003.02.025 PG 11 WC Oncology SC Oncology GA 662XB UT WOS:000181973400007 PM 12663710 ER PT J AU Ayanian, JZ Zaslavsky, AM Fuchs, CS Guadagnoli, E Creech, CM Cress, RD O'Connor, LC West, DW Allen, ME Wolf, RE Wright, WE AF Ayanian, JZ Zaslavsky, AM Fuchs, CS Guadagnoli, E Creech, CM Cress, RD O'Connor, LC West, DW Allen, ME Wolf, RE Wright, WE TI Use of adjuvant chemotherapy and radiation therapy for colorectal cancer in a population-based cohort SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLON-CANCER; ELDERLY PATIENTS; RECTAL-CANCER; MEDICARE CLAIMS; LINKED MEDICARE; BREAST-CANCER; AGE; CARCINOMA; CARE; FLUOROURACIL AB Purpose: Randomized trials have demonstrated that adjuvant chemotherapy improves survival for patients with stage III colon cancer and that chemotherapy combined with radiation therapy improves survival for patients with stage II or III rectal cancer. This population-based study was designed to assess use of these treatments in clinical practice. Patients and Methods: From the California Cancer Registry, we identified all patients diagnosed during 1996 to 1997 with stage III colon cancer (n = 1,422) and stage 11 or III rectal cancer (n = 534) in 22 northern California counties. To supplement registry data on adjuvant therapies and ascertain reasons they were not used, we surveyed physicians or reviewed office records for 1,449 patients (74%). Results: Chemotherapy rates varied widely by age from 88% (age < 55 years) to 11% (age greater than or equal to 85 years), and radiation therapy varied similarly. Adjusting for demographic, clinical, and hospital characteristics, chemotherapy was used less often among older and unmarried patients, and radiation therapy was used less often among older patients, black patients, and those initially treated in low-volume hospitals. Adjusted rates of chemotherapy, varied significantly (P < .01) among individual hospitals: 79% and 51%, respectively, at one SD above and below average (67%). Physicians' reasons for not providing adjuvant therapy included patient refusal (30% for chemotherapy, 22% for radiation therapy), comorbid illness (22% and 14%, respectively), or lack of clinical indication (22% and 45%, respectively). Conclusion: Use of adjuvant therapy for colorectal cancer varies substantially by age, race, marital status, hospital volume, and individual hospital, indicating opportunities to improve care. With enhanced data on adjuvant therapies, population-based registries could become a valuable resource for monitoring the quality of cancer care. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA USA. Calif Dept Hlth Serv, Canc Surveillance Program, Sacramento, CA USA. Calif Dept Hlth Serv, Canc Surveillance Sect, Sacramento, CA USA. Inst Publ Hlth, Berkeley, CA USA. No Calif Canc Ctr, Union City, CA USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM ayanian@hcp.med.harvard.edu FU AHRQ HHS [R01 HS09869] NR 55 TC 209 Z9 211 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1293 EP 1300 DI 10.1200/JCO.2003.06.178 PG 8 WC Oncology SC Oncology GA 662XB UT WOS:000181973400014 PM 12663717 ER PT J AU Lewis, JH Kilgore, ML Goldman, DP Trimble, EL Kaplan, R Montello, MJ Housman, MG Escarce, JJ AF Lewis, JH Kilgore, ML Goldman, DP Trimble, EL Kaplan, R Montello, MJ Housman, MG Escarce, JJ TI Participation of patients 65 years of age or older in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; ACUTE MYELOID-LEUKEMIA; CHEMOTHERAPY; WOMEN; UNDERREPRESENTATION; REPRESENTATION AB Purpose: Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation. Patients and Methods: We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly. Results: Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P < .001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%. Conclusion: The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient. (C) 2003 by American Society of Clinical Oncology. C1 RAND Hlth, Santa Monica, CA 90407 USA. Calif State Univ Los Angeles, Los Angeles, CA 90032 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Lewis, JH (reprint author), RAND, 1700 Main St, Santa Monica, CA 90407 USA. NR 37 TC 486 Z9 492 U1 1 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2003 VL 21 IS 7 BP 1383 EP 1389 DI 10.1200/JCO.2003.08.010 PG 7 WC Oncology SC Oncology GA 662XB UT WOS:000181973400028 PM 12663731 ER PT J AU Kashket, S Maiden, MFJ Haffajee, AD Kashket, ER AF Kashket, S Maiden, MFJ Haffajee, AD Kashket, ER TI Accumulation of methylglyoxal in the gingival crevicular fluid of chronic periodontitis patients SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE chronic periodontitis; periodontal health; Bacteroides forsythus; gingival crevicular fluid; methylglyoxal; subgingival microorganisms ID SUBGINGIVAL PLAQUE; ESCHERICHIA-COLI; MICROBIOTA; PROTEIN; CELLS AB Background, aims: Methylglyoxal (MG), a toxic product of cellular metabolism, is elevated in tissues and fluids in a number of human diseases. A cross-sectional study was undertaken to determine whether MG accumulates in the gingival crevicular fluid (GCF) of chronic periodontitis patients. Methods: GCF samples were collected for 30 s each from three teeth with pocket depths greater than 3 mm (DD sites), from 14 chronic periodontitis patients. Control samples were taken from three healthy sites (DH sites) in the same patients, as well as from seven subjects who were periodontally healthy (HH sites). Fluid volumes were determined and the strips were placed in 0.5 N perchloric acid. Subsequently, samples were derivatized with o -phenylenediamine and the resulting methylquinoxaline was assayed by high-performance liquid chromatography on Lichrospher(R)-100 RP-18, with UV detection. Results: Mean pocket depths were 5.7+/-0.7, 2.7+/-0.6 and 2.7+/-0.5 mm (mean+/-SD) for the DD, DH and HH sites, respectively. Mean MG levels were found to be 208.7+/-241.7 and 142.9+/-235.7 pmol/site in the GCF from DD and DH sites, respectively (p = 0.0023), but only 11.5+/-4.4 pmol/site for the HH sites. Bacteroides forsythus has been found to accumulate high levels of MG in culture (unpublished data) and, consistent with this, the sampled diseased sites contained higher levels of B. forsythus than the corresponding healthy sites (2.7+/-4.2x10(5) versus 0.7+/-1.1x10(5), respectively; p =0.022). Total "red complex" microorganisms were significantly elevated in the DD sites. Conclusions: In view of the known protein- and DNA-modifying effects of MG, the finding of elevated levels of MG in the GCF from chronic periodontitis patients supports the hypothesis that MG may contribute to destructive tissue damage in this disease. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Kashket, S (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU DS NIH HHS [DS 12108]; NIDCR NIH HHS [DE 12861, DE 12886, DE 13232] NR 16 TC 12 Z9 13 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 APR PY 2003 VL 30 IS 4 BP 364 EP 367 DI 10.1034/j.1600-051X.2003.00322.x PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 667XB UT WOS:000182259200013 PM 12694437 ER PT J AU Hendrick, V Smith, LM Hwang, S Altshuler, LL Haynes, D AF Hendrick, V Smith, LM Hwang, S Altshuler, LL Haynes, D TI Weight gain in breastfed infants of mothers taking antidepressant medications SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MILK; FLUOXETINE; GROWTH AB Background. Little is known about the physical development of infants who are exposed to antidepressant medications through breast milk. Method: Seventy-eight breastfeeding women taking antidepressant medications were included in the study. Maternal mood was prospectively evaluated at 6, 12, and 18 months postpartum. Infants' weights were obtained from review of pediatric records. Data were gathered from 1997 to 2002. Results: Infants' weights were not significantly different from weights of 6-month-old breastfed infants from normative populations. However, infants of mothers who relapsed to relatively long-lasting major depressive episodes (lasting 2 months or more) following delivery weighed significantly (p = .002) less when compared with infants of mothers who relapsed to brief depressive episodes (< 2 months) and infants of mothers who did not relapse to depression in the postpartum period. This finding remained after including medication dosage and infant birth weight as covariates. Conclusion: Exposure to antidepressant medications through breast milk does not appear to affect infants' weight. However, infants exposed to maternal depression lasting 2 months or more appear to experience significantly lower weight gain than infants of euthymic mothers or mothers who experience brief (< 2 months) major depressive episodes. Maternal depression following delivery may influence behaviors that, over the course of 2 months or more, affect infants' weight gain. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Pediat, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Hendrick, V (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Dept Psychiat & Behav Sci, UCLA Med Plaza,Bldg 300,Ste 2345, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [M01 RR00425]; NIMH NIH HHS [MH01451-01] NR 14 TC 24 Z9 27 U1 1 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 APR PY 2003 VL 64 IS 4 BP 410 EP 412 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 672WH UT WOS:000182545700009 PM 12716242 ER PT J AU Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL Cohen, LS AF Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL Cohen, LS TI Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID HOT FLASHES; REPLACEMENT THERAPY; MENOPAUSAL WOMEN; CONTROLLED TRIAL; BREAST-CANCER; MOOD; MIRTAZAPINE; FLUOXETINE; PREVALENCE; SERTRALINE AB Background: Women frequently report depressive and vasomotor symptoms during the menopausal transition. Hormone therapy has been shown to improve some of these symptoms, although its safety as a long-term treatment has been questioned. It is still unclear whether the use of antidepressants alone may alleviate menopause-related mood and vasomotor symptoms or enhance the response observed with short-term use of estrogen therapy. Method: Perimenopausal and postmenopausal women with depressive disorders (DSM-IV criteria) and menopause-related symptoms received treatment with 20 to 60 mg/day of citalopram. alone (N = 22) or adjunctive to estrogen therapy (N = 13). Adjunctive treatment was offered to subjects who had failed to show remission of depression after 4 weeks with estrogen therapy (estradiol [E-2]) alone. Depressive symptoms, menopause-related symptoms, and global clinical improvement were assessed at baseline and at endpoint of adjunctive treatment (8 weeks) or citalopram monotherapy (12 weeks). Remission of depression was defined as a score of < 10 on the Montgomery-Asberg Depression Rating Scale and a score of less than or equal to 2 on the Clinical Global Impressions scale at endpoint. Data were collected from November 2000 to February 2002. Results: Twelve women (92.3%) concluded the 8-week adjunctive treatment; I I subjects (91.6%) achieved full remission of depression. Symptoms that had persisted after an initial 4-week treatment with E-2 alone (e.g., tension, anxiousness, tiredness, and difficulty in concentrating) improved significantly (p < .05). Fifteen subjects concluded the treatment with citalopram monotherapy; 13 subjects (86.6%) showed full remission of depression. Anxiety and other somatic complaints had significant improvement (p < .05), while there was a trend toward improvement in vasomotor symptoms in those receiving monotherapy (p = .06). Conclusion: Citalopram alone is an efficacious treatment for perimenopausal and postmenopausal women with depression. Citalopram also appears to be efficacious as an adjunctive treatment for depressed subjects who remain symptomatic after treatment with E-2 (i.e., E-2 nonremitters). The role of citalopram monotherapy for the management of vasomotor symptoms warrants further investigation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Soares, CN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 41 TC 60 Z9 63 U1 1 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 APR PY 2003 VL 64 IS 4 BP 473 EP 479 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 672WH UT WOS:000182545700019 PM 12716252 ER PT J AU Monnelly, EP Ciraulo, DA Knapp, C Keane, T AF Monnelly, EP Ciraulo, DA Knapp, C Keane, T TI Low-dose risperidone as adjunctive therapy for irritable aggression in posttraumatic stress disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID FLUOXETINE; PLACEBO AB Increased aggressive behavior can occur in association with posttraumatic stress disorder (PTSD). This study tested the hypothesis that low-dose risperidone reduces aggression and other PTSD-related symptoms in combat veterans. Subjects were male combat veterans with PTSD who scored 20 or higher on cluster D (hyperarousal) of the Patient Checklist for PTSD-Military Version (PCL-M). Subjects were randomly assigned to either risperidone or placebo treatment groups. Drugs were administered over a 6-week treatment period in a double-blind manner. Subjects received either risperidone (0.5 mg/day; n = 7) or matched placebo (n = 8) tablets during the first 2 weeks of the treatment period. The dose of risperidone could then be increased up to 2.0 mg/day on the basis of response. Prerandomization psychotropic regimens were continued. Subjects were evaluated with the PCL-M and the Overt Aggression Scale-Modified for Outpatients (OAS-M). In comparison with placebo treatment, reductions in scores between baseline and the last week of treatment were significantly greater for OAS-M irritability and PCL-M cluster B (intrusive thoughts) subscales and on,the PCL-M total scale. These results suggest that low-dose risperidone administration reduces irritability and intrusive thoughts in combat-related PTSD. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Medicat Dev Res Unit, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Ciraulo, DA (reprint author), Boston Univ, Sch Med, Div Psychiat, Suite 914 DOB,720 Harrison Ave, Boston, MA 02118 USA. EM dciraulo@bu.edu NR 25 TC 99 Z9 100 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2003 VL 23 IS 2 BP 193 EP 196 DI 10.1097/00004714-200304000-00012 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 659ZN UT WOS:000181809500012 PM 12640221 ER PT J AU Namerow, LB Thomas, P Bostic, JQ Prince, J Monuteaux, MC AF Namerow, LB Thomas, P Bostic, JQ Prince, J Monuteaux, MC TI Use of citalopram in pervasive developmental disorders SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE citalopram; pediatrics; antidepressants; pervasive developmental disorder; autism ID AUTISTIC DISORDER; FLUOXETINE TREATMENT; MENTAL-RETARDATION; DOUBLE-BLIND; CHILDREN; ADULTS; YOUNG; ADOLESCENTS AB This study assessed the effectiveness and tolerability of the selective serotonin reuptake inhibitor citalopram in the treatment of patients with pervasive developmental disorders (PDDs). The medical charts of 15 children and adolescents (aged 6-16 yr) with Asperger syndrome, autism, or PDD not otherwise specified treated with citalopram were retrospectively reviewed. The final dose of citalopram was 16.9 +/- 12.1 mg/day with a treatment duration of 218.8 +/- 167.2 days. Independent ratings of the Clinical Global Impression (CGI) Severity and Improvement scales allowed comparison between baseline and PDD symptoms at the last visit. Eleven adolescents (73%) exhibited significant improvement in PDD, anxiety, or mood CGI score (z = 2.95; p = .003). Anxiety symptoms associated with PDDs improved significantly in 66% of patients (z = 2.83, p = .005), and mood symptoms improved significantly in 47% of patients (z = 2.78, p = .005). Mild side effects were reported by five patients (33%). These data suggest citalopram may be effective, safe, and well tolerated as part of the treatment of PDDs. C1 Hartford Hosp, Dept Psychiat, Connecticut Childrens Med Ctr, Inst Living, Hartford, CT 06106 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA USA. RP Namerow, LB (reprint author), Hartford Hosp, Dept Psychiat, Connecticut Childrens Med Ctr, Inst Living, 282 Washington St, Hartford, CT 06106 USA. NR 25 TC 71 Z9 71 U1 2 U2 4 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 APR PY 2003 VL 24 IS 2 BP 104 EP 108 PG 5 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 669LB UT WOS:000182351800004 PM 12692455 ER PT J AU Lucenti, MJ Nadel, ES Mick, NW Brown, DFM AF Lucenti, MJ Nadel, ES Mick, NW Brown, DFM TI Acute shortness of breath SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; MITRAL REGURGITATION; ACC/AHA GUIDELINES; MANAGEMENT; DISEASE C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD APR PY 2003 VL 24 IS 3 BP 319 EP 324 DI 10.1016/S0736-4679(02)00003-9 PG 6 WC Emergency Medicine SC Emergency Medicine GA 662WP UT WOS:000181972300016 PM 12676305 ER PT J AU von Stechow, D Balto, K Stashenko, P Muller, R AF von Stechow, D Balto, K Stashenko, P Muller, R TI Three-dimensional quantitation of periradicular bone destruction by micro-computed tomography SO JOURNAL OF ENDODONTICS LA English DT Article ID TRABECULAR BONE; MORPHOMETRIC ANALYSIS; CANCELLOUS BONE AB We have previously shown that two-dimensional, high-resolution, micro-computed tomography is a rapid, reproducible, and noninvasive method for measuring periradicular bone resorption in mice, giving results virtually identical to histology. In this study, we determined whether a three-dimensional volumetric quantitation of bone resorption could be achieved and whether this correlates with two-dimensional measurements. Periradicular lesions were induced in the lower first molars of mice by pulp exposure and infection; unexposed teeth served as controls. Mandibles were harvested on day 21 and subjected to: (a) three-dimensional micro-computed tomography imaging; and (b) conventional histology. Using a three-dimensional model and a semiautomatic contouring algorithm we determined three-dimensional void volume: void surface, void thickness, and the standard deviation of the thickness distribution. The results showed a significant correlation between lesion void volume and two-dimensional lesion area by histology (r(2) = 0.73), as well as high correlations between void volume and void thickness' (r(2) = 0.86) and standard deviation of the void thickness (r(2) = 0.87), but no relationship with void surface. These results show that three-dimensional analysis of micro-computed tomography images is highly correlated with two-dimensional cross-sectional measures of periradicular lesions. Nevertheless, micro-computed tomography allows assessment of additional microstructural features as well as sub-regional analysis of lesion development. C1 Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Endodont, Boston, MA 02115 USA. RP Muller, R (reprint author), Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. RI Muller, Ralph/A-1198-2008 OI Muller, Ralph/0000-0002-5811-7725 FU NIA NIH HHS [AG-13333]; NIDCR NIH HHS [DE-09018, DE-11664] NR 20 TC 39 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD APR PY 2003 VL 29 IS 4 BP 252 EP 256 DI 10.1097/00004770-200304000-00005 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 663RN UT WOS:000182019500005 PM 12701773 ER PT J AU Chao, W Matsui, T Novikov, MS Tao, JZ Li, L Liu, HL Ahn, Y Rosenzweig, A AF Chao, W Matsui, T Novikov, MS Tao, JZ Li, L Liu, HL Ahn, Y Rosenzweig, A TI Strategic advantages of insulin-tike growth factor-1 expression for cardioprotection SO JOURNAL OF GENE MEDICINE LA English DT Article DE apoptosis; growth factors; gene therapy; ischemia ID CARDIOMYOCYTES IN-VITRO; TRANSGENIC MICE; HEART-FAILURE; APOPTOSIS; GENE; OVEREXPRESSION; REPERFUSION; ACTIVATION; RAT; ORGANIZATION AB Background Insulin-like growth factor-I (IGF-I) peptide has beneficial effects on cardiomyocyte function and survival, many of which are mediated through the serine-threonine kinase, Akt. However, concerns about systemic effects of IGF-I peptide limit its clinical application. The present study tested whether local IGF-I expression could mediate cardioprotection without elevating serum [IGF-I]. Methods The ability of a recombinant adenovirus encoding IGF-IB (Ad.IGF-I) to activate Akt and protect cardiomyocytes from hypoxia-induced apoptosis in vitro was compared with the effects of IGF-I peptide or expression of constitutively active Akt (myr-Akt). In vivo, cardiac IGF-I gene transfer was performed prior to ischemia-reperfusion injury (IRI). Effects on the ischemic and infarcted areas were assessed while serum [IGF-I] was measured by radioimmunoassay. Results Compared with IGF-I peptide, Ad.IGF-I achieved more sustained activation of Akt and reduced hypoxia-induced apoptosis at lower media IGF-I concentrations. In a co-culture system, Ad.IGF-I protected both infected and uninfected cells from hypoxic injury, while myr-Akt protected only infected cells. In vivo cardiac injection of Ad.IGF-I mediated significant local IGF-I expression, without affecting serum [IGF-I] levels. After IRI, Ad.IGF-I did not affect the ischemic area but reduced infarct size similar to50% (32 +/- 13 vs. 64 +/- 14% AAR in Ad.GFP rats, p < 0.003), although the transgene was expressed in only similar to15% of the ischemic region, consistent with possible paracrine benefit. Conclusions Somatic gene transfer of IGF-I may offer strategic advantages over both systemic delivery of IGF-I peptide and expression of cell autonomous cardioprotective transgenes such as Akt by mediating autocrine and paracrine cardiomyocyte protection without elevating serum [IGF-I] levels. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Harvard Univ, Program Cardiovasc Gene Therapy, Massachusetts Gen Hosp, Sch Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. MGH, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. MGH, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. MGH, Div Cardiol, Charlestown, MA 02129 USA. RP Rosenzweig, A (reprint author), Harvard Univ, Program Cardiovasc Gene Therapy, Massachusetts Gen Hosp, Sch Med,Cardiovasc Res Ctr, 114 16th St,Room 2600, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-04250, HL-04336, HL-59521, HL-61557] NR 29 TC 46 Z9 49 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD APR PY 2003 VL 5 IS 4 BP 277 EP 286 DI 10.1002/jgm.347 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 669FR UT WOS:000182341700002 PM 12692862 ER PT J AU Olstein, J Gordon, A Conigliaro, J AF Olstein, J Gordon, A Conigliaro, J TI Intravenous ethanol and treatment for alcohol withdrawal syndrome in the perioperative period. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 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 APR PY 2003 VL 18 SU 1 BP 77 EP 77 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300220 ER PT J AU Rehman, SU Basile, JN Clyburn, EB Shakaib, A Johnson, RH AF Rehman, SU Basile, JN Clyburn, EB Shakaib, A Johnson, RH TI Not every "OA" is due to "DJD" - Hemochromatosis presenting as "OA" SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Mt Pleasant, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 83 EP 83 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300248 ER PT J AU Graham, GN Mankey, CG Rich, J Grigsby, D Barry, MJ Stone, VE AF Graham, GN Mankey, CG Rich, J Grigsby, D Barry, MJ Stone, VE TI Community medicine and medical education: Boston men's cardiovascular health project. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Publ Hlth Commiss, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 103 EP 103 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300344 ER PT J AU Pearlman, RA Beneda, HW Neuzil, KM AF Pearlman, RA Beneda, HW Neuzil, KM TI Ensuring clinician-patient communication with HIV testing. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 135 EP 135 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300483 ER PT J AU Arterburn, DE Crane, PK Sullivan, SD AF Arterburn, DE Crane, PK Sullivan, SD TI The coming epidemic of obesity in elderly Americans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RI Crane, Paul/C-8623-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 140 EP 140 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300505 ER PT J AU Arterburn, DE Crane, PK Veenstra, DL AF Arterburn, DE Crane, PK Veenstra, DL TI The efficacy and safety of sibutramine for weight loss: A systematic review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RI Crane, Paul/C-8623-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 140 EP 140 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300504 ER PT J AU Bryson, CL Davis, G Yueh, B McDonell, MB Micek, M Fihn, SD AF Bryson, CL Davis, G Yueh, B McDonell, MB Micek, M Fihn, SD TI Complimentary or alternative: Does alternative medicine use delay cancer therapy? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300509 ER PT J AU Chew, LD Nelson, KM Bradley, KA AF Chew, LD Nelson, KM Bradley, KA TI Association between alcohol consumption and diabetes care-data from the 2001 behavioral risk factor and surveillance system (BRFSS) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 142 EP 142 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300515 ER PT J AU Fang, MC Hylek, EM Rosand, J Greenberg, SM Singer, DE AF Fang, MC Hylek, EM Rosand, J Greenberg, SM Singer, DE TI Subtherapeutic INRS are not associated with a lower risk of intracranial hemorrhage in patients anticoagulated for atrial fibrillation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 145 EP 145 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300529 ER PT J AU Fultz, S Rabeneck, L Rodriguez-Barradas, M Justice, AC AF Fultz, S Rabeneck, L Rodriguez-Barradas, M Justice, AC TI Hepatitis C confection is associated with an increased symptom burden in HIV positive veterans SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, 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 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 APR PY 2003 VL 18 SU 1 BP 146 EP 146 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300534 ER PT J AU Grant, RW O'Leary, KM Weilberg, JB Meigs, JB AF Grant, RW O'Leary, KM Weilberg, JB Meigs, JB TI Impact of concurrent medication use on statin adherence among patients enrolled in a health maintenance organization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 147 EP 147 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300538 ER PT J AU Grant, RW Devita, NG Singer, DE Meigs, JB AF Grant, RW Devita, NG Singer, DE Meigs, JB TI Polypharmacy and medication adherence in patients with type 2 diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Partners Community Healthcare, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 147 EP 147 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300537 ER PT J AU Mrus, JM Sherman, SN Ho, ML Hornung, RW Feinberg, J Fultz, SL Justice, AC Puchalski, CM Mandell, KL Tsevat, J AF Mrus, JM Sherman, SN Ho, ML Hornung, RW Feinberg, J Fultz, SL Justice, AC Puchalski, CM Mandell, KL Tsevat, J TI Factors associated with "short-term" and "long-term" adherence to antiretroviral therapy in patients with HIV/AIDS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VAMC, Cincinnati, OH USA. Univ Cincinnati, Cincinnati, OH USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 152 EP 152 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300560 ER PT J AU Nelson, K Bradley, K AF Nelson, K Bradley, K TI Self-perception of weight among a national sample of overweight and obese Americans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 153 EP 153 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300564 ER PT J AU Nguyen, J McDonell, MB Young, BA Fihn, SD AF Nguyen, J McDonell, MB Young, BA Fihn, SD TI Validation of patient self-report of diabetes mellitus. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Washington, Sch Med, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 153 EP 153 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300565 ER PT J AU Tsevat, J Sherman, SN Feinberg, J Mrus, JM Leonard, AC Mandell, KL Holmes, WC Justice, AC Fultz, SL Puchalski, CM AF Tsevat, J Sherman, SN Feinberg, J Mrus, JM Leonard, AC Mandell, KL Holmes, WC Justice, AC Fultz, SL Puchalski, CM TI Can life improve after developing HIV/AIDS? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Cincinnati, Cincinnati, OH USA. Cincinnati VAMC, Cincinnati, OH USA. Univ Penn, Philadelphia, PA 19104 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. George Washington Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 160 EP 160 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300596 ER PT J AU Yeh, GY Eisenberg, DM Wood, MJ Wayne, PM Lorell, BH Stevenson, LW Goldberger, AL Davis, RB Phillips, RS AF Yeh, GY Eisenberg, DM Wood, MJ Wayne, PM Lorell, BH Stevenson, LW Goldberger, AL Davis, RB Phillips, RS TI Tai Chi as an adjunctive intervention for patients with heart failure: A pilot study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Sch Acupuncture, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 6 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 APR PY 2003 VL 18 SU 1 BP 161 EP 161 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300604 ER PT J AU Beers, BB McDonald, VJ Quistberg, DA Ravenell, KL Asch, DA Shea, JA AF Beers, BB McDonald, VJ Quistberg, DA Ravenell, KL Asch, DA Shea, JA TI Disparities in health literacy between African American and now African American primary care patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 PVAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RI Quistberg, D Alex/C-7953-2009 OI Quistberg, D Alex/0000-0001-9730-2686 NR 0 TC 12 Z9 12 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 APR PY 2003 VL 18 SU 1 BP 169 EP 169 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300637 ER PT J AU Chew, LD Bradley, KA AF Chew, LD Bradley, KA TI Brief questions to detect inadequate health literacy among VA patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU 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 APR PY 2003 VL 18 SU 1 BP 170 EP 170 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300644 ER PT J AU Long, JA Bamba, MI Kressin, NR AF Long, JA Bamba, MI Kressin, NR TI Occupation classification: No easy short cuts. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 180 EP 180 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300691 ER PT J AU Long, JA Gomez, A Cox, M Asch, DA Shea, JA AF Long, JA Gomez, A Cox, M Asch, DA Shea, JA TI Racial sensitivity among first and second year medical students. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 180 EP 180 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300690 ER PT J AU Long, JA Melissa, BI Shea, JA AF Long, JA Melissa, BI Shea, JA TI Missing race data in VA based disparities research: A systematic review. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 180 EP 181 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300692 ER PT J AU O'Malley, KJ Haidet, PM Sharf, B Collins, TC Tranh, A Johnson, ML Wray, NP AF O'Malley, KJ Haidet, PM Sharf, B Collins, TC Tranh, A Johnson, ML Wray, NP TI Trust in physician, facility, and system: Qualitative differences between ethnic groups. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. Texas A&M Univ, College Stn, TX USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. NR 0 TC 3 Z9 3 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 APR PY 2003 VL 18 SU 1 BP 184 EP 184 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300708 ER PT J AU Petersen, LA Normand, S Druss, B Rosenheck, R AF Petersen, LA Normand, S Druss, B Rosenheck, R TI Process of care and outcome after acute myocardial infarction for patients with mental illness: Are there disparities? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Houston VAMC, Houston, TX USA. Harvard Univ, Boston, MA 02115 USA. Yale Univ, West Haven, CT USA. NR 0 TC 11 Z9 13 U1 1 U2 3 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 APR PY 2003 VL 18 SU 1 BP 185 EP 186 DI 10.1046/j.1440-1746.2003.02943.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300714 PM 12542604 ER PT J AU Shea, JA Guerra, C Weiner, J Aguirre, A Schaffer, M Asch, DA AF Shea, JA Guerra, C Weiner, J Aguirre, A Schaffer, M Asch, DA TI Health literacy and patient satisfaction. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Penn, Philadelphia, PA 19104 USA. Hlth Partners, Philadelphia, PA USA. PVAMC, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 1 Z9 1 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 APR PY 2003 VL 18 SU 1 BP 187 EP 188 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300724 ER PT J AU Volpp, KG Epstein, A Williams, SV AF Volpp, KG Epstein, A Williams, SV TI Race-specific mortality effects of market reform in New Jersey. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 189 EP 189 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300732 ER PT J AU Evans-Molina, C Henault, L Regan, S Shea, C Hylek, EM AF Evans-Molina, C Henault, L Regan, S Shea, C Hylek, EM TI Nurse assessment of warfarin candidacy among geriatric patients with atrial fibrillation (AF) referred to an anticoagulation clinic. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 193 EP 193 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300749 ER PT J AU Hightower, A Boyko, E Asthana, S Borson, S Falzgraf, S Baker, L Gleason, C Cholerton, B AF Hightower, A Boyko, E Asthana, S Borson, S Falzgraf, S Baker, L Gleason, C Cholerton, B TI Literacy predicts cognitive function in older adults. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 194 EP 194 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300754 ER PT J AU Lawrence, VA Hazuda, HP Bradshaw, P Cornell, JE Mulrow, CD AF Lawrence, VA Hazuda, HP Bradshaw, P Cornell, JE Mulrow, CD TI Predicting elders' functional recovery after major abdominal surgery. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 195 EP 195 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300761 ER PT J AU Roman, GC Perdomo, CA Pratt, RD AF Roman, GC Perdomo, CA Pratt, RD TI Patients with vascular dementia differ from patients with Alzheimer's disease with respect to population characteristics and pattern of cognitive decline. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Vet Adm Hosp, San Antonio, TX USA. Eisai Inc, Teaneck, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 198 EP 199 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300776 ER PT J AU Roman, GC Perdomo, CA Pratt, RD AF Roman, GC Perdomo, CA Pratt, RD TI Donepezil improves cognition, global function and ability to perform activities of daily living in patients with vascular dementia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Vet Adm Hosp, San Antonio, TX USA. Eisai Inc, Teaneck, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 198 EP 198 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300775 ER PT J AU Fang, MC McCarthy, E Singer, DE AF Fang, MC McCarthy, E Singer, DE TI Are women preferentially seeking care from female physicians? National patterns of outpatient primary care and screening. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 205 EP 205 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300808 ER PT J AU Goldzweig, C Washington, D Lanto, AB Yano, E AF Goldzweig, C Washington, D Lanto, AB Yano, E TI Organizational predictors of breast and cervical cancer screening. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 206 EP 206 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300811 ER PT J AU Linder, JA Singer, DE AF Linder, JA Singer, DE TI Desire for antibiotics and antibiotic prescribing for adults with upper respiratory tract infections. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med 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 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 APR PY 2003 VL 18 SU 1 BP 209 EP 209 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300826 ER PT J AU Petersen, LA Normand, S AF Petersen, LA Normand, S TI Access to coronary angiography in the regionalized veterans affairs (VA) health care delivery system. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Houston VAMC, Houston, TX USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300842 ER PT J AU Pirraglia, P Sanyal, P Singer, DE Ferris, TG AF Pirraglia, P Sanyal, P Singer, DE Ferris, TG TI Burden of depressive symptoms as a barrier to breast cancer and cervical cancer screening in the SWAN cohort. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 213 EP 214 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300845 ER PT J AU Rehman, SU Cope, DW Kilpatrick, AO Neitert, PJ Shakaib, A AF Rehman, SU Cope, DW Kilpatrick, AO Neitert, PJ Shakaib, A TI What to wear this morning? Effect of doctors' dress on patients' trust and confidence. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Med Univ S Carolina, Ralph Johnson VA Med Ctr, Mt Pleasant, MI USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Med Univ S Carolina, Mt Pleasant, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 214 EP 214 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300848 ER PT J AU Schnipper, JL Krier, JB Ackerman, RH Rahbar, S AF Schnipper, JL Krier, JB Ackerman, RH Rahbar, S TI Diagnostic yield and utility of neurovascular ultrasound in the evaluation of patients with syncope. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med 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 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 APR PY 2003 VL 18 SU 1 BP 216 EP 216 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300856 ER PT J AU Shi, C Gralnek, IM Dulai, G Asch, SM AF Shi, C Gralnek, IM Dulai, G Asch, SM TI Are patients substituting over-the-counter H2-receptor antagonists for physician care? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 216 EP 216 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300858 ER PT J AU Stahl, J AF Stahl, J TI Using and misusing midlevel clinicians - The effect on outpatient clinic performance. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 218 EP 218 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300867 ER PT J AU Stahl, J AF Stahl, J TI The effect of phlebotomy stations in outpatient clinics-patient flow and staff utilization. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 218 EP 218 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300865 ER PT J AU Stahl, J AF Stahl, J TI Outpatient clinic scheduling accuracy - The effect on outpatient clinic performance. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 218 EP 218 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300866 ER PT J AU Volpp, KG Epstein, A Ketcham, J Williams, SV AF Volpp, KG Epstein, A Ketcham, J Williams, SV TI Market reform in New Jersey and its effect on mortality for inpatient medical conditions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 219 EP 219 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300873 ER PT J AU Yano, E Lanto, A Lee, M Rubenstein, LM Sherman, SE AF Yano, E Lanto, A Lee, M Rubenstein, LM Sherman, SE TI Does guideline-concordant clinical reorganization of smoking cessation care improve patient quit rates?: Results of a group randomized trial. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Greater Los Angeles HSR&D Ctr Excellence, Sepulveda, CA USA. RAND Corp, Sepulveda, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 221 EP 221 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300880 ER PT J AU Mortensen, E Restrepo, M Anzueto, A Pugh, J AF Mortensen, E Restrepo, M Anzueto, A Pugh, J TI Guideline-concordant antimicrobial therapy and mortality in patients with community-acquired pneumonia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 226 EP 227 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300908 ER PT J AU Hughes, MT Nolan, MT Terry, PB Forman, JH Kub, J Vettese, M Thompson, RE Astrow, A Clawson, L Sulmasy, DP AF Hughes, MT Nolan, MT Terry, PB Forman, JH Kub, J Vettese, M Thompson, RE Astrow, A Clawson, L Sulmasy, DP TI Patient preferences for control over health care decisions after diagnosis of a life-threatening illness. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Johns Hopkins Univ, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 232 EP 233 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300936 ER PT J AU Tsevat, J Puchalski, CM Sherman, SN Holmes, WC Feinberg, J Leonard, AC Mrus, JM Mandell, KL Pargament, KI Justice, AC Fultz, SL Ellison, CG McCullough, ME Peterman, AH AF Tsevat, J Puchalski, CM Sherman, SN Holmes, WC Feinberg, J Leonard, AC Mrus, JM Mandell, KL Pargament, KI Justice, AC Fultz, SL Ellison, CG McCullough, ME Peterman, AH TI Spirituality and religion in patients with HIV/AIDS. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Cincinnati, Cincinnati, OH USA. Cincinnati VAMC, Cincinnati, OH USA. George Washington Univ, Washington, DC USA. Univ Penn, Philadelphia, PA 19104 USA. Bowling Green State Univ, Bowling Green, OH 43403 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Texas, Austin, TX 78712 USA. Univ Miami, Coral Gables, FL 33124 USA. Evanston NW Healthcare, Evanston, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 234 EP 234 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300943 ER PT J AU Haidet, P Kelly, P Kuebeler, M Richards, B Helmer, D Paterniti, D Snow, A Fortin, A Wagner, D Bentley, S Hatem, D Gracey, C Harrell, H Babu, V Wray, N Inui, T AF Haidet, P Kelly, P Kuebeler, M Richards, B Helmer, D Paterniti, D Snow, A Fortin, A Wagner, D Bentley, S Hatem, D Gracey, C Harrell, H Babu, V Wray, N Inui, T TI Measuring the hidden curricula of medical schools. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. UMDNJ, Newark, NJ USA. Univ Calif Davis, Sacramento, CA 95817 USA. Yale Univ, New Haven, CT USA. MSUCHM, E Lansing, MI USA. MSUCOM, E Lansing, MI USA. Univ Massachusetts, Worcester, MA 01605 USA. Univ Rochester, Rochester, NY USA. Univ Florida, Gainesville, FL USA. Penn State Univ, Hershey, PA USA. Indiana Univ, Indianapolis, IN 46204 USA. NR 0 TC 1 Z9 1 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 APR PY 2003 VL 18 SU 1 BP 243 EP 243 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564300984 ER PT J AU Park, ER Betancourt, J Nathan, M Miller, E Ananeh-Firempong, O MacDonald, E Stone, VE AF Park, ER Betancourt, J Nathan, M Miller, E Ananeh-Firempong, O MacDonald, E Stone, VE TI Identifying internal medicine residents' cross-cultural training needs. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 251 EP 251 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301023 ER PT J AU Rosenfeld, KE Lorenz, K Hauser, J AF Rosenfeld, KE Lorenz, K Hauser, J TI To "Wit": Understanding the impact of the dramatic arts in medical education. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 253 EP 253 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301033 ER PT J AU Rubenstein, LV Swanson, KA Meredith, L Lee, ML Ford, DE Rost, KM AF Rubenstein, LV Swanson, KA Meredith, L Lee, ML Ford, DE Rost, KM TI Are discomfort with depression care and/or clinical uncertainty associated with burnout among primary care clinicians? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RAND, Santa Monica, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 254 EP 254 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301036 ER PT J AU Conroy, M McPhee, SJ AF Conroy, M McPhee, SJ TI Tools to move: A randomized, controlled trial to increase residents' exercise counseling. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 261 EP 261 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301069 ER PT J AU Conroy, MB Majchrjak, N Regan, S Schneider, LI Rigotti, NA AF Conroy, MB Majchrjak, N Regan, S Schneider, LI Rigotti, NA TI Provider counseling is associated with higher smoker satisfaction regardless of readiness to quit. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med 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 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 APR PY 2003 VL 18 SU 1 BP 261 EP 261 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301070 ER PT J AU Johnson, KM Bradley, KA AF Johnson, KM Bradley, KA TI Exercise, television viewing, and obesity among female veterans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 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 APR PY 2003 VL 18 SU 1 BP 266 EP 267 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301096 ER PT J AU Stahl, JE Roberts, MS Gazelle, S AF Stahl, JE Roberts, MS Gazelle, S TI Optimizing management and financial performance of the teaching ambulatory care clinic SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE ambulatory care; teaching clinics; optimization; computer simulation ID PATIENT SATISFACTION; WAITING TIME; HEALTH-CARE; EMERGENCY; QUALITY; PHYSICIANS; MEDICINE AB OBJECTIVE: To examine how to optimize teaching ambulatory care clinics performance with regard to access to care, access to teaching, and financial viability. DESIGN: Optimization analysis using computer simulation. METHODS: A discrete-event simulation model of the teaching ambulatory clinic setting was developed. This method captures flow time, waiting time, competition for resources, and the interdependency of events, providing insight into system dynamics. Sensitivity analyses were performed on staffing levels, room availability, patient characteristics such as "new" versus "established" status, and clinical complexity and pertinent probabilities. MAIN RESULTS: In the base-case, 4 trainees:preceptor, patient flow time (registration to check out) was 148 minutes (SD 5), wait time was 20.6 minutes (SD 4.4), the wait for precepting was 6.2 minutes (SD 1.2), and average daily net clinic income was $1,413. Utilization rates were preceptors (59%), trainees (61%), medical assistants (64%), and room (68%). Flow time and the wait times remained relatively constant for strategies with trainee:preceptor ratios <4:1 but increased with number of trainees steadily thereafter. Maximum revenue occurred with 3 preceptors and 5 trainees per preceptor. The model was relatively insensitive to the proportion of patients presenting who were new, and relatively sensitive to average evaluation and management (E/M) level. Flow and wait times rose on average by 0.05 minutes and 0.01 minutes per percent new patient, respectively. For each increase in average E/M level, flow time increased 8.4 minutes, wait time 1.2 minutes, wait for precepting 0.8 minutes, and net income increased by $490. CONCLUSION: Teaching ambulatory care clinics appear to operate optimally, minimizing flow time and waiting time while maximizing revenue, with trainee-to-preceptor ratios between 3 and 7 to 1. C1 Massachusetts Gen Hosp, Dept Med, Decis Anal & Technol Assessment Grp, Harvard Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Harvard Med Sch, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Dept Med, Med Ctr, Pittsburgh, PA USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Decis Anal & Technol Assessment Grp, Harvard Sch Med, 0 Emerson Bldg,Suite 2H, Boston, MA 02114 USA. RI Plumley, Daniel/B-6823-2012 NR 35 TC 12 Z9 13 U1 2 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 IS 4 BP 266 EP 274 DI 10.1046/j.1525-1497.2003.20726.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 668YD UT WOS:000182323400005 PM 12709093 ER PT J AU Collins, MM Fowler, F Caubet, J Bates, D Lee, J Hauser, A Barry, M AF Collins, MM Fowler, F Caubet, J Bates, D Lee, J Hauser, A Barry, M TI Impact of suspicious prostate cancer screening tests. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Boston, MA 02125 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 268 EP 269 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301105 ER PT J AU Takahashi, TA Johnson, KM Bradley, KA AF Takahashi, TA Johnson, KM Bradley, KA TI Young US adults at risk for HIV: Perceptions of risk and HIV testing practices. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 271 EP 271 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301116 ER PT J AU Fancher, T Price, M Haidet, PM Paterniti, D AF Fancher, T Price, M Haidet, PM Paterniti, D TI Prolonged suffering or failure of conservative therapy: Considering patients' perspectives on elective total knee replacement. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Calif Davis, Sacramento, CA 95817 USA. Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 273 EP 273 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301128 ER PT J AU Asch, SM McGlynn, EA Hogan, MM Shekelle, PG Rod, H Keesey, J Adams, J Rubenstein, L Kerr, EA AF Asch, SM McGlynn, EA Hogan, MM Shekelle, PG Rod, H Keesey, J Adams, J Rubenstein, L Kerr, EA TI Global quality of care in the veteran's administration as compared to a national sample. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. VA, Ann Arbor, MI USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 278 EP 279 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301153 ER PT J AU Shi, CW Asch, SM Fielder, E Gelberg, L Brook, RH Leake, B Shapiro, MF Dowling, P Nichol, M AF Shi, CW Asch, SM Fielder, E Gelberg, L Brook, RH Leake, B Shapiro, MF Dowling, P Nichol, M TI Usage patterns of over-the-counter phenazopyridine (pyridium) SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pharmacy; survey; over-the-counter; phenazopyridine ID TO-OTC SWITCH; MEDICATION PRESCRIBING PATTERNS; SELF-MEDICATION; PHYSICIAN SERVICES; DRUGS; PRESCRIPTION; AVAILABILITY; ANTAGONISTS; RX; RECLASSIFICATION AB OBJECTIVES: Little is known about how the public uses formerly prescription medications that are available over-the-counter (OTC). This study examines whether consumers inappropriately use and substitute a recently widely distributed OTC urinary analgesic, phenazopyridine, for provider care. DESIGN/SETTING: We conducted a cross-sectional survey of a stratified cluster random sample of OTC phenazopyridine purchasers (N = 434) in 31 Los Angeles retail pharmacies over 5 months. Recruited by shelf advertisements, participants were 18 years or older who purchased a phenazopyridine product. Each completed a 25-item self-administered anonymous questionnaire. Inappropriate use was defined as 1) having medical contraindications to phenazopyridine, or 2) not having concurrent antibiotic and/or provider evaluation for the urinary symptoms. RESULTS: The survey response rate was 58%. Fifty-one percent of the respondents used OTC phenazopyridine inappropriately, and 38% substituted it for medical care. Multiple logistic regression analyses revealed that inappropriate use was correlated with having little time to see a provider (odds ratio [OR], 1.57; 95% confidence interval [95% CI], 1.26 to 1.96), receiving friend's or family's advice (OR, 1.25; 95% CI, 1.05 to 1.47), having prior urinary tract infections (OR, 0.49; 95% CI, 0.30 to 0.80), having used prescription phenazopyridine, (OR, 0.40; 95% CI, 0.25 to 0.63), and having back pain (OR, 0.34; 95% CI, 0.16 to 0.74). Similar correlates were found in those who substituted OTC phenazopyridine for provider care. Respondents with incorrect knowledge about phenazopyridine's mode of action had 1.9 times greater odds of inappropriate use and 2.2 times greater odds of substitution than those who had correct knowledge about this drug. CONCLUSION: Inappropriate use of OTC phenazopyridine appears common. Increasing the public's knowledge about reclassified drugs may help to mitigate this problem. C1 Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Gen Internal Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Social Sci Res Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med & Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90095 USA. Univ So Calif, Dept Pharmaceut Econ & Policy, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Vet Affairs Greater Los Angeles, Dept Internal Med, Los Angeles, CA USA. RP Shi, CW (reprint author), Univ Calif Los Angeles, Dept Family Med, 924 Westwood Blvd,Suite 650, Los Angeles, CA 90095 USA. OI Dowling, Patrick /0000-0002-3492-1735 FU AHRQ HHS [F32 HS011507, F32 HS 11507-01] NR 41 TC 6 Z9 6 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 APR PY 2003 VL 18 IS 4 BP 281 EP 287 DI 10.1046/j.1525-1497.2003.20709.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 668YD UT WOS:000182323400007 PM 12709095 ER PT J AU Miller, R Li, Y Sun, H Kopjar, B Sales, AE Pineros, S Fihn, SD AF Miller, R Li, Y Sun, H Kopjar, B Sales, AE Pineros, S Fihn, SD TI Underuse of cardioprotective medications in IHD patients prior to acute myocardial infarction. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Puget Sound Hlth Care Syst, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 290 EP 290 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301208 ER PT J AU Murff, HJ Canter, JA Syngal, SK AF Murff, HJ Canter, JA Syngal, SK TI The value of family history information collected for cancer risk assessment in primary care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Vanderbilt Univ, Nashville, TN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 291 EP 291 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301213 ER PT J AU Pirraglia, P Weilburg, JB O'Leary, KM Singer, DE Meigs, JB AF Pirraglia, P Weilburg, JB O'Leary, KM Singer, DE Meigs, JB TI Antidepressant prescribing frequency is associated with treatment adequacy rates among primary care physicians. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 293 EP 293 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301220 ER PT J AU Poon, EG Gandhi, TK Sequist, I Webber, DR Murff, HJ Karson, AS Bates, DW AF Poon, EG Gandhi, TK Sequist, I Webber, DR Murff, HJ Karson, AS Bates, DW TI 'I wish I had seen this result earlier': Problems in the test result management systems in primary care physicians' offices. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med 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 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 APR PY 2003 VL 18 SU 1 BP 293 EP 293 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301222 ER PT J AU Ravenell, KL McDonald, VJ Asch, DA Henry, CA Fosnocht, KM Murphy, JJ Shea, JA AF Ravenell, KL McDonald, VJ Asch, DA Henry, CA Fosnocht, KM Murphy, JJ Shea, JA TI Comparing perceptions of access in VA and non-VA primary care. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 PVAMC, CHERP, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 294 EP 294 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301225 ER PT J AU Rubenstein, LV Meredith, LS Parker, LE Gordon, NP Lee, ML Hickey, S AF Rubenstein, LV Meredith, LS Parker, LE Gordon, NP Lee, ML Hickey, S TI Effectiveness of evidence-based quality improvement for depression. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 VA Greater Los Angeles, Los Angeles, CA USA. RAND Corp, Santa Monica, CA 90406 USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 295 EP 295 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301228 ER PT J AU Sequist, TD Gandhi, TK Poon, E Murff, H Karson, A Bates, DW AF Sequist, TD Gandhi, TK Poon, E Murff, H Karson, A Bates, DW TI Clinician attitudes towards health maintenance and disease specific practice guidelines and electronic clinical reminders. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 296 EP 296 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301233 ER PT J AU Sherman, SE Lanto, AB Nield, M Yano, E AF Sherman, SE Lanto, AB Nield, M Yano, E TI Smoking cessation care received by veterans with chronic obstructive pulmonary disease (COPD). SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Sepulveda, CA USA. VA Greater Los Angeles, HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 296 EP 296 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301235 ER PT J AU Sherman, SE Yano, E Lanto, AB Mittman, BS AF Sherman, SE Yano, E Lanto, AB Mittman, BS TI How well do smoking cessation quality measures predict clinical outcomes? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Calif Los Angeles, Sepulveda, CA USA. VA Greater Los Angeles, HSR&D Ctr Excellence, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 296 EP 296 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301234 ER PT J AU Steinman, MA Sauala, A Maselli, J Houck, P Gonzales, R AF Steinman, MA Sauala, A Maselli, J Houck, P Gonzales, R TI Processes and outcomes of care in elderly patients with acute bronchitis. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Ctr Medicare & Medicaid Serv, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2003 VL 18 SU 1 BP 296 EP 297 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 673DF UT WOS:000182564301236 ER PT J AU Standring, DN Lanford, R Wright, T Chung, RT Bichko, V Cretton-Scott, E Pan-Zhou, X Bergelson, S Qu, L Tausek, M Bridges, E Moussa, A Storer, R Pierra, C Benzaria, S Gosselin, G La Colla, P Sommadossi, JP AF Standring, DN Lanford, R Wright, T Chung, RT Bichko, V Cretton-Scott, E Pan-Zhou, X Bergelson, S Qu, L Tausek, M Bridges, E Moussa, A Storer, R Pierra, C Benzaria, S Gosselin, G La Colla, P Sommadossi, JP TI NM 283 has potent antiviral activity against genotype 1 chronic hepatitis C virus (HCV-1) infection in the chimpanzee SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY MAR 29-APR 01, 2003 CL ISTANBUL, TURKEY SP European Assoc Study Liver C1 SW Fdn, San Antonio, TX USA. VA Med Ctr, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Montpellier 2, Lab Cooperat Idenix, CNRS, Montpellier, France. Univ Cagliari, I-09124 Cagliari, Italy. NR 0 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2003 VL 38 SU 2 MA 3 BP 3 EP 3 DI 10.1016/S0168-8278(03)80421-X PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 666JQ UT WOS:000182174500004 ER PT J AU Rodriguez-Torres, M Gonzalez-Garcia, J Mendes-Correa, M Katlama, C Nelson, M Cooper, D Staszewski, S Carosi, G Smaill, F Brau, N Torriani, FJ AF Rodriguez-Torres, M Gonzalez-Garcia, J Mendes-Correa, M Katlama, C Nelson, M Cooper, D Staszewski, S Carosi, G Smaill, F Brau, N Torriani, FJ TI Prevalence of occult HBV in HIV/HCV coinfected patients in a large, multinational trial (APRICOT) SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY MAR 29-APR 01, 2003 CL ISTANBUL, TURKEY SP European Assoc Study Liver C1 Hosp La Paz, Madrid, Spain. Univ Sao Paulo, BR-05508900 Sao Paulo, Brazil. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Chelsea & Westminster Hosp, London, England. St Vincents Hosp, Sydney, NSW 2010, Australia. Univ Frankfurt, D-6000 Frankfurt, Germany. Clin Infect & Trop Dis, Brescia, Italy. Chedoke McMaster Hosp, Hamilton, ON, Canada. Bronx Vet Adm Med Ctr, New York, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. RI mendes correa, maria cassia /A-6779-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2003 VL 38 SU 2 MA 571 BP 165 EP 166 DI 10.1016/S0168-8278(03)80837-1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 666JQ UT WOS:000182174500564 ER PT J AU Shiffman, ML Goncales, FL Bronowicki, JP Fried, MW Wright, T Hadziyannis, S Brouwer, J Zeuzem, S Sederati, F Hoffman, J AF Shiffman, ML Goncales, FL Bronowicki, JP Fried, MW Wright, T Hadziyannis, S Brouwer, J Zeuzem, S Sederati, F Hoffman, J TI Hepatitis C virus (HCV) genotypes 2/3 infection: A curable disease SO JOURNAL OF HEPATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the European-Association-for-the-Study-of-the-Liver CY MAR 29-APR 01, 2003 CL ISTANBUL, TURKEY SP European Assoc Study Liver C1 Virginia Commonwealth Univ, Med Coll Virginia, Liver Transplant Program, Richmond, VA 23298 USA. UNICAMP, Hosp Das Clin, Sao Paulo, Brazil. CHU Nancy HE, Nancy, France. Univ N Carolina, Chapel Hill, NC 27599 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Henry Dunant Hosp, Athens, Greece. Univ Frankfurt, D-6000 Frankfurt, Germany. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2003 VL 38 SU 2 MA 590 BP 171 EP 171 DI 10.1016/S0168-8278(03)80856-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 666JQ UT WOS:000182174500583 ER PT J AU Draenert, R Altfeld, M Brander, C Basgoz, N Corcoran, C Wurcel, AG Stone, DR Kalams, SA Trocha, A Addo, MM Goulder, PJR Walker, BD AF Draenert, R Altfeld, M Brander, C Basgoz, N Corcoran, C Wurcel, AG Stone, DR Kalams, SA Trocha, A Addo, MM Goulder, PJR Walker, BD TI Comparison of overlapping peptide sets for detection of antiviral CD8 and CD4 T cell responses SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CD8 and CD4 T cell responses; overlapping peptides; Elispot assay; intracellular cytokine staining assay ID PERIPHERAL-BLOOD; HIV-1 INFECTION; CTL RESPONSES; ELISPOT-ASSAY; VIRAL LOAD; IDENTIFICATION; LYMPHOCYTES; EPITOPES; DEFINITION; ANTIGENS AB Increasing efforts are directed towards the development of effective vaccines through induction of virus-specific T cell responses. Although emerging data indicate a significant role of these cells in determining viral set point in infections such as HIV, there is as yet no consensus as to the best methods for assaying the breadth of these responses. In this study, we used sensitive interferon gamma-based intracellular cytokine staining (ICS) and Elispot assays to-determine-the optimal overlapping peptide set to screen for these responses. Twenty persons with established HIV infection were studied, focusing on responses to the highly immunogenic Nef protein. Six different HIV-1 Nef peptide sets were used, ranging in length from 15 to 20 amino acids (aa), in overlap from 10 to 11 amino acids, and derived from two different B clade sequences. A total of 54 CD8 T cell responses to Nef peptides were found in this cohort, of which only 12 were detected using previously defined Nef optimal epitopes. No single peptide set detected all responses. Though there was a trend of the shorter peptides detecting more CD8 T cell responses than the 20 amino acid long peptides and longer peptides detecting more CD4 T cell responses, neither was statistically significant. There was no difference between an overlap of 10 or 11 amino acids. All responses detected with the six different sets of overlapping peptides were towards the more highly conserved regions of Nef. We conclude that peptides ranging from 15 to 20 amino acids yield similar results in IFN-gamma-based Elispot and ICS assays, and that all are likely to underestimate the true breadth of responses to a given reference strain of virus. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Lemuel Shattuck Hosp, Boston, MA USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. RP Walker, BD (reprint author), Partners AIDS Res Ctr, MGH E,149 13th St, Charlestown, MA 02129 USA. OI Brander, Christian/0000-0002-0548-5778 NR 23 TC 97 Z9 100 U1 2 U2 3 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 APR 1 PY 2003 VL 275 IS 1-2 BP 19 EP 29 DI 10.1016/S0022-1759(02)00541-0 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 665XB UT WOS:000182145600003 PM 12667667 ER PT J AU Zhu, LX Sharma, S Gardner, B Escuadro, B Atianzar, K Tashkin, DP Dubinett, SM AF Zhu, LX Sharma, S Gardner, B Escuadro, B Atianzar, K Tashkin, DP Dubinett, SM TI IL-10 mediates sigma(1) receptor-dependent suppression of antitumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; CLASS-I EXPRESSION; TUMOR-CELL-LINES; TGF-BETA; LUNG-CANCER; T-CELL; CYTOKINE PRODUCTION; PROSTAGLANDIN E(2); HABITUAL SMOKERS; DENDRITIC CELLS AB Sigma receptors are unique endoplasmic reticulum proteins that mediate signaling for a variety of drugs. We determined the effect of sigma(1) receptor agonists on immune responses in a syngeneic lung cancer model. Sigma(1) receptor agonists, including cocaine, up-regulated splenocyte IL-10 mRNA and protein production in vitro in a sigma receptor-dependent, pertussis toxin-sensitive manner. In vivo, sigma(1) receptor agonists promoted tumor growth and induced IL-10 at the tumor site. Increased tumor growth was prevented by administration of specific Abs to IL-10 or by administration of specific sigma(1) receptor antagonists. We report that sigma(1) receptor ligands, including cocaine, augment tumor growth through an IL-10 dependent mechanism. C1 Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr,Ctr Hlth Sci 37 131, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr,Ctr Hlth Sci 37 131, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu FU NCI NIH HHS [R01 CA71818]; NIDA NIH HHS [R01 DA08254]; PHS HHS [P50 90388] NR 60 TC 26 Z9 27 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2003 VL 170 IS 7 BP 3585 EP 3591 PG 7 WC Immunology SC Immunology GA 659AL UT WOS:000181754100018 PM 12646621 ER PT J AU Ishii, T Ohnuma, K Murakami, A Takasawa, N Yamochi, T Iwata, S Uchiyama, M Dang, NH Tanaka, H Morimoto, C AF Ishii, T Ohnuma, K Murakami, A Takasawa, N Yamochi, T Iwata, S Uchiyama, M Dang, NH Tanaka, H Morimoto, C TI SS-A/Ro52, an autoantigen involved in CD28-Mediated IL-2 production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CULTURED-MAMMALIAN-CELLS; SS-A/RO AUTOANTIGEN; T-CELLS; MONOCLONAL-ANTIBODIES; CD28 COSTIMULATION; SJOGRENS SYNDROME; RNA INTERFERENCE; ACTIVATION; PROTEIN; EXPRESSION AB An autoantibody against SS-A/Ro52 (Ro52) is most frequently found in the sera of patients with Sjogren's syndrome, systemic lupus erythematosus, and congenital heart block from anti-Ro52 Ab-positive mother. However, the physiological function of the autoantigen SS-A/Ro52 has not yet been elucidated. In this study, we describe the role of Ro52 protein in T cell activation. Overexpression of SS-A/Ro52 in Jurkat T cell resulted in enhanced IL-2 production following CD28 stimulation. Furthermore, transfection of anti-Ro52-specific small RNA duplexes partially blocked the expression of native and overexpressed Ro52 in Jurkat T cell, resulting in decreased IL-2 production via CD28 pathway in these cells. Finally, intracellular localization of Ro52. dramatically changed following CD28 stimulation. Our data reveal a novel function of Ro52 in CD28-mediated pathway, which eventually contributes to cytokine production and expression of the T cell biological programs. C1 Univ Tokyo, Div Clin Immunol, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. RP Morimoto, C (reprint author), Univ Tokyo, Div Clin Immunol, Adv Clin Res Ctr, Inst Med Sci,Minato Ku, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. EM morimoto@ims.u-tokyo.ac.jp RI Iwata, Satoshi/A-8819-2011 FU NIAMS NIH HHS [AR33713] NR 35 TC 33 Z9 36 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 APR 1 PY 2003 VL 170 IS 7 BP 3653 EP 3661 PG 9 WC Immunology SC Immunology GA 659AL UT WOS:000181754100027 PM 12646630 ER PT J AU Montefiori, DC Altfeld, M Lee, PK Bilska, M Zhou, JT Johnston, MN Gao, F Walker, BD Rosenberg, ES AF Montefiori, DC Altfeld, M Lee, PK Bilska, M Zhou, JT Johnston, MN Gao, F Walker, BD Rosenberg, ES TI Viremia control despite escape from a rapid and potent autologous neutralizing antibody response after therapy cessation in an HIV-1-infected individual SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM NONPROGRESSORS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN MONOCLONAL-ANTIBODY; HIV-1/SIV CHIMERIC VIRUS; TYPE-1 ENVELOPE PROTEIN; T-CELL RESPONSES; PRIMARY INFECTION; IMMUNE-RESPONSES; RHESUS-MONKEYS AB The neutralizing Ab response after primary HIV-1 infection is delayed relative to the virus-specific CD8(+) T cell response and the initial decline in plasma viremia. Because nearly all HIV-1 infections result in AIDS, it would be instructive to study cases where neutralizing Ab production commenced sooner. This was done in subject AC10, an individual treated during early infection and in whom a rapid autologous neutralizing Ab response was detected after therapy cessation as rebound viremia declined and remained below 1000 RNA copies/ml of blood for over 2.5 years. This subject's Abs were capable of reducing the infectivity of his rebound virus by >4 logs in vitro at a time when rebound viremia was down-regulated and virus-specific CD8(+) T cells were minimal, suggesting that neutralizing Abs played an important role in the early control of viremia. The rebound virus did not exhibit an unusual phenotype that might explain its high sensitivity to neutralization by autologous sera. Neutralization escape occurred within 75 days and was proceeded by neutralizing Ab production to the escape variant and subsequent escape. Notably, escape was not associated with a significant rise in plasma viremia, perhaps due to increasing CD8(+) T cell responses. Sequence analysis of gp160 revealed a growing number of mutations over time, suggesting ongoing viral evolution in the face of potent antiviral immune responses. We postulate that an early effective neutralizing Ab response can provide long-term clinical benefits despite neutralization escape. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. EM monte@acpub.duke.edu FU NIAID NIH HHS [AI40237, AI50429, AI01541] NR 82 TC 31 Z9 32 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 APR 1 PY 2003 VL 170 IS 7 BP 3906 EP 3914 PG 9 WC Immunology SC Immunology GA 659AL UT WOS:000181754100057 PM 12646660 ER PT J AU Nguyen, BC Kochevar, IE AF Nguyen, BC Kochevar, IE TI Influence of hydration on dihydroxyacetone-induced pigmentation of stratum corneum SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE dihydroxyacetone; hydration; Maillard reaction; photoprotection; pigmentation; stratum corneum ID MAILLARD REACTION; WATER ACTIVITY; PROTECTION AB Dihydroxyacetone, the browning ingredient in sunless tanning formulations, reacts with amino acids in the outer stratum corneum to form a mixture of high molecular weight pigments. Our initial observations indicated that high hydration of dihydroxyacetone-treated skin completely inhibited development of pigmentation. To investigate the mechanism underlying this effect, studies were carried out in isolated murine epidermis, polyvinyl alcohol/lysine films, and lysine in glycerol/water solvent. Murine epidermis treated with dihydroxyacetone showed a biphasic dependence on relative humidity: maximum pigmentation developed at 84% relative humidity and minimum pigmentation at 0% and 100% relative humidity. Filaggrin proteolysis, which shows a similar dependence on relative humidity and provides free amino acids in the outer stratum corneum, did not account for the relative humidity dependence of dihydroxyacetone pigmentation. A similar biphasic pigmentation response was obtained when polyvinyl alcohol film containing lysine was treated with dihydroxyacetone and incubated at various relative humidities, indicating that the structure of the stratum corneum was not a major factor. To remove the influence of the matrix, the reaction of dihydroxyacetone with lysine was followed at varying concentrations of water in mixed glycerol/buffer solvent. Again, greater pigment formation was found at an intermediate level of water (6% vol/vol) and little pigmentation at 0% and 100% water content. These results are consistent with a requirement for water at low relative humidity, which facilitates formation of free amine groups needed for the initial reaction with dihydroxyacetone, and with inhibition of the dehydration reactions by water through the law of mass action at high relative humidity. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med,Dept Dermatol, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Sch Med,Dept Dermatol, WEL-224,50 Blossom St, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu NR 23 TC 13 Z9 13 U1 1 U2 8 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 APR PY 2003 VL 120 IS 4 BP 655 EP 661 DI 10.1046/j.1523-1747.2003.12089.x PG 7 WC Dermatology SC Dermatology GA 657VQ UT WOS:000181687400027 PM 12648231 ER PT J AU Mitsumori, LM Hatsukami, TS Ferguson, MS Kerwin, WS Cai, JM Yuan, C AF Mitsumori, LM Hatsukami, TS Ferguson, MS Kerwin, WS Cai, JM Yuan, C TI In vivo accuracy of multisequence MR imaging for identifying unstable fibrous caps in advanced human carotid plaques SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE magnetic resonance imaging; plaque rupture; atherosclerosis; carotid arteries; vulnerable plaque ID ATHEROSCLEROTIC PLAQUE; IN-VIVO; LIPID-RICH; RUPTURE; ULTRASOUND; ARTERY; COMPONENTS; DISEASE AB Purpose: To evaluate the in vivo accuracy of a multisequence MRI technique for prospectively identifying one feature of the vulnerable plaque-an unstable fibrous cap-in human carotid atherosclerosis. Materials and Methods: The carotid arteries of 18 endarterectomy patients were preoperatively imaged in a 1.5T scanner using a multisequence protocol that generated four contrast weightings (3D time of flight (ToF), T1, proton density (PD), and T2) at each slice location. With the use of previously published MR criteria, the images of the vessel wall were first examined for evidence of an unstable fibrous cap. The imaging findings were then correlated with the histology from the surgical specimens. Results: A blinded review of the MR findings with the histologic state of the fibrous cap revealed that 1) assessing the preoperative appearance of the fibrous cap has a high test sensitivity (0.81) and specificity (0.90) for identifying an unstable cap in vivo; and 2) the availability of different contrast weightings facilitated image interpretation when intimal. calcifications or flow artifacts obscured the lumen surface. Conclusion: Multisequence MRI can accurately characterize the in vivo state of the fibrous cap. This finding supports the use of these noninvasive techniques to prospectively identify vulnerable plaques. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Marina Ferguson Inc, Seattle, WA USA. Peoples Liberat Army Gen Hosp, Beijing, Peoples R China. RP Yuan, C (reprint author), Univ Washington, Dept Radiol, 1959 Pacific St NE,Box 357115, Seattle, WA 98195 USA. FU NHLBI NIH HHS [R01 HL56874, R01 HL60213] NR 28 TC 138 Z9 155 U1 0 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD APR PY 2003 VL 17 IS 4 BP 410 EP 420 DI 10.1002/jmri.10264 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 671EW UT WOS:000182453200003 PM 12655579 ER PT J AU Joffe, S Manocchia, M Weeks, JC Cleary, PD AF Joffe, S Manocchia, M Weeks, JC Cleary, PD TI What do patients value in their hospital care? An empirical perspective on autonomy centred bioethics SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID TREATMENT DECISION-MAKING; PATIENTS TRUST; PATIENTS WISH; PREFERENCES; PHYSICIANS; RESPECT; PARTICIPATE; BEHAVIORS; ENCOUNTER; MEDICINE AB Objective: Contemporary ethical accounts of the patient-provider relationship emphasise respect for patient autonomy and shared decision making. We sought to examine the relative influence of involvement in decisions, confidence and trust in providers, and treatment with respect and dignity on patients' evaluations of their hospital care. Design: Cross-sectional survey. Setting: Fifty one hospitals in Massachusetts. Participants: Stratified random sample of adults ( N=27 414) discharged from a medical, surgical, or maternity hospitalisation between January and March, 1998. Twelve thousand six hundred and eighty survey recipients responded. Main outcome measure: Respondent would definitely be willing to recommend the hospital to family and friends. Results: In a logistic regression analysis, treatment with respect and dignity ( odds ratio ( OR) 3.4, 99% confidence interval ( Cl) 2.8 to 4.2) and confidence and trust in providers ( OR 2.5, Cl 2.1 to 3.0) were more strongly associated with willingness to recommend than having enough involvement in decisions ( OR 1.4, Cl 1.1 to 1.6). Courtesy and availability of staff ( OR 2.5, Cl 2.1 to 3.1), continuity and transition ( OR 1.9, Cl 1.5 to 2.2), attention to physical comfort ( OR 1.8, Cl 1.5 to 2.2), and coordination of care ( OR 1.5, Cl 1.3 to 1.8) were also significantly associated with willingness to recommend. Conclusions: Confidence and trust in providers and treatment with respect and dignity are more closely associated with patients' overall evaluations of their hospitals than adequate involvement in decisions. These findings challenge a narrow emphasis on patient autonomy and shared decision making, while arguing for increased attention to trust and respect in ethical models of health care. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Univ Rhode Isl, Blue Cross Shield Rhode Isl Providence, Kingston, RI 02881 USA. Univ Rhode Isl, Dept Sociol, Kingston, RI 02881 USA. Brigham & Womens Hosp, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU AHRQ HHS [T32 HS00063] NR 54 TC 64 Z9 67 U1 0 U2 2 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 APR 1 PY 2003 VL 29 IS 2 BP 103 EP 108 DI 10.1136/jme.29.2.103 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 666BM UT WOS:000182155800013 PM 12672891 ER PT J AU Bounpheng, M McGrath, S Macias, D van Orsouw, N Suh, Y Rines, D Vijg, J AF Bounpheng, M McGrath, S Macias, D van Orsouw, N Suh, Y Rines, D Vijg, J TI Rapid, inexpensive scanning for all possible BRCA1 and BRCA2 gene sequence variants in a single assay: implications for genetic testing SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID MUTATIONS; ELECTROPHORESIS; ACCURATE C1 Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. Accelerated Genom Inc, San Antonio, TX 78229 USA. Seoul Natl Univ, Coll Med, Dept Biochem & Mol Biol, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110799, South Korea. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, 15355 Lambda Dr,STCBM 2-200, San Antonio, TX 78245 USA. FU NCI NIH HHS [P30 CA 54174] NR 17 TC 7 Z9 7 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2003 VL 40 IS 4 AR e33 DI 10.1136/jmg.40.4.e33 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 666BN UT WOS:000182155900015 PM 12676906 ER PT J AU Southwick, SM Axelrod, SR Wang, S Yehuda, R Morgan, CA Charney, D Rosenheck, R Mason, JW AF Southwick, SM Axelrod, SR Wang, S Yehuda, R Morgan, CA Charney, D Rosenheck, R Mason, JW TI Twenty-four-hour urine cortisol in combat veterans with PTSD and comorbid borderline personality disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER C1 VA Connecticut Healthcare Syst, Clin Neurosci Div, Natl Ctr PTSD 116A, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. NIA, Baltimore, MD 21224 USA. Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. NIMH, Bethesda, MD 20892 USA. VA Connecticut Healthcare Syst, NE Program Evaluat Ctr, West Haven, CT 06516 USA. RP Southwick, SM (reprint author), VA Connecticut Healthcare Syst, Clin Neurosci Div, Natl Ctr PTSD 116A, 950 Campbell Ave, West Haven, CT 06516 USA. NR 7 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2003 VL 191 IS 4 BP 261 EP 262 DI 10.1097/00005053-200304000-00009 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 668NL UT WOS:000182300000008 PM 12695738 ER PT J AU Quinn, J Montine, T Morrow, J Woodward, WR Kulhanek, D Eckenstein, F AF Quinn, J Montine, T Morrow, J Woodward, WR Kulhanek, D Eckenstein, F TI Inflammation and cerebral amyloidosis are disconnected in an animal model of Alzheimer's disease SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Alzheimer; animal model; cyclooxygenase; nonsteroidal anti-inflammatory drug; oxidative stress; indomethacin; F2-isoprostanes ID TRANSGENIC MOUSE MODEL; LIPID-PEROXIDATION; PLAQUE PATHOLOGY; OXIDATIVE DAMAGE; MICROGLIAL CELLS; MESSENGER-RNA; TG2576 MICE; PROSTAGLANDINS; CYTOKINES; PROTEIN AB The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)]. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Univ Vermont, Med Ctr, Dept Neurol, Burlington, VT USA. RP Quinn, J (reprint author), Portland Vet Affairs Med Ctr, P3 R&D,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NCCIH NIH HHS [AT00066-01]; NIA NIH HHS [AG16835, AG07424, AG08017, AG00774] NR 45 TC 71 Z9 79 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR PY 2003 VL 137 IS 1-2 BP 32 EP 41 DI 10.1016/S0165-5728(03)00037-7 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 671AZ UT WOS:000182443700004 PM 12667645 ER PT J AU Traynor, BJ Alexander, M Corr, B Frost, E Hardiman, O AF Traynor, BJ Alexander, M Corr, B Frost, E Hardiman, O TI An outcome study of riluzole in amyotrophic lateral sclerosis - A population-based study in Ireland, 1996-2000 SO JOURNAL OF NEUROLOGY LA English DT Article DE ALS; riluzole; survival; population-based; El Escorial criteria ID ALS; TRIAL AB Riluzole is the only therapy proven in clinical trials to prolong amyotrophic lateral sclerosis (ALS) survival (approximately three months). Questions remain concerning riluzole's effectiveness in everyday practice, the appropriate duration of treatment, which certain subtypes of ALS specifically benefit from the medication, and whether early administration prolongs survival in ALS patients. We report the results of a population-based outcome study of riluzole in the Irish ALS population over a five-year period. Using data from the Irish ALS Register, we examined the survival of patients diagnosed with ALS between 1 January 1996 and 31 December 2000 who attended a general neurology clinic (n = 264 patients, MD = 16). An intention to treat analysis is employed. 149 (61%) patients were prescribed riluzole and the remaining 99 (39%) were not. Riluzole therapy reduced mortality rate by 23% and 15% at 6 and 12 months respectively and prolonged survival by approximately four months. This beneficial effect was lost in prolonged follow-up. Suspected or possible ALS patients receiving riluzole experienced similar improvement in survival as the overall cohort. Survival benefit was more marked among patients with bulbar-onset disease. Multivariate analysis did not show riluzole to be an independent predictor of survival. We conclude that riluzole therapy improves ALS survival in everyday clinical practice by a short period of time. This beneficial effect is transient and stopping the medication in advanced ALS should be reconsidered. Bulbar-onset patients appear to particularly benefit from riluzole for unclear reasons. Our initial observations support riluzole use in early ALS. C1 Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Irish MND Assoc, Dublin 7, Ireland. RP Hardiman, O (reprint author), Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. RI Traynor, Bryan/G-5690-2010; OI Hardiman, Orla/0000-0003-2610-1291 NR 29 TC 77 Z9 80 U1 0 U2 10 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD APR PY 2003 VL 250 IS 4 BP 473 EP 479 DI 10.1007/s00415-003-1026-z PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 671PR UT WOS:000182473700013 PM 12700914 ER PT J AU Portera-Cailliau, C Doherty, CP Buonanno, FS Feske, SK AF Portera-Cailliau, C Doherty, CP Buonanno, FS Feske, SK TI Middle cerebral artery territory infarction sparing the precentral gyrus: report of three cases SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID SPECTACULAR SHRINKING DEFICIT; PREMOTOR CORTEX; RECOVERY; STROKE AB We report three patients with large middle cerebral artery infarctions in the non-dominant hemisphere, with striking recovery of motor function. In each case this excellent functional outcome correlated with selective sparing of the motor cortex in the precentral gyrus. We discuss some of the possible circulatory variants that might underlie this pattern of infarction. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Portera-Cailliau, C (reprint author), New York Hosp, Columbia Presbyterian Med Ctr, Ctr Parkinson Dis & Other Movement Disoders Neuro, Box 211 710 W 168th St, New York, NY 10032 USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD APR PY 2003 VL 74 IS 4 BP 510 EP 512 DI 10.1136/jnnp.74.4.510 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 660WD UT WOS:000181856300027 PM 12640076 ER PT J AU Sayin, U Osting, S Hagen, J Rutecki, P Sutula, T AF Sayin, U Osting, S Hagen, J Rutecki, P Sutula, T TI Spontaneous seizures and loss of axo-axonic and axo-somatic inhibition induced by repeated brief seizures in kindled rats SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; dentate gyrus; GABA; CCK; GAT-1; damage; epilepsy ID TEMPORAL-LOBE EPILEPSY; FIBER SYNAPTIC REORGANIZATION; GABA-MEDIATED INHIBITION; PAIRED-PULSE DEPRESSION; GAMMA-AMINOBUTYRIC-ACID; DENTATE GYRUS; GRANULE CELLS; IMMUNOREACTIVE NEURONS; HIPPOCAMPAL SCLEROSIS; STATUS EPILEPTICUS AB Repeated brief seizures evoked by kindling progressively increase seizure susceptibility and eventually induce spontaneous seizures. Previous studies have demonstrated that the initial seizures evoked by kindling increase paired-pulse inhibition at 15-25 msec interpulse intervals in the dentate gyrus and also induce apoptosis, progressive neuronal loss, mossy fiber sprouting, and neurogenesis, which could potentially alter the balance of excitation and/or inhibition and modify functional properties of hippocampal circuits. In these experiments, paired-pulse inhibition in the dentate gyrus was reduced or lost after similar to90-100 evoked seizures in association with emergence of spontaneous seizures. Evoked IPSCs examined by single electrode voltage-clamp methods in granule cells from kindled rats experiencing spontaneous seizures demonstrated altered kinetics (reductions of similar to48% in 10-90% decay time, similar to40% in tau, and similar to65% in charge transfer) and confirmed that decreased inhibition contributed to the reduced paired-pulse inhibition. The loss of inhibition was accompanied by loss of subclasses of inhibitory interneurons labeled by cholecystokinin and the neuronal GABA transporter GAT-1, which project axo-somatic and axo-axonic GABAergic inhibitory terminals to granule cells and axon initial segments. Seizure-induced loss of interneurons providing axo-somatic and axo-axonic inhibition may regulate spike output to pyramidal neurons in CA3 and could play an important role in generation of spontaneous seizures. The sequence of progressive cellular alterations induced by repeated seizures, particularly loss of GABAergic interneurons providing axo-somatic and axo-axonic inhibition, may be important in the development of intractable epilepsy. C1 Univ Wisconsin, Dept Neurol, Madison, WI 53792 USA. Univ Wisconsin, Dept Anat, Madison, WI 53792 USA. Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. RP Sutula, T (reprint author), Univ Wisconsin, Dept Neurol, H6-570,600 Highland Ave, Madison, WI 53792 USA. FU PHS HHS [R01 25020] NR 67 TC 92 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 APR 1 PY 2003 VL 23 IS 7 BP 2759 EP 2768 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 665ET UT WOS:000182107200029 PM 12684462 ER PT J AU Ohtani, N Goto, T Waeber, C Bhide, PG AF Ohtani, N Goto, T Waeber, C Bhide, PG TI Dopamine modulates cell cycle in the lateral ganglionic eminence SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ganglionic eminence; dopamine; cell cycle; striatum; neurogenesis; D1 receptor ID PRENATAL COCAINE EXPOSURE; ANTERIOR CINGULATE CORTEX; MOUSE CORPUS STRIATUM; RECEPTOR MUTANT MICE; NEOCORTICAL NEURONOGENESIS; GENE-EXPRESSION; D-3 RECEPTOR; RAT-BRAIN; IN-VITRO; ACTIVATING POLYPEPTIDE AB Dopamine is a neuromodulator the functions of which in the regulation of complex behaviors such as mood, motivation, and attention are well known. Dopamine appears in the brain early in the embryonic period when none of those behaviors is robust, raising the possibility that dopamine may influence brain development. The effects of dopamine on specific developmental processes such as neurogenesis are not fully characterized. The neostriatum is a dopamine-rich region of the developing and mature brain. If dopamine influenced neurogenesis, the effects would likely be pronounced in the neostriatum. Therefore, we examined whether dopamine influenced neostriatal neurogenesis by influencing the cell cycle of progenitor cells in the lateral ganglionic eminence (LGE), the neuroepithelial precursor of the neostriatum. We show that dopamine arrives in the LGE via the nigrostriatal pathway early in the embryonic period and that neostriatal neurogenesis progresses in a dopamine-rich milieu. Dopamine D1-like receptor activation reduces entry of progenitor cells from the G(1)- to S-phase of the cell cycle, whereas D-2-like receptor activation produces the opposite effects by promoting G(1)- to S-phase entry. D-1-like effects are prominent in the ventricular zone, and D2-like effects are prominent in the subventricular zone. The overall effects of dopamine on the cell cycle are D1-like effects, most likely because of the preponderance of D1-like binding sites in the embryonic neostriatum. These data reveal a novel developmental role for dopamine and underscore the relevance of dopaminergic signaling in brain development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02129 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NICHD NIH HHS [P01 HD005515, HD 05515]; NINDS NIH HHS [R01 NS043426, NS 43426, NS 62005] NR 68 TC 123 Z9 130 U1 0 U2 0 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 APR 1 PY 2003 VL 23 IS 7 BP 2840 EP 2850 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 665ET UT WOS:000182107200038 PM 12684471 ER PT J AU Sung, BK Lim, G Mao, JR AF Sung, BK Lim, G Mao, JR TI Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuropathic pain; allodynia; hyperalgesia; glutamate transporter; nerve injury; riluzole; tyrosine kinase; mitogen-activated protein kinase ID EXPERIMENTAL PERIPHERAL MONONEUROPATHY; REDUCE NOCICEPTIVE BEHAVIORS; CEREBELLAR GRANULE CELLS; AMINO-ACID TRANSPORTER; DORSAL-ROOT GANGLIA; NEUROTROPHIC FACTOR; MORPHINE-TOLERANCE; NMDA RECEPTOR; SCIATIC-NERVE; UP-REGULATION AB The central glutamatergic system has been implicated in the pathogenesis of neuropathic pain, and a highly active central glutamate transporter (GT) system regulates the uptake of endogenous glutamate. Here we demonstrate that both the expression and uptake activity of spinal GTs changed after chronic constriction nerve injury (CCI) and contributed to neuropathic pain behaviors in rats. CCI induced an initial GT upregulation up to at least postoperative day 5 primarily within the ipsilateral spinal cord dorsal horn, which was followed by a GT downregulation when examined on postoperative days 7 and 14 by Western blot and immunohistochemistry. Intrathecal administration of the tyrosine kinase receptor inhibitor K252a and the mitogen-activated protein kinase inhibitor PD98059 for postoperative days 1-4 reduced and nearly abolished the initial GT upregulation in CCI rats, respectively. Prevention of the CCI-induced GT upregulation by PD98059 resulted in exacerbated thermal hyperalgesia and mechanical allodynia reversible by the noncompetitive NMDA receptor antagonist MK-801, indicating that the initial GT upregulation hampered the development of neuropathic pain behaviors. Moreover, CCI significantly reduced glutamate uptake activity of spinal GTs when examined on postoperative day 5, which was prevented by riluzole (a positive GT activity regulator) given intrathecally twice a day for postoperative days 1-4. Consistently, riluzole attenuated and gradually reversed neuropathic pain behaviors when the 4 d riluzole treatment was given for postoperative days 1-4 and 5-8, respectively. These results indicate that changes in the expression and glutamate uptake activity of spinal GTs may play a critical role in both the induction and maintenance of neuropathic pain after nerve injury via the regulation of regional glutamate homeostasis, a new mechanism relevant to the pathogenesis of neuropathic pain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Massachusetts Gen Hosp Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Massachusetts Gen Hosp Pain Ctr, Dept Anesthesia & Crit Care, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01DA08835] NR 82 TC 221 Z9 239 U1 1 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 APR 1 PY 2003 VL 23 IS 7 BP 2899 EP 2910 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 665ET UT WOS:000182107200044 PM 12684477 ER PT J AU Glorioso, JC Mata, M Fink, DJ AF Glorioso, JC Mata, M Fink, DJ TI Therapeutic gene transfer to the nervous system using viral vectors SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE gene therapy; pain; Parkinson disease; mucopolysaccharidosis; neuropathy ID MUCOPOLYSACCHARIDOSIS TYPE-VII; NEUROTROPHIC FACTOR; PARKINSONS-DISEASE; LYSOSOMAL STORAGE; IN-VIVO; ADENOVIRAL VECTOR; SPINAL-CORD; MEDIATED EXPRESSION; BETA-GLUCURONIDASE; FACTOR PROTECTS AB The past few years have been marked by substantial progress in preclinical studies of therapeutic gene transfer for neurologic disease using viral-based vectors. In this article, the authors review the data regarding (1) treatment of focal neuronal degeneration, exemplified by Parkinson disease, ischemia, and trauma models; (2) treatment of global neurologic dysfunction, exemplified by the mucopolysaccharidoses and other storage diseases; (3) peripheral nervous system diseases including motor neuron disease and sensory neuropathies; and (4) the use of vectors expressing neurotransmitters to modulate functional neural activity in the treatment of pain. The results suggest that a number of different viral vectors may be appropriate for gene transfer to the central nervous system for specific disease processes, and that for the peripheral nervous system herpes simplex virus-based vectors appear to have special utility. The results of the first human gene therapy trials for neurologic disease, which are just now beginning, will be crucial in defining the next step in the development of this therapy. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. RP Fink, DJ (reprint author), S-520 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 62 TC 28 Z9 33 U1 0 U2 1 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 APR PY 2003 VL 9 IS 2 BP 165 EP 172 DI 10.1080/13550280390193984 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 671LQ UT WOS:000182466600004 PM 12707847 ER PT J AU Branowicki, P O'Neill, JB Dwyer, JL Marino, BL Houlahan, K Billett, A AF Branowicki, P O'Neill, JB Dwyer, JL Marino, BL Houlahan, K Billett, A TI Improving complex medication systems - An interdisciplinary approach SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. PHT Corp, Charlestown, MA USA. Harvard Univ, Cambridge, MA 02138 USA. RP O'Neill, JB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD APR PY 2003 VL 33 IS 4 BP 199 EP 200 DI 10.1097/00005110-200304000-00003 PG 2 WC Nursing SC Nursing GA 667DV UT WOS:000182216600003 PM 12690250 ER PT J AU Blaeser, BF August, MA Donoff, RB Kaban, LB Dodson, TB AF Blaeser, BF August, MA Donoff, RB Kaban, LB Dodson, TB TI Panoramic radiographic risk factors for inferior alveolar nerve injury after third molar extraction SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 78th General Session of the International-Association-for-Dental-Research CY APR 05-09, 2000 CL WASHINGTON, D.C. SP Int Assoc Dent Res ID MANDIBULAR 3RD MOLARS; COMPUTED-TOMOGRAPHY; SURGERY; REMOVAL; DAMAGE; COMPLICATIONS; DYSESTHESIA AB Purpose: The purpose of this study was to estimate the association between specific panoramic radiographic signs and inferior alveolar nerve (IAN) injury during mandibular third molar removal. Patients and Methods: A case-control study design was used; the sample consisted of patients who underwent removal of impacted mandibular third molars. Cases were defined as patients with confirmed IAN injury after third molar extraction, whereas controls were defined as patients without nerve injury. Five surgeons, who were blinded to injury status, independently assessed the preoperative panoramic radiographs for the presence of high-risk radiographic signs. Bivariate analyses were completed to assess the relationship between radiographic findings and IAN injury. The sensitivity, specificity, and positive and negative predictive values were computed for each radiographic sign. Results: The sample was composed of 8 cases and 17 controls. Positive radiographic signs were statistically associated with an IAN injury (P < .0001). The presence of radiographic sign(s) had positive predictive values that ranged from 1.4% to 2.7%, representing a 40% or greater increase over the baseline likelihood of injury (1%) for the individual patient. Absence of these radiographic findings had a strong negative (> 99%) predictive value. Conclusions: This study confirms previous analyses showing that panoramic findings of diversion of the inferior alveolar canal, darkening of the third molar root, and interruption of the cortical white line are statistically associated with IAN injury. Based on the estimated predictive values, the absence of positive radiographic findings was associated with a minimal risk of nerve injury, whereas, the presence of one or more of these findings was associated with an increased risk for nerve injury. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Dodson, TB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. FU NIDCR NIH HHS [K24-DE00448] NR 23 TC 73 Z9 76 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2003 VL 61 IS 4 BP 417 EP 421 DI 10.1053/joms.2003.50088 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 662BG UT WOS:000181925400002 PM 12684956 ER PT J AU Casarett, DJ AF Casarett, DJ TI Assessing decision-making capacity in the setting of palliative care research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT Meeting on the Ethics of End-of-Life Research CY SEP 12-13, 2002 CL NIH CAMPUS, BETHESDA, MARYLAND SP NINR, Off Rare Dis HO NIH CAMPUS DE palliative medicine research; decision-making capacity; informed consent; research ethics; competence ID RANDOMIZED CONTROLLED TRIAL; INFORMED CONSENT PROCESS; ILL CANCER-PATIENTS; CLINICAL-TRIALS; HOSPICE INPATIENTS; DEPRESSED-PATIENTS; PAIN; MORPHINE; DELIRIUM; COMPREHENSION AB This paper begins with a discussion of why concerns about decision-making capacity are warranted in palliative medicine research. Next, procedures for assessing decision-making capacity are discussed. It concludes with recommendations to guide the judicious use of these procedures in the design of palliative care research. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Else-vier All rights reserved. C1 Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Casarett, DJ (reprint author), Univ Penn, Div Geriatr, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 69 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2003 VL 25 IS 4 BP S6 EP S13 DI 10.1016/S0885-3924(03)00097-6 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 666HJ UT WOS:000182171300016 PM 12691692 ER PT J AU Casarett, DJ Knebel, A Helmers, K AF Casarett, DJ Knebel, A Helmers, K TI Ethical challenges of palliative care research SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Editorial Material C1 Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Philadelphia Vet Adm Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NINR, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Casarett, DJ (reprint author), Univ Penn, Div Geriatr, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 8 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2003 VL 25 IS 4 BP S3 EP S5 DI 10.1016/S0885-3924(03)00058-7 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 666HJ UT WOS:000182171300015 PM 12723543 ER PT J AU Daly, BJ Rosenfeld, K AF Daly, BJ Rosenfeld, K TI Maximizing benefits and minimizing risks in health services research near the end of life SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT Meeting on the Ethics of End-of-Life Research CY SEP 12-13, 2002 CL NIH CAMPUS, BETHESDA, MARYLAND SP NINR, Off Rare Dis HO NIH CAMPUS DE health services research; informed consent; research ethics; quality improvement ID PALLIATIVE CARE; CONSENT AB This article explores the ethical issues specific to Health Services Research (HSR) in palliative care, with particular attention to similarities and differences between HSR and institutional quality improvement (QI) initiatives. We focus on the challenges of determining what level of protection is warranted by investigations of health services and programs of care, in contrast to the traditional randomized clinical trial design, and how best to assure subject protection. A decision algorithm regarding the requirements for full IRB review and informed consent is proposed as a mechanism to assure that the level of protection is commensurate with the level of fisk. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier. All rights reserved. C1 Case Western Reserve Univ, Sch Nursing, Cleveland, OH 44106 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Daly, BJ (reprint author), Case Western Reserve Univ, Sch Nursing, Cleveland, OH 44106 USA. NR 15 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2003 VL 25 IS 4 BP S33 EP S42 DI 10.1016/S0885-3924(03)00059-9 PG 10 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 666HJ UT WOS:000182171300019 PM 12691695 ER PT J AU Berde, C Wolfe, J AF Berde, C Wolfe, J TI Pain, anxiety, distress, and suffering: Interrelated, but not interchangeable SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID POSTOPERATIVE BEHAVIORAL OUTCOMES; FLOW NITROUS-OXIDE; MEDICAL PROCEDURES; EUTECTIC MIXTURE; INTRAVENOUS INSERTION; CHILDRENS DISTRESS; ADVERSE EVENTS; SEDATION; LIDOCAINE; ANESTHETICS C1 Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Pain Treatment Serv, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP Berde, C (reprint author), Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Pain Treatment Serv, 333 Longwood Ave,Room 555, Boston, MA 02115 USA. EM charles.berde@tch.harvard.edu NR 43 TC 21 Z9 21 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2003 VL 142 IS 4 BP 361 EP 363 DI 10.1067/mpd.2003.194 PG 3 WC Pediatrics SC Pediatrics GA 676CF UT WOS:000182733800002 PM 12712049 ER PT J AU Laffel, LMB Vangsness, L Connell, A Goebel-Fabbri, A Butler, D Anderson, BJ AF Laffel, LMB Vangsness, L Connell, A Goebel-Fabbri, A Butler, D Anderson, BJ TI Impact of ambulatory, family-focused teamwork intervention on glycemic control in youth with type 1 diabetes SO JOURNAL OF PEDIATRICS LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Diabetes-Association CY JUN 14-18, 2002 CL SAN FRANCISCO, CA SP Amer Diabet Assoc ID QUALITY-OF-LIFE; INTENSIVE THERAPY; COMPLICATIONS TRIAL; METABOLIC-CONTROL; MELLITUS; ADOLESCENTS; CHILDREN; INVOLVEMENT; PREDICTORS; MANAGEMENT AB Objective To evaluate an ambulatory, family-focused intervention aimed at optimizing glycemic control, minimizing diabetes-related family conflict (DFC), and maintaining quality of life in youth with type I diabetes (T1DM). Study design We randomly assigned 105 children and adolescents, 8 to 17 years of age, with T1DM for less than or equal to6 years, to a family-focused teamwork (TW) intervention or to standard multidisciplinary diabetes care (SC). Patients in both study groups were seen at 3- to 4-month intervals and were followed prospectively for 1 year. Measures of family involvement in diabetes tasks, DFC, and quality of life were performed at baseline and after 1 year. Hemoglobin Ale was measured at each visit. Results Patients (n = 100) completed follow-up, (50 in TW and 50 in SC). At entry, Ale was 8.4% +/- 1.3% in TW and 8.3% +/- 1.0% in SC. After I year, Ale was 8.2% +/- 1.1% in TW compared with 8.7% +/- 1.5% in SC (P < .05). Both groups had similar frequencies of blood glucose monitoring (BGM) and insulin dosing. Families exposed to the TW intervention maintained or increased family involvement significantly more than families exposed to SC (P = .05). In multivariate analysis, the TW intervention and the daily frequency of BGM significantly predicted Ale (R-2 = 0.17, P = .05). Despite increased family involvement, the TW group reported no increase in DFC or decrease in quality of life. Conclusions The ambulatory TW intervention prevented the expected deterioration in glycemic control seen with SC in youths with T1DM of less than or equal to6 years' duration. Successful family involvement may assist in the preservation of health and the prevention of long-term diabetes complications for youth with diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Behav Res & Mental Hlth Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Pediat & Adolescent Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM Lori.Laffel@joslinl.harvard.edu FU NIDDK NIH HHS [DK-46887, R01 DK046887] NR 34 TC 148 Z9 153 U1 6 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2003 VL 142 IS 4 BP 409 EP 416 DI 10.1067/mpd.2003.138 PG 8 WC Pediatrics SC Pediatrics GA 676CF UT WOS:000182733800012 PM 12712059 ER PT J AU Blais, MA AF Blais, MA TI Applying the Rasch model: Fundamental measurement in human science SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 2003 VL 80 IS 2 BP 208 EP 210 DI 10.1207/S15327752JPA8002_10 PG 3 WC Psychology, Clinical; Psychology, Social SC Psychology GA 676GY UT WOS:000182744000010 ER PT J AU Kohno, T Moore, KA Baba, H Woolf, CJ AF Kohno, T Moore, KA Baba, H Woolf, CJ TI Peripheral nerve injury alters excitatory synaptic transmission in lamina II of the rat dorsal horn SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SUBSTANTIA-GELATINOSA NEURONS; SPINAL-CORD SLICES; MYELINATED AFFERENTS; CENTRAL TERMINALS; NEUROPATHIC PAIN; C-AFFERENT; REORGANIZATION; FIBERS; AXOTOMY; MODEL AB Using the blind whole cell patch-clamp recording technique, we investigated peripheral nerve injury-induced changes in excitatory synaptic transmission to neurones in lamina II of the dorsal horn. Partial (i.e. chronic constriction injury (CCI) and spared nerve injury (SNI)) and complete (i.e. sciatic nerve transection (SNT)) peripheral nerve injury altered the mean threshold intensity for eliciting A fibre-mediated EPSCs in lamina II neurones. Following SNT and CCI, EPSC threshold was significantly decreased, but following SNI, EPSC threshold was increased (naive: 32 +/- 2 muA, SNT: 22 +/-2 muA, CCL 23 +/- 2 muA, SNI: 49 +/- 4 muA; P < 0.01, Student's impaired t test). Despite this disparity between models, dorsal root compound action potential recordings revealed no significant difference in the conduction velocity or activation threshold of A and Ad fibres in naive, SNT, CCI and SNI rats. In addition to the changes in EPSC threshold, we also observed a shift in the distribution of EPSCs. In spinal cord slices from naive rats, polysynaptic A fibre-evoked EPSCs were observed in 24 % of lamina II neurones, monosynaptic Ad fibre EPSCs were observed in 34 % and polysynaptic Ad fibre EPSCs were observed in 7 %. Following SNT and CCI, the percentage of neurones with polysynaptic Adelta fibre EPSCs increased to greater than or equal to 65 % of the sampled population, while the percentage of neurones with monosynaptic Adelta fibre EPSCs decreased to < 10 %. The percentage of neurones with polysynaptic Ad fibre EPSCs was unchanged. In contrast, following SNI, Abeta fibre EPSCs decreased in incidence while the percentage of neurones with polysynaptic Adelta fibre EPSCs increased to 44 %. Similar to the other injury models, however, monosynaptic Ad fibre EPSCs decreased in frequency following SNI. Thus, excitatory synaptic transmission is subject to divergent plasticity in different peripheral nerve injury models, reflecting the complexity of responses to different forms of deafferentation. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Kohno, T (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 38253, NS 11076, R01 NS038253, F32 NS011076] NR 23 TC 98 Z9 102 U1 0 U2 9 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2003 VL 548 IS 1 BP 131 EP 138 DI 10.1113/jphysiol.2002.036186 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VH UT WOS:000183570800011 PM 12576493 ER PT J AU Cooper, NP Guinan, JJ AF Cooper, NP Guinan, JJ TI Separate mechanical processes underlie fast and slow effects of medial olivocochlear efferent activity SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GUINEA-PIG COCHLEA; BASILAR-MEMBRANE DISPLACEMENT; OUTER HAIR-CELLS; ACETYLCHOLINE; STIMULATION; CALCIUM; CAT AB Sound-evoked vibrations of the basilar membrane (BM) in anaesthetised guinea-pigs are shown to be affected over two distinct time scales by electrical stimulation of the medial olivocochlear efferent system: one is fast (10-100 ms), the other much slower (10-1100 s). For low and moderate level tones near the BM's characteristic frequency, both fast and slow effects inhibited BM motion. However, fast inhibition was accompanied by phase leads, while slow inhibition was accompanied by phase lags. These findings are consistent with a hypothesis that both fast and slow effects decrease sound amplification in the cochlea. However, the opposing directions of the phase changes indicate that separate mechanical processes must underlie fast and slow effects. One plausible interpretation of these findings is that efferent slow effects are caused by outer-hair-cell stiffness decreases, while efferent fast effects are caused by reductions in 'negative damping'. C1 Univ Keele, MacKay Inst Commun & Neurosci, Keele ST5 5BG, Staffs, England. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA 02114 USA. RP Cooper, NP (reprint author), Univ Keele, MacKay Inst Commun & Neurosci, Keele ST5 5BG, Staffs, England. FU NIDCD NIH HHS [R01 DC00235, R01 DC000235] NR 23 TC 64 Z9 65 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2003 VL 548 IS 1 BP 307 EP 312 DI 10.1113/jphysiol.2003.039081 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VH UT WOS:000183570800024 PM 12611913 ER PT J AU Przybylowski, T Bangash, MF Reichmuth, K Morgan, BJ Skatrud, JB Dempsey, JA AF Przybylowski, T Bangash, MF Reichmuth, K Morgan, BJ Skatrud, JB Dempsey, JA TI Mechanisms of the cerebrovascular response to apnoea in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CEREBRAL-BLOOD-FLOW; OBSTRUCTIVE SLEEP-APNEA; MUELLER MANEUVER; CARBON-DIOXIDE; HEMODYNAMICS; PRESSURE; VELOCITY; ARTERY; PERFUSION; DIAMETER AB We measured ventilation, arterial O-2 saturation, end-tidal CO2 (P-ET,P-CO2), blood pressure (intra-arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 +/- 1.1 mg min(-1) (mean +/- S.D.)). Under control conditions, breath holding caused increases in P-ET,P-CO2 (7 +/- 1 mmHg) and in mean arterial pressure (MAP) (15 +/- 2 mmHg). A transient hyperventilation (P-ET,P-CO2 -7 +/- 1 mmHg vs. baseline) occurred post-apnoea. CFV increased during apnoeas (by 42 +/- 3%) and decreased below baseline (by 20 +/- 2%) during post-apnoea hyperventilation. In the post-apnoea recovery period, CFV returned to baseline in 45 +/- 4 s. The post-apnoea decrease in CFV did not occur when hyperventilation was prevented. During ganglionic blockade, which abolished the increase in MAP, apnoea-induced increases in CFV were partially attenuated (by 26 +/- 2%). Increases in P-ET,P-CO2 and decreases in oxyhaemoglobin saturation (S-a,S-O2) (by 2 +/- 1%) during breath holds were identical in the intact and blocked conditions. Ganglionic blockade had no effect on the slope of the CFV response to hypocapnia but it reduced the CFV response to hypercapnia (by 17 +/- 5%). We attribute this effect to abolition of the hypercapnia-induced increase in MAP. Peak increases in CFV during 20 s Mueller manoeuvres (40 +/- 3%) were the same as control breath holds, despite a 15 mmHg initial, transient decrease in MAP. Hyperoxia also had no effect on the apnoea-induced increase in CFV (40 +/- 4%). We conclude that apnoea-induced fluctuations in CFV were caused primarily by increases and decreases in arterial partial pressure of CO2 (P-a,P-CO2) and that sympathetic nervous system activity was not required for either the initiation or the maintenance of the cerebrovascular response to hyper- and hypocapnia. Increased MAP or other unknown influences of autonomic activation on the cerebral circulation played a smaller but significant role in the apnoea-induced increase in CFV; however, negative intrathoracic pressure and the small amount of oxyhaemoglobin desaturation caused by 20 s apnoea did not affect CFV. C1 Univ Wisconsin, John Rankin Lab Pulm Med, Dept Populat Hlth Sci, Madison, WI 53705 USA. Univ Wisconsin, John Rankin Lab Pulm Med, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, John Rankin Lab Pulm Med, Dept Orthopaed & Rehabil, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Przybylowski, T (reprint author), Katedra & Klin Chorob Wewnetrznych, Ul Banacha 1A, PL-02097 Warsaw, Poland. NR 31 TC 56 Z9 57 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2003 VL 548 IS 1 BP 323 EP 332 DI 10.1113/jphysiol.2002.029678 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VH UT WOS:000183570800026 PM 12588894 ER PT J AU Hadlock, TA Sheahan, T Cheney, ML Vacanti, JP Sundback, CA AF Hadlock, TA Sheahan, T Cheney, ML Vacanti, JP Sundback, CA TI Biologic activity of nerve growth factor slowly released from microspheres SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE NGF; microspheres; slow release ID BOVINE SERUM-ALBUMIN; IN-WATER TECHNIQUE; POLY(LACTIDE-CO-GLYCOLIDE) MICROSPHERES; BIODEGRADABLE MICROSPHERES; DELIVERY SYSTEMS; STRUCTURAL PERTURBATIONS; NGF STABILITY; ENCAPSULATION; REGENERATION; PROTEIN AB Efficient and sustained delivery of neurotrophic factors to the regenerating nerve in biologically active form presents a challenge. Protein delivery in biodegradable microsphere vehicles has been difficult, based on destabilization and breakdown during both the loading and release phases. This study examines the extravasation and stability of Nerve Growth Factor (NGF) in polylactic-co-glycolic acid (PLGA) microspheres, via both ELISA and PC-12 bioassays. PLGA microspheres co-loaded with bovine serum albumin (BSA) and NGF were prepared by a water-in-oil-in-water (W/O/W) technique, using chloroform for the organic phase and 1 percent polyvinyl alcohol (PVA) for the emulsion step. Aliquots of lyophilized microspheres were incubated in double distilled water (dd H2O) at 37degrees C, and the supernatants assayed over time for NGF activity. ELISA was utilized for quantitative determination of NGF concentration, and a PC-12 cell neurite outgrowth assay assessed biologic activity. Both ELISA and PC-12 assays demonstrated the extravasation of NGF from microspheres. Over time, the predicted concentration of NGF via the two assays differed, suggesting possible preservation of recognizable epitopes for ELISA, but loss of biologic activity. NGF can be stored and released from microspheres. Extravasation studies should include biologically relevant assays for activity. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 11 Z9 16 U1 1 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD APR PY 2003 VL 19 IS 3 BP 179 EP 184 PG 6 WC Surgery SC Surgery GA 680KP UT WOS:000182976900008 PM 12806579 ER PT J AU Zimmerer, JL Leon, JB Covinsky, KE Desai, U Sehgal, AR AF Zimmerer, JL Leon, JB Covinsky, KE Desai, U Sehgal, AR TI Diet monotony as a correlate of poor nutritional intake among hemodialysis patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID FOOD-INTAKE; VARIETY; MEAL; WEIGHT AB Objective: Nutritional guidelines recommend eating a variety of foods, yet the renal diet restricts the intake of many foods. Poor appetite, present in 10% to 30% of hemodialysis patients, further narrows the range of foods consumed. We sought to determine the relationship between diet monotony and nutritional intake in patients on chronic hemodialysis. Design: Cross-sectional study. Setting: Eight freestanding hemodialysis units in northeast Ohio. Subjects: Forty-eight randomly selected hemodialysis patients. Intervention: We used the Block-National Cancer Institute questionnaire to obtain a detailed food frequency and also asked patients to rate their appetite for 10 specific high-protein foods. Outcome Measure: We adapted the Herfindahl index (a measure of hospital market concentration) to calculate a diet monotony index and then examined the relationship between monotony index and energy and protein intake. Results: When stratified into tertiles by monotony index, patients with the most varied diets had the highest energy (33 kcal/kg/d) and protein (1.35 g/kg/d) intake, whereas patients with the most monotonous diets had the lowest energy (21 kcal/kg/d) and protein (0.83 g/kg/d) intake. A 5-point increase in monotony index was independently associated with a 10 kcal/kg/d decrease in energy intake (P = .004) and a 0.43 g/kg/d decrease in protein intake (P = .006) after adjustment for patient demographic and medical characteristics. Patients with the most monotonous diets reported a good appetite for an average of 3.1 high-protein foods that they were eating less than once per week. Conclusion: Diet monotony strongly correlates with nutritional intake. However, patients with monotonous diets have a good appetite for several high-protein foods that they are not eating. Helping patients to identify and increase the intake of these foods may both enhance diet variety and improve nutritional status. (C) 2003 by the National Kidney Foundation, Inc. C1 Metrohlth Med Ctr, Div Nephrol, Cleveland, OH 44109 USA. San Francisco Vet Adm Med Ctr, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Metrohlth Med Ctr, Ctr Hlth Care Res & Policy, Cleveland, OH USA. Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Biomed Eth, Cleveland, OH 44106 USA. RP Zimmerer, JL (reprint author), Metrohlth Med Ctr, Div Nephrol, 2500 MetroHlth Dr-R229, Cleveland, OH 44109 USA. FU NIDDK NIH HHS [DK51472, DK54178] NR 24 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD APR PY 2003 VL 13 IS 2 BP 72 EP 77 DI 10.1053/jren.2003.50025 PG 6 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 666TB UT WOS:000182191600002 PM 12671828 ER PT J AU Molz, FJ Partin, JI Kirkpatrick, JS AF Molz, FJ Partin, JI Kirkpatrick, JS TI The acute effects of posterior fusion instrumentation on kinematics and intradiscal pressure of the human lumbar spine SO JOURNAL OF SPINAL DISORDERS & TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Meeting of the SOA CY JUL 20-22, 2000 CL SOUTHHAMPTON, BERMUDA SP SOA DE lumbar spine; biomechanics; nondestructive testing; spinal instrumentation; adjacent segment degeneration; intradiscal pressure; range of motion ID POSTEROLATERAL FUSION; ADJACENT-SEGMENT; BIOMECHANICAL ANALYSIS; HYDROSTATIC-PRESSURE; INTERVERTEBRAL DISC; LUMBOSACRAL SPINE; MATRIX SYNTHESIS; DISCOGENIC PAIN; MOTION SEGMENTS; AXIAL ROTATION AB Nine cadaver lumbar spines were analyzed by applying nonconstraining nondestructive bending moments while measuring global range of motion, mechanical reaction at the sacrum, applied moment at the top of the specimen, segmental range of motion at L1-L5, and IDP at L1-L4. Each specimen was examined in an intact and instrumented state (with L3-L4 posterior instrumentation) using range of motion-based biomechanical testing, while achieving a similar global ROM in the sagittal, frontal, and transverse planes. An increase in applied moment was required during instrumented testing when compared with intact, and a significant increase in segmental range of motion during instrumented testing was found at all uninstrumented levels. Significant decreases in segmental range of motion were measured at the instrumented level when compared with intact testing. The most significant decreases and increases in IDP occurred at the instrumented level during sagittal and transverse plane testing. C1 Birmingham VA Med Ctr, Spine Biomech Lab, Birmingham, AL USA. Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. Univ Alabama, Div Orthopaed Surg, Birmingham, AL 35294 USA. RP Molz, FJ (reprint author), Medtron Sofamore Danek, Technol Dev, 1800 Pyramid Pl, Memphis, TN 38132 USA. NR 55 TC 10 Z9 13 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1536-0652 J9 J SPINAL DISORD TECH JI J. Spinal Disord. Tech. PD APR PY 2003 VL 16 IS 2 BP 171 EP 179 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 664HM UT WOS:000182055700009 PM 12679672 ER PT J AU Wilens, T Pelham, W Stein, M Conners, CK Abikoff, H Atkins, M August, G Greenhill, L McBurnett, K Palumbo, D Swanson, J Wolraich, M AF Wilens, T Pelham, W Stein, M Conners, CK Abikoff, H Atkins, M August, G Greenhill, L McBurnett, K Palumbo, D Swanson, J Wolraich, M TI ADHD treatment with once-daily OROS methylphenidate: Interim 12-month results from a long-term open-label study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; methylphenidate; long-term study; safety ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CONTROLLED TRIAL; TIC DISORDER; CHILDREN; STIMULANTS; GROWTH; EFFICACY; BOYS AB Objective: Few treatment studies of attention-deficit/hyperactivity disorder (ADHD) extend beyond a few months. This article reports an interim analysis of a 24-month study evaluating the 12-month tolerability and effectiveness of a once-daily OROS(R) formulation of methylphenidate (OROS MPH) in children with ADHD. Method: Children, aged 6-13 years, with ADHD who participated in previous controlled studies and were MPH responders, received once-daily OROS MPH in this multicenter, open-label, nonrandomized study. Effectiveness was evaluated monthly by parents/caregivers and schoolteachers using validated rating scales (e.g., IOWA Conners). Safety and adverse events assessments involved objective (e.g., vital signs, growth) and subjective (sleep quality, tics) reporting. Results: Seventy-one percent of subjects (289/407) completed 12 months' treatment. Effectiveness was maintained throughout 12 months as demonstrated by stable IOWA Conners ratings and sustained improvements in peer interaction and Global Assessment Scale scores. OROS MPH was well tolerated, with adverse events similar to those expected with short-acting stimulant medication. OROS MPH had minimal impact on sleep quality and tics. There were no clinically meaningful changes in blood pressure, pulse, or height. The apparent absence of meaningful changes is tempered by the fact that children were MPH responders and were medicated at baseline, most for extended periods prior to enrollment. Conclusion: In this open-label study, once-daily OROS MPH treatment appears to be well tolerated and effectiveness was maintained for up to 12 months in these children with ADHD. C1 Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. SUNY Buffalo, Dept Psychol, Buffalo, NY USA. Childrens Natl Med Ctr, Dept Psychol, Washington, DC 20010 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. NYU Med Ctr, Dept Psychiat, New York, NY 10016 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. New York State Psychiat Inst & Hosp, Pediat Psychopharmacol Res Unit, New York, NY 10032 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Rochester, Strong Neurol ADHD Clin, Rochester, NY 14627 USA. Univ Calif Irvine, Child Dev Ctr, Irvine, CA USA. Univ Oklahoma, Ctr Child Study, Oklahoma City, OK USA. RP Wilens, T (reprint author), Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, 15 Parkham St, Boston, MA 02114 USA. EM wilens@helix.mgh.harvard.edu NR 48 TC 94 Z9 97 U1 3 U2 11 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 APR PY 2003 VL 42 IS 4 BP 424 EP 433 DI 10.1097/01.CHI.0000046814.95464.7D PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 658DN UT WOS:000181706500008 PM 12649629 ER PT J AU Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Paller, AS Stevens, SR Whitaker-Worth, DL Tong, KB AF Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Paller, AS Stevens, SR Whitaker-Worth, DL Tong, KB TI Cost-effectiveness analysis of tacrolimus ointment versus high-potency topical corticosteroids in adults with moderate to severe atopic dermatitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PHARMACOECONOMIC ANALYSIS; FLUTICASONE PROPIONATE; ECZEMA; PSORIASIS; 0.05-PERCENT; CYCLOSPORINE; GUIDELINES; MANAGEMENT; CHILDREN; THERAPY AB Background Few cost-effectiveness analyses have been conducted on topical therapies for atopic dermatitis. Objective: We sought to compare cost-effectiveness of high-potency topical corticosteroids (HPTCs) and tacrolimus ointment for the treatment of moderate to severe atopic dermatitis for patients who are not responsive to or not well controlled with mid-potency topical corticosteroids. Methods: A Markov model represented the cyclic nature of atopic dermatitis. Clinical outcomes were derived from published literature. "Efficacy" was defined as disease-controlled days on which patients experienced a greater than 75% improvement in their disease. Resource use and changes in management were on the basis of opinions of a physician panel; secondary treatment was an oral antibiotic with topical corticosteroids. Sensitivity analyses were conducted for all variables. Results: The model was sensitive to duration of continuous treatment with HPTCs. HPTCs, when limited to 2-week treatment cycles, were associated with the highest total costs ($1682 per year) and the least efficacy (185 disease-controlled days). HPTCs in 4-week treatment intervals and tacrolimus ointment were similar in total costs and efficacy ($1317 vs $1323 for 194 vs 190 disease-controlled days, respectively). Although primary drug costs were higher for patients treated with tacrolimus ointment, patients treated with regimens of HPTCs incurred higher secondary drug costs. Conclusion. In the base case analyses, tacrolimus ointment was more cost-effective than HPTCs administered in 2-week treatment cycles, and similar in cost-effectiveness to 4-week cycles of HPTCs. (J Am Acad Dermatol 2003;48:553-63.). C1 Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48109 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Fujisawa Hlthcare Inc, Deerfield, IL USA. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Texas, SW Med Sch, Dallas, TX USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Mississippi, Jackson, MS 39216 USA. NYU, Mt Sinai Sch Med, New York, NY USA. Northwestern Univ, Sch Med, Chicago, IL USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Quorom Consulting Inc, San Francisco, CA USA. RP Ellis, CN (reprint author), Univ Michigan, Sch Med, Dept Dermatol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 41 TC 39 Z9 40 U1 0 U2 5 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 APR PY 2003 VL 48 IS 4 BP 553 EP 563 DI 10.1067/mjd.2003.240 PG 11 WC Dermatology SC Dermatology GA 662NK UT WOS:000181953500011 PM 12664019 ER PT J AU Kuo, WP Whipple, ME Jenssen, TK Todd, R Epstein, JB Ohno-Machado, L Sonis, ST Park, PJ AF Kuo, WP Whipple, ME Jenssen, TK Todd, R Epstein, JB Ohno-Machado, L Sonis, ST Park, PJ TI Microarrays and clinical dentistry SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DNA MICROARRAYS; HYBRIDIZATION; ARRAYS; HETEROZYGOSITY; IDENTIFICATION; PROTEIN; CHIPS; YEAST AB Background. The Human Genome Project, or HGP, has inspired a great deal of exciting biology recently by enabling the development of new technologies that will be essential for understanding the different types of abnormalities in diseases related to the oral cavity. Literature Reviewed. The authors review current literature pertaining to the advanced microarray technologies arising from the HGP and how they can contribute to dentistry. This technology has become a standard tool for monitoring activities of genes at both academic and pharmaceutical research institutions. Results. With the availability of the DNA sequences for the entire human genome, attention now is focused on understanding various diseases at the genome level. Deciphering the molecular behavior of genetically encoded proteins is crucial to obtaining a more comprehensive picture of disease processes. Important progress has been made using microarrays, which have been shown to be effective in identifying gene expression patterns and variations that correlate with cellular development, physiology and function. Arrays can be used to classify tissue samples accurately based on molecular profiles and to select candidate genes related to a number of cancers, including oral cancer. This type of oral genetic approach will aid in the understanding of disease progression, thus improving diagnosis and treatment for patients. Clinical Implications. Microarrays hold much promise for the analysis of diseases in the oral cavity. As the technology evolves, dentists may see these tools as screening tests for better managing patients' dental care. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Decis Syst Grp, Boston, MA USA. Univ Illinois, Dept Oral Med & Diagnost Sci, Chicago, IL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. Norwegian Radium Hosp, Dept Tumor Biol, Montebello, Norway. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. EM winston-kuo@hms.harvard.edu OI Ohno-Machado, Lucila/0000-0002-8005-7327 NR 27 TC 8 Z9 11 U1 0 U2 2 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2003 VL 134 IS 4 BP 456 EP 462 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 668ZZ UT WOS:000182328600020 PM 12733779 ER PT J AU Covinsky, KE Palmer, RM Fortinsky, RH Counsell, SR Stewart, AL Kresevic, D Burant, CJ Landefeld, CS AF Covinsky, KE Palmer, RM Fortinsky, RH Counsell, SR Stewart, AL Kresevic, D Burant, CJ Landefeld, CS TI Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: Increased vulnerability with age SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospitalization; activities of daily living; frail elderly; geriatric assessment; health status ID FUNCTIONAL STATUS; SERIOUSLY ILL; ACUTE-CARE; OUTCOMES; TRIAL; VALIDATION; MORBIDITY; ADMISSION; MORTALITY; SUPPORT AB OBJECTIVES: To describe the changes in activities of daily living (ADL) function occurring before and after hospital admission in older people hospitalized with medical illness and to assess the effect of age on loss of ADL function. DESIGN: Prospective observational study. SETTING: The general medical service of two hospitals. PARTICIPANTS: Two thousand two hundred ninety-three patients aged 70 and older (mean age 80, 64% women, 24% nonwhite). MEASUREMENTS: At the time of hospital admission, patients or their surrogates were interviewed about their independence in five ADLs (bathing, dressing, eating, transferring, and toileting) 2 weeks before admission (baseline) and at admission. Subjects were interviewed about ADL function at discharge. Outcome measures included functional decline between baseline and discharge and functional changes between baseline and admission and between admission and discharge. RESULTS: Thirty-five percent of patients declined in ADL function between baseline and discharge. This included the 23% of patients who declined between baseline and admission and failed to recover to baseline function between admission and discharge and the 12% of patients who did not decline between baseline and admission but declined between hospital admission and discharge. Twenty percent of patients declined between baseline and admission but recovered to baseline function between admission and discharge. The frequency of ADL decline between baseline and discharge varied markedly with age (23%, 28%, 38%, 50%, and 63% in patients aged 70-74, 75-79, 80-84, 85-89, and greater than or equal to90, respectively, P < .001). After adjustment for potential confounders, age was not associated with ADL decline before hospitalization (odds ratio (OR) for patients aged greater than or equal to90 compared with patients aged 70-74 = 1.26, 95% confidence interval (CI) = 0.88-1.82). In contrast, age was associated with the failure to recover ADL function during hospitalization in patients who declined before admission (OR for patients aged greater than or equal to90 compared with patients aged 70-74 = 2.09, 95% CI = 1.20-3.65) and with new losses of ADL function during hospitalization in patients who did not decline before admission (OR for patients aged greater than or equal to90 compared with patients aged 70-74 = 3.43, 95% CI = 1.92-6.12). CONCLUSION: Many hospitalized older people are discharged with ADL function that is worse than their baseline function. The oldest patients are at particularly high risk of poor functional outcomes because they are less likely to recover ADL function lost before admission and more likely to develop new functional deficits during hospitalization. C1 San Francisco VAMC, San Francisco, CA 94122 USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. Cleveland Clin Fdn, Dept Gen Internal Med, Cleveland, OH 44195 USA. Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Div Geriatr, Farmington, CT USA. Case Western Reserve Univ, Dept Sociol & Bioeth, Cleveland, OH 44106 USA. RP Covinsky, KE (reprint author), San Francisco VAMC, 181G,4150 Clement, San Francisco, CA 94122 USA. FU AHRQ HHS [K02HS00006-01]; NIA NIH HHS [AG00912] NR 37 TC 443 Z9 452 U1 9 U2 37 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 APR PY 2003 VL 51 IS 4 BP 451 EP 458 DI 10.1046/j.1532-5415.2003.51152.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 659XD UT WOS:000181803000002 PM 12657063 ER PT J AU Unutzer, J Katon, W Callahan, CM Williams, JW Hunkeler, E Harpole, L Hoffing, M Della Penna, RD Noel, PH Lin, EHB Tang, LQ Oishi, S AF Unutzer, J Katon, W Callahan, CM Williams, JW Hunkeler, E Harpole, L Hoffing, M Della Penna, RD Noel, PH Lin, EHB Tang, LQ Oishi, S TI Depression treatment in a sample of 1,801 depressed older adults in primary care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; primary care; quality of care ID LATE-LIFE DEPRESSION; RANDOMIZED CONTROLLED TRIAL; MENTAL-HEALTH-SERVICES; PATIENTS AGED 65; MAJOR DEPRESSION; MINOR DEPRESSION; ANTIDEPRESSANT PHARMACOTHERAPY; MEDICAID POPULATION; DISORDERS; SYMPTOMS AB OBJECTIVES: To examine rates and predictors of lifetime and recent depression treatment in a sample of 1,801 depressed older primary care patients DESIGN: Cross sectional survey data collected from 1999 to 2001 as part of a treatment effectiveness trial. SETTING: Eighteen primary care clinics belonging to eight organizations in five states. PARTICIPANTS: One thousand eight hundred one clinic users aged 60 and older who met diagnostic criteria for major depression or dysthymia. MEASUREMENTS: Lifetime depression treatment was defined as ever having received a prescription medication, counseling, or psychotherapy for depression. Potentially effective recent depression treatment was defined as 2 or more months of antidepressant medications or four or more sessions of counseling or psychotherapy for depression in the past 3 months. RESULTS: The mean age +/- standard deviation was 71.2 +/- 7.5; 65% of subjects were women. Twenty-three percent of the sample came from ethnic minority groups (12% were African American, 8% were Latino, and 3% belonged to other ethnic minorities). The median household income was $23,000. Most study participants (83%) reported depressive symptoms for 2 or more years, and most (71%) reported two or more prior depressive episodes. About 65% reported any lifetime depression treatment, and 46% reported some depression treatment in the past 3 months, although only 29% reported potentially effective recent depression treatment. Most of the treatment provided consisted of antidepressant medications, with newer antidepressants such as selective serotonin reuptake inhibitors constituting the majority (78%) of antidepressants used. Most participants indicated a preference for counseling or psychotherapy over antidepressant medications, but only 8% had received such treatment in the past 3 months, and only 1% reported four or more sessions of counseling. Men, African Americans, Latinos, those without two or more prior episodes of depression, and those who preferred counseling to antidepressant medications reported significantly lower rates of depression care. CONCLUSION: The findings suggest that there is considerable opportunity to improve care for older adults with depression. Particular efforts should be focused on improving access to depression care for older men, African Americans, Latinos, and patients who prefer treatments other than antidepressants. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. Indiana Univ, Ctr Aging Res, Regenstrief Inst Hlth Care, Indianapolis, IN 46204 USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. Kaiser Permanente No Calif, Div Res, Oakland, CA USA. Desert Med Grp, Palm Springs, CA USA. Kaiser Permanente So Calif, San Diego, CA USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. RP Unutzer, J (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Ctr Hlth Serv Res, 10920 Wilshire Blvd, Los Angeles, CA 90024 USA. RI Williams, Jr., John/A-3696-2008; OI Williams, Jr., John/0000-0002-5267-5558; Penna, Maria Pietronilla/0000-0002-0982-3893 NR 74 TC 124 Z9 125 U1 8 U2 12 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 APR PY 2003 VL 51 IS 4 BP 505 EP 514 DI 10.1046/j.1532-5415.2003.51159.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 659XD UT WOS:000181803000009 PM 12657070 ER PT J AU Ahmed, A Allman, RM DeLong, JF AF Ahmed, A Allman, RM DeLong, JF TI Pattern of cardiology consultation by primary care physician specialty and its association with quality and outcomes of care. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Alabama, Div Geriatr Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, GRECC, Birmingham, AL USA. Alabama Qual Assurance Fdn, Heart Failure Study Grp, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P233 BP S122 EP S122 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100279 ER PT J AU Ahmed, A Allman, RM DeLong, JF AF Ahmed, A Allman, RM DeLong, JF TI Association between physician specialty and inappropriate use of digoxin in older adults with heart failure. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Alabama, Div Geriatr Med, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, GRECC, Birmingham, AL USA. Alabama Qual Assurance Fdn, Birmingham, AL USA. RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P222 BP S118 EP S119 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100268 ER PT J AU Braun, UK Urbauer, D Wray, NP Beyth, RJ AF Braun, UK Urbauer, D Wray, NP Beyth, RJ TI Racial disparities in tube feeding practices for patients with dementia SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, HSR&D Ctr Excellence, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P373 BP S167 EP S167 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100417 ER PT J AU Burton, LC Leff, B Guido, S Greenough, W Steinwachs, D Naughton, B Mader, S Burl, J Donius, M Saltzman, S AF Burton, LC Leff, B Guido, S Greenough, W Steinwachs, D Naughton, B Mader, S Burl, J Donius, M Saltzman, S TI Importance of having of an accessible confidant in patients' decision to be treated in a home hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. Portland Vet Affairs Med Ctr, Portland, OR USA. SUNY Buffalo, Buffalo, NY 14260 USA. Fallon Hlth Syst, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P376 BP S168 EP S168 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100420 ER PT J AU Carey, EC Walter, LC Lindquist, K Covinsky, KE AF Carey, EC Walter, LC Lindquist, K Covinsky, KE TI Development of a functional morbidity index to predict mortality in community-dwelling elders. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Div Geriatr, Dept Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P182 BP S105 EP S105 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100228 ER PT J AU Casarett, D Crowley, R Hirschman, KB AF Casarett, D Crowley, R Hirschman, KB TI If only we had known: What should physicians tell patients and families about hospice? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P496 BP S209 EP S209 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100541 ER PT J AU Chong, K Olson, E Banc, T Cohen, S Anderson-Malico, R Penrod, J AF Chong, K Olson, E Banc, T Cohen, S Anderson-Malico, R Penrod, J TI Types and rate of implementation of palliative care team recommendations for care of hospitalized veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 New York Med Coll, Valhalla, NY 10595 USA. Bronx Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P535 BP S223 EP S223 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100580 ER PT J AU Chun, AK Cohen, S Penrod, JD AF Chun, AK Cohen, S Penrod, JD TI Effect of palliative care education on housestaff practice. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Mt Sinai Sch Med, Brookdale Dept Geriatr & Adult Dev, New York, NY USA. Bronx Vet Adm Med Ctr, GRECC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P56 BP S62 EP S63 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100102 ER PT J AU Collins, J Conn, V Fox, A Guthrie, M Siddle, J AF Collins, J Conn, V Fox, A Guthrie, M Siddle, J TI Tools and autonomy: Recipe for successful nursing case management in diabetes care. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Home Based Primary Care, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P534 BP S222 EP S223 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100579 ER PT J AU Collins, M Crowley, R Karlawish, J Casarett, D AF Collins, M Crowley, R Karlawish, J Casarett, D TI Are depressed patients near the end of life more likely to delegate decision-making to others? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P386 BP S171 EP S172 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100430 ER PT J AU Day, HD Tulsky, AA Fox, AR Hennon, J Granieri, EC AF Day, HD Tulsky, AA Fox, AR Hennon, J Granieri, EC TI Jump starting the future: A geriatrics track within an internal medicine residency training program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. Univ Pittsburgh, UCSUR, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P52 BP S61 EP S61 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100098 ER PT J AU Fan, E Royall, DR Chiodo, L Polk, MJ Mouton, C AF Fan, E Royall, DR Chiodo, L Polk, MJ Mouton, C TI Insight into financial capacity in non-institutionalized retirees. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P108 BP S80 EP S80 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100154 ER PT J AU Joudeh, F Gleason, CE Baker, LD Lofgreen, T Cholerton, B Craft, S Asthana, S AF Joudeh, F Gleason, CE Baker, LD Lofgreen, T Cholerton, B Craft, S Asthana, S TI Raloxifene improves cognitive function for older women with Alzheimer's disease. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Wisconsin, Geriatr & Gerontol Sect, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, GRECC, Madison, WI USA. Geriatr Res Educ VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, GRECC, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P104 BP S79 EP S79 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100150 ER PT J AU Karlawish, JH Casarett, D Coyne, J Katz, I AF Karlawish, JH Casarett, D Coyne, J Katz, I TI Are depressed elderly more likely to refuse a screening colonoscopy? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P199 BP S110 EP S111 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100245 ER PT J AU Karlawish, JH James, BD Casarett, DJ Kim, S Sankar, P AF Karlawish, JH James, BD Casarett, DJ Kim, S Sankar, P TI Can people with Alzheimers disease make a decision about treating Alzheimers disease? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Rochester, Rochester, NY 14627 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA A34 BP S39 EP S39 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100035 ER PT J AU Legner, VJ Doerner, D Reilly, DF McCormick, WC AF Legner, VJ Doerner, D Reilly, DF McCormick, WC TI Risk factors for nursing home placement following non-emergent major surgery. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P568 BP S234 EP S234 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100613 ER PT J AU Reid, MC Otis, J Barry, LC Kerns, RD AF Reid, MC Otis, J Barry, LC Kerns, RD TI Cognitive-behavioral therapy for older persons with chronic low back pain: A pilot study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 VA Connecticut Healthcare Syst, West Haven, CT USA. VA Boston Healthcare Syst, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P441 BP S190 EP S190 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100485 ER PT J AU Silverman, GK Justice, AC AF Silverman, GK Justice, AC TI Why are older patients better at adhering to medication: Patient-provider relationship and other factors SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P375 BP S168 EP S168 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100419 ER PT J AU Sims, RV Ball, K Roth, D Clay, O McKinney, Y Allman, RM AF Sims, RV Ball, K Roth, D Clay, O McKinney, Y Allman, RM TI Shared associations for falls and motor vehicle crashes among older veterans. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P476 BP S202 EP S202 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100521 ER PT J AU Sims, RV Ball, K Roth, D McKinney, Y Clay, O Allman, RM AF Sims, RV Ball, K Roth, D McKinney, Y Clay, O Allman, RM TI Falls among older veteran drivers. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA A44 BP S42 EP S42 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100045 ER PT J AU Vernon, C Vig, EK AF Vernon, C Vig, EK TI Stability of views about the end of life. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Western Univ Hlth Sci, Pomona, CA USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P129 BP S87 EP S87 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100175 ER PT J AU Vig, EK Hopley, EK AF Vig, EK Hopley, EK TI What do surrogate decision-makers know about hospice? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr & Extended Care, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P131 BP S87 EP S88 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100177 ER PT J AU Walter, LC de Garmo, P Covinsky, KE AF Walter, LC de Garmo, P Covinsky, KE TI Older age and female sex are associated with inadequate reach of screening flexible sigmoidoscopy. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA P123 BP S85 EP S85 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100169 ER PT J AU Wenger, N Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Adams, J Louie, R Venus, P Schnelle, J Shekelle, P AF Wenger, N Solomon, DH Roth, CP MacLean, CH Saliba, D Kamberg, CJ Rubenstein, LZ Young, RT Sloss, EM Adams, J Louie, R Venus, P Schnelle, J Shekelle, P TI The quality of medical care provided to vulnerable older patients. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-Geriatrics-Society CY MAY 14-18, 2003 CL BALTIMORE, MARYLAND SP American Geriatr Soc C1 RAND Corp, Hlth, Santa Monica, CA 90406 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. United Hlth Grp, Ctr Hlth Policy & Evaluat, Minneapolis, MN USA. Borun Ctr Gerontol Res, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2003 VL 51 IS 4 SU S MA A20 BP S33 EP S34 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 667VP UT WOS:000182255100021 ER PT J AU Smith, KD Wrenshall, LE Nicosia, RF Pichler, R Marsh, CL Alpers, CE Polissar, N Davis, CL AF Smith, KD Wrenshall, LE Nicosia, RF Pichler, R Marsh, CL Alpers, CE Polissar, N Davis, CL TI Delayed graft function and cast nephropathy associated with tacrolimus plus rapamycin use SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID RENAL-ALLOGRAFT REJECTION; ACUTE TUBULAR-NECROSIS; NEOINTIMAL PROLIFERATION; INTRAVASCULAR ULTRASOUND; EPITHELIAL-CELLS; VASCULAR-DISEASE; PROXIMAL TUBULE; RISK-FACTORS; FOLLOW-UP; SIROLIMUS AB Delayed graft function (DGF) occurs in 15 to 25% (range, 10 to 62%) of cadaveric kidney transplant recipients and up to 9% of living donor recipients. In addition to donor, recipient, and procedural factors, the choice of immunosuppression may influence the development of DGF. The impact of immunosuppression on DGF was studied. The frequency of DGF was evaluated in first cadaveric or living donor kidney allograft recipients (n = 144) transplanted at the University of Washington from November 1999 through September 1, 2001. Donor, recipient, and procedural factors, as well as biopsy results, were compared between patients who developed DGF and those who did not. DGF was more common in patients treated with rapamycin than without (25% versus 8.9%, P = 0.02) and positively correlated with rapamycin dose (P = 0.008). In those developing DGF, the duration of posttrans- plant dialysis increased with donor age (P = 0.003) but decreased with mycophenolate mofetil use (P = 0.01). All biopsies during episodes of DGF demonstrated changes of acute tubular injury. Of the patients with tubular injury, 12 treated with rapamycin and tacrolimus developed intratubular cast formation indistinguishable from myeloma cast nephropathy. Histologic, immunohistochemical, and ultrastructural studies indicated that these casts were composed at least in part of degenerating renal tubular epithelial cells. These findings suggest that rapamycin therapy exerts increased toxicity on tubular epithelial cells and/or retards healing, leading to an increased incidence of DGF. Additionally, raparnycin treatment combined with a calcineurin inhibitor may lead to extensive tubular cell injury and death and a unique form of cast nephropathy. C1 Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Div Transplantat, Seattle, WA 98195 USA. Mt Whisper Light Stat Consulting, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Davis, CL (reprint author), Box 356174,1959 NE Pacific St, Seattle, WA 98195 USA. EM cdavis@u.washington.edu NR 48 TC 105 Z9 109 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2003 VL 14 IS 4 BP 1037 EP 1045 DI 10.1097/01.ASN.0000057542.86377.5A PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 659LD UT WOS:000181777400024 PM 12660339 ER PT J AU Minneci, PC Mathisen, DJ AF Minneci, PC Mathisen, DJ TI Minor challenges: Modified diverticulectomy and myotomy for recurrent Zenker diverticulum SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID CRICOPHARYNGEAL C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2003 VL 125 IS 4 BP 969 EP 971 DI 10.1067/mtc.2003.40 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 668ZP UT WOS:000182327700035 PM 12698170 ER PT J AU Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Morrison, PR AF Shankar, S vanSonnenberg, E Silverman, SG Tuncali, K Morrison, PR TI Management of pneumothorax during percutaneous radiofrequency ablation of a lung tumor: Technical note SO JOURNAL OF THORACIC IMAGING LA English DT Editorial Material DE pneumothoras; radiofrequency ablation; lung cancer AB Percutaneous radiofrequency ablation (RFA) is a new procedure to treat lung cancer. Pneumothorax (PTX) may occur intraprocedurally, especially with the large RFA probes, and complicate the completion of the treatment. The authors describe a case of PTX developing during RFA and its successful management. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP vanSonnenberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 7 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD APR PY 2003 VL 18 IS 2 BP 106 EP 109 DI 10.1097/00005382-200304000-00011 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668MU UT WOS:000182298400011 PM 12700487 ER PT J AU Noble, VE Legome, E Marshburn, T AF Noble, VE Legome, E Marshburn, T TI Long bone ultrasound: Making the diagnosis in remote locations SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Founders 150, Boston, MA 02114 USA. NR 0 TC 12 Z9 12 U1 1 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 APR PY 2003 VL 54 IS 4 BP 800 EP 800 DI 10.1097/01.TA.0000061492.98012.BD PG 1 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 675AT UT WOS:000182671400039 PM 12707550 ER PT J AU Smith-Bindman, R Chu, PW Ecker, J Feldstein, VA Filly, RA Bacchetti, P AF Smith-Bindman, R Chu, PW Ecker, J Feldstein, VA Filly, RA Bacchetti, P TI Adverse birth outcomes in relation to prenatal sonographic measurements of fetal size SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE birth outcomes; fetal biometry; fetal weight; intrauterine growth restriction; neonatal morbidity; neonatal mortality; neonatal outcomes; prenatal sonography ID INTRAUTERINE GROWTH-RETARDATION; ABDOMINAL CIRCUMFERENCE; WEIGHT; RESTRICTION; PREDICTION; DIAGNOSIS; MORBIDITY; MORTALITY; AGE AB Objective. To evaluate and quantify the prediction of multiple neonatal outcomes by sonographically estimated fetal weight across a broad range of gestational ages. Methods. A retrospective cohort analysis was conducted among women with certain gestational age (n = 1376) seen at the University of California San Francisco from 1994 through 1997. The relative risks for small size at birth, small (low birth weight) for gestational age, and adverse neonatal outcomes were compared between small and average-sized fetuses. Results. Fetuses with an estimated fetal weight in the 5th percentile or less for gestational age were at increased risk of a birth weight less than 2000 g (relative risk, 6.5), a birth weight in less than the 3rd percentile for gestational age (relative risk, 10.1), preterm birth (relative risk, 2.2), extreme preterm birth (relative risk, 5.7), prolonged neonatal hospital stay (relative risk, 2.7), neonatal intensive care unit admission (relative risk, 3.2), and stillbirth or neonatal death (relative risk, 7.7) compared with average-sized fetuses (all P <.0001). With intrauterine growth restriction defined as an estimated fetal weight in the 5th percentile or less for gestational age, up to 29% of fetuses with adverse neonatal outcomes were detected, for false-positive rates of only 4% to 5%. After adjusting for confounding variables, low estimated fetal weight remained a significant predictor of neonatal morbidity and mortality. Conclusions. Morbidity and mortality are significantly increased among fetuses with an estimated fetal weight in the 5th percentile or less for gestational age. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, Dept Radiol, UCSF Mt Zion Campus,1600 Divisadero St, San Francisco, CA 94115 USA. NR 24 TC 6 Z9 7 U1 0 U2 0 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 APR PY 2003 VL 22 IS 4 BP 347 EP 356 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 676TT UT WOS:000182769000005 PM 12693618 ER PT J AU D'Amico, AV Cote, K Loffredo, M Renshaw, AA Chen, MH AF D'Amico, AV Cote, K Loffredo, M Renshaw, AA Chen, MH TI Pretreatment predictors of time to cancer specific death after prostate specific antigen failure SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; mortality ID RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; DISEASE RECURRENCE; RADIOTHERAPY; VALIDATION; BIOPSIES AB Purpose: Whether pretreatment factors that predict for time to prostate specific antigen (PSA) failure also predict for time to prostate cancer specific death after PSA failure for patients with competing causes of mortality treated during the PSA era was the subject of this study. Materials and Methods: Of 415 men with a median age of 73 years who underwent external beam radiation therapy between 1988 and 2001 for clinically localized prostate cancer 160 (39%) experienced PSA failure and 96 (23%) died. In 46 men (48%) the cause of death was prostate cancer. Cox regression multivariable analyses (multivariable analysis) were performed to evaluate the ability of the pretreatment PSA and centrally reviewed biopsy Gleason score to predict time to prostate cancer specific death after PSA failure. Results: When analyzed as categorical variables using multivariable analysis, biopsy Gleason score 4 + 3 (p = 0.02), 8 to 10 (p = 0.02) disease and a pretreatment PSA greater than 20 ng./ml. (p = 0.03) were significant predictors of time to prostate cancer specific death after PSA failure. Estimates of prostate cancer specific death 5 years after PSA failure were 24%, 40% and 59% (p = 0.01) for patients with a biopsy Gleason score :56, 3 + 4, 4 + 3 or higher and 22%, 40% and 60% (p = 0.04) for patients with a pretreatment PSA of 10 or less, greater than 10 and 20 or less, or greater than 20 ng./ml., respectively. Conclusions: Patients at high risk for PSA failure after radiation therapy based on pretreatment PSA greater than 20 ng./ml. or biopsy Gleason score 4 + 3 or greater are also at high risk for death from prostate cancer after PSA failure despite competing causes of mortality. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 50 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2003 VL 169 IS 4 BP 1320 EP 1324 DI 10.1097/01.ju.0000049200.30192.d1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 656YY UT WOS:000181639700022 PM 12629352 ER PT J AU Freedland, SJ deGregorio, F Sacoolidge, JC Elshimali, YI Csathy, GS Dorey, F Reiter, RE Aronson, WJ AF Freedland, SJ deGregorio, F Sacoolidge, JC Elshimali, YI Csathy, GS Dorey, F Reiter, RE Aronson, WJ TI Preoperative p27 status is an independent predictor of prostate specific antigen failure following radical prostatectomy SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostatectomy; prostate-specific antigen; cell cycle proteins ID DEPENDENT KINASE INHIBITOR; RADIATION-THERAPY; P27(KIP1) PROTEIN; CANCER; EXPRESSION; RECURRENCE; SURVIVAL; ADENOCARCINOMA; MARKERS; STAGE AB Purpose: p27 is an important cell cycle regulator, and decreased expression in radical prostatectomy specimens is associated with an increased risk of prostate specific antigen (PSA) failure. To our knowledge no prior study has shown that preoperative p27 status independently predicts recurrence after radical prostatectomy. Materials and Methods: The prostate needle biopsy specimens of 161 men treated with radical prostatectomy were examined for p27 expression using immunohistochemistry. Various p27 cut points were examined for their ability to separate patients into groups with different risk for time to biochemical recurrence following radical prostatectomy. The best p27 cut point was compared to other clinical variables (PSA, clinical stage, age, biopsy Gleason score and percent of prostate needle biopsy with cancer) on multivariate analysis to determine which variables independently predicted biochemical failure. Results: A p27 cut point of less than 45% positive staining cells resulted in significant preoperative risk stratification for time to PSA failure (HR 2.41, p = 0.010). On multivariate analysis serum PSA (HR 1.04, p = 0.011), biopsy Gleason score (HR 1.51, p = 0.011), percent of biopsy tissue with cancer (HR 10.01, p = 0.001) and less than 45% p27 positive cells (HR 2.44, p = 0.014) were all independent predictors of biochemical recurrence. Conclusions: Preoperative p27 expression is an independent predictor of time to biochemical recurrence following radical prostatectomy. Patients with less than 45% p27 positive cells in the prostate needle biopsy specimen have almost a 2.5-fold increased risk of biochemical recurrence. To our knowledge this study is the first to show that p27 status of the prostate needle biopsy specimen can be used before radical prostatectomy to predict biochemical failure. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. Olive View UCLA Med Ctr, Dept Pathol, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Pathol, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P50 CA92131-01A1] NR 22 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2003 VL 169 IS 4 BP 1325 EP 1330 DI 10.1097/01.ju.0000054004.08958.f3 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 656YY UT WOS:000181639700023 PM 12629353 ER PT J AU Latini, DM Penson, DF Lubeck, DP Wallace, KL Henning, JM Lue, TF AF Latini, DM Penson, DF Lubeck, DP Wallace, KL Henning, JM Lue, TF TI Longitudinal differences in disease specific quality of life in men with erectile dysfunction: Results from the exploratory comprehensive evaluation of erectile dysfunction study SO JOURNAL OF UROLOGY LA English DT Article DE penis; impotence; quality of life; questionnaires ID OF-LIFE; PROSTATE-CANCER; INTERNATIONAL INDEX; SILDENAFIL CITRATE; SEXUAL FUNCTION; EFFICACY; UROLOGY AB Purpose: We assessed the impact of erectile dysfunction therapy on 1-year health related quality of life using a validated erectile dysfunction specific instrument. Materials and Methods: Using an observational erectile dysfunction registry clinical, sociodemographic and health related quality of life information was collected at baseline, and 3, 6 and 12 months later. Only men who reported undergoing erectile dysfunction treatment were included in this analysis sub-sample. Patients were classified as treatment responders based on improvements in International Index of Erectile Function scores. Changes in health related quality of life scores from baseline were compared between responders and nonresponders. Results: The cohort consisted of 89 patients, of whom 40 (45%) responded to therapy by International Index of Erectile Function criteria. Responders and nonresponders had comparable baseline disease severity and health related quality of life. At 1 year responders reported significantly better health related quality of life and greater improvement from baseline in sexual experience (mean change -1.64 versus 3.19) and emotional life (mean -3.01 for responders versus 1.75) domains of the Psychological Impact of Erectile Dysfunction scales (p <0.01). This 4.5 to 5 point difference in mean change score (1/2 SD) was considered moderately clinically significant. Conclusions: Men who respond to erectile dysfunction treatment report significantly better health related quality of life 1 year after initial presentation for erectile dysfunction than nonresponders. This finding should motivate providers to be more proactive in diagnosing and treating men with erectile dysfunction since successful therapy appears to improve health related quality of life. These data suggest that men in whom primary therapy for erectile dysfunction fails should be offered secondary treatment because many men in this study in whom previous therapies failed reported improved health related quality of life when they began effective secondary treatment. C1 Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Urol Outcomes Res Grp, San Francisco, CA 94143 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Latini, DM (reprint author), Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. OI Latini, David/0000-0002-6161-4861 NR 18 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2003 VL 169 IS 4 BP 1437 EP 1442 DI 10.1097/01.ju.0000049203.33463.9e PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 656YY UT WOS:000181639700049 PM 12629379 ER PT J AU Penson, DF Latini, DM Lubeck, DP Wallace, K Henning, JM Lue, T AF Penson, DF Latini, DM Lubeck, DP Wallace, K Henning, JM Lue, T TI Is quality of life different for men with erectile dysfunction and prostate cancer compared to men with erectile dysfunction due to the exceed other causes? Results from data base SO JOURNAL OF UROLOGY LA English DT Article DE impotence; prostate neoplasms; quality of life ID OF-LIFE; PATIENT PREFERENCES AB Purpose: To our knowledge the relationship between the underlying etiology of erectile dysfunction and its impact on health related quality of life has not been studied. Such a study is important for men with prostate cancer, as the potential negative quality of life impact of erectile dysfunction may affect clinical decision making in newly diagnosed disease. We compare health related quality of life in impotent men with prostate cancer to that of impotent men without prostate cancer using the Exploratory and Comprehensive Evaluation of Erectile Dysfunction (ExCEED, TAP Pharmaceutical Products, Inc., Lake Forest, Illinois) data base, which is a multicenter, observational disease registry of men with erectile dysfunction. Materials and Methods: The cohort included 168 men in ExCEED who had baseline health related quality of life measurement. Of these men 47 reported a history of prostate cancer while 121 did not. Appropriate univariate and multivariate analyses were performed comparing health related quality of life outcomes between impotent men with and without prostate cancer. Results: Men with erectile dysfunction and prostate cancer had worse sexual self-efficacy, erectile function, intercourse satisfaction and orgasmic function than those with erectile dysfunction without prostate cancer (all p <0.001). However, men with erectile dysfunction and prostate cancer experienced less psychological impact of erectile dysfunction on sexual experience (p = 0.05) and emotional life (p = 0.03) than those with erectile dysfunction without prostate cancer. The findings regarding the psychological impact of erectile dysfunction persisted in multivariate linear regression models. Conclusions: Men with erectile dysfunction and prostate cancer appear to have better disease specific health related quality of life than those with erectile dysfunction and no history of prostate cancer. This finding has important ramifications for clinicians when counseling patients newly diagnosed with prostate cancer and also when treating patients who present with erectile dysfunction of various etiologies. C1 VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Penson, DF (reprint author), VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. NR 14 TC 27 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2003 VL 169 IS 4 BP 1458 EP 1461 DI 10.1097/01.ju.0000054462.88306.43 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 656YY UT WOS:000181639700053 PM 12629383 ER PT J AU Lin, CW Engelman, A AF Lin, CW Engelman, A TI The barrier-to-autointegration factor is a component of functional human immunodeficiency virus type 1 preintegration complexes SO JOURNAL OF VIROLOGY LA English DT Article ID INTEGRATION IN-VITRO; VIRAL NUCLEIC-ACIDS; RETROVIRAL DNA; NUCLEOPROTEIN COMPLEX; MONOCLONAL-ANTIBODIES; CDNA INTEGRATION; CELLULAR FACTOR; PROTEIN; INVITRO; ENDS AB Retroviral integration in vivo is mediated by preintegration complexes (PICs) derived from infectious virions. In addition to the integrase enzyme and cDNA substrate, PICs contain a variety of viral and host cell proteins. Whereas two different cell proteins, high-mobility group protein A1 (HMGA1) and the barrier-to-autointegration factor (BAF), were identified as integration cofactors based on activities in in vitro PIC assays, only HMGA1 was previously identified as a PIC component. By using antibodies against known viral and cellular PIC components, we demonstrate here functional coimmunoprecipitation of endogenous BAF protein with human immunodeficiency virus type 1 (HIV-1) PICs. Since integrase protein and integration activity were also coimmunoprecipitated by anti-BAF antibodies, we conclude that BAF is a component of HIV-1 PICs. These data are consistent with the model that BAF functions as an integration cofactor in vivo. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R37 AI039394, AI39394, AI28691, AI53812, P30 AI028691, R01 AI039394] NR 38 TC 106 Z9 112 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2003 VL 77 IS 8 BP 5030 EP 5036 DI 10.1128/JVI.77.8.5030-5036.2003 PG 7 WC Virology SC Virology GA 662VU UT WOS:000181970200060 PM 12663813 ER PT J AU Asthana, S AF Asthana, S TI Estrogen and cognition: The story so far SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE; CONTROLLED TRIAL; DOUBLE-BLIND; DEMENTIA C1 Univ Wisconsin, Madison Med Sch, Sect Geriatr & Gerontol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Asthana, S (reprint author), Univ Wisconsin, Madison Med Sch, Sect Geriatr & Gerontol, Madison, WI 53706 USA. NR 18 TC 17 Z9 17 U1 1 U2 1 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 APR PY 2003 VL 58 IS 4 BP 322 EP 323 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 663NN UT WOS:000182011800005 PM 12663695 ER PT J AU Talcott, JA AF Talcott, JA TI New era in prostate-cancer care: what we know and what we don't SO LANCET ONCOLOGY LA English DT Editorial Material ID COMPARING RADICAL PROSTATECTOMY; TRIAL C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD APR PY 2003 VL 4 IS 4 BP 204 EP 205 DI 10.1016/S1470-2045(03)01030-1 PG 2 WC Oncology SC Oncology GA 666VK UT WOS:000182197000015 PM 12681261 ER PT J AU Poe, DS Metson, RB Kujawski, O AF Poe, DS Metson, RB Kujawski, O TI Laser eustachian tuboplasty: A preliminary report SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the Triological-Society CY MAY 12-14, 2002 CL BOCA RATON, FLORIDA SP Triol Soc DE eustachian tuboplasty; eustachian tube dysfunction ID VIDEO ENDOSCOPY; MIDDLE-EAR; TUBE; REFLUX AB Objectives/Hypothesis: Surgical correction of eustachian tube dysfunction remains an elusive challenge. Repeat ventilation tube placement is often inadequate to prevent tympanic membrane and middle ear complications. Endoscopic analyses of eustachian tube dynamics have localized the site of primary pathophysiology to within the cartilaginous tube. The study investigated the feasibility, safety, and efficacy of a new endoluminal eustachian tube operation for the treatment of eustachian tube dysfunction. Study Design: Prospective, institutional review board-approved surgical trial in a tertiary-care medical center. Methods: Ten patients with more than 5 consecutive years of intractable otitis media with effusion recurring after two or more tympanostomy tube placements were treated with unilateral laser eustachian tuboplasty. Surgery was performed on an outpatient basis with the use of general anesthesia and combined both transnasal and transoral approaches. A 980-nm diode or argon laser was used to vaporize an appropriate amount of mucosa and cartilage on the posterior wall of the tubal lumen. Preoperative and postoperative dynamic video eustachian tube function analyses were compared. Outcome measures were presence or absence of middle ear effusion and impedance tympanograms. Results: Five patients had at least 12 months of follow-up, and three of them had absence of any effusion (60%). Two patients had recurrence of their otitis media with effusion and required tympanostomy tubes again. Five patients had at least 6 months of follow-up, and four of them had absence of any effusion. The remaining patient had recurrence of otitis media with effusion and received a tympanostomy tube again. Overall results for all 10 patients after 6 months were 7 free of effusion (70%). There were no intraoperative complications. Postoperative complications were limited to minimal peritubal adhesions and one intranasal synechia. Conclusions: Preliminary results suggest that laser eustachian tuboplasty is safe and efficacious in the treatment of intractable eustachian tube dysfunction. Further study will be necessary to determine whether laser eustachian tuboplasty is a suitable alternative to repeated tympanostomy tube placement in selected patients. C1 Harvard Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Clin Grangettes, Eustachian Tube Disorders Ctr, Geneva, Switzerland. RP Poe, DS (reprint author), 0 Emerson Pl,Suite 2C, Boston, MA 02114 USA. NR 23 TC 29 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2003 VL 113 IS 4 BP 583 EP 591 DI 10.1097/00005537-200304000-00001 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 664EM UT WOS:000182048800001 PM 12671411 ER PT J AU Pui, CH Chessells, JM Camitta, B Baruchel, A Biondi, A Boyett, JM Carroll, A Eden, OB Evans, WE Gadner, H Harbott, J Harms, DO Harrison, CJ Harrison, PL Heerema, N Janka-Schaub, G Kamps, W Masera, G Pullen, J Raimondi, SC Richards, S Riehm, H Sallan, S Sather, H Shuster, J Silverman, LB Valsecchi, MG Vilmer, E Zhou, Y Gaynon, PS Schrappe, M AF Pui, CH Chessells, JM Camitta, B Baruchel, A Biondi, A Boyett, JM Carroll, A Eden, OB Evans, WE Gadner, H Harbott, J Harms, DO Harrison, CJ Harrison, PL Heerema, N Janka-Schaub, G Kamps, W Masera, G Pullen, J Raimondi, SC Richards, S Riehm, H Sallan, S Sather, H Shuster, J Silverman, LB Valsecchi, MG Vilmer, E Zhou, Y Gaynon, PS Schrappe, M TI Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements SO LEUKEMIA LA English DT Article DE 11q23; t(4;11); t(11;19); acute lymphoblastic leukemia; MLL rearrangement; infant leukemia; transplantation ID CHILDRENS CANCER GROUP; TYROSINE KINASE INHIBITOR; PEDIATRIC-ONCOLOGY-GROUP; MLL-GENE REARRANGEMENTS; POOR-PROGNOSIS; IN-VITRO; INFANTS; FEATURES; AGE; T(11/19)(Q23,P13.3) AB To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-5% vs 23.4+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over I year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-8% (high risk) vs 83+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy. C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Memphis, TN USA. MRC, Childhood Leukaemia Working Party, London W1N 4AL, England. Childrens Oncol Grp, Arcadia, CA USA. Dutch Childhood Leukemia Study Grp, The Hague, Netherlands. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. European Org Res Treatment Canc, Brussels, Belgium. RP Pui, CH (reprint author), St Jude Childrens Res Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. RI Schrappe, Martin/A-8109-2010 FU NCI NIH HHS [CA51001, CA 31566, CA21765, CA29139, CA37379, CA78824] NR 41 TC 118 Z9 125 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2003 VL 17 IS 4 BP 700 EP 706 DI 10.1038/sj.leu.2402883 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 669QP UT WOS:000182362200002 PM 12682627 ER PT J AU Gopal, DV Rosen, HR AF Gopal, DV Rosen, HR TI Duration of antiviral therapy for cholestatic HCV recurrence may need to be indefinite SO LIVER TRANSPLANTATION LA English DT Article ID ORTHOTOPIC LIVER-TRANSPLANTATION; HEPATITIS-C RECURRENCE; COMBINATION INTERFERON; RIBAVIRIN; EFFICACY; INJURY AB Progressive liver allograft injury related to hepatitis C virus (HCV) recurrence occurs in 20% to 30% of liver transplant recipients within the first 5 years. In particular the subset of patients who develop the severe cholestatic variant has an extremely high mortality. We report our center's experience with 7 cholestatic patients who were treated with interferon alfa-2b (3 million IU three times per week initially) in combination with ribavirin. In 4 of the 7 patients, HCV-RNA in serum became undetectable, and in an additional patient, normalization of serum bilirubin was achieved despite persistent viremia. Discontinuation of antiviral therapy by patient choice, intolerance of side effects, or occurrence of infection were followed temporally by rapid relapses of the cholestatic syndrome, allograft failure, and death. The only 2 patients alive in remission of this syndrome have been maintained on antiviral therapy for an average of 32 months. Thus, based on our experience, we recommend that duration of antiviral therapy in the subset of patients with cholestatic HCV recurrence should be indefinite. C1 US Vet Hosp, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Hepatol Liver Transplantat Program, Portland, OR 97207 USA. Oregon Hlth & Sci Ctr, Div Gastroenterol, Portland, OR USA. RP Gopal, DV (reprint author), US Vet Hosp, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Hepatol Liver Transplantat Program, 3710 SW,P3-GI, Portland, OR 97207 USA. NR 18 TC 46 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD APR PY 2003 VL 9 IS 4 BP 348 EP 353 DI 10.1053/jlts.2003.50062 PG 6 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 663ML UT WOS:000182009300004 PM 12682884 ER PT J AU Chan, JL Abrahamson, MJ AF Chan, JL Abrahamson, MJ TI Pharmacological management of type 2 diabetes mellitus: Rationale for rational use of insulin SO MAYO CLINIC PROCEEDINGS LA English DT Review ID IMPROVES GLYCEMIC CONTROL; BEDTIME NPH INSULIN; CONTROLLED TRIAL; GLUCOSE CONTROL; MICROVASCULAR COMPLICATIONS; PIOGLITAZONE HYDROCHLORIDE; NOCTURNAL HYPOGLYCEMIA; SUBCUTANEOUS INJECTION; SECRETORY DYSFUNCTION; COMBINATION THERAPY AB Type 2 diabetes mellitus is a chronic metabolic disorder associated with high morbidity and mortality from longterm microvascular and macrovascular complications. Evidence from randomized controlled trials indicates that aggressive treatment directed at improving glycemic control reduces the incidence of diabetes-related microvascular complications. Traditionally, oral monotherapy for type 2 diabetes is initiated when diet and exercise do not control hyperglycemia, followed by the sequential, stepwise addition of oral agents as glycemic control deteriorates. Insulin is the last therapeutic option used, generally reserved for advanced stages of the disease when multiple oral combination treatment fails. Despite a better understanding of the pathophysiologic disease mechanisms in the past decade, the expanded armamentarium of targeted,oral antidiabetic. drugs, and the conclusive evidence of the benefits of stringent glycemic control, actual treatment outcomes in clinical practice remain suboptimal relative to established treatment goals (glycosylated hemoglobin A,. level <7%). Earlier detection and aggressive treatment are critical to address the natural progression of diabetes because multiple defects (insulin resistance, insulin insufficiency, glucotoxicity, and lipotoxicity) and vascular complications may be present at the time of diagnosis. Acknowledging the inadequacy of traditional strategies and underscoring the importance of insulin as an integral part of the therapeutic armamentarium, clinical trends are moving toward earlier use of insulin combined with 1 or more oral. agents. Such strategies can address the multiple abnormalities present early in the disease course and may restore optimal control. A new treatment paradigm for patients with type 2 diabetes to achieve and maintain near-normal glycemic control is warranted. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Abrahamson, MJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl,Rm 243, Boston, MA 02215 USA. NR 80 TC 37 Z9 41 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD APR PY 2003 VL 78 IS 4 BP 459 EP 467 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 662KV UT WOS:000181946600008 PM 12683698 ER PT J AU Cooper, LA Gonzales, JJ Gallo, JJ Rost, KM Meredith, LS Rubenstein, LV Wang, NY Ford, DE AF Cooper, LA Gonzales, JJ Gallo, JJ Rost, KM Meredith, LS Rubenstein, LV Wang, NY Ford, DE TI The acceptability of treatment for depression among African-American, Hispanic, and white primary care patients SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 12th International-National-Institute-of-Mental-Health Conference on Mental Health Problems in the General Health Sector CY JUL 13-14, 1998 CL BALTIMORE, MARYLAND SP Int Natl Inst Mental Hlth DE depression; patient attitudes; ethnic minorities; disparities; African Americans; Hispanics ID MENTAL-HEALTH-CARE; MAJOR DEPRESSION; QUALITY IMPROVEMENT; SERVICE UTILIZATION; MEXICAN-AMERICANS; ATTITUDE-CHANGE; UNITED-STATES; PREFERENCES; DISORDERS; PREVALENCE AB BACKGROUND. Ethnic minority patients are less likely than white patients to receive guideline-concordant care for depression. It is uncertain whether racial and ethnic differences exist in patient beliefs, attitudes, and preferences for treatment. METHODS. A telephone survey was conducted of 829 adult patients (659 non-Hispanic whites, 97 African Americans, 73 Hispanics) recruited from primary care offices across the United States who reported 1 week or more of depressed mood or loss of interest within the past month and who met criteria for Major Depressive Episode in the past year. Within this cohort, we examined differences among African Americans, Hispanics, and whites in acceptability of antidepressant medication and acceptability of individual counseling. RESULTS. African Americans (adjusted OR, 0.30; 95% CI 0.19-0.48) and Hispanics (adjusted OR, 0.44; 95% CI, 0.26-0.76) had lower odds than white persons of finding antidepressant medications acceptable. African Americans had somewhat lower odds (adjusted OR, 0.63; 95% CI, 0.35-1.12), and Hispanics had higher odds (adjusted OR, 3.26; 95% CI, 1.08-9.89) of finding counseling acceptable than white persons. Some negative beliefs regarding treatment were more prevalent among ethnic minorities; however adjustment for these beliefs did not explain differences in acceptability of treatment for depression. CONCLUSIONS. African Americans are less likely than white persons to find antidepressant medication acceptable. Hispanics are less likely to find antidepressant medication acceptable, and more likely to find counseling acceptable than white persons. Racial and ethnic differences in beliefs about treatment modalities were found, but did not explain differences in the acceptability of depression treatment. Clinicians should consider patients' cultural and social context when negotiating treatment decisions for depression. Future research should identify other attitudinal barriers to depression care among ethnic minority patients. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA. NIMH, Rockville, MD 20857 USA. Univ Penn, Dept Family Med, Philadelphia, PA 19104 USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO 80202 USA. RAND Corp, Hlth Program, Santa Monica, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Cooper, LA (reprint author), Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-500, Baltimore, MD 21205 USA. OI Wang, Nae-Yuh/0000-0001-6513-9730 FU NIMH NIH HHS [MH5443, MH5444, MH57992] NR 43 TC 370 Z9 371 U1 4 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2003 VL 41 IS 4 BP 479 EP 489 DI 10.1097/00005650-200304000-00004 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 663LE UT WOS:000182006400004 PM 12665712 ER PT J AU Biggs, PJ AF Biggs, PJ TI Review of the energy check of an electron-only linear accelerator over a 6 year period: Sensitivity of the technique to energy shift SO MEDICAL PHYSICS LA English DT Article DE intra-operative radiation therapy; electrons; energy; timer error; dose calibration ID THERAPY AB The calibration and monthly QA of an electron-only linear accelerator dedicated to intra-operative radiation therapy has been reviewed. Since this machine is calibrated prior to every procedure, there was no necessity to adjust the output calibration at any time except, perhaps, when the magnetron is changed, provided the machine output is reasonably stable. This gives a unique opportunity to study the dose output of the machine per monitor unit, variation in the timer error, flatness and symmetry of the beam and the energy check as a function of time. The results show that, although the dose per monitor unit varied within +/-2%, the timer error within +/-0.005 MU and the asymmetry within 1-2%, none of these parameters showed any systematic change with time. On the other hand, the energy check showed a linear drift with time for 6, 9, and 12 MeV (2.1, 3.5, and 2.5%, respectively, over 5 years), while at 15 and 18 MeV, the energy check was relatively constant. It is further shown that based on annual calibrations and RPC TLD checks, the energy of each beam is constant and that therefore the energy check is an exquisitely sensitive one. The consistency of the independent checks is demonstrated. (C) 2003 American Association of Physicists in Medicine. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 4 TC 5 Z9 6 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD APR PY 2003 VL 30 IS 4 BP 635 EP 639 DI 10.1118/1.1560891 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 668HM UT WOS:000182284300017 PM 12722815 ER PT J AU Berthiaume, F MacDonald, AD Kang, YH Yarmush, ML AF Berthiaume, F MacDonald, AD Kang, YH Yarmush, ML TI Control analysis of mitochondrial metabolism in intact hepatocytes: effect of interleukin-1 beta and interleukin-6 SO METABOLIC ENGINEERING LA English DT Article DE liver; collagen sandwich culture; metabolic control analysis; antimycin A; oligomycin ID TUMOR-NECROSIS-FACTOR; CULTURED RAT HEPATOCYTES; NITRIC-OXIDE PRODUCTION; ACUTE-PHASE RESPONSE; FACTOR-ALPHA; OXIDATIVE-PHOSPHORYLATION; SANDWICH CONFIGURATION; ATP TURNOVER; MULTIDRUG-RESISTANCE; ENERGY-METABOLISM AB Interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are produced by hepatic nonparenchymal cells after systemic injury and have been reported to inhibit ATP synthesis in hepatocytes, which may contribute to hepatic dysfunction in inflammatory states. To elucidate the mechanisms of action of IL-1beta and IL-6 on hepatocellular ATP synthesis, we measured the oxygen uptake rate (OUR) and mitochondrial membrane potential (NIMP) of stable hepatocyte cultures, and analyzed the dynamic MMP response following the addition of mitochondrial inhibitors (antimycin A and oligomycin) with a model of mitochondrial metabolism. IL-1beta reduced mitochondrial OUR coupled to ATP synthesis via inhibition of phosphorylation reactions which dissipate the MMP, including ATP synthesis and consumption. Furthermore, the ATP synthesis rate in cytokine-free and IL-1beta-treated hepatocytes was controlled primarily by phosphorylation reactions, which corresponds to a state where the ATP synthesis rate closely follows the cellular energy demand. Thus, IL-1beta-mediated effects on electron transport and substrate oxidation reactions are not likely to significantly impact on ATP synthesis. IL-6 did not reduce mitochondrial OUR coupled to ATP synthesis, but shifted the control for ATP synthesis towards processes which generate the MMP, indicating that IL-6 induces a metabolic state where cellular functions are limited by the mitochondrial energy supply. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Sci, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Sci, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM58125] NR 70 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7176 J9 METAB ENG JI Metab. Eng. PD APR PY 2003 VL 5 IS 2 BP 108 EP 123 DI 10.1016/S1096-7176(03)00010-7 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 701PN UT WOS:000184176100005 PM 12850133 ER PT J AU Jafari, M Leaf, DA MacRae, H Kasem, J O'Conner, P Pullinger, C Malloy, M Kane, JP AF Jafari, M Leaf, DA MacRae, H Kasem, J O'Conner, P Pullinger, C Malloy, M Kane, JP TI The effects of physical exercise on plasma prebeta-1 high-density lipoprotein SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID APOLIPOPROTEIN-A-I; CHOLESTEROL ACYLTRANSFERASE ACTIVITY; ESTER TRANSFER PROTEIN; PROLONGED EXERCISE; HDL-CHOLESTEROL; SERUM-LIPIDS; OVERWEIGHT MEN; WEIGHT-LOSS; METABOLISM; LIPASE AB The impact of physical exercise on high-density lipoprotein (HDL) metabolism is recognized as a major mechanism of coronary artery disease (CAD) risk reduction. Prebeta-1 HDL subparticle species play a pivotal role in initiating reverse cholesterol transport (IRCT). We examined the effect of acute physical exercise on plasma prebeta-1 HDL levels. Nineteen nonsmoking, healthy men (n = 11) and women (n = 8) not receiving lipid-altering medications completed dietary surveys, and had percent body fat determinations, and fasting blood drawn for measurements of plasma lipids, lipoproteins, apolipoprotein A-I (Apo A-I), and absolute and percent prebeta-1 HDL. Each subject completed cardiopulmonary exercise stress testing to Vo(2max) followed by a 4-km course of run-jogging. Laboratory measurements were repeated from blood drawn immediately after exercise. Mean +/- SD values were determined for age, percent body fat, dietary calories, dietary cholesterol, dietary fat, and plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta-1 HDL using 1-way analysis of variance (ANOVA). One-way ANOVA comparisons were made for measurements of plasma lipids, lipoproteins, Apo A-I, and absolute and percent prebeta HDL measurements taken before and after exercise for all subjects combined. Entry characteristics showed the following (mean SD): age, 24 +/- 5.8 years; body mass index (BMI), 22.4 +/- 2.6; percent body fat, 13 +/- 5.7; and Vo(max), 49.1 +/- 7.9 mL O-2/kg/min. Exercise significantly increased absolute plasma prebeta HDL (0.10 +/- 0.05 to 0.130 +/- 0.07 mug/mL, P = .039) and decreased plasma HDL-triglycerides (23.3 +/- 10.8 to 12.5 +/- 5.6 mg/dL, P = .012). Our findings indicate that prebeta-1 HDL and HDL-triglyceride metabolism are significant components of the effect of acute exercise on RCT. These findings have important relevance for studies pertaining to exercise-related effects on HDL metabolism as pertains to CAD risk reduction. Copyright 2003 Elsevier, Inc. All rights reserved. C1 Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. Pepperdine Univ, Dept Sports Med, Malibu, CA 90265 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Leaf, DA (reprint author), Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, 111G,Wilshire & Sawtelle Blvd, Los Angeles, CA 90073 USA. NR 59 TC 20 Z9 20 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2003 VL 52 IS 4 BP 437 EP 442 DI 10.1053/meta.2003.50086 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 668YX UT WOS:000182326000010 PM 12701055 ER PT J AU Ren, B Hoti, N Rabasseda, X Wang, YZ Wu, M AF Ren, B Hoti, N Rabasseda, X Wang, YZ Wu, M TI The antiangiogenic and therapeutic implications of endostatin SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Review DE angiogenesis; antiangiogenesis; endostatin; endothelial cells; therapy; tumor ID ANGIOGENESIS INHIBITOR ENDOSTATIN; ENDOTHELIAL GROWTH-FACTOR; RECOMBINANT HUMAN ENDOSTATIN; CELL LUNG-CANCER; TUMOR-GROWTH; ANTITUMOR-ACTIVITY; COLLAGEN-XVIII; GENE-TRANSFER; SOLID TUMORS; IN-VITRO AB Angiogenesis plays a vital role in the pathology of cancer, ischemic diseases and chronic inflammation, among other conditions. Endostatin, a newly found protein that is distributed in some parts of the human body, has been demonstrated to have a strong inhibitory role in angiogenesis. It specifically inhibits the proliferation of endothelial cells and induces their apoptosis both in vitro and in vivo. Preclinical research has proven its effective role in the treatment (if various experimental tumors in rodents. Although endostatin therapy has entered phase II clinical trials in the USA, the exact mechanism and its effects on antiangiogenesis, especially the action on the suppression of endothelial cell proliferation and induction of apoptosis, remain unclear The treatment modality for malignancies and other angiogenesis-related diseases still requires further analysis. (C) 2003 Prous Science. All rights reserved. C1 Univ Sci & Technol, Sch Life Sci, Anhua, Peoples R China. BIDMC, Div Canc Biol & Angiogensis, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Med Informat Dept, Barcelona, Spain. RP Wu, M (reprint author), Univ Sci & Technol, Sch Life Sci, Anhua, Peoples R China. RI Hoti, Naser/A-2530-2011 NR 96 TC 15 Z9 21 U1 2 U2 8 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD APR PY 2003 VL 25 IS 3 BP 215 EP 224 DI 10.1358/mf.2003.25.3.769643 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 681HX UT WOS:000183031700009 PM 12743627 ER PT J AU Bingaman, S Huxley, VH Rumbaut, RE AF Bingaman, S Huxley, VH Rumbaut, RE TI Fluorescent dyes modify properties of proteins used in microvascular research SO MICROCIRCULATION LA English DT Article DE alpha-lactalbumin; arteriole; bovine serum albumin; coronary; electrophoresis; fluorescent dyes; isoelectric point; pig; venule ID PAIRWISE MULTIPLE COMPARISONS; HAMSTER-CHEEK POUCH; NITRIC-OXIDE; ALBUMIN; PERMEABILITY; GLYCOCALYX; VOLUME; MICROSCOPY; MECHANISMS; VARIANCE AB Objective: Fluorescent dyes, used frequently to label proteins for microvascular experiments, are assumed to not alter the protein's physicochemical characteristics. We tested the validity of that assumption for two probes, bovine serum albumin (BSA) and alpha-lactalbumin. Methods: Standard electrophoretic techniques were used to examine the influence of five fluorescent dyes on the following three properties of BSA: molecular size (sodium dodecyl sulfate-polyacrylamide gel electrophoresis [PAGE])- relative molecular charge (native PACE); and isoelectric point (pI) (i.e., isoelectric focusing). Also examined were the influence of the dyes on the relative charge of alpha-lactalbumin (native PAGE). Paired measures of single-vessel flux were made using two commercial preparations of dye-BSA on porcine coronary arterioles and ventiles. Results: The addition of fluorescein isothiocyanate (FITC) to BSA altered significantly its size (p < 0.01; n = 6), relative charge (p < 0.02; n = 7), and pI. The other dyes caused minimal, yet significant, changes on the relative charge of BSA without influencing size or pI. Only FITC altered the relative charge of a-lactalbumin. While arteriolar fluxes of FITC-BSA and tetramethyl rhodamine isothiocyanate (TRITC)-BSA did not differ (p = 0.43; n = 5), in venules the FITC-B A flux was greater than the TRITC-BSA flux (p < 0.001; n = 6). Conclusions: The addition of fluorescent dyes, particularly FITC, alters the physicochemical characteristics of two widely used protein probes. These findings may affect the interpretation of microvascular permeability experiments performed using fluorescent dyes, and they suggest care in the selection of dyes for such experiments. C1 Univ Missouri, Dept Physiol, Columbia, MO 65212 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. RP Huxley, VH (reprint author), Univ Missouri, Dept Physiol, MA 415,Med Sci Bldg, Columbia, MO 65212 USA. FU NHLBI NIH HHS [P01 HL052490, R01 HL-64721, R01 HL064721, R37 HL-42528] NR 38 TC 37 Z9 37 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD APR PY 2003 VL 10 IS 2 BP 221 EP 231 DI 10.1038/sj.mn.7800186 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 670VM UT WOS:000182429900010 PM 12700589 ER PT J AU Faber, R Hill, VM Kim, BJ AF Faber, R Hill, VM Kim, BJ TI Frontotemporal dementia affecting a US Air Force officer SO MILITARY MEDICINE LA English DT Article ID FRONTAL-LOBE DEGENERATION; NON-ALZHEIMER TYPE; CLINICAL PICTURE; TESTS; PERFORMANCE; DIAGNOSIS; CRITERIA; DISEASE AB We present the case of a 51-year-old former U.S. Air Force officer who developed marked behavioral and personality changes over a 9-year period, ultimately leading to his discharge from the Air Force at a rank below that which he achieved during service. Clinical diagnostic features, neuropsychological testing and neuroimaging together confirmed a diagnosis of frontotemporal dementia. This form of presenile dementia is discussed with reference to his case. C1 Audie L Murphy Mem Vet Adm Med Ctr, Psychiat Serv, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Faber, R (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Psychiat Serv, 7400 Merton Minter, San Antonio, TX 78229 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD APR PY 2003 VL 168 IS 4 BP 333 EP 336 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 743AE UT WOS:000186549600013 PM 12733681 ER PT J AU Gao, G Bracken, AP Burkard, K Pasini, D Classon, M Attwooll, C Sagara, M Imai, T Helin, K Zhao, JY AF Gao, G Bracken, AP Burkard, K Pasini, D Classon, M Attwooll, C Sagara, M Imai, T Helin, K Zhao, JY TI NPAT expression is regulated by E2F and is essential for cell cycle progression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID S-PHASE ENTRY; HISTONE GENE-TRANSCRIPTION; MICROARRAY ANALYSIS; RNA INTERFERENCE; MAMMALIAN-CELLS; RB/E2F PATHWAY; MESSENGER-RNA; ATM GENE; PROTEIN; PROLIFERATION AB NPAT is an in vivo substrate of cyclin E-Cdk2 kinase and is thought to play a critical role in coordinated transcriptional activation of histone genes during the G(1)/S-phase transition and in S-phase entry in mammalian cells. Here we show that NPAT transcription is up-regulated at the G,/S-phase boundary in growth-stimulated cells and that the NPAT promoter responds to activation by E2F proteins. We demonstrate that endogenous E2F proteins interact with the promoter of the NPAT gene in vivo and that induced expression of E2F1 stimulates NPAT mRNA expression, supporting the idea that the expression of NPAT is regulated by E2F. Consistently, we find that the E2F sites in the NPAT promoter are required for its activation during the G,/S-phase transition. Moreover, we show that the expression of NPAT accelerates S-phase entry in cells released from quiescence. The inhibition of NPAT expression by small interfering RNA duplexes impedes cell cycle progression and histone gene expression in tissue culture cells. Thus, NPAT is an important E2F target that is required for cell cycle progression in mammalian cells. As NPAT is involved in the regulation of S-phase-specific histone gene transcription, our findings indicate that NPAT links E2F to the activation of S-phase-specific histone gene transcription. C1 Univ Rochester, Dept Biomed Genet, Rochester, NY 14642 USA. Ist Europeo Oncol, Dept Expt Oncol, I-20141 Milan, Italy. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Natl Inst Radiol Sci, Frontier Res Ctr, Inage Ku, Chiba 263, Japan. RP Zhao, JY (reprint author), Univ Rochester, Dept Biomed Genet, 601 Elmwood Ave,Box 633, Rochester, NY 14642 USA. RI Pasini, Diego/J-9674-2012; OI Pasini, Diego/0000-0002-9879-6486; Helin, Kristian/0000-0003-1975-6097 FU NIGMS NIH HHS [R01 GMO65814] NR 56 TC 38 Z9 42 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2003 VL 23 IS 8 BP 2821 EP 2833 DI 10.1128/MCB.23.8.2821-2833.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EZ UT WOS:000182049900016 PM 12665581 ER PT J AU Wei, WY Jobling, WA Chen, W Hahn, WC Sedivy, JM AF Wei, WY Jobling, WA Chen, W Hahn, WC Sedivy, JM TI Abolition of cyclin-dependent kinase inhibitor p16(Ink4a) and p21(Cip1/Waf1) functions permits Ras-induced anchorage-independent growth in telomerase-immortalized human fibroblasts SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN PHOSPHATASE 2A; LARGE-T-ANTIGEN; HUMAN PAPILLOMAVIRUS TYPE-16; HUMAN CELL-TRANSFORMATION; SIMIAN-VIRUS-40 LARGE-T; ACTIVATED HA-RAS; PREMATURE SENESCENCE; SIMIAN VIRUS-40; ONCOGENIC TRANSFORMATION; EMBRYO FIBROBLASTS AB Human cells are more resistant to both immortalization and malignant transformation than rodent cells. Recent studies have established the basic genetic requirements for the transformation of human cells, but much of this work relied on the expression of transforming proteins derived from DNA tumor viruses. We constructed an isogenic panel of human fibroblast cell lines using a combination of gene targeting and ectopic expression of dominantly acting mutants of cellular genes. Abolition of p21(CipI/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis. Deletion of the tumor suppressor p53 combined with abolition of p16(Ink4a) function failed to mimic the introduction of simian virus 40 large T antigen, indicating that large T antigen may target additional cellular functions. Ha-Ras and Myc cooperated only to a limited extent, but in the absence of Ras, Myc cooperated strongly with the simian virus 40 small t antigen to elicit aggressive anchorage-independent growth. The experiments reported here further define specific components of human transformation pathways. C1 Brown Univ, Dept Mol Biol Cell Biol & Biochem, J W Wilson Lab, Providence, RI 02912 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sedivy, JM (reprint author), Brown Univ, Dept Mol Biol Cell Biol & Biochem, J W Wilson Lab, 69 Brown St, Providence, RI 02912 USA. FU NCI NIH HHS [K01CA94223, K01 CA094223]; NIA NIH HHS [R01 AG016694, R01AG16694]; NIGMS NIH HHS [R01GM41690, R01 GM041690] NR 84 TC 58 Z9 60 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2003 VL 23 IS 8 BP 2859 EP 2870 DI 10.1128/MCB.23.8.2859-2870.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EZ UT WOS:000182049900019 PM 12665584 ER PT J AU Durda, PJ Dunn, IS Rose, LB Butera, D Benson, EM Pandolfi, F Kurnick, JT AF Durda, PJ Dunn, IS Rose, LB Butera, D Benson, EM Pandolfi, F Kurnick, JT TI Induction of "antigen silencing" in melanomas by oncostatin M: Down-modulation of melanocyte antigen expression SO MOLECULAR CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MICROPHTHALMIA TRANSCRIPTION FACTOR; CELL-LINES; METASTATIC MELANOMA; IMMUNE RECOGNITION; GENE-EXPRESSION; CANCER-CELLS; IN-VITRO; T-CELLS; INTERFERON AB We previously reported that antigen expression in melanoma cell lines is down-regulated by proteins secreted by antigen-negative melanoma cells. Here we report the purification and characterization of one of these down-regulatory factors, the cytokine, oncostatin M (OSM), which transmits its signal via the gp130 cell surface receptor, resulting in the selective down-modulation of the melanocyte lineage antigens: MelanA/MART-1, gp100, tyrosinase, tyrosinase-related proteins 1 and 2, and the M isoform of microphthalmia transcription factor. Furthermore, we have found that some melanoma cell lines produce as yet uncharacterized factors distinct from OSM which also down-modulate antigen expression via signaling pathways different from that employed by OSM. These data indicate that there may be several regulatory pathways and molecules involved in the antigen-silencing process which may be related to the state of differentiation of the tumor cell and may affect the outcome of antitumor vaccine immunotherapies. C1 CytoCure LLC, Beverly, MA USA. Boston Biomed Res Inst, Watertown, MA USA. Westmead Hosp, Inst Immunol & Allergy Res, ICPMR, Westmead, NSW 2145, Australia. Westmead Hosp, Dept Immunopathol, Westmead, NSW 2145, Australia. Catholic Univ, Rome, Italy. RP Durda, PJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 508,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [1R43CA086153] NR 51 TC 21 Z9 21 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2003 VL 1 IS 6 BP 411 EP 419 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 668YU UT WOS:000182325600001 PM 12692260 ER PT J AU Jiang, YD Zhang, W Kondo, K Klco, JM St Martin, TB Dufault, MR Madden, SL Kaelin, WG Nacht, M AF Jiang, YD Zhang, W Kondo, K Klco, JM St Martin, TB Dufault, MR Madden, SL Kaelin, WG Nacht, M TI Gene expression profiling in a renal cell carcinoma cell line: Dissecting VHL and hypoxia-dependent pathways SO MOLECULAR CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; UROKINASE RECEPTOR EXPRESSION; INDUCIBLE FACTOR 1-ALPHA; HIPPEL-LINDAU-DISEASE; MATRIX METALLOPROTEINASES; MOLECULAR-CLONING; SERIAL ANALYSIS; MESSENGER-RNA; POSTTRANSCRIPTIONAL REGULATION AB The von Hippel-Lindau tumor suppressor, pVHL, is a key player in one of the best characterized hypoxia signaling pathways, the VHL-hypoxia-inducible factor (VHL-HIF) pathway. To better understand the role of VHL in the hypoxia signaling pathways of tumor cells, we used serial analysis of gene expression (SAGE) to investigate hypoxia-regulated gene expression in renal carcinoma cells (786-0), with and without VHL. The gene expression profiles of the cancer cells were compared to SAGE profiles from normal renal proximal tubule cells grown under both normoxia and hypoxia. The data suggest that the role of VHL as a tumor suppressor may be more complex than previously thought. Further, the data reveal that renal carcinoma cells have evolved an alternative hypoxia signaling pathway(s) compared with normal renal cells. These alternative hypoxia pathways demonstrate VHL-dependent and VHL-independent regulation. The genes involved in such pathways include those with potential importance in the physiological and pathological regulation of tumor growth and angiogenesis. Some of the genes identified as showing overexpression in the cancer cells, particularly those encoding secreted or membrane-bound proteins, could be potential biomarkers for tumors or targets for rational therapeutics that are dependent on VHL status. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. OI Klco, Jeffery/0000-0003-2961-6960 NR 77 TC 96 Z9 102 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD APR PY 2003 VL 1 IS 6 BP 453 EP 462 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 668YU UT WOS:000182325600006 PM 12692265 ER PT J AU Payami, H Nutt, J Gancher, S Bird, T McNeal, MG Seltzer, WK Hussey, J Lockhart, P Gwinn-Hardy, K Singleton, AA Singleton, AB Hardy, J Farrer, M AF Payami, H Nutt, J Gancher, S Bird, T McNeal, MG Seltzer, WK Hussey, J Lockhart, P Gwinn-Hardy, K Singleton, AA Singleton, AB Hardy, J Farrer, M TI SCA2 may present as levodopa-responsive parkinsonism SO MOVEMENT DISORDERS LA English DT Article DE parkinsonism; SCA2 mutation; levodopa ID SPINOCEREBELLAR ATAXIA TYPE-2; DISEASE; EXPANSION AB Some kindreds with familial parkinsonism exhibit genetic anticipation, suggesting possible involvement of trinucleotide repeat expansion. Recent reports have shown trinucleotide repeat expansions in the spinocerebellar ataxia 2 (SCA2) gene in patients with levodopa-responsive parkinsonism. We tested 136 unrelated patients with familial parkinsonism for SCA2 mutations. Two probands had borderline mutations; the rest were normal. (less than or equal to31 repeats is normal, 32-35 is borderline, greater than or equal to36 is pathogenic). The expanded allele segregated with neurological signs in one kindred. The absence of borderline mutations in the normal population, and the co-segregation of the expanded allele with neurological signs in one kindred suggest that SCA2 mutations may be responsible for a subset of familial parkinsonism. (C) 2002 Movement Disorder Society. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Kaiser Permanente, Portland, OR USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Oregon Hlth Sci Univ, Dept Mol Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med Genet, Portland, OR 97201 USA. Athena Diagnost Inc, Worcester, MA USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. NINDS, Neurogenet Lab, Bethesda, MD 20892 USA. Wadsworth Ctr, Albany, NY 12208 USA. RP Payami, H (reprint author), Wadsworth Ctr, 120 New Scotland Ave, Albany, NY 12208 USA. RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Lockhart, Paul/E-7753-2011; OI Lockhart, Paul/0000-0003-2531-8413; Gwinn, Katrina/0000-0002-8277-651X FU NCRR NIH HHS [5M01 RR00334]; NIA NIH HHS [AG0817]; NINDS NIH HHS [NS40256, R01 NS36960] NR 10 TC 45 Z9 46 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2003 VL 18 IS 4 BP 425 EP 429 DI 10.1002/mds.10375 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 667ZH UT WOS:000182264800011 PM 12671950 ER PT J AU Yang, Y Seed, B AF Yang, Y Seed, B TI Site-specific gene targeting in mouse embryonic stem cells with intact bacterial artificial chromosomes SO NATURE BIOTECHNOLOGY LA English DT Article ID ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; DNA; REPLACEMENT; GENOME AB Homologous recombination in Escherichia coli simplifies the generation of gene targeting constructs for transduction into mouse embryonic stem (ES) cells(1-7). Taking advantage of the extensive homology provided by intact bacterial artificial chromosomes (BACs), we have developed an efficient method for preparing targeted gene disruptions in ES cells. Correctly integrated clones were identified by a simple screening procedure based on chromosomal fluorescence in situ hybridization (FISH). To date, five mutant lines have been generated and bred to homozygosity by this approach. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Seed, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL66678]; NIAID NIH HHS [AI27849, AI46731] NR 19 TC 64 Z9 66 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2003 VL 21 IS 4 BP 447 EP 451 DI 10.1038/nbt803 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 664VH UT WOS:000182082400029 PM 12627171 ER PT J AU Puls, I Jonnakuty, C LaMonte, BH Holzbaur, ELF Tokito, M Mann, E Floeter, MK Bidus, K Drayna, D Oh, SJ Brown, RH Ludlow, CL Fischbeck, KH AF Puls, I Jonnakuty, C LaMonte, BH Holzbaur, ELF Tokito, M Mann, E Floeter, MK Bidus, K Drayna, D Oh, SJ Brown, RH Ludlow, CL Fischbeck, KH TI Mutant dynactin in motor neuron disease SO NATURE GENETICS LA English DT Article ID FAST AXONAL-TRANSPORT; DROSOPHILA-MELANOGASTER; P150(GLUED) COMPONENT; CYTOPLASMIC DYNEIN; SWISS-MODEL; COMPLEX AB Impaired axonal transport in motor neurons has been proposed as a mechanism for neuronal degeneration in motor neuron disease. Here we show linkage of a lower m neuron disease to a region of 4 Mb at chromosome 2p13. Mutation analysis of a gene this interval that encodes the largest subunit of the axonal transport protein dynactin showed a single base-pair change resulting in an amino-acid substitution that is p dicted to distort the folding of dynactin's microtubule-binding domain. Binding assays show decreased binding of the mutant protein to microtubules. Our results show the dysfunction of dynactin-mediated transport can lead to human motor neuron disease. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. NINDS, Electromyography Sect, NIH, Bethesda, MD 20892 USA. NIDCD, Sect Syst Biol Commun Disorders, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Puls, I (reprint author), NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 15 TC 550 Z9 567 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2003 VL 33 IS 4 BP 455 EP 456 DI 10.1038/ng1123 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 662CM UT WOS:000181928600011 PM 12627231 ER PT J AU Reich, DE Gabriel, SB Altshuler, D AF Reich, DE Gabriel, SB Altshuler, D TI Quality and completeness of SNP databases SO NATURE GENETICS LA English DT Article AB To address the quality and completeness of single-nucleotide polymorphism (SNP) databases, we resequenced 173 kb (spanning 17 loci) in 150 chromosomes of west African and European ancestry. Over 88% of SNPs in the public (TSC and BAC overlap) and Celera databases were confirmed in independent resequencing. Approximately 45% of all human heterozygosity is attributable to SNPs already available from the two databases, and of SNPs with minor-allele frequencies >10%, more than half are represented. C1 MIT, Program Med & Populat Genet, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Reich, DE (reprint author), MIT, Program Med & Populat Genet, Whitehead Inst, Ctr Genome Res, 1 Kendall Sq, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 134 Z9 138 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2003 VL 33 IS 4 BP 457 EP 458 DI 10.1038/ng1133 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 662CM UT WOS:000181928600012 PM 12652301 ER PT J AU Stewart, SA Ben-Porath, I Carey, VJ O'Connor, BF Hahn, WC Weinberg, RA AF Stewart, SA Ben-Porath, I Carey, VJ O'Connor, BF Hahn, WC Weinberg, RA TI Erosion of the telomeric single-strand overhang at replicative senescence SO NATURE GENETICS LA English DT Article ID NORMAL HUMAN-CELLS; HUMAN FIBROBLASTS; LIFE-SPAN; IN-VITRO; HUMAN-CHROMOSOMES; VIVO; END; LOOP AB Cultured primary human cells inevitably enter a state of replicative senescence for which the specific molecular trigger is unknown. We show that the single-strand telomeric overhang, a key component of telomere structure, is eroded at senescence. Expression of telomerase prevents overhang loss, suggesting that this enzyme prevents senescence by maintaining proper telomere structure. In contrast, progressive overhang loss occurs in cells that avoid senescence through the inactivation of p53 and Rb, indicating that overhang erosion is the result of continuous cell division and not a consequence of senescence. We thus provide evidence for a specific molecular alteration in telomere structure at senescence and suggest that this change, rather than overall telomere length, serves to trigger this state. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Channing Lab, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Stewart, Sheila/C-5213-2012 NR 28 TC 222 Z9 234 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2003 VL 33 IS 4 BP 492 EP 496 DI 10.1038/ng1127 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 662CM UT WOS:000181928600020 PM 12652299 ER PT J AU Wilson, CB Uittenbogaart, CH Mathis, DJ AF Wilson, CB Uittenbogaart, CH Mathis, DJ TI Immunology at Asilomar: from molecules to mice SO NATURE IMMUNOLOGY LA English DT Editorial Material ID CELL; EXPRESSION; PROTEINS; MEMORY; NKG2D; CD4 AB The Midwinter Conference of Immunologists is a popular annual fixture for immunologists to discuss the hot topics in immunology while enjoying the mild weather of the West Coast. C1 Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Mol Genet, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Wilson, CB (reprint author), Univ Washington, Dept Immunol, Box 357650, Seattle, WA 98195 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2003 VL 4 IS 4 BP 300 EP 302 DI 10.1038/ni0403-300 PG 3 WC Immunology SC Immunology GA 663CG UT WOS:000181987700003 PM 12660724 ER PT J AU Iwakoshi, NN Lee, AH Vallabhajosyula, P Otipoby, KL Rajewsky, K Glimcher, LH AF Iwakoshi, NN Lee, AH Vallabhajosyula, P Otipoby, KL Rajewsky, K Glimcher, LH TI Plasma cell differentiation and the unfolded protein response intersect at the transcription factor XBP-1 SO NATURE IMMUNOLOGY LA English DT Article ID GLUCOSE-REGULATED PROTEINS; ENDOPLASMIC-RETICULUM; MESSENGER-RNA; TRANSMEMBRANE PROTEIN; ER STRESS; INTERLEUKIN-6-DEFICIENT MICE; MULTIPLE-MYELOMA; BINDING-PROTEIN; B-LYMPHOCYTES; KINASE AB The transcription factor X-box binding protein 1 (XBP-1) is essential for the differentiation of plasma cells and the unfolded protein response (UPR). Here we show that UPR-induced splicing of XBP-1 by the transmembrane endonuclease IRE1 is required to restore production of immunoglobulin in XBP-1(-/-) mouse B cells, providing an integral link between XBP-1, the UPR and plasma cell differentiation. Signals involved in plasma cell differentiation, specifically interleukin-4, control the transcription of XBP-1, whereas its post-transcriptional processing is dependent on synthesis of immunoglobulins during B cell differentiation. We also show that XBP-1 is involved in controlling the production of interleukin-6, a cytokine that is essential for plasma cell survival. Thus, signals upstream and downstream of XBP-1 integrate plasma cell differentiation with the UPR. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave, Boston, MA 02115 USA. NR 54 TC 497 Z9 521 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2003 VL 4 IS 4 BP 321 EP 329 DI 10.1038/ni907 PG 9 WC Immunology SC Immunology GA 663CG UT WOS:000181987700010 PM 12612580 ER PT J AU Wang, HY Moon, EY Azouz, A Wu, X Smith, A Schneider, H Hogg, N Rudd, CE AF Wang, HY Moon, EY Azouz, A Wu, X Smith, A Schneider, H Hogg, N Rudd, CE TI SKAP-55 regulates integrin adhesion and formation of T cell-APC conjugates SO NATURE IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ADAPTER PROTEIN; ANTIGEN RECEPTOR; INTERLEUKIN-2 PRODUCTION; IMMUNOLOGICAL SYNAPSE; ACTIN CYTOSKELETON; MOLECULAR-CLONING; DENDRITIC CELLS; CUTTING EDGE; LIPID RAFTS AB Src kinase-associated phosphoprotein of 55 kDa (SKAP-55; encoded by SCAP1) is a T cell adaptor protein of unknown function that contains a pleckstrin homology and an SH3 domain. Here we show that SKAP-55 regulates integrin-mediated adhesion and conjugate formation between T cells and antigen-presenting cells (APCs). SKAP-55 enhances adhesion to fibronectin and intercellular adhesion molecule-1 (ICAM-1), colocalizes with actin at the T cell-APC synapse and promotes the clustering of lymphocyte-associated antigen-1 (LFA-1). Enhanced conjugation is comparable to that induced by adhesion and degranulation-promoting adaptor protein (ADAP), a binding partner of SKAP-55, and is abrogated by deletion of the SKAP-55 SH3 domain. Conjugate formation is accompanied by the translocation of SKAP-55 to membrane rafts, an event that is regulated by both LFA-1 and T cell receptor ligation. Our findings identify a mechanism by which SKAP-55 modulates T cell responses to antigen. C1 Hammersmith Hosp, Imperial Coll London, Fac Med, Div Invest Sci,Dept Haematol, London W12 0NN, England. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Immunol & AIDS, Boston, MA 02115 USA. Canc Res UK, London Res Inst, London W2A3PX, England. RP Rudd, CE (reprint author), Hammersmith Hosp, Imperial Coll London, Fac Med, Div Invest Sci,Dept Haematol, Du Cane Rd, London W12 0NN, England. NR 50 TC 85 Z9 92 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2003 VL 4 IS 4 BP 366 EP 374 DI 10.1038/ni913 PG 9 WC Immunology SC Immunology GA 663CG UT WOS:000181987700017 PM 12652296 ER PT J AU Greenberg, SM Bacskai, BJ Hyman, BT AF Greenberg, SM Bacskai, BJ Hyman, BT TI Alzheimer disease's double-edged vaccine SO NATURE MEDICINE LA English DT Editorial Material ID BETA; IMMUNOTHERAPY AB The first examination of a brain from a patient enrolled in a halted clinical trial for an Alzheimer disease vaccine reveals striking-and potentially dangerous-effects (pages 448-452). C1 Massachusetts Gen Hosp, Serv Neurol, Charlestown, MA 02129 USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Serv Neurol, Charlestown, MA 02129 USA. NR 10 TC 33 Z9 37 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2003 VL 9 IS 4 BP 389 EP 390 DI 10.1038/nm847 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 663CD UT WOS:000181987400018 PM 12640449 ER PT J AU Puglielli, L Tanzi, RE Kovacs, DM AF Puglielli, L Tanzi, RE Kovacs, DM TI Alzheimer's disease: the cholesterol connection SO NATURE NEUROSCIENCE LA English DT Review ID AMYLOID PRECURSOR PROTEIN; LOW-DENSITY-LIPOPROTEIN; TRANSGENIC MOUSE MODEL; APOLIPOPROTEIN-E POLYMORPHISM; RECEPTOR-RELATED PROTEIN; BETA-PEPTIDE; A-BETA; CEREBROTENDINOUS XANTHOMATOSIS; CEREBROSPINAL-FLUID; PLAQUE-FORMATION AB A hallmark of all forms of Alzheimer's disease (AD) is an abnormal accumulation of the beta-amyloid protein (AD) in specific brain regions. Both the generation and clearance of A-beta are regulated by cholesterol. Elevated cholesterol levels increase A-beta in cellular and most animals models of AD, and drugs that inhibit cholesterol synthesis lower A-beta in these models. Recent studies show that not only the total amount, but also the distribution of cholesterol within neurons, impacts A-beta biogenesis. The identification of a variant of the apolipoprotein E (APOE) gene as a major genetic risk factor for AD is also consistent with a role for cholesterol in the pathogenesis of AD. Clinical trials have recently been initiated to test whether lowering plasma and/or neuronal cholesterol levels is a viable strategy for treating and preventing AD. In this review, we describe recent findings concerning the molecular mechanisms underlying the cholesterol-AD connection. C1 Harvard Univ, Sch Med, Neurobiol Dis Lab, CAGN,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Genet & Aging Res Unit, CAGN,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Neurobiol Dis Lab, CAGN,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 70 TC 456 Z9 491 U1 1 U2 53 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2003 VL 6 IS 4 BP 345 EP 351 DI 10.1038/nn0403-345 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 660KV UT WOS:000181833100011 PM 12658281 ER PT J AU Prados, MD Schold, SC Fine, HA Jaeckle, K Hochberg, F Mechtler, L Fetell, MR Phuphanich, S Feun, L Janus, TJ Ford, K Graney, W AF Prados, MD Schold, SC Fine, HA Jaeckle, K Hochberg, F Mechtler, L Fetell, MR Phuphanich, S Feun, L Janus, TJ Ford, K Graney, W TI A randomized, double-blind, placebo-controlled, phase 2 study of RMP-7 in combination with carboplatin administered intravenously for the treatment of recurrent malignant glioma SO NEURO-ONCOLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; INTRACAROTID INFUSION; BRADYKININ AGONIST; CEREPORT RMP-7; PERMEABILITY; TUMORS; SURVIVAL AB RMP-7, a bradykinin analog, temporarily increases the permeability of the blood-brain tumor barrier to chemotherapy drugs like carboplatin. We conducted a randomized, controlled trial of carboplatin and RMP-7 versus carboplatin and placebo in patients with recurrent malignant glioma. The primary outcome measure was time to tumor progression (TTP). Adults with recurrent glioblastoma multiforme or anaplastic glioma were randomized in a 1:1 ratio to receive carboplatin and either RMP-7 or placebo. Radiation therapy had failed in all patients, and they may have received prior chemotherapy. Carboplatin (dosed to achieve an area under the curve of 5 mg/ml x time for patients who had received prior chemotherapy, or 7 mg/ml x time for those who had not) was given intravenously every 4 weeks, followed by intravenous infusion of either RMP-7 or placebo (300 ng/kg). TTP, tumor response, neuropsychological assessments, functional independence, and quality of life assessments were analyzed every 4 weeks. There were 122 patients enrolled, 62 in the RMP-7 and carboplatin group and 60 in the placebo and carboplatin group. Median TTP was 9.7 weeks (95% CI, 8.3-12.6 weeks) for the RMP-7 and carboplatin group and 8.0 weeks (95% Cl, 7.4-12.6 weeks) for the placebo and carboplatin group. Median survival times were 26.9 weeks (95% CI, 21.3-37.6 weeks) for the RMP-7 group and 19.9 weeks (95% CI, 15.0-31.3 weeks) for the placebo group. No differences were noted for time to worsening of neuropsychological assessments, functional independence, or quality of life assessments. The use of RMP-7 had no effect on the pharmacokinetics or toxicity of carboplatin. At the dose and schedule used in this trial, RMP-7 did not improve the efficacy of carboplatin. Recent preclinical pharmacokinetic modeling of RMP-7 suggests that higher doses of RMP-7 may be required to increase carboplatin delivery to tumor. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75390 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02214 USA. SUNY Buffalo, Dept Neurol, Buffalo, NY 14209 USA. Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Miami, Sch Med, Div Hematol Oncol, Miami, FL 33136 USA. Alkermes Inc, Cambridge, MA 02139 USA. Univ Iowa Hosp & Clin, Dept Med Oncol, Iowa City, IA 52242 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA13525]; NCRR NIH HHS [M01-RR00079] NR 15 TC 75 Z9 77 U1 0 U2 7 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2003 VL 5 IS 2 BP 96 EP 103 DI 10.1215/15228517-5-2-96 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 661LG UT WOS:000181891600003 PM 12672281 ER PT J AU Baehring, JM Damek, D Martin, EC Betensky, RA Hochberg, FH AF Baehring, JM Damek, D Martin, EC Betensky, RA Hochberg, FH TI Neurolymphomatosis SO NEURO-ONCOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; T-CELL LYMPHOMA; SCIATIC-NERVE; ADHESION MOLECULES; PERIPHERAL NEUROPATHY; L-SELECTIN; B-CELLS; INVOLVEMENT AB The term "neurolymphomatosis" (NL) has included infiltration of the peripheral nervous system by lymphoma and nontumor lymphocytes. We describe NL as a lymphoma entity that affects cranial and peripheral nerves and roots. We reviewed the medical records of patients at the Massachusetts General Hospital (MGH) who registered between 1972 and 2000, as well as cases published in the English-language literature. Inclusion criteria were (A) histopathologic demonstration of lymphoma within peripheral nerve, nerve root/plexus, or cranial nerve or (B) CT/MRI or intraoperative evidence of nerve enlargement and/or enhancement beyond the dural sleeve in the setting of prior or concurrent lymphoma in systemic or CNS sites. We identified 25 patients with NL in addition to 47 reported by others. Four clinical presentations were (1) painful involvement of nerves or roots, (2) cranial neuropathy with or without pain, (3) painless involvement of peripheral nerves, (4) painful or painless involvement of a single peripheral nerve. Twenty of our patients and 44 of those reported had histopathologic confirmation of lymphoma infiltrating root or nerve. In the remainder, diagnosis was based upon clinical presentation, nodular nerve enlargement or enhancement, and lymphoma cells in spinal fluid or extraneural sites. For antemortem diagnosis, imaging studies were of greatest utility, followed by biopsy. Thirty-three patients of the combined series were not correctly diagnosed until postmortem examination. Systemic chemotherapy was used to address the multiple potential sites of involvement. When properly treated, NL carries a prognosis similar to primary CNS lymphoma in the modern era. C1 Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, 100 Blossom St,Cox 315, Boston, MA 02114 USA. NR 88 TC 126 Z9 133 U1 3 U2 5 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2003 VL 5 IS 2 BP 104 EP 115 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 661LG UT WOS:000181891600004 PM 12672282 ER PT J AU Strangman, G Franceschini, MA Boas, DA AF Strangman, G Franceschini, MA Boas, DA TI Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters SO NEUROIMAGE LA English DT Article ID TISSUE OPTICAL-PROPERTIES; HUMAN BRAIN; ADULT HEAD; HEMOGLOBIN CONCENTRATION; CEREBRAL HEMODYNAMICS; WAVELENGTH DEPENDENCE; CYTOCHROME-OXIDASE; PIGLET BRAIN; PATHLENGTH; MODEL AB Near-infrared spectroscopy (NIRS) can be used to noninvasively measure changes in the concentrations of oxy- and deoxyhemoglobin in tissue. We have previously shown that while global changes can be reliably measured, focal changes can produce erroneous estimates of concentration changes (NeuroImage 13 (2001), 76). Here, we describe four separate sources for systematic error in the calculation of focal hemoglobin changes from NIRS data and use experimental methods and Monte Carlo simulations to examine the importance and mitigation methods of each. The sources of error are: (1) the absolute magnitudes and relative differences in pathlength factors as a function of wavelength, (2) the location and spatial extent of the absorption change with respect to the optical probe, (3) possible differences in the spatial distribution of hemoglobin species, and (4) the potential for simultaneous monitoring of multiple regions of activation. We found wavelength selection and optode placement to be important variables in minimizing such errors, and our findings indicate that appropriate experimental procedures could reduce each of these errors to a small fraction (<10%) of the observed concentration changes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neural Syst Grp, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. Tufts Univ, Ctr Bioengn, Dept Elect Engn & Comp Sci, Medford, MA 02155 USA. RP Strangman, G (reprint author), Neural Syst Grp, 149 13th St,Room 9103, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR14075]; NIMH NIH HHS [R01 MH062854-03, R01 MH062854, R01 MH062854-02, R01-MH62854]; NINDS NIH HHS [F32-NS10567, R29-NS38842] NR 43 TC 261 Z9 263 U1 2 U2 12 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 APR PY 2003 VL 18 IS 4 BP 865 EP 879 DI 10.1016/S1053-8119(03)00021-1 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 673XK UT WOS:000182606000006 PM 12725763 ER PT J AU Halgren, E Mendola, J Chong, CDR Dale, AM AF Halgren, E Mendola, J Chong, CDR Dale, AM TI Cortical activation to illusory shapes as measured with magnetoencephalography SO NEUROIMAGE LA English DT Article DE Kanizsa; lateral occipital; visual cortex; fMRI; feedback; middle level vision ID PRIMARY VISUAL-CORTEX; DEPTH-RECORDED POTENTIALS; SURFACE-BASED ANALYSIS; BRAIN ACTIVITY; ORIENTATION DISCRIMINATION; SPATIOTEMPORAL STAGES; CONTOUR PERCEPTION; COORDINATE SYSTEM; FUNCTIONAL MRI; ALERT MONKEYS AB Spatiotemporal patterns of cortical activation during the perceptual grouping of elements to form illusory shapes were estimated using anatomically constrained magnetoencephalography. Subjects were shown an array of Kanizsa-style figures which were either aligned to form illusory squares or misaligned so that no illusory contour or shape was perceived. Differential activity is more pronounced in the right hemisphere. After a weakly significant modulation at similar to110 ms in the occipital pole, a prominent peak appears at similar to155 ms in the lateral occipital cortex. Modulation then appears to spread back from this location toward the occipital pole, as well as ventrally to involve ventral occipital and temporal cortices for the next 180 ms, eventually involving ventral orbitofrontal cortex at 325 ms. The prominent lateral occipital response is consistent with fMRI studies with similar stimuli which found activation in that region as well as in V3A, V4v, V7, and V8. Furthermore, the timing of this activation, after the occipital pole but before ventral temporal, is consistent with a putative role for this region in midlevel vision. The late ventral temporal response (235 ms) is centered in the lingual and fusiform areas implicated in object identification. The V1/V2 modulation at this time may reflect top-down modulation by lateral occipitotemporal and ventral temporal areas. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MIT,Athinoula A Martinos Biomed Imaging Ctr, Charlestown, MA 02129 USA. Fac Med, INSERM E9926, Marseille, France. W Virginia Univ, Dept Radiol, Ctr Adv Imaging, Sch Med, Morgantown, WV 26506 USA. Univ Utah, Program Neurosci, Salt Lake City, UT 84112 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84112 USA. RP Halgren, E (reprint author), NMR Ctr, Room 2301,149 13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NIBIB NIH HHS [R01 EB000790, R01 EB003070, EB00790, EB00307]; NINDS NIH HHS [NS18741, NS39581, R01 NS018741] NR 51 TC 92 Z9 95 U1 0 U2 6 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 APR PY 2003 VL 18 IS 4 BP 1001 EP 1009 DI 10.1016/S1053-8119(03)00045-4 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 673XK UT WOS:000182606000017 PM 12725774 ER PT J AU Kensinger, EA Shearer, DK Locascio, JJ Growdon, JH Corkin, S AF Kensinger, EA Shearer, DK Locascio, JJ Growdon, JH Corkin, S TI Working memory in mild Alzheimer's disease and early Parkinson's disease SO NEUROPSYCHOLOGY LA English DT Article ID TEMPORAL-LOBE LESIONS; COGNITIVE CONTROL; BASAL GANGLIA; SEMANTIC KNOWLEDGE; SHIFTING DEFICIT; INTERNAL CUES; PATIENT HM; ATTENTION; DEMENTIA; TASK AB Alzheimer's disease (AD) and Parkinson's disease (PD) impair working memory (WM). It is unclear, however, whether the deficits seen early in the course of these diseases are similar. To address this issue, the authors compared the performance of 22 patients with mild AD, 20 patients with early PD and without dementia, and 112 control participants on tests of inhibition, short-term memory, and 2 commonly administered tests of WM. The results suggest that although mild AD and early PD both impair WM, the deficits may be related to the interruption of different processes that contribute to WM performance. Early PD disrupted inhibitory processes, whereas mild AD did not. The WM deficits seen in patients with AD may be secondary to deficits in other cognitive capacities, including semantic memory. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP MIT, Dept Brain & Cognit Sci, NE20-392, Cambridge, MA 02139 USA. EM ekensing@mit.edu FU NCRR NIH HHS [RR00088]; NIA NIH HHS [AG05134, AG06605, AG08812]; NINDS NIH HHS [NS38372] NR 82 TC 72 Z9 74 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD APR PY 2003 VL 17 IS 2 BP 230 EP 239 DI 10.1037/0894-4105.17.2.230 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 682JX UT WOS:000183089400006 PM 12803428 ER PT J AU Hunter, CL Isacson, O Nelson, M Bimonte-Nelson, H Seo, H Lin, L Ford, K Kindy, MS Granholm, C AF Hunter, CL Isacson, O Nelson, M Bimonte-Nelson, H Seo, H Lin, L Ford, K Kindy, MS Granholm, C TI Regional alterations in amyloid precursor protein and nerve growth factor across age in a mouse model of Down's syndrome SO NEUROSCIENCE RESEARCH LA English DT Article DE amyloid precursor protein; hippocampus; Ts65Dn; Down's syndrome; neurodegeneration; Alzheimer's disease; nerve growth factor ID BASAL FOREBRAIN NEURONS; ALZHEIMERS-DISEASE; TS65DN MICE; NUCLEUS BASALIS; RETROGRADE TRANSPORT; MENTAL-RETARDATION; TROPHIC FACTORS; FACTOR NGF; DYSFUNCTION; DEFICITS AB Individuals with Down's syndrome (DS) develop the pathological hallmarks of Alzheimer's (AD) disease at an early age, subsequently followed by memory decline and dementia. We have utilized an animal model for DS, mice with segmental trisomy of chromosome 16 (Ts65Dn), to study biological events linked to memory loss. Previous studies demonstrated a cognitive decline and loss of cholinergic markers after 6-8 months of age. In the current study, we found increased levels of amyloid precursor protein (APP) in the striatum by 6-8 months of age, and in the hippocampus and parietal cortex by 13-16 months of age in Ts65Dn but not in normosomic mice. Additionally, Ts65Dn mice exhibited alterations in nerve growth factor (NGF) levels in the basal forebrain and hippocampus. Ts65Dn mice demonstrated a significant decline in NGF levels in the basal forebrain with age, as well as a reduction in hippocampal NGF by 13-16 months of age. These findings demonstrate that elevated APP and decreased NGF levels in limbic areas correlate with the progressive memory decline and cholinergic degeneration seen in middle-aged trisomic mice. (C) 2003 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Neurosci Program, McLean Hosp,Neuroregenerat Lab, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Med Univ Chicago, Dept Pharmacol, N Chicago, IL USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Neurol, Charleston, SC 29425 USA. RP Granholm, C (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, 173 Ashley Ave, Charleston, SC 29425 USA. FU NIA NIH HHS [R01 AG012122, AG12122, AG04418] NR 65 TC 51 Z9 53 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD APR PY 2003 VL 45 IS 4 BP 437 EP 445 DI 10.1016/S0168-0102(03)00005-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 670LT UT WOS:000182410300010 PM 12657457 ER PT J AU Hoh, BL Carter, BS Putman, CM Ogilvy, CS AF Hoh, BL Carter, BS Putman, CM Ogilvy, CS TI Important factors for a combined neurovascular team to consider in selecting a treatment modality for patients with previously clipped residual and recurrent intracranial aneurysms SO NEUROSURGERY LA English DT Article DE aneurysm; clipping; coiling; endovascular; recurrent; residual ID CEREBRAL ANEURYSMS; COIL EMBOLIZATION; ENDOVASCULAR TECHNIQUES; MANAGEMENT AB OBJECTIVE: Intracranial residual and recurrent aneurysms can occur after surgical clipping, with risks of growth and rupture. In the past, surgical reoperation, which can be associated with higher risk than the initial operation, was the only available treatment. A combined neurovascular team that uses both surgical and endovascular therapies could maximize efficacy and outcomes while minimizing risks in these difficult cases. The indications for which surgical or endovascular treatment should be used to treat patients with residual or recurrent aneurysms, however, have not been elucidated well. We have reviewed the 10-year experience of our combined neurovascular team to determine in a retrospective manner which-factors were important to treatment modality selection for patients with these residual and recurrent lesions. METHODS: From 1991 to 2001, the combined neurovascular unit at the Massachusetts general hospital treated 25 residual and recurrent previously clipped aneurysms (15 had been clipped at other centers). Only patients in whom a clip had been placed were included in the study; patients who did not have a clip placed or whose aneurysms were wrapped or coated were excluded. The radiographic studies and clinical data were reviewed retrospectively to determine the efficacy, outcomes, and factors important to the selection of treatment strategy in these patients. RESULTS: The patients' clinical presentations were radiographic follow-up, 17 patients, rehemorrhage, 3; mass effect, 3; and thromboembolism, 2. The mean aneurysm recurrence or residual size was I I mm (range, 4-26 mm). The mean interval until representation was 6.6 years (range, 1 wk-25 yr). Treatment consisted of: coiling, 11 patients; reclipping, 8; proximal parent vessel balloon occlusion, 2; extracranial-intracranial bypass with coil occlusion of aneurysm and parent vessel, 2; extracranial-intracranial bypass with clip trapping, 1; and extracranial-intracranial bypass with proximal clip occlusion of parent vessel, 1. The mean radiographic follow-up period was 11 months. Complete angiographic occlusion was found in 19 aneurysms (76%), at least 90% occlusion was found in 4 aneurysms (16%), intentional partial coil obliteration i was found in 1 fusiform lesion (4%), and intentional retrograde flow was found in I fusiform lesion (4%). Clinical outcomes were excellent or good in 19 patients (76%). Twenty-one patients (84%) were neurologically the same after retreatment (13 remained neurologically intact, and 8 had preexisting neurological deficits that did not change). Three patients (12%) had new neurological deficits after retreatment, and one patient (4%) died. There were four complications of retreatment (16%), one of which was a fatal hemorrhage in a patient 1 month after intentional partial coil obliteration of a fusiform vertebrobasilar junction aneurysm. Factors important to the selection of treatment modality were recurrence or residual location (all posterior circulation lesions were treated endovascularly), lesion size (lesions larger than 10 mm were treated endovascularly or with the use of combined techniques), and aneurysm morphology (fusiform and wide-necked lesions were treated endovascularly or with the use of combined techniques). CONCLUSION: The proper selection of surgical or endovascular treatment for residual and recurrent previously clipped aneurysms can achieve excellent radiographic efficacy with low mortality. Factors important to the selection of treatment by this combined neurovascular team were posterior circulation location, aneurysm size larger than 10 mm, and fusiform morphology, which were treated endovascularly or with the use of combined techniques because of the higher surgical risk associated with these factors. For aneurysms with lower surgical risk, such as some anterior circulation aneurysms and aneurysms smaller than 10 mm, we prefer to perform a reoperation because of superior radiographic cure without compromising the outcome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AVM Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg & Endovasc Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Inova Fairfax Hosp, Intervent Neuroradiol Serv, Falls Church, VA USA. RP Ogilvy, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AVM Ctr, VBK-710,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 23 Z9 24 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 APR PY 2003 VL 52 IS 4 BP 732 EP 738 DI 10.1227/01.NEU.0000053209.61909.F2 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 664GH UT WOS:000182053000013 PM 12657168 ER PT J AU Greenberg, BD Price, LH Rauch, SL Friehs, G Noren, G Malone, D Carpenter, LL Rezai, AR Rasmussen, SA AF Greenberg, BD Price, LH Rauch, SL Friehs, G Noren, G Malone, D Carpenter, LL Rezai, AR Rasmussen, SA TI Neurosurgery for intractable obsessive-compulsive disorder and depression: critical issues SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID STEREOTACTIC SUBCAUDATE TRACTOTOMY; TERM FOLLOW-UP; LIMBIC LEUKOTOMY; PSYCHOSURGICAL OPERATION; CINGULOTOMY; DISEASE; EPIDEMIOLOGY; ATTITUDES; ILLNESS; MOOD AB Some patients with obsessive-compulsive disorder or depression have severe chronic illness that is refractory to the best conventional treatment. For them, modem neurosurgical procedures remain a therapeutic option. This article considers the efficacy and safety of current lesion procedures. The evidence has important limitations but sheds light on critical issues in assessing the long-term effectiveness and morbidity associated with existing procedures, including anterior cingulotomy, anterior capsulotomy, subcaudate tractotomy, and limbic leucotomy. The same methodologic issues arise when considering newer nondestructive techniques in development for intractable psychiatric illness, including deep brain stimulation. Determining the effectiveness and side effect burden of neurosurgery for intractable psychiatric illness is a task primarily for psychiatrists, collaborating closely with neurosurgeons and other clinical neuroscientists in specialized multidisciplinary teams. C1 Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Brown Med Sch, Dept Clin Neurosci, Providence, RI USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Cleveland Clin Fdn, Dept Neurosurg, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Psychiat, Cleveland, OH 44195 USA. RP Greenberg, BD (reprint author), Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, 345 Blackstone Blvd, Providence, RI 02906 USA. NR 65 TC 143 Z9 145 U1 0 U2 12 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2003 VL 14 IS 2 BP 199 EP + DI 10.1016/S1042-3680(03)00005-6 PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 672PL UT WOS:000182529500004 PM 12856488 ER PT J AU Cosgrove, GR Rauch, SL AF Cosgrove, GR Rauch, SL TI Stereotactic cingulotomy SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; TERM FOLLOW-UP; INTRACTABLE PSYCHIATRIC DISEASE; CEREBRAL GLUCOSE-METABOLISM; LONG-TERM; LIMBIC LEUKOTOMY; LESIONS; ABNORMALITIES; TOMOGRAPHY; PREDICTORS AB Cingulotomy can be helpful in certain patients with severe, disabling, and treatment-refractory major affective disorders, obsessive-compulsive disorder, and chronic anxiety states. This form of psychosurgical treatment should only be carried out by an expert multidisciplinary team with experience in these disorders. Cingulotomy should be considered as one part of an entire treatment plan and must be followed by an appropriate psychiatric rehabilitation program. Many patients are greatly improved after cingulotomy, and the complications or side effects are few. Cingulotomy remains an important therapeutic option for disabling psychiatric disease and is probably underutilized. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Cosgrove, GR (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, 15 Parkman St,ACC Suite 331, Boston, MA 02114 USA. NR 51 TC 45 Z9 47 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 2003 VL 14 IS 2 BP 225 EP + DI 10.1016/S1042-3680(02)00115-8 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 672PL UT WOS:000182529500006 PM 12856490 ER PT J AU Feltmate, CM Batorfi, J Fulop, V Goldstein, DP Doszpod, J Berkowitz, RS AF Feltmate, CM Batorfi, J Fulop, V Goldstein, DP Doszpod, J Berkowitz, RS TI Human chorionic gonadotropin follow-up in patients with molar pregnancy: A time for reevaluation SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID GESTATIONAL TROPHOBLASTIC DISEASE; HYDATIDIFORM MOLE; EXPERIENCE; TUMORS AB OBJECTIVE: To determine how often patients with molar pregnancy do not complete recommended follow-up and to identify factors that may predict failure to complete human chorionic gonadotropin (hCG) monitoring. This study also sought to determine how often patients with molar pregnancy who do not complete follow-up relapse after attaining at least one undetectable hCG value. METHODS: Four hundred randomly selected patients with molar pregnancy were analyzed regarding the serum hCG levels after molar evacuation. Demographic factors were determined for each patient: age, marital status, gravidity, parity, health insurance type, and distance from patient residence to trophoblastic center. RESULTS: Recommended hCG follow-up was completed in 63% of the uncomplicated 333 cases (n = 211). Three hundred twenty patients achieved at least one undetectable serum hCG level. Among the 320 patients, 33% achieved undetectable hCG values but did not complete recommended follow-up. However, none had any evidence of relapse. A distance of greater than 20 miles from the patient's residence to our center was associated with failure to complete hCG follow-up (P =.001). CONCLUSION: Because none of die 320 patients who achieved at least one undetectable hCG level has been diagnosed with gestational trophoblastic tumor relapse, it may be appropriate to reassess the duration of hCG monitoring for patients with molar pregnancy. C1 Harvard Univ, Brigham & Womens Hosp,Sch Med,Div Gynecol Oncol, Dana Farber Harvard Canc Ctr,Dana Farber Canc Ins, Gillette Ctr Womens Canc,Dept Obstet & Gynecol, Boston, MA 02115 USA. Natl Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. RP Berkowitz, RS (reprint author), Harvard Univ, Brigham & Womens Hosp,Sch Med,Div Gynecol Oncol, Dana Farber Harvard Canc Ctr,Dana Farber Canc Ins, Gillette Ctr Womens Canc,Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 17 TC 41 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2003 VL 101 IS 4 BP 732 EP 736 DI 10.1016/S0029-7844(03)00009-7 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 661PV UT WOS:000181899700020 PM 12681878 ER PT J AU Papaliodis, GN Chu, D Foster, CS AF Papaliodis, GN Chu, D Foster, CS TI Treatment of ocular inflammatory disorders with daclizumab SO OPHTHALMOLOGY LA English DT Article ID TRANSPLANTATION; REJECTION; BLOCKADE; RECEPTOR; THERAPY; UVEITIS AB Purpose: To evaluate the efficacy and safety of daclizumab therapy for patients with various ophthalmologic inflammatory disorders (all having previously failed standard treatment methods). Design: Retrospective, nonrandomized case series. Participants: Fourteen patients. Methods: Fourteen patients were treated with daclizumab after previously failing standard treatment methods. Main Outcome Measures: Inflammation and visual acuity. Results: Twelve of 27 (44%) eyes and 5 of 14 (36%) patients had improvement in visual acuity; 9 of 27 (33%) eyes and 5 of 14 (36%) patients had no change in visual acuity; and 6 of 27 (22%) eyes and 4 of 14 (27%) patients had continued visual loss. Based on degree of inflammation, 16 of 27 eyes (59%) had improvement, 3 of 27 (11%) eyes had no change, and 8 of 27 (30%) eyes worsened. Conclusions: Daclizumab is safe and, at least in some patients, appears to be an effective medication in the treatment of ocular inflammatory disorders. (C) 2003 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 55 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2003 VL 110 IS 4 BP 786 EP 789 DI 10.1016/S0161-6420(02)01932-2 PG 4 WC Ophthalmology SC Ophthalmology GA 673EE UT WOS:000182566600042 PM 12689903 ER PT J AU Busaba, NY Salman, SD AF Busaba, NY Salman, SD TI Ethmoid mucocele as a late complication of endoscopic ethmoidectomy SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the American-Academy-of-Otoaryngology-Head-and-Neck-Surgery CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg ID SINUS MUCOCELES; MARSUPIALIZATION AB OBJECTIVE. Our goal was to describe ethmoid mucocele as a late complication of endoscopic ethmoidectomy. STUDY DESIGN: This was a retrospective review of 14 patients who were diagnosed with ethmoid mucoceles after endoscopic ethmoidectomy. Reviewed data included patient demographics, indication for the original surgery, presenting symptoms, computed tomography results, surgical treatment, operative findings, and recurrence of disease. RESULTS: The mucoceles were diagnosed 1 to 13 years after endoscopic ethmoidectomy. The most common presenting symptom was facial pressure or pain. Twelve patients had middle meatal adhesions. A round mass was seen by endoscopy in the ethmoid cavity in 5 patients. Nine mucoceles were located in the anterior ethmoid and 3 were located in the posterior ethmoid, and 2 involved both. The mucoceles were marsupialized via revision endoscopic ethmoidectomy in 12 patients, whereas 2 had both external and endoscopic approaches taken. CONCLUSION: Ethmoid mucocele can form as a late complication of endoscopic ethmoidectomy. It is commonly associated with middle meatal adhesions. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. VA Boston HealthCare Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 10 Z9 16 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 2003 VL 128 IS 4 BP 517 EP 522 DI 10.1016/mhn.2003.126 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 669HQ UT WOS:000182346200011 PM 12707654 ER PT J AU Buchler, P Gukovskaya, TS Mouria, T Buchler, MC Buchler, MW Friess, H Pandol, TJ Reber, HA Hines, OJ AF Buchler, P Gukovskaya, TS Mouria, T Buchler, MC Buchler, MW Friess, H Pandol, TJ Reber, HA Hines, OJ TI Prevention of metastatic pancreatic cancer growth in vivo by induction of apoptosis with genistein, a naturally occurring isoflavonoid SO PANCREAS LA English DT Article DE apoptosis; genistein; isoflavonoid; metastasis; pancreatic cancer ID NF-KAPPA-B; CELL-DEATH; IN-VITRO; EPITHELIAL-CELLS; ANGIOGENESIS; CARCINOMA; ADENOCARCINOMA; INHIBITION; PROLIFERATION; ACTIVATION AB Introduction: The critical need for novel therapeutic approaches to pancreatic cancer treatment is clear. Genistein, a naturally occurring isoflavonoid, is active against certain solid malignancies, but its effect on pancreatic cancer is unknown. Aims: To investigate the bioactivity of genistein in experimental pancreatic cancer in vitro and in vivo. Methodology: The effect of intraperitoneal genistein administration on local tumor growth and metastatic disease was determined in an orthotopic nude mouse model. Apoptosis in tumor specimens was determined by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) technique. In vitro, the effect of genistein on cell growth was assessed by cell count and MTT (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyl tetrazolium bromide) colorimetric assay. Apoptosis was determined in vitro by DNA laddering and annexin-V. Caspase-3 and nuclear factor-kappaB activity were measured following genistein treatment. Results: In vivo, genistein significantly improved survival, almost completely inhibited metastasis, and increased apoptosis in an orthotopic model of pancreatic cancer. In vitro genistein treatment resulted in apoptosis in all pancreatic cancer cell lines tested, and this appeared to be mediated by activation of caspase-3. Conclusion: These findings suggest that the antimetastatic effect of genistein treatment in vivo is mediated by induction of apoptosis. Genistein may have a therapeutic benefit for patients with pancreatic cancer, in particular after surgery, to prevent recurrence of metastatic disease. C1 Univ Calif Los Angeles, Sch Med, Div Gen Surg, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Bern, Dept Surg, Bern, Switzerland. Insel Hosp, Bern, Switzerland. RP Hines, OJ (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Surg, Dept Surg, 72-231 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 49 TC 54 Z9 58 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2003 VL 26 IS 3 BP 264 EP 273 DI 10.1097/00006676-200304000-00010 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 661TL UT WOS:000181905800010 PM 12657953 ER PT J AU Solomon, TE Keire, DA Gong, PX Zong, YM Reeve, JR AF Solomon, TE Keire, DA Gong, PX Zong, YM Reeve, JR TI Receptor subtypes: Species variations in secretin affect potency for pancreatic but not gastric secretion SO PANCREAS LA English DT Article DE rat; secretin biochemistry; secretin physiology ID ACID-SECRETION; RAT; MECHANISM; SEQUENCE; PACAP; VIP AB Introduction: Receptor subtypes can be distinguished by different actions of agonists on physiologic responses. In this study, we compared effects of four species variants of secretin (rat, porcine, canine, and human) on pancreatic secretion and gastrin-induced acid secretion in urethane-anesthetized rats. These secretins differ by one to three residues in position 14, 15, or 16 and were used to probe for the presence of different secretin receptor subtypes in the rat. Methodology: Pancreatic responses were measured in a two-point parallel line bioassay with porcine secretin (3 and 30 pmol/kg IV bolus) as standard. Inhibition of gastric acid secretion by each secretin (100 pmol/[kg (.) h]) was quantitated against a threshold dosage of gastrin-17 (200 pmol/[kg (.) h]), and percent inhibition of incremental acid responses was determined. Results: Rat secretin was significantly more potent than other secretins for pancreatic secretion, in the order of rat > porcine > canine > human. The four secretins significantly inhibited gastrin-induced acid secretion by 37% to 49%, with no statistically significant differences among the forms. Conclusions: Stimulation of pancreatic secretion was influenced by species variations in secretin structure, but inhibition of gastric acid secretion was not. This finding suggests that secretin receptor subtypes with different recognition patterns mediate these responses. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Reeve, JR (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151, CURE Digest Dis Res Ctr, Bldg 115,Room 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK41301] NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2003 VL 26 IS 3 BP 300 EP 305 DI 10.1097/00006676-200304000-00015 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 661TL UT WOS:000181905800015 PM 12657958 ER PT J AU Misra, M Miller, KK Herzog, DB Hackman, A Chung, J Levitsky, LL Klibanski, A AF Misra, M Miller, KK Herzog, DB Hackman, A Chung, J Levitsky, LL Klibanski, A TI Physiology of growth hormone secretion in adolescent girls with anorexia nervosa SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 839 BP 147A EP 147A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897900840 ER PT J AU Wang, L Coffinier, C Thomas, MK Gresh, L Unterman, SE Manor, T Yaniv, M Levitsky, LL Rhoads, DB AF Wang, L Coffinier, C Thomas, MK Gresh, L Unterman, SE Manor, T Yaniv, M Levitsky, LL Rhoads, DB TI Impaired insulin secretion in mice with selective loss of HNF1 beta in beta cells SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Inst Pasteur, Unite Virus Oncogenes, Paris, France. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 871 BP 153A EP 153A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897900872 ER PT J AU Lee, KC Lieu, TA Miroshnik, I Rusinak, D Santoli, J Lett, SM Platt, R Finkelstein, JA AF Lee, KC Lieu, TA Miroshnik, I Rusinak, D Santoli, J Lett, SM Platt, R Finkelstein, JA TI The impact of pneumococcal conjugate vaccine on provider-reported approach to the febrile infant SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Harvard Combined Pediat Hlth Serv Res Fellowship, Boston, MA USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Massachusetts Dept Publ Hlth, Div Epidemiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1017 BP 179A EP 179A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901018 ER PT J AU McGrath, ME Li, W Kharasch, S Perron, C O'Malley, P Sege, RD AF McGrath, ME Li, W Kharasch, S Perron, C O'Malley, P Sege, RD CA Boston ED Surveillance Syst TI Has the decline in youth violence stalled?: Data from Boston emergency departments, 1998-2001 SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Biostat Res Ctr, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Floating Hosp Children, Boston, MA USA. Boston Publ Hlth Comm, Res Off, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1246 BP 219A EP 219A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901247 ER PT J AU Kuhlthau, KA Nyman, RM Ferris, TG Beal, AC Perrin, JM AF Kuhlthau, KA Nyman, RM Ferris, TG Beal, AC Perrin, JM TI Insurance, race/ethnicity, socio-economic status, health status and use of subspecialists SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Massachusetts Gen Hosp Children, Boston, MA USA. Hlth Syst Res Inc, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Commonwealth Fund, Qual Care Underserved Populat, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1267 BP 223A EP 223A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901268 ER PT J AU Tanski, SE Winickoff, JP McMillen, R Klein, JD Weitzman, M AF Tanski, SE Winickoff, JP McMillen, R Klein, JD Weitzman, M TI Dose response relationship between number of tobacco cessation advice-sites and likelihood of quit attempts SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Univ Rochester, AAP Ctr Child Hlth Res, Rochester, NY 14627 USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY 14627 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Mississippi State Univ, Social Sci Res Ctr, Mississippi State, MS 39762 USA. RI McMillen, Robert/A-9326-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1510 BP 265A EP 265A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901509 ER PT J AU Shimamura, A Macari, T Moreau, LA Svenson, JL D'Andrea, AD AF Shimamura, A Macari, T Moreau, LA Svenson, JL D'Andrea, AD TI The Fanconi anemia DNA repair pathway is deficient in acute myeloid leukemia SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1532 BP 268A EP 268A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901531 ER PT J AU Fluchel, M Hawkins, DS Felgenhauer, J Douglas, JJ Sanders, JE Park, JR AF Fluchel, M Hawkins, DS Felgenhauer, J Douglas, JJ Sanders, JE Park, JR TI Outcome of children with high-risk neuroblastoma SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Deaconess Med Ctr, Spokane, WA USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Transplant Serv, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1715 BP 300A EP 301A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901714 ER PT J AU Lee, KC Finkelstein, JA Miroshnik, I Rusinak, D Santoli, J Lett, SM Platt, R Lieu, TA AF Lee, KC Finkelstein, JA Miroshnik, I Rusinak, D Santoli, J Lett, SM Platt, R Lieu, TA TI The impact of pneumococcal conjugate vaccine on provider immunization practices SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Harvard Combined Pediat Hlth Serv, Res Fellowship Program, Boston, MA USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. Massachusetts Dept Publ Hlth, Div Epidemiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 1747 BP 306A EP 306A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897901746 ER PT J AU Claud, EC Cheravil, B Walker, WA AF Claud, EC Cheravil, B Walker, WA TI Developmental regulation of the enterocyte inflammatory response to bacteria SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the Pediatric-Academic-Society CY MAY 03-06, 2003 CL SEATTLE, WASHINGTON SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ C1 Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 SU S MA 2219 BP 392A EP 392A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 661PA UT WOS:000181897902217 ER PT J AU Walker-Smith, J Walker, WA AF Walker-Smith, J Walker, WA TI The development of pediatric gastroenterology: A historical overview SO PEDIATRIC RESEARCH LA English DT Article ID INTESTINAL-BIOPSY CAPSULE; ORAL REHYDRATION SOLUTION; COELIAC DISEASE; DUODENAL MUCOSA; CROHNS-DISEASE; NEEDLE BIOPSY; CHILDREN; DIARRHEA; DEFICIENCY; INFANTS C1 UCL, Wellcome Trust Ctr Hist Med, London, England. Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, 114 16th St 114-3503, Charlestown, MA 02129 USA. EM wwalker@partners.org NR 60 TC 5 Z9 5 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2003 VL 53 IS 4 BP 706 EP 715 DI 10.1203/01.PDR.0000057207.94133.82 PG 10 WC Pediatrics SC Pediatrics GA 661NU UT WOS:000181897300027 PM 12612197 ER PT J AU Fortescue, EB Kaushal, R Landrigan, CP McKenna, KJ Clapp, MD Federico, F Goldmann, DA Bates, DW AF Fortescue, EB Kaushal, R Landrigan, CP McKenna, KJ Clapp, MD Federico, F Goldmann, DA Bates, DW TI Prioritizing strategies for preventing medication errors and adverse drug events in pediatric inpatients SO PEDIATRICS LA English DT Article DE medication error; prevention strategy; pediatric inpatient ID PHYSICIAN ORDER ENTRY; INTENSIVE-CARE UNIT; OF-MEDICINE REPORT; HOSPITALIZED-PATIENTS; INFORMATION TECHNOLOGY; HEALTH-CARE; IMPROVEMENT; PHARMACISTS; MANAGEMENT AB Objectives. Medication errors in pediatric inpatients occur at similar rates as in adults but have 3 times the potential to cause harm. Error prevention strategies in this setting remain largely untested. The objective of this study was to classify the major types of medication errors in pediatric inpatients and to determine which strategies might most effectively prevent them. Methods. A prospective cohort study was conducted of 1020 patients who were admitted to 2 academic medical centers during a 6-week period in April and May 1999. Medication errors were characterized by subtype. Physician raters evaluated error prevention strategies and identified those that might be most effective in preventing errors. Results. Of 10 778 medication orders reviewed, 616 contained errors. Of these, 120 (19.5%) were classified as potentially harmful, including 115 potential adverse drug events (18.7%) and 5 preventable adverse drug events (0.8%). Most errors occurred at the ordering stage (74%) and involved errors in dosing (28%), route (18%), or frequency (9%). Three interventions might have prevented most potentially harmful errors: 1) computerized physician order entry with clinical decision support systems (76%); 2) ward-based clinical pharmacists (81%); and 3) improved communication among physicians, nurses, and pharmacists (86%). Interrater reliability of error prevention strategy assignment was good (agreement: 0.92; kappa: 0.82). Conclusions. Of the assessed interventions, computerized physician order entry with clinical decision support systems; ward- based clinical pharmacists; and improved communication among physicians, nurses, and pharmacists had the greatest potential to reduce medication errors in pediatric inpatients. Development, implementation, and assessment of such interventions in the pediatric inpatient setting are needed. C1 Brigham & Womens Hosp, Div Gen Internal Med, Partners Healthcare Syst, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Qual Improvement, Boston, MA 02115 USA. Childrens Hosp, Dept Risk Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Risk Management Fdn, Cambridge, MA USA. RP Kaushal, R (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, Partners Healthcare Syst, PBBA3,75 Francis St, Boston, MA 02115 USA. NR 42 TC 191 Z9 202 U1 6 U2 26 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2003 VL 111 IS 4 BP 722 EP 729 DI 10.1542/peds.111.4.722 PG 8 WC Pediatrics SC Pediatrics GA 662RA UT WOS:000181960600002 PM 12671103 ER PT J AU Savellano, MD Hasan, T AF Savellano, MD Hasan, T TI Targeting cells that overexpress the epidermal growth factor receptor with polyethylene glycolated BPD verteporfin photosensitizer immunoconjugates SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; PHOTODYNAMIC THERAPY; NUDE-MICE; MODEL; PHOTOIMMUNOTHERAPY; HEMATOPORPHYRIN; CANCER; PROLIFERATION; RADIATION; CONJUGATE AB Photoimmunotherapy was introduced two decades ago but has been studied infrequently in vivo and is virtually untested clinically. Progress has been limited because high-quality, well-characterized photosensitizer immunoconjugates (PICs) have been difficult to make. Here, we describe the development of an innovative conjugation method for producing water-soluble PICs that are free of insoluble aggregates and free of unacceptable amounts of noncovalently associated photosensitizer impurities. The method exploits two procedures previously untried in this research area. First, a small number of antibody lysines (<3 per antibody) are polyethylene glycolated (PEGylated) using a 10 kDa branched polyethylene glycol (PEG), which dramatically enhances PIC solubility and reduces PIC aggregation. Second, a 50% dimethyl sulfoxide-50% aqueous two-solvent system is used to prevent photosensitizer aggregation and noncovalent interactions. These measures allow efficient covalent linkage of the photosensitizer BPD Verteporfin (BPD) to antibody lysines, thorough purification of the resulting PICs (verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis), maintenance of PIC antigen-binding activity (verified by cellular binding-uptake assays) and reduction of nonspecific cellular uptake (e.g. macrophage capture) of the PICs. Loading levels could be varied controllably in the range &LE;11 BPD/antibody. PICs of the C225 anti-epidermal growth factor receptor (EGFR) chimeric monoclonal antibody killed EGFR-overexpressing A-431 cells photodynamically but did not significantly affect EGFR-negative NR6 cells. Although fluorescence measurements demonstrated that the PICs were quenched by as much as an order of magnitude compared with free BPD, an impressive 90% reduction in A-431 cell viability was achieved using 20 J/cm(2) of 690 nm light after a 40 h incubation with the C225 PICs. The results suggest that PEGylated BPD-C225 PICs merit further investigation in animal models of EGFR-overexpressing cancers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed, 314A Bartlett Bldg,40 Blossom St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01AR40352] NR 46 TC 47 Z9 51 U1 1 U2 15 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 2003 VL 77 IS 4 BP 431 EP 439 DI 10.1562/0031-8655(2003)077<0431:TCTOTE>2.0.CO;2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 667UJ UT WOS:000182251700013 PM 12733655 ER PT J AU Gerber, A Lehtinen, JT Warner, JJP AF Gerber, A Lehtinen, JT Warner, JJP TI Glenhohumeral Osteoarthritis in active patients - Diagnostic tips and complete management options SO PHYSICIAN AND SPORTSMEDICINE LA English DT Article ID SHOULDER; DISEASE AB In the normal glenohumeral joint, the humeral head and the glenoid articulate via smooth and congruent articular surfaces. In the osteoarthritic shoulder, however, both the articular surface anatomy and orientation may be severely distorted and the soft tissues grossly contracted, leading to pain and loss of function. While replacement arthroplasty is the treatment of choice in the elderly,therapeutic options for young active patients include conservative treatment, arthroplasty, and corrective osteotomy and are directed, whenever possible, toward joint preservation. C1 Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), 275 Cambridge St,Box 403, Boston, MA 02114 USA. NR 28 TC 2 Z9 3 U1 1 U2 3 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD APR PY 2003 VL 31 IS 4 BP 33 EP 40 PG 8 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 664KT UT WOS:000182060800008 PM 20086464 ER PT J AU Natarajan, S Nietert, PJ AF Natarajan, S Nietert, PJ TI National trends in screening, prevalence, and treatment of cardiovascular risk factors SO PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 29-MAY 01, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Gen Internal Med DE hypertension; hypercholesterolemia; smoking; trends; population survey ID MINNESOTA-HEART-SURVEY; CIGARETTE-SMOKING; UNITED-STATES; HYPERTENSION PREVALENCE; SOCIOECONOMIC-STATUS; SECULAR TRENDS; TIME TRENDS; DISEASE; CHOLESTEROL; HEALTH AB Background. Few studies have documented national trends in screening, awareness, and treatment of cardiovascular risk factors. We evaluated trends in screening, prevalence, and treatment of hypertension, hypercholesterolemia, and smoking. Methods. Data were analyzed from the 1984-1998 Behavioral Risk Factor Surveillance System, a series of yearly cross-sectional population-based surveys of U.S. adults. Unadjusted and adjusted time trends (age-, gender-, ethnicity-, education-, and income-adjusted) in screening, prevalence, and treatment were evaluated. Results. From 1984 to 1998, a larger proportion of U.S. adults were older, more educated, richer, and Hispanic. Hypertension screening was >97% (1988-1998), prevalence ranged from 21 to 24% (1984-1998), and approximately 58% (1984-1992) were prescribed blood-pressure-lowering medications. Hypercholesterolemia screening increased from 47 to 67% (1987-1998), prevalence from 18 to 31% (1987-1998), and cholesterol-lowering prescriptions from 22 to 25% (1988-1990). Smoking prevalence remained around 28% (19841998), while quit attempts declined from 63 to 47% (1990-1998). Conclusions. Although screening for hypertension and hypercholesterolemia has increased, a substantial proportion of cases were not being prescribed medications. While the prevalence of smoking remains constant, quit attempts have fallen. Continuing challenges for cardiovascular disease prevention include identification of individuals with hypercholesterolemia, appropriate prescription (initiation and/or maintenance) of antihypertensive and lipid-lowering medications, and intensifying smoking cessation efforts. (C) 2003 American Health Foundation and Elsevier Science (USA). All rights reserved. C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 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. RP Natarajan, S (reprint author), VA New York Harbor Healthcare Syst, Dept Med, 423 E 23rd St,Room 11101-5, New York, NY 10010 USA. OI Nietert, Paul/0000-0002-3933-4986 NR 42 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 2003 VL 36 IS 4 BP 389 EP 397 DI 10.1016/S0091-7435(02)00057-9 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 662RK UT WOS:000181961700001 PM 12649046 ER PT J AU Peng, S Urbanc, B Cruz, L Hyman, BT Stanley, HE AF Peng, S Urbanc, B Cruz, L Hyman, BT Stanley, HE TI Neuron recognition by parallel Potts segmentation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONTE-CARLO SIMULATIONS; NUMERICAL DENSITY; CLUSTER ALGORITHM; CRITICAL-POINTS; MODELS; TESSELLATION; DYNAMICS; SYSTEMS; CORTEX; NUMBER AB Identifying neurons and their spatial coordinates in images of the cerebral cortex is a necessary step in the quantitative analysis of spatial organization in the brain. This is especially important in the study of Alzheimer's disease (AD), in which spatial neuronal organization and relationships are highly disrupted because of neuronal loss. To automate neuron recognition by using high-resolution confocal microscope images from human brain tissue, we propose a recognition method based on statistical physics that consists of image preprocessing, parallel image segmentation, and cluster selection on the basis of shape, optical density, and size. We segment a preprocessed digital image into clusters by applying Monte Carlo simulations of a q-state inhomogeneous Potts model. We then select the range of Potts segmentation parameters to yield an ideal recognition of simplified objects in the test image. We apply our parallel segmentation method to control individuals and to AD patients and achieve recognition of 98% (for a control) and 93% (for an AD patient), with at most 3% false clusters. C1 Boston Univ, Dept Phys, Ctr Polymer Studies, Boston, MA 02215 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. RP Peng, S (reprint author), Boston Univ, Dept Phys, Ctr Polymer Studies, 590 Commonwealth Ave, Boston, MA 02215 USA. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013 OI Urbanc, Brigita/0000-0001-9159-7698; FU NIA NIH HHS [AG08487, R01 AG008487] NR 28 TC 10 Z9 10 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 2003 VL 100 IS 7 BP 3847 EP 3852 DI 10.1073/pnas.0230490100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664JR UT WOS:000182058400058 PM 12651959 ER PT J AU Zhao, Y Hong, DH Pawlyk, B Yue, GH Adamian, M Grynberg, M Godzik, A Li, TS AF Zhao, Y Hong, DH Pawlyk, B Yue, GH Adamian, M Grynberg, M Godzik, A Li, TS TI The retinitis pigmentosa GTPase regulator (RPGR)-interacting protein: Subserving RPGR function and participating in disk morphogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOTORECEPTOR CONNECTING CILIUM; RDS MUTANT MICE; TRANSGENIC MICE; OUTER SEGMENTS; CYTOCHALASIN-D; TRANSPORT; ROD; RHODOPSIN; ACTIN; IDENTIFICATION AB Retinitis pigmentosa is a photoreceptor degenerative disease leading to blindness in adulthood. Leber congenital amaurosis (LCA) describes a more severe condition with visual deficit in early childhood. Defects in the retinitis pigmentosa GTPase regulator (RPGR) and an RPGR-interacting protein (RPGRIP) are known causes of retinitis pigmentosa and LCA, respectively. Both proteins localize in the photoreceptor connecting cilium (CC), a thin bridge linking the cell body and the light-sensing outer segment. We show that RPGR is absent in the CC of photoreceptors lacking RPGRIP, but not vice versa. Mice lacking RPGRIP elaborate grossly oversized outer segment disks resembling a cytochalasin D-induced defect and have a more severe disease than mice lacking RPGR. Mice lacking both proteins are phenotypically indistinguishable from mice lacking RPGRIP alone. In vitro, RPGRIP forms homodimer and elongated filaments via interactions involving its coiled-coil and C-terminal domains. We conclude that RPGRIP is a stable polymer in the CC where it tethers RPGR and that RPGR depends on RPGRIP for subcellular localization and normal function. Our data suggest that RPGRIP is also required for disk morphogenesis, putatively by regulating actin cytoskeleton dynamics. The latter hypothesis may be consistent with a distant homology between the C-terminal domain of RPGRIP and an actin-fragmin kinase, predicted by fold recognition algorithms. A defect in RPGRIP encompasses loss of both functions, hence the more severe clinical manifestation as LCA. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Burnham Inst, La Jolla, CA 92037 USA. Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RI Godzik, Adam/A-7279-2009 OI Godzik, Adam/0000-0002-2425-852X FU NEI NIH HHS [R01 EY010309, EY10309, EY10581, R01 EY010581]; NIGMS NIH HHS [GM60049] NR 33 TC 130 Z9 134 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 APR 1 PY 2003 VL 100 IS 7 BP 3965 EP 3970 DI 10.1073/pnas.0637349100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664JR UT WOS:000182058400079 PM 12651948 ER PT J AU Rhee, J Inoue, Y Yoon, JC Puigserver, P Fan, ML Gonzalez, FJ Spiegelman, BM AF Rhee, J Inoue, Y Yoon, JC Puigserver, P Fan, ML Gonzalez, FJ Spiegelman, BM TI Regulation of hepatic fasting response by PPAR gamma coactivator-1 alpha (PGC-1): Requirement for hepatocyte nuclear factor 4 alpha in gluconeogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROLIFERATOR-ACTIVATED RECEPTOR; PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; TRANSCRIPTION FACTOR FKHR; MITOCHONDRIAL BIOGENESIS; DEHYDROGENASE GENE; ACCESSORY FACTOR; FACTOR-IV; EXPRESSION; INSULIN; ALPHA AB The liver plays several critical roles in the metabolic adaptation to fasting. We have shown previously that the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) is induced in fasted or diabetic liver and activates the entire program of gluconeogenesis. PGC-1alpha interacts with several nuclear receptors known to bind gluconeogenic promoters including the glucocorticoid receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), and the peroxisome proliferator-activated receptors. However, the genetic requirement for any of these interactions has not been determined. Using hepatocytes from mice lacking HNF4alpha in the liver, we show here that PGC-1alpha completely loses its ability to activate key genes of gluconeogenesis such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase when HNF4alpha is absent. It is also shown that PGC-1alpha can induce genes of beta-oxidation and ketogenesis in hepatocytes, but these effects do not require HNF4alpha. Analysis of the glucose-6-phosphatase promoter indicates a key role for HNF4alpha-binding sites that function robustly only when HNF4alpha is coactivated by PGC-1alpha. These data illustrate the involvement of PGC-1alpha in several aspects of the hepatic fasting response and show that HNF4alpha is a critical component of PGC-1alpha-mediated gluconeogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK061562, DK 61562] NR 41 TC 342 Z9 352 U1 4 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 2003 VL 100 IS 7 BP 4012 EP 4017 DI 10.1073/pnas.0730870100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664JR UT WOS:000182058400087 PM 12651943 ER PT J AU Farris, W Mansourian, S Chang, Y Lindsley, L Eckman, EA Frosch, MP Eckman, CB Tanzi, RE Selkoe, DJ Guenette, S AF Farris, W Mansourian, S Chang, Y Lindsley, L Eckman, EA Frosch, MP Eckman, CB Tanzi, RE Selkoe, DJ Guenette, S TI Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ONSET ALZHEIMERS-DISEASE; GLYCATION END-PRODUCTS; C-TERMINAL FRAGMENTS; DIABETES-MELLITUS; NEURODEGENERATIVE DISEASES; SUSCEPTIBILITY LOCUS; EXTRACELLULAR LEVELS; GAMMA-SECRETASE; A-BETA; DEGRADATION AB Two substrates of insulin-degrading enzyme (IDE), amyloid beta-protein (Abeta) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively. We previously identified IDE as a principal regulator of Abeta levels in neuronal and microglial cells. A small chromosomal region containing a mutant IDE allele has been associated with hyperinsulinemia and glucose intolerance in a rat model of DM2. Human genetic studies have implicated the IDE region of chromosome 10 in both AD and DM2. To establish whether IDE hypofunction decreases Abeta and insulin degradation in vivo and chronically increases their levels, we characterized mice with homozygous deletions of the IDE gene (IDE -/-). IDE deficiency resulted in a >50% decrease in Abeta degradation in both brain membrane fractions and primary neuronal cultures and a similar deficit in insulin degradation in liver. The IDE -/- mice showed increased cerebral accumulation of endogenous Abeta, a hallmark of AD, and had hyperinsulinemia and glucose intolerance, hallmarks of DM2. Moreover, the mice had elevated levels of the intracellular signaling domain of the beta-amyloid precursor protein, which was recently found to be degraded by IDE in vitro. Together with emerging genetic evidence, our in vivo findings suggest that IDE hypofunction may underlie or contribute to some forms of AD and DM2 and provide a mechanism for the recently recognized association among hyperinsulinemia, diabetes, and AD. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Boston, MA 02129 USA. Mayo Clin, Jacksonville, FL 32224 USA. RP Guenette, S (reprint author), Massachusetts Gen Hosp E, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG1247, AG15379, AG15903, P01 AG015379, R01 AG015903] NR 58 TC 770 Z9 800 U1 7 U2 63 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 1 PY 2003 VL 100 IS 7 BP 4162 EP 4167 DI 10.1073/pnas.0230450100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664JR UT WOS:000182058400113 PM 12634421 ER PT J AU Kern, RS Green, MF Mintz, J Liberman, RP AF Kern, RS Green, MF Mintz, J Liberman, RP TI Does 'errorless learning' compensate for neurocognitive impairments in the work rehabilitation of persons with schizophrenia? SO PSYCHOLOGICAL MEDICINE LA English DT Article ID COGNITIVE REMEDIATION; SUPPORTED EMPLOYMENT; ENHANCEMENT THERAPY; MEMORY; PERFORMANCE; DISORDERS; INDIVIDUALS; DEFICITS; CAPACITY; TIME AB Background. Because neurocognitive impairments of schizophrenia appear to be 'rate limiting' in the acquisition of skills for community functioning, it is important to develop efficacious rehabilitative interventions that can compensate for these impairments. Procedures based on errorless learning may facilitate work rehabilitation because they effectively automate training of work and other skills, thereby reducing the cognitive burden on persons with schizophrenia. Method. The present study examined the ability of a training method based on errorless learning to compensate for neurocognitive deficits in teaching two entry-level job tasks (index card filing and toilet-tank assembly) to a sample of 54 unemployed, clinically stable schizophrenic and schizo-affective disorder out-patients. Participants were randomly assigned to one of two training groups, errorless learning v. conventional trial-and-error type instruction. Prior to randomization, all subjects were administered a neurocognitive battery. Job task performance was assessed by percentage accuracy scores immediately after training. Results. For three of the six inter-relationships among neurocognitive functioning and training condition, the pattern was the same: the errorless learning group scored high in job task performance regardless of neurocognitive impairment, whereas the conventional instruction group showed a close correspondence between job task performance and degree of neurocognitive impairment. Conclusions. These findings support errorless learning as a technique that can compensate for neurocognitive deficits as they relate to the acquisition of new skills and abilities in the work rehabilitation of persons with schizophrenia. C1 Dept Vet Affairs, VISN 22, MIRECC, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Kern, RS (reprint author), VA Greater Los Angeles Healthcare ctr, MIRECC 210 A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH 30911-21S1] NR 59 TC 37 Z9 37 U1 3 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2003 VL 33 IS 3 BP 433 EP 442 DI 10.1017/S0033291702007298 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 671TB UT WOS:000182479200006 PM 12701664 ER PT J AU Roy-Byrne, P Russo, J Pollack, M Stewart, R Bystrisky, A Bell, J Rosenbaum, J Corrigan, MH Stolk, J Rush, AJ Ballenger, J AF Roy-Byrne, P Russo, J Pollack, M Stewart, R Bystrisky, A Bell, J Rosenbaum, J Corrigan, MH Stolk, J Rush, AJ Ballenger, J TI Personality and symptom sensitivity predictors of alprazolam withdrawal in panic disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article ID TERM THERAPEUTIC USE; COGNITIVE-BEHAVIOR THERAPY; BENZODIAZEPINE WITHDRAWAL; DISCONTINUATION; DEPENDENCE; ANXIETY; DIAZEPAM; TAPER; QUESTIONNAIRE; SEVERITY AB Background. Discontinuation of benzodiazepine (BZ) treatment results in a well-characterized withdrawal syndrome in 40-50 % of anxious patients. While numerous studies have established the role of BZ dose, treatment duration, half-life, potency, rate of withdrawal and severity of underlying anxiety disorder in predicting severity of withdrawal symptoms, fewer studies have examined the role of psychological and personality factors. Method. In 123 panic disorder patients undergoing gradual tapered discontinuation of alprazolam in conjunction with pre-treatment with carbamazepine or placebo, the relationship between measures of 'symptom sensitivity' and 'harm avoidance', and severity of withdrawal symptoms measured as peak severity of symptoms, time before taper needed to be slowed due to symptoms, and ability to complete taper, was examined. Results. After controlling for the less substantial effects of dose, treatment duration, pre-taper anxiety and panic attack frequency, measures of symptom sensitivity and harm avoidance accounted for an additional 3-6 % of withdrawal variance. Conclusions. These results show an effect of symptom sensitivity and harm avoidance on BZ withdrawal symptoms, comparable to prior findings linking dependent personality characteristics to withdrawal severity. Failure to show the expected effect on ability to complete taper may be due to either the more symptomatic nature of the patients in this study. C1 Univ Washington, Harborview Med Ctr, Dept Psychiat, Seattle, WA 98104 USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Colorado, Denver, CO 80202 USA. RP Roy-Byrne, P (reprint author), Univ Washington, Harborview Med Ctr, Dept Psychiat, 325 9Th Ave,Box 359911, Seattle, WA 98104 USA. OI Rush, Augustus/0000-0003-2004-2382 NR 31 TC 5 Z9 6 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD APR PY 2003 VL 33 IS 3 BP 511 EP 518 DI 10.1017/S0033291703007402 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 671TB UT WOS:000182479200013 PM 12701671 ER PT J AU Naidoo, U Goff, DC Klibanski, A AF Naidoo, U Goff, DC Klibanski, A TI Hyperprolactinemia and bone mineral density: the potential impact of antipsychotic agents SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE schizophrenia; bone mineral density; hyperprolactinemia; antipsychotics; osteoporosis; fractures ID D-2 RECEPTOR OCCUPANCY; SCHIZOPHRENIC-PATIENTS; ALKALINE-PHOSPHATASE; HYDROXYPROLINE EXCRETION; POSTMENOPAUSAL WOMEN; PLASMA PROLACTIN; SERUM PROLACTIN; OSTEOPOROSIS; HALOPERIDOL; OLANZAPINE AB The prevalence of schizophrenia is about 1% worldwide. Individuals with schizophrenia are at increased risk for osteoporosis and fractures for several reasons, including poor diet, lack of exercise, cigarette smoking, and polydipsia. Some antipsychotic medications may further increase the risk of fractures by causing dizziness, orthostatic hypotension, and falls. Studies in women with hyperprolactinemia resulting from pituitary tumors have demonstrated high rates of osteoporosis believed to result from hypoestrogenism. Similarly, hyperprolactinemia in men results in hypogonadism and bone loss. Preliminary surveys have indicated that schizophrenia patients also may have elevated rates of osteoporosis and pathological fractures, possibly resulting in part from the long-term administration of antipsychotic agents that produce hyperprolactinemia and secondarily lower estrogen and testosterone levels. This potential complication of treatment with certain antipsychotic agents requires careful study and could represent a serious public health problem. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Schizophrenia Program, Dept Psychol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. NR 63 TC 65 Z9 69 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2003 VL 28 SU 2 BP 97 EP 108 DI 10.1016/S0306-430(02)00129-4 PG 12 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 673CM UT WOS:000182562100006 PM 12650684 ER PT J AU Cavallerano, AA Cavallerano, JD Katalinic, P Tolson, AM Aiello, LP Aiello, LM AF Cavallerano, AA Cavallerano, JD Katalinic, P Tolson, AM Aiello, LP Aiello, LM CA Joslin Vision Network Clinical TI Use of Joslin Vision Network digital-video nonmydriatic retinal imaging to assess diabetic retinopathy in a clinical program SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Annual Meeting of the American-Telemedicine-Association (ATA 2000) CY MAY 22, 2000 CL PHOENIX, AZ SP Amer Telemed Assoc DE Joslin Vision Network; digital-video retinal imaging; diabetic retinopathy; diabetic macular edema AB Purpose: To incorporate a nonmydriatic, digital-video retinal imaging system into a Diabetes Outpatient Intensive Treatment Program and to evaluate the system's ability to assess diabetic retinopathy (DR), determine follow-up, and appropriately refer to retinal specialist ophthalmologists. Methods: Fundus images were obtained according to Joslin Vision Network (JVN) protocol and evaluated by certified JVN readers. Patients with significant retinal disease underwent evaluation by retinal specialists. Results: A total of 268 (51.0%) of 525 imaged patients had comprehensive eye examination by a retinal specialist owing to referable JVN-assessed clinical level of DR, nondiabetic ocular disease, ungradeable images, last eye examination greater than or equal to12 months prior, or patient request for examination. JVN diagnosis of a clinical level of DR agreed exactly with clinical findings in 388 eyes (72.5%) or within one level in 478 eyes (89.3%). JVN referral based on most severe diagnosis in either eye matched retinal specialist-recommended follow-up in 248/268 of patients (92.5%). A total of 136/525 (25.9%) of JVN patients had nondiabetic ocular abnormalities requiring referral. Conclusions: Recommended follow-up from JVN imaging compared favorably to clinical examination by a retinal specialist. Nondiabetic ocular pathology was identified. JVN assessment of DR level compares favorably to clinical practice, potentially improving access to eye care and enhancing diabetes management. C1 Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA 02210 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02210 USA. RP Aiello, LM (reprint author), Harvard Univ, Sch Med, Beetham Eye Inst, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02210 USA. NR 8 TC 54 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD APR PY 2003 VL 23 IS 2 BP 215 EP 223 DI 10.1097/00006982-200304000-00013 PG 9 WC Ophthalmology SC Ophthalmology GA 679AK UT WOS:000182898700013 PM 12707602 ER PT J AU Stewart, SA Dykxhoorn, DM Palliser, D Mizuno, H Yu, EY An, DS Sabatini, DM Chen, ISY Hahn, WC Sharp, PA Weinberg, RA Novina, CD AF Stewart, SA Dykxhoorn, DM Palliser, D Mizuno, H Yu, EY An, DS Sabatini, DM Chen, ISY Hahn, WC Sharp, PA Weinberg, RA Novina, CD TI Lentivirus-delivered stable gene silencing by RNAi in primary cells SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE retrovirus; hairpin RNA; siRNA; knockdown; dendritic cells ID SHORT-INTERFERING RNAS; DENDRITIC CELLS; MAMMALIAN-CELLS; RETROVIRAL VECTORS; ADENOVIRUS VECTOR; HAIRPIN RNAS; HIGH-TITER; IN-VIVO; EXPRESSION; IMMUNITY AB Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis elegans, but similar techniques have proven difficult to apply to mammalian systems. Although manipulation of the murine genome has led to identification of genes and their function, this approach is laborious, expensive, and often leads to lethal phenotypes. RNA interference (RNAi) is an evolutionarily conserved process of gene silencing that has become a powerful tool for investigating gene function by reverse genetics. Here we describe the delivery of cassettes expressing hairpin RNA targeting green fluorescent protein (GFP) using Moloney leukemia virus-based and lentivirus-based retroviral vectors. Both transformed cell lines and primary dendritic cells, normally refractory to transfection-based gene transfer, demonstrated stable silencing of targeted genes, including the tumor suppressor gene TP53 in normal human fibroblasts. This report demonstrates that both Moloney leukemia virus and lentivirus vector-mediated expression of RNAi can achieve effective, stable gene silencing in diverse biological systems and will assist in elucidating gene functions in numerous cell types including primary cells. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif Los Angeles, AIDS Inst, David Geffen Sch Med, Dept Microbiol Immunol Mol Genet & Med, Los Angeles, CA 90025 USA. RP Stewart, SA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Stewart, Sheila/C-5213-2012; Dykxhoorn, Derek/D-1357-2015; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [F32 CA093033, F32 CA93033-01, K01 CA094223, KO1CA94223, P01 CA042063, P01-CA42063, P30 CA014051, P30-CA14051, R01 CA078461, R01CA78461-04]; NIAID NIH HHS [F32 AI010523, F32 AI10523, R01-AI32486]; NIGMS NIH HHS [R37-GM34277, R37 GM034277] NR 35 TC 488 Z9 544 U1 1 U2 30 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD APR PY 2003 VL 9 IS 4 BP 493 EP 501 DI 10.1261/rna.2192803 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706HE UT WOS:000184447600012 PM 12649500 ER PT J AU Faraone, SV Seidman, LJ Kremen, WS Kennedy, D Makris, N Caviness, VS Goldstein, J Tsuang, MT AF Faraone, SV Seidman, LJ Kremen, WS Kennedy, D Makris, N Caviness, VS Goldstein, J Tsuang, MT TI Structural brain abnormalities among relatives of patients with schizophrenia: implications for linkage studies SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; MRI phenotype; structural brain abnormalities ID QUANTITATIVE-TRAIT LOCI; DISCORDANT SIB PAIRS; GENETICALLY COMPLEX TRAITS; NONPSYCHOTIC RELATIVES; HIGH-RISK; TOPOGRAPHIC PARCELLATION; MORPHOMETRIC ANALYSIS; DIAGNOSTIC-ACCURACY; CEREBRAL-CORTEX; WHITE-MATTER AB Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Univ Calif Davis, Sch Med, Dept Psychiat, Davis, CA 95616 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Faraone, SV (reprint author), Harvard Univ, Suite 255,750 Washington St, S Easton, MA 02375 USA. RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH43518, R01MH46318, R25MH60485] NR 92 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 1 PY 2003 VL 60 IS 2-3 BP 125 EP 140 DI 10.1016/S0920-9964(02)00304-3 PG 16 WC Psychiatry SC Psychiatry GA 652PW UT WOS:000181388400003 PM 12591577 ER PT J AU Manoach, DS AF Manoach, DS TI Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings SO SCHIZOPHRENIA RESEARCH LA English DT Article DE prefrontal cortex dysfunction; working memory; schizophrenia ID CEREBRAL-BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; ATYPICAL ANTIPSYCHOTIC-DRUGS; LINKING BASAL GANGLIA; FRONTAL-LOBE FUNCTION; CARD SORTING TEST; PHYSIOLOGICAL DYSFUNCTION; NEGATIVE SYMPTOMS; PERCEPTUAL ORGANIZATION; FUNCTIONAL MRI AB Working memory (WM) deficits are a persistent, disabling and relatively treatment-resistant feature of schizophrenia that may underlie many cognitive deficits and symptoms. They are associated with prefrontal cortex dysfunction. While most neuroimaging studies of WM demonstrate "task-related hypofrontality" in schizophrenic relative to healthy subjects, several recent studies have reported equal or increased prefrontal activity. These findings challenge central assumptions regarding cognitive deficits and prefrontal cortex dysfunction in schizophrenia. The goal of this review is to reconcile these seemingly discrepant findings. Methodological factors addressed include the use of intersubject averaging, WM task parameters and the reliability of the measures. Factors intrinsic to schizophrenia and their relevance to the selection of experimental methods and the interpretation of group data are also discussed. Both hypo- and hyperfrontality are hypothesized to be valid and informative reflections of prefrontal cortex dysfunction in schizophrenia. Due to the heterogeneity and variability of both performance and regional recruitment in schizophrenia, whether individual data is considered, the level and type of WM demands and the composition of the sample with regard to performance deficits all influence study outcome and contribute to discrepancies. Although the prefrontal cortex is consistently implicated in WM deficits, the basis of its dysfunction and its exact contribution remain unclear. Future work might focus on delineating the exact WM processes, domains and components that are deficient. In addition, variability in behavior and activation might best be regarded as intrinsic to schizophrenia and having a neural basis that requires explanation. In combination with other techniques, neuroirnaging can identify the neural circuitry responsible for WM deficits and elucidate the contribution of each anatomical component. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp East, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02129 USA. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, 36 1st Ave,Room 420, Boston, MA 02129 USA. FU NIMH NIH HHS [K23MH01829-01] NR 99 TC 431 Z9 448 U1 5 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 1 PY 2003 VL 60 IS 2-3 BP 285 EP 298 DI 10.1016/S0920-9964(02)00294-3 PG 14 WC Psychiatry SC Psychiatry GA 652PW UT WOS:000181388400016 PM 12591590 ER PT J AU Sattler, M Griffin, JD AF Sattler, M Griffin, JD TI Molecular mechanisms of transformation by the BCR-ABL oncogene SO SEMINARS IN HEMATOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; BCR/ABL TYROSINE KINASE; BINDING-PROTEIN ICSBP; C-ABL; REDOX REGULATION; ADAPTER PROTEIN; SH2 DOMAIN; CELL-LINE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 95 TC 115 Z9 120 U1 3 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2003 VL 40 IS 2 SU 2 BP 4 EP 10 DI 10.1053/shem.2003.50034 PG 7 WC Hematology SC Hematology GA 683PX UT WOS:000183159200002 PM 12783368 ER PT J AU Daley, GQ AF Daley, GQ TI Towards combination target-directed chemotherapy for chronic myeloid leukemia: Role of farnesyl transferase inhibitors SO SEMINARS IN HEMATOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ABL TYROSINE KINASE; BCR-ABL; FARNESYLTRANSFERASE INHIBITORS; PHILADELPHIA-CHROMOSOME; BLAST CRISIS; RAS; CELLS; SCH66336 C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, Cambridge Ctr 9, Cambridge, MA 02142 USA. NR 29 TC 13 Z9 14 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2003 VL 40 IS 2 SU 2 BP 11 EP 14 DI 10.1053/shem.2003.50035 PG 4 WC Hematology SC Hematology GA 683PX UT WOS:000183159200003 PM 12783369 ER PT J AU Treon, SP Dimopoulos, M Kyle, RA AF Treon, SP Dimopoulos, M Kyle, RA TI Defining Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Editorial Material ID CLASSIFICATION C1 Harvard Univ, Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Dept Med, Boston, MA 02115 USA. Univ Athens, Athens, Greece. Mayo Clin, Rochester, MN USA. RP Treon, SP (reprint author), Harvard Univ, Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, Dept Med Oncol, LG100,44 Binney St, Boston, MA 02115 USA. NR 12 TC 14 Z9 14 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 107 EP 109 DI 10.1053/sonc.2003.50081 PG 3 WC Oncology SC Oncology GA 673VY UT WOS:000182602000001 PM 12720117 ER PT J AU Owen, RG Treon, SP Al-Katib, A Fonseca, R Greipp, PR McMaster, ML Morra, E Pangalis, GA Miguel, JFS Branagan, AR Dimopoulos, MA AF Owen, RG Treon, SP Al-Katib, A Fonseca, R Greipp, PR McMaster, ML Morra, E Pangalis, GA Miguel, JFS Branagan, AR Dimopoulos, MA TI Clinicopathological definition of Waldenstrom's macroglobulinemia: Consensus panel recommendations from the second international workshop on Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID IGM MONOCLONAL GAMMOPATHY; B-CELL LYMPHOMA; PROGNOSTIC FACTORS; CHROMOSOMAL-ABNORMALITIES; CLINICAL COURSE; SCORING SYSTEM; FEATURES; MYELOMA; PROPOSAL; CLASSIFICATION C1 Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, Boston, MA 02115 USA. Leeds Gen Infirm, Leeds, W Yorkshire, England. Van Elslander Canc Ctr, Grosse Point Woods, MI USA. Mayo Clin, Rochester, MN USA. NCI, Bethesda, MD 20892 USA. Niguardia CaGranda Hosp, Milan, Italy. Univ Salamanca, E-37008 Salamanca, Spain. Univ Athens, Athens, Greece. RP Owen, RG (reprint author), Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, LG100,44 Binney St, Boston, MA 02115 USA. OI Fonseca, Rafael/0000-0002-5938-3769; Branagan, Andrew/0000-0002-3868-9267 NR 41 TC 407 Z9 428 U1 0 U2 16 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 110 EP 115 DI 10.1053/sonc.2003.50082 PG 6 WC Oncology SC Oncology GA 673VY UT WOS:000182602000002 PM 12720118 ER PT J AU Kyle, RA Treon, SP Alexanian, R Barlogie, B Bjorkholm, M Dhodapkar, M Lister, TA Merlini, G Morel, P Stone, M Branagan, AR Leblond, W AF Kyle, RA Treon, SP Alexanian, R Barlogie, B Bjorkholm, M Dhodapkar, M Lister, TA Merlini, G Morel, P Stone, M Branagan, AR Leblond, W TI Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: Consensus panel recommendations from the second international workshop on Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID CLINICAL COURSE; FEATURES C1 Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, Boston, MA 02215 USA. Mayo Clin, Rochester, MN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Myeloma Inst Res & Therapy, Little Rock, AR USA. Karolinska Hosp & Inst, Dept Med, Stockholm, Sweden. Rockefeller Univ, Lab Tumor Immunol & Immunotherapy, New York, NY 10021 USA. St Bartholomews Hosp, Dept Oncol, London, England. Univ Hosp Pavia, Biotechnol Res Labs, IRCCS, Policlin San Matteo, Pavia, Italy. Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. Ctr Hosp Schaffner, Serv Hematol Clin, Lens, France. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Hop La Pitie Salpetriere, Dept Hematol, Paris, France. RP Kyle, RA (reprint author), Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, LG100,44 Binney St, Boston, MA 02215 USA. RI Merlini, Giampaolo/A-3817-2008; OI Merlini, Giampaolo/0000-0001-7680-3254; Branagan, Andrew/0000-0002-3868-9267 NR 17 TC 131 Z9 135 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 116 EP 120 DI 10.1053/sonc.2003.50038 PG 5 WC Oncology SC Oncology GA 673VY UT WOS:000182602000003 PM 12720119 ER PT J AU Gertz, MA Anagnostopoulos, A Anderson, K Branagan, AR Coleman, M Frankel, SR Giralt, S Levine, T Munshi, N Pestronk, A Rajkumar, V Treon, SP AF Gertz, MA Anagnostopoulos, A Anderson, K Branagan, AR Coleman, M Frankel, SR Giralt, S Levine, T Munshi, N Pestronk, A Rajkumar, V Treon, SP TI Treatment recommendations in Waldenstrom's macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waidenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; ANTIBODY-MEDIATED IMMUNOTHERAPY; NON-HODGKINS-LYMPHOMA; MONOCLONAL GAMMOPATHY; FLUDARABINE THERAPY; PLASMA-EXCHANGE; 2-CHLORODEOXYADENOSINE THERAPY; UNDETERMINED SIGNIFICANCE; RITUXIMAB C1 Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. MD Anderson Canc Ctr, Houston, TX USA. Cornell Univ, Weill Med Coll, New York, NY USA. Greenbaum Canc Ctr, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Washington Univ, Sch Med, St Louis, MO USA. RP Gertz, MA (reprint author), Harvard Univ, Sch Med, Waldenstroms Macroglobulinemia Program, Dana Farber Canc Inst, LG100,44 Binney St, Boston, MA 02115 USA. NR 59 TC 65 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 121 EP 126 DI 10.1053/sonc.2003.50039 PG 6 WC Oncology SC Oncology GA 673VY UT WOS:000182602000004 PM 12720120 ER PT J AU Weber, D Treon, SP Emmanouilides, C Branagan, AR Byrd, JC Blade, J Kimby, E AF Weber, D Treon, SP Emmanouilides, C Branagan, AR Byrd, JC Blade, J Kimby, E TI Uniform response criteria in Waldenstrom's macroglobulinemia: Consensus panel recommendations from the Second International Workshop on Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID MONOCLONAL GAMMOPATHIES; GUIDELINES; DIAGNOSIS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. Ohio State Univ, Arthur James Comprehens Canc Ctr, Columbus, OH 43210 USA. Univ Barcelona, Inst Hematol & Oncol, Barcelona, Spain. Huddinge Univ Hosp, Karolinska Inst, Dept Hematol, Stockholm, Sweden. RP Weber, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Waldenstroms Macroglobulinemia Program, LG100,44 Binney St, Boston, MA 02115 USA. OI Branagan, Andrew/0000-0002-3868-9267 NR 12 TC 62 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 127 EP 131 DI 10.1053/sonc.2003.50037 PG 5 WC Oncology SC Oncology GA 673VY UT WOS:000182602000005 PM 12720121 ER PT J AU Kriangkum, K Taylor, BJ Mant, MJ Treon, SP Belch, AR Pilarski, LM AF Kriangkum, K Taylor, BJ Mant, MJ Treon, SP Belch, AR Pilarski, LM TI The malignant clone in Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID ISOTYPE SWITCH EVENTS; H GENE ANALYSIS; MULTIPLE-MYELOMA; SOMATIC MUTATION; CELL; LEUKEMIA; IGM; DIFFERENTIATION; EXPRESSION; EVOLUTION C1 Univ Alberta, Dept Oncol, Edmonton, AB T6G 1Z2, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Alberta, Dept Med, Edmonton, AB T6G 1Z2, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pilarski, LM (reprint author), Univ Alberta, Dept Oncol, 11560 Univ Ave, Edmonton, AB T6G 1Z2, Canada. NR 16 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 132 EP 135 DI 10.1053/sonc.2003.50061 PG 4 WC Oncology SC Oncology GA 673VY UT WOS:000182602000006 ER PT J AU Mitsiades, CS Mitsiades, N Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Treon, SP Anderson, KC TI Proteomic analyses in Waldenstrom's macroglobulinemia and other plasma cell dyscrasias SO SEMINARS IN ONCOLOGY LA English DT Review ID MULTIPLE-MYELOMA CELLS; THERAPEUTIC IMPLICATIONS; KAPPA-B; CANCER; INHIBITION; DISCOVERY; PROTEINS; SEQUELAE; PATTERNS; SERUM C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, 44 Binney St,Mayer Bldg,Room M555, Boston, MA 02115 USA. NR 16 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 156 EP 160 DI 10.1053/sonc.2003.50066 PG 5 WC Oncology SC Oncology GA 673VY UT WOS:000182602000011 PM 12720127 ER PT J AU Treon, SP Kelliher, A Keele, B Frankel, S Emmanouilides, C Kimby, E Schlossman, R Mitsiades, N Mitsiades, C Preffer, F Anderson, KC AF Treon, SP Kelliher, A Keele, B Frankel, S Emmanouilides, C Kimby, E Schlossman, R Mitsiades, N Mitsiades, C Preffer, F Anderson, KC TI Expression of serotherapy target antigens in Waldenstrom's macroglobulinemia: Therapeutic applications and considerations SO SEMINARS IN ONCOLOGY LA English DT Review ID ANTI-CD20 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMA; PHASE-II; MEDIATED IMMUNOTHERAPY; LOW-GRADE; RITUXIMAB C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA 90024 USA. Huddinge Univ, Huddinge, Sweden. RP Treon, SP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dana Farber Canc Inst, M555,44 Binney St, Boston, MA 02115 USA. NR 21 TC 19 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 248 EP 252 DI 10.1053/sonc.2003.50047 PG 5 WC Oncology SC Oncology GA 673VY UT WOS:000182602000030 PM 12720146 ER PT J AU Munshi, NC Barlogie, B AF Munshi, NC Barlogie, B TI Role for high-dose therapy with autologous hematopoietic stem cell support in Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID MULTIPLE-MYELOMA; TRANSPLANTATION; CHEMOTHERAPY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston VA Healthcare Ctr, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Munshi, NC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,M557, Boston, MA 02115 USA. FU NCI NIH HHS [CA55819] NR 15 TC 16 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 282 EP 285 DI 10.1053/sonc.2003.50080 PG 4 WC Oncology SC Oncology GA 673VY UT WOS:000182602000037 PM 12720153 ER PT J AU Mitsiades, CS Mitsiades, N Richardson, PG Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Richardson, PG Treon, SP Anderson, KC TI Novel biologically based therapies for Waldenstrom's macroglobulinemia SO SEMINARS IN ONCOLOGY LA English DT Review ID ACTIVATED RECEPTOR-GAMMA; OVERCOMES DRUG-RESISTANCE; MULTIPLE-MYELOMA CELLS; THALIDOMIDE C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Dept Med, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, 44 Binney St,Mayer Bldg,Room M555, Boston, MA 02215 USA. NR 18 TC 31 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2003 VL 30 IS 2 BP 309 EP 312 DI 10.1053/sonc.2003.50065 PG 4 WC Oncology SC Oncology GA 673VY UT WOS:000182602000043 PM 12720159 ER PT J AU Bromley, B Benacerraf, BR AF Bromley, B Benacerraf, BR TI The Genetic Sonogram Scoring Index SO SEMINARS IN PERINATOLOGY LA English DT Review ID FETAL DOWN-SYNDROME; 2ND-TRIMESTER FETUSES; 2ND TRIMESTER; AUTOSOMAL TRISOMY; RISK ASSESSMENT; MATERNAL RACE; NUCHAL FOLD; ULTRASOUND; MARKERS; SIGN C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. NR 31 TC 5 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD APR PY 2003 VL 27 IS 2 BP 124 EP 129 DI 10.1053/sper.2003.50011 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 676DP UT WOS:000182736900002 PM 12769198 ER PT J AU Miller, YE Fain, P AF Miller, YE Fain, P TI Genetic susceptibility to lung cancer SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE lung cancer; genetic susceptibility; genomic instability; carcinogen metabolism ID OBSTRUCTIVE PULMONARY-DISEASE; GROWTH-FACTOR-I; BREAST-CANCER; ENVIRONMENTAL COMPONENTS; CARDIOVASCULAR-DISEASE; NEUTRAL ENDOPEPTIDASE; SEGREGATION ANALYSIS; FAMILIAL BREAST; BETA-CAROTENE; RECEPTOR GENE AB Lung cancer is the most common cause of cancer death in the world. Environmental factors, particularly cigarette smoking, are of paramount importance in determining lung cancer risk. Lung cancer and chronic obstructive lung disease are likely to share some common susceptibility genes, but these have not yet been identified. Evidence from various sources, including twin studies, segregation analyses, and case-control studies, support a heritable component to lung cancer risk in humans. As with many common diseases, susceptibility genes for lung cancer appear to be of low penetrance. Family studies of lung cancer susceptibility using linkage analysis and positional cloning have not been reported; however, a consortium is currently carrying out such studies, and results may soon be available. Association studies support lung cancer risk being partly determined by genes that control the metabolism of carcinogens found in tobacco smoke, with the heritable effects being most prominent in smokers with shorter smoking histories. Of these, the CYP1A1 and GSTM1 polymorphisms have been most consistently implicated. In the mouse, an oligonucleotide repeat polymorphism within an intron of the Ki-ras oncogene is the major lung cancer susceptibility locus; however this locus is not clearly involved in susceptibility to lung cancer in the human. Further understanding of the genetic basis of lung cancer susceptibility has many important implications, ranging from targeting prevention and screening efforts to the most highly susceptible population to developing novel chemopreventive therapies. C1 Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Ctr Canc, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO USA. RP Miller, YE (reprint author), VA Med Ctr, Respir 111A,1055 Clermont St, Denver, CO 80220 USA. NR 63 TC 7 Z9 8 U1 3 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEM RESP CRIT CARE M JI Semin. Respir. Crit. Care Med. PD APR PY 2003 VL 24 IS 2 BP 197 EP 204 DI 10.1055/s-2003-39018 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 674XY UT WOS:000182663900008 PM 16088539 ER PT J AU Mullins, ME Rhea, JT Novelline, RA AF Mullins, ME Rhea, JT Novelline, RA TI Review of suspected acute appendicitis in adults and children using CT and colonic contrast material SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID UNENHANCED HELICAL CT; LOWER QUADRANT PAIN; COMPUTED-TOMOGRAPHY; DIAGNOSING APPENDICITIS; NEGATIVE APPENDECTOMY; PERFORATION RATES; ULTRASONOGRAPHY; MANAGEMENT; EMERGENCY; SCANS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders House, Boston, MA 02114 USA. NR 60 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD APR PY 2003 VL 24 IS 2 BP 107 EP 113 DI 10.1053/sult.2003.S0887-2171(03)00017-9 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 672RW UT WOS:000182536100009 PM 12744504 ER PT J AU Ubel, PA Jepson, C Baron, J Hershey, JC Asch, DA AF Ubel, PA Jepson, C Baron, J Hershey, JC Asch, DA TI The influence of cost-effectiveness information on physicians' cancer screening recommendations SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE decision making; physician survey; cost-effectiveness; USA ID MAIL SURVEYS AB Physicians are increasingly faced with choices in which one screening strategy is both more effective and more expensive than another. One way to make such choices is to examine the cost-effectiveness of the more costly strategy over the less costly one. However, little is known about how cost-effectiveness information influences physicians' screening decisions. We surveyed 900 primary care US physicians, and presented each with a hypothetical cancer-screening scenario. We created three familiar screening scenarios, involving cervical, colon, and breast cancer. We also created three unfamiliar screening scenarios. Physicians were randomized to receive one of nine questionnaires, each containing one screening scenario. Three questionnaires posed one of the familiar screening scenarios without cost-effectiveness information, three posed one of the familiar scenarios with cost-effectiveness information, and three posed one of the unfamiliar scenarios with cost-effectiveness information. The cost-effectiveness information for familiar scenarios was drawn from the medical literature. The cost-effectiveness information for unfamiliar scenarios was fabricated to match that of a corresponding familiar scenario. In all questionnaires, physicians were asked what screening alternative they would recommend. A total of 560 physicians responded (65%). For familiar scenarios, providing cost-effectiveness information had at most a small influence on physicians' screening recommendations; it reduced the proportion of physicians recommending annual Pap smears (p = 0.003), but did not significantly alter the aggressiveness of colon cancer and breast cancer screening (both p's < 0.1). For all three unfamiliar scenarios, physicians were significantly less likely to recommend expensive screening strategies than in corresponding familiar scenarios (all p's < 0.001). Physicians' written explanations revealed a number of factors that moderated the influence of cost-effectiveness information on their screening recommendations. Providing physicians with cost-effectiveness information had only a moderate influence on their screening recommendations for cervical, colon, and breast cancer. Significantly, fewer physicians recommended aggressive screening for unfamiliar cancers than for familiar ones, despite similar cost-effectiveness. Physicians are relatively reluctant to abandon common screening strategies, even when they learn that they are expensive, and are hesitant to adopt unfamiliar screening strategies, even when they learn that they are inexpensive. Published by Elsevier Science Ltd. C1 Univ Michigan, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv, Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Ubel, PA (reprint author), Univ Michigan, Program Improving Hlth Care Decis, 300 N Ingalls,Room 7B20, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01-CA78052-01] NR 16 TC 24 Z9 24 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 2003 VL 56 IS 8 BP 1727 EP 1736 AR PII S0277-9536(02)00167-3 DI 10.1016/S0277-9536(02)00167-3 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 665HJ UT WOS:000182113700012 PM 12639589 ER PT J AU Frisbie, JH Zahn, EH AF Frisbie, JH Zahn, EH TI Earwax and level of paralysis SO SPINAL CORD LA English DT Article DE spinal cord injury; earwax; cerumen; sebum; tetraplegia; quadriplegia AB Study design: Inception cohort. Objectives: The clinical impression that earwax is uncommonly frequent among spinal cord injury patients with high levels of paralysis was tested. Setting: Veterans Administration Hospital, USA. Methods: A cohort of 15 chronically paralyzed patients, motor complete, living as residents in a long-term care facility was offered monthly irrigations of the ears for removal of wax over a 6-month period. The number of requests was tabulated. All cars were examined once on a single day to determine point prevalence. The accumulated wax graded as absent or small, moderate or large. Results: Two patients with C2 lesions, aged 37 and 52 years and paralyzed 15 and 16 years, were compared with 13 patients at C4-T6 aged 44-78 years, median 62 years, and paralyzed 2-33 years, median 24 years. Over a 6-month observation period, 10 irrigations were requested by the C2 patients and three by the C4-T6 patients. The reasons were hearing loss. Wax was found and removed, and symptoms were relieved in all instances, P<0.001. The spot survey revealed earwax of moderate or large amounts in four of four C2 patient cars and in two of 24 C4-T6 patient ears, P = 0.001. Conclusion: Patients with C2 tetraplegia accumulate more earwax and request its removal more often than patients with lower levels of paralysis. C1 Dept Vet Affairs Med Ctr, Spinal Cord Injury Serv, W Roxbury, MA 02492 USA. Dept Vet Affairs Med Ctr, Med Serv, W Roxbury, MA 02492 USA. Harvard Med Sch, Boston, MA USA. RP Frisbie, JH (reprint author), Dept Vet Affairs Med Ctr, Spinal Cord Injury Serv, 1400 Vet Foreign Wars Pkwy, W Roxbury, MA 02492 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1362-4393 J9 SPINAL CORD JI Spinal Cord PD APR PY 2003 VL 41 IS 4 BP 247 EP 248 DI 10.1038/sj.sc.3101444 PG 2 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 669YG UT WOS:000182378300007 PM 12669090 ER PT J AU Albert, ML AF Albert, ML TI Aphasia therapy works! Editorial comment SO STROKE LA English DT Editorial Material ID METAANALYSIS; EFFICACY C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol,Harold Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. RP Albert, ML (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol,Harold Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. NR 9 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2003 VL 34 IS 4 BP 992 EP 993 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 663PQ UT WOS:000182014300040 ER PT J AU Nguyen-Huynh, MN Lev, MH Rordorf, G AF Nguyen-Huynh, MN Lev, MH Rordorf, G TI Spontaneous recanalization of internal carotid artery occlusion SO STROKE LA English DT Article DE angiography; carotid artery occlusion; recanalization ID CEREBRAL INFARCTION; CT ANGIOGRAPHY; COMPLICATIONS; DISEASE AB Background and Purpose-Spontaneous recanalization of an acutely occluded internal carotid artery (ICA) is an important phenomenon, the natural history and incidence of which have been incompletely studied. Although conventional catheter arteriography remains the gold standard for distinguishing total arterial occlusion from hairline residual lumen, CT angiography (CTA) is able to make this distinction noninvasively and more sensitively than either unenhanced MR angiography or ultrasound. The purpose of this report is to raise awareness of spontaneous recanalization and to demonstrate the possible use of CTA in following up cases of ICA occlusion. Methods-We describe here 2 cases of acute cervical ICA occlusion seen on CTAs done at our institution. Results-Follow-up CTAs in both cases showed spontaneous recanalization of the ICA requiring ipsilateral carotid endarterectomy within 1 month of the initial presentation. Conclusions-CTA, an accurate, rapid, and less invasive modality than conventional catheter arteriography, can be used to serially monitor anticoagulated patients with new-onset ICA occlusion for potential spontaneous vascular recanalization. The ability to conveniently assess ICA patency not only may influence management of individual patients but also could help us better establish the true incidence of spontaneous carotid recanalization in future studies. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rordorf, G (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. NR 13 TC 29 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2003 VL 34 IS 4 BP 1032 EP 1034 DI 10.1161/01.STR.0000060872.85874.33 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 663PQ UT WOS:000182014300049 PM 12637693 ER PT J AU Prelack, K Sheridan, R Yu, YM Stamatelatos, IE Dwyer, J Dallal, GE Lydon, M Petras, L Kehayias, JJ AF Prelack, K Sheridan, R Yu, YM Stamatelatos, IE Dwyer, J Dallal, GE Lydon, M Petras, L Kehayias, JJ TI Sodium bromide by instrumental neutron activation analysis quantifies change in extracellular water space with wound closure in severely burned children SO SURGERY LA English DT Article ID GROWTH-HORMONE; BODY-COMPOSITION; NUTRITIONAL REHABILITATION; METABOLIC RESPONSE; CHLORIDE; DILUTION; INFANTS; VOLUME; SALIVA; TISSUES AB Background. The ability to measure extracellular water (ECW) in critically ill patients can significantly enhance current methods of assessing fluid homeostasis, body composition, and response to nutritional therapy. We measured corrected bromide space to determine change in ECW with wound closure among acutely burned children. Methods. Fifteen children with burns over 30% of their total body surface area had their ECW determined following hemodynamic stabilization and when wound closure was complete. Plasma samples were obtained at baseline and 4 hours after receiving 25 mg/kg of sodium bromide. Plasma bromide was quantified by instrumental neutron activation analysis. Results. Mean CBS decreased with wound closure (9.1 +/- 4.1 vs 7.9 +/- 3.9 liters; P =.04), indicating a significant decrease in ECW over the course of recovery. A decline in weight also occurred over the same period (32.4 +/- 15.2 vs 29.1 +/- 13.5 kg; P =.007); however, change in corrected bromide space as a proportion of weight was not statistically significant. Conclusion. A significant decrease in ECW accompanies the weight loss observed in patients following wound closure. Measurement of bromide dilution space is a convenient method for monitoring ECW that can be done at the bedside. C1 Tufts Univ, Shriners Hosp Children, Boston, MA 02114 USA. Tufts Univ, Frances Stern Nutr Ctr, Boston, MA 02114 USA. Tufts Univ, Tufts New England Med Ctr, Boston, MA 02114 USA. Tufts Univ, Jean Mayer USDA Human Res Ctr Aging, Boston, MA 02114 USA. Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCSR Demokritos, Inst Nucl Technol & Radiat Protect, Aghia Paraskevi, Greece. RP Prelack, K (reprint author), Tufts Univ, Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 44 TC 4 Z9 4 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2003 VL 133 IS 4 BP 396 EP 403 DI 10.1067/msy.2003.108 PG 8 WC Surgery SC Surgery GA 674MN UT WOS:000182640700010 PM 12717357 ER PT J AU Nasseri, BA Pomerantseva, I Kaazempur-Mofrad, MR Sutherland, FWH Perry, T Ochoa, E Thompson, CA Mayer, JE Oesterle, SN Vacanti, JP AF Nasseri, BA Pomerantseva, I Kaazempur-Mofrad, MR Sutherland, FWH Perry, T Ochoa, E Thompson, CA Mayer, JE Oesterle, SN Vacanti, JP TI Dynamic rotational seeding and cell culture system for vascular tube formation SO TISSUE ENGINEERING LA English DT Article ID GROWN IN-VITRO; PULMONARY-ARTERY; BLOOD-VESSEL; TISSUE; CARTILAGE AB Optimization of cell seeding and culturing is an important step for the successful tissue engineering of vascular conduits. We evaluated the effectiveness of using a hybridization oven for rotational seeding and culturing of ovine vascular myofibroblasts onto biodegradable polymer scaffolds suitable for replacement of small- and large-diameter blood vessels. Large tubes ( 12 mm internal diameter and 60 mm length, n = 4) and small tubes (5 mm internal diameter and 20 mm length, n = 4) were made from a combination of polyglycolic acid/poly-4-hydroxybutyrate and coated with collagen solution. Tubes were then placed in culture vessels containing a vascular myofibroblast suspension (10(6) cells/cm(2)) and rotated at 5 rpm in a hybridization oven at 37degreesC. Light and scanning electron microscopy analyses were performed after 5, 7, and 10 days. Myofibroblasts had formed confluent layers over the outer and inner surfaces of both large and small tubular scaffolds by day 5. Cells had aligned in the direction of flow by day 7. Multiple spindle-shaped cells were observed infiltrating the polymer mesh. Cell density increased between day 5 and day 10. All conduits maintained their tubular shape throughout the experiment. We conclude that dynamic rotational seeding and culturing in a hybridization oven is an easy, effective, and reliable method to deliver and culture vascular myofibroblasts onto tubular polymer scaffolds. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. MIT, Dept Mech, Cambridge, MA 02139 USA. MIT, Dept Biol Engn, Cambridge, MA 02139 USA. Childrens Hosp, Dept Cardiovasc Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Vacanti, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 16 TC 62 Z9 66 U1 0 U2 11 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 APR PY 2003 VL 9 IS 2 BP 291 EP 299 DI 10.1089/107632703764664756 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 669DG UT WOS:000182336200010 PM 12740091 ER PT J AU Bush, AI AF Bush, AI TI The metallobiology of Alzheimer's disease SO TRENDS IN NEUROSCIENCES LA English DT Review ID AMYLOID PRECURSOR PROTEIN; A-BETA; OXIDATIVE DAMAGE; TRANSGENIC MICE; CEREBRAL-CORTEX; SUPEROXIDE-DISMUTASE; CATALYZED OXIDATION; CEREBROSPINAL-FLUID; SYNAPTIC VESICLES; HYDROGEN-PEROXIDE AB The cause of Alzheimer's disease (AD) is closely related to the aggregation of a normal protein, beta-amyloid (Abeta), within the neocortex. Recently, evidence has been gathered to suggest that Abeta precipitation and toxicity in AD are caused by abnormal interactions with neocortical metal ions, especially Zn, Cu and Fe. However, Abeta might also participate in normal metal-ion homeostasis. An inevitable, age-dependent rise in brain Cu and Fe might hypermetallate the Abeta peptide, causing the catalysis of H2O2 production that mediates the toxicity and auto-oxidation of Abeta. The greater incidence of AD in females could be due to greater constitutive activity of the synaptic Zn transporter ZnT3, and attenuated binding of metal ions to the rodent homologue of Abeta might explain why these animals are spared Alzheimer's pathology. Compounds that interdict metal-ion binding to Abeta dissolve brain deposits in vitro and one such compound, clioquinol, inhibits Abeta deposition in the Tg2576 mouse model for AD and could be useful clinically. These insights could also apply to other degenerative disorders in which metal-ion-protein interactions have been implicated. C1 Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Univ Melbourne, Oxidat Disorders Res Unit, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [2R01 AG 12686] NR 78 TC 773 Z9 798 U1 21 U2 144 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD APR PY 2003 VL 26 IS 4 BP 207 EP 214 DI 10.1016/S0166-2236(03)00067-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 671ZR UT WOS:000182496100011 PM 12689772 ER PT J AU Freedland, SJ Presti, JC Amling, CL Kane, CJ Aronson, WJ Dorey, F Terris, MK AF Freedland, SJ Presti, JC Amling, CL Kane, CJ Aronson, WJ Dorey, F Terris, MK CA Search Database Study Grp TI Time trends in biochemical recurrence after radical prostatectomy: Results of the search database SO UROLOGY LA English DT Article ID SEXTANT BIOPSIES; EXTRACAPSULAR EXTENSION; CANCER INCIDENCE; ANTIGEN; RATES; MORTALITY; STAGE; DISEASE; ERA AB Objectives. To determine whether in the prostate-specific antigen (PSA) era stage and/or grade migration of patients treated with radical prostatectomy (RP) has occurred. We also examined whether the biochemical recurrence rates after RIP have changed with time. Methods. A total of 1654 patients from the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed for time trends in age, preoperative PSA level, clinical stage, biopsy Gleason score, prostatectomy Gleason grade, pathologic stage, margin status, and recurrence rates after RP. Results were stratified into three 4-year blocks of time between 1988 and 2002 for analysis. Results. The preoperative PSA level, patient age, tumor stage, rate of capsular penetration, and lymph node involvement decreased with time. Both biopsy and pathologic Gleason grade steadily increased with time. The positive margin rate and incidence of seminal vesicle involvement remained stable. On multivariate analysis, only serum PSA level (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of the time to recurrence after RP. The year of surgery was not a significant independent predictor of biochemical recurrence after RP in multivariate analysis. Conclusions. Despite lower stage and lower PSA levels with time, we found no improvement in PSA recurrence rates over time. This may reflect lead-time bias in detecting PSA recurrence by the use of more sensitive PSA assays. in recent years. (C) 2003, Elsevier Science Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Sch Med, Dept Urol, San Francisco, CA 94143 USA. USN, Med Ctr, Dept Urol, San Diego, CA 92152 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, 10833 Le Comte Ave,66-124 CHS,Box 951738, Los Angeles, CA 90095 USA. OI Terris, Martha/0000-0002-3843-7270 NR 27 TC 73 Z9 77 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 APR PY 2003 VL 61 IS 4 BP 736 EP 741 DI 10.1016/S0090-4295(02)02526-8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 666TX UT WOS:000182193500015 PM 12670557 ER PT J AU Freedland, SJ Aronson, WJ Csathy, GS Kane, CJ Amling, CL Presti, JC Dorey, F Terris, MK AF Freedland, SJ Aronson, WJ Csathy, GS Kane, CJ Amling, CL Presti, JC Dorey, F Terris, MK CA Search Database Study Grp TI Comparison of percentage of total prostate needle biopsy tissue with cancer to percentage of cores with cancer for predicting PSA recurrence after radical prostatectomy: Results from the search database SO UROLOGY LA English DT Article ID SEXTANT BIOPSIES; EXTRACAPSULAR EXTENSION; CLINICAL UTILITY; RELAPSE; RISK AB Objectives. Tumor volume in the prostate needle biopsy is an important prognosticator for patients with prostate cancer. However, the best method to measure tumor volume in the prostate needle biopsy is unknown. We compared the total percentage of biopsy tissue with cancer to the percentage of cores positive for their ability to predict adverse pathologic findings and biochemical failure after radical prostatectomy (RP). Methods. A retrospective survey of 355 patients from the Shared Equal Access Regional Cancer Hospital database treated with RID between 1990 and 2002 was undertaken. Multivariate analysis was used to compare the percentage of cores and percentage of tissue with cancer to the standard clinical variables of age, prostate-specific antigen (PSA) level, biopsy Gleason score, and clinical stage for their ability to predict positive surgical margins, non-organ-confined disease, seminal vesicle invasion, and time to PSA recurrence after RP. Results. On multivariate analysis, the percentage of tissue with cancer significantly predicted non-organ-confined disease and seminal vesicle invasion, but the percentage of cores did not significantly predict any of the pathologic features examined. In separate multivariate analysis, only the percentage of tissue with cancer, but not the percentage of cores with cancer, significantly predicted PSA failure. Moreover, when compared in the same multivariate analysis, only the percentage of tissue with cancer (hazard ratio 8.25, 95% confidence interval 3.06 to 22.22, P <0.001) was a significant predictor. The area under the receiver operating curves for predicting PSA failure was significantly greater for the percentage of tissue with cancer (0.697) than for the percentage of cores (0.644, P = 0.022). Cutpoints for the percentage of tissue with cancer (less than 20%, 20% to 40%, and greater than 40%) and the percentage of cores (less than 34%, 34% to 50%, greater than 50%) both provided significant preoperative risk stratification for biochemical failure, although the percentage of tissue with cancer cutpoints provided better risk stratification (higher hazard ratios and lower P value). Cutpoints for the percentage of tissue with cancer but not the percentage of cores positive further stratified patients who were at low (P = 0.041), intermediate (P = 0.002), and high (P = 0.023) risk on the basis of the PSA level and biopsy Gleason score. Conclusions. The percentage of tissue with cancer was better than the percentage of cores at predicting advanced pathologic features and PSA recurrence after RP. Unlike the percentage of cores, the percentage of tissue with cancer cutpoints further stratified low, intermediate, and high-risk patients on the basis of PSA level and biopsy Gleason score. Although the percentage of tissue with cancer is a slightly more cumbersome measurement than the percentage of positive cores, it provided statistically and clinically superior preoperative risk stratification for biochemical failure after RP. (C) 2003, Elsevier Science Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg & Pathol, Los Angeles, CA USA. USN, Med Ctr, Dept Urol, San Diego, CA 92152 USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, 10833 Le Conte Ave,66-124 CHS,Box 951738, Los Angeles, CA 90095 USA. OI Terris, Martha/0000-0002-3843-7270 NR 15 TC 45 Z9 47 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD APR PY 2003 VL 61 IS 4 BP 742 EP 747 DI 10.1016/S0090-4295(02)02525-6 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 666TX UT WOS:000182193500016 PM 12670558 ER PT J AU Wilkinson, D Halligan, P AF Wilkinson, D Halligan, P TI The effects of stimulus size on bisection judgements in near and far space SO VISUAL COGNITION LA English DT Article ID LEFT VISUOSPATIAL NEGLECT; LINE BISECTION; VISUAL NEGLECT; EXTRAPERSONAL SPACE; UNILATERAL NEGLECT; PSEUDONEGLECT; ATTENTION; ASYMMETRIES; DISTANCE; CORTEX AB Primate data suggest that near (peripersonal) and far (extrapersonal) space are coded within distinct representations. Support for this claim has been gained from human studies of line bisection, many of which have focused on neuropsychological, rather than normative, samples. One important aspect of these bisection studies has been to control for the changes in angular extent of stimuli that normally accompany changes in viewing distance. The control of angular information, however, requires alterations in the linear dimensions (actual stimulus size) of stimuli. We report two experiments in which normal subjects made manual bisection judgements on stimuli positioned in near or far space, and which were oriented in either the left-right (Experiment 1) or radial plane (Experiment 2). Both experiments were designed to enable the separable effects of linear and angular extent to be disentangled. Viewing distance effects were obtained when angular information was controlled, but many of these were dependent on changes in linear extent, and were only apparent at the individual subject level. Our data confirm that genuine near/far effects may be observed in normative bisection, but that many previous studies which appeared to support a near/far distinction in both normal and brain-damaged bisection behaviour may reflect a failure to control for changes in stimulus size. C1 Univ Oxford, Dept Expt Psychol, Oxford OX1 2JD, England. Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales. RP Wilkinson, D (reprint author), VA Boston Healthcare Syst, GRECC, Geriatr Neuropsychol Lab, 150 S Huntington Ave, Boston, MA 02130 USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1350-6285 J9 VIS COGN JI Vis. Cogn. PD APR PY 2003 VL 10 IS 3 BP 319 EP 340 DI 10.1080/13506280244000113 PG 22 WC Psychology, Experimental SC Psychology GA 667LW UT WOS:000182234500003 ER PT J AU Collins, MM AF Collins, MM TI The impact of chronic prostatitis/chronic pelvic pain syndrome on patients SO WORLD JOURNAL OF UROLOGY LA English DT Article DE prostatitis; health related quality of life; chronic pain ID QUALITY-OF-LIFE; NONBACTERIAL PROSTATITIS; SYMPTOM INDEX; QUESTIONNAIRE; VALIDATION AB Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common condition, affecting men of all ages. Since mortality and serious complications are extremely uncommon, CP/CPPS is primarily a quality-of-life disease, and, therefore, the patient's perspective is of paramount importance. As with other non-life threatening diseases, the goal of treatment is to maximize quality not quantity of life. Scientifically validated methods to measure patients' health related quality of life have been applied in other urological diseases such as benign prostatic hyperplasia and interstitial cystitis; the same process is now underway in the study of CP/CPPS. Recent studies have shown that CP/CPPS takes a substantial toll on physical and mental health. In addition to examining the health related quality of life of patients with CP/CPPS, future studies should address additional patient-centered outcomes, such as satisfaction with care and the economic burden of the illness, in order to allow a more comprehensive understanding of the impact of this condition on patients. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 20 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD APR PY 2003 VL 21 IS 2 BP 86 EP 89 DI 10.1007/s00345-003-0331-6 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 692AY UT WOS:000183639200008 ER PT J AU Takahashi, S Riley, DE Krieger, JN AF Takahashi, S Riley, DE Krieger, JN TI Application of real-time polymerase chain reaction technology to detect prostatic bacteria in patients with chronic prostatitis/chronic pelvic pain syndrome SO WORLD JOURNAL OF UROLOGY LA English DT Article DE chronic prostatitis; chronic pelvic pain syndrome; bacteria; polymerase chain reaction ID DNA-SEQUENCES; RESPIRATORY SPECIMENS; RAPID DETECTION; PCR ASSAYS; LIGHTCYCLER; MEN; TISSUE AB To investigate the potential association between prostate infection and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we used molecular approaches described in previous reports. These methods employed standard polymerase chain (PCR) reaction assays to provide a qualitative evaluation of prostatic bacterial species. Here, we report on the detection of prostatic bacteria using a real-time PCR. Template DNAs were examined from prostatic tissue samples from patients with CP/CPPS. Two PCR primer sets were used: one that amplifies a portion of all known bacterial ribosomal DNAs (16S rDNAs) and one that is specific for Escherichia coli as opposed to related, E. coli-like bacteria. The 16S rDNA real-time PCR assay detected bacterial DNAs in eight (26%) of 31 samples from patients with CP/CPPS, including three samples (10%) that were also positive by the E. coli real-time PCR assay. These E. coli positives were quantified at approximately 10(3) cfu/ml of tissue digested. Quantification, speed and specificity make real-time PCR a promising approach for the quantitative detection and identification of prostatic bacteria from CP/CPPS patients. C1 Univ Washington, Sch Med, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Krieger, JN (reprint author), Univ Washington, Sch Med, Dept Urol, VA Puget Sound Hlth Care Syst, 112-GU,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK38955] NR 20 TC 8 Z9 11 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD APR PY 2003 VL 21 IS 2 BP 100 EP 104 DI 10.1007/s00345-003-0326-3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 692AY UT WOS:000183639200011 PM 12743735 ER PT J AU Cavacini, L Duval, M Song, L Sangster, R Xiang, SH Sodroski, J Posner, M AF Cavacini, L Duval, M Song, L Sangster, R Xiang, SH Sodroski, J Posner, M TI Conformational changes in env oligomer induced by an antibody dependent on the V3 loop base SO AIDS LA English DT Article DE env oligomer; conformational changes; monoclonal antibody ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZATION EPITOPES; RECEPTOR-BINDING; VARIABLE LOOPS; HIV-1; VIRIONS; REGION; INTACT AB Objective: The HIV-1 env oligomer is structured such that conserved, neutralizing epitopes are obscured by gp120 variable loops. We have studied the ability of an IgG2 human monoclonal antibody (hmAb), F425 B4e8 (B4e8), dependent upon the base of the V3 loop, to induce conformational changes in the env oligomer. Design: The effect of B4e8 antibody on the exposure of neutralizing epitopes and viral neutralization was studied in combination with other hmAb. Methods: Epitope exposure and viral neutralization was determined using native, intact primary isolate virions. Results: B4e8 antibody neutralizes infection and binds to HIV-infected cells and primary isolate virions. B4e8 and 2G12 enhanced the binding of each other to infected cells or virus and the combination resulted in synergistic neutralization. B4e8 also enhanced the binding of CD4i and CD4 binding site antibodies. Conclusions: The conserved epitopes exposed by B4e8 are similar to those exposed by the movement of the variable loops following CD4 engagement. Further studies with select antibody combinations should provide important information for the design of effective immunotherapeutic agents. (C) 2003 Lippincott Williams Wilkins. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. RP Cavacini, L (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, 330 Brookline Ave,Burl556, Boston, MA 02215 USA. FU NIAID NIH HHS [AI24030, AI24755, AI26926, AI31783, AI41851, AI42848, AI45320, AI46725] NR 32 TC 43 Z9 43 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 MAR 28 PY 2003 VL 17 IS 5 BP 685 EP 689 DI 10.1097/01.aids.0000050822.06065.4a PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 673EF UT WOS:000182566700006 PM 12646791 ER PT J AU Shin, H Wyszynski, M Huh, KH Valtschanoff, JG Lee, JR Ko, J Streuli, M Weinberg, RJ Sheng, M Kim, E AF Shin, H Wyszynski, M Huh, KH Valtschanoff, JG Lee, JR Ko, J Streuli, M Weinberg, RJ Sheng, M Kim, E TI Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AXONAL-TRANSPORT; C-ELEGANS; MEMBRANE-TRANSPORT; VESICLE TRANSPORT; MONOMERIC MOTOR; AMPA RECEPTORS; FAMILY; GRIP; UNC-104; DOMAIN AB Liprin-alpha/SYD-2 is a multimodular scaffolding protein important for presynaptic differentiation and postsynaptic targeting of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid glutamate receptors. However, the molecular mechanisms underlying these functions remain largely unknown. Here we report that liprin-a interacts with the neuron-specific kinesin motor KIF1A. KIF1A colocalizes with liprin-alpha in various subcellular regions of neurons. KIF1A coaccumulates with liprin-alpha in ligated sciatic nerves. KIF1A cofractionates and coimmunopreciptates with liprin-a and various liprin-alpha-associated membrane, signaling, and scaffolding proteins including alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors, GRIP/ABP, RIM, GIT1, and betaPIX. These results suggest that liprin-alpha functions as a KIF1A receptor, linking KIF1A to various liprin-alpha-associated proteins for their transport in neurons. C1 Korea Adv Inst Sci & Technol, Dept Sci Biol, Taejon 305701, South Korea. MIT, Ctr Learning & Memory, RIKEN, Ctr Res Neurosci, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kim, E (reprint author), Korea Adv Inst Sci & Technol, Dept Sci Biol, Taejon 305701, South Korea. RI Kim, Eunjoon/C-1566-2011; OI Weinberg, Richard/0000-0001-9689-7278 NR 56 TC 110 Z9 115 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 28 PY 2003 VL 278 IS 13 BP 11393 EP 11401 DI 10.1074/jbc.M211874200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 660VU UT WOS:000181855400068 PM 12522103 ER PT J AU Xu, HS Zhao, HY Tian, W Yoshida, K Roullet, JB Cohen, DM AF Xu, HS Zhao, HY Tian, W Yoshida, K Roullet, JB Cohen, DM TI Regulation of a transient receptor potential (TRP) channel by tyrosine phosphorylation - Src family kinase-dependent tyrosine phosphorylation of TRPV4 on Tyr-253 mediates its response to hypotonic stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHLORIDE CURRENT; CATION CHANNELS; PROTEIN-KINASE; CELL-LINE; ACTIVATION; SITES; EXPRESSION; SEQUENCE; MOUSE AB The recently identified transient receptor potential (TRP) channel family member, TRPV4 (formerly known as OTRPC4, VR-OAC, TRP12, and VRL-2) is activated by hypotonicity. It is highly expressed in the kidney as well as blood-brain barrier-deficient hypothalamic nuclei responsible for systemic osmosensing. Apart from its gating by hypotonicity, little is known about TRPV4 regulation. We observed that hypotonic stress resulted in rapid tyrosine phosphorylation of TRPV4 in a heterologous expression model and in native murine distal convoluted tubule cells in culture. This tyrosine phosphorylation was sensitive to the inhibitor of Src family tyrosine kinases, PP1, in a dose-dependent fashion. TRPV4 associated with Src family kinases by co-immunoprecipitation studies and confocal immunofluorescence microscopy, and this interaction required an intact Src family kinase SH2 domain. One of these kinases, Lyn, was activated by hypotonic stress and phosphorylated TRPV4 in an immune complex kinase assay and an in vitro kinase assay using recombinant Lyn and TRPV4. Transfection of wild-type Lyn dramatically potentiated hypotonicity-dependent TRPV4 tyrosine phosphorylation whereas dominant negative-acting Lyn modestly inhibited it. Through mutagenesis studies, the site of tonicity-dependent tyrosine phosphorylation was mapped to Tyr-253, which is conserved across all species from which TRPV4 has been cloned. Importantly, point mutation of Tyr-253 abolished hypotonicity-dependent channel activity. In aggregate, these data indicate that hypotonic stress results in Src family tyrosine kinase-dependent tyrosine phosphorylation of the tonicity sensor TRPV4 at residue Tyr-253 and that this residue is essential for channel function in this context. This is the first example of direct regulation of TRP channel function through tyrosine phosphorylation. 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. Vet Affairs Med Ctr, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Nephrol, Mailcode PP262,3314SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIDDK NIH HHS [DK52494] NR 41 TC 127 Z9 141 U1 3 U2 8 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 MAR 28 PY 2003 VL 278 IS 13 BP 11520 EP 11527 DI 10.1074/jbc.M211061200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 660VU UT WOS:000181855400084 PM 12538589 ER PT J AU Zimmerman, RK Raymund, M Janosky, JE Nowalk, MP Fine, MJ AF Zimmerman, RK Raymund, M Janosky, JE Nowalk, MP Fine, MJ TI Sensitivity and specificity of patient self-report of influenza and pneumococcal polysaccharide vaccinations among elderly outpatients in diverse patient care strata SO VACCINE LA English DT Article DE validity; vaccination; self-report ID QUESTIONNAIRE; VALIDATION AB National surveys of adult vaccination indicate moderate self-reported immunization rates in the US, with limited validity data. We compared self-report with medical record abstraction for 820 persons aged greater than or equal to66 years from inner-city health centers, Veterans Affairs (VA) outpatient clinics, rural and suburban practices. For influenza vaccine, sensitivity was 98% (95% CI: 96-99%); specificity was 38% (95% CI: 33-43%). For pneurnococcal polysaccharide vaccine, sensitivity was 85% (95% CI: 82-89%) and specificity was 46% (95% CI: 42-50%). The VA had the highest sensitivity and lowest specificity for both vaccines while the converse was true in inner-city centers. High negative predictive values indicate that clinicians can confidently vaccinate based on negative patient self-report. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav Sci & Community Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Zimmerman, RK (reprint author), Univ Pittsburgh, Sch Med, Dept Family Med & Clin Epidemiol, 3518 5th Ave, Pittsburgh, PA 15261 USA. OI Zimmerman, Richard/0000-0001-5941-6092 NR 16 TC 168 Z9 179 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 28 PY 2003 VL 21 IS 13-14 BP 1486 EP 1491 AR PII S0264-410X(02)00700-4 DI 10.1016/S0264-410X(02)00700-4 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 663LV UT WOS:000182007800023 PM 12615445 ER PT J AU Shimizu, K Chen, W Ashique, AM Moroi, R Li, YP AF Shimizu, K Chen, W Ashique, AM Moroi, R Li, YP TI Molecular cloning, developmental expression, promoter analysis and functional characterization of the mouse CNBP gene SO GENE LA English DT Article DE transcriptional regulation; chromosomal localization; zinc-finger protein; proliferation; c-Myc ID ACID-BINDING-PROTEIN; XENOPUS-LAEVIS; C-MYC; ANTERIOR NEUROECTODERM; FINGER PROTEIN; MESSENGER-RNA; IDENTIFICATION; ELEMENT; EMBRYO; CDNA AB Striking conservation in various organisms suggests that cellular nucleic acid-binding protein (CNBP) plays a fundamental biological role across different species. However, the regulated expression and physiological properties of the CNBP gene are unknown. In this study, we report the molecular cloning, promoter characterization, developmental expression and functional analysis of the mouse CNBP gene. The gene contains five exons and is localized to chromosome 6 in the region corresponding to band 6 D1-D2. Primer extension assay indicates that the transcription start site is located 230 bp upstream of the initiator Met codon. Our promoter analysis indicates that strong transcription enhancer and silencer regions lie within the 1.6 kb proximal region of the promoter and the upstream -3.0 to -1.6 kb region, respectively. The promoter activity is 10 fold higher in embryonic carcinoma cells than that in fibroblast, as determined by CAT assay. Consistent with its function as a transcription factor, CNBP protein is located in the nucleus of cells. During mouse embryogenesis, CNBP is expressed in the anterior region of the early embryo and in the limb, tail and craniofacial region. Overexpression of CNBP strongly stimulates cell proliferation and increases c-myc promoter activity. Our finds suggest that CNBP may play an important role in cell proliferation and tissue patterning during anterior-posterior axis, craniofacial and limb development by targeting c-Myc. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Forsyth Dent Ctr, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Li, YP (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR44741, AR48133] NR 39 TC 32 Z9 34 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 27 PY 2003 VL 307 BP 51 EP 62 DI 10.1016/S0378-1119(03)00406-2 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 677EC UT WOS:000182793100006 PM 12706888 ER PT J AU Husain, SS Ziebell, MR Ruesch, D Hong, F Arevalo, E Kosterlitz, JA Olsen, RW Forman, SA Cohen, JB Miller, KW AF Husain, SS Ziebell, MR Ruesch, D Hong, F Arevalo, E Kosterlitz, JA Olsen, RW Forman, SA Cohen, JB Miller, KW TI 2-(3-methyl-3H-diaziren-3-yl) ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate: A derivative of the stereoselective general anesthetic etomidate for photolabeling ligand-gated ion channels SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GAMMA-AMINOBUTYRIC-ACID; GLYCINE RECEPTORS; GABA(A) RECEPTORS; SELF-INHIBITION; RICH MEMBRANES; AMINO-ACID; MODULATION; TORPEDO; BINDING AB To locate general anesthetic binding sites on ligand-gated ion channels, a diazirine derivative of the potent intravenous anesthetic, R-(+)-etomidate (2-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate), has been synthesized and characterized. R-(+)-Azietomidate [2-(3-methyl-3H-diaziren-3-yl)ethyl 1-(l-phenylethyl)-1H-imidazole-5-carboxylate] anesthetizes tadpoles with an EC50 of 2.2 muM, identical to that of R-(+)-etomidate. At this concentration both agents equally enhanced GABA-induced currents and decreased binding of the caged-convulsant [S-35]TBPS to GABA(A) receptors. In all of the above actions R-(+)-azietomidate is about an order of magnitude more potent than S-(-)-azietomidate, an enantioselectivity comparable to etomidate's. R-(+)-Azietomidate also inhibits acetylcholine-induced currents in nicotinic acetylcholine receptors, with about twice the potency of the parent compound. [H-3]Azietomidate photoincorporated into Torpedo nicotinic acetylcholine receptor-rich membranes. Desensitization decreased photoincorporation into the delta-subunit and increased that into the alpha-subunit. The latter increase was confined to a proteolytic fragment containing the first three transmembrane segments. Thus, R-(+)-azietomidate is a potent stereoselective general anesthetic and an effective photolabel. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu FU NIGMS NIH HHS [GM58448] NR 50 TC 59 Z9 60 U1 2 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 27 PY 2003 VL 46 IS 7 BP 1257 EP 1265 DI 10.1021/jm020465v PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 658YY UT WOS:000181749900020 PM 12646036 ER PT J AU Cole, GM AF Cole, GM TI Ironic fate: Can a banned drug control metal heavies in neurodegenerative diseases? SO NEURON LA English DT Editorial Material C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Alzheimers Dis Res Ctr, Sepulveda, CA 91343 USA. RP Cole, GM (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Alzheimers Dis Res Ctr, Sepulveda, CA 91343 USA. NR 12 TC 14 Z9 14 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 MAR 27 PY 2003 VL 37 IS 6 BP 889 EP 890 DI 10.1016/S0896-6273(03)00160-0 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 661PU UT WOS:000181899600001 PM 12670416 ER PT J AU Kaur, D Yantiri, F Rajagopalan, S Kumar, J Mo, JO Boonplueang, R Viswanath, V Jacobs, R Yang, L Beal, MF DiMonte, D Volitaskis, I Ellerby, L Cherny, RA Bush, AI Andersen, JK AF Kaur, D Yantiri, F Rajagopalan, S Kumar, J Mo, JO Boonplueang, R Viswanath, V Jacobs, R Yang, L Beal, MF DiMonte, D Volitaskis, I Ellerby, L Cherny, RA Bush, AI Andersen, JK TI Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: A novel therapy for Parkinson's disease SO NEURON LA English DT Article ID SUBSTANTIA-NIGRA; BASAL GANGLIA; BRAIN IRON; RAT-BRAIN; CELLULAR-DISTRIBUTION; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; FREE-RADICALS; MOUSE MODEL; DOPAMINERGIC NEURODEGENERATION AB Studies on postmortem brains from Parkinson's patients reveal elevated iron in the substantia nigra (SN). Selective cell death in this brain region is associated with oxidative stress, which may be exacerbated by the presence of excess iron. Whether iron plays a causative role in cell death, however, is controversial. Here, we explore the effects of iron chelation via either transgenic expression of the iron binding protein ferritin or oral administration of the bioavailable metal chelator clioquinol (CO) on susceptibility to the Parkinson's-inducing agent 1 -methyl-4-phenyl-1,2,3,6-tetrapyridine (MPTP). Reduction in reactive iron by either genetic or pharmacological means was found to be well tolerated in animals in our studies and to result in protection against the toxin, suggesting that iron chelation may be an effective therapy for prevention and treatment of the disease. C1 Buck Inst Age Res, Novato, CA 94945 USA. Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Div Neurogerontol, Los Angeles, CA 90089 USA. CALTECH, Biol Imaging Ctr, Pasadena, CA 91125 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Parkinsons Inst, Sunnyvale, CA 94089 USA. Univ Melbourne, Mental Hlth Res Inst, Dept Pathol, Parkville, Vic 3052, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Lab Oxidant Biol, Dept Psychiat,Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Andersen, JK (reprint author), Buck Inst Age Res, Novato, CA 94945 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [2R01AG12686, R01 AG12141, R01 AG41264] NR 89 TC 378 Z9 387 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 27 PY 2003 VL 37 IS 6 BP 899 EP 909 DI 10.1016/S0896-6273(03)00126-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 661PU UT WOS:000181899600005 PM 12670420 ER PT J AU Cools, J DeAngelo, DJ Gotlib, J Stover, EH Legare, RD Cortes, J Kutok, J Clark, J Galinsky, I Griffin, JD Cross, NCP Tefferi, A Malone, J Alam, R Schrier, SL Schmid, J Rose, M Vandenberghe, P Verhoef, G Boogaerts, M Wlodarska, I Kantarjian, H Marynen, P Coutre, SE Stone, R Gilliland, DG AF Cools, J DeAngelo, DJ Gotlib, J Stover, EH Legare, RD Cortes, J Kutok, J Clark, J Galinsky, I Griffin, JD Cross, NCP Tefferi, A Malone, J Alam, R Schrier, SL Schmid, J Rose, M Vandenberghe, P Verhoef, G Boogaerts, M Wlodarska, I Kantarjian, H Marynen, P Coutre, SE Stone, R Gilliland, DG TI A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; FACTOR RECEPTOR-BETA; BCR-ABL; CLINICAL RESISTANCE; BLAST CRISIS; IN-VITRO; C-KIT; GROWTH; INHIBITOR AB BACKGROUND: Idiopathic hypereosinophilic syndrome involves a prolonged state of eosinophilia associated with organ dysfunction. It is of unknown cause. Recent reports of responses to imatinib in patients with the syndrome suggested that an activated kinase such as ABL, platelet-derived growth factor receptor (PDGFR), or KIT, all of which are inhibited by imatinib, might be the cause. METHODS: We treated 11 patients with the hypereosinophilic syndrome with imatinib and identified the molecular basis for the response. RESULTS: Nine of the 11 patients treated with imatinib had responses lasting more than three months in which the eosinophil count returned to normal. One such patient had a complex chromosomal abnormality, leading to the identification of a fusion of the Fip1-like 1 (FIP1L1) gene to the PDGFR(alpha) (PDGFRA) gene generated by an interstitial deletion on chromosome 4q12. FIP1L1-PDGFR(alpha) is a constitutively activated tyrosine kinase that transforms hematopoietic cells and is inhibited by imatinib (50 percent inhibitory concentration, 3.2 nM). The FIP1L1-PDGFRA fusion gene was subsequently detected in 9 of 16 patients with the syndrome and in 5 of the 9 patients with responses to imatinib that lasted more than three months. Relapse in one patient correlated with the appearance of a T674I mutation in PDGFRA that confers resistance to imatinib. CONCLUSIONS: The hypereosinophilic syndrome may result from a novel fusion tyrosine kinase - FIP1L1-PDGFR(alpha) - that is a consequence of an interstitial chromosomal deletion. The acquisition of a T674I resistance mutation at the time of relapse demonstrates that FIP1L1-PDGFR(alpha) is the target of imatinib. Our data indicate that the deletion of genetic material may result in gain-of-function fusion proteins. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA. Brown Univ, Women & Infants Hosp, Sch Med, Providence, RI USA. Westerly Hosp, Westerly, RI USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Wessex Reg Genet Lab, Salisbury, Wilts, England. Mayo Clin, Rochester, MN USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Tulane Univ, Sch Med, New Orleans, LA 70112 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Hosp Leuven, Louvain, Belgium. Flanders Interuniv Inst Biotechnol, Louvain, Belgium. Catholic Univ Louvain, Ctr Human Genet, B-3000 Louvain, Belgium. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Inst Med, 4 Blackfan Cir,Rm 418, Boston, MA 02115 USA. RI Cross, Nicholas/B-4817-2009; OI Cross, Nicholas/0000-0001-5481-2555; Vandenberghe, Peter/0000-0003-4719-1935 FU NCI NIH HHS [CA66996]; NHLBI NIH HHS [K23HL04409]; NIDDK NIH HHS [DK50654]; NIGMS NIH HHS [T32 GM007753, T32GMO7753-24] NR 29 TC 1069 Z9 1131 U1 6 U2 20 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 MAR 27 PY 2003 VL 348 IS 13 BP 1201 EP 1214 DI 10.1056/NEJMoa025217 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 659RG UT WOS:000181790800002 PM 12660384 ER PT J AU Foss, FM Aquino, SL Ferry, JA Harris, NL Park, D Spitzer, TR Colvin, RB AF Foss, FM Aquino, SL Ferry, JA Harris, NL Park, D Spitzer, TR Colvin, RB TI Case 10-2003: A 72-year-old man with rapidly progressive leukemia, rash, and multiorgan failure - Adult T-cell leukemia-lymphoma, HTLV-I-associated, acute form SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENDEMIC AREA; VIRUS-I; MONOCLONAL-ANTIBODY; LEUKEMIA/LYMPHOMA; PATIENT; STRONGYLOIDIASIS; TRANSPLANTATION; OVEREXPRESSION; INTERLEUKIN-2; COMBINATION C1 Tufts Univ New England Med Ctr, Dept Hematol Oncol, Boston, MA 02111 USA. Tufts Univ, Med Ctr, Dept Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foss, FM (reprint author), Tufts Univ New England Med Ctr, Dept Hematol Oncol, 750 Washington St, Boston, MA 02111 USA. NR 29 TC 8 Z9 9 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 MAR 27 PY 2003 VL 348 IS 13 BP 1267 EP 1275 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 659RG UT WOS:000181790800009 PM 12660391 ER PT J AU Mezrich, JD Haller, GW Arn, JS Houser, SL Madsen, JC Sachs, DH AF Mezrich, JD Haller, GW Arn, JS Houser, SL Madsen, JC Sachs, DH TI Histocompatible miniature swine: An inbred large-animal model SO TRANSPLANTATION LA English DT Article ID CARDIAC ALLOGRAFT VASCULOPATHY; TRANSPLANTATION; COMPLEX AB Three herds of miniature swine, each homozygous for a different set of alleles at the major histocompatibility complex (MHC), and five intra-MHC recombinant strains, have been reported by the authors' laboratory. One herd (SLA(dd)) was selected for further inbreeding to achieve a histocompatible line. It has undergone seven additional generations of sequential brother-sister or father-daughter matings (termed G7). To determine the level of histocompatibility of these animals, the authors performed skin and heart transplantation without immunosuppression. In contrast to MHC-matched, minor antigen-mismatched animals that rejected skin in 11 days (median survival time [MST], n=6) and hearts in 35 days (MST, n=4), G7 animals accepted skin for greater than 340 days (>340, >448, and >677 days) and hearts for greater than 265 days (>265 and >269 days). Nevertheless, rejection of second grafts could be induced by sensitization, indicating that weak minor antigens remain, requiring further inbreeding to achieve full histocompatibility. We conclude that G7 animals are sufficiently inbred to accept first set skin and heart grafts indefinitely. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 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. EM sachs@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646-24, R01 HL54211-05] NR 9 TC 49 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 27 PY 2003 VL 75 IS 6 BP 904 EP 907 DI 10.1097/01.TP.0000054839.43852.BF PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 660BT UT WOS:000181814500032 PM 12660524 ER PT J AU Shekelle, PG Hardy, ML Morton, SC Maglione, M Mojica, WA Suttorp, MJ Rhodes, SL Jungvig, L Gagne, J AF Shekelle, PG Hardy, ML Morton, SC Maglione, M Mojica, WA Suttorp, MJ Rhodes, SL Jungvig, L Gagne, J TI Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance - A meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID DOUBLE-BLIND; CONTROLLED TRIAL; ENERGY-EXPENDITURE; COMBINED CAFFEINE; BODY-COMPOSITION; CLINICAL-TRIALS; OBESE PATIENTS; SIBUTRAMINE; ORLISTAT; INGESTION AB Context Ephedra and ephedrine sometimes are used for weight loss or enhanced athletic performance, but the efficacy and safety of these compounds are uncertain. Objective To assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performance. Data Sources We searched 9 databases using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic. We included unpublished trials and non-English-language documents. Adverse events reported to the US Food and Drug Administration MedWatch program were assessed. Study Selection Eligible studies were controlled trials of ephedra or ephedrine used for weight loss or athletic performance and case reports of adverse events associated with such use. Eligible studies for weight loss were human studies with at least 8 weeks of follow-up; and for athletic performance, those having no minimum follow-up. Eligible case reports documented that ephedra or ephedrine was consumed within 24 hours prior to an adverse event or that ephedrine or an associated product was found in blood or urine, and that other potential causes had been excluded. Of the 530 articles screened, 52 controlled trials and 65 case reports were included in the adverse events analysis. Of more than 18000 other case reports screened, 284 underwent detailed review. Data Extraction Two reviewers independently identified trials of efficacy and safety of ephedra and ephedrine on weight loss or athletic performance; disagreements were resolved by consensus. Case reports were reviewed with explicit and implicit methods. Data Synthesis No weight loss trials assessed duration of treatment greater than 6 months. Pooled results. for trials comparing placebo with ephedrine (n=5), ephedrine and caffeine (n=12), ephedra (n=1), and ephedra and herbs containing caffeine (n=4) yielded estimates of weight loss (more than placebo) of 0.6 (95% confidence interval, 0.2-1.0), 1.0 (0.7-1.3), 0:8 (0.4-1.2), and 1.0 (0.6-1.3) kg/mo, respectively. Sensitivity analyses did not substantially alter the latter 3 results. No trials of ephedra and athletic performance were found; 7 trials of ephedrine were too heterogeneous to synthesize. Safety data from 50 trials yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. Data are insufficient to draw conclusions about adverse events occurring at a rate less than 1.0 per thousand. The majority of case reports are insufficiently documented to allow meaningful assessment. Conclusions Ephedrine and ephedra promote modest short-term weight loss (approximate to0.9 kg/mo more than placebo) in clinical trials. There are no data regarding long-term weight loss, and evidence to support use of ephedra for athletic performance is insufficient. Use of ephedra or ephedrine and caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. C1 RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90407 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ So Calif, Dept Family Med, Los Angeles, CA USA. RP Shekelle, PG (reprint author), RAND Corp, So Calif Evidence Based Practice Ctr, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU PHS HHS [290-97-0001] NR 56 TC 246 Z9 264 U1 6 U2 41 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 MAR 26 PY 2003 VL 289 IS 12 BP 1537 EP 1545 DI 10.1001/jama.289.12.1537 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 659XE UT WOS:000181803100032 PM 12672771 ER PT J AU Murray, DR Freeman, GL AF Murray, DR Freeman, GL TI Proinflammatory cytokines - Predictors of a failing heart? SO CIRCULATION LA English DT Editorial Material DE editorials; heart failure; cytokines; tumor necrosis factor; interleukins ID NECROSIS-FACTOR-ALPHA; LEFT-VENTRICULAR DYSFUNCTION; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; CARDIAC MYOCYTES; FAILURE; INTERLEUKIN-6; RECEPTORS; RISK C1 Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, San Antonio, TX 78229 USA. S Texas Vet Healthcare Syst, Audie L Murphy Div, San Antonio, TX USA. RP Murray, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr,MSC 7872, San Antonio, TX 78229 USA. EM MurrayD@uthscsa.edu NR 25 TC 39 Z9 42 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 MAR 25 PY 2003 VL 107 IS 11 BP 1460 EP 1462 DI 10.1161/01.CIR.0000060808.79274.0C PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 659EM UT WOS:000181764600002 PM 12654598 ER PT J AU Fox, CS Vasan, RS Parise, H Levy, D O'Donnell, CJ D'Agostino, RB Benjamin, EJ AF Fox, CS Vasan, RS Parise, H Levy, D O'Donnell, CJ D'Agostino, RB Benjamin, EJ TI Mitral annular calcification predicts cardiovascular morbidity and mortality - The Framingham Heart Study SO CIRCULATION LA English DT Article DE calcium; echocardiography; cardiovascular diseases; mortality ID CORONARY-ARTERY CALCIFICATION; BEAM COMPUTED-TOMOGRAPHY; AORTIC-VALVE SCLEROSIS; STAGE RENAL-DISEASE; RISK-FACTORS; MYOCARDIAL-INFARCTION; ANULAR CALCIUM; OLDER ADULTS; ATRIAL-FIBRILLATION; MEDIA THICKNESS AB Background-Mitral annular calcification (MAC) has been associated with stroke in longitudinal, community-based cohorts and cardiovascular disease (CVD) outcomes in many small retrospective studies. Prospective data are limited on the relation of MAC with CVD morbidity and mortality. Methods and Results-We examined the association between MAC assessed by M-mode echocardiography and the incidence of CVD, CVD death, and all-cause death over 16 years of follow-up in the Framingham Heart Study subjects who attended a routine examination between 1979 and 1981. Cox proportional hazards models were used to estimate hazard ratios (HRs) associated with the presence of MAC for each outcome. Of 1197 (445 male, 752 female) subjects who had adequate echocardiographic assessment, 14% had MAC. There were 307 incident CVD events and 621 deaths. In multivariable adjusted analyses, MAC was associated with an increased risk of incident CVD (HR, 1.5; 95% CI, 1.1, 2.0), CVD death (HR, 1.6; 95% CI, 1.1, 2.3), and all-cause death (HR, 1.3; 95% CI, 1.04, 1.6). For each 1-mm increase in MAC, the risk of incident CVD, CVD death, and all-cause death increased by approximate to 10%. Conclusions-The independent association of MAC with incident CVD and CVD death underscores that cardiac calcification is a marker of increased CVD risk. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM emelia@fram.nhlbi.nih.gov OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1K24HL04334, N01-HC-25195]; NINDS NIH HHS [5R01-NS-17950] NR 39 TC 151 Z9 157 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 MAR 25 PY 2003 VL 107 IS 11 BP 1492 EP 1496 DI 10.1161/01.CIR.0000058168.26163.BC PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 659EM UT WOS:000181764600009 PM 12654605 ER PT J AU Pei, L Arvholm, IL Lonnies, L Flock, JI AF Pei, L Arvholm, IL Lonnies, L Flock, JI TI GST-Fbe can recognize beta-chains of fibrin(ogen) on explanted materials SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article; Proceedings Paper CT European Workshop on From Gene to Functional Protein CY JUN 10-11, 2002 CL PARIS, FRANCE DE purification; Staphylococcus epidermidis; fibrin; fibrinogen ID FIBRINOGEN-BINDING-PROTEIN; STAPHYLOCOCCUS-EPIDERMIDIS; PLASMA-PROTEINS; ADHERENCE; ADHESION; AUREUS; FIBRONECTIN; MOLECULES; CATHETERS AB Staphylococcus epidermidis, a coagulase-negative staphylococcus (CoNS), is one of the leading pathogens of nosocormal infections, particularly associated with foreign body infections. Adherence of S. epidermidis to fibrinogen deposited on the surfaces of implants is important for the development of foreign body infections. A gene (fbe) encoding a fibrinogen-binding protein from S. epidermidis (Fbe) was identified by shotgun phage display. A portion of The was cloned into a GST-fusion vector. Affinity to glutathione-Sepharose by the GST-tag and affinity to fibrinogen-Sepharose by the Fbe part were applied to purify the recombinant Fbe. The purity and efficacy of the methods used in protein purification was compared. Furthermore, the potential physiological role of Fbe was studied by the interaction between GST-Fbe and components extracted from explanted materials in vitro. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Huddinge Univ Hosp, Karolinska Inst, Dept Microbiol Pathol & Immunol, Div Clin Bacteriol, SE-14186 Stockholm, Sweden. RP Pei, L (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAR 25 PY 2003 VL 786 IS 1-2 BP 319 EP 325 DI 10.1016/S1570-0232(02)00744-4 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 652XQ UT WOS:000181406500035 PM 12651029 ER PT J AU Greenberg, SM Shin, Y Grabowski, TJ Cooper, GE Rebeck, GW Iglesias, S Chapon, F Tournier-Lasserve, E Baron, JC AF Greenberg, SM Shin, Y Grabowski, TJ Cooper, GE Rebeck, GW Iglesias, S Chapon, F Tournier-Lasserve, E Baron, JC TI Hemorrhagic stroke associated with the Iowa amyloid precursor protein mutation SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-2; ANGIOPATHY; ALLELE; DEMENTIA AB The authors searched for mutations in the beta-amyloid precursor protein in a Spanish family with a hereditary syndrome of hemorrhagic stroke, dementia, leukoencephalopathy, and occipital calcifications. DNA from two affected members demonstrated the Iowa amyloid precursor protein mutation previously identified as a cause of severe amyloid angiopathy without hemorrhagic stroke. These data point to other genetic or environmental factors that may determine the occurrence of symptomatic hemorrhage in amyloid angiopathy. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Iowa, Coll Med, Dept Neurol & Radiol, Iowa City, IA USA. Sanders Brown Ctr Aging, Lexington, KY USA. Univ Caen, INSERM, U320, F-14032 Caen, France. Fac Med Lariboisiere, INSERM, EMI 9921, Paris, France. Hop AP HP Lariboisiere, Paris, France. Univ Cambridge, Dept Neurol, Cambridge CB2 1TN, England. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. OI baron, jean-claude/0000-0002-5264-2588 FU NIA NIH HHS [R03 AG19507] NR 10 TC 33 Z9 34 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 MAR 25 PY 2003 VL 60 IS 6 BP 1020 EP 1022 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 679YB UT WOS:000182948600027 PM 12654973 ER PT J AU Azam, M Latek, RR Daley, GQ AF Azam, M Latek, RR Daley, GQ TI Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL SO CELL LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; TYROSINE KINASE; C-ABL; PHILADELPHIA-CHROMOSOME; CLINICAL RESISTANCE; BLAST CRISIS; SH3 DOMAINS; INTRAMOLECULAR INTERACTIONS AB The Bcr-Abl fusion protein kinase causes chronic myeloid leukemia and is targeted by the signal transduction inhibitor STI-571/Gleevec/imatinib (STI-571). Sequencing of the BCR-ABL gene in patients who have relapsed after STI-571 chemotherapy has revealed a limited set of kinase domain mutations that mediate drug resistance. To obtain a more comprehensive survey of the amino acid substitutions that confer STI-571 resistance, we performed an in vitro screen of randomly mutagenized BCR-ABL and recovered all of the major mutations previously identified in patients and numerous others that illuminate novel mechanisms of acquired drug resistance. Structural modeling implies that a novel class of variants acts allosterically to destabilize the autoinhibited conformation of the ABL kinase to which STI-571 preferentially binds' This screening strategy is a paradigm applicable to a growing list of target-directed anti-cancer agents and provides a means of anticipating the drug-resistant amino acid substitutions that are likely to be clinically problematic. C1 Whitehead Inst, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM daley@wi.mit.edu FU NCI NIH HHS [CA76418, CA86991] NR 48 TC 434 Z9 449 U1 4 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 21 PY 2003 VL 112 IS 6 BP 831 EP 843 DI 10.1016/S0092-8674(03)00190-9 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 660DL UT WOS:000181818500010 PM 12654249 ER PT J AU Friedmann, AM Oliva, E Zietman, AL Aquino, SL Scully, RE Harris, NL O'Connor, PG AF Friedmann, AM Oliva, E Zietman, AL Aquino, SL Scully, RE Harris, NL O'Connor, PG TI An 18-year-old man with back and leg pain and a nondiagnostic biopsy specimen - Mediastinal germinoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GERM-CELL TUMORS; NEEDLE-BIOPSY; SEMINOMAS; CHILDHOOD; CHILDREN C1 Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 20 PY 2003 VL 348 IS 12 BP 1150 EP 1158 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 656UY UT WOS:000181628400011 PM 12646672 ER PT J AU List, JF Habener, JF AF List, JF Habener, JF TI Defective melanocortin 4 receptors in hyperphagia and morbid obesity SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MUTATIONS; DISORDERS C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. RP List, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. NR 15 TC 28 Z9 34 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 MAR 20 PY 2003 VL 348 IS 12 BP 1160 EP 1163 DI 10.1056/NEJMe030013 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 656UY UT WOS:000181628400012 PM 12646673 ER PT J AU Donta, ST Clauw, DJ Engel, CC Guarino, P Peduzzi, P Williams, DA Skinner, JS Barkhuizen, A Taylor, T Kazis, LE Sogg, S Hunt, SC Dougherty, CM Richardson, RD Kunkel, C Rodriguez, W Alicea, E Chiliade, P Ryan, M Gray, GC Lutwick, L Norwood, D Smith, S Everson, M Blackburn, W Martin, W Griffiss, JM Cooper, R Renner, E Schmitt, J McMurtry, C Thakore, M Mori, D Kerns, R Park, M Pullman-Mooar, S Bernstein, J Hershberger, P Salisbury, DC Feussner, JR AF Donta, ST Clauw, DJ Engel, CC Guarino, P Peduzzi, P Williams, DA Skinner, JS Barkhuizen, A Taylor, T Kazis, LE Sogg, S Hunt, SC Dougherty, CM Richardson, RD Kunkel, C Rodriguez, W Alicea, E Chiliade, P Ryan, M Gray, GC Lutwick, L Norwood, D Smith, S Everson, M Blackburn, W Martin, W Griffiss, JM Cooper, R Renner, E Schmitt, J McMurtry, C Thakore, M Mori, D Kerns, R Park, M Pullman-Mooar, S Bernstein, J Hershberger, P Salisbury, DC Feussner, JR CA VA Cooperative Study 470 Study Grp TI Cognitive behavioral therapy and aerobic exercise for Gulf War veterans' illnesses - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; LINEAR MIXED MODELS; FIBROMYALGIA; HEALTH; QUESTIONNAIRE; INTERVENTIONS; MANAGEMENT; INFERENCE; ADHERENCE; OUTCOMES AB Context Gulf War veterans' illnesses (GWVI), multisymptom illnesses characterized by persistent pain, fatigue, and cognitive symptoms, have been reported by many Gulf War veterans. There are currently no effective therapies available to treat GWVI. Objective To compare the effectiveness of cognitive behavioral therapy (CBT), exercise, and the combination of both for improving physical functioning and reducing the symptoms,of GWVI. Design, Setting, and Patients Randomized controlled 2 x 2 factorial trial conducted from April 1999 to September 2001 among 1092 Gulf War veterans who reported at least 2 of 3 symptom types (fatigue, pain, and cognitive) for more than 6 months and at the time of screening. Treatment assignment was unmasked except or a masked assessor of study outcomes at each clinical site (18 Department of Veterans Affairs [VA] and 2 Department of Defense [DOD] medical centers). Interventions Veterans were randomly assigned to receive usual care (n=271), consisting of any and all care received from inside or outside the VA or DOD health care systems; CBT plus usual care (n=286); exercise plus usual care (n=269); or CBT plus exercise plus usual care (n=266). Exercise sessions were 60 minutes and CBT sessions were 60 to 90 minutes; both met weekly for 12 weeks. Main Outcome Measures The primary end point was a 7-point or greater increase (improvement) on the Physical Component Summary scale of the Veterans Short Form 36-Item Health Survey at 12 months. Secondary outcomes were standardized measures of pain, fatigue, cognitive symptoms, distress, and mental health functioning. Participants were evaluated at baseline and at 3, 6, and 12 months. Results The percentage of veterans with improvement in physical function at 1 year was 11.5% for usual care, 11.7% for exercise alone, 18.4% for CBT plus exercise, and 18.5% for CBT alone. The adjusted odds ratios (OR) for improvement in exercise, CBT, and exercise plus CBT vs usual care were 1.07 (95% confidence interval [CI], 0.63-1.82), 1.72 (95% CI, 0.91-3.23), and 1.84 (95% CI, 0.95-3.55), respectively. OR for the overall (marginal) effect of receiving CBT (n=552) vs no CBT (n=535) was 1.71 (95% CI, 1.15-2.53) and for exercise (n=531) vs no exercise (n=556) was 1.07 (95% CI, 0.76-1.50). For secondary outcomes, exercise alone or in combination with CBT significantly improved fatigue, distress, cognitive symptoms, and mental health functioning, while CBT alone significantly improved cognitive symptoms and menial health functioning. Neither treatment had a significant impact on pain. Conclusion Our results suggest that CBT and/or exercise can provide modest relief for some of the symptoms of chronic multisymptom illnesses such as GWVI. C1 VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr 151A, West Haven, CT 06516 USA. VA Med Ctr, Boston, MA USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Indiana Univ, Bloomington, IN USA. Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR USA. VA Med & Reg Off Ctr, White River Jct, VT USA. VA Med Ctr, Bedford, MA USA. VA Puget Sound Healthcare Syst, Seattle Div, Seattle, WA USA. New Mexico VA Hlth Care Syst, Albuquerque, NM USA. San Juan VA Med Ctr, San Juan, PR USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. USN, Hlth Res Ctr, San Diego, CA 92152 USA. New York Harbor VA Healthcare Syst, New York, NY USA. Birmingham VA Med Ctr, Birmingham, AL USA. John Cochran VA Med Ctr, St Louis, MO USA. San Francisco VA Med Ctr, San Francisco, CA USA. Fargo VA Med & Reg Off Ctr, Fargo, ND USA. HH McGuire VA Med Ctr, Richmond, VA USA. VA New Jersey Hlth Care Syst, E Orange, NJ USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Dayton VA Med Ctr, Dayton, OH USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Peduzzi, P (reprint author), VA Connecticut Healthcare Syst, Cooperat Studies Program Coordinating Ctr 151A, 950 Campbell Ave, West Haven, CT 06516 USA. RI Williams, David/A-1180-2007 NR 51 TC 61 Z9 61 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 19 PY 2003 VL 289 IS 11 BP 1396 EP 1404 DI 10.1001/jama.289.11.1396 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 656PM UT WOS:000181616200031 PM 12636462 ER PT J AU Kirtane, AJ Murphy, SA Karha, J Wong, GC Giugliano, RP Antman, EM Gibson, CM AF Kirtane, AJ Murphy, SA Karha, J Wong, GC Giugliano, RP Antman, EM Gibson, CM CA TIMI Study Grp TI A mathematical model of preventing plaque rupture with drug-eluting stents based upon distance from the ostium to the culprit lesion in ST elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 20A EP 20A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500089 ER PT J AU Rodriguez, A Abizaid, AA Moguel, R Torres, W Fernandez, C Rodriguez, M Staico, R Feres, F Sousa, JEM Palacios, IF Vaz, V AF Rodriguez, A Abizaid, AA Moguel, R Torres, W Fernandez, C Rodriguez, M Staico, R Feres, F Sousa, JEM Palacios, IF Vaz, V TI Randomized trial of balloon angioplasty versus stenting for the treatment of long coronary lesions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 20A EP 20A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500088 ER PT J AU Mac Neill, BD Lowe, HC Pomeranstev, E DeJoseph, D Yabushita, H Tearney, GJ Bouma, BE Jang, IK AF Mac Neill, BD Lowe, HC Pomeranstev, E DeJoseph, D Yabushita, H Tearney, GJ Bouma, BE Jang, IK TI In-vivo characterization of plaque morphology by optical coherence tomography predicts coronary artery remodeling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 42A EP 42A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500182 ER PT J AU Jang, IK Lewis, BE Matthai, WH Kleiman, NS AF Jang, IK Lewis, BE Matthai, WH Kleiman, NS TI Combination of a direct thrombin inhibitor, argatroban, and glycoprotein IIb/IIIa inhibitor is effective and safe in patients undergoing percutaneous coronary intervention SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 68A EP 68A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500293 ER PT J AU Whang, W Mittleman, MA Wang, PJ Merlan, JC Rich, D Muller, JE Ruskin, JN Albert, CM AF Whang, W Mittleman, MA Wang, PJ Merlan, JC Rich, D Muller, JE Ruskin, JN Albert, CM TI A multicenter study of heart failure as a predictor for internal cardioverter defibrillator shocks SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 95A EP 96A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500413 ER PT J AU Singh, JP Mittleman, MA Wang, PJ Merlan, JC Rich, D Muller, JE Ruskin, JN Albert, CM AF Singh, JP Mittleman, MA Wang, PJ Merlan, JC Rich, D Muller, JE Ruskin, JN Albert, CM TI Smoking is associated with increased risk of shocks after cardioverter defibrillator implantation (TOVA study) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 116A EP 116A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500503 ER PT J AU Kopecky, SL Regan, S McClelland, R Stewart, S Hylek, EM AF Kopecky, SL Regan, S McClelland, R Stewart, S Hylek, EM TI National trends of lower target intensity among elderly patients taking warfarin: The anticoagulation consortium to improve outcomes nationally (ACTION) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 153A EP 153A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500665 ER PT J AU Wu, GF Wu, JP Li, J Kang, P Laham, R AF Wu, GF Wu, JP Li, J Kang, P Laham, R TI Exercise-induced expression of angiogenic cytokines in normal and infarcted hearts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Harvard Univ, Sch Med, BIDMC, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 199A EP 199A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500856 ER PT J AU Chen, AA Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Fifer, MA AF Chen, AA Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Fifer, MA TI Heart block after alcohol septal ablation: Predictors and consequences SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 212A EP 212A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500915 ER PT J AU Song, YL Jones, J Walker, J Cardoso, W Beppu, H Li, E Zhang, YY Loscalzo, J AF Song, YL Jones, J Walker, J Cardoso, W Beppu, H Li, E Zhang, YY Loscalzo, J TI Overexpression of 5-lipoxygenase induces pulmonary hypertension in bone morphongenetic protein receptor-2-deficient mice SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 223A EP 223A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669500959 ER PT J AU Bossone, E Mehta, RH Trimarchi, S Cooper, JV Smith, DE Evangelista, A Myrmel, T Oh, J Neinaber, CA Eagle, KA Isselbacher, EM AF Bossone, E Mehta, RH Trimarchi, S Cooper, JV Smith, DE Evangelista, A Myrmel, T Oh, J Neinaber, CA Eagle, KA Isselbacher, EM CA Int Registry Acute Aortic Dissecti TI Coronary artery involvement in patients with acute type A aortic dissection: Clinical characteristics and in-hospital outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 235A EP 235A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501018 ER PT J AU Samaha, FF Seshadri, P Iqbal, N Stern, L AF Samaha, FF Seshadri, P Iqbal, N Stern, L TI Effects of a carbohydrate-restricted diet versus a fat-and calorie-restricted diet on lipid subtractions SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Philadephia VA Med Ctr, Philadelphia, PA USA. Univ Penn, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 243A EP 243A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501057 ER PT J AU Januzzi, JL Isselbacher, EM Fattori, R Cooper, JV Smith, DE Eagle, KA Nienaber, CA Pape, LA AF Januzzi, JL Isselbacher, EM Fattori, R Cooper, JV Smith, DE Eagle, KA Nienaber, CA Pape, LA TI Characterizing the young patient with aortic dissection: Results from the international registry of aortic dissection (IRAD) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Univ Massachusetts, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Boston, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 253A EP 253A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501099 ER PT J AU Dominguez, H Rask-Madsen, C Ihlemann, N Hermann, T Kober, L Torp-Pedersen, C AF Dominguez, H Rask-Madsen, C Ihlemann, N Hermann, T Kober, L Torp-Pedersen, C TI Tumor necrosis factor-a infusion impairs endothelial function and induces endothelial and metabolic insulin resistance in humans SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Gentofte Univ Hosp, Hellerup, Denmark. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. RI Torp-Pedersen, Christian/E-5931-2013 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 302A EP 302A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501326 ER PT J AU Tawakol, A Fischman, A Gewirtz, H Muller, JE Brady, T Hamblin, M AF Tawakol, A Fischman, A Gewirtz, H Muller, JE Brady, T Hamblin, M TI Intravascular detection of inflammed atherosclerotic plaques with a novel macrophage-targeted fluorescent photodynamic compound SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 306A EP 306A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501341 ER PT J AU Ahn, Y Novikov, M Meiler, S Matsui, T Rosenzweig, A AF Ahn, Y Novikov, M Meiler, S Matsui, T Rosenzweig, A TI In vivo myocardial gene transfer of dominant negative IKK-beta reduces injury in ischemia-reperfusion but not straight infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 331A EP 331A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501449 ER PT J AU Roe, MT Giugliano, RP Tuttle, R Hasselblad, V Murphy, S Antman, EM Ohman, EM Harrington, RA Granger, CB Mahaffey, KW Cannon, CP Lincoff, AM Gibson, CM Armstrong, PW van de Werf, FJ Califf, RM Topol, EJ Braunwald, E AF Roe, MT Giugliano, RP Tuttle, R Hasselblad, V Murphy, S Antman, EM Ohman, EM Harrington, RA Granger, CB Mahaffey, KW Cannon, CP Lincoff, AM Gibson, CM Armstrong, PW van de Werf, FJ Califf, RM Topol, EJ Braunwald, E TI Safety of adjunctive glycoprotein IIb/IIIa blockade during rescue/early percutaneous coronary intervention following full-dose fibrinolytic therapy for acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Duke Clin Res Inst, Durham, NC USA. TIMI Study Grp, Boston, MA USA. RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 NR 0 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 332A EP 332A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501452 ER PT J AU Sonel, AF Good, CB Kelley, ME Wall, L Whittle, J Fine, MJ AF Sonel, AF Good, CB Kelley, ME Wall, L Whittle, J Fine, MJ TI A deadly combination: Elevated troponin I and peripheral white blood cell count imply poor prognosis in patients with suspected myocardial injury SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 341A EP 342A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501491 ER PT J AU O'Halloran, D O'Donnell, CJ Giugliano, RP Camargo, CA Allen, L Lloyd-Jones, DM AF O'Halloran, D O'Donnell, CJ Giugliano, RP Camargo, CA Allen, L Lloyd-Jones, DM TI The TIMI risk index predicts long-term mortality in patients admitted with primary unstable angina SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 349A EP 350A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501525 ER PT J AU Kathiresan, S Newell, JB Servoss, SJ Trani, D MacGillivray, TE Lewandrowski, K Lewandrowski, EL Januzzi, JL AF Kathiresan, S Newell, JB Servoss, SJ Trani, D MacGillivray, TE Lewandrowski, K Lewandrowski, EL Januzzi, JL TI Troponin T elevation following cardiac surgery is associated with increased one-year mortality and morbidity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 352A EP 352A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501535 ER PT J AU Servoss, SJ Wan, Y Snapinn, SM DiBattiste, PM Theroux, P Jang, IK Januzzi, JL AF Servoss, SJ Wan, Y Snapinn, SM DiBattiste, PM Theroux, P Jang, IK Januzzi, JL TI Glycoprotein IIb/IIIa receptor antagonism in patients with acute coronary syndromes and prior coronary artery bypass grafting: Results from PRISM PLUS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 364A EP 364A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501587 ER PT J AU Jordan, MK Cohen, DE Wong, GC Cannon, CP Braunwald, E Gibson, CM AF Jordan, MK Cohen, DE Wong, GC Cannon, CP Braunwald, E Gibson, CM CA TIMI Study Grp TI Association of major bleeding with adverse clinical outcomes and length of stay: A TACTICS TIMI 18 substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 375A EP 375A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501631 ER PT J AU Gibson, CM Jennings, LK Giugliano, RP Harrington, RA Roe, MT Murphy, SA Cholera, S Baran, KW Hobbach, HP Braunwald, E AF Gibson, CM Jennings, LK Giugliano, RP Harrington, RA Roe, MT Murphy, SA Cholera, S Baran, KW Hobbach, HP Braunwald, E TI Increased platelet receptor occupancy following eptifibatide therapy is associated with improved patency, tissue level perfusion, and ST-segment resolution in ST-segment elevation myocardial infarction: An INTEGRITI substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 TIMI Study Grp, Boston, MA USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 391A EP 391A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501699 ER PT J AU Gibson, CM Karha, J Murphy, SA Cannon, CP Giugliano, RP Antman, EM Braunwald, E AF Gibson, CM Karha, J Murphy, SA Cannon, CP Giugliano, RP Antman, EM Braunwald, E TI Percutaneous coronary intervention during the index hospitalization is associated with reduced recurrent myocardial infarction and improved survival following thrombolytic administration SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Brigham & Womens Hosp, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 398A EP 398A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501725 ER PT J AU Wong, GC Murphy, SA Morrow, DA Giugliano, RP Cannon, CP de Lemos, J Sabatine, MS Gibson, CM AF Wong, GC Murphy, SA Morrow, DA Giugliano, RP Cannon, CP de Lemos, J Sabatine, MS Gibson, CM TI A simple ECG method using high-risk infarct territory is superior to ECGs using summed ST elevation for assessing risk in ST elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 SW Texas State Univ, Sch Med, Dallas, TX USA. Brigham & Womens Hosp, TIMI Study Grp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 402A EP 402A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501742 ER PT J AU Samaha, FF Varello, M Kahn, ML AF Samaha, FF Varello, M Kahn, ML TI Platelet collagen receptor glycoprotein VI as a novel risk factor for myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 404A EP 404A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501750 ER PT J AU Achenbach, S Menendez, T Pohle, K Ropers, D Sacher, D Schlundt, C Flachskampf, FA Nixdorff, U Daniel, WG AF Achenbach, S Menendez, T Pohle, K Ropers, D Sacher, D Schlundt, C Flachskampf, FA Nixdorff, U Daniel, WG TI Electron-beam tomography for the detection of left atrial thrombi in patients with atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Univ Erlangen Nurnberg, Erlangen, Germany. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 422A EP 422A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669501826 ER PT J AU Afridi, NA AF Afridi, NA TI Is there an incremental value of contrast transesophageal echo to assess intracardiac shunt in patients with negative contrast transthoracic echo? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 464A EP 464A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502012 ER PT J AU Achenbach, S Ropers, D Hofmann, U Baum, U Anders, K Pohle, K Wicky, S Daniel, WG Brady, TJ AF Achenbach, S Ropers, D Hofmann, U Baum, U Anders, K Pohle, K Wicky, S Daniel, WG Brady, TJ TI Assessment of coronary remodeling in stenotic and nonstenotic coronary atherosclerotic lesions by 16-slice spiral computed tomography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Erlangen, Germany. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 468A EP 468A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502030 ER PT J AU Uemura, T Otsuji, Y Kumanohoso, T Takasaki, K Yuasa, T Kim, WS Kisanuki, A Minagoe, S Levine, RA Tei, C AF Uemura, T Otsuji, Y Kumanohoso, T Takasaki, K Yuasa, T Kim, WS Kisanuki, A Minagoe, S Levine, RA Tei, C TI Papillary muscle dysfunction attenuates ischemic mitral regurgitation in patients with localized basal inferior left ventricular remodeling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Kagoshima Univ, Kagoshima 890, Japan. 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 501A EP 501A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502172 ER PT J AU Yoerger, DM Leavitt, MB Picard, MH AF Yoerger, DM Leavitt, MB Picard, MH TI Heterogeneity of response to pressure overload in aortic stenosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 501A EP 501A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502174 ER PT J AU Yuge, K Otsuji, Y Nakashiki, K Mizukami, N Zhou, XY Hasegawa, W Ueno, T Kisanuki, A Minagoe, S Sakata, R Levine, RA Tei, C AF Yuge, K Otsuji, Y Nakashiki, K Mizukami, N Zhou, XY Hasegawa, W Ueno, T Kisanuki, A Minagoe, S Sakata, R Levine, RA Tei, C TI Mechanism of late onset ischemic mitral regurgitation following Dor's procedure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Kagoshima Univ, Sch Med, Kagoshima 890, Japan. Massachusetts Gen Hosp, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 503A EP 503A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502183 ER PT J AU Rumsfeld, JS Magid, DJ Plomondon, ME Westfall, JM Peterson, LA Sales, AE AF Rumsfeld, JS Magid, DJ Plomondon, ME Westfall, JM Peterson, LA Sales, AE TI The impact of admission to primary versus tertiary care VA medical centers on outcomes following acute coronary syndromes: The VA access to cardiology study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Adm Med Ctr, Denver, CO 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 533A EP 533A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502304 ER PT J AU Sonel, AF Good, CB Kelley, ME Wall, L Whittle, J Fine, MJ AF Sonel, AF Good, CB Kelley, ME Wall, L Whittle, J Fine, MJ TI What is the meaning of high-risk? A prospective comparison of three risk stratification models recommended in non-ST elevation myocardial infarction and unstable angina SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 52nd Annual Scientific Session of the American-College-of-Cardiology CY MAR 30-APR 02, 2003 CL CHICAGO, ILLINOIS SP American Coll Cardiol C1 Univ Pittsburgh, Va Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 19 PY 2003 VL 41 IS 6 SU A BP 534A EP 534A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 657LW UT WOS:000181669502309 ER PT J AU Knight, EL Stampfer, MJ Hankinson, SE Spiegelman, D Curhan, GC AF Knight, EL Stampfer, MJ Hankinson, SE Spiegelman, D Curhan, GC TI The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION RATE; FOOD FREQUENCY QUESTIONNAIRE; CREATININE CLEARANCE; DIETARY-PROTEIN; MEASUREMENT-ERROR; HEALTHY-SUBJECTS; CONFIDENCE-INTERVALS; PHOSPHORUS INTAKE; SERUM CREATININE; BLOOD-PRESSURE AB Background: In individuals with moderate to severe renal insufficiency, low protein intake may slow renal function decline. However, the long-term impact of protein intake on renal function in persons with normal renal function or mild renal insufficiency is unknown. Objective: To determine whether protein intake influences the rate of renal function change in women over an 11-year period. Design: Prospective cohort study. Setting: Nurses' Health Study. Participants: 1624 women enrolled in the Nurses' Health Study who were 42 to 68 years of age in 1989 and gave blood samples in 1989 and 2000. Ninety-eight percent of women were white, and 1% were African American. Measurements: Protein intake was measured in 1990 and 1994 by using a semi-quantitative food-frequency questionnaire. Creatinine concentration was used to estimate glomerular filtration rate (GFR) and creatinine clearance. Results: In multivariate linear regression analyses, high protein intake was not significantly associated with change in estimated GFR in women with normal renal function (defined as an estimated GFR greater than or equal to 80 mL/min per 1.73 m(2)). Change in estimated GFR in this subgroup over the 11-year period was 0.25 mL/min per 1.73 m(2) (95% Cl, -0.78 to 1.28 mL/min per 1.73 m(2)) per 10-g increase in protein intake; the change in estimated GFR was 1.14 mL/min per 1.73 m(2) (Cl, -3.63 to 5.92 mL/min per 1.73 m(2)) after measurement-error adjustment for protein intake. In women with mild renal insufficiency (defined as an estimated GFR > 55 mL/min per 1.73 m(2) but <80 mL/min per 1.73 m(2)), protein intake was significantly associated with a change in estimated GFR of -1.69 mL/min per 1.73 m(2) (Cl, -2.93 to -0.45 mL/min per 1.73 m 2) per 10-g increase in protein intake. After measurement-error adjustment, the change in estimated GFR was -7.72 mL/min per 1.73 m(2) (Cl, -15.52 to 0.08 mL/min per 1.73 m(2)) per 10-g increase in protein intake, an association of borderline statistical significance. High intake of nondairy animal protein in women with mild renal insufficiency was associated with a significantly greater change in estimated GFR (-1.21 mL/min per 1.73 M2 [Cl, -2.34 to -0.33 mL/min per 1.73 m(2)] per 10-g increase in nondairy animal protein intake). Conclusions: High protein intake was not associated with renal function decline in women with normal renal function. However, high total protein intake, particularly high intake of nondairy animal protein, may accelerate renal function decline in women with mild renal insufficiency. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02115 USA. RP Knight, EL (reprint author), Channing Labs, Nurses Hlth Study, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL34594]; NIDDK NIH HHS [T32DK07791, DK52866, T32DK0740] NR 48 TC 152 Z9 156 U1 0 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 18 PY 2003 VL 138 IS 6 BP 460 EP 467 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 655PV UT WOS:000181562400003 PM 12639078 ER PT J AU Bent, S Tiedt, TN Odden, MC Shlipak, MG AF Bent, S Tiedt, TN Odden, MC Shlipak, MG TI The relative safety of ephedra compared with other herbal products SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MA-HUANG; SUPPLEMENTS; TOXICITY; SYSTEM AB Background: Ephedra is widely used in dietary supplements that are marketed to promote weight loss or increase energy; however, the safety of this product has been questioned because of numerous case reports of adverse events. Objective: To compare the risk for adverse events attributable to ephedra and other herbal products. Design: Comparative case series. Setting: American Association of Poison Control Centers Toxic Event Surveillance System Database Annual Report, 2001. Measurements: The relative risk and 95% confidence interval for experiencing an adverse reaction after ephedra. use compared with other herbs. This risk was defined as the ratio of adverse reactions to ephedra. versus other products, divided by the ratio of their relative use in the United States. Results: Products containing ephedra accounted for 64% of all adverse reactions to herbs in the United States, yet these products represented only 0.82% of herbal product sales. The relative risks for an adverse reaction in persons using ephedra compared with other herbs were extremely high, ranging from 100 (95% Cl, 83 to 140) for kava to 720 (Cl, 520 to 1100) for Ginkgo biloba. Conclusions: Ephedra use is associated with a greatly increased risk for adverse reactions compared with other herbs, and its use should be restricted. C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. Med Tox Grp, Longboat Key, FL USA. RP Bent, S (reprint author), San Francisco Vet Affairs Med Ctr, 111-A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCCIH NIH HHS [1 K08 AT01338-01] NR 16 TC 74 Z9 80 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 MAR 18 PY 2003 VL 138 IS 6 BP 468 EP 471 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 655PV UT WOS:000181562400004 PM 12639079 ER PT J AU Milan, DJ Peterson, TA Ruskin, JN Peterson, RT MacRae, CA AF Milan, DJ Peterson, TA Ruskin, JN Peterson, RT MacRae, CA TI Drugs that induce repolarization abnormalities cause bradycardia in zebrafish SO CIRCULATION LA English DT Article DE drugs; electrophysiology; arrhythmia; genes ID TORSADE-DE-POINTES; CARDIAC-ARRHYTHMIA; LONG; MECHANISMS; RISK AB Background-Drug-induced QT prolongation and torsades de pointes remain significant and often unpredictable clinical problems. Current in vitro preclinical assays are limited by biological simplicity, and in vivo models suffer from expense and low throughput. Methods and Results-During a screen for the effects of 100 small molecules on the heart rate of the zebrafish, Danio rerio, we found that drugs that cause QT prolongation in humans consistently caused bradycardia and AV block in the zebrafish. Of 23 such drugs tested, 18 were positive in this initial screen. Poor absorption explained 4 of 5 false-negative results, as demonstrated by microinjection. Overall, 22 of 23 compounds that cause repolarization abnormalities were positive in this assay. Antisense "knockdown" of the zebrafish KCNH2 ortholog yielded bradycardia in a dose dependent manner confirming the effects of reduction of repolarizing potassium current in this model. Classical drug-drug interactions between erythromycin and cisapride, as well as cimetidine and terfenadine, were also reproduced. Conclusion-This simple high-throughput assay is a promising addition to the repertoire of preclinical tests for drug-induced repolarization abnormalities. The genetic tractability of the zebrafish will allow the exploration of heritable modifiers of such drug effects. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP MacRae, CA (reprint author), Cardiovasc Res Ctr, 149 13th St,4th Floor, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL68711, K08 HL068711]; NIGMS NIH HHS [R21 GM075946] NR 18 TC 223 Z9 243 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2003 VL 107 IS 10 BP 1355 EP 1358 DI 10.1161/01.CIR.0000061912.88753.87 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 656MW UT WOS:000181612400006 PM 12642353 ER PT J AU Henry, TD Annex, BH McKendall, GR Azrin, MA Lopez, JJ Giordano, FJ Shah, PK Willerson, JT Benza, RL Berman, DS Gibson, CM Bajamonde, A Rundle, AC Fine, J McCluskey, ER AF Henry, TD Annex, BH McKendall, GR Azrin, MA Lopez, JJ Giordano, FJ Shah, PK Willerson, JT Benza, RL Berman, DS Gibson, CM Bajamonde, A Rundle, AC Fine, J McCluskey, ER CA VIVA Investigators TI Vascular endothelial growth factor in ischemia for vascular angiogenesis SO CIRCULATION LA English DT Article DE angiogenesis; growth substances; ischemia; angina; heart disease ID CORONARY-ARTERY DISEASE; CHRONIC MYOCARDIAL-ISCHEMIA; GENE-THERAPY; DOUBLE-BLIND; HEART-DISEASE; BLOOD-FLOW; TRIAL; DELIVERY AB Background-Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF. Methods and Results-A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng . kg(-1) . min(-1)), or high-dose rhVEGF (50 ng . kg(-1) . min(-1)) by intracoronary infusion on day 0, followed by intravenous infusions on days 3, 6, and 9. Exercise treadmill tests, angina class, and quality of life assessments were performed at baseline, day 60, and day 120. Myocardial perfusion imaging was performed at baseline and day 60. At day 60, the change in exercise treadmill test (ETT) time from baseline was not different between groups (placebo, +48 seconds; low dose, +30 seconds; high dose, +30 seconds). Angina class and quality of life were significantly improved within each group, with no difference between groups. By day 120, placebo-treated patients demonstrated reduced benefit in all three measures, with no significant difference compared with low-dose rhVEGF. In contrast, high-dose rhVEGF resulted in significant improvement in angina class (P=0.05) and nonsignificant trends in ETT time (P=0.15) and angina frequency (P=0.09) as compared with placebo. Conclusions-rhVEGF seems to be safe and well tolerated. rhVEGF offered no improvement beyond placebo in all measurements by day 60. By day 120, high-dose rhVEGF resulted in significant improvement in angina and favorable trends in ETT time and angina frequency. C1 Univ Minnesota, Div Cardiol, Minneapolis, MN USA. Hennepin Cty Med Ctr, Div Cardiol, Minneapolis, MN 55415 USA. Duke Univ, Med Ctr, Durham, NC USA. Durham Vet Affair Med Ctr, Durham, NC USA. Rhode Isl Hosp, Brown Med Sch, Providence, RI USA. Univ Connecticut, Med Ctr, Farmington, CT USA. Univ Iowa, Iowa City, IA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Texas, Houston, TX USA. Univ Alabama, Birmingham, AL USA. TIMI Data Coordinating Ctr, Boston, MA USA. Genentech Inc, San Francisco, CA 94080 USA. RP Henry, TD (reprint author), Minneapolis Heart Inst Fdn, 920 E 28th St,Ste 40, Minneapolis, MN 55407 USA. NR 22 TC 602 Z9 637 U1 3 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 18 PY 2003 VL 107 IS 10 BP 1359 EP 1365 DI 10.1161/01.CIR.0000061911.47710.8A PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 656MW UT WOS:000181612400007 PM 12642354 ER PT J AU Chao, MY Hart, AC AF Chao, MY Hart, AC TI Sensory biology: How the nose knows SO CURRENT BIOLOGY LA English DT Editorial Material ID GLR-1 GLUTAMATE-RECEPTOR; CAENORHABDITIS-ELEGANS; C-ELEGANS; LOCOMOTION; RESPONSES; RELEASE; NEURON; TOUCH AB Sensory information is encoded as patterns of synaptic activity. Recent evidence suggests that differential synaptic release and use of postsynaptic glutamate receptors is critical for encoding information from polymodal neurons. C1 Harvard Univ, Sch Med 149 7202, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hart, AC (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St, Charlestown, MA 02129 USA. EM hart@helix.mgh.harvard.edu NR 15 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 18 PY 2003 VL 13 IS 6 BP R226 EP R228 DI 10.1016/S0960-9822(03)00156-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 657ZH UT WOS:000181696800009 PM 12646147 ER PT J AU Lee, JT AF Lee, JT TI Molecular links between X-inactivation and autosomal imprinting: X-inactivation as a driving force for the evolution of imprinting? SO CURRENT BIOLOGY LA English DT Review ID HISTONE METHYLTRANSFERASE ACTIVITY; COMPARATIVE SEQUENCE-ANALYSIS; MOUSE XIST GENE; CHROMOSOME INACTIVATION; ANTISENSE RNA; DOSAGE COMPENSATION; DNA METHYLATION; FEMALE MAMMALS; STEM-CELLS; CPG ISLAND AB In classical Mendelian inheritance, each parent donates a set of chromosomes to its offspring so that maternally and paternally encoded information is expressed equally. The phenomena of X-chromosome inactivation (XCI) and autosomal imprinting in mammals violate this dogma of genetic equality. In XCI, one of the two female X chromosomes is silenced to equalize X-linked gene dosage between XX and XY individuals. In genomic imprinting, parental marks determine which of the embryo's two autosomal alleles will be expressed. Although XCI and imprinting appear distinct, molecular evidence now shows that they share a surprising number of features. Among them are cis-acting control centers, long-distance regulation and differential DNA methylation. Perhaps one of the most intriguing similarities between XCI and imprinting has been their association with noncoding and antisense RNAs. Very recent data also suggest the common involvement of histone modifications and chromatin-associated factors such as CTCF. Collectively, the evidence suggests that XCI and genomic imprinting may have a common origin. Here, I hypothesize that the need for X-linked dosage compensation was a major driving force in the evolution of genomic imprinting in mammals. I propose that imprinting was first fixed on the X chromosome for XCI and subsequently acquired by autosomes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Genet, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. EM lee@frodo.mgh.harvard.edu NR 115 TC 86 Z9 87 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 18 PY 2003 VL 13 IS 6 BP R242 EP R254 DI 10.1016/S0960-9822(03)00162-3 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 657ZH UT WOS:000181696800015 PM 12646153 ER PT J AU Beltran, S Blanco, E Serras, F Perez-Villamil, B Guigo, R Artavanis-Tsakonas, S Corominas, M AF Beltran, S Blanco, E Serras, F Perez-Villamil, B Guigo, R Artavanis-Tsakonas, S Corominas, M TI Transcriptional network controlled by the trithorax-group gene ash2 in Drosophila melanogaster SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENOME-WIDE ANALYSIS; SACCHAROMYCES-CEREVISIAE; GROUP PROTEINS; POLYCOMB-GROUP; FASCICLIN-II; EXPRESSION; MICROARRAYS; ULTRABITHORAX; PREDICTION; COMPLEXES AB The transcription factor absent, small, or homeotic discs 2 (ash2) gene is a member of the trithorax group of positive regulators of homeotic genes. Mutant alleles for ash2 are larval/pupal lethals and display imaginal disc and brain abnormalities. The allele used in this study is a true mutant for the trithorax function and lacks the longest transcript present in wild-type flies. In an attempt to identify gene targets of ash2, we have performed an expression analysis by using cDNA microarrays. Genes involved in cell cycle, cell proliferation, and cell adhesion are among these targets, and some of them are validated by functional and expression studies. Even though trithorax proteins act by modulating chromatin structure at particular chromosomal locations, evidence of physical aggregation of ash2-regulated genes has not been found. This work represents the first microarray analysis, to our knowledge, of a trithorax-group gene. C1 Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain. Univ Pompeu Fabra, Inst Municipal Invest Med, Grp Recerca Informat Med, Ctr Regulacio Genom, Barcelona 08003, Spain. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Corominas, M (reprint author), Univ Barcelona, Dept Genet, Diagonal 645, E-08028 Barcelona, Spain. EM mcorominas@ub.edu RI Serras, Florenci/L-2353-2014; Guigo, Roderic/D-1303-2010; Blanco, Enrique/I-5902-2015; Beltran, Sergi/I-3408-2015; Gasull, Martina/A-6630-2013 OI Serras, Florenci/0000-0003-1184-5386; Guigo, Roderic/0000-0002-5738-4477; Blanco, Enrique/0000-0001-6261-7370; Beltran, Sergi/0000-0002-2810-3445; NR 43 TC 19 Z9 20 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3293 EP 3298 DI 10.1073/pnas.0538075100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200057 PM 12626737 ER PT J AU Conlon, EM Liu, XS Lieb, JD Liu, JS AF Conlon, EM Liu, XS Lieb, JD Liu, JS TI Integrating regulatory motif discovery and genome-wide expression analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sequence motif discovery; microarray data; correlation; transcription regulation ID YEAST SACCHAROMYCES-CEREVISIAE; BINDING-SITES; CELL-CYCLE; DNA; IDENTIFICATION; GENES; SEQUENCES AB We propose MOTIF REGRESSOR for discovering sequence motifs upstream of genes that undergo expression changes in a given condition. The method combines the advantages of matrix-based motif finding and oligomer motif-expression regression analysis, resulting in high sensitivity and specificity. MOTIF REGRESSOR is particularly effective in discovering expression-mediating motifs of medium to long width with multiple degenerate positions. When applied to Saccharomyces cerevisiae, MOTIF REGRESSOR identified the ROX1 and YAP1 motifs from Rox1p and Yap1p overexpression experiments, respectively; predicted that Gcn4p may have increased activity in YAP1 deletion mutants; reported a group of motifs (including GCN4, PHO4, MET4, STRE, USR1, RAN, M3A, and M3B) that may mediate the transcriptional response to amino acid starvation; and found all of the known cell-cycle regulation motifs from 18 expression microarrays over two cell cycles. C1 Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. RP Liu, JS (reprint author), Harvard Univ, Dept Stat, 1 Oxford St, Cambridge, MA 02138 USA. EM jliu@stat.harvard.edu FU NHGRI NIH HHS [R01 HG 02518-01, R01 HG002518]; NLM NIH HHS [1F37 LM 07626-01, F37 LM007626] NR 32 TC 227 Z9 231 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3339 EP 3344 DI 10.1073/pnas.0630591100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200066 PM 12626739 ER PT J AU Schmollinger, JC Vonderheide, RH Hoar, KM Maecker, B Schultze, JL Hodi, FS Soiffer, RJ Jung, K Kuroda, MJ Letvin, NL Greenfield, EA Mihm, M Kutok, JL Dranoff, G AF Schmollinger, JC Vonderheide, RH Hoar, KM Maecker, B Schultze, JL Hodi, FS Soiffer, RJ Jung, K Kuroda, MJ Letvin, NL Greenfield, EA Mihm, M Kutok, JL Dranoff, G TI Melanoma inhibitor of apoptosis protein (ML-IAP) is a target for immune-mediated tumor destruction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; IN-SITU HYBRIDIZATION; GRANZYME-B; INFILTRATING LYMPHOCYTES; T-LYMPHOCYTES; ANTITUMOR IMMUNITY; FAMILY; CELLS; RESPONSES; ANTIGENS AB The identification of antigens associated with tumor destruction is a major goal of cancer immunology. Vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor generates potent, specific, and long-lasting antitumor immunity through improved tumor antigen presentation by dendritic cells and macrophages. A phase I clinical trial of this immunization strategy in patients with disseminated melanoma revealed the consistent induction in distant metastases of dense T and B cell infiltrates that effectuated substantial tumor necrosis and fibrosis. To delineate the target antigens of this vaccine-stimulated tumor destruction, we screened a melanoma cDNA expression library with postimmunization sera from a long-term responding patient (K030). High-titer IgG antibodies recognized melanoma inhibitor of apoptosis protein (ML-IAP), a caspase antagonist containing a single baculoviral IAP repeat and a COOH-terminal RING domain. Although K030 harbored antibodies to ML-IAP at the time of study entry, multiple courses of vaccination over 4 years increased antibody titers and elicited isotype switching. Moreover, lymphocyte infiltrates in necrotic metastases included CD4(+). and CD8(+) T cells specific for ML-IAP, as revealed by proliferation, tetramer, enzyme-linked immunospot, and cytotoxicity analysis. Whereas melanoma cells in densely infiltrated lesions showed strong ML-IAP expression by immunohistochemistry, lethal disease progression was associated with the loss of ML-IAP staining and the absence of lymphocyte infiltrates. These findings demonstrate that ML-IAP can serve as a target for immune-mediated tumor destruction, but that antigen-loss variants can accomplish immune escape. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510 E,44 Binney St, Boston, MA 02115 USA. EM glenn.dranoff@dfci.harvard.edu RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA 39542, CA 66996, CA 74886, CA 78880, P01 CA039542, P01 CA066996, R01 CA074886] NR 40 TC 79 Z9 95 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 18 PY 2003 VL 100 IS 6 BP 3398 EP 3403 DI 10.1073/pnas.0530311100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 657PH UT WOS:000181675200076 PM 12626761 ER PT J AU Bernards, A AF Bernards, A TI GAPs galore! A survey of putative Ras superfamily GTPase activating proteins in man and Drosophila SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE GTPase activating protein; Ras superfamily; Drosophila and human genome survey ID GUANINE-NUCLEOTIDE-EXCHANGE; GDP DISSOCIATION INHIBITOR; LINKED MENTAL-RETARDATION; RHO-FAMILY GTPASES; INOSITOL POLYPHOSPHATE 5-PHOSPHATASE; TUBEROUS SCLEROSIS COMPLEX; RIBOSYLATION FACTOR DOMAIN; RECEPTOR TYROSINE KINASE; TRANSITION-STATE ANALOG; GROWTH-FACTOR RECEPTOR AB Typical members of the Ras superfamily of small monomeric GTP-binding proteins function as regulators of diverse processes by cycling between biologically active GTP- and inactive GDP-bound conformations. Proteins that control this cycling include guanine nucleotide exchange factors or GEFs, which activate Ras superfamily members by catalyzing GTP for GDP exchange, and GTPase activating proteins or GAPs, which accelerate the low intrinsic GTP hydrolysis rate of typical Ras superfamily members, thus causing their inactivation. Two among the latter class of proteins have been implicated in common genetic disorders associated with an increased cancer risk, neurofibromatosis-1, and tuberous sclerosis. To facilitate genetic analysis, I surveyed Drosophila and human sequence databases for genes predicting proteins related to GAPs for Ras superfamily members. Remarkably, close to 0.5% of genes in both species (173 human and 64 Drosophila genes) predict proteins related to GAPs for Arf, Rab, Ran, Rap, Ras, Rho, and Sar family GTPases. Information on these genes has been entered into a pair of relational databases, which can be used to identify evolutionary conserved proteins that are likely to serve basic biological functions, and which can be updated when definitive information on the coding potential of both genomes becomes available. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Bernards, A (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 349 TC 256 Z9 264 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAR 17 PY 2003 VL 1603 IS 2 BP 47 EP 82 DI 10.1016/S0304-419X(02)00082-3 PG 36 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 655JW UT WOS:000181549100001 PM 12618308 ER PT J AU Yoshida, K Wang, HG Miki, Y Kufe, D AF Yoshida, K Wang, HG Miki, Y Kufe, D TI Protein kinase C delta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9 SO EMBO JOURNAL LA English DT Article DE apoptosis; DNA damage; PKC delta; Rad9; RNAi ID ABL TYROSINE KINASE; SCHIZOSACCHAROMYCES-POMBE RAD1(+); CHECKPOINT PROTEIN; IONIZING-RADIATION; FISSION YEAST; PROTEOLYTIC ACTIVATION; HUMAN HOMOLOG; HRAD9; INTERACTS; APOPTOSIS AB The mammalian homolog of the Schizosaccharomyces pombe Rad9 is involved in checkpoint signaling and the induction of apoptosis. While the mechanisms responsible for the regulation of human Rad9 (hRad9) are not known, hRad9 is subject to hyperphosphorylation in the response of cells to DNA damage. The present results demonstrate that protein kinase Cdelta (PKCdelta) associates with Rad9 and that DNA damage induces this interaction. PKCdelta phosphorylates hRad9 in vitro and in cells exposed to genotoxic agents. The functional significance of the interaction between hRad9 and PKCdelta is supported by the finding that activation of PKCdelta is necessary for formation of the Rad9-Hus1-Rad1 complex. We also show that PKCdelta is required for binding of hRad9 to Bcl-2. In concert with these results, inhibition of PKCdelta attenuates Rad9-mediated apoptosis. These findings demonstrate that PKCdelta is responsible for the regulation of Rad9 in the Hus1-Rad1 complex and in the apoptotic response to DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, Coll Med, H Lee Moffit Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL USA. Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Genet, Tokyo, Japan. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA029431, CA55241, R01 CA090315, CA90315, CA29431] NR 39 TC 114 Z9 121 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 17 PY 2003 VL 22 IS 6 BP 1431 EP 1441 DI 10.1093/emboj/cdg134 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 655HV UT WOS:000181546000020 PM 12628935 ER PT J AU Bhattacharjee, A Xu, B Roy, B Frank, DA Feldman, GM Cathcart, MK AF Bhattacharjee, A Xu, B Roy, B Frank, DA Feldman, GM Cathcart, MK TI PKCdelta regulates IL-13-induced Stat3 serine (727) phosphorylation and 15-lipoxygenase gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1354 EP A1354 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902836 ER PT J AU Brown, D AF Brown, D TI The ins and outs of aquaporin 2 trafficking SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1219 EP A1219 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902193 ER PT J AU Burns, AR Gagen, D Murphy, A Zheng, ZL Bowden, RA Smith, CW Rumbaut, RE AF Burns, AR Gagen, D Murphy, A Zheng, ZL Bowden, RA Smith, CW Rumbaut, RE TI PECAM-1 (CD31): A novel regulator of neutrophil transendothelial migration velocity and endothelial barrier function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Baylor Coll Med, Houston, TX 77025 USA. WRAIR, Silver Spring, MD USA. VA Med Ctr, Med Care Line, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1188 EP A1188 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902053 ER PT J AU Chao, W Shen, Y Li, L Meiler, S Cook, S Rosenzweig, A AF Chao, W Shen, Y Li, L Meiler, S Cook, S Rosenzweig, A TI Cell-type specific inhibition of NF-kappa B activation in cardiomyocytes by Fas-associated death domain protein (FADD) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1358 EP A1358 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902852 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 Interaction of collagenase-3 with its specific receptor and LRP-1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Arthrit Unit, Sch Med, Cambridge, MA 02138 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 FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A998 EP A999 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901158 ER PT J AU Drummond, IA AF Drummond, IA TI Blood vessel: epithelial interactions in the forming kidney SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1209 EP A1209 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902150 ER PT J AU Garnovskaya, MN Mukhin, YV Raymond, JR AF Garnovskaya, MN Mukhin, YV Raymond, JR TI The Na+/H+ exchanger regulates mitogen-activated protein kinase upstream of Ras in vascular smooth muscle cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1016 EP A1016 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901245 ER PT J AU Goetinck, PF AF Goetinck, PF TI Syndecan and associated cytoplasmic proteins in signal transduction and tissue homeostasis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1172 EP A1172 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901973 ER PT J AU Graham, WV Deplancke, B Yoon, B Gaskins, HR AF Graham, WV Deplancke, B Yoon, B Gaskins, HR TI Cdx2 transactivates the intestinal trefoil factor promoter in a redox-sensitive manner SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Illinois, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Deplancke, Bart/B-3250-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1204 EP A1204 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902127 ER PT J AU Harimoto, J Maarek, JM Holschneider, DP Yang, J Scremin, OU AF Harimoto, J Maarek, JM Holschneider, DP Yang, J Scremin, OU TI Functional brain mapping using an implantable microbolus infusion pump: Validation in a locomotor paradigm SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ So Calif, Los Angeles, CA 90089 USA. Univ So Calif, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1211 EP A1211 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902159 ER PT J AU Makris, N Kennedy, DN McInerney, SC Caviness, VS Pandya, DN AF Makris, N Kennedy, DN McInerney, SC Caviness, VS Pandya, DN TI Quantitative DT-MRI analysis of the human superior longitudinal fascicle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Ctr Morphometr Anal Neurol, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A784 EP A784 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900143 ER PT J AU Mukhin, YV Raymond, JR Garnovskaya, MN AF Mukhin, YV Raymond, JR Garnovskaya, MN TI Novel mechanism of EGF receptor transactivation by bradykinin B-2 receptor in kidney cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1013 EP A1013 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901229 ER PT J AU Narlikar, GJ Fan, HY He, X Kingston, R AF Narlikar, GJ Fan, HY He, X Kingston, R TI ATP-dependent chromatin remodelers use distinct strategies to make nucleosomal DNA accessible SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A973 EP A973 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901033 ER PT J AU Scremin, OU Shih, TM Huynh, LTK Rocb, MM Sun, W Chialvo, DR D'Elia, J Cable, C Jenden, DJ AF Scremin, OU Shih, TM Huynh, LTK Rocb, MM Sun, W Chialvo, DR D'Elia, J Cable, C Jenden, DJ TI Delayed effects of low-dose cholinesterase inhibitors on cardiovascular regulation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Sch Med, Los Angeles, CA 90073 USA. USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A875 EP A875 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900571 ER PT J AU Spiegelman, BM Puigserver, P Lin, J Tarr, P Accili, D AF Spiegelman, BM Puigserver, P Lin, J Tarr, P Accili, D TI Hormonal regulation of glucose and energy homeostasis through the transcriptional coactivator PGC-1 alpha SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Columbia Univ, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A971 EP A971 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901024 ER PT J AU Tung, CH AF Tung, CH TI Novel optical technology for in vivo protease activity sensing SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1301 EP A1301 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902579 ER PT J AU Turner, JH Garnovskaya, MN Mukhin, YV Raymond, JR AF Turner, JH Garnovskaya, MN Mukhin, YV Raymond, JR TI Regulation of the type 1 Na+/H+ exchanger by Janus kinase 2 and Ca2+/calmodulin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1029 EP A1029 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901306 ER PT J AU Van Auken, K Nesterova, A Shao, JH Friedman, J AF Van Auken, K Nesterova, A Shao, JH Friedman, J TI Insulin suppression of hepatic PEPCK gene transcription via C/EBP beta requires glucose metabolism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver Res Inst, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1020 EP A1020 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901263 ER PT J AU Van Winkle, DM Cao, ZP Liu, LJ AF Van Winkle, DM Cao, ZP Liu, LJ TI Cellular signaling associated with enkephalin-induced cardioprotection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A877 EP A877 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900578 ER PT J AU Vidal, M AF Vidal, M TI Toward a proteome atlas for C-elegans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A972 EP A972 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901029 ER PT J AU Xu, B Bhattacharjee, A Roy, B Xu, HM Frank, DA Feldman, GM Cathcart, MK AF Xu, B Bhattacharjee, A Roy, B Xu, HM Frank, DA Feldman, GM Cathcart, MK TI IL-13 induction of 15-Lipoxygenase gene expression requires p38 MAPK-dependent serine phosphorylation of Stat1 and Stat3 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1354 EP A1354 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902835 ER PT J AU Yelick, PC Perrino, M Tong, K Payne, TL AF Yelick, PC Perrino, M Tong, K Payne, TL TI Alk8 in patterning and differentiation of craniofacial tissues SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Forsyth Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1169 EP A1169 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796901957 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, LY Quinn, DA Garg, HG Hales, CA TI Antiproliferative activity in human non-small cell lung cancer cells by chemically modified heparin with low anticoagulant properties SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A829 EP A829 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796900356 ER PT J AU Yu, WH Woessner, JF Stamenokovic, I AF Yu, WH Woessner, JF Stamenokovic, I TI Matrilysin mediate CD44HSPG Transactivating erbB Family from reproductive organs remodeling to neuron protection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. MGH Canc Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 2003 VL 17 IS 5 SU S BP A1303 EP A1303 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 659UY UT WOS:000181796902588 ER PT J AU Mairbaurl, H Weymann, J Mohrlein, A Swenson, ER Maggiorini, M Gibbs, JSR Bartsch, P AF Mairbaurl, H Weymann, J Mohrlein, A Swenson, ER Maggiorini, M Gibbs, JSR Bartsch, P TI Nasal epithelium potential difference at high altitude (4,559 m) - Evidence for secretion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hypoxia; nasal potential; sodium ion transport; chloride ion secretion; nasal dryness ID CYSTIC-FIBROSIS; PULMONARY-EDEMA; FLUID TRANSPORT; SODIUM-CHANNELS; ION-TRANSPORT; LIQUID CLEARANCE; MESSENGER-RNAS; NA-TRANSPORT; LUNG; EXPRESSION AB Hypoxia inhibits activity and expression of ion transport proteins of cultured lung alveolar epithelial cells. Here we tested, whether in vivo hypoxia at high altitude (4,559 m) also inhibits lung ion transport. Transepithelial nasal potentials (NP) were determined as a surrogate measure of lung ion transport activity before and during the stay at altitude. In normoxia, total NP was approximately 20% higher in control subjects than in susceptibles to high-altitude pulmonary edema, but there was no difference between groups I amiloride-inhibitable NPs. At high altitude total NP increased 250% in both groups, whereas amiloride-sensitive NP decreased in control subjects only (-80%), and the chloride ion (Cl-)-sensitive portion of NP almost doubled. Because many mountaineers suffer from nasal dryness at high altitude, a control study was performed in normobaric hypoxia (12% oxygen, 6 hours) at a controlled humidity of 50%. In this study, no change in total NP or its amiloride- and Cl-sensitive portions was observed. The increased Cl- secretion at high altitude but no such change in normobaric hypoxia suggests that nasal dryness may stimulate local active Cl- and fluid secretion in the upper respiratory tract. It is therefore uncertain whether similar changes also occur at the alveolar epithelium. C1 Univ Heidelberg, Dept Med, Div Sports Med, D-69115 Heidelberg, Germany. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med & Res Serv, Seattle, WA 98195 USA. Univ Zurich Hosp, Dept Internal Med, Intens Care Unit, Zurich, Switzerland. Univ London Imperial Coll Sci Technol & Med, Sch Sci Technol & Med, Natl Heart & Lung Inst, London, England. RP Mairbaurl, H (reprint author), Univ Heidelberg, Dept Med, Div Sports Med, Luisenstr 5,Geb 4100, D-69115 Heidelberg, Germany. NR 38 TC 35 Z9 36 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2003 VL 167 IS 6 BP 862 EP 867 DI 10.1164/rccm.200208-864OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 653MA UT WOS:000181439100011 PM 12522027 ER PT J AU Kohen, R Neumaier, JF Hamblin, MW Edwards, E AF Kohen, R Neumaier, JF Hamblin, MW Edwards, E TI Congenitally learned helpless rats show abnormalities in intracellular signaling SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; mood disorders; learned helplessness; animal models; gene expression; second messengers ID PROTEIN-KINASE-C; BIPOLAR AFFECTIVE-DISORDER; ELEMENT-BINDING PROTEIN; AMP-RESPONSIVE ELEMENT; CHRONIC ANTIDEPRESSANT TREATMENT; GLYCOGEN-SYNTHASE KINASE-3-BETA; RECURRENT MAJOR DEPRESSION; GENE-TRANSCRIPTION FACTOR; NEUROTROPHIC-FACTOR BDNF; MOOD-STABILIZING AGENTS AB Background: Affective disorders and the drugs used to treat them lead to changes in intracellular signaling. We used a genetic animal model to investigate to what extent changes in intracellular signal transduction confer a vulnerability to mood or anxiety disorders. Methods: Levels of gene expression in a selectively bred strain of rats with a high vulnerability to develop congenitally learned helplessness (cLH), a strain highly resistant to the same behavior (cNLH) and outbred Sprague-Dawley (SD) control animals were compared using quantitative reverse transcription polymerase chain reaction. Results: Congenitally learned helpless animals had a 24%-30% reduced expression of the cyclic adenosine monophosphate response element binding protein messenger ribonucleic acid (mRNA) in the hippocampus and a 40%-41% increased level of the antiapoptotic protein bcl-2 mRNA in the prefrontal cortex compared to cNLH and SD rats. Other significant changes included changes in the expression levels of the alpha catalytic subunit of protein kinase A, glycogen synthase kinase 3beta, and protein kinase C epsilon. Conclusions: Congenitally learned helpless animals show evidence of altered signal transduction and regulation of apoptosis compared to cNLH and SD control animals. (C) 2003 Society of Biological Psychiatry. C1 GRECC 182B, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Washington, DC USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NINDS, Bethesda, MD 20892 USA. RP Kohen, R (reprint author), GRECC 182B, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIMH NIH HHS [MH57049, MH63303] NR 77 TC 18 Z9 18 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2003 VL 53 IS 6 BP 520 EP 529 DI 10.1016/S0006-3223(03)01503-2 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 655TZ UT WOS:000181569900007 PM 12644357 ER PT J AU Klein, C Nguyen, D Liu, CH Mizoguchi, A Bhan, AK Miki, H Takenawa, T Rosen, FS Alt, FW Mulligan, RC Snapper, SB AF Klein, C Nguyen, D Liu, CH Mizoguchi, A Bhan, AK Miki, H Takenawa, T Rosen, FS Alt, FW Mulligan, RC Snapper, SB TI Gene therapy for Wiskott-Aldrich syndrome: rescue of T-cell signaling and amelioration of colitis upon transplantation of retrovirally transduced hematopoietic stem cells in mice SO BLOOD LA English DT Article ID ACTIN-DEPOLYMERIZING PROTEIN; BONE-MARROW TRANSPLANTATION; IN-VIVO REVERSION; N-WASP; CYTOSKELETAL REARRANGEMENT; LYMPHOCYTES; ACTIVATION; POLYMERIZATION; CHEMOTAXIS; CARRIER AB The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency that is caused by mutations in the recently identified WASP gene. WASP plays an important role in T-cell receptor-mediated signaling to the actin cytoskeleton. In these studies we assessed the feasibility of using retroviral gene transfer into WASP-deficient hematopoietic stem cells (HSCs) to rescue the T-cell signaling defect that is characteristic of WAS. Upon transplantation of WASP-deficient (WKO) HSCs that have been transduced with WASP-expressing retroviruses, mature B and T cells developed in normal numbers. Most importantly, the defect in antigen receptor-induced proliferation was significantly improved in T cells. Moreover, the susceptibility of colitis by WKO HSCs was prevented or ameliorated in recipient bone marrow chimeras by retrovirus-mediated expression of WASP. A partial reversal of the T-cell signaling defect could also be achieved following transplantation of WASP-deficient HSCs expressing the WASP-homologous protein N-WASP. Furthermore, we have documented, a selective advantage of WT over WKO cells in lymphoid tissue using competitive repopulation experiments and Southern blot analysis. Our results provide proof of principle that the WAS-associated T-cell signaling defects can be improved upon transplantation of retrovirally transduced HSCs without overt toxicity and may encourage clinical gene therapy trials. C1 Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Immunopathol Unit, Boston, MA 02114 USA. Childrens Hosp, Howard Hughes Med Inst, Div Mol Med & Pediat Hematol Oncol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Biochem, Minato Ku, Tokyo 108, Japan. Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Immunopathol Unit, 55 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03749, HL59561]; NIAID NIH HHS [AI50950]; NIDDK NIH HHS [DK43551] NR 44 TC 82 Z9 84 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2003 VL 101 IS 6 BP 2159 EP 2166 DI 10.1182/blood-2002-05-1423 PG 8 WC Hematology SC Hematology GA 653JT UT WOS:000181432600015 PM 12433691 ER PT J AU Mitsiades, N Mitsiades, CS Richardson, PG Poulaki, V Tai, YT Chauhan, D Fanourakis, G Gu, XS Bailey, C Joseph, M Libermann, TA Schlossman, R Munshi, NC Hideshima, T Anderson, KC AF Mitsiades, N Mitsiades, CS Richardson, PG Poulaki, V Tai, YT Chauhan, D Fanourakis, G Gu, XS Bailey, C Joseph, M Libermann, TA Schlossman, R Munshi, NC Hideshima, T Anderson, KC TI The proteasome inhibitor PS-341 potentiates sensitivity of multiple myeloma cells to conventional chemotherapeutic agents: therapeutic applications SO BLOOD LA English DT Article ID MEDIATED DRUG-RESISTANCE; NF-KAPPA-B; CAM-DR; APOPTOSIS; ADHESION; GROWTH; SEQUELAE; REPAIR; LIGAND; LINES AB The proteasome inhibitor PS-341 inhibits nuclear factor-kappaB (NF-kappaB) activation, induces apoptosis in cancer cells, including multiple myeloma (MM) cells, and has marked clinical activity as a monotherapy for MM. In this study, we found that subtoxic concentrations of PS-341 potently sensitized MM cell lines and patient cells to DNA-damaging chemotherapeutic agents such as doxorubicin and melphalan, including cells resistant to these drugs and those isolated from a patient who had relapsed after PS-341 monotherapy. Moreover, PS-341 abolished cell adhesion-mediated drug resistance. Using gene expression profiling and proteomic analysis, we demonstrate that PS-341, among its other proapoptotic effects, down-regulates the expression of several effectors involved in the cellular response to genotoxic stress. These data suggest that, in addition to down-regulating the expression of apoptosis inhibitors, PS-341 inhibits genotoxic stress response pathways and thereby restores sensitivity to DNA-damaging chemotherapeutic agents. These studies, therefore, provide the framework for clinical use of this agent in combination with conventional chemotherapy. C1 Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Genom Ctr, Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Boston VA Hlth Care Syst, Boston, MA USA. RP Anderson, KC (reprint author), Harvard Univ, Jerome Lipper Multiple Myeloma Ctr, Dept Adult Oncol, Dana Farber Canc Inst,Sch Med, 44 Binney St, Boston, MA 02115 USA. RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU NIDDK NIH HHS [R24 DK58739]; PHS HHS [P0-1 78378, R0-1 50947] NR 25 TC 499 Z9 528 U1 1 U2 14 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 MAR 15 PY 2003 VL 101 IS 6 BP 2377 EP 2380 DI 10.1182/blood-2002-06-1768 PG 4 WC Hematology SC Hematology GA 653JT UT WOS:000181432600048 PM 12424198 ER PT J AU Ganz, T Gabayan, V Liao, HI Liu, LD Oren, A Graf, T Cole, AM AF Ganz, T Gabayan, V Liao, HI Liu, LD Oren, A Graf, T Cole, AM TI Increased inflammation in lysozyme M-deficient mice in response to Micrococcus luteus and its peptidoglycan SO BLOOD LA English DT Article ID GRAM-NEGATIVE BACTERIA; CELL WALL COMPONENTS; RECOGNITION PROTEIN; STAPHYLOCOCCUS-AUREUS; RESPIRATORY BURST; ACTIVATION; DROSOPHILA; COMPLEMENT; NEUTROPHILS; DUPLICATION AB More than 70 years ago, Alexander Fleming discovered lysozyme and proposed that nonpathogenic bacteria fall to cause disease because they are very susceptible to destruction by lysozyme, an enzyme that is one of the principal proteins of phagocytes. Although much has been learned about the effects of lysozyme in vitro, its biological role in vivo has not been determined. We examined transgenic mice deficient in lysozyme M after challenge by the normally nonpathogenic and highly lysozyme-sensitive bacterium Micrococcus luteus. Despite partial compensation by newly expressed lysozyme P in macrophages, lysozyme M-deficient mice developed much more severe lesions than wild-type mice. The tissue injury was due to the failure of lysozyme M-deficient mice to inactivate peptidoglycan, resulting in an intense and prolonged inflammatory response. Our data indicate that tissue injury is normally limited by prompt degradation of bacterial macromolecules that trigger innate immunity and inflammation. C1 Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, W Los Angeles Vet Adm Hosp, Los Angeles, CA USA. Albert Einstein Coll Med, Bronx, NY USA. RP Ganz, T (reprint author), Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, 37-055 CHS, Los Angeles, CA 90095 USA. RI Graf, Thomas/B-4252-2015; OI Graf, Thomas/0000-0003-2774-4117; Ganz, Tomas/0000-0002-2830-5469 FU NCI NIH HHS [R01 CA89590-01] NR 32 TC 50 Z9 51 U1 5 U2 10 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 MAR 15 PY 2003 VL 101 IS 6 BP 2388 EP 2392 DI 10.1182/blood-2002-07-2319 PG 5 WC Hematology SC Hematology GA 653JT UT WOS:000181432600050 PM 12411294 ER PT J AU Szatrowski, TP Dodge, RK Reynolds, C Westbrook, CA Frankel, SR Sklar, J Stewart, CC Hurd, DD Kolitz, JE Velez-Garcia, E Stone, RM Bloomfield, CD Schiffer, CA Larson, RA AF Szatrowski, TP Dodge, RK Reynolds, C Westbrook, CA Frankel, SR Sklar, J Stewart, CC Hurd, DD Kolitz, JE Velez-Garcia, E Stone, RM Bloomfield, CD Schiffer, CA Larson, RA TI Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine - Cancer and leukemia group B study 9311 SO CANCER LA English DT Article DE adult acute lymphoblastic leukemia; anti-B4-blocked ricin; high-dose cytarabine; lineage specific therapy; minimal residual disease ID NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; CONTINUOUS-INFUSION; MYELOID-LEUKEMIA; CLINICAL-TRIALS; BLOCKED RICIN; CHEMOTHERAPY; REGIMEN; CONSOLIDATION AB BACKGROUND. Anti-B4-blocked ricin is an immunotoxin comprised of an anti-CD19 murine monoclonal antibody (134) conjugated to blocked ricin, which has cytotoxic activity in patients with lymphoid malignancies. METHODS. Adults with untreated acute lymphoblastic leukemia (ALL) were treated with a previously developed and tested chemotherapeutic regimen. Patients with CD19 positive ALL were given anti-B4-blocked ricin as 2 7-day continuous infusions 1 week apart. Patients with CD19 negative ALL received high-dose cytarabine. Serial polymerase chain reaction (PCR) assays of BCR-ABL, immunoglobulin heavy chain (IGH), and T-cell receptor (TCR) genes were used to measure the impact of lineage specific intensification treatment on minimal residual disease. RESULTS. Eighty-two adults were enrolled, and 78 were eligible. The median age was 34 years (range, 17-81 years). Sixty-six patients (85%) achieved complete remission. Forty-six patients received the anti-B4-blocked ricin, which generally was well tolerated; 80% were able to receive both courses. The most common toxicity was asymptomatic transient elevation of liver function tests in 72% of patients. Lymphopenia occurred in 46% of patients. Two patients developed antibodies to the anti-B4-blocked ricin. Molecular monitoring before and after the experimental course of intensification did not show a consistent change in the number of leukemia cells remaining, and the immediate posttreatment PCR studies did not correlate with remission duration. CONCLUSIONS. intensification therapy with anti-B4-blocked ricin is feasible for patients with CD19 positive ALL, although there is little evidence of an additional clinical benefit from the anti-B4-blocked ricin. (C) 2003 American Cancer Society. C1 Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Duke Univ, Canc & Leukemia Grp B Stat Ctr, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Maryland, Baltimore, MD 21201 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Puerto Rico, San Juan, PR 00936 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. Wayne State Univ, Detroit, MI USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Canc & Leukemia Grp B, Chicago, IL USA. RP Larson, RA (reprint author), Univ Chicago, Hematol Oncol Sect, MC-2115,5841 S Maryland Ave, Chicago, IL 60637 USA. OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA32291, CA02599, CA03927, CA04326, CA07968, CA08025, CA11789, CA16450, CA21060, CA31946, CA31983, CA33601, CA35279, CA41287, CA47555, CA47559, CA47577, CA47642, CA77658] NR 35 TC 44 Z9 45 U1 4 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2003 VL 97 IS 6 BP 1471 EP 1480 DI 10.1002/cncr.11219 PG 10 WC Oncology SC Oncology GA 652CL UT WOS:000181361900014 PM 12627512 ER PT J AU Lai, CL Dienstag, J Schiff, E Leung, NWY Atkins, M Hunt, C Brown, N Woessner, M Boehme, R Condreay, L AF Lai, CL Dienstag, J Schiff, E Leung, NWY Atkins, M Hunt, C Brown, N Woessner, M Boehme, R Condreay, L TI Prevalence and clinical correlates of YMDD variants during lamivudine therapy for patients with chronic hepatitis B SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LIVER-TRANSPLANTATION; VIRUS-INFECTION; ACUTE EXACERBATION; UNITED-STATES; RESISTANT; POLYMERASE; MUTATIONS; EMERGENCE; MUTANTS; TRIAL AB YMDD variants of hepatitis B virus (HBV) emerge in some patients with chronic hepatitis B who receive lamivudine. YMDD variants were examined in 794 patients in 4 controlled studies of 1 year's duration. The long-term effects of YMDD variants were examined in a subset of patients treated up to 4 years. YMDD variants were detected by polymerase chain reaction (PCR) and restriction fragment-length polymorphism assays. After 1 year, YMDD variants were detected in 81 (24%) of 335 patients. In these patients, the median serum HBV DNA concentration at 1 year was <20% of the baseline level, and serum alanine transaminase (ALT) levels and liver histologic findings had significantly improved. In patients with YMDD variants who were treated for up to 4 years, median HBV DNA and ALT levels showed improvements. Sex, baseline body mass index, and HBV DNA level were associated with emergence of YMDD variants. Patients with YMDD variants losing clinical response with a significant increase in the HBV DNA and ALT levels may require additional therapy. C1 Queen Mary Hosp, Univ Dept Med, Hong Kong, Hong Kong, Peoples R China. Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Miami, Sch Med, Ctr Liver Dis, Miami, FL USA. GlaxoSmithKline, Res Triangle Pk, NC USA. GlaxoSmithKline, Greenford, Middx, England. RP Lai, CL (reprint author), Queen Mary Hosp, Univ Dept Med, Rm 407,Professorial Block, Hong Kong, Hong Kong, Peoples R China. RI Lai, Ching Lung/C-4298-2009 FU NCRR NIH HHS [M01RR01066] NR 43 TC 454 Z9 487 U1 0 U2 5 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 MAR 15 PY 2003 VL 36 IS 6 BP 687 EP 696 DI 10.1086/368083 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RQ UT WOS:000181451200003 PM 12627352 ER PT J AU Frolov, MV Stevaux, O Moon, NS Dimova, D Kwon, EJ Morris, EJ Dyson, NJ AF Frolov, MV Stevaux, O Moon, NS Dimova, D Kwon, EJ Morris, EJ Dyson, NJ TI G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression SO GENES & DEVELOPMENT LA English DT Article DE E2F; G1 cyclins; Drosophila ID S-PHASE; CELL-CYCLE; IN-VIVO; DROSOPHILA EMBRYOGENESIS; TRANSCRIPTION FACTOR; E2F FAMILY; PROGRESSION; EXPRESSION; PROLIFERATION; INHIBITOR AB Here we show that the cell cycle defects of dE2F1-depleted cells depend on the cooperative effects of dE2F2 and DACAPO (DAP), an inhibitor of Cyclin E/cyclindependent kinase 2 (CycE/cdk2). The different properties of cells lacking dE2F1/dE2F2 and dE2F1/DAP lead to the surprising observation that dE2F2-mediated repression differs from retinoblastoma family protein 1 (RBF1) inhibition of dE2F1, and is resistant to both CycE/cdk2 and Cyclin D/cyclin-dependent kinase 4 (CycD/cdk4). This resistance occurs even though dE2F2/RBF1 complexes are disrupted by CycE/cdk2, and may explain why dE2F2 is so potent in the absence of de2f1. The implication of these results is that cells containing dE2F2 require dE2F1 to either prevent, or reverse, dE2F7-mediated repression. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [F32 CA093045, F32 CA 88474, F32 CA 93045, F32 CA088474]; NIGMS NIH HHS [GM 53203, R01 GM053203] NR 27 TC 25 Z9 26 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2003 VL 17 IS 6 BP 723 EP 728 DI 10.1101/gad.1031803 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 661MZ UT WOS:000181895500005 PM 12651890 ER PT J AU Zhang, F Barboric, M Blackwell, TK Peterlin, BM AF Zhang, F Barboric, M Blackwell, TK Peterlin, BM TI A model of repression: CTD analogs and PIE-1 inhibit transcriptional elongation by P-TEFb SO GENES & DEVELOPMENT LA English DT Article DE P-TEFb; CTD; PIE-1; transcription; repression; elongation ID RNA-POLYMERASE-II; C-TERMINAL DOMAIN; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; PROTEIN; KINASE; TAT; ACTIVATION; ENHANCER AB The positive transcription elongation factor b (P-TEFb) contains cyclin T1 (CycT1) and cyclin-dependent kinase 9 (Cdk9). For activating the expression of eukaryotic genes, the histidine-rich sequence in CycT1 binds the heptapeptide repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII), whereupon Cdk9 phosphorylates the CTD. We found that alanine-substituted heptapeptide repeats that cannot be phosphorylated also bind CycT1. When placed near transcription units, these CTD analogs block effects of P-TEFb. Remarkably, the transcriptional repressor PIE-1 from Caenorhabditis elegans behaves analogously. It binds CycT1 via an alanine-containing heptapeptide repeat and inhibits transcriptional elongation. Thus, our findings reveal a new mechanism by which repressors inhibit eukaryotic transcription. C1 Univ Calif San Francisco, Rosalind Russell Med Res Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Rosalind Russell Med Res Ctr, Dept Microbiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Rosalind Russell Med Res Ctr, Dept Immunol, San Francisco, CA 94143 USA. Univ Ljubljana, Fac Med, Inst Biochem, Ljubljana 61000, Slovenia. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Barboric, M (reprint author), Univ Calif San Francisco, Rosalind Russell Med Res Ctr, Dept Med, San Francisco, CA 94143 USA. RI Barboric, Matjaz/C-9918-2009 NR 53 TC 79 Z9 83 U1 1 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2003 VL 17 IS 6 BP 748 EP 758 DI 10.1101/gad.1068203 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 661MZ UT WOS:000181895500008 PM 12651893 ER PT J AU Gribnau, J Hochedlinger, K Hata, K Li, E Jaenisch, R AF Gribnau, J Hochedlinger, K Hata, K Li, E Jaenisch, R TI Asynchronous replication timing of imprinted loci is independent of DNA methylation, but consistent with differential subnuclear localization SO GENES & DEVELOPMENT LA English DT Article DE asynchronous replication; genomic imprinting; nuclear localization; DNA methylation; Igf2-H19; replication fork ID BETA-GLOBIN LOCUS; HISTONE H4 ACETYLATION; EMBRYONIC STEM-CELLS; DEVELOPMENTAL REGULATION; CHROMOSOME TERRITORIES; SPATIAL-ORGANIZATION; GENE-EXPRESSION; X-INACTIVATION; ALPHA-GLOBIN; H19 GENE AB Genomic imprinting in mammals marks the two parental alleles resulting in differential gene expression. Imprinted loci are characterized by distinct epigenetic modifications such as differential DNA methylation and asynchronous replication timing. To determine the role of DNA methylation in replication timing of imprinted loci, we analyzed replication timing in Dnmt1- and Dnmt3L-deficient embryonic stem (ES) cells, which lack differential DNA methylation and imprinted gene expression. Asynchronous replication is maintained in these ES cells, indicating that asynchronous replication is parent-specific without the requirement for differential DNA methylation. imprinting centers are required for regional control of imprinted gene expression. Analysis of replication fork movement and three-dimensional RNA and DNA fluoroscent in situ hybridization (FISH) analysis of the Igf2-H19 locus in various cell types indicate that the Igf2-H19 imprinting center differentially regulates replication timing of nearby replicons and subnuclear localization. Based on these observations, we suggest a model in which cis elements containing nonmethylation imprints are responsible for the movement of parental imprinted loci to distinct nuclear compartments with different replication characteristics resulting in asynchronous replication timing. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr,Dept Dermatol, Charlestown, MA 02129 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Jaenisch, R (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA 82389, R01 CA082389]; NIGMS NIH HHS [GM 52106] NR 45 TC 69 Z9 73 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2003 VL 17 IS 6 BP 759 EP 773 DI 10.1101/gad.1059603 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 661MZ UT WOS:000181895500009 PM 12651894 ER PT J AU Henderson, IC Berry, DA Demetri, GD Cirrincione, CT Goldstein, LJ Martino, S Ingle, JN Cooper, MR Hayes, DF Tkaczuk, KH Fleming, G Holland, JF Duggan, DB Carpenter, JT Frei, E Schilsky, RL Wood, WC Muss, HB Norton, L AF Henderson, IC Berry, DA Demetri, GD Cirrincione, CT Goldstein, LJ Martino, S Ingle, JN Cooper, MR Hayes, DF Tkaczuk, KH Fleming, G Holland, JF Duggan, DB Carpenter, JT Frei, E Schilsky, RL Wood, WC Muss, HB Norton, L TI Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; CYCLOPHOSPHAMIDE; THERAPY; FLUOROURACIL; INTENSITY; CARCINOMA AB Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 Mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 Mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 Mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%,66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P = .0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% ( +/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer. J Clin Oncol 21:976-983. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. CALGB Stat Ctr, Canc & Leukemia Grp B, Durham, NC USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Texas, MD Anderson Canc Ctr, Sw Oncol Grp Operat, San Antonio, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp Operat, Philadelphia, PA USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Michigan, Ann Arbor, MI USA. Greenbuam Canc Ctr, Baltimore, MD USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. CALGB Cent Off, Chicago, IL USA. Mt Sinai Sch Med, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. SUNY Syracuse, Hlth Sci Ctr, Syracuse, NY 13210 USA. Univ Alabama, Birmingham, AL USA. Univ Vermont, Burlington, VT USA. RP Henderson, IC (reprint author), Univ Calif San Francisco, 1600 Divisadero St,Box 1710, San Francisco, CA 94143 USA. EM craig.henderson@accessoncology.com OI Norton, Larry/0000-0003-3701-9250 FU NCI NIH HHS [CA31946] NR 24 TC 707 Z9 733 U1 2 U2 13 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 MAR 15 PY 2003 VL 21 IS 6 BP 976 EP 983 DI 10.1200/JCO.2003.02.063 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300005 PM 12637460 ER PT J AU Esteva, FJ Glaspy, J Baidas, S Laufman, L Hutchins, L Dickler, M Tripathy, D Cohen, R DeMichele, A Yocum, RC Osborne, CK Hayes, DF Hortobagyi, GN Winer, E Demetri, GD AF Esteva, FJ Glaspy, J Baidas, S Laufman, L Hutchins, L Dickler, M Tripathy, D Cohen, R DeMichele, A Yocum, RC Osborne, CK Hayes, DF Hortobagyi, GN Winer, E Demetri, GD TI Multicenter phase II study of oral bexarotene for patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RETINOID-X RECEPTOR; SELECTIVE AROMATASE INHIBITOR; T-CELL LYMPHOMA; MEGESTROL-ACETATE; POSTMENOPAUSAL WOMEN; PROMYELOCYTIC LEUKEMIA; MAMMARY-CARCINOMA; TAMOXIFEN FAILURE; CLINICAL-TRIAL; ACID AB Purpose : Bexarotene is a retinoid X receptor-selective retinoid that has preclinical antitumor activity in breast cancer. We evaluated the efficacy and safety of oral bexarotene in the treatment of patients with metastatic breast cancer. Patients and Methods: The following three groups of patients were treated: hormone-refractory, chemotherapy-refractory, and tamoxifen-resistant patients. Patients in the first two groups were treated with bexarotene alone, whereas the tamoxifen-resistant patients received both tamoxifen and bexarotene. Patients in all groups were randomly assigned to receive bexarotene at either 200 or 500 mg/m(2)/d. Results: One hundred forty-eight patients were randomixed; 145 patients were treated. Of 48 hormone-refractory patients, there were two partial responses (6%) and 10 patients with stable disease lasting more than 6 months; of 47 chemotherapy-refractory patients, there were two partial responses (6%) and five patients with stable disease; and of 51 tamoxifen-resistant patients, there was one partial response (3%) and 11 patients with stable disease. All partial responses occurred at the 200-mg/m(2)/d dose. The projected median time to progression across all of the arms was 8 to 10 weeks. There were no drug-related deaths, and only two patients had drug-related serious adverse events. The most common drug-related adverse events were hypertriglyceridemia (84%), dry skin (34%), asthenia (30%), and headache (27%). There were no cases of pancreatitis. Conclusion: The efficacy of bexarotene in patients with refractory metastatic breast cancer is limited. However, it is an oral agent with minimal toxicity and a unique mechanism of action, which produced clinical benefit in approximately 20% of patients. Future efforts should define populations likely to benefit from this agent. J Clin Oncol 21:999-1006. (C) 2003 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Hematol Oncol Consultants, Columbus, OH USA. Ligand Pharmaceut Inc, San Diego, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Little Rock, AR USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Univ Virginia, Charlottesville, VA USA. RP Esteva, FJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd,Box 424, Houston, TX 77030 USA. EM festeva@mdanderson.org OI Esteva, Francisco/0000-0003-2437-3920 FU NCI NIH HHS [CA82119] NR 29 TC 69 Z9 69 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 MAR 15 PY 2003 VL 21 IS 6 BP 999 EP 1006 DI 10.1200/JCO.2003.05.068 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300008 PM 12637463 ER PT J AU Buzdar, A O'Shaughnessy, JA Booser, DJ Pippen, JE Jones, SE Munster, PN Peterson, P Melemed, AS Winer, E Hudis, C AF Buzdar, A O'Shaughnessy, JA Booser, DJ Pippen, JE Jones, SE Munster, PN Peterson, P Melemed, AS Winer, E Hudis, C TI Phase II, randomized, double-blind study of two dose levels of arzoxifene in patients with locally advanced or metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SURGICAL-ADJUVANT-BREAST; TAMOXIFEN; TRIAL AB Purpose : To select a daily dose of arzoxifene (LY3S3381), a selective estrogen receptor modulator, for use in future studies in women with locally advanced or metastatic breast cancer who are either potentially tamoxifen sensitive (TS) or tamoxifen refractory (TR). Patients and Methods: This trial was a randomized, double-blind, phase 11 study of arzoxifene 20 mg (n = 55) and 50 mg (n = 57) in women with advanced or metastatic breast cancer. Patients were randomly assigned to balance for number of metastatic disease sites, prior tomoxifen therapy, and estrogen receptor status. The primary end point was tumor response rate (RR). Secondary end points included clinical benefit rate (CBR), time to progression (TTP), and toxicity. Results: Forty-nine patients were TS and 63 were TR. According to independent review, among TS patients, RR was higher in the 20-mg arm than the 50-mg arm (26.1% v 8.0%), with a longer TTP (8.3 v 3.2 months; P > .05). Among the TR patients, response rate was the same in the 20-mg and 50-mg arms (10.3%) with similar TTP (2.7 and 2.8 months, respectively, P > .05). CBR was higher in the 20-mg arm than in the 50-mg arm among TS patients (39.1% v 20.0%) and TR patients (13.8% v 10.3%). Arzoxifene was well tolerated. Dose-dependent toxicity was not demonstrated. There were no deaths during study, Conclusion: Arzoxifene is effective in the treatment of TS and TR patients with advanced or metastatic breast cancer at the 20-mg and 50-mg dose levels. Toxicities are minimal, and the therapy is tolerated. The 20-mg dose seems to be at least as effective as the 50-mg dose. Accordingly, arzoxifene 20 mg/d was selected for further study in patients with breast cancer. J Clin Oncol 21:1007-1014. (C) 2003 by American Society of Clinical Oncology. C1 MD Anderson Canc Ctr, Houston, TX 77030 USA. US Oncol Res, Dallas, TX USA. Baylor Sammons Canc Ctr, Dallas, TX USA. Texas Oncol, Dallas, TX USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Buzdar, A (reprint author), MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 424, Houston, TX 77030 USA. EM abuzdar@mdanderson.org NR 21 TC 55 Z9 57 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 MAR 15 PY 2003 VL 21 IS 6 BP 1007 EP 1014 DI 10.1200/JCO.2003.06.108 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300009 PM 12637464 ER PT J AU Batchelor, T Carson, K O'Neill, A Grossman, SA Alavi, J New, P Hochberg, F Priet, R AF Batchelor, T Carson, K O'Neill, A Grossman, SA Alavi, J New, P Hochberg, F Priet, R TI Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: A report of NABTT 96-07 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NON-HODGKINS-LYMPHOMA; HIGH-DOSE METHOTREXATE; PHASE-II; CHEMOTHERAPY; THERAPY; SURVIVAL; CYCLOPHOSPHAMIDE; DEXAMETHASONE; MULTICENTER AB Purpose: A multicenter, phase II study of single-agent, intravenous methotrexate in newly diagnosed non-AIDS-related primary CNS lymphoma was conducted in the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. Methods: Methotrexate (8 g/m(2)) was initially administered every 2 weeks. The primary end point was radiographic CR or PR, as defined by standard radiographic criteria, and secondary end points were survival and drug-related toxicity. Results: Twenty-five patients were enrolled with a mean age of 60 years and median Karnofsky Performance Score of 80. Three of 14 patients who underwent lumbar puncture had malignant cells on CSF cytopathology, and five of 25 patients had ocular involvement. Two patients could not be evaluated for the primary end point because of the absence of measurable disease in one and death before radiologic imaging in another. All patients have completed the treatment program or progressed. Among 23 patients, there were 12 CR (52%), five PR (22%), one (4%) with stable disease, and five progressions (22%) while on therapy. Seven patients died of tumor progression, and two died of other causes. Median progression-free survival was 12.8 months. Median overall survival for the entire group had not been reached at 22.8+ months. The toxicity of this regimen was modest, with no grade 3 or 4 toxicity in 13 of 25 patients, grade 3 toxicity in eight of 25 patients, and grade 4 toxicity in four of 25 patients after 287 cycles of chemotherapy. Conclusion: These results indicate that high-dose methotrexate is associated with modest toxicity and a radiographic response proportion (74%) comparable to more toxic regimens. J Clint Oncol 21:1044-1049. (C) 2003 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Birmingham, Birmingham, AL USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. RP Batchelor, T (reprint author), NABTT CNS Consortium, Canc Res Bldg,Room G87,1650 Orleans St, Baltimore, MD 21231 USA. EM jfisher@jhmi.edu NR 32 TC 254 Z9 267 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2003 VL 21 IS 6 BP 1044 EP 1049 DI 10.1200/JCO.2003.03.036 PG 6 WC Oncology SC Oncology GA 657QR UT WOS:000181678300014 PM 12637469 ER PT J AU Earle, CC Park, ER Lai, B Weeks, JC Ayanian, JZ Block, S AF Earle, CC Park, ER Lai, B Weeks, JC Ayanian, JZ Block, S TI Identifying potential indicators of the quality of end-of-life cancer care from administrative data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH; HOME; PHYSICIANS; OUTCOMES; SERVICES; FAMILY; TRIAL; PLACE; DEATH AB Purpose : To explore potential indicators of the quality of end-of-life services for cancer patients that could be monitored using existing administrative data. Methods: Quality indicators were identified and assessed by literature review for proposed indicators, focus groups with cancer patients and family members to assess candidate indicators and generate new ideas, and an expert panel ranking the meaningfulness and importance of each potential indicator using a modified Delphi approach. Results: There were three major concepts of poor quality of end-of-life cancer care that could be examined using currently-available administrative data (such as Medicare claims): institution of new anticancer therapies or continuation of ongoing treatments very near death; a high number of emergency room visits, inpatient hospital admissions, or intensive care unit days near the end of life; and a high proportion of patients never enrolled in hospice, only admitted in the last few days of life, or dying in an acute-care setting. Concepts such as access to psychosocial and other multidisciplinary services and pain and symptom control are important and may eventually be feasible, but they cannot currently be applied in most data systems. Indicators based on limiting the use of treatments with low probability of benefit or indicators based on economic efficiency were not acceptable to patients, family members, or physicians. Conclusion: Several promising claims-based quality indicators were identified that, if found to be valid and reliable within data systems, could be useful in identifying healthcare systems in need of improving end-of-life services. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Dept Psychiat, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu FU NCI NIH HHS [CA91753-02] NR 41 TC 265 Z9 268 U1 3 U2 6 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 MAR 15 PY 2003 VL 21 IS 6 BP 1133 EP 1138 DI 10.1200/JCO.2003.03.059 PG 6 WC Oncology SC Oncology GA 657QR UT WOS:000181678300026 PM 12637481 ER PT J AU Polsky, D Mandelblatt, JS Weeks, JC Venditti, L Hwang, YT Glick, HA Hadley, J Schulman, KA AF Polsky, D Mandelblatt, JS Weeks, JC Venditti, L Hwang, YT Glick, HA Hadley, J Schulman, KA TI Economic evaluation of breast cancer treatment: Considering the value of patient choice SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; QUALITY-OF-LIFE; COMPARING TOTAL MASTECTOMY; CONSERVING SURGERY; CONSERVATIVE SURGERY; GEOGRAPHIC-VARIATION; COST-EFFECTIVENESS; RADIATION-THERAPY; ELDERLY WOMEN; OLDER WOMEN AB Purpose : To use 5 years of primary data to compare the incremental cost-effectiveness of breast conservation and radiation versus mastectomy with the restriction of choice to a single therapy versus providing a choice of either therapy. Patients and Methods: We evaluated a random retrospective cohort of 2,517 Medicare beneficiaries treated for newly diagnosed stage I or II breast cancer from 1992 through 1994. The outcome measures were quality-adjusted life-years (QALYs) and 5-year medical costs. Risk and propensity score adjustments were used in the analysis. Results: A breast conservation and radiation regimen has significantly higher costs than mastectomy in the first year after surgery; the adjusted 5-year costs are $14,054 (95% confidence interval, $9,791 to $18,312) greater than those of mastectomy. The adjusted incremental cost-effectiveness ratio comparing breast conservation and radiation to mastectomy was $219,594 per QALY for the comparison of the two strategies. If the possibility of patient choice from maintaining the availability of multiple treatments versus restricting choice to mastectomy alone provides a quality-of-life gain of 0.031 QALYs, then the cost-effectiveness ratio of this choice option is $80,440 per QALY. Conclusion: The current system of providing a choice between mastectomy and breast conservation surgery is economically attractive when the economic analysis includes the benefit of patient choice of treatment. C1 Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Georgetown Univ, Washington, DC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC USA. RP Polsky, D (reprint author), Univ Penn, Div Gen Internal Med, Blockley Hall 1212, Philadelphia, PA 19104 USA. EM polsky@mail.med.upenn.edu FU AHRQ HHS [HS08395]; NCI NIH HHS [U01/CA88283A] NR 33 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2003 VL 21 IS 6 BP 1139 EP 1146 DI 10.1200/JCO.2003.03.126 PG 8 WC Oncology SC Oncology GA 657QR UT WOS:000181678300027 PM 12637482 ER PT J AU Earle, CC AF Earle, CC TI Influenza vaccination in elderly patients with advanced colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; COMORBIDITY INDEX; CHEMOTHERAPY; POPULATION; IMPACT; VALIDATION; EPIDEMICS; ADULTS; CLAIMS AB Purpose: To examine influenza vaccination use in patients undergoing chemotherapy for advanced cancer. Methods: All Medicare patients treated for stage IV colorectal cancer between 1993 and 1998 while living in one of the regions monitored by the Survival, Epidemiology, and End Results Program who were alive in the fall months and who survived at least 4 months with their cancer were considered eligible to have received vaccination. Their medical bills were analyzed to determine receipt of influenza vaccination and subsequent outcomes. Results: Eligibility criteria were met by 1,225 patients who were undergoing chemotherapy during 1,577 person-years of observation. Overall, 39.7% of patients received influenza vaccination, increasing from 26% in 1993 to 43% in 1998. When vaccination was administered, it was provided by primary care physicians 68% of the time. Vaccinated patients were more likely to be white, of higher socioeconomic status, and to have more comorbidity. Fewer diagnoses of influenza and pneumonia infections were made in vaccinated patients while undergoing treatment. Those patients who were immunized also had fewer chemotherapy interruptions and were more likely to survive through to the beginning of the next fall (hazard ratio, 0.88; 95% confidence interval, 0.77 to 0.99). There was a trend toward decreased resource use among immunized patients. Conclusion: This study observed outcomes associated with influenza vaccination that are similar to those reported for patients without cancer. However, rates of immunization are relatively low, and disparities exist for vulnerable populations. As part of delivering high-quality care, oncologists should promote influenza vaccination for their patients who are undergoing treatment for advanced cancer. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu FU NCI NIH HHS [CA 91753-02] NR 38 TC 31 Z9 31 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 MAR 15 PY 2003 VL 21 IS 6 BP 1161 EP 1166 DI 10.1200/JCO.2003.06.008 PG 6 WC Oncology SC Oncology GA 657QR UT WOS:000181678300030 PM 12637485 ER PT J AU Cao, H Kaleebu, P Hom, D Flores, J Agrawal, D Jones, N Serwanga, J Okello, M Walker, C Sheppard, H El-Habib, R Klein, M Mbidde, E Mugyenyi, P Walker, B Ellner, J Mugerwa, R AF Cao, H Kaleebu, P Hom, D Flores, J Agrawal, D Jones, N Serwanga, J Okello, M Walker, C Sheppard, H El-Habib, R Klein, M Mbidde, E Mugyenyi, P Walker, B Ellner, J Mugerwa, R CA HIV Network Prevention Trials TI Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-Seronegative Ugandan volunteers: Results of the HIV Network for Prevention Trials 007 vaccine study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-LYMPHOCYTE RESPONSES; TYPE-1; AIDS; NEUTRALIZATION; CELLS; ANTIBODIES; ANTIGENS; IMMUNITY; AFRICA; GP120 AB In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n=20), control vector containing the rabies virus glycoprotein gene (n=10), or saline placebo (n=10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients. C1 Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Uganda Virus Res Inst Labs, Entebbe, Uganda. Joint Clin Res Ctr, Kampala, Uganda. Makerere Univ, Kampala, Uganda. Aventis Pasteur, Marcy Letoile, France. RP Cao, H (reprint author), Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, 850 Marina Bay Pkwy, Richmond, CA 94804 USA. NR 27 TC 50 Z9 52 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2003 VL 187 IS 6 BP 887 EP 895 DI 10.1086/368020 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 653RL UT WOS:000181450800002 PM 12660934 ER PT J AU Jacob, TC Kaplan, JM AF Jacob, TC Kaplan, JM TI The EGL-21 carboxypeptidase E facilitates acetylcholine release at Caenorhabditis elegans neuromuscular junctions SO JOURNAL OF NEUROSCIENCE LA English DT Article DE carboxypeptidase E; CPE; proprotein convertase; PC2; egl-21; egl-3; neuromuscular junction; neuropeptide; dense-core vesicle; DCV; synapse; C. elegans ID DEFICIENT FAT MICE; OBESE FAT/FAT MICE; C-ELEGANS; NEUROPEPTIDE GENE; SYNAPTIC TRANSMISSION; CPE(FAT)/CPE(FAT) MICE; DROSOPHILA; PEPTIDES; MUTATION; FAMILY AB Proneuropeptides are packaged into dense-core vesicles in which they are processed into active peptides by copackaged enzymes. Proprotein convertases (PCs) cleave precursors after dibasic residues, and carboxypeptidases remove basic residues from the C terminals. We show here that the Caenorhabditis elegans egl-21 gene encodes a protein that is very similar to carboxypeptidase E (CPE) and is broadly expressed in the nervous system. Mutants lacking either egl-21 CPE or egl-3, which encodes the C. elegans ortholog of PC type 2 (PC2), were defective for processing endogenously expressed FMRFamide (Phe-Met-Arg-Phe-NH2)-related peptides (FaRPs). Mutants lacking the unc-104 kinesin motor protein were defective for anterograde movement of dense-core vesicle components, including egl-3 PC2, egl-21 CPE, and FaRPs. We provide evidence that egl-3 PC2 and egl-21 CPE mutants have diminished acetylcholine release at neuromuscular junctions (NMJs). Taken together, these results suggest that egl-21 CPE and egl-3 PC2 process endogenous neuropeptides that facilitate acetylcholine release at C. elegans NMJs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Kaplan, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Wellman 8,50 Blossom St, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NINDS NIH HHS [NS32196] NR 74 TC 88 Z9 92 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2003 VL 23 IS 6 BP 2122 EP 2130 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900018 PM 12657671 ER PT J AU Feschenko, MS Donnet, C Wetzel, RK Asinovski, NK Jones, LR Sweadner, KJ AF Feschenko, MS Donnet, C Wetzel, RK Asinovski, NK Jones, LR Sweadner, KJ TI Phospholemman, a single-span membrane protein, is an accessory protein of Na,K-ATPase in cerebellum and choroid plexus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Na,K-ATPase; phospholemman; FXYD; cerebellum; choroid plexus; Purkinje cell; Bergmann glia ID CARDIAC SARCOLEMMAL VESICLES; CENTRAL-NERVOUS-SYSTEM; NA-K-ATPASE; GAMMA-SUBUNIT; KINASE-C; ALPHA-SUBUNITS; IMMUNOCYTOCHEMICAL LOCALIZATION; SARCOPLASMIC-RETICULUM; RENAL NA,K-ATPASE; FUNCTIONAL-ROLE AB Phospholemman (FXYD1) is a homolog of the Na,K-ATPase gamma subunit (FXYD2), a small accessory protein that modulates ATPase activity. Here we show that phospholemman is highly expressed in selected structures in the CNS. It is most abundant in cerebellum, where it was detected in the molecular layer, in Purkinje neurons, and in axons traversing the granule cell layer. Phospholemman was particularly enriched in choroid plexus, the organ that secretes CSF in the ventricles, where it colocalized with Na,K-ATPase in the apical membrane. It was also enriched, with Na, K-ATPase, in certain tanycytes or ependymal cells of the ventricle wall. Two different experimental approaches demonstrated that phospholemman physically associated with the Na, K-ATPase in cerebellum and choroid plexus: the proteins copurified after detergent treatment and co-immunoprecipitated from solubilized crude membranes using either antiphospholemman or anti-Na,K-ATPase antibodies. Phospholemman antibodies precipitated all three Na, K-ATPase alpha subunit isoforms (alpha1-alpha3) from cerebellum, indicating that the interaction is not specific to a particular alpha isoform and consistent with the presence of phospholemman in both neurons and glia. Antibodies against the C-terminal domain of phospholemman reduced Na, K-ATPase activity in vitro without effect on Na+ affinity. At least two other FXYD family members have been detected in the CNS, suggesting that additional complexity of sodium pump regulation will be found. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. RP Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149-6118,149 13th St, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NINDS NIH HHS [R01-NS27653] NR 58 TC 70 Z9 70 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 MAR 15 PY 2003 VL 23 IS 6 BP 2161 EP 2169 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900022 PM 12657675 ER PT J AU McLellan, ME Kajdasz, ST Hyman, BT Bacskai, BJ AF McLellan, ME Kajdasz, ST Hyman, BT Bacskai, BJ TI In vivo imaging of reactive oxygen species specifically associated with thioflavine S-positive amyloid plaques by multiphoton microscopy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid-beta; free radicals; multiphoton; in vivo imaging; oxidative stress; Alzheimer's disease ID TRANSGENIC MOUSE MODEL; BETA-PROTEIN TOXICITY; NITRIC-OXIDE SYNTHASE; BUTYL NITRONE PBN; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; LIPID-PEROXIDATION; PRECURSOR PROTEIN; A-BETA; COGNITIVE PERFORMANCE AB Amyloid-beta, the primary constituent of senile plaques in Alzheimer's disease, is hypothesized to cause neuronal damage and cognitive failure, but the mechanisms are unknown. Using multiphoton imaging, we show a direct association between amyloid-beta deposits and free radical production in vivo in live, transgenic mouse models of Alzheimer's disease and in analogous ex vivo experiments in human Alzheimer tissue. We applied two fluorogenic compounds, which become fluorescent only after oxidation, before imaging with a near infrared laser. We observed fluorescence associated with dense core plaques, but not diffuse plaques, as determined by subsequent addition of thioflavine S and immunohistochemistry for amyloid-beta. Systemic administration of N-tert-butyl-alpha-phenylnitrone, a free radical spin trap, greatly reduced oxidation of the probes. These data show directly that a subset of amyloid plaques produces free radicals in living, Alzheimer's models and in human Alzheimer tissue. Antioxidant therapy neutralizes these highly reactive molecules and may therefore be of therapeutic value in Alzheimer's disease. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St,2750, Charlestown, MA 02129 USA. EM bbacskai@partners.org FU NIA NIH HHS [AG05134, AG08487] NR 54 TC 101 Z9 111 U1 1 U2 14 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 MAR 15 PY 2003 VL 23 IS 6 BP 2212 EP 2217 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 659KY UT WOS:000181776900027 PM 12657680 ER PT J AU Lorenzl, S Albers, DS LeWitt, PA Chirichigno, JW Hilgenberg, SL Cudkowicz, ME Beal, MF AF Lorenzl, S Albers, DS LeWitt, PA Chirichigno, JW Hilgenberg, SL Cudkowicz, ME Beal, MF TI Tissue inhibitors of matrix metalloproteinases are elevated in cerebrospinal fluid of neurodegenerative diseases SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE neurodegeneration; MMP-2; MMP-9; TIMP-1; TIMP-2; cerebrospinal fluid ID AMYOTROPHIC-LATERAL-SCLEROSIS; MICROVASCULAR ENDOTHELIAL-CELLS; BLOOD-BRAIN-BARRIER; GELATINASE-B; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; EXPRESSION; MATRIX-METALLOPROTEINASE-9; MMP-9; ASTROCYTES AB Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of diseases such as Alzheimer's Disease (AD) and amyotrophic lateral sclerosis (ALS). Increased expression of MMP-9 and TIMPs has been reported in postmortem AD and ALS brain tissue, as well as in ALS cerebrospinal fluid (CSF) and plasma. Although individual studies of MMP and TIMP expression in CSF have included AD and ALS samples, there are no studies comparing the expression of these proteins between neurodegenerative diseases. We measured the levels of matrix metalloproteinases (MMPs)-2 and -9 and the tissue inhibitor of MMPs (e.g. TIMP-1 and TIMP-2) in CSF samples from patients with Parkinson's Disease (PD), Huntington's Disease (HD), AD and ALS as compared to age-matched control patients. There was constitutive expression of the proform of gelatinase A (proMMP-2) on zymography gels in all CSF samples. Unexpectedly, there was an additional gelatinolytic band at 130 kDa of unknown etiology in the CSF samples of patients with PD (61% of patients studied), AD (61%), HD (25%) and ALS (39%). Levels of TIMP-1 were significantly elevated in CSF samples from all disease groups. TIMP-2 was significantly increased in CSF of AD and HD patients. MMP-2 levels did not differ significantly between groups. These findings show that TIMPs are elevated in the CSF of patients with neurodegenerative diseases suggesting a potential role of these endogenous inhibitors of matrix metalloproteinases in neurodegenerative diseases. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Wayne State Univ, Sch Med, Dept Neurol Psychiat & Behav Neurosci, Detroit, MI 48201 USA. Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St Room A-501, New York, NY 10021 USA. NR 34 TC 83 Z9 84 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD MAR 15 PY 2003 VL 207 IS 1-2 BP 71 EP 76 AR PII S0022-510X(02)00398-2 DI 10.1016/S0022-510X(02)00398-2 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 655CJ UT WOS:000181533500012 PM 12614934 ER PT J AU Kaur, M Makrigiorgos, GM AF Kaur, M Makrigiorgos, GM TI Novel amplification of DNA in a hairpin structure: towards a radical elimination of PCR errors from amplified DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; POLYMERASE CHAIN-REACTIONS; HUMAN MITOCHONDRIAL-DNA; MUTATIONAL SPECTROMETRY; GENOTYPIC SELECTION; UNKNOWN MUTATIONS; POINT MUTATIONS; FIDELITY; LIGATION; PERFORMANCE AB Errors introduced during PCR amplification set a selectivity limit for microsatellite analysis and molecular mutation detection methods since polymerase misincorporations invariably get confused with genuine mutations. Here we present hairpin-PCR, a new form of PCR that completely separates genuine mutations from polymerase misincorporations. Hairpin-PCR operates by converting a DNA sequence to a hairpin following ligation of oligonucleotide caps to DNA ends. We developed conditions that allow a DNA hairpin to be efficiently PCR-amplified so that, during DNA synthesis, the polymerase copies both DNA strands in a single pass. Consequently, when a misincorporation occurs it forms a mismatch following DNA amplification, and is distinguished from genuine mutations that remain fully matched. Error-free DNA can subsequently be isolated using one of many approaches, such as dHPLC or enzymatic depletion. We present feasibility for the main technical steps involved in this new strategy, conversion of a sequence to a hairpin that can be PCR-amplified from human genomic DNA, exponential amplification from picogram amounts, conversion of misincorporations to mismatches and separation of homoduplex from heteroduplex hairpins using dHPLC. The present hairpin-PCR opens up the possibility for a radical elimination of PCR errors from amplified DNA and a major improvement in mutation detection. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Brigham & Womens Hosp, Level L2,75 Francis St, Boston, MA 02115 USA. NR 35 TC 10 Z9 10 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 2003 VL 31 IS 6 AR e26 DI 10.1093/nar/gng026 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655JE UT WOS:000181546900003 PM 12626725 ER PT J AU Barnett, BE Josiassen, RC AF Barnett, BE Josiassen, RC TI Risk factors for suicide in schizophrenia and schizoaffective disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 VA Pittsburgh Healthcare Syst, MISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 3 EP 4 DI 10.1016/S0920-9964(03)80004-X PG 2 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700005 ER PT J AU Shemansky, WJ Barnett, BE Goldstein, G AF Shemansky, WJ Barnett, BE Goldstein, G TI Suicide in "neuropsychologically normal" schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 8 EP 8 DI 10.1016/S0920-9964(03)80020-8 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700021 ER PT J AU Ongur, D Freudenreich, O Henderson, DC Goff, DC AF Ongur, D Freudenreich, O Henderson, DC Goff, DC TI Obsessive-compulsive symptoms among people with schizophrenia: Relation to psychotic symptoms, cognitive performance and antipsychotic medications SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Massachusetts Gen Hosp, Schizophrenia Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 23 EP 23 DI 10.1016/S0920-9964(03)80068-3 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700069 ER PT J AU Goldstein, JM Buka, SL Seidman, LJ Donatelli, JL Denny, LR Tsuang, MT AF Goldstein, JM Buka, SL Seidman, LJ Donatelli, JL Denny, LR Tsuang, MT TI Impact of genetic vulnerability, pre and perinatal complications and sex on seven-year outcomes in offspring high risk for psychosis SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 39 EP 39 DI 10.1016/S0920-9964(03)80114-7 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700114 ER PT J AU Yao, JK Thomas, EA Reddy, RD Keshavan, MS AF Yao, JK Thomas, EA Reddy, RD Keshavan, MS TI Association of apolipoproteins D with membrane arachidonic acid levels in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 103 EP 103 DI 10.1016/S0920-9964(03)80834-4 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700307 ER PT J AU Wood, AE Kern, RS Tapp, A AF Wood, AE Kern, RS Tapp, A TI Errorless learning in patients with schizophrenia and non-affected controls SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 VA Puget Sound Hlth Care Syst, Tacoma, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 186 EP 186 DI 10.1016/S0920-9964(03)81089-7 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700561 ER PT J AU Kuperberg, GR Broome, M McGuire, PK David, AS Eddy, M Ozawa, F Goff, D West, WC Williams, SR van der Kouwe, AW Salat, D Dale, AM Fischl, B AF Kuperberg, GR Broome, M McGuire, PK David, AS Eddy, M Ozawa, F Goff, D West, WC Williams, SR van der Kouwe, AW Salat, D Dale, AM Fischl, B TI Regionally localized thinning of the cerebral cortex in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI David, Anthony/C-1315-2011 OI David, Anthony/0000-0003-0967-774X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 199 EP 200 DI 10.1016/S0920-9964(03)81127-1 PG 2 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700601 ER PT J AU Heckers, S Weiss, A Goff, D Deckersbach, T Bush, G AF Heckers, S Weiss, A Goff, D Deckersbach, T Bush, G TI Selective anterior cingulate dysfunction during cognitive interference in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 220 EP 220 DI 10.1016/S0920-9964(03)81185-4 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700659 ER PT J AU Koenigsberg, HW Buchsbaum, MS Harvey, PD Tang, C New, AS Goodman, M Siever, LJ AF Koenigsberg, HW Buchsbaum, MS Harvey, PD Tang, C New, AS Goodman, M Siever, LJ TI Bold fMRI activation in schizotypal personality disorder patients during a visuospatial working memory task SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Bronx Vet Adm Med Ctr, Mental Hlth PCC, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 226 EP 226 DI 10.1016/S0920-9964(03)81203-3 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700677 ER PT J AU Weiss, AP Goff, DC Rosen, BR DeWitt, I Heckers, S AF Weiss, AP Goff, DC Rosen, BR DeWitt, I Heckers, S TI Neural correlates of recognition memory in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 236 EP 237 DI 10.1016/S0920-9964(03)81234-3 PG 2 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700707 ER PT J AU Adler, LE Cawthra, EM Nagamoto, HT McRae, KA Waldo, MC AF Adler, LE Cawthra, EM Nagamoto, HT McRae, KA Waldo, MC TI Atypical antipsychotics differ in effects on P50 auditory sensory gating SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Denver VAMC, Mental Hlth Serv, Denver, CO USA. Denver VAMC, Res Serv, Denver, CO USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 248 EP 248 DI 10.1016/S0920-9964(03)81264-1 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700737 ER PT J AU Casey, D Saha, A Marcus, R Carson, WH McQuade, RD Torbeyns, AF Stock, E AF Casey, D Saha, A Marcus, R Carson, WH McQuade, RD Torbeyns, AF Stock, E TI Aripiprazole versus placebo for relapse prevention in patients with chronic schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Portland Vet Affairs Med Ctr, Portland, OR USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 276 EP 276 DI 10.1016/S0920-9964(03)80440-1 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700819 ER PT J AU Rossotto, E Wirshing, D Wirshing, W Boyd, J Liberman, R Marder, S AF Rossotto, E Wirshing, D Wirshing, W Boyd, J Liberman, R Marder, S TI Reducing rehospitalization rates for patients with schizophrenia: The community re-entry supplemental intervention SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 W Los Angeles Vet Affairs, Schizophrenia Res Clin, Los Angeles, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 328 EP 328 DI 10.1016/S0920-9964(03)80300-6 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705700975 ER PT J AU Matchett, JL Fishman, NB Radmaker, SB Casey, DE AF Matchett, JL Fishman, NB Radmaker, SB Casey, DE TI The effect of atypical antipsychotic drugs in patients with preexisting diabetes SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract CT 9th International Congress on Schizophrenia Research CY MAR 29-APR 02, 2003 CL COLORADO SPINGS, COLORADO C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 15 PY 2003 VL 60 IS 1 SU S BP 362 EP 362 DI 10.1016/S0920-9964(03)80185-8 PG 1 WC Psychiatry SC Psychiatry GA 658DE UT WOS:000181705701077 ER PT J AU Strong, R Reddy, V Morley, JE AF Strong, R Reddy, V Morley, JE TI Cholinergic deficits in the septal-hippocampal pathway of the SAM-P/8 senescence accelerated mouse SO BRAIN RESEARCH LA English DT Article DE SAM-P/8 mouse; SAM-R/l; senescence accelerated mouse; aging; Alzheimer's disease; choline acetyltransferase; glutamic acid decarboxylase; muscarinic acetylcholine receptor; nicotinic acetylcholine receptor; cerebral cortex; hippocampus; septal nucleus/nucleus of the diagonal band nucleus basalis ID AGE-RELATED-CHANGES; BASAL FOREBRAIN; SAMP8 MICE; MEMORY; RETENTION; NEURONS; BRAIN; FACILITATION; ACQUISITION; HYPOTHESIS AB Senescence accelerated prone mouse strains (SAM-P) and resistant strains (SAM-R) have proven useful in elucidating aspects of the aging process. The senescence accelerated mouse SAM-P/8 strain exhibits severe age-related learning and memory impairments well before the median age of survival. Disruption of the brain cholinergic system produces learning and memory impairments as severe as those seen in aging SAM-P/8 mice. Therefore, we compared the effects of aging on cholinergic parameters in the septal-hippocampal pathway, a region known to play a role in learning and memory, in SAM-P/8 mice and mice of the senescence resistant SAM-R/1 strain. Between 4 and 12 months of age we observed a 40-50% decrease in choline acetyltransferase (ChAT) activity in two of three subregions of the hippocampus in the SAM-P/8, but not the SAM-R/1 strain. Between 4 and 12 months, SAM-P/8 mice also showed a 40-50% decrease in ChAT activity in the septal region that was maximal by 8 months of age. By contrast, these age-related changes were not observed in the control SAM-R/1 mouse strain. The changes in ChAT in the SAMP/8 mouse strain were limited to the septal-hippocampal cholinergic pathway. There were no differences in ChAT activity in the nucleus basalis of Meynert, nor any of several neocortical areas to which it projects. To determine the neurochemical specificity of these alterations, the activity of glutamic acid decarboxylase (GAD), was also measured in the septum and hippocampus of SAM-P/8 mice. There were no age-related alterations in the hippocampus, but a significant 50% increase in GAD activity in the septal nucleus at 12 months of age. There were no age-related alterations in either nicotinic (H-3-cytisine) or muscarinic (H-3-QNB) cholinergic receptor binding in the cortex or hippocampus of SAM-P/8 mice. However, there were significant strain differences. At 2 months of age, 3H-QNB binding was higher in hippocampus of the SAM-R/1 than in SAM-P/8 mice. Similarly, H-3-cytisine binding in cortex of SAM-R/1 mice was higher at both 2 and 13 months than in SAM-P/8 mice. The results suggest that a compromised septal-hippocampal cholinergic pathway may contribute to the previously reported early onset of impaired learning and memory in the SAM-P/8 mouse strain. Published by Elsevier Science B.V. C1 Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. St Louis Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, St Louis, MO 63125 USA. St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO 63125 USA. RP Strong, R (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 FU NIA NIH HHS [AG14674] NR 25 TC 35 Z9 37 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 14 PY 2003 VL 966 IS 1 BP 150 EP 156 DI 10.1016/S0006-8993(02)04192-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 654KG UT WOS:000181495400017 PM 12646318 ER PT J AU Ball, SS Nhalil, A Mah, VH AF Ball, SS Nhalil, A Mah, VH TI Senex: An electronic reference for medicine and molecular pathology SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 VA Greater Los Angeles Healtcare Syst, GRECC, Los Angeles, CA 90073 USA. Senex, Anat, Los Angeles, CA USA. Senex, Pathol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A387 EP A387 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101840 ER PT J AU Chew, DKW Khalil, RA AF Chew, DKW Khalil, RA TI Elastase-induced inhibition of Ca2+-dependent mechanisms of vascular contraction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A56 EP A56 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100274 ER PT J AU Green, GM Coleman, DA Khalil, RA AF Green, GM Coleman, DA Khalil, RA TI Physiological increases in extracellular sodium enhance [Ca2+]i and contraction in mesenteric artery smooth muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Va Boston Hlth Care Syst, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A57 EP A57 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100276 ER PT J AU Hamrah, P Chen, L Zhang, Q Dana, MR AF Hamrah, P Chen, L Zhang, Q Dana, MR TI Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on bone marrow-derived dendritic cells and monocytes in the cornea and conjunctiva SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A244 EP A244 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101172 ER PT J AU Kahn, NN Bauman, WA Sinha, AK AF Kahn, NN Bauman, WA Sinha, AK TI Circulating IgG recognizes platelet receptors of both prostacyclin and insulin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Mt Sinai Sch Med, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A512 EP A512 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102414 ER PT J AU Khan, M Sekhon, BK Sekhon, CS Singh, I Singh, AK AF Khan, M Sekhon, BK Sekhon, CS Singh, I Singh, AK TI Protection by N-acetyl cysteine against brain injury in a rat model of stroke SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A606 EP A606 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102858 ER PT J AU Khan, M Sekhon, BK Sekhon, CS Kawada, Y Singh, I Singh, AK AF Khan, M Sekhon, BK Sekhon, CS Kawada, Y Singh, I Singh, AK TI S-nitrosoglutathione modulates cerebroprotection and activities of sphingomyelinases and phospholipases in a rat model of experimental stroke SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A607 EP A607 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102861 ER PT J AU Kling, DE Aidlen, JT Fisher, JC Kinane, TB Schnitzer, JJ AF Kling, DE Aidlen, JT Fisher, JC Kinane, TB Schnitzer, JJ TI Nitrofen induces apoptosis in P19 teratocarcinoma cells that is cellular redox-dependent and is associated with increases in reactive oxygen species and p38 MAP kinase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A681 EP A681 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103209 ER PT J AU Luckey, AE Suto, G Kiraly, A Tache, Y AF Luckey, AE Suto, G Kiraly, A Tache, Y TI Endotoxin(EDX)-induced inhibition of gastric emptying (GE) involves interleukin-1 beta (IL-1 beta) and CRF2 receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 VA Greater LA Healthcare Syst, UCLA CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Pecs, Dept Med 1, Pecs, Hungary. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A41 EP A42 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100202 ER PT J AU Mascarenhas, MM Ochoa, CD Hales, CA Quinn, DA AF Mascarenhas, MM Ochoa, CD Hales, CA Quinn, DA TI Multiple mechanisms of IL-8 production in ventilator induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ponifical Bolivarian Univ, Sch Med, Medellin, Colombia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A89 EP A89 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100429 ER PT J AU Na, SY Lichtenthaler, S Xavier, R Radoja, S Ketteler, R Holmes, T Seed, B AF Na, SY Lichtenthaler, S Xavier, R Radoja, S Ketteler, R Holmes, T Seed, B TI Pathway dissection by automated expression screens SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Munich, Adolph Butenandt Inst, Munich, Germany. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RI Lichtenthaler, Stefan/B-6587-2016 OI Lichtenthaler, Stefan/0000-0003-2211-2575 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A149 EP A149 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100718 ER PT J AU Pastor-Soler, N Beaulieu, V Da Silva, N Zhou, WL Chen, YQ Litvin, TN Levin, LR Buck, J Brown, D Breton, S AF Pastor-Soler, N Beaulieu, V Da Silva, N Zhou, WL Chen, YQ Litvin, TN Levin, LR Buck, J Brown, D Breton, S TI Role of the novel bicarbonate sensor, "soluble" adenylyl cyclase (sA, in H(+)ATPase recycling in the epididymis and vas deferens (VD) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Cornell Univ, Weill Med Coll, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A463 EP A463 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733102190 ER PT J AU Patil, VRS Tang, Y Snyder, EY Weissleder, R Allport, JR AF Patil, VRS Tang, Y Snyder, EY Weissleder, R Allport, JR TI Murine progenitor cells ate preferentially recruited to tumor, vasculature via an alpha 4-integrin independent mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A684 EP A684 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733103224 ER PT J AU Perell, KL Scremin, OU Chialvo, DR AF Perell, KL Scremin, OU Chialvo, DR TI The relationship between plantar pressure and plantar kin perfusion in diabetic peripheral neuropathy older adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A127 EP A127 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100613 ER PT J AU Quinn, DA Jafari, B Li, LF Mascarenhas, MM Bin, OY Syrkina, O Hales, CA AF Quinn, DA Jafari, B Li, LF Mascarenhas, MM Bin, OY Syrkina, O Hales, CA TI Pulmonary epithelial cells, endothelial cells and fibroblasts contribute to lung stretch-induced cytokine production found in ventilator-induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 01908 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A88 EP A88 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100428 ER PT J AU Shah, EH Giri, S Singh, I Singh, AK AF Shah, EH Giri, S Singh, I Singh, AK TI Molecular mechanism of Psychosine induced oligodendrocyte cell death SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A171 EP A171 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733100826 ER PT J AU Xu, XL Fishman, MC AF Xu, XL Fishman, MC TI A transcriptional mediator component is required for cardiac cushion formation in zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2003 Meeting CY APR 11-15, 2003 CL SAN DIEGO, CALIFORNIA C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 14 PY 2003 VL 17 IS 4 SU S BP A351 EP A351 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 658QZ UT WOS:000181733101672 ER PT J AU Sato, M Markiewicz, M Yamanaka, M Bielawska, A Mao, CG Obeid, LM Hannun, YA Trojanowska, M AF Sato, M Markiewicz, M Yamanaka, M Bielawska, A Mao, CG Obeid, LM Hannun, YA Trojanowska, M TI Modulation of transforming growth factor-beta (TGF-beta) signaling by endogenous sphingolipid mediators SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2(I) COLLAGEN GENE; FYVE DOMAIN PROTEIN; SACCHAROMYCES-CEREVISIAE; SPHINGOSINE KINASE; EXPRESSION; SMAD; CERAMIDE; RECEPTOR; TRANSCRIPTION; FIBROBLASTS AB Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that plays a critical role in tissue repair and fibrosis. Sphingolipid signaling has been shown to regulate a variety of cellular processes and has been implicated in collagen gene regulation. The present study was undertaken to determine whether endogenous sphingolipids are involved in the TGF-beta signaling pathway. TGF-beta treatment induced endogenous ceramide levels in a time-dependent manner within 5-15 min of cell stimulation. Using human fibroblasts transfected with a alpha2(l) collagen promoter/reporter gene construct (COL1A2), C.-ceramide (10 muM) exerted a stimulatory effect on basal and TGF-beta-induced activity of this promoter. Next, to define the effects of endogenous sphingolipids on TGF-beta signaling we employed ectopic expression of enzymes involved in sphingolipid metabolism. Sphingosine 1-phosphate phosphatase (YSR2) stimulated basal COL1A2 promoter activity and cooperated with TGF-beta in activation of this promoter. Furthermore, overexpression of YSR2 resulted in the pronounced increase of COL1A1 and COL1A2 mRNA levels. Conversely, overexpression of sphingosine kinase (SPHK1) inhibited basal and TGF-beta-stimulated COL1A2 promoter activity. These results suggest that endogenous ceramide, but not sphingosine or sphingosine 1-phosphate, is a positive regulator of collagen gene expression. Mechanistically, we demonstrate that Smad3 is a target of YSR2. TGF-beta-induced Smad3 phosphorylation was elevated in the presence of YSR2. Cotransfection of YSR2 with wild-type Smad3, but not with the phosphorylation-deficient mutant of Smad3 (Smad3A), resulted in a dramatic increase of COL1A2 promoter activity. In conclusion, this study demonstrates a direct role for the endogenous sphingolipid mediators in regulating the TGF-beta signaling pathway. C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29425 USA. RP Trojanowska, M (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA. OI Trojanowska, Maria/0000-0001-9550-7178 FU NIA NIH HHS [AG16583]; NIAMS NIH HHS [AR 44883, AR 42334]; NIGMS NIH HHS [GM43825] NR 43 TC 37 Z9 37 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 MAR 14 PY 2003 VL 278 IS 11 BP 9276 EP 9282 DI 10.1074/jbc.M211529200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654YF UT WOS:000181524000052 PM 12515830 ER PT J AU Perfettini, JL Ojcius, DM Andrews, CW Korsmeyer, SJ Rank, RG Darville, T AF Perfettini, JL Ojcius, DM Andrews, CW Korsmeyer, SJ Rank, RG Darville, T TI Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) and the host inflammatory response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENITAL-TRACT INFECTION; NECROSIS-FACTOR-ALPHA; CELL-DEATH; APOPTOTIC CELLS; EPITHELIAL-CELLS; IMMUNE-RESPONSE; MUTATIONAL INACTIVATION; BILIARY EPITHELIA; CYTOCHROME-C; FAS RECEPTOR AB The BCL-2 family member BAX plays a critical role in regulating apoptosis. Surprisingly, bax-deficient mice display limited phenotypic abnormalities. Here we investigate the effect of BAX on infection by the sexually transmitted pathogen, Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis). Bax(-/-) cells are relatively resistant to Chlamydia-induced apoptosis, and fewer bacteria are recovered after two infection cycles from Bax(-/-) cells than from wildtype cells. These results suggest that BAX-dependent apoptosis may be used to initiate a new round of infection, most likely by releasing Chlamydia-containing apoptotic bodies from infected cells that could be internalized by neighboring uninfected cells. Nonetheless, infected Bax(-/-) cells die through necrosis, which is normally associated with inflammation, more often than infected wild-type cells. These studies were confirmed in mice infected intravaginally with C. muridarum; since the infection disappears more quickly from Bax(-/-) mice than from wild-type mice, secretion of proinflammatory cytokines is increased in Bax(-/-) mice, and large granulomas are present in the genital tract of Bax(-/-) mice. Taken together, these data suggest that chlamydia-induced apoptosis via BAX contributes to bacterial propagation and decreases inflammation. Bax deficiency results in lower infection and an increased inflammatory cytokine response associated with more severe pathology. C1 Univ Paris 07, Inst Jacques Monod, F-75251 Paris 05, France. Univ Paris 07, Inst Pasteur, Unite Biol Mol Gene, U277, Paris, France. Sacred Heart Med Ctr, Dept Lab Med, Spokane, WA 99220 USA. 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. Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. RP Ojcius, DM (reprint author), Univ Paris 07, Inst Jacques Monod, 2 Pl Jussieu,Tour 43, F-75251 Paris 05, France. FU NIAID NIH HHS [AI054624] NR 82 TC 36 Z9 40 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 MAR 14 PY 2003 VL 278 IS 11 BP 9496 EP 9502 DI 10.1074/jbc.M211275200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654YF UT WOS:000181524000083 PM 12509420 ER PT J AU Straight, AF Cheung, A Limouze, J Chen, I Westwood, NJ Sellers, JR Mitchison, TJ AF Straight, AF Cheung, A Limouze, J Chen, I Westwood, NJ Sellers, JR Mitchison, TJ TI Dissecting temporal and spatial control of cytokinesis with a myosin II inhibitor SO SCIENCE LA English DT Article ID CONTRACTILE RING; PROTEIN-KINASE; MAMMALIAN-CELLS; CLEAVAGE FURROW; MITOTIC SPINDLE; MICROTUBULES; LOCALIZATION; PROTEOLYSIS; ANAPHASE; ANTIBODY AB Completion of cell division during cytokinesis requires temporally and spatially regulated communication from the microtubule cytoskeleton to the actin cytoskeleton and the cell membrane. We identified a specific inhibitor of nonmuscle myosin II, blebbistatin, that inhibited contraction of the cleavage furrow without disrupting mitosis or contractile ring assembly. Using blebbistatin and other drugs, we showed that exit from the cytokinetic phase of the cell cycle depends on ubiquitin-mediated proteolysis. Continuous signals from microtubules are required to maintain the position of the cleavage furrow, and these signals control the localization of myosin II independently of other furrow components. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ St Andrews, Sch Chem, St Andrews KY16 9AJ, Fife, Scotland. RP Straight, AF (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 250 Longwood Ave, Boston, MA 02115 USA. OI Straight, Aaron/0000-0001-5885-7881 FU NIGMS NIH HHS [GM23928, GM62566] NR 32 TC 831 Z9 843 U1 3 U2 44 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 MAR 14 PY 2003 VL 299 IS 5613 BP 1743 EP 1747 DI 10.1126/science.1081412 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654WM UT WOS:000181519500049 PM 12637748 ER PT J AU Morris, DG Huang, XZ Kaminski, N Wang, YN Shapiro, SD Dolganov, G Glick, A Sheppard, D AF Morris, DG Huang, XZ Kaminski, N Wang, YN Shapiro, SD Dolganov, G Glick, A Sheppard, D TI Loss of integrin alpha v beta 6-mediated TGF-beta activation causes Mmp12-dependent emphysema SO NATURE LA English DT Article ID MACROPHAGE METALLOELASTASE; CYTOPLASMIC DOMAIN; LUNG INFLAMMATION; FOCAL CONTACTS; EXPRESSION; MICE; SUBUNIT; REVEALS; LOCALIZATION; INHIBITION AB Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alphavbeta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta)(1,2). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)-a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema(3). Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease. C1 Univ Calif San Francisco, San Francisco Gen Hosp, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Div Pulm & Crit Care Med, Pittsburgh, PA 15261 USA. Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. RP Sheppard, D (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Lung Biol Ctr, Dept Med, San Francisco, CA 94143 USA. NR 27 TC 296 Z9 308 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 MAR 13 PY 2003 VL 422 IS 6928 BP 169 EP 173 DI 10.1038/nature01413 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 654HG UT WOS:000181488900046 PM 12634787 ER PT J AU Sayegh, MH Colvin, RB AF Sayegh, MH Colvin, RB TI A 35-year-old man with early dysfunction of a second renal transplant - Acute humoral rejection, persistent. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID KIDNEY-TRANSPLANTATION; PATHOLOGICAL FEATURES; ALLOGRAFT RECIPIENTS; CROSS-MATCH; ANTIBODY; PLASMAPHERESIS; CLASSIFICATION; SENSITIZATION; TOLERANCE; GLOBULIN C1 Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St, Boston, MA 02115 USA. NR 28 TC 7 Z9 7 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 MAR 13 PY 2003 VL 348 IS 11 BP 1033 EP 1044 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 653YT UT WOS:000181465200009 PM 12637614 ER PT J AU Sung, NS Crowley, WF Genel, M Salber, P Sandy, L Sherwood, LM Johnson, SB Catanese, V Tilson, H Getz, K Larson, EL Scheinberg, D Reece, EA Slavkin, H Dobs, A Grebb, J Martinez, RA Korn, A Rimoin, D AF Sung, NS Crowley, WF Genel, M Salber, P Sandy, L Sherwood, LM Johnson, SB Catanese, V Tilson, H Getz, K Larson, EL Scheinberg, D Reece, EA Slavkin, H Dobs, A Grebb, J Martinez, RA Korn, A Rimoin, D TI Central challenges facing the national clinical research enterprise SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID ACADEMIC MEDICAL-CENTERS; INFORMATION TECHNOLOGY; INFORMED CONSENT; HEALTH-CARE; BIOMEDICAL-RESEARCH; FUTURE CHALLENGES; TRIALS; PRIVACY; PARTICIPATION; INVESTIGATORS AB Medical scientists and public health policy makers are increasingly concerned that the scientific discoveries of the past generation are failing to be translated efficiently into tangible human benefit. This concern has generated several initiatives, including the Clinical Research Roundtable at the Institute of Medicine, which first convened in June 2000. Representatives from a diverse group of stakeholders in the nation's clinical research enterprise have collaborated to address the issues it faces. The context of clinical research is increasingly encumbered by high costs, slow results, lack of funding, regulatory burdens, fragmented infrastructure, incompatible databases, and a shortage of qualified investigators and willing participants. These factors have contributed to 2 major obstacles, or translational blocks: impeding the translation of basic science discoveries into clinical studies and of clinical studies into medical practice and health decision making in systems of care. Considering data from across the entire health care system, it has become clear that these 2 translational blocks can be removed only by the collaborative efforts of multiple system stakeholders. The goal of this article is to articulate the 4 central challenges facing clinical research at present-public participation, information systems, workforce training, and funding; to make recommendations about how they might be addressed by particular stakeholders; and to invite a broader, participatory dialogue with a view to improving the overall performance of the US clinical research enterprise. C1 Burroughs Wellcome Fund, Res Triangle Pk, NC 27709 USA. Harvard Univ, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Ctr Watch, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. Blue Shield Calif, Calif Publ Employees Retirement Syst, San Francisco, CA USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Univ Penn, MEDSA, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Columbia Univ, Dept Med Informat, New York, NY USA. Columbia Univ, Sch Nursing, New York, NY USA. NYU, Sch Med, New York, NY USA. Amer Federat Med Res Fdn, New York, NY USA. Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY USA. Sloan Kettering Inst, Leukemia Serv, New York, NY USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. Univ Arkansas, Coll Med, Little Rock, AR 72205 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. Cedars Sinai Med Ctr, Dept Pediat, Los Angeles, CA 90048 USA. Cedars Sinai Med Ctr, Ctr Med Genet Birth Defects, Los Angeles, CA 90048 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Clin Res Unit, Baltimore, MD USA. Johnson & Johnson, Janssen Res Fdn, Global CNS Analgesia Clin Res & Dev, Titusville, NJ USA. Johnson & Johnson, Corp & Community Relat, Med Affairs, New Brunswick, NJ USA. Blue Cross Blue Shield Assoc, Chicago, IL USA. RP Sung, NS (reprint author), Burroughs Wellcome Fund, POB 13901,21 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Tao, Youyou/D-2367-2014 NR 101 TC 597 Z9 609 U1 5 U2 54 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 MAR 12 PY 2003 VL 289 IS 10 BP 1278 EP 1287 DI 10.1001/jama.289.10.1278 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 653ZG UT WOS:000181466500030 PM 12633190 ER EF