FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Andersen, G Wegner, L Yanagisawa, K Rose, CS Lin, J Glumer, C Drivsholm, T Borch-Johnsen, K Jorgensen, T Hansen, T Spiegelman, BM Pedersen, O AF Andersen, G Wegner, L Yanagisawa, K Rose, CS Lin, J Glumer, C Drivsholm, T Borch-Johnsen, K Jorgensen, T Hansen, T Spiegelman, BM Pedersen, O TI Evidence of an association between genetic variation of the coactivator PGC-1 beta and obesity SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID RECEPTOR-GAMMA COACTIVATOR-1; DIABETES-MELLITUS; MITOCHONDRIAL BIOGENESIS; INDEPENDENT REPLICATION; HEPATIC GLUCONEOGENESIS; SUSCEPTIBILITY LOCUS; INSULIN-RESISTANCE; MUSCLE-CELLS; POLYMORPHISM; GLUCOSE AB Background: Peroxisome proliferator activated receptor-gamma coactivator-1 beta ( PGC-1 beta) is a recently identified homologue of the tissue specific coactivator PGC-1 alpha, a coactivator of transcription factors such as the peroxisome proliferators activated receptors and nuclear respiratory factors. PGC-1 alpha is involved in adipogenesis, mitochondrial biogenesis, fatty acid beta oxidation, and hepatic gluconeogenesis. Methods: We studied variation in the coding region of human PPARGC1B in Danish whites and related these variations to the prevalence of obesity and type 2 diabetes in population based samples. Results: Twenty nucleotide variants were identified. In a study of 525 glucose tolerant subjects, the Ala203Pro and Val279Ile variants were in almost complete linkage disequilibrium (R-2 = 0.958). In a case control study of obesity involving a total of 7790 subjects, the 203Pro allele was significantly less frequent among obese participants ( p = 0.004; minor allele frequencies: normal weight subjects 8.1% (95% confidence interval: 7.5 to 8.8), overweight subjects 7.6% ( 7.0 to 8.3), obese subjects 6.5% (5.6 to 7.3)). In a case - control study involving 1433 patients with type 2 diabetes and 4935 glucose tolerant control subjects, none of the examined variants were associated with type 2 diabetes. Conclusions: Variation of PGC-1 beta may contribute to the pathogenesis of obesity, with a widespread Ala203 allele being a risk factor for the development of this common disorder. C1 Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark. Univ Aarhus, Fac Hlth Sci, DK-8000 Aarhus, Denmark. RP Andersen, G (reprint author), Steno Diabet Ctr, Niels Steensens Vej 2,NSH2-16, DK-2820 Gentofte, Denmark. EM gtta@steno.dk RI Wegner, Lise/E-6715-2011; OI Jorgensen, Torben/0000-0001-9453-2830 NR 33 TC 37 Z9 43 U1 0 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2005 VL 42 IS 5 BP 402 EP 407 DI 10.1136/jmg.2004.026278 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 921ZZ UT WOS:000228806200005 PM 15863669 ER PT J AU Betensky, RA Nutt, CL Batchelor, TT Louis, DN AF Betensky, RA Nutt, CL Batchelor, TT Louis, DN TI Statistical considerations for immunohistochemistry panel development after gene expression profiling of human cancers SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MICROARRAY EXPERIMENTS; DESIGN AB In recent years there have been a number of microarray expression studies in which different types of tumors were classified by identifying a panel of differentially expressed genes. Immunohistochemistry is a practical and robust method for extending gene expression data to common pathological specimens with the advantage of being applicable to paraffin-embedded tissues. However, the number of assays required for successful immunohistochemical classification remains unclear. We propose a simulation-based method for assessing sample size for an immunohistochemistry investigation after a promising gene expression study of human tumors. The goals of such an immunohistochemistry study would be to develop and validate a marker panel that yields improved prognostic classification of cancer patients. We demonstrate how the preliminary gene expression data, coupled with certain realistic assumptions, can be used to estimate the number of immunohistochemical assays required for development. These assumptions are more tenable than alternative assumptions that would be required for crude analytic sample size calculations and that may yield underpowered and inefficient studies. We applied our methods to the design of an immunohistochemistry study for glioma classification and estimated the number of assays required to ensure satisfactory technical and prognostic validation. Simulation approaches for computing power and sample size that are based on existing gene expression data provide a powerful tool for efficient design of follow-up genomic studies. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM betensky@hsph.harvard.edu RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [CA75971, R01 CA057683, R01 CA075971, R29 CA075971] NR 15 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2005 VL 7 IS 2 BP 276 EP 282 DI 10.1016/S1525-1578(10)60555-7 PG 7 WC Pathology SC Pathology GA 921AP UT WOS:000228736900016 PM 15858152 ER PT J AU Liu, J Shinobu, LA Ward, CM Young, D Cleveland, DW AF Liu, J Shinobu, LA Ward, CM Young, D Cleveland, DW TI Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE heat shock protein 70; motor neuron death; neurodegenerative disease; protein aggregates; stress response ID CU/ZN-SUPEROXIDE-DISMUTASE; ALS-LINKED SOD1; MOTOR-NEURON DEGENERATION; HEAT-SHOCK PROTEINS; TRANSGENIC MICE; DISEASE PROGRESSION; UP-REGULATION; MITOCHONDRIA; MUTATIONS; HEAT-SHOCK-PROTEIN-70 AB Mutations in copper/zinc superoxide dismutase (SOD1) account for 10-20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both aggregate formation and toxicity in primary motor neurons in culture. However, chronic increase in an inducible form of Hsp70 to about 10-fold its normal level is shown here not to affect disease course or pathology developed in mice from accumulation of any of three familial ALS causing SOD1 mutants with different underlying biochemical characteristics. Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1-mediated toxicity. C1 Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. RP Cleveland, DW (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM dcleveland@ucsd.edu FU NINDS NIH HHS [R37 NS027036, NS27036] NR 37 TC 58 Z9 62 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2005 VL 93 IS 4 BP 875 EP 882 DI 10.1111/j.1471-4159.2005.03054.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 920WB UT WOS:000228721200009 PM 15857390 ER PT J AU Xie, Z Harris-White, ME Wals, PA Frautschy, SA Finch, CE Morgan, TE AF Xie, Z Harris-White, ME Wals, PA Frautschy, SA Finch, CE Morgan, TE TI Apolipoprotein J (clusterin) activates rodent microglia in vivo and in vitro SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's; apoJ; clusterin; microglia; neurotoxicity; nitric oxide; tumor necrosis factor-alpha ID NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE SYNTHASE; A-BETA OLIGOMERS; ALZHEIMERS-DISEASE; AMYLOID-BETA; CELL-DEATH; OXIDATIVE STRESS; RAT-BRAIN; GENE-EXPRESSION; PROTEIN AB Apolipoprotein J (apoJ; also known as clusterin and sulfated glycoprotein (SGP)-2) is associated with senile plaques in degenerating regions of Alzheimer's disease brains, where activated microglia are also prominent. We show a functional link between apoJ and activated microglia by demonstrating that exogenous apoJ activates rodent microglia in vivo and in vitro. Intracerebroventricular infusion of purified human plasma apoJ (similar to 4 mu g over 28 days) activated parenchymal microglia to a phenotype characterized by enlarged cell bodies and processes (phosphotyrosine immunostaining). In vitro, primary rat microglia were also activated by apoJ, with changes in morphology and induction of major histocompatibility complex class II (MHCII) antigen. ApoJ increased the secretion of reactive nitrogen intermediates in a dose-dependent manner (EC50 112 nM), which was completely blocked by aminoguanidine (AG), a nitric oxide synthase inhibitor. However, AG did not block the increased secretion of tumor necrosis factor-alpha by apoJ (EC50 55 nM). Microglial activation by apoJ was also blocked by an anti-apoJ monoclonal antibody (G7), and by chemical cleavage of apoJ with 2-nitro-5-thiocyanobenzoate. The mitogen-activated protein kinase kinase and protein kinase C inhibitors PD98059 and H7 inhibited apoJ-mediated induction of reactive nitrogen intermediate secretion from cultured microglia. As a functional measure, apoJ-activated microglia secreted neurotoxic agents in a microglia-neuron co-culture model. We hypothesize that ApoJ contributes to chronic inflammation and neurotoxicity through direct effects on microglia. C1 Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, GRECC, Sepulveda, CA USA. RP Xie, Z (reprint author), Univ So Calif, Ethel Percy Andrus Gerontol Ctr, 3715 McClintock Ave, Los Angeles, CA 90089 USA. EM z-xie@north-western.edu RI Xie, Zhong/B-6829-2011 OI Xie, Zhong/0000-0002-8348-4455 FU NIA NIH HHS [AG10685, AG13499, R01 AG010685, P50 AG016570] NR 63 TC 17 Z9 17 U1 0 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2005 VL 93 IS 4 BP 1038 EP 1046 DI 10.1111/j.1471-4159.2005.03065.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 920WB UT WOS:000228721200026 PM 15857407 ER PT J AU Goebel, A Vogel, H Caneris, O Bajwa, Z Clover, L Roewer, N Schadel, R Karch, H Sprotte, G Vincent, A AF Goebel, A Vogel, H Caneris, O Bajwa, Z Clover, L Roewer, N Schadel, R Karch, H Sprotte, G Vincent, A TI Immune responses to Campylobacter and serum autoantibodies in patients with complex regional pain syndrome SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE CRPS; autoantibody; autoimmune; Campylobacter; pain ID REFLEX SYMPATHETIC DYSTROPHY; PATHOLOGICAL PAIN; ANTIBODIES; IMMUNOGLOBULIN AB We hypothesised that some complex regional pain syndromes (CRPS) may have a postinfectious and/or autoimmune basis. Sera from 92 patients with CRPS and 92 controls were investigated for immunoreactivity to Campylobacter strains and to rodent tissues. Both IgA-antibodies to Campylobacter and tissue-specific reactivity were often present in patients with short disease duration (&LE; 1.5 years). Patients with minimal preceding trauma had stronger nervous tissue-specific reactivity than other patients, regardless of disease duration. These results provide preliminary evidence for immune activation early in CRPS and, additionally, that patients with minimal trauma may comprise an autoimmune subgroup. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Neurosci Grp, Oxford OX3 9DS, England. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Anaesthet, Oxford OX3 9DS, England. Univ Wurzburg, Anasthesiol Klin, D-97080 Wurzburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr,Dept Anesthesia, Boston, MA 02114 USA. Comprehens Pain Management Clin, NE Rehabil Network, Salem, NH 03079 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Arnold Pain Ctr,Dept Anesthesia, Boston, MA 02115 USA. Univ Wurzburg, Inst Hyg & Mikrobiol, D-97080 Wurzburg, Germany. RP Goebel, A (reprint author), Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Neurosci Grp, Oxford OX3 9DS, England. EM andreasgoebel@rocketmail.com NR 21 TC 28 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAY PY 2005 VL 162 IS 1-2 BP 184 EP 189 DI 10.1016/j.jneuroim.2005.01.018 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 923UF UT WOS:000228934100022 PM 15833374 ER PT J AU Vallat, JM Magy, L Sindou, P Magdelaine, C Cros, D AF Vallat, JM Magy, L Sindou, P Magdelaine, C Cros, D TI IgG neuropathy: An immunoelectron microscopic study SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE monoclonal dysglobulinemia; myelin lesion; myeloma; nerve biopsy; polyneuropathy ID GAMMOPATHY; WIDENINGS; DEPOSITS AB There are many potential mechanisms of peripheral nerve impairment by a monoclonal IgG dysglobulinemia. In this study, using electron microscopy, we observed widening of the myelin lamellae comparable to that commonly described in IgM neuropathies with anti myelin-associated glycoprotein activity. Such features have yet to be described in IgG neuropathies. In addition, we observed deposits of a granular material in the interstitial tissue of the nerve. By immunoelectron microscopy, we demonstrated the presence of the IgG in the lesions of myelin and the endoneurial space. A direct link between monoclonal dysglobulinemia (regardless of type) and polyneuropathy should be confirmed by nerve biopsy, because the result may influence treatment. C1 Univ Hosp, Dept Neurol, Limoges, France. Univ Hosp, Biochem Lab, Limoges, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Vallat, JM (reprint author), Univ Hosp, Dept Neurol, Limoges, France. EM vallat@unilim.fr OI sindou, p/0000-0003-1938-8319 NR 10 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 BP 386 EP 390 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800004 PM 15892295 ER PT J AU Vanderburg, CR Pfannl, R Tian, D Kiehl, TR Hsi, T Hedley-Whyte, ET Frosch, MP AF Vanderburg, CR Pfannl, R Tian, D Kiehl, TR Hsi, T Hedley-Whyte, ET Frosch, MP TI Factors influencing post-mortem RNA integrity in human brain. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Harvard Ctr Neurodegenerat & Repair, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 50 BP 443 EP 443 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800061 ER PT J AU Freeman, SH Tian, D Frosch, MP Hedley-Whyte, ET AF Freeman, SH Tian, D Frosch, MP Hedley-Whyte, ET TI Adult onset leukodystrophy with neuroaxonal spheroids (AOLNAS), report of three cases. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 68 BP 447 EP 447 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800077 ER PT J AU Mueller, WC Riemenschneider, MJ Nutt, CL Louis, DN AF Mueller, WC Riemenschneider, MJ Nutt, CL Louis, DN TI The methylome in glioblastoma. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Nutt, Catherine/K-8794-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 BP 455 EP 455 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800106 ER PT J AU Mikolaenko, I Roth, C Rajit, S Chi, S Scott, RM Folkerth, RD AF Mikolaenko, I Roth, C Rajit, S Chi, S Scott, RM Folkerth, RD TI Anaplastic progression of pilocytic astrocytoma of the medulla. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Brigham & Womens Hosp, Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Tech Univ Dresden, Sch Med, D-8027 Dresden, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 107 BP 457 EP 457 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800115 ER PT J AU Riemenschneider, MJ Mueller, W Betensky, RA Mohapatra, G Louis, DN AF Riemenschneider, MJ Mueller, W Betensky, RA Mohapatra, G Louis, DN TI In situ analysis of the integrin signaling pathway in human glioblastomas. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 111 BP 458 EP 458 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800119 ER PT J AU Snuderl, M Chi, SN Chan, JA Rubin, MA Kieran, MW Ligon, KL AF Snuderl, M Chi, SN Chan, JA Rubin, MA Kieran, MW Ligon, KL TI Oligodendroglial lineage marker expression in ependymal tumors. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 109 BP 458 EP 458 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800118 ER PT J AU Ligon, KL Sun, T Arnett, HA Kitada, M Alberta, JA Stiles, CD Rowitch, DH AF Ligon, KL Sun, T Arnett, HA Kitada, M Alberta, JA Stiles, CD Rowitch, DH TI Olig2 function is required for NG2 cell development. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 139 BP 465 EP 465 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800147 ER PT J AU Tian, D Chou, RC Henson, JW Reginato, AM Hedley-Whytel, ET Kubik, CS AF Tian, D Chou, RC Henson, JW Reginato, AM Hedley-Whytel, ET Kubik, CS TI A case report of rheumatoid leptomeningitis and pachymeningitis. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Lab Neuropathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Rheumatol Allergy & Clin Immunol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stephen E & Catherine Pappas Ctr Neur, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 138 BP 465 EP 465 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800148 ER PT J AU Stemmer-Rachamimov, AO Poliani, PL DeSantis, S Betensky, RA Hurwitz, E Nutt, CL MacCollin, M AF Stemmer-Rachamimov, AO Poliani, PL DeSantis, S Betensky, RA Hurwitz, E Nutt, CL MacCollin, M TI Schwannoma histology revisited: Correlation of histological features to clinical diagnosis of schwannomatosts. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Brescia, Brescia, Italy. RI Poliani, Pietro Luigi/E-8145-2010; Nutt, Catherine/K-8794-2012 OI Poliani, Pietro Luigi/0000-0002-5662-8978; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 158 BP 470 EP 470 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800168 ER PT J AU Dawkins, R Keller, SL Sewell, WF AF Dawkins, R Keller, SL Sewell, WF TI Pharmacology of acetylcholine-mediated cell signaling in the lateral line organ following efferent stimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID OUTER HAIR-CELLS; GUINEA-PIG COCHLEA; CA2+-ACTIVATED K+ CHANNELS; AFFERENT SYNAPTIC-TRANSMISSION; GENE-RELATED PEPTIDE; XENOPUS-LAEVIS; SMALL-CONDUCTANCE; PHENYLMETHYLSULFONYL FLUORIDE; OLIVOCOCHLEAR ACTIVATION; CHOLINERGIC INHIBITION AB Cholinergic efferent fibers modify hair cell responses to mechanical stimulation. It is hypothesized that calcium entering the hair cell through a nicotinic receptor activates a small-conductance (SK), calcium-activated potassium channel to hyperpolarize the hair cell. The calcium signal may be amplified by calcium-induced calcium release from the synaptic cisternae. Pharmacological tests of these ideas in the intact cochlea have been technically difficult because of the complex and fragile structure of the mammalian inner ear. We turned to the Xenopus laevis lateral line organ, whose simplicity and accessibility make it a model for understanding hair cell organ function in a relatively intact system. Drugs were applied to the inner surface of the skin while monitoring the effects of efferent stimulation on afferent fiber discharge rate. Efferent effects were blocked by antagonists of SK channels including apamin (EC(50) = 0.5 mu M) and dequalinium (EC(50) = 12 mu M). The effect of apamin was not enhanced by co-administration of phenylmethylsulfonyl fluoride, a proteolysis inhibitor. Efferent effects were attenuated by ryanodine, an agent that can interfere with calcium-induced calcium release, although relatively high (mM) concentrations of ryanodine were required. Fluorescent cationic styryl dyes, 4-di-2-asp and fm 1-43, blocked efferent effects, although it was not possible to observe specific entry of the dye into the base of hair cells. These pharmacological findings in the Xenopus lateral line organ support the hypothesis that effects of efferent stimulation are mediated by calcium entry through the nicotinic receptor via activation of SK channels and suggest the generality of this mechanism in meditating cholinergic efferent effects. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM wfs@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC000767, R01 DC000767-13, R01 DC000767-15, R01 DC000767-12, R01 DC000767-14, R01 DC000767-16A1, DC-00767, R01 DC000767-11] NR 69 TC 10 Z9 12 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2005 VL 93 IS 5 BP 2541 EP 2551 DI 10.1152/jn.01283.2004 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 918VH UT WOS:000228575200017 PM 15615825 ER PT J AU Ariano, MA Cepeda, C Calvert, CR Flores-Hernandez, J Hernandez-Echeagaray, E Klapstein, GJ Chandler, SH Aronin, N DiFiglia, M Levine, MS AF Ariano, MA Cepeda, C Calvert, CR Flores-Hernandez, J Hernandez-Echeagaray, E Klapstein, GJ Chandler, SH Aronin, N DiFiglia, M Levine, MS TI Striatal potassium channel dysfunction in Huntington's disease transgenic mice SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEOSTRIATAL NEURONS; MOUSE MODELS; SPINY NEURONS; K+ CHANNELS; INTRANUCLEAR INCLUSIONS; INWARD RECTIFICATION; RECEPTOR ACTIVATION; RAT-BRAIN; CURRENTS; RECTIFIER AB Huntington's disease (HD) is a neurodegenerative disorder that mainly affects the projection neurons of the striatum and cerebral cortex. Genetic mouse models of HD have shown that neurons susceptible to the mutation exhibit morphological and electrophysiological dysfunctions before and during development of the behavioral phenotype. We used HD transgenic mouse models to examine inwardly and outwardly rectifying K+ conductances, as well as expression of some related K+ channel subunits. Experiments were conducted in slices and dissociated cells from two mouse models, the R6/2 and TgCAG100, at the beginning and after full development of overt behavioral phenotypes. Striatal medium-sized spiny neurons (MSNs) from symptomatic transgenic mice had increased input resistances, depolarized resting membrane potentials, and reductions in both inwardly and outwardly rectifying K+ currents. These changes were more dramatic in the R6/2 model than in the TgCAG100. Parallel immunofluorescence studies detected decreases in the expression of K+ channel subunit proteins, Kir2.1, Kir2.3, and Kv2.1 in MSNs, which contribute to the formation of the channel ionophores for these currents. Attenuation in K+ conductances and channel subunit expression contribute to altered electrophysiological properties of MSNs and may partially account for selective cellular vulnerability in the striatum. C1 Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Physiol Sci, David Geffen Sch Med, Los Angeles, CA 90095 USA. Massachusetts Med Ctr, Dept Med, Div Endocrinol, Worcester, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Rosalind Franklin Univ Med & Sci, Dept Neurosci, Chicago Med Sch, N Chicago, IL USA. RP Cepeda, C (reprint author), Univ Calif Los Angeles, Mental Retardat Res Ctr, NPI Room 58-258,760 Westwood Plaza, Los Angeles, CA 90095 USA. EM ccepeda@mednet.ucla.edu FU NINDS NIH HHS [NS-38194, NS-41574] NR 51 TC 58 Z9 59 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2005 VL 93 IS 5 BP 2565 EP 2574 DI 10.1152/jn.00791.2004 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 918VH UT WOS:000228575200019 PM 15625098 ER PT J AU Vuletic, S Peskind, ER Marcovina, SM Quinn, JF Cheung, MC Kennedy, H Kaye, JA Jin, LW Albers, JJ AF Vuletic, S Peskind, ER Marcovina, SM Quinn, JF Cheung, MC Kennedy, H Kaye, JA Jin, LW Albers, JJ TI Reduced CSFPLTP activity in Alzheimer's disease and other neurologic diseases; PLTP induces apoE secretion in primary human astrocytes in vitro SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; cerebrospinal fluid; lipoproteins ID PHOSPHOLIPID TRANSFER PROTEIN; FLUID APOLIPOPROTEIN-E; CEREBROSPINAL-FLUID; HUMAN PLASMA; CHOLESTEROL EFFLUX; LIPOPROTEINS; CELLS; ONSET; BETA; HIPPOCAMPUS AB Phospholipid transfer protein (PLTP) plays a pivotal role in cellular lipid efflux and modulation of lipoprotein metabolism. PLTP is distributed widely in the central nervous system (CNS), is synthesized by glia and neurons, and is active in cerebrospinal fluid (CSF). The aims of this study were to test the hypothesis that patients with Alzheimer's disease (AD) have altered PLTP-mediated phospholipid transfer activity in CSF, and to examine the potential relationship between PLTP activity and apolipoprotein E (apoE) levels in CSF We assessed PLTP activity and apoE concentration in CSF of patients with probable AD (n = 50), multiple sclerosis (MS; n = 9), other neurologic diseases (n = 21), and neurologically healthy controls (n = 40). PLTP activity in AD was reduced compared to that in controls (P < 0.001), with approximately half of the AD patients with PLTP activity values below all controls. Patients with MS had lower PLTP activity than AD patients (P < 0.001). PLTP activity was highly correlated with PLTP mass, as estimated by Western blot (r = 0.006; P < 0.01). CSF PLTP activity positively correlated with apoE concentration in AD (P = 0.435; P = 0.002) and controls (R = 0.456; P = 0.003). Anti-apoE immunoaffinity chromatography and Western blot analyses indicated that some CSF PLTP is associated with apoE-containing lipoproteins. Exogenous addition of recombinant PLTP to primary human astrocytes significantly increased apoE secretion to the conditioned medium. The findings of reduced PLTP activity in AD CSF, and the observation that PLTP can influence apoE secretion in astrocytes suggest a potential link between alterations in the brain lipid metabolism and AD pathogenesis. (c) 2005 Wiley-Liss, Inc. C1 Univ Washington, Dept Med, NW Lipid Metab & Diabet Res Labs, Seattle, WA 98109 USA. Univ Washington, Sch Med, Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98109 USA. VA Med Ctr, Dept Neurol, Portland, OR USA. Univ Calif Davis, Mind Inst, Dept Med, Davis, CA 95616 USA. RP Albers, JJ (reprint author), Univ Washington, Dept Med, NW Lipid Metab & Diabet Res Labs, 401 Queen Anne Ave N, Seattle, WA 98109 USA. EM jja@u.washington.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [5 M01 RR000334]; NHLBI NIH HHS [HL30086]; NIA NIH HHS [AG05136, AG05136-18, AG08419, P30 AG08017] NR 46 TC 32 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAY 1 PY 2005 VL 80 IS 3 BP 406 EP 413 DI 10.1002/jnr.20458 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 918RT UT WOS:000228566000011 PM 15795933 ER PT J AU King, JT Moossy, JJ Tsevat, J Roberts, MS AF King, JT Moossy, JJ Tsevat, J Roberts, MS TI Multimodal assessment after surgery for cervical spondylotic myelopathy SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE cervical spine; spinal stenosis; surgery; health status; outcome assessment; quality of life ID QUALITY-OF-LIFE; POSTERIOR LONGITUDINAL LIGAMENT; SURGICAL-TREATMENT; MEDICAL OUTCOMES; CONTROLLED-TRIAL; SHORT FORM-36; FOLLOW-UP; ANTERIOR; FUSION; REHABILITATION AB Object. Investigators reporting decompressive surgery to treat patients with cervical spondylotic myelopathy (CSM) have described inconsistent benefits. In the present study the authors used three types of outcomes instruments to assess the results of CSM surgery. Methods. The authors collected prospective baseline and 6-month follow-up data in a cohort of 62 patients with CSM. Data collection included those pertaining to demographics; symptoms; physical findings; myelopathy severity; health status measured with the Short Form-36; and health values according to the standard gamble, time trade-off, visual analog scale, and willingness to pay. Rank-order methods were used to compare surgical and nonsurgical patients, and multivariate regression techniques adjusting for baseline characteristics were performed to examine the effects of surgery. During the study period, 28 patients underwent surgery, 34 did not, and there were no baseline differences between the two groups in demographics, symptoms, myelopathy scores, health status. or health values (p >= 0.120 in all domains); there was a greater prevalence of hand intrinsic muscle atrophy (p = 0.035) and Hoffmann sign (p = 0.006) in the surgery-treated group. Neither raw comparisons nor regression analyses showed a consistent surgery-related benefit. There were sporadic associations between worse outcomes and older patients, higher income, Babinski sign, longer duration of CSM symptoms, hand clumsiness, lower-extremity numbness, and multilevel surgery (p <= 0.049 for all). Conclusions. Analysis of results obtained in the 62 patients with CSM failed to show a surgery-related benefit despite the use of three classes of outcomes instruments. Patient demographics, symptoms, physical signs, and the surgical approach may explain some of the variation in outcomes in patients with CSM. C1 Vet Adm Connecticut Healthcare Syst, Neurosurg Sect, West Haven, CT 06516 USA. Yale Univ, Dept Neurosurg, New Haven, CT 06520 USA. Vet Affairs Pittsburgh Healthcare Syst, Neurosurg Sect, Surg Serv Line, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Cincinnati, Med Ctr, Sect Outcomes Res & Decis Sci,Dept Internal Med, Div Gen Internal Med, Cincinnati, OH 45221 USA. Univ Cincinnati, Med Ctr, Inst Hlth Policy & Hlth Serv Res, Ctr Clin Effectiveness, Cincinnati, OH 45221 USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. RP King, JT (reprint author), Vet Adm Connecticut Healthcare Syst, Neurosurg Sect, 112-950 Campbell Ave, West Haven, CT 06516 USA. EM Joseph.KingJr@med.va.gov FU NINDS NIH HHS [1K23 NS02169-05] NR 44 TC 24 Z9 25 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD MAY PY 2005 VL 2 IS 5 BP 526 EP 534 DI 10.3171/spi.2005.2.5.0526 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 927EU UT WOS:000229176000005 PM 15948295 ER PT J AU Tawakol, A Migrino, RQ Hoffmann, U Abbara, S Houser, S Gewirtz, H Muller, JE Brady, TJ Fischman, AJ AF Tawakol, A Migrino, RQ Hoffmann, U Abbara, S Houser, S Gewirtz, H Muller, JE Brady, TJ Fischman, AJ TI Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE atherosclerosis; fluorodeoxyglucose; macrophage; vulnerable plaque ID COLONY-STIMULATING FACTOR; FDG-PET; PERITONEAL-MACROPHAGES; SUPEROXIDE PRODUCTION; CORONARY-THROMBOSIS; RESPIRATORY BURST; GLUCOSE-TRANSPORT; UNKNOWN ORIGIN; BLOOD-FLOW; CELL-LINE AB Background. Fluorine 18 fluorodeoxyglucose (FDG) has been shown to accumulate in inflamed tissues. However, it is not known whether vascular inflammation can be measured noninvasively. The aim of this study was to test the hypothesis that vascular inflammation can be measured noninvasively by use of positron emission tomography (PET) with FDG. Methods and Results. Inflamed atherosclerotic lesions were induced in 9 male New Zealand white rabbits via balloon injury of the aortoiliac arterial segment and exposure to a high cholesterol diet. Ten rabbits fed standard chow served as controls. Three to six months after balloon injury, the rabbits were injected with FDG (1 mCi/kg), after which aortic uptake of FDG was assessed (3 hours after injection). Biodistribution of FDG activity within aortic segments was obtained by use of standard well gamma counting. FDG uptake was also determined noninvasively in a subset of 6 live atherosclerotic rabbits and 5 normal rabbits, via PET imaging and measurement of standardized uptake values over the abdominal aorta. Plaque macrophage density and smooth muscle cell density were determined by planimetric analysis of RAM-11 and smooth muscle actin staining, respectively. Biodistribution of FDG within nontarget organs was similar between atherosclerotic and control rabbits. However, well counter measurements of FDG uptake were significantly higher within atherosclerotic aortas compared with control aortas (P < .001). Within the upper abdominal aorta of the atherosclerotic group (area of greatest plaque formation), there was an approximately 19-fold increase in FDG uptake compared with controls (108.9 +/- 55.6 percent injected dose [%ID]/g X 10(3) vs 5.7 +/- 1.2 %ID/g X 10(3) [mean +/- SEM], P < .001). In parallel with these findings, FDG uptake, as determined by PET, was higher in atherosclerotic aortas (standardized uptake value for atherosclerotic aortas vs control aortas, 0.68 +/- 0.06 vs 0.13 +/- 0.01; P < .001). Moreover, macrophage density, assessed histologically, correlated with noninvasive (PET) measurements of FDG uptake (r = 0.93, P < .0001). In contrast to this finding, FDG uptake did not correlate with either aortic wall thickness or smooth muscle cell staining of the specimens. Conclusion. These data show that FDG accumulates in macrophage-rich atherosclerotic plaques and demonstrate that vascular macrophage activity can be quantified noninvasively with FDG-PET. As such, measurement of vascular FDG uptake with PET holds promise for the noninvasive characterization of vascular inflammation. C1 Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tawakol, A (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Boston, MA 02114 USA. EM atawakol@partners.org FU NCRR NIH HHS [RR16046]; NIBIB NIH HHS [EB02102E20] NR 56 TC 178 Z9 185 U1 1 U2 8 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 2005 VL 12 IS 3 BP 294 EP 301 DI 10.1016/j.nuclcard.2005.03.002 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 933GH UT WOS:000229616400008 PM 15944534 ER PT J AU Morrow, AL Ruiz-Palacios, GM Jiang, X Newburg, DS AF Morrow, AL Ruiz-Palacios, GM Jiang, X Newburg, DS TI Human-milk glycans that inhibit pathogen binding protect breast-feeding infants against infectious diarrhea SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE oligosaccharide; anti-adhesion agents; innate immunity; receptor analogs; histo-blood groups ID BLOOD GROUP ANTIGENS; NORWALK VIRUS-INFECTION; FUCOSYLATED OLIGOSACCHARIDES; BLOCK BINDING; INDIVIDUALS; NOROVIRUSES; LACTATION; CHILDREN; LEWIS; CELLS AB Breast-feeding is a highly effective strategy for preventing morbidity and mortality in infancy. The human-milk glycans, which include oligosaccharides in their free and conjugated forms, constitute a major and an innate immunologic mechanism by which human milk protects breast-fed infants against infections. The glycans found in human milk function as soluble receptors that inhibit pathogens from adhering to their target receptors on the mucosal surface of the host gastrointestinal tract. The α 1,2-linked fucosylated glycans, which require the secretor gene for expression in human milk, are the dominant glycan structure found in the milk of secretor mothers, who constitute the majority (&SIM; 80%) of mothers worldwide. In vitro and in vivo binding studies have demonstrated that α 1,2-linked fucosylated glycans inhibit binding by campylobacter, stable toxin of enterotoxigenic Escherichia coli, and major strains of caliciviruses to their target host cell receptors. Consistent with these findings, recently published epidemiologic data demonstrate that higher relative concentrations of α 1,2-linked fucosylated glycans in human milk are associated with protection of breast-fed infants against diarrhea caused by campylobacter, caliciviruses, and stable toxin of enterotoxigenic E coli, and moderate-to-severe diarrhea of all causes. These novel data open the potential for translational research to develop the human-milk glycans as a new class of antimicrobial agents that prevent infection by acting as pathogen anti-adhesion agents. C1 Univ Cincinnati, Coll Med, Ctr Biostat & Epidemiol, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH 45221 USA. Univ Cincinnati, Coll Med, Div Infect Dis, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH 45221 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH 45221 USA. Inst Nacl Ciencias Med & Nutr, Dept Infectol, Mexico City, DF, Mexico. Massachusetts Gen Hosp, Mucosal Immun Lab, Program Glycobiol, Boston, MA 02114 USA. RP Morrow, AL (reprint author), Univ Cincinnati, Coll Med, Ctr Biostat & Epidemiol, Cincinnati Childrens Hosp,Med Ctr, Cincinnati, OH 45221 USA. EM ardythe.morrow@cchmc.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NICHD NIH HHS [P01 HD13021] NR 27 TC 143 Z9 155 U1 9 U2 42 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1304 EP 1307 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600064 PM 15867329 ER PT J AU Newburg, DS AF Newburg, DS TI Innate immunity and human milk SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE innate immunity; disease; human milk; neonates; protection AB Human neonates are born with an immature and naive acquired immune system, and many of the innate components of mucosal immunity are not fully developed. Thus, the innate immune system of human milk is an important complement to the mucosal barrier of the developing gut. The nursing mother provides her infant many protective agents through milk, a growing number of which have been identified as isolates of milk in laboratory models of infection. The number, the potency, and the importance of these protective agents are probably greater than previously thought. For example, many potent protective agents are not found in milk until digestion releases antimicrobial agents such as fatty acids and peptides. An alternate conformer of a-lactalbumin forms from milk in the stomach and inhibits cancer cells. Many of the protective constituents of human milk inhibit different aspects of a pathogenic process, creating a synergy, where much lower concentrations of each component become protective. Some components have a temporal and a spatial specificity that would cause their protective role to go unrecognized by most laboratory models of infection. Some protective components had remained underappreciated because of technical challenges in their isolation and testing. Recent reports suggest that human milk contains a highly potent mixture of protective agents that constitute an innate immune system, whereby the mother protects her infant from enteric and other diseases. These human-milk components may represent a rich source of novel classes of therapeutic agents against human pathogens. C1 Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Charlestown, MA USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Charlestown, MA USA. EM dnewburg@partners.org FU NICHD NIH HHS [P01 HD13021] NR 7 TC 112 Z9 116 U1 2 U2 16 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1308 EP 1312 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600065 PM 15867330 ER PT J AU Williams, DL Cummings, DE AF Williams, DL Cummings, DE TI Regulation of ghrelin in physiologic and pathophysiologic states SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE ghrelin; food intake; obesity ID GASTRIC BYPASS-SURGERY; GASTROINTESTINAL SATIETY SIGNALS; PLASMA GHRELIN; CIRCULATING GHRELIN; OBESE SUBJECTS; FOOD-INTAKE; WEIGHT-LOSS; BILIOPANCREATIC DIVERSION; BARIATRIC SURGERY; ACYLATED PEPTIDE AB Ghrelin, a ligand for the growth hormone secretagogue receptor, is an orexigenic hormone produced in the gastrointestinal tract. In humans and other animals, circulating ghrelin levels fluctuate over the course of the day in relation to food intake. If circulating ghrelin plays a role in determining food intake from meal to meal, it will be important to understand the factors that regulate plasma ghrelin levels in relation to feeding. Circulating ghrelin levels also appear to reflect body weight changes over the longer term, raising the possibility that ghrelin functions as an adiposity signal. This review discusses some of the factors known to affect ghrelin levels, including nutrient stimulation of the gastrointestinal tract, diet composition, and weight loss. We also consider potential hormonal and neural mediators of the effects of nutrients and weight change on ghrelin levels. C1 Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Harborview Med Ctr, Seattle, WA 98104 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Williams, DL (reprint author), Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. EM dianalw@u.washington.edu RI Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 NR 62 TC 81 Z9 89 U1 0 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1320 EP 1325 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600068 PM 15867333 ER PT J AU Li, GA Papannagari, R Most, E Park, SE Johnson, T Tanamal, L Rubash, HE AF Li, GA Papannagari, R Most, E Park, SE Johnson, T Tanamal, L Rubash, HE TI Anterior tibial post impingement in a posterior stabilized total knee arthroplasty SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID IN-SITU FORCES; CRUCIATE LIGAMENT; FOLLOW-UP; BIOMECHANICAL CONSEQUENCES; REPLACEMENT; PROSTHESIS; VITRO; SURVIVAL; FRACTURE; LOADS AB Despite the numerous long-term success reports of posterior stabilized (PS) total knee arthroplasty (TKA), recent retrieval studies of various PS TKA designs revealed wear and deformation oil the anterior side of the tibial post. This study investigated the mechanisms of anterior impingement of the post with the femoral component. Seven cadaveric knees were tested to study kinematics and tibial post biomechanics during simulated heel strike using an in vitro robotic testing system. Intact knee kinematics and in situ anterior cruciate ligament (ACL) forces were determined at hyperextension (0 degrees to -9 degrees) and low flexion angles (0 degrees to 30 degrees) under the applied loads. The same knee was reconstructed using a PS TKA. The kinematics and the tibial post contact forces of the TKA were measured under the same loading condition. The ACL in the intact knee carried load and contributed to knee stability at low flexion angles and hyperextension. After TKA, substantial in situ contact forces (252.4 +/- 173 N at 9 degrees of hyperextension) occurred in the tibial post, indicating anterior impingement with the femoral component. Consequently, the TKA showed less posterior femoral translation compared-to the intact knee after the impingement. At 9 degrees of hyperextension, the medial condyle of the intact knee translated 0.1 +/- 1.1 min whereas the medial condyle of the TKA knee translated 5.6 +/- 6.9 mm anteriorly. The lateral condyle of the intact knee translated 1.5 +/- 1.0 mm anteriorly whereas the lateral condyle of the TKA knee translated 2.1 +/- 5.8 mm anteriorly. The data demonstrated that anterior tibial post impingement functions as a substitute for the ACL during hyperextension, contributing to anterior stability. However, anterior post impingement may result in additional polyethylene wear and tibial post failure. Transmitted impingement forces might cause backside wear and component loosening. Understanding the advantages and disadvantages of the tibial post function at low flexion angles may help to further improve component design and surgical techniques and thus enhance knee stability and component longevity after TKA. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. Zimmer Inc, Warsaw, IN 46581 USA. RP Li, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Bioengn Lab, Boston, MA 02114 USA. EM gli1@partners.org NR 29 TC 44 Z9 46 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2005 VL 23 IS 3 BP 536 EP 541 DI 10.1016/j.orhtres.2004.09.005 PG 6 WC Orthopedics SC Orthopedics GA 929VP UT WOS:000229375000005 PM 15885472 ER PT J AU Behnam, K Murray, SS Brochmann, EJ AF Behnam, K Murray, SS Brochmann, EJ TI Identification and characterization of valosin-containing protein (VCP/p97) in untransformed osteoblast-like cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE valosin-containing protein p97; osteoblast; proteomics ID PAGET-DISEASE; AAA-ATPASE; 2-DIMENSIONAL ELECTROPHORESIS; TYROSINE PHOSPHORYLATION; ENDOPLASMIC-RETICULUM; BINDING PROTEIN; BONE; VCP; LOCALIZATION; EXPRESSION AB A 97-kDa protein called valosin-containing protein (VCP) has been implicated in osteosarcoma metastasis and Paget's disease of gene expression is bone, two conditions that complicate the course and outcome of orthopaedic surgery. High VCP g.. associated with high metastatic potential in osteosarcoma cells, while loss-of-function VCP Mutations cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). VCP protein expression and regulation have not been examined in normal osteoblasts. The purpose of these studies was to characterize VCP protein expression in control and stressed untransformed osteoblasts. Proteins from confluent MC3T3-E1 mouse osteoblast-like cells were separated by 2D IEF/SDS-PAGE. An abundant spot with a M-r. of 94 kDa and a pI of 5.4 was identified as VCP by MALDI/ToF and peptide mass fingerprint analysis. High constitutive VCP protein expression in subconfluent and confluent resting and mildly physiologically stressed MC3T3-E1 I cells was confirmed by Western blotting. When assessed by indirect immunofluorescence in fixed cells or Western blotting of subcellular fractions, VCP was more abundant in the cytoplasm than in the nucleus. Induction of mild physiological stress sufficient to stimulate the ubiquitin-proteasome pathway, which is partially dependent on VCP-mediated targeting of polyubiquitinylated Substrates, did not affect steady-state VCP levels or distribution. Thus, VCP is a constitutively abundant protein in untransformed osteoblastic cells under all conditions tested. Such high levels of VCP protein expression in untransformed osteoblastic cells argue against a major causative role for it in metastasis, while the occurrence of Paget's disease in patients with missense VCP mutations supports a major role for VCP in normal osteoblast proliferation and regulation. (c) 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Brochmann, EJ (reprint author), VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, 16111 Plummer St, Sepulveda, CA 91343 USA. EM Elsa.Murray@ined.va.gov NR 31 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2005 VL 23 IS 3 BP 618 EP 624 DI 10.1016/j.orthres.2004.12.012 PG 7 WC Orthopedics SC Orthopedics GA 929VP UT WOS:000229375000016 PM 15885483 ER PT J AU Bhattacharyya, T McCarty, LP Harris, MB Morrison, SM Wixted, JJ Vrahas, MS Smith, RM AF Bhattacharyya, T McCarty, LP Harris, MB Morrison, SM Wixted, JJ Vrahas, MS Smith, RM TI The posterior shearing tibial plateau fracture - Treatment and results via a posterior approach SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE tibial plateau fracture; posterior approach; functional outcome ID REDUCTION AB Objectives: This study was designed to describe the fracture patterns and early results of treatment of posterior shearing tibial plateau fractures. Design: Retrospective case series. Setting: Tertiary care hospital. Patients: Thirteen patients identified from prospective trauma database with posterior shearing tibial plateau fractures. Intervention: Open reduction and internal fixation through a posterior approach to the knee. Main Outcome Measurements: Functional outcome assessed by Musculoskeletal Functional Assessment score and Visual Analogue Scale pain scores. Clinical and radiographic outcome. Results: A consistent fracture pattern was identified with a primary, inferiorly displaced posteromedial shear fracture with variable amounts of lateral condylar impaction. The average duration of clinical patient follow-up was 20 (range, 13-27) months. All fractures healed after index surgery. Two complications (1 wound dehiscence and 1 flexion contracture) were all managed no it operatively. Three independent surgeons graded patients' articular reduction, with good interobserver reliability (intraclass correlation coefficient = 0.82). The average Musculoskeletal Function Assessment dysfunction score for the 9 patients who responded was 19.5/100, and average resting Visual Analogue Scale pain score was 1.8 cm/10 cm, indicating good function. The functional outcome score was significantly related to the quality of articular reduction (P < 0.017, R = 0.456). Conclusions: Posterior shearina tibial plateau fractures form a consistent pattern. They can be Successfully managed using a posterior approach with direct reduction and buttress fixation of articular fragments. Quality of articular reduction is one factor that influences short-term functional outcome. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Smith, RM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Partners Orthopaed Trauma Serv, WACC 525,55 Fruit St, Boston, MA 02114 USA. EM msmith23@partners.org NR 13 TC 80 Z9 113 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD MAY-JUN PY 2005 VL 19 IS 5 BP 305 EP 310 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 930DJ UT WOS:000229395700002 PM 15891538 ER PT J AU O'Mahony, S Goulet, J Kornblith, A Abbatiello, G Clarke, B Kless-Siegel, S Breitbart, W Payne, R AF O'Mahony, S Goulet, J Kornblith, A Abbatiello, G Clarke, B Kless-Siegel, S Breitbart, W Payne, R TI Desire for hastened death, cancer pain and depression: Report of a longitudinal observational study SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE cancer pain; depression; desire for hastened death ID PHYSICIAN-ASSISTED SUICIDE; QUALITY-OF-LIFE; TERMINALLY-ILL; ATTITUDES; EUTHANASIA; ANXIETY; OREGON; WASHINGTON; DISORDERS; SCHEDULE AB Desire for hastened death (DHD) is reported in the literature as being common in patients with cancer pain. However, there is currently little evidence to suggest that improvement in pain results in improvement in DHD. Our objectives were to assess 1) the impact of improvements in cancer pain severity and pain's interference with daily functioning and depression on DHD, and 2) the role of factors such as social and spiritual well-being, educational level, and patient age in moderating the impact of pain and depression on DHD. This observational study included patient-rated and clinician-rated scales administered twice at 4-week intervals. We enrolled 131 newly-referred patients to the Pain and Palliative Care Service at Memorial Sloan-Kettering Cancer Center or newly-admitted patients to Calvary Hospital in New York. One hundred and sixteen patients completed the baseline measures and 64 patients completed both baseline and follow-up measures. The main outcome measures included the Brief Pain Inventory (BPI), Beck Depression Inventory (BDI), and the Desire for Hastened Death Scale (DHD). Sixty-six percent of patients had no DHD at baseline and 45% of patients had BDI scores of 4 or greater ('mild' depression). Only 40% of patients with moderate/severe depression were receiving antidepressants. BPI scores improved significantly from baseline to follow-up (6.36 vs. 4.86, P < 0.01). DHD scores increased significantly from baseline to follow-up (0.84 to 1.38, P = 0.03). All other measures including depression were stable. DHD scores were moderately correlated with depression (r = 0.43), low social support (r = 0.38), poor spiritual well-being (r = -0.38) religious well being (r = -0.25), pain interference (r = 0.27), higher educational level (F = 4.50, P = 0.02) and lower physical functioning (KPRS, r = -0.40), but were unrelated to sex, age, race, or marital status. In multivariate regression analyses, baseline DHD (beta = 0.30, P = 0.05) and change in depression (beta = 0.36, P = 0.02) were predictive of follow-up DHD. Improvement in pain interference was not predictive of follow-up DHD. The results suggest that improvement in depression moderated the severity (of desire for hastened death in a population of Patients with cancer pain. Depression was common in this population (and was often untreated. Improvements in functional impairment due to pain did not moderate the severity of DHD in a setting of aggressive pain management. Strategies to preemptively screen for depression in the routine assessment of patients with cancer pain may be important to address DHD. (c) 2005 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Montefiore Med Ctr, Palliat Care Serv, Dept Family & Social Med, Bronx, NY 10467 USA. Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Coll Mt St Vincent, Riverdale, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Duke Univ, Sch Divin, Durham, NC USA. RP O'Mahony, S (reprint author), Montefiore Med Ctr, Palliat Care Serv, Dept Family & Social Med, 3335 Steuben Ave, Bronx, NY 10467 USA. OI Goulet, Joseph/0000-0002-0842-804X NR 45 TC 79 Z9 82 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAY PY 2005 VL 29 IS 5 BP 446 EP 457 DI 10.1016/j.jpainsymman.2004.08.010 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 933PX UT WOS:000229646500006 PM 15904747 ER PT J AU Colombo, APV Teles, RP Torres, MC Rosalem, W Mendes, MCS Souto, RM de Uzeda, M AF Colombo, APV Teles, RP Torres, MC Rosalem, W Mendes, MCS Souto, RM de Uzeda, M TI Effects of non-surgical mechanical therapy on the subgingival microbiota of Brazilians with untreated chronic periodontitis: 9-month results SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Brazil; comparison studies; DNA probes; follow-up studies; periodontitis/pathogenesis; periodontitis/therapy; planing; scaling ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; MICROBIOLOGICAL PARAMETERS; DEBRIDEMENT; BACTERIA; METRONIDAZOLE; COLONIZATION; AMOXICILLIN; PATHOGENS; DISEASES; SURGERY AB Background: Mechanical periodontal therapy is the most common treatment of periodontal infections. It is directed primarily towards removing biofilm and calculus from the root surfaces, leading to ecological changes in the subgingival environment. Thus, the purpose of this study was to evaluate the effects of scaling and root planing (SRP) on the subgingival microbiota of Brazilian subjects with untreated chronic periodontitis over a 9-month period. Methods: Twenty-five untreated chronic periodontitis patients (mean age 43 5 years; 20% smokers; 45% males) were selected from a Brazilian population. At baseline, probing depth (PD), clinical attachment level (CAL), visible supragingival biofilm (SB), bleeding on probing (BOP), and suppuration (SUP) were measured at six sites/tooth. Subgingival plaque samples were obtained from 10 sites with the deepest PD (>= 5 mm) of each subject and tested for the presence of 25 oral species by DNA probes and the checker-board technique. Patients received full mouth SRP and oral hygiene instructions. Clinical and microbiological assessments were repeated at 3, 6, and 9 months after therapy. During this period, all patients received maintenance therapy, including supragingival prophylaxis and reinforcement in home care procedures. The clinical and microbiological parameters examined were computed for each subject and at each visit. Differences over time were sought using the Friedman test. Results: Significant reductions in mean CAL and PD (P < 0.01), percent of sites with SB (P < 0.01), BOP and SUP (P < 0.05) were observed during the course of the study. In general, microbial changes were more pronounced for the mean counts than for the frequency of the microorganisms, particularly at 3 months post-therapy. Significant reductions in prevalence and levels were observed for certain periodontal pathogens including P gingivalis (P < 0.05; P < 0.01), T forsythensis (P < 0.01), C. rectus (P < 0.01), and A. actinomycetemcomitans (P < 0.01; P < 0.05). Nevertheless, the frequency of A. actinomycetemcomitans increased to baseline values at 9 months after therapy. Treponema ssp. and Prevotella spp. showed a modest decrease in prevalence, whereas marked reductions in their levels were observed. In contrast, the frequency and counts of the suspected pathogens P micros and F nucleatum increased after treatment. Species considered beneficial including Actinomyces spp., some oral streptococci, and V parvula increased in prevalence, although these two last species tended to return to baseline levels at 9 months. Conclusion: In Brazilians with untreated chronic periodontitis, SRP led to clinical improvement associated with a decrease of certain periodontal pathogens, and an increase of beneficial species for up to 9 months after therapy. C1 Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo de Goes, Dept Med Microbiol, Rio De Janeiro, Brazil. Forsyth Inst, Dept Periodontol, Boston, MA USA. Estacio Sa Univ, Sch Dent, Dept Periodontol, Rio De Janeiro, Brazil. RP Colombo, APV (reprint author), 60 Apt 804 Humaita, BR-22271050 Rio De Janeiro, Brazil. EM anapaulacolombo@yahoo.com NR 33 TC 25 Z9 29 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAY PY 2005 VL 76 IS 5 BP 778 EP 784 DI 10.1902/jop.2005.76.5.778 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 928VM UT WOS:000229299800016 PM 15898939 ER PT J AU Norman, L Buerhaus, PI Donelan, K McCloskey, B Dittus, R AF Norman, L Buerhaus, PI Donelan, K McCloskey, B Dittus, R TI Nursing students assess nursing education SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article ID WORKFORCE; OUTCOMES; NURSES; CARE AB This study assessed the characteristics of nursing students currently enrolled in nursing education programs, how students finance their nursing education, their plans for clinical practice and graduate education, and the rewards and difficulties of being a nursing student. Data are from a survey administered to a national sample of 496 nursing students. The students relied on financial aid and personal savings and earnings to finance their education. Parents, institutional scholarships, and government loans are also important sources, but less than 15% of the students took out bank loans. Nearly one quarter of the students, particularly younger and minority students, plan to enroll in graduate school immediately after graduation and most want to become advanced nursing practitioners. Most of the nursing students (88%) are satisfied with their nursing education and nearly all (95%) provided written answers to two open-ended questions. Comments collapsed into three major categories reflecting the rewards (helping others, status, and job security) and three categories reflecting the difficulties (problems with balancing demands, quality of nursing education, and the admissions process) of being a nursing student. Implications for public policymaking center on expanding the capacity of nursing education programs, whereas schools themselves should focus on addressing the financial needs of students, helping them strike a balance among their school, work, and personal/family responsibilities and modifying certain aspects of the curriculum. (c) 2005 Published by Elsevier Inc. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Div Gen Internal Med, Nashville, TN USA. Vanderbilt Univ, Ctr Htlh Serv Res, Nashville, TN USA. RP Norman, L (reprint author), Vanderbilt Univ, Sch Nursing, 101 Godchaux Hall,21st Ave S, Nashville, TN 37240 USA. EM linda.norman@vanderbilt.edu NR 23 TC 23 Z9 23 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 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD MAY-JUN PY 2005 VL 21 IS 3 BP 150 EP 158 DI 10.1016/j.profnurs.2005.04.003 PG 9 WC Nursing SC Nursing GA 941TK UT WOS:000230236900005 PM 16021558 ER PT J AU Kawamura, DH Hadlock, TA Fox, IK Brenner, MJ Hunter, DA Mackinnon, SE AF Kawamura, DH Hadlock, TA Fox, IK Brenner, MJ Hunter, DA Mackinnon, SE TI Regeneration through nerve isografts is independent of nerve geometry SO JOURNAL OF RECONSTRUCTIVE MICROSURGERY LA English DT Article DE peripheral nerve; graft configuration; nerve regeneration ID FACIAL-NERVE; ERECTILE FUNCTION; CAVERNOUS NERVES; SCHWANN-CELLS; GROWTH-FACTOR; REPAIR; SUTURE; MOTOR; RAT; TENSION AB Investigators have theorized that tortuosity in nerve grafts may adversely affect nerve regeneration. This study investigated the effect of graft configuration and redundancy on regeneration across 2.5-cm rat sciatic nerve isografts. Thirty-two Lewis rats were randomized to four nerve grafting groups defined by gap distance and isograft conformation. In Group 1, grafts were interposed into a 2-cm gap, resulting in mild graft redundancy. In Groups 2 and 3, grafts were tacked in sinusoidal or omega-shaped configurations, respectively, to bridge a 0.5-cm gap. In Group 4, grafts were interposed after 1 cm of native sciatic nerve was resected, resulting in no graft redundancy and an interstump distance of 2.5 cm. At 6 weeks, nerve tissue was harvested; subsequent histomorphometric analysis revealed no significant differences in regeneration between groups. These data suggest that regeneration through isografts is independent of the graft geometry and redundancy. C1 Washington Univ, Sch Med, Dept Surg, Div Plast & Reconstruct Surg, St Louis, MO 63110 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO 63110 USA. RP Mackinnon, SE (reprint author), Washington Univ, Sch Med, Dept Surg, Div Plast & Reconstruct Surg, Box 8238,660 S Euclid St, St Louis, MO 63110 USA. NR 41 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0743-684X J9 J RECONSTR MICROSURG JI J. Reconstr. Microsurg. PD MAY PY 2005 VL 21 IS 4 BP 243 EP 249 DI 10.1055/s-2005-871751 PG 7 WC Surgery SC Surgery GA 928GM UT WOS:000229259400006 PM 15971142 ER PT J AU Chen, W Qu, J Wang, QM Lu, F Barabino, S AF Chen, W Qu, J Wang, QM Lu, F Barabino, S TI Automated lamellar keratoplasty for recurrent granular corneal dystrophy after phototherapeutic keratectomy SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID PENETRATING KERATOPLASTY; EXCIMER-LASER; MICROKERATOME AB Purpose: To evaluate the safety and efficacy of automated lamellar keratoplasty for the treatment of recurrent granular corneal dystrophy after phototherapeutic keratectomy (PTK). Methods: We performed a prospective interventional noncomparative case study of nine eyes (seven patients) with severe recurrent granular corneal dystrophy after PTK. An automated microkeratome was used to cut partial-thickness sections through the anterior surface of the donor and host corneas. The donor disc was placed on the recipient bed with four or eight interrupted sutures. The sutures were removed between 4 and 6 weeks postoperatively. Visual acuity, corneal clarity, corneal thickness, and corneal topography were assessed before and at different time points after surgery. Results: During a mean follow-up periods of 18.9 +/- 4.1 months, all grafts were transparent without visible opacity at the interface, and no serious complications occurred. In all cases, the visual acutity improved: seven eyes had best spectacle-corrected visual acuity of >= 20/40; two eyes reached 2-/25. At last follow-up > 12 months postoperatively, the mean corneal refractive power had significantly increased by 2.34 +/- 0.93 diopters (D) (P< .001), and the corneal astigmatism significantly decreased by 0.91 +/- 0.98 D (P < .05). The mean corneal thickness was 477.4 +/- 26.9 mu m preoperatively and 507.8 +/- 23.4 mu m at last follow-up (P < .001). Conclusions: Our findings suggest that automated lamellar keratoplasy for the treatment of recurrent granular corneal dystrophy is a safe and effective method of improving visual acuity, but recurrence remains a risk. C1 Wenzhou Med Coll, Affiliated Eye Hosp, Dept Ophthalmol, Wenzhou 325027, Zhejiang, Peoples R China. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Qu, J (reprint author), Wenzhou Med Coll, Affiliated Eye Hosp, Dept Ophthalmol, Wenzhou 325027, Zhejiang, Peoples R China. EM Qujiamd@hotmail.com NR 25 TC 10 Z9 11 U1 2 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD MAY-JUN PY 2005 VL 21 IS 3 BP 288 EP 293 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 973RZ UT WOS:000232541600011 PM 15977887 ER PT J AU Wang, WC Ledoux, WR Sangeorzan, BJ Reinhall, PG AF Wang, WC Ledoux, WR Sangeorzan, BJ Reinhall, PG TI A shear and plantar pressure sensor based on fiber-optic bend loss SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE anterior/posterior shear; biomechanics; biosensing techniques; diabetes mellitus; foot ulcers; gait; lower-limb complications; plantar pressure; plantar ulcers; ulcer ID FORCE DISTRIBUTION; FOOT PRESSURE; ULCERATION AB Lower-limb complications associated with diabetes include the development of plantar ulcers that can lead to infection and subsequent amputation. While we know from force-plate analyses that medial/lateral and anterior/posterior shear components of ground-reaction forces exist, little is known about the actual distribution of these stresses during daily activities or about the role that shear stresses play in causing plantar ulceration. Furthermore, one critical reason why these data have not been obtained previously is the lack of a validated, widely used, commercially available shear sensor, partly because of the various technical issues associated with measuring shear. In this study, we present a novel means of transducing plantar pressure and shear stress with a fiber-optic sensor. The pressure/shear sensor consists of an array of optical fibers lying in perpendicular rows and columns separated by elastomeric pads. We constructed a map of normal and shear stresses based on observed macrobending through the intensity attenuation from the physical deformation of two adjacent perpendicular fibers. Initial results show that this sensor exhibits low noise and responds to applied normal and shear loads with good repeatability. C1 Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. Ctr Excellence Limb Loss Prevent & Prosthet Engn, Dept Vet Affairs VA Rehabil Res & Dev, VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Wang, WC (reprint author), Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. EM abong@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 18 TC 26 Z9 27 U1 0 U2 16 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2005 VL 42 IS 3 BP 315 EP 325 DI 10.1682/JRRD.2004.07.0076 PG 11 WC Rehabilitation SC Rehabilitation GA 953MN UT WOS:000231080600006 PM 16187244 ER PT J AU Dvorznak, M Cooper, R Boninger, M AF Dvorznak, M Cooper, R Boninger, M TI Kinematic analysis for determination of bioequivalence of a modified Hybrid III test dummy and a wheelchair user SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE accident prevention; bioequivalence; electrically powered wheelchairs; Hybrid test dummy; injury assessment; injury biomechanics; kinematics; spinal cord injury; statistical measures; tips and falls; wheelchair safety ID BIOMECHANICS; ACCIDENTS; MOMENTS; FORCES; BELT AB We investigated whether a modified 50th-percentile Hybrid III test dummy (HTD) (First Technology Safety Systems, Plymouth, MI) would have motion similar to a wheelchair test pilot (TP) with T8 paraplegia. Test cases were seated in a Quickie P100 electrically powered wheelchair (Sunrise Medical, Inc., Phoenix, AZ) driven at three speeds (0.8, 1.4, and 2.0 m/s). Three braking conditions-joystick release, joystick full reverse, and emergency power-off-were used to stop the wheelchair. The subsequent upper-body motion was recorded for the creation of kinematic exposure profiles of the wheelchair riders. The maximum concentration (Cmax) and area under the trunk angular displacement, velocity, and acceleration curves (AUC(0-Cmax)) were calculated. Assessments of average, individual, and population bioequivalence were conducted after data were subjected to natural logarithmic transforms. Only the Cmax of the trunk angular acceleration of the HTD and TP was average bioequivalent (0.82-1.04). Both Cmax and AUC(0-Cmax) measures for all kinematic exposures between the TP and HTD were individual and population bioequivalent (95% upper-confidence bound < 0, linearized bioequivalence criteria). This indicates that the HTD is a suitable surrogate for a wheelchair user in low-speed, low-impact wheelchair studies. C1 Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Vet Affairs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, R (reprint author), Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Dept Vet Affairs, 7180 Highland Dr,151R-1, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Boninger, Michael/0000-0001-6966-919X NR 18 TC 2 Z9 2 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2005 VL 42 IS 3 BP 343 EP 351 DI 10.1682/JRRD.2004.07.0082 PG 9 WC Rehabilitation SC Rehabilitation GA 953MN UT WOS:000231080600008 PM 16187246 ER PT J AU Gordon, JS Phillips, DS Helt, WJ Konrad-Martin, D Fausti, SA AF Gordon, JS Phillips, DS Helt, WJ Konrad-Martin, D Fausti, SA TI Evaluation of insert earphones for high-frequency bedside ototoxicity monitoring SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE circumaural earphones; early detection; hearing thresholds; high-frequency testing; insert earphones; instrumentation; intrasubject reliability; ototoxicity monitoring; test-retest reliability; threshold reliability ID HEARING THRESHOLDS; ADULTS; VARIABILITY; AUDIOMETRY; RANGE AB Ototoxic hearing loss is usually detected earliest through monitoring of the highest audible frequencies in individuals administered ototoxic medications. Conducting ototoxicity monitoring may require testing patients in the hospital room. This study evaluated the use of insert earphones for obtaining reliable threshold responses at bedside. Twenty adult subjects were tested during two different sessions in the sound booth and on the ward. Thresholds were obtained for frequencies from 5 to 16 kHz and at 2 kHz with the use of the KOSS Pro/4X Plus earphones and Etymotic ER-4B MicroPro insert earphones. Results indicate that ER-4B insert earphones are as reliable as KOSS earphones for testing on the ward for high-frequency ototoxicity monitoring. C1 Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, VA Rehabil Res & Dev, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR USA. RP Fausti, SA (reprint author), Natl Ctr Rehabil Auditory Res, Dept Vet Affairs, VA Rehabil Res & Dev, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,NCRAR, Portland, OR 97239 USA. EM stephen.fausti@med.va.gov NR 26 TC 9 Z9 9 U1 2 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2005 VL 42 IS 3 BP 353 EP 361 DI 10.1682/JRRD.2004.06.0093 PG 9 WC Rehabilitation SC Rehabilitation GA 953MN UT WOS:000231080600009 PM 16187247 ER PT J AU Monga, U Kerrigan, AJ Thornby, J Monga, TN Zimmermann, KP AF Monga, U Kerrigan, AJ Thornby, J Monga, TN Zimmermann, KP TI Longitudinal study of quality of life in patients with localized prostate cancer undergoing radiotherapy SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE depression; fatigue; Functional Assessment of Cancer Therapy; outcomes; physical well-being; Piper Fatigue Scale; prostate cancer; quality of life; radiotherapy; sleep disturbance ID EXTERNAL RADIATION-THERAPY; EPWORTH SLEEPINESS SCALE; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; MEN; FATIGUE; DIAGNOSIS; DISTRESS; OUTCOMES; CHEMOTHERAPY AB This study prospectively evaluated quality of life (QOL) in localized prostate cancer patients undergoing radiotherapy, and it examined the relationships between QOL, depression, fatigue, and sleep disturbance. Instruments that were used are Functional Assessment of Cancer Therapy for Prostate (FACT-P), Beck Depression Inventory (13131), Piper Fatigue Scale (PFS), and Epworth Sleepiness Scale (ESS). We evaluated patients at preradiotherapy (PRT), midway radiotherapy (MRT), completion of radiotherapy (CRT), follow-up radiotherapy (4 to 8 wk) (FRT), and long-term follow-up radiotherapy (FRT2) (12 mo or more). Forty participants with a mean age of 67.8 yr were studied. Duration of radiotherapy was 7-8 wk. Mean long-term follow-up period post-CRT was 16.2 mo (range 1224 mo). All patients had clinical T1c to T2b prostate cancer. Prostate Cancer Specific (PCS) and Physical Well-Being (PWB) subscales of FACT-P, scores at MRT and CRT were significantly lower than at PRT. At FRT2, PWB scores declined further, while PCS scores increased. PFS median scores were significantly higher at CRT and at FRT2 as compared with PRT. Patients scoring higher on PFS were more likely to report a poorer QOL and PWB as measured with FACT-P questionnaire. No significant changes were noted in the BDI and ESS scores during the study periods. The PWB declined during and at CRT and worsened at FRT2. Decline in PCS subscale scores during and at CRT reflects worsening of urinary symptoms and appearance of bowel problems. The scores improved at long-term follow-up. A relationship was found to exist between physical well-being and fatigue. C1 Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Kerrigan, AJ (reprint author), Michael E DeBakey Dept Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM KERRIGAN.ANTHONYJ@med.va.gov NR 44 TC 30 Z9 31 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2005 VL 42 IS 3 BP 391 EP 399 DI 10.1682/JRRD.2004.06.0071 PG 9 WC Rehabilitation SC Rehabilitation GA 953MN UT WOS:000231080600013 PM 16187251 ER PT J AU Popa-Lisseanu, MGG Greisinger, A Richardson, M O'Malley, KJ Janssen, NM Marcus, DM Tagore, J Suarez-Almazor, ME AF Popa-Lisseanu, MGG Greisinger, A Richardson, M O'Malley, KJ Janssen, NM Marcus, DM Tagore, J Suarez-Almazor, ME TI Determinants of treatment adherence in ethnically diverse, economically disadvantaged patients with rheumatic disease SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; treatment adherence; systemic lupus erythematosus; focus groups ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FORMAL EDUCATION LEVEL; HEALTH BELIEF MODEL; SOCIOECONOMIC-STATUS; ARTHRITIS PATIENTS; REVISED CRITERIA; CLINICAL STATUS; AMERICAN; THERAPY; RACE AB Objective. To explore the determinants of adherence to medical recommendations, including drug therapy and appointment-keeping, among ethnically diverse and economically disadvantaged patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Methods. Patients with RA and SLE were identified through chart review and were invited to participate in focus groups to examine their attitudes and beliefs regarding adherence to treatment and medical appointments. Eight focus groups'(4 RA, 4 SLE) were conducted, with a total of 40 participants (22 SLE patients and 18 RA patients). Transcripts were analyzed using grounded theory techniques and qualitative analysis software to facilitate coding interpretation. Results. The majority of participants reported experiencing difficulty in adhering to their treatment at least occasionally. Both SLE and RA patients reported similar barriers to treatment adherence: fear of side effects, financial problems, difficulty in navigating the public health system, and perceived treatment inefficacy. RA and SLE patients also revealed barriers to appointment keeping, including difficulties in scheduling, financial costs, transportation, and functional impairment limiting their ability to attend the clinic. Conclusion. Patients' perceptions of and experiences with the health system, physicians, medication effectiveness, and side effects influence their adherence to treatment and other medical recommendations. Strategies to improve adherence could include the following: attempting to modify patients' beliefs and perceptions regarding medication effectiveness, promoting realistic expectations about risk/benefit ratios, and improving access to health care by reducing barriers that limit the interaction between patients and the health system. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Kelsey Res Fdn, Houston, TX USA. RP Suarez-Almazor, ME (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM mes@bcm.tmc.edu NR 43 TC 49 Z9 49 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2005 VL 32 IS 5 BP 913 EP 919 PG 7 WC Rheumatology SC Rheumatology GA 926AH UT WOS:000229094600026 ER PT J AU Hutter, AM AF Hutter, AM TI Invited comments on McMahon, C. Comparison of efficacy, safety, and tolerability of on-demand tadalafil and daily dosed tadalafil for the treatment of erectile dysfunction SO JOURNAL OF SEXUAL MEDICINE LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hutter, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1743-6095 J9 J SEX MED JI J. Sex. Med. PD MAY PY 2005 VL 2 IS 3 BP 425 EP 425 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 935MB UT WOS:000229785300021 ER PT J AU Nieto-Castanon, A Guenther, FH Perkell, JS Curtin, HD AF Nieto-Castanon, A Guenther, FH Perkell, JS Curtin, HD TI A modeling investigation of articulatory variability and acoustic stability during American English vertical bar r vertical bar production SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TRACT AREA FUNCTIONS; VOCAL-TRACT; POINTING ERRORS; MOTOR CONTROL; SPEECH; REPRESENTATIONS; MOVEMENTS; SHAPE AB This paper investigates the functional relationship between articulatory variability and stability of acoustic cues during American English /r/ production. The analysis of articulatory movement data on seven subjects shows that the extent of intrasubject articulatory variability along any given articulatory direction is strongly and inversely related to a measure of acoustic stability (the extent of acoustic variation that displacing the articulators in this direction would produce). The presence and direction of this relationship is consistent with a speech motor control mechanism that uses a third formant frequency (F3) target; i.e., the final articulatory variability is lower for those articulatory directions most relevant to determining the F3 value. In contrast, no consistent relationship across speakers and phonetic contexts was found between hypothesized vocal-tract target variables and articulatory variability. Furthermore, simulations of two speakers' productions using the DIVA model of speech production, in conjunction with a novel speaker-specific vocal-tract model derived from magnetic resonance imaging data, mimic the observed range of articulatory gestures for each subject, while exhibiting the same articulatory/acoustic relations as those observed experimentally. Overall these results provide evidence for a common control scheme that utilizes an acoustic, rather than articulatory, target specification for American English /r/. (c) 2005 Acoustical Society of America. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Nieto-Castanon, A (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM alfnie@bu.edu FU NIDCD NIH HHS [R01 DC01925, R01 DC02852] NR 22 TC 23 Z9 25 U1 1 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2005 VL 117 IS 5 BP 3196 EP 3212 DI 10.1121/1.1893271 PG 17 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 925QV UT WOS:000229068700052 PM 15957787 ER PT J AU Carlson, JA Ross, JS Slominski, A Linette, G Mysliborski, J Hill, J Mihm, M AF Carlson, JA Ross, JS Slominski, A Linette, G Mysliborski, J Hill, J Mihm, M TI Molecular diagnostics in melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Review ID CUTANEOUS MALIGNANT-MELANOMA; SENTINEL LYMPH-NODES; POLYMERASE-CHAIN-REACTION; AMERICAN-JOINT-COMMITTEE; TYROSINASE-MESSENGER-RNA; ENDOTHELIAL GROWTH-FACTOR; BENIGN MELANOCYTIC NEVI; CIRCULATING TUMOR-CELLS; MICROPHTHALMIA TRANSCRIPTION FACTOR; SIGNIFICANT PROGNOSTIC-FACTOR AB Molecular pathology is rapidly evolving, featuring continuous technologic improvements that offer novel clinical opportunities for the recognition of disease predisposition, for identifying sub-clinical disease, for more accurate diagnosis, for selecting efficacious and non-toxic therapy, and for monitoring of disease outcome. Currently, the identification and prognosis of primary cutaneous melanoma is based on histologic factors (tumor depth and ulceration) and clinical factors (number of lymph node and/or distant metastases). However, metastasis can occur in patients with thin melanomas, and sentinel lymph node biopsy does not identify all patients at risk for distant metastasis. New markets exist that correlate with melanoma progression, which may aid in melanoma identification, prognostication, and detection of minimal residual disease/early recurrence. Moreover, not many therapeutic options exist for melanoma as no regimen prolongs survival. Emerging data with investigational therapies suggest that certain markers might play a crucial role in identifying patients who will respond to therapy or show utility in the monitoring the response to therapy. Herein, molecular diagnostics that can potentially benefit the individual melanoma patient will be discussed. C1 Albany Med Coll, Div Dermatopathol, Albany, NY 12208 USA. Albany Med Coll, Div Dermatol, Albany, NY 12208 USA. Capital Dist Dermatol Assoc, Albany, NY USA. Washington Univ, Div Oncol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02114 USA. Millennium Pharmaceut Inc, Div Mol Med, Cambridge, England. Albany Med Coll, Albany Med Ctr, Dept Pathol & Lab Med, Albany, NY 12208 USA. Univ Tennessee, Hlth Sci Ctr, Dept Pathol, Knoxville, TN 37996 USA. RP Carlson, JA (reprint author), Albany Med Coll, Div Dermatopathol, MC-81, Albany, NY 12208 USA. EM carlsoa@mail.amc.edu OI Carlson, John Andrew/0000-0002-6866-6314 NR 347 TC 101 Z9 105 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 MAY PY 2005 VL 52 IS 5 BP 743 EP 775 DI 10.1016/j.jaad.2004.08.034 PG 33 WC Dermatology SC Dermatology GA 926JT UT WOS:000229120200001 PM 15858465 ER PT J AU Kimball, AB Weinstock, MA AF Kimball, AB Weinstock, MA TI Mandatory registration of clinical trials: A major step forward for evidence-based medicine SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dermatol Clin Studies Unit, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dept Vet Affairs Med Ctr, Dermatoepidemiol Unit, Providence, RI USA. Rhode Isl Hosp, Providence, RI 02903 USA. Brown Univ, Providence, RI 02912 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dermatol Clin Studies Unit, 221 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM akimball@partners.org NR 13 TC 0 Z9 3 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2005 VL 52 IS 5 BP 890 EP 892 DI 10.1016/j.jaad.2004.12.020 PG 3 WC Dermatology SC Dermatology GA 926JT UT WOS:000229120200019 PM 15858483 ER PT J AU Nicolaidis, C Curry, MA Gerrity, M AF Nicolaidis, C Curry, MA Gerrity, M TI Health care workers' expectations and empathy toward patients in abusive relationships SO JOURNAL OF THE AMERICAN BOARD OF FAMILY PRACTICE LA English DT Article; Proceedings Paper CT National Conference on Domestic Violence and Healthcare CY OCT 20-22, 2004 CL Boston, MA ID INTIMATE PARTNER VIOLENCE; DOMESTIC VIOLENCE; BARRIERS; INTERVENTION; EXPERIENCES; PHYSICIANS; SERVICES; WOMEN AB Purpose: To understand attitudes that may affect health care workers' ability to provide appropriate long-term care for patients who stay with abusive partners. Methods: We surveyed 278 health care workers in 31 primary care practices before their participation in an educational intervention. Results: More than half of participants (51% to 60%) found it easy to empathize with a patient who decided to remain in an abusive relationship if the patient was described as poor or disabled, but few (25% to 39%) could empathize if the patient was described as educated or financially secure. A majority (57% to 59%) agreed with a statement meant to assess unrealistic expectations. ("A provider's responsibility includes making sure a patient gets to a shelter right away if he or she discloses abuse.") Participants who agreed with this statement had more difficulty empathizing with patients who decided to stay with an abusive partner (P = .0045). Conclusions: Training efforts must focus on screening and on helping providers develop more realistic expectations about the complex nature of leaving an abusive relationship. Health care workers need a better understanding of the barriers patients face and why patients may choose to remain in abusive relationships, even in the absence of economic or health limitations. C1 Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97215 USA. Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97215 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Nicolaidis, C (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med, L475, Portland, OR 97215 USA. EM nicolaid@ohsu.edu NR 21 TC 10 Z9 11 U1 1 U2 5 PU AMER BOARD FAMILY PRACTICE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 0893-8652 J9 J AM BOARD FAM PRACT JI J. Am. Board Fam. Pract. PD MAY-JUN PY 2005 VL 18 IS 3 BP 159 EP 165 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 923TT UT WOS:000228932900001 PM 15879562 ER PT J AU Kaafarani, HM Itani, KMF Giobbie-Hurder, A Gleysteen, JJ McCarthy, M Gibbs, J Neumayer, L AF Kaafarani, HM Itani, KMF Giobbie-Hurder, A Gleysteen, JJ McCarthy, M Gibbs, J Neumayer, L TI Does surgeon frustration and satisfaction with the operation predict outcomes of open or laparoscopic inguinal hernia repair? SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID TOTAL HIP-ARTHROPLASTY; OF-VETERANS-AFFAIRS; SURGICAL CARE; HOSPITAL VOLUME; LEARNING-CURVE; QUALITY; PATIENT; IMPROVEMENT; PERFECT; PROGRAM AB BACKGROUND: A surgeon's level of frustration when performing an operation and level of satisfaction at completion may be correlated with patients' outcomes. We evaluated the relationship between the attending surgeons' frustration and satisfaction and recurrence and complications of open and laparoscopic inguinal hernia repair. STUDY DESIGN: Men with detectable inguinal hernias were randomized to undergo open or laparoscopic herniorrhaphy at 14 Veterans Affairs hospitals. After completion of the procedure, surgeons were asked to assess their level of frustration during the operation and their overall satisfaction with the operative result. Two subjective scales ranging from 1 (not frustrated/not satisfied) to 5 (very frustrated/very satisfied) were used to independently assess both parameters. Reasons for surgeon frustration were evaluated. Patients were followed for 2 years for recurrence and complications. RESULTS: Of 1,983 patients who underwent hernia repair, 1,622 were available for analysis; 808 had open repair and 813 had laparoscopic repair. Surgeons reported less frustration and more satisfaction with open than with laparoscopic repair (p = 0.0001 and 0.0001, respectively). Frustration was associated with a higher rate of hernia recurrence at 2 years (adjusted odds ratio, 2.01, 95% CI, 1.15-3.51) in open repair, and a higher overall rate of postoperative complications (adjusted odds ratio, 1.27, 95% CI, 1.03-1.56) in both open and laparoscopic hernia repair. Satisfaction was not correlated with recurrence or complications. CONCLUSIONS: The level of a surgeon's frustration during performance of an inguinal hermorrhaphy was a better predictor of outcomes of the operation than was satisfaction with the procedure. Sources of intraoperative frustration should be controlled to improve outcomes. (c) 2005 by the American College of Surgeons. C1 Univ Utah, Surg Serv, Salt Lake City, UT 84148 USA. Salt Lake City Vet Affairs Med Ctr, Dept Surg, Salt Lake City, UT 84148 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Vet Affairs Boston Hlth Care Sst, Dept Surg, Boston, MA USA. Boston Med Ctr, Boston, MA USA. Vet Affairs Cooperat Studies Program Coordinating, Hines, IL USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. RP Neumayer, L (reprint author), Univ Utah, Surg Serv, 500 Foothill Dr, Salt Lake City, UT 84148 USA. NR 22 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAY PY 2005 VL 200 IS 5 BP 677 EP 683 DI 10.1016/j.jamcollsurg.2004.11.018 PG 7 WC Surgery SC Surgery GA 921PC UT WOS:000228775800005 PM 15848357 ER PT J AU Friedlander, AH Garrett, NR Chin, EE Baker, JD AF Friedlander, AH Garrett, NR Chin, EE Baker, JD TI Ultrasonographic confirmation of cartoid artery athermoas diagnosed via panoramic radiography SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE atherosclerosis; panoramic radiography; Doppler ultrasonography ID COMMON CAROTID ATHEROSCLEROSIS; ENDARTERECTOMY TRIAL; DUPLEX CRITERIA; STENOSIS; RISK; DISEASE; CALCIFICATION; ASSOCIATION; ULTRASOUND; STROKE AB Background. Studies have shown that panoramic radiographs can capture images of calcified atheromas in the internal carotid artery (ICA) in some neurologically asymptomatic patients receiving routine dental care. However, the prevalence of these hemodynamically significant lesions-that is, those causing greater than 50 percent vessel lumen occlusion with the consequent heightened risk of stroke-has been evaluated rarely. The purpose of this study was to use Doppler ultrasonography (DUS) to determine the prevalence of large occlusive lesions detected initially via panoramic radiography. Aggressive medical and surgical interventions directed toward these large lesions have been shown to moderate the risk of stroke. Study Design. The authors analyzed the panoramic radiographs of 1,548 consecutively treated, neurologically asymptomatic dental patients who were 50 years or older. Those with presumptive atheromas underwent DUS for confirmation of the diagnosis and for determination of the degree of stenosis. Results. The radiographs of 65 patients (4.2 percent) showed at least one ICA atheroma. Thirty-eight patients had bilateral opacities and 27 had unilateral opacities. DUS evaluation of the 103 sides of the neck with a radiographically identified atheroma revealed that none of the ICAs were normal, 81 (79 percent) had less than 50 percent stenosis, 18 (17 percent) had 50 to 69 percent stenosis and four (4 percent) had 70 percent or greater stenosis. Four of the ICAs on the 27 sides without calcifications were deemed normal and 23 had less than 50 percent stenosis. Conclusions. These results demonstrate that a subset of patients (15 [23 percent] of 65) with an occult atheroma discovered on panoramic radiography had significant (>= 50 percent) levels of ICA stenosis. Clinical Implications. Dentists should refer all patients with radiographically identified atheromas to a physician for confirmation of the diagnosis and a determination of the magnitude of,disease, because antiatherogenic interventions have been shown to prevent a stroke. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov NR 23 TC 31 Z9 34 U1 0 U2 4 PU AMER DENTAL ASSN 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 MAY PY 2005 VL 136 IS 5 BP 635 EP 640 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 928AI UT WOS:000229243100021 PM 15966651 ER PT J AU Chang, YC Singer, DE Wu, YA Keller, RB Atlas, SJ AF Chang, YC Singer, DE Wu, YA Keller, RB Atlas, SJ TI The effect of surgical and nonsurgical treatment on longitudinal outcomes of lumbar spinal stenosis over 10 years SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE lumbar spinal stenosis; prospective cohort study; outcomes; lumbar disc surgery; natural history ID TERM-FOLLOW-UP; DECOMPRESSIVE LAMINECTOMY; SURGERY; MANAGEMENT; 10-YEAR; TRENDS; IMPACT AB OBJECTIVES: To assess the relative effect of initial surgical and nonsurgical treatment on longitudinal outcomes of patients with lumbar spinal stenosis over a 10-year follow-up period. DESIGN: A prospective observational cohort study. SETTING: Enrollment from community-based specialist practices throughout Maine. PARTICIPANTS: One hundred forty-four patients with lumbar spinal stenosis who had at least one follow-up: 77 initially treated surgically and 67 initially treated nonsurgically. INTERVENTION: Initial surgical or nonsurgical treatment. MEASUREMENTS: Clinical data were obtained at baseline and outcomes followed at regular intervals over 10 years with mailed questionnaires including patient-reported symptoms of back pain, leg symptoms, back-specific functional status, and satisfaction. Longitudinal data were analyzed using general linear mixed models. In addition to treatment (initial surgical or nonsurgical care), time period, and the interaction between treatment and time, the models included baseline score, patient age and sex, and a time-varying general health status score. The effects of these covariates in explaining differences between treatment groups were also examined. The effect of subsequent surgical procedures was assessed using different analysis strategies. RESULTS: The 10-year rate of subsequent surgical procedures was 23% and 38% for patients initially treated surgically and nonsurgically, respectively, and the overall 10-year survival rate was 69%. Patients undergoing initial surgical treatment had worse baseline symptoms and functional status than those initially treated nonsurgically. For all outcomes and at each time point, surgically treated patients reported greater improvement in symptoms and functional status and higher satisfaction scores, indicative of better outcomes, than nonsurgically treated patients. However, the relative magnitude of the benefit diminished over time such that the relative differences for low back pain and satisfaction were no longer significant over long-term follow-up (both P=.08 for treatment effect between 5 and 10 years after controlling for covariates). Regardless of initial treatment received, patients undergoing subsequent surgical procedures reported less improvement in outcomes over time than patients who did not undergo subsequent procedures, but the relative differences between treatment groups were similar in analyses that controlled for outcomes after subsequent procedures. CONCLUSION: After controlling for covariates, patients initially treated surgically demonstrated better outcomes on all measures than those initially treated nonsurgically. Although outcomes of initial surgical treatment remained superior over time, the relative benefit of surgery diminished in later years, especially for low back pain and satisfaction. Patients undergoing subsequent surgery had worse outcomes regardless of initial treatment received, but excluding them did not change overall treatment group comparisons. The analytical methods described may be helpful in the design and analysis of future studies comparing treatment outcomes for patients with lumbar spinal stenosis. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Clin Epidemiol Unit, Boston, MA 02114 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Ctr Evaluat Clin Sci, Hanover, NH 03756 USA. RP Chang, YC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM ychang@partners.org FU AHRQ HHS [HS-09804, HS-08194, HS-06344]; NIA NIH HHS [P60 AG08812] NR 37 TC 30 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2005 VL 53 IS 5 BP 785 EP 792 DI 10.1111/j.1532-5415.2005.53254.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921GB UT WOS:000228751100006 PM 15877553 ER PT J AU Rickerson, E Harrold, J Kapo, J Carroll, JT Casarett, D AF Rickerson, E Harrold, J Kapo, J Carroll, JT Casarett, D TI Timing of hospice referral and families' perceptions of services: Are earlier hospice referrals better? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospice; home care; caregiver burden ID ILL HOSPITALIZED ADULTS; OF-LIFE CARE; PALLIATIVE CARE; END; SATISFACTION; RELIABILITY; CANCER; SCALE; NEEDS AB OBJECTIVES: To determine whether families of patients who enroll in hospice near the end of life believe that they receive less benefit from hospice services than families of patients who enroll earlier. DESIGN: Semistructured interviews at the time of hospice enrollment and 1 month after the patient's death. SETTING: This study was conducted at the Hospice of Lancaster County, Lancaster, PA, over a 12-month period spanning 2003-2004. PARTICIPANTS: First-time hospice admissions. MEASUREMENTS: Interviews assessed the anticipated helpfulness of six hospice services (enrollment interviews) and the actual helpfulness of the same services (follow-up interviews). RESULTS: Length of stay in hospice was associated with families' reports of the number of services provided (Spearman rho=0.34, P <.001), and with the mean helpfulness ratings for the services that were provided (Spearman rho=0.34, P <.001), although even with short lengths of stay, most families reported that they received the services that they anticipated and that those services were helpful. CONCLUSION: These results indicate that families feel they receive greater benefits from longer lengths of stay in hospice. Future efforts to define an "optimal" length of stay in hospice should consider patients' and families' perceptions of the benefits that hospice offers. C1 Univ Penn, Div Geriatr Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Hospice Lancaster Cty, Lancaster, PA USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Casarett, D (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 21 TC 62 Z9 62 U1 4 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2005 VL 53 IS 5 BP 819 EP 823 DI 10.1111/j.1532-5415.2005.53259.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921GB UT WOS:000228751100010 PM 15877557 ER PT J AU Willrich, A Angirasa, AK Sage, RA AF Willrich, A Angirasa, AK Sage, RA TI Percutaneous tendo Achillis lengthening to promote healing of diabetic plantar foot ulceration SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID EQUINUS DEFORMITY; PRESSURE; ANKLE; MELLITUS AB The etiology of ulcerations related to increased plantar pressure in patients with diabetes mellitus is complex but frequently includes a component of gastrocnemius soleus equinus. One viable treatment option is percutaneous tendo Achillis lengthening as a means of increasing dorsiflexory range of motion and decreasing forefoot shear forces. This article presents three case reports illustrating the importance of reducing plantar pressure as a crucial component of treatment of diabetic forefoot ulcerations. C1 Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, Maywood, IL 60152 USA. Loyola Univ, Med Ctr, Podiatry Sect, Maywood, IL 60152 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Sage, RA (reprint author), Loyola Univ, Med Ctr, Dept Orthopaed Surg & Rehabil, 2160 S 1st Ave,Bldg 105,Ste 1700, Maywood, IL 60152 USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAY-JUN PY 2005 VL 95 IS 3 BP 281 EP 284 PG 4 WC Orthopedics SC Orthopedics GA 928CT UT WOS:000229249400011 PM 15901817 ER PT J AU Perkins, BA Nelson, RG Ostrander, BEP Blouch, KL Krolewski, AS Myers, BD Warram, JH AF Perkins, BA Nelson, RG Ostrander, BEP Blouch, KL Krolewski, AS Myers, BD Warram, JH TI Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: Results of a 4-year follow-up study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; KIDNEY-FUNCTION; PIMA-INDIANS; CREATININE; MARKER; CLEARANCE; PERFORMANCE; PROGRESSION; MELLITUS; HUMANS AB Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR > 20 ml/min per 1.73 m 2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual's trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual's trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Stanford Univ, Sch Med, Div Nephrol, Stanford, CA USA. RP Warram, JH (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM james.warram@joslin.harvard.edu RI Nelson, Robert/B-1470-2012 FU Intramural NIH HHS [Z01 DK069063-10]; NIDDK NIH HHS [DK41526, DK58549, DK67638, R01 DK041526, R01 DK058549, R01 DK067638] NR 34 TC 224 Z9 237 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2005 VL 16 IS 5 BP 1404 EP 1412 DI 10.1681/ASN.2004100854 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 920UN UT WOS:000228715700028 PM 15788478 ER PT J AU Horner, MD Ferguson, PL Selassie, AW Labbate, LA Kniele, K Corrigan, JD AF Horner, MD Ferguson, PL Selassie, AW Labbate, LA Kniele, K Corrigan, JD TI Patterns of alcohol use 1 year after traumatic brain injury: A population-based, epidemiological study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE alcohol abuse; alcohol drinking; alcoholism; epidemiological studies; follow-up studies; substance abuse; traumatic brain injury ID NATIONAL PROBABILITY SAMPLE; AMERICAN DRINKING PRACTICES; SPINAL-CORD-INJURY; SUBSTANCE-ABUSE; PSYCHIATRIC-DISORDERS; HEAD-INJURY; AXIS-I; EXTENT AB This study delineated patterns of alcohol use 1 year after traumatic brain injury (TBI) in a large, population-based, epidemiological, nonclinical sample, and identified predictors of heavy alcohol use in these individuals. Participants were 1,606 adults identified by review of a South Carolina statewide hospital discharge data set, on the basis of satisfying the Centers for Disease Control case definition of TBI, and were interviewed by telephone 1 year after TBI-related discharge. Alcohol use in the month prior to interview was classified according to categories from the Quantity-Frequency-Variability Index; heavy drinking was defined as nearly daily use with &GE; 5 drinks at least occasionally, or at least three occasions with &GE; 5 drinks. A polychotomous logistic regression with 3 response levels (heavy, moderate, and abstinent/infrequent/light drinking) was used to identify predictors of heavy drinking. Heavy drinking in the month prior to interview was reported by 15.4% of participants, while 14.3% reported moderate drinking and 70.3% reported abstinence or light/infrequent drinking. Risk factors for heavy drinking included male gender, younger age, history of substance abuse prior to TBI, diagnosis of depression since TBI, fair/moderate mental health, and better physical functioning. There was no association between drinking patterns and TBI severity. C1 Ralph H Johnson Dept VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC USA. Ohio State Univ, Dept Phys Med & Rehabil, Columbus, OH USA. RP Horner, MD (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 109 Bee St, Charleston, SC 29401 USA. EM hornermd@musc.edu NR 38 TC 41 Z9 41 U1 2 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2005 VL 11 IS 3 BP 322 EP 330 DI 10.1017/S135561770505037X PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 924UL UT WOS:000229005900011 PM 15892908 ER PT J AU Gaissert, HA Grillo, HC Shadmehr, BM Wright, CD Gokhale, M Wain, JC Mathisen, DJ AF Gaissert, HA Grillo, HC Shadmehr, BM Wright, CD Gokhale, M Wain, JC Mathisen, DJ TI Laryngotracheoplastic resection for primary tumors of the proximal airway SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID THYROID-CARCINOMA; MANAGEMENT; RECONSTRUCTION; TRACHEAL; STENOSIS; ANASTOMOSIS; EXPERIENCE; CARTILAGE; LARYNGEAL; GRAFTS AB Background: Primary tumors of the airway with proximity to vocal cords and recurrent laryngeal nerves can be resected with sparing of the larynx. Long-term data on survival and local recurrence after laryngotracheal resection are scarce. Methods: We conducted a retrospective study of laryngotracheal resection and reconstruction for primary tumors of the airway since 1972. Results: Twenty-five patients aged 15 to 77 years presented with adenoid cystic carcinomas (n = 9), squamous cell carcinomas (n = 6), and other airway tumors (n = 10). Subglottic resection consisted of anterior cricoid in 5 patients; posterior cricoid mucosa in 9 patients, with resection of the posterior cricoid plate in 3 patients; lateral resection in 7 patients; and combined anterior and posterior elements in 4 patients. Vascularized trachea was tailored to reconstruct the defect. Seven patients without hoarseness required resection of the recurrent laryngeal nerve, and 4 other patients with hoarseness did not. There were no operative deaths. Two (8.0%) patients who had received prior high-dose cervical radiation had anastomotic separation, one requiring laryngectomy. One patient needed permanent tracheostomy, and temporary (< 2 months) airway tubes were used in 5 patients. Sixteen patients received postoperative radiation. Median follow-up was 101 months. Four (16%) patients died of disease. Overall survival at 5 and 10 years was 79% and 64%, respectively. No patient underwent laryngectomy for recurrence. Conclusion: Laryngotracheal resection and immediate reconstruction for subglottic tumors is achieved with good preservation of voice, low morbidity, and no compromise of long-term survival. C1 Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Policy Anal Inc, Brookline, MA USA. RP Gaissert, HA (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,Fruit St, Boston, MA 02114 USA. EM hgaissert@partners.org OI shadmehr, mohammad behgam/0000-0002-3303-6750 NR 15 TC 19 Z9 22 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2005 VL 129 IS 5 BP 1006 EP 1009 DI 10.1016/j.jtcvs.2004.07.043 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 923ZD UT WOS:000228947200008 PM 15867773 ER PT J AU D'Amico, AV Moul, J Carroll, PR Sun, L Lubeck, D Chen, MH AF D'Amico, AV Moul, J Carroll, PR Sun, L Lubeck, D Chen, MH TI Surrogate end point for prostate cancer specific mortality in patients with nonmetastatic hormone refractory prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostate-specific antigen; prostatic neoplasms; mortality; salvage therapy ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; ANTIGEN FAILURE; CLINICAL-TRIALS; GUIDELINES; DATABASE; CAPSURE; DISEASE; DEATH; TIME AB Purpose: We determined whether prostate specific antigen (PSA) velocity can serve as surrogate end point for prostate cancer specific mortality (PCSM) in patients with nonmetastatic, hormone refractory prostate cancer. Materials and Methods: The study cohort comprised 919 men treated from 1988 to 2002 at 1 of 44 institutions with surgery (560) or radiation therapy (359) for clinical stages T1c-4NxMo prostate cancer, followed by salvage hormonal therapy for PSA failure. All patients experienced PSA defined recurrence while on hormonal therapy. Prentice criteria require that the surrogate should be a prognostic factor and the treatment used did not alter time to PCSM following achievement of the surrogate end point. These criteria were tested using Cox regression. All statistical tests were 2-sided. Results: PSA velocity greater than 1.5 ng/ml yearly was statistically significantly associated with time to PCSM and all cause mortality following PSA defined recurrence while undergoing hormonal therapy (Cox p < 0.0001). While initial treatment was statistically associated with time to PCSM and all cause mortality (Cox p = 0.001 and 0.01), this association became insignificant when PSA velocity and potential confounding variables were included in the Cox model (p = 0.22 and 0.93, respectively). The adjusted HR for PCSM in patients who experienced a greater than 1.5 ng/ml increase in PSA within 1 year while on hormonal therapy was 239 (95% CI 10 to 5,549). Conclusions: These data provide evidence to support PSA velocity greater than 1.5 ng/ml yearly as a surrogate end point for PCSM in patients with nonmetastatic, hormone refractory prostate cancer. Enrolling these men onto clinical trials evaluating the impact of chemotherapy on time to bone metastases and PCSM is warranted. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg & Urol Serv, Washington, DC USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu NR 20 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 2005 VL 173 IS 5 BP 1572 EP 1576 DI 10.1097/01.ju.0000157569.59229.72 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300027 PM 15821488 ER PT J AU Febbo, PG Lowenberg, M Thorner, AR Brown, M Loda, M Golub, TR AF Febbo, PG Lowenberg, M Thorner, AR Brown, M Loda, M Golub, TR TI Androgen mediated regulation and functional implications of FKBP51 expression in prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; androgen receptor; gene expression; gene; FKBP51 ID IMMUNOPHILIN FKBP51; RECEPTOR GENE; OVEREXPRESSION; LOCALIZATION; CARCINOMA; PROTEIN; CELLS AB Purpose: Androgen ablation continues to be the most effective therapy for metastatic prostate cancer, although the biologically active androgen receptor (AR) target genes remain largely unknown. Because AR signaling continues in hormone refractory disease, effector AR target genes may have therapeutic import. Materials and Methods: We used oligonucleotide microarrays to identify genes with expression induced by androgen and associated with androgen independent growth. The androgen induced expression of FKBP51, a steroid receptor chaperone, was further investigated in LNCaP cells by Northern and Western analysis, and in primary prostate specimens using immunohistochemistry. We used stable clones over expressing FKBP51 to test the functional effects of FKBP51. Results: Many genes had expression that correlates with androgen stimulation in LNCaP cells but relatively few had reproducible, androgen mediated changes in expression across multiple prostate cancer cell lines. FYBP51 had androgen induced RNA and protein expression in LNCaP cells and decreased expression in normal prostate epithelial cells following castration. Further study demonstrated that FKBP51 induction was not a generalized response to cell proliferation, FKBP51 protein physically interacts with AR and LNCaP cells constitutively over expressing FKBP51 have increased ligand mediated AR activation of an exogenous AR reporter construct and endogenous prostate specific antigen. Conclusions: Taken together these results confirm FYBP51 as an androgen induced gene, demonstrate a physical interaction between FKBP51 and AR and suggest that FKBP51 over expression increases AR transcriptional activity in prostate cancer. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med 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, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Univ Amsterdam, Acad Med Ctr, Dept Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Lab Expt Internal Med, NL-1105 AZ Amsterdam, Netherlands. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Golub, TR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM Golub@broad.mit.edu RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [5U01-CA84995, IP50-CA090381] NR 20 TC 57 Z9 60 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 MAY PY 2005 VL 173 IS 5 BP 1772 EP 1777 DI 10.1097/01.ju.0000155845.44729.ba PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300069 PM 15821585 ER PT J AU LaMuraglia, GM Stoner, MC Brewster, DC Watkins, MT Juhola, KL Kwolek, C Dorer, DJ Cambria, RP AF LaMuraglia, GM Stoner, MC Brewster, DC Watkins, MT Juhola, KL Kwolek, C Dorer, DJ Cambria, RP TI Determinants of carotid endarterectomy anatomic durability: Effects of serum lipids and lipid-lowering drugs SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 03-06, 2004 CL Anaheim, CA SP Soc Vasc Surg ID ARTERY STENOSIS; CLINICAL RESTENOSIS; RECURRENT; MANAGEMENT; DISEASE; TRIAL; ANGIOPLASTY; OCCLUSION; STATINS; EVENTS AB Objectives. Carotid endarterectomy (CEA) remains the gold standard for treatment of carotid stenosis. With inevitable comparisons of catheter-based therapy to all aspects of CEA, this study of a large contemporary series was undertaken to evaluate the determinants of anatomic durability of CEA. Methods: During the interval (1989 through 1999), 2,127 primary, isolated CEAs with selective patching (50.2%) were performed in 1,853 patients (61.8% male, 36.1% symptomatic). End points included patient longevity and perioperative morbidity as well as evidence of CEA anatomic durability as defined by duplex evaluation: CEA restenosis (moderate, > 50%, or greater recurrent stenosis), which included CEA anatomic failure (severe, > 70%, restenosis/carotid occlusion). The incidence of CEA recurrent stenosis was temporally assessed early (< 2 years) and late (> 2 years) after operation. Clinical and surgical variables potentially associated with the study endpoints were analyzed by univariate and multivariate methods. Results. The perioperative stroke and death rate was 1.4% and the 2-year and 10-year survival was 88.1% and 44.9%, respectively. Anatomic failure after CEA developed in 3.9% at 2 years and in 8.5% at 5 years; only 3.2% of CEA patients underwent reoperation during a mean follow-up of 73.4 months. Early (< 2 years) analysis revealed 12.2% restenosis, whereas late (> 2 years) results identified 9.8% progression of carotid stenosis and a 5.8% rate of anatomic failure. Multivariate analysis determined elevated creatinine (odds ratio [OR], 1.719, P <.001) and female gender (OF, 1.564; P <.02) correlated with early restenosis. Surgical patch closure and lipid-lowering drugs were protective for both early restenosis, with ORs of 0.543 (P <.0.001) and 0.601 (P <.007) and early anatomic failure ORs of 0.469 (P <.02) and 0.517 (P <.03), respectively. Although only elevated serum cholesterol (OR, 1.009; P <.03) correlated with late anatomic failure, only lipid-lowering drugs were protective for both late freedom from progression of disease (OF, 0.202; P <.0002) or late CEA anatomic failure (OR, 0.128; P <.0003). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Surg Serv,Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr,Med Practices Evaluat Unit, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Surg Serv,Div Vasc & Endovasc Surg, 15 Parkman St,WAC 464, Boston, MA 02114 USA. NR 36 TC 59 Z9 59 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2005 VL 41 IS 5 BP 762 EP 768 DI 10.1016/j.jvs.2005.01.035 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 925ZM UT WOS:000229092300005 PM 15886657 ER PT J AU Stange, A Mannigel, I Peters, K Heinkelein, M Stanke, N Cartellieri, M Gottlinger, H Rethwilm, A Zentgraf, H Lindemann, D AF Stange, A Mannigel, I Peters, K Heinkelein, M Stanke, N Cartellieri, M Gottlinger, H Rethwilm, A Zentgraf, H Lindemann, D TI Characterization of prototype foamy virus Gag late assembly domain motifs and their role in particle egress and infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; ENVELOPE GLYCOPROTEIN; VIRAL INFECTIVITY; VIRION RELEASE; MATRIX PROTEIN; AMINO-ACID; PEPTIDE; TSG101; ENV; MORPHOGENESIS AB Foamy viruses (FV) are unusual among retroviruses since they require both Gag and Env structural proteins for particle egress. Recently significant progress has been made towards the mechanistic understanding of the viral release process, in particular that of retroviruses, and the viral domains and cellular pathways involved. However little is currently known about domains of FV structural proteins and cellular proteins engaged in this process. By mutational analysis of sequence motifs in prototype FV (PFV) Gag, bearing homology to known late assembly (L) domains, a PSAP motif with L domain function that was functionally interchangeable by heterologous L domains was identified. In contrast the inactivation of a PPPI motif had no significant influence on PFV particle release, although mutant viral particles displayed reduced infectivity. Similarly mutation of an evolutionary conserved YXXL motif revealed no classical L-domain function but resulted in release of noninfectious viruslike particles. Biochemical and electron microscopy analysis demonstrated that these mutant particles incorporated all viral structural proteins but contained aberrantly capsid structures, suggesting a role in capsid assembly for this PFV Gag sequence motif. In line with the mutational analysis, overexpression of dominant negative (DN) mutants and wild-type TSG101 but not the DN mutant of AIP-1/ALIX reduced PFV particle release and infectivity. Furthermore, DN mutants of Vps4A, Vps4B, and CHMP3 inhibited PFV egress and infectivity. Taken together these results demonstrate that PFV, like other viruses, requires components of the vacuolar protein sorting (VPS) machinery for egress and enters the VPS pathway through interaction with TSG101. C1 Tech Univ Dresden, Inst Virol, Med Fak Carl Gustav Carus, D-01307 Dresden, Germany. Univ Wurzburg, Inst Virol & Immunobiol, Wurzburg, Germany. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Deutsch Krebsforschungszentrum, Angew Tumorvirol, D-6900 Heidelberg, Germany. RP Lindemann, D (reprint author), Tech Univ Dresden, Inst Virol, Med Fak Carl Gustav Carus, Fetscherstasse 74, D-01307 Dresden, Germany. EM dirk.lindemann@mailbox.tu-dresden.de RI Lindemann, Dirk/H-5857-2013; Cartellieri, Marc/M-3281-2013 OI Lindemann, Dirk/0000-0002-0320-4223; Cartellieri, Marc/0000-0002-4672-3963 FU NIAID NIH HHS [R37 AI029873] NR 49 TC 40 Z9 42 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 9 BP 5466 EP 5476 DI 10.1128/JVI.79.9.5466-5476.2005 PG 11 WC Virology SC Virology GA 917CH UT WOS:000228433100024 PM 15827161 ER PT J AU Ren, XP Sodroski, J Yang, XZ AF Ren, XP Sodroski, J Yang, XZ TI An unrelated monoclonal antibody neutralizes human immunodeficiency virus type 1 by binding to an artificial epitope engineered in a functionally neutral region of the viral envelope glycoproteins SO JOURNAL OF VIROLOGY LA English DT Article ID HIV TYPE-1; VARIABLE REGIONS; RECEPTOR-BINDING; NONNEUTRALIZING ANTIBODIES; CONFORMATIONAL-CHANGES; GP120 GLYCOPROTEIN; SUBTYPE-C; IDENTIFICATION; CORECEPTOR; INFECTION AB Neutralizing antibodies often recognize regions of viral envelope glycoproteins that play a role in receptor binding or other aspects of virus entry. To address whether this is a necessary feature of a neutralizing antibody, we identified the V4 region of the gp120 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) as a sequence that is tolerant of drastic change and thus appears to play a negligible role in envelope glycoprotein function. An artificial epitope tag was inserted into the V4 region without a significant effect on virus entry or neutralization by antibodies that recognize HIV-1 envelope glycoprotein sequences. An antibody directed against the artificial epitope tag was able to neutralize the modified, but not the wild-type, HIV-1. Thus, the specific target of a neutralizing antibody need not contribute functionally to the process of virus entry. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Yang, XZ (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM xinzhen_yang@dfci.harvard.edu FU NIAID NIH HHS [AI39420, AI24755, AI31783, AI42848, P30 AI042848, R01 AI031783, R01 AI039420, R37 AI024755] NR 76 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 9 BP 5616 EP 5624 DI 10.1128/JVI.79.9.5616-5624.2005 PG 9 WC Virology SC Virology GA 917CH UT WOS:000228433100039 PM 15827176 ER PT J AU Sui, JH Li, WH Roberts, A Matthews, LJ Murakami, A Vogel, L Wong, SK Subbarao, K Farzan, M Marasco, WA AF Sui, JH Li, WH Roberts, A Matthews, LJ Murakami, A Vogel, L Wong, SK Subbarao, K Farzan, M Marasco, WA TI Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants SO JOURNAL OF VIROLOGY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME-2; SARS-ASSOCIATED CORONAVIRUS; PROTEIN; MICE; INFECTION; VIRUS; CHINA; NEUTRALIZATION; TRANSMISSION; REPLICATION AB In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Microbiol & Mol Genet, Brigham & Womens Hosp,Partners AIDS Res Ctr, Boston, MA 02115 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dept Med, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu OI Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [AI061318, AI053822, AI28691, AI28785, AI48436, P30 AI028691, R01 AI048436, R21 AI053822, U01 AI061318] NR 35 TC 78 Z9 87 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 5900 EP 5906 DI 10.1128/JVI.79.10.5900-5906.2005 PG 7 WC Virology SC Virology GA 922CV UT WOS:000228814400002 PM 15857975 ER PT J AU Xiang, SH Farzan, M Si, ZH Madani, N Wang, L Rosenberg, E Robinson, J Sodroski, J AF Xiang, SH Farzan, M Si, ZH Madani, N Wang, L Rosenberg, E Robinson, J Sodroski, J TI Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a neutralizing monoclonal antibody SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; V3 LOOP; HIV-1 GP120; TYROSINE SULFATION; RECEPTOR-BINDING; CELL TROPISM; N-TERMINUS; CCR5; ENTRY; IDENTIFICATION AB Interaction of the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein with the primary receptor, CD4, promotes binding to a chemokine receptor, either CCR5 or CXCR4. The chemokine receptor-binding site on gp120 elicits CD4-induced (CD4i) antibodies in some HIV-1-infected individuals. Like CCR5 itself, the CD4i antibody 412d exhibits a preference for CCR5-using HIV-1 strains and utilizes sulfated tyrosines to achieve binding to gp120. Here, we show that 412d binding requires the gp120 beta 19 strand and the base of the V3 loop, elements that are important for the binding of the CCR5 N terminus. Two gp120 residues in the V3 loop base determined 412d preference for CCR5-using HIV-1 strains. A chimeric molecule in which the 412d heavy-chain third complementarity-determining loop sequence replaces the CCR5 N terminus functioned as an efficient second receptor, selectively supporting the entry of CCR5-using HIV-1 strains. Sulfation of N-terminal tyrosines contributed to the function of this chimeric receptor. These results emphasize the close mimicry of the CCR5 N terminus by the gp120-interactive region of a naturally elicited CD4i antibody. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Massachusetts Gen Hosp,Partners AIDS Res Ctr, Boston, MA 02115 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NIAID NIH HHS [R01 AI024030, AI42848, AI40895, AI39420, AI31783, AI24030, AI24755, P30 AI042848, R01 AI031783, R01 AI039420, R01 AI040895, R37 AI024755] NR 49 TC 27 Z9 29 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6068 EP 6077 DI 10.1128/JVI.79.10.6068-6077.2005 PG 10 WC Virology SC Virology GA 922CV UT WOS:000228814400019 PM 15857992 ER PT J AU Song, BW Gold, B O'hUigin, C Javanbakht, H Li, X Stremlau, M Winkler, C Dean, M Sodroski, J AF Song, BW Gold, B O'hUigin, C Javanbakht, H Li, X Stremlau, M Winkler, C Dean, M Sodroski, J TI The B30.2(SPRY) domain of the retroviral restriction factor TRIM5 alpha exhibits line age-specific length and sequence variation in primates SO JOURNAL OF VIROLOGY LA English DT Article ID PROMYELOCYTIC LEUKEMIA PROTEIN; IMMUNODEFICIENCY-VIRUS TYPE-1; BABOON ENDOGENOUS VIRUS; OLD-WORLD MONKEYS; CYCLOPHILIN-A; SIMIAN CELLS; POSTENTRY RESTRICTION; REVERSE TRANSCRIPTION; B30.2-LIKE DOMAIN; MOTIF PROTEIN AB Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5 alpha, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5a has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5 alpha was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5 alpha B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5a B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5 alpha in innate immunity against retroviruses. C1 Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dept Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dept Pathol,Dana Farber Canc Inst, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NHLBI NIH HHS [HL54785, P50 HL054785]; NIAID NIH HHS [P30 AI028691, P30 AI28691] NR 65 TC 154 Z9 172 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6111 EP 6121 DI 10.1128/JVI.79.10.6111-6121.2005 PG 11 WC Virology SC Virology GA 922CV UT WOS:000228814400023 PM 15857996 ER PT J AU Holm, GH Gabuzda, D AF Holm, GH Gabuzda, D TI Distinct mechanisms of CD4(+) and CD8(+) T-cell activation and bystander apoptosis induced by human immunodeficiency virus type 1 virions SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-INFECTED INDIVIDUALS; CHEMOKINE RECEPTOR CXCR4; MACROPHAGE-TROPIC HIV; HUMAN LYMPHOID-TISSUE; ENVELOPE GLYCOPROTEINS; FAS LIGAND; HOST-CELL; COSTIMULATORY MOLECULES; MEDIATED APOPTOSIS; VIRAL INFECTIVITY AB Apoptosis of uninfected bystander T cells contributes to T-cell depletion during human immunodeficiency virus type 1 (HIV-1) infection. HIV-1 envelope/receptor interactions and immune activation have been implicated as contributors to bystander apoptosis. To better understand the relationship between T-cell activation and bystander apoptosis during HIV-1 pathogenesis, we investigated the effects of the highly cytopathic CXCR4-tropic HIV-1 variant ELI6 on primary CD4(+) and CD8(+) T cells. Infection of primary T-cell cultures with EL16 induced CD4(+) T-cell depletion by direct cell lysis and bystander apoptosis. Exposure of primary CD4(+) and CD8(+) T cells to nonreplicating ELI6 virions induced bystander apoptosis through a Fas-independent mechanism. Bystander apoptosis of CD4(+) T cells required direct contact with virions and Env/CXCR4 binding. In contrast, the apoptosis of CD8(+) T cells was triggered by a soluble factor(s) secreted by CD4(+) T cells. HIV-1 virions activated CD4(+) and CD8(+) T cells to express CD25 and HLA-DR and preferentially induced apoptosis in CD25(+)HLA-DR+ T cells in a CXCR4-dependent manner. Maximal levels of binding, activation, and apoptosis were induced by virions that incorporated MHC class II and B7-2 into the viral membrane. These results suggest that nonreplicating HIV-1 virions contribute to chronic immune activation and T-cell depletion during HIV-1 pathogenesis by activating CD4(+) and CD8(+) T cells, which then proceed to die via apoptosis. This mechanism may represent a viral immune evasion strategy to increase viral replication by activating target cells while killing immune effector cells that are not productively infected. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Holm, Geoffrey/C-3188-2009 FU NIMHD NIH HHS [L60 MD003100]; NINDS NIH HHS [NS35734, R01 NS035734] NR 87 TC 61 Z9 64 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6299 EP 6311 DI 10.1128/JVI.79.10.6299-6311.2005 PG 13 WC Virology SC Virology GA 922CV UT WOS:000228814400041 PM 15858014 ER PT J AU Hazzard, WR AF Hazzard, WR TI Preventive gerontology: Edging ever closer to the "barrier to immortality" SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, S-GEC182,1660 S Columbian Way, Seattle, WA 98108 USA. EM william.hazzard@med.va.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2005 VL 60 IS 5 BP 594 EP 595 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 937JU UT WOS:000229921200008 PM 15972607 ER PT J AU Jones, CA Krolewski, AS Rogus, J Xue, JL Collins, A Warram, JH AF Jones, CA Krolewski, AS Rogus, J Xue, JL Collins, A Warram, JH TI Epidemic of end-stage renal disease in people with diabetes in the United States population: Do we know the cause? SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes mellitus; end-stage renal disease (ESRD); secular trends; ACE inhibitors; antihypertensive treatments; USRDS ID CONVERTING ENZYME-INHIBITION; TYPE-2 DIABETES/; BLOOD-PRESSURE; NEPHROPATHY; TRENDS; MICROALBUMINURIA; PREVALENCE; MORTALITY; MELLITUS; OUTCOMES AB Background. The number of individuals initiating renal replacement therapy in the United States population grew exponentially over the past two decades. Cases of end-stage renal diseae (ESRD) attributed to diabetes accounted for most of this increase. In this report we examined factors that may account for the increase to determine whether it truly represents an epidemic of ESRD due to diabetes. Methods. We reviewed time trends in data of the United States Renal Data system, the Diabetes Surveillance Program of the Centers for Disease Control and Prevention, and diabetes literature. Results. Recent growth of the number of individuals with diabetes accounted for less than 10% of the increase in the number of diabetes-related ESRD. Instead, most of it was due to a threefold increase in risk of ESRD in people with diabetes and, therefore, qualifies as an epidemic. Curiously, this epidemic occurred despite widening implementation of effective renoprotective therapies. Individuals with type 2 diabetes, regardless of gender, age, or race, experienced the greatest increase in risk. There is no evidence that diabetic patients have been surviving longer, so the increased risk was not attributable to the high risk associated with long duration diabetes. Conclusion. We hypothesize that an epidemic of ESRD has occurred in people with diabetes in the United States population over the last two decades. The nature of the factor responsible for the epidemic and the reasons it affects patients with type 2 diabetes particularly are unknown. Research efforts to identify the putative factor deserve high priority, as does a commitment of resources to provide care for the burgeoning number of patients with ESRD and type 2 diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Res Div, Boston, MA 02215 USA. Minnesota Med Res Fdn, Minneapolis, MN USA. RP Warram, JH (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM james.warram@joslin.harvard.edu FU NIDDK NIH HHS [DK041526, DK058549, DK067638] NR 44 TC 122 Z9 128 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2005 VL 67 IS 5 BP 1684 EP 1691 DI 10.1111/j.1523-1755.2005.00265.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 918XM UT WOS:000228582900011 PM 15840014 ER PT J AU Atkins, M AF Atkins, M TI Management of advanced renal cancer SO KIDNEY INTERNATIONAL LA English DT Article DE cytokine-based immunotherapy; von Hippel-Lindau disease; cytoreductive nephrectomy; interleukin-2; carbonic anhydrase IX; bevacizumab; erlotinib; sorafenib ID DOSE RECOMBINANT INTERLEUKIN-2; HIPPEL-LINDAU GENE; HOGG-DUBE-SYNDROME; CELL CARCINOMA; INTERFERON-ALPHA; RANDOMIZED-TRIAL; SUBCUTANEOUS INTERLEUKIN-2; CLINICAL-TRIALS; FOLLOW-UP; PHASE-II C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Atkins, M (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM matkins@bidmc.harvard.edu NR 59 TC 6 Z9 7 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2005 VL 67 IS 5 BP 2069 EP 2082 DI 10.1111/j.1523-1755.2005.00309.x PG 14 WC Urology & Nephrology SC Urology & Nephrology GA 918XM UT WOS:000228582900062 PM 15840065 ER PT J AU Jyung, RW Wacharasindhu, C AF Jyung, RW Wacharasindhu, C TI Quantification of angiogenesis in otosclerosis SO LARYNGOSCOPE LA English DT Article DE otoselerosis; angiogenesis; quantification; image analysis; microvessel density; temporal bone; endochondral ossification; globuli interossei ID ENDOCHONDRAL BONE-FORMATION; OTIC CAPSULE; EXPRESSION; HISTOPATHOLOGY; GROWTH AB Objectives/Hypothesis: The determinants of clinical versus histologic otosclerosis are unknown, but angiogenesis is associated with active disease. We hypothesized that quantification of angiogenesis in otosclerotic human temporal bones could reveal significant differences between clinical and histologic cases. Study Design: We reviewed all otosclerosis specimens meeting criteria from the temporal bone collection of the Massachusetts Eye and Ear Infirmary and 10 normal controls. Methods. Digital images were taken at predilection sites, followed by computer-assisted analysis. Canalicular area (CA), the aggregate of vascular spaces within bone, microvessel density (MVD), area, and depth were the main measures. Evidence of a direct connection between local vessels and the vasculature of the otosclerotic focus was also recorded for each specimen. Results. The average area (nuns) and depth (number of sections containing otosclerosis) of clinical lesions was significantly greater than histologic lesions. Total microvessel counts were significantly greater in clinical versus histologic lesions, and both clinical and histologic lesions contained significantly greater numbers of microvessels than the normal otic capsule. CA was also significantly higher in clinical lesions. MVD was slightly but not significantly higher in clinical lesions. Importantly, a direct connection between named vessels and the otosclerotic vasculature was significantly more frequent in clinical lesions. Conclusions. Computer-assisted quantification revealed significantly greater measures of angiogenesis in clinical versus histologic otosclerosis. Direct connection to adjacent vessels may support angiogenesis in this disease. Sustained angiogenesis may be an important determinant of clinical otosclerosis. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Jyung, RW (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, 185 S Orange Ave, Newark, NJ 07103 USA. EM jyungrw@umdnj.edu NR 20 TC 3 Z9 3 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 MAY PY 2005 VL 115 IS 5 BP 811 EP 816 DI 10.1097/01.MLG.0000156476.07876.6B PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 925IW UT WOS:000229047800012 PM 15867645 ER PT J AU Atlas, SJ Metson, RB Singer, DE Wu, YA Gliklich, RE AF Atlas, SJ Metson, RB Singer, DE Wu, YA Gliklich, RE TI Validity of a new health-related quality of life instrument for patients with chronic sinusitis SO LARYNGOSCOPE LA English DT Article DE quality of life; sinusitis; sinus surgery; instrument ID ADULTS AB Objective/Hypothesis: To assess the validity and responsiveness of a new health-related quality of life (HRQL) instrument for patients with chronic sinusitis. Study Design: Prospective case series. Methods. Patients with chronic sinusitis undergoing endoscopic sinus surgery were assessed in two otolaryngology practices affiliated with an academic hospital. Patient-reported HRQL was assessed using a new instrument (includes symptom frequency, bothersomeness, and impact scales), the Chronic Sinusitis Survey (CSS), and the generic SF-12 at baseline and 3 months postsurgery. The psychometric properties of the new instrument were assessed including reliability, validity, responsiveness, and interpretability. Results. Among 50 enrolled patients, 49 underwent surgery and 39 (80%) completed 3-month follow-up. Internal consistency was high for the symptom impact scale. The symptom frequency and, especially, bothersomeness scales had lower internal consistency and were comparable with the CSS. Correlation analyses support the construct validity of the new measure compared with the CSS and SF-12. The responsiveness of the new instrument was excellent and similar to or better than the CSS. The mean score change was linearly related to the patient's global self-assessment, although the CSS symptom and total score better discriminated patients with major or moderate degrees of improvement. Conclusions: This study demonstrates the validity and responsiveness of a new rhinosinusitis-specific HRQL instrument, the Rhinosinusitis Quality of Life survey, in patients with chronic sinusitis. The instrument's symptom frequency, bothersomeness, and impact scales compare favorably with a previously validated disease-specific and a generic HRQL measure. If validated in other patient populations, this disease-specific instrument may be useful in assessing severity and outcomes of treatment for sinusitis. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Epidemiol Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. RP Atlas, SJ (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 15 TC 31 Z9 36 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 MAY PY 2005 VL 115 IS 5 BP 846 EP 854 DI 10.1097/01.MLG.0000157693.92975.02 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 925IW UT WOS:000229047800019 PM 15867652 ER PT J AU Lee, DJ Driver, M AF Lee, DJ Driver, M TI Cochlear implant fixation using titanium screws SO LARYNGOSCOPE LA English DT Article C1 Univ Massachusetts, Div Otol & Neurotol, Mem Med Ctr, Dept Otolaryngol Head & Neck Surg, Worcester, MA 01655 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA 02118 USA. RP Lee, DJ (reprint author), Univ Massachusetts, Div Otol & Neurotol, Mem Med Ctr, Dept Otolaryngol Head & Neck Surg, 55 Lake Ave N, Worcester, MA 01655 USA. EM otologist@danieljlee.com NR 5 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 2005 VL 115 IS 5 BP 910 EP 911 DI 10.1097/01.MLG.0000154537.05252.A0 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 925IW UT WOS:000229047800031 PM 15867664 ER PT J AU Nogi, T Yuan, YE Sorocco, D Perez-Tomas, R Levin, M AF Nogi, T Yuan, YE Sorocco, D Perez-Tomas, R Levin, M TI Eye regeneration assay reveals an invariant functional left-right asymmetry in the early bilaterian, Dugesia japonica SO LATERALITY LA English DT Article ID PLANARIAN SCHMIDTEA-MEDITERRANEA; LEISHMANIA-DONOVANI; ATPASE; LATERALIZATION; EVOLUTION; MEMBRANE; MICE; PUMP; MALFORMATIONS; ESTABLISHMENT AB Consistent visceral asymmetry in vertebrates raises fascinating questions about the developmental mechanisms and evolutionary origin of fixed chirality of the left-right axis. One persistent controversy is whether consistently biased asymmetry is a later innovation imposed on a bilaterally symmetrical primitive body-plan, or whether asymmetry is a fundamental property predating the bilateria. The morphology of planaria suggests proximity to the origin of the bilateral body-plan, and they are commonly thought to be left-right symmetrical, as no consistent anatomical asymmetries have been described despite over a century of study of regeneration. Here, we show that D. japonica possess a consistent functional asymmetry in eye patterning defects caused by inhibition of H+/K+-ATPase activity (an ion flux mechanism recently shown to be an important early step in the asymmetry of several vertebrate embryos). Moreover, an endogenous transcript of the non-gastric H+/K+-ATPase subunit a is expressed in the head blastema shortly after amputation. Taken together, these data suggest that (1) left-right asymmetry is at least as old as planaria, (2) subtle functional asymmetries should be sought in other more primitive model systems that are believed to be symmetrical, and (3) symmetrical paired structures may in fact contain information about their position on the L or R side. C1 Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Univ Barcelona, E-08007 Barcelona, Spain. RP Levin, M (reprint author), Forsyth Inst, Cytokine Biol Dept, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org RI Nogi, Taisaku/C-7657-2009 FU NCI NIH HHS [CO6RR11244]; NIGMS NIH HHS [R21-GM-068483-A1] NR 62 TC 19 Z9 20 U1 0 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1357-650X J9 LATERALITY JI Laterality PD MAY PY 2005 VL 10 IS 3 BP 193 EP 205 DI 10.1080/1357650054200001440 PG 13 WC Psychology, Multidisciplinary; Psychology, Experimental SC Psychology GA 930DG UT WOS:000229395400001 PM 16028337 ER PT J AU Baron, F Maris, MB Storer, BE Sandmaier, BM Panse, JP Chauncey, TR Sorror, M Little, MT Maloney, DG Storb, R Heimfeld, S AF Baron, F Maris, MB Storer, BE Sandmaier, BM Panse, JP Chauncey, TR Sorror, M Little, MT Maloney, DG Storb, R Heimfeld, S TI High doses of transplanted CD34(+) cells are associated with rapid T-cell engraftment and lessened risk of graft rejection, but not more graft-versus-host disease after nonmyeloablative conditioning and unrelated hematopoietic cell transplantation SO LEUKEMIA LA English DT Article DE cell dose; CD34; T-cell; transplantation; nonmyeloablative ID BONE-MARROW-TRANSPLANTATION; IDENTICAL SIBLING TRANSPLANTATION; TOTAL-BODY IRRADIATION; HEMATOLOGIC MALIGNANCIES; LYMPHOCYTES-T; STEM-CELLS; INTENSITY; MORTALITY; DONORS; CHIMERISM AB This report examines the impact of graft composition on outcomes in 130 patients with hematological malignancies given unrelated donor granulocyte-colony-stimulating-factor-mobilized peripheral blood mononuclear cells (G-PBMC) ( n = 116) or marrow ( n = 14) transplantation after nonmyeloablative conditioning with 90 mg/m(2) fludarabine and 2Gy TBI. The median number of CD34(+) cells transplanted was 6.5 x 10(6)/ kg. Higher numbers of grafted CD14(+) ( P = 0.0008), CD3(+) ( P = 0.0007), CD4(+) ( P = 0.001), CD8(+) ( P = 0.004), CD3 - CD56(+) ( P = 0.003), and CD34(+) ( P = 0.0001) cells were associated with higher levels of day 28 donor T-cell chimerism. Higher numbers of CD14(+) ( P = 0.01) and CD34(+) ( P = 0.0003) cells were associated with rapid achievement of complete donor T-cell chimerism, while high numbers of CD8(+) ( P = 0.005) and CD34(+) ( P = 0.01) cells were associated with low probabilities of graft rejection. When analyses were restricted to G-PBMC recipients, higher numbers of grafted CD34(+) cells were associated with higher levels of day 28 donor T-cell chimerism ( P = 0.01), rapid achievement of complete donor T-cell chimerism ( P = 0.02), and a trend for lower risk for graft rejection ( P = 0.14). There were no associations between any cell subsets and acute or chronic GVHD nor relapse/progression. These data suggest more rapid engraftment of donor T cells and reduced rejection rates could be achieved by increasing the doses of CD34(+) cells in unrelated grafts administered after nonmyeloablative conditioning. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Liege, Dept Hematol, B-4000 Liege, Belgium. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Maris, MB (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM mmaris@fhcrc.org FU NCI NIH HHS [CA18029, CA15704, CA78902, CA92058, P01 CA078902]; NHLBI NIH HHS [HL36444]; NICHD NIH HHS [HD44175]; NIDDK NIH HHS [DK56465] NR 32 TC 68 Z9 69 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2005 VL 19 IS 5 BP 822 EP 828 DI 10.1038/sj.leu.2403718 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 920MA UT WOS:000228692500018 PM 15772701 ER PT J AU Bhidayasiri, R Bronstein, JM Sinha, S Krahl, SE Ahn, S Behnke, EJ Cohen, MS Frysinger, R Shellock, FG AF Bhidayasiri, R Bronstein, JM Sinha, S Krahl, SE Ahn, S Behnke, EJ Cohen, MS Frysinger, R Shellock, FG TI Bilateral neuro stimulation systems used for deep brain stimulation: in vitro study of MRI-related heating at 1.5 T and implications for clinical imaging of the brain SO MAGNETIC RESONANCE IMAGING LA English DT Article DE deep brain stimulation; magnetic resonance imaging safety; neurostimulation systems; implants; specific absorption rate; Parkinson's disease ID VARYING MAGNETIC-FIELDS; SUBTHALAMIC NUCLEUS; IMPLANTED NEUROSTIMULATORS; ELECTRODES; DEVICES; RECOMMENDATIONS; 1.5-TESLA; DYSTONIA; DISEASE AB Deep brain stimulation (DBS) is used increasingly in the field of movement disorders. The implanted electrodes create not only a prior risk to patient safety during MRI, but also a unique opportunity in the collection of functional MRI data conditioned by direct neural stimulation. We evaluated MRI-related heating for bilateral neurostimulation systems used for DBS with an emphasis on assessing clinically relevant imaging parameters. Magnetic resonance imaging was performed using transmit body radiofrequency (RF) coil and receive-only head RF coil at various specific absorption rates (SARs) of RF power. In vitro testing was performed using a gel-filled phantom with temperatures recorded at the electrode tips. Each DBS electrode was positioned with a single extension loop around each pulse generator and a single loop at the "head" end of the phantom. Various pulse sequences were used for MRI including fast spin-echo, echo-planar imaging, magnetization transfer contrast and gradient-echo techniques. The MRI sequences had calculated whole-body averaged SARs and local head SARs ranging from 0.1 to 1.6 W/kg and 0.1 to 3.2 W/kg, respectively. Temperature elevations of less than 1.0&DEG; C were found with the fast spin-echo, magnetization transfer contrast, gradient-echo and echo-planar clinical imaging sequences. Using the highest SAR levels, wholebody averaged, 1.6 W/kg, local exposed-body, 3.2 W/kg, and local head, 2.9 W/kg, the temperature increase was 2.1&DEG; C. These results showed that temperature elevations associated with clinical sequences were within an acceptable physiologically safe range for the MR conditions used in this evaluation, especially for the use of relatively low SAR levels. Notably, these findings are highly specific to the neurostimulation systems, device positioning technique, MR system and imaging conditions used in this investigation. © 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Radiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Psychiat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Dept Biomed Engn, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, Div Neurosurg, Los Angeles, CA 90095 USA. Univ So Calif, Parkinsons Dis Res Educ & Clin Ctr, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90073 USA. RP Bhidayasiri, R (reprint author), Univ Calif Los Angeles, Med Ctr, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. EM rbh@ucla.edu OI Bhidayasiri, Roongroj/0000-0002-6901-2064 FU NIDA NIH HHS [DA15549]; NINDS NIH HHS [NS44575-01] NR 29 TC 35 Z9 35 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD MAY PY 2005 VL 23 IS 4 BP 549 EP 555 DI 10.1016/j.mri.2005.02.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 933DA UT WOS:000229603200004 PM 15919600 ER PT J AU Palmer, AA Verbitsky, M Suresh, R Kamens, HM Reed, CL Li, N Burkhart-Kasch, S McKinnon, CS Belknap, JK Gilliam, TC Phillips, TJ AF Palmer, AA Verbitsky, M Suresh, R Kamens, HM Reed, CL Li, N Burkhart-Kasch, S McKinnon, CS Belknap, JK Gilliam, TC Phillips, TJ TI Gene expression differences in mice divergently selected for methamphetamine sensitivity SO MAMMALIAN GENOME LA English DT Article ID QUANTITATIVE-TRAIT LOCI; FUNCTIONAL GENOMICS APPROACH; NUCLEUS-ACCUMBENS; CANDIDATE GENES; LOCOMOTOR STIMULATION; DOPAMINE RELEASE; DRUG-ADDICTION; COMPLEX TRAITS; ALCOHOL; COCAINE AB In an effort to identify genes that may be important for drug-abuse liability, we mapped behavioral quantitative trait loci (bQTL) for sensitivity to the locomotor stimulant effect of methamphetamine (MA) using two mouse lines that were selectively bred for high MA-induced activity (HMACT) or low MA-induced activity (LMACT). We then examined gene expression differences between these lines in the nucleus accumbens, using 20 U74Av2 Affymetrix microarrays and quantitative polymerase chain reaction (qPCR). Expression differences were detected for several genes, including Casein Kinase I Epsilon (Csnkle), glutamate receptor, ionotropic, AMPA1 (GluR1), GABA B1 receptor (Gabbr1), and dopamine- and cAMP-regulated phosphoprotein of 32 kDa (Darpp-32). We used the www.WebQTL.org database to identify QTL that regulate the expression of the genes identified by the microarrays (expression QTL; eQTL). This approach identified an eQTL for Csnkle on Chromosome 15 (LOD = 3.8) that comapped with a bQTL for the MA stimulation phenotype (LOD = 4.5), suggesting that a single allele may cause both traits. The chromosomal region containing this QTL has previously been associated with sensitivity to the stimulant effects of cocaine. These results suggest that selection was associated with (and likely caused) altered gene expression that is partially attributable to different frequencies of gene expression polymorphisms. Combining classical genetics with analysis of whole-genome gene expression and bioinformatic resources provides a powerful method for provisionally identifying genes that influence complex traits. The identified genes provide excellent candidates for future hypothesis driven studies, translational genetic studies, and pharmacological interventions. C1 Columbia Univ, Columbia Genome Ctr, New York, NY 10032 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Portland Alcohol Res Ctr, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Res Serv, Portland, OR 97239 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. RP Palmer, AA (reprint author), Columbia Univ, Columbia Genome Ctr, 1150 St Nicholas Ave, New York, NY 10032 USA. EM aap20l0@columbia.edu RI Palmer, Abraham/L-2158-2014; OI Palmer, Abraham/0000-0003-3634-0747; Kamens, Helen/0000-0001-5085-8847 FU NIAAA NIH HHS [AA07468]; NIDA NIH HHS [DA10913]; NIMH NIH HHS [MH70933] NR 57 TC 67 Z9 69 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 2005 VL 16 IS 5 BP 291 EP 305 DI 10.1007/s00335-004-2451-8 PG 15 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 933NS UT WOS:000229640800001 PM 16104378 ER PT J AU Craft, DL Wein, LM Wilkins, AH AF Craft, DL Wein, LM Wilkins, AH TI Analyzing bioterror response logistics: The case of anthrax SO MANAGEMENT SCIENCE LA English DT Article DE bioterrorism; queueing ID EMERGENCY RESPONSE; SMALLPOX; ATTACK; OUTBREAK AB To aid in understanding how best to respond to a bioterror anthrax attack, we analyze a system of differential equations that includes an atmospheric release model, a spatial array of biosensors, a dose-response model, a disease progression model, and a set of spatially distributed tandem queues for distributing antibiotics and providing hospital care. We derive approximate closed-form expressions for the number of deaths as a function of key parameters and management levers, including the size of the attack, the time at which the attack is detected via symptomatic patients, the number of days to distribute antibiotics, the efficacy (both for treatment and prevention) of antibiotics, the prophylactic antibiotic distribution strategy, the prioritization of the antibiotics queue, and the detection limit, deployment density and delay time of biosensors. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Stanford Univ, Grad Sch Business, Stanford, CA 94306 USA. RP Craft, DL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org; lwein@stanford.edu; awilkins@stanford.edu NR 30 TC 24 Z9 25 U1 1 U2 12 PU INST OPERATIONS RESEARCH MANAGEMENT SCIENCES PI LINTHICUM HTS PA 901 ELKRIDGE LANDING RD, STE 400, LINTHICUM HTS, MD 21090-2909 USA SN 0025-1909 J9 MANAGE SCI JI Manage. Sci. PD MAY PY 2005 VL 51 IS 5 BP 679 EP 694 DI 10.1287/mnsc.1040.0348 PG 16 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA 934FJ UT WOS:000229692000001 ER PT J AU Pickard, AS Knight, SJ AF Pickard, AS Knight, SJ TI Proxy evaluation of health-related quality of life - A Conceptual framework for understanding multiple proxy perspectives SO MEDICAL CARE LA English DT Article DE proxy; health status; caregiving; quality of life; provider/patient communication ID METASTATIC PROSTATE-CANCER; SIGNIFICANT OTHERS; RESPONSE COMPARABILITY; DECISION-MAKING; CLINICAL-TRIALS; UTILITIES INDEX; CHRONIC DISEASE; CARE PROVIDERS; FAMILY-MEMBERS; PATIENT HEALTH AB Proxy assessment of health-related quality of life (HRQL) may be sought to substitute for, or to complement, patient self-assessment. The viewpoint from which the proxy is asked to assess the patient is a subtle yet important aspect of proxy assessment. Proxy assessments can be elicited by asking a proxy to assess the patient as they think the patient would respond (ie, proxy-patient perspective) or for the proxy to provide their own perspective on the patient's HRQL (ie, proxy-proxy perspective). In this article, we introduce a framework for differentiating between and understanding HRQL assessments according to rater viewpoint. The difference between patient self-assessment and the proxy-patient perspective is defined as the inter-rater gap, whereas the difference between the proxy-patient and proxy-proxy perspective is described as the intra-proxy gap. The inter-rater gap represents the difference between patient self-assessed HRQL and the proxy ability to comprehend the patient view. The extent to which the proxy-proxy perspective is informative will depend upon the proxy's ability to provide reinforcing or complementary information, ie, represented by the intraproxy gap, on the HRQL of the patient. We refer to the framework to emphasize the importance of delineating between proxy perspectives in study design and HRQL measurement and to guide inquiries into the validity and interpretation of the meaningfulness of the proxy HRQL assessments from each viewpoint. Future research and use of proxy raters of HRQL in clinical trials, population health monitoring, resource allocation, and clinical management can be informed by explicit consideration of the suggested framework. C1 Univ Illinois, Coll Pharm, Ctr Pharmacoecon Res, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Pharm, Chicago, IL 60612 USA. San Francisco Vet Affairs Med Ctr, Hlth & Urol Serv, Dept Vet Affairs,Res Enhancement Award Program Hl, Interdisciplinary Res Program Improve Care Older, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Pickard, AS (reprint author), Univ Illinois, Coll Pharm, Ctr Pharmacoecon Res, Room 164,MC 886,833 S Wood St, Chicago, IL 60612 USA. EM pickardl@uic.edu FU NCI NIH HHS [R03 CA10839-01, R03 CA108395-01] NR 66 TC 75 Z9 77 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2005 VL 43 IS 5 BP 493 EP 499 DI 10.1097/01.mlr.0000160419.27642.a8 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 921XE UT WOS:000228798100011 PM 15838415 ER PT J AU Atherly, A Hebert, PL Maciejewski, ML AF Atherly, A Hebert, PL Maciejewski, ML TI An analysis of disenrollment from Medicare managed care plans by medicare beneficiaries with diabetes SO MEDICAL CARE LA English DT Article DE medicare; managed care; diabetes; disenrollment ID FEE-FOR-SERVICE; HEALTH-MAINTENANCE-ORGANIZATIONS; PREPAID GROUP-PRACTICE; RHEUMATOID-ARTHRITIS; CHRONICALLY ILL; OUTCOMES; HMOS; SYSTEMS; HYPERTENSION; SPECIALTIES AB Research Objective: The purpose of this work is to determine whether high-cost high-risk Medicare patients with diabetes in managed care plans disenroll more quickly than lower-cost lower-risk Medicare patients with diabetes, If high-cost high-risk patients with diabetes do disenroll more quickly, Medicare managed care plans benefit financially from favorable disenrollment. Study Design: Time in a health maintenance organization (HMO) was modeled using a duration model with the number of months in the HMO as the dependent variable, controlling for censoring. Data were drawn from a representative sample of Medicare patients with diabetes in the FFS sector in 1994. The panel was followed for 4 years, 1995-1998. The sample included all 6839 individuals who enrolled in a Medicare HMO for at least 1 month during the 48-month observation window. Principal Findings: We found a statistically significant negative association between the time in an HMO and pre-enrollment Part B expenditures (beta = -0.00001, t = -4.39) and any Part A expenditures (beta = -0.465, t = -1.98), and 2 of 4 diabetic complications (heart complications: beta = -0.0773 t = -4.61, vision complications beta = -0.2474, t = -1.94). Of the plan characteristics, only the drug benefit variable (beta = 0.151, t = 5.64) had a statistically significant coefficient. C1 Emory Univ, Dept Hlth Policy & Management, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, NE Ctr Outcomes Res Older Adults, Seattle, WA 98195 USA. RP Atherly, A (reprint author), Emory Univ, Dept Hlth Policy & Management, Rollins Sch Publ Hlth, 1518 Clifton Rd NE, Atlanta, GA 30322 USA. EM aatherl@sph.emory.edu FU AHRQ HHS [HS500-92-0014] NR 28 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 2005 VL 43 IS 5 BP 500 EP 506 DI 10.1097/01.mlr.0000160420.82977.ae PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 921XE UT WOS:000228798100012 PM 15838416 ER PT J AU Singh, AK AF Singh, AK TI Chronic kidney disease SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Singh, AK (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St,Med Bldg MRB,Room 404B, Boston, MA 02115 USA. EM asingh@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAY PY 2005 VL 89 IS 3 BP XV EP XVI DI 10.1016/j.mcna.2004.12.003 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 911WH UT WOS:000228036700001 ER PT J AU Gonzalez, GM Fothergill, AW Sutton, DA Rinaldi, MG Loebenberg, D AF Gonzalez, GM Fothergill, AW Sutton, DA Rinaldi, MG Loebenberg, D TI In vitro activities of new and established triazoles against opportunistic filamentous and dimorphic fungi SO MEDICAL MYCOLOGY LA English DT Article DE fluconazole; itraconazole; posaconazole; ravuconazole; voriconazole ID AMPHOTERICIN-B; ORAL TRIAZOLE; ITRACONAZOLE; VORICONAZOLE; SUSCEPTIBILITIES; SCEDOSPORIUM; ASPERGILLUS; INFECTION; EFFICACY; ER-30346 AB The in vitro activities of three new triazoles were determined and compared to those of itraconazole and fluconazole against 306 clinical isolates of Blastomyces dermatitidis, Cladophialophora carrionii, Coccidioides immitis, Fonsecaea pedrosoi, Fusarium spp., Histoplasma capsulatum, Paecilomyces lilacinus, Pseudallescheria boydii and Sporothrix schenckii. Minimum inhibitory concentrations ( MIC) were determined by a broth macrodilution method of the National Committee for Clinical Laboratory Standards M38-A procedure. Itraconazole ( geometric mean MIC, 0.16-0.65 mu g/ml), voriconazole ( geometric mean MIC, 0.18-1.44 mu g/ml), ravuconazole ( geometric mean MIC, 0.18-1.09 mu g/ml), and posaconazole ( geometric mean MIC, 0.18-1.38 mu g/ml), had relatively uniform values showing potent in vitro inhibitory activity against B. dermatitidis, C. carrionii, C. immitis, F. pedrosoi, H. capsulatum, and S. schenckii. The in vitro activity was variable with strains of P. boydii, P. lilacinus and Fusarium spp. C1 Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Colonia Mitras Ctr, Monterrey 64460, NL, Mexico. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Gonzalez, GM (reprint author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Colonia Mitras Ctr, Madero & Dr Eduardo A Pequeno S-N, Monterrey 64460, NL, Mexico. EM gmglez@yahoo.com.mx NR 22 TC 59 Z9 64 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 IS 3 BP 281 EP 284 DI 10.1080/13693780500088416 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 938HT UT WOS:000229991200010 PM 16010855 ER PT J AU Greene, R AF Greene, R TI The radiological spectrum of pulmonary aspergillosis SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Advances Against Aspergillosis Conference CY SEP 09-11, 2004 CL San Francisco, CA DE aspergillosis; computed tomography; halo sign ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; AIR CRESCENT SIGN; INVASIVE ASPERGILLOSIS; PATHOLOGICAL FINDINGS; CYSTIC-FIBROSIS; EARLY DIAGNOSIS; AMPHOTERICIN-B; ACUTE-LEUKEMIA; CT; CAVITARY AB Imaging findings in the pulmonary aspergilloses can answer important clinical questions. Steroid-responsive chronic asthma due to allergic bronchopulmonary aspergillosis can be differentiated from simple asthma by computed tomography (CT) evidence of extensive and severe central bronchiectasis, mucoid impaction, or small airways lesions. The simple aspergilloma can be differentiated from the complex aspergilloma by the absence of: constitutional symptoms, para-cystic lung opacities, cyst expansion, or progressive pleural thickening. The CT halo sign is a transient finding that can provide a probable diagnosis of early invasive pulmonary aspergillosis in patients who are at extraordinarily high risk of the infection. Patients with a halo sign at baseline are more likely to have a satisfactory treatment response than those without this indicator. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Founders 202,55 Fruit St, Boston, MA 02114 USA. EM greene.reginald@mgh.harvard.edu NR 53 TC 42 Z9 50 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 SU 1 BP S147 EP S154 DI 10.1080/13693780500064771 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 950YW UT WOS:000230896300025 PM 16110807 ER PT J AU Fricchione, G Stefano, GB AF Fricchione, G Stefano, GB TI Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries SO MEDICAL SCIENCE MONITOR LA English DT Article DE placebo; morphine; nitric oxide; mu3 opiate receptor; limbic; reward ID ENDOTHELIAL-CELL SENESCENCE; TRIALS COMPARING PLACEBO; ENDOGENOUS MORPHINE; OPIATE RECEPTOR; RELAXATION RESPONSE; SUBTHALAMIC NUCLEUS; BASAL GANGLIA; NO TREATMENT; L-ARGININE; NEURONS AB Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a vole in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be all important signal molecule working at mu receptor's on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects oil these dopamine systems as well as oil periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions. C1 Massachusetts Gen Hosp, Div Psychiat & Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Mind Body Med Inst, Boston, MA USA. SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. RP Fricchione, G (reprint author), Massachusetts Gen Hosp, Div Psychiat & Med, Dept Psychiat, Warren 6,55 Fruit St, Boston, MA 02114 USA. EM gfricchione@partners.org FU NIDA NIH HHS [DA09010]; NIMH NIH HHS [MH47392] NR 89 TC 43 Z9 44 U1 2 U2 4 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD MAY PY 2005 VL 11 IS 5 BP MS54 EP MS65 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 931EZ UT WOS:000229469900022 PM 15874901 ER PT J AU Stefano, GB Fricchione, GL Goumon, Y Esch, T AF Stefano, GB Fricchione, GL Goumon, Y Esch, T TI Pain, immunity, opiate and opioid compounds and health SO MEDICAL SCIENCE MONITOR LA English DT Article DE morphine; pain; amygdala; nitric oxide; mu 3 opiate receptor; opioid peptides; methionine enkephalin; enkelytin ID NITRIC-OXIDE RELEASE; ENDOGENOUS MORPHINE LEVELS; RECEPTOR SUBTYPE; CARDIOPULMONARY BYPASS; HEROIN-ADDICTION; HIV GP120; INVERTEBRATE; EXPOSURE; ANANDAMIDE; INCREASES AB We surmise that opioid peptides, i.e., methionine enkephalin, first arose during evolution as modulators of cellular immune function given their immune actions and the presence of enkelytin a potent antibacterial peptide, and its precursor proenkephalin in animals 500 million years divergent in evolution. Pain probably emerged from this peispective because of its association with proinflammatory events. Endogenous morphine appears to exert positive effects on homeostasis by limiting the defence of excitation. Supporting this view is the fact that the mu3 opiate receptor subtype, which is opioid peptide insensitive and morphine selective, is coupled to constitutive nitric oxide release, which also has this down regulating action in neural, immune, vascular and gastrointestinal tissues. Thus, morphine down regulates immune processes in addiction, an action/function that it appears to normally perform when the situation calls for this action and by so doing in this natural setting, sustains life. C1 SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. Massachusetts Gen Hosp, Dept Psychiat, Div Psychiat & Med, Boston, MA USA. INSERM 575 Physiopathol Nervous Syst, Strasbourg, France. Charite Univ Med Berlin, Inst Gen Practice & Family Med, Berlin, Germany. RP Stefano, GB (reprint author), SUNY Coll Old Westbury, Neurosci Res Inst, Old Westbury, NY 11568 USA. EM gstefano@sunynri.org RI Esch, Tobias/J-3812-2013 OI Esch, Tobias/0000-0001-5176-4367 FU NIDA NIH HHS [DA09010]; NIMH NIH HHS [MH47392] NR 51 TC 39 Z9 40 U1 1 U2 2 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD MAY PY 2005 VL 11 IS 5 BP MS47 EP MS53 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 931EZ UT WOS:000229469900021 PM 15874900 ER PT J AU Bennett, GG Wolin, KY Avrunin, JS Stoddard, AM Barbeau, E Emmons, KM AF Bennett, Gary G. Wolin, Kathleen Y. Avrunin, Jill S. Stoddard, Anne M. Barbeau, Elizabeth Emmons, Karen M. TI Do Psychosocial Occupational Characteristics Contribute To Racial And Ethnic Differences In Leisure Physical Activity? SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Bennett, Gary G.; Wolin, Kathleen Y.; Barbeau, Elizabeth; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. [Avrunin, Jill S.] Univ Massachusetts, Amherst, MA 01003 USA. [Stoddard, Anne M.] New England Res Inst, Boston, MA USA. EM gbennett@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2005 VL 37 SU 5 MA 1666 BP S321 EP S321 DI 10.1097/00005768-200505001-01662 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070302160 ER PT J AU Kallio, J Leinonen, A Ulvila, J Valanne, S Ezekowitz, RA Ramet, M AF Kallio, J Leinonen, A Ulvila, J Valanne, S Ezekowitz, RA Ramet, M TI Functional analysis of immune response genes in Drosophila identifies JNK pathway as a regulator of antimicrobial peptide gene expression in S2 cells SO MICROBES AND INFECTION LA English DT Article DE Drosophila melanogaster; innate immunity; JNK signaling ID PEPTIDOGLYCAN RECOGNITION PROTEIN; COMPLEMENT-LIKE PROTEIN; GRAM-NEGATIVE BACTERIA; GENOME-WIDE ANALYSIS; NF-KAPPA-B; INNATE IMMUNITY; SCAVENGER RECEPTOR; POSITIVE BACTERIA; TOLL; PHAGOCYTOSIS AB The templates of innate immunity have ancient origins. Thus, such model animals as the fruit fly, Drosophila metanogaster, can be used to identify gene products that also play a key role in the innate immunity in mammals. We have used oligonucleotide microarrays to identify genes that are responsive to Gram-negative bacteria in Drosophila macrophage-like S2 cells. In total, 53 genes were induced by greater than threefold in response to Escherichia coli. The induction of all these genes was peptidoglycan recognition protein LC (PGRP-LC) dependent. Twenty-two genes including 10 of the most strongly induced genes are also known to be up-regulated by septic injury in vivo. Importantly, we identified 31 genes that are not known to respond to bacterial challenge. We carried out targeted dsRNA treatments to assess the functional importance of these gene products for microbial recognition, phagocytosis and antimicrobial peptide release in Drosophila S2 cells in vitro. RNAi targeting three of these genes, CG7097, CG15678 and beta-Tubulin 60D, caused altered,antimicrobial peptide release in vitro. Our results indicate that the JNK pathway is essential for normal antimicrobial peptide release in Drosophila in vitro. (c) 2005 Elsevier SAS. All rights reserved. C1 Univ Tampere, Inst Med Technol, Tampere 33014, Finland. Univ Oulu, Bioctr, Oulu, Finland. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Tampere Univ Hosp, Dept Pediat, Tampere, Finland. RP Ramet, M (reprint author), Univ Tampere, Inst Med Technol, Tampere 33014, Finland. EM mika.ramet@uta.fi NR 34 TC 49 Z9 49 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAY PY 2005 VL 7 IS 5-6 BP 811 EP 819 DI 10.1016/j.micinf.2005.03.014 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 941OP UT WOS:000230224400001 PM 15890554 ER PT J AU Kushner, JA Ciemerych, MA Sicinska, E Wartschow, LM Teta, M Long, SY Sicinski, P White, MF AF Kushner, JA Ciemerych, MA Sicinska, E Wartschow, LM Teta, M Long, SY Sicinski, P White, MF TI Cyclins D2 and D1 are essential for postnatal pancreatic beta-cell growth SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-2; DIABETES-MELLITUS; MICE; PROLIFERATION; CDK4; GENE; ONCOGENESIS; DISRUPTION; ACTIVATION; INDUCTION AB Regulation of adult P-cell mass in pancreatic islets is essential to preserve sufficient insulin secretion in order to appropriately regulate glucose homeostasis. In many tissues mitogens influence development by stimulating D-type cyclins (D1, D2, or D3) and activating cyclin-dependent kinases (CDK4 or CDK6), which results in progression through the G, phase of the cell cycle. Here we show that cyclins D2 and D1 are essential for normal postnatal islet growth. In adult murine islets basal cyclin D2 mRNA expression was easily detected, while cyclin D1 was expressed at lower levels and cyclin D3 was nearly undetectable. Prenatal islet development occurred normally in cyclin D2(-/-) or cyclin D1(+/-) D2(-/-) mice. However, beta-cell proliferation, adult mass, and glucose tolerance were decreased in adult cyclin D2(-/-) mice, causing glucose intolerance that progressed to diabetes by 12 months of age. Although cyclin D1(-/-) mice never developed diabetes, life-threatening diabetes developed in 3-month-old cyclin D1(-/+) D2(-/-) mice as beta-cell mass decreased after birth. Thus, cyclins D2 and D1 were essential for beta-cell expansion in adult mice. Strategies to tightly regulate D-type cyclin activity in beta cells could prevent or cure diabetes. C1 Univ Penn, Sch Med, Div Endocrinol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kushner, JA (reprint author), Univ Penn, Sch Med, Div Endocrinol, Childrens Hosp Philadelphia, 3615 Civic Ctr Blvd, Philadelphia, PA 19104 USA. EM kushnerj@mail.med.upenn.edu FU NCI NIH HHS [R01 CA083688]; NIDDK NIH HHS [DK 55326, DK 02024, DK 064101, DK 38712, DK 43808, K08 DK064101, R01 DK038712, R01 DK043808, R01 DK055326] NR 31 TC 229 Z9 239 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2005 VL 25 IS 9 BP 3752 EP 3762 DI 10.1128/MCB.25.9.3752-3762.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 920HF UT WOS:000228679300033 PM 15831479 ER PT J AU Oberdoerffer, P Kanellopoulou, C Heissmeyer, V Paeper, C Borowski, C Aifantis, I Rao, A Rajewsky, K AF Oberdoerffer, P Kanellopoulou, C Heissmeyer, V Paeper, C Borowski, C Aifantis, I Rao, A Rajewsky, K TI Efficiency of RNA interference in the mouse hematopoietic system varies between cell types and developmental stages SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; MAMMALIAN-CELLS; TRANSGENIC MICE; T-LYMPHOCYTES; A1/BFL-1 EXPRESSION; STEM-CELLS; B-CELLS; GENE; A1; ARGONAUTE2 AB RNA interference (RNAi) is a naturally occurring posttranscriptional gene-silencing mechanism that has been adapted as a genetic tool for loss-of-function studies of a variety of organisms. It is more widely applicable than classical gene targeting and allows for the simultaneous inactivation of several homologous genes with a single transgene. Recently, RNAi has been used for conditional and conventional gene inactivation in mice. Unlike gene targeting, RNAi is a dynamic process, and its efficiency may vary both between cell types and throughout development. Here we demonstrate that RNAi can be used to target three separately encoded isoforms of the bcl-2 family gene bfl-1/A1 in a conditional manner in mice. The extent of gene inactivation varies between different cell types and is least efficient in mature lymphocytes. Our data suggest that RNAi is affected by factors beyond small interfering RNA-mRNA stoichiometry. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Australian Natl Univ, Canberra, ACT 0200, Australia. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Oberdoerffer, P (reprint author), Harvard Univ, Sch Med, Dept Pathol, NRB, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM philober@hms.harvard.edu; rajewsky@cbr.med.harvard.edu FU NIAID NIH HHS [U19 AI056900]; PHS HHS [P01 A156900] NR 46 TC 55 Z9 57 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2005 VL 25 IS 10 BP 3896 EP 3905 DI 10.1128/MCB.25.10.3896-3905.2005 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100005 PM 15870264 ER PT J AU Yang, J Gao, JG Adamian, M Wen, XH Pawlyk, B Zhang, L Sanderson, MJ Zuo, J Makino, CL Li, TS AF Yang, J Gao, JG Adamian, M Wen, XH Pawlyk, B Zhang, L Sanderson, MJ Zuo, J Makino, CL Li, TS TI The ciliary rootlet maintains long-term stability of sensory cilia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERMEDIATE-FILAMENT NETWORKS; EPITHELIAL-CELLS; PHOTORECEPTORS; PROTEIN; MICE; DYNAMICS; MECHANISM; MOVEMENT AB The striated ciliary rootlet is a prominent cytoskeleton originating from basal bodies of ciliated cells. Although a familiar structure in cell biology, its function has remained unresolved. In this study, we carried out targeted disruption in mice of the gene for rootletin, a component of the rootlet. In the mutant, ciliated cells are devoid of rootlets. Phototransduction and ciliary beating in sensory and motile cilia initially exhibit no apparent functional deficits. However, photoreceptors degenerate over time, and mutant lungs appear prone to pathological changes consistent with insufficient mucociliary clearance. Further analyses revealed a striking fragility at the ciliary base in photoreceptors lacking rootlets. In vitro assays suggest that the rootlet is among the least dynamic of all cytoskeletons and interacts with actin filaments. Thus, a primary function of the rootlet is to provide structural support for the cilium. Inasmuch as photoreceptors elaborate an exceptionally enlarged sensory cilium, they are especially dependent on the rootlet for structural integrity and long-term survival. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Howe Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. St Jude Childrens Res Hosp, Memphis, TN USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA USA. RP Yang, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM tli@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU NEI NIH HHS [R01 EY011358, EY11358, EY12950, EY14104, EY16442, P30 EY014104, R01 EY012950, R29 EY011358] NR 29 TC 71 Z9 73 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2005 VL 25 IS 10 BP 4129 EP 4137 DI 10.1128/MCB.25.10.4129-4137.2005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100024 PM 15870283 ER PT J AU Bardeesy, N Kim, M Xu, J Kim, RS Shen, Q Bosenberg, MW Wong, WH Chin, L AF Bardeesy, N Kim, M Xu, J Kim, RS Shen, Q Bosenberg, MW Wong, WH Chin, L TI Role of epidermal growth factor receptor signaling in RAS-driven melanoma SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID THYROID EPITHELIAL-CELLS; MALIGNANT-MELANOMA; ONCOGENIC RAS; CUTANEOUS MELANOMA; TUMOR PROGRESSION; PLASMA-MEMBRANE; IN-VIVO; TRANSFORMATION; MUTATIONS; GENE AB The identification of essential genetic elements in pathways governing the maintenance of fully established tumors is critical to the development of effective antioncologic agents. Previous studies revealed an essential role for H-RAS(V12G) in melanoma maintenance in an inducible transgenic model. Here, we sought to define the molecular basis for RAS-dependent tumor maintenance through determination of the H-RAS(V12G)-directed transcriptional program and subsequent functional validation of potential signaling surrogates. The extinction of H-RAS(V12G) expression in established tumors was associated with alterations in the expression of proliferative, antiapoptotic, and angiogenic genes, a profile consistent with the observed phenotype of tumor cell proliferative arrest and death and endothelial cell apoptosis during tumor regression. In particular, these melanomas displayed a prominent RAS-dependent regulation of the epidermal growth factor (EGF) family, leading to establishment of an EGF receptor signaling loop. Genetic complementation and interference studies demonstrated that this signaling loop is essential to H-RAS(V12G)-directed tumorigenesis. Thus, this inducible tumor model system permits the identification and validation of alternative points of therapeutic intervention without neutralization of the primary genetic lesion. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Dept Stat & Biostat, Cambridge, MA USA. Univ Vermont, Dept Pathol, Burlington, VT USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA USA. RP Bardeesy, N (reprint author), Massachusetts Gen Hosp, Canc Ctr, 13th St,Bldg 148,Room 7204, Charlestown, MA 02129 USA. EM nelbardeesy@partners.org; Lynda_chin@dfci.harvard.edu FU NCI NIH HHS [K08 CA089124, R01 CA093947, R01 CA93947, U01 CA084313, U01 CA84313, CA89124, P20 CA096470, P20 CA96470, P50 CA093683, P50 CA93683] NR 64 TC 33 Z9 34 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 MAY PY 2005 VL 25 IS 10 BP 4176 EP 4188 DI 10.1128/MCB.25.10.4176-4188.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100028 PM 15870287 ER PT J AU Dejean, LM Martinez-Caballero, S Guo, L Hughes, C Teijido, O Ducret, T Ichas, F Korsmeyer, SJ Antonsson, B Jonas, EA Kinnally, KW AF Dejean, LM Martinez-Caballero, S Guo, L Hughes, C Teijido, O Ducret, T Ichas, F Korsmeyer, SJ Antonsson, B Jonas, EA Kinnally, KW TI Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID CELL-DEATH; PROAPOPTOTIC BAX; OUTER-MEMBRANE; BCL-2 FAMILY; CONDUCTANCE CHANNEL; FORMING ACTIVITY; EXPRESSION; PROTEIN; PERMEABILITY; PURIFICATION AB Bcl-2 family proteins regulate apoptosis, in part, by controlling formation of the mitochondrial apoptosis-induced channel (MAC), which is a putative cytochrome c release channel induced early in the intrinsic apoptotic pathway. This channel activity was never observed in Bcl-2-overexpressing cells. Furthermore, MAC appears when Bax translocates to mitochondria and cytochrome c is released in cells dying by intrinsic apoptosis. Bax is a component of MAC of staurosporine-treated HeLa cells because MAC activity is immunodepleted by Bax antibodies. MAC is preferentially associated with oligomeric, not monomeric, Bax. The single channel behavior of recombinant oligomeric Bax and MAC is similar. Both channel activities are modified by cytochrome c, consistent with entrance of this protein into the pore. The mean conductance of patches of mitochondria isolated after green fluorescent protein-Bax translocation is significantly higher than those from untreated cells, consistent with onset of MAC activity. In contrast, the mean conductance of patches of mitochondria indicates MAC activity is present in apoptotic cells deficient in Bax but absent in apoptotic cells deficient in both Bax and Bak. These findings indicate Bax is a component of MAC in staurosporine-treated HeLa cells and suggest Bax and Bak are functionally redundant as components of MAC. C1 NYU, Coll Dent, Dept Basic Sci, New York, NY 10010 USA. Inst Natl Sante & Rech Med, Ctr Lutte Contre Canc Biol, F-33600 Pessac, France. Inst Europeen Chim & Biol, F-33600 Pessac, France. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Serono Int SA, Serono Pharmaceut Res Inst, Geneva, Switzerland. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. RP Kinnally, KW (reprint author), NYU, Coll Dent, Dept Basic Sci, New York, NY 10010 USA. EM kck1@nyu.edu RI Martinez Caballero, Sonia/B-7583-2013 FU NIGMS NIH HHS [R01 GM057249, GM-57249]; NINDS NIH HHS [NS-45876, R37 NS045876, R01 NS045876] NR 46 TC 149 Z9 162 U1 0 U2 8 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2005 VL 16 IS 5 BP 2424 EP 2432 DI 10.1091/mbc.E04-12-1111 PG 9 WC Cell Biology SC Cell Biology GA 921AU UT WOS:000228737400024 PM 15772159 ER PT J AU Qian, WJ Monroe, ME Liu, T Jacobs, JM Anderson, GA Shen, YF Moore, RJ Anderson, DJ Zhang, R Calvano, SE Lowry, SF Xiao, WZ Moldawer, LL Davis, RW Tompkins, RG Camp, DG Smith, RD AF Qian, WJ Monroe, ME Liu, T Jacobs, JM Anderson, GA Shen, YF Moore, RJ Anderson, DJ Zhang, R Calvano, SE Lowry, SF Xiao, WZ Moldawer, LL Davis, RW Tompkins, RG Camp, DG Smith, RD CA Inflammation Host Response Injury TI Quantitative proteome analysis of human plasma following in vivo lipopolysaccharide administration using O-16/O-18 labeling and the accurate mass and time tag approach SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CATALYZED O-16-TO-O-18 EXCHANGE; HUMAN SERUM PROTEOME; LIQUID-CHROMATOGRAPHY; SPECTROMETRY; PEPTIDE; O-18; IDENTIFICATION; TECHNOLOGY; QUANTIFICATION; PREDICTION AB Identification of novel diagnostic or therapeutic biomarkers from human blood plasma would benefit significantly from quantitative measurements of the proteome constituents over a range of physiological conditions. Herein we describe an initial demonstration of proteome-wide quantitative analysis of human plasma. The approach utilizes postdigestion trypsin-catalyzed O-16/O-18 peptide labeling, two-dimensional LC-FTICR mass spectrometry, and the accurate mass and time (AMT) tag strategy to identify and quantify peptides/proteins from complex samples. A peptide accurate mass and LC elution time AMT tag data base was initially generated using MS/MS following extensive multidimensional LC separations to provide the basis for subsequent peptide identifications. The AMT tag data base contains >8,000 putative identified peptides, providing 938 confident plasma protein identifications. The quantitative approach was applied without depletion of high abundance proteins for comparative analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Accurate quantification of changes in protein abundance was demonstrated by both 1: 1 labeling of control plasma and the comparison between the plasma samples following LPS administration. A total of 429 distinct plasma proteins were quantified from the comparative analyses, and the protein abundances for 25 proteins, including several known inflammatory response mediators, were observed to change significantly following LPS administration. C1 Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08901 USA. Stanford Univ, Sch Med, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Shriners Burn Ctr, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, RD (reprint author), Pacific NW Natl Lab, Environm Mol Sci Lab, POB 999,MSIN K8-98, Richland, WA 99352 USA. RI Qian, Weijun/C-6167-2011; Smith, Richard/J-3664-2012; Liu, Tao/A-9020-2013 OI Smith, Richard/0000-0002-2381-2349; Liu, Tao/0000-0001-9529-6550 FU NCRR NIH HHS [P41 RR018522, RR18522]; NIGMS NIH HHS [U54 GM-62119-02, U54 GM062119] NR 35 TC 126 Z9 137 U1 1 U2 18 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAY PY 2005 VL 4 IS 5 BP 700 EP 709 DI 10.1074/mcp.M500045-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 923TS UT WOS:000228932800010 PM 15753121 ER PT J AU Spaczynski, RZ Tilly, JL Mansour, A Duleba, AJ AF Spaczynski, RZ Tilly, JL Mansour, A Duleba, AJ TI Insulin and insulin-like growth factors inhibit and luteinizing hormone augments ovarian theca-interstitial cell apoptosis SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE apoptosis; insulin; insulin-like growth factors; LH; ovary; theca-interstitial cells ID MESSENGER-RIBONUCLEIC-ACID; RAT THECAL/INTERSTITIAL CELLS; BCL-2 GENE FAMILY; GRANULOSA-CELLS; FACTOR-I; PREOVULATORY FOLLICLES; FOLLICULAR ATRESIA; BINDING PROTEIN-1; FACTOR-ALPHA; FAS ANTIGEN AB Theca-interstitial (T-I) cells play a fundamental role in the control of ovarian function. Steroidogenic activity and growth of the T-I cells are regulated by many paracrine and endocrine factors. However, little is known about the mechanisms controlling T-I death. In an in vitro model of apoptosis, purified rat T-I cells were cultured for 24 h with serum and subsequently for up to an additional 24 h with serum or in serum-free medium with or without insulin, insulin-like growth factors (IGF-I and IGF-II) and LH or 8-bromo-cyclic AMP (8Br-cAMP). Apoptosis was identified by histological assessment of nuclear morphology and by detection of internucleosomal cleavage and quantified by determination of [alpha(32)P]-dideoxy-ATP 3'-end labeling of low molecular weight DNA. Serum withdrawal resulted in nuclear condensation and fragmentation into apoptotic bodies of T-I cells and led to pronounced DNA cleavage. Insulin (10 nM) protected T-I cells from apoptosis, reducing DNA fragmentation by 39 +/- 8% compared to serum-free controls. IGF-I (10 nM) and IGF-II (10 nM) had comparable antiapoptotic effects, decreasing DNA fragmentation by 55 +/- 9% and 37 +/- 14%, respectively. In contrast, LH (100 ng/ml) and 8Br-cAMP (1 mM) augmented the pro-apoptotic effect of serum withdrawal, increasing DNA fragmentation by 85 +/- 55% and 72 +/- 42%, respectively. The antiapoptotic effects of insulin and IGFs and the pro-apoptotic effect of LH, acting via the cAMP system, may be important in the maintenance of T-I homeostasis. Moreover, excessive levels of insulin and free IGFs may lead to T-I cell hyperplasia characteristic of conditions such as polycystic ovary syndrome. C1 Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA. Poznan Univ Med Sci, Dept Gynecol & Obstet, Div Infertil & Reprod Endocrinol, PL-60535 Poznan, Poland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Ctr Reprod Biol,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Duleba, AJ (reprint author), Yale Univ, Sch Med, Dept Obstet & Gynecol, 333 Cedar St, New Haven, CT 06520 USA. EM antoni.duleba@yale.edu FU NICHD NIH HHS [R01 HD40207] NR 44 TC 15 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 EI 1460-2407 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAY-JUN PY 2005 VL 11 IS 5-6 BP 319 EP 324 DI 10.1093/molehr/gah168 PG 6 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 949KV UT WOS:000230786200001 PM 15833775 ER PT J AU Burrell, SC Van den Abbeele, AD AF Burrell, SC Van den Abbeele, AD TI 2-Deoxy-2-[F-18]fluoro-D-glucose-positron emission tomography of the head and neck: An atlas of normal uptake and variants SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE PET; FDG; head and neck carcinoma; imaging atlas ID FDG UPTAKE; PET-CT; 2-FLUORO-2-DEOXY-D-GLUCOSE; THYMUS; CANCER AB In the evaluation of tumors of the head and neck region, positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (FIDG) is increasingly playing a valuable clinical role. However, assessment of this region can be challenging because of the large number of structures in this area which may demonstrate physiologically increased uptake of FDG. Furthermore, these structures are generally small, and uptake patterns can be quite variable, rendering the head and neck region one of the most difficult areas of the body to assess with FDG-PET. To assist in this endeavor, a pictorial of normal FDG uptake, including commonly encountered variants, is presented. C1 Dalhousie Med Sch, QE II Hlth Sci Ctr, Dept Radiol, Halifax, NS B3H 3A7, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Nucl Med, Boston, MA 02115 USA. RP Burrell, SC (reprint author), Dalhousie Med Sch, QE II Hlth Sci Ctr, Dept Radiol, 1796 Summer St, Halifax, NS B3H 3A7, Canada. EM sburrell@dal.ca NR 16 TC 15 Z9 16 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD MAY-JUN PY 2005 VL 7 IS 3 BP 244 EP 256 DI 10.1007/s11307-005-4112-x PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 936FB UT WOS:000229839800008 PM 15912429 ER PT J AU Zemlin, M Ippolito, GC Zemlin, C Link, J Monestier, M Schroeder, HW AF Zemlin, M Ippolito, GC Zemlin, C Link, J Monestier, M Schroeder, HW TI Adult lupus-prone MRL/MpJ(2+) mice express a primary antibody repertoire that differs in CDR-H3 length distribution and hydrophobicity from that expressed in the C3H parental strain SO MOLECULAR IMMUNOLOGY LA English DT Article; Proceedings Paper CT 2nd International Con ference on B Cells and Autoimmunity - New Concepts and Therapeutiv Perspective CY JUL 15-18, 2004 CL Quebec City, CANADA DE MRL; auto-antibodies; immunoglobulin heavy chain complernentarity determining region hydrophobicity; B-cell repertoire ID COMPLEMENTARITY-DETERMINING REGION; B-CELL DEVELOPMENT; AMINO-ACID-COMPOSITION; IG HEAVY-CHAINS; V-H; SOMATIC MUTATION; MRL MICE; AUTOIMMUNE ANTIBODIES; COMBINING SITE; CDR3 REGIONS AB Anti-dsDNA antibodies tend to be enriched for heavy chain complementarity determining region 3 (CDR-H3) intervals of above average length that contain an increased frequency of charged amino acids. It is unclear whether these types of CDR-H3s are more common in the primary B-cell repertoire of auto-immune prone strains or whether their increased prevalence in affected individuals reflects positive selection and expansion of atypical CDR-H3s in the pathogenic response to self-antigen. Here, we present evidence that when compared to C3H, a MRL/MpJ(2+) parental strain, CDR-H3 intervals from pre-B cells of adult lupus-prone MRL/MpJ(2+) mice are longer on average and are enriched for charged amino acids. The predicted prevalence of deformed loops per Shirai H3 criteria is also higher. In contrast, the frequency of charge, the distribution of length, and the pattern of predicted deformed loop structures did not differ in sequences obtained from neonates of the same two strains. These observations suggest that the mechanisms that serve to shape the initial CDR-H3 repertoire in adults, but not neonates, are being regulated differently in C3H versus MRL/MpJ(2+). Dysregulation of the adult pre-B CDR-H3 antibody repertoire could be a contributing factor for the development of florid auto-immune disease in MRL/MpJ(2+) mice. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Alabama, Div Dev & Clin Immunol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. Univ Texas, Inst Cellular & Mol Biol Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Marburg, Dept Gynecol Gynecol Oncol & Endocrinol, D-35037 Marburg, Germany. Univ Marburg, Clin Neonatol & Neuropediat, D-35037 Marburg, Germany. RP Schroeder, HW (reprint author), Univ Alabama, Div Dev & Clin Immunol, WTI 378,1530 3rd Ave S, Birmingham, AL 35294 USA. EM harry.schroeder@ccc.uab.edu OI Link, Jason/0000-0002-6892-0431 FU NIAID NIH HHS [AI42732, R01 AI048115, R01 AI047322, AI48115]; NIAMS NIH HHS [AR050777, R21 AR050777] NR 48 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY PY 2005 VL 42 IS 7 BP 789 EP 798 DI 10.1016/j.molimm.2004.07.049 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 923DG UT WOS:000228888600006 PM 15829267 ER PT J AU Marasco, WA AF Marasco, WA TI Therapeutic antibody gene transfer SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID VECTORS AB AAV vectors containing the combined furin-site and 2A 'self-cleaving' peptide facilitate high-level expression of monoclonal antibodies in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu NR 9 TC 11 Z9 11 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2005 VL 23 IS 5 BP 551 EP 552 DI 10.1038/nbt0505-551 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 923XS UT WOS:000228943500019 PM 15877069 ER PT J AU Golde, TE Bacskai, BJ AF Golde, TE Bacskai, BJ TI Bringing amyloid into focus SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID IN-VIVO; ALZHEIMERS-DISEASE; TRANSGENIC MICE; CONTRAST AGENT; MOUSE MODEL; PLAQUES; VISUALIZATION AB Amyloid deposits can be rapidly detected in the brains of living mice using a novel ligand and near-infrared fluorescence imaging. C1 Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. RP Golde, TE (reprint author), Mayo Clin, Coll Med, Dept Neurosci, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM tgolde@mayo.edu; bbacskai@partners.org NR 14 TC 4 Z9 4 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 2005 VL 23 IS 5 BP 552 EP 554 DI 10.1038/nbt0505-552 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 923XS UT WOS:000228943500020 PM 15877070 ER PT J AU Kumar, S Anderson, KC AF Kumar, S Anderson, KC TI Drug Insight: thalidomide as a treatment for multiple myeloma SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE immunomodulatory drug; multiple myeloma; stroma; thalidomide; tumor microenvironment ID BONE-MARROW ANGIOGENESIS; THERAPEUTIC IMPLICATIONS; STROMAL CELLS; IN-VIVO; DEXAMETHASONE; GROWTH; ADHESION; COMBINATION; RESISTANCE; DISEASE AB Multiple myeloma (MM) - a malignancy of the bone marrow-remains incurable by current therapies, and there is an urgent need for new drugs based on a better understanding of the underlying disease biology. MM is characterized by monoclonal plasma cells that accumulate in the bone marrow, which provides a microenvironment that promotes tumor cell growth and survival and protection against various therapeutic agents. The MM cell interacts with bone marrow stromal cells and endothelial cells, as well as osteoblasts and osteoclasts. Our understanding of the tumor microenvironment has already prompted the development of new agents that are aimed at disrupting the multiple facets of these interactions. It has also enabled the development of a comprehensive and rational approach to preclinical evaluation of new agents, facilitating the translation of in vitro studies to in vivo tumor models and, subsequently, to clinical trials. In this review, we describe the preclinical studies that led to the development of clinical trials of thalidomide and its immunomodulatory derivatives as therapeutic agents for MM. These drugs, alone or in combination, have shown impressive activity at all stages of the disease, and these demonstrations of clinical benefit have in turn validated our model systems for drug discovery in MM. Integration of data from clinical trials and laboratory studies will allow the design of future clinical trials that combine tbalidomide and its derivatives with other drugs, ultimately leading to more effective therapies and better outcomes in patients with MM. C1 Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Coll Med, Rochester, MN USA. Harvard Univ, Sch Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Neoplasia, 44 Binney St, Boston, MA 02115 USA. EM Kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 58 TC 24 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAY PY 2005 VL 2 IS 5 BP 262 EP 270 DI 10.1038/ncponc0174 PG 9 WC Oncology SC Oncology GA 932ZT UT WOS:000229594200012 PM 16264962 ER PT J AU Kochi, Y Yamada, R Suzuki, A Harley, JB Shirasawa, S Sawada, T Bae, SC Tokuhiro, S Chang, XT Sekine, A Takahashi, A Tsunoda, T Ohnishi, Y Kaufman, KM Kang, CSP Kang, CW Otsubo, S Yumura, W Mimori, A Koike, T Nakamura, Y Sasazuki, T Yamamoto, K AF Kochi, Y Yamada, R Suzuki, A Harley, JB Shirasawa, S Sawada, T Bae, SC Tokuhiro, S Chang, XT Sekine, A Takahashi, A Tsunoda, T Ohnishi, Y Kaufman, KM Kang, CSP Kang, CW Otsubo, S Yumura, W Mimori, A Koike, T Nakamura, Y Sasazuki, T Yamamoto, K TI A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities SO NATURE GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENETIC SUSCEPTIBILITY; REVISED CRITERIA; CHROMOSOME 1Q21; B-CELLS; FAMILY; POLYMORPHISMS; IDENTIFICATION; POPULATION; PSORIASIS AB Rheumatoid arthritis is a common autoimmune disease with a complex genetic etiology. Here we identify a SNP in the promoter region of FCRL3, a member of the Fc receptor-like family, that is associated with susceptibility to rheumatoid arthritis ( odds ratio = 2.15, P = 0.00000085). This polymorphism alters the binding affinity of nuclear factor-κ B and regulates FCRL3 expression. We observed high FCRL3 expression on B cells and augmented autoantibody production in individuals with the disease-susceptible genotype. We also found associations between the SNP and susceptibility to autoimmune thyroid disease and systemic lupus erythematosus. FCRL3 may therefore have a pivotal role in autoimmunity. C1 RIKEN, SNP Res Ctr, Lab Rheumat Dis, Yokohama, Kanagawa 2300045, Japan. Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo 1130033, Japan. Univ Oklahoma, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Int Med Ctr Japan, Tokyo 1628655, Japan. Hanyang Univ, Hosp Rheumat Dis, Div Rheumatol, Dept Internal Med, Seoul 133792, South Korea. RIKEN, SNP Res Ctr, Lab SNP Anal, Yokohama, Kanagawa 2300045, Japan. RIKEN, SNP Res Ctr, Lab Genotyping, Yokohama, Kanagawa 2300045, Japan. RIKEN, SNP Res Ctr, Lab Med Informat, Yokohama, Kanagawa 2300045, Japan. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo 1088639, Japan. Tokyo Womens Med Univ, Kidney Ctr, Dept Med, Tokyo 1628666, Japan. Hokkaido Univ, Sch Med, Dept Med 2, Sapporo, Hokkaido 0608638, Japan. RIKEN, SNP Res Ctr, Res Grp Personalized Med, Yokohama, Kanagawa 2300045, Japan. RP Yamada, R (reprint author), RIKEN, SNP Res Ctr, Lab Rheumat Dis, Yokohama, Kanagawa 2300045, Japan. EM ryamada@src.riken.go.jp RI Kang, Changwon/C-1938-2011; Tsunoda, Tatsuhiko/K-2061-2014; Yamamoto, Kazuhiko/N-5096-2015 FU NCRR NIH HHS [P20 RR020143]; NIAID NIH HHS [R01 AI024717]; NIAMS NIH HHS [P01 AR049084, R01 AR042460]; NIDCR NIH HHS [R01 DE015223] NR 50 TC 238 Z9 261 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2005 VL 37 IS 5 BP 478 EP 485 DI 10.1038/ng1540 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 922TU UT WOS:000228862300016 PM 15838509 ER PT J AU Umetsu, SE Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, GJ Nagumo, H Freeman, GJ Umetsu, DT DeKruyff, RH AF Umetsu, SE Lee, WL McIntire, JJ Downey, L Sanjanwala, B Akbari, O Berry, GJ Nagumo, H Freeman, GJ Umetsu, DT DeKruyff, RH TI TIM-1 induces T cell activation and inhibits the development of peripheral tolerance SO NATURE IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; SEVERE COMBINED IMMUNODEFICIENCY; COLONY-STIMULATING FACTOR; MOUSE BONE-MARROW; IMMUNOLOGICAL-TOLERANCE; DENDRITIC CELLS; GENE FAMILY; DISEASE; ANTIGEN; HYPERREACTIVITY AB We have examined the function of TIM-1, encoded by a gene identified as an 'atopy susceptibility gene' (Havcr1), and demonstrate here that TIM-1 is a molecule that costimulates T cell activation. TIM-1 was expressed on CD4(+) T cells after activation and its expression was sustained preferentially in T helper type 2 (T(H)2) but not T(H)1 cells. In vitro stimulation of CD4+ T cells with a TIM-1-specific monoclonal antibody and T cell receptor ligation enhanced T cell proliferation; in T(H)2 cells, such costimulation greatly enhanced synthesis of interleukin 4 but not interferon-gamma. In vivo, the use of antibody to TIM-1 plus antigen substantially increased production of both interleukin 4 and interferon-gamma in unpolarized T cells, prevented the development of respiratory tolerance, and increased pulmonary inflammation. Our studies suggest that immunotherapies that regulate TIM-1 function may downmodulate allergic inflammatory diseases. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP DeKruyff, RH (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM rosemarie.dekruyff@childrens.harvard.edu RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 FU NHLBI NIH HHS [R01 HL69507]; NIAID NIH HHS [P01 AI54456] NR 27 TC 179 Z9 205 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2005 VL 6 IS 5 BP 447 EP 454 DI 10.1038/ni1186 PG 8 WC Immunology SC Immunology GA 919RC UT WOS:000228634300016 PM 15793575 ER PT J AU Hahn, M Nicholson, MJ Pyrdol, J Wucherpfennig, KW AF Hahn, M Nicholson, MJ Pyrdol, J Wucherpfennig, KW TI Unconventional topology of self peptide-major histocompatibility complex binding by a human autoimmune T cell receptor SO NATURE IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; MHC CLASS-II; MULTIPLE-SCLEROSIS; CRYSTAL-STRUCTURE; IMMUNOLOGICAL SYNAPSE; POSITIVE SELECTION; STRUCTURAL BASIS; RECOGNITION; ANTIGEN; THYMUS AB Autoimmune diseases are caused by self-reactive lymphocytes that have escaped deletion. Here we have determined the structure of the trimolecular complex for a T cell receptor (TCR) from a patient with multiple sclerosis that causes autoimmunity in transgenic mice. The structure showed a TCR topology notably different from that of antimicrobial TCRs. Rather than being centered on the peptide-major histocompatibility complex, this TCR contacted only the N-terminal peptide segment and made asymmetrical interactions with the major histocompatibility complex helices. The interaction was dominated by the hypervariable complementarity-determining region 3 loops, indicating that unconventional topologies are possible because of the unique complementarity-determining region 3 sequences created during rearrangement. This topology reduces the interaction surface with peptide and alters the geometry for CD4 association. We propose that unusual TCR-binding properties can permit autoreactive T cells to escape deletion. C1 Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [AI045757, AI064177, P01 AI045757, R01 AI064177] NR 49 TC 157 Z9 161 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2005 VL 6 IS 5 BP 490 EP 496 DI 10.1038/ni1187 PG 7 WC Immunology SC Immunology GA 919RC UT WOS:000228634300021 PM 15821740 ER PT J AU Shamri, R Grabovsky, V Gauguet, JM Feigelson, S Manevich, E Kolanus, W Robinson, MK Staunton, DE von Andrian, UH Alon, R AF Shamri, R Grabovsky, V Gauguet, JM Feigelson, S Manevich, E Kolanus, W Robinson, MK Staunton, DE von Andrian, UH Alon, R TI Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines SO NATURE IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; FUNCTION-ASSOCIATED ANTIGEN-1; I-DOMAIN; VASCULAR ENDOTHELIUM; INTEGRIN AVIDITY; SHEAR-FLOW; L-SELECTIN; CA2+-DEPENDENT EPITOPE; CYTOPLASMIC DOMAIN; TALIN BINDING AB It is widely believed that rolling lymphocytes require successive chemokine-induced signaling for lymphocyte function associated antigen 1 (LFA-1) to achieve a threshold avidity that will mediate lymphocyte arrest. Using an in vivo model of lymphocyte arrest, we show here that LFA-1-mediated arrest of lymphocytes rolling on high endothelial venules bearing LFA-1 ligands and chemokines was abrupt. In vitro flow chamber models showed that endothelium-presented but not soluble chemokines triggered instantaneous extension of bent LFA-1 in the absence of LFA-1 ligand engagement. To support lymphocyte adhesion, this extended LFA-1 conformation required immediate activation by its ligand, intercellular adhesion molecule 1. These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion. C1 Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Bonn, Inst Mol Physiol & Dev Biol, Dept Cellular Biochem, D-53115 Bonn, Germany. Celltech Grp, Slough SL1 4EN, Berks, England. RP Alon, R (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. EM ronen.alon@weizmann.ac.il RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL056949] NR 49 TC 255 Z9 263 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2005 VL 6 IS 5 BP 497 EP 506 DI 10.1038/ni1194 PG 10 WC Immunology SC Immunology GA 919RC UT WOS:000228634300022 PM 15834409 ER PT J AU Larkin, JE Frank, BC Gavras, H Sultana, R Quackenbush, J AF Larkin, JE Frank, BC Gavras, H Sultana, R Quackenbush, J TI Independence and reproducibility across microarray platforms SO NATURE METHODS LA English DT Article ID GENE-EXPRESSION; OLIGONUCLEOTIDE MICROARRAYS; TECHNOLOGIES AB Microarrays have been widely used for the analysis of gene expression, but the issue of reproducibility across platforms has yet to be fully resolved. To address this apparent problem, we compared gene expression between two microarray platforms: the short otigonucleotide Affymetrix Mouse Genome 430 2.0 GeneChip and a spotted cDNA array using a mouse model of angiontensin II-induced hypertension. RNA extracted from treated mice was analyzed using Affymetrix and cDNA platforms and then by quantitative RT-PCR (qRT-PCR) for validation of specific genes. For the 11,710 genes present on both arrays, we assessed the relative impact of experimental treatment and platform on measured expression and found that biological treatment had a far greater impact on measured expression than did platform for more than 90% of genes, a result validated by qRT-PCR. In the small number of cases in which platforms yielded discrepant results, qRT-PCR generally did not confirm either set of data, suggesting that sequence-specific effects may make expression predictions difficult to make using any technique. C1 Inst Genom Res, Rockville, MD 20850 USA. Boston Univ, Med Ctr, Boston, MA 02118 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. George Washington Univ, Dept Biochem, Washington, DC 20037 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Stat, Baltimore, MD 21205 USA. RP Quackenbush, J (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. EM johnq@jimmy.harvard.edu FU NHLBI NIH HHS [U01 HL66617-01, R33 HL73712, U01 HL66580-01] NR 21 TC 299 Z9 316 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAY PY 2005 VL 2 IS 5 BP 337 EP 343 DI 10.1038/nmeth757 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 921UH UT WOS:000228790200011 PM 15846360 ER PT J AU Irizarry, RA Warren, D Spencer, F Kim, IF Biswal, S Frank, BC Gabrielson, E Garcia, JGN Geoghegan, J Germino, G Griffin, C Hilmer, SC Hoffman, E Jedlicka, AE Kawasaki, E Martinez-Murillo, F Morsberger, L Lee, H Petersen, D Quackenbush, J Scott, A Wilson, M Yang, YQ Ye, SQ Yu, W AF Irizarry, RA Warren, D Spencer, F Kim, IF Biswal, S Frank, BC Gabrielson, E Garcia, JGN Geoghegan, J Germino, G Griffin, C Hilmer, SC Hoffman, E Jedlicka, AE Kawasaki, E Martinez-Murillo, F Morsberger, L Lee, H Petersen, D Quackenbush, J Scott, A Wilson, M Yang, YQ Ye, SQ Yu, W TI Multiple-laboratory comparison of microarray platforms SO NATURE METHODS LA English DT Article ID OLIGONUCLEOTIDE AB Microarray technology is a powerful tool for measuring RNA expression for thousands of genes at once. Various studies have been published comparing competing platforms with mixed results: some find agreement, others do not. As the number of researchers starting to use microarrays and the number of cross-platform meta-analysis studies rapidly increases, appropriate platform assessments become more important. Here we present results from a comparison study that offers important improvements over those previously described in the literature. In particular, we noticed that none of the previously published papers consider differences between tabs. For this study, a consortium of ten laboratories from the Washington, DC-Baltimore, USA, area was formed to compare data obtained from three widely used platforms using identical RNA samples. We used appropriate statistical analysis to demonstrate that there are relatively large differences in data obtained in tabs using the same platform, but that the results from the best-performing tabs agree rather well. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Surg, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, JHU, NIDDK,Gene Profiling Ctr, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Inst Gen Res, Gaithersburg, MD 20878 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. NCIs Microarray Core Facil, Ctr Adv Technol, Gaithersburg, MD 20877 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. George Washington Univ, Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20052 USA. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NIAID, Res Technol Branch, DIR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21231 USA. RP Irizarry, RA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. EM rafa@jhu.edu RI Garcia, Joe/E-8862-2010; OI Germino, Gregory/0000-0002-3609-5588 FU NIDDK NIH HHS [U24DK58757] NR 15 TC 558 Z9 582 U1 3 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAY PY 2005 VL 2 IS 5 BP 345 EP 349 DI 10.1038/nmeth756 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 921UH UT WOS:000228790200012 PM 15846361 ER PT J AU Berkers, CR Verdoes, M Lichtman, E Fiebiger, E Kessler, BM Anderson, KC Ploegh, HL Ovaa, H Galardy, PJ AF Berkers, CR Verdoes, M Lichtman, E Fiebiger, E Kessler, BM Anderson, KC Ploegh, HL Ovaa, H Galardy, PJ TI Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib SO NATURE METHODS LA English DT Article ID LIVING CELLS; PROTEINS; TOOLS AB Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma, many of the basic pharmacologic parameters of bortezomib and its mode of action on myeloma cells remain to be determined. We describe the synthesis and use of a cell-permeant active site-directed probe, which allows profiling of proteasomal activities in living cells. When we compared proteasome activity patterns in cultured cells and crude cell extracts with this probe, we observed substantial differences, stressing the importance for bioassays compatible with live cells to ensure accuracy of such measurements. Using this probe, we investigated the in vivo subunit specificities of bortezomib and another inhibitor, MG132. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Program Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ovaa, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM h.ovaa@nki.nl RI Verdoes, Martijn/A-4911-2015; Berkers, Celia/I-3848-2016; OI Verdoes, Martijn/0000-0001-8753-3528; Kessler, Benedikt/0000-0002-8160-2446 NR 24 TC 150 Z9 155 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD MAY PY 2005 VL 2 IS 5 BP 357 EP 362 DI 10.1038/nmeth759 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 921UH UT WOS:000228790200014 PM 15846363 ER PT J AU Tolias, AS Keliris, GA Smirnakis, SM Logothetis, NK AF Tolias, AS Keliris, GA Smirnakis, SM Logothetis, NK TI Neurons in macaque area V4 acquire directional tuning after adaptation to motion stimuli SO NATURE NEUROSCIENCE LA English DT Article ID VISUAL AREA; SELECTIVE ATTENTION; RHESUS-MONKEY; MT; CONNECTIONS; LESIONS; CORTEX AB Neurons in area V4 of the macaque are generally not selective for direction of motion, as judged from their response to directional stimuli presented after a baseline condition devoid of movement. We used motion adaptation to investigate whether stimulation history influences direction-of-motion selectivity. We found that classically nondirectional V4 neurons develop direction-of-motion selectivity after adaptation, an observation that underscores the dynamic nature of functional cortical architecture. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Tolias, AS (reprint author), Max Planck Inst Biol Cybernet, Spemannstr 38, D-72076 Tubingen, Germany. EM andreas.tolias@tuebingen.mpg.de RI Keliris, Georgios A/B-6692-2008 OI Keliris, Georgios A/0000-0001-6732-1261 NR 15 TC 85 Z9 85 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2005 VL 8 IS 5 BP 591 EP 593 DI 10.1038/nn1446 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 923FM UT WOS:000228895100018 PM 15834417 ER PT J AU Huynh, KD Lee, JT AF Huynh, KD Lee, JT TI X-chromosome inactivation: a hypothesis linking ontogeny and phylogeny SO NATURE REVIEWS GENETICS LA English DT Review ID EARLY MOUSE EMBRYOS; HUMAN Y-CHROMOSOME; SEX-CHROMOSOMES; DOSAGE COMPENSATION; PREIMPLANTATION EMBRYOS; DNA-REPLICATION; LINKED GENES; XIST GENE; SPERMATOGENESIS; EXPRESSION AB In mammals, sex is determined by differential inheritance of a pair of dimorphic chromosomes: the gene-rich X chromosome and the gene-poor Y chromosome. To balance the unequal X-chromosome dosage between the XX female and XY male, mammals have adopted a unique form of dosage compensation in which one of the two X chromosomes is inactivated in the female. This mechanism involves a complex, highly coordinated sequence of events and is a very different strategy from those used by other organisms, such as the fruitfly and the worm. Why did mammals choose an inactivation mechanism when other, perhaps simpler, means could have been used? Recent data offer a compelling link between ontogeny and phylogeny. Here, we propose that X-chromosome inactivation and imprinting might have evolved from an ancient genome-defence mechanism that silences unpaired DNA. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@frodo.mgh.harvard.edu NR 92 TC 80 Z9 82 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD MAY PY 2005 VL 6 IS 5 BP 410 EP 418 DI 10.1038/nrg1604 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 922TZ UT WOS:000228862900016 PM 15818384 ER PT J AU Bouix, S Pruessner, JC Collins, DL Siddiqi, K AF Bouix, S Pruessner, JC Collins, DL Siddiqi, K TI Hippocampal shape analysis using medial surfaces SO NEUROIMAGE LA English DT Article DE MRI; structural analysis; medial temporal lobe; medial surfaces; hippocampus; shape analysis ID NONLINEAR DIMENSIONALITY REDUCTION; COORDINATE SYSTEM; CEREBRAL-CORTEX; SEGMENTATION; MODELS; IMAGES; MRI; REGISTRATION; MORPHOMETRY; ALGORITHM AB In magnetic resonance imaging (MRI) research, significant attention has been paid to the analysis of the hippocampus (HC) within the medial temporal lobe because of its importance in memory and learning, and its role in neurodegenerative diseases. Manual segmentation protocols have established a volume decline in the HC in conjunction with Alzheimer's disease, epilepsy, post-traumatic stress disorder, and depression. Furthermore, recent studies have investigated age-related changes of HC volume which show an interaction with,,ender: in earl, adulthood, volume reduction of the HC is found in men but not in women. In this paper, we investigated gender differences in normal subjects in young adulthood by employing a shape analysis of the HC using medial surfaces. For each subject, the most prominent medial manifold of the HC was extracted and flattened. The flattened sheets were then registered using both a rigid and a non-rigid alignment technique, and the medial surface radius was expressed as a height function over them. This allowed for an investigation of the association between subject variables and the local width of the HC. With regard to the effects of age and gender, it could be shown that the previously observed gender differences were mostly due to volume loss in males in the lateral areas of the HC head and tail. We suggest that the analysis of HC shape using medial surfaces might thus serve as a complimentary technique to investigate group differences to the established segmentation protocols for volume quantification in MRI. © 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston VA Healthcare Syst, Boston, MA 02115 USA. McGill Univ, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. McGill Univ, Sch Comp Sci, Montreal, PQ, Canada. RP Bouix, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab, Boston, MA 02115 USA. EM sylvain@bwh.harvard.edu; jens@bic.mni.mcgill.ca; louis@bic.mni.mcgill.ca; siddiqi@cim.mcgill.ca OI Bouix, Sylvain/0000-0003-1326-6054 NR 46 TC 61 Z9 62 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2005 VL 25 IS 4 BP 1077 EP 1089 DI 10.1016/j.neuroimage.2004.12.051 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 924WJ UT WOS:000229011200006 PM 15850726 ER PT J AU Makris, N Schlerf, JE Hodge, SM Haselgrove, C Albaugh, MD Seidman, LJ Rauch, SL Harris, G Biederman, J Caviness, VS Kennedy, DN Schmahmann, JD AF Makris, N Schlerf, JE Hodge, SM Haselgrove, C Albaugh, MD Seidman, LJ Rauch, SL Harris, G Biederman, J Caviness, VS Kennedy, DN Schmahmann, JD TI MRI-based surface-assisted parcellation of human cerebellar cortex: An anatomically specified method with estimate of reliability SO NEUROIMAGE LA English DT Article DE human cerebellum; MRI; morphometry; volumetrics; functional MRI; reliability ID DEFICIT HYPERACTIVITY DISORDER; CEREBRAL-BLOOD-FLOW; FUNCTIONAL-ANATOMY; RHESUS-MONKEY; HUMAN BRAIN; ATTENTION; ORGANIZATION; LOCALIZATION; INVOLVEMENT; PROJECTIONS AB We revisit here a surface assisted parcellation (SAP) system of the human cerebellar cortex originally described in Makris, N., Hodge, S.M., Haselgrove, C., Kennedy, D.N., Dale, A., Fischl, B., Rosen, MR., Harris, G., Caviness, V.S., Jr., Schmahmann, J.D., 2003. Human cerebellum: surface-assisted cortical parcellation and volumetry with magnetic resonance imaging. J Cogn Neurosci 15, 584-599. This system preserves the topographic and morphologic uniqueness of the individual cerebellum and allows for volumetric analysis and representation of multimodal structural and functional data on the cerebellar cortex. This methodology integrates features of automated routines of the program FreeSurfer as well as semi-automated and manual procedures of the program Cardviews to create 64 cerebellar parcellation units based on fissure information and anatomical landmarks of the cerebellar surface. Using this technique, we undertook the parcellation of ten cerebella by two independent raters. The reliability of the resulting parcellation units (64 total) was high, with an average Intraclass Correlation Coefficient (ICC) of 0.724 in the vermis and 0.853 in the hemispheres. Clusters of parcellation units were then created, based on lobar and connectivity data and functional hypotheses. These 36 clusters, when treated as anatomical units, had an average ICC of 0.933. Where-as the individual units provide a high level of detail and anatomical specificity, the clusters add flexibility to the analysis by providing higher reliability. © 2005 Elsevier Inc. All rights reserved. C1 CMA, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, A Martinos Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol Comp Aided Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Makris, N (reprint author), CMA, MGH East,149 13th St, Charlestown, MA 02129 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012; Albaugh, Matthew/R-4349-2016 FU NIDCD NIH HHS [P01 DC 03610]; NIMH NIH HHS [1R01 MH 067980, MH 60219] NR 57 TC 57 Z9 59 U1 5 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY 1 PY 2005 VL 25 IS 4 BP 1146 EP 1160 DI 10.1016/j.neuroimage.2004.12.056 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 924WJ UT WOS:000229011200012 PM 15850732 ER PT J AU Lev, MH AF Lev, MH TI Stroke I: Overview and current clinical practice SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lev, MH (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM mlev@partners.org NR 0 TC 1 Z9 1 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP XV EP XVI DI 10.1016/j.nic.2005.09.001 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900001 ER PT J AU Smith, EE Rosand, J Greenberg, SM AF Smith, EE Rosand, J Greenberg, SM TI Hemorrhagic stroke SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; GRADIENT-ECHO MRI; PRIMARY INTRACEREBRAL HEMORRHAGE; APOLIPOPROTEIN-E EPSILON-2; INTRACRANIAL HEMORRHAGE; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; RISK-FACTORS; CLINICAL-FEATURES; SPIN-ECHO AB Neuroimaging by CT or MR imaging is necessary for the identification of hemorrhagic stroke and provides information about its cause. The appearance of intracranial hematoma (ICH) on CT and MR imaging evolves over time and must be understood to facilitate accurate diagnosis. The cause of ICH varies by location. New evidence suggests that MR imaging alone may be adequate to identify hemorrhagic stroke in the acute setting, and that MR imaging is superior to CT for identification of chronic microbleeds and hemorrhagic conversion of infarction. C1 Massachusetts Gen Hosp, Stroke Service, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Stroke Service, VBK 802, Boston, MA 02114 USA. EM eesmith@partners.org OI Smith, Eric/0000-0003-3956-1668 FU NINDS NIH HHS [K23 NS046327] NR 81 TC 14 Z9 17 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP 259 EP + DI 10.1016/j.nic.2005.05.003 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900003 PM 16198939 ER PT J AU Camargo, ECS Bacheschi, LA Massaro, AR AF Camargo, ECS Bacheschi, LA Massaro, AR TI Stroke in Latin America SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL VENOUS THROMBOSIS; SICKLE-CELL-DISEASE; CHAGAS-DISEASE; CEREBROVASCULAR-DISEASE; HEART-DISEASE; YOUNG-ADULTS; INTRACEREBRAL HEMORRHAGE; ISCHEMIC-STROKE; SOUTH-AMERICA; BUENOS-AIRES AB Stroke is one of the leading causes of mortality in Latin America, with variable incidence and prevalence throughout the continent reflecting regional socioeconomic differences. In Latin America, uncontrolled hypertension is one of the major causes of stroke, but other modifiable risk factors also play a role, such as heavy alcohol consumption and smoking. Intracerebral hemorrhage and lacunar stroke are more frequent in Latin America than in North America and Europe. There are multiple causes of stroke that are endemic to Latin America, including neurocysticercosis, Chagas' disease, sickle cell anemia, malaria, hemorrhagic fever, and snake bites. C1 Harvard Univ, Dept Neurol, Stoke Service, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. Univ Sao Paulo, Fac Med, Div Neurol & Neurosurg, Sao Paulo, Brazil. Univ Fed Sao Paulo, Escola Paulista Med, Dept Neurol, Sao Paulo, Brazil. Univ Fed Sao Paulo, Escola Paulista Med, Stroke Serv, Hosp Sao Paulo, Sao Paulo, Brazil. RP Camargo, ECS (reprint author), Harvard Univ, Dept Neurol, Stoke Service, Massachusetts Gen Hosp,Med Sch, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM ecamargo@partners.org NR 84 TC 8 Z9 9 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP 283 EP + DI 10.1016/j.nic.2005.07.002 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900005 PM 16198941 ER PT J AU Makris, N Caviness, VS Kennedy, DN AF Makris, N Caviness, VS Kennedy, DN TI An introduction to MR imaging-based stroke morphometry SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL-ISCHEMIA; CLINICAL-APPLICATIONS; COORDINATE SYSTEM; VASCULAR PATTERN; CORTICAL SURFACE; FRONTAL-CORTEX; RHESUS-MONKEY; HUMAN BRAIN; SEGMENTATION; DIFFUSION AB The anatomic description of the stroke lesion is an essential component of clinical diagnosis and treatment and has become an established tool in investigations into underlying stroke pathophysiology. Magnetic resonance (MR) imaging permits quantitative evaluation of the distributed consequences of the pathologic stroke insult. General properties of stroke effects have emerged using these tools. This article surveys the classes of morphometric data that are available from conventional MR images, the methods for extracting quantitative results, and samples of the application of these methods to stroke. These samples highlight anatomic-based considerations regarding the nature of stroke and its repercussions within the brain parenchyma. C1 Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Makris, N (reprint author), Massachusetts Gen Hosp, Ctr Morphometr Anal, MGH E Bldg,149 13th St, Charlestown, MA 02139 USA. EM nikos@cma.mgh.harvard.edu RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA 09467]; NINDS NIH HHS [NS34189, P01 NS27950] NR 58 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP 325 EP + DI 10.1016/j.nic.2005.06.004 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900007 PM 16198943 ER PT J AU Romero, JM Ackerman, RH Dault, NA Lev, MH AF Romero, JM Ackerman, RH Dault, NA Lev, MH TI Noninvasive evaluation of carotid artery stenosis: Indications strategies, and accuracy SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID ENHANCED MR-ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; COMPUTED-TOMOGRAPHY ANGIOGRAPHY; IN-VIVO ACCURACY; ATHEROSCLEROTIC PLAQUE; SYMPTOMATIC PATIENTS; DOPPLER ULTRASOUND; DUPLEX ULTRASOUND; ISCHEMIC SYMPTOMS; CT ANGIOGRAPHY AB Carotid artery occlusive disease is an important stroke risk factor and accounts for a significant proportion of stroke morbidity and mortality. In this article we review the major clinical trials related to stroke risk in symptomatic and asymptomatic patients who have internal carotid artery (ICA) stenosis; techniques for noninvasive screening of ICA stenosis including ultrasound, MR angiography, and CT angiography; and evolving algorithms for ICA evaluation. We comment on current interest in plaque morphology as a risk factor for stroke. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Romero, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Gray Bldg 254,55 Fruit St, Boston, MA 02114 USA. EM Javier_Romero@hms.harvard.edu NR 62 TC 13 Z9 14 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP 351 EP + DI 10.1016/j.nic.2005.06.005 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900009 PM 16198945 ER PT J AU Sims, J Schwamm, LH AF Sims, J Schwamm, LH TI The evolving role of acute stroke imaging in intravenous thrombolytic therapy: Patient selection and outcomes assessment SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN-ACTIVATOR; INTERNAL CAROTID-ARTERY; RANDOMIZED CONTROLLED-TRIAL; PERFUSION COMPUTED-TOMOGRAPHY; ACUTE HEMISPHERIC STROKE; DIFFUSION-WEIGHTED MRI; CEREBRAL-BLOOD-FLOW; CT ANGIOGRAPHY; HYPERACUTE STROKE AB In early trials of thrombolysis, unenhanced CT was used to exclude patients with brain hemorrhage or large infarctions but was insensitive to stroke pathophysiology or early signs of cerebral ischemia or infarction. Currently, CT angiography, CT perfusion, and MR imaging can provide information about stroke mechanisms and prognosis, quantify penumbral tissue, and support risk stratification and patient selection. This article reviews the role of neuroimaging in the original intravenous thrombolytic trials, current application of these technologies, and the potential future role of imaging to extend the time window for thrombolysis and to augment therapeutic success. C1 Massachusetts Gen Hosp, Dept Neurol, TeleStroke & Acute Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. MIT, Clin Res Ctr, Boston, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, TeleStroke & Acute Stroke Serv, 55 Fruit St,VBK915, Boston, MA 02114 USA. EM Lschwamm@partners.org OI Schwamm, Lee/0000-0003-0592-9145 NR 121 TC 14 Z9 17 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2005 VL 15 IS 2 BP 421 EP + DI 10.1016/j.nic.2005.06.001 PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 976PF UT WOS:000232744900014 PM 16198950 ER PT J AU Walker, M Meekins, G Hu, SC AF Walker, M Meekins, G Hu, SC TI Yoga neuropathy - A snoozer SO NEUROLOGIST LA English DT Article DE sciatic nerve; yoga; compression neuropathy ID SATURDAY NIGHT PALSY; SCIATIC NEUROPATHY AB Sciatic nerve compression very rarely occurs bilaterally. The authors present a woman with profound lower extremity weakness and sensory abnormality after falling asleep in the head-to-knees yoga position (also called "Paschimottanasana"). Clinical and electrodiagnostic findings are discussed in detail and a brief review of the literature is presented. C1 Univ Washington, Dept Neurol, Med Ctr, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Walker, M (reprint author), Univ Washington, Dept Neurol, Med Ctr, 1959 NE Pacif,Box 356465, Seattle, WA 98195 USA. EM MWalkerMD@aol.com NR 5 TC 15 Z9 15 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD MAY PY 2005 VL 11 IS 3 BP 176 EP 178 DI 10.1097/01.nrl.0000159986.75426.d5 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 925KY UT WOS:000229053200005 PM 15860140 ER PT J AU Finnema, SJ Seneca, N Farde, L Shchukin, E Sovago, J Gulyas, B Wikstrom, HV Innis, RB Neumeyer, JL Halldin, C AF Finnema, SJ Seneca, N Farde, L Shchukin, E Sovago, J Gulyas, B Wikstrom, HV Innis, RB Neumeyer, JL Halldin, C TI A preliminary PET evaluation of the new dopamine D-2 receptor agonist [C-11]MNPA in cynomolgus monkey SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dopamine agonist; D-2 receptor; high-affinity state; PET; monkey; [C-11]MNPA ID POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN-PRIMATES; ANTERIOR-PITUITARY; D2-DOPAMINE RECEPTORS; C-11 RACLOPRIDE; AFFINITY STATES; BINDING; BRAIN; RELEASE; RODENTS AB This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D-2-like receptor agonist, (R)-2(11)-CH3O-N-n-propylnorapomorphine ([C-11]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D-2 receptor (D2R). MNPA is a selective D2-like receptor agonist with a high affinity (K-i=0.17 nM). [C-11]MNPA was successfully synthesized by direct O-methylation of(R)-2-hydroxy-NPA using [C-11]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D2R, with a maximum striatum-to-cerebellum ratio of 2.23 +/- 0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37 +/- 0.06 at 72 min. The pretreatment study demonstrated high specific binding to D2R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [C-11]MNPA has potential as an agonist radioligand for the D-2-like receptor and has potential for examination of the high-affinity state of the D2R in human subjects and patients with neuropsychiatric disorders. (c) 2005 Elsevier Inc. All rights reserved. C1 Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Univ Groningen, Univ Ctr Pharm, Dept Med Chem, NL-9913 AV Groningen, Netherlands. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. RP Halldin, C (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM christer.halldin@cns.ki.se RI Sovago, Judit/G-7961-2011; Gulyas, Balazs/F-9508-2015 NR 38 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2005 VL 32 IS 4 BP 353 EP 360 DI 10.1016/j.nucmedbio.2005.01.007 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 930MR UT WOS:000229420600005 PM 15878504 ER PT J AU Buerhaus, PI Donelan, K Ulrich, BT Kirby, L Norman, L Dittus, R AF Buerhaus, PI Donelan, K Ulrich, BT Kirby, L Norman, L Dittus, R TI Registered nurses' perception of nursing SO NURSING ECONOMICS LA English DT Article ID SATISFACTION AB In Part I of this series (March/April 2005), findings from a 2002 and 2004 survey highlighted changes in nurse perceptions of the workforce shortage with respect to its effects on practice, directional trends, causes, and solutions. In Part 11 of this series the authors analyze and compare findings from the 2002 and 2004 surveys with respect to job satisfaction including the quality of professional relationships. Reports of being "very satisfied" with your job increased significantly from 21% (2002) to 34% (2004) and were predicted by the organization's emphasis on patient care, management recognition for personal lives, satisfaction with salary and benefits, job security, and positive relationship with other nurses and management. For those reporting decreased satisfaction, burnout, the burden of non-nursing tasks, a higher number of patient care assignments, and a negative view of the health care systems predicted the decline. Perception of relationships between nurses reported as "very good" or "excellent" increased significantly from 53% (2002) to 72% (2004). Currently, only 57% reported "very good" or "excellent" relationships with LPNs and 43% with support staff. While the majority of RNs would recommend a career in nursing, fewer than half of RNs agreed that nursing was a good career for individuals seeking respect in their career. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Nursing Spectrum NurseWeek, Pearland, TX USA. Vanderbilt Univ, Dept Med, Nashville, TN 37240 USA. RP Buerhaus, PI (reprint author), Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. NR 16 TC 17 Z9 17 U1 0 U2 4 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD MAY-JUN PY 2005 VL 23 IS 3 BP 110 EP + PG 10 WC Nursing SC Nursing GA 046HJ UT WOS:000237801900002 PM 16033139 ER PT J AU Taveras, EM Rifas-Shiman, S Berkey, CS Rockett, HRH Field, AE Frazir, AL Colditz, GA Gillman, MW AF Taveras, EM Rifas-Shiman, S Berkey, CS Rockett, HRH Field, AE Frazir, AL Colditz, GA Gillman, MW TI Family dinner and adolescent overweight SO OBESITY RESEARCH LA English DT Article DE family dinner; overweight; adolescents; longitudinal studies ID FOOD FREQUENCY QUESTIONNAIRE; CHILDHOOD OVERWEIGHT; EATING BEHAVIORS; OLDER CHILDREN; PATTERNS; TRENDS; ASSOCIATIONS; PREVALENCE; VALIDATION; WEIGHT AB Objective: The purpose of this study was to examine both cross-sectional and longitudinal associations between frequency of family dinner and overweight status in a large sample of 9- to 14-year-old children. Research Methods and Procedures: We studied a cohort of 7784 girls and 6647 boys, 9 to 14 years of age at baseline in 1996, participating in the Growing Up Today Study. From annual mailed surveys, we calculated BMI from self-reported height and weight and assessed frequency of family dinner over the previous year. We defined, "overweight" as age- and sex-specific BMI >85th percentile. We performed multiple logistic regression analyses; the longitudinal analyses assessed the association of previous year family dinner consumption with 1-year incidence of becoming overweight, using prospective data from 1996 through 1999. Results: At baseline in 1996, 16% of participants had family dinner "never or some days," 40% on "most days," and 44% every day." Across these categories, overweight prevalence for girls was 19.4%, 16.6%, and 16.7% and for boys was 24.6%, 23.3% and 22.7%, respectively. In cross-sectional analyses,. adjusting for potential confounders, the odds of being overweight-was 0.85 [95% confidence interval (Cl): 0.76,496] among children who ate family dinner on "most days" or "every day" compared with those who ate family dinner "never or Some days." In longitudinal multivariate, models, the odds ratios between previous year frequency of eating family dinner and 1-year incidence of becoming overweight were 0.95 (95% CI: 0.78, 1.16) and 1.04 (95% CI: 0.95, 1.27) for children who ate family dinner on "most days" and "every day," respectively, compared with those whoa ate family dinner "never or some days." Discussion: The frequency of eating family dinner was inversely associated with overweight prevalence at baseline but not with likelihood of becoming overweight in longitudinal analyses. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA 02115 USA. Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Gillman, MW (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM Matthew_Gillman@harvardpilgrim.org RI Brower, Susan/C-7090-2009; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL68041]; NIDDK NIH HHS [DK46200, DK46834, DK59570] NR 29 TC 138 Z9 141 U1 0 U2 5 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD MAY PY 2005 VL 13 IS 5 BP 900 EP 906 DI 10.1038/oby.2005.104 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 932DH UT WOS:000229533900015 PM 15919844 ER PT J AU DeBernardo, RL Perkins, RB Littell, RD Krasner, CN Duska, LR AF DeBernardo, RL Perkins, RB Littell, RD Krasner, CN Duska, LR TI Low-molecular-weight heparin (dalteparin) in women with gynecologic malignancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 07-11, 2004 CL San Diego, CA SP Soc Gynecol Oncol ID LOW-DOSE HEPARIN; DEEP-VEIN-THROMBOSIS; VENOUS THROMBOEMBOLISM PROPHYLAXIS; PNEUMATIC CALF COMPRESSION; UNFRACTIONATED HEPARIN; RANDOMIZED TRIAL; ONCOLOGY SURGERY; PREVENTION; RISK; SAFETY AB OBJECTIVE: To compare the efficacy of dalteparin, a low-molecular-weight heparin, to unfractionated heparin (UFH) in the prevention of deep venous thrombosis (DVT) and pulmonary embolism in patients after surgery for gynecologic malignancy. METHODS: The medical records of all patients undergoing major surgery on the Gynecologic Oncology Service at the Massachusetts General Hospital from July 2002 through April 2003 were reviewed. Patients with confirmed malignancy were included. Between July 1, 2002, and November 15, 2002, dalteparin (5,000 U subcutaneously each day) was used for postoperative prophylaxis for DVT and pulmonary embolus. After November 15, 2002, the method of prophylaxis was changed to UFH (5,000 U subcutaneously every 8 hours) exclusively. Patients were evaluated for DVT or pulmonary embolus based on clinical suspicion using computed tomographic angiography, ventilation and perfusion scan, or lower extremity doppler. RESULTS: A total of 214 patients were identified who met study criteria. Dalteparin was administered to 103 patients, and UFH was administered to 111. The rates of clinically significant DVT or pulmonary embolus in patients receiving dalteparin and UFH were 8.9% and 1.2%, respectively (P = .009). Major risk factors for DVT or pulmonary embolus, including age, obesity, duration of surgery, and type of malignancy, did not differ between groups. There were no significant differences in bleeding complications or transfusion requirements between groups. CONCLUSION: The low-molecular-weight heparin dalteparin dosed 5,000 U daily is inadequate postoperative prophylaxis in women undergoing surgery for gynecologic cancer. In addition, heparin administered every 8 hours was not associated with increased bleeding complications. The use of dalteparin at the doses used in this study should be questioned until a large randomized trial shows efficacy m these high-risk patients. (c) 2005 by The American College of Obstetricians and Gynecologists. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, 100 Blossom St,Cox 5, Boston, MA 02114 USA. EM lduska@partners.org OI Littell, Ramey/0000-0001-6096-6075 NR 21 TC 5 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 2005 VL 105 IS 5 BP 1006 EP 1011 DI 10.1097/01.AOG.0000153026.61249.c7 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 920FG UT WOS:000228674200012 PM 15863537 ER PT J AU Seixas, NS Goldman, B Sheppard, L Neitzel, R Norton, S Kujawa, SG AF Seixas, NS Goldman, B Sheppard, L Neitzel, R Norton, S Kujawa, SG TI Prospective noise induced changes to hearing among construction industry apprentices SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID PRODUCT OTOACOUSTIC EMISSIONS; EXPOSURE; COCHLEA; WORKERS AB Aims: To characterise the development of noise induced damage to hearing. Methods: Hearing and noise exposure were prospectively monitored among a cohort of newly enrolled construction industry apprentices and a comparison group of graduate students, using standard pure tone audiometry and distortion product otoacoustic emissions (DPOAEs). A total of 328 subjects ( 632 ears) were monitored annually an average of 3.4 times. In parallel to these measures, noise exposure and hearing protection device (HPD) use were extensively monitored during construction work tasks. Recreational/non-occupational exposures also were queried and monitored in subgroups of subjects. Trade specific mean exposure L-eq levels, with and without accounting for the variable use of hearing protection in each trade, were calculated and used to group subjects by trade specific exposure level. Mixed effects models were used to estimate the change in hearing outcomes over time for each exposure group. Results: Small but significant exposure related changes in DPOAEs over time were observed, especially at 4 kHz with stimulus levels (L1) between 50 and 75 dB, with less clear but similar patterns observed at 3 kHz. After controlling for covariates, the high exposure group had annual changes in 4 kHz emissions of about 0.5 dB per year. Pure tone audiometric thresholds displayed only slight trends towards increased threshold levels with increasing exposure groups. Some unexpected results were observed, including an apparent increase in DPOAEs among controls over time, and improvement in behavioural thresholds among controls at 6 kHz only. Conclusions: Results indicate that construction apprentices in their first three years of work, with average noise exposures under 90 dBA, have measurable losses of hearing function. Despite numerous challenges in using DPOAEs for hearing surveillance in an industrial setting, they appear somewhat more sensitive to these early changes than is evident with standard pure tone audiometry. C1 Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Seixas, NS (reprint author), Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. EM nseixas@u.washington.edu RI Neitzel, Richard/P-7733-2015 OI Neitzel, Richard/0000-0001-5500-2589 FU NIOSH CDC HHS [5 R01 OH03912] NR 30 TC 47 Z9 52 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 2005 VL 62 IS 5 BP 309 EP 317 DI 10.1136/oem.2004.018143 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 917KV UT WOS:000228461300010 PM 15837852 ER PT J AU Patel, V Shrager, JB AF Patel, V Shrager, JB TI Which patients with stage III non-small cell lung cancer should undergo surgical resection? SO ONCOLOGIST LA English DT Article DE non-small cell lung carcinoma; neoadjuvant therapy; pulmonary surgical procedures; neoplasm staging ID COMPARING PERIOPERATIVE CHEMOTHERAPY; SATELLITE NODULES; PLEURAL SPREAD; SURGERY; TRIAL; SURVIVAL; CARCINOMA; METASTASES; PROGNOSIS; REVISIONS AB The treatment of patients with stage III NSCLC remains controversial. Stage III NSCLC comprises a fairly heterogeneous group of tumors, and furthermore only sparse data from randomized clinical trials exist to guide therapy decisions. This review article proposes a management algorithm for patients with stage III NSCLC that is based upon the currently available data on surgical therapy, chemotherapy, and radiation therapy. By necessity, given the paucity of strong data, a good deal of opinion is offered. The choice to proceed with aggressive, combined modality treatment is presented in light of extent of local disease as well as patient performance status. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Shrager, JB (reprint author), Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA. EM jshrag@mail.med.upenn.edu NR 36 TC 11 Z9 12 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2005 VL 10 IS 5 BP 335 EP 344 DI 10.1634/theoncologist.10-5-335 PG 10 WC Oncology SC Oncology GA 925BH UT WOS:000229026000014 PM 15851792 ER PT J AU Perez-Soler, R Delord, JP Halpern, A Kelly, K Krueger, J Suresa, BM von Pawel, J Temel, J Siena, S Soulieres, D Saltz, L Leyden, J AF Perez-Soler, R Delord, JP Halpern, A Kelly, K Krueger, J Suresa, BM von Pawel, J Temel, J Siena, S Soulieres, D Saltz, L Leyden, J TI HER1/EGFR inhibitor-associated rash: Future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum SO ONCOLOGIST LA English DT Article DE HER1/EGFR; rash; adverse event; survival; NSCLC; tyrosine kinase inhibitor; monoclonal antibody ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; CELL LUNG-CANCER; PHASE-II TRIAL; COLORECTAL-CANCER; ANTIBODY CETUXIMAB; GEFITINIB ZD1839; PLUS IRINOTECAN; SOLID TUMORS; EGF RECEPTOR AB Skin rash associated with HER1/epidermal growth factor receptor (EGFR) inhibitors is common. The lack of clinical and patient guidance for this often chronic and sometimes distressing side effect makes rash management and etiology investigation high priorities. To address this, oncologists and dermatologists with experience with HER1/EGFR inhibitors attended the HER1/EGFR Inhibitor Rash Management Forum. Recommendations include continued analysis of the correlation between rash and clinical outcome and improving the accuracy and reproducibility of terminology and grading systems. Because acne vulgaris has a unique pathology, and the pathology and etiology of rash are unclear yet distinct from acne vulgaris, using such terms as acne, acne-like, or acneiform should be avoided. Until there is a specific dermatological definition, rash is best described using phenotypic terms for its appearance and location. It is currently unknown which agents are best for treating rash. Clinical trials of rash treatments are urgently required, and suggestions for agents to consider are made based on current knowledge. The effect of dose reduction or interruption on rash should also be investigated. Secondarily infected rash may be more frequent than has been previously recognized, and some investigators favor empiric use of an oral antibiotic if this appears to be the case. Suggestions for patients include makeup to camouflage the rash and an emollient to prevent and alleviate skin dryness. The increasing use of HER1/EGFR-targeted agents makes managing rash important. We hope the outcomes from this Forum provide background for future studies. C1 Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oncol, Bronx, NY 10467 USA. Inst Claudius Regaud, Toulouse, France. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. Rockefeller Univ, Dermatol Lab, New York, NY 10021 USA. Hosp Gen Univ Alicante, Med Oncol Serv, Alicante, Spain. Asklepios Fachklin, Gauting, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Osped Niguarda Ca Granda, Div Oncol Med Falck, Milan, Italy. CHUM, Ctr Oncol, Montreal, PQ, Canada. Hosp Univ Penn, Malvern, PA USA. RP Perez-Soler, R (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Dept Oncol, Hofheimer 100,111 E 210th St, Bronx, NY 10467 USA. EM rperezso@montefiore.org RI DELORD, Jean-Pierre/I-8866-2014; OI SIENA, SALVATORE/0000-0002-2681-2846; Saltz, Leonard/0000-0001-8353-4670 NR 48 TC 145 Z9 152 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAY PY 2005 VL 10 IS 5 BP 345 EP 356 DI 10.1634/theoncologist.10-5-345 PG 12 WC Oncology SC Oncology GA 925BH UT WOS:000229026000015 PM 15851793 ER PT J AU Partridge, A Schapira, L AF Partridge, A Schapira, L TI Pregnancy and breast cancer - Epidemiology, treatment, and safety issues SO ONCOLOGY-NEW YORK LA English DT Article ID CARCINOMA; WOMEN; RISK; SURVIVAL; TERM; OUTCOMES AB The relationship between pregnancy and breast cancer is complex, and a paucity of available data further complicates decision-making for many women diagnosed with breast cancer during pregnancy or desiring to become pregnant after such a diagnosis. Treatment of breast cancer during pregnancy requires a multidisciplinary care team and careful consideration of the risk of the disease and gestational age of the fetus, in conjunction with the patient's preferences. Chemotherapy should be deferred beyond the first trimester. There is no evidence that pregnancy in a breast cancer survivor will decrease long-term survival; in fact, studies suggest a potential protective effect of pregnancy after breast cancer in terms of the risk of recurrence. However, the available studies are limited by substantial potential biases, and concerns remain for some women and their doctors about the risks of pregnancy after breast cancer. This article reviews what is known about the association between pregnancy and breast cancer, discusses treatment options for women diagnosed with the disease during pregnancy, and summarizes evidence regarding the safety of pregnancy after breast cancer. C1 Brigham & Womens Hosp, Breat & Gynecol Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Partridge, A (reprint author), Brigham & Womens Hosp, Breat & Gynecol Ctr, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD MAY PY 2005 VL 19 IS 6 BP 693 EP 697 PG 5 WC Oncology SC Oncology GA 052EJ UT WOS:000238214000003 PM 15971447 ER PT J AU Chang, EL Hayes, J Hatton, M Rubin, PAD AF Chang, EL Hayes, J Hatton, M Rubin, PAD TI Acquired lower eyelid epiblepharon in patients with thyroid eye disease SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CONGENITAL ENTROPION; DECOMPRESSION; ORBITOPATHY; HEIGHT; REPAIR AB Purpose: To describe a series of patients with acquired epiblepharon secondary to thyroid-related orbitopathy. Methods: Retrospective case series of 9 patients with thyroid-related orbitopathy who had epiblepharon. Results: Seven patients had epiblepharon in both lower eyelids and 2 patients had it in one lower eyelid. Six of the 9 patients were Asian. Each patient had punctate keratopathy. Epiblepharon resolved in all but one patient after treating coexisting manifestations of thyroid-related orbitopathy. One patient required epiblepharon repair. Conclusions: We describe a new finding of acquired epiblepharon in the setting of thyroid-related orbitopathy. The majority of patients have spontaneous resolution of the epiblepharon after other surgical procedures for thyroid-related orbitopathy. C1 Doheny Eye Inst, Los Angeles, CA 90033 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chang, EL (reprint author), Div Ophtalm Plast & Reconstruct Surg, 1450 San Pablo St,Room 4705, Los Angeles, CA 90033 USA. EM elichang@usc.edu; eye_plastics@meei.harvard.edu NR 16 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY PY 2005 VL 21 IS 3 BP 192 EP 196 DI 10.1097/01/IOP.0000160597.59156.79 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 935OE UT WOS:000229790800005 PM 15942493 ER PT J AU Hatton, MP Durand, ML Rubin, PAD AF Hatton, MP Durand, ML Rubin, PAD TI Chronic Staphylococcus aureus infection leading to pyogenic granuloma and preventing socket re-epithelialization after orbital exenteration SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GRAFT AB A 71-year-old woman underwent extenteration for conjunctival melanoma with orbital invasion. Her socket failed to epithelialize and contained a diffuse pyogenic granuloma that was caused by chronic Staphylococcus aureus infection. Extensive debridement and long-term intravenous antibiotics resulted in normal healing. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM eye-plastics@meei.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD MAY PY 2005 VL 21 IS 3 BP 236 EP 238 DI 10.1097/01.IOP.0000161994.54151.33 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 935OE UT WOS:000229790800015 PM 15942503 ER PT J AU Framme, C Alt, C Schnell, S Brinkmann, R Lin, CP AF Framme, C Alt, C Schnell, S Brinkmann, R Lin, CP TI Selective RPE laser treatment with a scanned cw laser beam in rabbits SO OPHTHALMOLOGE LA German DT Article DE selective RPE laser therapy; RPE defect; cw laser beam; diabetic maculopathy; age-related macular degeneration ID RETINAL-PIGMENT EPITHELIUM; PHOTOCOAGULATION; LESIONS AB Background. Selective RPE laser therapy with sparing of the neurosensory layer is possible by applying repetitive microsecond laser pulses. Macular diseases such as diabetic maculopathy, soft confluent drusen due to age-related macular degeneration or central serous chorioretinopathy were shown to be treated successfully - without concurrent laser scotoma - by this technique. It was the goal of this study to show, if selectivity could also be achieved using a conventional green cw-laser by scanning the beam across the retina during irradiation. Material and methods. A cw-laser beam at 532 nm was coupled to a slitlamp via a single mode optical fiber. The spot (18 mu m) was scanned across the retina of Dutch-belted rabbits through a contact lens using a two-dimensional acusto-optical deflector. The scan-field was 300 mu m x 300 mu m in size and consisted of six separate scan lines. The scanning speed was adjusted so as to produce 5 mu s exposure at each absorber in the center of the scan line. The entire scan pattern was applied 100 times at each site at a frame rate of 100 Hz. Dose response curve was measured by variation of the laser power. ED50-thresholds for RPE damage were calculated by fluorescein angiographic leakage in irradiated areas after exposure to different laser intensities. The extent of selectivity was examined by light microscopy. Results. Clinically the selective laser-induced RPE defect was demonstrated by fluorescein angiographic leakage and concurrent absence of ophthalmoscopic visibility. The angiographic ED50-damage threshold was 161 mJ/cm(2) (66 mW). Ophthalmoscopic visibility was not noticed even with the maximum available radiant exposure of 438 mJ/cm(2) (180 mW). Thus the safety range between angiographic and ophthalmoscopic thresholds had a factor of at least 2.7. First histological examinations revealed selective RPE destruction with intact photoreceptors for irradiation at laser power levels 2 times above angiographic threshold. Conclusion. Selective RPE targeting is feasible with a conventional green cw-laser when scanning the focused laser beam across the fundus with a speed such that every point in exposed RPE is irradiated for duration of 5 mu s. C1 Univ Regensburg, Augenklin, D-90342 Regensburg, Germany. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Laserzentrum, Lubeck, Germany. RP Framme, C (reprint author), Univ Regensburg, Augenklin, Franz Josef Str Allee 11, D-90342 Regensburg, Germany. EM carsten.framme@klinik.uni-regensburg.de RI Brinkmann, Ralf/E-6701-2012 NR 15 TC 2 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0941-293X J9 OPHTHALMOLOGE JI Ophthalmologe PD MAY PY 2005 VL 102 IS 5 BP 491 EP 496 DI 10.1007/s00347-004-1139-5 PG 6 WC Ophthalmology SC Ophthalmology GA 931GH UT WOS:000229473300005 PM 15883846 ER PT J AU Nussenblatt, RB Peterson, JS Foster, CS Rao, NA See, RF Letko, E Buggage, RR AF Nussenblatt, RB Peterson, JS Foster, CS Rao, NA See, RF Letko, E Buggage, RR TI Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis - A multicenter noncomparative interventional case series SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Academy-of-Ophthalmology/Annual Meeting of the ISRS CY NOV 14-18, 2003 CL ANAHEIM, CA SP Amer Acad Ophthalmol, ISRS ID OCULAR INFLAMMATORY DISORDERS; RECEPTOR MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; ALLOGRAFT SURVIVAL; POSTERIOR UVEITIS; TAC; INTERLEUKIN-2-RECEPTOR; INTERMEDIATE AB Purpose: To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Design: Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial. Participants: Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation. Methods: After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. Main Outcome Measures: Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales. Results: Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events. Conclusions: Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks. (c) 2005 by the American Academy of Ophthalmology. C1 NEI, Lab Immunol, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. RP Nussenblatt, RB (reprint author), NEI, Lab Immunol, Bldg 10 Room 10S219,10 Ctr Dr,MSC 1857, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-1-2113] NR 19 TC 65 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2005 VL 112 IS 5 BP 764 EP 770 DI 10.1016/j.ophtha.2004.12.034 PG 7 WC Ophthalmology SC Ophthalmology GA 923NC UT WOS:000228915600005 PM 15878055 ER PT J AU Cao, WH Cavacini, LA Tillman, KC Posner, MR AF Cao, WH Cavacini, LA Tillman, KC Posner, MR TI CD40 function in squamous cell cancer of the head and neck SO ORAL ONCOLOGY LA English DT Article DE CD40; head and neck cancer; IL-8; VEGF; PGE(2); EGFr ID IN-VIVO; GROWTH-FACTOR; B-CELLS; KAPPA-B; HUMAN KERATINOCYTES; MEDIATED APOPTOSIS; METASTATIC SPREAD; TUMOR-CELLS; EXPRESSION; LIGAND AB CD40 is expressed on basal keratinocytes and Squamous Cell Cancer of the Head and Neck (SCCHN) tumor cells in vivo and in vitro. CD40 ligation reduces proliferation of SCCHN cell lines and enhances EGFr mediated inhibition of proliferation. We investigated the mechanisms of CD40 function and EGFr cross-communication in SCCHN cell tines. CD40 ligation inhibited spontaneous and Fas-induced apoptosis. CD40 ligation specifically increased the secretion of IL-8, VEGF and PGE(2) but not IL-6, IL-10, FasL, GM-CSF, or TGF alpha. Co-ligation with EGFr further increased IL-8, VEGF and PGE(2) secretion. CD40 ligation also induced delayed activation and tyrosine phosphorytation of EGFr. CD40 induces secretion of specific proinflammatory and proangiogenic cytokines, inhibits spontaneous and Fas-induced apoptosis and increases EGFr phosphorylation. CD40 signaling may enhance the survival of SCCHN and tumor stroma. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Human Monoclonal Antibody Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Posner, MR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02215 USA. EM marshall_posner@dfci.harvard.edu FU NIDCR NIH HHS [P01 DE12467] NR 33 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 2005 VL 41 IS 5 BP 462 EP 469 DI 10.1016/j.oraloncology.2004.11.005 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 931FN UT WOS:000229471300004 PM 15878750 ER PT J AU Lehtinen, JT Tingart, MJ Apreleva, M Warner, JJP AF Lehtinen, JT Tingart, MJ Apreleva, M Warner, JJP TI Quantitative morphology of the scapula: Normal variation of the superomedial scapular angle, and superior, and inferior pole thickness SO ORTHOPEDICS LA English DT Article ID SNAPPING SCAPULA; ANATOMY; RESECTION AB This study examined the normal variation of the superomedial scapular angle and the thickness of the superior and inferior scapular borders. Scapulae of 53 cadaver shoulders were dissected free from all soft tissue. A line was drawn from the most superior to the most inferior point on each scapula, and the scapulae were cut along this line to obtain cross sections. The superomedial scapular angle (a) was measured with a goniometer from the cross section as a ABC: through the inferior tip (A), base of the spine (13), and superior tip (C). Superior and inferior pole thickness was measured with a digital caliper from he thickest portions on the cross section of the poles. Average superomedial angle was 139 degrees +/- 6 degrees (range: 125 degrees-156 degrees). Average thickness for the superior and inferior poles was 3.9 +/- 0.9 mm (range: 2.1-8.3 mm) and 7.5 +/- 1.5 mm (range: 4-11 mm), respectively. The thickness of both superior and inferior poles was significantly different between male and female specimens (P <.05), with male scapulae having the higher values. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02115 USA. RP Lehtinen, JT (reprint author), Kanta Hame Cent Hosp, Dept Surg, Hameenlinna 13530, Finland. NR 25 TC 6 Z9 6 U1 0 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD MAY PY 2005 VL 28 IS 5 BP 481 EP 486 PG 6 WC Orthopedics SC Orthopedics GA 929PI UT WOS:000229357800010 PM 15945605 ER PT J AU Kronenberg, H AF Kronenberg, H TI The growth plate and endochondral bone formation in males SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 3rd International Conference on Osteoporosis CY MAY 12-14, 2005 CL Genova, ITALY ID ESTROGEN C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2005 VL 16 IS 5 BP S1 EP S1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 924JG UT WOS:000228974500019 ER PT J AU Leder, B AF Leder, B TI Aromatase inhibition as a novel approach to androgen replacement in men SO OSTEOPOROSIS INTERNATIONAL LA English DT Meeting Abstract CT 3rd International Conference on Osteoporosis CY MAY 12-14, 2005 CL Genova, ITALY ID LOW SERUM TESTOSTERONE; BONE-MINERAL DENSITY; ELDERLY-MEN; ESTROGEN; PROSTATE; AGE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 2005 VL 16 IS 5 BP S16 EP S17 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 924JG UT WOS:000228974500043 ER PT J AU Zwolan, TA Kileny, PR Smith, T Waltzman, T Chute, P Domico, I Firszt, J Hodges, A Mills, T Whearty, M Osberger, MJ Fisher, L AF Zwolan, TA Kileny, PR Smith, T Waltzman, T Chute, P Domico, I Firszt, J Hodges, A Mills, T Whearty, M Osberger, MJ Fisher, L TI Comparison of continuous interleaved sampling and simultaneous analog stimulation speech processing strategies in newly implanted adults with a clarion 1.2 cochlear implant SO OTOLOGY & NEUROTOLOGY LA English DT Article DE cochlear implants; speech recognition; clarion 1.2 enhanced bipolar device; Simultaneous Analog Stimulation (SAS); Continous Interleaved Sampling (CIS) ID PERFORMANCE; RECOGNITION; NUMBER; PERCEPTION; INERAID; TIME AB Objective: This study consisted of a within-subjects comparison of speech recognition and patient preference when subjects used two different cochlear implant speech processing strategies with a Clarion 1.2 (enhanced bipolar) device: Simultaneous Analog Stimulation (SAS), and Continuous Interleaved Sampling (CIS). These two strategies used two different electrode configurations: the SAS strategy used bipolar stimulation, whereas the CIS strategy used monopolar stimulation. Study Design: This was a multicenter study that used a within-subjects balanced crossover design. Experience with the two strategies was replicated in each subject using an ABAB design. Order of strategy use was balanced across all subjects. Setting: The study was carried out at several cochlear implant centers affiliated with tertiary medical centers. Patients: Subjects consisted of 25 postlingually deafened adults who received a Clarion cochlear implant. Interventions: Total involvement by each subject was 14 weeks. Speech perception testing and sound quality assessments were per-formed after use with each strategy. Main Outcome Measures: Primary outcome measures include speech perception data and patient responses to questionnaires regarding speech and sound quality. Results: Analyses revealed that performance did not differ significantly by the strategy encountered first as relative to the strategy encountered second and that the order in which a strategy was used did not appear to affect subjects' eventual preference for a particular strategy. Although speech recognition scores tended to be higher for CIS for most of the test measures at most of the test intervals, the analysis of variance to evaluate differences in strategy did not reveal a significant effect of strategy. Further analysis of scores obtained at the replication interval, however, revealed that scores obtained with CIS were significantly higher than scores obtained with SAS on the Hearing in Noise Test sentences in quiet and noise. In addition, significantly more patients indicated a final preference for the CIS strategy than for the SAS strategy. Importantly, both the analysis evaluating order and the analysis evaluating strategy revealed significant effects of evaluation period, indicating that time/experience with the implant had a significant effect on scores for each strategy, regardless of the order in which it was used (first or second). Conclusions: This study demonstrates that important learning occurs during the first several weeks of cochlear implant use, making it difficult to adequately compare performance with different speech processing strategies. However, the finding that patients often prefer the strategy they understand speech the best with supports the clinical practice of letting adult patients select their preferred strategy without formally evaluating speech perception with each available strategy. C1 Univ Michigan, Cochlear Implant Program, Ann Arbor, MI 48108 USA. Univ Minnesota, Minneapolis, MN USA. NYU, New York, NY USA. Mercy Coll, New York, NY USA. Memphis Oral Sch Deaf, Memphis, TN USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Miami, Miami, FL 33152 USA. House Ear Clin, Los Angeles, CA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Adv Bion Corp, Sylmar, CA USA. RP Zwolan, TA (reprint author), Univ Michigan, Cochlear Implant Program, 475 Market Pl,Bldg 1,Suite A, Ann Arbor, MI 48108 USA. EM zwolan@umich.edu NR 26 TC 7 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2005 VL 26 IS 3 BP 455 EP 465 DI 10.1097/01.mao.0000169794.76072.16 PG 11 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 957ZJ UT WOS:000231411800026 PM 15891649 ER PT J AU Godinho, RA Kamil, SH Lubianca, TN Keogh, IJ Eavey, RD AF Godinho, RA Kamil, SH Lubianca, TN Keogh, IJ Eavey, RD TI Pediatric cholesteatoma: Canal wall window alternative to canal wall down mastoidectomy SO OTOLOGY & NEUROTOLOGY LA English DT Article DE hybrid mastoidectomy technique; canal wall window (CWW); canal wall down (CWD); pediatric cholesteatoma; canal wall slit ID EAR SURGERY; RECONSTRUCTION; CHILDREN; MANAGEMENT; CARTILAGE; TYMPANOMASTOIDECTOMY; TYMPANOPLASTY; OBLITERATION; FLAP AB Objective: A previous pilot series described a hybrid mastoidectomy technique, canal wall window (CWW), which substituted for the canal wall down (CWD) procedure and involved slitting the posterior canal wall. The current, larger series compares the results of the CWW procedure with conventional surgical techniques. Study Design: Retrospective analysis of 78 pediatric ears. Setting: Academic tertiary referral center. Patients: The mean patient age was 13.5 years. Main Outcome Measure(s): The data analyzed included ears later requiring conversion from CWW to CWD, dry/moist ear results, recidivation determined by two separate methods, and audiometric data statistically analyzed using independent-samples analysis (unpaired, two-tailed Student's t test). Results: First, of 42 CWW ear procedures, 6 (14%) later required conversion to CWD. Second, dry ear results were as follows: for CWW, 94%; for CWD, 92%; and for CWU (canal wall up), 90%. Third, recidivation determined at I year (standard rate) was, for CWW, 19.5%; for CWD, 0%; and for CWU, 7.7%; the at-risk calculation rate was, for CWW, 27%; for CWD, 0%; and for CWU, 8.3%. The 6-year recidivation rate for all three surgical techniques was 0%. 4). The mean preoperative-to-postoperative four-tone air-bone gap change was, for CWW, from 29.7 to 26.4 dB; for CWD, from 32.9 to 39.0 dB; and for CWU, from 21.0 to 25.2 dB (postoperative CWW to CWD, p < 0.005). A postoperative air-bone gap result of 0 to 20 dB was achieved as follows: with CWW, in 13 of 36 ears; with CWD, in 2 of 14 ears; and with CWU, in 9 of 22 ears. Conclusion: Frequently, a CWW procedure can be substituted for a traditional CWD procedure. In the extended series, the CWW technique continued to provide hearing results similar to CWU rather than to CWD procedures in a young population who will bear the surgical outcome for many decades. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Pediat Otolaryngol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Pontificia Univ Catocica Minas Gerais, Inst Ciencias Biol & Saude, Belo Horizonte, MG, Brazil. Fdn Fed Fac Med Sci, Dept Otorhinolaryngol, Porto Alegre, RS, Brazil. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM roland_eavey@meei.harvard.edu RI KEOGH, IVAN/M-2704-2016 OI KEOGH, IVAN/0000-0001-6358-6377 NR 41 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAY PY 2005 VL 26 IS 3 BP 466 EP 471 DI 10.1097/01.mao.0000169768.93173.96 PG 6 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 957ZJ UT WOS:000231411800027 PM 15891650 ER PT J AU Woodard, LD Hernandez, MT Lees, E Petersen, LA AF Woodard, LD Hernandez, MT Lees, E Petersen, LA TI Racial differences in attitudes regarding cardiovascular disease prevention and treatment: a qualitative study SO PATIENT EDUCATION AND COUNSELING LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 01-05, 2002 CL ATLANTA, GA SP Soc Gen Internal Med DE coronary heart disease; racial disparities; physician-patient relationship ID ACUTE MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; NUTRITION EXAMINATION SURVEY; AFRICAN-AMERICANS; MEDICAL-RESEARCH; SECONDARY PREVENTION; EDUCATION-PROGRAM; NATIONAL-HEALTH; MENTAL STRESS; UNITED-STATES AB The objective of this study was to explore coronary heart disease (CHD) health care experiences and beliefs of African-American and white patients to elicit potential causes of racial disparities in CHD outcomes. Twenty-four patients (14 white, 10 African-American) with established CHD participated in one of four focus groups. Using qualitative methods, verbatim transcripts of the groups were analyzed by independent investigators to identify key themes. We identified four themes: risk factor knowledge, physician-patient relationship, medical system access, and treatment beliefs. Racial differences were apparent in the experience of racism as a stress, knowledge of specifics of CHD risk factors, and assertiveness in the physician-patient relationship. These findings suggest that strategies to improve risk factor knowledge and to enable African-American patients to become active partners in their medical care may lead to improved CHD morbidity and mortality in this population. The efficacy of such interventions would need to be tested in further work. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston Baptist Univ, Houston, TX USA. RP Woodard, LD (reprint author), Houston Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Dept Vet Affairs, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. EM lwoodard@bcm.tmc.edu FU AHRQ HHS [P01 HS10876]; BHP HRSA HHS [1 T32 PE 10031-01] NR 44 TC 14 Z9 14 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD MAY PY 2005 VL 57 IS 2 BP 225 EP 231 DI 10.1016/j.pec.2004.06.004 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 935UM UT WOS:000229808900012 PM 15911197 ER PT J AU New, HV Cale, CM Tischkowitz, M Jones, A Telfer, P Veys, P D'Andrea, A Mathew, CG Hann, I AF New, HV Cale, CM Tischkowitz, M Jones, A Telfer, P Veys, P D'Andrea, A Mathew, CG Hann, I TI Nijmegen breakage syndrome diagnosed as Fanconi anaemia SO PEDIATRIC BLOOD & CANCER LA English DT Article DE bone marrow transplant; DNA cross-linking agents; Fanconi anaemia; immunodeficiency; Nijmegen breakage syndrome ID DNA-DAMAGE RESPONSE; FOLLOW-UP; MUTATION; PATHWAY; TRANSPLANTATION; FAMILIES; PROTEIN; REPAIR; FANCD2; NBS1 AB Background Fanconi anaemia (FA) and Nijmegen breakage syndrome (NBS) are rare chromosomal instability disorders with overlapping clinical features. it has recently been shown that, like FA, NBS is also associated with increased chromosomal sensitivity to DNA cross-linking agents. Procedure. We report a family that was initially diagnosed with FA on the basis of increased sensitivity to DNA cross-linking agents. They were atypical in that there were associated severe infection problems. In view of these features we performed immune function studies together with molecular analysis of the FA genes and subsequently the NBSI gene. Results. Two children in the kindred have died, one from sepsis, and the other with a plasma cell malignancy. A third child under-went bone marrow transplantation because of recurrent infections. All affected members had severe immunological abnormalities. The genetic defect was shown to be a novel mutation in the NBSI gene, so the diagnosis was revised to that of NBS. Conclusions. This family illustrates the importance of awareness of the lack of specificity of DNA cross-linking agent tests for FA, particularly in situations where the clinical features are atypical. In addition, one of the cases represents the first use of bone marrow transplantation for NBS that we are aware of; this treatment may have a future role for other patients with the syndrome. (c) 2004 Wiley-Liss, Inc. C1 St Marys Hosp, Dept Paediat, London W2 1NY, England. Great Ormond St Hosp Children, Dept Haematol & Oncol, London WC1N 3JH, England. Great Ormond St Hosp Children, Dept Immunol, London WC1N 3JH, England. Guys King & St Thomas Sch Med, Div Genet & Dev, London, England. Royal London Hosp, Dept Haematol, London E1 1BB, England. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP New, HV (reprint author), St Marys Hosp, Dept Paediat, Praed St, London W2 1NY, England. EM helen.new@st-marys.nhs.uk RI Mathew, Christopher/G-3434-2015 OI Mathew, Christopher/0000-0003-4178-1838 NR 24 TC 16 Z9 17 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2005 VL 44 IS 5 BP 494 EP 499 DI 10.1002/pbc.20271 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 911GI UT WOS:000227990200011 PM 15593232 ER PT J AU Price, VE Fletcher, JA Zielenska, M Cole, W Viero, S Manson, DE Stuart, M Pappo, AS AF Price, VE Fletcher, JA Zielenska, M Cole, W Viero, S Manson, DE Stuart, M Pappo, AS TI Imatinib mesylate: An attractive alternative in young children with large, surgically challenging dermatofibrosarcoma protuberans SO PEDIATRIC BLOOD & CANCER LA English DT Article DE childhood; dermatofibrosarcoma; imatinib; mesylate; protuberans ID GIANT-CELL FIBROBLASTOMA; CHILDHOOD; SARCOMA; STI571; TUMORS AB To document the clinical activity of imatinib mesyalte in a child with a dermatofibrosarcoma protuberans (DFSP). An 18-month-old girl presented with a large extremity DFSP. As surgical resection would have caused unacceptable functional defects, imatinib mesylate was administered to induce tumor reduction and or stabilization. After 23 weeks of therapy, magnetic resonance imaging(MRI) of the tumor showed a reduction in the, subcutaneous thickness in the transvers plane. The drug was tolerated well without any adverse reactions. Imatinib mesylate offers a non-surgical alternative for the treatment of large DFSP in children. (c) 2004 Wiley-Liss, Inc. C1 Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Toronto, Hosp Sick Children, Dept Pediat Lab Med Mol Pathol, Div Pathol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Dept Orthopaed Surg, Toronto, ON M5G 1X8, Canada. Univ Toronto, Fac Med, Dept Lab Med & Pathobiol, Toronto, ON, Canada. Univ Toronto, Hosp Sick Children, Dept Diagnost Imaging, Toronto, ON M5G 1X8, Canada. Univ Toronto, Hosp Sick Children, Dept Nursing, Toronto, ON M5G 1X8, Canada. RP Pappo, AS (reprint author), Univ Toronto, Hosp Sick Children, Dept Pediat, Div Hematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM alberto.pappo@sickkids.ca NR 16 TC 42 Z9 46 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2005 VL 44 IS 5 BP 511 EP 515 DI 10.1002/pbc.20249 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 911GI UT WOS:000227990200014 PM 15503291 ER PT J AU Anupindi, S Perumpillichira, J Israel, EK Zalis, ME Jaramillo, D AF Anupindi, S Perumpillichira, J Israel, EK Zalis, ME Jaramillo, D TI Low-dose CT colonography in children: initial experience, technical feasibility, and utility SO PEDIATRIC RADIOLOGY LA English DT Article DE CT colonography; children; juvenile polyposis coli; virtual colonoscopy ID CONVENTIONAL COLONOSCOPY; VIRTUAL COLONOSCOPY; INCOMPLETE COLONOSCOPY; EXTRACOLONIC FINDINGS; COLORECTAL NEOPLASIA; BOWEL; CANCER AB Background: CT colonography (CTC) is utilized as a diagnostic tool in the detection of colon polyps and early colorectal cancer in adults. Large studies in the literature, although focused on adult populations, have shown CTC to be a safe, accurate, non-invasive technique. Objective: We evaluated the technical feasibility of CTC in children using a low-dose technique. Materials and methods: From November 2001 to April 2004 we evaluated eight patients ( 3 - 17 years) with non-contrast CTC. Seven of the patients had CTC, followed by standard colonoscopy (SC) the same day; in one patient, CTC followed a failed SC. CTC results were compared to results of SC. The estimated effective dose from each CTC was calculated and compared to that of standard barium enema. Results: CTC results were consistent with those of SC. Sensitivity for polyps 5 10 mm was 100%, and sensitivity for polyps 10 mm and larger was 66.7%. The estimated mean effective dose was 2.17 mSv for CTC, compared to the 5 - 6 mSv for a standard air-contrast barium enema in a small child. Conclusion: Our initial experience shows CTC in children is well-tolerated, safe, and useful. The procedure can be performed successfully with a low radiation dose, and preliminary results compare well with SC. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Gastroenterol & Nutr, Boston, MA 02115 USA. RP Anupindi, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02115 USA. EM sanupindi@partners.org NR 25 TC 11 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAY PY 2005 VL 35 IS 5 BP 518 EP 524 DI 10.1007/s00247-004-1394-2 PG 7 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 918CU UT WOS:000228517500007 PM 15789249 ER PT J AU Aidlen, J Anupindi, SA Jaramillo, D Doody, DP AF Aidlen, J Anupindi, SA Jaramillo, D Doody, DP TI Malrotation with midgut volvulus: CT findings of bowel infarction SO PEDIATRIC RADIOLOGY LA English DT Article DE bowel infarction; malrotation; midgut volvulus; CT ID DIAGNOSIS; ADULT AB Midgut volvulus, the most common serious complication of malrotation, can be diagnosed using conventional contrast fluoroscopy, US or CT. CT is a quick and comprehensive examination in the evaluation of complex acute abdominal pathology in children. Contrast-enhanced CT can readily help the radiologist recognize perfusion abnormalities of the bowel, which is vital for reducing morbidity and mortality in affected children. Our case emphasizes and demonstrates additional CT features of bowel infarction in a child with a proven malrotation with midgut volvulus. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Surg, Worcester, MA USA. RP Anupindi, SA (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, 34 Fruit St,White 246, Boston, MA 02114 USA. EM sanupindi@partners.org NR 9 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAY PY 2005 VL 35 IS 5 BP 529 EP 531 DI 10.1007/s00247-004-1355-9 PG 3 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 918CU UT WOS:000228517500009 PM 15536561 ER PT J AU Maynard, SE Venkatesha, S Thadhani, R Karumanchi, SA AF Maynard, SE Venkatesha, S Thadhani, R Karumanchi, SA TI Soluble fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia SO PEDIATRIC RESEARCH LA English DT Review ID PLACENTAL GROWTH-FACTOR; MYOMETRIAL RESISTANCE ARTERIES; PREGNANCY-INDUCED HYPERTENSION; MATERNAL SUSCEPTIBILITY LOCUS; ELEVATED LIVER-ENZYMES; BED SPIRAL ARTERIES; IN-VITRO; AT(1) RECEPTOR; HELLP-SYNDROME; NEUROKININ-B AB Preeclampsia, a pregnancy-specific syndrome of hypertension and proteinuria, is characterized by defective placental vasculogenesis and widespread maternal endothelial dysfunction. Although the manifestations of preeclampsia are primarily maternal, the burden of morbidity and mortality is often on the neonate, since the only effective treatment - delivery of the fetus and placenta - often results in iatrogenic prematurity. In this review, we summarize recent advances in our understanding of the pathophysiology of preeclampsia, including normal and aberrant placental vascular development and evidence for endothelial dysfunction. We describe recent evidence that supports a novel mechanism in which a maladaptive shift in placental production of angiogenic factors such as soluble fms-like tyrosine kinase 1 (a circulating antiangiogenic protein) may play an important role in the pathogenesis of preeclampsia. C1 Beth Israel Deaconess Med Ctr, Div Renal, Dept Med Obstet & Gynecol, Boston, MA 02215 USA. Dept Med, Boston, MA 02215 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, Div Renal, Dept Med Obstet & Gynecol, 330 Brookline Ave,Dana 517, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU NICHD NIH HHS [HD39223]; NIDDK NIH HHS [DK065997, DK64255] NR 110 TC 83 Z9 84 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 2005 VL 57 IS 5 BP 1R EP 7R DI 10.1203/01.PDR.0000159567.85157.B7 PN 2 PG 7 WC Pediatrics SC Pediatrics GA 919VQ UT WOS:000228646100001 PM 15817508 ER PT J AU Batton, DG Blackmon, LR Adamkin, DH Bell, EF Denson, SE Engle, WA Martin, GI Stark, AR Barrington, KJ Raju, TNK Riley, L Tomashek, KM Wallman, C Couto, J AF Batton, DG Blackmon, LR Adamkin, DH Bell, EF Denson, SE Engle, WA Martin, GI Stark, AR Barrington, KJ Raju, TNK Riley, L Tomashek, KM Wallman, C Couto, J CA Comm Fetus Newborn 2004-2005 TI Underwater births SO PEDIATRICS LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; NEAR-DROWNING EXPERIENCE; WATER BIRTH; FIRST STAGE; LABOR; IMMERSION; BABIES C1 William Beaumont Hosp, Dept Pediat, Royal Oak, MI 48073 USA. Univ Maryland, Sch Med, Dept Pediat, Div Neonatol, Baltimore, MD 21201 USA. Univ Louisville, Dept Pediat, Louisville, KY 40202 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Texas, Dept Pediat Neonatol, Houston, TX 77030 USA. Indiana Univ, Med Ctr, James Whitcomb Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA. Citrus Valley Med Ctr, W Covina, CA 91790 USA. Baylor Coll Med, Dept Neonatol, Houston, TX 77030 USA. Royal Victoria Hosp, Dept Neonatol, Montreal, PQ H3A 1A1, Canada. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20847 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Maternal & Infant Hlth Branch, Atlanta, GA 30333 USA. Natl Assoc Neonatal Nurses, Wellington, CO 80549 USA. Amer Acad Pediat, Div Hosp & Surg Serv, Elk Grove Village, IL 60007 USA. RP Batton, DG (reprint author), William Beaumont Hosp, Dept Pediat, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM dgbatton@beaumont.edu OI Barrington, Keith/0000-0001-9669-5094 NR 22 TC 6 Z9 6 U1 0 U2 3 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 MAY PY 2005 VL 115 IS 5 BP 1413 EP 1414 DI 10.1542/peds.2004-1738 PG 2 WC Pediatrics SC Pediatrics GA 922JM UT WOS:000228833500045 PM 15867054 ER PT J AU Anselmi, L Lakhter, A Hirano, AA Tonini, M Sternini, C AF Anselmi, L Lakhter, A Hirano, AA Tonini, M Sternini, C TI Expression of galanin receptor messenger RNAs in different regions of the rat gastrointestinal tract SO PEPTIDES LA English DT Article DE real-time RT-PCR; intestine; stomach; enteric nervous system ID PIG SMALL-INTESTINE; FEEDING-BEHAVIOR; GUT; TRANSMISSION; PHARMACOLOGY; CONTRACTION; PROJECTIONS; ACTIVATION; MOTILITY; SUBTYPES AB Galanin effects are mediated by three G-protein-coupled receptors: galanin receptor 1 (GalR1), GalR2 and GalR3. We quantified mRNA levels of GalR1, GalR2 and GalR3 in the rat stomach, small and large intestine using real-time RT-PCR. All three GalR mRNAs were detected throughout the gut at different levels. GalR1 and GalR2 mRNA levels were higher in the large than in the small intestine. GalR2 mRNA was most abundant in the stomach. GalR3 mRNA levels were generally quite low. The differential regional distribution of GalRs suggests that the complex effects of galanin in the gut are the result of activating multiple receptor subtypes, whose density, subtype and signaling vary along the gastrointestinal tract. (c) 2005 Elsevier Inc. All rights reserved. C1 VAGLAHS, CURE Digest Dis Res Ctr, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Pavia, Dept Physiol & Pharmacol Sci, I-27100 Pavia, Italy. RP Anselmi, L (reprint author), VAGLAHS, CURE Digest Dis Res Ctr, Div Digest Dis, Bldg 115,Room 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM lanselmi@mednet.ucla.edu FU NIDDK NIH HHS [DK57037, R01 DK057037, P30 DK041301, DK41301] NR 28 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD MAY PY 2005 VL 26 IS 5 BP 815 EP 819 DI 10.1016/j.peptides.2004.12.011 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 919BZ UT WOS:000228594600013 PM 15808911 ER PT J AU Xu, JW Johnson, TS Motarjem, PM Peretti, GM Randolph, MA Yaremchuk, MJ AF Xu, JW Johnson, TS Motarjem, PM Peretti, GM Randolph, MA Yaremchuk, MJ TI Tissue-engineered flexible ear-shaped cartilage SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PERSONAL-EXPERIENCE; FIBRIN GLUE; RECONSTRUCTION; CHONDROCYTES; TRANSPLANTATION; MICROTIA; SCAFFOLD; AURICLE; POLYMER AB Background: Previous attempts to engineer human ear-shaped constructs mimicked human shape but lacked the flexibility and size of a human car. Recently, the authors engineered flexible cartilage by incorporating a perichondrium-like layer into the construct. In this study, they used lyophilized swine perichondrium as a pseudoperichondrium, examined its ability to confer flexibility to tissue-engineered cartilage, and used it to engineer flexible cartilage in the shape and size of a human ear. Methods: Auricular chondrocytes and perichondrium were isolated from swine. Chondrocytes were mixed with fibrin polymer and gelled to form 5 X 20-mm constructs. Constructs alone (control, n = 6) or constructs sandwiched between two layers of lyophilized swine perichondrium (experimental, n = 6) were implanted into athymic mice. Auricular chondrocytes in fibrin polymer and lyophilized perichondrium were also used to form a tri-layer, car-shaped construct, which was implanted into an athymic rat and externally stented for 6 weeks (n = 1). At 12 weeks, constructs were analyzed with histology and gross mechanical testing. Results: New cartilaginous tissue was engineered in both the experimental and control groups. In samples laminated with lyophilized swine perichondrium, the intimate integration of the laminate with the neocartilage closely resembled the histoarchitecture of the native swine ear. Experimental constructs had mechanical properties similar to those of the native swine ear, while control constructs fractured with similar testing. The engineered ear could not be fractured with gross mechanical testing, and its size, shape, and flexibility remained stable. Conclusions: This study demonstrates that it is possible to engineer a cartilage construct that resembles the human car not only in shape but also in size and flexibility. This study also confirms that lamination is a reliable method to confer elastic-like flexibility to an engineered cartilage construct. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02130 USA. Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai, Peoples R China. Fudan Univ, Shanghai, Peoples R China. RP Yaremchuk, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, WACC 453,15 Parkham St, Boston, MA 02130 USA. EM myaremchuk@partners.org RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 28 TC 41 Z9 44 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2005 VL 115 IS 6 BP 1633 EP 1641 DI 10.1097/01.PRS.0000161465.21513.5D PG 9 WC Surgery SC Surgery GA 923BV UT WOS:000228884600022 PM 15861068 ER PT J AU Rubin, JP Xie, ZC Davidson, C Rosow, CE Chang, YC May, JW AF Rubin, JP Xie, ZC Davidson, C Rosow, CE Chang, YC May, JW TI Rapid absorption of tumescent lidocaine above the clavicles: A prospective clinical study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOCAL-ANESTHETIC AGENTS; LIPOSUCTION; SURGERY; EPINEPHRINE; MG/KG AB Background: Tumescent local anesthesia has been adapted for surgery of the face and neck, but there are no data regarding drug absorption when tumescent injection is used in this region. The aim of this study was to characterize the changes in plasma lidocaine concentrations over time when a tumescent solution is injected into the subcutaneous tissue of the neck. The study was carried out in human volunteer subjects, and injection of lidocaine to the thighs provided control data, Methods: Eight healthy female volunteer subjects were studied twice using a prospective, crossover design. Tumescent lidocaine solution was injected into the subcutaneous tissue of the neck in one session and the thighs in another session. The order of injection was randomized. Blood samples were collected for 14 hours after injection, and the plasma concentration of lidocaine measured. The injected solution consisted of lidocaine 0.1%, NaHCO3 12.5 mEq/L, and epinephrine 1:1,000,000 in normal saline. A standardized dose of lidocaine (7 mg/kg) was used for each injection and no surgical procedure was performed. Results: All subjects completed the study. Subject weight was 66.1 &PLUSMN; 12.8 kg, body fat was 29.0 &PLUSMN; 4.7 percent, and body mass index was 23.8 &PLUSMN; 3.1 kg/m(2). The average time to reach peak lidocaine concentration after neck injection was 5.8 hours, whereas peak lidocaine concentration after thigh injection did not occur until 12.0 hours. This difference of 6.2 hours was highly significant (p = 0.009). The average peak concentration after neck injection was 16 percent greater than that after thigh injection (0.94 μ g/ml versus 0.81 μ g/ml), with the difference approaching significance (p = 0.06). No adverse reactions were noted. Conclusions: Tumescent injection above the clavicles results in a rapid rise in plasma lidocaine concentration when compared with injection to the lower extremities. Toxic symptoms could occur much earlier than expected for lower extremity tumescent anesthesia. In addition, dangerous plasma levels could occur if tumescent anesthesia in the lower extremities is followed by tumescent injection above the clavicles, because the absorption curves would be superimposed. C1 Univ Pittsburgh, Dept Surg, Div Plast & Reconstruct Surg, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Surg, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Rubin, JP (reprint author), Univ Pittsburgh, Dept Surg, Div Plast & Reconstruct Surg, 497 Scaife Hall, Pittsburgh, PA USA. EM rubinjp@upmc.edu NR 26 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2005 VL 115 IS 6 BP 1744 EP 1751 DI 10.1016/01.PRS.0000161678.10555.53 PG 8 WC Surgery SC Surgery GA 923BV UT WOS:000228884600040 PM 15861085 ER PT J AU Siegel, JM AF Siegel, JM TI Functional implications of sleep development SO PLOS BIOLOGY LA English DT Editorial Material ID RETICULAR-FORMATION NEURONS; IN-VIVO MICRODIALYSIS; REM-SLEEP; LOCUS-COERULEUS; DEPRIVATION; PONTINE; CYCLE; ACTIVATION; DISCHARGE; RELEASE C1 Vet Adm Greater Los Angeles Hlth Care Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. RP Siegel, JM (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Sepulveda, CA 91343 USA. EM jsiegel@ucla.edu FU NHLBI NIH HHS [R01 HL041370, R37 HL041370, P50 HL060296, HL060296, HL41370]; NIMH NIH HHS [MH64109, R01 MH064109]; NINDS NIH HHS [NS14610, R01 NS014610, R37 NS014610] NR 32 TC 9 Z9 9 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD MAY PY 2005 VL 3 IS 5 BP 756 EP 758 AR e178 DI 10.1371/journal.pbio.0030178 PG 3 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 926LT UT WOS:000229125400004 PM 15884980 ER PT J AU Emmons, KM McBride, CM Puleo, E Pollak, KI Marcus, BH Napolitano, M Clipp, E Onken, J Farraye, FA Fletcher, R AF Emmons, KM McBride, CM Puleo, E Pollak, KI Marcus, BH Napolitano, M Clipp, E Onken, J Farraye, FA Fletcher, R TI Prevalence and predictors of multiple behavioral risk factors for colon cancer SO PREVENTIVE MEDICINE LA English DT Article DE colorectal cancer prevention; multiple risk factors ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; PRIMARY-CARE; EPIDEMIOLOGIC EVIDENCE; FACTOR INTERVENTIONS; CIGARETTE-SMOKING; TOBACCO SMOKING; DIETARY HEME AB Objectives. This paper examines the prevalence of behavioral risk factors for colorectal cancer (CRC) (e.g., red meat consumption, fruit and vegetable intake, multivitamin intake, alcohol, smoking, and physical inactivity), co-occurrence among these behaviors, and motivation for change among patients at increased risk. Methods. The study sample included 1,247 patients with recent diagnosis of adenomatous colorectal polyps. Within 4 weeks following the polypectomy, participants completed a baseline survey by telephone. Results. Sixty-six percent of participants had not been diagnosed with polyps before. Fifty-eight percent of the sample had red meat as a risk factor, 63% bad fruit and vegetable consumption as a risk factor, 54% did not take a daily multivitamin, and 44% had physical activity as a risk factor. In contrast, only 9% of the sample had alcohol consumption as a risk factor and only 14% were current smokers. The prevalence of the six individual risk factors was combined into an overall multiple risk factor score (MRF). The average number of risk factors was 2.43. Men, those with a high school education or below, those reporting fair or poor health status, and those with less self-efficacy about risk factor change had more risk factors. Conclusions. There is a need for multiple risk factor interventions that capitalize on natural intersections among intra- and interpersonal factors that maintain them. (c) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Duke Univ, Dept Community & Family Med, Durham, NC 27710 USA. Univ Massachusetts, Amherst, MA 01003 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Miriam Hosp, Providence, RI 02912 USA. Duke Univ, Sch Nursing & Geriatr Res Educ, Durham VA Med Ctr, Durham, NC 27706 USA. Duke Univ, Ctr Clin, Durham, NC 27706 USA. Duke Univ, Dept Med, Durham, NC 27706 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Vanguard Med Associates, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM karen_m_Emmons@dfci.harvard.edu OI Farraye, Francis/0000-0001-6371-2441 FU NCI NIH HHS [5 R01 CA74000-04] NR 50 TC 36 Z9 36 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 0091-7435 J9 PREV MED JI Prev. Med. PD MAY PY 2005 VL 40 IS 5 BP 527 EP 534 DI 10.1016/j.ypmed.2004.10.001 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 914AH UT WOS:000228196300005 PM 15749134 ER PT J AU Kornstein, SG Harvey, AT Rush, AJ Wisniewski, SR Trivedi, MH Svikis, DS McKenzie, ND Bryan, C Harley, R AF Kornstein, SG Harvey, AT Rush, AJ Wisniewski, SR Trivedi, MH Svikis, DS McKenzie, ND Bryan, C Harley, R TI Self-reported premenstrual exacerbation of depressive symptoms in patients seeking treatment for major depression SO PSYCHOLOGICAL MEDICINE LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; ILLNESS RATING-SCALE; STAR-ASTERISK-D; MENSTRUAL-CYCLE; MOOD DISORDERS; SYMPTOMATOLOGY; RATIONALE; INVENTORY; IDS AB Background. Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings. Method. This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5-10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life. Results. Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30.7 (S.D. =73.7) months versus 13.5 (S.D. = 13.2) months; p=0-001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity. Conclusions. PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice. C1 Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. Via Christi Res Inc, Wichita, KS USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kornstein, SG (reprint author), Virginia Commonwealth Univ, Dept Psychiat, POB 980710, Richmond, VA 23298 USA. EM skornste@mail2.vcu.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 26 TC 33 Z9 33 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD MAY PY 2005 VL 35 IS 5 BP 683 EP 692 DI 10.1017/S0033291704004106 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EL UT WOS:000231499800008 PM 15918345 ER PT J AU Kim, YH Saini, S Sahani, D Hahn, PF Mueller, PR Auh, YH AF Kim, YH Saini, S Sahani, D Hahn, PF Mueller, PR Auh, YH TI Imaging diagnosis of cystic pancreatic lesions: Pseudocyst versus nonpseudocyst SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, IL SP Radiol Soc N Amer ID RADIOLOGIC-PATHOLOGICAL CORRELATION; PAPILLARY MUCINOUS TUMORS; DIFFERENTIAL-DIAGNOSIS; FLUID ANALYSIS; HELICAL CT; NEOPLASMS; EUS AB Although the clinical, radiologic, and pathologic features of cystic pancreatic lesions are well known, preoperative diagnosis is difficult. Differentiation between a pancreatic pseudocyst and a cystic pancreatic neoplasm is crucial in determining the proper treatment. Careful evaluation of the patient's clinical history is important for accurate diagnosis of a pseudocyst. Clinical scenarios include a pseudocyst developing after acute pancreatitis and a pseudocyst superimposed on chronic pancreatitis. However, a pseudocyst in a patient with no clinical history of pancreatitis poses a diagnostic problem. The differential diagnosis of a neoplastic cystic lesion of the pancreas includes serous cystadenoma, mucinous cystic neoplasms, intraductal papillary mucinous tumor, and solid and papillary epithelial neoplasm. Definitive diagnosis is often possible when the lesion has a typical radiologic appearance, but in many cases characterization with imaging alone is impossible. Thin-section computed tomography with multiplanar reformation, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography have emerged as modalities that can provide additional diagnostic information. Familiarity with the range of imaging appearances and awareness of the diagnostic strengths and limitations of each imaging modality are important for accurate diagnosis and management of cystic pancreatic lesions. C1 Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Cornell Univ, Presbyterian Hosp, Dept Radiol, New York, NY USA. RP Kim, YH (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM kimy@ummhc.org NR 23 TC 61 Z9 70 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 2005 VL 25 IS 3 BP 671 EP 685 DI 10.1148/rg.253045104 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 034OV UT WOS:000236940400011 PM 15888617 ER PT J AU Aquino, SL AF Aquino, SL TI Imaging of metastatic disease to the thorax SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; HIGH-RESOLUTION CT; NON-HODGKINS-LYMPHOMA; CAVITARY PULMONARY METASTASES; MALIGNANT PLEURAL EFFUSIONS; CHEST COMPUTED-TOMOGRAPHY; RENAL-CELL CARCINOMA; DIFFERENTIATED THYROID-CARCINOMA; RISK MELANOMA PATIENTS; LUNG-CANCER AB Tumor imaging is at the forefront of radiology technology and is the focus of most cutting edge research. Radiologic applications for imaging of metastases are applied to initial staging, restaging after neoadjuvant therapy, and follow-up surveillance after therapy for tumor recurrence. CT is the routine imaging choice in staging, restaging, and detection of recurrence. Fluorodeoxyglucose-positron emission tomography has evolved as an imaging modality that further improves staging as well as the detection of recurrent and metastatic disease. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM saquino@partners.org NR 118 TC 10 Z9 10 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 2005 VL 43 IS 3 BP 481 EP + DI 10.1016/j.rcl.2005.02.006 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 928IQ UT WOS:000229265400004 PM 15847812 ER PT J AU Shaffer, K AF Shaffer, K TI Radiology education in the digital era SO RADIOLOGY LA English DT Editorial Material ID MEMORY C1 Dana Farber Canc Inst, Dept Diagnost Radiol, Boston, MA 02115 USA. RP Shaffer, K (reprint author), Dana Farber Canc Inst, Dept Diagnost Radiol, 44 Binney St, Boston, MA 02115 USA. EM kitt_shaffer@dfci.harvard.edu OI Shaffer, Kitt/0000-0001-6488-6988 NR 19 TC 9 Z9 9 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 359 EP 360 DI 10.1148/radiol.2352041497 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200003 PM 15858078 ER PT J AU Gazelle, GS McMahon, PM Siebert, U Beinfeld, MT AF Gazelle, GS McMahon, PM Siebert, U Beinfeld, MT TI Cost-effectiveness analysis in the assessment of diagnostic Imaging technologies SO RADIOLOGY LA English DT Review ID COMPUTED BODY TOMOGRAPHY; HEALTH-CARE; CLINICAL EFFICACY; LUNG-CANCER; MEDICAL IMPLICATIONS; COLORECTAL-CANCER; ALZHEIMER-DISEASE; DECISION-ANALYSIS; OUTCOMES RESEARCH; ELDERLY-PATIENTS AB in many ways, diagnostic technologies differ from therapeutic medical technologies. Perhaps most important, diagnostic technologies do not generally directly affect long-term patient outcomes. Instead, the results of diagnostic tests can influence the care of patients; in that way, diagnostic tests may affect long-term outcomes. Because of this, the benefits associated with the use of a specific diagnostic technology will depend on the performance characteristics (eg, sensitivity and specificity) of the test, as well as other factors, such as prevalence of disease and effectiveness of available treatments for the disease in question. The fact that diagnostic tests affect short-term, or "surrogate," outcomes, rather than long-term patient outcomes makes evaluation of these tests more complicated than the evaluation of therapeutic technologies. This article will trace the history of technology assessment in medicine, address the role of cost-effectiveness and decision analysis in health technology assessment, and describe unique features and approaches to assessing diagnostic technologies. The article will then conclude with a consideration of the limits of medical technology assessment. (C) RSNA, 2005. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, PhD Program Hlth Policy, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM scott@mgh-ita.org NR 117 TC 37 Z9 37 U1 2 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 361 EP 370 DI 10.1148/radiol.2352040330 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200004 PM 15858079 ER PT J AU Lentz, MR Kim, JP Westmoreland, SV Greco, JB Fuller, RA Ratai, EM He, J Sehgal, PK Halpern, EF Lackner, AA Masliah, E Gonzalez, RG AF Lentz, MR Kim, JP Westmoreland, SV Greco, JB Fuller, RA Ratai, EM He, J Sehgal, PK Halpern, EF Lackner, AA Masliah, E Gonzalez, RG TI Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain SO RADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; SIMIAN IMMUNODEFICIENCY VIRUS; PROTON MR SPECTROSCOPY; AIDS DEMENTIA COMPLEX; HIV-INFECTED PATIENTS; H-1 MRS; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; ANTIRETROVIRAL THERAPY; METABOLIC ALTERATIONS AB PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee,on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton (H-1) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution H-1 MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed, Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis-was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic, markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection,with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction. (C) RSNA, 2005. C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Tulane Univ, Hlth Sci Ctr, Tulane Natl Primate Res Ctr, Covington, LA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, NMR Ctr, 55 Fruit St,GRB 285, Boston, MA 02114 USA. EM rggonzalez@partners.org FU NCRR NIH HHS [RR 00168-39, P41 RR 14075, RR 13213, P41 RR 00995]; NIMH NIH HHS [MH 61192, MH 45294]; NINDS NIH HHS [NS 34626, NS 30769] NR 60 TC 40 Z9 40 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 461 EP 468 DI 10.1148/radiol.2352040003 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200016 PM 15798152 ER PT J AU Ahmed, M Liu, ZJ Lukyanov, AN Signoretti, S Horkan, C Monsky, WL Torchilin, VP Goldberg, SN AF Ahmed, M Liu, ZJ Lukyanov, AN Signoretti, S Horkan, C Monsky, WL Torchilin, VP Goldberg, SN TI Combination radiofrequency ablation with intratumoral liposomal doxorubicin: Effect on drug accumulation and coagulation in multiple tissues and tumor types in animals SO RADIOLOGY LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, IL SP Radiol Soc N Amer ID THERMAL ABLATION; HEPATIC-TUMORS; HEPATOCELLULAR-CARCINOMA; INCREASED NECROSIS; PORCINE LIVER; MODEL; HYPERTHERMIA; SIZE; METASTASES; DELIVERY AB PURPOSE: To determine whether use of radiofrequency (RF) ablation combined with intravenously (IV) administered liposomal doxorubicin, as compared with use of RF ablation or doxorubicin alone, facilitates increased tissue coagulation and interstitial drug accumulation in animal models. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. In experiment 1, multiple canine sarcomas were implanted in seven mildly immunosuppressed dogs and grown to a mean diameter of 4.8 cm. Tumors were assigned to three treatment groups: internally cooled RF ablation (12 minutes, 2000-mA pulsed technique) followed by IV liposomal doxorubicin (10 mg per animal) (n = 6), RF ablation alone (n = 6), and liposomal doxorubicin alone (n = 4). In experiment 2, the livers and kidneys of 10 rabbits and the thigh muscles of 10 rats were randomly assigned to one of two treatment groups I : conventional RF ablation (90 degrees C 2, 5 minutes) followed by IV liposomal doxorubicin (5 mg per rabbit, 1 mg per rat) or RF ablation alone (n = 5, each). Coagulation diameter and interstitial doxorubicin concentration (tissues were homogenized in,acid alcohol, with doxorubicin extracted for 24 hours at 5 degrees C and quantified with fluorimetry) were measured 48 hours after treatment and compared. Multivariate analysis of variance and subsequent pairwise t tests (alpha = .05, two-tailed test) were performed. RESULTS: Data are means +/- standard errors of the mean. A larger diameter of tumor destruction was observed in canine sarcomas treated with RF ablation-liposomal doxorubicin (3.7 cm +/- 0.6) compared with that in tumors treated with RF ablation (2.3 cm +/- 0.1) or liposomal doxorubicin (0.0 cm +/- 0.0) alone (P < .01). A new finding was a completely necrotic red zone (1.6 cm +/- 0.7) surrounding the central RF ablation-induced white. coagulation zone. Greater but nonuniform drug uptake was observed particularly in this red zone (77.0 ng/g +/- 18.2) compared with uptake in the central zone (15.1 ng/g +/- 3.2), peripheral area of untreated tumor (38.9 ng/g +/- 8.0), and tumors treated with liposomal doxorubicin alone (43.9 ng/g +/- 6.7 for all regions) (P < .01 for all individual comparisons). In experiment 2 use of combined therapy led to increased coagulation in all tissues (liver 17.6 mm +/- 3.1, P = .03; kidney: 11.0 mm +/- 3.1, P = .03; muscle: 13.1 mm +/- 1.3, P < .01) compared with use of RF ablation alone (liver, 13.4 mm +/- 1.5; kidney, 7.9 mm +/- 0.7; muscle, 8.6 mm +/- 0.5). Combined therapy, as compared with liposomal doxorubicin therapy alone, was also associated with increased doxorubicin accumulation in liver, kidney, and muscle (1.56 mu g/g +/- 0.34,,4.36 mu g/g +/- 1.78, and 3.63 mu g/g +/- 1.43, respectively,,vs 1.00 mu g/g +/- 0.18,1.23 mu g/g +/- 0.32, and 0.87 mu g/g +/- 0.53, respectively) (P <= .01 for all individual comparisons). CONCLUSION: Use of RF ablation combined with liposomal doxorubicin facilitates increased tissue coagulation and interstitial doxorubicin accumulation in multiple tissues and tumor types and may be useful,for treatment of large tumors and achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors. (C) RSNA, 2005. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu FU NCI NIH HHS [R01 CA 87992-01A1] NR 46 TC 58 Z9 60 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 469 EP 477 DI 10.1148/radiol.2352031856 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200017 PM 15858089 ER PT J AU Kalra, MK Maher, MM D'Souza, RV Rizzo, S Halpern, EF Blake, MA Saini, S AF Kalra, MK Maher, MM D'Souza, RV Rizzo, S Halpern, EF Blake, MA Saini, S TI Detection of urinary tract stones at low-radiation-dose CT with Z-axis automatic tube current modulation: Phantom and clinical studies SO RADIOLOGY LA English DT Article ID UNENHANCED MULTIDETECTOR CT; HELICAL CT; COMPUTED-TOMOGRAPHY; IMAGE QUALITY; ABDOMINAL CT; REDUCTION; URETEROLITHIASIS; OPTIMIZATION; STRATEGIES AB PURPOSE: To evaluate depiction of urinary tract calculi at computed tomography (CT) with a z-axis modulation technique at various noise indexes to reduce radiation reserve image quality. MATERIALS AND METHODS: Sixteen radiopaque kidney stones (2.5-19.2 mm in diameter) were embedded in the collecting systems of two bovine kidneys immersed in a water bath. A kidney phantom was made by placing the kidneys in an elliptical Plexiglas phantom (32 x 20 x 20 cm) filled with physiologic saline. The phantom was scanned at 16-detector row CT with a fixed tube current (300 mA) and z-axis modulation at noise indexes of 14, 20, 25, 35, and 50; remaining imaging parameters were held constant. Two abdominal radiologists reviewed images from most to least noisy. Images were evaluated for presence of stones and size, site, and attenuation value of each stone. Readers also graded conspicuity and margins of each stone on a five-point scale. In addition, follow-up studies of 22 patients (mean age, 46 years; range, 26-57 years; male-female ratio, 14:8) with kidney and ureteral stones who underwent CT with z-axis modulation (noise index, 14 and 20) were evaluated in the same manner. Statistical analysis was performed with the Student t test, Wilcoxon signed rank test, and kappa test of interobserver agreement. Institutional review board approval was obtained, and informed consent was not needed. RESULTS: In the phantom study, all 16 stones were identified on images obtained with a fixed tube current and z-axis modulation at noise indexes of 14, 20, and 25 (with a reduction in radiation dose of up to 77% compared with that of fixed tube current scanning). Three stones (<5 mm) were not visualized with z-axis modulation at noise indexes of 35 and 50. No significant difference was shown for conspicuity of kidney stones in 22 patients who underwent CT with z-axis modulation (with a 43%-66% reduction in radiation dose) when compared with results of previous fixed tube current studies (P > .05). CONCLUSION: Kidney stones (<= 2.5 mm) can be adequately depicted with the z-axis modulation technique, with a 56%-77% reduction in radiation dose. In patients with urinary tract stones, the technique results in a 43%-66% reduction in radiation dose at noise indexes of 14 and 20 without compromising stone depiction. (C) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Kalra, MK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270-E,32 Fruit St, Boston, MA 02114 USA. EM mannudeep_k_kalra@yahoo.com NR 17 TC 69 Z9 80 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 523 EP 529 DI 10.1148/radiol.2352040331 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200024 PM 15770037 ER PT J AU Desmond, DO AF Desmond, DO TI Lowering the risk of pneumonitis: a dose volume histogram analysis of the ipsilateral lung with accelerated intracavitary partial breast irradiation SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Meeting of the Groupe-Europeen-de-Curietherapie/European-Society-for-Therapeutic-Radiol ogy-and-Oncology (GEC-ESTRO) CY MAY 06-07, 2005 CL Budapest, HUNGARY SP Grp Europeen Curietherapie, European Soc therapeut Radiol & Oncol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2005 VL 75 SU 1 MA 128 BP S51 EP S51 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 945IU UT WOS:000230497000129 ER PT J AU Stewart, A AF Stewart, A TI Fetal radiation dose: a phantom study of potential dose to the uterus at 12 and 24 weeks gestation with accelerated intracavitary partial breast irradiation SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT Meeting of the Groupe-Europeen-de-Curietherapie/European-Society-for-Therapeutic-Radiol ogy-and-Oncology (GEC-ESTRO) CY MAY 06-07, 2005 CL Budapest, HUNGARY SP Grp Europeen Curietherapie, European Soc therapeut Radiol & Oncol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD MAY PY 2005 VL 75 SU 1 MA 125 BP S50 EP S50 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 945IU UT WOS:000230497000126 ER PT J AU Mackin, RS Horner, MD Harvey, RT Stevens, LA AF Mackin, RS Horner, MD Harvey, RT Stevens, LA TI The relationship between neuropsychological measures and employment problems in outpatients with substance abuse SO REHABILITATION PSYCHOLOGY LA English DT Article ID ADDICTION SEVERITY INDEX; TRAUMATIC BRAIN-INJURY; DEPENDENT PATIENTS; COCAINE ABUSERS; ALCOHOL; TESTS AB Objective: To determine the relation between standard clinical neuropsychological tests and employment problems in persons with substance abuse. Participants: Sixty-four patients enrolled in an intensive outpatient substance abuse treatment program. Measures: Employment Problem Severity Score (EPSS) of the Addiction Severity Index and a comprehensive neuropsychological evaluation, including standard measures of attention, executive function, and memory. Results: Multiple regression analyses showed that response latency on the Vigilance trial of the Gordon Diagnostic System and scores on list acquisition and long-delay free recall of the California Verbal Learning Test were significant predictors of EPSS. Performance on measures of executive function did not predict EPSS. Conclusions: Neuropsychological tests may help to identify individuals at risk for employment problems, thereby improving outcomes for patients with substance abuse problems and cognitive deficits. C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Mackin, RS (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave,Box OVS-0984, San Francisco, CA 94143 USA. EM scottm@lppi.ucsf.edu NR 31 TC 4 Z9 4 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD MAY PY 2005 VL 50 IS 2 BP 158 EP 163 DI 10.1037/0090-5550.50.2.158 PG 6 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 931ND UT WOS:000229491100009 ER PT J AU Fernandez-del Castillo, C AF Fernandez-del Castillo, C TI Malignance prediction in pancreas endocrine neoplasias SO REVISTA DE INVESTIGACION CLINICA LA Spanish DT Article ID ISLET-CELL TUMORS; NEUROENDOCRINE TUMORS; CLASSIFICATION; SURVIVAL; HYPERINSULINISM; PROLIFERATION C1 Massachusetts Gen Hosp, Escuela Med, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Escuela Med, 15 Parkman St,WAN 336, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU INST NACIONAL NUTRICION PI TLALPAN PA VASCO DE QUIROZA #15, TLALPAN 14000 D F, MEXICO SN 0034-8376 J9 REV INVEST CLIN JI Rev. Invest. Clin. PD MAY-JUN PY 2005 VL 57 IS 3 BP 481 EP 487 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 959XC UT WOS:000231551600012 PM 16187709 ER PT J AU Vilaichone, RK Mahachai, V Tumwasorn, S Wu, JY Graham, DY Yamaoka, Y AF Vilaichone, RK Mahachai, V Tumwasorn, S Wu, JY Graham, DY Yamaoka, Y TI Gastric mucosal cytokine levels in relation to host interleukin-1 polymorphisms and Helicobacter pylori cagA genotype SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE cytokines; gastric diseases; Helicobacter pylori; interleukin-1; interleukin-8; polymorphisms ID NECROSIS-FACTOR-ALPHA; ATROPHIC GASTRITIS; VIRULENCE FACTORS; INCREASED RISK; INFECTION; GENE; CARCINOMA; DISEASE; CANCER; EXPRESSION AB Objective. The outcome of a Helicobacter pylori infection is related in part to interrelationships among H. pylori virulence factors and the H. pylori-induced mucosal response. The host inflammatory response is partly governed by polymorphisms in pro-inflammatory genes. Material and methods. Cytokine levels ( interleukin (IL)-1 beta, IL-6 and IL-8) were examined in H. pylori - infected and uninfected normal-appearing mucosa from patients with non-ulcer dyspepsia (NUD), margins of gastric ulcers and cancer tissues. Cytokine levels were compared with cagA genotypes and host interleukin ( IL)- 1 polymorphisms. Results. The study comprised 168 Thai patients. All infected patients possessed anti-CagA antibody. Gastric mucosal IL-8 levels were significantly higher in H. pylori - positive cases than in - negative cases in all three tissue types ( e. g. 1115 versus 217 pg/mg protein for NUD) ( p< 0.001). Normal-appearing but H. pylori - infected antral mucosa of patients with cagA type 1a strains had higher IL-8 levels than those with type 2a strains ( 2632 versus 1036 pg/mg protein) (p< 0.005). IL-1B-511T/ T carriers had higher antral mucosal IL-1 beta levels versus non-carriers (pg/mg protein) (T/T = 221, T/C = 178, C/C = 70) ( p = 0.005). IL-1B-511T/ T carriers also had higher IL-1 beta levels versus non-carriers in H. pylori negative patients. Conclusions. It was found that both the host factors (IL-1 polymorphisms) and bacterial factors ( cagA type 1a versus type 2a) influenced gastric mucosal cytokine levels. Future studies should concentrate on interactions among host factors ( e. g. genetics and tissue responses) and bacterial and environmental factors. C1 Thammasat Univ Hosp, Dept Med, Gastroenterol Unit, Pathum Thani, Thailand. Michael E Debakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Chulalongkorn Univ Hosp, Dept Med, Bangkok, Thailand. Chulalongkorn Univ Hosp, Dept Microbiol, Bangkok, Thailand. RP Yamaoka, Y (reprint author), Michael E Debakey Vet Affairs Med Ctr 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu NR 39 TC 24 Z9 29 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD MAY PY 2005 VL 40 IS 5 BP 530 EP 539 DI 10.1080/00365520510012299 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 920IT UT WOS:000228683300006 PM 16036505 ER PT J AU Moller-Kristensen, M Wang, W Ruseva, M Thiel, S Nielsen, S Takahashi, K Shi, L Ezekowitz, A Jensenius, JC Gadjeva, M AF Moller-Kristensen, M Wang, W Ruseva, M Thiel, S Nielsen, S Takahashi, K Shi, L Ezekowitz, A Jensenius, JC Gadjeva, M TI Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID RENAL ISCHEMIA/REPERFUSION INJURY; COMPLEMENT ACTIVATION; OXIDATIVE STRESS; DEFICIENT MICE; PATHWAY; APOPTOSIS; PROTEIN; MBL; INFLAMMATION; INHIBITION AB Organ damage as a consequence of ischaemia and reperfusion (I/R) is a major clinical problem in an acute renal failure and transplantation. Ligands on surfaces of endothelial cells that are exposed due to the ischaemia. may be recognized by pattern recognition molecules such as mannan-binding lectin (MBL), inducing complement activation. We examined the contribution of the MBL complement pathway in a bilateral renal I/R model (45 min of ischaemia followed by 24 h of reperfusion), using transgenic mice deficient in MBL-A and MBL-C [MBL double knockout (MBL DKO)] and in wildtype (WT) mice. Kidney damages, which were evaluated by levels of blood urea nitrogen (BUN) and creatinine, showed that MBL DKO mice were significantly protected compared with WT mice. MBL DKO mice, reconstituted with recombinant human MBL, showed a dose-dependent severity of kidney injury increasing to a comparable level to WT mice. Acute tubular necrosis was evident in WT mice but not in MBL DKO mice after I/R, confirming renal damages in WT mice. MBL ligands in kidneys were observed to be present after I/R but not in sham-operated mice. C3a (desArg) levels in MBL DKO mice were decreased after I/R compared with that in WT mice, indicating less complement activation that was correlated with less C3 deposition in the kidneys of MBL DKO mice. Our data implicate a role of MBL in I/R-induced kidney injury. C1 Univ Aarhus, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. Univ Aarhus, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Massachusetts Gen Hosp, Dept Immunol, Boston, MA 02114 USA. RP Moller-Kristensen, M (reprint author), Univ Aarhus, Dept Med Microbiol & Immunol, DK-8000 Aarhus, Denmark. EM mmk@microbiology.au.dk NR 48 TC 95 Z9 96 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2005 VL 61 IS 5 BP 426 EP 434 DI 10.1111/j.1365-3083.2005.01591.x PG 9 WC Immunology SC Immunology GA 929UW UT WOS:000229373100005 PM 15882434 ER PT J AU Thermenos, HW Goldstein, JM Buka, SL Poldrack, RA Koch, JK Tsuang, MT Seidman, LJ AF Thermenos, HW Goldstein, JM Buka, SL Poldrack, RA Koch, JK Tsuang, MT Seidman, LJ TI The effect of working memory performance on functional MRI in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; functional MRI; working memory; prefrontal cortex; N-back ID DORSOLATERAL PREFRONTAL CORTEX; ATTENUATED FRONTAL ACTIVATION; AUDITORY HALLUCINATIONS; N-ACETYLASPARTATE; BRAIN ACTIVATION; PHYSIOLOGICAL DYSFUNCTION; CORTICAL DYSFUNCTION; NEGATIVE SYMPTOMS; THOUGHT-DISORDER; SEX-DIFFERENCES AB Introduction: Studies of prefrontal cortical (PFC) function in schizophrenia have been inconsistent, with studies showing both increased and decreased PFC activation compared to healthy controls. Discrepant findings may be due to task performance effects or demographic differences between samples. We report functional magnetic resonance imaging (fMRI) data comparing subjects with schizophrenia and healthy controls performing a 2-back working memory (WM) task, addressing the effects of task performance. Methods: Twenty-two controls and 14 patients with DSM-lV schizophrenia, scanned on a Siemens 1.5 T scanner, performed a visual letter 2-back task and control task (CPT-X) during fMRI. Data were analyzed using Statistical Parametric Mapping (SPM)-99. Results: After statistical adjustment for performance differences, persons with schizophrenia showed significantly greater activation than controls in the right medial frontal gyrus and left inferior parietal lobule/medial temporal gyrus region (BA 39/40), and a trend toward greater activation in the left ventrolateral PFC. This pattern was also observed in demographically matched subgroups of participants. Conclusions: Data are consistent with findings reported in recent studies showing increased PFC and parietal activation in schizophrenia when the effects of reduced WM task performance in patients with schizophrenia are addressed. Further studies are needed to clarify the pathophysiological basis of WM load sensitivity in schizophrenia and its relationship to genes. (C) 2004 Elsevier B.V All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Div Womens Hlth,Connors Ctr Womens Hlth & Gender, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Inst Brain Res, Los Angeles, CA 90095 USA. Univ Calif San Diego, Dept Psychiat, Inst Behav Genom, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury VA Med Ctr, Cambridge, MA 02140 USA. RP Thermenos, HW (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Nucl Magnet Resonance Imaging Ctr, Bldg 149,Room 2602E,13th St, Charlestown, MA 02129 USA. EM heidi_wencef@hms.harvard.edu RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [MH-63951, MH 56956, MH-16259, MH-43518, MH-50647, R25 MH 60485] NR 75 TC 68 Z9 69 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 1 PY 2005 VL 74 IS 2-3 BP 179 EP 194 DI 10.1016/j.schres.2004.07.021 PG 16 WC Psychiatry SC Psychiatry GA 904FP UT WOS:000227481800006 PM 15721998 ER PT J AU Cather, C Penn, D Otto, MW Yovel, I Mueser, KT Goff, DC AF Cather, C Penn, D Otto, MW Yovel, I Mueser, KT Goff, DC TI A pilot study of functional Cognitive Behavioral Therapy (fCBT) for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; therapy; cognitive-behavioral therapy ID RANDOMIZED CONTROLLED-TRIAL; NEGATIVE SYNDROME SCALE; FAMILY INTERVENTION; PSYCHOTIC SYMPTOMS; RESISTANT; MEDICATION; RECOVERY; IMPACT; PHASE AB Background: The feasibility and preliminary efficacy of a novel cognitive behavioral treatment for decreasing psychotic symptoms and improving social functioning was evaluated in a pilot study. This represents the first treatment outcome study of CBT for psychosis with a manualized, active comparison condition. Methods: Thirty outpatients with schizophrenia or schizoaffective disorder, depressed type with residual psychotic symptoms were randomly assigned to either 16 weekly sessions of functional cognitive behavioral therapy (fCBT) or psychoeducation (PE) with assessments conducted at baseline and post-treatment by blind evaluators. Results: Attrition was only 7% and did not differ between fCBT and PE, indicating good tolerability of both treatments. For this sample with persistent symptoms, between groups effects were not significantly different, but within group effect sizes indicated greater treatment benefit for fCBT on positive symptoms, particularly for the PSYRATS voices subscale. Conclusion: The results suggest that fCBT is well tolerated and holds promise for reducing persistent positive symptoms. (C) 2004 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC USA. Dartmouth Coll Sch Med, Psychiat Res Ctr, Hanover, NH USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ccather@partners.org NR 37 TC 68 Z9 69 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 1 PY 2005 VL 74 IS 2-3 BP 201 EP 209 DI 10.1016/j.schres.2004.05.002 PG 9 WC Psychiatry SC Psychiatry GA 904FP UT WOS:000227481800008 PM 15722000 ER PT J AU Green, MF Barnes, TR Danion, JM Gallhofer, B Meltzer, HY Pantelis, C AF Green, MF Barnes, TR Danion, JM Gallhofer, B Meltzer, HY Pantelis, C TI The FOCIS international survey on psychiatrists' opinions on cognition in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognitive deficit; schizophrenia; survey; functional outcome ID QUALITY-OF-LIFE; NEUROCOGNITIVE DEFICITS; CLOZAPINE; RISPERIDONE; OLANZAPINE; SYMPTOMS AB Background: The goal of this project was to develop an interview to evaluate psychiatrists' views on the nature of cognitive dysfunction in schizophrenia, its importance as a potential treatment target, and its relative importance as a treatment target across different phases of schizophrenia. Materials and methods: A survey (available in paper or on-line) consisting of 27 questions, was developed by the Focus on Cognition in Schizophrenia (FOCIS) group, and distributed in a single wave mailing to 63,295 psychiatrists in 21 countries worldwide. Results: The overall response rate was 4.7% (n=2975). The surveyed psychiatrists perceived cognition as a high treatment priority in stabilized schizophrenia patients, but less so for first episode or acute schizophrenia patients. The potential of atypical antipsychotics to improve cognitive dysfunction in schizophrenia was identified by 81% of the respondent psychiatrists. Conclusions: Cognitive deficits in people with schizophrenia are seen by clinical psychiatrists as relevant to treatment and rehabilitation plans. They were, however, regarded as a higher treatment priority in stabilized chronic rather than in first episode patients. The results suggest clinical psychiatrists need additional education regarding the nature of cognitive dysftinction in schizophrenia and its importance for psychosocial rehabilitation and community re-entry. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ London Imperial Coll Sci & Technol, Div Neurosci & Psychol Med, London, England. Hop Univ, Strasbourg, France. Univ Giessen, Sch Med, Giessen, Germany. Vanderbilt Univ, Nashville, TN USA. Univ Melbourne, Neuropsychiat Ctr, Melbourne, Vic, Australia. RP Green, MF (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Med Plaza Bldg 300,Rm 2263, Los Angeles, CA 90095 USA. EM mgreen@ucla.edu RI Meltzer, Herbert/E-8131-2013; Pantelis, Christos/H-7722-2014 OI Pantelis, Christos/0000-0002-9565-0238 NR 26 TC 13 Z9 13 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 MAY 1 PY 2005 VL 74 IS 2-3 BP 253 EP 261 DI 10.1016/j.schres.2004.05.023 PG 9 WC Psychiatry SC Psychiatry GA 904FP UT WOS:000227481800012 PM 15722004 ER PT J AU Myaskovsky, L Unikel, E Dew, MA AF Myaskovsky, L Unikel, E Dew, MA TI Effects of gender diversity on performance and interpersonal behavior in small work groups SO SEX ROLES LA English DT Article DE gender composition; group performance; interpersonal behavior ID MIXED-SEX GROUPS; JURY DELIBERATIONS; TRANSACTIVE MEMORY; SOCIAL-INTERACTION; TEAM PERFORMANCE; TOKEN STATUS; MALE-FEMALE; WOMEN; MEN; PERCEPTIONS AB We examined the separate and combined impact of gender composition and training method on both the performance and interpersonal behaviors exhibited in small work groups. Participants were scheduled in groups of three for two 1-h sessions that occurred 1 week apart. In Session 1, groups were trained to assemble the AM portion of a radio. In Session 2, groups were tested on their training. Analyses indicated that groups whose members were trained together took longer to assemble their radios and made more errors than groups whose members were trained apart. No performance differences were found between mixedgender and same-gender groups. However, women were less task-oriented in mixed-gender than in same-gender groups, but men were more task-oriented in mixed-gender than in same-gender groups. Further, solo women were less talkative than women in the majority, whereas men were more talkative when they were solos rather than in the majority. Implications for the nature of training and gender composition in groups in the workplace are discussed. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Myaskovsky, L (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C 151-C, Pittsburgh, PA 15240 USA. EM Larissa.Myaskovsky@med.va.gov NR 74 TC 27 Z9 27 U1 7 U2 34 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-0025 J9 SEX ROLES JI Sex Roles PD MAY PY 2005 VL 52 IS 9-10 BP 645 EP 657 DI 10.1007/s11199-005-3732-8 PG 13 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA 946IV UT WOS:000230566500008 ER PT J AU Skatrud, JB Morgan, BJ AF Skatrud, JB Morgan, BJ TI Probing the link between sleep apnea and cardiovascular disease - Comment on Phillips C; Hedner J; Berend N et al. Diurnal and obstructive sleep apnea influences on arterial stiffness and central blood pressure in men. SLEEP 2005;28(5): 604-609 SO SLEEP LA English DT Editorial Material ID POSITIVE AIRWAY PRESSURE; ENDOTHELIAL GROWTH-FACTOR; CORONARY HEART-DISEASE; SMOOTH-MUSCLE-CELLS; C-REACTIVE PROTEIN; ANGIOTENSIN-II; VASCULAR WALL; HYPERTENSION; EXPRESSION; HYPOXIA C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Orthoped & Rehabil, Madison, WI 53706 USA. RP Skatrud, JB (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM james.skatrud2@med.va.gov NR 30 TC 1 Z9 1 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2005 VL 28 IS 5 BP 545 EP 547 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 926PX UT WOS:000229136200003 PM 16171266 ER PT J AU Myaskovsky, L Dew, MA Switzer, GE McNulty, ML DiMartini, AF McCurry, KR AF Myaskovsky, L Dew, MA Switzer, GE McNulty, ML DiMartini, AF McCurry, KR TI Quality of life and coping strategies among lung transplant candidates and their family caregivers SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-Behavioral-Medicine CY MAR, 2004 CL Baltimore, MD SP Soc Behav Med DE transplant candidates; caregivers; coping; quality of life (QOL); USA ID CARDIOVASCULAR HEALTH; RECIPIENTS; DEPRESSION; SIMILARITY; DEMENTIA; DISEASE; RISK AB Although numerous studies have examined coping strategies and quality of life (QOL) among patients with chronic diseases and their family caregivers, no studies have examined the reciprocal effects of patient and caregiver coping strategies on their dyad partner's QOL. Because most people who cope with stressful health experiences do so within the context of interpersonal relation ships, it is important to understand the ways in which the two partners' coping strategies may reciprocally affect each other's QOL. Adult lung transplant candidates and their caregivers (N = 114 pairs) participated in semi-structured interviews that included measures of QOL and coping with patients' health-related problems. Multivariate, canonical correlation analyses were performed to examine unique patterns of associations between coping and QOL in patient-caregiver dyads. Better patient QOL, across multiple domains, was associated with better caregiver QOL. Multiple elements of patients' coping, including greater use of active coping and emotionally oriented coping were related to generally poorer patient QOL in psychosocial and physical domains. Similarly, caregivers who used more emotionally oriented coping had poorer QOL. There was no statistically reliable relationship between either (a) patient and caregiver use of coping strategies, or (b) caregiver coping and patient QOL. However, patients' coping strategies were important correlates of caregivers' QOL. These findings belie common clinical beliefs that family members' coping responses to patients' health are likely to affect patient well-being. instead, patients' coping and QOL may be critical for understanding caregiver well-being, especially in the current era in which caregivers are assuming increased responsibility for providing patient care. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. Dept Psychol, Pittsburgh, PA 15213 USA. Dept Med, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. UPMC Presbyterian, Dept Surg, Pittsburgh, PA 15213 USA. RP Myaskovsky, L (reprint author), Univ Pittsburgh, Dept Psychiat, Suite 502 Iroquois Bldg,3600 Forbes Ave, Pittsburgh, PA 15213 USA. EM myaskovskyl@uipmc.edu NR 44 TC 30 Z9 30 U1 3 U2 7 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 MAY PY 2005 VL 60 IS 10 BP 2321 EP 2332 DI 10.1016/j.socscimed.2004.10.001 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 908HX UT WOS:000227779200015 PM 15748679 ER PT J AU Rehman, SU Cope, DW Senseney, AD Brzezinski, W AF Rehman, SU Cope, DW Senseney, AD Brzezinski, W TI Thyroid disorders in elderly patients SO SOUTHERN MEDICAL JOURNAL LA English DT Review DE elderly; hyperthyroidism; hypothyroidism; thyroid disease ID HYPERTHYROIDISM; DISEASE; AGE; HYPOTHYROIDISM; DYSFUNCTION; MANAGEMENT AB Thyroid disorders are common in the elderly and are associated with significant morbidity if left untreated. Typical symptoms may be absent and may be erroneously attributed to normal aging or coexisting disease. Physical examination of the thyroid gland may not be helpful, as the gland is often shrunken and difficult to palpate. Usually only myxedema coma requires levothyroxine parenterally; all other forms of hypothyroidism can be treated with oral levothyroxine. Low-dose levothyroxine should be initiated and increased gradually over several months. In unstable elderly patients with hyperthyroidism, antithyroid medication can quickly produce a euthyroid state. Radioactive iodine therapy is more definitive and is well tolerated, effective, and preferred. Surgical thyroid ablation may be necessary in patients who fail to respond to radioactive iodine therapy and in patients with multinodular goiter. If there is a suspicion of malignant disease, early biopsy or fine needle aspiration for cytology should be considered. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Geriatr Serv Line, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Olive View UCLA Med Ctr, Dept Med, Sylmar, CA 91342 USA. RP Rehman, SU (reprint author), 214 Hist Dr, Mt Pleasant, SC 29464 USA. EM Shakaib.rehman@med.va.gov NR 46 TC 14 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2005 VL 98 IS 5 BP 543 EP 549 DI 10.1097/01.SMJ.0000152364.57566.6D PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 928IE UT WOS:000229264100009 PM 15954511 ER PT J AU Thieke, C Kufer, KH Monz, M Scherrer, A Alonso, F Debus, J Thilmann, C Bortfeld, T AF Thieke, C Kufer, KH Monz, M Scherrer, A Alonso, F Debus, J Thilmann, C Bortfeld, T TI Inverse radiation planning in the multi-criterial optimisation concept SO STRAHLENTHERAPIE UND ONKOLOGIE LA German DT Meeting Abstract CT 11th Annual Congress of the German-Society-for-Radiooncology CY MAY 26-29, 2005 CL Karlsruhe, GERMANY SP German Soc Radiooncol C1 Fraunhofer ITWM Techno & Wirtschaftsmath, Abt Optimierung, Kaiserslautern, Germany. Radiol Univ Klin, Abt Klin Radiol, Heidelberg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Deutsch Krebsforschungszentrum, Abt Strahlentherapie, D-6900 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0179-7158 J9 STRAHLENTHER ONKOL JI Strahlenther. Onkol. PD MAY PY 2005 VL 181 SU 1 BP 88 EP 89 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 932YL UT WOS:000229590600319 ER PT J AU Huang, CC Stricher, F Martin, L Decker, JM Majeed, S Barthe, P Hendrickson, WA Robinson, J Roumestand, C Sodroski, J Wyatt, R Shaw, GM Vita, C Kwong, PD AF Huang, CC Stricher, F Martin, L Decker, JM Majeed, S Barthe, P Hendrickson, WA Robinson, J Roumestand, C Sodroski, J Wyatt, R Shaw, GM Vita, C Kwong, PD TI Scorpion-toxin mimics of CD4 in complex with human immunodeficiency virus gp120: Crystal structures, molecular mimicry, and neutralization breadth SO STRUCTURE LA English DT Article ID ENVELOPE GLYCOPROTEIN; HIV-1 ENVELOPE; SOLUBLE CD4; RECEPTOR-BINDING; ATOMIC-STRUCTURE; TYPE-1; ANTIBODY; DESIGN; ENTRY; SITE AB The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth. C1 Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. CEA Saclay, Dept Prot Engn & Res, F-91191 Gif Sur Yvette, France. Univ Alabama, Howard Hughes Med Inst, Dept Med, Dept Microbiol, Birmingham, AL 35294 USA. Fac Pharm Montpellier, Struct Biol Ctr, F-34093 Montpellier, France. Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kwong, PD (reprint author), Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM pdkwong@nih.gov RI MARTIN, loic/E-1627-2011 OI MARTIN, loic/0000-0002-7940-2955 NR 54 TC 79 Z9 84 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2005 VL 13 IS 5 BP 755 EP 768 DI 10.1016/j.str.2005.03.006 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 929GU UT WOS:000229330900011 PM 15893666 ER PT J AU Velmahos, GC Petrone, P Chan, LS Hanks, SE Brown, CV Demetriades, D AF Velmahos, GC Petrone, P Chan, LS Hanks, SE Brown, CV Demetriades, D TI Electrostimulation for the prevention of deep venous thrombosis in patients with major trauma: A prospective randomized study SO SURGERY LA English DT Article ID CALF MUSCLE STIMULATION; MOLECULAR-WEIGHT HEPARIN; LOW-DOSE HEPARIN; VEIN-THROMBOSIS; POSTOPERATIVE THROMBOEMBOLISM; INJURED PATIENTS; PROPHYLAXIS; RISK AB Background. Current methods of posttraumatic thromboprophylaxis (heparins and sequential compression devices) are inadequate. New methods should be tested. Muscle electrostimulation (MEST) has been used over the years with mixed-but predominantly encouraging results for a variety of conditions, including prevention of deep venous thrombosis (DVT). It has not been tested in multiple trauma patients. Methods. Trauma patients with Injury Severity Score higher than 9 who were admitted to the intensive care unit and had a contraindication for prophylactic heparinization were randomized to groups MEST and control. MEST patients received 30-minute MEST sessions twice daily for 7 to 14 days. Venous flow velocity and venous diameter were measured by duplex venous scan. Venography-or, if not available, duplex-was used to evaluate the Presence of proximal and peripheral DVT between days 7 and 15. Results. After exclusions, 26 MEST and 21 control patients completed the study and received outcome evaluation by venography (25) or duplex (22). Three patients in each group developed proximal DVT (11.5% vs 14%, P = .79), and an additional 4 (15%) MEST group and 3 (14%) control group patients developed peripheral DVT (P 96). There was no difference in venous flow velocity or venous diameter between the groups. Conclusions. MEST was not effective in decreasing DVT rates in major trauma patients. C1 Los Angeles Cty & Univ So Calif Med Ctr, Dept Surg, Div Trauma & Crit Care, Los Angeles, CA USA. Los Angeles Cty & Univ So Calif Med Ctr, Dept Surg, Dept Biostat & Outcomes Res, Los Angeles, CA USA. Los Angeles Cty & Univ So Calif Med Ctr, Dept Surg, Dept Radiol, Los Angeles, CA USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Warren 1212, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 20 TC 16 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2005 VL 137 IS 5 BP 493 EP 498 DI 10.1016/j.surg.2005.01.010 PG 6 WC Surgery SC Surgery GA 924BF UT WOS:000228952900002 PM 15855919 ER PT J AU Stahl, JE Egan, MT Goldman, JM Tenney, D Wiklund, RA Sandberg, WS Gazelle, S Rattner, DW AF Stahl, JE Egan, MT Goldman, JM Tenney, D Wiklund, RA Sandberg, WS Gazelle, S Rattner, DW TI Introducing new technology into the operating room: Measuring the impact on job performance and satisfaction SO SURGERY LA English DT Article ID BURNOUT; NURSES; EMERGENCY; SURGEONS; STRESS AB Background. The Massachusetts General Hospital (MGH) Operating Room of the future (ORF) project is a test site for evaluating new surgical technologies and processes. Here we evaluate the effect on staff satisfaction and burnout of introducing a set of new technologies. Methods. Staff satisfaction and burnout were measured via sequential surveys based on the Maslach Burnout Inventory during the introduction of a new technology system. Functional behavior of the OR was measured in terms of flow time (time to transit the OR) and wait time (time to access the OR). These data were gathered using time-motion analysis methods. Results. Significant functional improvements were found in the ORF (more than 35% reduction inflow time and wait time, P < .05). During the same period, more exposure to the ORF resulted in greater sense of personal accomplishment among surgeons, a worse sense of personal accomplishment among nurses, more emotional exhaustion among surgeons. and less emotional exhaustion among nurses. However the responses for emotional exhaustion were reversed the greater the time from exposure to the ORF. Staff with 6 to 10 years' experience were at highest risk for burnout across all categories. General surgeons experienced more emotional exhaustion than other physicians. Conclusions. Tracking the response of all users and identifying groups at high risk for burnout when exposed to new systems should be a central Part of any new technology project. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Dept Nursing, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Dept Operating Room Adm & Surg, Boston, MA 02114 USA. RP Stahl, JE (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Dept Med, 101 Merimac St,10th Floor, Boston, MA 02114 USA. EM James@mgh-ita.org OI Sandberg, Warren/0000-0002-9246-777X NR 27 TC 28 Z9 28 U1 3 U2 8 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2005 VL 137 IS 5 BP 518 EP 526 DI 10.1016/j.surg.2004.12.015 PG 9 WC Surgery SC Surgery GA 924BF UT WOS:000228952900006 PM 15855924 ER PT J AU Shifrin, AL Chirmule, N Zhang, Y Raper, SE AF Shifrin, AL Chirmule, N Zhang, Y Raper, SE TI Macrophage ablation attenuates adenoviral vector-induced pancreatitis SO SURGERY LA English DT Article ID MEDIATED GENE-TRANSFER; IN-VIVO; RECOMBINANT ADENOVIRUS; DEPLETION; EXPRESSION; MURINE; INTERLEUKIN-6; CONSEQUENCES; CYTOKINES; RESPONSES AB Background. The objective of these studies is to determine the effects of macrophage ablation on the course of acute viral pancreatitis. Macrophages secrete poinflammatory cytokines triggering local pancreatic and systemic inflammation in the acute phase of virus-induced pancreatitis. We hypothesized that ablation of macrophages should attenuate the host inflammatory response in a mouse model of adenovirus-induced pancreatitis. Methods. Liposome encapsulated dichloromethylene diphosphonate, a macrophage-depleting agent, was used before direct pancreatic injection of a recombinant adenovirus expressing a marker gene in C57Bl/6 and IL-6 knockout (KO) mice. Results. C57Bl/6 mice depleted of macrophages had diminished pancreatic inflammation in the first 24 hours after vector administration. IL-6 KO mice depleted of macrophages had more severe inflammation than similarly treated C57Bl/6 mice. C57Bl/6 mice depleted of macrophages, and IL-6 KO mice had prolonged transgene expression and diminished cytotoxic T lymphocyte responses to adenoviral vector. Mortality was highest in IL-6 KO mice depleted of macrophages. Depletion of macrophages also prevented delectable serum IL-6, IL-10, or IL-12 levels in C57Bl/6 mice. Conclusions. The data suggest that macrophages play a role in the acute inflammatory response to viral vector-induced pancreatitis and that IL-6 may be protective. Understanding of the mechanisms that initiate the host immune cascade will allow more effective use of adenoviral vector-based pancreatic gene delivery. C1 Univ Penn, Dept Surg, Hlth Syst, Philadelphia, PA 19104 USA. Merck Res Labs, Wayne, NJ USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Raper, SE (reprint author), Univ Penn, Dept Surg, Hlth Syst, 4 Silverstein Pavil 3400 Spruce St, Philadelphia, PA 19104 USA. EM rapers@uphs.upenn.edu FU NIDDK NIH HHS [DK 54207, DK 47757] NR 25 TC 20 Z9 23 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2005 VL 137 IS 5 BP 545 EP 551 DI 10.1016/j.surg.2005.01.004 PG 7 WC Surgery SC Surgery GA 924BF UT WOS:000228952900009 PM 15855927 ER PT J AU Hershman, JM AF Hershman, JM TI In my view ... Perchlorate and thyroid function: What are the environmental issues? SO THYROID LA English DT Article ID LOW-DOSE PERCHLORATE; DRINKING-WATER; SUBCLINICAL HYPOTHYROIDISM; POTASSIUM PERCHLORATE; ARIZONA PERCHLORATE; IODINE; EXPOSURE; NEWBORNS; THYROTOXICOSIS; CONTAMINATION AB Ammonium Perchlorate, used in the solid-propellant of rocket engines, has contaminated some water supplies and represents a potential public health hazard. Its toxicity is the result of the inhibition of the sodium iodide symporter resulting in reduced iodide uptake, possibly leading to reduced production of thyroid hormone. The fetus is the most vulnerable subject. Studies of newborn screening for thyroid function have yielded conflicting results and have not measured Perchlorate or iodine intake. Based on short-term clinical studies in adults, less than 0.5 mg Perchlorate per 70-kg adult will not lower thyroid uptake of radioiodine, while 1.6 mg/kg per day will lower thyroid uptake by 20%. To avoid interference with thyroid function, the California Office of Environmental Health Hazard Assessment recommended a public health goal of 6 μ g Perchlorate per liter of drinking water, but approximately three times that concentration is likely to be safe. C1 Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, Los Angeles, CA 90073 USA. RP Hershman, JM (reprint author), Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Endocrinol & Diabet Div, 111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jhershmn@ucla.edu NR 34 TC 16 Z9 17 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD MAY PY 2005 VL 15 IS 5 BP 427 EP 431 DI 10.1089/thy.2005.15.427 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 932JO UT WOS:000229550200005 PM 15929663 ER PT J AU Handley-Goldstone, HM Grow, MW Stegeman, JJ AF Handley-Goldstone, HM Grow, MW Stegeman, JJ TI Cardiovascular gene expression profiles of dioxin exposure in zebrafish embryos SO TOXICOLOGICAL SCIENCES LA English DT Article ID REACTIVE OXYGEN PRODUCTION; APOPTOTIC CELL-DEATH; HYDROCARBON RECEPTOR; CYTOCHROME-P450 1A; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN EXPOSURE; DILATED CARDIOMYOPATHY; CIRCULATION FAILURE; MOUSE-LIVER; TOXICITY; STAGE AB 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a widespread environmental contaminant that causes altered heart morphology, circulatory impairment, edema, hemorrhage, and early life stage mortality in fish. TCDD toxicity is dependent, in large part, on the aryl hydrocarbon receptor (AHR), but understanding of the molecular mechanism of cardiovascular embryotoxicity remains incomplete. To identify genes potentially involved in cardiovascular effects, we constructed custom cDNA microarrays consisting of 4896 zebrafish adult heart cDNA clones and over 200 genes with known developmental, toxicological and housekeeping roles. Gene expression profiles were obtained for 3-day-old zebrafish after early embryonic exposure to either 0.5 or 5.0 nM TCDD. In all, 516 clones were significantly differentially expressed (p < 0.005) under at least one treatment condition; 123 high-priority clones were selected for further investigation. Cytochromes P450 1A and 1B1, and other members of the AHR gene battery, were strongly and dose-dependently induced by TCDD. Importantly, altered expression of cardiac sarcomere components, including cardiac troponin T2 and multiple myosin isoforms, was consistent with the hypothesis that TCDD causes dilated cardiomyopathy. Observed increases in expression levels of mitochondrial energy transfer genes also may be related to cardiomyopathy. Other TCDD-responsive genes included fatty acid and steroid metabolism enzymes, ribosomal and signal-transduction proteins, and 18 expressed sequence tags (ESTs) with no known protein homologs. As the first broad-scale study of TCDD-modulated gene expression in a non-mammalian system, this work provides an important perspective on mechanisms of TCDD toxicity. C1 Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. Indiana Univ, Sch Med, Ctr Med Genom, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Handley-Goldstone, HM (reprint author), Woods Hole Oceanog Inst, Dept Biol, Redfield 3-52,MS 32, Woods Hole, MA 02543 USA. EM hhandley@alum.mit.edu NR 49 TC 67 Z9 73 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2005 VL 85 IS 1 BP 683 EP 693 DI 10.1093/toxsci/kfi116 PG 11 WC Toxicology SC Toxicology GA 916PO UT WOS:000228398000028 PM 15716485 ER PT J AU Smogorzewska, A Dzik, W AF Smogorzewska, A Dzik, W TI Volume-reduced apheresis platelets SO TRANSFUSION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dzik, W (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM sdzik@partners.org RI Smogorzewska, Agata/B-8891-2011 NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2005 VL 45 IS 5 BP 651 EP 651 DI 10.1111/j.1537-2995.2005.04486.x PG 1 WC Hematology SC Hematology GA 916OS UT WOS:000228395600001 PM 15847649 ER PT J AU Cardarelli, F Pascual, M Tolkoff-Rubin, N Delmonico, FL Wong, W Schoenfeld, DA Hui, Z Cosimi, AB Saidman, SL AF Cardarelli, F Pascual, M Tolkoff-Rubin, N Delmonico, FL Wong, W Schoenfeld, DA Hui, Z Cosimi, AB Saidman, SL TI Prevalence and significance of anti-HLA and donor-specific antibodies long-term after renal transplantation SO TRANSPLANT INTERNATIONAL LA English DT Article DE chronic rejection; donor-specific antibodies; enzyme-linked immunosorbent assay; human leukocyte antigen antibodies; humoral rejection; kidney transplantation ID ALLOGRAFT-REJECTION; PERITUBULAR CAPILLARIES; HUMORAL REJECTION; GRAFT-SURVIVAL; C4D DEPOSITS; IMMUNITY; ALLOANTIBODY AB Post-transplant circulating anti-human leukocyte antigens (HLA)-antibodies and C4d in allograft biopsies may be important in chronic rejection in renal transplant recipients (RTR). We determined the prevalence and significance of anti-HLA-antibodies and donor-specific antibodies (DSA). Sera were collected from 251 RTR > 6 months post-transplant. Sera were tested using enzyme-linked immunosorbent assay (ELISA) screening for anti-HLA antibodies. Positive sera were retested with ELISA-specific panel for antibody specificity. A 11.2% of patients had anti-HLA antibodies and 4.4% had DSA. Anti-HLA antibodies were significantly associated with pretransplant sensitization, acute rejection and in multivariate analysis, higher serum creatinine (2.15 &PLUSMN; 0.98 vs. 1.57 &PLUSMN; 0.69 mg/dl in negative anti-HLA antibodies group). Allograft biopsies performed in a subset of patients with anti-HLA antibodies revealed that 66% had C4d in peritubular capillaries (0% in patients without antibodies). Anti-HLA antibodies were associated with a worse allograft function and in situ evidence of anti-donor humoral alloreactivity. Long-term RTR with an increase in creatinine could be screened for anti-HLA antibodies and C4d in biopsy. C1 Univ Parma, Clin Med & Nefrol, I-43100 Parma, Italy. CHU Vaudois, Transplantat Ctr, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Histocompatibil Lab, Boston, MA 02114 USA. RP Cardarelli, F (reprint author), Arcispedale S Maria Nuova, Viale Risorgimento 80, I-42100 Reggio Emilia, Italy. EM cardarelli.francesca@asmn.re.it NR 30 TC 61 Z9 63 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD MAY PY 2005 VL 18 IS 5 BP 532 EP 540 DI 10.1111/j.1432-2277.2005.00085.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 924HE UT WOS:000228968900007 PM 15819801 ER PT J AU Akiyama, Y Caucheteux, SM Iwamoto, Y Guimezanes, A Kanellopoulos-Langevin, C Benichou, G AF Akiyama, Y Caucheteux, SM Iwamoto, Y Guimezanes, A Kanellopoulos-Langevin, C Benichou, G TI Effects of noninherited maternal antigens on allotransplant rejection in a transgenic mouse model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd International Congress on Immunosuppression CY DEC 08-11, 2004 CL San Diego, CA SP Int Soc Heart & Lung Transplantat, Thomson Profess Postgrad Serv, Thomson Amer Hlth Consultants ID HLA ANTIGENS; TOLERANCE; MICE AB We studied the influence of noninherited maternal antigen (NIMA) on allotransplant rejection using a mouse transgenic model. CBK transgenic (CBA [H-2(k)] expressing K MHC class I transgene) mice were used as donors in heart transplantation experiments. Offspring of BM3.3 (CBA anti-K-b TCR transgenic) male mice and (CBA X CBK)F1 females were used as NIMA (offspring that did not inherit K-b) and IMA (offspring that inherited Kb maternal antigen) recipient mice. Survival of allografts was monitored and the alloimmune response evaluated using an ELISPOT assay. IMA mice accepted CBK heart allografts and displayed no alloresponse to Kb+ cells. In contrast, mice never exposed to K (offspring of BM3.3 males and CBA females) acutely rejected their grafts within 18 days posttransplantation and exhibited potent inflammatory alloresponses to Kb+ cells. NIMA mice displayed prolonged survival of allotransplants (MST > 60 days). Although no deletion of anti-K-b TCR transgenic cells was detected in these mice, they had a marked reduction in the frequency of activated alloreactive T cells producing type 1 (IFN-gamma and IL-2) cytokines and concomitant expansion of type 2 (IL-4) cytokine-secreting cells. Finally, depletion of CD4(+) T cells from NIMA mice restored acute rejection of CBK hearts. This study is the first demonstration of the tolerogenic effects of NIMA on alloimmunity and allotransplant rejection in a transgenic model. It is shown that, although the NIMA tolerogenic effect is not due to deletion of alloreactive T cells, it is mediated by CD4(+) T cells producing type 2 cytokines. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CNRS, Inst Jacques Monod, Lab Immune Regulat & Dev, Paris, France. Univ Paris 06, Paris, France. Univ Paris 07, Paris, France. CIML, Marseille, France. RP Benichou, G (reprint author), Massachusetts Gen Hosp, Dept Surg, WHT 535,55 Fruit St, Boston, MA 02114 USA. EM gbenichou@partners.org NR 6 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 2005 VL 37 IS 4 BP 1940 EP 1941 DI 10.1016/j.transproceed.2005.02.115 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 931EB UT WOS:000229467500091 PM 15919511 ER PT J AU Carducci, MA Carroll, PR Dipaola, RS Nelson, JB Petrylak, DP Smith, MR Thompson, IM AF Carducci, MA Carroll, PR Dipaola, RS Nelson, JB Petrylak, DP Smith, MR Thompson, IM TI Hormone-refractory prostate cancer: Issues, approaches, and recommendations SO UROLOGY LA English DT Editorial Material ID MITOXANTRONE; PREDNISONE; DOCETAXEL C1 Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Univ Calif San Francisco, Sch Med, UCSF Ctr Comprehens Canc, San Francisco, CA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Inst Canc, New Brunswick, NJ USA. Univ Pittsburgh, Med Ctr, Dept Urol, Pittsburgh, PA USA. Columbia Univ, Med Ctr, Genitourinary Oncol Program, New York, NY USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX USA. RP Carducci, MA (reprint author), Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Butting Blaustein Canc Res Bldg,1650 Orleans St,R, Baltimore, MD 21231 USA. EM carducci@jhmi.edu NR 3 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2005 VL 65 IS 5A SU S BP 1 EP 2 DI 10.1016/j.urology.2005.02.034 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 929PV UT WOS:000229359100001 ER PT J AU Smith, MR Nelson, JB AF Smith, MR Nelson, JB TI Future therapies in hormone-refractory prostate cancer SO UROLOGY LA English DT Article; Proceedings Paper CT Symposium on Moving Beyond Hormone Refractory Prostate Cancer CY SEP 18, 2004 CL Chicago, IL ID GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-II; HUMAN MONOCLONAL-ANTIBODY; PLACEBO-CONTROLLED TRIAL; MEMBRANE ANTIGEN; EXTRACELLULAR DOMAIN; IMATINIB MESYLATE; ZOLEDRONIC ACID; GENE-EXPRESSION; DOWN-REGULATION AB Hormone-refractory prostate cancer (HRPC) remains true to its name: it is largely refractory to attempts to delay its progression. Although the number of men presenting with metastatic prostate cancer has decreased significantly over the last several years, the death rate for those men is essentially unchanged. To alter the currently inevitable progression of HRPC to death, new targets and new therapies are needed. This article reviews investigational therapies directed against standard targets (eg, the hypothalamic-pituitary-gonadal axis) as well as novel targets (eg, the endothelin axis). C1 Univ Pittsburgh, Med Ctr, Dept Urol, Pittsburgh, PA 15232 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Nelson, JB (reprint author), Univ Pittsburgh, Med Ctr, Dept Urol, Shadyside Med Bldg,Suite 209,5200 Ctr Ave, Pittsburgh, PA 15232 USA. EM nelsonjb@msx.upmc.edu NR 71 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAY PY 2005 VL 65 IS 5A SU S BP 9 EP 16 DI 10.1016/j.urology.2005.03.043 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 929PV UT WOS:000229359100004 PM 15885273 ER PT J AU Nadler, E Eckert, B Neumann, P AF Nadler, E Eckert, B Neumann, P TI Oncologists' cost-effectiveness thresholds for new cancer therapies SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2005 VL 8 IS 3 BP 239 EP 239 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 918PE UT WOS:000228559300014 ER PT J AU Thompson, D O'Sullivan, AK Stokes, M Montoya, E Earle, C Winer, EP Kulig, K Weinstein, MC AF Thompson, D O'Sullivan, AK Stokes, M Montoya, E Earle, C Winer, EP Kulig, K Weinstein, MC TI Survival and cost following breast cancer recurrence: Estimates from SEER-Medicare data SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Innovus Res Inc, Medford, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Inc, New York, NY USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Innovus Res Inc, 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2005 VL 8 IS 3 BP 347 EP 347 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 918PE UT WOS:000228559300356 ER PT J AU Bloom, MA Barghout, V Kahler, KH Bentkover, JD Kurth, H Gralnek, IM Spiegel, B AF Bloom, MA Barghout, V Kahler, KH Bentkover, JD Kurth, H Gralnek, IM Spiegel, B TI The budget impact of tegaserod on a managed care organization formulary SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Innovat Hlth Solut, Brookline, MA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Gastroenterol & Hepatol, 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2005 VL 8 IS 3 BP 370 EP 370 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 918PE UT WOS:000228559300428 ER PT J AU Thamer, M Zhang, Y Stefanik, K Kaufman, J Cotter, DJ AF Thamer, M Zhang, Y Stefanik, K Kaufman, J Cotter, DJ TI Factors influencing the route of administration for epoetin treatment among US hemodialysis patients SO VALUE IN HEALTH LA English DT Meeting Abstract C1 MTPPI, Bethesda, MD USA. VA Boston Healthcare Syst, 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 1098-3015 J9 VALUE HEALTH JI Value Health PD MAY-JUN PY 2005 VL 8 IS 3 BP 417 EP 417 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 918PE UT WOS:000228559300577 ER PT J AU Sheikh, AY Rollins, MD Hopf, HW Hunt, TK AF Sheikh, AY Rollins, MD Hopf, HW Hunt, TK TI Hyperoxia improves microvascular perfusion in a murine wound model SO WOUND REPAIR AND REGENERATION LA English DT Article ID HYPERBARIC-OXYGEN THERAPY; GROWTH-FACTOR EXPRESSION; CUTANEOUS BLOOD-FLOW; LASER-DOPPLER; INSPIRED OXYGEN; BURN SCARS; ANGIOGENESIS; SKIN; TENSION; TISSUE AB There is a need for a noninvasive method that measures wound angiogenesis. Hyperoxia is known to increase the appearance of new blood vessels in wounds, yet no study has confirmed increases in wound bed perfusion with periodic hyperbaric oxygen (HBO) exposure. This study investigates whether laser Doppler imaging is able to detect and quantify the enhancement of wound angiogenesis that is known to occur with intermittent HBO treatments. Full-thickness dorsal dermal wounds were created on mice randomized to hyperoxic (n = 14) and control (n = 15) groups. Hyperbaric oxygen was administered twice daily for 90 minutes each at 2.1 atmospheres for 7 days. Wound bed perfusion was measured by laser Doppler imaging on days 0, 7, and 10 postwounding. Wound blood flow increased significantly over baseline on day 7 and 10 in the hyperoxic group, but only on day 10 in the control group. Comparison between groups showed a 20% statistically significant increase in wound perfusion in HBO-treated animals compared to control on day 10 (p = 0.05). Laser Doppler imaging was able to detect and quantify the increase in wound bed perfusion resulting from intermittent HBO treatments and shows promise as a noninvasive measure of angiogenesis and wound healing. C1 Univ Calif San Francisco, Dept Surg, Wound Healing Res Lab, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA. Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. RP Hunt, TK (reprint author), Univ Calif San Francisco, Dept Surg, Wound Healing Res Lab, 513 Parnassus Ave,HSW-1652, San Francisco, CA 94143 USA. EM huntt@surgery.ucsf.edu FU NIGMS NIH HHS [GM27345, NIGMS P50] NR 58 TC 31 Z9 34 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAY-JUN PY 2005 VL 13 IS 3 BP 303 EP 308 DI 10.1111/j.1067-1927.2005.130313.x PG 6 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 931NI UT WOS:000229491600013 PM 15953050 ER PT J AU Hoffman, WH Jueppner, HW DeYoung, BR O'Dorisio, MS Given, KS AF Hoffman, WH Jueppner, HW DeYoung, BR O'Dorisio, MS Given, KS TI Elevated fibroblast growth factor-23 in hypophosphatemic linear nevus sebaceous syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE fibroblast growth factor-23; hypophosphatemic rickets; linear nevus sebaceous syndrome; octreotide; tumor-induced osteomalacia ID TUMOR-INDUCED OSTEOMALACIA; ONCOGENIC OSTEOMALACIA; RESISTANT RICKETS; FGF-23; PATHOGENESIS; CHILDREN; THERAPY; ANALOGS; BONE; GENE AB We report on an adolescent who experienced the onset of linear nevus sebaceous syndrome (LNSS) prior to 1 year of age. At 7 years of age he was diagnosed to have hypophosphatemic rickets. He was suboptimally controlled with phosphate and calcitriol treatment and sustained numerous insufficiency fractures ipsilateral to the linear sebaceous nevus. Fibroblast growth factor-23 (FGF-23), the phosphaturic peptide, was elevated in the plasma. Treatment with the somatostatin agonist, octreotide, and excision of the nevus were followed by normalization of FGF-23 and clinical improvement. The patient also had hyperimmunoglobulinemia E, which responded to octreotide and surgery. We speculate that in some patients with LNSS there may be more than one mediator of hypophosphatemia and that FGF-23 is the mediator of hyperphosphaturia in this and other hypophosphatemic syndromes. (c) 2005 Wiley-Liss, Inc. C1 Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Iowa, RJ & LA Carver Coll Med, Dept Pathol, Iowa City, IA USA. Univ Iowa, RJ & LA Carver Coll Med, Dept Pediat, Iowa City, IA USA. Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA. RP Hoffman, WH (reprint author), Med Coll Georgia, Dept Pediat, BG-1012, Augusta, GA 30912 USA. EM whoffman@mail.mcg.edu NR 40 TC 41 Z9 41 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR 30 PY 2005 VL 134A IS 3 BP 233 EP 236 DI 10.1002/ajmg.a.30599 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 912MT UT WOS:000228083600001 PM 15742370 ER PT J AU Kamin, DS Grinspoon, SK AF Kamin, DS Grinspoon, SK TI Cardiovascular disease in HIV-positive patients SO AIDS LA English DT Review DE HIV; cardiovascular disease; lipids; glucose; insulin ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CORONARY-HEART-DISEASE; PROTEASE INHIBITOR THERAPY; SUBCUTANEOUS ADIPOSE-TISSUE; RANDOMIZED CONTROLLED-TRIAL; VISCERAL FAT ACCUMULATION; REGIONAL BODY-COMPOSITION; C-REACTIVE PROTEIN; INSULIN-RESISTANCE C1 Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIDDK NIH HHS [DK 59535] NR 152 TC 40 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 APR 29 PY 2005 VL 19 IS 7 BP 641 EP 652 DI 10.1097/01.aids.0000166087.08822.bc PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 921BT UT WOS:000228739900001 PM 15821390 ER PT J AU Dewald, O Zymek, P Winkelmann, K Koerting, A Ren, GF Abou-Khamis, T Michael, LH Rollins, BJ Entman, ML Frangogiannis, NG AF Dewald, O Zymek, P Winkelmann, K Koerting, A Ren, GF Abou-Khamis, T Michael, LH Rollins, BJ Entman, ML Frangogiannis, NG TI CCL2/monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts SO CIRCULATION RESEARCH LA English DT Article DE monocyte chemoattractant protein-1; myocardial infarction; myocardial inflammation; pathology; cytokines ID CC-CHEMOKINE RECEPTOR-2; COLLATERAL ARTERY GROWTH; GENE-EXPRESSION; HUMAN MONOCYTES; MICE; REPERFUSION; CYTOKINE; INJURY; ISCHEMIA; CELLS AB The CC chemokine Monocyte Chemoattractant Protein (MCP)-1/CCL2 has potent mononuclear cell chemoattractant properties, modulates fibroblast and endothelial cell phenotype and may play an important role in wound healing. In order to examine whether MCP-1 critically regulates myocardial infarct healing, we studied the effects of MCP-1 gene disruption and antibody neutralization in a closed-chest model of reperfused murine myocardial infarction. MCP-1(-/-) mice had decreased and delayed macrophage infiltration in the healing infarct and demonstrated delayed replacement of injured cardiomyocytes with granulation tissue. In contrast, the time course and density of neutrophil infiltration was similar in MCP-1 null and wild-type animals. MCP-1(-/-) infarcts had decreased mRNA expression of the cytokines TNF-alpha, IL-1 beta, TGF-beta(2), -beta(3), and IL-10 and demonstrated defective macrophage differentiation evidenced by decreased Osteopontin-1 expression. MCP-1 deficiency diminished myofibroblast accumulation but did not significantly affect infarct angiogenesis. Despite showing delayed phagocytotic removal of dead cardiomyocytes, MCP-1(-/-) mice had attenuated left ventricular remodeling, but similar infarct size when compared with wild-type animals. MCP-1 antibody inhibition resulted in defects comparable with the pathological findings noted in infarcted MCP-1(-/-) animals without an effect on macrophage recruitment. MCP-1 has important effects on macrophage recruitment and activation, cytokine synthesis and myofibroblast accumulation in healing infarcts. Absence of MCP-1 results in attenuated post-infarction left ventricular remodeling, at the expense of a prolonged inflammatory phase and delayed replacement of injured cardiomyocytes with granulation tissue. C1 Baylor Coll Med, Cardiovasc Sci Sect, DeBakey Heart Ctr, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frangogiannis, NG (reprint author), Baylor Coll Med, Cardiovasc Sci Sect, DeBakey Heart Ctr, 1 Baylor Plaza M-S F-602, Houston, TX 77030 USA. EM ngf@bcm.tmc.edu RI Dewald, Oliver/A-3126-2008 FU NHLBI NIH HHS [HL-42550] NR 37 TC 275 Z9 286 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 29 PY 2005 VL 96 IS 8 BP 881 EP 889 DI 10.1161/01.RES.0000163017.13772.3a PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 920YK UT WOS:000228731200012 PM 15774854 ER PT J AU Iype, T Francis, J Garmey, JC Schisler, JC Nesher, R Weir, GC Becker, TC Newgard, CB Griffen, SC Mirmira, RG AF Iype, T Francis, J Garmey, JC Schisler, JC Nesher, R Weir, GC Becker, TC Newgard, CB Griffen, SC Mirmira, RG TI Mechanism of insulin gene regulation by the pancreatic transcription factor Pdx-1 - Application of pre-mRNA analysis and chromatin immunoprecipitation to assess formation of functional transcriptional complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSGENIC MICE; BETA-CELLS; ACTIVATION DOMAINS; DIABETES-MELLITUS; POLYMERASE-II; TARGET GENES; IN-VITRO; EXPRESSION; GLUCOSE; P300 AB The homeodomain factor Pdx-1 regulates an array of genes in the developing and mature pancreas, but whether regulation of each specific gene occurs by a direct mechanism ( binding to promoter elements and activating basal transcriptional machinery) or an indirect mechanism ( via regulation of other genes) is unknown. To determine the mechanism underlying regulation of the insulin gene by Pdx-1, we performed a kinetic analysis of insulin transcription following adenovirus-mediated delivery of a small interfering RNA specific for pdx-1 into insulinoma cells and pancreatic islets to diminish endogenous Pdx-1 protein. insulin transcription was assessed by measuring both a long half-life insulin mRNA ( mature mRNA) and a short half-life insulin pre-mRNA species by real-time reverse transcriptase-PCR. Following progressive knock-down of Pdx-1 levels, we observed coordinate decreases in pre-mRNA levels ( to about 40% of normal levels at 72 h). In contrast, mature mRNA levels showed strikingly smaller and delayed declines, suggesting that the longer half-life of this species underestimates the contribution of Pdx-1 to insulin transcription. Chromatin immunoprecipitation assays revealed that the decrease in insulin transcription was associated with decreases in the occupancies of Pdx-1 and p300 at the proximal insulin promoter. Although there was no corresponding change in the recruitment of RNA polymerase II to the proximal promoter, its recruitment to the insulin coding region was significantly reduced. Our results suggest that Pdx-1 directly regulates insulin transcription through formation of a complex with transcriptional coactivators on the proximal insulin promoter. This complex leads to enhancement of elongation by the basal transcriptional machinery. C1 Univ Virginia, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Ctr Diabet, Charlottesville, VA 22908 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. Duke Univ, Med Ctr, Sarah W Stedman Nutr & Metab Ctr, Durham, NC 27704 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27704 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27704 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27704 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Univ Calif Davis, Dept Internal Med, Sacramento, CA 95817 USA. RP Mirmira, RG (reprint author), Univ Virginia Hlth Syst, 450 Ray C Hunt Dr,Box 801407, Charlottesville, VA 22908 USA. EM mirmira@virginia.edu OI Schisler, Jonathan/0000-0001-7382-2783 FU NIDDK NIH HHS [U01 DK56047, K08 DK002619, R01 DK60581, U19 DK61251] NR 55 TC 71 Z9 74 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 2005 VL 280 IS 17 BP 16798 EP 16807 DI 10.1074/jbc.M414381200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500032 PM 15743769 ER PT J AU Connor, KM Subbaram, S Regan, KJ Nelson, KK Mazurkiewicz, JE Bartholomew, PJ Aplin, AE Tai, YT Aguirre-Ghiso, J Flores, SC Melendez, JA AF Connor, KM Subbaram, S Regan, KJ Nelson, KK Mazurkiewicz, JE Bartholomew, PJ Aplin, AE Tai, YT Aguirre-Ghiso, J Flores, SC Melendez, JA TI Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-SUPPRESSOR PTEN; PHOSPHATIDYLINOSITOL 3-KINASE/AKT PATHWAY; MATRIX-METALLOPROTEINASE EXPRESSION; PROTEIN-TYROSINE PHOSPHATASES; INDUCIBLE FACTOR 1-ALPHA; HYDROGEN-PEROXIDE; SIGNAL-TRANSDUCTION; REDOX REGULATION; PHOSPHORYLATION SITES AB Recent studies have demonstrated that the tumor suppressor PTEN ( phosphatase and tensin homolog deleted from chromosome 10), the antagonist of the phosphosphoinositol-3- kinase ( PI3K) signaling cascade, is susceptible to H2O2-dependent oxidative inactivation. This study describes the use of redox-engineered cell lines to identify PTEN as sensitive to oxidative inactivation by mitochondrial H2O2. Increases in the steady state production of mitochondrial derived H2O2, as a result of manganese superoxide dismutase ( Sod2) overexpression, led to PTEN oxidation that was reversed by the coexpression of the H2O2- detoxifying enzyme catalase. The accumulation of an oxidized inactive fraction of PTEN favored the formation of phosphatidylinositol 3,4,5-triphosphate at the plasma membrane, resulting in increased activation of Akt and modulation of its downstream targets. PTEN oxidation in response to mitochondrial H2O2 enhanced PI3K signaling, leading to increased expression of the key regulator of angiogenesis, vascular endothelial growth factor. Overexpression of PTEN prevented the H2O2- dependent increase in vascular endothelial growth factor promoter activity and immunoreactive protein, whereas a mutant PTEN (G129R), lacking phosphatase activity, did not. Furthermore, mitochondrial generation of H2O2 by Sod2 promoted endothelial cell sprouting in a three-dimensional in vitro angiogenesis assay that was attenuated by catalase coexpression or the PI3K inhibitor LY2949002. Moreover, Sod2 overexpression resulted in increased in vivo blood vessel formation that was H2O2- dependent as assessed by the chicken chorioallantoic membrane assay. Our findings provide the first evidence for the involvement of mitochondrial H2O2 in regulating PTEN function and the angiogenic switch, indicating that Sod2 can serve as an alternative physiological source of the potent signaling molecule, H2O2. C1 Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. Albany Med Coll, Ctr Neuropharmacol & Neurosci, Albany, NY 12208 USA. Albany Med Coll, Ctr Cell Biol & Canc Res, Albany, NY 12208 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. SUNY Albany, Dept Biomed Sci, Sch Publ Hlth, Rensselaer, NY 12144 USA. Univ Colorado, Hlth Sci Ctr, Webb Waring Inst Canc Aging & Antioxidant Res, Denver, CO 80262 USA. RP Melendez, JA (reprint author), Albany Med Coll, Ctr Immunol & Microbial Dis, MC 151,47 New Scotland Ave, Albany, NY 12208 USA. EM melenda@mail.amc.edu OI Aguirre-Ghiso, Julio/0000-0002-6694-6507; Connor, Kip/0000-0002-2048-9080 FU NCI NIH HHS [CA095011, CA77068]; NIAID NIH HHS [AI49822] NR 65 TC 131 Z9 137 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 2005 VL 280 IS 17 BP 16916 EP 16924 DI 10.1074/jbc.M410690200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500046 PM 15701646 ER PT J AU Taha, TA Kitatani, K Bielawski, J Cho, W Hannun, YA Obeid, LM AF Taha, TA Kitatani, K Bielawski, J Cho, W Hannun, YA Obeid, LM TI Tumor necrosis factor induces the loss of sphingosine kinase-1 by a cathepsin B-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEDIATED HEPATOCYTE APOPTOSIS; CELL-DEATH; TNF-ALPHA; LYSOSOMAL PERMEABILIZATION; PROTEASE PATHWAYS; SPHINGOSINE-1-PHOSPHATE; ACTIVATION; RELEASE; CASPASE AB Sphingosine kinase-1 (SK1) has emerged as a key component of cytokine responses, including roles in apoptosis, yet the specific mechanisms by which cytokines regulate SK1 in the apoptotic responses have not been studied. In this study, we show that prolonged treatment of MCF-7 cells with tumor necrosis factor (TNF) induces a dose- and time-dependent decrease in SK1 protein. Inhibition of the upstream caspase 8 by IETD significantly rescued TNF effects on SK1, yet the caspase 7 inhibitor DEVD failed to have any effect, suggesting that the decline in SK1 occurs downstream of the initiator caspase but upstream of the effector caspase. In addition to caspase activation, TNF caused disruption of lysosomes with relocation of the cysteine protease cathepsin B into the cytosol. Down-regulation of cathepsin B using small interfering RNA significantly restored SK1 levels following exposure to TNF, suggesting that SK1 loss was dependent on cathepsin B activity. The regulation of SK1 by the lysosomal protease was further supported by the colocalization of SK1 with the lysosome and cathepsin B in cells and the loss of the colocalization following exposure to TNF. The ability of cathepsin B to regulate SK1 was further corroborated by an in vitro approach where recombinant cathepsin B cleaved SK1 at multiple sites to produce several cleavage fragments. Therefore, these studies show that SK1 down-regulation by TNF is dependent on the "lysosomal pathway" of apoptosis and specifically on cathepsin B, which functions as an SK1 protease in cells. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Univ Illinois, Dept Chem, Chicago, IL 60607 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI Kitatani, Kazuyuki/0000-0002-8516-6135; obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132]; NIDDK NIH HHS [DK59340] NR 21 TC 58 Z9 60 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 2005 VL 280 IS 17 BP 17196 EP 17202 DI 10.1074/jbc.M413744200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500081 PM 15710602 ER PT J AU Moir, RD Tseitlin, KA Soscia, S Hyman, BT Irizarry, MC Tanzi, RE AF Moir, RD Tseitlin, KA Soscia, S Hyman, BT Irizarry, MC Tanzi, RE TI Autoantibodies to redox-modified oligomeric A beta are attenuated in the plasma of Alzheimer's disease patients SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBRAL AMYLOID ANGIOPATHY; CENTRAL-NERVOUS-SYSTEM; MOUSE MODEL; PROTEIN; ANTIBODIES; PEPTIDE; BRAIN; PATHOLOGY; DEMENTIA; SERUM AB Accumulation of A beta protein in beta-amyloid deposits is a hallmark event in Alzheimer's disease ( AD). Recent findings suggest anti-A beta autoantibodies may have a role in AD pathology. However, a consensus has yet to emerge as to whether endogenous anti-A beta autoantibodies are elevated, depressed, or unchanged in AD patients. Whereas experiments to date have used synthetic unmodified monomeric A beta (A beta(mon)) to test autoimmunity, up to 40% of the A beta pool in AD brain consists of low molecular weight oligomeric cross-linked beta-amyloid protein species ( CAPS). Recent studies also suggest that CAPS may be the primary neurotoxic agent in AD. In the present study, AD and nondemented control plasma were analyzed for immunoreactivity to CAPS and A beta(mon). Plasma of both nondemented and AD patients were found to contain autoantibodies specific for soluble CAPS. Nondemented control and AD plasmas demonstrated similar immunoreactivity to A beta(mon). In contrast, anti-CAPS antibodies in AD plasma were found to be significantly reduced compared with nondemented controls ( p = 0.018). Furthermore, age at onset for AD correlated significantly ( p = 0.041) with plasma immunoreactivity to CAPS. These data suggest that autoantibodies to CAPS are depleted in AD patients and raise the prospect that immunization with anti-CAPS antibodies might provide therapeutic benefit for AD. C1 Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp E, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu NR 55 TC 71 Z9 76 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 2005 VL 280 IS 17 BP 17458 EP 17463 DI 10.1074/jbc.M414176200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500112 PM 15728175 ER PT J AU Ahn, YK Lim, SY Jeong, MH Kim, YS Nam, KI Lee, MC Song, HC Hur, YJ Bae, EH Hong, YJ Park, HW Kim, JH Kim, W Cho, JG Park, JC Kang, JC Rosenzweig, A Matsui, T AF Ahn, YK Lim, SY Jeong, MH Kim, YS Nam, KI Lee, MC Song, HC Hur, YJ Bae, EH Hong, YJ Park, HW Kim, JH Kim, W Cho, JG Park, JC Kang, JC Rosenzweig, A Matsui, T TI Effects of Mesenchymal stem cells transduced with Akt on porcine myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 10th Annual Interventional Vascular Therapeutics Angioplasty Summit-Transcatheter Cardiovascular Therapeutics Asis Pacific Symposium CY APR 28-30, 2005 CL Seoul, SOUTH KOREA C1 Chonnam Natl Univ, Sch Med, Kwangju, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 28 PY 2005 VL 95 IS 8A SU S BP 52A EP 52A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 916QK UT WOS:000228400400138 ER PT J AU Johnson, RP Kaur, A AF Johnson, RP Kaur, A TI HIV - Viral blitzkrieg SO NATURE LA English DT Editorial Material ID T-CELL DEPLETION; GASTROINTESTINAL-TRACT; INFECTION; LYMPHOCYTES; SIV C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu NR 11 TC 7 Z9 7 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 28 PY 2005 VL 434 IS 7037 BP 1080 EP 1081 DI 10.1038/4341080a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920MD UT WOS:000228693300025 PM 15858559 ER PT J AU Korf, BR Henson, JW Harris, NL MacCollin, M Smith, ER Stemmer-Rachamimov, A AF Korf, BR Henson, JW Harris, NL MacCollin, M Smith, ER Stemmer-Rachamimov, A TI A 48-year-old man with weakness of the limbs and multiple tumors of spinal nerves - Neurofibromatosis type 1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NF1 GENE; MUTATIONS; SCHWANNOMATOSIS; MOSAICISM; PHENOTYPE; SPECTRUM; FAMILIES; VARIANT C1 Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Korf, BR (reprint author), Univ Alabama Birmingham, Dept Genet, Birmingham, AL 35294 USA. NR 22 TC 5 Z9 5 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 2005 VL 352 IS 17 BP 1800 EP 1808 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 920KY UT WOS:000228689000012 PM 15858190 ER PT J AU Hideshima, T Chauhan, D Ishitsuka, K Yasui, H Raje, N Kumar, S Podar, K Mitsiades, C Hideshima, H Bonham, L Munshi, NC Richardson, PG Singer, JW Anderson, KC AF Hideshima, T Chauhan, D Ishitsuka, K Yasui, H Raje, N Kumar, S Podar, K Mitsiades, C Hideshima, H Bonham, L Munshi, NC Richardson, PG Singer, JW Anderson, KC TI Molecular characterization of PS-341 (bortezomib) resistance: implications for overcoming resistance using lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitors SO ONCOGENE LA English DT Article DE lysophosphatidic acid acyltransferase-beta inhibitor; bortezomib; PS-341; caspase; necrosis; cell cycle ID PROTEASOME INHIBITOR PS-341; MULTIPLE-MYELOMA CELLS; REFRACTORY HEMATOLOGIC MALIGNANCIES; ACID ACYLTRANSFERASE-BETA; DNA FRAGMENTATION FACTOR; HIGH-DOSE THERAPY; NF-KAPPA-B; LYSOPHOSPHATIDIC ACID; DRUG-RESISTANCE; CAM-DR AB PS-341 (bortezomib, Velcade(TM)) is a promising novel agent for treatment of advanced multiple myeloma ( MM); however, 65% of patients with relapsed refractory disease in a phase II study do not respond to PS-341. We have previously shown that lysophosphatidic acid acyltransferase (LPAAT)-beta inhibitor CT-32615 triggers caspase-dependent apoptosis, and can overcome resistance to conventional therapeutics (i.e., dexamethasone, doxorubicin, melphalan) in MM cells. In this study, we therefore determined whether CT-32615 could also overcome resistance to PS- 341. We first characterized molecular mechanisms of resistance to PS- 341 in DHL-4 cells. DHL-4 cells express low levels of caspase-3 and caspase-8; furthermore, no cleavage in caspase-8, caspase-9, caspase-3, poly ADP-ribose polymerase ( PARP), or DNA fragmentation factor 45 was triggered by PS- 341 treatment. We have previously shown that PS- 341 treatment triggers phosphorylation of c-Jun NH2-terminal kinase (JNK), which subsequently induces caspase-dependent apoptosis; conversely, JNK inhibition blocks PS- 341-induced apoptosis. We here show that phosphorylation of SEK-1, JNK, and c-Jun are not induced by PS-341 treatment, suggesting that PS- 341 does not trigger a stress response in DHL-4 cells. Importantly, CT-32615 inhibits growth of DHL-4 cells in a time-and dose-dependent fashion: a transient G2/M cell cycle arrest induced by CT-32615 is mediated via downregulation of cdc25c and cdc2. CT-32615 triggered swelling and lysis of DHL-4 cells, without caspase/PARP cleavage or TUNEL-positivity, suggesting a necrotic response. Our studies therefore demonstrate that LPAAT-beta inhibitor CT-32615 triggers necrosis, even in PS-341-resistant DHL-4 cells, providing the framework for its evaluation to overcome clinical PS- 341 resistance and improve patient outcome. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cell Therapeut Inc, Seattle, WA 98119 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu OI Singer, Jack/0000-0003-4001-4549 FU NCI NIH HHS [R0-1 CA 50947, IP50 CA10070-01] NR 34 TC 27 Z9 27 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 28 PY 2005 VL 24 IS 19 BP 3121 EP 3129 DI 10.1038/sj.onc.1208522 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 920XF UT WOS:000228728100006 PM 15735676 ER PT J AU Querol, M Chen, JW Weissleder, R Bogdanov, A AF Querol, M Chen, JW Weissleder, R Bogdanov, A TI DTPA-bisamide-based MR sensor agents for peroxidase imaging SO ORGANIC LETTERS LA English DT Article ID CONTRAST AGENTS; IN-VIVO; HORSERADISH-PEROXIDASE; MYELOPEROXIDASE AB The synthesis and some properties of two novel DTPA-bisamides are reported. These derivatives were designed as enzyme-activated contrast agents (CA) for magnetic resonance imaging. Both derivatives bear tyramido or 5-hydroxytryptamido groups that could be oligomerized in situ in the presence of peroxidase/H2O2 pair resulting in a net increase in longitudinal (R1) relaxivity. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Querol, M (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM abogdanov@helix.mgh.harvard.edu FU NIBIB NIH HHS [1RO1EB00858] NR 23 TC 70 Z9 71 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD APR 28 PY 2005 VL 7 IS 9 BP 1719 EP 1722 DI 10.1021/ol050208v PG 4 WC Chemistry, Organic SC Chemistry GA 920FT UT WOS:000228675500012 PM 15844889 ER PT J AU Sawamura, H Georgieva, S Vogels, R Vanduffel, W Orban, GA AF Sawamura, H Georgieva, S Vogels, R Vanduffel, W Orban, GA TI Using functional magnetic resonance imaging to assess adaptation and size invariance of shape processing by humans and monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE functional imaging; object adaptation; size invariance; vision; cerebral cortex; human and macaque ID INFERIOR TEMPORAL CORTEX; HUMAN VISUAL-CORTEX; LATERAL OCCIPITAL COMPLEX; MACAQUE CEREBRAL-CORTEX; EVENT-RELATED FMRI; SHORT-TERM-MEMORY; INFEROTEMPORAL CORTEX; INTRAPARIETAL CORTEX; OBJECT RECOGNITION; PREFRONTAL CORTEX AB Functional magnetic resonance imaging in awake monkeys and humans was used to compare object adaptation in shape-sensitive regions of these two species under identical and different size conditions. Object adaptation was similar in humans and monkeys under both conditions. Neither species showed complete size invariance, in agreement with single-cell studies. Both the macaque inferotemporal ( IT) complex and human lateral occipital complex (LOC) displayed an anteroposterior gradient in object adaptation and size invariance, with the more anterior regions being more adaptable and size invariant. The results provide additional evidence for the homology between the macaque IT cortex and human LOC but also add to the growing list of differences between human and monkey intraparietal sulcus regions. C1 Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychofysiol, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp,MIT, Charlestown, MA 02129 USA. RP Orban, GA (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychofysiol, Campus Gasthuisberg,Herestr 49,Bus 801, B-3000 Louvain, Belgium. EM guy.orban@med.kuleuven.ac.be NR 70 TC 91 Z9 91 U1 2 U2 5 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 27 PY 2005 VL 25 IS 17 BP 4294 EP 4306 DI 10.1523/JNEUROSCI.0377-05.2005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 920PP UT WOS:000228702900011 PM 15858056 ER PT J AU Nakazawa, T Endo, E Shimura, M Kondo, M Ueno, S Tamai, M AF Nakazawa, T Endo, E Shimura, M Kondo, M Ueno, S Tamai, M TI Retinal G-substrate, potential downstream component of NO/cGMP/PKG pathway, is located in subtype of retinal ganglion cells and amacrine cells with protein phosphatases SO MOLECULAR BRAIN RESEARCH LA English DT Article DE nitric oxide; cyclic GMP; signal transduction; excitatory amino acids; protein kinase ID NITRIC-OXIDE SYNTHASE; SIGNALING PATHWAYS; CYCLIC-GMP; KINASE; BRAIN; INHIBITION; APOPTOSIS; DISEASE; MODEL AB The aim of this study was to determine the distribution and function of G-substrate, a specific substrate of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase (PKG) signaling pathway, in normal rat retina and in G-substrate knockout mice. The retinas of adult wild-type rats and mice and G-substrate knockout mice were studied immunohistologically to characterize the upstream and downstream components of the NO-cGMP-PKG pathway. Immunoblot analysis showed that the molecular weight of retinal G-substrate was similar to that of cerebellar G-substrate. In adult rats and mice, retinal G-substrate was located in a subpopulation of amacrine cells and in C38-positive retinal ganglion cells (RGCs) but not in alpha RGCs. In addition, retinal G-substrate was co-expressed with other upstream and downstream signaling components of the NO-cGMP-PKG-G-substrate-phosphatase pathway in the adult retina. Electroretinographic (ERG) analysis demonstrated that there was no significant difference between the ERGs of wild-type and G-substrate knockout mice. These results suggest that retinal G-substrate plays a role as a downstream component of the NO-cGMP-PKG pathway. The co-localization of retinal G-substrate with protein Ser/Thr phosphatases suggests that it acts as an endogenous protein phosphatase inhibitor as in the cerebellum. (c) 2004 Elsevier B.V. All rights reserved. C1 Tohoku Grad Sch Med, Dept Optometry & Visual Sci, Sendai, Miyagi 9808574, Japan. RIKEN, Brain Sci Inst, Neuronal Circuit Mech Res Grp, Wako, Saitama 3510198, Japan. JST Gushikawa, Unit Mol Neurobiol Learning, OIST, Okinawa 9042234, Japan. JST Gushikawa, Memory Initial Res Project, OIST, Okinawa 9042234, Japan. Nagoya Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 466, Japan. RP Nakazawa, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Retina, Angiogenesis Lab, 3rd Floor,325 Cambridge St, Boston, MA 02114 USA. EM ntoru@fa2.so-net.ne.jp RI Ueno, Shinji/M-5063-2014 NR 32 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 27 PY 2005 VL 135 IS 1-2 BP 58 EP 68 DI 10.1016/j.molbrainres.2004.12.006 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 927PN UT WOS:000229206100007 ER PT J AU Szot, P White, SS Shen, DD Anderson, GD AF Szot, P White, SS Shen, DD Anderson, GD TI Valproic acid, but not lamotrigine, suppresses seizure-induced c-fos and c-Jun mRNA expression SO MOLECULAR BRAIN RESEARCH LA English DT Article DE valproic acid; lamotrigine; c-fos; c-Jun; flurothyl; bipolar disorder; seizure ID CEREBELLAR GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; PRIMARY CULTURES; TRANSCRIPTION FACTOR; INDUCED APOPTOSIS; BIPOLAR DISORDER; CHRONIC LITHIUM; CALCIUM INFLUX; RAT-BRAIN; IN-VITRO AB Seizure-induced activity has been shown to increase the expression of immediate early genes (IEGs) c-fos and c-Jun in the CNS. Anti-epileptic drugs (AEDs) can suppress the induction of a seizure, but it is unknown if AEDs affect the expression of seizure-induced IEGs. We found that valproic acid (VPA), but not lamotrigine (LTG), was capable of suppressing seizure-induced c-fos and c-Jun mRNA expression in rats despite a similar anticonvulsant effect. LTG in some regions of the CM enhanced seizure-induced IEG expression. These studies indicate that the older AED (VPA), as compared to the newer AED (LTG), can suppress seizure-induced IEG expression. The consequence of this suppression of IEGs following a generalized seizure may be viewed either as a neuroprotective or detrimental effect upon the brain. Published by Elsevier B.V. C1 VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. RP Szot, P (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, 1660 S Columbian Way, Seattle, WA 98108 USA. EM szot@u.washington.edu NR 35 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 27 PY 2005 VL 135 IS 1-2 BP 285 EP 289 DI 10.1016/j.molbrainres.2004.11.011 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 927PN UT WOS:000229206100029 ER PT J AU Sabatine, MS Morrow, DA Giugliano, RP Burton, PBJ Murphy, SA McCabe, CH Gibson, CM Braunwald, E AF Sabatine, MS Morrow, DA Giugliano, RP Burton, PBJ Murphy, SA McCabe, CH Gibson, CM Braunwald, E TI Association of hemoglobin levels with clinical outcomes in acute coronary syndromes SO CIRCULATION LA English DT Article DE anemia; coronary disease; hemoglobin; myocardial infarction; risk factors ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; DOSE-RANGING TRIAL; CONSERVATIVE STRATEGIES; CARDIOVASCULAR-DISEASE; INDEPENDENT PREDICTOR; THROMBIN INHIBITION; BLOOD-TRANSFUSION; OXYGEN DELIVERY; UNSTABLE ANGINA AB Background - In the setting of an acute coronary syndrome (ACS), anemia has the potential to worsen myocardial ischemia; however, data relating anemia to clinical outcomes in ACS remain limited. Methods and Results - We examined the association between baseline hemoglobin values and major adverse cardiovascular events through 30 days in 39 922 patients enrolled in clinical trials of ACS. After adjustment for differences in baseline characteristics and index hospitalization treatments, a reverse J-shaped relationship between baseline hemoglobin values and major adverse cardiovascular events was observed. In patients with ST-elevation myocardial infarction, when those with hemoglobin values between 14 and 15 g/dL were used as the reference, cardiovascular mortality increased as hemoglobin levels fell below 14 g/dL, with an adjusted OR of 1.21 ( 95% CI 1.12 to 1.30, P < 0.001) for each 1-g/dL decrement in hemoglobin. At the other end of the range of hemoglobin, patients with hemoglobin values > 17 g/dL also had excess mortality ( OR 1.79, 95% CI 1.18 to 2.71, P = 0.007). In patients with non - ST-elevation ACS, with those with hemoglobin 15 to 16 g/dL used as the reference, the likelihood of cardiovascular death, myocardial infarction, or recurrent ischemia increased as the hemoglobin fell below 11 g/dL, with an adjusted OR of 1.45 ( 95% CI 1.33 to 1.58, P < 0.001) for each 1 g/dL decrement in hemoglobin. Patients with hemoglobin values > 16 g/dL also had an increased rate of death or ischemic events ( OR 1.31, 95% CI 1.03 to 1.66, P = 0.027). Conclusions - Anemia is a powerful and independent predictor of major adverse cardiovascular events in patients across the spectrum of ACS. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM msabatine@partners.org FU NHLBI NIH HHS [R01 HL072872, R01 HL072879] NR 43 TC 305 Z9 334 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 26 PY 2005 VL 111 IS 16 BP 2042 EP 2049 DI 10.1161/01.CIR.0000162477.70955.5F PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 920BA UT WOS:000228660800006 PM 15824203 ER PT J AU Long, X Lin, Y Ortiz-Vega, S Yonezawa, K Avruch, J AF Long, X Lin, Y Ortiz-Vega, S Yonezawa, K Avruch, J TI Rheb binds and regulates the mTOR kinase SO CURRENT BIOLOGY LA English DT Article ID P70 S6 KINASE; TUMOR-SUPPRESSOR PROTEINS; CELL-CYCLE PROGRESSION; TSC2 GAP ACTIVITY; TUBEROUS-SCLEROSIS; MAMMALIAN TARGET; GROWTH-FACTOR; DISTINCT ROLES; RAPAMYCIN TOR; EIF-4E BP1 AB Background: The target of rapamycin (TOR), in complex with the proteins raptor and LST8 (TOR complex 1), phosphorylates the p70S6K and 4E-BP1 to promote mRNA translation. Genetic evidence establishes that TOR complex activity in vivo requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from inactivation in vivo by amino-acid withdrawal. The Tuberous Sclerosis heterodimer (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in vivo. Results: Here, we show that Rheb binds to the TOR complex specifically, independently of its ability to bind TSC2, through separate interactions with the mTOR catalytic domain and with LST8. Rheb binding to the TOR complex in vivo and in vitro does not require Rheb guanyl nucleotide charging but is modulated by GTP and impaired by certain mutations (Ile39Lys) in the switch 1 loop. Nucleotide-deficient Rheb mutants, although capable of binding mTOR in vivo and in vitro, are inhibitory in vivo, and the mTOR polypeptides that associate with nucleotide-deficient Rheb in vivo lack kinase activity in vitro. Reciprocally, mTOR polypeptides bound to Rheb(GIn64Leu), a mutant that is nearly 90% GTP charged, exhibit substantially higher protein kinase specific activity than mTOR bound to wild-type Rheb. Conclusions: The TOR complex 1 is a direct target of Rheb-GTP, whose binding enables activation of the TOR kinase. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 6578501, Japan. Japan Sci & Technol Agcy, CREST, Kawaguchi 3320012, Japan. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. EM avruch@helix.mgh.harvard.edu FU NCI NIH HHS [CA-73818]; NIDDK NIH HHS [DK-17776, DK007028] NR 46 TC 464 Z9 482 U1 6 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 26 PY 2005 VL 15 IS 8 BP 702 EP 713 DI 10.1016/j.cub.2005.02.053 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923VE UT WOS:000228936600018 PM 15854902 ER PT J AU van Gorp, WG Hinkin, CH AF van Gorp, WG Hinkin, CH TI Triple trouble - Cognitive deficits from hepatitis C, HIV, and methamphetamine SO NEUROLOGY LA English DT Editorial Material ID NEUROPSYCHOLOGICAL IMPAIRMENT; DYSFUNCTION; IMPACT; VIRUS C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10022 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. RP van Gorp, WG (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 16 E 60th St,Suite 400, New York, NY 10022 USA. EM wvangorp@aol.com NR 10 TC 6 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 26 PY 2005 VL 64 IS 8 BP 1328 EP 1329 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 920AY UT WOS:000228660600002 PM 15851716 ER PT J AU Ostrem, JL Kang, GA Subramanian, I Guarnieri, M Hubble, J Rabinowicz, AL Bronstein, J AF Ostrem, JL Kang, GA Subramanian, I Guarnieri, M Hubble, J Rabinowicz, AL Bronstein, J TI The effect of entacapone on homocysteine levels in Parkinson disease SO NEUROLOGY LA English DT Editorial Material ID LEVODOPA C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Parkinsons Dis Res Educ & Clin Ctr, San Francisco, CA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. RP Bronstein, J (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM jbronste@ucla.edu NR 6 TC 17 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 26 PY 2005 VL 64 IS 8 BP 1482 EP 1482 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 920AY UT WOS:000228660600044 PM 15851757 ER PT J AU Shen, XC Valencia, CA Szostak, J Dong, B Liu, RH AF Shen, XC Valencia, CA Szostak, J Dong, B Liu, RH TI Scanning the human proteome for calmodulin-binding proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mRNA display; binding motif; protein-protein interactions; calcium-dependent ID IN-VITRO SELECTION; MESSENGER-RNA DISPLAY; CALCIUM-BINDING; PROTEASOME; RAD23; RECOGNITION; IDENTIFICATION; LIBRARIES; PEPTIDES; DOMAINS AB The calcium ion (Ca2+) is a ubiquitous second messenger that is crucial for the regulation of a wide variety of cellular processes. The diverse transient signals transduced by Ca2+ are mediated by intracellular Ca2+-binding proteins, also known as Ca2+ sensors. A key obstacle to studying many Ca2+-sensing proteins is the difficulty in identifying the numerous downstream target interactions that respond to Ca2+-induced conformational changes. Among a number of Ca2+ sensors in the eukaryotic cell, calmodulin (CaM) is the most widespread and the best studied. Employing the mRNA display technique, we have scanned the human proteome for CaM-binding proteins and have identified and characterized a large number of both known and previously uncharacterized proteins that interact with CaM in a Ca2+-dependent manner. The interactions of several identified proteins with Ca2+/CaM were confirmed by using pull-down assays and coimmunoprecipitation. Many of the CaM-binding proteins identified belong to protein families such as the DEAD/H box proteins, ribosomal proteins, proteasome 26S subunits, and deubiquitinating enzymes, suggesting the possible involvement of Ca2+/CaM in different signaling pathways. The selection method described herein could be used to identify the binding partners of other calcium sensors on the proteome-wide scale. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Liu, RH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA. EM rliu@email.unc.edu FU NIGMS NIH HHS [GM53936, R01 GM053936] NR 49 TC 92 Z9 98 U1 2 U2 12 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 26 PY 2005 VL 102 IS 17 BP 5969 EP 5974 DI 10.1073/pnas.0407928102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 921BI UT WOS:000228738800016 PM 15840729 ER PT J AU Sacerdote, MG Szostak, JW AF Sacerdote, MG Szostak, JW TI Semipermeable lipid bilayers exhibit diastereoselectivity favoring ribose SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE membranes; prebiotic chemistry; RNA world ID FATTY-ACID MEMBRANES; PERMEABILITY; VESICLES; ALDITOLS; WATER; RNA; CONFORMATIONS; TRANSPORT; GROWTH; CELL AB Nutrient uptake by a primitive cell would have been limited by the permeability characteristics of its membrane. We measured the permeabilities of model protocellular membranes to water, five of the six pentoses, and selected aldohexoses, ketohexoses, and three to six carbon alditols by following volume changes of vesicles after the addition of solute to the external medium. Solute hydrophobicities correlated poorly with permeability coefficients within one structural class of compounds. The permeability coefficients of diastereomeric sugars differed by as much as a factor of 10, with ribose being the most permeable aldopentose. Flexible alditols and sugars, sugars biased toward or restricted to furanose forms, and sugars having anomers with hydrophobic faces permeated more quickly than compounds lacking these features. Among the aldopentoses, only ribose possesses all of these properties. Ribose permeated both fatty acid and phospholipid membranes more rapidly than the other aldopentoses or hexoses. The enhanced permeability conferred by the unique conformational preferences of ribose would have allowed faster assimilation of ribose by primitive cells as they passively absorbed materials from the environment. The kinetic advantage of ribose over the other aldopentoses in crossing membranes may therefore have been one factor that facilitated the emergence of the RNA world. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu NR 35 TC 62 Z9 66 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 26 PY 2005 VL 102 IS 17 BP 6004 EP 6008 DI 10.1073/pnas.0408440102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 921BI UT WOS:000228738800022 PM 15831588 ER PT J AU Langenau, DM Feng, H Berghmans, S Kanki, JP Kutok, JL Look, AT AF Langenau, DM Feng, H Berghmans, S Kanki, JP Kutok, JL Look, AT TI Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lymphoma; tal1/scl; lmo2 ID ONCOGENIC TRANSCRIPTION FACTORS; VERTEBRATE DEVELOPMENT; V(D)J RECOMBINATION; DANIO-RERIO; GENE; EXPRESSION; MUTATIONS; HOX11; TRANSLOCATION; RECURRENT AB We have created a stable transgenic rag2-EGFP-mMyc zebrafish line that develops GFP-labeled T cell acute lymphoblastic leukemia (T-ALL), allowing visualization of the onset and spread of this disease. Here, we show that leukemias from this transgenic line are highly penetrant and render animals moribund by 80.7 +/- 17.6 days of life (+/-1 SD, range = 50-158 days). These T cell leukemias are clonally aneuploid, can be transplanted into irradiated recipient fish, and express the zebrafish orthologues of the human T-ALL oncogenes tal1/scl and Imo2, thus providing an animal model for the most prevalent molecular subgroup of human T-ALL. Because T-ALL develops very rapidly in rag2-EGFP-mMyc transgenic fish (in which "mMyc" represents mouse c-Myc), this line can only be maintained by in vitro fertilization. Thus, we have created a conditional transgene in which the EGFP-mMyc oncogene is preceded by a loxed dsRED2 gene and have generated stable rag2-loxP-dsRED2-loxP-EGFP-mMyc transgenic zebrafish lines, which have red fluorescent thymocytes and do not develop leukemia. Transgenic progeny from one of these lines can be induced to develop T-ALL by injecting Cre RNA into one-cell-stage embryos, demonstrating the utility of the Cre/lox system in the zebrafish and providing an essential step in preparing this model for chemical and genetic screens designed to identify modifiers of Myc-induced T-ALL. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Feng, Hui/0000-0003-1318-821X; Berghmans, Stephane/0000-0001-5414-8674 FU NCI NIH HHS [P30 CA006516, CA-06516, CA-68484, P01 CA068484] NR 41 TC 146 Z9 159 U1 2 U2 13 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 26 PY 2005 VL 102 IS 17 BP 6068 EP 6073 DI 10.1073/pnas.0408708102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 921BI UT WOS:000228738800033 PM 15827121 ER PT J AU Gottlieb, DJ Punjabi, NM Newman, AB Resnick, HE Redline, S Baldwin, CM Nieto, FJ AF Gottlieb, DJ Punjabi, NM Newman, AB Resnick, HE Redline, S Baldwin, CM Nieto, FJ TI Association of sleep time with diabetes mellitus and impaired glucose tolerance SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID VISCERAL ADIPOSE-TISSUE; CORONARY-HEART-DISEASE; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; METABOLIC SYNDROME; ALAMEDA-COUNTY; HEALTH; OBESITY; DURATION; MORTALITY AB Background: Experimental sleep restriction causes impaired glucose tolerance (IGT); however, little is known about the metabolic effects of habitual sleep restriction. We assessed the cross-sectional relation of usual sleep time to diabetes mellitus (DM) and IGT among participants in the Sleep Heart Health Study, a community-based prospective study of the cardiovascular consequences of sleep-disordered breathing. Methods: Participants were 722 men and 764 women, aged 53 to 93 years. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more ( >= 7.0 mmoVL) fasting or 200 mg/dL or more ( >= 11. 1 mmoVL) 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour postchallenge glucose level of 140 mg/dL or more ( >= 7.8 mmoVL) and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression with adjustment for age, sex, race, body habitus, and apnea-hypopnea index. Results: The median sleep time was 7 hours per night, with 27.1% of subjects sleeping 6 hours or less per night. Compared with those sleeping 7 to 8 hours per night, subjects sleeping 5 hours or less and 6 hours per night had adjusted odds ratios for DM of 2.51 (95% confidence interval, 1.57-4.02) and 1.66 (95% confidence interval, 1.15-2.39), respectively. Adjusted odds ratios for IGT were 1.33 (95% confidence interval, 0.83-2.15) and 1.58 (95% confidence interval, 1.15-2.18), respectively. Subjects sleeping 9 hours or more per night also had increased odds ratios for DM and IGT. These associations persisted when subjects with insomnia symptoms were excluded. Conclusions: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02215 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA USA. Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. Univ Pittsburgh, Sch Med, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. MedStar Res Inst, Hyattsville, MD USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Div Clin Epidemiol, Cleveland, OH 44106 USA. Arizona State Univ, Coll Nursing, Tempe, AZ USA. Univ Wisconsin, Sch Med, Dept Populat Hlth Sci, Madison, WI USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, Ctr Pulm, 715 Albany St,Mail Stop R-304, Boston, MA 02215 USA. EM dgottlieb@lung.bumc.bu.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Baldwin, Carol/0000-0002-0732-2307 FU NHLBI NIH HHS [U01 HL64360, HL53938-07S1, U01 HL53916, U01 HL53931, U01 HL53934, U01 HL53937, U01 HL53938, U01 HL53940, U01 HL53941, U01 HL63429, U01 HL63463] NR 39 TC 404 Z9 419 U1 6 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 25 PY 2005 VL 165 IS 8 BP 863 EP 868 DI 10.1001/archinte.165.8.863 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 919DT UT WOS:000228599200006 PM 15851636 ER PT J AU Faquin, WC Cibas, ES Renshaw, AA AF Faquin, WC Cibas, ES Renshaw, AA TI "Atypical" cells in fine-needle aspiration biopsy specimens of benign thyroid cysts SO CANCER CYTOPATHOLOGY LA English DT Article DE cytopathology; fine-needle aspiration biopsy; thyroid; atypical cells; papillary carcinoma; cysts ID PAPILLARY CARCINOMA; CYTOLOGIC FEATURES; NODULES; LESIONS; MANAGEMENT; DIAGNOSIS; PATHOLOGY AB BACKGROUND. Cystic lesions of the thyroid are common. Most are benign nodules with degenerative changes in a multinodular goiter. Fine-needle aspiration biopsy (FNAB) specimens from these cystic nodules usually are easily interpreted as benign. However, occasionally, cells with atypical features are encountered, increasing the possibility of a cystic malignant neoplasm. To the authors ' knowledge, the microscopic features of these benign cells, presumed to be of cyst-lining origin, have not been well described to date. To refine the description of their morphologic features, with the belief that better recognition will avoid unnecessary surgery, the authors examined the cytologic and corresponding histologic features of thyroid cysts with "atypical" cells. METHODS. A total of 149 FNAB specimens from thyroid cysts containing atypical cells were identified. Seventy-five specimens with subsequent histologic correlation showing a benign cystic thyroid nodule were selected for study. The cytologic features of the atypical cyst-lining cells were reviewed and correlations were made with histologic, immunohistochermical, and clinical features. In addition, 12 FNAB specimens of histologically proven cystic papillary carcinoma diagnosed as atypical were reviewed for comparison. RESULTS. The majority of specimens (94%) were diagnosed cytologically as atypical thyroid cysts. However, in 29% of these specimens, a papillary or Hilahle cell neoplasm could not be excluded. The cytologic features of the atypical cells most often resembled classic reparative epithelial cells consistent with a cyst-lining origin. The most common features were cohesive flat sheets (84%), distinct cell borders (96%), nuclear enlargement (92%), nuclear grooves (79%), dense granular cytoplasm (79%), small distinct nucleoli (85%), fine chromatin (87%), and elongate to spindled cytomorphology (57%). In contrast to the atypical cells from benign cysts, cystic papillary carcinomas lacked the repair-like spindled cytomorphology, and showed nuclear crowding (100%), as well as papillary microarchitecture (50%), and rare intranuclear pseudoinclusions (42%). Histologically, the atypical cells in aspirate specimens corresponded to cyst-lining cells, which exhibited a spectrum ranging from flattened elongate cells with eosinophilic cytoplasm to more polygonal cells with abundant eosinophilic cytoplasm, enlarged irregular nuclei with pale chromatin, prominent nuclear grooves, and distinct nucleoli. Immunohistochemical staining of a subset of the resected thyroid cysts showed that the cyst-lining cells were positive for keratin and thyroglobulin, consistent with thyroid follicular cells. CONCLUSIONS. Atypical cyst-lining cells were found to have characteristic features (e.g., distinct cell borders, elongated shape, eosinophflic cytoplasm, and distinct nocleoli) and lacked nuclear crowding, intranuclear pseudoinclusions, and papillary architecture that, in many specimens, allowed them to be recognized as benign. The authors recommended that the subset of cells with the characteristic features described in the current study be reported as "consistent with benign cyst lining cells". Cancer (Cancer Qrtopathol) 2005; 105:71-9. (c) 2005 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM WFaquin@Partners.org NR 30 TC 23 Z9 23 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2005 VL 105 IS 2 BP 71 EP 79 DI 10.1002/cncr.20832 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 915RP UT WOS:000228322000004 PM 15662703 ER PT J AU Colston, JT de la Rosa, SD Strader, JR Anderson, MA Freeman, GL AF Colston, JT de la Rosa, SD Strader, JR Anderson, MA Freeman, GL TI H2O2 activates Nox4 through PLA(2)-dependent arachidonic acid production in adult cardiac fibroblasts SO FEBS LETTERS LA English DT Article DE Nox4; NADPH oxidase; reactive oxygen species; cardiac fibroblasts; arachidonic acid ID SMOOTH-MUSCLE-CELLS; NADPH OXIDASE; NAD(P)H OXIDASE; SIGNALING CASCADE; PHORBOL ESTER; SUPEROXIDE; EXPRESSION; SYSTEM; KINASE; ALPHA AB Stimulated production of reactive oxygen species (ROS) by plasma membrane-associated nicotinamide adenine dinucleotide phosphate oxidases (Nox) in non-phagocytic cells regulates a number of biological processes including growth, vessel tone, and oxygen sensing. The purpose of this study was to investigate H2O2-stimulated ROS production in primary adult cardiac fibroblasts (CF). Results demonstrate that CF express an H2O2-inducible oxidant generating system that is inhibitable by diphenylene iodonium (DPI) and sensitive to antioxidants. In addition to H2O2, generation of ROS was stimulated potently by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and arachidonic acid (AA) in a protein kinase C-independent manner. Pretreatment with arachidonyl trifluoromethyl ketone was nearly as effective as DPI at reducing H2O2- and OAG-stimulated oxidant generation indicating a central role for phospholipase A(2) (PLA(2)) in this signaling pathway. Co-stimulation with H2O2 and OAG did not increase ROS generation as compared to OAG alone suggesting both agonists signal through a shared, rate-limited enzymatic pathway involving PLA(2). Co-stimulation with H2O2 and AA had additive effects indicating these two agonists stimulate oxidant production through a parallel activation pathway. Reverse transcriptase-coupled polymerase chain reaction and Western blotting demonstrate primary cardiac fibroblasts express transcripts and protein for Nox4, p22, p47, and p67 phox. Transfections with Nox4 small inhibitory ribonucleic acid oligonucleotides or p22 phox antisense oligonucleotides significantly downregulated stimulated Nox activity. Inhibitors of nitric oxide synthases were without effect. We conclude adult CF express Nox4/p22 phox-containing oxidant generating complex activated by H2O2, OAG, and AA through a pathway that requires activation of PLA(2). (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Janey Briscoe Ctr Excellence Cardiovasc Dis,Div C, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Colston, JT (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Janey Briscoe Ctr Excellence Cardiovasc Dis,Div C, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM colstonj@uthscsa.edu NR 41 TC 56 Z9 59 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 25 PY 2005 VL 579 IS 11 BP 2533 EP 2540 DI 10.1016/j.febslet.2005.03.057 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 921IA UT WOS:000228756400048 PM 15848200 ER PT J AU Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, P AF Soares, JC Kochunov, P Monkul, ES Nicoletti, MA Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, DJ Lancaster, J Fox, P TI Structural brain changes in bipolar disorder using deformation field morphometry SO NEUROREPORT LA English DT Article DE bipolar disorder; mood disorders; magnetic resonance imaging; morphometry; neuroimaging; structural ID REGIONAL SPATIAL NORMALIZATION; VENTRICULAR ENLARGEMENT; MOOD DISORDERS; SCHIZOPHRENIA; ABNORMALITIES; TARGET; MRI AB The objective of this study was to investigate anatomical brain abnormalities in adult bipolar patients using a deformation field morphometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women=16/16) and 32 right-handed, age and gender matched healthy controls. Deformation field morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found genderspecific structural differences between bipolar patients and healthy individuals. Bipolar men had significantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the findings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients.© 2005 Lippincott Williams & Wilkins. C1 Audie L Murpy Div, S Texas Vet Hlth Care Syst, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX USA. Audie L Murpy Div, S Texas Vet Hlth Care Syst, Dept Radiol, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, Res Imaging Ctr, San Antonio, TX 78285 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. RP Soares, JC (reprint author), Audie L Murpy Div, S Texas Vet Hlth Care Syst, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX USA. EM soares@uthscsa.edu RI Lancaster, Jack/F-2994-2010; Kochunov, Peter/E-4711-2010; brambilla, paolo/B-4184-2010; Fox, Peter/B-4725-2010 OI brambilla, paolo/0000-0002-4021-8456; Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [MH 01736, MH 068662, MH 29618, MH 30915] NR 25 TC 31 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 25 PY 2005 VL 16 IS 6 BP 541 EP 544 DI 10.1097/00001756-200504250-00004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 925XK UT WOS:000229086700004 PM 15812303 ER PT J AU Akashi, K Traver, D Zon, LI AF Akashi, K Traver, D Zon, LI TI The complex cartography of stem cell commitment SO CELL LA English DT Editorial Material ID BONE-MARROW; LYMPHOID PROGENITOR; LINEAGE COMMITMENT; FLT3 AB In this issue of Cell, a study by Adolfsson and coworkers (Adolfsson et al., 2005) provides insight into the early lineage commitment events of multipotent hematopoietic stem cells (HSCs). These studies demonstrate the importance of the Flt3 receptor tyrosine kinase as the earliest marker of hematopoietic cell fate commitment in that erythrocyte and megakaryocyte potentials are lost first as HSCs; differentiate to lymphocyte progenitors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 9 TC 24 Z9 26 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 22 PY 2005 VL 121 IS 2 BP 160 EP 162 DI 10.1016/j.cell.2005.04.005 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 920QK UT WOS:000228705000004 PM 15851023 ER PT J AU He, ZH Way, KJ Arikawa, E Chou, E Opland, DM Clermont, A Isshiki, K Ma, RCW Scott, JA Schoen, FJ Feener, EP King, GL AF He, ZH Way, KJ Arikawa, E Chou, E Opland, DM Clermont, A Isshiki, K Ma, RCW Scott, JA Schoen, FJ Feener, EP King, GL TI Differential regulation of angiotensin II-induced expression of connective tissue growth factor by protein kinase C isoforms in the myocardium SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR GENE-EXPRESSION; HIGH GLUCOSE; DIABETIC-NEPHROPATHY; DELTA-PKC; IN-VIVO; ACTIVATION; BETA; HEART; CARDIOMYOPATHY; INHIBITION AB Protein kinase C ( PKC) and angiotensin II ( AngII) can regulate cardiac function in pathological conditions such as in diabetes or ischemic heart disease. We have reported that expression of connective tissue growth factor ( CTGF) is increased in the myocardium of diabetic mice. Now we showed that the increase in CTGF expression in cardiac tissues of streptozotocin- induced diabetic rats was reversed by captopril and islet cell transplantation. Infusion of AngII in rats increased CTGF mRNA expression by 15- fold, which was completely inhibited by co- infusion with AT1 receptor antagonist, candesartan. Similarly, incubation of cultured cardiomyocytes with AngII increased CTGF mRNA expression by 2- fold, which was blocked by candesartan and a general PKC inhibitor, GF109203X. The role of PKC isoform- dependent action was further studied using adenoviral vector- mediated gene transfer of dominant negative ( dn) PKC or wild type PKC isoforms. Expression of dnPKC alpha, -epsilon, and - zeta isoforms suppressed AngII- induced CTGF expression in cardiomyocytes. In contrast, expression of dominant negative PKC delta significantly increased AngII- induced CTGF expression, whereas expression of wild type PKC delta inhibited this induction. This inhibitory effect was further confirmed in the myocardium of transgenic mice with cardiomyocyte-specific overexpression of PKC delta ( delta Tg mice). Thus, AngII can regulate CTGF expression in cardiomyocytes through a PKC activation- mediated pathway in an isoform-selective manner both in physiological and diabetic states and may contribute to the development of cardiac fibrosis in diabetic cardiomyopathy. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU NIDDK NIH HHS [DK59725, DK60165, P30 DK036836, DK36836] NR 42 TC 48 Z9 56 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 2005 VL 280 IS 16 BP 15719 EP 15726 DI 10.1074/jbc.M413493200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800033 PM 15699040 ER PT J AU Novgorodov, SA Szulc, ZM Luberto, C Jones, JA Bielawski, J Bielawska, A Hannun, YA Obeid, LM AF Novgorodov, SA Szulc, ZM Luberto, C Jones, JA Bielawski, J Bielawska, A Hannun, YA Obeid, LM TI Positively charged ceramide is a potent inducer of mitochondrial permeabilization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER MITOCHONDRIA; TRANSITION PORE; RESPIRATORY-CHAIN; CALCIUM SIGNALS; GOLGI-APPARATUS; CELL-DEATH; APOPTOSIS; MEMBRANE; PHOSPHORYLATION; MECHANISM AB Ceramide-induced cell death is thought to be mediated by change in mitochondrial function, although the precise mechanism is unclear. Proposed models suggest that ceramide induces cell death through interaction with latent binding sites on the outer or inner mitochondrial membranes, followed by an increase in membrane permeability, as an intermediate step in ceramide signal propagation. To investigate these models, we developed a new generation of positively charged ceramides that readily accumulate in isolated and in situ mitochondria. Accumulated, positively charged ceramides increased inner membrane permeability and triggered release of mitochondrial cytochrome c. Furthermore, the positively charged ceramide-induced permeability increase was suppressed by cyclosporin A (60%) and 1,3-dicyclohexylcarbodiimide (90%). These observations suggest that the inner membrane permeability increase is due to activation of specific ion transporters, not the generalized loss of lipid bilayer barrier functions. The difference in sensitivity of ceramide-induced ion fluxes to inhibitors of mitochondrial transporters suggests activation of at least two transport systems: the permeability transition pore and the electrogenic H+ channel. Our results indicate the presence of specific ceramide targets in the mitochondrial matrix, the occupation of which triggers permeability alterations of the inner and outer mitochondrial membranes. These findings also suggest a novel therapeutic role for positively charged ceramides. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [IPO1CA097132]; NIA NIH HHS [AG16583]; NIDDK NIH HHS [DK59340] NR 44 TC 72 Z9 74 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 2005 VL 280 IS 16 BP 16096 EP 16105 DI 10.1074/jbc.M411707200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800077 PM 15722351 ER PT J AU Ferreira, AM Rollins, BJ Faunce, DE Burns, AL Zhu, XF DiPietro, LA AF Ferreira, AM Rollins, BJ Faunce, DE Burns, AL Zhu, XF DiPietro, LA TI The effect of MCP-1 depletion on chemokine and chemokine-related gene expression: evidence for a complex network in acute inflammation SO CYTOKINE LA English DT Article DE inflammation; monocyte chemoattractant protein I; chemokines; microarray ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; MACROPHAGE-STIMULATING PROTEIN; NEUROTROPHIC FACTOR; PULMONARY-FIBROSIS; ENDOTHELIAL-CELLS; MICE; DECORIN; NEUTROPHIL; RECRUITMENT; CYTOKINES AB The expression of chemokines has been suggested to involve an interdependent network, with the absence of a single chemokine affecting the expression of multiple other chemokines. Monocyte chemoattractant protein (MCP-1), a member of C-C chemokine superfamily, plays a critical role in the recruitment and activation of leukocytes during acute inflammation. To examine the effect of the loss of MCP-1 on expression of the chemokine network, we compared the mRNA expression profiles of MCP-1(-/-) and wild type mice during the acute inflammatory phase of excisional wounds. Utilizing a mouse cDNA array containing 514 chemokine and chemokine related genes, the loss of MCP-1 was observed to cause a significant upregulation of nine genes (Decorin, Persephin, IL-1 beta, MIP-2, MSP, IL1ra, CCR5, CCR3, IL-11) and significant downregulation of two genes (CCR4 and CD3Z) in acute wounds. The array data was confirmed by semi-quantitative RT-PCR. The effect of MCP-1 deletion on chemokine expression was further examined in isolated macrophages. Compared to wild type, LPS-stimulated peritoneal macrophages from MCP-1(-/-) mice showed a significant increase in the expression of RANTES, MIP-1 beta, MIP-1 alpha and MIP-2 mRNA. The data suggest that loss of a single chemokine perturbs the chemokine network not only in the setting of acute inflammation but even in an isolated inflammatory cell, the macrophage. (c) 2005 Elsevier Ltd. All rights reserved. C1 Loyola Univ, Med Ctr, Burn & Shock Trauma Inst, Dept Surg, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Program Mol Biol, Maywood, IL 60153 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DiPietro, LA (reprint author), Loyola Univ, Med Ctr, Burn & Shock Trauma Inst, Dept Surg, 2160 S 1st Ave, Maywood, IL 60153 USA. EM ldipiet@lumc.edu FU NIGMS NIH HHS [R01-GM55238] NR 38 TC 34 Z9 35 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD APR 21 PY 2005 VL 30 IS 2 BP 64 EP 71 DI 10.1016/j.cyto.2004.12.00 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 917TJ UT WOS:000228491800003 PM 15804597 ER PT J AU Athale, C Mansury, Y Deisboeck, TS AF Athale, C Mansury, Y Deisboeck, TS TI Simulating the impact of a molecular 'decision-process' on cellular phenotype and multicellular patterns in brain tumors SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE glioma; epidermal growth factor receptor; gene-protein network; agent-based model; migration; proliferation ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR TRAFFICKING; STEADY-STATE MODEL; HUMAN GLIOMA-CELLS; EGF-RECEPTOR; FACTOR-ALPHA; TGF-ALPHA; MATHEMATICAL-MODEL; COMPUTATIONAL ANALYSIS; MALIGNANT GLIOMAS AB Experimental evidence indicates that human brain cancer cells proliferate or migrate, yet do not display both phenotypes at the same time. Here, we present a novel computational model simulating this cellular decision-process leading up to either phenotype based on a molecular interaction network of genes and proteins. The model's regulatory network consists of the epidermal growth factor receptor (EGFR), its ligand transforming growth factor-alpha (TGF alpha), the downstream enzyme phospholipaseC-gamma (PLC gamma) and a mitosis-associated response pathway. This network is activated by autocrine TGFa secretion, and the EGFR-dependent downstream signaling this step triggers, as well as modulated by an extrinsic nutritive glucose gradient. Employing a framework of mass action kinetics within a multiscale agent-based environment, we analyse both the emergent multicellular behavior of tumor growth and the single-cell molecular profiles that change over time and space. Our results show that one can indeed simulate the dichotomy between cell migration and proliferation based solely on an EGFR decision network. It turns out that these behavioral decisions on the single cell level impact the spatial dynamics of the entire cancerous system. Furthermore, the simulation results yield intriguing experimentally testable hypotheses also on the sub-cellular level such as spatial cytosolic polarization of PLC gamma towards an extrinsic chemotactic gradient. Implications of these results for future works, both on the modeling and experimental side are discussed. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, MIT,Complex Biosyst Modeling Lab, HST,Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Deisboeck, TS (reprint author), Harvard Univ, MIT,Complex Biosyst Modeling Lab, HST,Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM deisboec@helix.mgh.harvard.edu RI Athale, Chaitanya/G-8883-2011 OI Athale, Chaitanya/0000-0002-9506-2153 FU NCI NIH HHS [CA 085139, CA 09502] NR 76 TC 62 Z9 64 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD APR 21 PY 2005 VL 233 IS 4 BP 469 EP 481 DI 10.1016/j.jtbi.2004.10.019 PG 13 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 905JU UT WOS:000227565200003 PM 15748909 ER PT J AU Cannon, CP Braunwald, E McCabe, CH Grayston, JT Muhlestein, B Giugliano, RP Cairns, R Skene, AM AF Cannon, CP Braunwald, E McCabe, CH Grayston, JT Muhlestein, B Giugliano, RP Cairns, R Skene, AM CA Prevastatin Atorvastatin Evaluatio TI Antibiotic treatment of Chlamydia pneumoniae after acute coronary syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEART-DISEASE; RABBIT MODEL; AZITHROMYCIN PREVENTS; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; INFECTION; ARTERIES; EVENTS; ROXITHROMYCIN AB BACKGROUND: Chlamydia pneumoniae has been found within atherosclerotic plaques, and elevated titers of antibody to this organism have been linked to a higher risk of coronary events. Pilot studies have suggested that antibiotic treatment may reduce the risk of cardiovascular events. METHODS: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and evaluated the efficacy of long-term treatment with gatifloxacin, a bactericidal antibiotic known to be effective against C. pneumoniae, in a double-blind, randomized, placebo-controlled trial. Subjects received 400 mg of gatifloxacin daily during an initial 2-week course of therapy that began 2 weeks after randomization, followed by a 10-day course every month for the duration of the trial (mean duration, 2 years), or placebo. The primary end point was a composite of death from all causes, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. RESULTS: A Kaplan-Meier analysis revealed that the rates of primary-end-point events at two years were 23.7 percent in the gatifloxacin group and 25.1 percent in the placebo group (hazard ratio, 0.95; 95 percent confidence interval, 0.84 to 1.08; P=0.41). No benefit was seen in any of the prespecified secondary end points or in any of the prespecified subgroups, including patients with elevated titers to C. pneumoniae or C-reactive protein. CONCLUSIONS: Despite long-term treatment with a bactericidal antibiotic effective against C. pneumoniae, no reduction in the rate of cardiovascular events was observed. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. Nottingham Clin Res Grp, Nottingham, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 24 TC 167 Z9 180 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 2005 VL 352 IS 16 BP 1646 EP 1654 DI 10.1056/NEJMoa043528 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 918CE UT WOS:000228515200006 PM 15843667 ER PT J AU Calin, GA Trapasso, F Shimizu, M Dumitru, CD Yendamuri, S Godwin, AK Ferracin, M Bernardi, G Chatterjee, D Baldassarre, G Rattan, S Alder, H Mabuchi, H Shiraishi, T Hansen, LL Overgaard, J Herlea, V Mauro, FR Dighiero, G Movsas, B Rassenti, L Kipps, T Baffa, R Fusco, A Mori, M Russo, G Liu, CG Neuberg, D Bullrich, F Negrini, M Croce, CM AF Calin, GA Trapasso, F Shimizu, M Dumitru, CD Yendamuri, S Godwin, AK Ferracin, M Bernardi, G Chatterjee, D Baldassarre, G Rattan, S Alder, H Mabuchi, H Shiraishi, T Hansen, LL Overgaard, J Herlea, V Mauro, FR Dighiero, G Movsas, B Rassenti, L Kipps, T Baffa, R Fusco, A Mori, M Russo, G Liu, CG Neuberg, D Bullrich, F Negrini, M Croce, CM TI Familial cancer associated with a polymorphism in ARLTS1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; TUMOR-SUPPRESSOR LOCUS; DOWN-REGULATION; GENE; 13Q14; SEQUENCE; REGION; IDENTIFICATION; EXPRESSION; DELETIONS AB BACKGROUND: The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. METHODS: We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. RESULTS: We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. CONCLUSIONS: A genetic variant of ARLTS1 predisposes patients to familial cancer. C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Ferrara, I-44100 Ferrara, Italy. Natl Canc Inst, Aviano, Italy. Aarhus Univ, Aarhus, Denmark. Fundeni Clin Hosp, Bucharest, Romania. Univ Roma La Sapienza, Rome, Italy. Inst Pasteur, Paris, France. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Catanzaro, Catanzaro, Italy. Kyushu Univ, Beppu, Oita, Japan. Ist Ricovero & Cura Carattere Sci, Rome, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Croce, CM (reprint author), Ohio State Univ, Ctr Comprehens Canc, 385K Wiseman Hall,400 W 12th Ave, Columbus, OH 43210 USA. EM carlo.croce@osumc.edu RI Hansen, Lise Lotte/I-3377-2016; Negrini, Massimo/J-2377-2016; Ferracin, Manuela/K-2097-2016; Baldassarre, Gustavo/K-1350-2016; OI Hansen, Lise Lotte/0000-0001-7915-2506; Negrini, Massimo/0000-0002-0007-1920; Ferracin, Manuela/0000-0002-1595-6887; Baldassarre, Gustavo/0000-0002-9750-8825; Yendamuri, Sai/0000-0001-6654-3487; Fusco, Alfredo/0000-0003-3332-5197 FU NCI NIH HHS [P01CA76259, P01CA81534, P30CA56036] NR 30 TC 84 Z9 93 U1 2 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 2005 VL 352 IS 16 BP 1667 EP 1676 DI 10.1056/NEJMoa042280 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 918CE UT WOS:000228515200008 PM 15843669 ER PT J AU Beroukhim, R Aquino, SL Shipp, MA Harris, NL Hales, CA AF Beroukhim, R Aquino, SL Shipp, MA Harris, NL Hales, CA TI Case 12-2005: A 30-year-old woman with a mediastinal mass - Primary mediastinal diffuse large-B-cell lymphoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CLASSICAL HODGKIN LYMPHOMA; TUMOR; REL; 9P; GAINS; 2P C1 Massachusetts Gen Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Beroukhim, R (reprint author), Massachusetts Gen Hosp, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02114 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 2005 VL 352 IS 16 BP 1697 EP 1704 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 918CE UT WOS:000228515200013 PM 15843673 ER PT J AU Romero-Gallo, J Sozmen, EG Chytil, A Russell, WE Whitehead, R Parks, WT Holdren, MS Her, MF Gautam, S Magnuson, M Moses, HL Grady, WM AF Romero-Gallo, J Sozmen, EG Chytil, A Russell, WE Whitehead, R Parks, WT Holdren, MS Her, MF Gautam, S Magnuson, M Moses, HL Grady, WM TI Inactivation of TGF-beta signaling in hepatocytes results in an increased proliferative response after partial hepatectomy SO ONCOGENE LA English DT Article DE TGF-beta; liver regeneration ID TRANSFORMING-GROWTH-FACTOR; CELL-CYCLE ARREST; LIVER EPITHELIAL-CELLS; RAT-LIVER; DNA-SYNTHESIS; II RECEPTOR; C-MYC; HEPATOCELLULAR-CARCINOMA; NUCLEAR-LOCALIZATION; GENE-EXPRESSION AB The transforming growth factor beta (TGF-beta) signaling pathway, which is activated by the TGF-beta receptor complex consisting of type I and type II TGF-beta receptors (TGFBR1 and TGFBR2), regulates cell growth and death. TGF-beta and components of its signaling pathway, particularly TGFBR2, have been implicated as tumor suppressor genes and important antimitogenic factors in the gastrointestinal tract and liver. An in vivo approach to study these effects has been hindered by the embryonic lethality of Tgfbr2(-/-) mice and poor viability of the Tgfb1(-/-) mice. Consequently, we have developed a hepatocyte-specific Tgfbr2 knockout mouse, the Alb-cre Tgfbr2(flx/flx) mouse, to study the physiologically relevant effects of TGF-beta signaling on epithelial cell proliferation in vivo. After 70% hepatectomy, we observed increased proliferation and an increased liver mass : body weight ratio in the Alb-cre Tgfbr2(flx/flx) mice compared to Tgfbr2(flx/flx) mice. We also observed decreased expression and increased phosphorylation of p130 in the livers from the Alb-cre Tgfbr2(flx/flx) mice as well as increased expression of cyclin E, which is transcriptionally regulated, in part, by p130:E2F4. Consistent with these results, in a hepatocyte cell line derived from the Tgfbr2(flx/flx) mice, we found that TGF-beta increases the nuclear localization of E2F4, and presumably the transcriptional repression of the p130: E2F4 complex. Thus, we have demonstrated that TGF-beta signaling in vivo regulates the mitogenic response in the regenerating liver, affecting the liver mass : body weight ratio after partial hepatectomy, and that these mitogenic responses are accompanied by alterations in p130 expression and phosphorylation, implicating p130 as one of the proteins regulated in vivo by TGF-beta during liver regeneration. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vanderbilt Univ, Dept Canc Biol, Nashville, TN USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Beth Israel Deaconess Med Ctr, Dept Biostat, Boston, MA 02215 USA. Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Grady, WM (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D4-100,POB 19024, Seattle, WA 98104 USA. EM wgrady@fhcrc.org RI Russell, William/A-7307-2009; Magnuson, Mark/B-1335-2009 OI Magnuson, Mark/0000-0002-8824-6499 FU NCI NIH HHS [R01 CA102162, R01CA85492]; NIDDK NIH HHS [R01 DK53804, R01 DK60669-01] NR 84 TC 62 Z9 68 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 21 PY 2005 VL 24 IS 18 BP 3028 EP 3041 DI 10.1038/sj.onc.1208475 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 919WY UT WOS:000228649500012 PM 15735717 ER PT J AU Li, WH Zhang, CS Sui, JH Kuhn, JH Moore, MJ Luo, SW Wong, SK Huang, IC Xu, KM Vasilieva, N Murakami, A He, YQ Marasco, WA Guan, Y Choe, HY Farzan, M AF Li, WH Zhang, CS Sui, JH Kuhn, JH Moore, MJ Luo, SW Wong, SK Huang, IC Xu, KM Vasilieva, N Murakami, A He, YQ Marasco, WA Guan, Y Choe, HY Farzan, M TI Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2 SO EMBO JOURNAL LA English DT Article DE angiotensin-converting enzyme 2; coronavirus; severe acute respiratory syndrome; viral adaptation ID ACUTE-RESPIRATORY-SYNDROME; ANGIOTENSIN-CONVERTING ENZYME-2; SPIKE PROTEIN; S-PROTEIN; FUNCTIONAL RECEPTOR; CELL TROPISM; DC-SIGN; GLYCOPROTEIN; VIRUS; EXPRESSION AB Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002-2003 SARS outbreak and during the much less severe 2003-2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002-2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002-2003 SARS epidemic. C1 Univ Hong Kong, Queen Mary Hosp, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Free Univ Berlin, Dept Biol Chem Pharm, D-1000 Berlin, Germany. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Ctr Dis Control & Prevent Shenzhen, Shenzhen, Guangdong Prov, Peoples R China. RP Guan, Y (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Microbiol, Hong Kong, Hong Kong, Peoples R China. EM yguan@hkucc.hku.hk; hyeryun.choe@tch.harvard.edu; farzan@hms.harvard.edu RI Xu, Kemin/G-2825-2011; Kuhn, Jens H./B-7615-2011; OI Kuhn, Jens H./0000-0002-7800-6045; Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [R01 AI043891] NR 45 TC 183 Z9 203 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 20 PY 2005 VL 24 IS 8 BP 1634 EP 1643 DI 10.1038/sj.emboj.7600640 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923XW UT WOS:000228943900013 PM 15791205 ER PT J AU Nihal, M Ahmad, N Mukhtar, H Wood, GS AF Nihal, M Ahmad, N Mukhtar, H Wood, GS TI Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: Possible implications for the chemoprevention of melanoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE green tea; EGCG; melanoma; apoptosis; Bcl-2 family; caspase; cell cycle ID MALIGNANT-MELANOMA; CELL-SURVIVAL; BCL-2 FAMILY; APOPTOSIS; CANCER; TEA; THERAPY; TUMOR AB Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present,in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar, EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16(INK4a), p21(WAF1/CIP1) and p27(KIP1). Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma. (C) 2004 Wiley-Liss, Inc. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1300 Univ Ave,MSC 25B, Madison, WI 53706 USA. EM gwood@dermatology.wisc.edu FU NIAMS NIH HHS [AR002136-06] NR 33 TC 130 Z9 139 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 20 PY 2005 VL 114 IS 4 BP 513 EP 521 DI 10.1002/ijc.20785 PG 9 WC Oncology SC Oncology GA 904YV UT WOS:000227535400002 PM 15609335 ER PT J AU Lipshultz, SE Lipsitz, SR Sallan, SE Dalton, VM Mone, SM Gelber, RD Colan, SD AF Lipshultz, SE Lipsitz, SR Sallan, SE Dalton, VM Mone, SM Gelber, RD Colan, SD TI Chronic progressive cardiac dysfunction years after doxorubicin therapy for childhood acute lymphoblastic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ANTHRACYCLINE CARDIOTOXICITY; TROPONIN-T; FOLLOW-UP; PROSPECTIVE (PCHIV)-C-2-H-2; INDUCED CARDIOMYOPATHY; PEDIATRIC-PATIENTS; MYOCARDIAL INJURY; 5-YEAR SURVIVORS; LATE MORTALITY; HEART-FAILURE AB Purpose Cross-sectional studies show that cardiac abnormalities are common in long-term survivors of doxorubicin-treated childhood malignancies. Longitudinal data, however, are rare. Methods Serial echocardiograms (N = 499) were obtained from 115 doxorubicin-treated long-term survivors of childhood acute lymphoblastic leukemia (median age at diagnosis, 4.8 years; median follow-up after completion of doxorubicin, 11.8 years). Results were expressed as z scores to indicate the number of standard deviations (SDs) above (+) or below (-) the normal predicted value. Median individual and cumulative doxorubicin doses were 30 mg/m per dose and 352 mg/m(2), respectively. Results Left ventricular fractional shortening was significantly reduced after doxorubicin therapy, and the reduction was related to cumulative dose. z scores for fractional shortening transiently improved before failing to -2.76 more than 12 years after diagnosis. Reduced fractional shortening was related to impaired contractility and increasing afterload, consequences of a progressive reduction of ventricular mass, and wall thickness relative to body-surface area. Left ventricular contractility fell significantly over time and was depressed at last follow-up in patients receiving more than 300 mg/m(2) of doxorubicin. Systolic and diastolic blood pressures were below normal more than 9 years after diagnosis. Even patients receiving lower cumulative doxorubicin doses experienced reduced mass and dimension. Fractional shortening and dimension at the end of therapy predicted these parameters 11.8 years later. Conclusion Cardiac abnormalities were persistent and progressive after doxorubicin therapy. Inadequate ventricular mass with chronic afterload excess was associated with progressive contractile deficit and possibly reduced cardiac output and restrictive cardiomyopathy. The deficits were worst after highest cumulative doses of doxorubicin, but appeared even after low doses. C1 Univ Miami, Holtz Childrens Hosp, Miller Sch Med, Dept Pediat, Miami, FL 33101 USA. Sylvester Comprehens Canc Ctr, Miami, FL USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Lipshultz, SE (reprint author), Univ Miami, Miller Sch Med, Dept Pediat D820, POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu FU NCI NIH HHS [CA 68484, CA 55576, CA06516, CA79060]; NHLBI NIH HHS [HL 53392, HL 59837, HL 69800, HL 72705, HR 96041] NR 40 TC 277 Z9 297 U1 0 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 APR 20 PY 2005 VL 23 IS 12 BP 2629 EP 2636 DI 10.1200/JCO.2005.12.121 PG 8 WC Oncology SC Oncology GA 918QV UT WOS:000228563600009 PM 15837978 ER PT J AU Li, FP Fletcher, JA Heinrich, MC Garber, JE Sallan, SE Curiel-Lewandrowski, C Duensing, A van de Rijn, MV Schnipper, LE Demetri, GD AF Li, FP Fletcher, JA Heinrich, MC Garber, JE Sallan, SE Curiel-Lewandrowski, C Duensing, A van de Rijn, MV Schnipper, LE Demetri, GD TI Familial gastrointestinal stromal tumor syndrome: Phenotypic and molecular features in a kindred SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID C-KIT GENE; SOFT-TISSUE TUMORS; GERMLINE MUTATION; INTERSTITIAL-CELLS; TYROSINE KINASE; ACTIVATION; DOMAIN; HYPERPIGMENTATION; PROLIFERATION; EXPRESSION AB Purpose Members of a family with hereditary gastrointestinal stromal tumors (GIST) and a germline KIT oncogene mutation were evaluated for other potential syndrome manifestations. A tumor from the proband was analyzed to compare features. with sporadic GISTS. Patients and Methods Members of a kindred in which six relatives in four consecutive generations comprised an autosomal dominant pattern of documented GISTS and cutaneous lesions underwent physical examination, imagining studies, and germline KIT analysis. A recurrent GIST from the proband was studied using microarray, karyotypic, immunohistochemical, and immunoblotting techniques. Results In addition to evidence of multiple GISTS, lentigines, malignant melanoma, and an angioleiomyoma were identified in relatives. A previously reported gain-of-function missense mutation in KIT exon 11 (T -> C) that results in a V559A substitution within the juxtamembrane domain was identified in three family members. The proband's recurrent gastric GIST had a 44,XY 14,-22 karyotype and immunohistochemical evidence of strong diffuse cytoplasmic KIT expression without expression of actin, desmin, or S-100. Immunoblotting showed strong expression of phosphorylated KIT and downstream signaling intermediates (AKT and MAPK) at levels comparable with those reported in sporadic GISTS. cDNA array profiling demonstrated clustering with sporadic GISTS, and expression of GIST markers comparable to sporadic GISTs. Conclusion These studies provide the first evidence that gene expression and mechanisms of cytogenetic progression and cell signaling are indistinguishable in familial and sporadic GISTS. Current investigations of molecularly targeted therapies in GIST patients provide opportunities to increase the understanding of features of the hereditary syndrome, and risk factors and molecular pathways of the neoplastic phenotypes. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM fli@partners.org OI Duensing, Anette/0000-0002-0168-4067 NR 45 TC 89 Z9 94 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 20 PY 2005 VL 23 IS 12 BP 2735 EP 2743 DI 10.1200/JCO.2005.06.009 PG 9 WC Oncology SC Oncology GA 918QV UT WOS:000228563600021 PM 15837988 ER PT J AU Rockall, AG Sohaib, SA Harisinghani, MG Babar, SA Singh, N Jeyarajah, AR Oram, DH Jacobs, IJ Shepherd, JH Reznek, RH AF Rockall, AG Sohaib, SA Harisinghani, MG Babar, SA Singh, N Jeyarajah, AR Oram, DH Jacobs, IJ Shepherd, JH Reznek, RH TI Diagnostic performance of nanoparticle-enhanced magnetic resonance Imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, IL SP Radiol Soc N Amer ID GYNECOLOGIC-ONCOLOGY-GROUP; POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; CARCINOMA; MR; LYMPHANGIOGRAPHY; ECHO; NECK; PET AB Purpose Lymph node metastases affect management and prognosis of patients with gynecologic malignancies. Preoperative nodal assessment with computed tomography or magnetic resonance imaging (MRI) is inaccurate. A new lymph node-specific contrast agent, ferumoxtran-10, composed of ultrasmall particles of iron oxide (USPIO), may enhance the detection of lymph node metastases independent of node size. Our aim was to compare the diagnostic performance of MRI with USPIO against standard size criteria. Methods Forty-four patients with endometrial (n = 15) or cervical (n = 29) cancer were included. MRI was performed before and after administration of USPIO. Two independent observers viewed the MR images before lymph node sampling. Lymph node metastases were predicted using size criteria and USPIO criteria Lymph node sampling was performed in all patients. Results Lymph node sampling provided 768 pelvic or para-aortic nodes for pathology, of which 335 were correlated on MRI; 17 malignant nodes were found in 11 of 44 patients (25 %). On a node-by-node basis, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) by size criteria were 29 %*, 99 %, 56 %, and 96 %, and by USPIO criteria (reader 1/reader 2) were 93 %/82 %* (*P = 008/ 004) 97 %/97 % 61 %/59 % and 100 %/99 %, respectively (where [*] indicates the statistical difference of P = x/x between the two results marked by the asterisk). On a patient-by-patient basis, sensitivity, specificity, PPV, and NPV by size criteria were 27 %*, 94 %, 60 %, and 79 %, and by USPIO criteria (reader 1/reader 2) were 100 %/91 %* (*P = .031/.06), 94 %/87 %, 82 %/71 %, and 100 %/ 96 %, respectively. The kappa statistic was 0.93. Conclusion Lymph node characterization with USPIO increases the sensitivity of MRI in the prediction of lymph node metastases, with no loss of specificity. This may greatly improve preoperative treatment planning. C1 St Bartholomews Hosp, Dept Radiol, London EC1A 7ED, England. St Bartholomews Hosp, Dept Gyneoncol & Histopathol, London EC1A 7ED, England. Royal Marsden Hosp, Dept Radiol, London SW3 6JJ, England. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rockall, AG (reprint author), St Bartholomews Hosp, Dept Radiol, Domin House, London EC1A 7ED, England. EM a.g.rockall@qmul.ac.uk RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 24 TC 183 Z9 191 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 APR 20 PY 2005 VL 23 IS 12 BP 2813 EP 2821 DI 10.1200/JCO.2005.07.166 PG 9 WC Oncology SC Oncology GA 918QV UT WOS:000228563600030 PM 15837995 ER PT J AU Huppenbauer, CB Tanzer, L DonCarlos, LL Jones, KJ AF Huppenbauer, CB Tanzer, L DonCarlos, LL Jones, KJ TI Gonadal steroid attenuation of developing hamster facial motoneuron loss by axotomy: Equal efficacy of testosterone, dihydrotestosterone, and 17-beta estradiol SO JOURNAL OF NEUROSCIENCE LA English DT Article DE androgen receptor; testosterone; estrogen; dihydrotestosterone; motoneuron; development; peripheral nerve injury ID ANDROGEN RECEPTOR IMMUNOREACTIVITY; NUCLEAR HORMONE-RECEPTORS; MALE SYRIAN-HAMSTER; ESTROGEN-RECEPTOR; NERVE TRANSECTION; RAT PROSTATE; MEDIATED NEUROPROTECTION; RUBROSPINAL MOTONEURONS; IMMUNODEFICIENT MICE; INDUCED ACCELERATION AB In the hamster facial nerve injury paradigm, we have established that androgens enhance both functional recovery from facial nerve paralysis and the rate of regeneration in the adult, through intrinsic effects on the nerve cell body response to injury and via an androgen receptor (AR)-mediated mechanism. Whether these therapeutic effects of gonadal steroids encompass neuroprotection from axotomy-induced cell death is the focus of the present study. Virtually 100% of adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo substantial axotomy-induced cell death. The first part of the present study focuses on determining when ARs are first expressed in developing hamster FMNs. Using AR immunocytochemistry, it was found that males express ARs by P2 and females by P4, which is the earliest demonstration of AR expression in mammalian motoneurons reported thus far in the literature. The second half examines the neuroprotective effects of testosterone propionate, 17-beta estradiol, and dihydrotestosterone on FMNs of P7 hamsters after facial nerve transection at the SMF. The results demonstrate that androgens and estrogens are equally able to rescue similar to 20% of FMNs from axotomy-induced cell death, with the effects permanent. This study is the first to investigate the effects of both androgens and estrogens on axotomy-induced cell death in one system and, with our previously published work, to validate the hamster FMN injury paradigm as a model of choice in the investigation of both neurotherapeutic and neuroprotective actions of gonadal steroids. C1 Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. RP Jones, KJ (reprint author), Loyola Univ, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, 5th Floor,2160 S 1st Ave, Maywood, IL 60153 USA. EM kjones1@lumc.edu FU NIMH NIH HHS [MH48794, MH62588]; NINDS NIH HHS [NS-28238] NR 80 TC 42 Z9 42 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 20 PY 2005 VL 25 IS 16 BP 4004 EP 4013 DI 10.1523/JNEUROSCI.5279-04.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 918LF UT WOS:000228542600002 PM 15843602 ER PT J AU Kurth, T Gaziano, JM Rexrode, KM Kase, CS Cook, NR Manson, JE Buring, JE AF Kurth, T Gaziano, JM Rexrode, KM Kase, CS Cook, NR Manson, JE Buring, JE TI Prospective study of body mass index and risk of stroke in apparently healthy women SO CIRCULATION LA English DT Article DE obesity; stroke; epidemiology; women ID C-REACTIVE PROTEIN; HONOLULU-HEART-PROGRAM; ACUTE ISCHEMIC-STROKE; FAT DISTRIBUTION; CARDIOVASCULAR-DISEASE; THROMBOEMBOLIC STROKE; PHYSICAL-ACTIVITY; ADIPOSE-TISSUE; BLOOD-PRESSURE; UNITED-STATES AB Background-Obesity is an escalating pandemic in the United States, and its association with coronary heart disease is well understood. Several studies have found positive associations between body mass index (BMI) and stroke in men, but the association with stroke and its subtypes is less clear in women. Methods and Results-This was a prospective cohort study among 39 053 women participating in the Women's Health Study. BMI was measured as self-reported weight ( in kilograms) divided by height (in meters) squared. Incident stroke was self-reported and confirmed by medical record review. We used the Cox proportional hazards model to evaluate the association between BMI and stroke. After a mean follow-up of 10 years, a total of 432 strokes ( 347 ischemic, 81 hemorrhagic, and 4 undefined) occurred. We found a statistically significant trend for increased risk of total and ischemic stroke across 7 BMI categories. With World Health Organization criteria, women who were obese (BMI >= 30 kg/m(2)) had hazard ratios of 1.50 (95% CI 1.16 to 1.94) for total stroke, 1.72 (95% CI 1.30 to 2.28) for ischemic stroke, and 0.82 (95% CI 0.43 to 1.58) for hemorrhagic stroke compared with women with BMI <25 kg/m(2). Additional control for history of hypertension, diabetes, and elevated cholesterol substantially attenuated the hazard ratios for total and ischemic stroke. There was no effect modification for age, exercise, or smoking. Conclusions-In this large prospective cohort study among women, BMI was a strong risk factor for total and ischemic stroke but not for hemorrhagic stroke. The association was highly mediated by hypertension, diabetes, and elevated cholesterol. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Aging, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Cardiovasc Dis, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. RP Kurth, T (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012; OI Kurth, Tobias/0000-0001-7169-2620; Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-43851] NR 49 TC 119 Z9 127 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 19 PY 2005 VL 111 IS 15 BP 1992 EP 1998 DI 10.1161/01.CIR.0000161822.83163.B6 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 917KS UT WOS:000228461000020 PM 15837954 ER PT J AU Koreth, J van den Heuvel, S AF Koreth, J van den Heuvel, S TI Cell-cycle control in Caenorhabditis elegans: how the worm moves from G1 to S SO ONCOGENE LA English DT Review DE C. elegans cell cycle; G1-S; cyclin D; Cdk4/6; lin-35 Rb; cki-1; Cip/Kip ID DEPENDENT KINASE INHIBITOR; C-ELEGANS; VULVAL DEVELOPMENT; SACCHAROMYCES-CEREVISIAE; DEVELOPMENTAL REGULATION; PHOSPHATASE CDC14; CDK INHIBITORS; LIN-35 RB; PROGRESSION; NEMATODE AB The nematode Caenorhabditis elegans offers a powerful model system to study cell division control during animal development. Progress from the one- cell zygote to adult stage follows a nearly invariant pattern of divisions. This, combined with a transparent body and efficient genetics, allows for sensitive identification and quantitative analysis of cell- cycle mutants. Nearly all G1 control genes identified in C. elegans have mammalian homologs. Examples include a D- type cyclin and CDK4/ 6- related kinase, a member of the retinoblastoma protein family and CDK inhibitors of the Cip/ Kip family. Genetic studies have placed the currently known G1 regulators into pathways similar to those in mammals. Together, this validates the use of C. elegans in identifying additional regulators of cell- cycle entry and exit. For instance, we recently found that the CDC- 14 phosphatase promotes maintenance of the quiescent state. Here, we describe cell-cycle control as an integral part of C. elegans development, summarize current knowledge of G1 control genes in the worm, compare the results with those obtained in other species, and discuss the possible implications of cellcycle studies in C. elegans for higher organisms, including humans. C1 Harvard Univ, Sch Med, MGH Canc Ctr, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP van den Heuvel, S (reprint author), Harvard Univ, Sch Med, MGH Canc Ctr, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI van den Heuvel, Sander/B-8892-2011 NR 55 TC 21 Z9 22 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2005 VL 24 IS 17 BP 2756 EP 2764 DI 10.1038/sj.onc.1208607 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 917MI UT WOS:000228465800002 PM 15838512 ER PT J AU Dimova, DK Dyson, NJ AF Dimova, DK Dyson, NJ TI The E2F transcriptional network: old acquaintances with new faces SO ONCOGENE LA English DT Review DE E2F; cell cycle; transcriptional network ID S-PHASE ENTRY; CYCLIN-DEPENDENT KINASES; RETINOBLASTOMA TUMOR-SUPPRESSOR; ANAPHASE-PROMOTING COMPLEX; SQUAMOUS-CELL CARCINOMA; DNA-REPLICATION; C/EBP-ALPHA; TARGET GENES; IN-VIVO; DEREGULATED EXPRESSION AB The E2 factor ( E2F) family of transcription factors are downstream targets of the retinoblastoma protein. E2F factors have been known for several years to be important regulators of S- phase entry. Recent studies have improved our understanding of the molecular mechanisms of action used by this transcriptional network. In addition, they have given us an appreciation of the fact that E2F has functions that reach beyond G1/ S control and impact cell proliferation in several different ways. The discovery of new family members with unusual properties, the unexpected phenotypes of mutant animals, a diverse collection of biological activities, a large number of new putative target genes and the new modes of transcriptional regulation have all contributed to an increasingly complex view of E2F function. In this review, we will discuss these recent developments and describe how they are beginning to shape a new and revised picture of the E2F transcriptional program. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM dyson@hekix.mgh.harvard.edu FU NCI NIH HHS [CA64402]; NIGMS NIH HHS [GM53203] NR 220 TC 414 Z9 425 U1 3 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2005 VL 24 IS 17 BP 2810 EP 2826 DI 10.1038/sj.onc.1208612 PG 17 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 917MI UT WOS:000228465800007 PM 15838517 ER PT J AU Ciemerych, MA Sicinski, P AF Ciemerych, MA Sicinski, P TI Cell cycle in mouse development SO ONCOGENE LA English DT Review DE mouse embryo; development; cell cycle ID DEPENDENT KINASE INHIBITOR; BECKWITH-WIEDEMANN-SYNDROME; RETINOBLASTOMA GENE FAMILY; CENTRAL-NERVOUS-SYSTEM; SKIN TUMOR-DEVELOPMENT; RB-DEFICIENT CELLS; RNA-POLYMERASE-II; B-TYPE CYCLIN; MICE LACKING; S-PHASE AB Mice likely represent the most- studied mammalian organism, except for humans. Genetic engineering in embryonic stem cells has allowed derivation of mouse strains lacking particular cell cycle proteins. Analyses of these mutant mice, and cells derived from them, facilitated the studies of the functions of cell cycle apparatus at the organismal and cellular levels. In this review, we give some background about the cell cycle progression during mouse development. We next discuss some insights about in vivo functions of the cell cycle proteins, gleaned from mouse knockout experiments. Our text is meant to provide examples of the recent experiments, rather than to supply an extensive and complete list. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Warsaw, Fac Biol, Inst Zool, Dept Embryol, PL-02096 Warsaw, Poland. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA085296] NR 290 TC 83 Z9 85 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2005 VL 24 IS 17 BP 2877 EP 2898 DI 10.1038/sj.onc.1208608 PG 22 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 917MI UT WOS:000228465800012 PM 15838522 ER PT J AU Deshpande, A Sicinski, P Hinds, PW AF Deshpande, A Sicinski, P Hinds, PW TI Cyclins and cdks in development and cancer: a perspective SO ONCOGENE LA English DT Review DE cell cycle; cancer; development; cyclin; cdk; retinoblastoma; knockout ID HUMAN BREAST-CANCER; SQUAMOUS-CELL CARCINOMA; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; TRANSCRIPTION FACTOR; GENE AMPLIFICATION; CHROMOSOME SEGREGATION; ANDROGEN RECEPTOR; ESTROGEN-RECEPTOR; D1 AB A fundamental aspect of cancer is dysregulated cell cycle control. Unlike normal cells that only proliferate when compelled to do so by developmental or other mitogenic signals in response to tissue growth needs, the proliferation of cancer cells proceeds essentially unchecked. This does not mean that cancer cell cycles are necessarily different from those found in normal cycling cells, but rather implies that cancer cells proliferate because they are no longer subject to proliferation- inhibitory influences arising from the stroma or from gene expression pattern changes consequent to 'terminal' differentiation, nor do they necessarily require extrinsic growth factors to recruit them into or maintain their proliferative state. Finally, cancer cells have also often avoided normal controls linked to cell cycle progression that halt proliferation in the presence of damaged DNA or other physiological insults. The result of these alterations is the inappropriate proliferation commonly associated with cancerous tumor formation. This review will summarize the current understanding of dysregulation of the G0/ G1- to- S- phase transition in cancer cells, with particular emphasis on recent in vivo studies that suggest a need to rethink existing models of cell cycle control in development and tumorigenesis. C1 Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Dept Radiat Oncol, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hinds, PW (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Dept Radiat Oncol, Boston, MA 02111 USA. EM phinds@tufts-nemc.org FU NCI NIH HHS [CA085296, CA096527]; NIA NIH HHS [AG20208]; NIDCR NIH HHS [DE015302] NR 101 TC 178 Z9 198 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2005 VL 24 IS 17 BP 2909 EP 2915 DI 10.1038/sj.onc.1208618 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 917MI UT WOS:000228465800014 PM 15838524 ER PT J AU Januzzi, JL Camargo, CA Anwaruddin, S Baggish, AL Chen, AA Krauser, DG Tung, R Cameron, R Nagurney, JT Chae, CU Lloyd-Jones, DM Brown, DF Foran-Melanson, S Sluss, PM Lee-Lewandrowski, EL Lewandrowski, KB AF Januzzi, JL Camargo, CA Anwaruddin, S Baggish, AL Chen, AA Krauser, DG Tung, R Cameron, R Nagurney, JT Chae, CU Lloyd-Jones, DM Brown, DF Foran-Melanson, S Sluss, PM Lee-Lewandrowski, EL Lewandrowski, KB TI The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BRAIN NATRIURETIC PEPTIDE; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; GENERAL-POPULATION; SYSTOLIC FUNCTION; LARGE-SAMPLE; DIAGNOSIS; DISEASE; UTILITY; ASSAY AB The utility of aminoterminal pro-brain natriuretic pepticle (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p < 0.001). NT-proBNP at cutpoints of > 450 pg/ml for pallients < 50 years of age and > 900 pg/ml for patients 50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p < 0.001). An NT-proBNP level < 300 pg/ml was optimal for ruling out acute CHF, With a negative predictive value of. 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF(odds ratio 44, 95% confidence interval 21.0 to 91.0, p < 0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHIF in the emergency department setting. (c) 2005 by Excerpta Medica Inc. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Clin Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Yawkey 5800,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Lloyd-Jones, Donald/C-5899-2009 NR 24 TC 559 Z9 602 U1 1 U2 15 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2005 VL 95 IS 8 BP 948 EP 954 DI 10.1016/j.amjcard.2004.12.032 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 915WX UT WOS:000228343200005 PM 15820160 ER PT J AU Zahid, M Sonel, AF Kelley, ME Wall, L Whittle, J Fine, MJ Good, CB AF Zahid, M Sonel, AF Kelley, ME Wall, L Whittle, J Fine, MJ Good, CB TI Effect of both elevated troponin-I and peripheral white blood cell count on prognosis in patients with suspected myocardial injury SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; UNSTABLE ANGINA; TISSUE FACTOR; MORTALITY; ASSOCIATION; INFARCTION; REVASCULARIZATION; EXPRESSION; MONOCYTES AB We found a high white blood cell count (> 11,000/mu l) to be of additive prognostic value to high troponin-l levels in predicting risk of recurrent nonfatal myocardial infarctions and all-cause mortality in patients who present with acute coronary syndromes and non-ST-elevation myocardial infarctions. A high troponin-I level or white blood cell count increased the odds ratio of an event to 2.2 (95% confidence interval 1.0 to 4.73, p = 0.05), but high values for the 2 markers increased the odds ratio to 4.5 (95% confidence interval 1.42 to 14.21, p = 0.01). (c) 2005 by Excerpta Medica Inc. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Cardiovasc Inst, Pittsburgh, PA 15260 USA. Univ Kansas, Kansas City, MO USA. RP Zahid, M (reprint author), 111C-U Univ Dr, Pittsburgh, PA 15240 USA. EM ali.sonel@med.va.gov NR 14 TC 4 Z9 4 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2005 VL 95 IS 8 BP 970 EP 972 DI 10.1016/j.amjcard.2004.12.037 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 915WX UT WOS:000228343200010 PM 15820165 ER PT J AU Vaturi, M Levine, RA Yosefy, C O'Neil, MJ Picard, MH Hung, J AF Vaturi, M Levine, RA Yosefy, C O'Neil, MJ Picard, MH Hung, J TI Usefulness of left atrial emptying fraction to predict exercise capacity in patients with normal systolic left ventricular function and without myocardial ischemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK; ECHOCARDIOGRAPHY; REHABILITATION; SURVIVAL; DISEASE; VOLUME; SIZE AB The association of left atrial volume at rest and the left atrial emptying fraction with exercise capacity during stress echocardiography was examined in patients with normal left ventricular function and without ischemia. The left atrial emptying fraction, along with body mass index, was found to be an independent predictor of poor exercise capacity (< 5 METs). (c) 2005 by Excerpta Medica Inc. C1 Massachusetts Gen Hosp, Dept Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Vaturi, M (reprint author), Massachusetts Gen Hosp, Dept Cardiol, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 19 TC 7 Z9 14 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2005 VL 95 IS 8 BP 1014 EP 1017 DI 10.1016/j.amjcard.2004.12.053 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 915WX UT WOS:000228343200026 PM 15820181 ER PT J AU Navratilova, I Sodroski, J Myszka, DG AF Navratilova, I Sodroski, J Myszka, DG TI Solubilization, stabilization, and purification of chemokine receptors using biosensor technology SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE biacore; surface plasmon resonance; GPCR; membrane receptor; HIV ID SMALL-MOLECULE; HIV-1 GP120; CCR5; BINDING; PROTEIN; CORECEPTOR; EXPRESSION; DISTINCT; ENTRY; ASSAY AB Establishing solubilization conditions for membrane-associated receptors is often a tedious empirical process. Here we describe a novel application of SPR biosensor technology to screen solubilization conditions automatically and to assess receptor activity directly. We focus On two chemokine receptors, CXCR4 and CCR5, which are important in HIV cell invasion. The autosampler in Biacore 3000 permitted whole cells expressing C-terminally tagged receptors to be automatically lysed Under a given solubilization condition and the Mates to be injected over an antibody surface. The total amount of solubilized receptor could be quantitated from the antibody capture level, whereas the amount of active receptor could be quantitated Using a subsequent injection of conformationally sensitive antibody or protein. Using this approach, we identified detergent/lipid/buffer combinations that enhanced and maintained receptor activity. We also used the biosensor to demonstrate CD4-dependent binding of gp120 to solubilized CCR5 and to develop affinity chromatography-based purification methods that increased receptor activity more than 300%. Together, these results illustrate the benefits Of using, the biosensor as a tool for isolating functional membrane receptors and for analyzing ligand receptor interactions. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. RP Myszka, DG (reprint author), Univ Utah, Sch Med, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. EM dmyszka@cores.utah.edu FU NIAID NIH HHS [P30 AI28691]; NIGMS NIH HHS [P01 GM66521] NR 18 TC 71 Z9 71 U1 2 U2 19 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 15 PY 2005 VL 339 IS 2 BP 271 EP 281 DI 10.1016/j.ab.2004.12.017 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 913YX UT WOS:000228192700011 PM 15797568 ER PT J AU Spiegel, BMR Chiou, CF Ofman, JJ AF Spiegel, BMR Chiou, CF Ofman, JJ TI Minimizing complications from nonsteroidal antiinflammatory drugs: Cost-effectiveness of competing strategies in varying risk groups SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE cost-effectiveness; nonsteroidal antiinflammatory drugs; cox-2 inhibitors; proton pump inhibitors ID RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE ASPIRIN; RHEUMATOID-ARTHRITIS; PEPTIC-ULCER; DOUBLE-BLIND; HELICOBACTER-PYLORI; CYCLOOXYGENASE-2 INHIBITOR; GASTROINTESTINAL ENDOSCOPY; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION AB Objective. To appraise the cost-effectiveness of competing therapeutic strategies in patient cohorts eligible for aspirin prophylaxis with varying degrees of gastrointestinal (GI) and cardiovascular risk. Methods. Cost-effectiveness and cost-utility analyses were performed to evaluate 3 competing strategies for the management of chronic arthritis: 1) a generic nonselective nonsteroidal antiinflammatory drug (NSAID(NS)) alone; 2) NSAID(NS) plus a proton pump inhibitor (PPI); and 3) a cyclooxygenase 2-selective inhibitor (coxib) alone. Cost estimates were from a third-party payer perspective. The outcomes were incremental cost per ulcer complication avoided and incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analysis was performed to evaluate the impact of varying patient GI risks and aspirin use. Results. In average-risk patients, the NSAID(NS) + PPI strategy costs an incremental $45,350 per additional ulcer complication avoided and $309,666 per QALY gained compared with the NSAID(NS) strategy. The coxib strategy was less effective and more expensive than the NSAID(NS) + PPI strategy. Sensitivity analysis revealed that the NSAID(NS) + PPI strategy became the dominant approach in patients at high risk for an NSAID adverse event (i.e., patients taking aspirin with >= 1 risk factor for a GI complication). Conclusion. Generic nonselective NSAIDs are most cost-effective in patients at low risk for an adverse event. However, the addition of a PPI to a nonselective NSAID may be the preferred strategy in patients taking aspirin or otherwise at high risk for a GI or cardiovascular adverse event. C1 Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, 11301 Wilshire Blvd,Bldg 115 Room 215E, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 73 TC 45 Z9 47 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2005 VL 53 IS 2 BP 185 EP 197 DI 10.1002/art.21065 PG 13 WC Rheumatology SC Rheumatology GA 916CK UT WOS:000228362800006 PM 15818647 ER PT J AU Su, FX Ouyang, NY Zhu, PC Ouyang, NT Jia, WJ Gong, C Ma, XX Xu, HB Song, EW AF Su, FX Ouyang, NY Zhu, PC Ouyang, NT Jia, WJ Gong, C Ma, XX Xu, HB Song, EW TI Psychological stress induces chemoresistance in breast cancer by upregulating mdr1 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE psychological stress; restraint stress; breast cancer; chemotherapy; multi-drug resistance; adrenaline; RNA interference ID RESTRAINT STRESS; INDUCED MIGRATION; GENE-EXPRESSION; CARCINOMA CELLS; TUMOR-GROWTH; CHEMOTHERAPY; MODEL; NEUROTRANSMITTERS; ADENOCARCINOMAS; ISOPROTERENOL AB Psychological distress reduces the efficacy of chemotherapy in breast cancer patients. The mechanism may be related to the altered neuronal or hormonal secretions during stress. Here, we reported that adrenaline, a hormone mediating the biological activities of stress, upregulates mdr1 gene expression in MCF-7 breast cancer cells via alpha(2)-adrenerdric receptors in a dose-dependent manner. Mdr1 upregulation can be specifically inhibited by pretreatment with mdr1-siRNA. Consequently, adrenergic stimulation enhances the pump function of P-glycoprotein and confers resistance of MCF-7 cells to paclitaxel. In vivo, restraint stress increases mdr1 gene expression in the MCF-7 cancers that are inoculated subcutaneously into the SCID mice and provokes resistance to doxorubicin in the implanted tumors. The effect can be blocked by injection of yohimbine, an alpha(2)-adrenergic inhibitor, but not by metyrapone, a corticosterone synthesis blocker. Therefore, we conclude that breast cancers may develop resistance against chemotherapeutic drugs under psychological distress by over-expressing mdr1 via adrenergic stimulation. (c) 2005 Elsevier Inc. All rights reserved. C1 Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Breast Surg, Guangzhou 510120, Peoples R China. Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Gynecol, Guangzhou 510120, Peoples R China. Fudan Univ, Inst Genet, Shanghai 200433, Peoples R China. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Guangzhou Med Inst, Dept Pathol, Guangzhou 510120, Peoples R China. RP Song, EW (reprint author), Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Breast Surg, Guangzhou 510120, Peoples R China. EM songerwei02@yahoo.com.cn NR 35 TC 35 Z9 36 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 15 PY 2005 VL 329 IS 3 BP 888 EP 897 DI 10.1016/j.bbrc.2005.02.056 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 909UI UT WOS:000227885800013 PM 15752739 ER PT J AU Inada, A Weir, GC Bonner-Weir, S AF Inada, A Weir, GC Bonner-Weir, S TI Induced ICER I gamma down-regulates cyclin A expression and cell proliferation in insulin-producing beta cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cyclic AMP-responsive element; ICER; cyclin A ID TRANSCRIPTION FACTOR ATF; AMP RESPONSE ELEMENT; GENE-TRANSCRIPTION; MAMMALIAN-CELLS; EARLY REPRESSOR; PROMOTER; CREM; BINDING; OVEREXPRESSION; ACTIVATION AB We have previously found that cyclin A expression is markedly reduced in pancreatic beta-cells by cell-specific overexpression of repressor inducible cyclic AMP early repressor (ICER I gamma) in transgenic mice. Here we further examined regulatory effects of ICER I gamma on cyclin A gene expression using Min6 cells, an insulin-producing cell line. The cyclin A promoter luciferase assay showed that ICER I gamma directly repressed cyclin A gene transcription. In addition, upon ICER I gamma overexpression, cyclin A mRNA levels markedly decreased, thereby confirming an inhibitory effect of ICER I gamma on cyclin A expression. Suppression of cyclin A results in inhibition of BrdU incorporation. Under normal culture conditions endogenous cyclin A is abundant in these cells, whereas ICER is hardly detectable. However, serum starvation of Min6 cells induces ICER I gamma expression with a concomitant very low expression level of cyclin A. Cyclin A protein is not expressed unless the cells are in active DNA replication. These results indicate a potentially important anti-proliferative effect of ICER I gamma in pancreatic beta cells. Since ICER I gamma is greatly increased in diabetes as well as in FFA- or high glucose-treated islets, this effect may in part exacerbate diabetes by limiting beta-cell proliferation. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. EM susan.bonner-weir@joslin.harvard.edu FU NIDDK NIH HHS [DK 36836, DK 44523] NR 34 TC 16 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 15 PY 2005 VL 329 IS 3 BP 925 EP 929 DI 10.1016/j.bbrc.2005.02.046 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 909UI UT WOS:000227885800018 PM 15752744 ER PT J AU Moore, CM Biederman, J Renshaw, PF AF Moore, CM Biederman, J Renshaw, PF TI Bipolar Disorder plus ADHD versus ADHD: A proton magnetic resonance study (MRS) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Harvard Univ, McLean Hosp, Sch Med, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 30 BP 9S EP 10S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600032 ER PT J AU Cannistraro, PA Makris, N Howard, JD Wedig, MM Hodge, SM Wilhelm, S Rauch, SL AF Cannistraro, PA Makris, N Howard, JD Wedig, MM Hodge, SM Wilhelm, S Rauch, SL TI A diffusion tensor imaging study of white matter tracts in obsessive compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 33 BP 10S EP 10S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600035 ER PT J AU Shenton, ME Salisbury, DF Kasai, K Kubicki, M Park, HJ McCarley, RW AF Shenton, ME Salisbury, DF Kasai, K Kubicki, M Park, HJ McCarley, RW TI In vivo neuroimaging data in support of auditory processing abnormalities in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Brockton, MA 02401 USA. VA Boston Healthcare Syst, HMS, Dept Psychiat 116A, Brockton, MA USA. McLean Hosp, HMS, Dept Psychiat, Brockton, MA USA. Univ Tokyo, Dept Psychiat, Tokyo, Japan. Yonsei Univ, Dept Radiol, Seoul 120749, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 66 BP 18S EP 19S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600068 ER PT J AU Trivedi, MH Gharabawi, GM Canuso, CM Bossie, CA Turkoz, I Fava, M AF Trivedi, MH Gharabawi, GM Canuso, CM Bossie, CA Turkoz, I Fava, M TI Predictors of symptom resolution with risperidone augmentation in patients with resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, SW Med Ctr, Dallas, TX USA. Janssen Med Affairs LLC, Med Affairs, Titusville, NJ USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 99 BP 28S EP 28S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600101 ER PT J AU Wedig, MM Rauch, SL Albert, MS Wright, CI AF Wedig, MM Rauch, SL Albert, MS Wright, CI TI Differential amygdala habituation to neutral faces in healthy young and elderly adults SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gerontol Res Unit, Charlestown, MA USA. Brigham & Womens Hosp, Dept Neurol, Brigham Behav Neurol 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 130 BP 37S EP 38S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600132 ER PT J AU Biederman, J Faraone, SV AF Biederman, J Faraone, SV TI The economic impact of adult ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Upstate Med Univ, Syracuse, NY USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 147 BP 42S EP 42S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600149 ER PT J AU Biederman, J Mick, E Harpold, T Hammerness, P Aleardi, M Dougherty, M Menard, C AF Biederman, J Mick, E Harpold, T Hammerness, P Aleardi, M Dougherty, M Menard, C TI Treatment of preschoolers with pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 146 BP 42S EP 42S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600148 ER PT J AU Short, EB Kose, S Newberg, A George, MS Kozel, FA AF Short, EB Kose, S Newberg, A George, MS Kozel, FA TI FMRI investigation of meditation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Univ Penn, Med Ctr, Div Nucl Med, Philadelphia, PA 19104 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. RI Kozel, Frank/I-5366-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 157 BP 45S EP 45S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600159 ER PT J AU Biederman, J Mick, E AF Biederman, J Mick, E TI Treatment of psychotic symptoms in children and adolescents with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 163 BP 47S EP 47S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600165 ER PT J AU Nery, FG Borba, EF Soares, JC Bonfa, E Neto, FL AF Nery, FG Borba, EF Soares, JC Bonfa, E Neto, FL TI Associations of depressive disorder, psychosocial stress and disease activity in systemic lupus erythematosus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div mood & Anxiety Disorders, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, Psychiat, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Internal Med, Div Rheumatol, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 198 BP 56S EP 56S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600198 ER PT J AU Nery, FG Borba, EF Soares, JC Bonfa, E Neto, FL AF Nery, FG Borba, EF Soares, JC Bonfa, E Neto, FL TI Prevalence of psychiatric manifestations in patients with systemic lupus erythematosus and association with anti-ribosomal P autoantibodies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Internal Med, Div Rheumatol, Sao Paulo, Brazil. S Texas Vet Hlth Care Syst, Psychiat, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 199 BP 56S EP 56S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600199 ER PT J AU Radant, AD Olincy, A Calkins, ME Dobie, DJ Meichle, S Tsuang, DW David, AC AF Radant, AD Olincy, A Calkins, ME Dobie, DJ Meichle, S Tsuang, DW David, AC TI Saccadic latencies are related to diagnosis and overall antisaccade task performance: Analysis of antisaccade data from the consortium on the genetics of schizophrenia (COGS) data set SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, NW Network Mental Illness res Educ & Clin Ctr VIS, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO USA. Univ Penn, Sch Med, Schizophrenia Res Ctr, Neuropsychiat Sect, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 243 BP 68S EP 68S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600242 ER PT J AU Miguel, EC Hounie, AG Rosario-Campos, MC Mercadante, MT Mathis, A Mathis, ME Alvarenga, PG Shavitt, RG Curi, M Guilherme, L Pauls, DL AF Miguel, EC Hounie, AG Rosario-Campos, MC Mercadante, MT Mathis, A Mathis, ME Alvarenga, PG Shavitt, RG Curi, M Guilherme, L Pauls, DL TI Obsessive-compulsive spectrum disorders and rheumatic fever: A family study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Sao Paulo, Sch Med, Inst Immunol Invest, InCor, Sao Paulo, Brazil. Univ Fed Bahia, Dept Neuropsychiat, Sao Paulo, Brazil. Univ Presbyterian Univ, Pervas Dev Disorders Program, Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA USA. RI Guglielmi, Luiza/E-7676-2013; Curi, Mariana/E-8468-2011; do Rosario, Maria Conceicao/E-5213-2012 OI do Rosario, Maria Conceicao/0000-0002-9687-0072 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 259 BP 72S EP 72S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600257 ER PT J AU Brody, A Mandelkern, MA London, ED Olmestead, R Scheibal, D Jou, J Allen, V Tiongson, N Chefer, S Mukhin, A AF Brody, A Mandelkern, MA London, ED Olmestead, R Scheibal, D Jou, J Allen, V Tiongson, N Chefer, S Mukhin, A TI Effect of variable levels of cigarette smoking on nicotinic acetylcholine receptor availability during early smoking abstinence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Psychiat, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Nucl Med, Los Angeles, CA USA. Univ Calif Irvine, Irvine, CA USA. NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 357 BP 98S EP 98S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600349 ER PT J AU Iosifescu, DV Greenwald, SD Devlin, P Alpert, JE Hamill, SK Fava, M AF Iosifescu, DV Greenwald, SD Devlin, P Alpert, JE Hamill, SK Fava, M TI Frontal EEG predicts treatment response in MDD irrespective of clinical subtypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Aspect Med Syst Inc, Div Neurosci, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 360 BP 99S EP 99S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600352 ER PT J AU Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Sullivan, LK Hamner, MB Bohning, DE Arana, GW George, MS AF Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Sullivan, LK Hamner, MB Bohning, DE Arana, GW George, MS TI Regional brain activity in mothers and fathers listening to infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Clin, Charleston, SC USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. NICHHD, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 369 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600361 ER PT J AU Kose, S Lorberbaum, JP Johnson, MR Arana, GW Sullivan, LK Hamner, MB Ballenger, JC Lydiard, RB Brodrick, PS Bohning, DE George, MS AF Kose, S Lorberbaum, JP Johnson, MR Arana, GW Sullivan, LK Hamner, MB Ballenger, JC Lydiard, RB Brodrick, PS Bohning, DE George, MS TI The functional neuroanatomy of speech anticipatory anxiety in generalized social phobia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Clin, Charleston, SC 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 368 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600360 ER PT J AU Najib, A Lorberbaum, JP Kose, S Bohning, DE George, MS AF Najib, A Lorberbaum, JP Kose, S Bohning, DE George, MS TI Regional brain activity in women grieving the loss of a romantic relationship SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Univ Tubingen, Med Ctr, Sch Med, Tubingen, Germany. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 370 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600362 ER PT J AU Biederman, J Spencer, T Surman, C Aleardi, M Dougherty, M Schweitzer, K Mick, E AF Biederman, J Spencer, T Surman, C Aleardi, M Dougherty, M Schweitzer, K Mick, E TI Open-label study of OROS methylphenidate in the treatment of adults with ADHD - Not otherwise specified (NOS) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 384 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600375 ER PT J AU Biederman, J Spencer, T Surman, C Mick, E Dunkel, S Dougherty, M Aleardi, M AF Biederman, J Spencer, T Surman, C Mick, E Dunkel, S Dougherty, M Aleardi, M TI A double-blind placebo-controlled randomized study of OROS methylphenidate in the treatment of adults with attention deficit hyperactivity disorder (ADHD): An interim analysis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 385 BP 106S EP 106S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600376 ER PT J AU Biederman, J Harpold, T Hammerness, P Mick, E Dougherty, M Aleardi, M Randall, E AF Biederman, J Harpold, T Hammerness, P Mick, E Dougherty, M Aleardi, M Randall, E TI An open-label study of ziprasidone in children with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 386 BP 106S EP 107S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600377 ER PT J AU Biederman, J Faraone, SV Mick, E AF Biederman, J Faraone, SV Mick, E TI A 10-year follow-up study of males with ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Upstate Med Univ, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 388 BP 107S EP 107S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600379 ER PT J AU Biederman, J Faraone, SV Mick, E AF Biederman, J Faraone, SV Mick, E TI Females with ADHD: A 5-year follow-up study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Upstate Med Univ, Syracuse, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 387 BP 107S EP 107S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600378 ER PT J AU Biederman, J Mick, E AF Biederman, J Mick, E TI Effectiveness of risperidone for the treatment of ADHD in children and adolescents with BPD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Boston, MA 02114 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 391 BP 108S EP 108S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600382 ER PT J AU Dougherty, DD Bonab, A Ottowitz, WE Livni, E Alpert, NM Rauch, SL Fischman, AJ Fava, M AF Dougherty, DD Bonab, A Ottowitz, WE Livni, E Alpert, NM Rauch, SL Fischman, AJ Fava, M TI Decreased striatal D1 binding as measured using PET and [11C]SCH 23,390 in patients with major depression with anger attacks SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 410 BP 112S EP 113S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601008 ER PT J AU Milad, MR Fischl, B Pitman, RK Orr, SP Quinn, BT Rauch, SL AF Milad, MR Fischl, B Pitman, RK Orr, SP Quinn, BT Rauch, SL TI Thickness of ventromedial prefrontal cortex in humans predicts the magnitude of extinction memory SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Nucl Magnet Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Ctr Vet Med, Dept Vet Affairs, Manchester, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 428 BP 117S EP 117S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601026 ER PT J AU Dracheva, S Chin, B Woo, DA Davis, KL Gorman, JM Haroutunian, V AF Dracheva, S Chin, B Woo, DA Davis, KL Gorman, JM Haroutunian, V TI Differential expression of myelin-related genes in schizophrenic brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 443 BP 121S EP 121S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601041 ER PT J AU Kozel, FA Nahas, Z Ramsey, D Molnar, C Johnson, K Grenesko, E Kose, S George, MS AF Kozel, FA Nahas, Z Ramsey, D Molnar, C Johnson, K Grenesko, E Kose, S George, MS TI Measuring scalp to cortex distances in order to adjust TMS stimulation parameters SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 MUSC, Ctr Adv Imaging Res, Charleston, SC USA. Ralph H Johnson VA Med Ctr, Ctr Adv Imaging Res, Mental Hlth Serv, Charleston, SC USA. S Carolina Res Author, Bioinformat Res, Charleston, SC USA. RI Kozel, Frank/I-5366-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 442 BP 121S EP 121S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601040 ER PT J AU Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Masood, A Licinio, J Gold, HK Chrousos, GP Gold, PW Kling, MA AF Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Masood, A Licinio, J Gold, HK Chrousos, GP Gold, PW Kling, MA TI Major depression is associated with significant diurnal elevations in plasma IL-6 levels, a shift of its circadian rhythm, and loss of physiologic complexity in its secretion: Clinical implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Lab Pharmacogenom, Los Angeles, CA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RI Kling, Mitchel/F-4152-2010; Licinio, Julio/L-4244-2013 OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 454 BP 124S EP 124S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601052 ER PT J AU Fonseca, M Caetano, SC Kaur, S Nicoletti, M Olvera, RL Hunter, K Ortiz, O Hatch, JP Bowden, C Pliska, S Soares, JC AF Fonseca, M Caetano, SC Kaur, S Nicoletti, M Olvera, RL Hunter, K Ortiz, O Hatch, JP Bowden, C Pliska, S Soares, JC TI MRI study of the cingulate cortex in children and adolescents with bipolar disorder: A replication study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Psychiat Serv, San Antonio, TX USA. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 458 BP 125S EP 126S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601056 ER PT J AU Fonseca, M Soares, JC Hatch, JP Santin, AP Kapczinski, F AF Fonseca, M Soares, JC Hatch, JP Santin, AP Kapczinski, F TI An open trial of escitalopram in bipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Fed Rio Grande Sul, Psychiat Res Unit, Sch Med, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audies L Murphy Div, Psychiat Serv, San Antonio, TX USA. Univ Fed Rio Grande Sul, Sch Med, Clin Hosp Porto Alegre, Psychiat Serv, Porto Alegre, RS, Brazil. RI Cloninger, Claude/F-5357-2012; Kapczinski, Flavio/D-3175-2013; Caetano, Sheila/H-5010-2012; Kapczinski, Flavio/J-5803-2014 OI Cloninger, Claude/0000-0003-3096-4807; Caetano, Sheila/0000-0001-8403-7078; NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 459 BP 126S EP 126S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601057 ER PT J AU Fonseca, M Caetano, SC Olvera, RL Hatch, JP Hunter, K Nicoletti, M Pliszka, S Bowden, C Cloninger, CR Soares, JC AF Fonseca, M Caetano, SC Olvera, RL Hatch, JP Hunter, K Nicoletti, M Pliszka, S Bowden, C Cloninger, CR Soares, JC TI Assessment of personality traits in pediatric bipolar disorder using the junior temperament and character inventory SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care syst, Audie L Murphy Div, Psychiat Serv, San Antonio, TX USA. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Cloninger, Claude/F-5357-2012; Kapczinski, Flavio/D-3175-2013; Caetano, Sheila/H-5010-2012; Kapczinski, Flavio/J-5803-2014 OI Cloninger, Claude/0000-0003-3096-4807; Caetano, Sheila/0000-0001-8403-7078; NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 460 BP 126S EP 126S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601058 ER PT J AU Caetano, SC Olvera, RL Hunter, K Fonseca, M Hatch, JP Bowden, C Pliszka, S Soares, JC AF Caetano, SC Olvera, RL Hunter, K Fonseca, M Hatch, JP Bowden, C Pliszka, S Soares, JC TI Comorbid bipolar disorder and anxiety in pediatric patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Psychiat, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 463 BP 127S EP 127S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601061 ER PT J AU Najt, P Nicoletti, M Chen, HH Hatch, JP Sassi, R Axelson, D Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Najt, P Nicoletti, M Chen, HH Hatch, JP Sassi, R Axelson, D Brambilla, P Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Anatomical measurements of the orbitofrontal cortex in child and adolescent patients with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX 78284 USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 461 BP 127S EP 127S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601059 ER PT J AU Pekary, AE Sattin, A Stevens, SA AF Pekary, AE Sattin, A Stevens, SA TI Kinetics of TRH and TRH-LIKE peptide response to corticosterone in rat brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Ctr Ulcer Res & Educ, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 496 BP 136S EP 137S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601094 ER PT J AU Glahn, DC Beardene, CE Caetano, SC Fonseca, M Najt, P Hunter, K Pliszka, S Olvera, RL Soares, JC AF Glahn, DC Beardene, CE Caetano, SC Fonseca, M Najt, P Hunter, K Pliszka, S Olvera, RL Soares, JC TI Declarative memory impairment in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 UTHSCSA, Psychiat, San Antonio, TX USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 498 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601096 ER PT J AU Griffith, JM Gasper, JJ Waldo, M Nagamoto, HT Adler, LE AF Griffith, JM Gasper, JJ Waldo, M Nagamoto, HT Adler, LE TI Metabolic risks associated with typical and atypical antipsychotic medications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Denver VAMC, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 591 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601188 ER PT J AU Byne, WM Buchsbaum, MS Haroutunian, V AF Byne, WM Buchsbaum, MS Haroutunian, V TI The pulvinar in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 601 BP 165S EP 165S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601198 ER PT J AU Olincy, A Ellis, J Freedman, R AF Olincy, A Ellis, J Freedman, R TI The Consortium on the Genetics of Schizophrenia (COGS): Utility of the P50 auditory evoked potential to explore the genetics of schizophrenia in a multisite study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 657 BP 181S EP 181S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601254 ER PT J AU Nery, FG Hatch, JP Glahn, DC Nicoletti, M Monkul, S Najt, P Kaur, S Fonseca, M Bowden, C Cloninger, CR Soares, JC AF Nery, FG Hatch, JP Glahn, DC Nicoletti, M Monkul, S Najt, P Kaur, S Fonseca, M Bowden, C Cloninger, CR Soares, JC TI Personality traits in bipolar disorder with alcohol or anxiety co-morbidity SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 669 BP 184S EP 184S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601266 ER PT J AU Nery, FG Hatch, JP Glahn, DC Nicoletti, M Monkul, S Najt, P Kaur, S Fonseca, M Bowden, C Cloninger, CR Soares, JC AF Nery, FG Hatch, JP Glahn, DC Nicoletti, M Monkul, S Najt, P Kaur, S Fonseca, M Bowden, C Cloninger, CR Soares, JC TI Temperament and character in symptomatic bipolar patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RI Cloninger, Claude/F-5357-2012 OI Cloninger, Claude/0000-0003-3096-4807 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 668 BP 184S EP 184S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601265 ER PT J AU Bearden, CE Glahn, DC Monkul, S Barrette, J Najit, P Sanches, M Villarreal, V Bowden, C Soares, JC AF Bearden, CE Glahn, DC Monkul, S Barrette, J Najit, P Sanches, M Villarreal, V Bowden, C Soares, JC TI Sources of declarative memory impairment in bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 716 BP 197S EP 198S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601313 ER PT J AU Peluso, MAM Glahn, DC Monkul, S Najt, P Zamarripa, F Li, J Lancaster, J Fox, P Gao, JH Soares, JC AF Peluso, MAM Glahn, DC Monkul, S Najt, P Zamarripa, F Li, J Lancaster, J Fox, P Gao, JH Soares, JC TI Right amygdala hyperactivation in untreated depressed individuals SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 UTHSCSA, RIC, San Antonio, TX USA. Univ Sao Paulo, Sao Paulo, Brazil. Dokuz Eylul Univ, Sch Med, Izmir, Turkey. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RI Lancaster, Jack/F-2994-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 723 BP 199S EP 199S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601320 ER PT J AU Rauch, SL Wedig, MM Wright, CI Martis, B Cannistraro, PA McMullin, KG Wilhelm, S AF Rauch, SL Wedig, MM Wright, CI Martis, B Cannistraro, PA McMullin, KG Wilhelm, S TI Abnormalities in striatal and hippocampal activation during implicit sequence learning in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Massachusetts Gen Hosp, Psychiat Neuroimaging Res Program, Charlestown, MA USA. Brigham & Womens Hosp, Brigham Behav Neurol Grp, Boston, MA 02115 USA. VA Healthcare Syst, Dept Psychiat, Ann Arbor, MI USA. Univ Michigan, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 722 BP 199S EP 199S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601319 ER PT J AU Peluso, MAM Hatch, JP Glahn, D Monkul, S Sanches, M Najt, P Kaur, S Bowden, C Barratt, ES Soares, JC AF Peluso, MAM Hatch, JP Glahn, D Monkul, S Sanches, M Najt, P Kaur, S Bowden, C Barratt, ES Soares, JC TI Impulsivity and hostility in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 UTHSCSA, San Antonio, TX USA. Univ Sao Paulo, Sao Paulo, Brazil. Dokuz Eylul Univ, Sch Med, Izmir, Turkey. Univ Texas, Med Branch, Galveston, TX 77550 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 724 BP 200S EP 200S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601321 ER PT J AU Koenigsber, HW Siever, LJ Guo, XD New, AS Goodman, M Cheng, H Prohovnik, I AF Koenigsber, HW Siever, LJ Guo, XD New, AS Goodman, M Cheng, H Prohovnik, I TI Cerebral processing of negative emotion in borderline personality disorder: An fMRI perspective SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Affairs Med Ctr, Mirrec, Bronx, NY 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 731 BP 201S EP 202S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601328 ER PT J AU Solomon, BD Nicoletti, M Hatch, JP Monkul, S Villarreal, V Bowden, C Soares, JC AF Solomon, BD Nicoletti, M Hatch, JP Monkul, S Villarreal, V Bowden, C Soares, JC TI Anatomical examination of sub-genual prefrontal cortex in adult bipolar patients: A non-replication study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Sch Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Dokuz Eylul Univ, Sch Med, Izmir, Turkey. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 737 BP 203S EP 204S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601334 ER PT J AU Levitt, JJ Rosow, LK Connor, EE Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME AF Levitt, JJ Rosow, LK Connor, EE Ungar, LP Kuroki, N Kikinis, R Jolesz, FA McCarley, RW Shenton, ME TI The limbic striatum in schizophrenia: An MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, MRI Div, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 738 BP 204S EP 204S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601335 ER PT J AU Soares, JC Bearden, CE Dalwani, M Hayashi, KM Lee, AD Glahn, DC Nicoletti, M Trahkenbroit, M Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, D Thompson, PM AF Soares, JC Bearden, CE Dalwani, M Hayashi, KM Lee, AD Glahn, DC Nicoletti, M Trahkenbroit, M Brambilla, P Sassi, RB Mallinger, AG Frank, E Kupfer, D Thompson, PM TI Cortical gray matter abnormalities mapped in patients with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Lab Neuro Imaging, Los Angeles, CA 90024 USA. Univ Udine, Sect Psychiat, Dept Pathol, I-33100 Udine, Italy. Univ Udine, Sect Psychiat, Dept Expt & Clin Med, I-33100 Udine, Italy. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 747 BP 207S EP 207S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601344 ER PT J AU Kuperberg, GR AF Kuperberg, GR TI Making sense of nonsense: The cognitive neuroscience of language comprehension in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 759 BP 210S EP 210S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601356 ER PT J AU Ritz, J AF Ritz, J TI NK cell cytokine secretion regulated by SHIP1 SO BLOOD LA English DT Editorial Material ID NATURAL-KILLER-CELLS; DOSE RECOMBINANT INTERLEUKIN-2; PROLONGED INFUSION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3003 EP 3003 DI 10.1182/blood-2005-02-0445 PG 1 WC Hematology SC Hematology GA 915XK UT WOS:000228344500003 ER PT J AU Langenau, DM Jette, C Berghmans, S Palomero, T Kanki, JP Kutok, JL Look, AT AF Langenau, DM Jette, C Berghmans, S Palomero, T Kanki, JP Kutok, JL Look, AT TI Suppression of apoptosis by bcl-2 overexpression in lymphoid cells of transgenic zebrafish SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; C-MYC PROTEIN; IN-VIVO; CAENORHABDITIS-ELEGANS; BH3-ONLY PROTEINS; CYCLE PROGRESSION; DEFICIENT MICE; IMMUNE-SYSTEM; DANIO-RERIO; DEATH AB The zebrafish is an attractive vertebrate model for genetic studies of development, apoptosis, and cancer. Here we describe a transgenic zebrafish line in which T- and B-lymphold cells express a fusion transgene that encodes the zebrafish bcl-2 protein fused to the enhanced green fluorescence protein (EGFP). Targeting EGFP-bcl-2 to the developing thymocytes of transgenic fish resulted in a 2.5-fold increase in thymocyte numbers and a 1.8-fold increase in GFP-labeled B cells in the kidney marrow. Fluorescent microscopic analysis of living rag2-EGFP-bcl-2 transgenic fish showed that their thymocytes were resistant to irradiation- and dexamethasone-induced apoptosis, when compared with control rag2-GFP transgenic zebrafish. To test the ability of bcl-2 to block irradiation-induced apoptosis in malignant cells, we compared the responsiveness of Myc-induced leukemias with and without EGFP-bcl-2 expression in living transgenic zebrafish. T-cell leukemias induced by the rag2-EGFP-Myc transgene were ablated by irradiation, whereas leukemias in double transgenic fish expressing both Myc and EGFP-bcl-2 were resistant to irradiation-induced apoptotic cell death. The forward genetic capacity of the zebrafish model system and the ability to monitor GFP-positive thymocytes in vivo make this an ideal transgenic line for modifier screens designed to identify genetic mutations or small molecules that modify bcl-2-mediated antiapoptotic pathways. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Berghmans, Stephane/0000-0001-5414-8674 FU NCI NIH HHS [CA-06516, CA-68484]; NHLBI NIH HHS [5T32HL07 623-17] NR 61 TC 74 Z9 76 U1 1 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3278 EP 3285 DI 10.1182/blood-2004-08-3073 PG 8 WC Hematology SC Hematology GA 915XK UT WOS:000228344500047 PM 15618471 ER PT J AU Taylor, PA Panoskaltsis-Mortari, A Freeman, GJ Sharpe, AH Noelle, RJ Rudensky, AY Mak, TW Serody, JS Blazar, BR AF Taylor, PA Panoskaltsis-Mortari, A Freeman, GJ Sharpe, AH Noelle, RJ Rudensky, AY Mak, TW Serody, JS Blazar, BR TI Targeting of inducible costimulator (ICOS) expressed on alloreactive T cells down-regulates graft-versus-host disease (GVHD) and facilitates engraftment of allogeneic bone marrow (BM) SO BLOOD LA English DT Article ID GRANZYME-B; ACTIVATION; ANTIBODY; MICE; TRANSPLANTATION; REJECTION; RESPONSES; SELECTION; SURVIVAL; RECEPTOR AB Inducible costimulator (ICOS), a CD28/ cytotoxic T lymphocyte antigen 4 (CTLA-4) family member, is expressed on activated T cells. ICOS ligand, a B7 family member, is constitutively expressed on B cells, macrophages, and dendritic cells and is up-regulated on antigen-presenting cells (APCs) and some nonlymphoid tissues by tumor necrosis factor alpha (TNF alpha) or lipopolysaccharide (LPS). Thus, ICOS: ICOS ligand (ICOSL) blockade could reduce alloreactive T cell-APC interactions responsible for graft-versus-host disease (GVHD) and bone marrow (BM) graft rejection. ICOS blockade, achieved with ICOS-/- mice or anti-ICOS monoclonal antibody (mAb) administration, resulted in significant inhibition of GVHD in multiple strain combinations whether mediated by CD4(+) and/or CD8(+) T cells, alloantigen-specific T-cell receptor (TCR) transgenic (Tg) T cells, or CD28-, T helper 1 (Th1)-, or Th2-deficient T cells. Anti-ICOS significantly delayed GVHD mortality even when mAb infusions were delayed until day 5 after transplantation. ICOS blockade reduced the number of alloantigen-specific effector cells but did not prevent their activation. Imaging of green fluorescent protein-positive (GFP(+)) effectors indicated that ICOS blockade inhibited expansion of GVHD-causing effector T cells in secondary lymphoid and GVHD target organs. Engraftment rates were significantly higher in ICOS-/- versus wild-type (WT) mice receiving allogeneic BM, and ICOS blockade significantly inhibited expansion of host antidonor alloantigen-specific BM graft-rejecting T cells. These data suggest that the ICOS pathway may be a beneficial therapeutic target for GVHD inhibition, GVHD therapy, and BM graft promotion. C1 Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Div BMT, Dept Pediat, Minneapolis, MN USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, USA Dept Med Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH USA. Univ Washington, Sch Med, Dept Immunol, Seattle, WA USA. Adv Med Discovery Inst, Dept Med Biophys & Immunol, Toronto, ON, Canada. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Blazar, BR (reprint author), Univ Minnesota, Ctr Canc, MMC 109,420 Delaware St,SE, Minneapolis, MN 55455 USA. EM blaza001@tc.umn.edu OI Serody, Jonathan/0000-0003-4568-1092 FU NHLBI NIH HHS [2R37HL56067, R01 HL63452]; NIAID NIH HHS [P01 AI056299, R01 AI34495] NR 26 TC 66 Z9 75 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3372 EP 3380 DI 10.1182/blood-2004-10-3869 PG 9 WC Hematology SC Hematology GA 915XK UT WOS:000228344500060 PM 15618467 ER PT J AU Cheng, LL Burns, MA Taylor, JL He, WL Halpern, EF McDougal, WS Wu, CL AF Cheng, LL Burns, MA Taylor, JL He, WL Halpern, EF McDougal, WS Wu, CL TI Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy SO CANCER RESEARCH LA English DT Article ID EXTERNAL-BEAM RADIOTHERAPY; RESOLUTION; BIOPSIES; MEN AB Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (> 70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA. RP Cheng, LL (reprint author), Pathol Res CNY-7,149 13th St, Charlestown, MA 02129 USA. EM cheng@nmr.mgh.harvard.edu FU NCI NIH HHS [CA095624, CA80901]; NIBIB NIH HHS [EB002026] NR 23 TC 105 Z9 108 U1 0 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3030 EP 3034 PG 5 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800010 PM 15833828 ER PT J AU Zea, AH Rodriguez, PC Atkins, NB Hernandez, C Signoretti, S Zabaleta, J McDermott, D Quiceno, D Youmans, A O'Neill, A Mier, J Ochoa, AC AF Zea, AH Rodriguez, PC Atkins, NB Hernandez, C Signoretti, S Zabaleta, J McDermott, D Quiceno, D Youmans, A O'Neill, A Mier, J Ochoa, AC TI Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion SO CANCER RESEARCH LA English DT Article ID T-CELLS; L-ARGININE; EXPRESSION; APOPTOSIS; LYMPHOCYTES; GRANULOCYTES; RECEPTOR AB Myeloid suppressor cells with high arginase activity are found in tumors and spleen of mice with colon and lung cancer. These cells, described as macrophages or immature dendritic cells, deplete arginine and impair T cell proliferation and cytokine production. Although arginase activity has been described in cancer patients, it is thought to originate from tumor cells metabolizing arginine to ornithine needed to sustain rapid cell proliferation. The goal of this study was to determine whether myeloid suppressor cells producing high arginase existed in renal cell carcinoma patients. Peripheral blood mononuclear cells from 123 patients with metastatic renal cell carcinoma, prior to treatment, were found to have a significantly increased arginase activity. These patients had a markedly decreased cytokine production and expressed low levels of T cell receptor CD3 zeta chain. Cell separation studies showed that the increased arginase activity was limited to a specific subset of CD11b+, CD14-, CD15+ cells with a polymorphonuclear granulocyte morphology and markers, instead of macrophages or dendritic cells described in mouse models. Furthermore, these patients had low levels of arginine and high levels of ornithine in plasma. Depletion of the CD11b+, CD14- myeloid suppressor cells reestablished T cell proliferation and CD3 chain expression. These results showed, for the first time, the existence of suppressor myeloid cells producing arginase in human cancer patients. In addition, it supports the concept that blocking arginase may be an important step in the success of immunotherapy. C1 Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, Dept Immunol & Microbiol, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, Dept Pediat, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, Dept Pathol, New Orleans, LA 70112 USA. Harvard Univ, Dana Farber Canc Ctr, Renal Canc Program, Boston, MA 02115 USA. RP Ochoa, AC (reprint author), Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, Dept Immunol & Microbiol, New Orleans, LA 70112 USA. EM aochoa@lsuhsc.edu FU NCI NIH HHS [P50CA101942, R01-CA107974, R01-CA88885] NR 18 TC 456 Z9 481 U1 1 U2 18 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3044 EP 3048 PG 5 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800013 PM 15833831 ER PT J AU Lee, SA Ndisang, D Patel, C Dennis, JH Faulkes, DJ D'Arrigo, C Samady, L Farooqui-Kabir, S Heads, RJ Latchman, DS Budhram-Mahadeo, VS AF Lee, SA Ndisang, D Patel, C Dennis, JH Faulkes, DJ D'Arrigo, C Samady, L Farooqui-Kabir, S Heads, RJ Latchman, DS Budhram-Mahadeo, VS TI Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter SO CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR; CATHEPSIN-D; CELL-PROLIFERATION; DRUG-RESISTANCE; GENE-EXPRESSION; FAMILY; HSP27; APOPTOSIS; GROWTH; INVASIVENESS AB In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies. Conversely, HSP-27 is decreased on loss of Brn-3b. In cotransfection assays, Brn-3b can strongly transactivate the HSP-27 promoter, supporting a role for direct regulation of HSP-27 expression. Brn-3b also cooperates with the estrogen receptor (ER) to facilitate maximal stimulation of the HSP-27 promoter, with significantly enhanced activity of this promoter observed on coexpression of Brn-3b and ER compared with either alone. RNA interference and site-directed mutagenesis support the requirement for the Brn-3b binding site on the HSP-27 promoter, which facilitates maximal transactivation either alone or on interaction with the ER. Chromatin immunoprecipitation provides evidence for association of Brn-3b with the HSP-27 promoter in the intact cell. Thus, Brn-3b can, directly and indirectly (via interaction with the ER), activate HSP-27 expression, and this may represent one mechanism by which Brn-3b mediates its effects in breast cancer cells. C1 UCL, Inst Child Hlth, Med Mol Biol Unit, London WC1N 1EH, England. Kings Coll London, Guys Hosp, Canc Res UK, Hedley Atkins Breast Pathol Lab,Hedley Atkins Bre, London, England. St Thomas Hosp, Rayne Inst, GKT Sch Med, Dept Cardiol,Cardiovasc Div, London SE1 7EH, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA USA. RP Budhram-Mahadeo, VS (reprint author), UCL, Inst Child Hlth, Med Mol Biol Unit, 30 Guildford St, London WC1N 1EH, England. EM v.mahadeo@ich.uci.ac.uk NR 37 TC 32 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3072 EP 3080 PG 9 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800018 PM 15833836 ER PT J AU Pathak, A del Monte, F Zhao, W Schultz, JE Lorenz, JN Bodi, I Weiser, D Hahn, H Carr, AN Syed, F Mavila, N Jha, L Qian, J Marreez, Y Chen, GL McGraw, DW Heist, EK Guerrero, JL DePaoli-Roach, AA Hajjar, RJ Kranias, EG AF Pathak, A del Monte, F Zhao, W Schultz, JE Lorenz, JN Bodi, I Weiser, D Hahn, H Carr, AN Syed, F Mavila, N Jha, L Qian, J Marreez, Y Chen, GL McGraw, DW Heist, EK Guerrero, JL DePaoli-Roach, AA Hajjar, RJ Kranias, EG TI Enhancement of cardiac function and suppression of heart failure progression by inhibition of protein phosphatase 1 SO CIRCULATION RESEARCH LA English DT Article DE protein phosphatase 1; protein phosphatase 1 inhibitor 1; heart failure; hypertrophy; phospholamban; gene therapy ID FAILING HUMAN HEARTS; SARCOPLASMIC-RETICULUM; GENE-TRANSFER; DILATED CARDIOMYOPATHY; PHOSPHOLAMBAN ABLATION; HYPERTROPHY; RECEPTOR; MOUSE AB Abnormal calcium cycling, characteristic of experimental and human heart failure, is associated with impaired sarcoplasmic reticulum calcium uptake activity. This reflects decreases in the cAMP-pathway signaling and increases in type 1 phosphatase activity. The increased protein phosphatase 1 activity is partially due to dephosphorylation and inactivation of its inhibitor-1, promoting dephosphorylation of phospholamban and inhibition of the sarcoplasmic reticulum calcium-pump. Indeed, cardiac-specific expression of a constitutively active inhibitor-1 results in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility at the cellular and intact animal levels. Furthermore, the beta-adrenergic response is enhanced in the transgenic hearts compared with wild types. On aortic constriction, the hypercontractile cardiac function is maintained, hypertrophy is attenuated and there is no decompensation in the transgenics compared with wild-type controls. Notably, acute adenoviral gene delivery of the active inhibitor-1, completely restores function and partially reverses remodeling, including normalization of the hyperactivated p38, in the setting of pre-existing heart failure. Thus, the inhibitor 1 of the type 1 phosphatase may represent an attractive new therapeutic target. C1 Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Cellular & Mol Physiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Internal Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Mol Genet & Biochem, Cincinnati, OH 45267 USA. Harvard Univ, Sch Med, Div Cardiol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. Indiana Univ, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. RP Kranias, EG (reprint author), Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, 231 Albert Sabin Way,POB 670575, Cincinnati, OH 45267 USA. EM Litsa.Kranias@uc.edu FU NHLBI NIH HHS [HL07382-27, HL 57623, HL52318, HL64018, HL26057]; NIDDK NIH HHS [DK36569] NR 34 TC 129 Z9 136 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 15 PY 2005 VL 96 IS 7 BP 756 EP 766 DI 10.1161/01.RES.0000161256.85833.fa PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 916LU UT WOS:000228387300011 PM 15746443 ER PT J AU Kelloff, G Hoffman, JM Johnson, B Scher, HI Siegel, BA Cheng, EY Cheson, BD O'Shaughnessy, J Guyton, KZ Mankoff, DA Shankar, L Larson, SM Sigman, CC Schilsky, RL Sullivan, DC AF Kelloff, G Hoffman, JM Johnson, B Scher, HI Siegel, BA Cheng, EY Cheson, BD O'Shaughnessy, J Guyton, KZ Mankoff, DA Shankar, L Larson, SM Sigman, CC Schilsky, RL Sullivan, DC TI Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; NON-HODGKINS-LYMPHOMA; SOFT-TISSUE SARCOMA; GROWTH-FACTOR-RECEPTOR; WHOLE-BODY PET; INDEPENDENT PROSTATE-CANCER; METASTATIC BREAST-CANCER; HYPOXIA-INDUCIBLE FACTOR; GASTROINTESTINAL STROMAL TUMORS AB 2- [F-18] Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile the apy. Moreover, a reduction in the FDG-PETsignal within days or weeks of initiating therapy (e.g., in lymphoma, non - small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDGPETcould facilitate drug development an early surrogate of clinical benefit. This article reviews the scientific basis of FIDG-PETand its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/II trial end point to accelerate evaluation and approval of novel regimens and therapies. C1 NCI, Div Canc Treatment & Diagnost, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Mallinckrodt Inst Radiol, Div Nucl Med, St Louis, MO USA. Fairview Univ, Med Ctr, Univ Minnesota & Orthopaed Surg Serv, Dept Orthopaed Surg, Minneapolis, MN USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. CCS Associates, Mountain View, CA USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Univ Chicago, Pritzker Sch Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Kelloff, G (reprint author), NCI, Div Canc Treatment & Diagnost, Canc Imaging Program, NIH, EPN 6130 Execut Blvd,Suite 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov RI Mankoff, David/F-9576-2010 NR 275 TC 307 Z9 318 U1 6 U2 40 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2005 VL 11 IS 8 BP 2785 EP 2808 DI 10.1158/1078-0432.CCR-04-2626 PG 24 WC Oncology SC Oncology GA 916SM UT WOS:000228406300001 PM 15837727 ER PT J AU Klyushnenkova, EN Link, J Oberle, WT Kodak, J Rich, C Vandenbark, AA Alexander, RB AF Klyushnenkova, EN Link, J Oberle, WT Kodak, J Rich, C Vandenbark, AA Alexander, RB TI Identification of HLA-DRB1*1501-Restricted T-cell epitopes from prostate-specific antigen SO CLINICAL CANCER RESEARCH LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GRANULOMATOUS PROSTATITIS; TRANSGENIC MICE; CANCER-PATIENTS; PEPTIDE; RECOGNITION; GENERATION; RESPONSES; MELANOMA; HLA-DR2 AB The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 Tcells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II - restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA) -derived VIHC class II -restricted peptides, we immunized mice transgenic for HLA-DRB1* 1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA(171-190) and PSA(221-240), which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer, These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactiveT cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation. C1 Univ Maryland, Sch Med, Urol Sect, VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Div Urol, Baltimore, MD 21201 USA. Oregon Hlth Sci Univ, Dept Neuroimmunol, Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Klyushnenkova, EN (reprint author), Univ Maryland, Sch Med, Dept Surg, Med Sch Teaching Facil, 10 S Pine St,Room 4-00A, Baltimore, MD 21201 USA. EM eklyustinenkova@smail.umaryland.edu OI Link, Jason/0000-0002-6892-0431 NR 23 TC 21 Z9 21 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2005 VL 11 IS 8 BP 2853 EP 2861 DI 10.1158/1078-0432.CCR-04-1927 PG 9 WC Oncology SC Oncology GA 916SM UT WOS:000228406300006 PM 15837732 ER PT J AU Wu, JD Odman, A Higgins, LM Haugk, K Vessella, R Ludwig, DL Plymate, SR AF Wu, JD Odman, A Higgins, LM Haugk, K Vessella, R Ludwig, DL Plymate, SR TI In vivo effects of the human type I insulin-like growth factor receptor antibody A12 on androgen-dependent and androgen-independent xenograft human prostate tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID IGF-BINDING PROTEIN-3; BREAST-CANCER CELLS; FACTOR SYSTEM; MONOCLONAL-ANTIBODY; EXPRESSION; APOPTOSIS; INHIBITION; PROGRESSION; TRANSFORMATION; PROLIFERATION AB Purpose: The type I insulin-like growth factor receptor (IGF-IR) and its ligands have been shown to play a critical role in prostate carcinoma development, growth, and metastasis. Targeting the IGF-IR may be a potential treatment for prostate cancer. A fully human monoclonal antibody, A12, specific to IGF-IR, has shown potent antitumor effects in breast, colon, and pancreatic cancers in vitro and in vivo. In this study, we tested the in vivo effects of A12 on androgen-dependent and androgen-independent prostate tumor growth. Experimental Design: Androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate tumors were implanted s.c. into intact and castrated severe combined immuno-deficient mice, respectively. When tumor volume reached about 150 to 200 mm(3), A12 was injected at 40 mg/kg body weight thrice a week for up to 5 weeks. Results: We find that A12 significantly inhibits growth of androgen-dependent LuCaP 35 and androgen-independent LuCaP 35V prostate xenografts, however, by different mechanisms, In LuCaP 35 xenografts, A12 treatment induces tumor cell apoptosis or G, cycle arrest. In LuCaP 35V xenografts, A12 treatment induces tumor cell G(2)-M cycle arrest. Moreover, we find that blocking the function of IGF-IR down-regulates androgen-regulated gene expression in androgen-independent LuCaP 35V tumor cells. Conclusions: Our findings suggest that A12 is a therapeutic candidate for both androgen-dependent and androgen-independent prostate cancer. Our findings also suggest an IGF-IR-dependent activity of the androgen receptor in androgen-independent prostate cancer cells. C1 Univ Washington, Dept Med, Seattle, WA 98104 USA. Univ Washington, Dept Gerontol & Geriatr Med, Seattle, WA 98104 USA. Univ Washington, Dept Urol & Immunol, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res & Educ Clin Ctr, Seattle, WA USA. ImClone Syst, New York, NY USA. RP Wu, JD (reprint author), Univ Washington, Dept Med, Box 359625, Seattle, WA 98104 USA. EM wuj@u.washington.edu FU NCI NIH HHS [P01-CA85859, K01 CA116002]; NIDDK NIH HHS [R01DK52683] NR 46 TC 121 Z9 125 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 15 PY 2005 VL 11 IS 8 BP 3065 EP 3074 DI 10.1158/1078-0432.CCR-04-1586 PG 10 WC Oncology SC Oncology GA 916SM UT WOS:000228406300036 PM 15837762 ER PT J AU Boutwell, AE Allen, SA Rich, JD AF Boutwell, AE Allen, SA Rich, JD TI Opportunities to address the hepatitis C epidemic in the correctional setting SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Hepatitis C Virus Infection and Substance Abuse CY NOV 11-13, 2003 CL Washington, DC SP Off AIDS Res, NIAID, Natl Inst Diabetes & Dugest & Kidney Dus, Dept Vet Affairs, Hlth Resources & Serv Adm ID PUBLIC-HEALTH OPPORTUNITY; VIRUS-INFECTION; FACILITIES; OFFENDERS; SERVICES; PROGRESS; THERAPY; INMATES; CARE AB An estimated 15%-40% of incarcerated persons in the United States are infected with hepatitis C virus (HCV). Approximately 1.4 million HCV-infected persons pass through the corrections system annually, accounting for one-third of the total number of HCV-infected persons in the United States. This high prevalence of HCV infection is due to the substantial increase in drug-related arrests over the past 2 decades. Although the hepatitis C epidemic in the corrections system may be viewed as a burden on correctional health systems, it is an important public health opportunity and an obligation. Research on the implementation of cost-effective HCV screening, prevention, and treatment programs among incarcerated persons is essential. Testing, education, and, when appropriate, treatment of prisoners should be a cornerstone of the public health response to the hepatitis C epidemic in the United States. C1 Brown Univ, Sch Med, Miriam Hosp, Providence, RI 02906 USA. State Rhode Isl Dept Correct, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rich, JD (reprint author), Brown Univ, Sch Med, Miriam Hosp, 164 Summit Ave, Providence, RI 02906 USA. EM jrich@lifespan.org RI Allen, Scott/D-2403-2015 OI Allen, Scott/0000-0001-8815-4714 FU NIAID NIH HHS [AI-42853] NR 32 TC 24 Z9 24 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2005 VL 40 SU 5 BP S367 EP S372 DI 10.1086/427455 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908WM UT WOS:000227820900019 PM 15768350 ER PT J AU Fireman, M Indest, DW Blackwell, A Whitehead, AJ Hauser, P AF Fireman, M Indest, DW Blackwell, A Whitehead, AJ Hauser, P TI Addressing tri-morbidity (Hepatitis C, psychiatric disorders, and substance use): The importance of routine mental health screening as a component of a comanagement model of care SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Conference on Hepatitis C Virus Infection and Substance Abuse CY NOV 11-13, 2003 CL Washington, DC SP Off AIDS Res, NIAID, Natl Inst Diabetes & Dugest & Kidney Dus, Dept Vet Affairs, Hlth Resources & Serv Adm ID INTERFERON-ALPHA; PLUS RIBAVIRIN; UNITED-STATES; DEPRESSION; VETERANS; THERAPY; VIRUS; INFECTION AB Background. Recent studies suggest that most patients with hepatitis C virus (HCV) infection commonly present to medical clinics with active psychiatric and substance use disorders. However, routine screening for these disorders is generally not done. Objectives. The purpose of our study was to assess prospectively the frequency of psychiatric and substance use disorders in patients presenting for initial assessment of a positive HCV antibody test result. Methods. A sample of 293 patients represented the majority of patients scheduled for their initial hepatology clinic visit at the Portland Veterans Affairs Medical Center between September 2002 and September 2003. The patient screening questionnaire, Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and the Beck Depression Inventory (BDI-II) were administered to all patients. Results. At screening, 93% of the patients had a current or past history of at least 1 psychiatric disorder, and 73% had >= 2 disorders. The most common disorders included depression (81%), posttraumatic stress disorder (62%), any substance use disorder (58%), bipolar disorder (20%), and other psychotic disorders (17%). One hundred two patients (35%) had baseline BDI-II scores in the moderate-to-severe range of depression (> 19), and 61 (21%) had AUDIT-C scores indicating current heavy alcohol use (>= 4). Conclusions. Psychiatric and substance use disorders are highly prevalent among veterans with chronic hepatitis C. Thirty-five percent have significant symptoms of depression before the initiation of treatment with interferon (IFN). Routine screening for underlying psychiatric and substance use disorders and early treatment intervention before initiating antiviral therapy is essential to prevent worsening of depression and to optimize the outcome of treatment with IFN. Comanagement treatment models involving mental health care may expand the pool of patients eligible to receive treatment with IFN, as well as enhance treatment outcomes. C1 Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Portland VA Med Ctr, Div Neurosci, Portland, OR 97239 USA. Portland VA Med Ctr, JENS Lab, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Hauser, P (reprint author), Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM peter.hauser2@med.va.gov RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 26 TC 59 Z9 60 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2005 VL 40 SU 5 BP S286 EP S291 DI 10.1086/427442 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908WM UT WOS:000227820900005 PM 15768336 ER PT J AU Fernandes, N Sun, YL Chen, SJ Paul, P Shaw, RJ Cantley, LC Price, BD AF Fernandes, N Sun, YL Chen, SJ Paul, P Shaw, RJ Cantley, LC Price, BD TI DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAKAGE SYNDROME GENE; S-PHASE CHECKPOINT; ATAXIA-TELANGIECTASIA; DEPENDENT PHOSPHORYLATION; TRANSCRIPTIONAL ACTIVITY; IONIZING-RADIATION; FUNCTIONAL-LINK; KINASE; P53; ACTIVATION AB The ATM protein kinase regulates the response of the cell to DNA damage by associating with and then phosphorylating proteins involved in cell cycle checkpoints and DNA repair. Here, we report on deletion studies designed to identify protein domains required for ATM to phosphorylate target proteins and to control cell survival following exposure to ionizing radiation. Deletion studies demonstrated that amino acids 1 - 150 of ATM were required for the ATM protein to regulate cellular radiosensitivity. Additional deletions and point mutations indicated that this domain extended from amino acids 81 - 106 of ATM, with amino acid substitutions located between amino acids 91 and 97 inactivating the functional activity of ATM. When ATM with mutations in this region ( termed ATM90) was expressed in AT cells, it was unable to restore normal radiosensitivity to the cells. However, ATM90 retained normal kinase activity and was autophosphorylated on serine 1981 following exposure to DNA damage. Furthermore, wild-type ATM displayed DNA-damage induced association with p53, brca1, and LKB1 in vivo, whereas ATM90 failed to form productive complexes with these target proteins either in vivo or in vitro. Furthermore, ATM90 did not phosphorylate p53 in vivo and did not form nuclear foci in response to ionizing radiation. We propose that amino acids 91 - 97 of ATM contain a protein interaction domain required for the DNA damage-induced association between ATM and its target proteins, including the brca1, p53, and LKB1 proteins. Furthermore, this domain of ATM is required for ATM to form nuclear foci following exposure to ionizing radiation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, JF513,44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA64585, CA93602]; NIGMS NIH HHS [R01 GM056203] NR 37 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 2005 VL 280 IS 15 BP 15158 EP 15164 DI 10.1074/jbc.M412065200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800099 PM 15713674 ER PT J AU Kattapuram, T Yang, S Maki, JL Stone, JR AF Kattapuram, T Yang, S Maki, JL Stone, JR TI Protein kinase CK1 alpha regulates mRNA binding by heterogeneous nuclear ribonucleoprotein c in response to physiologic levels of hydrogen peroxide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HNRNP-C; CASEIN KINASE-1; IN-VIVO; PHOSPHORYLATION SITES; SPATIAL-ORGANIZATION; ENDOTHELIAL-CELLS; PREMESSENGER RNA; BETA-CATENIN; IDENTIFICATION; TRANSCRIPTION AB At low concentrations, hydrogen peroxide (H2O2) is a positive endogenous regulator of mammalian cell proliferation and survival; however, the signal transduction pathways involved in these processes are poorly understood. In primary human endothelial cells, low concentrations of H2O2 stimulated the rapid phosphorylation of the acidic C-terminal domain (ACD) of heterogeneous nuclear ribonucleoprotein C (hnRNP-C), a nuclear restricted pre-mRNA-binding protein, at Ser(240) and at Ser(225)-Ser(228). A kinase activity was identified in mouse liver that phosphorylates the ACD of hnRNP-C at Ser(240) and at two sites at Ser(225)-Ser(228). The kinase was purified and identified by tandem mass spectrometry as protein kinase CK1 alpha (formerly casein kinase 1 alpha). Protein kinase CK1 alpha immunoprecipitated from primary human endothelial cell nuclei also phosphorylated the ACD of hnRNP-C at these positions. Pretreatment of endothelial cells with the protein kinase CK1-specific inhibitor IC261 prevented the H2O2-stimulated phosphorylation of hnRNP-C. Utilizing phosphoserine-mimicking Ser-to-Glu point mutations, the effects of phosphorylation on hnRNP-C function were investigated by quantitative equilibrium fluorescence RNA binding analyses. Wild-type hnRNP-C1 and hnRNP-C1 modified at the basal sites of phosphorylation (S247E and S286E) both avidly bound RNA with similar binding constants. In contrast, hnRNP-C1 that was also modified at the CK1 alpha phosphorylation sites exhibited a 14-500-fold decrease in binding affinity, demonstrating that CK1 alpha-mediated phosphorylation modulates the mRNA binding ability of hnRNP-C. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Warren 501B,55 Fruit St, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [HL074324] NR 49 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 2005 VL 280 IS 15 BP 15340 EP 15347 DI 10.1074/jbc.M500214200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800119 PM 15687492 ER PT J AU Xie, ZC Romano, DM Tanzi, RE AF Xie, ZC Romano, DM Tanzi, RE TI RNA interference-mediated silencing of X11 alpha and X11 beta attenuates amyloid beta-protein levels via differential effects on beta-amyloid precursor protein processing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-SECRETASE COMPLEX; ALZHEIMERS-DISEASE; A-BETA; PRESENILIN; CLEAVAGE; PEN-2; APP; NICASTRIN; BINDING; APH-1 AB Processing of the beta-amyloid precursor protein (APP) plays a key role in Alzheimer disease neuropathogenesis. APP is cleaved by beta- and alpha-secretase to produce APP-C99 and APP-C83, which are further cleaved by alpha-secretase to produce amyloid beta-protein (A beta) and p3, respectively. APP adaptor proteins with phosphotyrosine-binding domains, including XII alpha (MINT1, encoded by gene APBA1) and XII beta (MINT2, encoded by gene APBA2), can bind to the conserved YENPTY motif in the APP C terminus. Overexpression of XII alpha and XII beta alters APP processing and A beta production. Here, for the first time, we have described the effects of RNA interference (RNAi) silencing of XII alpha and XII beta expression on APP processing and A beta production. RNAi silencing of APBA1 in H4 human neuroglioma cells stably transfected to express either full-length APP or APP-C99 increased APP C-terminal fragment levels and lowered A beta levels in both cell lines by inhibiting gamma-secretase cleavage of APP. RNAi silencing of APBA2 also lowered A beta levels, but apparently not via attenuation of gamma-secretase cleavage of APP. The notion of attenuating gamma-secretase cleavage of APP via the APP adaptor protein XII alpha is particularly attractive with regard to therapeutic potential given that side effects of gamma-secretase inhibition due to impaired proteolysis of other gamma-secretase substrates, e.g. Notch, might be avoided. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, 114 16th St,C3009, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu FU NIA NIH HHS [P50 AG05134, AG 014713-07, AG 00294-17]; NIMH NIH HHS [MH 60009-03] NR 38 TC 40 Z9 43 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 2005 VL 280 IS 15 BP 15413 EP 15421 DI 10.1074/jbc.M414353200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 914OI UT WOS:000228236800128 PM 15699037 ER PT J AU Miyahara, N Takeda, K Miyahara, S Taube, C Joetham, A Koya, T Matsubara, S Dakhama, A Tager, AM Luster, AD Gelfand, EW AF Miyahara, N Takeda, K Miyahara, S Taube, C Joetham, A Koya, T Matsubara, S Dakhama, A Tager, AM Luster, AD Gelfand, EW TI Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8(+) T cells and airway hyperresponsiveness SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EFFECTOR; B-4; ASTHMA; INFLAMMATION; MICE; GENERATION; LYMPHOCYTES; SUBSETS; DIFFERENTIATION; INTERLEUKIN-13 AB Recent studies in both human and rodents have indicated that in addition to CD4(+) T cells, CD8(+) T cells play an important role in allergic inflammation. We previously demonstrated that allergen-sensitized and -challenged CD8-deficient (CD8(-/-)) mice develop significantly lower airway hyperresponsiveness (AHR), eosinophilic inflammation, and IL-13 levels in bronchoalveolar lavage fluid compared with wild-type mice, and that all these responses were restored by adoptive transfer of in vivo-primed CD8(+) T cells or in vitro-generated effector CD8(+) T cells (T-EFF). Recently, leukotriene B4 and its high affinity receptor, BLT1, have been shown to mediate in vitro-generated T-EEF recruitment into inflamed tissues. In this study we investigated whether BLT1 is essential for the development of CD8(+) T cell-mediated allergic AHR and inflammation. Adoptive trans fer of in vivo-primed BLT1(+/+), but not BLTI-/-, CD8(+) T cells into sensitized and challenged CD8(-/-) mice restored AHR, eosinophilic inflammation, and IL-13 levels. Moreover, when adoptively transferred into sensitized CD8(-/-) mice, in vitro-generated BLTI+/+, but not BLT1(-/-), T-EFF accumulated in the lung and mediated these altered airway responses to allergen challenge. These data are the first to show both a functional and an essential role for BLT1 in allergen-mediated CD8(+) T-EFF recruitment into the lung and development of AHR and airway inflammation. C1 Natl Jewish Ctr Immunol & Resp Med, Dept Pediat, Div Cell Biol, Denver, CO 80206 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Gelfand, EW (reprint author), Natl Jewish Ctr Immunol & Resp Med, Dept Pediat, Div Cell Biol, 1400 Jackson St, Denver, CO 80206 USA. EM gelfinde@nje.org FU NHLBI NIH HHS [HL36577, HL61005, P01 HL036577, P01 HL036577-21A15977]; NIAID NIH HHS [AI42246] NR 43 TC 71 Z9 76 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 15 PY 2005 VL 174 IS 8 BP 4979 EP 4984 PG 6 WC Immunology SC Immunology GA 914NN UT WOS:000228234600067 PM 15814727 ER PT J AU Jackson, LA Drevets, DA Dong, ZM Greenfield, RA Murphy, JW AF Jackson, LA Drevets, DA Dong, ZM Greenfield, RA Murphy, JW TI Levels of L-selectin (CD62L) on human leukocytes in disseminated cryptococcosis with and without associated HIV-1 infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; TRANSENDOTHELIAL MIGRATION; OXIDATIVE BURST; T-LYMPHOCYTES; CELL-SURFACE; IN-VITRO; GLUCURONOXYLOMANNAN; NEOFORMANS; NEUTROPHILS; MENINGITIS AB Patients with disseminated cryptococcosis typically have measurable levels of cryptococcal polysaccharide in serum samples but minimal leukocyte infiltration into infected tissues. In vitro data have shown that cryptococcal polysaccharide induces L-selectin (CD62L) shedding from leukocytes. To assess shedding in vivo, we compared leukocyte L-selectin levels in human immunodeficiency virus (HIV) type 1-negative and -positive subjects with and without circulating cryptococcal polysaccharide. Results showed that subjects with cryptococcal polysaccharide in serum samples have significantly lower percentages of neutrophils, monocytes, and CD3(+) T cells with L-selectin on their surfaces than do healthy subjects, regardless of HIV status. There was significantly more soluble L-selectin in serum samples from subjects with cryptococcosis than in those from uninfected subjects. Reduced L-selectin levels on leukocytes in subjects with circulating cryptococcal polysaccharide and increased serum levels of soluble L-selectin indicates that surface L-selectin shedding is a mechanism that likely explains reduced leukocyte extravasation into infected tissues of patients with disseminated cryptococcosis. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. Vet Affairs Med Ctr, Oklahoma City, OK 73104 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Murphy, JW (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA. EM juneann-murphy@ouhsc.edu FU NHLBI NIH HHS [HL-59852]; NIAID NIH HHS [AI-15716] NR 25 TC 7 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2005 VL 191 IS 8 BP 1361 EP 1367 DI 10.1086/428949 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 908QR UT WOS:000227804500022 PM 15776384 ER PT J AU Wang, XK Sarkar, A Cicchetti, F Yu, MX Zhu, AJ Jokivarsi, K Saint-Pierre, M Brownell, AL AF Wang, XK Sarkar, A Cicchetti, F Yu, MX Zhu, AJ Jokivarsi, K Saint-Pierre, M Brownell, AL TI Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE glucose metabolism; dopamine D2 receptor; neuroprotection; cystamime; Huntington's disease; cellular inclusion ID NEURONAL INTRANUCLEAR INCLUSIONS; POSITRON-EMISSION-TOMOGRAPHY; TOXIN 3-NITROPROPIONIC ACID; TISSUE TRANSGLUTAMINASE; POLYGLUTAMINE DOMAINS; GLUCOSE-UTILIZATION; MUTANT HUNTINGTIN; NEURODEGENERATIVE DISORDERS; PALLIDOLUYSIAN ATROPHY; STRIATAL NEURONS AB To investigate efficacy of cystamine induced neuroprotection, we conducted PET imaging studies of cerebral glucose metabolism with [F-18]FDG (2-deoxy-2-[F-18]fluoro-D-glucose) and striatal dopamine D2 receptor function with [C-11]raclopride in R6/2 transgenic Huntington mice. In the control mice, exponentially decreasing glucose utilization was observed in the striatum N-str [SUV]=(41.75 +/- 11.80)(58,str)* exp(-(0.041 +/- 0.007)*t [days]); cortex N-cort [SUV]=24.14 +/- 3.66)(58,cort)*exp(-(0.043 +/- 0.007)*t [days]); and cerebellum N-cer [SUV]= (34.97 +/- 10.58)(58,cer)*exp(-(0.037 +/- 0.008)*t [days]) as a function of age starting at 58 days. Given that the underlying degeneration rate in the cystamine treated mice is similar to that observed in control animals, the protection coefficient (beta) calculated from the equation N-t=N-58*exp(-(1-beta)*k*t) was 0.133 +/- 0.035 for the striatum; 0.122 +/- 0.028 for the cortex and 0.224 +/- 00.042 for the cerebellum with a dose of 100 mg/kg. The 50 mg/kg cystamine dose provided significant protection only for the striatum and only minor protection was obtained using lower doses. Striatal binding potential of [C-11]raclopride was 1.059 +/- 0.030 in the control mice, and enhanced in the cystamine treated animals in a dose dependent manner up to 1.245 +/- 0.063 using the 100 mg/kg dose. Histological analysis confirmed cystamine induced neuroprotection of striatal and cortical neurons and Nissl staining revealed that formation of cellular inclusions was reversed in a dose dependent manner. Cerebral imaging and histological evidence support the use of cystamine as a neuroprotective agent for Huntington's disease (HD) pathology. (c) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Ctr Rech Neurosci, Ste Foy, PQ G1V 2G2, Canada. RP Brownell, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. EM abrownell@partners.org NR 71 TC 46 Z9 46 U1 0 U2 7 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 APR 15 PY 2005 VL 231 IS 1-2 BP 57 EP 66 DI 10.1016/j.jns.2004.12.011 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 916RL UT WOS:000228403400010 PM 15792822 ER PT J AU Krutzfeldt, M Ellis, M Weekes, DB Bull, JJ Eilers, M Vivanco, MDM Sellers, WR Mittnacht, S AF Krutzfeldt, M Ellis, M Weekes, DB Bull, JJ Eilers, M Vivanco, MDM Sellers, WR Mittnacht, S TI Selective ablation of retinoblastoma protein function by the RET finger protein SO MOLECULAR CELL LA English DT Article ID NUCLEAR-BODIES; GENE-PRODUCT; RB; DIFFERENTIATION; ACTIVATION; EXPRESSION; CELLS; E2F; SENESCENCE; INHIBITOR AB The retinoblastoma tumor suppressor protein (Rb) affects gene transcription both negatively and positively and through this regulates distinct cellular responses. Although cell cycle regulation requires gene repression, Rb's ability to promote differentiation and part of its anti proliferative activity appears to rely on the activation of gene transcription. We present evidence here that the RET finger protein (RFP)/tripartite motif protein 27 (TRIM 27) inhibits gene transcription activation by Rb but does not affect gene repression. RFP binds to Rb and prevents the degradation of the EID-1 inhibitor of histone acetylation and differentiation. Furthermore, ablation of RFP in U2OS osteosarcoma cells augments a transcriptional program indicative of lineage-specific differentiation in response to Rb. These findings provide precedent for a regulatory pathway that uncouples different Rb-dependent activities and thus silences specific cellular responses to Rb in a selective way. C1 Chester Beatty Labs, Inst Canc Res, Ctr Cell & Mol Biol, London SW3 6JB, England. Chester Beatty Labs, Inst Canc Res, Breakthrough Ctr, London SW3 6JB, England. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Marburg, Inst Mol Biol & Tumor Res, D-35033 Marburg, Germany. RP Mittnacht, S (reprint author), Chester Beatty Labs, Inst Canc Res, Ctr Cell & Mol Biol, 237 Fulham Rd, London SW3 6JB, England. EM sibylle@icr.ac.uk RI Vivanco, Maria/G-2393-2011; cancer, biogune/H-7276-2012; OI Vivanco, Maria/0000-0002-9540-247X; Weekes, Daniel/0000-0001-8083-7617; Eilers, Martin/0000-0002-0376-6533 NR 40 TC 34 Z9 37 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 15 PY 2005 VL 18 IS 2 BP 213 EP 224 DI 10.1016/j.molcel.2005.03.009 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 917EB UT WOS:000228437700010 PM 15837424 ER PT J AU Hoge, RD Franceschini, MA Covolan, RJM Huppert, T Mandeville, JB Boas, DA AF Hoge, RD Franceschini, MA Covolan, RJM Huppert, T Mandeville, JB Boas, DA TI Simultaneous recording of task-induced changes in blood oxygenation, volume, and flow using diffuse optical imaging and arterial spin-labeling MRI SO NEUROIMAGE LA English DT Article DE optical imaging; functional MRI; hemodynamics; arterial spin-labeling; metabolism ID INFRARED ABSORPTION-SPECTRA; OXIDATIVE-METABOLISM; SENSORY STIMULATION; CONSUMPTION; SPECTROSCOPY; ACTIVATION; PARAMETERS; ACCURACY; DYNAMICS; CORTEX AB Increased neural activity in brain tissue is accompanied by an array of supporting physiological processes, including increases in blood flow and the rates at which glucose and oxygen are consumed. These responses lead to secondary effects such as alterations in blood oxygenation and blood volume, and are ultimately the primary determinants of the amplitude and temporal signature of the blood oxygenation level-dependent (BOLD) signal used prevalently to map brain function. We have performed experiments using a combination of optical and MRI-based imaging methods to develop a more comprehensive picture of the physiological events accompanying activation of primary motor cortex during a finger apposition task. Temporal profiles for changes in tissue hemoglobin concentrations were qualitatively similar to those observed for MRI-based flow and oxygenation signals. Quantitative analysis of these signals revealed peak changes of +16 +/- 2% for HbO, - 13 2% for HbR, +8 +/- 3% for total Hb, +83 +/- 9% for cerebral blood flow, and +1.4 +/- 0.1% for the BOLD MRI signal. A mass balance model was used to estimate the change in rate of oxidative metabolism implied by the optical and flow measurements, leading to a computed value of +47 +/- 5%. It should be noted that the optical and MRI observations may in general reflect changes over different volumes of tissue. The ratio of fractional changes in oxidative metabolism to fractional change in blood flow was found to be 0.56 +/- 0.08, in general agreement with previous studies of flow-metabolism coupling. (c) 2004 Published by Elsevier Inc. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ Estadual Campinas, Inst Fis Gleb Wataghin, BR-13083970 Campinas, SP, Brazil. RP Hoge, RD (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149 13th St, Charlestown, MA 02129 USA. EM rhoge@nmr.mgh.harvard.edu RI Inst. of Physics, Gleb Wataghin/A-9780-2017 FU NCRR NIH HHS [P41-RR14075, R01RR14543]; NIBIB NIH HHS [R01 EB001954, R01-EB002482] NR 25 TC 81 Z9 81 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 15 PY 2005 VL 25 IS 3 BP 701 EP 707 DI 10.1016/j.neuroimage.2004.12.032 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 916KJ UT WOS:000228383500006 PM 15808971 ER PT J AU Keller, RB Atlas, SJ AF Keller, RB Atlas, SJ TI Is there a continuing role for prospective observational studies in spine research? SO SPINE LA English DT Editorial Material ID RANDOMIZED-TRIALS; HOSPITALS; OUTCOMES; STENOSIS; WINNER; VOLVO C1 Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Epidemiol Unit, Boston, MA USA. RP Keller, RB (reprint author), 7 Parkinson Lane, Northport, ME 04849 USA. EM bmwm6@midmaine.com NR 17 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 15 PY 2005 VL 30 IS 8 BP 847 EP 849 DI 10.1097/01.brs.0000158955.62508.a8 PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 917OZ UT WOS:000228473400001 PM 15834324 ER PT J AU Atlas, SJ Keller, RB Wu, YA Deyo, RA Singer, DE AF Atlas, SJ Keller, RB Wu, YA Deyo, RA Singer, DE TI Long-term outcomes of surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation: 10 year results from the Maine Lumbar Spine Study SO SPINE LA English DT Article DE sciatica; herniated lumbar disc; prospective cohort study; outcome research; lumbar disc surgery; natural history ID LOW-BACK-PAIN; SURGERY; DISKECTOMY; WORKPLACE; PATIENT; RATES AB Study Design. A prospective cohort study. Objective. To assess 10-year outcomes of patients with sciatica resulting from a lumbar disc herniation treated surgically or nonsurgically. Summary of Background Data. There is little information comparing long-term outcomes of surgical and conservative therapy of lumbar disc herniation in contemporary clinical practice. Prior studies suggest that these outcomes are similar. Methods. Patients recruited from the practices of orthopedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with follow-up questionnaires mailed at regular intervals over 10 years. Clinical data were obtained at baseline from a physician questionnaire. Primary analyses were based on initial treatment received, either surgical or nonsurgical. Secondary analyses examined actual treatments received by 10 years. Outcomes included patient-reported symptoms of leg and back pain, functional status, satisfaction, and work and disability compensation status. Results. Of 507 eligible consenting patients initially enrolled, 10-year outcomes were available for 400 of 477 (84%) surviving patients; 217 of 255 (85%) treated surgically, and 183 of 222 (82%) treated nonsurgically. Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically. By 10 years, 25% of surgical patients had undergone at least one additional lumbar spine operation, and 25% of nonsurgical patients had at least one lumbar spine operation. At 10-year follow-up, 69% of patients initially treated surgically reported improvement in their predominant symptom ( back or leg pain) versus 61% of those initially treated nonsurgically ( P = 0.2). A larger proportion of surgical patients reported that their low back and leg pain were much better or completely gone (56% vs. 40%, P = 0.006) and were more satisfied with their current status (71% vs. 56%, P = 0.002). Treatment group differences persisted after adjustment for other determinants of outcome in multivariate models. Change in the modified Roland back-specific functional status scale favored surgical treatment, and the relative benefit persisted over the follow-up period. Despite these differences, work and disability status at 10 years were comparable among those treated surgically or nonsurgically. Conclusions. Surgically treated patients with a herniated lumbar disc had more complete relief of leg pain and improved function and satisfaction compared with nonsurgically treated patients over 10 years. Nevertheless, improvement in the patient's predominant symptom and work and disability outcomes were similar regardless of treatment received. For patients in whom elective discectomy is a treatment option, an individualized treatment plan requires patients and their physicians to integrate clinical findings with patient preferences based on their symptoms and goals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Epidemiol Unit,Med Serv, Boston, MA 02114 USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org FU AHRQ HHS [HS-06344, HS-08194, HS-09804] NR 35 TC 183 Z9 199 U1 2 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 15 PY 2005 VL 30 IS 8 BP 927 EP 935 DI 10.1097/01.brs.0000158954.68522.2a PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 917OZ UT WOS:000228473400014 PM 15834338 ER PT J AU Atlas, SJ Keller, RB Wu, YA Deyo, RA Singer, DE AF Atlas, SJ Keller, RB Wu, YA Deyo, RA Singer, DE TI Long-term outcomes of surgical and nonsurgical management of lumbar spinal stenosis: 8 to 10 year results from the Maine Lumbar Spine Study SO SPINE LA English DT Article DE lumbar spinal stenosis; prospective cohort study; outcomes; lumbar disc surgery; natural history ID DECOMPRESSIVE LAMINECTOMY; 1-YEAR OUTCOMES; FOLLOW-UP; SURGERY; SCIATICA; HERNIATION; TRENDS AB Study Design. A prospective observational cohort study. Objective. To assess long-term outcomes of patients with lumbar spinal stenosis treated surgically or nonsurgically. Summary of Background Data. The relative benefit of various treatments for lumbar spinal stenosis is uncertain. Surgical treatment has been associated with short-term improvement, but recurrence of symptoms has been documented. Few studies have compared long-term outcomes of surgical and nonsurgical treatments. Methods. Patients recruited from the practices of orthopaedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with follow-up questionnaires mailed at regular intervals over 10 years. Clinical data were obtained at baseline from a physician questionnaire. Most patients initially undergoing surgery had a laminectomy without fusion performed. Outcomes including patient-reported symptoms of leg and back pain, functional status, and satisfaction were assessed at 8- to 10-year follow-up. Primary analyses were based on initial treatment received with secondary analyses examining actual treatment received by 10 years. Results. Of 148 eligible consenting patients initially enrolled, 105 were alive after 10 years (67.7% survival rate). Among surviving patients, long-term follow-up between 8 and 10 years was available for 97 of 123 (79%) patients ( including 11 patients who died before the 10-year follow-up but completed a 8 or 9 year survey); 56 of 63 (89%) initially treated surgically and 41 of 60 (68%) initially treated nonsurgically. Patients undergoing surgery had worse baseline symptoms and functional status than those initially treated nonsurgically. Outcomes at 1 and 4 years favored initial surgical treatment. After 8 to 10 years, a similar percentage of surgical and nonsurgical patients reported that their low back pain was improved 53% vs. 50%, P = 0.8), their predominant symptom ( either back or leg pain) was improved (54% vs. 42%, P = 0.3), and they were satisfied with their current status (55% vs. 49%, P = 0.5). These treatment group findings persisted after adjustment for other determinants of outcome in multivariate models. However, patients initially treated surgically reported less severe leg pain symptoms and greater improvement in back-specific functional status after 8 to 10 years than nonsurgically treated patients. By 10 years, 23% of surgical patients had undergone at least one additional lumbar spine operation, and 39% of nonsurgical patients had at least one lumbar spine operation. Patients undergoing subsequent surgical procedures had worse outcomes than those continuing with their initial treatment. Outcomes according to actual treatment received at 10 years did not differ because individuals undergoing additional surgical procedures had worse outcomes than those continuing with their initial treatment. Conclusions. Among patients with lumbar spinal stenosis completing 8- to 10-year follow-up, low back pain relief, predominant symptom improvement, and satisfaction with the current state were similar in patients initially treated surgically or nonsurgically. However, leg pain relief and greater back-related functional status continued to favor those initially receiving surgical treatment. These results support a shared decision-making approach among physicians and patients when considering treatment options for lumbar spinal stenosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Epidemiol Unit,Med Serv, Boston, MA 02114 USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. EM satlas@partners.org FU AHRQ HHS [HS-06344, HS-08194, HS-09804] NR 32 TC 241 Z9 261 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 15 PY 2005 VL 30 IS 8 BP 936 EP 943 DI 10.1097/01.brs.0000158953.57966.c0 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 917OZ UT WOS:000228473400015 PM 15834339 ER PT J AU Cooke, DT Hoyt, EG Robbins, RC AF Cooke, DT Hoyt, EG Robbins, RC TI Overexpression of human Bcl-2 in syngeneic rat donor lungs preserves posttransplant function and reduces intragraft caspase activity and interleukin-1 ss production SO TRANSPLANTATION LA English DT Article DE lung transplantation; ischemia-reperfusion; apoptosis; Bcl-2; rat ID ISCHEMIA-REPERFUSION INJURY; CYTOCHROME-C; UP-REGULATION; CARDIAC ALLOGRAFTS; GRAFT FUNCTION; GENE-TRANSFER; TRANSPLANTATION; APOPTOSIS; ADENOVIRUS; EXPRESSION AB Background. A significant cause of primary graft failure in lung transplantation is ischemia-reperfusion (I/R). I/R injury generates proinflammatory cytokines, such as interleukin (IL)-1 beta, and activates the caspase-mediated pathways of alveolar epithelial apoptosis. The authors investigated whether gene transfer of the human antiapoptotic protein Bcl-2 by means of intratracheal adenoviral administration would preserve posttransplant lung function and reduce intragraft activated caspase activity and IL-1 beta production in syngeneic rat donor lung grafts. Methods. First, 1.0 X 10(9) plaque-forming units of AdvBcl-2 in phosphate-buffered saline (PBS), AdvNull empty vector in PBS, or PBS alone was administered intratracheally to ACI (RTIa) rats. Then, the left lungs were procured after 24 hr of in vivo incubation and orthotopically transplanted after I hr of cold ischemia into syngeneic recipients. After 2 hr of reperfusion, peak inspiratory pressures (PIP) and donor pulmonary vein PaO2 was measured in all grafts; grafts were then excised and protein extracts were analyzed by enzyme-linked immunosorbent assay (ELISA) and activated caspase-3 and caspase-9 assays. Results. Human l3cl-2 transgene overexpression in donor lung grafts was demonstrated by ELISA of tissue homogenates. Pretreatment of donor lungs with AdvBcl-2 resulted in reduced PIP and increased lung isograft pulmonary vein PaO2 compared with AdvNull or PBS-alone treated controls. In addition, AdvBcl-2 pretreatment led to diminished cytochrome c release into cytosolic extracts and reduced intragraft IL-1 beta production and inhibited intragraft caspase-3 and caspase-9 activity. Conclusions. Adenoviral overexpression of human Bcl-2 protein limits I/R injury in rat lung isografts. These data suggest that the use of Bcl-2 gene transfer to human lung donors may reduce the oxidative stress of pulmonary grafts after transplantation in clinical lung transplantation. C1 Stanford Univ, Med Ctr, Dept Cardiothorac Surg, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. RP Cooke, DT (reprint author), Stanford Univ, Med Ctr, Dept Cardiothorac Surg, 300 Pasteur Dr,Falk Cardiovasc Res Bldg, Stanford, CA 94305 USA. EM dcooke@partners.org NR 38 TC 12 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2005 VL 79 IS 7 BP 762 EP 767 DI 10.1097/01.TP.0000153368.08861.15 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 916GJ UT WOS:000228373100002 PM 15818317 ER PT J AU Schultz, JM Yang, Y Caride, AJ Filoteo, AG Penheiter, AR Lagziel, A Morell, RJ Mohiddin, SA Fananapazir, L Madeo, AC Penniston, JT Griffith, AJ AF Schultz, JM Yang, Y Caride, AJ Filoteo, AG Penheiter, AR Lagziel, A Morell, RJ Mohiddin, SA Fananapazir, L Madeo, AC Penniston, JT Griffith, AJ TI Modification of human hearing loss by plasma-membrane calcium pump PMCA2 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SENSORINEURAL DEAFNESS; MICE; ASSOCIATION; CADHERIN-23; MUTATION; DFNB12; MUTANT; CDH23; CELLS; 1D AB Five adult siblings presented with autosomal recessive sensorineural hearing loss: two had high-frequency loss, whereas the other three had severe-to-profound loss affecting all frequencies. Genetic evaluation revealed that a homozygous mutation in CDH23 (which encodes cadherin 23) caused the hearing loss in all five siblings and that a heterozygous, hypofunctional variant (V586M) in plasma-membrane calcium pump PMCA2, which is encoded by ATP2B2, was associated with increased loss in the three severely affected siblings. V586M was detected in two unrelated persons with increased sensorineural hearing loss, in the other caused by a mutation in MYO6 (which encodes myosin VI) in one and by noise exposure, suggesting that this variant may modify the severity of sensorineural hearing loss caused by a variety of factors. C1 NIDCD, Sect Gene Struct & Funct, NIH, Rockville, MD 20850 USA. NIDCD, Sect Human Genet, NIH, Rockville, MD 20850 USA. NIDCD, Hearing Sect, NIH, Rockville, MD 20850 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Griffith, AJ (reprint author), NIDCD, Sect Gene Struct & Funct, NIH, 5 Res Ct,Rm 2A-01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Madeo, Anne/K-2880-2012; OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [1 Z01 DC000064-02, 1 Z01 DC000039-05, 1 Z01 DC000060-02, DC04200]; NIGMS NIH HHS [GM28825] NR 24 TC 97 Z9 103 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 14 PY 2005 VL 352 IS 15 BP 1557 EP 1564 DI 10.1056/NEJMoa043899 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 915SH UT WOS:000228324200008 PM 15829536 ER PT J AU Holmes, LB Gargiulo, AR Nadel, AS Racowsky, C AF Holmes, LB Gargiulo, AR Nadel, AS Racowsky, C TI A 32-year-old pregnant woman with an abnormal fetal karyotype - Balanced maternal chromosomal translocation 46,XX,t(1;18)(q42.1;p11.2) resulting in an unbalanced fetal translocation 46,XY,der(18)t(1;18)(q42.1;p11.2)mat. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PREIMPLANTATION GENETIC DIAGNOSIS; EMBRYOS; PGD C1 Massachusetts Gen Hosp, MassGen Hosp Children, Genet & Teratol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Ctr Reprod Med, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Genet & Teratol Unit, Boston, MA 02114 USA. NR 11 TC 1 Z9 1 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 14 PY 2005 VL 352 IS 15 BP 1579 EP 1587 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915SH UT WOS:000228324200012 PM 15829539 ER PT J AU Zou, KY Horhota, A Yu, B Szostak, JW McLaughlin, LW AF Zou, KY Horhota, A Yu, B Szostak, JW McLaughlin, LW TI Synthesis of alpha-L-threofuranosyl nucleoside triphosphates (tNTPs) SO ORGANIC LETTERS LA English DT Article ID NUCLEIC-ACID STRUCTURE; IN-VITRO SELECTION; CHEMICAL ETIOLOGY; TNA; DNA; POLYMERASES; MOLECULES; LIGANDS; SYSTEM AB [GRAPHICS] The alpha-L-threofuranosyl nucleoside triphosphates of T, G, and D (tTTP, tGTP, and tDTP) were synthesized from the described 2'-O-DMT-protected derivatives using the Eckstein method, while the corresponding C derivative (tCTP) was prepared from the 2'-O-acetyl derivative. The prepared alpha-L-threofuranosyl nucleoside triphosphates, despite being one carbon shorter than the native 2'-deoxyfuranosyl nucleoside triphosphates, are effective substrates for selected DNA polymerases. C1 Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02184 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02184 USA. Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China. RP McLaughlin, LW (reprint author), Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. EM mclaughl@bc.edu FU NIGMS NIH HHS [R01 GM053936] NR 16 TC 13 Z9 13 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD APR 14 PY 2005 VL 7 IS 8 BP 1485 EP 1487 DI 10.1021/ol050081 PG 3 WC Chemistry, Organic SC Chemistry GA 915XH UT WOS:000228344200013 PM 15816733 ER PT J AU Armstrong, K Micco, E Carney, A Stopfer, J Putt, M AF Armstrong, K Micco, E Carney, A Stopfer, J Putt, M TI Racial differences in the use of BRCA1/2 testing among women with a family history of breast or ovarian cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AFRICAN-AMERICAN FAMILIES; GENERAL-POPULATION; ETHNIC-DIFFERENCES; HEREDITARY BREAST; INCREASED RISK; HEALTH-CARE; MUTATIONS; DECISIONS; ATTITUDES; RACE AB Context Given the current context of racial disparities in health and health care and the historical context of eugenics, racial disparities in the use of genetic susceptibility testing have been widely anticipated. However, to our knowledge there are no published studies examining the magnitude and determinants of racial differences in the use of genetic susceptibility testing. Objectives To investigate the relationship between race and the use of BRCA1/2 counseling among women with a family history of breast or ovarian cancer and to determine the contribution of socioeconomic characteristics, cancer risk perception and worry, attitudes about genetic testing, and interactions with primary care physicians to racial differences in utilization. Design, Setting, and Participants Case-control study (December 1999-August 2003) of 408 women with a family history of breast or ovarian cancer, of whom 217 underwent genetic counseling for BRCA1/2 testing (cases) and 191 women did not (controls). Participants received primary care within a large health system in greater Philadelphia, Pa. Main Outcome Measures Probability of carrying a BRCA1/2 mutation, socioeconomic characteristics, perception of breast and ovarian cancer risk, worry about breast and ovarian cancer, attitudes about BRCA1/2 testing, and primary care physician discussion of BRCA1/2 testing were measured prior to undergoing BRCA1/2 counseling for cases and at the time of enrollment for controls. Results African American women with a family history of breast or ovarian cancer were significantly less likely to undergo genetic counseling for BRCA1/2 testing than were white women with a family history of breast or ovarian cancer (odds ratio, 0.22; 95% confidence interval, 0.12-0.40). This association persisted after adjustment for probability of BRCA1/2 mutation, socioeconomic characteristics, breast and ovarian cancer risk perception and worry, attitudes about the risks and benefits of BRCA1/2 testing, and primary care physician discussion of BRCA1/2 testing (adjusted odds ratio for African American vs white, 0.28; 95% confidence interval, 0.09-0.89). Conclusions Racial disparities in the use of BRCA1/2 counseling are large and do not appear to be explained by differences in risk factors for carrying a BRCA1/2 mutation, socioeconomic factors, risk perception, attitudes, or primary care physician recommendations. The benefit of predictive genetic testing will not be fully realized unless these disparities can be addressed. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1204 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM karmstro@mail.med.upenn.edu NR 42 TC 164 Z9 164 U1 4 U2 24 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 13 PY 2005 VL 293 IS 14 BP 1729 EP 1736 DI 10.1001/jama.293.14.1729 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 915JS UT WOS:000228301100026 PM 15827311 ER PT J AU Shlipak, MG Fried, LF Cushman, M Manolio, TA Peterson, D Stehman-Breen, C Bleyer, A Newman, A Siscovick, D Psaty, B AF Shlipak, MG Fried, LF Cushman, M Manolio, TA Peterson, D Stehman-Breen, C Bleyer, A Newman, A Siscovick, D Psaty, B TI Cardiovascular mortality risk in chronic kidney disease - Comparison of traditional and novel risk factors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ATHEROSCLEROSIS RISK; RENAL-INSUFFICIENCY; HEALTH; COMMUNITIES; EVENTS; ASSOCIATION; DYSFUNCTION; POPULATION; CREATININE AB Context Elderly persons with chronic kidney disease have substantial risk for cardiovascular mortality, but the relative importance of traditional and novel risk factors is unknown. Objective To compare traditional and novel risk factors as predictors of cardiovascular mortality. Design, Setting, and Patients A total of 5808 community-dwelling persons aged 65 years or older living in 4 communities in the United States participated in the Cardiovascular Health Study cohort. Participants were initially recruited from 1989 to June 1990; an additional 687 black participants were recruited in 1992-1993. The average length of follow-up in this longitudinal study was 8.6 years. Main Outcome Measures Cardiovascular mortality among those with and without chronic kidney disease. Chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 mL/min per 1.73 m(2). Results Among the participants, 1249 (22%) had chronic kidney disease at baseline. The cardiovascular mortality risk rate was 32 deaths/1000 person-years among those with chronic kidney disease vs 16/1000 person-years among those without it. In multivariate analyses, diabetes, systolic hypertension, smoking, low physical activity, nonuse of alcohol, and left ventricular hypertrophy were predictors of cardiovascular mortality in persons with chronic kidney disease (all P values <.05). Among the novel risk factors, only log C-reactive protein (P=.05) and log interleukin 6 (P<.001) were associated with the outcome as linear predictors. Traditional risk factors were associated with the largest absolute increases in risks for cardiovascular deaths among persons with chronic kidney disease: for left ventricular hypertrophy, there were 25 deaths per 1000 person-years; current smoking, 20 per 1000 person-years; physical inactivity, 15 per 1000 person-years; systolic hypertension, 14 per 1000 person-years; diabetes, 14 per 1000 person-years; and nonuse of alcohol, 11 per 1000 person-years vs 5 deaths per 1000 person-years for those with increased C-reactive protein and 5 per 1000 person-years for those with increased interleukin 6 levels. A receiver operating characteristic analysis found that traditional risk factors had an area under the curve of 0.73 (95% confidence interval, 0.70-0.77) among those with chronic kidney disease. Adding novel risk factors only increased the area under the curve to 0.74 (95% confidence interval, 0.71-0.78; P for difference =. 15). Conclusions Traditional cardiovascular risk factors had larger associations with cardiovascular mortality than novel risk factors in elderly persons with chronic kidney disease. Future research should investigate whether aggressive lifestyle intervention in patients with chronic kidney disease can reduce their substantial cardiovascular risk. C1 Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Univ Vermont, Coll Med, Dept Med, Colchester, VT USA. Univ Vermont, Coll Med, Dept Pathol, Colchester, VT USA. Univ Vermont, Coll Med, Dept Biochem, Colchester, VT USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Wake Forest Univ, Bowman Gray Sch Med, Nephrol Sect, Winston Salem, NC USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85084, N01 HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85085, N01-HC-85086, R01 HL073208-01] NR 29 TC 355 Z9 374 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 13 PY 2005 VL 293 IS 14 BP 1737 EP 1745 DI 10.1001/jama.293.14.1737 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915JS UT WOS:000228301100027 PM 15827312 ER PT J AU Stone, PH Lloyd-Jones, DM Kinlay, S Frei, B Carlson, W Rubenstein, J Andrews, TC Johnstone, M Sopko, G Cole, H Orav, J Selwyn, AP Creager, MA AF Stone, PH Lloyd-Jones, DM Kinlay, S Frei, B Carlson, W Rubenstein, J Andrews, TC Johnstone, M Sopko, G Cole, H Orav, J Selwyn, AP Creager, MA CA Vascular Basis Study Grp TI Effect of intensive lipid lowering, with or without antioxidant vitamins, compared with moderate lipid lowering on myocardial ischemia in patients with stable coronary artery disease - The vascular basis for the treatment of myocardial ischemia study SO CIRCULATION LA English DT Article DE antioxidants; cholesterol; coronary disease; exercise; vasoconstriction ID ENDOTHELIUM-DEPENDENT VASODILATION; HYPERCHOLESTEROLEMIC HUMANS; CHOLESTEROL REDUCTION; ANGINA-PECTORIS; THERAPY; VASOMOTION; EXERCISE; IMPROVES; STATINS; ATHEROSCLEROSIS AB Background-Lipid lowering with statins prevents adverse cardiac events. Both lipid-lowering and antioxidant therapies may favorably affect vasomotor function and thereby improve ischemia. Methods and Results-In a randomized, double-blind, placebo-controlled trial, 300 patients with stable coronary disease, a positive exercise treadmill test, 48-hour ambulatory ECG with >= 1 episode of ischemia, and fasting total cholesterol of 180 to 250 mg/dL were assigned to 1-year treatment with intensive atorvastatin to reduce LDL to <80 mg/dL (n=96), intensive atorvastatin to reduce LDL to <80 mg/dL plus antioxidant vitamins C (1000 mg/d) and E (800 mg/d) (n=101), or diet and low-dose lovastatin, if needed, to reduce LDL to <130 mg/dL (n=103; control group). Ischemia end points, including ambulatory ECG monitoring and exercise treadmill testing, and endothelial assessment using brachial artery flow-mediated dilation were obtained at baseline and at 6 and 12 months. Baseline characteristics were similar in all groups. LDL decreased from approximate to 153 mg/dL at baseline in the 2 atorvastatin groups to approximate to 83 mg/dL at 12 months (each P<0.0001) and from 147 to 120 mg/dL in the control group (P<0.0001). During ambulatory ECG monitoring, mean number of ischemic episodes per 48 hours decreased 31% to 61% in each group (each P<0.001; P = 0.15 across groups), without a change in daily heart rate activity. Mean duration of ischemia for 48 hours decreased 26% to 62% in each group (each P<0.001; P=0.06 across groups). Mean exercise duration to 1-mm ST-segment depression significantly increased in each group, but total exercise duration and mean sum of maximum ST depression were unchanged. Angina frequency decreased in each group. There was no incremental effect of supplemental vitamins C and E on any ischemia outcome. Flow-mediated dilation studies indicated no meaningful changes. Conclusions-Intensive lipid lowering with atorvastatin to an LDL level of 80 mg/dL, with or without antioxidant vitamins, does not provide any further benefits in ambulatory ischemia, exercise time to onset of ischemia, and angina frequency than moderate lipid lowering with diet and low-dose lovastatin to an LDL level of <120 mg/dL. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Newton Wellesley Hosp, Newton, MA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Oregon State Univ, Corvallis, OR 97331 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Stone, PH (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM pstone@partners.org RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [R01-HL38780] NR 37 TC 31 Z9 33 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 BP 1747 EP 1755 DI 10.1161/01.CIR.0000160866.90148.76 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900005 PM 15809368 ER PT J AU Chen, JQ Tung, CH Allport, JR Chen, S Weissleder, R Huang, PL AF Chen, JQ Tung, CH Allport, JR Chen, S Weissleder, R Huang, PL TI Near-infrared fluorescent Imaging of matrix metalloproteinase activity after myocardial infarction SO CIRCULATION LA English DT Article DE matrix metalloproteinases; myocardial infarction; imaging; gelatinase; remodeling ID IN-VIVO; REPERFUSION INJURY; TARGETED DELETION; TISSUE INHIBITORS; HEART-FAILURE; FAILING HEART; MICE; ISCHEMIA; ACTIVATION; EXPRESSION AB Background-We used a molecular probe activated by protease cleavage to image expression of matrix metalloproteinases ( MMPs) in the heart after myocardial infarction. Methods and Results-We synthesized and characterized a near-infrared fluorescent (NIRF) probe that is activated by proteolytic cleavage by MMP2 and MMP9. The NIRF probe was injected into mice at various time points up to 4 weeks after myocardial infarction induced by ligation of the left anterior descending coronary artery. NIRF imaging of MMP activity increased in the infarct region, with maximal expression at 1 to 2 weeks, persisting to 4 weeks. Zymography and real-time polymerase chain reaction analysis showed that MMP9 expression is increased at 2 to 4 days, and MMP2 expression is increased at 1 to 2 weeks. Dual-label confocal microscopy showed colocalization of NIRF imaging with neutrophils on day 2, and flow cytometric analysis confirmed that NIRF signal is associated with leukocytes in the infarct zone. Conclusions-This study demonstrates that the activity of MMPs in the myocardium may be imaged by use of specific activity-dependent molecular probes. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA-86355, P50 CA086355]; NHLBI NIH HHS [HL-52818, R01 HL057818, R01 HL057818-09] NR 39 TC 128 Z9 130 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 BP 1800 EP 1805 DI 10.1161/01.CIR.0000160936.91849.9F PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900012 PM 15809374 ER PT J AU DeFaria, DE Grant, RW AF DeFaria, DE Grant, RW TI Cardiovascular risk factors in patients with elevated high-density lipoprotein and coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P278 BP E241 EP E241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900302 ER PT J AU Fox, CS Pencina, MJ Meigs, JB Vasan, RS D'Agostino, RB AF Fox, CS Pencina, MJ Meigs, JB Vasan, RS D'Agostino, RB TI Trends in the incidence of type 2 diabetes from the 1970s to the 1990s SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Boston Univ, Boston, MA 02215 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA 1 BP E249 EP E249 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900334 ER PT J AU Kathiresan, S Chen, Z Janssen I Wildman, RP Matthews, KA Edmundowicz, D Hollenberg, SM Sutton-Tyrrell, K Powell, LH AF Kathiresan, S Chen, Z Janssen, I Wildman, RP Matthews, KA Edmundowicz, D Hollenberg, SM Sutton-Tyrrell, K Powell, LH TI Metabolic syndrome is associated with aortic calcification in women at midlife: The SWAN Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent, Natl Heart, Lung & Blood Inst, Amer Heart Assoc, Council Nutr, Phys Activ & Metab C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Cooper Univ Hosp, Camden, NJ USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P63 BP E198 EP E198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900089 ER PT J AU Meigs, JB Wilson, PW Sullivan, L Fox, CS D'Agostino, RB AF Meigs, JB Wilson, PW Sullivan, L Fox, CS D'Agostino, RB TI Metabolic syndrome accounts for increased risk of type 2 diabetes or cardiovascular disease associated with overall obesity SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Boston Univ, Boston, MA 02215 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P73 BP E200 EP E200 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900099 ER PT J AU Newton-Cheh, C Larson, MG Guo, CY Musone, SL Drake, J Lochner, A Kathiresan, S Vasan, RS Levy, D Benjamin, EJ Hirschhorn, JN O'Donnell, CJ AF Newton-Cheh, C Larson, MG Guo, CY Musone, SL Drake, J Lochner, A Kathiresan, S Vasan, RS Levy, D Benjamin, EJ Hirschhorn, JN O'Donnell, CJ TI Association of genetic variants in KCNH2 with QT interval duration in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P170 BP E220 EP E220 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900195 ER PT J AU Powell, LH Chen, Z Sutton-Tyrrell, K Kathiresan, S Matthews, KA Lewis, T Hollenberg, S AF Powell, LH Chen, Z Sutton-Tyrrell, K Kathiresan, S Matthews, KA Lewis, T Hollenberg, S TI Androgen/estrogen balance is a novel risk factor for visceral fat in midlife women: The SWAN Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P229 BP E231 EP E231 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900254 ER PT J AU Powell, LH Kathiresan, S Chen, Z Wildman, R Sutton-Tyrrell, K Matthews, KA Hollenberg, SM AF Powell, LH Kathiresan, S Chen, Z Wildman, R Sutton-Tyrrell, K Matthews, KA Hollenberg, SM TI Total fat, not specific fat patterning, is responsible for the association between the metabolic syndrome and coronary calcification in women at midlife: The SWAN Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tulane Univ, New Orleans, LA 70118 USA. Univ Pittsburgh, Pittsburgh, PA USA. Cooper Univ Hosp, Camden, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P66 BP E198 EP E199 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900092 ER PT J AU van der Bom, JG Mukamal, KJ Maclure, M Muller, JE Mittleman, MA AF van der Bom, JG Mukamal, KJ Maclure, M Muller, JE Mittleman, MA TI Triggering of myocardial infarction by alcohol consumption SO CIRCULATION LA English DT Meeting Abstract CT 45th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY APR 29-MAY 02, 2005 CL Washington, DC SP Amer Heart Assoc, Council Epidemiol & Prevent & Nutr Phys Activity & Met, Natl Heart Lung & Blood Inst C1 Leiden Univ, Med Ctr, Leiden, Netherlands. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 12 PY 2005 VL 111 IS 14 MA P114 BP E208 EP E208 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 915EO UT WOS:000228280900139 ER PT J AU Lee, JT AF Lee, JT TI Sex chromosome inactivation: The importance of pairing SO CURRENT BIOLOGY LA English DT Editorial Material ID X-CHROMOSOME; SPERMATOGENESIS; MOUSE; PROTEIN; BRCA1; GENE; MICE; ATR; DNA AB In mammals, the process of making sperm is marked by inactivation of sex chromosomes. Why and how does this happen? The answer apparently lies in whether a chromosome finds a pairing partner. Similar mechanisms in mold and worms reveal a surprising and recurrent theme throughout evolution. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Gen Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Gen Genet, Boston, MA 02114 USA. EM lee@amber.mgh.harvard.edu NR 20 TC 12 Z9 12 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 12 PY 2005 VL 15 IS 7 BP R249 EP R252 DI 10.1016/j.cub.2005.03.024 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 919ZL UT WOS:000228656400012 PM 15823524 ER PT J AU Hall, DA Leehey, MA Filley, CM Steinbart, E Montine, T Schellenberg, GD Bosque, P Nixon, R Bird, T AF Hall, DA Leehey, MA Filley, CM Steinbart, E Montine, T Schellenberg, GD Bosque, P Nixon, R Bird, T TI PRNP H187R mutation associated with neuropsychiatric disorders in childhood and dementia SO NEUROLOGY LA English DT Article ID PRION PROTEIN GENE; ENCEPHALOPATHY; FEATURES AB Described is a large family with an autosomal dominant dementia associated with an H187R mutation in the prion protein gene (PRNP). Clinical features include neuropsychiatric disturbances in childhood and adolescence, dementia in young adulthood with frontotemporal manifestations, and long disease duration. Neuropathology revealed atrophy and mild gliosis, whereas prion protein analysis revealed an abnormal conformer with unusual sensitivity to protease digestion. Mutations in PRNP may cause neuropsychiatric disorders that predate dementia by many years. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Neurol, Denver, CO USA. Denver Hlth Med Ctr, Dept Med, Denver, CO USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Vet Affairs Med Ctr, Seattle, WA 98108 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. RP Hall, DA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, 4200 E 9th Ave, Denver, CO 80262 USA. EM deborah.hall@uchsc.edu FU NIA NIH HHS [AG05136] NR 8 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 12 PY 2005 VL 64 IS 7 BP 1304 EP 1306 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 915BO UT WOS:000228272800048 PM 15824374 ER PT J AU Padfield, KE Astrakas, LG Zhang, QH Gopalan, S Dai, G Mindrinos, MN Tompkins, RG Rahme, LG Tzika, AA AF Padfield, KE Astrakas, LG Zhang, QH Gopalan, S Dai, G Mindrinos, MN Tompkins, RG Rahme, LG Tzika, AA TI Burn injury causes mitochondrial dysfunction in skeletal muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; mitochondrial oxidative phosphorylation; muscle dysfunction; nuclear magnetic resonance ID THERMAL-INJURY; P-31 NMR; MAGNETIZATION-TRANSFER; INSULIN-RESISTANCE; COACTIVATOR PGC-1; PROTEIN-TURNOVER; GENE-EXPRESSION; BIOGENESIS; MECHANISMS; HYPERMETABOLISM AB Severe burn trauma is generally followed by a catabolic response that leads to muscle wasting and weakness affecting skeletal musculature. Here, we perform whole-genome expression and in vivo NMR spectroscopy studies to define respectively the full set of burn-induced changes in skeletal muscle gene expression and the role of mitochondria in the altered energy expenditure exhibited by burn patients. Our results show 1,136 genes differentially expressed in a mouse hind limb burn model and identify expression pattern changes of genes involved in muscle development, protein degradation and biosynthesis, inflammation, and mitochondrial energy and metabolism. To assess further the role of mitochondria in burn injury, we performed in Vivo P-31 NMR spectroscopy on hind limb skeletal muscle, to noninvasively measure high-energy phosphates and the effect of magnetization transfer on inorganic phosphate (P-i) and phosphocreatine (PCr) resonances during saturation of gamma ATP resonance, mediated by the ATP synthesis reactions. Although local burn injury does not alter high-energy phosphates or pH, apart from PCr reduction, it does significantly reduce the rate of ATP synthesis, to further implicate a role for mitochondria in burn trauma. These results, in conjunction with our genomic results showing down-regulation of mitochondrial oxidative phosphorylation and related functions, strongly suggest alterations in mitochondrial-directed energy expenditure reactions, advancing our understanding of skeletal muscle dysfunction suffered by burn injury patients. C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. RP Tzika, AA (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. EM atzika@partners.org RI Astrakas, Loukas/F-5918-2011 FU NIDDK NIH HHS [P30 DK040561-10, P30 DK040561]; NIGMS NIH HHS [P50 GM 021700, P50 GM021700, U54 GM 062119, U54 GM062119] NR 44 TC 72 Z9 73 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 2005 VL 102 IS 15 BP 5368 EP 5373 DI 10.1073/pnas.0501211102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916HS UT WOS:000228376600016 PM 15809440 ER PT J AU Choi, HK Atkinson, K Karlson, EW Curhan, G AF Choi, HK Atkinson, K Karlson, EW Curhan, G TI Obesity, weight change, hypertension, diuretic use, and risk of gout in men - The health professionals follow-up study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INSULIN-RESISTANCE SYNDROME; FOOD FREQUENCY QUESTIONNAIRE; CORONARY-HEART-DISEASE; URIC-ACID; HYPERURICEMIA; URATE; REPRODUCIBILITY; METABOLISM; VALIDITY; EXPOSURE AB Background: Limited prospective information exists on the relation between obesity,and weight change and the risk of gout. Similarly, both hypertension and diuretic use have been considered risk factors for gout; however, their independent contributions have not been established prospectively. Methods: We prospectively examined over a 12-year period (1986-1998) the relation between adiposity, weight change, hypertension, and diuretic use and incident gout in 47 150 male participants with no history of gout at baseline. We used a supplementary questionnaire to ascertain the American College of Rheumatology criteria for gout. Results: During 12 years we documented 730 confirmed incident cases of gout. Compared with men with a body mass index (BMI) of 21 to 22.9, the multivariate relative risks (RRs) of gout were 1.95 (95% confidence interval [CI], 1.44-2.65) for men with a BMI of 25 to 29.9, 2.33 (95% CI, 1.62-3.36) for men with a BMI of 30 to 34.9, and 2.97 (95% Cl, 1.73-5.10) for men with a BMI of 35 or greater (P for trend <.001). Compared with men who had maintained their weight (+/- 4 lb) since age 21 years, the multivariate RR of gout for men who had gained 30 lb or more since age 21 years was 1.99 (95% Cl, 1.49-2.66). In contrast, the multivariate RR for men who had lost 10 lb or more since the study baseline was 0.61 (95% Cl, 0.40-0.92). The multivariate RRs of gout were 2.31 (95% Cl, 1.96-2.72) for the presence of hypertension and 1.77 (95% Cl, 1.42-2.20) for diuretic use. Conclusions: Higher adiposity and weight gain are strong risk factors for gout in men, while weight loss is protective. Hypertension and diuretic use are also important independent risk factors for gout. C1 Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. EM hchoi@partners.org FU NIDDK NIH HHS [DK58573] NR 28 TC 235 Z9 259 U1 0 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 11 PY 2005 VL 165 IS 7 BP 742 EP 748 DI 10.1001/archinte.165.7.742 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 915MR UT WOS:000228308800005 PM 15824292 ER PT J AU Musi, N Hirshman, MF Arad, M Xing, YQ Fujii, N Pomerleau, J Ahmad, F Berul, CI Seidman, JG Tian, R Goodyear, LJ AF Musi, N Hirshman, MF Arad, M Xing, YQ Fujii, N Pomerleau, J Ahmad, F Berul, CI Seidman, JG Tian, R Goodyear, LJ TI Functional role of AMP-activated protein kinase in the heart during exercise SO FEBS LETTERS LA English DT Article DE AMP-activated protein kinase; acetyl CoA carboxylase; p38; heart; exercise ID SKELETAL-MUSCLE; GLUCOSE-UPTAKE; TRANSGENIC MICE; CARDIOMYOPATHY; SYSTEM; GENE; PHOSPHORYLATION; ISCHEMIA; SUBUNIT; DISEASE AB AMP-activated protein kinase (AMPK) plays a critical role in maintaining energy homeostasis and cardiac function during ischemia in the heart. However, the functional role of AMPK in the heart during exercise is unknown. We examined whether acute exercise increases AMPK activity in mouse hearts and determined the significance of these increases by studying transgenic (TG) mice expressing a cardiac-specific dominant-negative (inactivating) AMPK alpha 2 subunit. Exercise increased cardiac AMPK alpha 2 activity in the wild type mice but not in TG. We found that inactivation of AMPK did not result in abnormal ATP and glycogen consumption during exercise, cardiac function assessed by heart rhythm telemetry and stress echocardiography, or in maximal exercise capacity. (c) 2605 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Cardiovasc Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc Med, Dept NMR Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cardiol, Childrens Hosp, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Tian, Rong/0000-0002-3676-3830 FU NHLBI NIH HHS [HL67970]; NIAMS NIH HHS [AR45670] NR 28 TC 46 Z9 48 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 11 PY 2005 VL 579 IS 10 BP 2045 EP 2050 DI 10.1016/j.febslet.2005.02.052 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 915NK UT WOS:000228310700005 PM 15811316 ER PT J AU Corlu, A Choe, R Durduran, T Lee, K Schweiger, M Arridge, SR Hillman, EMC Yodh, AG AF Corlu, A Choe, R Durduran, T Lee, K Schweiger, M Arridge, SR Hillman, EMC Yodh, AG TI Diffuse optical tomography with spectral constraints and wavelength optimization SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY APR 01-10, 2005 CL Miami Beach, FL SP Opt Soc Amer ID FREQUENCY-DOMAIN; SCATTERING MEDIA; BREAST-TISSUE; ABSORPTION; SPECTROSCOPY; OXYGENATION; SYSTEM; IMAGES; LIGHT; BODY AB We present an algorithm that explicitly utilizes the wavelength dependence of tissue optical properties for diffuse optical tomography. We have previously shown that the method gives superior separation of absorption and scattering. Here the technique is described and tested in detail, and optimum wavelength sets for abroad range of chromophore combinations are discovered and analyzed. (c) 2005 Optical Society of America. C1 Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. UCL, Dept Comp Sci, London WC1E 6BT, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Corlu, A (reprint author), Univ Penn, Dept Phys & Astron, Philadelphia, PA 19104 USA. EM corlua@dept.physics.upenn.edu RI Lee, Kijoon/B-7247-2008; Hillman, Elizabeth/B-9854-2009; Lee, Kijoon/G-6212-2010; Durduran, Turgut/N-7768-2015; OI Durduran, Turgut/0000-0001-5838-1027; Hillman, Elizabeth M. C./0000-0001-5511-1451 FU NCI NIH HHS [2-R01-CA75124-04] NR 43 TC 135 Z9 135 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 10 PY 2005 VL 44 IS 11 BP 2082 EP 2093 DI 10.1364/AO.44.002082 PG 12 WC Optics SC Optics GA 917JT UT WOS:000228457800011 PM 15835357 ER PT J AU Arevalo, E Chiara, DC Forman, SA Cohen, JB Miller, KW AF Arevalo, E Chiara, DC Forman, SA Cohen, JB Miller, KW TI Gating-enhanced accessibility of hydrophobic sites within the transmembrane region of the nicotinic acetylcholine receptor's delta-subunit - A time-resolved photolabeling study SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACID TYPE-A; CHANNEL-LINING RESIDUES; GATED ION CHANNELS; BINDING-SITE; NONCOMPETITIVE ANTAGONIST; GENERAL-ANESTHETICS; GLYCINE RECEPTORS; ALPHA-SUBUNIT; RESTING STATE; M1 SEGMENT AB General anesthetics often interact more strongly with sites on open than on closed states of ligand-gated ion channels. To seek such sites, Torpedo membranes enriched in nicotinic acetylcholine receptors (nAChRs) were preincubated with the hydrophobic probe 3-(trifluoromethyl)3-(m-iodophenyl) diazirine ([I-125]TID) and exposed to agonist for either 0 ms (closed state), 1.5 and 10 ms (activated states), 1 s (fast desensitized state), or >= 1 h (equilibrium or slow desensitized state) and then rapidly frozen (<1 ms) and photolabeled. Within 1.5 ms, the fractional change in photoincorporation relative to the closed state decreased to 0.7 in the beta- and gamma-subunits, whereas in the alpha-subunit, it changed little. The most dramatic change occurred in the delta-subunit, where it increased to 1.6 within 10 ms but fell to 0.7 during fast desensitization. Four residues in the delta-subunit's transmembrane domain accounted for the enhanced photoincorporation induced by a 10-ms agonist exposure both when TID was added simultaneously with agonist and when it was preincubated with membranes. In the published closed state structure, two residues (delta Thr(274) and delta Leu(278)) are situated toward the extracellular end of helix M2, both contralateral to the ion channel and adjacent to the third residue (delta Phe(232)) on M1. The fourth labeled residue (delta Ile(288)) is toward the end of the M2-M3 loop. Contact with these residues occurs on the time scale of a rapid phase of TID inhibition in Torpedo nAChRs, suggesting the formation of a transient hydrophobic pocket between M1, M2, and M3 in the delta-subunit during gating. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM jonathan_cohen@hms.harvard.edu FU NIGMS NIH HHS [GM-58448] NR 52 TC 41 Z9 41 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 13631 EP 13640 DI 10.1074/jbc.M413911200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500057 PM 15664985 ER PT J AU Pannu, R Singh, AK Singh, I AF Pannu, R Singh, AK Singh, I TI A novel role of lactosylceramide in the regulation of tumor necrosis factor alpha-mediated proliferation of rat primary astrocytes - Implications for astrogliosis following neurotrauma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD-INJURY; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; LIPID RAFTS; REACTIVE ASTROCYTES; ERK/MAP KINASE; MESSENGER-RNA; CELL-LINE; TNF-ALPHA; EXPRESSION AB The present study describes the role of glycosphingolipids in neuroinflammatory disease and investigates tumor necrosis factor alpha (TNF alpha)-induced astrogliosis following spinal cord injury. Astrogliosis is the hallmark of neuroinflammation and is characterized by proliferation of astrocytes and increased glial fibrillary acidic protein (GFAP) gene expression. In primary astrocytes, TNF alpha stimulation increased the intracellular levels of lactosylceramide (LacCer) and induced GFAP expression and astrocyte proliferation. D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.HCl (PDMP), a glucosylceramide synthase and LacCer synthase (GalT-2) inhibitor, inhibited astrocyte proliferation and GFAP expression, which were reversed by exogenous supplementation of LacCer but not by other glycosphingolipids. TNF alpha caused a rapid increase in the activity of GalT-2 and synthesis of LacCer. Silencing of GalT-2 gene using antisense oligonucleotides also attenuated the proliferation of astrocytes and GFAP expression. The PDMP and antisense-mediated inhibition of proliferation and GFAP expression was well correlated with decreased Ras/ERK1/2 pathway activation. Furthermore, TNF alpha-mediated astrocyte proliferation and GFAP expression was also inhibited by LY294002, a phosphatidylinositol 3-kinase inhibitor, which was reversed by exogenous LacCer. LY294002 also inhibited TNF alpha-induced GalT-2 activation and LacCer synthesis, suggesting a phosphatidylinositol 3-kinase-mediated regulation of GalT-2. In vivo, PDMP treatment attenuated chronic ERK1/2 activation and spinal cord injury (SCI)-induced astrocyte proliferation with improved functional recovery post-SCI. Therefore, the in vivo studies support the conclusions drawn from cell culture studies and provide evidence for the role of LacCer in TNF alpha-induced astrogliosis in a rat model of SCI. To our knowledge, this is the first report demonstrating the role of LacCer in the regulation of TNF alpha-induced proliferation and reactivity of primary astrocytes. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Pediat, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Dept Pathol, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 316 Clin Sci Bldg,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM singhi@musc.edu FU NINDS NIH HHS [NS-22576, NS-37766, NS-40144, NS-34741] NR 50 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 13742 EP 13751 DI 10.1074/jbc.M411959200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500070 PM 15668227 ER PT J AU Samad, TA Rebbapragada, A Bell, E Zhang, Y Sidis, Y Jeong, SJ Campagna, JA Perusini, S Fabrizio, DA Schneyer, AL Lin, HY Brivanlou, AH Attisano, L Woolf, CJ AF Samad, TA Rebbapragada, A Bell, E Zhang, Y Sidis, Y Jeong, SJ Campagna, JA Perusini, S Fabrizio, DA Schneyer, AL Lin, HY Brivanlou, AH Attisano, L Woolf, CJ TI DRAGON, a bone morphogenetic protein co-receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPULSIVE GUIDANCE MOLECULE; GROWTH-FACTOR-BETA; SIGNAL-TRANSDUCTION; NEURAL INDUCTION; MOUSE; RECEPTOR; MEMBRANE; PATHWAY; FAMILY; CELLS AB Bone morphogenetic proteins (BMPs) are members of the transforming growth factor (TGF)beta superfamily of ligands that regulate many crucial aspects of embryonic development and organogenesis. Unlike other TGF beta ligands, co-receptors for BMP ligands have not been described. Here we show that DRAGON, a glycosylphosphatidylinositol-anchored member of the repulsive guidance molecule family, which is expressed early in the developing nervous system, enhances BMP but not TGF beta signaling. DRAGON binds directly to BMP2 and BMP4 but not to BMP7 or other TGF beta ligands. The enhancing action of DRAGON on BMP signaling is also reduced by administration of Noggin, a soluble BMP antagonist, indicating that the action of DRAGON is ligand-dependent. DRAGON associates directly with BMP type I (ALK2, ALK3, and ALK6) and type II (ActRII and ActRIIB) receptors, and its signaling is reduced by dominant negative Smad1 and ALK3 or -6 receptors. In the Xenopus embryo, DRAGON both reduces the threshold of the ability of Smad1 to induce mesodermal and endodermal markers and alters neuronal and neural crest patterning. The direct interaction of DRAGON with BMP ligands and receptors indicates that it is a BMP co-receptor that potentiates BMP signaling. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada. Rockefeller Univ, Lab Vertebrate Embryol, New York, NY 10021 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02129 USA. RP Samad, TA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. EM samad@helix.mgh.harvard.edu RI Bell, Esther/C-5329-2009 NR 42 TC 139 Z9 151 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 14122 EP 14129 DI 10.1074/jbc.M410034200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500115 PM 15671031 ER PT J AU Sugita, H Fujimoto, M Yasukawa, T Shimizu, N Sugita, M Yasuhara, S Martyn, JAJ Kaneki, M AF Sugita, H Fujimoto, M Yasukawa, T Shimizu, N Sugita, M Yasuhara, S Martyn, JAJ Kaneki, M TI Inducible nitric-oxide synthase and NO donor induce insulin receptor substrate-1 degradation in skeletal muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE; OXIDATIVE STRESS; S-NITROSYLATION; TYROSINE PHOSPHORYLATION; ENDOTHELIAL DYSFUNCTION; TARGETED DISRUPTION; MURINE MACROPHAGES; NITROSATIVE STRESS; DIABETES-MELLITUS AB Chronic inflammation plays an important role in insulin resistance. Inducible nitric- oxide synthase ( iNOS), a mediator of inflammation, has been implicated in many human diseases including insulin resistance. However, the molecular mechanisms by which iNOS mediates insulin resistance remain largely unknown. Here we demonstrate that exposure to NO donor or iNOS transfection reduced insulin receptor substrate ( IRS)- 1 protein expression without altering the mRNA level in cultured skeletal muscle cells. NO donor increased IRS- 1 ubiquitination, and proteasome inhibitors blocked NO donor- induced reduction in IRS- 1 expression in cultured skeletal muscle cells. The effect of NO donor on IRS- 1 expression was cGMP- independent and accentuated by concomitant oxidative stress, suggesting an involvement of nitrosative stress. Inhibitors for phosphatidylinositol- 3 kinase, mammalian target of rapamycin, and c- Jun amino- terminal kinase failed to block NO donor- induced IRS- 1 reduction, whereas these inhibitors prevented insulin- stimulated IRS- 1 decrease. Moreover iNOS expression was increased in skeletal muscle of diabetic ( ob/ ob) mice compared with lean wild- type mice. iNOS gene disruption or treatment with iNOS inhibitor ameliorated depressed IRS- 1 expression in skeletal muscle of diabetic ( ob/ ob) mice. These findings indicate that iNOS reduces IRS- 1 expression in skeletal muscle via proteasome- mediated degradation and thereby may contribute to obesity- related insulin resistance. C1 Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp,Dept Anesthesia & Crit Car, Charlestown, MA 02129 USA. RP Kaneki, M (reprint author), Harvard Univ, Sch Med, Shriners Hosp Children, Massachusetts Gen Hosp,Dept Anesthesia & Crit Car, 149 13th St,Rm 6604, Charlestown, MA 02129 USA. EM mkaneki@partners.org FU NIDDK NIH HHS [R01DK058127]; NIGMS NIH HHS [GM21700, R01GM061411, R01 GM055082, R01GM031569, R01GM055082] NR 77 TC 71 Z9 74 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 14203 EP 14211 DI 10.1074/jbc.M411226200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500123 PM 15805118 ER PT J AU Venegas, JG Winkler, T Musch, G Melo, MFV Layfield, D Tgavalekos, N Fischman, AJ Callahan, RJ Bellani, G Harris, RS AF Venegas, JG Winkler, T Musch, G Melo, MFV Layfield, D Tgavalekos, N Fischman, AJ Callahan, RJ Bellani, G Harris, RS TI Self-organized patchiness in asthma as a prelude to catastrophic shifts SO NATURE LA English DT Article ID AIRWAY SMOOTH-MUSCLE; VENTILATION; LUNG; PET; HYPERRESPONSIVENESS; METHACHOLINE; PERFUSION; VOLUME; TREE AB Asthma is a common disease affecting an increasing number of children throughout the world. In asthma, pulmonary airways narrow in response to contraction of surrounding smooth muscle. The precise nature of functional changes during an acute asthma attack is unclear. The tree structure of the pulmonary airways has been linked to complex behaviour in sudden airway narrowing(1,2) and avalanche-like reopening(3,4). Here we present experimental evidence that bronchoconstriction leads to patchiness in lung ventilation, as well as a computational model that provides interpretation of the experimental data. Using positron emission tomography, we observe that bronchoconstricted asthmatics develop regions of poorly ventilated lung. Using the computational model we show that, even for uniform smooth muscle activation of a symmetric bronchial tree, the presence of minimal heterogeneity breaks the symmetry and leads to large clusters of poorly ventilated lung units. These clusters are generated by interaction of short- and long-range feedback mechanisms, which lead to catastrophic shifts similar to those linked to self-organized patchiness in nature(5,6). This work might have implications for the treatment of asthma, and might provide a model for studying diseases of other distributed organs. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. RP Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM jvenegas@vqpet.mgh.harvard.edu RI Bellani, Giacomo/D-2379-2010; Winkler, Tilo/B-5337-2009 OI Bellani, Giacomo/0000-0002-3089-205X; Winkler, Tilo/0000-0002-7276-5550 NR 30 TC 262 Z9 267 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 7 PY 2005 VL 434 IS 7034 BP 777 EP 782 DI 10.1038/nature03490 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 913NU UT WOS:000228160700044 PM 15772676 ER PT J AU Wang, HB Woolf, CJ AF Wang, HB Woolf, CJ TI Pain TRPs SO NEURON LA English DT Review ID PRIMARY SENSORY NEURONS; TRANSDUCTION CHANNEL; THERMAL HYPERALGESIA; CAPSAICIN RECEPTOR; HEAT HYPERALGESIA; MICE LACKING; NOCICEPTION; ACTIVATION; SENSITIZATION; CALMODULIN AB Transient receptor potential (TRIP) ion channels are molecular gateways in sensory systems, an interface between the environment and the nervous system. Several TRPs transduce thermal, chemical, and mechanical stimuli into inward currents, an essential first step for eliciting thermal and pain sensations. Precise regulation of the expression, localization, and function of the TRP channels is crucial for their sensory role in nociceptor terminals, particularly after inflammation, when they contribute to pain hypersensitivity by undergoing changes in translation and trafficking as well as diverse posttranslational modifications. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM cwoolf@partners.org NR 28 TC 84 Z9 89 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 7 PY 2005 VL 46 IS 1 BP 9 EP 12 DI 10.1016/j.neuron.2005.03.011 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 914LH UT WOS:000228228600004 PM 15820689 ER PT J AU Dreier, L Burbea, M Kaplan, JM AF Dreier, L Burbea, M Kaplan, JM TI LIN-23-mediated degradation of beta-catenin regulates the abundance of GLR-1 glutamate receptors in the ventral nerve cord of C elegans SO NEURON LA English DT Article ID UBIQUITIN LIGASE COMPLEX; I-KAPPA-B; LONG-TERM POTENTIATION; HOX GENE LIN-39; CAENORHABDITIS-ELEGANS; PROTEASOME SYSTEM; ALPHA UBIQUITINATION; SYNAPTIC PLASTICITY; PROTEIN-DEGRADATION; SURFACE EXPRESSION AB Ubiquitin-mediated protein degradation has been proposed to play an important role in regulating synaptic transmission. Here we show that LIN-23, the substrate binding subunit of a Skp1/Cullin/F Box (SCF) ubiquitin ligase, regulates the abundance of the glutamate receptor GLR-1 in the ventral nerve cord of C. elegans. Mutants lacking lin-23 had an increased abundance of GLR-1 in the ventral cord. The increase of GLR-1 was not caused by changes in the ubiquitination of GLR-1. Instead, SCFLIN-23 regulates GLR-1 through the P-catenin homolog BAR-1 and the TCF/Lef transcription factor homolog POP-1. We hypothesize that LIN-23-mediated degradation of BAR-1 P-catenin regulates the transcription of Wnt target genes, which in turn alter postsynaptic properties. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu FU NINDS NIH HHS [NS32196, F32 NS41705] NR 79 TC 67 Z9 75 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 7 PY 2005 VL 46 IS 1 BP 51 EP 64 DI 10.1016/j.neuron.2004.12.058 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 914LH UT WOS:000228228600008 PM 15820693 ER PT J AU Leeper, NJ Wener, LS Dhaliwal, G Saint, S Wachter, RM AF Leeper, NJ Wener, LS Dhaliwal, G Saint, S Wachter, RM TI One surprise after another SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYOCARDITIS C1 Univ Calif San Francisco, Dept Med, Sch Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor Vet Affairs Hlth Serv Res & Dev Ctr Exc, Ann Arbor, MI USA. Ann Arbor Vet Affairs Med Ctr, Patient Safety Enhancement Program, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. RP Wachter, RM (reprint author), Univ Calif San Francisco, Dept Med, Sch Med, Box 0120,Room M-994, San Francisco, CA 94143 USA. EM bobw@medicine.ucsf.edu FU AHRQ HHS [P20-HS11540] NR 8 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 7 PY 2005 VL 352 IS 14 BP 1474 EP 1479 DI 10.1056/NEJMcps040755 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 913IP UT WOS:000228145200012 PM 15814884 ER PT J AU Cao, C Li, YP Leng, YM Li, P Ma, QJ Kufe, D AF Cao, C Li, YP Leng, YM Li, P Ma, QJ Kufe, D TI Ubiquitination and degradation of the Arg tyrosine kinase is regulated by oxidative stress SO ONCOGENE LA English DT Article DE Arg; c-Abl; oxidative stress; phosphorylation; ubiquitination; proteosomal degradation ID C-ABL; APOPTOTIC RESPONSE; CELLULAR-RESPONSE; ACTIVATION; DNA; NUCLEAR; AUTOINHIBITION; MITOCHONDRIA; BINDING; DAMAGE AB The c-Abl and Arg nonreceptor tyrosine kinases are activated in the response of cells to oxidative stress. The present studies demonstrate that treatment of cells with 0.1mM H2O2 is associated with increased tyrosine phosphorylation of Arg and little effect on Arg levels. By contrast, exposure to 1.0mM H2O2 decreased Arg phosphorylation. Treatment with 1.0mM H2O2 was also associated with ubiquitination and degradation of Arg. The results show that Arg is stabilized in response to 0.1mM H2O2 by autophosphorylation of Y-261, consistent with involvement of the Arg kinase function in regulating Arg levels. The results further demonstrate that c-Abl-mediated phosphorylation of Arg on Y-261 similarly confers Arg stabilization. In concert with these results, phosphorylation of Arg on Y-261 blocked H2O2-induced ubiquitination and thereby Arg degradation and inactivation. These findings demonstrate that Arg phosphorylation and degradation are differentially regulated by the degree of oxidative stress, and that Arg stability is conferred by phosphorylation of Y-261. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beijing Inst Biotechnol, Beijing 100850, Peoples R China. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA98628, CA42802] NR 31 TC 14 Z9 15 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 7 PY 2005 VL 24 IS 15 BP 2433 EP 2440 DI 10.1038/sj.onc.1208454 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 913UV UT WOS:000228180600001 PM 15735735 ER PT J AU Wright, JT Dunn, JK Cutler, JA Davis, BR Cushman, WC Ford, CE Haywood, LJ Leenen, FHH Margolis, KL Papademetriou, V Probstfield, JL Whelton, PK Habib, GB AF Wright, JT Dunn, JK Cutler, JA Davis, BR Cushman, WC Ford, CE Haywood, LJ Leenen, FHH Margolis, KL Papademetriou, V Probstfield, JL Whelton, PK Habib, GB CA ALLHAT Collaborative Res Grp TI Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LIPID-LOWERING TREATMENT; HEART-ATTACK TRIAL; CONVERTING-ENZYME-INHIBITOR; CALCIUM-CHANNEL BLOCKER; HIGH BLOOD-PRESSURE; ISOLATED SYSTOLIC HYPERTENSION; LEFT-VENTRICULAR DYSFUNCTION; MAJOR CARDIOVASCULAR EVENTS; JOINT NATIONAL COMMITTEE; RANDOMIZED-TRIAL AB Context Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs). Objective To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease (CVD) incidence in racial subgroups. Design, Setting, and Participants Prespecified subgroup analysis of ALLHAT, a randomized, double-blind, active-controlled, clinical outcome trial conducted between February 1994 and March 2002 in 33 357 hypertensive US and Canadian patients aged 55 years or older (35% black) with at least 1 other cardiovascular risk factor. Interventions Anti hypertensive regimens initiated with a CCB (amlodipine) or an ACE inhibitor (lisinopril) vs a thiazide-type diuretic (chlorthalidone). Other medications were added to achieve goal blood pressures (BPs) less than 140/90 mm Hg. Main Outcome Measures The primary outcome was combined fatal coronary heart disease (CHD) or nonfatal myocardial infarction (MI), analyzed by intention-to-treat. Secondary outcomes included all-cause mortality, stroke, combined CVD (CND death, nonfatal MI, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. Results No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup. For amlodipine vs chlorthalidone only, HF was the only prespecified clinical outcome that differed significantly (overall: relative risk [RR], 1.37; 95% confidence interval [Cl], 1.24-1.51; blacks: RR, 1.46; 95% CI, 1.24-1.73; nonblacks: RR, 1.32; 95% CI, 1.17-1.49; P<.001 for each comparison) with no difference in treatment effects by race (P=.38 for interaction). For lisinopril vs chlorthalidone, results differed by race for systolic BP (greater decrease in blacks with chlorthalidone), stroke, and combined CVD outcomes (P<.001, P=.01, and P=.04, respectively, for interactions). In blacks and nonblacks, respectively, the RRs for stroke were 1.40 (95% CI, 1.17-1.68) and 1.00 (95% CI, 0.85-1.17) and for combined CVD were 1.19 (95% CI, 1.09-1.30) and 1.06(95% CI, 1.00-1.13). For HF, the RRs were 1.30 (95% CI, 1.10-1.54) and 1.13 (95% CI, 1.00-1.28), with no significant interaction by race. Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks. Conclusions In blacks and nonblack subgroups, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome, and diuretic-based treatment resulted in the lowest risk of heart failure. While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks, thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients. C1 Case Western Reserve Univ, Gen Clin Res Ctr, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Memphis Vet Affairs Med Ctr, Memphis, TN USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Berman Ctr Outcomes & Clin Res, Minneapolis, MN USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Univ Washington, Seattle, WA 98195 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Wright, JT (reprint author), Case Western Reserve Univ, Gen Clin Res Ctr, 11000 Euclid Ave,Bowell Bldg,5th Floor, Cleveland, OH 44106 USA. EM jackson.wright@case.edu OI Papademetriou, Vasilios/0000-0002-2882-2757 FU NHLBI NIH HHS [N01-HC-35130] NR 52 TC 187 Z9 193 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 6 PY 2005 VL 293 IS 13 BP 1595 EP 1607 DI 10.1001/jama.293.13.1595 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 913EV UT WOS:000228135300022 PM 15811979 ER PT J AU Garbutt, JC Kranzler, HR O'Malley, SS Gastfriend, DR Pettinati, HM Silverman, BL Loewy, JW Ehrich, EW AF Garbutt, JC Kranzler, HR O'Malley, SS Gastfriend, DR Pettinati, HM Silverman, BL Loewy, JW Ehrich, EW CA Vivitrex Study Grp TI Efficacy and tolerability of long-acting injectable for alcohol dependence - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CONTROLLED CLINICAL-TRIAL; UNITED-STATES; PRIMARY-CARE; NALTREXONE; METAANALYSIS; VIVITREX(R); MULTICENTER; CONSUMPTION; DRINKERS AB Context Alcohol dependence is a common disorder associated with significant morbidity and mortality. Naltrexone, an opioid antagonist, has been shown to be effective for treatment of alcohol dependence. However, adherence to daily oral pharmacotherapy can be problematic, and clinical acceptance and utility of oral naltrexone have been limited. Objective To determine efficacy and tolerability of a long-acting intramuscular formulation of naltrexone for treatment of alcohol-dependent patients. Design, Setting, and Participants A 6-month, randomized, double-blind, placebo-controlled trial conducted between February 2002 and September 2003 at 24 US public hospitals, private and Veterans Administration clinics, and tertiary care medical centers. Of the 899 individuals screened, 627 who were diagnosed as being actively drinking alcohol-dependent adults were randomized to receive treatment and 624 received at least 1 injection. Intervention An intramuscular injection of 380 mg of long-acting naltrexone (n = 205) or 190 mg of long-acting naltrexone (n = 210) or a matching volume of placebo (n = 209) each administered monthly and combined with 12 sessions of low-intensity psychosocial intervention. Main Outcome Measure The event rate of heavy drinking days in the intent-to-treat population. Results Compared with placebo, 380 mg of long-acting naltrexone resulted in a 25% decrease in the event rate of heavy drinking days (P = .03) and 190 mg of naltrexone resulted in a 17% decrease (P = .07). Sex and pretreatment abstinence each showed significant interaction with the medication group on treatment outcome, with men and those with lead-in abstinence both exhibiting greater treatment effects. Discontinuation due to adverse events occurred in 14.1% in the 380-mg and 6.7% in the 190-mg group and 6.7% in the placebo group. Overall, rate and time to treatment discontinuation were similar among treatment groups. Conclusions Long-acting naltrexone was well tolerated and resulted in reductions in heavy drinking among treatment-seeking alcohol-dependent patients during 6 months of therapy. These data indicate that long-acting naltrexone can be of benefit in the treatment of alcohol dependence. C1 Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Alkermes Inc, Cambridge, MA USA. RP Garbutt, JC (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CB 7160, Chapel Hill, NC 27599 USA. EM jc_garbutt@med.unc.edu FU NIAAA NIH HHS [N43AA01002, K24-AA13736]; NIDA NIH HHS [K24-DA00427] NR 48 TC 299 Z9 321 U1 5 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 6 PY 2005 VL 293 IS 13 BP 1617 EP 1625 DI 10.1001/jama.293.13.1617 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 913EV UT WOS:000228135300024 PM 15811981 ER PT J AU Michaud, DS Skinner, HG Wu, K Hu, F Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Michaud, DS Skinner, HG Wu, K Hu, F Giovannucci, E Willett, WC Colditz, GA Fuchs, CS TI Dietary patterns and pancreatic cancer risk in men and women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PAST MEDICAL HISTORY; DIABETES-MELLITUS; COLORECTAL-CANCER; COLON-CANCER; MORTALITY; OBESITY; COHORT; METAANALYSIS; ALCOHOL; SMOKING AB Background: Diabetes appears to be associated with the development of pancreatic cancer. Three large prospective cohort studies observed a statistically significant relation between obesity and pancreatic cancer risk. Dietary patterns have been associated with fasting insulin levels and risk of diabetes. To determine whether dietary patterns are associated with pancreatic cancer risk, we analyzed data from two large prospective cohort studies. Methods: We combined data for men and women to obtain a total of 366 cases of incident pancreatic cancer from a total of 124 672 eligible participants. Dietary data were obtained from food frequency questionnaires in 1986 for men and in 1984 for women. We identified two major dietary patterns, prudent and western, by factor analysis. The prudent pattern was characterized by high fruit and vegetable intake; the western pattern was characterized by high meat and high fat intakes. Multivariable relative risks (RRs) were adjusted for potential confounders, including smoking and body mass index. Results: In the pooled analysis of men and women, no associations were observed between the prudent pattern (RR = 1.32, 95% confidence interval [CI] = 0.66 to 2.63, for highest versus lowest quintile) or the western pattern (RR = 0.91, 95% CI = 0.57 to 1.47, for highest versus lowest quintile) and the risk of pancreatic cancer. Stratifying by body mass index or physical activity did not change the associations. Conclusion: Dietary patterns were not associated with the risk of pancreatic cancer in two large cohort studies of men and women. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michaud, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Kresge 920,677 Huntington Ave, Boston, MA 02115 USA. EM dmichaud@hsph.harvard.edu RI Skinner, Halcyon/A-1049-2009; Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA86102, CA55075, CA87969, CA95589] NR 44 TC 52 Z9 54 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 6 PY 2005 VL 97 IS 7 BP 518 EP 524 DI 10.1093/jnci/dji094 PG 7 WC Oncology SC Oncology GA 953WT UT WOS:000231113100013 PM 15812077 ER PT J AU Sarnak, MJ Katz, R Stehman-Breen, CO Fried, LF Jenny, NS Psaty, BM Newman, AB Siscovick, D Shlipak, MG AF Sarnak, MJ Katz, R Stehman-Breen, CO Fried, LF Jenny, NS Psaty, BM Newman, AB Siscovick, D Shlipak, MG CA Cardio Hlth Study TI Cystatin C concentration as a risk factor for heart failure in older adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; EARLY RENAL IMPAIRMENT; MYOCARDIAL-INFARCTION; CARDIOVASCULAR OUTCOMES; SERUM CREATININE; ELDERLY PATIENTS; BLOOD-PRESSURE; INSUFFICIENCY; MARKER; DYSFUNCTION AB Background: Previous studies that evaluated the association of kidney function with incident heart failure may be limited by the insensitivity of serum creatinine concentration for detecting abnormal kidney function. Objective: To compare serum concentrations of cystatin C (a novel marker of kidney function) and creatinine as predictors of incident heart failure. Design: Observational study based on measurement of serum cystatin C from frozen sera obtained at the 1992-1993 visit of the Cardiovascular Health Study. Follow-up occurred every 6 months. Setting: Adults 65 years of age or older from 4 communities in the United States. Participants: 4384 persons without previous heart failure who had measurements of serum cystatin C and serum creatinine. Measurements: incident heart failure. Results: The mean ( +/- SD) serum concentrations of cystatin C and creatinine were 82 +/- 25 nmol/L (1.10 +/- 0.33 mg/L) and 89 +/- 34 mu mol/L (1.01 +/- 0.39 mg/dL, respectively. During a median follow-up of 8.3 years (maximum, 9.1 years), 763 (17%) participants developed heart failure. After adjustment for demographic factors, traditional and novel cardiovascular risk factors, cardiovascular disease status, and medication use, sequential quintiles of cystatin C concentration were associated with a stepwise increased risk for heart failure in Cox proportional hazards models (hazard ratios, 1.0 [reference], 1.30 [95% Cl, 0.96 to 1.75], 1.44 [CI, 1.07 to 1.94], 1.58 [CI, 1.18 to 2.12], and 2.16 [CI, 1.61 to 2.91]). In contrast, quintiles of serum creatinine concentration were not associated with risk for heart failure in adjusted analysis (hazard ratios, 1.0 [reference], 0.77 [Cl, 0.59 to 1.01), 0.85 [CI, 0.64 to 1.131, 0.97 [Cl, 0.72 to 1.29], and 1.14 [CI, 0.87 to 1.491). Limitations: The mechanism by which cystatin C concentration predicts risk for heart failure remains unclear. Conclusions: The cystatin C concentration is an independent risk factor for heart failure in older adults and appears to provide a better measure of risk assessment than the serum creatinine concentration. C1 Tufts New England Med Ctr, Boston, MA USA. Collaborat Hlth Studies Coordinating Ctr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Vermont, Burlington, VT USA. RP Shlipak, MG (reprint author), Vet Affairs Med Ctr 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM shlip@itsa.ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01 HC-15103, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-35129, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, R01 HL073208-01]; NIDDK NIH HHS [K23 DK67303] NR 40 TC 197 Z9 214 U1 1 U2 6 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 APR 5 PY 2005 VL 142 IS 7 BP 497 EP 505 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 913QL UT WOS:000228167800003 PM 15809461 ER PT J AU Li, ZP Maglione, M Tu, WL Mojica, W Arterburn, D Shugarman, LR Hilton, L Suttorp, M Solomon, V Shekelle, PG Morton, SC AF Li, ZP Maglione, M Tu, WL Mojica, W Arterburn, D Shugarman, LR Hilton, L Suttorp, M Solomon, V Shekelle, PG Morton, SC TI Meta-analysis: Pharmacologic treatment of obesity SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; TYPE-2 DIABETIC-PATIENTS; LONG-TERM MAINTENANCE; WEIGHT-LOSS; DOUBLE-BLIND; BODY-WEIGHT; CLINICAL-TRIALS; US ADULTS AB Background: in response to the increase in obesity, pharmacologic treatments for weight loss have become more numerous and more commonly used. Purpose: To assess the efficacy and safety of weight loss medications approved by the U.S. Food and Drug Administration and other medications that have been used for weight loss. Data Sources: Electronic databases, experts in the field, and unpublished information. Study Selection: Up-to-date meta-analyses of sibutramine, phentermine, and diethylpropion were identified. The authors assessed in detail 50 studies of orlistat, 13 studies of fluoxetine, 5 studies of bupropion, 9 studies of topiramate, and 1 study each of sertraline and zonisamide. Meta-analysis was performed for all medications except sertraline, zonisamide, and fluoxetine, which are summarized narratively. Data Extraction: The authors abstracted information about study design, intervention, co-interventions, population, outcomes, and methodologic quality, as well as weight loss and adverse events from controlled trials of medication. Data Synthesis: All pooled weight loss values are reported relative to placebo. A meta-analysis of sibutramine reported a mean difference in weight loss of 4.45 kg (95% Cl, 3.62 to 5.29 kg) at 12 months. In the meta-analysis of orlistat, the estimate of the mean weight loss for orlistat-treated patients was 2.89 kg (Cl, 2.27 to 3.51 kg) at 12 months. A recent meta-analysis of phentermine and diethylpropion reported pooled mean differences in weight loss at 6 months of 3.6 kg (Cl, 0.6 to 6.0 kg) for phentermine-treated patients and 3.0 kg (Cl, -1.6 to 11.5 kg) for diethyl propion -treated patients. Weight loss in fluoxetine studies ranged from 14.5 kg of weight lost to 0.4 kg of weight gained at 12 or more months. For bupropion, 2.77 kg (Cl, 1.1 to 4.5 kg) of weight was lost at 6 to 12 months. Weight loss due to topiramate at 6 months was 6.5% (Cl, 4.8% to 8.3%) of pretreatment weight. With one exception, long-term studies of health outcomes were lacking. Significant side effects that varied by drug were reported. Limitations: Publication bias may exist despite a comprehensive search and despite the lack of statistical evidence for the existence of bias. Evidence of heterogeneity was observed for all metaanalyses. Conclusions: Sibutramine, orlistat, phentermine, probably diethylpropion, bupropion, probably fluoxetine, and topiramate promote modest weight loss when given along with recommendations for diet. Sibutramine and orlistat are the 2 most-studied drugs. C1 So Calif Evidence Based Practice Ctr, RAND Hlth Div, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Dept Vet Affairs, Cincinnati, OH USA. RP Li, ZP (reprint author), LA Vet Affairs Med Ctr, W111A,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 96 TC 389 Z9 401 U1 4 U2 44 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 APR 5 PY 2005 VL 142 IS 7 BP 532 EP 546 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 913QL UT WOS:000228167800007 PM 15809465 ER PT J AU Maggard, MA Shugarman, LR Suttorp, M Maglione, M Sugarman, HJ Livingston, EH Nguyen, NT Li, ZP Mojica, WA Hilton, L Rhodes, S Morton, SC Shekelle, PG AF Maggard, MA Shugarman, LR Suttorp, M Maglione, M Sugarman, HJ Livingston, EH Nguyen, NT Li, ZP Mojica, WA Hilton, L Rhodes, S Morton, SC Shekelle, PG TI Meta-analysis: Surgical treatment of obesity SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID VERTICAL BANDED GASTROPLASTY; QUALITY-OF-LIFE; ROUX-EN-Y; GASTRIC BYPASS-SURGERY; INDUCED WEIGHT-LOSS; MORBID-OBESITY; BARIATRIC SURGERY; LONG-TERM; RANDOMIZED-TRIAL; SUBJECTS SOS AB Background: controversy exists regarding the effectiveness of surgery for weight loss and the resulting improvement in healthrelated outcomes. Purpose: To perform a meta-analysis of effectiveness and adverse events associated with surgical treatment of obesity. Data Sources: MEDLINE, EMBASE, Cochrane Controlled Trials Register, and systematic reviews. Study Selection: Randomized, controlled trials; observational studies; and case series reporting on surgical treatment of obesity. Data Extraction: Information about study design, procedure, population, comorbid conditions, and adverse events. Data Synthesis: The authors assessed 147 studies. Of these, 89 contributed to the weight loss analysis, 134 contributed to the mortality analysis, and 128 contributed to the complications analysis. The authors identified 1 large, matched cohort analysis that reported greater weight loss with surgery than with medical treatment in individuals with an average body mass index (BMI) of 40 kg/m(2) or greater. Surgery resulted in a weight loss of 20 to 30 kg, which was maintained for up to 10 years and was accompanied by improvements in some comorbid conditions. For BMIs of 35 to 39 kg/m(2), data from case series strongly support superiority of surgery but cannot be considered conclusive. Gastric bypass procedures result in more weight loss than gastroplasty. Bariatric procedures in current use (gastric bypass, laparoscopic adjustable gastric band, vertical banded gastroplasty, and biliopancreatic diversion and switch) have been performed with an overall mortality rate of less than 1%. Adverse events occur in about 20% of cases. A laparoscopic approach results in fewer wound complications than an open approach. Limitations: only a few controlled trials were available for analysis. Heterogeneity was seen among studies, and publication bias is possible. Conclusions: Surgery is more effective than nonsurgical treatment for weight loss and control of some comorbid conditions in patients with a BMI of 40 kg/m(2) or greater. More data are needed to determine the efficacy of surgery relative to nonsurgical therapy for less severely obese people. Procedures differ in efficacy and incidence of complications. C1 Univ Calif Los Angeles, Med Ctr, Dept Surg, Los Angeles, CA 90095 USA. So Calif Evidence Based Practice Ctr, RAND Hlth Div, Santa Monica, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Surg, CHS Room 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu NR 94 TC 787 Z9 806 U1 6 U2 53 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 APR 5 PY 2005 VL 142 IS 7 BP 547 EP 559 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 913QL UT WOS:000228167800008 PM 15809466 ER PT J AU Aoyama, T Matsui, T Novikov, M Park, J Hemmings, B Rosenzweig, A AF Aoyama, T Matsui, T Novikov, M Park, J Hemmings, B Rosenzweig, A TI Serum and glucocorticoid-responsive kinase-1 regulates cardiomyocyte survival and hypertrophic response SO CIRCULATION LA English DT Article DE apoptosis; hypertrophy; signal transduction ID GLYCOGEN-SYNTHASE KINASE-3-BETA; PHOSPHOINOSITIDE 3-KINASE PATHWAY; PROTEIN-KINASE; CARDIAC-HYPERTROPHY; SIGNALING PATHWAY; ORGAN GROWTH; IN-VITRO; AKT; HEART; SGK AB Background - Serum- and glucocorticoid-responsive kinase-1 (SGK1), a serine-threonine kinase that is highly expressed in the heart, has been previously reported to regulate sodium channels. Because SGK1 is a PI 3-kinase - dependent kinase with structural homology to Akt, we examined its regulation in the heart and its effects on cardiomyocyte ( CM) apoptosis and hypertrophy in vitro. Methods and Results - Rats were subjected to aortic banding, and expression of total and phosphorylated SGK1 was examined. Both phospho- and total SGK1 increased 2 to 7 days after banding. Phospho- SGK1 was also upregulated in CMs stimulated in vitro with IGF-I or phenylephrine. Infection of CMs with an adenoviral vector encoding constitutively active SGK1 ( Ad. SGK1. CA) inhibited apoptosis after serum-deprivation or hypoxia ( P < 0.05), whereas expression of kinase-dead SGK1 ( Ad. SGK1. KD) increased it and partially mitigated the protective effects of IGF-I ( P < 0.05). SGK1 activation was also sufficient to increase cell size, protein synthesis, sarcomere organization, and ANF expression both at baseline and in response to phenylephrine but was not necessary for the hypertrophic response to phenylephrine. Evaluation of potential downstream signaling pathways demonstrated that SGK1 induces phosphorylation of tuberin, p70s6kinase, and GSK3 beta in CMs, which may contribute to its effects. Conclusions - SGK1 is dynamically regulated during acute biomechanical stress in the heart and inhibits CM apoptosis while enhancing the hypertrophic response. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Cardiovasc Gene Therapy, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Friedrich Miescher Inst, CH-4002 Basel, Switzerland. RP Rosenzweig, A (reprint author), MGH, 114 16th St,Room 2600, Charlestown, MA 02129 USA. EM arosenzweig@partners.org RI Park, Jongsun/E-7465-2010 OI Park, Jongsun/0000-0002-4690-1854 FU NHLBI NIH HHS [HL-04250, HL-073363, HL-59521, HL-61557] NR 34 TC 76 Z9 79 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1652 EP 1659 DI 10.1161/01.CIR.0000160352.58142.06 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900012 PM 15795328 ER PT J AU Mably, JD Chen, JN Mohideen, MAP Fishman, MC AF Mably, JD Chen, JN Mohideen, MAP Fishman, MC TI Patterning of myocardial growth is regulated by the novel endocardial genes heart of glass, santa, and valentine SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Penn State Univ, Coll Med, Hershey, PA USA. Novartis Inst Biomed Res Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1721 EP 1721 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900032 ER PT J AU Arany, ZP He, HM Lin, JD Hoyer, K Schoen, FJ Ingwall, J Spiegelman, B AF Arany, ZP He, HM Lin, JD Hoyer, K Schoen, FJ Ingwall, J Spiegelman, B TI The transcriptional coactivator PGC-1 alpha regulates cardiac mitochondrial function and dictates the supply of ATP available for contractile reserve SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1722 EP 1722 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900040 ER PT J AU Mann, DL AF Mann, DL TI Clinical evaluation of the CorCap Cardiac Support Device in patients with dilated cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1725 EP 1725 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900051 ER PT J AU Whang, W Albert, CM Sears, SF Lampert, R Conti, JB Wang, PJ Singh, JP Ruskin, JN Muller, JE Mittleman, MA AF Whang, W Albert, CM Sears, SF Lampert, R Conti, JB Wang, PJ Singh, JP Ruskin, JN Muller, JE Mittleman, MA CA TOVA Study Investigators TI Depression as a predictor for appropriate shocks among patients with Implantable cardioverter-defibrillators - Results from the Triggers of Ventricular Arrhythmias (TOVA) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-LIFE; SUDDEN CARDIAC DEATH; INTRAVENOUS AMIODARONE; MAJOR DEPRESSION; FATTY-ACIDS; RISK; SYMPTOMS; MORTALITY; ICD AB OBJECTIVES We sought to examine the relationship between symptoms of depression and shock-treated ventricular arrhythmias among implantable cardioverter-defibrillator (ICD) patients. BACKGROUND Depression predicts mortality in patients with coronary artery disease (CAD), but whether this is via an increased risk of fatal ventricular arrhythmias is unclear. METHODS We prospectively analyzed data on symptoms of depression and risk of ventricular arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) resulting in ICD discharge in the Triggers of Ventricular Arrhythmias (TOVA) study. Symptoms were assessed by the Center for Epidemiologic Studies-Depression (CES-D) scale. Scores of 16 to 26 and >= 27 represented mild and moderate/severe depression, respectively. The Cox and Anderson-Gin proportional hazards models were used to test for associations among all patients and patients with CAD. RESULTS Among 645 patients with baseline assessments, 90 (14%) were mildly depressed and 25 (3.9%) were moderately to severely depressed. Moderate/severe depression was associated with time to first shock for VT/VF (hazard ratio [HR] 3.2, 95% confidence interval [CI] 1.1 to 9.9) and all shocks for VT/VF including recurrent episodes (HR 3.2, 95% CI 1.2 to 8.6). Among the 476 CAD patients, the association with time to first shock (HR 6.4, 95% CI 1.9 to 21.1) and an shocks (HR 8.3, 95% CI 2.9 to 23.3) remained. The risk of shock for VT/VF was associated with depression severity in the total population (p for trend = 0.02) and among patients with CAD (p < 0.01), even after controlling for multiple confounders. CONCLUSIONS More severe symptoms of depression predict shocks for VT/VF among ICD patients. The elevated risk of VT/VF among patients with CAD and depression suggests that arrhythmia may contribute significantly to total mortality in this subgroup. (c) 2005 by the American College of Cardiology Foundation. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Univ Florida, Hlth Sci Ctr, Gainesville, FL 32611 USA. Yale Univ, New Haven Med Ctr, New Haven, CT 06520 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. RP Whang, W (reprint author), Massachusetts Gen Hosp, Div Cardiol, Mailstop GRB 109,55 Fruit St, Boston, MA 02114 USA. EM wwhang@partners.org OI sears, samuel/0000-0002-7863-3591 FU NHLBI NIH HHS [HL 041016] NR 37 TC 120 Z9 121 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 5 PY 2005 VL 45 IS 7 BP 1090 EP 1095 DI 10.1016/j.jacc.2004.12.053 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 912CU UT WOS:000228055500020 PM 15808769 ER PT J AU Pirard, S Sharon, E Kang, SK Angarita, GA Gastfriend, DR AF Pirard, S Sharon, E Kang, SK Angarita, GA Gastfriend, DR TI Prevalence of physical and sexual abuse among substance abuse patients and impact on treatment outcomes SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE physical abuse; sexual abuse; substance use disorder; outcomes; treatment ID POSTTRAUMATIC-STRESS-DISORDER; ADDICTION SEVERITY INDEX; DRUG-TREATMENT OUTCOMES; CHILDHOOD TRAUMA; CHEMICAL DEPENDENCY; HISTORY; WOMEN; INPATIENTS; ASSAULT; PTSD AB More than half of substance abusers entering addiction treatment report a history of physical or sexual abuse. It is unclear if such a history impacts treatment outcomes. This one-year follow-up study of 700 substance abusers sought to clarify the relationship between lifetime physical and/or sexual abuse and addiction treatment outcome to help address the specific needs of this population. To achieve this goal, baseline characteristics, no-show for treatment status, post-treatment clinical outcomes, and treatment history were studied for subjects with lifetime history of abuse (47.3%) versus without. Abused subjects, predominantly women, were significantly more impaired at baseline on clinical dimensions including family/social severity and psychiatric severity as measured by the Addiction Severity Index (ASI), and general level of functioning. The two groups endorsed different drugs as primary, with the abused group less frequently endorsing heroin and cocaine in favor of alcohol and polydrug use. Abused subjects reported more prior medical and psychiatric treatments. Abuse history was not a predictor of no-show for treatment. Over the 1-year follow-up, lifetime physical and/or sexual abuse was significantly associated with worse psychiatric status and more psychiatric hospitalizations and outpatient treatment despite receiving similar intensive addiction treatment. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Addict Res Program, Boston, MA 02115 USA. Univ Liege, Dept Psychiat, B-4000 Cointe Ougree, Belgium. RP Pirard, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM spirard@partners.org FU NIDA NIH HHS [K24-DA0042, R01-DA08781] NR 35 TC 41 Z9 42 U1 2 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 4 PY 2005 VL 78 IS 1 BP 57 EP 64 DI 10.1016/j.drugalcep.2004.09.005 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 911LR UT WOS:000228004500006 PM 15769558 ER PT J AU Hirakawa, S Kodama, S Kunstfeld, R Kajiya, K Brown, LF Detmar, M AF Hirakawa, S Kodama, S Kunstfeld, R Kajiya, K Brown, LF Detmar, M TI VEGF-A induces tumor and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TRANSGENIC MICE; FACTOR-C; CANCER METASTASIS; ANGIOGENESIS; CELLS; SKIN; EXPRESSION; INDUCTION; RECEPTOR AB The mechanisms of tumor metastasis to the sentinel lymph nodes are poorly understood. Vascular endothelial growth factor ( VEGF)-A plays a principle role in tumor progression and angiogenesis; however, its role in tumor-associated lymphangiogenesis and lymphatic metastasis has remained unclear. We created transgenic mice that overexpress VEGF-A and green fluorescent protein specifically in the skin, and subjected them to a standard chemically-induced skin carcinogenesis regimen. We found that VEGF-A not only strongly promotes multistep skin carcinogenesis, but also induces active proliferation of VEGF receptor-2-expressing tumor-associated lymphatic vessels as well as tumor metastasis to the sentinel and distant lymph nodes. The lymphangiogenic activity of VEGF-A-expressing tumor cells was maintained within metastasis-containing lymph nodes. The most surprising finding of our study was that even before metastasizing, VEGF-A-overexpressing primary tumors induced sentinel lymph node lymphangiogenesis. This suggests that primary tumors might begin preparing their future metastatic site by producing lymphangiogenic factors that mediate their efficient transport to sentinel lymph nodes. This newly identified mechanism of inducing lymph node lymphangiogenesis likely contributes to tumor metastasis, and therefore, represents a new therapeutic target for advanced cancer and/or for the prevention of metastasis. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Immunobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM michael.detmar@pharma.ethz.ch FU NCI NIH HHS [CA69184, CA86410, CA92644, P01 CA092644, R01 CA069184, R01 CA086410] NR 39 TC 412 Z9 434 U1 1 U2 15 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 4 PY 2005 VL 201 IS 7 BP 1089 EP 1099 DI 10.1084/jem.20041896 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300010 PM 15809353 ER PT J AU Jin, JK Choi, JK Wasco, W Buxbaum, JD Kozlowski, PB Carp, RI Kim, YS Choi, EK AF Jin, JK Choi, JK Wasco, W Buxbaum, JD Kozlowski, PB Carp, RI Kim, YS Choi, EK TI Expression of calsenilin in neurons and astrocytes in the Alzheimer's disease brain SO NEUROREPORT LA English DT Article DE apoptosis; calsenilin; caspase-3; reactive astrocytes ID PRESENILIN-1; CALSENILIN/DREAM/KCHIP3; SUBSTRATE; INTERACTS; FRAGMENT; PROTEIN; FAMILY; MICE AB Calsenilin, a multifunctional Ca2+-binding protein, has been identified as an Alzheimer's disease-associated presenilin interactor. Here, we investigated the histochemical localization of calsenilin and its expression levels in the brains of sporadic Alzheimer's disease. Both messenger RNA and protein expression of calsenilin were observed in neurons of the cerebral cortex and hippocampus of control brains, and more intense staining was in Alzheimer's disease brains. Although calsenilin is primarily expressed in neurons, its immunoreactivity was also detected in reactive astrocytes of the Alzheimer's disease brains. In Alzheimer's disease brains, the caspase-derived fragment of calsenilin was only detected in cytosolic fraction. Our findings suggest that calsenilin overexpression in both neurons and reactive astrocytes may play an important role in apoptosis and in Alzheimer's disease pathology. (c) 2005 Lippincott Williams C Wilkins. C1 Hallym Univ, Ilsong Inst Life Sci, Anyang 431060, Kyonggi Do, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. CUNY Mt Sinai Sch Med, Lab Mol Neuropsychiat, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Lab Mol Neuropsychiat, Dept Neurobiol, New York, NY 10029 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. RP Choi, EK (reprint author), Hallym Univ, Ilsong Inst Life Sci, 1605-4 Gwanyang Dong, Anyang 431060, Kyonggi Do, South Korea. EM ekchoi@hallym.ac.kr OI Buxbaum, Joseph/0000-0001-8898-8313 NR 21 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 4 PY 2005 VL 16 IS 5 BP 451 EP 455 DI 10.1097/00001756-200504040-00007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 912ZK UT WOS:000228119000007 PM 15770150 ER PT J AU Kim, S Hohrmann, JL Clark, S Munoz, KN Braun, JE Doshi, A Radeos, MS Camargo, CA AF Kim, S Hohrmann, JL Clark, S Munoz, KN Braun, JE Doshi, A Radeos, MS Camargo, CA TI A multicenter study of complementary and alternative medicine usage among ED patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY, 2003 CL BOSTON, MA SP Soc Acad Emergency Med DE complementary and; alternative medicine; emergency department ID EMERGENCY-DEPARTMENT PATIENTS; HERB-DRUG INTERACTIONS AB Objectives: To estimate the prevalence of complementary and alternative medicine (CAM) usage among emergency department (ED) patients. Methods: This study was a cross-sectional study in four Boston-area EDs. For two 24-hour periods, the authors interviewed consecutive patients age 18 and older about whether they had ever used or had recently (within the past year) used CAM "remedies" (e.g., herbal treatments) or "therapies" (e.g., chiropractic). The authors also asked about the patient's disclosure of CAM usage to allopathic health care providers. Results: Of 978 patients, 752 patients were eligible. Among these, 539 (72%) were interviewed. Of these patients, ever having used CAM was reported by 57% (95% CI = 52% to 61%), and 37% (95% CI = 33% to 41%) reported use in the past year. In a multivariate model of recent CAM usage, independent predictors were younger age, higher education level, and chronic pain. Patients who spoke Spanish as their primary language were less likely to report CAM usage. Disclosure of CAM usage to allopathic providers was low, yet > 80% reported that they would be comfortable discussing their CAM usage with allopathic providers. Conclusions: CAM usage was. common among ED patients enrolled in our study, despite underreporting to ED staff. Given the growing evidence of benefits and hazards from popular CAM remedies and therapies, ED staff should consider raising this health, issue with their patients. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Lincoln Med & Mental Hlth Ctr, Dept Emergency Med, New York, NY USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 10 TC 8 Z9 9 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD APR PY 2005 VL 12 IS 4 BP 377 EP 380 DI 10.1197/j.aem.2005.02.008 PG 4 WC Emergency Medicine SC Emergency Medicine GA 913YA UT WOS:000228190300018 PM 15805333 ER PT J AU Mueller, W Lass, U Wellmann, S Kunitz, F von Deimling, A AF Mueller, W Lass, U Wellmann, S Kunitz, F von Deimling, A TI Mutation analysis of DKK1 and in vivo evidence of predominant p53-independent DKK1 function in gliomas SO ACTA NEUROPATHOLOGICA LA English DT Article DE DKK1; p53; mutation analysis; glioma ID BETA-CATENIN GENE; WNT ANTAGONIST; DICKKOPF-1; APOPTOSIS; CANCER; P53; CARCINOMAS; EXPRESSION; PATHWAY; CELLS AB DKK1 protein belongs to a family of inhibitors of the Wnt/beta 1-catenin signaling pathway. Sporadic mutations affecting almost each major player of the Wnt/beta 1-catenin pathway have been described in a variety of human carcinomas. DKK1 translation can be induced by p53, thereby linking TP53 and Wnt/beta 1-catenin signaling pathways. These findings raise questions in regard to human gliomas, which similar to carcinomas carry a high rate of mutations in TP53. To analyze DKK1 for its role in initiation or progression, we screened a series of 73 brain tumors for structural alterations in the entire coding sequence by single-strand conformation polymorphism and direct sequencing. While several sequence variants were detected, there were no obvious mutations affecting DKK1. Further, we analyzed the prevalence of mRNA from TP53, DKK1 and CTNNB1 and of p53 and beta 1-catenin protein in a series of human gliomas with and without mutations in TP53. Transcription and expression of CTNNB1/beta 1-catenin and DKK1 proved to be independent of TP53/p53. These data support in vivo function of DKK1, independent of p53, in human gliomas with no major impact on their pathogenesis. C1 Humboldt Univ, Charite, Dept Neuropathol, D-13353 Berlin, Germany. Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Humboldt Univ, Charite, Dept Pediat Oncol Hematol, D-13353 Berlin, Germany. RP von Deimling, A (reprint author), Humboldt Univ, Charite, Dept Neuropathol, Augustenburger Pl 1, D-13353 Berlin, Germany. RI von Deimling, Andreas/F-7774-2013; Wellmann, Sven/A-2771-2017 OI von Deimling, Andreas/0000-0002-5863-540X; NR 36 TC 5 Z9 8 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2005 VL 109 IS 3 BP 314 EP 320 DI 10.1007/s00401-004-0969-1 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 919SM UT WOS:000228637900010 PM 15668788 ER PT J AU Kreiger, PA Okada, Y Simon, S Rorke, LB Louis, DN Golden, JA AF Kreiger, PA Okada, Y Simon, S Rorke, LB Louis, DN Golden, JA TI Losses of chromosomes 1p and 19q are rare in pediatric oligodendrogliomas SO ACTA NEUROPATHOLOGICA LA English DT Article DE chromosome 1p; chromosome 19q; fluorescence in situ hybridization; oligodendroglioma; pediatric ID ARMS 1P; PREDICTORS; DIAGNOSIS; SURVIVAL AB Pediatric oligodendrogliomas are rare neoplasms and have not been characterized extensively either pathologically or genetically. Given the recent interest in the significance of chromosomal losses in predicting the clinical course and in establishing uniform diagnoses of adult oligodendrogliomas, we reviewed the pathological and clinical features of a series of pediatric oligodendrogliomas and determined their 1p and 19q status using fluorescence in situ hybridization. Of 19 tumors originally diagnosed as oligodendroglioma, 7 were oligodendroglioma, 3 were anaplastic oligodendroglioma, 3 were oligoastrocytoma, and 6 were reclassified. Only one tumor, an anaplastic oligodendroglioma, had 1p loss; none had 19q loss. The single patient whose tumor had 1p loss did not have a particularly favorable clinical course. These results suggest that pediatric oligodendrogliomas arise by molecular alterations distinct from adult oligodendrogliomas, and such molecular alterations do not hold immediate promise as an adjunct to the diagnosis of pediatric oligodendrogliomas. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Res Ctr,Dept Pathol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Canc, Boston, MA 02115 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Neurosurg, Philadelphia, PA 19104 USA. RP Golden, JA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Abramson Res Ctr,Dept Pathol, Rm 516,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM goldenj@mail.med.upenn.edu FU NCI NIH HHS [CA57683] NR 15 TC 59 Z9 60 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2005 VL 109 IS 4 BP 387 EP 392 DI 10.1007/s00401-004-0976-2 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 924SK UT WOS:000229000400005 PM 15739101 ER PT J AU Androudi, S Ahmed, M Brazitikos, P Foster, CS AF Androudi, S Ahmed, M Brazitikos, P Foster, CS TI Valsalva retinopathy: diagnostic challenges in a patient with pars-planitis SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE vitreous hemorrhage; pars planitis; valsalva retinopathy ID LABOR AB Purpose: To describe a case of Valsalva retinopathy in a patient with parsplanitis and to discuss its management Methods: We present a case of a 19-year-old male with a six-month history of bilateral intermediate uveitis, referred for evaluation of recent-onset spontaneous bilateral vitreous hemorrhages. Clinical evaluation and fluorescein angiography were negative for the presence of neovascularization. On closer questioning the patient revealed that he had his most recent symptoms after heavy weight lifting. Results: The patient was instructed to avoid heavy weight lifting. Over the next two months, vitreal hemorrhages had resolved. However, despite the treatment with systemic prednisone, the patient's intermediate uveitis was still active, and cystoid macular edema had developed. Therefore, we proceeded to systemic immunomodulatory therapy, which controlled the inflammation and preserved vision in each eye. Conclusions: Although a very rare cause, Valsalva maneuver should be included in the differential diagnosis of bilateral vitreous hemorrhages. Ophthalmologists should advise patients with known eye problems that can predispose to vitreal hemorrhages to refrain from it. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst,Sch Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Fdn, Massachusetts Eye Res & Surg Inst,Sch Med, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 11 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD APR PY 2005 VL 83 IS 2 BP 256 EP 257 DI 10.1111/j.1600-0420.2005.00456.x PG 2 WC Ophthalmology SC Ophthalmology GA 910ZB UT WOS:000227969600023 PM 15799745 ER PT J AU Placha, G Canani, LH Warram, JH Krolewski, AS AF Placha, G Canani, LH Warram, JH Krolewski, AS TI Evidence for different susceptibility genes for proteinuria and ESRD in type 2 diabetes SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE diabetic kidney disease; type 2 diabetes; genetics; proteinuria; end-stage renal disease ID OXIDE SYNTHASE GENE; URINARY ALBUMIN EXCRETION; STAGE RENAL-DISEASE; APOLIPOPROTEIN EPSILON-2 ALLELE; NITRIC-OXIDE; LINKAGE ANALYSIS; PIMA-INDIANS; MICROVASCULAR COMPLICATIONS; FAMILIAL PREDISPOSITION; AFRICAN-AMERICANS AB Proteinuria and impaired kidney function are 2 major traits of diabetic nephropathy that aggregate (are heritable) in families of diabetic individuals. Although both traits are heritable, they are not genetically correlated. These findings not only support the hypothesis that the development of diabetic nephropathy consists of 2 distinct disease processes (ie, increasing proteinuria and declining kidney function) but also strongly justify searches for the putative genes that separately determine variation in these processes. These searches have used both genome-wide scans and candidate-gene approaches. By use of genome-scan approaches, several research groups have identified genetic regions on chromosomes 7q, 18q, and 22q that harbor genes that determine either variation in urinary albumin excretion or susceptibility to proteinuria in families who have type 2 diabetes. The evidence for linkage in these 3 genetic regions was suggestive or strong, but, except for 7q, the regions did not overlap across studies. Two genome scans performed in families who have type 2 diabetes identified genetic regions on chromosome 3q, 6q, 7p, and 18q that harbor susceptibility genes that determine variation in glomerular filtration rate or susceptibility to the development of end-stage renal disease (ESRD). The region on 7p overlapped in both studies. Optimism is growing that a positional cloning approach applied to these putative genetic regions will lead to the isolation of the susceptibility genes for proteinuria and ESRD. Meanwhile, significant efforts that make use of the candidate-gene approach have been directed to the search for susceptibility genes for diabetic nephropathy. Unfortunately, positive findings have not been consistent. (c) 2005 by the National Kidney Foundation, Inc. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Fed Rio Grande Sul, Hosp Clin Porto Alegre, Div Endocrine, Porto Alegre, RS, Brazil. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU NIDDK NIH HHS [DK-58549, DK-67638] NR 69 TC 50 Z9 51 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2005 VL 12 IS 2 BP 155 EP 169 DI 10.1053/j.ackd.2005.02.002 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 920RS UT WOS:000228708400005 PM 15822051 ER PT J AU Williams, ME Tuttle, KR AF Williams, ME Tuttle, KR TI The next generation of diabetic nephropathy therapies: An update SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE diabetic nephropathy; sulodexide; pyridoxamine; advanced glycation end-product inhibition; protein kinase C inhibition; novel therapies ID PROTEIN-KINASE-C; GLYCATION END-PRODUCTS; PKC-BETA INHIBITOR; MESANGIAL CELLS; OXIDATIVE STRESS; VASCULAR-DISEASE; RANDOMIZED-TRIAL; RENAL-DISEASE; CROSS-LINKS; RATS AB Although treatments for diabetic kidney disease are available, many patients still have progressive disease. More effective therapies are urgently needed. Novel agents currently under evaluation in clinical trials are described in this review. Sulodexide, a mixture of three glycosaminoglycans, appears to prevent diabetic nephropathy in experimental models by ameliorating abnormalities in the glomerular basement membrane and mesangial matrix. Pyridoxamine is an inhibitor of advanced glycation end-product (AGE) formation derived from vitamin B-6.. Alagebrium is an AGE cross-link breaker. AGEs injure the kidneys and other vascular targets by mechanisms such as oxidative stress, inflammation, and protein cross-linking, among others. By inhibiting AGE formation or breaking AGE cross-links, experimental models have demonstrated kidney protection. Ruboxistaurin is an inhibitor of protein kinase C beta (PKC-beta), a mediator of signal transduction that leads to cell growth, fibrosis, and tissue injury. In diabetes, PKC-beta is up-regulated and activated in the kidney. Ruboxistaurin prevents diabetic kidney disease in animal models. These agents have appeared promising (by reduction of albuminuria and preservation of kidney function) in phase 11 studies. To determine whether clinical outcomes (mortality, renal, and cardiovascular events) are improved beyond the current standard of care, phase III trials are planned. (c) 2005 by the National Kidney Foundation, Inc. C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. Heart Inst Spokane, Spokane, WA USA. Sacred Heart Med Ctr, Spokane, WA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 89 TC 20 Z9 24 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 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD APR PY 2005 VL 12 IS 2 BP 212 EP 222 DI 10.1053/j.ackd.2005.01.011 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 920RS UT WOS:000228708400011 PM 15822057 ER PT J AU Tsuang, D Simpson, KL Li, G Barnhart, RL Edland, SD Bowen, J McCormick, W Teri, L Nochlin, D Larson, EB Thompson, ML Leverenz, JB AF Tsuang, D Simpson, KL Li, G Barnhart, RL Edland, SD Bowen, J McCormick, W Teri, L Nochlin, D Larson, EB Thompson, ML Leverenz, JB TI Evaluation of selection bias in an incident-based dementia autopsy case series SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; selection bias; autopsy; dementia ID ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; LEWY BODIES; PREVALENCE; FREQUENCY; DIAGNOSIS; JAPANESE; SAMPLE AB Neuropathological (np) relative frequency estimates of dementia may be biased if the autopsied subjects are not representative of all dementia subjects within a target population. We identified characteristics that differed between autopsied and nonautopsied subjects from an incident-based dementia case series and compared autopsy-based estimates of the relative frequency of np diagnoses before and after adjusting for potential selection bias. Clinically demented subjects who were autopsied (n = 206), had died but were not autopsied (n = 271), were still alive (n = 71), or had dropped out of the study (n = 82) were included. Compared with non-autopsied subjects, autopsied subjects were more likely to be Caucasian, educated beyond high school, and married. They also tended to have a lower baseline Mini-Mental State Examination score and were more likely to have a clinical diagnosis of Alzheimer disease (AD) than non-autopsied subjects. Neuropathological AD with Lewy bodies (LB) had the largest crude relative frequency estimate at 38% of the autopsy sample, followed by 25% for AD with vascular lesions, 13% for pure AD, 13% for LB (with or without vascular lesions), and 8% for pure vascular pathologies. Adjustment for potential sources of selection bias had little effect on relative frequency estimates, suggesting that np diagnoses in the autopsied subjects provide reasonable dementia relative frequency estimates among all clinically demented cases in this series. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Mayo Clin & Mayo Fdn, Div Clin Epidemiol, Rochester, MN 55905 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. RP Tsuang, D (reprint author), VAPSHCS, 1660 S Columbian Way, Seattle, WA 98108 USA. EM dwt1@u.washington.edu RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU NIA NIH HHS [AG05136, AG06781, P50 AG005136, U01 AG006781]; NINDS NIH HHS [R01 NS048595, R01 NS48595] NR 19 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2005 VL 19 IS 2 BP 67 EP 73 DI 10.1097/01.wad.0000165507.67993.47 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 939FM UT WOS:000230057800003 PM 15942323 ER PT J AU Gomberg-Maitland, M Murphy, SA Moliterno, DJ Cannon, CP AF Gomberg-Maitland, M Murphy, SA Moliterno, DJ Cannon, CP TI Are we appropriately triaging patients with unstable angina? SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; CHEST-PAIN; GUARANTEE REGISTRY; CLINICAL-TRIAL; MANAGEMENT; UNIT; CARE; MULTICENTER AB Background It is uncertain how aggressively patients should be monitored and admitted to the hospital for chest pain syndromes and if the monitoring itself affects patient care, process, or outcomes. We assessed the appropriateness of care based on retrospective analysis of admission bed assignment (nonmonitored vs monitored) and Thrombolysis in Myocardial Infarction (TIMI) risk score in patients from the Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) Registry. Methods Baseline characteristics, process of care, and outcomes were compared among 2939 patients admitted to 1 of 35 hospitals in the United States. Patients were stratified into low (0-2), intermediate (3 or 4), and high (5-7) risk based on TIMI risk score. Results Among the patients, 92 (3%) were admitted to the cardiac care unit (CCU), 1602 (56%) were admitted to the telemetry unit, and 1163 (41%) were admitted to an unmonitored bed. Paradoxically, high-risk patients comprised only 1% of those in the CCU, 5% of those in telemetry, and 10% of those in nonmonitored units. Conversely, low-risk patients were 64% of those in the CCU, 53% of those in telemetry, and 42% of those in unmonitored beds. Procedures were done more often on patients admitted to nonmonitored units than those on telemetry or in the CCU irrespective of TIMI risk score. Conclusions This registry suggests that triage of patients does not routinely follow the risk-based approach suggested in the American College of Cardiology and American Heart Association guidelines and could therefore potentially lead to inefficiencies in care. Better implementation of risk stratification for acute coronary syndrome evaluation and management is necessary. C1 Univ Chicago Hosp, Cardiol Sect, Adv Heart Failure & Pulm Hypertens Program, Chicago, IL 60637 USA. Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Kentucky, Gill Heart Inst, Lexington, KY USA. Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA. RP Gomberg-Maitland, M (reprint author), Univ Chicago Hosp, Cardiol Sect, Adv Heart Failure & Pulm Hypertens Program, 5841 S Maryland Ave,MC 2016,Rm A621, Chicago, IL 60637 USA. EM mgomberg@medicine.bsd.uchicago.edu NR 23 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2005 VL 149 IS 4 BP 613 EP 618 DI 10.1016/j.ahj.2004.09.035 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 920VF UT WOS:000228717600008 PM 15990742 ER PT J AU Krauser, DG Lloyd-Jones, DM Chae, CU Cameron, R Anwaruddin, S Baggish, AL Chen, A Tung, R Januzzi, JL AF Krauser, DG Lloyd-Jones, DM Chae, CU Cameron, R Anwaruddin, S Baggish, AL Chen, A Tung, R Januzzi, JL TI Effect of body mass index on natriuretic peptide levels in patients with acute congestive heart failure: A ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) substudy SO AMERICAN HEART JOURNAL LA English DT Article ID OBESE HYPERTENSIVES; RECEPTOR GENE; EXPRESSION; PREDICTION; DIAGNOSIS; IMPACT; CREATININE; CLEARANCE; ADIPOSE; TISSUES AB Background Obesity is associated with lower B-type natriuretic peptide (BNP) levels in healthy individuals and patients with chronic congestive heart failure (CHF). Neither the mechanism of natriuretic peptide suppression in the obese patient nor whether obesity affects natriuretic peptide levels among patients with acute CHF is known. Methods The associations of amino-terminal pro-BNP (NT-prPBNP), BNP, and body mass index (BMI) were examined in 204 subjects with acute CHF. Multivariable regression analyses were performed to identify factors independently related to NT-proBNP and BNP levels. Results Across clinical strata of normal (<25 kg/m(2)), overweight (25-29.9 kg /m(2)), and obese (>= 30 kg /m(2)) patients, median NT-proBNP and BNP levels decreased with increasing BMI (both P values <.001). In multivariable analyses adjusting for covariates known to affect BNP levels, the inverse relationship between BMI and both NT-proBNP and BNP remained (P <.05 for both). Using a cut point of 900 pg/mL, NT-proBNP was falsely negative in up to 10% of CHF cases in overweight patients (25-29.9 kg/m(2)) and 15% in obese patients (>= 30 kg/m(2)). Using the standard cut point of 100 pg/mL, BNP testing was falsely negative in 20% of CHF cases in both overweight and obese patients. The assays for NT-proBNP and BNP exhibited similar overall sensitivity for the diagnosis of CHF. Conclusions When adjusted for relevant covariates, compared with normal counterparts, overweight and obese patients with acute CHIF have lower circulating NT-proBNP and BNP levels, suggesting a BMI-related defect in natriuretic peptide secretion. NT-proBNP fell below the diagnostic cutoff for CHF less often than BNP in overweight and obese individuals; however, when used as a diagnostic tool to identify CHF in such patients, both markers may have reduced sensitivity. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Bulfinch 019,55 Fruit St, Boston, MA 02114 USA. EM jjanuzzi@partners.org RI Lloyd-Jones, Donald/C-5899-2009 NR 23 TC 127 Z9 137 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2005 VL 149 IS 4 BP 744 EP 750 DI 10.1016/j.ahj.2004.07.010 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 920VF UT WOS:000228717600028 PM 15990762 ER PT J AU Fox, CS Evans, JC Larson, MG Lloyd-Jones, DM O'Donnell, CJ Sorlie, PD Manolio, TA Kannel, WB Levy, D AF Fox, CS Evans, JC Larson, MG Lloyd-Jones, DM O'Donnell, CJ Sorlie, PD Manolio, TA Kannel, WB Levy, D TI A comparison of death certificate out-of-hospital coronary heart disease death with physician-adjudicated sudden cardiac death SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID AUTOMATED EXTERNAL DEFIBRILLATORS; FRAMINGHAM; RISK AB The number of deaths due to out-of-hospital coronary heart disease as determined by death certificates was compared with the number physician-adjudicated sudden cardiac deaths in the Framingham Heart Study from 1950 to 1999. Out-of-hospital coronary heart disease deaths overestimated sudden cardiac death by 47%, suggesting that out-of-hospital coronary heart disease death rates derived from death certificates should be interpreted with caution. (c) 2005 by Excerpta Medica Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009; OI Larson, Martin/0000-0002-9631-1254 FU NHLBI NIH HHS [N01-HC-25195] NR 14 TC 39 Z9 39 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 2005 VL 95 IS 7 BP 856 EP 859 DI 10.1016/j.amjcard.2004.12.011 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 914MA UT WOS:000228230600008 PM 15781015 ER PT J AU Torriani, M Grinspoon, S AF Torriani, M Grinspoon, S TI Racial differences in fat distribution: the importance of intermuscular fat SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID ADIPOSE-TISSUE DISTRIBUTION; INSULIN-RESISTANCE; ABDOMINAL FAT; LIPODYSTROPHY; OBESITY C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Musculoskeletal Imaging, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 10 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2005 VL 81 IS 4 BP 731 EP 732 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 915CO UT WOS:000228275400001 PM 15817844 ER PT J AU Izikson, L Bhan, A Zembowicz, A AF Izikson, L Bhan, A Zembowicz, A TI Androgen receptor expression helps to differentiate basal cell carcinoma from benign trichoblastic tumors SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE basal cell carcinoma; trichoepithelioma; trichoblastoma; androgen receptor ID FOLLICULAR DIFFERENTIATION; TRICHOEPITHELIOMA; NEOPLASMS; GROWTH; SKIN AB Histologic differentiation between basal cell carcinoma and benign trichoblastic neoplasms such as trichoepithelioma and trichoblastoma can be difficult on small biopsies. Therefore, several attempts have been made to identify immunohistochemical differences between these entities. Recent studies have shown androgen receptor expression in a number of mature epithelial structures in the skin and in epithelial neoplasms including basal cell carcinoma. In contrast, androgen receptor expression was absent in mature hair follicles or the few trichogenic neoplasms studied to date. These findings suggested that androgen receptor expression might be a useful adjunct in the histologic differential diagnosis between basal cell carcinoma and benign trichoblastic neoplasms. Therefore, we performed immunohistochemical analysis of androgen receptor expression in 32 basal cell carcinomas and 10 benign trichoblastic tumors (6 trichoepitheliomas and 4 trichoblastomas). In our study, at least focal expression of androgen receptor was detected in 78% of basal cell carcinomas. None of the trichoblastic tumors showed any androgen receptor immunoreactivity. These results confirm the lack of expression of androgen receptor in benign trichoblastic neoplasms and indicate that androgen receptor expression by tumor cells points to basal cell carcinoma as the most likely diagnosis. C1 Massachusetts Gen Hosp, Dept Pathol, Dermatol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Med Ctr, Dept Dermatol, Pittsburgh, PA USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Dermatol Unit, Warren 820, Boston, MA 02114 USA. EM azembowicz@partners.org NR 19 TC 41 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 2005 VL 27 IS 2 BP 91 EP 95 DI 10.1097/01.dad.0000154392.92099.aa PG 5 WC Dermatology SC Dermatology GA 913GP UT WOS:000228139900001 PM 15798431 ER PT J AU Dulai, GS Shekelle, PG Jensen, DM Spiegel, BMR Chen, J Oh, D Kahn, KL AF Dulai, GS Shekelle, PG Jensen, DM Spiegel, BMR Chen, J Oh, D Kahn, KL TI Dysplasia and risk of further neoplastic progression in a regional veterans administration Barrett's cohort SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID COLUMNAR-LINED ESOPHAGUS; LOW-GRADE DYSPLASIA; FLOW-CYTOMETRY; CANCER-RISK; ENDOSCOPIC SURVEILLANCE; OBSERVER VARIATION; ADENOCARCINOMA; DIAGNOSIS; PREDICTORS; REPRODUCIBILITY AB OBJECTIVES: No published data are available on the risk of further neoplastic progression in Barrett's patients stratified by baseline dysplasia status. Our aims were to estimate and compare the risk of progression to high-grade dysplasia or cancer in groups of Barrett's patients stratified by baseline dysplasia status. METHODS: Consecutive Barrett's cases from 1988-2002 were identified via pathology databases in a regional VA health-care system and medical record data were abstracted. The risk of progression to high-grade dysplasia or cancer was measured and compared in cases with versus without low-grade dysplasia within 1 yr of index endoscopy using survival analysis. RESULTS: A total of 575 Barrett's cases had 2,775 patient-years of follow-up. There were 13 incident cases of high-grade dysplasia and two of cancer. The crude rate of high-grade dysplasia or cancer was 1 of 78 patient-years for those with baseline dysplasia versus 1 of 278 patient-years for those without (p = 0.001). One case of high-grade dysplasia in each group underwent successful therapy. One incident cancer case underwent successful resection and the other was unresectable. Two cases with high-grade dysplasia later developed cancer, one died postoperatively, the other was unresectable. When these two cases were included (total of four cancers), the crude rate of cancer was 1 of 274 patient-years for those with baseline dysplasia versus 1 of 1,114 patient-years for those without. CONCLUSIONS: In a large cohort study of Barrett's, incident malignancy was uncommon. The rate of progression to high-grade dysplasia or cancer was significantly higher in those with baseline low-grade dysplasia. These data may warrant reevaluation of current Barrett's surveillance strategies. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Sch Med,Dept Med, Div Gastroenterol,Div Gen Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, UCLA Ctr Study Digest Healthcare Qual & Outcomes, Dept Med,Div Digest Dis, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RAND Corp, Hlth, Santa Monica, CA USA. RP Dulai, GS (reprint author), Greater Los Angeles Vet Adm Healthcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, Bldg 115,Room 215C,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [K23 RR 1618801]; NIDDK NIH HHS [K24 DK 02650] NR 50 TC 67 Z9 68 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2005 VL 100 IS 4 BP 775 EP 783 DI 10.1111/j.1572-0241.2005.41300.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 907LU UT WOS:000227720400009 PM 15784018 ER PT J AU Tillisch, K Labus, JS Naliboff, BD Bolus, R Shetzline, M Mayer, EA Chang, L AF Tillisch, K Labus, JS Naliboff, BD Bolus, R Shetzline, M Mayer, EA Chang, L TI Characterization of the alternating bowel habit subtype in patients with irritable bowel syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID DIARRHEA-PREDOMINANT; SYMPTOMS; CONSTIPATION; SUBGROUPS; COMMUNITY; RESPONSES; PATTERNS; SAMPLES; IMPACT; WOMEN AB Background: Due to a wide range of symptom patterns, patients with irritable bowel syndrome (IBS) are often subgrouped by bowel habit. However, the IBS subgroup with alternating bowel habits (IBS-A) has been poorly characterized. Objectives: (I) To determine a set of bowel habit symptom criteria, which most specifically identifies IBS patients with an alternating bowel habit, (II) to describe IBS-A bowel symptom patterns, and (III) to compare clinical characteristics among IBS-A, constipation-predominant (IBS-C), and diarrhea-predominant IBS (IBS-D). Methods: One thousand one hundred and two Rome I positive IBS patients were analyzed. Three sets of potential criteria for IBS-A were developed and compared by multirater Kappa test. Gastrointestinal, psychological, extraintestinal symptoms, and health-related quality of life were compared in IBS-A, IBS-C, and IBS-D using 2 test and analysis of variance (ANOVA). Results: Stool consistency was determined to be the most specific criteria for alternating bowel habits. IBS-A patients reported rapid fluctuations in bowel habits with short symptom flares and remissions. There was a greater prevalence of psychological and extraintestinal symptoms in the IBS-A subgroup compared to IBS-C and IBS-D. No differences were seen between bowel habit subtypes in health-related quality of life. Conclusions: IBS-A patients have rapidly fluctuating symptoms and increased psychological comorbidity, which should be taken into account for clinical practice and clinical trials. C1 Univ Calif Los Angeles, CNS WH Ctr Neurovisceral Sci & Womens Hlth, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CNS WH Ctr Neurovisceral Sci & Womens Hlth, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CNS WH Ctr Neurovisceral Sci & Womens Hlth, Dept Psychiat & Behav Sci, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Nova Pharmaceut Corp, E Hanover, NJ USA. RP Tillisch, K (reprint author), Univ Calif Los Angeles, CNS WH Ctr Neurovisceral Sci & Womens Hlth, Dept Med, CURE Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [P50 DK64539] NR 29 TC 74 Z9 78 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2005 VL 100 IS 4 BP 896 EP 904 DI 10.1111/j.1572-0241.2005.41211.x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 907LU UT WOS:000227720400029 PM 15784038 ER PT J AU Johnston, JJ Olivos-Glander, I Killoran, C Elson, E Turner, JT Peters, KF Abbott, MH Aughton, DJ Aylsworth, AS Bamshad, MJ Booth, C Curry, CJ David, A Dinulos, MB Flannery, DB Fox, MA Graham, JM Grange, DK Guttmacher, AE Hannibal, MC Henn, W Hennekam, RCM Holmes, LB Hoyme, HE Leppig, KA Lin, AE MacLeod, P Manchester, DK Marcelis, C Mazzanti, L McCann, E McDonald, MT Mendelsohn, NJ Moeschler, JB Moghaddam, B Neri, G Newbury-Ecob, R Pagon, RA Phillips, JA Sadler, LS Stoler, JM Tilstra, D Vockley, CMW Zackai, EH Zadeh, TM Brueton, L Black, GCM Biesecker, LG AF Johnston, JJ Olivos-Glander, I Killoran, C Elson, E Turner, JT Peters, KF Abbott, MH Aughton, DJ Aylsworth, AS Bamshad, MJ Booth, C Curry, CJ David, A Dinulos, MB Flannery, DB Fox, MA Graham, JM Grange, DK Guttmacher, AE Hannibal, MC Henn, W Hennekam, RCM Holmes, LB Hoyme, HE Leppig, KA Lin, AE MacLeod, P Manchester, DK Marcelis, C Mazzanti, L McCann, E McDonald, MT Mendelsohn, NJ Moeschler, JB Moghaddam, B Neri, G Newbury-Ecob, R Pagon, RA Phillips, JA Sadler, LS Stoler, JM Tilstra, D Vockley, CMW Zackai, EH Zadeh, TM Brueton, L Black, GCM Biesecker, LG TI Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: Robust phenotype prediction from the type and position of GLI3 mutations SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID INTERSTITIAL DELETION; HYPOTHALAMIC HAMARTOMA; ACROCALLOSAL SYNDROME; POINT MUTATIONS; FAMILIES; DISEASE; MICRODELETION; DELINEATION; ANOMALIES; SPECTRUM AB Mutations in the GLI3 zinc-finger transcription factor gene cause Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS), which are variable but distinct clinical entities. We hypothesized that GLI3 mutations that predict a truncated functional repressor protein cause PHS and that functional haploinsufficiency of GLI3 causes GCPS. To test these hypotheses, we screened patients with PHS and GCPS for GLI3 mutations. The patient group consisted of 135 individuals: 89 patients with GCPS and 46 patients with PHS. We detected 47 pathological mutations ( among 60 probands); when these were combined with previously published mutations, two genotype- phenotype correlations were evident. First, GCPS was caused by many types of alterations, including translocations, large deletions, exonic deletions and duplications, small in-frame deletions, and missense, frameshift/ nonsense, and splicing mutations. In contrast, PHS was caused only by frameshift/ nonsense and splicing mutations. Second, among the frameshift/ nonsense mutations, there was a clear genotype- phenotype correlation. Mutations in the first third of the gene ( from open reading frame [ORF] nucleotides [nt] 1 - 1997) caused GCPS, and mutations in the second third of the gene ( from ORF nt 1998 - 3481) caused primarily PHS. Surprisingly, there were 12 mutations in patients with GCPS in the 3' third of the gene ( after ORF nt 3481), and no patients with PHS had mutations in this region. These results demonstrate a robust correlation of genotype and phenotype for GLI3 mutations and strongly support the hypothesis that these two allelic disorders have distinct modes of pathogenesis. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Cent Manchester Univ Hosp, Natl Hlth Serv Trust, St Marys Hosp, Dept Clin Genet, Manchester, Lancs, England. Manchester Childrens Univ Hosp, Natl Hlth Serv Trust, St Marys Hosp, Dept Clin Genet, Manchester, Lancs, England. Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Baltimore Huntington Dis Ctr, Dept Psychiat, Baltimore, MD USA. William Beaumont Hosp, Dept Pediat, Div Genet, Royal Oak, MI 48072 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Univ Utah, Hlth Sci Ctr, Eccles Inst Human Genet, Salt Lake City, UT USA. Lutheran Gen Hosp, Park Ridge, IL 60068 USA. Univ Calif, Fresno, CA USA. Ctr Hosp Univ, Serv Genet, Nantes, France. Dartmouth Coll, Childrens Hosp, Div Genet & Child Dev, Lebanon, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA USA. St Louis Childrens Hosp, Dept Pediat, Div Med Genet, St Louis, MO 63110 USA. Univ Washington, Childrens Hosp Reg Med Ctr, Div Genet & Dev Med, Seattle, WA 98195 USA. Univ Washington, Childrens Hosp Reg Med Ctr, Dept Pediat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Genet Serv, Seattle, WA 98121 USA. Univ Saarland, Inst Humangenet, Homburg, Germany. Univ Amsterdam, Childrens Acad Med Ctr, Div Emma Childrens Hosp, Amsterdam, Netherlands. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Pediat, Div Med Genet, Stanford, CA 94305 USA. Natl Birth Defects Ctr, Waltham, MA USA. Victoria Gen Hosp, Med Genet Sect, Victoria, BC, Canada. Childrens Hosp, Denver, CO 80218 USA. Univ Med Ctr Nijmegen, Dept Clin Genet, Nijmegen, Netherlands. SantOrsola Malpighi Hosp, Dept Pediat, Bologna, Italy. Royal Liverpool Childrens Hosp, Dept Clin Genet, Liverpool L7 7DG, Merseyside, England. Duke Univ, Med Ctr, Div Med Genet, Durham, NC USA. Childrens Hosp & Clin, Minneapolis, MN USA. Univ Oklahoma, Schusterman Ctr, HA Chapman Inst, Tulsa, OK USA. Univ Cattolica, Inst Med Genet, Rome, Italy. St Michaels Hosp, Dept Clin Genet, Bristol, Avon, England. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Childrens Hosp, Dept Pediat, Div Genet, Buffalo, NY 14222 USA. CentraCare Clin, Dept Pediat, St Cloud, MN USA. Mayo Fdn, Dept Med Genet, Rochester, MN USA. Childrens Hosp Philadelphia, Div Human Genet & Mol Biol, Philadelphia, PA 19104 USA. Genet Ctr, Orange, CA USA. Kennedy Galton Ctr, Dept Clin Genet, London, England. RP Johnston, JJ (reprint author), NHGRI, NIH, Bldg 49 Room 4B75,MSC4472,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jjohnsto@mail.nih.gov OI Black, Graeme/0000-0001-8727-6592 FU NICHD NIH HHS [HD22657-11, P01 HD022657]; NIGMS NIH HHS [GM08243, T32 GM008243] NR 49 TC 121 Z9 127 U1 2 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2005 VL 76 IS 4 BP 609 EP 622 DI 10.1086/429346 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 904RS UT WOS:000227516000007 PM 15739154 ER PT J AU Gutierrez, O Isakova, T Rhee, E Holmes, J AF Gutierrez, O Isakova, T Rhee, E Holmes, J TI FGF-23 and phosphate homeostasis in chronic kidney disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 04-08, 2005 CL Washington, DC SP Natl Kindney Fdn C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2005 VL 45 IS 4 MA 46 BP A28 EP A28 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 920VJ UT WOS:000228718000077 ER PT J AU Seliger, SL Sampson, J Kestenbaum, B Young, B Rudser, K Andress, DL Sherrard, DJ AF Seliger, SL Sampson, J Kestenbaum, B Young, B Rudser, K Andress, DL Sherrard, DJ TI Anemia and adverse outcomes in veterans with chronic kidney disease (CKD) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY MAY 04-08, 2005 CL Washington, DC SP Natl Kindney Fdn C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA USA. VA Puget Sound Healthcare Syst, Div Gen Internal Med, Seattle, WA USA. NR 0 TC 1 Z9 1 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2005 VL 45 IS 4 MA 120 BP A46 EP A46 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 920VJ UT WOS:000228718000151 ER PT J AU Jackson, GL Yano, EM Edelman, D Krein, SL Ibrahim, MA Carey, TS Lee, SYD Hartmann, KE Dudley, TK Weinberger, M AF Jackson, GL Yano, EM Edelman, D Krein, SL Ibrahim, MA Carey, TS Lee, SYD Hartmann, KE Dudley, TK Weinberger, M TI Veterans affairs primary care organizational characteristics associated with better diabetes control SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Review ID QUALITY-OF-CARE; BLOOD-GLUCOSE CONTROL; CHRONIC ILLNESS CARE; HEALTH-CARE; GLYCEMIC CONTROL; UNITED-STATES; PUBLIC-HEALTH; ADMINISTRATIVE DATA; MULTILEVEL MODELS; MEDICAL-RECORDS AB Objective: To examine organizational features of Veterans Affairs (VA) primary care programs hypothesized to be associated with better diabetes control, as indicated by hemoglobin A(1c) (HbA(1c)) levels. Study Design: Cross-sectional cohort. Methods: We established a cohort of 224 221 diabetic patients using the VA Diabetes Registry and Dataset and VA corporate databases. The 1999 VHA (Veterans Health Administration) Survey of Primary Care Practices results were combined with individual patient data. A 2-level hierarchical model was used to determine the relationship between organizational characteristics and HbA(1c) levels in 177 clinics with 82 428 cohort members. Results: The following attributes were associated with lower (better) HbA(1c) and were statistically significant at P < .05: greater authority to establish or implement clinical policies (lower by 0.21%), greater staffing authority (0.28%), computerized diabetes reminders (0.17%), notifying all patients of their assigned provider (0.21%), hiring needed new staff during fiscal year 1999 (0.18%), having nurses that report only to the program (0.16%), and being a large academic practice (0.27%). Associated with higher (worse) HbA(1c) were programs reporting that patients almost always see their assigned provider (greater by 0.18%), having a quality improvement program involving all nurses without all physicians (0.38%), having general internal medicine physicians report only to the program (0.20%), and being located at an acute care hospital (0.20%). Conclusion: Programs that are associated with better diabetes control simultaneously have teams that actively involve physicians in quality improvement, use electronic health information systems, have authority to respond to staffing and programmatic issues, and engage patients in care. C1 Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence Hlth Serv Res, HSR&D Serv 152, Durham, NC 27705 USA. Duke Univ, Div Gen Internal Med, Durham, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC USA. Univ N Carolina, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC USA. Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA. Vet Affairs Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev Ctr Excellence Study Healthca, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. Ann Arbor Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence Pratice Manage, Ann Arbor, MI USA. Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Jackson, GL (reprint author), Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev Ctr Excellence Hlth Serv Res, HSR&D Serv 152, 508 Fulton St, Durham, NC 27705 USA. EM georg_jackson@alumni.unc.edu RI Krein, Sarah/E-2742-2014 OI Krein, Sarah/0000-0003-2111-8131 FU AHRQ HHS [2T32HS000079-06] NR 89 TC 29 Z9 29 U1 0 U2 5 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 2005 VL 11 IS 4 BP 225 EP 237 PG 13 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 913YH UT WOS:000228191000004 PM 15839183 ER PT J AU Aujesky, D Auble, TE Yealy, DM Stone, RA Obrosky, DS Meehan, TP Graff, LG Fine, JM Fine, MJ AF Aujesky, D Auble, TE Yealy, DM Stone, RA Obrosky, DS Meehan, TP Graff, LG Fine, JM Fine, MJ TI Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE clinical prediction rule; community-acquired pneumonia ID MANAGEMENT; SEVERITY; ADULTS; GUIDELINES; TRIAL; ETIOLOGY; INTERVENTION; UPDATE; INDEX AB PURPOSE: We assessed the performance of 3 validated prognostic rules in predicting 30-day mortality in community-acquired pneumonia: the 20 variable Pneumonia Severity Index and the easier to calculate CURB (confusion, urea nitrogen, respiratory rate, blood pressure) and CURB-65 severity scores. SUBJECTS AND METHODS: We prospectively followed 3181 patients with community-acquired pneumonia from 32 hospital emergency departments (January-December 2001) and assessed mortality 30 days after initial presentation. Patients were stratified into Pneumonia Severity Index risk classes (I-V) and CURB (0-4) and CURB-65 (0-5) risk strata. We compared the discriminatory power (area under the receiver operating characteristic curve) of these rules to predict mortality and their accuracy based on sensitivity, specificity, predictive values, and likelihood ratios RESULTS: The Pneumonia Severity Index (risk classes I-III) classified a greater proportion of patients as low risk (68% [2152/3181]) than either a CURB score < 1 (51% [1635/3181]) or a CURB-65 score < 2 (61% [1952/3181]). Low-risk patients identified based on the Pneumonia Severity Index had a slightly lower mortality (1.4% [31/2152]) than patients classified as low-risk based on the CURB (1.7% [28/1635]) or the CURB-65 (1.7% [33/1952]). The area under the receiver operating characteristic curve was higher for the Pneumonia Severity Index (0.81) than for either the CURB (0.73) or CURB-65 (0.76) scores (P < 0.001, for each pairwise comparison). At comparable cut-points, the Pneumonia Severity Index had a higher sensitivity and a somewhat higher negative predictive value for mortality than either CURB score. CONCLUSIONS: The more complex Pneumonia Severity Index has a higher disciminatory power for short-term mortality, defines a greater proportion of patients at low risk, and is slightly more accurate in identifying patients at low risk than either CURB score. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Emergency Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Connecticut, Sch Med, Dept Traumatol & Emergency Med, Storrs, CT 06269 USA. RP Aujesky, D (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Bldg 28 Suite 1A129,Univ Dr C, Pittsburgh, PA 15240 USA. EM aujesky@swissonline.ch FU AHRQ HHS [R01 HS 10049-03] NR 28 TC 160 Z9 164 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD APR PY 2005 VL 118 IS 4 BP 384 EP 392 DI 10.1016/j.amjmed.2005.01.006 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 915CM UT WOS:000228275200010 PM 15808136 ER PT J AU Kim, JP Lentz, MR Westmoreland, SV Greco, JB Ratai, EM Halpern, E Lackner, AA Masliah, E Gonzalez, RG AF Kim, JP Lentz, MR Westmoreland, SV Greco, JB Ratai, EM Halpern, E Lackner, AA Masliah, E Gonzalez, RG TI Relationships between astrogliosis and H-1 MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; SIMIAN IMMUNODEFICIENCY VIRUS; FIBRILLARY ACIDIC PROTEIN; AIDS DEMENTIA COMPLEX; MULTIPLE-SCLEROSIS; ALZHEIMERS-DISEASE; MACAQUE MODEL; SIV INFECTION; INJURY; SCHIZOPHRENIA AB BACKGROUND AND PURPOSE: In vivo H-1 MR spectroscopy demonstrates elevated choline (Cho)/creatine (Cr) and myo-inositol (MI)/Cr in many neurologic diseases that has been ascribed to gliosis. We tested the hypotheses that in vivo Cho/Cr and/or MI/Cr levels are correlated with glial fibrillary acidic protein (GFAP) immunostains and that the changes are water-soluble metabolites. METHODS: We performed postmortem H-1 MR spectroscopy and GFAP immunohistochemistry in brains from seven rhesus macaques acutely infected with simian immunodeficiency virus (SIV) and in four controls and compared the findings with previous in vivo MR spectroscopic results. Changes in neuropathologic and MR spectroscopic markers after infection and relationships among plasma viral load, GFAP immunostaining results, and ex vivo and in vivo MR spectroscopic measures were statistically evaluated. RESULTS: On GFAP immunostaining and in vivo MR spectroscopy, GFAP, Cho/Cr and MI/Cr were highest near the time of peak plasma viral load at 11 days postinfection (dpi). Immunostains returned to baseline by 14 dpi, whereas Cho/Cr and MI/Cr had different time courses, with the former dropping below baseline and the latter remaining elevated. Viral load and immunostains were significantly correlated. No correlation was found between ex vivo Cho/Cr or MI/Cr and viral load or between metabolite ratios from in vivo and ex vivo MR spectroscopy. CONCLUSION. In acute SIV infection, plasma viral load was significantly correlated with brain GFAP immunostains and in vivo H-1 MR spectroscopic Cho/Cr. In vivo changes in Cho/Cr and MI/Cr were principally due to contributions other than those of low-molecular-weight water-soluble metabolites. C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. New England Reg Primate Res Ctr, Southborough, MA USA. Tulane Univ, Natl Primate Res Ctr, Hlth Sci Ctr, Covington, LA USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [P41RR14075, P41RR00995, RR00168-39, RR13213]; NIMH NIH HHS [MH61192, MH45294]; NINDS NIH HHS [NS30769, NS34626] NR 44 TC 19 Z9 19 U1 1 U2 5 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 2005 VL 26 IS 4 BP 752 EP 759 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 915BU UT WOS:000228273400016 PM 15814917 ER PT J AU McCarley, PB Salai, PB AF McCarley, PB Salai, PB TI Cardiovascular disease in chronic kidney disease - Recognizing and reducing the risk of a common CKD comorbidity. SO AMERICAN JOURNAL OF NURSING LA English DT Article ID CHRONIC RENAL-DISEASE; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; HIGH BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; DYSFUNCTION; PREVENTION; FAILURE; REDUCTION; STATEMENT C1 Diablo Nephrol Med Grp, Walnut Creek, CA 94598 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP McCarley, PB (reprint author), Diablo Nephrol Med Grp, 112 La Casa Via,Suite 210, Walnut Creek, CA 94598 USA. EM bargo1@pacbell.net; triumphantrn@aol.com NR 56 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2005 VL 105 IS 4 BP 40 EP 52 PG 13 WC Nursing SC Nursing GA 912MP UT WOS:000228083200027 PM 15791076 ER PT J AU Grace, PJ McLaughlin, M AF Grace, PJ McLaughlin, M TI When consent isn't informed enough SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material ID ADVOCACY C1 Boston Coll, William F Connell Sch Nursing, Family Nursing Practice Program, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Trauma & Gen Surg Dept, Boston, MA 02114 USA. RP Grace, PJ (reprint author), Boston Coll, William F Connell Sch Nursing, Family Nursing Practice Program, Chestnut Hill, MA 02167 USA. EM gracepa@bc.edu NR 14 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2005 VL 105 IS 4 BP 79 EP + PG 5 WC Nursing SC Nursing GA 912MP UT WOS:000228083200044 PM 15791089 ER PT J AU Cavallerano, AA Cavallerano, JD Katalinic, P Blake, B Rynne, M Conlin, PR Hock, K Tolson, AM Aiello, LP Aiello, LM AF Cavallerano, AA Cavallerano, JD Katalinic, P Blake, B Rynne, M Conlin, PR Hock, K Tolson, AM Aiello, LP Aiello, LM CA Joslin Vision Network Res Team TI A telemedicine program for diabetic retinopathy in a veterans affairs medical center - the Joslin Vision Network eye health care model SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Telemedicine-Association CY JUN 04, 2002 CL Los Angeles, CA SP Amer Telemed Assoc ID MACULAR DEGENERATION; FRAMINGHAM EYE; PREVALENCE; AGE AB PURPOSE: To extend access to diabetic eye care and characterize the extent of diabetic retinopathy (DR) and other ocular findings using the Joslin Vision Network (JVN). DESIGN: Retrospective observational cohort study. METHODS: Outpatients at the Togus VA Medical enter with diabetes mellitus, impaired fasting glucose, or impaired glucose tolerance underwent JVN protocol imaging. Images were transmitted to the Joslin Diabetes Center for grading and recommended treatment plan. RESULTS: The study included 1,219 patients (2,437 eyes); 1,536 eyes (63.0%) had no (DR), 389 (16.0%) had mild nonproliferative DR (NPDR), 105 (4.3%) moderate NPDR, 35 (1.4%) severe NPDR, 20 (0.8%) very severe NPDR, and 21 (0.9%) had proliferative DR (PDR). Regarding diabetic macular edema (DME), 1,907 eyes (78.3%) had no DME, 34 (1.4%) had early DME, and 16 (0.7%) had clinically significant macular edema (CSME). Of all patients, 354 (29.0%) had either no DR or mild NPDR in both eyes, no evidence of DME, and no significant nondiabetic findings; 679 (55.7%) had no DR in either eye, and 229 (18.8%) had mild NPDR in the more severe eye. Of the 908 patients (74.5%) with either no DR or mild NPDR in the more severe eye, 533 (58.7%) had at least one nondiabetic ocular finding necessitating referral. Finally, 320 eyes (13.1%) were ungradable for both DR and DME and 160 (6.6%) were ungradable for DME alone. CONCLUSION: In a non-ophthalmic setting, JVN iden, tifies the severity of DR and nondiabetic ocular condi, tions, permitting appropriate triage for eye care. (Am J Ophthalmol 2005;139:597-604. (c) 2005 by Elsevier Inc. All rights reserved). C1 Harvard Univ, Beetham Eye Inst, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. VA Med Ctr, Togus, ME USA. RP Aiello, LM (reprint author), Harvard Univ, Beetham Eye Inst, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM Lloyd.m.aiello@joslin.harvard.edu NR 21 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2005 VL 139 IS 4 BP 597 EP 604 DI 10.1016/j.ajo.2004.10.064 PG 8 WC Ophthalmology SC Ophthalmology GA 914IY UT WOS:000228222300002 PM 15808153 ER PT J AU Arroyo, JG Yang, L Bula, D Chen, DF AF Arroyo, JG Yang, L Bula, D Chen, DF TI Photoreceptor apoptosis in human retinal detachment SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE VITREORETINOPATHY; EXPERIMENTAL-MODEL; VISUAL RECOVERY; REATTACHMENT; EVENTS AB PURPOSE: Although photoreceptor cell apoptosis has been demonstrated in various animal models of retinal detachment (RD), little is known about its occurrence in human RD. We sought to determine whether human photoreceptor cells undergo apoptosis in response to primary and recurrent RD. DESIGN: Prospective, clinical-pathologic, case series. METHODS: Retinal tissue fragments excised during the course of vitreous surgery for RD and recurrent RD were frozen, cut into 4-mu m sections, and analyzed using a TdT-dUTP terminal nick-end labeling assay for cell apoptosis. The onset of patient symptoms was used to estimate the duration of the RD. RESULTS: There were eight patients with primary RD and four patients with recurrent RD enrolled in this study. Duration of RD ranged from 1 to 180 days in the primary RD group, and 2 to 15 days in the recurrent RD group. All retinal tissue specimens had TUNEL,positive cells localized to the outer nuclear layer of the retina, consistent with the localization of photoreceptor cell bodies. TUNEL-positive cells were first identified at 24 hours, peaked by 2 days, and dropped to a low level by 7 days after RD. Recurrent RD induced a greater number of TUNEL-positive cells/mm(2) in the ONL compared with primary RD at corresponding timepoints after the onset of RD. CONCLUSIONS: In response to primary and recurrent D, human photoreceptor cells follow a pattern of apoptosis that is similar to that seen in animal models of RD. This study suggests that photoreceptor cell apoptosis may be one of the causes of reduced vision after RD, especially those that involve the macula. Drugs that inhibit photoreceptor apoptosis may help improve the final visual prognosis of patients with RD. (Am J Ophthalmol 2005;139:605-610. (c) 2005 by Elsevier Inc. All rights reserved). C1 Beth Israel Deaconess Med Ctr, Retina Serv, Boston, MA 02215 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Retina Serv, Shapiro 5th Floor,330 Brookline Ave, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu FU PHS HHS [K-23] NR 17 TC 88 Z9 93 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2005 VL 139 IS 4 BP 605 EP 610 DI 10.1016/j.ajo.2004.11.046 PG 6 WC Ophthalmology SC Ophthalmology GA 914IY UT WOS:000228222300003 PM 15808154 ER PT J AU Yi, DH Rashid, S Cibas, ES Arrigg, PG Dana, MR AF Yi, DH Rashid, S Cibas, ES Arrigg, PG Dana, MR TI Acute unilateral leukemic hypopyon in an adult with relapsing acute lymphoblastic leukemia SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID UVEITIS AB PURPOSE: To report acute unilateral hypopyon uveitis as an initial presenting feature of relapsing acute lymphoblastic leukemia (ALL) in an adult patient. DESIGN: Observational case report. METHODS: Anterior chamber paracentesis was performed in a 56-year-old male presenting with treatment-resistant unilateral hypopyon while in the remission phase of ALL. RESULTS: Examination of the aqueous humor aspirate revealed presence of malignant cells compatible with the previous bone marrow biopsy and subsequent spinal tap results. CONCLUSIONS: Atypical hypopyon uveitis can be an indication of relapsing ALL, even in adults. Prompt anterior chamber aspiration is required for the correct diagnosis and subsequent treatment. (c) 2005 by Elsevier Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Dana, MR (reprint author), 20 Stanford St, Boston, MA USA. EM dana@vision.eri.harvard.edu NR 5 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2005 VL 139 IS 4 BP 719 EP 721 DI 10.1016/j.ajo.2004.09.074 PG 3 WC Ophthalmology SC Ophthalmology GA 914IY UT WOS:000228222300025 PM 15808176 ER PT J AU Jia, LG Donnet, C Bogaev, RC Blatt, RJ McKinney, CE Day, KH Berr, SS Jones, LR Moorman, JR Sweadner, KJ Tucker, AL AF Jia, LG Donnet, C Bogaev, RC Blatt, RJ McKinney, CE Day, KH Berr, SS Jones, LR Moorman, JR Sweadner, KJ Tucker, AL TI Hypertrophy, increased ejection fraction, and reduced Na-K-ATPase activity in phospholemman-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE FXYD protein family; heart; mouse; knockout ID RAT CARDIAC MYOCYTES; PROTEIN-KINASE-C; GAMMA-SUBUNIT; SODIUM-PUMP; SARCOLEMMAL PROTEIN; INTACT MYOCARDIUM; CHANNEL MOLECULES; XENOPUS-OOCYTES; NA,K-ATPASE; EXPRESSION AB Phospholemman (FXYD1), a 72-amino acid transmembrane protein abundantly expressed in the heart and skeletal muscle, is a major substrate for phosphorylation in the cardiomyocyte sarcolemma. Biochemical, cellular, and electrophysiological studies have suggested a number of possible roles for this protein, including ion channel modulator, taurine-release channel, Na+/Ca2+ exchanger modulator, and Na-K-ATPase-associated subunit. We have generated a phospholemman-deficient mouse. The adult null mice exhibited increased cardiac mass, larger cardiomyocytes, and ejection fractions that were 9% higher by magnetic resonance imaging compared with wild-type animals. Notably, this occurred in the absence of hypertension. Total Na-K-ATPase activity was 50% lower in the phospholemman-deficient hearts. Expression ( per unit of membrane protein) of total Na-K-ATPase was only slightly diminished, but expression of the minor alpha 2-isoform, which has been specifically implicated in the control of contractility, was reduced by 60%. The absence of phospholemman thus results in a complex response, including a surprisingly large reduction in intrinsic Na-K-ATPase activity, changes in Na-K-ATPase isoform expression, increase in ejection fraction, and increase in cardiac mass. We hypothesize that a primary effect of phospholemman is to modulate the Na-K-ATPase and that its reduced activity initiates compensatory responses. C1 Univ Virginia, Hlth Syst, Div Cardiovasc Med, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Dept Radiol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Syst, Dept Biomed Engn, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Lab Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. Penn State Univ, University Pk, PA 16802 USA. RP Univ Virginia, Hlth Syst, Div Cardiovasc Med, Box 801394 MR5, Charlottesville, VA 22908 USA. EM alt8t@virginia.edu FU NHLBI NIH HHS [R01 HL 70548, R01 HL 36271] NR 40 TC 60 Z9 62 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2005 VL 288 IS 4 BP H1982 EP H1988 DI 10.1152/ajpheart.00142.2004 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 907AF UT WOS:000227686100063 PM 15563542 ER PT J AU Weinberg, EO Scherrer-Crosbie, M Picard, MH Nasseri, BA MacGillivray, C Gannon, J Lian, QY Bloch, KD Lee, RT AF Weinberg, EO Scherrer-Crosbie, M Picard, MH Nasseri, BA MacGillivray, C Gannon, J Lian, QY Bloch, KD Lee, RT TI Rosuvastatin reduces experimental left ventricular infarct size after ischemia-reperfusion injury but not total coronary occlusion SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide; neutrophil; myocardial salvage; stem cells ID ENDOTHELIAL PROGENITOR CELLS; COA REDUCTASE INHIBITOR; NITRIC-OXIDE SYNTHASE; MYOCARDIAL-ISCHEMIA; STATIN THERAPY; SIMVASTATIN; BLOOD; PHARMACOLOGY; NEUTROPHILS; PROTECTS AB This study compared the effects of rosuvastatin on left ventricular infarct size in mice after permanent coronary occlusion vs. 60 min of ischemia followed by 24 h of reperfusion. Statins can inhibit neutrophil adhesion, increase nitric oxide synthase ( NOS) expression, and mobilize progenitor stem cells after ischemic injury. Mice received blinded and randomized administration of rosuvastatin ( 20 mg (.) kg(-1) (.) day(-1)) or saline from 2 days before surgery until death. After 60 min of ischemia with reperfusion, infarct size was reduced by 18% ( P = 0.03) in mice randomized to receive rosuvastatin (n = 18) vs. saline (n = 22) but was similar after permanent occlusion in rosuvastatin (n = 17) and saline (n = 20) groups ( P = not significant). Myocardial infarct size after permanent left anterior descending coronary artery occlusion (n = 6) tended to be greater in NOS3-deficient mice than in the wild-type saline group (33 +/- 4 vs. 23 +/- 2%, P = 0.08). Infarct size in NOS3-deficient mice was not modified by treatment with rosuvastatin ( 34 +/- 5%, n = 6, P = not significant vs. NOS3-deficient saline group). After 60 min of ischemia-reperfusion, neutrophil infiltration was similar in rosuvastatin and saline groups as was the percentage of CD34(+), Sca-1(+), and c-Kit(+) cells. Left ventricular NOS3 mRNA and protein levels were unchanged by rosuvastatin. Rosuvastatin reduces infarct size after 60 min of ischemia-reperfusion but not after permanent coronary occlusion, suggesting a potential anti-inflammatory effect. Although we were unable to demonstrate that the myocardial protection was due to an effect on neutrophil infiltration, stem cell mobilization, or induction of NOS3, these data suggest that rosuvastatin may be particularly beneficial in myocardial protection after ischemia-reperfusion injury. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Dept Med, Div Cardiovasc, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lee, RT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 65 Landsdowne St, Cambridge, MA 02139 USA. EM rlee@rics.bwh.harvard.edu OI Picard, Michael/0000-0002-9264-3243 NR 32 TC 26 Z9 29 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2005 VL 288 IS 4 BP H1802 EP H1809 DI 10.1152/ajpheart.00962.2004 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 907AF UT WOS:000227686100041 PM 15563531 ER PT J AU Baker, FC Shah, S Stewart, D Angara, C Gong, H Szymusiak, R Opp, MR McGinty, D AF Baker, FC Shah, S Stewart, D Angara, C Gong, H Szymusiak, R Opp, MR McGinty, D TI Interleukin 1 beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE cytokines; preoptic area; rapid eye movement sleep ID WAKING DISCHARGE PATTERNS; IN-VITRO; BRAIN TEMPERATURE; RAT-BRAIN; NEURONS; AREA; ACTIVATION; DEPRIVATION; INVOLVEMENT; INJECTION AB Interleukin 1 beta (IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic area (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats injected intracerebroventricularly with IL-1 (10 ng) at dark onset spent significantly more time in NREM sleep 4-5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR was also increased in the extended VLPO 2 h postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that had been sleep deprived for 2 h postinjection, but it was increased in VLPO core. Taken together, these results suggest that Fos IR in the MnPN after IL-1 is not independent of behavioral state and may require some threshold amount of sleep for its expression. Our results support a hypothesis that IL-1 enhances NREM sleep, in part, through activation of neurons in the MnPN of the hypothalamus. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Witwatersrand, Sch Physiol, Brain Funct Res Unit, Johannesburg, South Africa. Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI USA. RP McGinty, D (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NIMH NIH HHS [MH-47480, MH-66323] NR 46 TC 32 Z9 37 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2005 VL 288 IS 4 BP R998 EP R1005 DI 10.1152/ajpregu.00615.2004 PG 8 WC Physiology SC Physiology GA 908YV UT WOS:000227827000028 PM 15604300 ER PT J AU Johnson, FK Johnson, RA Peyton, KJ Durante, W AF Johnson, FK Johnson, RA Peyton, KJ Durante, W TI Arginase inhibition restores arteriolar endothelial function in Dahl rats with salt-induced hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE salt-sensitive hypertension; vascular tone; arterioles ID OXIDE SYNTHASE ACTIVITY; HEME OXYGENASE INHIBITOR; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE; L-ARGININE; SENSITIVE HYPERTENSION; CORPUS CAVERNOSUM; CELLS; EXPRESSION; DYSFUNCTION AB Vascular tissues express arginase that metabolizes L-arginine to L-ornithine and urea and thus reduces substrate availability for nitric oxide formation. Dahl salt-sensitive (Dahl-S) rats with salt-induced hypertension show endothelial dysfunction, including decreased vascular nitric oxide formation. This study tests the hypothesis that increased vascular arginase activity contributes to endothelial dysfunction in hypertensive Dahl-S rats. Male Dahl-S rats (5-6 wk) were placed on high (8%) or low (0.3%) NaCl diets for 4 wk. With respect to the low-salt group, mean arterial blood pressure was increased in the high-salt animals. Immunohistochemical stainings for arginase I and II were enhanced in arterioles isolated from high-salt Dahl-S rats. Experiments used isolated Krebs buffer-superfused first-order gracilis muscle arterioles with constant pressure (80 mmHg) and no luminal flow or constant midpoint but altered endpoint pressures to establish graded levels of luminal flow (0-50 mu l/min). In high-salt arterioles, responses to an endothelium-dependent vasodilator acetylcholine (1 nmol/l to 3 mu mol/l) and flow-induced dilation were decreased. Acute in vitro treatment with an inhibitor of arginase, 100 mu mol/l (S)-(2-boronoethyl)-L-cystine, or the nitric oxide precursor, 1 mmol/l L-arginine, similarly enhanced acetylcholine and flow-induced maximal dilations and abolished the differences between high- and low-salt arterioles. These data show that arteriolar arginase expression is increased and that endothelium-dependent vasodilation is decreased in high-salt Dahl-S rats. Acute pretreatment with an arginase inhibitor or with L-arginine restores endothelium-dependent vasodilation and abolishes the differences between high- and low-salt groups. These results suggest that enhanced vascular arginase activity contributes to endothelial dysfunction in Dahl-S rats with salt-induced hypertension and identifies arginase as a potential therapeutic target to prevent endothelial dysfunction. C1 Houston Vet Adm Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70118 USA. Tulane Univ, Hlth Sci Ctr, Tulane Hypertens & Renal Ctr Excellence, New Orleans, LA 70118 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Durante, W (reprint author), Houston Vet Adm Med Ctr, 2002 Holcombe Blvd,Bldg 109,Rm 130, Houston, TX 77030 USA. EM wdurante@bcm.tmc.edu FU NCRR NIH HHS [P20 RR-017659]; NHLBI NIH HHS [R01 HL-76187, R01 HL-59976, R01 HL-64577] NR 34 TC 78 Z9 83 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2005 VL 288 IS 4 BP R1057 EP R1062 DI 10.1152/ajpregu.00758.2004 PG 6 WC Physiology SC Physiology GA 908YV UT WOS:000227827000035 PM 15591155 ER PT J AU Katz-Brull, R Rofsky, NM Morrin, MM Pedrosa, I George, DJ Michaelson, MD Marquis, RP Maril, M Noguera, C Lenkinski, RE AF Katz-Brull, R Rofsky, NM Morrin, MM Pedrosa, I George, DJ Michaelson, MD Marquis, RP Maril, M Noguera, C Lenkinski, RE TI Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE clinical study; proton magnetic resonance spectroscopy; 3T ID PROTON MR SPECTROSCOPY; PROSTATE-CANCER; INTERFERON-ALPHA; CONTRAST; H-1-NMR; INTERLEUKIN-2; MICELLAR; CHOLINE; TISSUES; BILE AB Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy. Am J Physiol Renal Physiol 288: F637-F641, 2005. First published November 30, 2004;doi:10.1152/ajprenal.00140.2004. Increased utilization of cross-sectional imaging has resulted in increased detection of incidental renal tumors. The noninvasive characterization of renal tissue has important implications for the diagnosis of renal malignancies and treatment monitoring. Recently, multiple breath-hold averaged proton magnetic resonance spectroscopy (H-1-MRS) performed at high field has enabled the use of this noninvasive metabolic profiling technique for the investigation of the abdomen. Multiple breath-hold averaged H-1-MRS at high field (3T) was obtained in the kidneys of 10 healthy volunteers and in renal cell carcinoma tumors of 14 patients. The spectra of normal kidneys showed four main groups of resonances: 1) at 5.4-5.6 ppm, attributed to C6 of cholesterol and the unsaturated parts of the olefinic region of fatty acids; 2) at 4.7 ppm, attributed to the residual water signal; 3) at 3.2 ppm, attributed to trimethylamine moiety of choline metabolites; and 4) at 1.3 and 0.9 ppm, attributed to the methylenes and terminal methyls of lipids. The ratio of the signal at 5.4 ppm to that of 1.3 ppm was 19-fold lower in renal cell carcinomas than in healthy kidneys, tied P = 0.0003 Mann-Whitney U-test, suggesting a decrease in both free cholesterol and the degree of unsaturation of fatty acids in the malignant tissue. This metabolic shift is in agreement with previous ex vivo studies of human renal cell carcinoma. The ability to detect renal metabolic shifts noninvasively may improve the specificity of preoperative renal tissue characterization and may provide a new modality for treatment monitoring. C1 Harvard Univ, Dept Radiol, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lenkinski, RE (reprint author), Harvard Univ, Dept Radiol, Sch Med, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. EM rlenkins@bidmc.harvard.edu RI Morrin, Maureen/F-2010-2011; Lenkinski, Robert/F-9045-2014; OI Michaelson, Dror/0000-0001-9249-6338; Lenkinski, Robert/0000-0001-7371-5048 NR 32 TC 13 Z9 15 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2005 VL 288 IS 4 BP F637 EP F641 DI 10.1152/ajprenal.00140.2004 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 904JY UT WOS:000227495000004 PM 15572523 ER PT J AU Xu, HS Tian, W Lindsley, JN Oyama, TT Capasso, JM Rivard, CJ Cohen, HT Bagnasco, SM Anderson, S Cohen, DM AF Xu, HS Tian, W Lindsley, JN Oyama, TT Capasso, JM Rivard, CJ Cohen, HT Bagnasco, SM Anderson, S Cohen, DM TI EphA2: expression in the renal medulla and regulation by hypertonicity and urea stress in vitro and in vivo SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE osmotic; cell volume regulation; receptor tyrosine kinase; signal transduction; rat; kidney ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; CELLS REQUIRES TRANSACTIVATION; NA-K-ATPASE; EPITHELIAL-CELLS; GENE-TRANSCRIPTION; ENDOTHELIAL-CELLS; SIGNAL TRANSDUCER; DEPENDENT PATHWAY; ACTIVATION AB EphA2, a member of the large family of Eph receptor tyrosine kinases, is highly expressed in epithelial tissue and has been implicated in cell-cell and cell-matrix interactions, as well as cell growth and survival. Expression of EphA2 mRNA and protein was markedly upregulated by both hypertonic stress and by elevated urea concentrations in cells derived from the murine inner medullary collecting duct. This upregulation likely required transactivation of the epidermal growth factor (EGF) receptor tyrosine kinase and metalloproteinase-dependent ectodomain cleavage of an EGF receptor ligand, based on pharmacological inhibitor studies. A human EphA2 promoter fragment spanning nucleotides -4030 to +21 relative to the putative EphA2 transcriptional start site was responsive to tonicity but insensitive to urea. A promoter fragment spanning -1890 to +128 recapitulated both tonicity- and urea-dependent upregulation of expression, consistent with transcriptional activation. Neither the bona fide p53 response element at approximately -1.5 kb nor a pair of putative TonE elements at approximately -3 kb conferred the tonicity responsiveness. EphA2 mRNA and protein were expressed at low levels in rat renal cortex but at high levels in the collecting ducts of the renal medulla and papilla. Water deprivation in rats increased EphA2 expression in renal papilla, whereas dietary supplementation with 20% urea increased EphA2 expression in outer medulla. These data indicate that transcription and expression of the EphA2 receptor tyrosine kinase are regulated by tonicity and urea in vitro and suggest that this phenomenon is also operative in vivo. Renal medullary EphA2 expression may represent an adaptive response to medullary hypertonicity or urea exposure. C1 Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Boston Univ, Sch Med, Dept Med, Nephrol Sect, Boston, MA 02215 USA. Boston Med Ctr, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Dept Renal Dis & Hypertens, Denver, CO 80202 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol & Hypertens, Mailcode PP262,3314 SW,US Vet Hosp Rd, Portland, OR 97201 USA. EM cohend@ohsu.edu FU NCI NIH HHS [R01 CA079830]; NIA NIH HHS [AG-14699]; NIDDK NIH HHS [R01 DK067569, DK-52494] NR 57 TC 14 Z9 15 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2005 VL 288 IS 4 BP F855 EP F866 DI 10.1152/alprenal.00347.2004 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 904JY UT WOS:000227495000031 PM 15561974 ER PT J AU Allison, JJ Kiefe, CI Wall, T Casebeer, L Ray, MN Spettell, CM Hook, EW Oh, MK Person, SD Weissman, NW AF Allison, JJ Kiefe, CI Wall, T Casebeer, L Ray, MN Spettell, CM Hook, EW Oh, MK Person, SD Weissman, NW TI Multicomponent Internet continuing medical education to promote chlamydia screening SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID PELVIC-INFLAMMATORY-DISEASE; DNA AMPLIFICATION ASSAYS; COST-EFFECTIVENESS; PAP-SMEAR; TRACHOMATIS; INFECTIONS; CARE; WOMEN; PERFORMANCE; PREVALENCE AB Background: Low Chlamydia trachomatis screening rates create an opportunity to test innovative continuing medical education (CME) programs. Few studies of Internet-based physician learning have been evaluated with objective data on practice patterns. Design: This randomized controlled trial tested a multicomponent Internet CME (mCME) intervention for increasing chlamydia screening of at-risk women aged 16 to 26 years. Setting: Eligible physician offices had >= 20 patients at risk for chlamydia as defined by the Health Plan Employer Data and Information Set (HEDIS), had at least one primary care physician (internal medicine, family medicine/general practice, pediatrics) with Internet access, and participated in the study managed care organization. The 191 randomized primary care offices represented 20 states. Intervention: The intervention, available from February to December 2001, consisted of four case-based learning modules, was tailored in real time to each physician based on theory of behavior change, and included office-level feedback of chlamydia screening rates. Main outcome measures: HEDIS chlamydia screening rates for the pre-intervention (2000) and post-intervention (2002) periods. Results: Pre-intervention screening rates for the intervention and comparison offices were 18.9% and 16.2% (p =0.135). Post-intervention screening rates for the intervention and comparison offices were 15.5% and 12.4%, respectively (p =0.044, adjusting for baseline performance). Conclusions: The substantial decline in chlamydia screening rates observed in the comparison offices was significantly attenuated for the intervention offices. The mCME favorably influenced chlamydia screening by primary care physicians. (Am J Prev Med 2005;28 (3):285-290) (c) 2005 American Journal of Preventive Medicine. C1 Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Div Prevent Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectivness Res & Educ, Birmingham, AL 35294 USA. Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. Univ Alabama, Div Continuing Med Educ, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Div Infect Dis, Birmingham, AL 35294 USA. Aetna Integrated Informat Inc, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Allison, JJ (reprint author), Univ Alabama, Div Gen Internal Med, 720 Fac Off Tower,1530 3rd Ave S, Birmingham, AL 35294 USA. EM jallison@uab.edu OI Allison, Jeroan/0000-0003-4472-2112 FU AHRQ HHS [HS 11124] NR 46 TC 42 Z9 42 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2005 VL 28 IS 3 BP 285 EP 290 DI 10.1016/j.amepre.2004.12.013 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 908MA UT WOS:000227789900007 PM 15766617 ER PT J AU Alexopoulos, GS Katz, IR Bruce, ML Heo, M Ten Have, T Raue, P Bogner, HR Schulberg, HC Mulsant, BH Reynolds, CF AF Alexopoulos, GS Katz, IR Bruce, ML Heo, M Ten Have, T Raue, P Bogner, HR Schulberg, HC Mulsant, BH Reynolds, CF CA PROSPECT Grp TI Remission in depressed geriatric primary care patients: A report from the PROSPECT study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; SUICIDAL IDEATION; COLLABORATIVE CARE; MAJOR DEPRESSION; OLDER-ADULTS; MANAGEMENT; SYMPTOMS; HOPELESSNESS; SCALE; SETTINGS AB Objective: This study compared time to first remission for elderly depressed patients in primary care for practices that implemented a care management model versus those providing usual care. In addition, it sought to identify risk factors for nonremission that could guide treatment planning and referral to care managers or specialists. Method: Prevention of Suicide in Primary Care Elderly: Collaborative Trial ( PROSPECT) data were analyzed. Participants were older patients (>= 60 years) selected following screening of 9,072 randomly identified primary care patients. The present analysis examined patients with major depression and a 24-item Hamilton Depression Rating Scale score of 18 or greater who were followed for at least 4 months ( N = 215). Primary care practices were randomly assigned to offer the PROSPECT intervention or usual care. The intervention consisted of services of trained care managers, who offered algorithm-based recommendations to physicians and helped patients with treatment adherence over 18 months. Results: First remission occurred earlier and was more common among patients receiving the intervention than among those receiving usual care. For all patients, limitations in physical and emotional functions predicted poor remission rate. Patients experiencing hopelessness were more likely to achieve remission if treated in intervention practices. Similarly, the intervention was more effective in patients with low baseline anxiety. Conclusions: Longitudinal assessment of depression, hopelessness, anxiety, and physical and emotional functional limitations in depressed older primary care patients is critical. Patients with prominent symptoms or impairment in these areas may be candidates for care management or mental health care, since they are at risk for remaining depressed and disabled. C1 Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Alexopoulos, GS (reprint author), Cornell Med Ctr, Westchester Div, 21 Bloomingdale Rd, White Plains, NY 10605 USA. EM gsalexop@med.cornell.edu FU NIMH NIH HHS [R01 MH059366, P30 MH-52247, P30 MH066270, P30 MH066270-01, P30 MH068638, P30 MH068638-01, R01 MH-59318, R01 MH059380, R37 MH051842, P30 MH-066270, P30 MH-68638, P30 MH052247, P30 MH052247-10, R01 MH-059380, R01 MH-59366, R01 MH059366-02, R01 MH059380-02, R037 MH-51842, R37 MH051842-06] NR 40 TC 99 Z9 100 U1 3 U2 8 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2005 VL 162 IS 4 BP 718 EP 724 DI 10.1176/appi.ajp.162.4.718 PG 7 WC Psychiatry SC Psychiatry GA 911XR UT WOS:000228040600014 PM 15800144 ER PT J AU Bradley, TD Miller, YE Martinez, FJ Angus, DC MacNee, W Abraham, E AF Bradley, TD Miller, YE Martinez, FJ Angus, DC MacNee, W Abraham, E TI Interstitial lung disease, lung cancer, lung transplantation, pulmonary vascular disorders, and sleep-disordered breathing in AJRCCM in 2004 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID POSITIVE AIRWAY PRESSURE; BRONCHIOLITIS OBLITERANS SYNDROME; ARTERIAL-HYPERTENSION; ENDOTHELIAL FUNCTION; NATRIURETIC PEPTIDE; APNEA SYNDROME; RISK-FACTORS; SARCOIDOSIS; FIBROSIS; RATS C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Dept Med & Pulm Sci,Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Dept Crit Care Med, Denver, CO 80262 USA. Univ Toronto, Toronto Gen Hosp, Hlth Network, Toronto, ON M5G 1L7, Canada. Univ Michigan, Div Pulm & Crit Care Med, Hlth Syst, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. Univ Edinburgh, MRC, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland. RP Abraham, E (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Dept Med & Pulm Sci,Div Pulm Sci & Crit Care Med, 4200 E 9th Ave,Box C272,Room 5503, Denver, CO 80262 USA. EM edward.abraham@uchsc.edu RI Angus, Derek/E-9671-2012 NR 70 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2005 VL 171 IS 7 BP 675 EP 685 DI 10.1164/rccm.2412008 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 912BV UT WOS:000228053000004 PM 15790865 ER PT J AU Melo, MFV Harris, RS Layfield, JDH Venegas, JG AF Melo, MFV Harris, RS Layfield, JDH Venegas, JG TI Topographic basis of bimodal ventilation-perfusion distributions during bronchoconstriction in sheep SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 12-16, 2002 CL ORLANDO, FL SP Amer Soc Anesthesiologists DE lung imaging; positron emission tomography; pulmonary gas exchange; theoretical models ID SECONDARY PULMONARY LOBULE; HIGH-RESOLUTION CT; METHACHOLINE CHALLENGE; COLLATERAL VENTILATION; REGIONAL VENTILATION; VA/Q DISTRIBUTIONS; ASTHMATIC SUBJECTS; CHEST RADIOGRAPHS; PRACTICAL CONCEPT; GAS-EXCHANGE AB The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional VA/Q ratios were calculated from the imaged kinetics of intravenously injected (NN)-N-13-saline bolus, assembled into global VA/Q distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived VA/Q distributions during bronchoconstriction were consistently bimodal, with areas Of low VA/Q receiving a large fraction of Q. The standard deviation of the VA/Q distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm(3)) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa-o2 (r(2) = 0.91, p < 0.01) and Pa-co2 (r(2) = 0.90, p < 0.01). We conclude that the bimodality of VA/Q distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional VA/Q heterogeneity. Assessment of the subresolution VA/Q heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Cardiac Anesthesia Gr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Cardiac Anesthesia Gr, 55 Fruit St, Boston, MA 02114 USA. EM mvidaimelo@partners.org FU NHLBI NIH HHS [HL-68011] NR 45 TC 31 Z9 32 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 1 PY 2005 VL 171 IS 7 BP 714 EP 721 DI 10.1164/rccm.200409-1296OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 912BV UT WOS:000228053000008 PM 15640360 ER PT J AU Bredella, MA Steinbach, L Caputo, G Segall, G Hawkins, R AF Bredella, MA Steinbach, L Caputo, G Segall, G Hawkins, R TI Value of FDG PET in the assessment of patients with multiple myeloma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SOLITARY PLASMACYTOMA; F-18-FDG PET; LESIONS; BONE; SPINE AB OBJECTIVE. Our objective was to evaluate if whole-body PET with FDG is able to detect bone marrow involvement in patients with multiple myeloma and to assess its appearance and distribution pattern. MATERIALS AND METHODS. Seventeen whole-body FDG PET scans were performed in 13 patients with multiple myeloma. Four patients were referred for evaluation of extent of disease pretherapy and nine patients were referred for assessment of therapy response (chemotherapy, radiation therapy, bone marrow transplant). FDG PET images were evaluated for distribution and uptake pattern. Standardized uptake values were obtained to quantify FDG uptake. Results of other imaging examinations (MRI, CT, radiography), laboratory data, biopsies, and the clinical course were used for verification of detected lesions. RESULTS. FDG PET was able to detect medullary involvement of multiple myeloma. There were two false-negative results. In one patient, the radiographic skeletal survey showed subcentimeter lytic lesions within the ribs that were not detected on FDG PET and in the other patient, a lytic lesion detected on radiographs showed only mildly increased FDG uptake that was not identified prospectively. There was one false-positive FDG PET result in a patient who had undergone radiation therapy 3 weeks before PET. FDG PET was helpful in differentiating between posttherapeutic changes and residual/recuffent tumor and in assessing response to therapy. FDG PET resulted in upstaging of disease in four patients, which influenced subsequent management and prognosis. Sensitivity of FDG PET in detecting myelomatous involvement was 85% and specificity was 92%. CONCLUSION. FDG PET is able to detect bone marrow involvement inpatients with multiple myeloma. FDG PET is useful in assessing extent of disease at time of initial diagnosis, contributing to staging that is more accurate. FDG PET is also useful for evaluating therapy response. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. VA Palo Alto Hlth Care Syst, Dept Nucl Med, Palo Alto, CA 94304 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. EM mbredella@yahoo.com NR 27 TC 120 Z9 128 U1 0 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2005 VL 184 IS 4 BP 1199 EP 1204 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 911VY UT WOS:000228035600025 PM 15788594 ER PT J AU Chirieac, LR Shen, LL Catalano, PJ Issa, JP Hamilton, SR AF Chirieac, LR Shen, LL Catalano, PJ Issa, JP Hamilton, SR TI Phenotype of microsatellite-stable colorectal carcinomas with CpG island methylation SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 06-12, 2004 CL Vancouver, CANADA SP US & Canadian Acad Pathol DE colorectal cancer; methylation; microsatellite instability ID COLON-CANCER; DNA METHYLATION; PROMOTER HYPERMETHYLATION; GENOMIC INSTABILITY; LYMPHOID REACTION; GENES; INACTIVATION; MUTATIONS; NEOPLASIA; HMLH1 AB A distinctive pathway of colorectal carcinogenesis termed CpG island methylator phenotype is characterized by extensive DNA methylation in colorectal carcinoma (CRC) cells but not in nonneoplastic mucosa. Many CRCs with CpG island methylator phenotype have methylation of the hMLH1 mismatch repair gene and consequently have high levels of microsatellite instability (MSI-H). MSI-H confers distinctive clinical-pathologic features, but the phenotype of microsatellite-stable CRC with methylation has not been characterized in detail. We therefore examined the clinical-pathologic features of 87 sporadic microsatellite-stable CRCs that had been characterized for methylation of p 16, p 14, MGMT, hMLH1, MINT1, MINT2, and MINT31. Regression analyses of each clinical-pathologic characteristic were run against the individual and aggregated methylation markers to evaluate and quantify associations. CpG island methylation was associated with right-sided carcinoma (odds ratio = 6.9, P = 0.03). Paucity of gland formation, indicating poor differentiation, was strongly associated with methylation (beta -42.6, P = 0.0008), as were presence of cribriform glands (beta = 34.3, P = 0.02) and lack of corkscrew/serrated glandular pattern (beta = -32.5, P = 0.03). Our epigenotype-phenotype correlation study shows that microsatellite-stable CRC with CpG island methylation have a distinctive pathologic phenotype with both similarities to and differences from MSI-H tumors. C1 Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Unit 85,Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Div Canc Med, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Hamilton, SR (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Unit 85,Dept Pathol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM shamilto@mdanderson.org FU NCI NIH HHS [CA21115] NR 48 TC 42 Z9 44 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2005 VL 29 IS 4 BP 429 EP 436 DI 10.1097/01.pas.0000155144.53047.7d PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 910IM UT WOS:000227924600001 PM 15767794 ER PT J AU Lauwers, GY Mino, M Ban, S Forcione, D Eatherton, DE Shimizu, M Sevestre, H AF Lauwers, GY Mino, M Ban, S Forcione, D Eatherton, DE Shimizu, M Sevestre, H TI Cytokeratins 7 and 20 and mucin core protein expression in esophageal cervical inlet patch SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervical inlet patch; Barrett esophagus; ectopic gastric mucosa; cytokeratin; mucin core protein ID HETEROTOPIC GASTRIC-MUCOSA; BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA; PROXIMAL ESOPHAGUS; COLUMNAR EPITHELIUM; ADENOCARCINOMA; STRICTURE; JUNCTION; REGENERATION; PATHOGENESIS AB Cervical inlet patch (CIP) is defined by the presence of gastric mucosa within the first few centimeters of the esophagus. Several endoscopic series have demonstrated a frequent association of CIP with Barrett's esophagus (BE) suggesting a pathogenetic link. A histochemical study reporting the presence of acid mucin in CIP, including sulfomucin, supports this hypothesis. We evaluated mucin core protein expression and cytokeratins 7 and 20 (CK7/CK20) pattern in biopsies of CIP. normal antrum, and BE to comment on a possible relationship of CIP with BE. We observed that both lesions have similar cytokeratin patterns with mixed CK7/CK20 reactivity on the surface and pits and lone CK7 positivity in the glands. MUC5AC was strongly expressed on the surface and pits but not in the glands of CIP and antral mucosa. Within BE, MUC5AC positivity was noted not only on the surface and pits but also in the glands. MUC6 similarly decorated the glands of CIP and BE. MUC2 was expressed rarely in CIP with goblet cells but conspicuously on the surface and pits of BE. MUM was seen in both CIP and BE and rarely in the antral mucosa. The similarities between CIP and BE but not with normal antral mucosa fits with the hypothesis that both lesions may originate from submucosal esophageal mucous glands. Two pathogenetic pathways can be entertained: focal upper esophageal mucosal misdevelopment in pediatric population and patchy metaplastic replacement of squamous mucosa in adults with gastroesophageal reflux disease. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. Ctr Hosp Univ Amiens, Dept Anatopathol, Amiens, France. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, 55 Fruit St Warren 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 59 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2005 VL 29 IS 4 BP 437 EP 442 DI 10.1097/01.pas.0000155155.46434.da PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 910IM UT WOS:000227924600002 PM 15767795 ER PT J AU Ulbright, TM Young, RH AF Ulbright, TM Young, RH TI Seminoma with tubular, microcystic, and related patterns - A study of 28 cases of unusual morphologic variants that often cause confusion with yolk sac tumor SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE seminoma; spaces; microcysts; tubules ID GERM-CELL TUMORS; C-KIT PROTOONCOGENE; CORD-STROMAL TUMORS; SPERMATOCYTIC SEMINOMA; INHIBIN; EXPRESSION; NEOPLASMS; MARKER AB We report 28 testicular seminomas with cystic spaces of variable nature, sometimes accompanied by solid and hollow tubular patterns (12 cases). The spaces often suggested reticular or microcystic patterns of yolk sac tumor, and the solid and hollow tubular patterns often added to the diagnostic confusion. The tumors occurred in men 21 to 55 years old and on gross examination had typical appearance of seminoma. On microscopic examination, the spaces ranged from small, closely packed and relatively regular to dilated, more dispersed and somewhat irregular. The hollow tubules appeared to result from central discohesion within nests of tumor. The spaces, particularly when large, often contained occasional tumor cells or inflammatory cells within pale edema fluid. The cytologic appearance of the cells lining the spaces, and in the surrounding tumor, retained the typical features of seminoma cells. Thirteen tumors (46%) either lacked (8 cases) or had very scant (5 cases) lymphocytes in the cystic and tubular areas, and hyaline globules were absent. Thirteen of 13 tumors were immunopositive for OCT-3/4 in the nontypical and typical areas; 9 of 10 were placental alkaline phosphatase positive, and 7 of 10 were c-Kit (CD 117) positive. The same 13 cases were negative with cytokeratin (AE1/AE3) and alpha-fetoprotein stains. Distinction from yolk sac tumor is aided by the observation that the spaces of yolk sac tumor are often more irregular in their individual shapes and frequently form anastomosing channels. Additionally, the spaces of yolk sac tumor randomly merge with various other yolk sac tumor patterns. The cells lining spaces in yolk sac tumor are often flattened with compressed nuclei and lack the typical prominent nucleoli of seminoma cells. Paucity of lymphocytes and intracystic edema, however, are not differentially helpful, although basophilic fluid favors yolk sac tumor. A panel of immunostains (AE1/AE3, OCT-3/4, and alpha-fetoprotein) is helpful in the differential with yolk sac tumor in especially problematic cases. The edema and paucity of lymphocytes may suggest spermatocytic seminoma, but the varied cell types of that neoplasm are absent. C1 Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46204 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02115 USA. RP Ulbright, TM (reprint author), Indiana Univ Hosp, Dept Pathol, 550 N Univ Blvd,3465, Indianapolis, IN 46202 USA. EM tulbrigh@iupui.edu NR 22 TC 32 Z9 33 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2005 VL 29 IS 4 BP 500 EP 505 DI 10.1097/01.pas.0000155146.60670.3f PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 910IM UT WOS:000227924600012 PM 15767805 ER PT J AU Aydin, H Young, RH Ronnett, BM Epstein, JI AF Aydin, H Young, RH Ronnett, BM Epstein, JI TI Clear cell papillary cystadenoma of the epididymis and mesosalpinx - Immunohistochemical differentiation from metastatic clear cell renal cell carcinoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE papillary cystadenoma; immunohistochemistry; von Hippel-Lindau disease; renal cell carcinoma; epididymis ID HIPPEL-LINDAU-DISEASE; VONHIPPELLINDAU SYNDROME; INFERTILITY; COMPONENT; TUMOR AB Clear cell papillary cystadenoma is a rare epithelial tumor of the epididymis, which may present as an isolated lesion or as a component of von Hippel-Lindau disease (VHLD). Recently, tumors have also been described in the female genital tract with similar histology. Recognition of clear cell papillary cystadenoma is critical because of its association with VHLD and its potential diagnostic confusion with metastatic renal cell carcinoma because of a shared architecture and clear cells. In this study, we report on the immunohistochemical differentiation of 5 clear cell papillary cystadenomas, 3 of the epididymis and 2 of the mesosalpinx, from metastatic renal cell carcinoma. In 2 cases, there was a history of renal cell carcinoma in the setting of VHLD; and in 1 of these cases, an epididymal papillary cystadenoma was initially considered to be metastatic renal cell carcinoma. Immunohistochemically, tumor cells were moderately intensely positive for cytokeratin AE1/AE3 and epithelial membrane antigen, strongly positive for CK7 and negative for CK20 and RCC. Four of 5 cases were negative for CD10. This staining profile contrasts with that reported for clear cell renal cell carcinomas, which are typically negative for CK7 and immunoreactive for renal cell carcinoma (RCC) and CD10. Our findings indicate that, in cases where there is uncertainty about the histologic diagnosis of clear cell papillary cystadenoma, the above immunohistochemical panel helps to rule out metastatic renal cell carcinoma. C1 Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21231 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Epstein, JI (reprint author), Johns Hopkins Univ Hosp, Dept Pathol, Weinberg Bldg,401 N Broadway,Rm 2242, Baltimore, MD 21231 USA. EM jepstein@jhmi.edu NR 24 TC 30 Z9 34 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2005 VL 29 IS 4 BP 520 EP 523 DI 10.1097/01.pas.0000155160.36154.mL PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 910IM UT WOS:000227924600015 PM 15767808 ER PT J AU Lovich, MA Doles, J Peterfreund, RA AF Lovich, MA Doles, J Peterfreund, RA TI The impact of carrier flow rate and infusion set dead-volume on the dynamics of intravenous drug delivery SO ANESTHESIA AND ANALGESIA LA English DT Article ID SYRINGE PUMPS; NITROPRUSSIDE; PERFORMANCE; SIZE AB The dynamics of IV drug delivery resulting from drug infusions connected to main-line crystalloid carriers can be complex and depend on infusion set dead-volume, drug flow rate, and carrier flow rate. While the concept of dead-volume is intuitive, a lack of appreciation of the interaction with the carrier and drug flow rates can lead to unintended clinical effects resulting from large variations in the delivery rate of potent drugs. We derived mathematical models to quantify these interactions. Experimental simulation with methylene blue infusions tested these predictions. The models predict a lag in response time to changes in carrier or drug flow, which is proportional to the dead-volume and inversely related to the total flow rate. Increasing the carrier rate provides an acute drug bolus. Temporary reduction or cessation of carrier flow decreases the rate of drug delivery, potentially for prolonged periods. Furthermore, a drug bolus results from restoration of the carrier flow. The method of connecting an infusion to a carrier and the use history affects the dynamics of drug delivery. Thus, although complex, the impact of infusion set architecture and changes in carrier and drug flow rates are predictable. These quantitative studies may help optimize the safe use of IV drug infusion systems. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3,55 Fruit St, Boston, MA 02114 USA. EM rpeterfreund@partners.org NR 16 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2005 VL 100 IS 4 BP 1048 EP 1055 DI 10.1213/01.ANE.0000146942.51020.88 PG 8 WC Anesthesiology SC Anesthesiology GA 908MZ UT WOS:000227792400023 PM 15781520 ER PT J AU Singla, AK Campagna, JA Wright, CD Sandberg, WS AF Singla, AK Campagna, JA Wright, CD Sandberg, WS TI Surgical field fire during a repair of bronchoesophageal fistula SO ANESTHESIA AND ANALGESIA LA English DT Article ID ONE-LUNG VENTILATION; END-EXPIRATORY PRESSURE; POSITIVE AIRWAY PRESSURE; SUPPLEMENTAL OXYGEN; OPERATING-ROOM; TRACHEOSTOMY; FLAMMABILITY; TUBES AB Most surgical fires involve the airway but they can also occur in the surgical field. Herein, we report an intraoperative fire in the surgical field during repair of a bronchoesophageal fistula. During the portion of the surgery after the fistula was divided and the bronchus was open to atmosphere, continuos positive airway pressure was applied to the nondependent lung, and in conjunction with the use of electrocautery and dry sponges in the field, resulted in a fire. Anesthesia for thoracic surgery carries unique risks of fire because these patients frequently require large oxygen concentrations, special interventions for improving oxygenation, and have variable degrees of airway disruption. This report highlights unique safety concerns during anesthesia for thoracic surgery, and addresses more general safety issues relating to fire risk in all surgical patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. RP Campagna, JA (reprint author), Univ Penn, Dept Anesthesia, 3620 Hamilton Walk,John Morgan Bldg 305, Philadelphia, PA 19104 USA. EM jcampagna@doctorsoffice.org OI Sandberg, Warren/0000-0002-9246-777X NR 21 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2005 VL 100 IS 4 BP 1062 EP 1064 DI 10.1213/01.ANE.0000146515.62610.10 PG 3 WC Anesthesiology SC Anesthesiology GA 908MZ UT WOS:000227792400026 PM 15781523 ER PT J AU Rusch, D Forman, SA AF Rusch, D Forman, SA TI Classic benzodiazepines modulate the open-close equilibrium in alpha(1)beta(2L) gamma-aminobutyric acid type A receptors SO ANESTHESIOLOGY LA English DT Article ID RAT HIPPOCAMPAL-NEURONS; MOUSE SPINAL NEURONS; GABA(A) RECEPTOR; ALLOSTERIC MODULATION; XENOPUS OOCYTES; PARTIAL AGONIST; DIAZEPAM; CHANNEL; FLUMAZENIL; ACTIVATION AB Background: Classic benzodiazepine agonists induce their clinical effects by binding to a site on gamma-aminobutyric acid type A (GABA,) receptors and enhancing receptor activity. There are conflicting data regarding whether the benzodiazepine site is allostericalty coupled toy-aminobutyric acid binding versus the channel open-close (gating) equilibrium. The authors tested the hypothesis that benzodiazepine site ligands modulate alpha(1)beta(2)gamma(2L) GABA(A) receptor gating both in the absence of orthosteric agonists; and when the orthosteric sites are occupied. Methods: GABA(A) receptors were recombinantly expressed in Xenopus oocytes and studied using two-microelectrode voltage clamp electrophysiology. To test gating effects in the absence of orthosteric agonist, the authors used spontaneously active GABA(A) receptors containing a leucine-to-threonine mutation at residue 264 on the a, subunit. To examine effects on gating when orthosteric sites were fully occupied, they activated wildtype receptors with high concentrations of a partial agonist, piperidine-4-sulfonic acid. Results: In the absence of orthosteric agonists, the channel activity of alpha(1)L264T beta(2)gamma(2L) receptors was increased by diazepam and midazolam and reduced by the inverse benzodiazepine agonist FG7142. Flumazenil displayed very weak agonism and blocked midazolam from further activating mutant channels. in wild-type receptors activated with saturating concentrations of piperidine-4-sulfonic acid, midazolam increased maximal efficacy. Conclusions: independent of orthosteric site occupancy, classic benzodiazepines modulate the gating equilibrium in alpha(1)beta(2)gamma(2L). GABA(A) receptors and are therefore allosteric coagonists. A Monod-Wyman-Changeux coagonist gating model quantitatively predicts these effects, suggesting that benzodiazepines minimally alter orthosteric ligand binding. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Univ Hosp, Dept Anesthesia & Crit Care, Marburg, Germany. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3, Boston, MA 02114 USA. EM saforman@partners.org FU NIGMS NIH HHS [R01 GM 66724, P01 GM 58448] NR 37 TC 40 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2005 VL 102 IS 4 BP 783 EP 792 PG 10 WC Anesthesiology SC Anesthesiology GA 910IG UT WOS:000227923900013 PM 15791108 ER PT J AU Lim, G Wang, SX Zeng, Q Sung, B Mao, JR AF Lim, G Wang, SX Zeng, Q Sung, B Mao, JR TI Spinal glucocorticoid receptors contribute to the development of morphine tolerance in rats SO ANESTHESIOLOGY LA English DT Article ID ABNORMAL PAIN SENSITIVITY; PROTEIN KINASE-C; NEUROPATHIC PAIN; DOWN-REGULATION; OPIOID THERAPY; NEURONS; MECHANISMS; EXPRESSION; MICE; ACTIVATION AB Background: Opioid analgesic tolerance is a pharmacologic phenomenon involving the mechanisms of cellular adaptation. Central glucocorticoid receptors (GRs) have been implicated in the cellular mechanism of neuronal plasticity that has many cellular steps in common with the mechanism of opioid tolerance. In a rat model of morphine tolerance, the authors examined the hypothesis that spinal GRs would play a significant role in the development of tolerance to the antinociceptive effect of morphine. Methods: In experiment 1, each group of rats received the GR antagonist RU38486 (0.5 or 1 mu g), the mineralocorticoid receptor antagonist spironolactone (3 mu g), or a vehicle, given intrathecally with morphine (10 jig) twice daily for 6 days. In experiment 2, four groups of rats were used, and each group received intrathecally 10 mu g morphine plus 5 mu mol GR antisense oligodeoxynucleotide, sense oligodeoxynucleotide, mixed-base oligodeoxynucleotide, or vehicle. Western blotting was used to examine the expression of GRs within the spinal cord dorsal horn. In experiment 3, the GR agonist dexamethasone (4 mu g) was given intrathecally twice daily in combination with 10 mu g morphine. For all experiments, the development of morphine antinociceptive tolerance was assessed using the tail-flick test. Results: The development of tolerance to the antinociceptive effect of morphine was substantially attenuated when the GR antagonist RU38486 (1 > 0.5 mu g > vehicle) but not spironolactone was coadministered with morphine for 6 days. A single treatment with RU38486 did not affect morphine antinociception, nor did it reverse morphine tolerance on day 7. A similar reduction of morphine tolerance was observed in those rats treated with a GR antisense oligodeoxynucleotide but not a sense or mixed-base oligodeoxynucleotide. The administration of the GR antisense oligodeoxynucleotide also prevented GR up-regulation within the spinal cord dorsal horn. Moreover, the GR agonist dexamethasone facilitated the development of morphine tolerance. Conclusions: The results indicate an important role of spinal GRs in the cellular mechanisms of morphine tolerance in rats and may have significant implications in clinical opioid therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Res Grp,MGH Pain Ctr,Dept Anesthesia & Crit, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pain Res Grp,MGH Pain Ctr,Dept Anesthesia & Crit, 15 Parkman St, Boston, MA 02114 USA. EM imao@partners.org FU NIDA NIH HHS [R01 DA 08835]; NINDS NIH HHS [NS 45681, NS 42661] NR 46 TC 18 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2005 VL 102 IS 4 BP 832 EP 837 DI 10.1097/00000542-200504000-00020 PG 6 WC Anesthesiology SC Anesthesiology GA 910IG UT WOS:000227923900019 PM 15791114 ER PT J AU Letko, E Papaliodis, DN Papaliodis, GN Daoud, YJ Ahmed, AR Foster, CS AF Letko, E Papaliodis, DN Papaliodis, GN Daoud, YJ Ahmed, AR Foster, CS TI Stevens-Johnson syndrome and toxic epidermal necrolysis: a review of the literature SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Review ID SCALDED SKIN SYNDROME; INTRAVENOUS IMMUNOGLOBULIN THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; ELEVATED SERUM AMYLASE; NECROSIS-FACTOR-ALPHA; ERYTHEMA MULTIFORME; DRUG-REACTIONS; PLASMA-EXCHANGE; LYELL SYNDROME; BURN CENTER AB Objective: To perform a comprehensive review of Stevens-Johnson syndrome and toxic epidermal necrolysis. Data Sources: A MEDLINE search was performed for the years 1975 to 2003 using the keywords Stevens-Johnson. syndrome and toxic epidermal necrolysis to identify relevant articles published in English in peer-reviewed journals. Study Selection: All clinical studies that reported on 4 or more patients, review articles, and experimental studies that concerned disease mechanisms were selected and further analyzed. Clinical reports that included fewer than 4 patients were selected only if they were believed to carry a significant message about disease mechanism or therapy. Results: Stevens-Johnson syndrome and toxic epidermal necrolysis seem to be variants of the same disease with differing severities. A widely accepted consensus regarding diagnostic criteria and therapy does not exist at present. Despite the recent experimental studies, the pathogenic mechanisms of these diseases remain unknown. Although progress in survival through early hospitalization in specialized burn units has been made, the prevalence of life-long disability from the ocular morbidity of Stevens-Johnson syndrome and toxic epidermal necrolysis has remained unchanged for the past 35 years. Further progress depends on modification of the acute phase of the disease rather than continuation of supportive care. The available published evidence indicates that a principal problem in the pathogenesis is immunologic and that immunomodulatory intervention with short-term, high-dose , intravenous steroids or intravenous immunoglobulin holds the most promise for effective change in survival and long-term morbidity. Conclusions: The results of this review call for a widely accepted consensus on diagnostic criteria for Stevens-Johnson and toxic epidermal necrolysis and multicenter collaboration in experimental studies and clinical trials that investigate disease mechanisms and novel therapeutic interventions, respectively. C1 Harvard Univ, Immunol & Uveitis Serv, Massachusetts Eye & Ear Infirm, Med Sch,Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Immunol & Uveitis Serv, Massachusetts Eye & Ear Infirm, Med Sch,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 180 TC 132 Z9 137 U1 0 U2 9 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2005 VL 94 IS 4 BP 419 EP 436 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 918WM UT WOS:000228578300003 PM 15875523 ER PT J AU Rafi, A Crawford, W Klaustermeyer, W AF Rafi, A Crawford, W Klaustermeyer, W TI Declining cell-mediated immunity and increased chronic disease burden SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ILLNESS RATING-SCALE; DELAYED CUTANEOUS HYPERSENSITIVITY; NURSING-HOME; ADULTS; AGE; POPULATION; SYSTEM; IGE; ANTIGENS; ASTHMA AB Background: The effects of chronic disease have been proposed as an explanation for conflicting results in studies of age effects on cell-mediated immunity. Objective: To examine the hypothesis that declining cell-mediated immunity is more closely linked to chronic disease burden than to chronological age. Methods: Fifty-eight elderly individuals were tested for delayed-type hypersensitivity (DTH) responses to Candida and tetanus antigens. Disease burden was quantified using the Cumulative Illness Rating Scale (CIRS). Higher CIRS scores reflect,greater disease burden. Mean DTH response by age group (< 71, 71-78, and > 78 years) was compared with mean DTH response by CIRS score (< 11, 11-15, > 15). Total serum IgE levels were measured and similarly stratified by age and CIRS score. Results: Mean Candida DTH responsiveness declined progressively with increasing disease burden (increasing CIRS score). Mean DTH responses were 7.78, 3.05, and 0.0 mm for CIRS scores less than 11, 11 to 15, and greater than 15, respectively. Candida DTH responses showed no progressive decline with advancing age. Mean DTH responses were 4.7, 3.5, and 5.0 rum in participants younger than 71, 7 1 to 78, and older than 78 years, respectively. Total serum IgE levels increased with advancing age. Mean total IgE levels were 182, 249, and 342 IU/mL in participants younger than 71, 71 to 78, and older than 78 years, respectively. No correlation was observed between mean total I-E levels and CIRS scores. Conclusions: An inverse relationship between Candida DTH response and CIRS score suggests that increased chronic disease burden is associated with diminished cell-mediated immune response. Advancing age did not predict a diminished DTH response in our patients. No relationship was observed between chronic disease burden and total serum IgE level. C1 Univ Calif Los Angeles, Div Allergy & Immunol, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Rafi, A (reprint author), Univ Calif Los Angeles, Div Allergy & Immunol, David Geffen Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM asifrafi1@yahoo.com NR 33 TC 4 Z9 4 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 2005 VL 94 IS 4 BP 445 EP 450 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 918WM UT WOS:000228578300005 PM 15875525 ER PT J AU Czaja, C Crossette, L Metlay, JP AF Czaja, C Crossette, L Metlay, JP TI Accuracy of adult reported pneumococcal vaccination status of children SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE sensitivity and specificity; pneumococcal vaccines; interviews ID CONJUGATE VACCINE; MOTHERS REPORTS; INFECTIONS; COVERAGE; RECORDS; RECALL; CARDS AB PURPOSE: A pneumococcal conjugate vaccine was licensed in 2000 for use in children. To evaluate the accuracy of an adult's recall of children's vaccination status with the pneumococcal vaccine, the authors conducted a cross-sectional survey of adults in Philadelphia County from January to December 2003. METHODS: Subjects were identified by random digit dialing and interviewed regarding the age and vaccination status of all children 6 years old or younger with whom they had significant contact. The gold standard for determining the accuracy of vaccine status reports was the Kids Immunization Database/ Tracking System (KIDS) at the City of Philadelphia Department of Public Health. RESULTS: One hundred twenty-two interviews were completed with vaccination data collected on 185 children. One hundred sixty-six children (90%) were matched with records in the KIDS registry. The sensitivity and specificity of adult reported child vaccine status were 0.65 (95% CI, 0.55, 0.74) and 0.47 (95% CI, 0.34, 0.61), respectively. Agreement between adult report and the KIDS registry was 59%. Significant variation in agreement was not found to be related to demographic characteristics of the adult subjects. CONCLUSION: Adult report of the pneumococcal vaccination status of children was found to be relatively inaccurate and did not vary by known demographic characteristics. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Metlay, JP (reprint author), 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jmetlay@cceb.med.upenn.edu FU NIAID NIH HHS [AI46645-01] NR 16 TC 17 Z9 17 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD APR PY 2005 VL 15 IS 4 BP 253 EP 256 DI 10.1016/j.annepidem.2004.07.091 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 914RZ UT WOS:000228246600002 PM 15780771 ER PT J AU Augustinack, JC van der Kouwe, AJW Blackwell, ML Salat, DH Wiggins, CJ Frosch, MP Wiggins, GC Potthast, A Wald, LL Fischl, BR AF Augustinack, JC van der Kouwe, AJW Blackwell, ML Salat, DH Wiggins, CJ Frosch, MP Wiggins, GC Potthast, A Wald, LL Fischl, BR TI Detection of entorhinal layer II using tesla magnetic resonance imaging SO ANNALS OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; AREA 35 CORTICES; ALZHEIMERS-DISEASE; RHESUS-MONKEY; HUMAN BRAIN; PARAHIPPOCAMPAL GYRUS; MULTIPLE-SCLEROSIS; MOTION CORRECTION; CEREBRAL-CORTEX; MRI ASSESSMENT AB The entorhinal cortex lies in the mediotemporal lobe and has major functional, structural, and clinical significance. The entorhinal cortex has a unique cytoarchitecture with large stellate neurons in layer II that form clusters. The entorhinal cortex receives vast sensory association input, and its major output arises from the layer II and III neurons that form the perforant pathway. Clinically, the neurons in layer II are affected with neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's disease. We describe detection of the entorhinal layer II islands using magnetic resonance imaging. We scanned human autopsied temporal lobe blocks in a 7T human scanner using a solenoid coil. In 70 and 100 mu m isotropic data, the entorhinal islands were clearly visible throughout the anterior-posterior extent of entorhinal cortex. Layer II islands were prominent in both the magnetic resonance imaging and corresponding histological sections, showing similar size and shape in two types of data. Area borders and island location based on cytoarchitectural features in the mediotemporal lobe were robustly detected using the magnetic resonance images. Our ex vivo results could break ground for high-resolution in vivo scanning that could ultimately benefit early diagnosis and treatment of neurodegenerative disease. C1 Massachusetts Gen Hosp, CNY, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, HST, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neuropathol, Charlestown, MA 02129 USA. RP Augustinack, JC (reprint author), Massachusetts Gen Hosp, CNY, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2248, Charlestown, MA 02129 USA. EM jean@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [R01 RR016594, P41 RR006009, P41 RR014075, P41-RR14075, R01 RR16594-01A1, S10 RR019307, S10 RR023401]; NIA NIH HHS [K01 AG028521]; NIBIB NIH HHS [P41 EB015896, R01 EB006758, T32 EB001680, U54 EB005149]; NINDS NIH HHS [R01 NS052585, R01 NS070963, R21 NS072652] NR 48 TC 67 Z9 67 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2005 VL 57 IS 4 BP 489 EP 494 DI 10.1002/ana.20426 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 912CA UT WOS:000228053500004 PM 15786476 ER PT J AU Kim, HY Singhal, AB Lo, EH AF Kim, HY Singhal, AB Lo, EH TI Normobaric hyperoxia extends the reperfusion window in focal cerebral ischemia SO ANNALS OF NEUROLOGY LA English DT Article ID BRAIN-BARRIER DISRUPTION; MATRIX-METALLOPROTEINASE; HYPERBARIC-OXYGEN; STROKE; RATS; ABNORMALITIES; INFARCTION; RADICALS; DAMAGE; MODEL AB A major limitation in thrombolysis for acute ischemic stroke is the restricted time window for safe and effective therapy. Any method that can extend the reperfusion time window would be important. In this study, we show that normobaric hyperoxia extends the time window for effective reperfusion from 1 to 3 hours in rats subjected to focal cerebral ischemia. Normobaric hyperoxia did not increase cellular markers of superoxide generation or brain levels of matrix metalloproteinase-9. Normobaric hyperoxia may be a clinically feasible adjunct method for significantly increasing the time window for effective thrombolytic therapy in acute ischemic stroke. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Konkuk Univ, Sch Med, Dept Neurol, Seoul, South Korea. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, E 149-2401, Charlestown, MA 02129 USA. EM lo@helix.mgh.harvard.edu NR 20 TC 93 Z9 98 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 2005 VL 57 IS 4 BP 571 EP 575 DI 10.1002/ana.20430 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 912CA UT WOS:000228053500018 PM 15786465 ER PT J AU Taghian, A Mohiuddin, M Jagsi, R Goldberg, S Ceilley, E Powell, S AF Taghian, A Mohiuddin, M Jagsi, R Goldberg, S Ceilley, E Powell, S TI Current perceptions regarding surgical margin status after breast-conserving therapy - Results of a survey SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 19-23, 2003 CL Salt Lake City, UT SP Amer Soc Therapeut Radiol & Oncol ID PHYSICIAN-ASSISTED SUICIDE; COMPARING TOTAL MASTECTOMY; 20-YEAR FOLLOW-UP; CONSERVATIVE TREATMENT; RADIATION-THERAPY; STAGE-I; LOCAL RECURRENCE; RADICAL-MASTECTOMY; SYSTEMIC THERAPY; NORTH-AMERICA AB Objective: The surgical margin status after breast-conserving surgery is considered the strongest predictor for local failure. The purpose of this study is to survey how radiation oncologists in North America (NA) and Europe define negative or close surgical margins after lumpectomy and to determine the factors that govern the decision to recommend reexcision based on the margins status. Methods: A questionnaire was sent to active members of the European Society of Therapeutic Radiation Oncology and the American Society for Therapeutic Radiology and Oncology who had completed training in radiation oncology. Respondents were asked whether they would characterize margins to be negative or close for a variety of scenarios. A second survey was sent to 500 randomly selected radiation oncologists in the United States to assess when a reexcision would be recommended based on surgical margins. Results: A total of 702 responses were obtained from NA and 431 from Europe to the initial survey. An additional 130 responses were obtained from the United States to the second survey regarding reexcision recommendations. Nearly 46% of the North American respondents required only that there be "no tumor cells on the ink" to deem a margin negative (National Surgical Adjuvant Breast and Bowel Project definition). A total of 7.4% and 21.8% required no tumor cells seen at < 1 mm and < 2 mm, respectively. The corresponding numbers from European respondents were 27.6%, 11.2%, and 8.8%, respectively (P < 0.001). Europeans more frequently required a larger distance (> 5 mm) between tumor cells and the inked edges before considering a margin to be negative. Conclusion: This study revealed significant variation in the perception of negative and close margins among radiation oncologists in NA and Europe. Given these findings, a universal definition of negative margins and consistent recommendations for reexcision are needed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Taghian, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 302,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org OI Jagsi, Reshma/0000-0001-6562-1228 NR 57 TC 129 Z9 139 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 2005 VL 241 IS 4 BP 629 EP 639 DI 10.1097/01.sla.0000157272.04803.1b PG 11 WC Surgery SC Surgery GA 909KC UT WOS:000227857800013 PM 15798465 ER PT J AU Vauthey, JN Lauwers, GY AF Vauthey, JN Lauwers, GY TI Surgically resected hepatocellular carcinoma: Protean yet predictable SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID LIVER-TRANSPLANTATION; CLIP SCORE; INVASION; TUMOR; PROGNOSIS; CIRRHOSIS; DISEASE; SYSTEM; JAPAN C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77230 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Unit 444,1515 Holcombe Blvd, Houston, TX 77230 USA. EM jvauthey@mdanderson.org NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2005 VL 12 IS 4 BP 270 EP 272 DI 10.1245/ASO.2005.12.916 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 912BL UT WOS:000228052000002 PM 15827674 ER PT J AU Reed, MF Tolis, G Edil, BH Allan, JS Donahue, DM Gaissert, HA Moncure, AC Wain, JC Wright, CD Mathisen, DJ AF Reed, MF Tolis, G Edil, BH Allan, JS Donahue, DM Gaissert, HA Moncure, AC Wain, JC Wright, CD Mathisen, DJ TI Surgical treatment of esophageal high-grade dysplasia SO ANNALS OF THORACIC SURGERY LA English DT Article ID BARRETTS-ESOPHAGUS; UNITED-STATES; ADENOCARCINOMA; CANCER; MANAGEMENT; CARCINOMA; RESECTION; SURVIVAL; OUTCOMES; THERAPY AB Background. Barrett's esophagus, high-grade dysplasia (HGD), and invasive cancer are steps in the progression of esophageal adenocarcinoma. While surgery is recommended for resectable invasive adenocarcinoma, a number of treatment modalities are advocated for HGD. The purpose of this study is to determine the outcomes after surgery for HGD. Methods. We identified cases of HGD based on endoscopic biopsy in a single institution's databases from 1980 through 2001. Records were reviewed for patient characteristics, treatments, staging, and outcomes. Results. In a 22-year period, 869 cases of esophageal adenocarcinoma and 1,614 cases of Barrett's esophagus were diagnosed. Of these, 115 had HGD without pretreatment evidence of invasion. Forty-nine patients with HGD underwent resection (mean age, 59 years) as initial treatment. Forty-seven had endoscopic treatment (mean age, 70 years) by photodynamic therapy or endoscopic mucosal resection. Seven of the endoscopically treated patients failed, with three undergoing surgery and four observation. Nineteen patients were initially observed, with six eventually having surgery. For the 49 initially treated surgically, one (2%) operative mortality occurred. Invasive adenocarcinoma was present in 18 (37%). The five-year survival was 83% for all resected HGD patients (91% for those without invasion, 68% with invasion). Three of the eight deaths in those with invasion were from recurrent adenocarcinoma. Conclusions. Surgical resection of esophageal HGD can be performed with low mortality and allows longterm survival. A significant percentage with an initial diagnosis of HGD will have invasive disease at resection. Surgery is the optimal treatment for HGD unless contraindicated by severe comorbidities. (c) 2005 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 21 TC 51 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2005 VL 79 IS 4 BP 1110 EP 1115 DI 10.1016/j.arthorascur.2004.09.006 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 912PH UT WOS:000228091100003 PM 15797034 ER PT J AU Mutrie, CJ Donahue, DM Wain, JC Wright, CD Gaissert, HA Grillo, HC Mathisen, DJ Allan, JS AF Mutrie, CJ Donahue, DM Wain, JC Wright, CD Gaissert, HA Grillo, HC Mathisen, DJ Allan, JS TI Esophageal leiomyoma: A 40-year experience SO ANNALS OF THORACIC SURGERY LA English DT Article ID BENIGN-TUMORS; ENUCLEATION; CYSTS AB Background. Esophageal leiomyomas, although infrequent, are the most common benign intramural tumors of the esophagus. They represent 10% of all gastrointestinal leiomyomas and frequently cause symptoms, necessitating resection. Methods. The Massachusetts General Hospital Pathologic Database was reviewed over a 40-year period for patients who underwent surgical resection of esophageal leiomyomas. Data analyzed included demographic information, presenting symptoms, tumor location, tumor characteristics and histology, diagnostic procedures, and treatment modalities/outcomes. Fifty-three patients were identified; 31 patients were symptomatic from their leiomyomas. Results. Symptomatic patients presented at a mean age of 44 years old and exhibited a twofold male predominance. Mean tumor diameter among symptomatic patients was 5.3 cm, as compared to 1.5 cm in asymptomatic patients (p < 0.0001). Thirty of the symptomatic patients had solitary leiomyomas, and 1 patient had five separate leiomyomas. Eighty-four percent of the lesions in symptomatic patients occurred in the lower two-thirds of the esophagus, with epigastric discomfort being the most common presenting symptom. Among patients operated on solely for leiomyoma, 97% were enucleated without an esophageal resection. None of the leiomyomas showed malignant transformation or recurrence. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality. Conclusions. In a large pathologic series, over half of all patients with esophageal. leiomyomas were symptomatic. Larger tumors were significantly more likely to be symptomatic. Local enucleation by a variety of surgical approaches was accomplished in most patients. All symptomatic patients had relief of symptoms, with no perioperative morbidity or mortality. There was no observed tendency for malignant transformation or recurrence. (c) 2005 by The Society of Thoracic Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM jallan@partners.org NR 10 TC 60 Z9 70 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2005 VL 79 IS 4 BP 1122 EP 1125 DI 10.1016/j.arthorascur.2004.08.029 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 912PH UT WOS:000228091100005 PM 15797036 ER PT J AU Ho, PM Masoudi, FA Spertus, JA Peterson, PN Shroyer, AL McCarthy, M Grover, FL Hammermeister, KE Rumsfeld, JS AF Ho, PM Masoudi, FA Spertus, JA Peterson, PN Shroyer, AL McCarthy, M Grover, FL Hammermeister, KE Rumsfeld, JS TI Depression predicts mortality following cardiac valve surgery SO ANNALS OF THORACIC SURGERY LA English DT Article ID ARTERY-BYPASS-SURGERY; MENTAL-HEALTH; MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; HEART-FAILURE; GRAFT-SURGERY; PRIMARY-CARE; RISK; OUTCOMES; DISEASE AB Background. Depression is associated with mortality in several cardiovascular populations, but has not been evaluated in patients undergoing cardiac valve surgery. Because identifying nonsurgical mediators of survival is important for accurate risk adjustment and the development of interventions to improve outcomes of care, we evaluated the hypothesis that depression predicts mortality following cardiac valve surgery. Methods. This prospective cohort study enrolled 648 patients undergoing valve surgery at 14 Veteran Administration hospitals. A preoperative mental health inventory (MHI) depression screen was performed in all patients and patients were classified as depressed or not depressed using the standard MHI cutoff score of less than or equal to 52. Multivariable logistic regression was used to evaluate the association between depression and 6-month all-cause mortality, adjusting for other clinical risk variables. Results. Overall, 29.2% (189/648) of the patients were depressed at baseline. Depressed patients were younger, more frequently had New York Heart Association class III/IV symptoms, and more likely required emergent surgery, preoperative intravenous nitroglycerin, or intraaortic balloon pump. Unadjusted 6-month mortality was 13.2% for depressed patients compared with 7.6% for nondepressed patients (p = 0.03). In multivariable analyses, depression remained significantly associated with mortality (odds ratio 1.90; 95% confidence interval 1.07 to 3.40, P = 0.03). These findings were consistent across subgroups of patients undergoing aortic valve replacement, mitral valve replacement and valve replacement without coronary artery bypass graft. Conclusions. Preoperative depression is an independent risk factor for mortality following cardiac valve surgery. Depression screening should be incorporated into preoperative risk stratification, and future studies are warranted to determine if preoperative or postoperative interventions to treat depression can improve outcomes. (c) 2005 by The Society of Thoracic Surgeons. C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Ctr Hlth Sci, Dept Med, Colorado Hlth Outcomes Program, Denver, CO 80202 USA. Univ Colorado, Ctr Hlth Sci, Dept Surg, Colorado Hlth Outcomes Program, Denver, CO 80202 USA. Denver Hlth Med Ctr, Denver, CO USA. Mid Amer Heart Inst, Kansas City, MO USA. Univ Missouri, Kansas City, MO 64110 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Ho, PM (reprint author), Cardiol 111B,1055 Clermont St, Denver, CO 80220 USA. EM michael.ho@uchsc.edu RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 FU NHLBI NIH HHS [F32 HL69596]; NIA NIH HHS [K08-AG01011] NR 30 TC 33 Z9 34 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2005 VL 79 IS 4 BP 1255 EP 1259 DI 10.1016/j.arthoracsur.2004.09.047 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 912PH UT WOS:000228091100026 PM 15797059 ER PT J AU Lembcke, A Dohmen, PM Dewey, M Klessen, C Elgeti, T Hermann, KGA Konertz, WF Hamm, B Kivelitz, DE AF Lembcke, A Dohmen, PM Dewey, M Klessen, C Elgeti, T Hermann, KGA Konertz, WF Hamm, B Kivelitz, DE TI Multislice computed tomography for preoperative evaluation of right ventricular volumes and function: Comparison with magnetic resonance imaging SO ANNALS OF THORACIC SURGERY LA English DT Article ID CONGENITAL HEART-DISEASE; PULMONARY VALVE-REPLACEMENT; CORONARY-ARTERY STENOSES; MULTIDETECTOR ROW CT; INTERSTUDY REPRODUCIBILITY; CARDIOPULMONARY BYPASS; TEMPORAL RESOLUTION; MYOCARDIAL-FUNCTION; ADULTS LATE; HELICAL CT AB Background. This study was performed to validate preoperative right ventricular measurements obtained from multislice spiral computed tomography data sets in comparison with magnetic resonance imaging. Methods. Before cardiac surgery, 25 patients (among them 12 patients with compromised right ventricular function), underwent contrast-enhanced retrospectively electrocardiogram-gated multislice spiral computed tomography and cine magnetic resonance imaging in a standardized fashion., Right ventricular end-diastolic, end-systolic and stroke volume, ejection fraction, and myocardial mass were calculated according to the slice summation method. Measurements obtained with both modalities were compared using Pearson's correlation coefficient (r), Student's t test for paired samples, and Bland-Altman analysis. Results. The right ventricle was completely visualized with invariably adequate image quality on all multislice spiral computed tomography and magnetic resonance images. For all measurements a close correlation between multislice spiral computed tomography and magnetic resonance imaging was found (end-diastolic volume, r = 0.93; end-systolic volume, r = 0.95; stroke volume, r = 0.91; ejection fraction, r = 0.96; mass, r = 0.94). Mean values of all measurements did not differ significantly between both modalities, and limits of agreement were in an acceptable range. Conclusions. When compared with magnetic resonance imaging as a reference method, multislice spiral computed tomography seems to be an accurate and reliable noninvasive technique for evaluating right ventricular measurements. (c) 2005 by The Society of Thoracic Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Free Univ Berlin, Dept Radiol, Charite Univ Med Berlin, Sch Med, Berlin, Germany. Free Univ Berlin, Dept Cardiovasc Surg, Charite Univ Med Berlin, Sch Med, Berlin, Germany. Humboldt Univ, Berlin, Germany. RP Lembcke, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,White Bldg,Room 270, Boston, MA 02114 USA. EM alexander.lembcke@gmx.de OI Dewey, Marc/0000-0002-4402-2733; Hermann, Kay-Geert/0000-0001-6142-3814 NR 38 TC 43 Z9 46 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2005 VL 79 IS 4 BP 1344 EP 1351 DI 10.1016/j.athoracsur.2004.09.030 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 912PH UT WOS:000228091100039 PM 15797075 ER PT J AU Soukos, NS Som, S Abernethy, AD Ruggiero, K Dunham, J Lee, C Doukas, AG Goodson, JM AF Soukos, NS Som, S Abernethy, AD Ruggiero, K Dunham, J Lee, C Doukas, AG Goodson, JM TI Phototargeting oral black-pigmented bacteria SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID GRAM-NEGATIVE ANAEROBES; PROPIONIBACTERIUM-ACNES; PORPHYROMONAS-GINGIVALIS; PORPHYRIN FLUORESCENCE; SUBGINGIVAL PLAQUE; PROTOPORPHYRIN-IX; ARGON-LASER; LIGHT; BLUE; PERIODONTITIS AB We have found that broadband light (380 to 520 nm) rapidly and selectively kills oral black-pigmented bacteria (BPB) in pure cultures and in dental plaque samples obtained from human subjects with chronic periodontitis. We hypothesize that this killing effect is a result of light excitation of their endogenous porphyrins. Cultures of Prevotella intermedia and P. nigrescens were killed by 4.2 J/cm(2), whereas P. melaninogenica required 21 J/cm(2). Exposure to light with a fluence of 42 J/cm(2) produced 99% killing of P. gingivalis. High-performance liquid chromatography demonstrated the presence of various amounts of different porphyrin molecules in BPB. The amounts of endogenous porphyrin in BPB were 267 (P. intermedia), 47 (P. nigrescens), 41 (P. melaninogenica), and 2.2 (P. gingivalis) ng/mg. Analysis of bacteria in dental plaque samples by DNA-DNA hybridization for 40 taxa before and after phototherapy showed that the growth of the four BPB was decreased by 2 and 3 times after irradiation at energy fluences of 4.2 and 21 J/cm(2), respectively, whereas the growth of the remaining 36 microorganisms was decreased by 1.5 times at both energy fluences. The present study suggests that intraoral light exposure may be used to control BPB growth and possibly benefit patients with periodontal disease. C1 Forsyth Inst, Appl Mol Photomed Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Univ Texas, Med Branch, Sch Med, Div Human Nutr,Dept Prevent Med & Community Med, Galveston, TX 77550 USA. RP Soukos, NS (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. EM nsoukos@forsyth.org FU NIDCR NIH HHS [DE-14360, R01 DE014360] NR 30 TC 79 Z9 83 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2005 VL 49 IS 4 BP 1391 EP 1396 DI 10.1128/AAC.49.4.1391-1396.2005 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 912MK UT WOS:000228082500021 PM 15793117 ER PT J AU Yuan, S Devor, A Boas, DA Dunn, AK AF Yuan, S Devor, A Boas, DA Dunn, AK TI Determination of optimal exposure time for imaging of blood flow changes with laser speckle contrast imaging SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY APR, 2004 CL Miami Beach, FL SP Opt Soc Amer ID FUNCTIONAL ACTIVATION; VISUALIZATION; PHOTOGRAPHY; FLOWMETRY; DOPPLER; MODEL; FLOWGRAPHY; TISSUE; CORTEX; SKIN AB Laser speckle contrast imaging is becoming an established method for full-field imaging of cerebral blood flow dynamics in animal models. The sensitivity and noise in the measurement of blood flow changes depend on the camera exposure time. The relation among sensitivity, noise, and camera exposure time was investigated experimentally by imaging the speckle contrast changes in the brain after electrical forepaw stimulation in rats. The sensitivity to relative changes in speckle contrast was found to increase at longer exposure times and to reach a plateau for exposure times greater than approximately 2 ms. However, the speckle contrast noise also increases with exposure time and thus the contrast-to-noise ratio was found to peak at an exposure time of approximately 5 ms. Our results suggests that similar to 5 ms is an optimal exposure time for imaging of stimulus-induced changes in cerebral blood flow in rodents. (c) 2005 Optical Society of America. C1 Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Tufts Univ, Dept Elect & Comp Engn, Medford, MA 02145 USA. RP Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, 149 13th St, Boston, MA 02129 USA. EM adunn@nmr.mgh.harvard.edu RI Yuan, Shuai/A-5783-2011; Dunn, Andrew/I-9527-2014 FU NIBIB NIH HHS [EB000790] NR 24 TC 98 Z9 99 U1 0 U2 9 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2005 VL 44 IS 10 BP 1823 EP 1830 DI 10.1364/AO.44.001823 PG 8 WC Optics SC Optics GA 911WG UT WOS:000228036600008 PM 15813518 ER PT J AU Li, A Boverman, G Zhang, YH Brooks, D Miller, EL Kilmer, ME Zhang, Q Hillman, EMC Boas, DA AF Li, A Boverman, G Zhang, YH Brooks, D Miller, EL Kilmer, ME Zhang, Q Hillman, EMC Boas, DA TI Optimal linear inverse solution with multiple priors in diffuse optical tomography SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY APR, 2004 CL Miami Beach, FL SP Opt Soc Amer ID NONINVASIVE MEASUREMENT; BREAST; RECONSTRUCTION; SPECTROSCOPY; LIGHT; MRI; ABSORPTION; HEAD; LOCALIZATION; INFORMATION AB A general framework for incorporating single and multiple priors in diffuse optical tomography is described. We explore the use of this framework for simultaneously utilizing spatial and spectral priors in the context of imaging breast cancer. The utilization of magnetic resonance images of water and lipid content as a statistical spatial prior for the diffuse optical image reconstructions is also discussed. Simulations are performed to demonstrate the significant improvement in image quality afforded by combining spatial and spectral priors. (c) 2005 Optical Society of America. C1 Tufts Univ, Dept Phys, Medford, MA 02155 USA. Tufts Univ, Dept Math, Medford, MA 02155 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Marinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. RP Tufts Univ, Dept Phys, Medford, MA 02155 USA. EM angli@nmr.mgh.harvard.edu RI Miller, Eric/B-2546-2008; Hillman, Elizabeth/B-9854-2009 OI Miller, Eric/0000-0002-3156-6002; FU NCI NIH HHS [R01-CA97305, U54-CA105480] NR 35 TC 64 Z9 64 U1 0 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2005 VL 44 IS 10 BP 1948 EP 1956 DI 10.1364/AO.44.001948 PG 9 WC Optics SC Optics GA 911WG UT WOS:000228036600022 PM 15813531 ER PT J AU Boas, DA Dale, AM AF Boas, DA Dale, AM TI Simulation study of magnetic resonance imaging-guided cortically constrained diffuse optical tomography of human brain function SO APPLIED OPTICS LA English DT Article; Proceedings Paper CT Biomedical Topical Meeting CY APR, 2004 CL Miami Beach, FL SP Opt Soc Amer ID NEAR-INFRARED SPECTROSCOPY; PREMATURE-INFANT BRAIN; CEREBRAL-BLOOD-FLOW; HUMAN HEAD; SENSORY STIMULATION; SPATIAL-RESOLUTION; AWAKE INFANTS; TOPOGRAPHY; ACTIVATION; OXYGENATION AB Diffuse optical imaging can measure brain activity noninvasively in humans through the scalp and skull by measuring the light intensity modulation arising from localized-activity-induced absorption changes within the cortex. Spatial resolution and localization accuracy are currently limited by measurement geometry to approximately 3 cm in the plane parallel to the scalp. Depth resolution is a more significant challenge owing to the limited angle tomography permitted by reflectance-only measurements. We combine previously established concepts for improving image quality and demonstrate, through simulation studies, their application for improving the image quality of adult human brain function. We show in a three-dimensional human head model that localization accuracy is significantly improved by the addition of measurements that provide overlapping samples of brain tissue. However, the reconstructed absorption contrast is significantly underestimated because its depth is underestimated. We show that the absorption contrast amplitude accuracy can be significantly improved by providing a cortical spatial constraint in the image reconstruction to obtain a better depth localization. The cortical constraint makes physiological sense since the brain-activity-induced absorption changes are occurring in the cortex and not in the scalp, skull, and cerebral spinal fluid. This spatial constraint is provided by segmentation of coregistered structural magnetic resonance imaging (MRI). However, the absorption contrast deep within the cortex is reconstructed superficially, resulting in an underestimation of the absorption contrast. The synthesis of techniques described here indicates that multimodality imaging of brain function with diffuse optical imaging and MRI has the potential to provide more quantitative estimates of the total and deoxyhemoglobin response to brain activation, which is currently not provided by either method independently. However, issues of depth resolution within the cortex remain to be resolved. (c) 2005 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. EM dboas@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01-EB002482, R01-EB00790] NR 56 TC 91 Z9 92 U1 1 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD APR 1 PY 2005 VL 44 IS 10 BP 1957 EP 1968 DI 10.1364/AO.44.001957 PG 12 WC Optics SC Optics GA 911WG UT WOS:000228036600023 PM 15813532 ER PT J AU Stryker, JE Solky, BA Emmons, KM AF Stryker, JE Solky, BA Emmons, KM TI A content analysis of news coverage of skin cancer prevention and detection, 1979 to 2003 SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; BREAST-CANCER; MEDIA COVERAGE; SUN EXPOSURE; BASAL-CELL; MASS-MEDIA; SUNLIGHT-EXPOSURE; MALIGNANT-MELANOMA; CUTANEOUS MELANOMA; PUBLIC-HEALTH AB Objective: To analyze newspaper coverage between 1979 and 2003 to understand how print coverage may affect primary and secondary skin cancer prevention in the US population. Design: Content analysis of 921 skin cancer articles released by the Associated Press during the study period. Main Outcome Measures: Amount of attention given to primary and secondary prevention practices and to risk communication. Results: Media attention to skin cancer has not increased since 1986. Neither prevention (31.8% of all stories) nor detection (24.4% of all stories) received as much attention as treatment (47.0% of all stories). Specific sun protection practices were mentioned infrequently. Dermatologic detection (6.6%) or self-detection (5.5%) of skin cancer was rarely discussed. Risk communication about skin cancer was suboptimal: articles rarely presented absolute and relative risk. Conclusions: The media pay little attention to skin cancer, and, in general, stories do not contain important educational information. Strategies for generating increased media attention are discussed. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Stryker, JE (reprint author), Univ Illinois, Dept Speech Commun, 244 Lincoln Hall,702 S Wright St, Urbana, IL 61801 USA. EM jstryker@uiuc.edu NR 68 TC 34 Z9 35 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2005 VL 141 IS 4 BP 491 EP 496 DI 10.1001/archderm.141.4.491 PG 6 WC Dermatology SC Dermatology GA 914PB UT WOS:000228238800012 PM 15837868 ER PT J AU Huskamp, HA Deverka, PA Epstein, AM Epstein, RS McGuigan, KA Muriel, AC Frank, RG AF Huskamp, HA Deverka, PA Epstein, AM Epstein, RS McGuigan, KA Muriel, AC Frank, RG TI Impact of 3-tier formularies on drug treatment of attention-deficit/hyperactivity disorder in children SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Workshop on Costs and Assessment in Psychiatry CY MAR 27, 2003 CL Venice, ITALY ID INCENTIVE-BASED FORMULARIES; PRESCRIPTION AB Background: Expenditures for medications used to treat attention-deficit/hyperactivity disorder (ADHD) in children have increased rapidly. Many employers and health plans have adopted 3-tier formularies in an attempt to control costs for these and other drugs. Objective: To assess the effect of copayment increases associated with 3-tier formulary adoption on use and spending patterns for ADHD medications for children. Design and Setting: Observational study using quasi-experimental design to compare effects on ADHD medication use and spending for children enrolled as dependents in an employer-sponsored plan that made major changes to its pharmacy benefit design and a comparison group of children covered by the same insurer. The plan simultaneously moved from a 1-tier (same copayment required for all drugs) to a 3-tier formulary and implemented an across-the-board copayment increase. The plan later moved 3 drugs from tier 3 to tier 2. Participants: An intervention group of 20 326 and a comparison group of 15776 children aged 18 years and younger. Main Outcome Measures: Monthly probability of using an ADHD medication; plan, enrollee, and total ADHD medication spending; and medication continuation. Results: A 3-tier formulary implementation resulted in a 17% decrease in the monthly probability of using medication (P < .001), a 20% decrease in expected total medication expenditures, and a substantial shifting of costs from the plan to families (P < .001). Intervention group children using medications in the pre-period were more likely to change to a medication in a different tier after 3-tier adoption, relative to the comparison group (P = .08). The subsequent tier changes resulted in increased plan spending (P < .001) and decreased patient spending (P = .003) for users but no differences in continuation. Conclusions: The copayment increases associated with 3-tier formulary implementation by 1 employer resulted in lower total ADHD medication spending, sizeable increases in out-of-pocket expenditures for families of children with ADHD, and a significant decrease in the probability of using these medications. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Medco Hlth Solut Inc, Franklin Lakes, NJ USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Sect Hlth Serv & Policy Res, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Inst Genome Sci & Policy, Durham, NC USA. RP Huskamp, HA (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM huskamp@hcp.edu.harvard.edu FU AHRQ HHS [P01 HS010803, 5 P01 HS 10803]; NIMH NIH HHS [1 K01 MH 66109, K01 MH066109] NR 18 TC 46 Z9 46 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2005 VL 62 IS 4 BP 435 EP 441 DI 10.1001/archpsyc.62.4.435 PG 7 WC Psychiatry SC Psychiatry GA 913FO UT WOS:000228137200010 PM 15809411 ER PT J AU Carmosino, MJ Brousseau, KM Arciniegas, DB Corboy, JR AF Carmosino, MJ Brousseau, KM Arciniegas, DB Corboy, JR TI Initial evaluations for multiple sclerosis in a university multiple sclerosis center - Outcomes and role of magnetic resonance imaging in referral SO ARCHIVES OF NEUROLOGY LA English DT Article ID TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; ACADEMY-OF-NEUROLOGY; DIAGNOSTIC-CRITERIA; MRI; MS; CONVERSION; MISDIAGNOSIS; THERAPEUTICS; GUIDELINES; DISABILITY AB Objective: To evaluate diagnostic outcomes, especially as they relate to reason for referral, of patients referred to a university-based multiple sclerosis (MS) center for possible MS. Methods: Retrospective medical record review of all new patient visits to University of Colorado Multiple Sclerosis Center, Denver, from January 1, 2001, to June 30, 2003. Results: Of 281 patients referred to evaluate the possibility of MS, after initial review 33% were diagnosed with MS or possible MS by the McDonald criteria. The rest had other neurological conditions (31.5%), probable psychiatric diagnoses (22.5%), or no clear diagnosis was made (12.5%). Of patients with typical, possible, or atypical demyelinating syndromes, 71%, 27%, and 0%, respectively (P < .001), had MS or possible MS. Of the 63% of patients referred on the basis of clinical symptoms and signs, 46% were diagnosed with MS or possible MS vs 11% of patients referred primarily on the basis of abnormal brain magnetic resonance imaging (MRI) results (P < .001). Of patients referred because of abnormal MRI results who did not have MS or possible MS, 70% had a clear alternative etiology for the abnormal MRI results, including migraine, age older than 50 years, other neurological disease, or hypertension. Conclusions: A significant percentage of patients referred to a university-based MS center have little or no likelihood of having MS, and many have undiagnosed, untreated psychiatric illness or common conditions with abnormal brain MRI results. With respect to the diagnosis of MS, greater training of primary care professionals, neurologists, and radiologists is necessary. C1 Univ Colorado, Sch Med, Multiple Sclerosis Ctr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Corboy, JR (reprint author), Univ Colorado, Sch Med, Multiple Sclerosis Ctr, 4200 E 9th Ave,B 183, Denver, CO 80262 USA. EM john.corboy@uchsc.edu RI Arciniegas, David/A-3792-2009 NR 21 TC 34 Z9 36 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2005 VL 62 IS 4 BP 585 EP 590 DI 10.1001/archneur.62.4.585 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 914KZ UT WOS:000228227800009 PM 15824257 ER PT J AU Husain, D Kim, I Gauthier, D Lane, AM Tsilimbaris, MK Ezra, E Connolly, EJ Michaud, N Gragoudas, ES O'Neill, CA Beyer, JC Miller, JW AF Husain, D Kim, I Gauthier, D Lane, AM Tsilimbaris, MK Ezra, E Connolly, EJ Michaud, N Gragoudas, ES O'Neill, CA Beyer, JC Miller, JW TI Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; MACULAR DEGENERATION; PRIMATE; RETINA AB Objective: To study the safety and efficacy of intravitreal injections of anti-vascular endothelial growth factor antibody fragment (ranibizumab [formerly known as rhuFabV2], Lucentis; Genentech, South San Francisco, Calif) in combination with intravenous verteporfin (Visudyne; Novartis, East Hanover, NJ) photodynamic therapy (PDT) on experimental choroidal neovascularization in the monkey eye. Methods: Choroidal neovascularization was induced by laser injury in both eyes of cynomolgus monkeys and followed with weekly fundus photography and fluorescein angiography. Two weeks after induction, weekly treatments were initiated. These treatments included using either an intravitreal injection of ranibizumab (previously known as rhuFabV2) in combination with verteporfin PDT or a ranibizumab vehicle (placebo) in combination with verteporfin PDT (PDT only). Six animals (group 1) initially received intravitreal injections followed 1 week later by PDT. Four animals (group 2) initially received PDT followed I week later by intravitreal injection. Two animals (group 3) received injections and PDT on the same day at 2-week intervals. Photodynamic therapy was applied in all 3 groups every 2 weeks for 3 treatments with follow-up through 2 weeks after the last PDT treatment. Fluorescein angiograms were graded using a masked standardized protocol. The data were analyzed using the McNemar chi(2) test for matched pairs. Results: No choroidal neovascularization leakage was observed in the eyes of animals treated with ranibizumab and PDT at day 21 or 42 after the start of the first treatment. Leakage persisted in eyes treated with PDT alone at 21 days (3 of 12 eyes) and 42 days (2 of 12 eyes). At all time points studied, the ranibizumab and PDT-treated eyes experienced better angiographic outcomes than the eyes receiving PDT alone. Conclusion: These preliminary data indicate that an intravitreal ranibizumab injection in combination with verteporfin PDT (ranibizumab and PDT) causes a greater reduction in angiographic leakage than PDT and intravitreal vehicle injection (PDT only) in experimental choroidal neovascularization. Clinical Relevance: This combination therapy can potentially offer a new treatment modality for choroidal neovascularization in patients with macular degeneration and other diseases. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Miller, JW (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jwmiller@meei.harvard.edu NR 16 TC 65 Z9 72 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2005 VL 123 IS 4 BP 509 EP 516 DI 10.1001/archopht.123.4.509 PG 8 WC Ophthalmology SC Ophthalmology GA 913FQ UT WOS:000228137400012 PM 15824225 ER PT J AU Hua, HT Albadawi, H Entabi, F Conrad, M Stoner, MC Meriam, BT Sroufe, R Houser, S LaMuraglia, GM Watkins, MT AF Hua, HT Albadawi, H Entabi, F Conrad, M Stoner, MC Meriam, BT Sroufe, R Houser, S LaMuraglia, GM Watkins, MT TI Polyadenosine diphosphate-ribose polymerase inhibition modulates skeletal muscle injury following ischemia reperfusion SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the New-England-Surgical-society CY OCT 03, 2004 CL Montreal, CANADA SP New England Surg Soc ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; ISCHEMIA/REPERFUSION INJURY; LIMB ISCHEMIA; PROGENITOR CELLS; LUNG INJURY; SYNTHETASE; VEGF; RAT AB Hypothesis: Polyadenosine diphosphate-ribose polymerase (PARP) has been implicated as a mediator of inflammation and tissue necrosis in murine models of human stroke and myocardial infarction. This study was designed to determine whether PARP modulates skeletal muscle injury and cytokine-growth factor levels during ischemia-reperfusion. Design: Prospective controlled animal study. Setting: Medical school-affiliated university hospital. Interventions: Mice were divided into 2 groups-treated (PJ) and untreated; all mice were subjected to unilateral hind limb tourniquet ischemia followed by 4 or 48 hours of reperfusion. In treated mice, PJ34, an ultrapotent-specific PARP inhibitor was given immediately before ischemia and prior to reperfusion. A group of PARP-1 knockout mice (PARP(-/-)) were also subjected to hind limb ischemia followed by 48 hours of reperfusion. Main Outcome Measures: After ischemia-reperfusion, muscle was harvested for measurement of edema, viability, cytokine, and vascular endothelial growth factor content. Results: The PJ34-treated mice had increased skeletal muscle viability when compared with the untreated mice after 4 and 48 hours of reperfusion (P <.01). Viability between PARP(-/-) and PJ34-treated mice were similar at 48 hours of reperfusion (P >.05), and it exceeded that of untreated mice (P <.01). Tissue edema was unaltered by PARP inhibition. Tissue levels of cytokine were only different (P <.05) in PJ34-treated vs untreated mice at 48 hours of reperfusion. Vascular endothelial growth factor levels in FJ34-treated mice were markedly reduced when compared with untreated mice only after 4 hours of reperfusion (P <.01), and in PARP(-/-) mice (P <.01) at 48 hours of reperfusion. Conclusions: Polyadenosine diphosphate-ribose polymerase modulates skeletal muscle viability, cytokine and vascular endothelial growth factor synthesis during reperfusion. Polyadenosine diphosphate-ribose polymerase inhibition may represent a novel method to modulate skeletal muscle ischemia-reperfusion injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Vet Adm Boston Healthcare Syst, Boston, MA USA. RP Watkins, MT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc & Endovasc Surg, 15 Parkman St,Suite 458, Boston, MA 02114 USA. EM mtwatkins@partners.org NR 59 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2005 VL 140 IS 4 BP 344 EP 351 DI 10.1001/archsurg.140.4.344 PG 8 WC Surgery SC Surgery GA 914KW UT WOS:000228227500005 PM 15837884 ER PT J AU O'Brien, KD McDonald, TO Kunjathoor, V Eng, KL Knopp, EA Lewis, K Lopez, R Kirk, EA Chait, A Wight, TN deBeer, FC LeBoeuf, RC AF O'Brien, KD McDonald, TO Kunjathoor, V Eng, KL Knopp, EA Lewis, K Lopez, R Kirk, EA Chait, A Wight, TN deBeer, FC LeBoeuf, RC TI Serum amyloid A and lipoprotein retention in murine models of atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; lipoproteins; perlecan; proteoglycans; serum amyloid A ID C-REACTIVE PROTEIN; LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE-CELLS; TRIGLYCERIDE-RICH LIPOPROTEINS; AORTIC ENDOTHELIAL-CELLS; APOLIPOPROTEIN-B; BINDING SITE; PROTEOGLYCAN; BIGLYCAN; PLAQUES AB Objective - Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk in humans. Because SAA associates primarily with lipoproteins in plasma and has proteoglycan binding domains, we postulated that SAA might mediate lipoprotein retention on atherosclerotic extracellular matrix. Methods and Results - Immunohistochemistry was performed for SAA, apolipoprotein A-I ( apoA- I), apolipoprotein B ( apoB), and perlecan on proximal aortic lesions from chow-fed low-density lipoprotein receptor (LDLR)(-/-) and apoE(-/-) mice euthanized at 10, 50, and 70 weeks. SAA was detected on atherosclerotic lesion extracellular matrix at all time points in both strains. SAA area correlated highly with lesion areas (apoE(-/-), r = 0.76; LDLR-/-, r = 0.86), apoA-I areas (apoE(-/-), r = 0.88; LDLR-/-, r = 0.80), apoB areas (apoE(-/-), r = 0.74; LDLR-/-, r = 0.89), and perlecan areas ( apoE(-/-), r = 0.83; LDLR-/-, r = 0.79) ( all P < 0.0001). In vitro, SAA enrichment increased high-density lipoprotein (HDL) binding to heparan sulfate proteoglycans, and immunoprecipitation experiments using plasma from apoE(-/-) and LDLR-/- mice demonstrated that SAA was present on both apoA- I - containing and apoB-containing lipoproteins. Conclusions - In chow-fed apoE(-/-) and LDLR-/- mice, SAA is deposited in murine atherosclerosis at all stages of lesion development, and SAA immunoreactive area correlates highly with lesion area, apoA- I area, apoB area, and perlecan area. These findings are consistent with a possible role for SAA-mediated lipoprotein retention in atherosclerosis. C1 Univ Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bennaroya Res Inst, Hope Heart Program, Seattle, WA USA. Univ Kentucky, Dept Med, Lexington, KY 40506 USA. RP O'Brien, KD (reprint author), Univ Washington, Div Cardiol, Box 356422, Seattle, WA 98195 USA. EM cardiac@u.washington.edu FU NHLBI NIH HHS [HL02788, HL30086, HL52848] NR 37 TC 75 Z9 76 U1 6 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2005 VL 25 IS 4 BP 785 EP 790 DI 10.1161/01.ATV.0000158383.65277.2b PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 910AD UT WOS:000227900900022 PM 15692094 ER PT J AU Karackattu, SL Picard, MH Krieger, M AF Karackattu, SL Picard, MH Krieger, M TI Lymphocytes are not required for the rapid onset of coronary heart disease in scavenger receptor class B type I apolipoprotein E double knockout mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; HDL receptor; myocardial infarction; RAG2; echocardiography ID E-DEFICIENT MICE; MYOCARDIAL-INFARCTION; ECHOCARDIOGRAPHIC-ASSESSMENT; AUTOIMMUNE MYOCARDITIS; T-LYMPHOCYTES; ATHEROSCLEROTIC PLAQUE; NECROPSY VALIDATION; REPERFUSION INJURY; CARDIAC-FUNCTION; BALB/C MICE AB Objective - Scavenger receptor class B type I (SR-BI)/apolipoprotein E ( apoE) double knockout ( dKO) mice exhibit many features of human coronary heart disease (CHD), including occlusive coronary atherosclerosis, cardiac hypertrophy, myocardial infarctions, and premature death. Here we determined the influence of B and T lymphocytes, which can contribute to atherosclerosis, ischemia - reperfusion injury, and cardiomyocyte death, on pathology in dKO mice. Method and Results - The lymphocyte-deficient SR-BI/apoE/ recombination activating gene 2 (RAG2) triple knockout mice and corresponding dKO controls generated for this study exhibited essentially identical lipid-rich coronary occlusions, myocardial infarctions, cardiac dysfunction, and premature death ( average lifespans 41.6 +/- 0.6 and 42.0 +/- 0.5 days, respectively). Conclusions - B and T lymphocytes and associated immunoglobulin- mediated inflammation are not essential for the development and progression of CHD in dKO mice. Strikingly, the dKO mice bred for this study ( mixed C57BL/6 x SV129 x BALB/c background; strain 2) compared with the previously described dKO mice ( 75: 25 C57BL/6: SV129 background; strain 1) had a shorter mean lifespan and steeper survival curve, characteristics especially attractive for studying the effects of environmental, pharmacological, and genetic manipulations on cardiac pathophysiology. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Krieger, M (reprint author), MIT, Dept Biol, Room 68-483, Cambridge, MA 02139 USA. EM krieger@mit.edu OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL66105, HL64737] NR 47 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 2005 VL 25 IS 4 BP 803 EP 808 DI 10.1161/01.ATV.0000158310.64498.ac PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 910AD UT WOS:000227900900025 PM 15692099 ER PT J AU Major-Pedersen, A Ihlemann, N Hermann, T Dominguez, H Kveiborg, B Nielsen, D Rask-Madsen, C Torp-Pedersen, C AF Major-Pedersen, A Ihlemann, N Hermann, T Dominguez, H Kveiborg, B Nielsen, D Rask-Madsen, C Torp-Pedersen, C TI The Insulin Resistance Syndrome and endothelial dysfunction - Does nateglinide make a difference? SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Meeting Abstract CT 75th Congress of the European-Atherosclerosis-Society CY APR 23-26, 2005 CL Prague, CZECH REPUBLIC SP European Atherosclerosis Soc C1 Bispebjerg Hosp, Cardiol Clin, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. RI Torp-Pedersen, Christian/E-5931-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD APR PY 2005 VL 6 IS 1 BP 137 EP 137 DI 10.1016/S1567-5688(05)80533-1 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 921BK UT WOS:000228739000534 ER PT J AU Rubinszfein, DC DiFiglia, M Heintz, N Nixon, RA Qin, ZH Ravikumar, B Stefanis, L Tolkovsy, A AF Rubinszfein, David C. DiFiglia, Marion Heintz, Nathaniel Nixon, Ralph A. Qin, Zheng-Hong Ravikumar, Brinda Stefanis, Leonidas Tolkovsy, Aviva TI Autophagy and its possible roles in nervous system diseases, damage and repair SO AUTOPHAGY LA English DT Review DE autophagy; Alzheimer's disease; Parkinson's disease; Huntington's disease; prion; alpha-synuclein; amyloid; apoptosis ID AMYLOID PRECURSOR PROTEIN; PROGRAMMED CELL-DEATH; FAMILIAL ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN DEGRADATION; SUPERIOR CERVICAL GANGLION; CEREBELLAR PURKINJE-CELLS; INCLUSION-BODY MYOSITIS; SYMPATHETIC NEURONS; PARKINSONS-DISEASE; LURCHER MICE AB Increased numbers of autophagosomes/autophagic vacuoles are seen in a variety of physiological and pathological states in the nervous system. In many cases, it is unclear if this phenomenon is the result of increased autophagic activity or decreased autophagosome-lysosome fusion. The functional significance of autophagy and its relationship to cell death in the nervous system is also poorly understood. In this review, we have considered these issues in the context of acute neuronal injury and a range of chronic neurodegenerative conditions, including the Lurcher mouse, Alzheimer's, Parkinson's, Huntington's and prion diseases. While many issues remain unresolved, these conditions raise the possibility that autophagy can have either deleterious or protective effects depending on the specific situation and stage in the pathological process. C1 Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Cambridge CB2 2XY, England. Massachusetts Gen Hosp, Lab Cell Neurobiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Rockefeller Univ, Howard Hughes Med Inst, Mol Biol Lab, New York, NY 10021 USA. Nathan S Kline Inst Psychiat Res, Ctr Dement Res, Orangeburg, NY USA. NYU, Dept Psychiat, New York, NY 10016 USA. NYU, Dept Cell Biol, New York, NY 10016 USA. Acad Athens, Fdn Biomed Res, Neurobiol Lab, Athens, Greece. Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. RP Rubinszfein, DC (reprint author), Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Addenbrookes Hosp, Wellcome Trust-MRC Bldg,Hills Rd, Cambridge CB2 2XY, England. EM dcr1000@cus.com.ac.uk FU NINDS NIH HHS [NS16367, NS035711]; Wellcome Trust NR 182 TC 253 Z9 278 U1 2 U2 23 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD APR-JUN PY 2005 VL 1 IS 1 BP 11 EP 22 PG 12 WC Cell Biology SC Cell Biology GA 055PA UT WOS:000238461400002 PM 16874045 ER PT J AU Rosen, FS Davis, AE AF Rosen, FS Davis, AE TI Deficiencies of Cl inhibitor SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Article DE angioedema; complement; Cl inhibitor (CIINH); hereditary angioedema; acquired Cl inhibitor deficiency ID HEREDITARY ANGIONEUROTIC-EDEMA; MOLECULAR-WEIGHT KININOGEN; ACQUIRED C1-INHIBITOR DEFICIENCY; INCREASED VASCULAR-PERMEABILITY; C1 ESTERASE INHIBITOR; PLASMINOGEN-ACTIVATOR; PROTEASE INHIBITORS; ENDOTHELIAL-CELLS; BINDING-PROTEIN; HUMAN-PLASMA AB Hereditary and acquired deficiencies of the CI inhibitor result in a single prominent symptom, namely angioedema. Angioedema may involve the skin, the gastrointestinal tract or the upper airway. Genetically determined defects in CIINH cause hereditary angioedema. The defect may be acquired as the result of an auto-antibody to CIINH or be due to the generation of anti-idiotypic antibody to monoclonal immunoglobulins as occurs in various B cell lymphoproliferative diseases. Androgens provide prophylaxis against attacks of angioedema. There is no widely approved treatment for acute attacks of angioedema although several promising drugs are now in the final stages of clinical trials. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rosen, FS (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM rosen@cbr.med.harvard.edu; aldavis@cbr.med.harvard.edu NR 47 TC 15 Z9 15 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6918 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD APR PY 2005 VL 19 IS 2 BP 251 EP 261 DI 10.1016/j.bpg.2004.11.011 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 927YM UT WOS:000229238300006 PM 15833691 ER PT J AU Denslow, S Lomarev, M George, MS Bohning, DE AF Denslow, S Lomarev, M George, MS Bohning, DE TI Cortical and subcortical brain effects of transcranial magnetic stimulation (TMS)-induced movement: An interleaved TMS/functional magnetic resonance imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE BOLD; fMRI; motor cortex; motor circuits; transcranial magnetic stimulation ID PRIMARY MOTOR CORTEX; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; SENSORIMOTOR CORTEX; BASAL GANGLIA; FMRI SIGNAL; BOLD-FMRI; ACTIVATION; TMS AB Background: To date, interleaved transcranial magnetic stimulation and functional magnetic resonance imaging (TMS/fMRI) studies of motor activation have not recorded whole brain patterns. We hypothesized that TMS would activate known motor circuitry with some additional regions plus some areas dropping out. Methods: We used interleaved TMS/fMRI (11 subjects, three scans each) to elucidate whole brain activation patterns from 1-Hz TMS over left primary motor cortex. Results: Both TMS (110016 motor threshold) and volitional movement of the same muscles excited by TMS caused blood oxygen level-dependent (BOLD) patterns encompassing known motor circuitry. Additional activation was observed bilaterally in superior temporal auditory areas. Decreases in BOLD signal with unexpected posttask "rebounds" were observed for both tasks in the right motor area, right superior parietal lobe, and in occipital regions. Paired t test of parametric contrast maps failed to detect significant effects. Differences were detectable, however, in primary data time-intensity profiles differences between TMS- and volition-induced of diferrence. Conclusions: Using this interleaved TMS/fMRI technique, TMS over primary motor cortex produces a whole brain pattern of BOLD activation similar to known motor circuitry, without detectable differences from mimicked volitional movement. Some differences may exist between time courses of BOLD intensity during TMS circuit activation and volitional circuit activation. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Labs, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. NINDS, Bethesda, MD 20892 USA. Inst Human Brain, St Petersburg, Russia. RP Denslow, S (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. EM denslows@musc.edu FU NCRR NIH HHS [R01 RR14080-02] NR 45 TC 45 Z9 45 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2005 VL 57 IS 7 BP 752 EP 760 DI 10.1016/j.biopsych.2004.12.017 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913BK UT WOS:000228125000009 PM 15820232 ER PT J AU Wilens, TE Haight, BR Horrigan, JP Hudziak, JJ Rosenthal, NE Connor, DF Hampton, KD Richard, NE Modell, JG AF Wilens, TE Haight, BR Horrigan, JP Hudziak, JJ Rosenthal, NE Connor, DF Hampton, KD Richard, NE Modell, JG TI Bupropion XL in adults with attention-deficit/hyperactivity disorder: A randomized, placebo-controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY JUN 01-04, 2004 CL Phoenix, AZ SP New Clin Drug Evaluat Unit, NIMH DE ADHD; adults; bupropion; pharmacotherapy; antidepressant ID DEFICIT-HYPERACTIVITY DISORDER; SUSTAINED-RELEASE BUPROPION; CONTROLLED CLINICAL-TRIAL; PSYCHIATRIC STATUS; FOLLOW-UP; EXTRACELLULAR DOPAMINE; SMOKING-CESSATION; NUCLEUS-ACCUMBENS; DOUBLE-BLIND; METHYLPHENIDATE AB Background: Data remain limited on treatment strategies for adults with attention-deficit/hyperactivity disorder (ADHD). This study evaluated the efficacy and safety of an extended-release, once-daily formulation of bupropion (XL) in the treatment of adults with ADHD. Methods: This multisite, placebo-controlled, 8-week prospective trial evaluated 162 adult patients diagnosed with ADHD (combined and inattentive types). Subjects were treated with up to 450 mg/day of bupropion XL The primary efficacy endpoint was the proportion of ADHD responders (defined as at least a 30% reduction in the investigator-rated ADHD Rating Scale score) at week? 8 (last observation carried forward [LOCF]). Results: Bupropion XL responders (53%) exceeded placebo responders (31%) (p =.004 at week 8) with a significantly greater proportion of bupropion XL responders as early as week 2 (p =.01). Treatment effect size calculated for the ADHD Rating Scale total score was .6. Bupropion XL appeared to provide sustained benefit throughout the day compared with placebo (morning p =.033, afternoon p =.004, evening p =.024). Bupropion XL was safe and well tolerated, with no serious or unexpected adverse events and a low rate of drug-related study discontinuation (5%). Conclusions: The results from this multisite study indicate that bupropion XL is an effective and well-tolerated nonstimulant treatment for adult ADHD. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Vermont, Burlington, VT USA. Capital Clin Res Associates, Rockville, MD USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, YAW 6-6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org OI Hudziak, James/0000-0001-9653-758X; Connor, Daniel/0000-0002-7867-4094 NR 83 TC 95 Z9 96 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2005 VL 57 IS 7 BP 793 EP 801 DI 10.1016/j.biopsych.2005.01.027 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 913BK UT WOS:000228125000014 PM 15820237 ER PT J AU Zhou, XH AF Zhou, XH TI Nonparametric confidence intervals for the one- and two-sample problems SO BIOSTATISTICS LA English DT Article DE BCa; bootstrap; confidence interval; cost data; edgeworth expansion; positive skewness ID SKEWED DISTRIBUTIONS AB Confidence intervals for the mean of one sample and the difference in means of two independent samples based on the ordinary-t statistic suffer deficiencies when samples come from skewed families. In this article we evaluate several existing techniques and propose new methods to improve coverage accuracy. The methods examined include the ordinary-t, the bootstrap-t, the biased-corrected acceleration and three new intervals based on transformation of the t-statistic. Our study shows that our new transformation intervals and the bootstrap-t intervals give best coverage accuracy for a variety of skewed distributions, and that our new transformation intervals have shorter interval lengths. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98101 USA. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU AHRQ HHS [R01 HS 013105] NR 13 TC 26 Z9 26 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2005 VL 6 IS 2 BP 187 EP 200 DI 10.1093/biostatistics/kxi002 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 917AM UT WOS:000228428200002 PM 15772099 ER PT J AU Song, X Zhou, XH AF Song, X Zhou, XH TI A marginal model approach for analysis of multi-reader multi-test receiver operating characteristic (ROC) data SO BIOSTATISTICS LA English DT Article DE ANOVA; AUC; GEE; marginal model; ROC sparse correlation ID OF-VARIANCE MODELS AB The receiver operating characteristic curve is a popular tool to characterize the capabilities of diagnostic tests with continuous or ordinal responses. One common design for assessing the accuracy of diagnostic tests involves multiple readers and multiple tests, in which all readers read all test results from the same patients. This design is most commonly used in a radiology setting, where the results of diagnostic tests depend on a radiologist's subjective interpretation. The most widely used approach for analyzing data from such a study is the Dorfman-Berbaum-Metz (DBM) method (Dorfman et al., 1992) which utilizes a standard analysis of variance (ANOVA) model for the jackknife pseudovalues of the area under the ROC curves (AUCs). Although the DBM method has performed well in published simulation studies, there is no clear theoretical basis for this approach. In this paper, focusing on continuous outcomes, we investigate its theoretical basis. Our result indicates that the DBM method does not satisfy the regular assumptions for standard ANOVA models, and thus might lead to erroneous inference. We then propose a marginal model approach based on the AUCs which can adjust for covariates as well. Consistent and asymptotically normal estimators are derived for regression coefficients. We compare our approach with the DBM method via simulation and by an application to data from a breast cancer study. The simulation results show that both our method and the DBM method perform well when the accuracy of tests under the study is the same and that our method outperforms the DBM method for inference on individual AUCs when the accuracy of tests is not the same. The marginal model approach can be easily extended to ordinal outcomes. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA 98018 USA. RP Song, X (reprint author), Univ Washington, Dept Biostat, Box 357232,1705 NE Pacific St, Seattle, WA 98195 USA. EM xsong@stat.ncsu.edu; azhou@u.washington.edu FU AHRQ HHS [R01 HS 013105-01]; NIAID NIH HHS [U01 AI 46702] NR 12 TC 14 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2005 VL 6 IS 2 BP 303 EP 312 DI 10.1093/biostatistics/kxi011 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 917AM UT WOS:000228428200011 PM 15772108 ER PT J AU Baethge, C Baldessarini, RJ Freudenthal, K Streeruwitz, A Bauer, M Bschor, T AF Baethge, C Baldessarini, RJ Freudenthal, K Streeruwitz, A Bauer, M Bschor, T TI Hallucinations in bipolar disorder: characteristics and comparison to unipolar depression and schizophrenia SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; delusions; depression; hallucinations; insight; psychosis; schizophrenia ID SCHIZOAFFECTIVE DISORDER; MANIA; PSYCHOSIS; PHENOMENOLOGY; SYMPTOMS; FEATURES AB Objective: As there is very little research on the topic, we compared the frequency and the type hallucinations among hospitalized patients diagnosed with bipolar disorder (BPD) versus other major psychiatric illnesses. Methods: At admission, all patients hospitalized at the Department of Psychiatry at the Freie Universitat Berlin (1981-2001) underwent comprehensive assessments using the standardized Association for Methodology and Documentation in Psychiatry (AMDP) system. We used these data to compare risks and types of hallucinations and associated factors by bivariate and multivariate testing in patients diagnosed with BPD, major depression, or schizophrenia. Results: At admission, the cross-sectional prevalence of current hallucinations among 4972 hospitalized subjects ranked: schizophrenia (61.1%), bipolar mixed (22.9%), bipolar manic (11.2%), bipolar depressed (10.5%), unipolar depressed (5.9%). The most frequent hallucinations across all patients were auditory, followed by somatic and visual hallucinations. There were only minor age or sex differences in risk of hallucinations. Compared with patients diagnosed with schizophrenia, hallucinations among patients with BPD were less severe, more visual and less often auditory. Characteristics of hallucinations were similar among manic and both bipolar- and unipolar-depressed subjects. Among patients with major affective disorders, those with hallucinations were less well-educated, had higher anxiety scores, less insight into the illness, and their hospitalizations averaged 17% longer. Across all diagnoses, hallucinations, particularly olfactory, were significantly associated with delusions. Hallucinations in BPD were most often accompanied by persecutory delusions; delusions of grandeur were least associated with hallucinations. Conclusions: This study provides detailed descriptive data regarding the frequency (cross-sectional) and characteristics of hallucinations in a large sample of patients with BPD, major depression or schizophrenia. Our results suggest a link of lower education and the presence of hallucinations in major affective disorders. The significance of this finding, as well as the role of anxiety in hallucinating patients, requires further study. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,McLean Div, Dept Psychiat,Int Consortium Bipolar Disorder Res, Belmont, MA 02178 USA. Free Univ Berlin, Benjamin Franklin Hosp, Dept Psychiat & Psychotherapy, D-1000 Berlin, Germany. Univ London, Maudsley Inst Psychiat, London, England. Humboldt Univ, Charite Hosp, Dept Psychiat & Psychotherapy, Berlin, Germany. Tech Univ Dresden, Carl Gustav Carus Hosp, Dept Psychiat, D-8027 Dresden, Germany. RP Baethge, C (reprint author), Harvard Univ, Sch Med, McLean Hosp, Mailman Res Ctr 306,Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. EM cbaethge@mclean.harvard.edu NR 32 TC 59 Z9 60 U1 2 U2 19 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2005 VL 7 IS 2 BP 136 EP 145 DI 10.1111/j.1399-5618.2004.00175.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 905SG UT WOS:000227589400005 PM 15762854 ER PT J AU Sanches, M Roberts, RL Sassi, RB Axelson, D Nicoletti, M Brambilla, P Hatch, JP Keshavan, MS Ryan, ND Birmaher, B Soares, JC AF Sanches, M Roberts, RL Sassi, RB Axelson, D Nicoletti, M Brambilla, P Hatch, JP Keshavan, MS Ryan, ND Birmaher, B Soares, JC TI Developmental abnormalities in striatum in young bipolar patients: a preliminary study SO BIPOLAR DISORDERS LA English DT Article DE affective disorders; basal ganglia; magnetic resonance imaging; mood disorders; neuroimaging; pediatric ID BASAL GANGLIA VOLUMES; MOOD DISORDERS; CAUDATE NUCLEI; WHITE-MATTER; IN-VIVO; SCHIZOPHRENIA; NEUROPSYCHIATRY; 1ST-EPISODE; DEPRESSION; CHILDREN AB Objectives: Anatomical abnormalities in the basal ganglia of adult mood disorder patients have been reported. To investigate whether these abnormalities are present early in illness course, we compared the volume of striatal structures in young bipolar patients and healthy controls. Methods: Brain magnetic resonance images of 15 children and adolescents who met DSM-IV criteria for bipolar disorders and 21 healthy controls were obtained. Measurements were performed manually, by trained evaluators, who were blind to subjects' diagnosis. The volumes of caudate and putamen were compared in patients and controls. Results: The volumes of striatal structures were not significantly different in patients and controls (ANCOVA, p > 0.05). However, we found a significant inverse relationship between age and the volumes of left caudate (r = -0.72, p < 0.01), right caudate (r = -0.66, p = 0.02) and left putamen (r = -0.71, p = 0.01) in bipolar patients, not present in healthy controls. Conclusions: Abnormalities in striatal development may be involved in the pathophysiology of bipolar disorder. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Univ Udine, Dept Pathol & Expt & Clin Med, Sect Psychiat, I-33100 Udine, Italy. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, Div Mood & Anxiety Disorders, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010 OI brambilla, paolo/0000-0002-4021-8456 FU NIMH NIH HHS [MH 30915, MH 01736, MH 55123] NR 29 TC 38 Z9 38 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2005 VL 7 IS 2 BP 153 EP 158 DI 10.1111/j.1399-5618.2004.00178.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 905SG UT WOS:000227589400007 PM 15762856 ER PT J AU Deckersbach, T Savage, CR Dougherty, DD Bohne, A Loh, R Nierenberg, A Sachs, G Rauch, SL AF Deckersbach, T Savage, CR Dougherty, DD Bohne, A Loh, R Nierenberg, A Sachs, G Rauch, SL TI Spontaneous and directed application of verbal learning strategies in bipolar disorder and obsessive-compulsive disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; cognitive dysfunction; episodic memory; euthymic; executive functioning; obsessive-compulsive disorder ID GLUCOSE METABOLIC RATES; DORSOLATERAL PREFRONTAL CORTEX; EPISODIC MEMORY IMPAIRMENT; CEREBRAL BLOOD-FLOW; WORKING-MEMORY; ORBITOFRONTAL CORTEX; EUTHYMIC PATIENTS; NEUROPSYCHOLOGICAL FUNCTION; COGNITIVE DYSFUNCTIONS; EXPLICIT MEMORY AB Objectives: Individuals with bipolar disorder exhibit neuropsychological impairments when they are euthymic (neither depressed nor manic). One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in verbal episodic memory. Recent findings suggest that episodic memory difficulties in these individuals are attributable to difficulties using organizational strategies during encoding. The purpose of the present study was (i) to investigate whether difficulties using organizational strategies in bipolar disorder are due to a failure in spontaneously initiating verbal organization strategies or are due to difficulties implementing such strategies, and (ii) to compare the characteristics of verbal organizational impairment in bipolar disorder with those observed in individuals with obsessive-compulsive disorder (OCD). Methods: Study participants were 20 individuals with bipolar I disorder (BP-I), 20 individuals with OCD, and 20 healthy control participants matched for age, gender, and education. Participants completed a verbal encoding paradigm that involved spontaneous and directed use of verbal organization strategies during encoding of word lists. Results: Compared with control subjects, both BP-I and OCD participants showed impaired verbal organization in the spontaneous encoding condition. In the directed encoding condition, OCD patients organized the word lists as well as control participants whereas BP-I participants exhibited lower verbal organization than both control and OCD participants. OCD and BP-I participants' free recall performance did not differ from that of control participants in the spontaneous encoding condition. In the directed encoding condition, BP-I participants recalled fewer words than OCD or control participants. Conclusions: Episodic memory difficulties in OCD are associated with difficulties spontaneously initiating verbal organization strategies during encoding whereas the ability to implement verbal organization when instructed to do so is preserved. BP-I participants, on the other hand, exhibit difficulties in both spontaneously initiating verbal organization strategies and in the ability to implement such strategies when instructed to do so. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Psychiat Neurosci Program,Bipolar Res Program, Charlestown, MA 02129 USA. Univ Kansas, Med Ctr, Dept Psychiat & Behav Sci, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. Univ Munster, Dept Psychol, D-4400 Munster, Germany. RP Deckersbach, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Psychiat, Psychiat Neurosci Program,Bipolar Res Program, 149-2611,Bldg 149,13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 76 TC 35 Z9 35 U1 2 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2005 VL 7 IS 2 BP 166 EP 175 DI 10.1111/j.1399-5618.2004.00168.x PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 905SG UT WOS:000227589400009 PM 15762858 ER PT J AU Bauer, KA AF Bauer, KA TI Functional tissue factor in blood? SO BLOOD LA English DT Editorial Material AB Several fines of evidence suggest that blood-borne tissue factor can promote thrombus growth. This study demonstrates that the amount of functional tissue factor in the blood of healthy individuals under nonflow conditions is vanishingly small. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Cambridge, MA 02138 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2620 EP 2621 DI 10.1182/blood-2005-01-0170 PG 2 WC Hematology SC Hematology GA 911YM UT WOS:000228042900003 ER PT J AU Sattler, M AF Sattler, M TI How to interfere with FLT3 SO BLOOD LA English DT Editorial Material ID TYROSINE KINASE INHIBITOR; LEUKEMIAS; PKC412 AB An siRNA approach targeting the FLT3 receptor with internal tandem duplication may increase the efficacy of the FLT3-specific tyrosine kinase inhibitor MLN518 in acute myeloid leukemias. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2625 EP 2626 DI 10.1182/blood-2005-01-0149 PG 2 WC Hematology SC Hematology GA 911YM UT WOS:000228042900009 ER PT J AU Walters, DK Stoffregen, EP Heinrich, MC Deininger, MW Druker, BJ AF Walters, DK Stoffregen, EP Heinrich, MC Deininger, MW Druker, BJ TI RNAi-induced down-regulation of FLT3 expression in AML cell lines increases sensitivity to MLN518 SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; TYROSINE KINASE; RISK GROUP; MUTATIONS; MALIGNANCIES; ACTIVATION; INTERFERENCE; INHIBITION AB FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase that is constitutively activated in approximately 30% of acute myelogenous leukemia (AML) patients and appears to confer an adverse prognosis. Thus, development of inhibitors and/or antibodies that specifically target FLT3 has been of substantial interest. In this regard, phase 1 and 2 trials involving FLT3 inhibitors have recently reported FLT3 inhibition and leukemic blast reduction in some patients. Despite this, issues such as specificity and resistance need to be addressed. Consequently, the development of alternative approaches for targeting FLT3 would be of great consequence. In the present report, we demonstrate that FLT3 siRNA effectively down-regulates FLT3 expression in Ba/F3 cells transfected with FLT3 containing an activating internal tandem duplication (ITD) in the juxtamembrane domain and FLT3-ITD-positive Molm-14 human leukemia cells. Treatment with the FLT3 siRNA results in growth inhibition and apoptosis of these cells. Furthermore, siRNA-induced down-regulation of FLT3 increased the sensitivity of both cell lines to treatment with the FLT3 inhibitor MLN518. This illustrates the potential benefit of combined therapeutic approaches. C1 Oregon Hlth & Sci Univ, Inst Canc, Howard Hughes Med Inst, Dept Hematol & Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. RP Walters, DK (reprint author), Oregon Hlth & Sci Univ, Inst Canc, Howard Hughes Med Inst, Dept Hematol & Oncol, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM waltersd@ohsu.edu NR 23 TC 31 Z9 33 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2952 EP 2954 DI 10.1182/blood-2004-07-2758 PG 3 WC Hematology SC Hematology GA 911YM UT WOS:000228042900055 PM 15585651 ER PT J AU Miklos, DB Kim, HT Miller, KH Guo, LX Zorn, E Lee, SJ Hochberg, EP Wu, CJ Alyea, EP Cutler, C Ho, V Soiffer, RJ Antin, JH Ritz, J AF Miklos, DB Kim, HT Miller, KH Guo, LX Zorn, E Lee, SJ Hochberg, EP Wu, CJ Alyea, EP Cutler, C Ho, V Soiffer, RJ Antin, JH Ritz, J TI Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission SO BLOOD LA English DT Article; Proceedings Paper CT 45th Annual Meeting and Exhibition of the American-Society-of-Hematology CY DEC 06-09, 2003 CL San Diego, CA SP Amer Soc Hematol ID STEM-CELL TRANSPLANTATION; RESTRICTED TISSUE DISTRIBUTION; BONE-MARROW-TRANSPLANTATION; CYTOTOXIC T-CELLS; B-CELL; MYELOID-LEUKEMIA; FEMALE DONORS; GENE CODES; RECOGNITION; RISK AB Minor histocompatibility antigens (mHAs) are known targets of donor T cells after allogeneic hematopoietic stem cell transplantation (HSCT). In contrast, B-cell responses to mHAs have not been extensively characterized and the clinical significance of antibodies to mHAs is unknown. We tested 121 patients who underwent HSCT and 134 healthy donors for immunoglobulin G (IgG) antibodies against 5 mHAs encoded by genes on the Y chromosome (DBY, UTY, ZFY, RPS4Y, and EIF1AY). Antibodies to at least one H-Y protein developed in 52% of male patients with female donors compared with 8.7% of male patients with male donors (P < .0001), and in 41.4% of healthy females compared with 7.8% of healthy males (P < .0001). H-Y antibodies develop 4 to 12 months after transplantation and persist for long periods. The clinical significance of H-Y antibodies was characterized in 75 male patients with hematologic malignancies who received stem cells from female donors (F -> M HSCT). The presence of H-Y antibodies correlated with chronic graft-versus-host disease (GVHD) by univarlate (odds ratio [OR] = 15.5; P < .0001) and multivariable logistic regression analysis (OR = 56.5; P < .0001). Antibody response to Y-chromosome encoded histocompatibility antigens (H-Y antigens) was also associated with maintenance of disease remission (P < .0001). B cells may provide a new target for immune intervention in chronic GVHD. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,M530, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [HL70149, K08 HL069132, K08 HL69132, P01 HL070149]; NIAID NIH HHS [U19 AI029530, AI29530, P01 AI029530] NR 44 TC 227 Z9 237 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2973 EP 2978 DI 10.1182/blood-2004-09-3660 PG 6 WC Hematology SC Hematology GA 911YM UT WOS:000228042900059 PM 15613541 ER PT J AU Loberiza, FR Zhang, MJ Lee, SJ Klein, JP Lemaistre, CF Serna, DS Eapen, M Bredeson, CN Horowitz, MM Rizzo, JD AF Loberiza, FR Zhang, MJ Lee, SJ Klein, JP Lemaistre, CF Serna, DS Eapen, M Bredeson, CN Horowitz, MM Rizzo, JD TI Association of transplant center and physician factors on mortality after hernatopoietic stem cell transplantation in the United States SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; QUALITY-OF-CARE; SURGICAL VOLUME; CANCER; OUTCOMES; LEUKEMIA; WORKLOAD; BLOOD AB The effect of the organization and delivery of health care at medical centers, referred to as "center effects," with clinical outcomes after hematopoietic stem cell transplantation (HSCT) is not clear. We examined the association between center and treatment provider factors and mortality after HSCT. We surveyed 163 (87% response rate) United States transplantation centers that performed HLA-identical sibling HSCT for leukemia or autologous HSCT for lymphoma between 1998 and 2000 among patients at least 18 years old. One hundred thirteen (69%) mortality in patients receiving transplants in centers with favorable versus unfavorable factors were greater in allogeneic than autologous HSCT. Greater physician involvement in patient care is important in producing favorable outcomes after HSCT. To more clearly establish the role of the factors we identified, further studies are recommended. C1 Univ Nebraska, Med Coll Wisconsin, Ctr Med, CIBMTR, Milwaukee, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Texas Transplant Inst, San Antonio, TX USA. RP Loberiza, FR (reprint author), Univ Nebraska, Ctr Med, Dept Internal Med, Hematol Oncol Sect, 987680 Nebraska Med Ctr, Omaha, NE 68618 USA. EM FLOBERIZA@unmc.edu FU AHRQ HHS [5R03 HS 13046-02]; NCI NIH HHS [U24-CA76518]; PHS HHS [5K23 A82350-04] NR 27 TC 49 Z9 50 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2005 VL 105 IS 7 BP 2979 EP 2987 DI 10.1182/blood-2004-10-3863 PG 9 WC Hematology SC Hematology GA 911YM UT WOS:000228042900060 PM 15598815 ER PT J AU Ballen, KK King, R Carston, M Kollman, C Nelson, G Lim, S Reece, D Giralt, S Vesole, DH AF Ballen, KK King, R Carston, M Kollman, C Nelson, G Lim, S Reece, D Giralt, S Vesole, DH TI Outcome of unrelated transplants in patients with multiple myeloma SO BONE MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; unrelated donor ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE THERAPY; GRAFT-VERSUS-MYELOMA; ALLOGENEIC TRANSPLANTATION; COMBINATION CHEMOTHERAPY; TANDEM AUTOTRANSPLANTS; PROGNOSTIC-FACTORS; HOST-DISEASE; SURVIVAL AB The outcome of patients with multiple myeloma treated with standard therapy is disappointing, with a historical median survival of 3 years. Although high-dose therapy with autologous stem cell transplant has improved treatment outcomes, cure is unlikely. Allogeneic transplant provides a tumor-free graft and a graft-versus-myeloma effect. However, only a minority of patients has a compatible sibling donor. Unrelated hematopoietic stem cell transplant is another option. We analyzed the outcome of patients who received an unrelated bone marrow transplant facilitated by the National Marrow Donor Program (NMDP). Between 1989 and 2000, 71 patients received a myeloablative unrelated transplant for multiple myeloma; 70 patients consented for this analysis. The median recipient age was 44 years. A total of 31% of patients had received a prior autologous transplant. In all, 91% of patients engrafted. The 3-year cumulative incidence estimate of relapse was 34+/-10%. The incidence of Grade II-IV GVHD was 47%. The Kaplan-Meier estimate for overall survival at 5 years was 9+/-7%. The 100-day treatment-related mortality was 42%. In multivariate analysis, only a male donor was a significant predictor for survival. Better strategies are needed to treat patients with multiple myeloma, perhaps by using less-toxic, nonmyeloablative conditioning regimens. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Albany Med Coll, Albany, NY 12208 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM kballen@partners.org FU PHS HHS [240-97-0036] NR 47 TC 16 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 2005 VL 35 IS 7 BP 675 EP 681 DI 10.1038/sj.bmt.1704868 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 908YW UT WOS:000227827100006 PM 15723085 ER PT J AU Beresford, TP Arciniegas, D Clapp, L Martin, B Alfers, J AF Beresford, TP Arciniegas, D Clapp, L Martin, B Alfers, J TI Reduction of affective lability and alcohol use following traumatic brain injury: A clinical pilot study of anti-convulsant medications SO BRAIN INJURY LA English DT Article ID RELAPSE PREVENTION; AFFECTIVE-DISORDER; GABA(A) RECEPTOR; AXIS-I; CARBAMAZEPINE; ASSOCIATION; DIVALPROEX; VALPROATE; RELEASE; GENE AB Objective: A large and under-recognized sub-set of patients suffer both traumatic brain injury (TBI) and alcohol dependence (ADep). This group appears to use alcohol to self-treat affective and anxiety lability following TBI, resulting in new ADep or worsened prior ADep. This study hypothesized that treatment of such patients with mood-stabilizing medications would relieve post-TBI emotional dysregulation and facilitate reduction in alcohol use. Design: This study reported retrospective medical record data from outpatients in the Substance Abuse Treatment Programme who were treated for labile mood. Medications followed clinical indication and were given in non-blind fashion. Method: Subjects included 18 patients who (1) complained of debilitating affective lability following TBI, ( 2) described drinking alcohol to ease lability symptoms, (3) met DSM-IV criteria for current ADep and (4) were treated with a mood stabilizing medication. Results: During 6 weeks of treatment, 16 (89%) achieved abstinence from alcohol. All but two (14/16 or 88%) also showed improvement in their affective and anxiety symptoms. Conclusions: These preliminary data are limited by the retrospective collection, clinical impression and non-blinded trial. Nonetheless, the results suggest further investigation of anti-convulsants as potentially useful agents in co-morbid emotional lability and ADep following TBI. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. Spalding Rehabil Hosp, Brain Injury Rehabil Unit, Aurora, CO USA. RP Beresford, TP (reprint author), Denver Vet Affairs Med Ctr, 151,1055 Clermont St, Denver, CO 80220 USA. EM thomas.beresford@uchsc.edu RI Arciniegas, David/A-3792-2009 FU NIAAA NIH HHS [AA12095] NR 21 TC 9 Z9 9 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD APR PY 2005 VL 19 IS 4 BP 309 EP 313 DI 10.1080/02699050410001720121 PG 5 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 917MN UT WOS:000228466400007 PM 15832875 ER PT J AU Martin, J Taylor, C Trehan, M Baron, E Anstey, A AF Martin, J Taylor, C Trehan, M Baron, E Anstey, A TI Phototesting in the Smith-Lemli-Opitz syndrome confirms sensitivity to UVA SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the British-Society-for-Investigative-Dermatology CY APR 11-13, 2005 CL Univ Cambridge, Cambridge, ENGLAND SP British Soc Investigat Dermatol HO Univ Cambridge C1 Royal Gwent Hosp, Dept Photodermatol, Newport NPT 2VB, Gwent, Wales. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Case Western Reserve Univ, Univ Cleveland, Cleveland, OH 44106 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2005 VL 152 IS 4 BP 848 EP 848 PG 1 WC Dermatology SC Dermatology GA 915NC UT WOS:000228309900091 ER PT J AU Crawford, LJ Morris, TCM Chauhan, D Anderson, KC Walker, B Irvine, AE AF Crawford, LJ Morris, TCM Chauhan, D Anderson, KC Walker, B Irvine, AE TI The novel proteasome inhibitor BzLLL-COCHO is a specific inhibitor of proteasome activity SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 45th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 11-13, 2005 CL Manchester, ENGLAND SP British Soc Haematol C1 Queens Univ Belfast, Dept Haematol, Belfast BT7 1NN, Antrim, North Ireland. Belfast City Hosp, Dept Haematol, Belfast, Antrim, North Ireland. Dana Farber Canc Inst, Boston, MA 02115 USA. Queens Univ Belfast, Dept Pharm, Belfast BT7 1NN, Antrim, North Ireland. RI IRVINE, ALEXANDRA/B-3497-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2005 VL 129 SU 1 MA 22 BP 8 EP 8 PG 1 WC Hematology SC Hematology GA 921HG UT WOS:000228754300023 ER PT J AU Forchielli, ML Walker, WA AF Forchielli, ML Walker, WA TI The role of gut-associated lymphoid tissues and mucosal defence SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE development of gut immunity; prebiotics and intestinal host defence; prebiotics and microbial function ID TOLL-LIKE RECEPTORS; REGULATORY T-CELLS; INTESTINAL EPITHELIAL-CELLS; ORAL TOLERANCE INDUCTION; DENDRITIC CELLS; IMMUNE-RESPONSE; CUTTING EDGE; MICE; EXPRESSION; BIFIDOBACTERIA AB The newborn infant leaves a germ-free intrauterine environment to enter a contaminated extrauterine world and must have adequate intestinal defences to prevent the expression of clinical gastrointestinal disease states. Although the intestinal mucosal immune system is fully developed after a full-term birth, the actual protective function of the gut requires the microbial stimulation of initial bacterial colonization. Breast milk contains prebiotic oligosaccharides, like inulin-type fructans, which are not digested in the small intestine but enter the colon as intact large carbohydrates that are then fermented by the resident bacteria to produce SCFA. The nature of this fermentation and the consequent pH of the intestinal contents dictate proliferation of specific resident bacteria. For example, breast milk-fed infants with prebiotics present in breast milk produce an increased proliferation of bifidobacteria and lactobacilli (probiotics), whereas formula-fed infants produce more enterococci and enterobacteria. Probiotics, stimulated by prebiotic fermentation, are important to the development and sustainment of intestinal defences. For example, probiotics can stimulate the synthesis and secretion of polymeric IgA, the antibody that coats and protects mucosal surfaces against harmful bacterial invasion. In addition, appropriate colonization with probiotics helps to produce a balanced T helper cell response (Th1=Th2=Th3/Tr1) and prevent an imbalance (Th1 > Th2 or Th2 > Th1) contributing in part to clinical disease (Th2 imbalance contributes to atopic disease and Th1 imbalance contributes to Crohn's disease and Helicobacter pylori-induced gastritis). Furthermore, a series of pattern recognition receptors, toll-like receptors on gut lymphoid and epithelial cells that interact with bacterial molecular patterns (e.g. endotoxin (lipopolysaccharide), flagellin, etc.), help modulate intestinal innate immunity and an appropriate adaptive immune response. Animal and clinical studies have shown that inulin-type fructans will stimulate an increase in probiotics (commensal bacteria) and these bacteria have been shown to modulate the development and persistence of appropriate mucosal immune responses. However, additional studies are needed to show that prebiotics can directly or indirectly stimulate intestinal host defences. If this can be demonstrated, then prebiotics can be used as a dietary supplement to stimulate a balanced and an appropriately effective mucosal immune system in newborns and infants. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Bologna, Bologna, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Labs, Boston, MA USA. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. EM allan_walker@hms.harvard.edu NR 56 TC 107 Z9 117 U1 0 U2 14 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD APR PY 2005 VL 93 SU 1 BP S41 EP S48 DI 10.1079/BJN20041356 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924UR UT WOS:000229006500007 PM 15877894 ER PT J AU Giza, E Mithofer, K Farrell, L Zarins, B Gill, T Drawer, S AF Giza, E Mithofer, K Farrell, L Zarins, B Gill, T Drawer, S TI Injuries in women's professional soccer SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; KNEE INJURY; EUROPEAN FOOTBALL; FEMALE PLAYERS; YOUTH SOCCER; RISK-FACTORS; PREVENTION; SEASON AB Objective: The injury data from the first two seasons of the Women's United Soccer Association (WUSA) were analysed to determine the injury incidence, anatomic location of injuries, and relation of player position. Methods: Injury data on 202 players from eight teams during the first two seasons of the WUSA were prospectively collected and analysed. Results: A total of 173 injuries occurred in 110 players with an overall injury incidence rate of 1.93 injuries per 1000 player hours. The incidence of injury during practice and games was 1.17 and 12.63 per 1000 player hours, respectively. Of the injuries 82% were acute and 16% were chronic. Most of the injuries (60%) were located in the lower extremities. Strains (30.7%), sprains (19.1%), contusions (16.2%), and fractures (11.6%) were the most common diagnoses and the knee (31.8%) and head (10.9%) were the most common sites of injury. Anterior cruciate ligament (ACL) injuries accounted for 4.6% of all injuries and the incidence of ACL tears was 0.09 per 1000 player hours (practice 0.04, game 0.90). Midfielders suffered the most injuries (p<0.007). Conclusion: We conclude that the injury incidence in the WUSA is lower than the 6.2 injuries per 1000 player hours found in the corresponding male professional league (Major League Soccer); however, knee injuries predominate even in these elite female athletes. C1 Cent Maine Orthopaed Grp, Auburn, ME 04210 USA. Hosp Special Surg, New York, NY 10021 USA. Boston Breakers, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. UK Sport, London WC1N 1ST, England. RP Giza, E (reprint author), Cent Maine Orthopaed Grp, 690 Minot Ave,Suite 1, Auburn, ME 04210 USA. EM egiz@massmed.org; scott.drawer@uksport.gov.uk NR 39 TC 71 Z9 72 U1 3 U2 16 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD APR 1 PY 2005 VL 39 IS 4 BP 212 EP 216 DI 10.1136/bjsm.2004.011973 PG 5 WC Sport Sciences SC Sport Sciences GA 911CV UT WOS:000227980000014 PM 15793089 ER PT J AU Cather, C AF Cather, C TI Functional cognitive-behavioural therapy: A brief, individual treatment for functional impairments resulting from psychotic symptoms in schizophrenia SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE cognitive-behavioural therapy; psychosis; schizophrenia ID FAMILY INTERVENTION; SCALE AB This paper describes a novel cognitive-behavioural approach to treating psychotic symptoms-functional cognitive-behavioural therapy (FCBT)-which was developed with the primary aim of remediating social functioning deficits in patients with residual psychotic symptoms. In FCBT, symptom-focused cognitive-behavioural therapy (CBT) interventions are delivered in the context of working on functional goals: a premise of FCBT is that the therapeutic alliance and patient motivation are enhanced by linking interventions to life goals. The paper outlines the rationale for expanding existing approaches to target social functioning impairment and uses case illustrations to exemplify particular phases of treatment as well as specific CBT interventions. Results from a pilot study of FCBT are summarized, together with suggestions for new research directions. C1 Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Cather, C (reprint author), Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ccather@partners.org NR 28 TC 7 Z9 9 U1 2 U2 5 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD APR PY 2005 VL 50 IS 5 BP 258 EP 263 PG 6 WC Psychiatry SC Psychiatry GA 003VA UT WOS:000234708500004 PM 15968840 ER PT J AU Strate, LL Syngal, S AF Strate, LL Syngal, S TI Hereditary colorectal cancer syndromes SO CANCER CAUSES & CONTROL LA English DT Article DE colon cancer; hereditary cancer syndromes; familial adenomatous polyposis; hereditary nonpolyposis colorectal cancer; Juvenile polyposis; Peutz-Jegers syndrome; hamartomatous polyps ID FAMILIAL ADENOMATOUS POLYPOSIS; PEUTZ-JEGHERS-SYNDROME; GERM-LINE MUTATIONS; JUVENILE POLYPOSIS; MICROSATELLITE INSTABILITY; LYNCH-SYNDROME; BETHESDA GUIDELINES; NATURAL-HISTORY; COLON-CANCER; RISK AB The purpose of this article is to review the genetic colorectal cancer syndromes including Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Family Polyposis (FAP) and the hamartomatous polyposis syndromes. HNPCC is the most common of the hereditary colorectal cancer syndromes, and is the result of defects in the mismatch repair genes. Individuals with HNPCC have an 80 lifetime risk of colorectal cancer, and in females a 30-50% risk of endometrial cancer, as well as predisposition for a number of other malignancies. Early screening and interval surveillance for colorectal and endometrial cancer are recommended. In FAP, mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene give rise to hundreds to thousands of colorectal polyps, some of which will inevitably progress to cancer. Early diagnosis and timely prophylactic colectomy prevent this outcome. Chemoprevention with nonsteroidal anti-inflammatory drugs can reduce adenoma number and size in FAP, but the effect is incomplete. In addtion, surveillance for upper gastrointestinal tract malignancies is necessary. Attenuated forms of FAP may be the result of mutations in the APC gene, or in the recently described MYH gene. Mutations in the MYH gene should be considered in individuals with multiple adenomas whose family history does not reflect an autosomal dominant pattern of inheritance. The hamartomatous polyposis syndromes are uncommon but distinctive disorders in which multiple hamartomatous polyps develop at a young age. Our understanding of the genetic basis of these disorders is improving, and a predisposition for gastrointestinal and other malignancies has recently been recognized. This article summarizes the genetics, clinical manifestations and clinical management of each of these syndromes with an emphasis on genetic testing and prevention. C1 Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Populat Sci, 44 Binney St, Boston, MA 02115 USA. EM ssyngal@partners.org NR 55 TC 65 Z9 70 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD APR PY 2005 VL 16 IS 3 BP 201 EP 213 DI 10.1007/s10552-004-3488-4 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 934VK UT WOS:000229736900002 PM 15947872 ER PT J AU Levine, RL Wadleigh, M Cools, J Ebert, BL Wernig, G Huntly, BJP Boggon, TJ Wlodarska, L Clark, JJ Moore, S Adelsperger, J Koo, S Lee, JC Gabriel, S Mercher, T D'Andrea, A Frohling, S Dohner, K Marynen, P Vandenberghe, P Mesa, RA Tefferi, A Griffin, JD Eck, MJ Sellers, WR Meyerson, M Golub, TR Lee, SJ Gilliland, DG AF Levine, RL Wadleigh, M Cools, J Ebert, BL Wernig, G Huntly, BJP Boggon, TJ Wlodarska, L Clark, JJ Moore, S Adelsperger, J Koo, S Lee, JC Gabriel, S Mercher, T D'Andrea, A Frohling, S Dohner, K Marynen, P Vandenberghe, P Mesa, RA Tefferi, A Griffin, JD Eck, MJ Sellers, WR Meyerson, M Golub, TR Lee, SJ Gilliland, DG TI Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis SO CANCER CELL LA English DT Article ID ERYTHROPOIETIN RECEPTOR GENE; MYELOMONOCYTIC LEUKEMIA; FAMILIAL POLYCYTHEMIA; RET PROTOONCOGENE; IMATINIB MESYLATE; LUNG-CANCER; CELL-LINE; STEM-CELL; BCR-ABL; PROTEIN AB Polycythemia vera (PV), essential thrombocythemia (ET), and myeloid metaplasia with myelofibrosis (MMM) are clonal disorders arising from hematopoietic progenitors. An internet-based protocol was used to collect clinical information and biological specimens from patients with these diseases. High-throughput DNA resequencing identified a recurrent somatic missense mutation JAK2V617F in granulocyte DNA samples of 121 of 164 PV patients, of which 41 had homozygous and 80 had heterozygous mutations. Molecular and cytogenetic analyses demonstrated that homozygous mutations were due to duplication of the mutant allele. JAK2V617F was also identified in granulocyte DNA samples from 37 of 115 ET and 16 of 46 MMM patients, but was not observed in 269 normal individuals. In vitro analysis demonstrated that JAK2V617F is a constitutively active tyrosine kinase. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Katholieke Univ Leuven VIB, Dept Human Genet, B-3000 Louvain, Belgium. Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Mayo Clin & Mayo Fdn, Div Hematol & Internal Med, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu RI Meyerson, Matthew/E-7123-2012; huntly, brian/E-6725-2014; Mercher, Thomas/J-2446-2014; OI huntly, brian/0000-0003-0312-161X; Mercher, Thomas/0000-0003-1552-087X; Vandenberghe, Peter/0000-0003-4719-1935; Cools, Jan/0000-0001-6626-5843 FU NCI NIH HHS [CA66996, T32 CA009172]; NIDDK NIH HHS [DK50654] NR 50 TC 1630 Z9 1744 U1 16 U2 76 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 2005 VL 7 IS 4 BP 387 EP 397 DI 10.1016/j.ccr.2005.03.023 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 921CL UT WOS:000228741700013 PM 15837627 ER PT J AU Weisberg, E Manley, PW Breitenstein, W Bruggen, J Cowan-Jacob, SW Ray, A Huntly, B Fabbro, D Fendrich, G Hall-Meyers, E Kung, AL Mestan, J Daley, GQ Callahan, L Catley, L Cavazzall, C Azam, M Neuberg, D Wright, RD Gilliland, G Griffin, JD AF Weisberg, E Manley, PW Breitenstein, W Bruggen, J Cowan-Jacob, SW Ray, A Huntly, B Fabbro, D Fendrich, G Hall-Meyers, E Kung, AL Mestan, J Daley, GQ Callahan, L Catley, L Cavazzall, C Azam, M Neuberg, D Wright, RD Gilliland, G Griffin, JD TI Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abi (vol 7, pg 129, 2005) SO CANCER CELL LA English DT Correction C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM james_griffin@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; huntly, brian/E-6725-2014 OI huntly, brian/0000-0003-0312-161X NR 1 TC 10 Z9 10 U1 1 U2 7 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 2005 VL 7 IS 4 BP 399 EP 399 DI 10.1016/j.ccr.2005.03.026 PG 1 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 921CL UT WOS:000228741700014 ER PT J AU Oh, K Willett, WC Fuchs, CS Giovannucci, E AF Oh, K Willett, WC Fuchs, CS Giovannucci, E TI Dietary marine n-3 fatty acids in relation to risk of distal colorectal adenoma in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; BREAST-CANCER MORTALITY; CORONARY-HEART-DISEASE; COLON-CANCER; OMEGA-3-FATTY-ACID INTAKE; EICOSAPENTAENOIC ACID; CELL-PROLIFERATION; RANDOMIZED-TRIAL; ASPIRIN USE; FISH-OIL AB Epidemiologic studies of dietary marine n-3 fatty acids and risk of colorectal cancer have been inconsistent, and their relation to risk of colorectal adenoma has not been evaluated in detail. We examined dietary marine n-3 fatty acids and the ratio of marine n-3 to total n-6 fatty acids (n-3/ n-6 ratio) in relation to risk of adenoma of the distal colon or rectum among 34,451 U.S. women who were initially free of colorectal cancer or polyps, who completed a semiquantitative food frequency questionnaire in 1980, and who underwent endoscopy from 1980 to 1998. We documented 1,719 distal colorectal adenoma cases (705 large adenomas, 897 small adenomas, 1,280 distal colon adenomas, and 505 rectal adenomas) during 18 years of follow-up. Neither dietary marine n-3 fatty acids nor n-3/n-6 ratio were associated with risk of total distal colorectal adenoma after adjustment for age and established risk factors [multivariable relative risk (RR) for extreme quintiles of dietary marine n-3 fatty acids = 1.04; 95% confidence interval (95% CD, 0.84-1.27, P-trend = 0.66; RR for extreme quintiles of n-3/ n-6 ratio = 1.02; 95% CI, 0.83-1.25; P-trend = 0.86]. Similarly, no significant associations were observed separately for distal colon or rectal adenoma. However, higher intake of dietary marine n-3 fatty acids was nonsignificantly but suggestively inversely associated with large adenoma (RR, 0.74; 95% CI, 0.54-1.01; P-trend = 0.16) but directly associated with small adenoma (RR, 1.36; 95% CI, 1.02-1.81; P-trend = 0.09). Our findings do not support the hypothesis that a higher intake of marine n-3 fatty acids or a higher n-3/n-6 ratio reduces the risk of distal colorectal adenoma but are suggestive that higher intake may reduce the progression of small adenomas to large adenomas. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM edward.giovannucci@channing.hanard.edu FU NCI NIH HHS [CA 87969, CA55075] NR 54 TC 27 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 835 EP 841 DI 10.1158/1055-9965.EPI-04-0545 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300014 PM 15824153 ER PT J AU Michels, KB Fuchs, CS Giovannucci, E Colditz, GA Hunter, DJ Stampfer, MJ Willett, WC AF Michels, KB Fuchs, CS Giovannucci, E Colditz, GA Hunter, DJ Stampfer, MJ Willett, WC TI Fiber intake and incidence of colorectal cancer among 76,947 women and 47,279 men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; COVARIANCE STRUCTURE MODELS; CORONARY-HEART-DISEASE; DIETARY FIBER; COLON-CANCER; MEASUREMENT ERROR; EPIDEMIOLOGIC EVIDENCE; DECREASED RISK; GLYCEMIC LOAD; VEGETABLES AB Prospective cohort studies have consistently found no important link between fiber intake and risk of colorectal cancer. The recent large, prospective European Prospective Investigation into Cancer and Nutrition has challenged this paradigm by suggesting significant protection by high fiber intake. We prospectively investigated the association of fiber intake with the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (76,947 women) and the Health Professionals Follow-up Study (47,279 men). Diet was assessed repeatedly in 1984, 1986, 1990, and 1994 among women and in 1986, 1990, and 1994 among men. The incidence of cancer of the colon and rectum was ascertained up to the year 2000. Relative risk estimates were calculated using a Cox proportional hazards model simultaneously controlling for potential confounding variables. During follow-up including 1.8 million person-years and 1,596 cases of colorectal cancer, we found little association with fiber intake after controlling for confounding variables. The hazard ratio for a 5-g/d increase in fiber intake was 0.91 (95% confidence interval, 0.87-0.95) after adjusting for covariates used in the European Prospective Investigation into Cancer and Nutrition study and 0.99 (95% confidence interval, 0.95-1.04) after adjusting for additional confounding variables. Our data from two large prospective cohorts with long follow-up and repeated assessment of fiber intake and of a large number of potential confounding variables do not indicate an important association between fiber intake and colorectal cancer but reveal considerable confounding by other dietary and lifestyle factors. C1 Harvard Univ, Sch Med,Dept Obstet & Gynecol, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michels, KB (reprint author), Harvard Univ, Sch Med,Dept Obstet & Gynecol, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. EM kmichels@rics.bwh.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA87969, P01 CA055075-14, P01 CA087969-06]; NIDDK NIH HHS [R01 DK054900-01A2, R01 DK54900] NR 46 TC 54 Z9 57 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 842 EP 849 DI 10.1158/1055-9965.EPI-04-0544 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300015 PM 15824154 ER PT J AU Wei, EK Ma, J Pollak, MN Rifai, N Fuchs, CS Hankinson, SE Giovannucci, E AF Wei, EK Ma, J Pollak, MN Rifai, N Fuchs, CS Hankinson, SE Giovannucci, E TI A prospective study of C-peptide, insulin-like growth factor-1, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DIETARY GLYCEMIC LOAD; PHYSICAL-ACTIVITY; COLON-CANCER; DIABETES-MELLITUS; PLASMA-INSULIN; UNITED-STATES; BODY-SIZE; IGF-I; CALORIC RESTRICTION; FACTOR (IGF)-I AB Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-1 have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-1 to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-1 levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Lady Davis Res Inst, Dept Oncol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal, PQ, Canada. RP Wei, EK (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM esther.wei@channing.harvard.edu RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU NCI NIH HHS [R01 CA049449-10, CA42182, CA49449, CA87969, CA90598, P01 CA087969-01, R01 CA042182-13, R01 CA090598-01A1, T32 CA 09001, T32 CA009001-23] NR 57 TC 134 Z9 140 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2005 VL 14 IS 4 BP 850 EP 855 DI 10.1158/1055-9965.EPI-04-0661 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 915ZS UT WOS:000228351300016 PM 15824155 ER PT J AU Marciniak, RA Cavazos, D Montellano, R Chen, QJ Guarente, L Johnson, FB AF Marciniak, RA Cavazos, D Montellano, R Chen, QJ Guarente, L Johnson, FB TI A novel telomere structure in a human alternative lengthening of telomeres cell line SO CANCER RESEARCH LA English DT Article ID IMMORTALIZED HUMAN-CELLS; WERNER-SYNDROME; DNA HELICASE; RECOMBINATION; MAINTENANCE; ABSENCE; CANCER; CHROMOSOMES; FIBROBLASTS; EXONUCLEASE AB Cancer cells require mechanisms to maintain telomeres. Most use telomerase, but 5% to 20% of tumors use alternative lengthening of telomeres (ALT), a telomerase-independent mechanism that seems to depend on recombination. ALT is characterized by amplification of telomere TTAGGG repeats to lengths beyond 50 kb, by elevated rates of telomere recombination, and by nuclear structures called ALT-associated promyelocytic leukemia bodies. In Saccharomyces cerevisiae, survivors of telomerase inactivation also use recombination to maintain telomeres. There are two types of survivors, which differ in telomere structure. The first possesses telomere repeats and the V subtelomeric element amplified together as a tandem array at chromosome termini (type 1), and the other possesses amplification of telomeric repeats alone (type 11), similar to previously described human ALT cells. Here, we describe the first human ALT cell line having "tandem array" telomeres with a structure similar to that of type I yeast survivors. The chromosome termini consist of a repeat unit containing similar to 2.5 kb of SV40 DNA and a variable amount of TTAGGG sequence repeated in tandem an average of 10 to 20 times. Similar to previously described ALT cells, they show evidence of telomere recombination, but unlike standard ALT cells, they lack ALT-associated promyelocytic leukemia bodies and their telomeres are transcribed. These findings have implications for the pathogenesis and diagnosis of cancer. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Change Labs 405A, Philadelphia, PA 19104 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Johnson, FB (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Stellar Change Labs 405A, 422 Curie Blvd, Philadelphia, PA 19104 USA. EM marciniak@uthsesa.edu; johnsonb@mail.med.upenn.edu FU NIA NIH HHS [K08AG000775] NR 41 TC 47 Z9 52 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2730 EP 2737 DI 10.1158/0008-5472.CAN-04-2888 PG 8 WC Oncology SC Oncology GA 911AB UT WOS:000227972300034 PM 15805272 ER PT J AU Kambara, H Okano, H Chiocca, EA Saeki, Y AF Kambara, H Okano, H Chiocca, EA Saeki, Y TI An oncolytic HSV-1 mutant expressing ICP34.5 under control of a nestin promoter increases survival of animals even when symptomatic from a brain tumor SO CANCER RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; CENTRAL-NERVOUS-SYSTEM; PHASE-I TRIAL; MALIGNANT GLIOMAS; PACKAGING SYSTEM; ADENOVIRUS; CELLS; HERPES-SIMPLEX-VIRUS-1; METASTASES; INJECTION AB Oncolytic herpes simplex virus-1 (HSV-1) mutants possessing mutations in the ICP34.5 and ICP6 genes have proven safe through clinical trials. However, ICP34.5-null viruses may grow poorly in cells due to their inability to prevent host-cell shut-off of protein synthesis caused by hyperphosphorylation of eukaryotic initiation factor 2 alpha. To increase tumor selectivity, glioma-selective expression of ICP34.5 in the context of oncolysis may be useful. Malignant gliomas remain an incurable disease. One molecular marker of malignant gliomas is expression of the intermediate filament nestin. Expression of nestin mRNA was confirmed in 6 of 6 human glioma lines and in 3 of 4 primary glioma cells. Normal human astrocytes were negative. A novel glioma-selective HSV-1 mutant (rQNestin34.5) was thus engineered by expressing ICP34.5 under control of a synthetic nestin promoter. Replication, cellular propagation, and cytotoxicity of rQNestin34.5 were significantly enhanced in cultured and primary human glioma cell lines compared with control virus. However, replication, cellular propagation, and cytotoxicity of rQNestin34.5 in normal human astrocytes remained quantitatively similar to that of control virus. In glioma cell lines infected with rQNestin34.5, the level of phosphoeukaryotic initiation factor 2 alpha was lower than that of cells infected by control rHsvQ1, confirming selective ICP34.5 expression in glioma cells. In vivo, rQNestin34.5 showed significantly more potent inhibition of tumor growth compared with control virus. Treatment in the brain tumor model was instituted on animal's display of neurologic symptoms, which usually led to rapid demise. rQNestinUZ treatment doubled the life span of these animals. These results show that rQNestin34.5 could be a potent agent for the treatment of malignant glioma. C1 Ohio State Univ, James Canc Hosp, Dept Neurol Surg,Med Ctr, Dardinger Ctr Neurooncol,Comprehens Canc Ctr, Columbus, OH 43210 USA. Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo, Japan. Japan Sci & Technol Agcy, Kawaguchi, Saitama, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Mol Neurooncol Labs, Boston, MA USA. RP Chiocca, EA (reprint author), Ohio State Univ, James Canc Hosp, Dept Neurol Surg,Med Ctr, Dardinger Ctr Neurooncol,Comprehens Canc Ctr, N-1017 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM Chiocca-1@medctr.osu.edu; saeki-1@medctr.osu.edu RI Hidokano, Hideyuki/J-5973-2013 FU NCI NIH HHS [P01 CA69246, R01 CA85139]; NINDS NIH HHS [R01 NS41571] NR 28 TC 108 Z9 114 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2832 EP 2839 DI 10.1158/0008-5472.CAN-04-3227 PG 8 WC Oncology SC Oncology GA 911AB UT WOS:000227972300046 PM 15805284 ER PT J AU Venkatasubbarao, K Choudary, A Freeman, JW AF Venkatasubbarao, K Choudary, A Freeman, JW TI Farnesyl transferase inhibitor (R115777)-induced inhibition of STAT3((Tyr705)) phosphorylation in human pancreatic cancer cell lines require extracellular signal-regulated kinases SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; STAT3 ACTIVATION; SERINE PHOSPHORYLATION; FARNESYLTRANSFERASE INHIBITORS; TRANSCRIPTIONAL ACTIVATION; TYROSINE PHOSPHORYLATION; ERK PHOSPHORYLATION; MOLECULAR TARGETS; SUPPRESSES GROWTH; INDUCED APOPTOSIS AB In this study, we report that R115777, a nonpeptidomimetic farnesyl transferase inhibitor, suppresses the growth of human pancreatic adenocarcinoma cell lines and that this growth inhibition is associated with modulation in the phosphorylation levels of signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinases (ERK). Treatment of cells with R115777 inhibited the tyrosine phosphorylation of STAT3((Tyr705)), while increasing the serine phosphorylation of STAT3((Ser727)). We found the differential phosphorylation of STAT3 was due to an increased and prolonged activation of ERKs. The biological significance of ERK-mediated inhibition of STAT3 (Tyr705) phosphorylation was further assessed by treating the cells with an inhibitor (PD98059) of mitogen-activated protein kinase kinase (MEK) or by transfecting the cells with a vector that expresses constitutively active MEK-1. Expression of constitutively active MEK-1 caused an increase of ERK activity and inhibited STAT3((Tyr705)) phosphorylation. Conversely, inhibition of ERK activity by PD98059 reversed the R115777-induced inhibition of STAT3((Tyr705)) phosphorylation. R115777 also caused the inhibition of the binding of STAT3 to its consensus binding element. An increase in the activation of ERKs either by overexpressing MEK-1 or treatment of cells with R115777 caused an up-regulation in the levels of a cyclin-dependent kinase (cdk) inhibitor, p21(cip1/waf1). These observations suggest that R115777-induced growth inhibition is partly due to the prolonged activation of ERKs that mediates an inhibition of STAT3((Tyr705)) phosphorylation and an increase in the levels of p21(cip1/waf1) in human pancreatic adenocarcinoma cell lines. C1 Univ Texas, Ctr Hlth, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX USA. Univ Texas, Ctr Hlth, Dept Cell & Struct Biol, San Antonio, TX 78229 USA. RP Freeman, JW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freemanjw@uthscsa.edu NR 73 TC 34 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2005 VL 65 IS 7 BP 2861 EP 2871 DI 10.1158/0008-5472.CAN-04-2396 PG 11 WC Oncology SC Oncology GA 911AB UT WOS:000227972300050 PM 15805288 ER PT J AU Xia, SH Wang, JD Kang, JX AF Xia, SH Wang, JD Kang, JX TI Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER; RISK-FACTORS; FISH-OIL; EXPRESSION; OMEGA-3-FATTY-ACIDS; EPIDEMIOLOGY; DESATURASE; ACTIVATION; COLLAGEN; ARRAYS AB Recent studies have shown opposing effects of n-6 and n-3 fatty acids on the development of cancer and suggest a role for the ratio of n-6 to n-3 fatty acids in the control of cancer. However, whether an alteration in the n-6/n-3 fatty acid ratio of cancer cells affects their invasive potential has not been well investigated. We recently developed a genetic approach to modify the n-6/n-3 ratio by expression of the Caenorhabditis elegans fat-1 gene encoding an n-3 desaturase that converts n-6 to n-3 fatty acids in mammalian cells. The objective of this study was to examine the effect of alteration in the n-6/n-3 fatty acid ratio on the invasive potential of human lung cancer A549 cells. Adenovirus-mediated gene transfer of the n-3 desaturase resulted in a marked reduction of the n-6/n-3 fatty acid ratio, particularly the ratio of arachidonic acid to eicosapentaenic acid. Cell adhesion assay showed that the cells expressing fat-1 gene had a delayed adhesion and retarded colonization. Matrigel assay for invasion potential indicated a 2-fold reduction of cell migration in the fat-1 transgenic cells when compared with the control cells. An increased apoptosis was also observed in the fat-1 transgenic cells. Microarray and quantitative polymerase chain reaction revealed a downregulation of several adhesion/invasion-related genes (MMP-1, integrin-alpha 2 and nm23-H4) in the fat-1 transgenic cells. These results demonstrate that a decreased n-6/n-3 fatty acid ratio reduces the invasion potential of human lung cancer cells by probably downregulating the cell adhesion/invasion-related molecules, suggesting a role for the ratio of n-6 to n-3 fatty acids in the prevention and treatment of cancer. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM kang.jing@mgh.harvard.edu NR 27 TC 49 Z9 60 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2005 VL 26 IS 4 BP 779 EP 784 DI 10.1093/carcin/bgi019 PG 6 WC Oncology SC Oncology GA 911BR UT WOS:000227976700009 PM 15661810 ER PT J AU Okumura, K Zhao, MJ DePinho, RA Furnari, FB Cavenee, WK AF Okumura, K Zhao, MJ DePinho, RA Furnari, FB Cavenee, WK TI PTEN - A novel anti-oncogenic function independent of phosphatase activity SO CELL CYCLE LA English DT Article DE PTEN; MSP58; C2 domain; GLTSCR2/PICT1; PDZ; FHA domain ID TUMOR-SUPPRESSOR PTEN; CELLULAR-TRANSFORMATION; PROTEIN STABILITY; GLIOMA-CELLS; PHOSPHORYLATION; DOMAIN; MIGRATION; MAGI-2; GENE AB The PTEN gene is an important tumor suppressor mutated in a number of cancers. To date, its growth regulatory properties have been intimately linked to its ability to act as a protein and phosphoinositol phosphatase. Inactivation of the enzymatic activity of PTEN is primarily due to direct mutation of its amino-terminal catalytic domain but similar to 20% of mutations are in the carboxy-terminus, which regulates membrane localization, protein stability, cellular migration and p53 function. We identified a novel protein that interacts with this domain, the v-jun transcriptional target, MSP58. Binding of MSP58 to PTEN results in the suppression of MSP58-mediated transformation. However, this PTEN effect does not require its catalytic activity, suggesting additional mechanisms of PTEN action. C1 Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Biomed Sci Grad Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai, Peoples R China. RP Cavenee, WK (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM wcavenee@ucsd.edu FU NCI NIH HHS [CA95616] NR 26 TC 20 Z9 25 U1 1 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR PY 2005 VL 4 IS 4 BP 540 EP 542 DI 10.4161/cc.4.4.1614 PG 3 WC Cell Biology SC Cell Biology GA 932FC UT WOS:000229538600009 PM 15753657 ER PT J AU Arany, Z He, HM Lin, JD Hoyer, K Handschin, C Toka, O Ahmad, F Matsui, T Chin, S Wu, PH Rybkin, II Shelton, JM Manieri, M Cinti, S Schoen, FJ Bassel-Duby, R Rosenzweig, A Ingwall, JS Spiegelman, BM AF Arany, Z He, HM Lin, JD Hoyer, K Handschin, C Toka, O Ahmad, F Matsui, T Chin, S Wu, PH Rybkin, II Shelton, JM Manieri, M Cinti, S Schoen, FJ Bassel-Duby, R Rosenzweig, A Ingwall, JS Spiegelman, BM TI Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle SO CELL METABOLISM LA English DT Article ID CONTROLLING MITOCHONDRIAL BIOGENESIS; RECEPTOR-GAMMA COACTIVATOR-1; SKELETAL-MUSCLE; 1-ALPHA PGC-1-ALPHA; HEART; PGC-1; EXPRESSION; METABOLISM; ALPHA; ACTIVATION AB Skeletal and cardiac muscle depend on high turnover of ATP made by mitochondria in order to contract efficiently. The transcriptional coactivator PGC-1α has been shown to function as a major regulator of mitochondrial biogenesis and respiration in both skeletal and cardiac muscle, but this has been based only on gain-of-function studies. Using genetic knockout mice, we show here that, while PGC-1α KO mice appear to retain normal mitochondrial volume in both muscle beds, expression of genes of oxidative phosphorylation is markedly blunted. Hearts from these mice have reduced mitochondrial enzymatic activities and decreased levels of ATR Importantly, isolated hearts lacking PGC-1α have a diminished ability to increase work output in response to chemical or electrical stimulation. As mice lacking PGC-1α age, cardiac dysfunction becomes evident in vivo. These data indicate that PGC-1α is vital for the heart to meet increased demands for ATP and work in response to physiological stimuli. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Chem, NMR Lab Physiol Chem, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Biol Mol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Ancona, Fac Med, Inst Normal Human Morphol, I-60020 Ancona, Italy. CVRC, Program Cardiovasc Gene Therapy, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NHLBI NIH HHS [HL052320, HL06296, HL063985, HL07604]; NIDDK NIH HHS [DK065584, DK54477, DK61562] NR 62 TC 334 Z9 345 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR PY 2005 VL 1 IS 4 BP 259 EP 271 DI 10.1016/j.cmet.2005.03.002 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 923IQ UT WOS:000228904000007 PM 16054070 ER PT J AU Spires, TL Molnar, Z Kind, PC Cordery, PM Upton, AL Blakemore, C Hannan, AJ AF Spires, TL Molnar, Z Kind, PC Cordery, PM Upton, AL Blakemore, C Hannan, AJ TI Activity-dependent regulation of synapse and dendritic spine morphology in developing barrel cortex requires phospholipase C-beta 1 signalling SO CEREBRAL CORTEX LA English DT Article DE cortical development; mGluR5; PLC-beta 1; stereology; synapse morphology; synaptogenesis ID CULTURED HIPPOCAMPAL-NEURONS; SOMATOSENSORY CORTEX; VISUAL-CORTEX; CEREBRAL-CORTEX; IN-VIVO; ARCUATE NUCLEUS; CRITICAL-PERIOD; FIELD CORTEX; RAT; PLASTICITY AB The phospholipase C-beta 1 (PLC-beta 1) signalling pathway, activated via metabotropic glutamate receptors (mGluRs), is implicated in activity-dependent development of the cerebral cortex, as both PLC-beta 1 and mGluR5 knockout mice exhibit disrupted barrel formation in somatosensory cortex. To characterize the effects of this signalling system on development of synaptic circuitry in barrel cortex, we have examined neuronal ultrastructure, synapse formation and dendritic spine morphology in PLC-beta 1 knockout mice. Qualitative ultrastructure of neurons and synapse density in layers 2-4 of barrel cortex were unchanged in PLC-beta 1 knockout mice during development [postnatal day (P) 5] and in mature cortex (P19-21). We found a decrease in the proportion of synapses with symmetric morphology at P5 that was gone by P19-21, indicating a transient imbalance in excitatory and inhibitory circuitry. We also investigated dendritic spines by back-labelling layer 5 pyramidal neurons with carbocyanine. We observed normal dendritic spine densities on apical dendrites as they passed through layer 4 of barrel cortex, but spine morphology was altered in PLC-beta 1 knockout mice at P9. These observations indicate that the PLC-beta 1 signalling pathway plays a role in the development of normal cortical circuitry. Interrupting this regulation leads to changes in synapse and dendritic spine morphology, possibly altering post-synaptic integration of signal. C1 Univ Oxford, Univ Physiol Lab, Oxford, England. Univ Oxford, Dept Human Anat & Genet, Oxford, England. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Spires, TL (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 114 16th St,Room 2021, Charlestown, MA 02129 USA. EM tara.spires@physiol.ox.ac.uk OI Molnar, Zoltan/0000-0002-6852-6004 NR 55 TC 44 Z9 47 U1 0 U2 1 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 2005 VL 15 IS 4 BP 385 EP 393 DI 10.1093/cercor/bhh141 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 905JL UT WOS:000227564300004 PM 15749982 ER PT J AU Patel, NR Lee, PS Kim, JH Weinhouse, GL Koziel, H AF Patel, NR Lee, PS Kim, JH Weinhouse, GL Koziel, H TI The influence of diagnostic bronchoscopy on clinical outcomes comparing adult autologous and allogeneic bone marrow transplant patients SO CHEST LA English DT Article; Proceedings Paper CT 98th International Conference of the American-Thoracic-Society CY MAY 17-23, 2002 CL ATLANTA, GA SP Amer Thorac Soc DE bone marrow transplantation; bronchoscopy; immunocompromised host ID INVASIVE PULMONARY ASPERGILLOSIS; DIFFUSE ALVEOLAR HEMORRHAGE; FIBEROPTIC BRONCHOSCOPY; BRONCHOALVEOLAR LAVAGE; COMPLICATIONS; RECIPIENTS AB Study objectives: To review our experience with diagnostic bronchoscopy in the evaluation of pulmonary infiltrates in adult hematopoietic stem cell transplantation (HSCT) recipients in the era of Pneumocystis prophylaxis and cytomegalovirus antigen testing. The study focused on diagnostic yields and the influence of bronchoscopic findings on pharmacologic therapy and mortality, comparing allogeneic (allo) HSCT patients to autologous (auto) HSCT patients. Design: Case series review. Setting: Tertiary care academic urban medical centers. Patients: All adult allo-HSCT and auto-HSCT patients undergoing bronchoscopy for the evaluation of pulmonary infiltrates from January 1997 to September 2001. Measurements and results: The review identified 169 bronchoscopies that had been performed on HSCT patients, representing 12.5% of all HSCT patients (allo-HSCT patients, 125 bronchoscopies; auto-HSCT patients, 44 bronchoscopies). Bronchoscopy was requested more often in allo-HSCT patients (18.7%) compared to auto-HSCT patients (6.6%). Findings at bronchoscopy provided a specific diagnosis more frequently in allo-HSCT patients (50%) compared to auto-HSCT patients (34%). For both allo-HSCT and auto-HSCT patients, most diagnoses were obtained by BAL alone, whereas transbronchial biopsy (TBBx) provided additional specific information in < 10% of cases. For select patients (n = 27), surgical lung biopsy following bronchoscopy provided unique diagnoses in 47 to 50% of cases. Information from bronchoscopy influenced clinical decisions more often in allo-HSCT patients (50%) than in auto-HSCT patients (36%), and allowed for the discontinuation. or addition of antimicrobial, corticosteroid, or antineoplastic agents to treatment. Complications from bronchoscopy occurred in 9% of all HSCT patients (n = 15), and were associated with higher in-hospital mortality rates in allo-HSCT patients (82%; n = 9) compared to auto-HSCT patients (50%; n = 2). The overall in-hospital mortality rates for allo-HSCT and auto-HSCT patients having bronchoscopy was similar (38% vs 27%, respectively, p = 0.25), and establishing a specific diagnosis by bronchoscopy did not improve the in-hospital mortality rate for allo-HSCT or auto-HSCT patients. Conclusions: Bronchoscopy may provide clinically useful information in the evaluation of adult allo-HSCT and auto-HSCT recipients with pulmonary infiltrates. The results of testing BAL fluid samples alone suggested an etiology in most cases, whereas the findings of TBBx provided unique diagnoses infrequently. Further studies are warranted to improve the utility of diagnostic bronchoscopy in the evaluation of HSCT patients. C1 BIDMC, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Koziel, H (reprint author), BIDMC, Div Pulm & Crit Care Med, Kirsten Hall,Room KSB-23,330 Brookline Ave, Boston, MA 02215 USA. EM hkoziel@bidmc.harvard.edu NR 15 TC 38 Z9 38 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2005 VL 127 IS 4 BP 1388 EP 1396 DI 10.1378/chest.127.4.1388 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 915ZG UT WOS:000228349900050 PM 15821221 ER PT J AU Morowitz, MJ Barr, R Wang, Q King, R Rhodin, N Pawel, B Zhao, HQ Erickson, SA Sheppard, GS Wang, JY Maris, JM Shusterman, S AF Morowitz, MJ Barr, R Wang, Q King, R Rhodin, N Pawel, B Zhao, HQ Erickson, SA Sheppard, GS Wang, JY Maris, JM Shusterman, S TI Methionine aminopeptidase 2 inhibition is an effective treatment strategy for neuroblastoma in preclinical models SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-RISK NEUROBLASTOMA; 67-KDA POLYPEPTIDE P67; ANGIOGENESIS INHIBITOR; NUDE-MICE; PHASE-I; TNP-470; EXPRESSION; GROWTH; CANCER; CELLS AB Tumor vascularity is correlated with an aggressive disease phenotype in neuroblastoma, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. We previously showed that the antiangiogenic compound TNP-470, an irreversible methionine aminopeptidase 2 (MetAP2) inhibitor, suppressed local and disseminated human neuroblastoma growth rates in murine models but had significant associated toxicity at the effective dose. We have recently shown that a novel, reversible MetAP2 inhibitor, A-357300, significantly inhibits CHP-134- derived neuroblastoma s.c. xenograft growth rate with a treatment-to-control (T/C) ratio at day 24 of 0.19 (P < 0.001) without toxicity. We now show that the combination of A-357300 with cyclophosphamide at the maximal tolerated dose sustained tumor regression with a T/C at day 48 of 0.16 (P < 0.001) in the CHP-134 xenograft model. A-357300 also significantly inhibited establishment and growth rate of hematogenous metastatic deposits following tail vein inoculation of CHP-134 cells and increased overall survival (P = 0.021). Lastly, A-357300 caused regression of established tumors in a genetically engineered murine model with progression-free survival in five of eight mice (P < 0.0001). There was no evidence of toxicity. These data show that MetAP2 may be an important molecular target for high-risk human neuroblastomas. We speculate that the growth inhibition may be through both tumor cell intrinsic and extrinsic (antiangiogenic) mechanisms, The potential for a wide therapeutic index may allow for treatment strategies that integrate MetAP2 inhibition with conventional cytotoxic compounds. C1 Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Biostat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. Abbott Labs, Canc Res, Global Pharmaceut R&D, Abbott Pk, IL 60064 USA. RP Shusterman, S (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Room 350C,Shields Warren Bldg,44 Binney St, Boston, MA 02118 USA. EM suzanne.shusterman@dfci.harvard.edu RI Pawel, Bruce/G-5466-2011 FU NCI NIH HHS [P01-CA97323, R01-CA87847] NR 49 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2005 VL 11 IS 7 BP 2680 EP 2685 DI 10.1158/1078-0432.CCR-04-1917 PG 6 WC Oncology SC Oncology GA 915QX UT WOS:000228320100031 PM 15814649 ER PT J AU Colby, KA Nagel, DS AF Colby, KA Nagel, DS TI Conjunctival melanoma arising from diffuse primary acquired melanosis in a young black woman SO CORNEA LA English DT Article DE conjunctival melanoma; black; mitomycin C; ocular surface tumor; primary acquired melanosis ID TOPICAL MITOMYCIN-C; MALIGNANT-MELANOMA; EXPERIENCE; LESIONS; ATYPIA AB Purpose: To report a case of conjunctival melanoma arising from diffuse primary acquired metanosis (PAM) with atypia in a young black woman in the context of previously published cases of this lesion in blacks. Methods: Retrospective case report with literature review. The number and percentage of conjunctival melanomas occurring in black patients were determined from case series in which race was specified, published from 1950 to the present. Results: Nodular multifocal conjunctival melanoma in a 30-year-old black woman was treated using surgical excision and adjuvant cryotherapy. Extensive PAM with severe atypia, including areas of microinvasive melanoma, was treated using topical mitomycin C. Literature review revealed 35 cases of conjunctival melanoma Occurring in black patients. No previous reports of mitomycin C use in black patients with melanoma or PAM were identified. Conclusions: Conjunctival melanoma is an exceedingly rare tumor in black patients. The current case brings the total of reported cases to 36. We successfully treated nodular melanoma and diffuse PAM in a young black woman using a combination of excision with cryotherapy and topical mitomycin C, suggesting that these lesions are amenable to the same types of therapy previously described for white patients. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Colby, KA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St,Suite 808, Boston, MA 02114 USA. EM kacolby@meei.harvard.edu NR 16 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD APR PY 2005 VL 24 IS 3 BP 352 EP 355 DI 10.1097/01.ico.0000141229.18472.a2 PG 4 WC Ophthalmology SC Ophthalmology GA 911LU UT WOS:000228004800022 PM 15778614 ER PT J AU Palevsky, PM AF Palevsky, PM TI Renal replacement therapy I: Indications and timing SO CRITICAL CARE CLINICS LA English DT Article ID CONTINUOUS VENOVENOUS HEMOFILTRATION; PROPHYLACTIC DIALYSIS; SODIUM-BICARBONATE; RANDOMIZED-TRIAL; LACTIC-ACIDOSIS; FAILURE; MORTALITY; HEMODIALYSIS; MULTICENTER; EXPERIENCE AB The indications for initiation of renal replacement therapy in acute renal failure are controversial. Although volume overload, metabolic acidosis, hyperkalemia and other electrolyte disturbances, and overt uremic manifestations are commonly accepted indications for renal replacement therapy, specific criteria for initiation of therapy based on these conditions are highly subjective. Progressive azotemia in the absence of overt uremia is another common indication for renal replacement therapy although there is no consensus on the degree of azotemia that warrants initiation of therapy. The clinical data regarding timing and initiation of renal support in patients who have acute renal failure are reviewed. Definitive resolution of the appropriate indications and timing for initiation of renal replacement therapy in acute renal failure requires prospective evaluation in a randomized clinical trial. C1 Univ Dr Div, VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Palevsky, PM (reprint author), Univ Dr Div, VA Pittsburgh Healthcare Syst, Renal Sect, Room 7E123, Pittsburgh, PA 15240 USA. EM palevsky@pitt.edu OI Palevsky, Paul/0000-0002-7334-5400 NR 34 TC 20 Z9 23 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 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD APR PY 2005 VL 21 IS 2 BP 347 EP + DI 10.1016/j.ccc.2004.12.002 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 915FE UT WOS:000228282600013 PM 15781167 ER PT J AU Silverman, HJ Luce, JM Lanken, PN Morris, AH Harabin, AL Oldmixon, CF Thompson, BT Bernard, GR AF Silverman, HJ Luce, JM Lanken, PN Morris, AH Harabin, AL Oldmixon, CF Thompson, BT Bernard, GR CA NHLBI ARDSNet TI Recommendations for informed consent forms for critical care clinical trials SO CRITICAL CARE MEDICINE LA English DT Review DE informed consent; research ethics; critical care; proxy consent; clinical trials ID ACUTE MYOCARDIAL-INFARCTION; THERAPEUTIC MISCONCEPTION; READABILITY; EMERGENCY; OUTCOMES; RISKS; DRUG AB Background., Many subjects enrolled in research studies have a limited understanding of the research to which they consented. Objective: To develop recommendations to enhance comprehensiveness and understanding of informed consent forms used in critical care clinical trials. Design: Consensus process. Recommendations. We provide recommendations regarding the U.S. federally required basic and additional elements of informed consent as applied to critical care clinical trials. We also identify issues that investigators need to address, if relevant, in the informed consent forms of critical care clinical trials. These include the description, in understandable language, of complex and detailed experimental protocols that are the focus of the clinical trial, disclosure of death as a risk factor if mortality is an outcome variable, and the identification of who can legally serve as the prospective subject's surrogate. We also offer suggestions to enhance subjects' understanding of informed consent forms. Conclusions. The literature on informed consent forms suggest that shorter informed consent forms written at a lower reading level, when read carefully, might provide better subject understanding. Prospective evaluation is needed to determine whether our recommendations enhance the informed consent process. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Penn, Sch Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. Univ Utah, Salt Lake City, UT 84112 USA. LDS Hosp, Div Pulm, Salt Lake City, UT USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Div Allergy Pulm & Crit Care Med, Nashville, TN 37212 USA. RP Silverman, HJ (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. FU NHLBI NIH HHS [N01 HR 46054-64] NR 49 TC 36 Z9 38 U1 2 U2 4 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 2005 VL 33 IS 4 BP 867 EP 882 DI 10.1097/01.CCM.0000159201.08203.10 PG 16 WC Critical Care Medicine SC General & Internal Medicine GA 915FF UT WOS:000228282700026 PM 15818118 ER PT J AU Morissette, MR Rosenzweig, A AF Morissette, MR Rosenzweig, A TI Targeting survival signaling in heart failure SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID GROWTH-FACTOR-I; PRESSURE-OVERLOAD HYPERTROPHY; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE AKT; NF-KAPPA-B; CELL-DEATH; PHOSPHATIDYLINOSITOL 3-KINASE; VENTRICULAR MYOCYTES; MYOCARDIAL-ISCHEMIA; CARDIAC-HYPERTROPHY AB Accumulating evidence suggests that apoptosis is not only a common feature of diverse forms of heart failure but also contributes to disease pathogenesis and progression. This contribution of apoptotic signaling to heart failure could reflect not only loss of cardiomyocytes but also dysfunction of surviving cells. The convergence of signaling mechanisms controlling both cardiomyocyte survival and function provides an opportunity for therapeutic strategies that target these pathways. However, significant hurdles must be overcome before the clinical application of these insights becomes possible. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Rosenzweig, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. EM arosenzweig@partners.org NR 50 TC 21 Z9 22 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD APR PY 2005 VL 5 IS 2 BP 165 EP 170 DI 10.1016/j.coph.2005.01.004 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 915HI UT WOS:000228288500009 PM 15780826 ER PT J AU Tsao, H Sober, AJ AF Tsao, H Sober, AJ TI Melanoma treatment update SO DERMATOLOGIC CLINICS LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; ACTIVE SPECIFIC IMMUNOTHERAPY; COOPERATIVE-ONCOLOGY-GROUP; GAMMA-KNIFE RADIOSURGERY; HIGH-RISK MELANOMA; MULTICENTER RANDOMIZED-TRIAL; PHASE-III; CUTANEOUS MELANOMA; DOSE INTERFERON-ALPHA-2B; ADJUVANT INTERFERON AB Except for high-dose interferon as adjuvant therapy in stage III disease, little success has emerged over the last 20 years for metastatic melanoma. Recent advances in melanoma biology suggest that disarming oncogenic mechanisms in melanoma may be an attractive approach to therapy. For instance, sustained expression of Bcl2 has been associated with an increased resistance to apoptosis, and recently, anti-sense-mediated reduction of Bcl2 levels was shown to chemosensitize patients to dacarbazine, dimethyl triazino imidazole carboxomide, or DTIC. Likewise, the identification of activating mutations in the RAS signaling pathway, including the NRAS and BRAF genes, opens up new therapeutic options for RAS and RAF inhibitors. A more thorough understanding of melanoma biology and tumor immunology will undoubtedly yield new promise for patients with advanced disease. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 48 Blossom St,Bartlett 622, Boston, MA 02114 USA. EM litsao@partners.org NR 77 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD APR PY 2005 VL 23 IS 2 BP 323 EP + DI 10.1016/j.det.2004.09.005 PG 12 WC Dermatology SC Dermatology GA 933PB UT WOS:000229644300012 PM 15837158 ER PT J AU Ji, JY Crest, J Schubiger, G AF Ji, JY Crest, J Schubiger, G TI Genetic interactions between Cdk1-CyclinB and the separase complex in Drosophila SO DEVELOPMENT LA English DT Article DE Cdk1-CycB; three rows; separase; anaphase; Drosophila ID SISTER-CHROMATID SEPARATION; ANAPHASE-PROMOTING COMPLEX; CYCLIN-A; CELL-CYCLE; CHROMOSOME SEGREGATION; SPINDLE CHECKPOINT; NUCLEAR MIGRATION; MITOTIC EXIT; MITOSIS; DESTRUCTION AB Cdk1-CycB plays a key role in regulating many aspects of cell-cycle events, such as cytoskeletal dynamics and chromosome behavior during mitosis. To investigate how Cdk1-CycB controls the coordination of these events, we performed a dosage-sensitive genetic screen, which is based on the observations that increased maternal CycB (four extra gene copies) leads to higher Cdk1-CycB activity in early Drosophila embryos, delays anaphase onset, and generates a sensitized non-lethal phenotype at the blastoderm stage (defined as six cycB phenotype). Here, we report that mutations in the gene three rows (thr) enhance, while mutations in pimples (pim, encoding Drosophila Securin) or separase (Sse) suppress, the sensitized phenotype. In Drosophila, both Pim and Thr are known to regulate Sse activity, and activated Sse cleaves a Cohesin subunit to initiate anaphase. Compared with the six cycB embryos, reducing Thr in embryos with more CycB further delays the initiation of anaphase, whereas reducing either Pim or Sse has the opposite effect. Furthermore, nuclei move slower during cortical migration in embryos with higher Cdk1-CycB activity, whereas reducing either Pim or Sse suppresses this phenotype by causing a novel nuclear migration pattern. Therefore, our genetic screen has identified all three components of the complex that regulates sister chromatid separation, and our observations indicate that interactions between Cdk1-CycB and the Pim-Thr-Sse complex are dosage sensitive. C1 Univ Washington, Dept Biol, Seattle, WA 98195 USA. RP Ji, JY (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. EM jji@partners.org NR 53 TC 8 Z9 8 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 2005 VL 132 IS 8 BP 1875 EP 1884 DI 10.1242/dev.01780 PG 10 WC Developmental Biology SC Developmental Biology GA 926DO UT WOS:000229103300012 PM 15772129 ER PT J AU Kramer-Zucker, AG Olale, F Haycraft, CJ Yoder, BK Schier, AF Drummond, IA AF Kramer-Zucker, AG Olale, F Haycraft, CJ Yoder, BK Schier, AF Drummond, IA TI Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis SO DEVELOPMENT LA English DT Article DE cilia; pronephros; Kupffer's vesicle; ependymal cell; spinal canal; kidney cyst; hydrocephalus; left-right asymmetry ID POLYCYSTIC KIDNEY-DISEASE; LEFT-RIGHT ASYMMETRY; RIGHT AXIS DETERMINATION; INTRAFLAGELLAR TRANSPORT; SITUS-INVERSUS; NODAL CILIA; CAENORHABDITIS-ELEGANS; SENSORY NEURONS; TUBULAR CELLS; MOUSE MODEL AB Cilia, as motile and sensory organelles, have been implicated in normal development, as well as diseases including cystic kidney disease, hydrocephalus and situs inversus. In kidney epithelia, cilia are proposed to be nonmotile sensory organelles, while in the mouse node, two cilia populations, motile and non-motile have been proposed to regulate situs. We show that cilia in the zebrafish larval kidney, the spinal cord and Kupffer's vesicle are motile, suggesting that fluid flow is a common feature of each of these organs. Disruption of cilia structure or motility resulted in pronephric cyst formation, hydrocephalus and left-right asymmetry defects. The data show that loss of fluid flow leads to fluid accumulation, which can account for organ distension pathologies in the kidney and brain. In Kupffer's vesicle, loss of flow is associated with loss of left-right patterning, indicating that the 'nodal flow' mechanism of generating situs is conserved in non-mammalian vertebrates. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. NYU, Sch Med, Skirball Inst Biomol Med, Dev Genet Program, New York, NY 10016 USA. Univ Alabama, Birmingham Med Ctr, Dept Cell Biol, Birmingham, AL 35294 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK53093, DK54711, DK65655, P30 DK074038, T32 DK07545]; NIGMS NIH HHS [5RO1 GM56211] NR 77 TC 373 Z9 383 U1 5 U2 33 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 2005 VL 132 IS 8 BP 1907 EP 1921 DI 10.1242/dev.01772 PG 15 WC Developmental Biology SC Developmental Biology GA 926DO UT WOS:000229103300015 PM 15790966 ER PT J AU Efimenko, E Bubb, K Mak, HY Holzman, T Leroux, MR Ruvkun, G Thomas, JH Swoboda, P AF Efimenko, E Bubb, K Mak, HY Holzman, T Leroux, MR Ruvkun, G Thomas, JH Swoboda, P TI Analysis of xbx genes in C-elegans SO DEVELOPMENT LA English DT Article DE X-box; DAF-19; ciliary genes; C. elegans ID NEMATODE CAENORHABDITIS-ELEGANS; INTRAFLAGELLAR TRANSPORT; SENSORY NEURON; DNA-BINDING; CHEMOSENSORY NEURONS; DISEASE GENE; TRANSCRIPTION FACTORS; RFX PROTEINS; CILIA; FAMILY AB Cilia and flagella are widespread eukaryotic subcellular components that are conserved from green algae to mammals. In different organisms they function in cell motility, movement of extracellular fluids and sensory reception. While the function and structural description of cilia and flagella are well established, there are many questions that remain unanswered. In particular, very little is known about the developmental mechanisms by which cilia are generated and shaped and how their components are assembled into functional machineries. To find genes involved in cilia development we used as a search tool a promoter motif, the X-box, which participates in the regulation of certain ciliary genes in the nematode Caenorhabditis elegans. By using a genome search approach for X-box promoter motif-containing genes (xbx genes) we identified a list of about 750 xbx genes (candidates). This list comprises some already known ciliary genes as well as new genes, many of which we hypothesize to be important for cilium structure and function. We derived a C elegans X-box consensus sequence by in vivo expression analysis. We found that xbx gene expression patterns were dependent on particular X-box nucleotide compositions and the distance from the respective gene start. We propose a model where DAF-19, the RFX-type transcription factor binding to the X-box, is responsible for the development of a ciliary module in C elegans, which includes genes for cilium structure, transport machinery, receptors and other factors. C1 Karolinska Inst, Dept Biosci, S-14189 Huddinge, Sweden. Sodertorn Univ Coll, Sect Nat Sci, S-14189 Huddinge, Sweden. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Simon Fraser Univ, Dept Mol Biol & Biochem, Burnaby, BC V5A 1S6, Canada. RP Swoboda, P (reprint author), Karolinska Inst, Dept Biosci, S-14189 Huddinge, Sweden. EM peter.swoboda@biosci.ki.se OI Mak, Ho Yi/0000-0002-1500-5328; Swoboda, Peter/0000-0001-6416-8572 FU NIDDK NIH HHS [R01 DK070147] NR 61 TC 123 Z9 161 U1 2 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 2005 VL 132 IS 8 BP 1923 EP 1934 DI 10.1242/dev.01775 PG 12 WC Developmental Biology SC Developmental Biology GA 926DO UT WOS:000229103300016 PM 15790967 ER PT J AU Kim, BM Buchner, G Miletich, I Sharpe, PT Shivdasani, RA AF Kim, BM Buchner, G Miletich, I Sharpe, PT Shivdasani, RA TI The stomach mesenchymal transcription factor Barx1 specifies gastric epithelial identity through inhibition of transient Wnt signaling SO DEVELOPMENTAL CELL LA English DT Article ID SONIC HEDGEHOG; INTESTINAL DEVELOPMENT; PANCREAS DEVELOPMENT; GENE-EXPRESSION; TRANSGENIC MICE; SERIAL ANALYSIS; GUT DEVELOPMENT; MORPHOGENESIS; MOUSE; DIFFERENTIATION AB Inductive interactions between gut endoderm and the underlying mesenchyme pattern the developing digestive tract into regions with specific morphology and functions. The molecular mechanisms behind these interactions are largely unknown. Expression of the conserved homeobox gene Barx1 is restricted to the stomach mesenchyme during gut organogenesis. Using recombinant tissue cultures, we show that Barx1 loss in the mesenchyme prevents stomach epithelial differentiation of overlying endoderm and induces intestine-specific genes instead. Additionally, Barx1 null mouse embryos show visceral homeosis, with intestinal gene expression within a highly disorganized gastric epithelium. Barx1 directs mesenchymal cell expression of two secreted Wnt antagonists, sFRP1 and sFRP2, and these factors are sufficient replacements for Barx1 function. Canonical Wnt signaling is prominent in the prospective gastric endoderm prior to epithelial differentiation, and its inhibition by Barx1-dependent signaling permits development of stomach-specific epithelium. These results define a transcriptional and signaling pathway of inductive cell interactions in vertebrate organogenesis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Univ London Kings Coll, Inst Craniofacial Biol, London SE1 9RT, England. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [R01-DK61139] NR 53 TC 101 Z9 104 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2005 VL 8 IS 4 BP 611 EP 622 DI 10.1016/i.devcel.2005.01.015 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 917DG UT WOS:000228435600019 PM 15809042 ER PT J AU Pold, R Jensen, LS Jessen, N Buhl, ES Schmitz, O Flyvbjerg, A Fujii, N Goodyear, LJ Gotfredsen, CF Brand, CL Lund, S AF Pold, R Jensen, LS Jessen, N Buhl, ES Schmitz, O Flyvbjerg, A Fujii, N Goodyear, LJ Gotfredsen, CF Brand, CL Lund, S TI Long-term AICAR administration and exercise prevents diabetes in ZDF rats SO DIABETES LA English DT Article ID ACTIVATED PROTEIN-KINASE; HUMAN SKELETAL-MUSCLE; IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE; INSULIN-RESISTANCE; EXPRESSION; GLUT-4; STIMULATION; IMPROVEMENT; HEXOKINASE AB Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-D-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, prediabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes. C1 Aarhus Univ Hosp, Med Dept M Endocrinol & Diabet, DK-8000 Aarhus, Denmark. Aarhus Univ Hosp, Med Res Lab, DK-8000 Aarhus, Denmark. Univ Aarhus, Dept Clin Pharmacol, Aarhus, Denmark. Brigham & Womens Hosp, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Novo Nordisk, Dept Res & Dev, Bagsvaerd, Denmark. RP Lund, S (reprint author), Aarhus Univ Hosp, Med Dept M Endocrinol & Diabet, DK-8000 Aarhus, Denmark. EM sl@dadlnet.dk RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274 NR 33 TC 146 Z9 149 U1 0 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2005 VL 54 IS 4 BP 928 EP 934 DI 10.2337/diabetes.54.4.928 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 912QM UT WOS:000228094300002 PM 15793229 ER PT J AU Tong, J Fujimoto, WY Kahn, SE Weigle, DS McNeely, MJ Leonetti, DL Shofer, JB Boyko, EJ AF Tong, J Fujimoto, WY Kahn, SE Weigle, DS McNeely, MJ Leonetti, DL Shofer, JB Boyko, EJ TI Insulin, C-peptide, and leptin concentrations predict increased visceral adiposity at 5-and 10-year follow-ups in nondiabetic Japanese Americans SO DIABETES LA English DT Article ID BODY-FAT DISTRIBUTION; DEPENDENT DIABETES-MELLITUS; IMPAIRED GLUCOSE-TOLERANCE; HIGH FASTING INSULIN; WEIGHT-GAIN; PLASMA LEPTIN; ABDOMINAL FAT; COMPUTED-TOMOGRAPHY; TISSUE DISTRIBUTION; GENE-EXPRESSION AB We prospectively examined the relationship between leptin and markers of insulin resistance and secretion and future visceral adipose tissue accumulation. In this study, 518 nondiabetic Japanese-American men and women underwent the following measurements at baseline and at 5- and 10-year follow-ups: plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, insulin secretion ratio (ISR) [(30-min insulin - fasting insulin)/30-min glucose], fasting C-peptide levels, plasma leptin (baseline only), and fat areas (intra-abdominal and subcutaneous) measured by computed tomography. Predictors of future intra-abdominal fat (IAF) were determined using multiple linear regression. Fasting insulin and C-peptide levels at baseline were significantly associated with IAF area at 5 years (coefficient = 0.041, P = 0.001 and coefficient = 1.283, P < 0.001, respectively) and 10 years (coefficient = 0.031, P = 0.020 and coefficient = 0.221, P = 0.035, respectively). ISR was not significantly associated with IAF at 5 or 10 years. Leptin level at baseline was positively associated with IAF at 5 years (coefficient = 0.055, P = 0.002) and 10 years (coefficient = 0.059, P = 0.003). In conclusion, higher levels of fasting insulin, C-peptide, and circulating leptin level predicted visceral fat accumulation independent from subcutaneous fat accumulation in nondiabetic Japanese-American men and women in both short-term (5 years) and long-term (10 years) followup. C1 VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. RP Tong, J (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, S-151,1660 S Columbian Way, Seattle, WA 98108 USA. EM tongj@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-02860, DK-55460] NR 53 TC 23 Z9 23 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2005 VL 54 IS 4 BP 985 EP 990 DI 10.2337/diabetes.54.4.985 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 912QM UT WOS:000228094300009 PM 15793236 ER PT J AU Bryer-Ash, M Garber, AJ AF Bryer-Ash, M Garber, AJ TI Point: Inpatient glucose management - The emperor finally has clothes SO DIABETES CARE LA English DT Editorial Material ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; II DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; HYPERGLYCEMIA; MORTALITY; INFUSION; ARTERY; RISK C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Gonda Diabet Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Endocrinol Sect, Los Angeles, CA USA. Baylor Coll Med, Div Endocrinol, Houston, TX 77030 USA. RP Bryer-Ash, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Gonda Diabet Ctr, 900 Veteran Ave,Suite 24-130, Los Angeles, CA 90095 USA. EM mbryerash@mednet.ucla.edu NR 25 TC 5 Z9 6 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2005 VL 28 IS 4 BP 973 EP 975 DI 10.2337/diacare.28.4.973 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001PE UT WOS:000234548000039 PM 15793209 ER PT J AU Kudolo, GB Delaney, D Blodgett, J AF Kudolo, GB Delaney, D Blodgett, J TI Short-term oral ingestion of Ginkgo biloba extract (EGb 761) reduces malondialdehyde levels in washed platelets of type 2 diabetic subjects SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Ginkgo biloba; EGb 761; type 2 diabetes; platelets; malondialdehyde ID HEALTHY MALE-VOLUNTEERS; BETA-CELL FUNCTION; INSULIN-RESISTANCE; DOUBLE-BLIND; MELLITUS; DISEASE; HYPERTENSION; INDIVIDUALS; ATHEROGENESIS; LIPOPROTEINS AB We have recently reported that ingestion of Ginkgo biloba extract (EGb 761) (a) significantly reduced collagen-induced platelet aggregation and thromboxane B-2 (TXB2) production in both non-diabetic individuals as well as those with type 2 diabetes mellitus (T2DM), (b) significantly reduced platelet malondialdehyde (MDA), an index of lipid peroxidation, in nondiabetic subjects. In the present study we report that ingestion of EGb 761 (120 mg daily for 3 months), significantly decreased platelet MDA-thiobarbituric acid reacting substances (TBARS) (41 +/- 9 pmol/ 10(7) platelets versus 30 +/- 11 Pruol/10(7) platelets) (p < 0.005) in T2DM subjects with normal cholestertol levels (total cholesterol, 164 +/- 22 mg/dl; age, 54 +/- 9 years; BMI, 35.0 +/- 28.8 kg/m(2), n = 12). In T2DM subjects with high cholesterol (total cholesterol, 218 +/- 15 mg/dl; age, 52 +/- 5 years; BMI, 36.2 +/- 6.6 kg/m(2), n = 7), EGb 761 ingestion reduced the platelet TBARS from 29 +/- 9 to 22 +/- 9 pmol/10(7) platelets (p < 0.04). Because ingestion of EGb 761 did not alter platelet counts it is concluded that EGb 761, probably due to the flavonoid fraction, reduced the TBARS by inhibiting cyclooxygenase (COX)-1-mediated arachidonic acid oxygenation or by reducing the arachidonic acid pool. This is likely to lead to a reduction of platelet hyperactivity, a significant contributor to the development of cardiovascular disease in T2DM patients. Because of other reported beneficial properties of EGb 761, such as stimulation of pancreatic beta-cell function in T2DM subjects with pancreatic exhaustion, it appears that T2DM subjects might benefit from ingesting EGb 761 as a dietary supplement. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Univ Texas, HSC, Dept Clin Lab Sci, San Antonio, TX 78229 USA. Audie L Murphy Vet Affairs Hosp, San Antonio, TX 78284 USA. RP Kudolo, GB (reprint author), Univ Texas, HSC, Dept Clin Lab Sci, MSC 6246,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kudolo@uthscsa.edu FU NCCIH NIH HHS [R01-AT-00832]; NCRR NIH HHS [M01-RR-01346] NR 49 TC 17 Z9 20 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD APR PY 2005 VL 68 IS 1 BP 29 EP 38 DI 10.1016/j.diabres.2004.08.007 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 920EF UT WOS:000228671500004 PM 15811563 ER PT J AU Price, LF AF Price, LF TI The biology of risk taking SO EDUCATIONAL LEADERSHIP LA English DT Article ID ADOLESCENT DEVELOPMENT; BRAIN; PUBERTY; CORTEX; GIRLS C1 Massachusetts Gen Hosp, Dept Psychiat, Sch Psychiat Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Price, LF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Sch Psychiat Program, 55 Fruit St,YAW 6900, Boston, MA 02114 USA. NR 16 TC 4 Z9 4 U1 1 U2 2 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 2005 VL 62 IS 7 BP 22 EP 26 PG 5 WC Education & Educational Research SC Education & Educational Research GA 915EZ UT WOS:000228282100004 ER PT J AU Ruiz-Vela, A Opferman, JT Cheng, EHY Korsmeyer, SJ AF Ruiz-Vela, A Opferman, JT Cheng, EHY Korsmeyer, SJ TI Proapoptotic BAX and BAK control multiple initiator caspases SO EMBO REPORTS LA English DT Article DE BCL-2; BAK; apoptosis; BAX; mitochondrial pathway ID INDUCED APOPTOSIS; ENDOPLASMIC-RETICULUM; DNA-DAMAGE; CELL-DEATH; ACTIVATION; P53; EXPRESSION; PATHWAYS; GENE AB BAX and BAK operate at both the mitochondria and endoplasmic reticulum ( ER) to regulate the intrinsic apoptotic pathway. An unresolved issue is whether any caspases can be activated in response to intrinsic apoptotic signals in the absence of BAX and BAK. Following organelle-specific intrinsic stress signals, including DNA damage and ER stress, we detected no activation of CARD-containing caspases ( initiator CASP)-1, -2, -9, -11 and -12 in Bax(-/-) Bak(-/-) doubly deficient (DKO) cells. BCL-2 overexpression in these DKO cells provided no further protection to their already strong protection from DNA damage and ER stress. Moreover, there was no activation of effector CASP-3 and -7 in DKO cells, consistent with the lack of initiator caspase activity and disfavouring a BAX, BAK-independent intrinsic apoptotic pathway to activate initiator caspases. Thus, BAX and BAK confer an essential gateway for the activation of caspases in the intrinsic apoptotic pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA 02115 USA. CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain. RP Ruiz-Vela, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, 44 Binney St, Boston, MA 02115 USA. EM aruiz@cnb.uam.es OI Ruiz-Vela, Antonio/0000-0002-4410-6208 NR 24 TC 76 Z9 77 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD APR PY 2005 VL 6 IS 4 BP 379 EP 385 DI 10.1038/sj.embor.7400375 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 915SR UT WOS:000228327200018 PM 15776018 ER PT J AU Seminara, SB Kaiser, UB AF Seminara, SB Kaiser, UB TI New gatekeepers of reproduction: GPR54 and its cognate ligand, KiSS-1 SO ENDOCRINOLOGY LA English DT Editorial Material ID METASTASIS-SUPPRESSOR GENE; PROTEIN-COUPLED RECEPTOR; RIBONUCLEIC-ACID EXPRESSION; HORMONE-RELEASING ACTIVITY; GNRH RECEPTOR; PEPTIDE; RAT; KISSPEPTINS; SECRETION; PUBERTY C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02115 USA. RP Kaiser, UB (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. EM ukaiser@partners.org FU NICHD NIH HHS [R01 HD043341, U54 HD028138, U54 HD28138] NR 23 TC 38 Z9 39 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 1686 EP 1688 DI 10.1210/en.2005-0070 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400005 PM 15769900 ER PT J AU Divieti, P Geller, AI Suliman, G Juppner, H Bringhurst, FR AF Divieti, P Geller, AI Suliman, G Juppner, H Bringhurst, FR TI Receptors specific for the carboxyl-terminal region of parathyroid hormone on bone-derived cells: Determinants of ligand binding and bioactivity SO ENDOCRINOLOGY LA English DT Article ID CALCIUM-CONCENTRATION; ALKALINE-PHOSPHATASE; OSTEOSARCOMA CELLS; PTH FRAGMENTS; INTACT-PTH; APOPTOSIS; RAT; ROS-17/2.8; PTH-(1-84); METABOLISM AB PTH comprises 84 amino acids of which the first 34 are sufficient for full activation of the classical PTH/PTHrP receptor, the type 1 PTH receptor. It is known that multiple carboxyl (C)-terminal fragments of PTH are present in the blood and that they comprise the majority of circulating PTH. C-PTH fragments, previously regarded as by-products of PTH metabolism, are directly secreted by the parathyroid glands or arise from the peripheral cleavage of the intact hormone. Compelling evidence now strongly suggests that these C-PTH fragments mediate biological effects via activation of a receptor that specifically recognizes the C-terminal portion of intact PTH, and this receptor is therefore named the carboxyl-terminal PTH receptor (CPTHR). We have previously reported that osteocytes abundantly express this novel receptor and that its activation is involved in cell survival and communication. Here we report the characterization of determinants of PTH that are required for high-affinity binding to the CPTHR. Using synthetic PTH peptides harboring alanine substitution or truncations, we showed the existence of discrete binding domains and critical residues within the intact hormone. We have furthermore identified eight amino acids within the PTH sequence that play key roles in optimizing the binding affinity of C-PTH fragments to CPTHRs. These include the tripeptide sequence Arg(25)-Lys(26)-Lys(27), the dibasic sequence Lys(53)-Lys(54), and three additional residues within the PTH ( 55 - 84) sequence, Asn(57), Lys(65), and Lys(72). Functional analysis of these residues demonstrated a strong correlation between binding affinity and biological effect and points to a potential role of CPTHR activation in regulating bone cell survival. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Divieti, P (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. EM divieti@helix.mgh.harvard.edu FU NIAMS NIH HHS [AR-47062]; NIDDK NIH HHS [DK-65032, DK-02889] NR 31 TC 44 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 1863 EP 1870 DI 10.1210/en.2004-1262 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400027 PM 15625242 ER PT J AU Burkart, AD Mukherjee, A Sterneck, E Johnson, PF Mayo, KE AF Burkart, AD Mukherjee, A Sterneck, E Johnson, PF Mayo, KE TI Repression of the inhibin alpha-subunit gene by the transcription factor CCAAT/enhancer-binding protein-beta SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RECEPTOR MESSENGER-RNA; RAT OVARIAN-FOLLICLES; NF-KAPPA-B; GRANULOSA-CELL LINES; C/EBP-BETA; DNA-BINDING; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; LEUCINE ZIPPER; CHORIONIC-GONADOTROPIN AB Inhibin is a dimeric peptide hormone produced in ovarian granulosa cells that suppresses FSH synthesis and secretion in the pituitary. Expression of inhibin alpha- and beta- subunit genes in the rodent ovary is positively regulated by FSH and negatively regulated after the preovulatory LH surge. We have investigated the role of the transcription factor CCAAT/ enhancer- binding protein- beta ( C/ EBP beta) in repressing the inhibin alpha- subunit gene. C/ EBP beta knockout mice fail to appropriately down- regulate inhibin alpha- subunit mRNA levels after treatment with human chorionic gonadotropin, indicating that C/ EBP beta may function to repress inhibin gene expression. The expression and regulation of C/ EBP beta were examined in rodent ovary, and these studies show that C/ EBP beta is expressed in ovary and granulosa cells and is induced in response to human chorionic gonadotropin. Transient cotransfections with an inhibin promoter- luciferase reporter in a mouse granulosa cell line, GRMO2 cells, show that C/ EBP beta is capable of repressing both basal and forskolin- stimulated inhibin gene promoter activities. An upstream binding site for C/ EBP beta in the inhibin alpha- subunit promoter was identified by electrophoretic mobility shift assays, which, when mutated, results in elevated inhibin promoter activity. However, C/ EBP beta also represses shorter promoter constructs lacking this site, and this component of repression is dependent on the more proximal promoter cAMP response element ( CRE). Electrophoretic mobility shift assays show that C/ EBP beta effectively competes with CRE- binding protein for binding to this atypical CRE. Thus, there are two distinct mechanisms by which C/ EBP beta represses inhibin alpha- subunit gene expression in ovarian granulosa cells. C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. Northwestern Univ, Ctr Reprod Sci, Evanston, IL 60208 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Mol Mech Dev Grp, Lab Prot Dynam & Signaling, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Eukaryot Transcript Regulat Sect, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. EM k-mayo@northwestern.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NICHD NIH HHS [P01-HD-21921, U54-HD-41857]; NIGMS NIH HHS [T32 GM008061, T32-GM-08061] NR 84 TC 32 Z9 34 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 1909 EP 1921 DI 10.1210/en.2004-0842 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400031 PM 15650079 ER PT J AU Ishizuka, S Kurihara, N Reddy, SV Cornish, J Cundy, T Roodman, GD AF Ishizuka, S Kurihara, N Reddy, SV Cornish, J Cundy, T Roodman, GD TI (23S)-25-dehydro-1 alpha-hydroxyvitamin D-3-26,23-lactone, a vitamin D receptor antagonist that inhibits osteoclast formation and bone resorption in bone marrow cultures from patients with Paget's disease SO ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 12th Workshop on Vitamin D CY 2003 CL Masstricht, NETHERLANDS ID 1-ALPHA,25-DIHYDROXYVITAMIN D-3-26,23-LACTONE ANALOGS; 1,25-DIHYDROXYVITAMIN D-3; VIRUS; CELLS; PRECURSORS; DIFFERENTIATION AB Osteoclast ( OCL) precursors from patients with Paget's disease ( PD) and normal OCL precursors transduced with the measles virus nucleocapsid protein gene ( MVNP) are hyperresponsive to 1 alpha, 25- dihydroxyvitamin D-3 [ 1 alpha, 25-( OH) D-2(3)] and can form OCLs at physiologic concentrations of 1 alpha, 25( OH) D-2(3). This hyperresponsivity to 1 alpha, 25-( OH)(2)D-3 is due to increased expression of TATA box- associated factor II- 17, a potential coactivator of the vitamin D receptor. Hyperresponsivity to 1 alpha, 25-( OH)(2)D-3 may permit OCL formation in PD patients with low levels of 1 alpha, 25-( OH)(2)D-3 and play a role in the pathogenesis of PD. Therefore, we tested the effects of a vitamin D antagonist, ( 23S)- 25- dehydro- 1 alpha- hydroxyvitamin D-3- 26,23- lactone ( TEI- 9647), to determine its potential to inhibit the enhanced OCL formation and bone resorption seen in patients with PD. TEI- 9647, by itself, was not a vitamin D receptor agonist and did not induce OCL formation in vitro, even at 10(-6) M. However, it dose- dependently ( 10(-10) M to 10(-6) M) inhibited osteoclast formation induced by concentrations of 1 alpha, 25-( OH)(2)D-3 ( 41 pg/ ml, 10(-10) M) detected in PD patients by bone marrow cells of patients with PD and MVNP- transduced colony- forming unit- granulocyte macrophage ( CFU- GM) cells, which form pagetic- like OCL. Moreover, bone resorption by OCLs derived from MVNP- transduced CFU- GM treated with 10(-9) M 1 alpha,25-( OH)(2)D-3 was dose- dependently inhibited by TEI- 9647 ( 10(-9) M to 10(-6) M). Furthermore, 10(-7) M TEI- 9647 by itself did not cause 1 alpha, 25-( OH)(2)D-3- dependent gene expression but almost completely suppressed expression of the TATA box- associated factor II- 17 and 25- hydroxyvitamin D-3- 24-hydroxylase genes induced by 1 alpha, 25-(OH)(2)D-3 treatment of MVNP- transduced CFU- GM cells. These results demonstrate that TEI- 9647 can suppress the excessive bone resorption and OCL formation seen in marrow cultures from patients with PD. C1 Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Teijin Inst Biomed Res, Tokyo 1918512, Japan. Univ Pittsburgh, Div Hematol Oncol, Pittsburgh, PA 15261 USA. Univ Auckland, Dept Med, Auckland 92019, New Zealand. RP Roodman, GD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr, Pittsburgh, PA 15240 USA. EM roodmangd@upmc.edu NR 19 TC 28 Z9 30 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2005 VL 146 IS 4 BP 2023 EP 2030 DI 10.1210/en.2004-1140 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 906TW UT WOS:000227667400044 PM 15618361 ER PT J AU Hauser, R Williams, P Altshul, L Calafat, AM AF Hauser, R Williams, P Altshul, L Calafat, AM TI Evidence of interaction between polychlorinated biphenyls and phthalates in relation to human sperm motility SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID HYDROXYLATED PCB METABOLITES; HUMAN SEMEN PARAMETERS; CELL FUNCTION-INVITRO; MONO-(2-ETHYLHEXYL) PHTHALATE; TESTICULAR ATROPHY; SERTOLI-CELLS; RAT; BLOOD; URINARY; SERUM AB Previously, we reported evidence of inverse associations between exposure to some polychlorinated biphenyls (PCBs) and some phthalate monoesters in relation to semen parameters, specifically sperm motility. Because humans are exposed to both phthalates and PCBs and because experimental studies suggest that PCBs may interact with glucuronidative enzymes that are responsible for phthalate metabolism, we explored the potential interaction between phthalates and PCBS in relation to human semen quality. We studied 303 men who were partners in subfertile couples seeking infertility diagnosis from the andrology laboratory at Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values, and plithalate and PCB levels were dichotomized at their respective medians. After adjusting for age and abstinence time, for below reference sperm motility there was a greater than additive interaction between monobenzyl plithalate and PCB-153 [relative excess risk due to interaction (RERI) = 1.40; 95% confidence interval (CI), 0.41-3.22], sum of PCBs (RERI = 1.24; 95% Cl, 0.15-2.94), and cytochrome P450 (CYP450)-inducing PCBs (RERI = 1.30; 95% CI, 0.21-3.06). For below-reference sperm motility, there was also a greater than additive interaction between monobutyl phthalate (MBP) and PCB-153 (RERI = 1.42; 95% CI, 0.09-3.76) and CYP450-inducing PCBs (RERI = 1.87; 95% CI, 0.56-4.52) and a suggestive interaction between MBP and sum of PCBs (RERI = 1.35; 95% CI, -0.11 to 3.48). In conclusion, because there are important risk assessment and public health implications of interactions between these two ubiquitous classes of compounds, further studies need to be conducted to confirm these results and identify potential mechanisms of interactions. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu FU NIEHS NIH HHS [ES00002, ES09718] NR 40 TC 80 Z9 86 U1 2 U2 17 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 2005 VL 113 IS 4 BP 425 EP 430 DI 10.1289/ehp.7305 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 913NO UT WOS:000228158900041 PM 15811833 ER PT J AU Morrow, DA Murphy, SA McCabe, CH Mackman, N Wong, HC Antman, EM AF Morrow, DA Murphy, SA McCabe, CH Mackman, N Wong, HC Antman, EM CA PROXIMATE-TIMI 27 Investigators TI Potent inhibition of thrombin with a monoclonal antibody against tissue factor (Sunol-cH36): results of the PROXIMATE-TIMI 27 trial SO EUROPEAN HEART JOURNAL LA English DT Article DE clinical trials; antithrombins; coronary artery disease; tissue factor ID PLATELET ACTIVATION; CORONARY SYNDROMES; BLOOD-COAGULATION; UNSTABLE ANGINA; THROMBOGENICITY; PROTEIN; VIIA AB Aims Exposure of tissue factor (TF) is a critical proximal step in the pathogenesis of acute coronary syndromes. Sunol-cH36, a chimaeric monoclonal antibody to TF, blocks binding of factor X to the TF:Vlla complex. This report describes the first completed trial of Sunol-cH36 in humans. Methods and results We assessed the safety and pharmacokinetics of Sunol-cH36 in an open-label, dose-escalating trial among subjects with stable coronary artery disease. The safety analysis included all adverse events with a focus on overt or occult bleeding. Five doses of Sunol-cH36 (0.03, 0.06, 0.08, 0.1, 0.3 mg/kg) were administered as a single intravenous bolus to 26 subjects (three to eight subjects per dose tier). No major bleeding (&GE; 2 g/dL haemoglobin decline) occurred. Spontaneous minor bleeding was observed with a dose-related pattern. Notably, the majority of spontaneous bleeding episodes were clinically consistent with platelet-mediated bleeding (e.g. gum, tongue) without thrombocytopenia. The median terminal half-life was 72.2 (25th, 75th: 28.4, 72.5) h. Conclusion Sunol-cH36 exhibited dose-dependent anticoagulant effects. We postulate that the mucosal bleeding observed with this potent inhibitor of thrombin generation may reflect antiplatelet effects resulting from networking between the coagulation cascade and platelet pathways that could prove clinically relevant with this novel class of anticoagulants. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Scripps Res Inst, La Jolla, CA USA. Sunol Mol Corp, Miramar, FL USA. RP Morrow, DA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM dmorrow@partners.org NR 22 TC 40 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2005 VL 26 IS 7 BP 682 EP 688 DI 10.1093/eurheartj/ehi094 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 923EV UT WOS:000228892900012 PM 15684280 ER PT J AU Talcott, JA Clark, JA AF Talcott, JA Clark, JA TI Quality of life in prostate cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE health-related quality of life; prostate cancer; treatment; measurements ID FORM HEALTH SURVEY; PHASE-III TRIAL; EXTERNAL-BEAM IRRADIATION; RADICAL PROSTATECTOMY; RANDOMIZED-TRIAL; EUROPEAN-ORGANIZATION; FUNCTIONAL ASSESSMENT; RADIATION-THERAPY; ANDROGEN DEPRIVATION; SOCIOECONOMIC-STATUS AB Little more than a decade ago, measurements of health-related quality of life (HRQOL) of prostate cancer patients began to enter the medical literature. Initially controversial and of little apparent relevance to clinical care, HRQOL has grown in importance in prostate cancer to the point that providing it in treatment discussions is now considered a core element of clinical care. The United States (US) Food and Drug Administration has used it to make approval decisions for prostate cancer drugs, and Europeans have endorsed its central role in prostate cancer as well [Altwein J, Ekman P, Barry M, et al. How is quality of life in prostate cancer patients influenced by modern treatment? The Wallenberg symposium. Urology 1997, 49(Suppl 4A), 66-76.]. We propose to characterise the treatment dilemmas facing patients with prostate cancer, the clinical relevance of HRQOL research, its central conceptual elements, the characteristics of some available instruments to measure it, the use of HRQOL in clinical studies, and some of the remaining challenges we have identified during our 13 years in the field. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Massachusetts Gen Canc Ctr, Ctr Outcomes Res, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Canc Ctr, Ctr Outcomes Res, 75 Blossom St,Suite 230, Boston, MA 02114 USA. EM jtalcott@partners.org OI Clark, Jack/0000-0002-7424-1670 NR 88 TC 13 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 2005 VL 41 IS 6 BP 922 EP 931 DI 10.1016/j.ejca.2004.12.030 PG 10 WC Oncology SC Oncology GA 920IU UT WOS:000228683400008 PM 15808958 ER PT J AU Homma, S Kikuchi, T Ishiji, N Ochiai, K Takeyama, H Saotome, H Sagawa, Y Hara, E Kufe, D Ryan, JL Ohno, T Toda, G AF Homma, S Kikuchi, T Ishiji, N Ochiai, K Takeyama, H Saotome, H Sagawa, Y Hara, E Kufe, D Ryan, JL Ohno, T Toda, G TI Cancer immunotherapy by fusions of dendritic and tumour cells and rh-IL-12 SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cell fusion; dendritic cell; IL-12; immunotherapy; tumour vaccine ID RECOMBINANT HUMAN INTERLEUKIN-12; CYTOTOXIC T-LYMPHOCYTES; ADVANCED MALIGNANCIES; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; GLIOMA PATIENTS; VACCINATION; IMMUNITY; ANTIGEN; MELANOMA AB Background Vaccination with fusion cells (FCs) comprising dendritic cells and tumour cells as well as administration of interleukin-12 (IL-12) showed a significant therapeutic effect against established tumours in mouse experimental models. We conducted immunotherapy against various malignant tumours using the FCs and rhIL-12, and investigated the safety and efficacy of the therapy. Materials and methods Patients' DCs were mixed with autologous irradiated tumour cells and treated with 50% polyethylene glycol to generate FCs. The FCs were inoculated intradermally, and then 30 ng kg(-1) of rhIL-12 was injected at the same sites 2 and 6 days later. This process was carried out as one cycle, and three of these cycles were repeated at 1-week intervals to comprise one course. After completing the course, its safety and therapeutic effects were estimated. Results The most frequently observed adverse event was fever, observed in 26% of patients in the first cycle. Decrease in white blood cell and an increase in serum ALT were observed in 28% and 25%, respectively. Three out of 12 patients with a malignant brain tumour (25%) achieved a partial response (PR), but other patients with a malignant tumour showed no regression of their tumours. Thirteen out of 16 patients with a brain tumour (81%) showed cutaneous delayed hypersensitivity responses. However, only one of 16 patients (6%) with a malignant tumour other than a brain tumour developed such responses. Conclusions Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour. C1 Jikei Univ, Sch Med, Inst DNA Med, Dept Oncol,Minato Ku, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Inst DNA Med, Dept Clin Data Bank, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Neurosurg, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Dermatol, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Gynecol, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Surg, Tokyo 1058461, Japan. AHP Serv Japan Co Ltd, Wyeth Res Dept, Tokyo, Japan. Saitama Canc Ctr, Res Inst Clin Oncol, Cell Therapy Lab, Kita Adachi, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. Wyeth Pharmaceut, Res & Dev, Expt Med, Cambridge, MA USA. RP Homma, S (reprint author), Jikei Univ, Sch Med, Inst DNA Med, Dept Oncol,Minato Ku, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan. EM sahya@jikei.ac.jp NR 34 TC 29 Z9 33 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD APR PY 2005 VL 35 IS 4 BP 279 EP 286 DI 10.1111/j.1365-2362.2005.01494.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 914DR UT WOS:000228205800008 PM 15816998 ER PT J AU Richardson-Burns, SM Tyler, KL AF Richardson-Burns, SM Tyler, KL TI Minocycline delays disease onset and mortality in reovirus encephalitis SO EXPERIMENTAL NEUROLOGY LA English DT Article DE apoptosis; central nervous system; microglia; neurons; mouse ID CENTRAL-NERVOUS-SYSTEM; HUNTINGTONS-DISEASE; MOUSE MODEL; TETRACYCLINE DERIVATIVES; MICROGLIAL ACTIVATION; PARKINSONS-DISEASE; LATERAL-SCLEROSIS; CYTOCHROME-C; NITRIC-OXIDE; CELL-DEATH AB Minocycline is neuroprotective in many experimental models of neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of viral encephalitis. Experimental infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal encephalitis caused by neuronal apoptosis throughout the CNS. Minocycline significantly delayed death in mice to 11.6 +/- 0.9 days post-infection vs. 8.6 +/- 0.7 days post-infection in controls (P < 0.01). Virus-induced CNS injury, apoptosis, viral titer and antigen expression were significantly decreased in the brains of minocycline-treated mice on 6 and 8 days post-infection compared to controls. Virus-induced injury and viral titer in minocycline-treated infected mice at 11 days post-infection were similar to those seen in untreated T3D-infected mice at 8 days post-infection. Little microglial or astrocytic invasion of brain regions with viral injury was found at any time-point in untreated or minocycline-treated mice, suggesting that in this model system the neuroprotective effect exerted by minocycline is more likely due to its anti-apoptotic properties rather than its capacity to inhibit microglial activation and limit gliosis. These findings, similar to those reported for neurodegenerative diseases, indicate that minocycline does not prevent development of fatal reovirus encephalitis but delays disease onset and progression, suggesting that minocycline treatment may provide a useful adjunctive therapy in viral CNS infections. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NINDS NIH HHS [R01 NS050138-04, R01 NS051403-03, 1R01NS050138, R01 NS050138] NR 38 TC 34 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2005 VL 192 IS 2 BP 331 EP 339 DI 10.1016/j.expneurol.2004.11.015 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 908ZH UT WOS:000227828200010 PM 15755550 ER PT J AU Book, SW Myrick, H AF Book, SW Myrick, H TI Novel anticonvulsants in the treatment of alcoholism SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE alcohol dependence; alcoholism; alcohol withdrawal; anticonvulsants; carbamazepine; gabapentin; recurrence; topiramate; valproic acid; vigabatrin ID RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; WITHDRAWAL SYNDROME; DIVALPROEX SODIUM; ORAL TOPIRAMATE; CARBAMAZEPINE; GABAPENTIN; DEPENDENCE; PLACEBO; CLOMETHIAZOLE AB There have been many recent developments in the pharmacological management of alcohol withdrawal and alcohol dependence. Although previous treatments had included benzodiazepines as their mainstay, the use of these agents in the alcoholic population is problematic. Benzodiazepines are themselves addictive and they may increase the risk of alcohol relapse. Non-benzodiazepine anticonvulsants such as carbamazepine, valproic acid, gabapentin, vigabatrin and topiramate have been shown to be excellent treatments of both alcohol withdrawal and the prevention of alcohol relapse. Although none of these agents have yet been approved by the FDA, there is growing evidence in the literature to support their use. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv Line, Charleston, SC 29401 USA. RP Book, SW (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston Alcohol Res Ctr, 67 President St, Charleston, SC 29425 USA. EM booksw@musc.edu FU NIAAA NIH HHS [2 P50 AA10761-03, K23 AA00314-01, K23 AA014430] NR 42 TC 43 Z9 45 U1 2 U2 7 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD APR PY 2005 VL 14 IS 4 BP 371 EP 376 DI 10.1517/13543784.14.4.371 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 930JC UT WOS:000229410900002 PM 15882114 ER PT J AU Podar, K Hideshima, T Chauhan, D Anderson, KC AF Podar, K Hideshima, T Chauhan, D Anderson, KC TI Targeting signalling pathways for the treatment of multiple myeloma SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE bone marrow microenvironment; chromosome aberration; IGF-1; IL-6; multiple myeloma (MM); translocation; vascular endothelial growth factor (VEGF) ID GROWTH-FACTOR-I; FACTOR-KAPPA-B; PROTEASOME INHIBITOR PS-341; TUMOR-NECROSIS-FACTOR; SOLUBLE INTERLEUKIN-6 RECEPTOR; OVERCOMES DRUG-RESISTANCE; PLASMA-CELL LEUKEMIA; 2-CYANO-3,12-DIOXOOLEANA-1,9-DIEN-28-OIC ACID CDDO; MITOCHONDRIA-DERIVED ACTIVATOR; BONE-MARROW MICROENVIRONMENT AB Multiple myeloma (MM) is characterised by the expansion of monoclonal immunoglobulin-secreting plasma cells. Despite recent advances in systemic and supportive therapy, it remains incurable, with a median survival of about three years. Development of MM is a multistep process associated with an increasing frequency of chromosomal abnormalities and complex translocations, which induce mutations in several proto-oncogenes and tumour suppressor genes. Furthermore, differentiation, maintenance, expansion and drug resistance of MM cells are dependent on multiple growth factors, cytokines, and chemokines, secreted by tumour cells, bone marrow stromal cells, and non-haematopoietic organs; as well as on direct tumour cell-stromal cell contact. Therefore, signalling pathways initiated by both mutated genes in MM cells as well as signals originating in the bone marrow micro-environment represent potential targets for intervention. Close collaboration between basic researchers and clinicians will be required to further improve our knowledge of MM pathophysiologically in order to translate advances from the bench to the bedside and improve patient outcome. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Podar, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU NCI NIH HHS [R01 CA50945, P50 CA100707]; PHS HHS [P01 78378] NR 236 TC 22 Z9 22 U1 1 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD APR PY 2005 VL 9 IS 2 BP 359 EP 381 DI 10.1517/14728222.9.2.359 PG 23 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 919VU UT WOS:000228646500012 PM 15934921 ER PT J AU Wang, HW Babic, AM Mitchell, HA Liu, K Wagner, DD AF Wang, HW Babic, AM Mitchell, HA Liu, K Wagner, DD TI Elevated soluble ICAM-1 levels induce immune deficiency and increase adiposity in mice SO FASEB JOURNAL LA English DT Article DE adhesion molecule; inflammation; contact hypersensitivity; obesity ID INTERCELLULAR-ADHESION MOLECULE-1; ISCHEMIA-REPERFUSION INJURY; TUMOR-NECROSIS-FACTOR; CELL-ADHESION; IN-VIVO; LEUKOCYTE ADHESION; INSULIN-RESISTANCE; LANGERHANS CELLS; LYMPH-NODES; OBESITY AB Elevated soluble intercellular adhesion molecule-1 (sICAM-1) levels have been found in many pathological conditions, including obesity. To determine the effects of elevated sICAM-1 on immune responses and metabolism, we generated a transgenic mouse model overexpressing the extracellular domain of mouse ICAM-1 in the liver. The mice, showing 10-fold higher sICAM-1 levels than wild-type mice, presented elevated neutrophil count. Despite this, after intraperitoneal injection of thioglycollate, neutrophil recruitment into the peritoneal cavity was reduced, and the delayed macrophage recruitment was also affected in the transgenic mice compared with wildtype mice. Inhibition of contact hypersensitivity response in the sICAM-1 transgenic mice was comparable to ICAM-1-deficient mice and characterized by significantly less ear swelling and inflammatory cell infiltration than in wild-type mice. sICAM-1transgenic mice were more susceptible to weight gain on a Western-type diet than wild-type mice, and older animals showed excessive fat accumulation, again reminiscent of ICAM-1-deficient mice. Together, these data indicate that sICAM-1 interferes with ICAM-1-mediated cell-cell interactions, which could produce immune-suppressant effects and alteration of metabolism in persons with high levels of this soluble adhesion receptor. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM Wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [R01 HL053756, R01 HL53756, R37 HL041002, R37 HL41002] NR 43 TC 26 Z9 27 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 APR PY 2005 VL 19 IS 6 BP 1018 EP + DI 10.1096/fi.04-3094fie PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 922UP UT WOS:000228865300020 PM 15817637 ER PT J AU Grall, FT Prall, WC Wei, WJ Gu, XS Cho, JY Choy, BK Zerbini, LF Inan, MS Goldring, SR Gravallese, EM Goldring, MB Oettgen, P Libermann, TA AF Grall, FT Prall, WC Wei, WJ Gu, XS Cho, JY Choy, BK Zerbini, LF Inan, MS Goldring, SR Gravallese, EM Goldring, MB Oettgen, P Libermann, TA TI The Ets transcription factor ESE-1 mediates induction of the COX-2 gene by LPS in monocytes SO FEBS JOURNAL LA English DT Article DE COX-2; ESE-1; Ets; gene expression; LPS ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; VASCULAR ENDOTHELIAL-CELLS; CYCLOOXYGENASE-2 GENE; NUCLEAR-FACTOR; PROMOTER ELEMENTS; NITRIC-OXIDE; C/EBP-BETA; EXPRESSION; MACROPHAGES AB Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandins that are major inflammatory agents. COX-2 production is triggered by exposure to various cytokines and to bacterial endotoxins. We present here a novel role for the Ets transcription factor ESE-1 in regulating the COX-2 gene in response to endotoxin and other pro-inflammatory stimuli. We report that the induction of COX-2 expression by lipopolysaccharide (LPS) and pro-inflammatory cytokines correlates with ESE-1 induction in monocyte/macrophages. ESE-1, in turn, binds to several E26 transformation specific (Ets) sites on the COX-2 promoter. In vitro analysis demonstrates that ESE-1 binds to and activates the COX-2 promoter to levels comparable to LPS-mediated induction. Moreover, we provide results showing that the induction of COX-2 by LPS may require ESE-1, as the mutation of the Ets sites in the COX-2 promoter or overexpression of a dominant-negative form of ESE-1 inhibits LPS-mediated COX-2 induction. The effect of ESE-1 on the COX-2 promoter is further enhanced by cooperation with other transcription factors such as nuclear factor-kappa B and nuclear factor of activated T cells. Neutralization of COX-2 is the goal of many anti-inflammatory drugs. As an activator of COX-2 induction, ESE-1 may become a target for such therapeutics as well. Together with our previous reports of the role of ESE-1 as an inducer of nitric oxide synthase in endothelial cells and as a mediator of pro-inflammatory cytokines in vascular and connective tissue cells, these results establish ESE-1 as an important player in the regulation of inflammation. C1 Beth Israel Deaconess Med Ctr, Harvard Inst Med, Dept Med, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Libermann, TA (reprint author), Beth Israel Deaconess Med Ctr, Harvard Inst Med, Dept Med, New England Baptist Bone & Joint Inst, 4 Blackfan Circle, Boston, MA 02115 USA. EM tliberma@bidmc.harvard.edu RI Libermann, Towia/F-9866-2010; Zerbini, Luiz /B-7720-2015; OI Libermann, Towia/0000-0002-4006-8179 FU NCI NIH HHS [KO8/CA 71429]; NIAID NIH HHS [R01/AI49527] NR 42 TC 41 Z9 42 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD APR PY 2005 VL 272 IS 7 BP 1676 EP 1687 DI 10.1111/j.1742-4658.2005.04592.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 909MU UT WOS:000227864800012 PM 15794755 ER PT J AU Wang, HJ Kochevar, IE AF Wang, HJ Kochevar, IE TI Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE human keratinocytes; UVB radiation; reactive oxygen species; transforming growth factor-beta activation; free radicals ID GROWTH-FACTOR-BETA; HUMAN DERMAL FIBROBLASTS; INDUCED OXIDATIVE DAMAGE; HUMAN SKIN FIBROBLASTS; TRANSFORMING GROWTH-FACTOR-BETA-1; FACTOR RECEPTOR; NADPH OXIDASE; ULTRAVIOLET-IRRADIATION; SINGLET OXYGEN; IN-VITRO AB TGF-beta produced by keratinocytes in response to UVB (290-320 nm) is a potential mediator for effects of acute and chronic solar radiation on skin. This study was designed to determine whether reactive oxygen species (ROS) mediate UVB-induced TGF-beta biosynthesis in keratinocytes and the subsequent activation of the latent TGF-beta complex. UVB irradiation elevated both total (latent plus active) and active TGF-beta in the keratinocyte supernatants, with a greater increase in the active form. UVB irradiation induced tip to a 30% increase in ROS, and the ROS were detected up to 90 min after irradiation. NAC and Trolox, cytoplasmic ROS scavengers, abolished the UVB-induced TGF-beta and intracellular ROS, suggesting that UVB-induced ROS are involved in TGF-beta regulation. Inhibitors of NADPH oxidase activity, DPI and apocynin, decreased UVB-induced ROS. The increase in NADPH oxidase activity was mediated by EGFR activation. UVB-induced ROS also activated latent TGF-beta complex by stimulating MMP-2 and -9 activities. In summary, physiological doses of UVB increase intracellular ROS, which upregulate TGF-beta biosynthesis and activation of TGF-beta through increased activity of MMPs. (c) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. EM kochevar@helix.mgh.harvard.edu FU NIAMS NIH HHS [R01 AR043895] NR 47 TC 70 Z9 74 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 1 PY 2005 VL 38 IS 7 BP 890 EP 897 DI 10.1016/j.freeradbiomed.2004.12.005 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 907ZG UT WOS:000227756200008 PM 15749385 ER PT J AU Lichtenstein, GR Yan, SK Bala, M Blank, M Sands, BE AF Lichtenstein, GR Yan, SK Bala, M Blank, M Sands, BE TI Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease SO GASTROENTEROLOGY LA English DT Article ID COST; FISTULAS; MANAGEMENT; ILLNESS; COUNTY; CARE AB Background & Aims: Infliximab is effective in closing fistulas in patients with Crohn's disease. We examined the effect of infliximab maintenance treatment on hospitalizations, surgeries, and procedures in patients with fistulizing Crohn's disease enrolled in the ACCENT II study. Methods: After 5 mg/kg infliximab at weeks 0, 2, and 6, a total of 282 patients were separately randomized at week 14 as responders (at least a 50% reduction from baseline in the number of draining fistulas at both weeks 10 and 14) or nonresponders to receive placebo or 5 mg/kg infliximab maintenance every 8 weeks. At week 22 and later, patients who lost response could be treated with a maintenance dose 5 mg/kg higher. Data on Crohn's disease-related hospitalizations, surgeries, and procedures were compared between the treatment groups for responders and all randomized patients. Results: A total of 282 patients were randomized at week 14, of whom 195 were randomized as responders. Among patients randomized as responders, those who received infliximab maintenance had significantly fewer mean hospitalization days (0.5 vs. 2.5 days; P <.05), mean numbers (per 100 patients) of hospitalizations (11 vs. 31; P <.05), all surgeries and procedures (65 vs. 126; P <.05), inpatient surgeries and procedures (7 vs. 41; P <.01), and major surgeries (2 vs. 11; P <.05), compared with those who received placebo maintenance. Conclusions: In patients with fistulizing Crohn's disease, infliximab 5 mg/kg every 8 weeks significantly reduced hospitalizations, surgeries, and procedures compared with placebo. C1 Centocor Inc, Malvern, PA 19355 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lichtenstein, GR (reprint author), Hosp Univ Penn, Sch Med, Div Gastroenterol, Dept Med, 3rd Floor,Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM grl@uphs.upenn.edu NR 16 TC 307 Z9 322 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2005 VL 128 IS 4 BP 862 EP 869 DI 10.1053/j.gastro.2005.01.048 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600012 PM 15825070 ER PT J AU Jutabha, R Jensen, DM Martin, P Savides, T Han, SH Gornbein, J AF Jutabha, R Jensen, DM Martin, P Savides, T Han, SH Gornbein, J TI Randomized study comparing banding and propranolol to prevent initial variceal hemorrhage in cirrhotics with high-risk esophageal varices SO GASTROENTEROLOGY LA English DT Article ID CONTROLLED-TRIAL; PRIMARY PROPHYLAXIS; ENDOSCOPIC LIGATION; INJECTION SCLEROTHERAPY; ISOSORBIDE MONONITRATE; PORTAL-HYPERTENSION; CLINICAL-TRIAL; 1ST HEMORRHAGE; LIVER-DISEASE; CIRRHOSIS AB Background & Aims: Standard care for prevention of first esophageal variceal hemorrhage is beta-blockade, but this may be ineffective or unsafe. Our purpose was to compare endoscopic banding with propranolol for prevention of first variceal hemorrhage. Methods: In a multicenter, prospective trial, 62 patients with cirrhosis with high-risk esophageal varices were randomized to propranolol (titrated to reducing resting pulse by 25%) or banding (performed monthly until varices were eradicated) and were followed up on the same schedule for a mean duration of 15 months. The primary end point was treatment failure, defined as the development of endoscopically documented variceal hemorrhage or a severe medical complication requiring discontinuation of therapy. Direct costs were estimated from Medicare reimbursements and fixed or variable charges for services up to treatment failure. Results: Background variables of the treatment groups were similar. The trial was stopped early after an interim analysis showed that the failure rate of propranolol was significantly higher than that of banding (6/31 vs. 0/31; difference, 1.9.4%; P =.0098; 95% confidence interval for true difference, 6.4%-37.2%). Significantly more propranolol than banding patients had esophageal variceal hemorrhage (4/31 vs. 0/31; difference, 12.9%; P =.0443; 95% confidence interval for true difference, 0.8%-29%), and the cumulative mortality rate was significantly higher in the propranolol than in the banding group (4/31 vs. 0/31; difference, 12.9%; P =.0443; 95% confidence interval for true difference, 0.8%-29%). Direct costs of care were not significantly different. Conclusions: For patients with cirrhosis with high-risk esophageal varices and no history of variceal hemorrhage, propranolol-treated patients had significantly higher failure rates of failure, first esophageal varix hemorrhage, and cumulative mortality than banding patients. Direct costs of medical care were not significantly different. C1 Univ Calif Los Angeles, David Geffen Sch Med, Hlth Sci Ctr, Dept Med,Div Digest Dis, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif San Diego, Med Ctr, Ctr Ulcer Res & Educ, Digest Dis Res Ctr, San Diego, CA 92103 USA. Univ Calif San Diego, Med Ctr, Cedars Sinai Med Ctr, San Diego, CA 92103 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. RP Jensen, DM (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM djensen@mednet.ucia.edu FU NCRR NIH HHS [5 M01-RR008658-25]; NIDDK NIH HHS [IK24 DK 02650, DK 41301] NR 44 TC 74 Z9 80 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2005 VL 128 IS 4 BP 870 EP 881 DI 10.1053/j.gastro.2005.01.047 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600013 PM 15825071 ER PT J AU Morgan, TR Weiss, DG Nemchausky, B Schiff, ER Anand, B Simon, F Kidao, J Cecil, B Mendenhall, CL Nelson, D Lieber, C Pedrosa, M Jeffers, L Bloor, J Lumeng, L Marsano, L McClain, C Mishra, G Myers, B Leo, M Ponomarenko, Y Taylor, D Chedid, A French, S Kanel, G Murray, N Pinto, P Fong, TL Sather, MR AF Morgan, TR Weiss, DG Nemchausky, B Schiff, ER Anand, B Simon, F Kidao, J Cecil, B Mendenhall, CL Nelson, D Lieber, C Pedrosa, M Jeffers, L Bloor, J Lumeng, L Marsano, L McClain, C Mishra, G Myers, B Leo, M Ponomarenko, Y Taylor, D Chedid, A French, S Kanel, G Murray, N Pinto, P Fong, TL Sather, MR TI Colchicine treatment of alcoholic cirrhosis: A randomized, placebo-controlled clinical trial of patient survival SO GASTROENTEROLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; CHRONIC HEPATITIS; URSODEOXYCHOLIC ACID; LIVER-CIRRHOSIS; DOUBLE-BLIND; FIBROSIS; DAMAGE; REVERSIBILITY; PREVENTION; SECRETION AB Background & Aims: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. Methods: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. Results: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P =.371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P =.337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in I patient (colchicine). Conclusions: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis. C1 Vet Adm Med Ctr, VA Long Beach Healthcare Syst, Long Beach, CA 90822 USA. VA Med Ctr, Perry Point, MD USA. VA Med Ctr, Hines, IL USA. VA Med Ctr, Miami, FL USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Denver, CO USA. VA Med Ctr, Louisville, KY USA. VA Med Ctr, Cincinnati, OH USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, Bronx, NY USA. VA Med Ctr, Boston, MA USA. VA Med Ctr, Indianapolis, IN USA. VA Med Ctr, Lexington, KY USA. VA Med Ctr, Gainesville, FL USA. VA Med Ctr, N Chicago, IL USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Univ So Calif, Med Ctr, LAC, Los Angeles, CA USA. Baylor Hosp, Dallas, TX USA. VA Med Ctr, Albuquerque, NM USA. RP Morgan, TR (reprint author), Vet Adm Med Ctr, VA Long Beach Healthcare Syst, 5901 E 7th St, Long Beach, CA 90822 USA. EM timothy.morgan@med.va.gov NR 38 TC 34 Z9 35 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2005 VL 128 IS 4 BP 882 EP 890 DI 10.1053/j.gastro.2005.01.057 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600014 PM 15825072 ER PT J AU Lin, WY Choe, WH Hiasa, Y Kamegaya, Y Blackard, JT Schmidt, EV Chung, RT AF Lin, WY Choe, WH Hiasa, Y Kamegaya, Y Blackard, JT Schmidt, EV Chung, RT TI Hepatitis C virus expression suppresses interferon signaling by degrading STAT1 SO GASTROENTEROLOGY LA English DT Article ID ALPHA/BETA-INTERFERON; MEMBRANE ASSOCIATION; INHIBITS INTERFERON; GAMMA-INTERFERON; PROTEIN-KINASE; V-PROTEIN; CELLS; REPLICATION; DEGRADATION; RNA AB Background B Aims: The molecular mechanisms by which hepatitis C virus (HCV) antagonizes the antiviral actions of interferon (IFN) have not been fully characterized. Specifically, how HCV proteins impact on IFN signaling components has yet to be elucidated. We used an HCV cell-based expression model to examine the interaction between HCV protein expression and host type I IFN signaling components in the Jak-STAT kinase pathway. Methods: Full-length HCV and HCV subgenomic constructs corresponding to structural and each of the nonstructural proteins were transiently transfected into Huh-T7 cells. HCV expression was monitored by an HCV core antigen enzyme-linked immunosorbent assay. STAT1, P-STAT1, and HCV protein expression was investigated with immunoprecipitation and Western blots. Results: Overexpression and small interfering RNA studies showed that STAT1 was indispensable for control of HCV expression. STAT1 and P-STAT1 expression were markedly reduced in HCV-transfected cells. Full-length HCV, HCV core/E1/E2, and NS3-4A were each associated with decreased STAT1 expression, which was attributable to proteasome-dependent degradation of STAT1. HCV core, but not HCV E1, E2, NS3, NS4, or NS5, bound to STAT1. STAT2 expression was not affected by HCV. Conclusions: HCV expression selectively degrades STAT1 and reduces P-STAT1 accumulation in the nucleus in a proteasome-dependent manner. HCV core protein binds STAT1, suggesting that this viral protein is associated with STAT1 degradation. STAT1 plays an indispensable role in innate antiviral immunity against HCV expression. In turn, HCV subverts the Jak-STAT kinase by selectively inducing STAT1 degradation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med, Boston, MA 02114 USA. RP Chung, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org FU NIDDK NIH HHS [DK57857] NR 36 TC 96 Z9 103 U1 1 U2 11 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 2005 VL 128 IS 4 BP 1034 EP 1041 DI 10.1053/j.gastro.2005.02.006 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600026 PM 15825084 ER PT J AU Xavier, R Podolsky, DK AF Xavier, R Podolsky, DK TI Commensal flora: Wolf in sheep's clothing SO GASTROENTEROLOGY LA English DT Editorial Material ID TOLL-LIKE RECEPTORS; INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; ENTEROCOCCUS-FAECALIS; BACTERIAL FLAGELLIN; GENE-EXPRESSION; INNATE IMMUNITY; PROTEINS; COLITIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. EM dpodolsky@partners.org NR 47 TC 13 Z9 14 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2005 VL 128 IS 4 BP 1122 EP 1126 DI 10.1053/j.gastro.2005.02.053 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600036 PM 15825094 ER PT J AU Fukumoto, T Levin, M AF Fukumoto, T Levin, M TI Asymmetric expression of Syndecan-2 in early chick embryogenesis SO GENE EXPRESSION PATTERNS LA English DT Article DE Syndecan-2; embryogenesis; left-fight asymmetry; chick ID RIGHT AXIS FORMATION; EMBRYO; GENES AB Chicken Syndecan-2 (cSyndecan-2) is the homologue of Xenopus Syndecan-2, a member of the heparan sulfate proteoglycan family with an important role in left-right patterning in frog embryos. A relationship to LR asymmetry in other species has not been reported. We show that cSyndecan-2 is expressed throughout the primitive streak between st. I and 3 in the chick embryo, and is restricted to the rostral and caudal tips of the primitive streak at st. 4. It displays distinct left-right asymmetry, being expressed in the right side of Hensen's node at st. 5. The asymmetric expression of cSyndecan-2 is maintained around the node between st. 5 and 7. At early somite stages, somites and neural folds express cSyndecan-2. The somite expression disappears by st. 11, but strong expression in the neural tube continues, Our data reveal a new asymmetric transcript in the chick embryo and indicate that in contrast to protein-level asymmetries, which underlie syndecan-2 function in Xenopus, chick syndecan-2 exhibits asymmetry at the mRNA level. (c) 2004 Elsevier B.V. All rights reserved. C1 Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Cytokine Biol Dept, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org NR 16 TC 8 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD APR PY 2005 VL 5 IS 4 BP 525 EP 528 DI 10.1016/j.modgep.2004.12.001 PG 4 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 911KO UT WOS:000228001300009 PM 15749081 ER PT J AU Liu, R Martuza, RL Rabkin, SD AF Liu, R Martuza, RL Rabkin, SD TI Intracarotid delivery of oncolytic HSV vector G47 Delta to metastatic breast cancer in the brain SO GENE THERAPY LA English DT Article DE blood-brain barrier; osmotic disruption; virotherapy; herpes simplex virus; brain tumors ID HERPES-SIMPLEX-VIRUS; REPLICATION-COMPETENT; BARRIER PERMEABILITY; MALIGNANT GLIOMA; DRUG-DELIVERY; TUMORS; CARCINOMA; G207; MODEL; THERAPY AB Delivery of viral vectors to tumors in the brain is a challenge, especially via systemic administration, which is key to targeting the invasive margins of malignant glioma and the multiple foci of metastatic disease. Like for other cancer therapeutics, the blood - brain barrier or even the blood tumor barrier significantly limits delivery and efficacy. Blood brain barrier disruption (BBBD) is one strategy for transiting the cerebrovasculature. G47D is a third-generation oncolytic replication-competent herpes simplex virus (HSV) vector, containing deletions of the gamma 34.5 and alpha 47 genes and an inactivating LacZ insertion in UL39 (ICP6). Intracarotid artery delivery of G47D after BBBD with 25% mannitol significantly extended the life of nude mice bearing intracerebral human MDA-MB-435 breast tumors, whereas, G47 Delta injection contralateral to the tumor, in the absence of mannitol or mannitol alone had no effect on survival. G47 Delta replication was extensive after BBBD, as visualized by X-gal staining. Staining of peripheral organs, lung and liver, was minimal and not altered by BBBD. This is the first demonstration of intracarotid arterial delivery of oncolytic HSV vectors and antitumor efficacy in a mouse model and opens the door to the use of mouse syngenic tumor models and transgenic/ knockout animals. C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabkin, SD (reprint author), Mol Neurosurg Lab, MGH E, 13th St,Bldg 149,Box 17, Charlestown, MA 02129 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 53 TC 35 Z9 38 U1 0 U2 1 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 2005 VL 12 IS 8 BP 647 EP 654 DI 10.1038/sj.gt.3302445 PG 8 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 913UW UT WOS:000228180700002 PM 15647762 ER PT J AU Wei, CC Lamesch, P Arumugam, M Rosenberg, J Hu, P Vidal, M Brent, MR AF Wei, CC Lamesch, P Arumugam, M Rosenberg, J Hu, P Vidal, M Brent, MR TI Closing in on the C elegans ORFeome by cloning TWINSCAN predictions SO GENOME RESEARCH LA English DT Article ID GENE-PREDICTION; EXPERIMENTAL-VERIFICATION; CAENORHABDITIS-ELEGANS; GENOMIC DNA; WORMBASE; RESOURCE; BIOLOGY; MOUSE AB The genome of Caenorhabditis elegans was the first animal genome to be sequenced. Although considerable effort has been devoted to annotating it, the standard WormBase annotation contains thousands of predicted genes for which there is no cDNA or EST evidence. We hypothesized that a more complete experimental annotation could be obtained by creating a more accurate gene-prediction program and then amplifying and sequencing predicted genes. Our approach was to adapt the TWINSCAN gene prediction system to C elegans and C briggsae and to improve its splice site and intron-length models. The resulting system has 60% sensitivity and 58% specificity in exact prediction of open reading frames (ORFs), and hence, proteins-the best results we are aware of any multicellular organism. We then attempted to amplify, clone, and sequence 265 TWINSCAN-predicted ORFs that did not overlap WormBase gene annotations. The success rate was 55%, adding 146 genes that were completely absent from WormBase to the ORF clone collection (ORFeome). The same procedure had a 7% success rate on 90 Worm Base "predicted" genes that do not overlap TWINSCAN predictions. These results indicate that the accuracy of WormBase could be significantly increased by replacing its partially curated predicted genes with TWINSCAN predictions. The technology described in this study will continue to drive the C elegans ORFeome toward completion and contribute to the annotation of the three Caenorhabditis species currently being sequenced. The results also suggest that this technology can significantly improve our knowledge of the "parts list" for even the best-studied model organisms. C1 Washington Univ, Lab Computat Genom, St Louis, MO 63130 USA. Washington Univ, Dept Comp Sci & Engn, St Louis, MO 63130 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Washington Univ, Lab Computat Genom, St Louis, MO 63130 USA. EM brent@cse.wustl.edu RI Arumugam, Manimozhiyan/E-1211-2011; OI Arumugam, Manimozhiyan/0000-0002-0886-9101; Wei, Chaochun/0000-0002-1031-034X FU NCI NIH HHS [7 R33 CA81658-02]; NHGRI NIH HHS [HG-02278, 5R01HG01715-02, R01 HG001715, R01 HG002278] NR 24 TC 29 Z9 32 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD APR PY 2005 VL 15 IS 4 BP 577 EP 582 DI 10.1101/gr.3329005 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 914CT UT WOS:000228203000014 PM 15805498 ER PT J AU Quiram, P Dumars, S Parwar, B Sarraf, D AF Quiram, P Dumars, S Parwar, B Sarraf, D TI Viagra-associated serous macular detachment SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID SILDENAFIL CITRATE VIAGRA; UVEAL EFFUSION; CHORIORETINOPATHY; DEGENERATION; FEATURES; THERAPY; SERIES AB Purpose: To describe the OCT findings in two cases of idiopathic serous macular detachments associated with Sildenafil ( Viagra) use. Methods: Two patients were identified with idiopathic serous macular detachments associated with Viagra use. Each patient underwent rigorous historical questioning to rule out known causes of serous macular detachments and to determine contributing factors. A comprehensive ocular examination was performed including dilated biomicroscopic examination of the macula and indirect ophthalmoscopic evaluation of the retinal periphery. Additional evaluation included color fundus photography with FA and ICG, OCT analysis of the macula and B-scan ultrasonography. Systemic workup included MRI of the brain and orbits, CT of the brain, orbits, chest and abdomen, blood chemistries and electrophoresis, lumbar puncture with CSF analysis and chest radiographs. Results: Both patients demonstrated idiopathic serous macular detachment associated with peri-macular vitelliform deposits. Although notable peripapillary atrophy and RPE mottling were present, there was no evidence of heme, exudate, or fibrosis to suggest a CNVM. FA showed no focal areas of leakage. Early and late frames of the ICG demonstrated engorged choroidal vessels without frank leakage. Extensive medical evaluation failed to reveal a systemic etiology. OCT findings demonstrated large serous macular detachments that corresponded to the use or discontinuation of Viagra. Discontinuation of Viagra coincided with complete resolution of the serous macular detachment in one patient and improvement of the serous macular detachment in the other. When one patient resumed Viagra use, he experienced a recurrent serous macular detachment. Conclusions: We report the OCT findings of two cases of idiopathic serous macular detachment associated with use of the potent vasodilator Sildenafil ( Viagra). C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Adm Healthcare Ctr, Los Angeles, CA USA. Charles Drew Univ Med, ML King Med Ctr, Los Angeles, CA USA. Kaiser Permanente Med Grp, Dept Ophthalmol, Woodland Hills, CA USA. Kaiser Permanente Med Grp, Dept Ophthalmol, Baldwin Pk, CA USA. RP Quiram, P (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM quiram@jsei.ucla.edu NR 37 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD APR PY 2005 VL 243 IS 4 BP 339 EP 344 DI 10.1007/s00417-004-1099-0 PG 6 WC Ophthalmology SC Ophthalmology GA 922RW UT WOS:000228856700010 PM 15756578 ER PT J AU Rivers, PA Dobalian, A Germinario, FA AF Rivers, PA Dobalian, A Germinario, FA TI A review and analysis of the clinical laboratory improvement amendment of 1988: Compliance plans and enforcement policy SO HEALTH CARE MANAGEMENT REVIEW LA English DT Review AB In 1988, Congress passed the Clinical Laboratory Improvement Amendment (CLIA), thereby extending coverage of the Clinical Laboratory Improvement Act of 1967 to include quality standards for all laboratory-based testing. The CLIA was enacted to ensure the accuracy, reliability, and timeliness of patient test results, regardless of the location where the tests were performed. This article assessed trends in the enforcement policy of the CLIA through an examination of the Laboratory Registry, an annual publication of those individuals or entities that have had sanctions imposed on them by the Centers for Medicare and Medicaid Services. We reviewed the CLIA, including its oversight, regulations that were promulgated based on it, and its enforcement procedures. We obtained the Laboratory Registries for 1993-2001. Sanctions were categorized into groups per the enforcement regulations (42 C.F.R . 493.2 2000). The data indicated an increasing use of more lenient sanctions from 1997 to 2001, and a gradual increase in fraudulent activity for that same period. One possible explanation for this finding is that implementation of compliance plans by participating clinical laboratories had a mitigating effect on enforcement policy. Compliance plan guidance from the OIG provides an opportunity for laboratory service providers to be proactive in their attempts to decrease errors, and thus improve accuracy and reliability by documenting laboratory policies, procedures, and objectives. C1 So Illinois Univ, Coll Appl Sci & Arts, Hlth Management Program, Carbondale, IL USA. VA Greater Los Angles Healthcare Syst, HSR&D Ctr Excellence Study Healthcare Provider Be, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Arizona State Univ, Coll Business, Sch Hlth Adm & Policy, Tempe, AZ 85287 USA. RP Rivers, PA (reprint author), So Illinois Univ, Coll Appl Sci & Arts, Hlth Management Program, Carbondale, IL USA. EM privers@siu.edu; adobalia@ucla.edu; franco.germinario@asu.edu NR 16 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD APR-JUN PY 2005 VL 30 IS 2 BP 93 EP 102 PG 10 WC Health Policy & Services SC Health Care Sciences & Services GA 924NJ UT WOS:000228985200003 PM 15923911 ER PT J AU Fergus, S Lewis, MA Darbes, LA Butterfield, RM AF Fergus, S Lewis, MA Darbes, LA Butterfield, RM TI HIV risk and protection among gay male couples: The role of gay community integration SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE gay men; couples; HIV risk behavior; social involvement; gay community integration ID UNPROTECTED ANAL INTERCOURSE; AIDS BEHAVIORAL-RESEARCH; SEXUAL-BEHAVIOR; HOMOSEXUAL-MEN; BISEXUAL MEN; SAN-FRANCISCO; SELF-ESTEEM; SAFER SEX; PREVENTION; HEALTH AB This study examined the association between different types of integration in the gay community and HIV risk among gay male couples. Previous research linking gay community integration and involvement among couples to HIV risk has been equivocal. Each partner in 59 gay couples completed a separate anonymous questionnaire that assessed two types of social involvement in the gay community, assimilation into the gay community, and sexual HIV risk behaviors. We used the actor-partner interdependence analysis approach, which maintains the couple as the unit of analysis while allowing for tests of within-couple, between-couple, actor, and partner effects. Analyses revealed that, controlling for symptoms of alcohol problems, going to gay bars and clubs independently predicted more HIV risk. C1 Univ Michigan, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Fergus, S (reprint author), Univ Michigan, Dept Hlth Behav & Hlth Educ, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM ferguss@umich.edu NR 65 TC 11 Z9 11 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2005 VL 32 IS 2 BP 151 EP 171 DI 10.1177/1090198104271964 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 907DH UT WOS:000227695000001 PM 15856614 ER PT J AU Nelson, KM Chapko, MK Reiber, G Boyko, EJ AF Nelson, KM Chapko, MK Reiber, G Boyko, EJ TI The association between health insurance coverage and diabetes care; Data from the 2000 Behavioral Risk Factor Surveillance System SO HEALTH SERVICES RESEARCH 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 DE quality of care; health insurance; diabetes ID UNITED-STATES; MEDICAL-CARE; ADULTS; RELIABILITY; MELLITUS; US AB To describe the association between type of health insurance coverage and the quality of care provided to individuals with diabetes in the United States. The 2000 Behavioral Risk Factor Surveillance System. Our study cohort included individuals who reported a diagnosis of diabetes (n=11,647). We performed bivariate and multivariate logistic regression analyses by age greater or less than 65 years to examine the association of health insurance coverage with diabetes-specific quality of care measures, controlling for the effects of race/ethnicity, annual income, gender, education, and insulin use. Most individuals with diabetes are covered by private insurance (39 percent) or Medicare (44 percent). Among persons under the age of 65 years, 11 percent were uninsured. The uninsured were more likely to be African American or Hispanic and report low incomes. The uninsured were less likely to report annual dilated eye exams, foot examinations, or hemoglobin A1c (HbA1c) tests and less likely to perform daily blood glucose monitoring than those with private health insurance. We found few differences in quality indicators between Medicare, Medicaid, or the Department of Veterans Affairs (VA) as compared with private insurance coverage. Persons who received care through the VA were more likely to report taking a diabetes education class and HbA1c testing than those covered by private insurance. Uninsured adults with diabetes are predominantly minority and low income and receive fewer preventive services than individuals with health insurance. Among the insured, different types of health insurance coverage appear to provide similar levels of care, except for higher rates of diabetes education and HbA1c testing at the VA. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98107 USA. RP Nelson, KM (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way,S-111-GIMC, Seattle, WA 98107 USA. NR 21 TC 67 Z9 68 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2005 VL 40 IS 2 BP 361 EP 372 DI 10.1111/j.1475-6773.2005.0d362.x PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 015ZK UT WOS:000235590000005 PM 15762896 ER PT J AU Shahidzadeh, R Opekun, A Shiotani, A Graham, DY AF Shahidzadeh, R Opekun, A Shiotani, A Graham, DY TI Effect of the carbonic anhydrase inhibitor, acetazolamide, on Helicobacter pylori infection in vivo: A pilot study SO HELICOBACTER LA English DT Article DE Helicobacter pylori; treatment; acetazolamide; clinical trial; urea breath testing ID RESISTANCE; UREASE AB Background. Carbonic anhydrase inhibitors have been successfully used to treat peptic ulcers. Although carbonic anhydrase restriction does not inhibit Helicobacter pylori in vitro, recent studies suggest that carbonic anhydrase inhibition reduces the ability of H. pylori to survive in an acid environment as present in the stomach. Methods. In a pilot study, we examined the effect of acetazolamide 500 mg as twice a day for 4 days in volunteers with active H. pylori infection. Effectiveness was judged by changes in the results of the urea breath test. Results. Eight H. pylori infected volunteers completed the test. No urea breath test reverted to negative and there was a trend for the urea breath test value to increase [e.g. delta over baseline (DOB) mean +/- SE increased from 50.9 +/- 13 at baseline to 64.9 +/- 13 at day 5] during treatment with acetazolamide. Conclusion. The potential effect of carbonic anhydrase inhibitors on acid secretion may prevent effect on H. pylori in vivo and/or the sites of infection at the surface of the stomach may have a pH higher for any postulated acid-dependent effect to have an effect clinically. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Rm 3 A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK56338] NR 10 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD APR PY 2005 VL 10 IS 2 BP 136 EP 138 DI 10.1111/j.1523-5378.2005.00306.x PG 3 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 905TN UT WOS:000227593200006 PM 15810944 ER PT J AU Spiegel, BMR Younossi, ZM Hays, RD Revicki, D Robbins, S Kanwal, F AF Spiegel, BMR Younossi, ZM Hays, RD Revicki, D Robbins, S Kanwal, F TI Impact of hepatitis C on health related quality of life: A systematic review and quantitative assessment SO HEPATOLOGY LA English DT Article ID CLINICALLY IMPORTANT DIFFERENCES; ANTIVIRAL THERAPY; VIRAL-HEPATITIS; VIRUS-INFECTION; LIVER-DISEASE; HCV-INFECTION; QUESTIONNAIRE; COMBINATION; DIFFERENCE; UTILITIES AB Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. C1 Univ Calif Los Angeles, David Geffen Sch Med,Div Gastroenterol, VA Greater Los Angeles Healthcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. Inova Fairfax Hosp, Ctr Study Digest Healthcare Qual & Outcomes, Falls Church, VA USA. Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Amgen Inc, Global Hlth Econ, Thousand Oaks, CA USA. RP Kanwal, F (reprint author), Univ Calif Los Angeles, David Geffen Sch Med,Div Gastroenterol, VA Greater Los Angeles Healthcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, 11301 Wilshire Blvd,Bldg 115 Room 215E, Los Angeles, CA 90073 USA. EM fkanwal@mednet.ucla.edu RI Hays, Ronald/D-5629-2013 FU NIA NIH HHS [AG-02-004]; NIMHD NIH HHS [P20-MD00148-01] NR 47 TC 198 Z9 207 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2005 VL 41 IS 4 BP 790 EP 800 DI 10.1002/hep.20659 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MD UT WOS:000228006000015 PM 15791608 ER PT J AU Lee, YH Harley, JB Nath, SK AF Lee, YH Harley, JB Nath, SK TI CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis SO HUMAN GENETICS LA English DT Article ID SIGNIFICANT ASSOCIATION; SUSCEPTIBILITY GENE; T-CELLS; PROMOTER; EXON-1; POPULATION; JAPANESE; DISEASE; AUTOIMMUNITY; ACTIVATION AB Several reports demonstrate association between variants of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune diseases. CTLA-4 may generate autoimmunity by immune dysregulation, making CTLA-4 an attractive candidate gene for systemic lupus erythematosus (SLE) susceptibility. Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 14 independent studies (to July 2004) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at four polymorphic sites found in exon-1 (at +49), the promoter region (at -318 and -1722), and the 3' untranslated region (3'UTR) (dinucleotide repeat). We have evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The data demonstrate that the exon-1 +49 polymorphism is significantly associated with SLE susceptibility. The overall risk, measured by odds ratio (OR), for exon-1 +49 GG genotype is 1.287 [95% confidence interval (CI)=1.031-1.562, P=0.011]. Stratification by ethnicity indicates the exon-1 +49 GG genotype is associated with SLE, at least in Asians (OR=1.293, 95% CI=1.031-1.620, P=0.026). European-derived populations have an effect of similar magnitude (OR=1.268, 95% CI=0.860-1.870, P=0.230), though not significant. Similar trends are found in allele-specific risk estimates and disease association. The OR for the exon-1 +49 risk allele (G) in Asians is 1.246 (95% CI=1.057-1.469, P=0.009), while Europeans have no evidence of allelic association (OR=0.978, 95% CI=0.833-1.148, P=0.780). In conclusion, this meta-analysis supports the CTLA-4 exon-1 +49 (A/G) polymorphism influencing the risk for developing SLE, especially in Asians. C1 Oklahoma Med Res Fdn, Arthritis & Immunol Res Program, Oklahoma City, OK 73104 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Nath, SK (reprint author), Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73190 USA. EM swapan-nath@omrf.ouhsc.edu FU NCRR NIH HHS [RR01577, RR020143, RR14467]; NIAID NIH HHS [AI24717, AI053747, AI063622]; NIAMS NIH HHS [AR048928, AR049084, AR12253, AR42460, AR48940]; NIDCR NIH HHS [DE15223] NR 37 TC 85 Z9 95 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2005 VL 116 IS 5 BP 361 EP 367 DI 10.1007/s00439-004-1244-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 914LZ UT WOS:000228230500005 PM 15688186 ER PT J AU Ding, D Cooper, RA AF Ding, D Cooper, RA TI Electric-powered wheel chairs SO IEEE CONTROL SYSTEMS MAGAZINE LA English DT Review ID ASSISTED WHEELCHAIR; SEAT-BELT; DESIGN; SYSTEM; STABILITY; DISABILITIES; PERFORMANCE; CONTROLLER; SUSPENSION; VIBRATION C1 Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. RP Univ Pittsburgh, Med Ctr, Vet Affairs Pittsburgh Hlth Care Syst, Human Engn Res Labs, 151-R1,7180 Highland Dr, Pittsburgh, PA 15260 USA. EM rcooper@pitt.edu NR 91 TC 91 Z9 92 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1066-033X EI 1941-000X J9 IEEE CONTR SYST MAG JI IEEE Control Syst. Mag. PD APR PY 2005 VL 25 IS 2 BP 22 EP 34 DI 10.1109/MCS.2005.1411382 PG 13 WC Automation & Control Systems SC Automation & Control Systems GA 907XY UT WOS:000227752800003 ER PT J AU Feng, JW Garrity, D Call, ME Moffett, H Wucherpfennig, KW AF Feng, JW Garrity, D Call, ME Moffett, H Wucherpfennig, KW TI Convergence on a distinctive assembly mechanism by unrelated families of activating immune receptors SO IMMUNITY LA English DT Article ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; HUMAN FC RECEPTOR; COLLAGEN RECEPTOR; GLYCOPROTEIN VI; COMPLEX; ASSOCIATION; TRANSMEMBRANE; RECOGNITION; EXPRESSION AB Activating receptors in cells of hematopoetic origin include members of two unrelated protein families, the immunoglobulin (Ig) and C type lectins, which differ even in the orientation of the transmembrane (TM) domains. We examined assembly of four receptors with diverse function: the NK receptors KIR2DS and NKG2C/CD94, the Fc receptor for IgA, and the GPVI collagen receptor. For each of the four different receptors studied here, assembly results in the formation of a three-helix interface in the membrane involving two acidic TM residues from the signaling dimer and a basic TM residue from the ligand recognition module, an arrangement remarkably similar to the T cell receptor (TCR)-CD3 complex. The fact that the TM domains of Ig family and C type lectins adopt opposite orientations proves that these receptor families independently evolved toward the same structural arrangement of the interacting TM helices. This assembly mechanism is thus widely utilized by receptors in cells of hematopoetic origin. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI054520, R01 AI54520] NR 33 TC 48 Z9 51 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2005 VL 22 IS 4 BP 427 EP 438 DI 10.1016/j.immuni.2005.02.005 PG 12 WC Immunology SC Immunology GA 923KU UT WOS:000228909600005 PM 15845448 ER PT J AU Villasenor, J Benoist, C Mathis, D AF Villasenor, J Benoist, C Mathis, D TI AIRE and APECED: molecular insights into an autoimmune disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID E3 UBIQUITIN LIGASE; NF-KAPPA-B; TRANSCRIPTIONAL ACTIVATION DOMAIN; ECTODERMAL DYSTROPHY PATIENTS; PROMISCUOUS GENE-EXPRESSION; T-CELL TOLERANCE; ZINC-FINGER; REGULATOR PROTEIN; MI-2 AUTOANTIGEN; EPITHELIAL-CELLS AB Mutations in the autoimmune regulator (AIRE) protein are the causative factor in development of the human disease autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). In mice, the absence of the analogous protein aire influences ectopic expression of peripheral tissue antigens in thymic medullary epithelial cells (MECs), resulting in the development of an autoimmune disorder similar to APECED and establishing aire/AIRE as an important player in the induction of central tolerance. However, the molecular mechanism of AIRE's function, in particular its ability to specifically control the expression of peripheral tissue antigens in MECs, is still unclear. Here, we review current evidence relating to the molecular mechanism of AIRE. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Joslin Diabet Ctr, Sect Immunol & Immunogenet,Dept Med, Boston, MA 02215 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Joslin Diabet Ctr, Sect Immunol & Immunogenet,Dept Med, Boston, MA 02215 USA. EM diane.mathis@joslin.harvard.edu NR 94 TC 69 Z9 75 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2005 VL 204 BP 156 EP 164 DI 10.1111/j.0105-2896.2005.00246.x PG 9 WC Immunology SC Immunology GA 906VN UT WOS:000227672500012 PM 15790357 ER PT J AU Paust, S Cantor, H AF Paust, S Cantor, H TI Regulatory T cells and autoimmune disease SO IMMUNOLOGICAL REVIEWS LA English DT Review ID IMMUNOLOGICAL SELF-TOLERANCE; INDUCED TNF RECEPTOR; EXPRESSING INDOLEAMINE 2,3-DIOXYGENASE; TRANSCRIPTION FACTOR FOXP3; IN-VITRO GENERATION; TGF-BETA; DENDRITIC CELLS; NEGATIVE SELECTION; TRYPTOPHAN CATABOLISM; IMMUNOSUPPRESSIVE DRUGS AB Although T-cell clones bearing T-cell receptors with high affinity for self-peptide major histocompatibility complex (MHC) products are generally eliminated in the thymus (recessive tolerance), the peripheral T-cell repertoire remains strongly biased toward self-peptide MHC complexes and includes autoreactive T cells. A search for peripheral T cells that might exert dominant inhibitory effects on autoreactivity has implicated a subpopulation of CD4(+)CD25(+) T cells called regulatory T cells (Tregs). Here, we discuss the role of cytokines and costimulatory molecules in the generation, maintenance, and function of Tregs. We also summarize evidence for the involvement of Tregs in controlling autoimmune diseases, including type 1 diabetes, experimental autoimmune encephalomyelitis, and inflammatory bowel disease. Last, we discuss our recent definition of the potential role of B7 expressed on activated T-effector cells as a target molecule for Treg-dependent suppression. These observations suggest that the engagement of B7 on effector T cells transmits an inhibitory signal that blocks or attenuates effector T-cell function. We restrict our comments to the suppression mediated by cells within the CD4 lineage; the impact of the cells within the CD8 lineage that may suppress via engagement of Qa-1 on effector T cells is not addressed in this review. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), 44 Binney St, Boston, MA 02115 USA. EM harvey_cantor@dfci.harvard.edu NR 96 TC 145 Z9 173 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 2005 VL 204 BP 195 EP 207 DI 10.1111/j.0105-2896.2005.00247.x PG 13 WC Immunology SC Immunology GA 906VN UT WOS:000227672500015 PM 15790360 ER PT J AU Yamaoka, Y Yamauchi, K Ota, H Sugiyama, A Ishizone, S Graham, DY Maruta, F Murakami, M Katsuyama, T AF Yamaoka, Y Yamauchi, K Ota, H Sugiyama, A Ishizone, S Graham, DY Maruta, F Murakami, M Katsuyama, T TI Natural history of gastric mucosal cytokine expression in Helicobacter pylori gastritis in Mongolian gerbils SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNE-RESPONSES; INTESTINAL METAPLASIA; GAMMA-INTERFERON; CELL RESPONSES; TH1 PHENOTYPE; PEPTIC-ULCER; CAGA GENE; INFECTION; CANCER; MICE AB Data regarding the chronological changes in gastric mucosal cytokines in the different phases of Helicobacter pylori infection are unavailable. We examined Mongolian gerbils for up to 52 weeks after H. pylori (ATCC 43504) inoculation. Levels of mRNAs of mucosal cytokines (interleukin-1 beta [IL-1 beta], gamma interferon [IFN-gamma], IL-4, IL-6, and IL-10) were assessed using real-time reverse transcription-PCR. Starting 26 weeks after H. pylori inoculation, two clinicohistologic patterns appeared: gastric ulcers in 32% and hyperplastic polyps in 68% of gerbils. High levels of mucosal IL-10 mRNA were observed early in the infection, reaching maximum at 4 weeks and then rapidly declining. Mucosal IFN-gamma mRNA also reached maximal levels at 4 weeks but remained high thereafter. Both IL-1 beta and IFN-gamma mRNA levels were consistently higher in the pyloric mucosa than in the fundic mucosa. In contrast, IL-4, IL-6, and IL-10 mRNA levels peaked at 8 to 26 weeks and levels were similar in the pyloric mucosa and the fundic mucosa. IFN-gamma mRNA levels were significantly higher in gerbils with ulcers than in those with hyperplastic polyps (median IFN-gamma/glyceraldehyde-3 -phosphate dehydrogenase ratio x 100,000 = 650 versus 338, respectively [antrum], and 172 versus 40, respectively [corpus]) (P < 0.05). We propose that the different outcomes (e.g., ulcers or hyperplastic polyps) might relate to imbalances among cytokines. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Shinshu Univ Hosp, Matsumoto, Nagano, Japan. Shinshu Univ, Sch Med, Dept Biomed Lab Sci, Sch Hlth Sci, Matsumoto, Nagano, Japan. Shinshu Univ, Sch Med, Dept Surg, Matsumoto, Nagano, Japan. Shinshu Univ, Sch Med, Dept Lab Med, Matsumoto, Nagano 390, Japan. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, 111D,Rm 3A-320,2002 Holcombe Blvd, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [R01 DK062813-02, R01 DK62813, R01 DK062813] NR 32 TC 35 Z9 35 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2005 VL 73 IS 4 BP 2205 EP 2212 DI 10.1128/IAI.73.4.2205-2212.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911BB UT WOS:000227975000035 PM 15784564 ER PT J AU Koh, AY Priebe, GP Pier, GB AF Koh, AY Priebe, GP Pier, GB TI Virulence of Pseudomonas aeruginosa in a murine model of gastrointestinal colonization and dissemination in neutropenia SO INFECTION AND IMMUNITY LA English DT Article ID III PROTEIN SECRETION; SOFT CONTACT-LENSES; BACTERIAL TRANSLOCATION; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; BONE-MARROW; ULCERATIVE KERATITIS; SYSTEMIC SPREAD; CANCER-PATIENTS; DEPLETED MICE AB Pseudomonas aeruginosa bacteremia in cancer patients develops from initial gastrointestinal (GI) colonization with translocation into the bloodstream in the setting of chemotherapy-induced neutropenia and GI mucosal damage. We established a reproducible mouse model of P. aeruginosa GI colonization and systemic spread during neutropenia. Mice received 2 mg of streptomycin/ml of drinking water and 1,500 U of penicillin G/ml for 4 days and then ingested 10(7) CFU of A aeruginosa per ml of drinking water for 5 days. After GI colonization levels were determined, cyclophosphamide (Cy) was then injected intraperitoneally (i.p.) three times every other day or an antineutrophil monoclonal antibody, RB6-8C5, was injected i.p. once. Dissemination was defined by the presence of P. aeruginosa in spleens of moribund or dead mice. In this mouse model, P. aeruginosa colonizes the GI tract and then disseminates systemically once Cy or RB6-8C5 is administered. The duration and intensity of neutropenia, related to Cy dose, was found to be a means to compare the virulence of different P. aeruginosa strains, as exhibited by comparisons of strains lacking or producing the virulence-enhancing ExoU cytotoxin. The lipopolysaccharide outer core polysaccharide and 0 side chains were critical in establishing GI colonization, and P. aeruginosa mutants lacking the aroA gene (necessary for synthesizing aromatic amino acids) were able to establish GI colonization but unable to disseminate. Both the colonization and dissemination phases of P. aeruginosa pathogenesis can be studied in this model, which should prove useful for evaluating pathogenesis, therapies, and associated means to control P. aeruginosa nosocomial infections. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol & Oncol, Boston, MA USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA USA. Dana Farber Canc Inst, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Anesthesia, Boston, MA USA. Dana Farber Canc Inst, Dept Crit Care Med, Boston, MA USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Koh, AY (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM Andrew_koh@dfci.harvard.edu OI Pier, Gerald/0000-0002-9112-2331 FU NIAID NIH HHS [K08 AI050036, AI22535, N01AI50036, R01 AI022535]; NICHD NIH HHS [T32 HD03034-01] NR 54 TC 40 Z9 41 U1 0 U2 4 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 2005 VL 73 IS 4 BP 2262 EP 2272 DI 10.1128/IAI.73.4.2262-2272.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 911BB UT WOS:000227975000041 PM 15784570 ER EF