FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hadigan, C Yawetz, S Thomas, A Havers, F Sax, PE Grinspoon, S AF Hadigan, C Yawetz, S Thomas, A Havers, F Sax, PE Grinspoon, S TI A randomized, double-blind, placebo-controlled study of rosiglitazone for patients with HIV lipodystrophy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY JUL 08-11, 2003 CL Paris, FRANCE C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrine, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD AUG PY 2003 VL 8 IS 4 MA 12 BP L12 EP L12 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 955YQ UT WOS:000231266500035 ER PT J AU Chauhan, D Anderson, KC AF Chauhan, D Anderson, KC TI Mechanisms of cell death and survival in multiple myeloma (MM): Therapeutic implications SO APOPTOSIS LA English DT Article DE apoptosis; mitochondria; multiple myeloma; protease inhibitor; protective signaling ID MARROW STROMAL CELLS; NF-KAPPA-B; CHROMATIN CONDENSATION; RESISTANT MYELOMA; BIOLOGIC SEQUELAE; INDUCED APOPTOSIS; ACTIVATION; KINASE; INTERLEUKIN-6; PROTEIN AB Multiple myeloma (MM), a hematologic malignancy, remains fatal despite all available therapies. Initial treatment with conventional drugs effectively induces MM cell death/apoptosis; however, prolonged drug exposures results in the development of de novo chemoresistance. Because MM is a bone marrow ( BM) cancer, the progression of disease and drug efficacy is highly influenced by the BM microenvironment. Novel agents, such as proteasome inhibitors (PS-341), 2-methoxyestradiol (2ME2), thalidomide and its immunomodulatory derivatives (IMiDs), and histone deacetylase ( HDAC) inhibitors target the MM cell in its BM microenvironment; thereby enhancing anti-MM activity as well as preventing development of drug-resistance. The transcriptional events and signaling pathways, which mediate these responses in MM cells are now being delineated, and may serve to identify novel therapeutic targets based upon interrupting MM cell growth or triggering MM cell death. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Harvard Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, M557,44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA78373]; PHS HHS [50947] NR 55 TC 46 Z9 47 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD AUG PY 2003 VL 8 IS 4 BP 337 EP 343 DI 10.1023/A:1024164700094 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 689DZ UT WOS:000183477500003 PM 12815276 ER PT J AU Kasai, K Shenton, ME Salisbury, DF Hirayasu, Y Onitsuka, T Spencer, MH Yurgelun-Todd, DA Kikinis, R Jolesz, FA McCarley, RW AF Kasai, K Shenton, ME Salisbury, DF Hirayasu, Y Onitsuka, T Spencer, MH Yurgelun-Todd, DA Kikinis, R Jolesz, FA McCarley, RW TI Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia - A longitudinal magnetic resonance imaging study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FIRST-EPISODE SCHIZOPHRENIA; HUMAN AUDITORY-CORTEX; LEFT-RIGHT ASYMMETRIES; MISMATCH NEGATIVITY; THOUGHT-DISORDER; P300 ABNORMALITIES; SPEECH REGION; HUMAN-BRAIN; MRI DATA; REDUCTION AB Background: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressives decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. Methods: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. Results: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. Conclusions: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed. C1 Vet Affairs Boston Healthcare Syst, Clin Neurosci Div, Neurosci Lab, Dept Psychiat,Brockton Div, Brockton, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. Brigham & Womens Hosp, Surg Planning Lab, Magnet Resonance Imaging Div, Boston, MA 02115 USA. Cognit Neurosci Lab, Belmont, MA USA. Brain Imaging Ctr, Belmont, MA USA. McLean Hosp, Belmont, MA 02178 USA. Kyorin Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. RP McCarley, RW (reprint author), Harvard Univ, Sch Med, Brockton Div, Dept Psychiat 116A,VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NCRR NIH HHS [P41 RR013218, P41 RR013218-010004, P41 RR013218-010011, R01 RR 11747, R01 RR011747, R01 RR011747-02]; NIMH NIH HHS [K02 MH001110-06, K02 MH001110, KO2 MH 01110, R01 MH 40799, R01 MH 50747, R01 MH040799, R01 MH040799-13, R01 MH050740, R01 MH050740-06]; OCPHP CDC HHS [P41 PR13218] NR 69 TC 221 Z9 223 U1 3 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2003 VL 60 IS 8 BP 766 EP 775 DI 10.1001/archpsyc.60.8.766 PG 10 WC Psychiatry SC Psychiatry GA 709HJ UT WOS:000184619500002 PM 12912760 ER PT J AU Chen, HL Zhang, SMM Hernan, MA Schwarzschild, MA Willett, WC Colditz, GA Speizer, FE Ascherio, A AF Chen, HL Zhang, SMM Hernan, MA Schwarzschild, MA Willett, WC Colditz, GA Speizer, FE Ascherio, A TI Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID MALE HEALTH-PROFESSIONALS; NF-KAPPA-B; ALZHEIMERS-DISEASE; DOPAMINERGIC-NEURONS; COLORECTAL-CANCER; SODIUM-SALICYLATE; CIGARETTE-SMOKING; SUBSTANTIA-NIGRA; ASPIRIN USE; WOMEN AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce dopaminergic neuron degeneration in animal models of Parkinson disease (PD). However, no epidemiological data have been available on NSAID use and the risk of PD. Objective: To investigate prospectively whether the use of nonaspirin NSAIDs or aspirin is associated with decreased PD risk. Design, Settings, and Participants: Prospective cohorts of 44057 men and 98845 women free of PD, stroke, or cancer (Health Professionals Follow-up Study, 19862000, and Nurses' Health Study, 1980-1998). Main Outcome Measure: Newly diagnosed PD. Results: We documented 415 incident PD cases (236 men and 179 women). Participants who reported regular use of nonaspirin NSAIDs at the beginning of the study had a lower risk of PD than nonregular users during the follow-up; the pooled multivariate relative risk was 0.55 (95% confidence interval, 0.32-0.96, P = .04). Compared with nonusers, a nonsignificantly lower risk of PD was also observed among men and women who took 2 or more tablets of aspirin per day (relative risk, 0.56; 95% confidence interval, 0.26-1.21). Conclusion: These findings are consistent with the hypothesis that use of NSAIDs may delay or prevent the onset of PD. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Chen, HL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Chen, Honglei/0000-0003-3446-7779 FU NCI NIH HHS [CA 87969]; NINDS NIH HHS [NS 35624] NR 35 TC 308 Z9 328 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2003 VL 60 IS 8 BP 1059 EP 1064 DI 10.1001/archneur.60.8.1059 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 710RE UT WOS:000184692600004 PM 12925360 ER PT J AU El Fakhri, G Kijewski, MF Johnson, KA Syrkin, G Killiany, RJ Becker, JA Zimmerman, RE Albert, MS AF El Fakhri, G Kijewski, MF Johnson, KA Syrkin, G Killiany, RJ Becker, JA Zimmerman, RE Albert, MS TI MRI-guided SPECT perfusion measures and volumetric MRI in prodromal Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID ABSOLUTE ACTIVITY QUANTITATION; MAGNETIC-RESONANCE; ENTORHINAL CORTEX; PRECLINICAL PREDICTION; COMPUTED-TOMOGRAPHY; TEMPORAL-LOBE; BRAIN; DEMENTIA; HIPPOCAMPUS; TECHNETIUM-99M-HMPAO AB Objective: To identify group differences in the prodromal phase of Alzheimer disease (AD) using quantitative single-photon emission computed tomography (SPECT) perfusion and magnetic resonance imaging (MRI) volume measures within specific volumes of interest. Setting: Gerontology research unit. Participants: There were 17 healthy controls, 56 non-demented patients with memory problems who did not develop AD during 3 to 5 years of follow-up (questionables), and 27 non-demented patients with memory problems who developed AD during follow-up (converters). Methods: A Tc 99m hexamethylpropyleneamine oxime SPECT study and an MRI were performed in each participant at baseline. Mean SPECT activity concentration and MRI volume were estimated within 9 structures: rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, basal forebrain, temporal horn, amygdala, and the banks of the superior temporal sulcus. Data were analyzed using overall and pairwise discriminant analysis, and performance in pairwise group discrimination was measured using correlated receiver operating characteristic curve analysis. Results: The overall (3-group) discriminant function was significant for SPECT (F test, P < .001) and MRI (F test, P < .0001). For the SPECT analysis, the ranking of structures for discriminating among the 3 groups was, in order of decreasing discriminating power, caudal anterior cingulate, temporal horn, superior temporal sulcus, entorhinal cortex, hippocampus, rostral anterior cingulate, amygdala, basal forebrain, and posterior cingulate. For the MRI analysis, this ranking was entorhinal cortex, superior temporal sulcus, temporal horn, hippocampus, amygdala, caudal anterior cingulate, rostral anterior cingulate, basal forebrain, and posterior cingulate. Combining the 2 modalities yielded significantly better discrimination performance than did either alone. Furthermore, the correlation between SPECT and MRI measures was low. Conclusion: Measures of structure activity concentration and volume carry independent information; both reveal group differences in prodromal AD. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Boston Univ, Med Ctr, Dept Anat, Boston, MA USA. Boston Univ, Med Ctr, Dept Neurobiol, Boston, MA USA. RP El Fakhri, G (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA 78936]; NIA NIH HHS [P01 AG 04953]; NIBIB NIH HHS [R01 EB 000802, R01 EB000802] NR 32 TC 47 Z9 48 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2003 VL 60 IS 8 BP 1066 EP 1072 DI 10.1001/archneur.60.8.1066 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 710RE UT WOS:000184692600005 PM 12925361 ER PT J AU Holtzer, R Wegesin, DJ Albert, SM Marder, K Bell, K Albert, M Brandt, J Stern, Y AF Holtzer, R Wegesin, DJ Albert, SM Marder, K Bell, K Albert, M Brandt, J Stern, Y TI The rate of cognitive decline and risk of reaching clinical milestones in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID TRAUMATIC BRAIN INJURY; NEUROPSYCHOLOGICAL TESTS; PATIENT DEPENDENCE; DEMENTIA; PREDICTION; OUTCOMES AB Background: Previous studies revealed that cognitive test scores were related to functional outcome in Alzheimer disease (AD). However, the relationship between the rate of cognitive decline at the initial disease phase and the risk of reaching clinical milestones in subsequent years has not yet been examined. Objective: To examine whether the rate of cognitive decline predicts the risk of reaching functional milestones in patients with probable AD. Design: A 5-year prospective study was conducted at 3 sites. Setting: Outpatient research and treatment centers. Participants: Patients diagnosed with probable AD (N = 236, mean age, 73 years; 59% women; mean years of education, 13). Main Outcome Measures: Modified Mini-Mental State Examination (mMMSE) scores were used to assess the rate of cognitive decline over time. Total dependence score and 2 clinical milestones: (1) the need to be dressed, groomed, and washed and (2) receiving a level of care equivalent to a placement in a health-related facility, were derived from the Dependence Scale. Results: General estimating equation analyses revealed that the rate of cognitive decline during the entire follow-up period was positively related to an increase in total dependence scores. Cox analyses showed that a fast rate of decline during the first year was related to an increase in the risk of reaching clinical milestones in subsequent years. Analyses controlled for age, sex, education, and baseline mMMSE scores. Conclusion: A fast rate of cognitive decline was associated with increasing risk of reaching clinical milestones in AD. C1 Columbia Univ Coll Phys & Surg, Segievsky Ctr, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Med Ctr, Dept Neurol, Boston, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Stern, Y (reprint author), Columbia Univ Coll Phys & Surg, Segievsky Ctr, 630 W 168th St,19th Floor,P&S Box 16, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244; Albert, Steven/0000-0001-6786-9956 FU NCRR NIH HHS [RR 00645]; NIA NIH HHS [AG 07370] NR 33 TC 21 Z9 23 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD AUG PY 2003 VL 60 IS 8 BP 1137 EP 1142 DI 10.1001/archneur.60.8.1137 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 710RE UT WOS:000184692600017 PM 12925372 ER PT J AU Hamrah, P Liu, Y Zhang, Q Dana, MR AF Hamrah, P Liu, Y Zhang, Q Dana, MR TI Alterations in corneal stromal dendritic cell phenotype and distribution in inflammation SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; MAJOR HISTOCOMPATIBILITY COMPLEX; CHEMOKINE GENE-EXPRESSION; LIGAND-TREATED MICE; LANGERHANS CELLS; RECEPTOR ANTAGONIST; LYMPH-NODES; DIFFERENTIAL REGULATION; TRANSPLANT REJECTION AB Background: The normal corneal stroma is endowed with large numbers of resident dendritic cells (DCs). The purpose of this study was to examine the phenotype and distribution of these cells in inflammation. Methods: Normal and inflamed murine corneas were excised at different time points and immunofluorescence staining with multiple antibodies was performed by confocal microscopy on whole-mounted corneal stromas to characterize and evaluate the distribution of DCs in inflammation. Results: CD11c(+)CD11b(+) myeloid DCs were present throughout the anterior stroma, In the periphery of the normal cornea, nearly one half were major histocompatibility complex (MHC) class II(+)CD80(+)CD86(+), while they were uniformly MHC class II(-)CD80(-)CD86(-) in the center. In inflammation, in addition to a significant increase in the number of DCs, a majority up-regulated their expression of MHC class II, CD80, and CD86, indicating their state of maturation. The up-regulation of MHC class II and costimulatory molecules on DCs was seen as early as 24 hours after induction of inflammation or transplantation. In addition to the CD11c(+)DCs in the anterior stroma, a CD11c(-)CD11b(+) population of monocytes/ macrophages was present almost exclusively in the posterior stroma of the cornea. These cells were found throughout all layers of the stroma, and in increased numbers, after induction of inflammation. Conclusion: The present study demonstrates, for the first time, the phenotypic changes and distribution of resident stromal DCs in corneal inflammation. Clinical Relevance: These novel data suggest that the cornea is capable of participating in immune and inflammatory responses by virtue of its own heterogeneous population of DCs. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01-EY-12963] NR 79 TC 62 Z9 66 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2003 VL 121 IS 8 BP 1132 EP 1140 DI 10.1001/archopht.121.8.1132 PG 9 WC Ophthalmology SC Ophthalmology GA 709HR UT WOS:000184620200008 PM 12912691 ER PT J AU Wiggs, JL Auguste, J Allingham, RR Flor, JD Pericak-Vance, MA Rogers, K LaRocque, KR Graham, FL Broomer, B Del Bono, E Haines, JL Hauser, M AF Wiggs, JL Auguste, J Allingham, RR Flor, JD Pericak-Vance, MA Rogers, K LaRocque, KR Graham, FL Broomer, B Del Bono, E Haines, JL Hauser, M TI Lack of association of mutations in optineurin with disease in patients with adult-onset primary open-angle glaucoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; NORMAL-TENSION GLAUCOMA; BALTIMORE EYE SURVEY; OPTIC-NERVE HEAD; INTRAOCULAR-PRESSURE; REGION; LOCALIZATION; POPULATION; AMERICANS; GENE AB Objective: To determine whether mutations in the optineurin gene contribute to susceptibility to adult-onset primary open-angle glaucoma. Methods: The optineurin gene was screened in 86 probands with adult-onset primary open-angle glaucoma and in 80 age-matched control subjects. Exons 4 and 5, containing the recurrent mutations identified in patients with normal-tension glaucoma, were sequenced in all individuals studied, while the remaining exons were screened for DNA sequence variants with denaturing high-performance liquid chromatography. Results: The recurrent mutation, Met98Lys, previously found to be associated with an increased risk of disease was found in 8 (9%) of 86 probands. We also found the Met98Lys mutation in 10% of individuals from a control population of similar age, sex, and ethnicity. Consistent segregation of the mutation with the disease was not demonstrated in any of the 8 families. No other DNA changes altering the amino acid structure of the protein were found. Conclusion: The mutations in the optineurin gene associated with normal-tension glaucoma are not associated with adult-onset primary open-angle glaucoma in this patient population. Clinical Relevance: Genetic abnormalities that render the optic nerve susceptible to degeneration are excellent candidates for genetic factors that could contribute to adult-onset primary open-angle glaucoma. Mutations in optineurin have been associated with normal-tension glaucoma, but are not associated with disease in patients with adult-onset primary open-angle glaucoma. This result may indicate that normal-tension glaucoma is not necessarily part of the phenotypic spectrum of adult open-angle glaucoma. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Duke Univ, Sch Med, Dept Ophthalmol, Durham, NC USA. Duke Univ, Sch Med, Ctr Human Genet, Durham, NC USA. Vanderbilt Univ Sch Med, Program Human Genet, Nashville, TN USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02411 USA. RI Haines, Jonathan/C-3374-2012 FU NEI NIH HHS [EY10886, R01 EY010886, R01 EY013315] NR 16 TC 58 Z9 64 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2003 VL 121 IS 8 BP 1181 EP 1183 DI 10.1001/archopht.121.8.1181 PG 3 WC Ophthalmology SC Ophthalmology GA 709HR UT WOS:000184620200014 PM 12912697 ER PT J AU Samaha, M Cosenza, MJ Metson, R AF Samaha, M Cosenza, MJ Metson, R TI Endoscopic frontal sinus drillout in 100 patients SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID LOTHROP PROCEDURE; SURGERY; EXPERIENCE; SYSTEMS AB Objective: To determine the efficacy of frontal sinus drill-out surgery for the treatment of chronic frontal sinusitis. Design: Retrospective case-control,study. Mean +/- SD follow-up was 4.1 +/- 1.53 years (range, 1.4-6.9 years). Setting: Academic medical center. Patients: One hundred consecutive patients with chronic sinusitis who underwent frontal sinus drillout surgery. Indications were failed previous frontal sinusotomy (n = 88) and frontal sinus mucocele (n = 12). Interventions: Endoscopic removal of the floor of the frontal sinus (unilateral, n = 34; bilateral, n = 66) with a surgical drill. An intraoperative image-guidance system was used in 65 patients. Main Outcome Measures: Frontal sinus patency and improvement of symptoms associated with frontal sinusitis. Results: Frontal sinus patency with control of symptoms was achieved in 80% of patients. There were no intraoperative complications. Postoperative epistaxis occurred in 4% of patients. Of the 20 patients who developed restenosis of the frontal sinus ostium, 11 underwent revision frontal sinus drillout and 9 proceeded to frontal sinus obliteration. The success rate was comparable for the image-guidance and non-image-guidame groups (83.1% vs 74.3%, respectively; P=.56). Conclusions: Frontal sinus drillout performed with or without an image-guidance system appears to be a safe and effective surgery for the treatment of patients with advanced disease of the frontal sinus. This procedure provides a reasonable alternative to frontal sinus obliteration, which remains a treatment option for patients who fail frontal drillout. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 14 TC 28 Z9 30 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2003 VL 129 IS 8 BP 854 EP 858 DI 10.1001/archotol.129.8.854 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 709HQ UT WOS:000184620100009 PM 12925344 ER PT J AU Estes, JD Stolpman, D Olyaei, A Corless, CL Ham, JM Schwartz, JM Orloff, SL AF Estes, JD Stolpman, D Olyaei, A Corless, CL Ham, JM Schwartz, JM Orloff, SL TI High prevalence of potentially hepatotoxic herbal supplement use in patients with fulminant hepatic failure SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 74th Annual Meeting of the Pacific-Coast-Surgical-Association CY FEB 16-18, 2003 CL MONTEREY, CALIFORNIA SP Pacific Coast Surg Assoc ID ACUTE LIVER-FAILURE; UNITED-STATES; MA-HUANG; INJURY; THERAPIES; INGESTION; PATTERNS AB Hypothesis: The use of potentially hepatotoxic herbal and dietary supplements is highly prevalent in the fulminant hepatic failure (FHF) patient population at our institution, and this subgroup of patients has a worse prognosis. Design: Retrospective case series. Settings: An adult tertiary care university hospital and a Veterans Affairs hospital in Oregon. Patients: All patients referred to the liver transplantation service for FHF from January 2001 through October 2002 (N = 20). We defined FHF as onset of encephalopathy within 8 weeks of onset of jaundice in the absence of preexisting liver disease. All patients underwent investigation for potential causes of liver injury. Potentially hepatotoxic supplements were defined as those with previously published reports of hepatic injury related to their use. Results: Ten patients (50%) were recent or active users of potentially hepatotoxic supplements or herbs; 10 had no history of supplement use. In. the supplement group, 7 patients (35%) had no other identified cause for hepatic failure. Six patients in the supplement group and 2 patients in the nonsupplement group underwent orthotopic liver transplantation. Five patients in each group died. There were no significant differences in transplantation rate (P = .07) or survival (P > .99) between groups. Supplement use alone accounted for the most cases of FHF during this period, exceeding acetaminophen toxicity and viral hepatitis. Conclusions: Herbal and dietary supplements were potential hepatotoxins, in a high proportion of patients with FHF at our institution. Enhanced public awareness of the potential hepatotoxicity of these commonly used agents and increased regulatory oversight of their use is strongly urged. C1 Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Orloff, SL (reprint author), Oregon Hlth Sci Univ, Div Liver Pancreas Transplantat, L590,3181 SW Jackson Pk Rd, Portland, OR 97201 USA. NR 37 TC 89 Z9 92 U1 5 U2 10 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 AUG PY 2003 VL 138 IS 8 BP 852 EP 856 DI 10.1001/archsurg.138.8.852 PG 5 WC Surgery SC Surgery GA 709HB UT WOS:000184618800009 PM 12912743 ER PT J AU Ferguson, CM AF Ferguson, CM TI The arguments against fellowship training and early specialization in general surgery SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ferguson, CM (reprint author), Massachusetts Gen Hosp, 15 Parkman St WACC 465,15 Parkman St, Boston, MA 02114 USA. NR 1 TC 10 Z9 11 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 AUG PY 2003 VL 138 IS 8 BP 915 EP 916 DI 10.1001/archsurg.138.8.915 PG 2 WC Surgery SC Surgery GA 709HB UT WOS:000184618800027 PM 12912754 ER PT J AU MacNeill, BD Lowe, HC Takano, M Fuster, V Jang, IK AF MacNeill, BD Lowe, HC Takano, M Fuster, V Jang, IK TI Intravascular modalities for detection of vulnerable plaque - Current status SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE atherosclerosis; acute coronary syndrome; coronary imaging ID OPTICAL COHERENCE TOMOGRAPHY; ATHEROSCLEROTIC CORONARY-ARTERIES; NEAR-INFRARED SPECTROSCOPY; IN-VIVO; ULTRASOUND ELASTOGRAPHY; MYOCARDIAL-INFARCTION; RAMAN-SPECTROSCOPY; INTRACORONARY ULTRASOUND; TISSUE CHARACTERIZATION; THERMAL HETEROGENEITY AB Progress in the diagnosis, treatment, and prevention of atherosclerotic coronary artery disease is dependent on a greater understanding of the mechanisms of coronary plaque progression. Autopsy studies have characterized a subgroup of high-risk, or vulnerable, plaques that result in acute coronary syndromes or sudden cardiac death. These angiographically modest plaques share certain pathologic characteristics: a thin, fibrous cap, lipid-rich core, and macrophage activity. Diagnostic techniques for vulnerable-plaque detection, including serologic markers and noninvasive and invasive techniques, are needed. Recent advances in intravascular imaging have significantly improved the ability to detect high-risk, or vulnerable, plaque in vivo by using various features of plaque vulnerability as methods of identification. The characteristic anatomy of a thin, fibrous cap overlying a lipid pool has promoted high-resolution imaging, such as intravascular ultrasound, optical coherence tomography, and intracoronary magnetic resonance. The lipid-rich core is identifiable by angioscopically detected color changes on the plaque surface or by its unique absorption of energy, or "Raman shift," of its cholesterol core, driving coronary spectroscopy. Finally, temperature heterogeneity arising at foci of plaque inflammation has prompted the development of intracoronary thermography. In this review, we will discuss these techniques, their relative advantages and limitations, and their potential clinical application. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow Gray 800,55 Fruit St, Boston, MA 02114 USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 89 TC 126 Z9 133 U1 0 U2 15 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 AUG PY 2003 VL 23 IS 8 BP 1333 EP 1342 DI 10.1161/01.ATV.0000080948.08888.BF PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 710JQ UT WOS:000184677400007 PM 12805071 ER PT J AU Knopp, RH Retzlaff, B Fish, B Walden, C Wallick, S Anderson, M Aikawa, K Kahn, SE AF Knopp, RH Retzlaff, B Fish, B Walden, C Wallick, S Anderson, M Aikawa, K Kahn, SE TI Effects of insulin resistance and obesity on lipoproteins and sensitivity to egg feeding SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE insulin-resistant; obesity; LDL cholesterol; dietary cholesterol ID LOW-CHOLESTEROL ABSORPTION; CORONARY HEART-DISEASE; HIGH BLOOD CHOLESTEROL; DIETARY-CHOLESTEROL; CARDIOVASCULAR-DISEASE; SYNDROME PREDICTS; APOLIPOPROTEIN-B; FOLLOW-UP; A-I; MEN AB Objective - This study was undertaken to determine if insulin resistance without and with obesity influences LDL response to dietary cholesterol and saturated fat. Methods and Results - We fed 0, 2, and 4 egg yolks per day to 197 healthy subjects in a 4-week, double-blind, randomized, crossover design. Subjects were dichotomized on body mass index ( <27.5 and &GE; 27.5 kg/m(2)) and insulin sensitivity (insulin-sensitivity index &GE; 4.2 x 1.0(-4) and <4.2 x 1.0(-4) min(-1) muU/mL), yielding insulin-sensitive (IS, n = 65), insulin-resistant (IR, n = 75), and obese insulin-resistant (OIR, n = 58) subjects. Mean fasting baseline LDL cholesterol (LDL-C) levels were higher in IR and OIR subjects (3.44 +/- 0.67 and 3.32 +/- 0.80 mol/ L) than in IS subjects (2.84 +/- 0.75 mmol/L) (P < 0.001). Progressive triglyceride elevations and HDL-C decreases were seen across the 3 groups. Ingesting 4 eggs daily yielded significant LDL-C increases of 7.8 +/- 13.7% (IS) and 3.3 +/- 13.2% (IR) (both P < 0.05) compared with 2.4 +/- 12.6% for OIR (NS). HDL-C increases were 8.8 +/- 10.4%, 5.2 +/- 10.4%, and 3.6 +/- 9.4% in IS, IR, and OIR, respectively ( all P < 0.01). Conclusions - Insulin resistance without and with obesity is associated with elevated LDL-C as well as elevated triglyceride and low HDL-C. The elevated LDL-C cannot be explained by dietary sensitivity, because the LDL-C rise with egg feeding is less in IR persons regardless of obesity status, probably attributable to diminished cholesterol absorption. The results suggest that dietary management of insulin resistance and obesity can focus more on restricting calories and less on restricting dietary fat. C1 Univ Washington, NW Lipid Res Clin, Div Cardiol, Seattle, WA 98104 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98104 USA. RP Knopp, RH (reprint author), Univ Washington, NW Lipid Res Clin, Div Cardiol, 325 9th Ave,Box 359720, Seattle, WA 98104 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR 00037]; NIDDK NIH HHS [DK17047, DK35816] NR 38 TC 57 Z9 58 U1 0 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 AUG PY 2003 VL 23 IS 8 BP 1437 EP 1443 DI 10.1161/01.ATV.0000082461.77557.C7 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 710JQ UT WOS:000184677400022 PM 12816878 ER PT J AU Pires, MD Salemi, VMC Cestari, IA Picard, MH Leirner, AA Mady, C Cestari, IN AF Pires, MD Salemi, VMC Cestari, IA Picard, MH Leirner, AA Mady, C Cestari, IN TI Noninvasive assessment of hemodynamic parameters in experimental stenosis of the ascending aorta SO ARTIFICIAL ORGANS LA English DT Article DE hypertrophy; tissue Doppler; hemodynamics; ascending aorta stenosis ID LEFT-VENTRICULAR MASS; LONG-AXIS FUNCTION; DOPPLER-ECHOCARDIOGRAPHY; PRESSURE; HYPERTROPHY; CARDIOMYOPATHY; HYPERTENSION; ARCHITECTURE; VALIDATION; VOLUME AB We sought to noninvasively evaluate left ventricular (LV) function after cardiac hypertrophy induced by experimental stenosis of the ascending aorta. Male Wistar rats (70-90 g) underwent ascending aorta constriction by the surgical placement of a titanium clip (n=5) or sham operation (n=6). High-resolution bidimensional, pulsed-wave Doppler (PWD) and pulsed-wave tissue Doppler imaging (TDI) were performed 22 weeks after surgery. PWD was used to obtain mitral flow velocities, and TDI was used to obtain velocities along the septal mitral annulus and LV posterior wall. Clip placement produced myocardial hypertrophy with decreased systolic myocardial peak velocity in both the long and short axes. Increased myocardial mass, that is, posterior wall and septal thickness, was indicative of ventricular remodeling. Diastolic dysfunction was observed, with an increased early to late ratio of mitral velocities and increased left atrium dimension, consistent with a left ventricular restrictive filling pattern. C1 Univ Sao Paulo, Sch Med, Bioengn Div, Heart Inst,InCor, Sao Paulo, Brazil. Univ Sao Paulo, Dept Physiol & Biophys, Inst Biomed Sci, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Cardiopathy Div, Heart Inst,InCor, Sao Paulo, Brazil. Massachusetts Gen Hosp, Clin Echocardiog Div, Boston, MA 02114 USA. RP Cestari, IN (reprint author), Univ Sao Paulo, Sch Med, Bioengn Div, Heart Inst,InCor, Av Dr Eneas Carvalho Aguiar 44-SS, Sao Paulo, Brazil. RI Cestari, Ismar /B-7286-2012; Cestari, Idagene/D-1012-2012; Mady, Charles/C-8870-2012; Salemi, Vera/C-9104-2013; OI Mady, Charles/0000-0002-8838-199X; Salemi, Vera/0000-0002-7152-1810; Picard, Michael/0000-0002-9264-3243 NR 24 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD AUG PY 2003 VL 27 IS 8 BP 695 EP 700 DI 10.1046/j.1525-1594.2003.07276.x PG 6 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 711CB UT WOS:000184720100006 PM 12911343 ER PT J AU Game, BA Xu, MF Lopes-Virella, MF Huang, Y AF Game, BA Xu, MF Lopes-Virella, MF Huang, Y TI Regulation of MMP-1 expression in vascular endothelial cells by insulin sensitizing thiazolidinediones SO ATHEROSCLEROSIS LA English DT Article; Proceedings Paper CT 61st Scientific Session of the American-Diabetes-Association CY JUN 22-26, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Diabet Assoc DE interstitial collagenase; matrix metalloproteinases; diabetes; PPAR-gamma; gene expression ID ACTIVATED-RECEPTOR-GAMMA; MONOCYTE CHEMOTACTIC PROTEIN-1; TYPE-2 DIABETES-MELLITUS; GENE-EXPRESSION; PPAR-GAMMA; ATHEROSCLEROTIC PLAQUES; IN-VITRO; TROGLITAZONE; LIGAND; ALPHA AB Matrix metalloproteinases (MMPs) have been implicated in the disruption of atherosclerotic plaques that leads to acute coronary events. The present study investigates the effect of thiazolidinediones (TZDs), new antidiabetic drugs, on MMP-1 expression by human vascular endothelial cells. Results show that troglitazone, but not pioglitazone and rosiglitazone, stimulated MMP-1 secretion and mRNA expression in both human umbilical vein and aortic endothelial cells, but had no effect on TIMP-1 and TIMP-2 secretion. Interestingly, troglitazone at high concentrations (greater than or equal to30 mumol/l) inhibited MMP-1 protein synthesis despite a marked stimulation on MMP-1 mRNA. Further studies revealed that troglitazone at higher concentrations inhibits de novo protein synthesis as determined by S-35-methionine/cysteine incorporation, suggesting that the inhibition of MMP-1 synthesis by troglitazone is due to the suppression of total protein synthesis. Finally, our studies showed that high concentrations of troglitazone inhibited the translation initiation factor 4E (eIF4E), but not eIF4G. In summary, the present study demonstrates that insulin sensitizers have different effects on MMP-1 expression, and troglitazone stimulates MMP-1 mRNA expression and protein synthesis at the pharmacological concentrations, but inhibits MMP-1 synthesis at higher doses. This study also suggests that supra-pharmacological concentrations of troglitazone that could be attained in body tissues may inhibit protein synthesis and cause cytotoxicity. Published by Elsevier Ireland Ltd. C1 Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. NR 42 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2003 VL 169 IS 2 BP 235 EP 243 DI 10.1016/S0021-9150(03)00165-5 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 717PK UT WOS:000185098400004 PM 12921974 ER PT J AU Gul, RM McGarry, FJ Bragdon, CR Muratoglu, OK Harris, WH AF Gul, RM McGarry, FJ Bragdon, CR Muratoglu, OK Harris, WH TI Effect of consolidation on adhesive and abrasive wear of ultra high molecular weight polyethylene SO BIOMATERIALS LA English DT Article DE ultra high molecular weight polyethylene; wear; total joint replacement; processing temperature; consolidation; fusion defects ID ARTHROPLASTY; REPLACEMENT AB Total hip replacement (THR) is widely performed to recover hip joint functions lost by trauma or disease and to relieve pain. The major cause of failure in THR is the wear of the ultra high molecular weight polyethylene (UHMWPE) component. The dominant wear mechanism in THR occurs through adhesion and abrasion. While poor consolidation of UHMWPE is known to increase the incidence of a different damage mode, delamination, which is the dominant wear mechanism in tibial inserts but uncommon in THR, the effect of consolidation on adhesive and abrasive wear of UHMWPE is not clear. In this Study UHMWPE resin was subjected to hot isostatic pressing under a pressure of 138 MPa at different temperatures (210degreesC, 250degreesC, and 300degreesC) to achieve varying degrees of consolidation. The extent of consolidation was determined by optical microscopy using thin sections, and by scanning electron microscopy using cryofractured and solvent etched specimens. Wear behavior of the samples with varying degree of consolidation was determined using a bi-directional pin-on-disc machine simulating conditions in a hip joint. Increasing the processing temperature decreased the incidence of fusion defects and particle boundaries reflecting the powder flakes of the virgin resin, improving the consolidation. However, the bi-directional pin-on-disc wear rate did not change with the processing temperature, indicating that adhesive and abrasive wear is independent of the extent of consolidation in the range of parameters studied here. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. GIK Inst Engn Sci & Technol, Fac Met & Mat Engn, Topi 23460, District Swabi, Pakistan. MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, GRJ 1206,55 Fruit St Jackson, Boston, MA 02114 USA. NR 17 TC 20 Z9 23 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD AUG PY 2003 VL 24 IS 19 BP 3193 EP 3199 DI 10.1016/S0142-9612(03)00165-0 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 687UQ UT WOS:000183395700003 PM 12763446 ER PT J AU Lyoo, IK Demopulos, CM Hirashima, F Ahn, KH Renshaw, PF AF Lyoo, IK Demopulos, CM Hirashima, F Ahn, KH Renshaw, PF TI Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy SO BIPOLAR DISORDERS LA English DT Article DE ATP; bipolar disorder; brain; choline; lithium; magnetic resonance spectroscopy; purine; rapid cycling ID MITOCHONDRIAL-DNA; IN-VIVO; GLOBAL-ISCHEMIA; BASAL GANGLIA; RATING-SCALE; CAT BRAIN; MANIA; METABOLISM; DEPRESSION; POLYMORPHISMS AB Objectives: Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (P-31) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder. Methods: Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using H-1- and Li-7-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n=40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. Results: There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef=-0.08, z=-2.17, df=22, p=0.030; purine/choline: coef=-0.12, z=-1.97, df=22, p=0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. Conclusions: The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis. C1 McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Res Program, Boston, MA 02114 USA. RP Lyoo, IK (reprint author), Seoul Natl Univ Hosp, Dept Psychiat, 28 Yongon Dong, Seoul 110744, South Korea. FU NIDA NIH HHS [DA09448]; NIMH NIH HHS [MH58681] NR 42 TC 15 Z9 15 U1 3 U2 4 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 AUG PY 2003 VL 5 IS 4 BP 300 EP 306 DI 10.1034/j.1399-5618.2003.00041.x PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 714EC UT WOS:000184898500008 PM 12895208 ER PT J AU Golden, CM Ryan, LM Holmes, LB AF Golden, CM Ryan, LM Holmes, LB TI Chorionic villus sampling: A distinctive teratogenic effect on fingers? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE limb deficiency; vascular disruption; CVS ID LIMB REDUCTION DEFECTS; AMNIOTIC BAND SEQUENCE; NEWBORN-INFANTS; FIRST-TRIMESTER; BIRTH-DEFECTS; MALFORMATIONS; PREGNANCY; ABNORMALITIES; DEFICIENCY; CONSTRICTION AB BACKGROUND: An increased frequency of major limb malformations, especially terminal transverse limb defects, have been described in several studies of birth defects in children who had been exposed to the prenatal diagnosis procedure known as chorionic villus sampling (CVS). Vascular disruption has been proposed as the mechanism behind the fetal effect. We postulate that this mechanism is more likely to affect one or two middle fingers, rather than all five fingers. A recent report of the frequency of defects in any or all fingers in an unexposed control population enabled us to assess whether CVS is associated with an increased frequency of defects involving one or two fingers, as well as terminal transverse limb defects. METHODS: The frequency of limb-reduction defects affecting one or more fingers or toes, including those with constriction rings and tissue loss, in published studies of 20,236 children who had been exposed to CVS was compared with the frequency in 161,252 newborn infants who had not been exposed to CVS. Children with recognized genetic disorders were excluded. RESULTS: Several aspects of the limb deficiencies were more common in the CVS-exposed infants than in unexposed controls. The former were more likely to have: 1) any type of limb deficiency involving one or more fingers (p < .001); 2) absence/hypoplasia of two fingers (1) < .001); and 3) absence/hypoplasia of all five fingers (p = .015). The absence of the distal portion of the third finger was a distinctive type of limb-reduction defect in CVS-exposed infants. CONCLUSIONS: The occurrence of deficiencies in one or two fingers, including those designated as "amniotic band deformities," are as common as terminal transverse limb defects in CVS-exposed infants, and both are much more common than in unexposed infants. The absence of the distal portion of the third finger, with tapering and stiff joints, appears to be a distinctive effect of exposure to CVS. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, MassGen Hosp Children, Sch Med, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Harvard Univ, MassGen Hosp Children, Sch Med, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [HD33222] NR 40 TC 19 Z9 21 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD AUG PY 2003 VL 67 IS 8 BP 557 EP 562 DI 10.1002/bdra.10078 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 735GD UT WOS:000186103300004 PM 14632304 ER PT J AU Sailer, M Fischl, B Salat, D Tempelmann, C Schonfeld, MA Busa, E Bodammer, N Heinze, HJ Dale, A AF Sailer, M Fischl, B Salat, D Tempelmann, C Schonfeld, MA Busa, E Bodammer, N Heinze, HJ Dale, A TI Focal thinning of the cerebral cortex in multiple sclerosis SO BRAIN LA English DT Article DE multiple sclerosis; cerebral cortex; atrophy; MRI ID MAGNETIC-RESONANCE SPECTROSCOPY; APPEARING WHITE-MATTER; SURFACE-BASED ANALYSIS; BRAIN ATROPHY; CORTICAL SURFACE; AXONAL DAMAGE; HUNTINGTONS-DISEASE; COORDINATE SYSTEM; PYRAMIDAL TRACT; GRAY-MATTER AB Brain atrophy as determined by quantitative MRI can be used to characterize disease progression in multiple sclerosis. Many studies have addressed white matter (WM) alterations leading to atrophy, while changes of the cerebral cortex have been studied to a lesser extent. In vivo, the cerebral cortex has been difficult to study due to its complex structure and regional variability. Measurement of cerebral cortex thickness at different disease stages may provide new insights into grey matter (GM) pathology. In the present investigation, we evaluated in vivo cortical thickness and its relationship to disability, disease duration, WM T-2 hyper-intense and T-1 hypo-intense lesion volumes. High-resolution MRI brain scans were obtained in 20 patients with clinically definite multiple sclerosis and 15 age-matched normal subjects. A novel method of automated surface reconstruction yielded measurements of the cortical thickness for each subject's entire brain and computed cross-subject statistics based on the cortical anatomy. Statistical thickness difference maps were generated by performing t-tests between patient and control groups and individual thickness measures were submitted to analyses of variance to investigate the relationship between cortical thickness and clinical variables. The mean overall thickness of the cortical ribbon was reduced in multiple sclerosis patients compared with controls [2.30 mm (SD 0.14) versus 2.48 mm (SD 0.11)], showing a significant main effect of group (controls versus patients). In patients, we found significant main effects for disability, disease duration, T-2 and T-1 lesion volumes. The visualization of statistical difference maps of the cortical GM thickness on inflated brains across the cortical surface revealed a distinct distribution of significant focal thinning of the cerebral cortex in addition to the diffuse cortical atrophy. Focal cortical thinning in frontal [2.37 mm (SD 0.17) versus 2.73 mm (SD 0.25)] and in temporal [2.65 mm (SD 0.15) versus 2.95 mm (SD 0.11)] brain regions was observed, even early in the course of the disease or in patients with mild disability. Patients with longstanding disease or severe disability, however, presented additionally with focal thinning of the motor cortex area [2.35 mm (SD 0.19) versus 2.74 mm (SD 0.15)]. We conclude that in vivo measurement of cortical thickness is feasible in patients suffering from multiple sclerosis. The data provide new insight into the cortical pathology in multiple sclerosis patients, revealing focal cortical thinning beside an overall reduction of the cortical thickness with disease progression. C1 Univ Magdeburg, Dept Neurol 2, D-39120 Magdeburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlstown, MA USA. MIT, Artificial Intelligence Lab, Cambridge, MA 02139 USA. RP Sailer, M (reprint author), Univ Magdeburg, Dept Neurol 2, Leipzigerstr 44, D-39120 Magdeburg, Germany. RI Dale, Anders/A-5180-2010; Schoenfeld, Mircea Ariel/G-2096-2013; OI Tempelmann, Claus/0000-0001-8570-4960; Schoenfeld, Mircea Ariel/0000-0001-9003-4092 FU NCRR NIH HHS [1R01 RR 16594-01A1, P41 RR 14075] NR 48 TC 252 Z9 261 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2003 VL 126 BP 1734 EP 1744 DI 10.1093/brain/awg175 PN 8 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 705GB UT WOS:000184386400003 PM 12805100 ER PT J AU Davalos, DB Kisley, MA Ross, RG AF Davalos, DB Kisley, MA Ross, RG TI Effects of interval duration on temporal processing in schizophrenia SO BRAIN AND COGNITION LA English DT Article DE schizophrenia; time perception; timing; interval discrimination ID TIME-ESTIMATION; WORKING-MEMORY; PARKINSONS-DISEASE; AUDITORY DURATION; FRONTAL-LOBE; DISCRIMINATION; PERCEPTION; CORTEX; INFORMATION; MASKING AB Introduction: Temporal processing has received scant attention in the literature pertaining to cognitive deficits in patients with schizophrenia. Previous research suggests that patients with schizophrenia exhibit temporal perception deficits on both auditory and visual stimuli. The current study investigated the effects of interval manipulation to (1) replicate the original findings with a larger sample and an increased number of trials (2) assess the degree to which both patients and controls can differentiate temporal changes in a range of experimental interstimulus intervals, and (3) explore whether different interstimulus interval durations pose different levels of difficulty for the patients with schizophrenia. Methods: Participants were asked to decide whether temporal intervals were shorter or longer than standard intervals on a computer-based auditory temporal perception task. The standard interval remained the same duration throughout the various tasks. The interstimulus interval separating the standard and experimental intervals varied in the range of 500, 1000, or 3000ms. Data are presented for a sample of 16 patients with schizophrenia and 15 controls. Results: Data suggest that patients with schizophrenia exhibit deficits in differentiating interval durations across all paradigms compared to their control-group peers on a range of auditory tasks (p <.001). Conclusions: These results are consistent with a general temporal deficit in schizophrenia. However, the roles of medication and localization are also addressed. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO 80206 USA. RP Davalos, DB (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, 4200 E 9th Ave, Denver, CO 80206 USA. FU NIMH NIH HHS [MH152442, MH56539] NR 53 TC 52 Z9 52 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD AUG PY 2003 VL 52 IS 3 BP 295 EP 301 DI 10.1016/S0278-2626(03)00157-X PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 712MA UT WOS:000184800400002 PM 12907174 ER PT J AU Nguyen, BC Kochevar, IE AF Nguyen, BC Kochevar, IE TI Factors influencing sunless tanning with dihydroxyacetone SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE dihydroxyacetone; epidermis; photoprotection; pigmentation; stratum corneum; tanning ID STRATUM-CORNEUM; WATER-CONTENT; PROTECTION; PUVA AB Background Sunless tanning preparations have been used for more than 50 years and are still very popular because they provide temporary pigmentation resembling an ultraviolet-induced tan. The pigment is the product of reactions between dihydroxyacetone (DHA) and amino acids in the stratum corneum. Objectives To understand the factors that influence the reactions of DHA with amino acids in the stratum corneum with the ultimate goal of producing pigmentation with greater photoprotection. Methods The influence of hydration and / or oxygen on the development of DHA-induced pigment was assessed in vivo using an occlusive dressing and ex vitro on human epidermal preparations. Two spectroscopic techniques, diffuse reflectance and fluorescence emission, were used to monitor the extent of pigment development. The optimal relative humidity for DHA-induced pigmentation was assessed on the epidermal preparations. The formation of products from reactions between DHA and nine amino acids was studied in solutions buffered at pH 5 and 7. Results Development of DHA-induced pigmentation was inhibited by a 24-h occlusive dressing but appeared after its removal, indicating that DHA was still present. High hydration but not the absence of oxygen inhibited coloration of occluded skin. The extent of pigmentation did not vary in a simple manner with hydration, as pigment formation was positively correlated with humidity from 0 to 75% but negatively correlated from 75 to 100%. Lysine, glycine and histidine reacted most rapidly with DHA, with reaction rates greater at pH 7 than at pH 5. The products absorbed with maxima at wavelengths up to 340 nm. Conclusions These results indicate that extent of hydration, pH and availability of certain amino acids influence the development of DHA-induced pigmentation in the stratum corneum and suggest that manipulation of these factors might produce pigmentation with greater photoprotection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, WEL-224,50 Blossom St, Boston, MA 02114 USA. NR 18 TC 14 Z9 16 U1 1 U2 7 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 AUG PY 2003 VL 149 IS 2 BP 332 EP 340 DI 10.1046/j.1365-2133.2003.05434.x PG 9 WC Dermatology SC Dermatology GA 717RW UT WOS:000185104900016 PM 12932240 ER PT J AU Targownik, LE Gralnek, IM Dulai, GS Spiegel, BMR Oei, T Bernstein, CN AF Targownik, LE Gralnek, IM Dulai, GS Spiegel, BMR Oei, T Bernstein, CN TI Managemert of acute nonvariceal upper gastrointestinal hemorrhage: Comparison of an American and a Canadian medical centre SO CANADIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/101st Annual Meeting of the American-Gastroenterological-Association CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Gastroenterol Assoc DE gastrointestinal hemorrhage; hospital length of stay; process of care; rebleeding ID HEALTH-CARE SYSTEM; ACUTE MYOCARDIAL-INFARCTION; UPPER GI HEMORRHAGE; LOW-RISK PATIENTS; UNITED-STATES; TRACT HEMORRHAGE; EARLY DISCHARGE; ENDOSCOPY; RESOURCES; HOSPITALIZATION AB OBJECTIVES: Acute nonvariceal upper gastrointestinal hemorrhage (UGIH) remains a common indication for hospital admission. Differences in the structure, process and outcomes of care in the management of acute nonvariceal UGIH between providers in Canada and the United States have not been previously characterized. The aim of the present study was to compare the structure, process and outcomes of care between a Canadian and an American tertiary care medical centre in the management of acute nonvariceal UGIH. METHODS: Data were collected from identified cases of acute nonvariceal UGIH at the two medical centres over two years. Process measures analyzed included the level of care (intensive care unit [ICU] monitored bed versus unmonitored bed) and hospital length of stay (HLOS). Outcomes assessed included rebleeding, inhospital mortality and readmission and/or death within 30 days of admission. RESULTS: One hundred seventy-five and 83 cases of acute nonvariceal UGIH were identified at the American and Canadian centres, respectively. Cases at the American centre had a lower median HLOS, (2.6 versus 3.9 days, P<0.001) but were significantly more likely to be treated in an ICU or monitored setting (67% versus 16%, P<0.001). There were no significant differences in rates of rebleeding or death in hospital or within 30 days of discharge. CONCLUSIONS: Marked differences exist in the process of care between the Canadian and American medical centres in the management of acute nonvariceal UGIH, despite similar patient severity. Outcomes between the two centres were similar. Minimizing disparity in the process of care of acute UGIH between the two centres may reduce excessive use of resources in the management of acute UGIH without promoting adverse outcomes. C1 Vet Affairs Greater Los Angeles, Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. Univ Manitoba, Fac Med, Dept Internal Med, Gastroenterol Sect,John Buhler Res Ctr, Winnipeg, MB R3E 3P5, Canada. RP Gralnek, IM (reprint author), Univ Manitoba, Fac Med, Dept Internal Med, Gastroenterol Sect,John Buhler Res Ctr, Room 804D,727 McDermot St, Winnipeg, MB R3E 3P5, Canada. FU NCRR NIH HHS [K23 NCRR 1618801] NR 32 TC 10 Z9 10 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0835-7900 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. PD AUG PY 2003 VL 17 IS 8 BP 489 EP 495 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 714DG UT WOS:000184896600004 PM 12945010 ER PT J AU Baethge, C Tondo, L Bratti, IM Bschor, T Bauer, M Viguera, AC Baldessarini, RJ AF Baethge, Christopher Tondo, Leonardo Bratti, Irene M. Bschor, Tom Bauer, Michael Viguera, Adele C. Baldessarini, Ross J. TI Prophylaxis Latency and Outcome in Bipolar Disorders SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Review DE anticonvulsants; bipolar disorder; delayed prophylaxis; kindling; latency; lithium; major affective disorder; outcome; prophylaxis; response; treatment AB Objective: To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis. Method: We analyzed our own new data and added findings from research reports identified by computerized searching. Results: We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment, Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading. Conclusions: Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders. (Can J Psychiatry 2003:48:449-457) C1 [Baethge, Christopher; Tondo, Leonardo; Baldessarini, Ross J.] Harvard Univ, Sch Med, Consolidated Dept Psychiat, Bipolar & Psychot Disorders Program,McLean Div,Ma, Belmont, MA 02178 USA. [Tondo, Leonardo] Univ Cagliari, Dept Psychol, I-09124 Cagliari, Italy. [Tondo, Leonardo] Lucio Bini Stanley Inst, Ctr Psychiat Res, Cagliari, Italy. [Bratti, Irene M.] UCLA Med Ctr, Dept Psychiat, Los Angeles, CA USA. [Bschor, Tom] Tech Univ Dresden, Dept Psychiat, D-01062 Dresden, Germany. [Bauer, Michael] Humboldt Univ, Charite, Dept Psychiat & Psychotherapy, D-10099 Berlin, Germany. [Viguera, Adele C.] Harvard Univ, Sch Med, Boston, MA USA. [Viguera, Adele C.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. RP Baethge, C (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM cbaethge@mclean.harvard.edu FU Max Kade Foundation; Bruce J Anderson Foundation; McLean Private Donors Psychopharmacology and Bipolar Disorder Research Fund; Stanley Research Institute; National Association for Research on Schizophrenia and Affective Disorders FX This study was supported by the Max Kade Foundation (Dr Baethge), the Bruce J Anderson Foundation and the McLean Private Donors Psychopharmacology and Bipolar Disorder Research Fund (Dr Baldessarini), and the Stanley Research Institute and the National Association for Research on Schizophrenia and Affective Disorders (NARSAD) (Dr Tondo). NR 43 TC 39 Z9 40 U1 0 U2 0 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 AUG PY 2003 VL 48 IS 7 BP 449 EP 457 PG 9 WC Psychiatry SC Psychiatry GA V24BV UT WOS:000208386800004 PM 12971014 ER PT J AU Meyerhardt, JA Catalano, PJ Haller, DG Mayer, RJ Benson, AB Macdonald, JS Fuchs, CS AF Meyerhardt, JA Catalano, PJ Haller, DG Mayer, RJ Benson, AB Macdonald, JS Fuchs, CS TI Influence of body mass index on outcomes and treatment-related toxicity in patients with colon carcinoma SO CANCER LA English DT Article DE colon carcinoma; obesity; body mass index; adjuvant chemotherapy; treatment-related toxicity ID COLORECTAL-CANCER RISK; IGF-BINDING PROTEIN-3; GROWTH-FACTOR-I; PHYSICAL-ACTIVITY; BREAST-CANCER; GENDER DIFFERENCES; ADJUVANT CHEMOTHERAPY; ADENOMATOUS POLYPS; INSULIN-RESISTANCE; DIABETES-MELLITUS AB BACKGROUND. Obesity is a risk factor for the development of colon carcinoma. The influence of body mass index (BMI) on long-term outcomes and treatment-related toxicity in patients with colon carcinoma has not been well characterized. METHODS. This cohort study was conducted within a large, randomized adjuvant chemotherapy trial of 3759 men and women with high-risk, Stage 11 and Stage III colon carcinoma who were treated between 1988 and 1992 throughout the United States. With a median follow-up of 9.4 years, the authors examined the influence of BMI on disease recurrence, overall survival, and treatment-related toxicity. RESULTS. Compared with women of normal weight (BMI, 21.0-24.9 kg/m(2)), obese women with colon carcinoma (BMI greater than or equal to 30.0 kg/m(2)) experienced significantly worse overall mortality (hazard ratio [HR], 1.34; 95% confidence interval [95% CI], 1.07-1.67) and a nonsignificant increase in the risk of disease recurrence (HR, 1.24; 95% Cl, 0.98-1.59). The influence of BMI among women was not related to any differences in chemotherapy dose-intensity across categories of BMI. In contrast, BMI was not related significantly to long-term outcomes among male patients in this cohort. Among all study participants, obese patients had significantly lower rates of Grade 3-4 leukopenia and lower rates of any Grade greater than or equal to 3 toxicity compared with patients of normal weight. CONCLUSIONS. Among women with Stage II-III colon carcinoma, obesity was associated with a significant increase in overall mortality as well as a borderline significant increase in disease recurrence. Nonetheless, obesity was not associated with any increase in chemotherapy-related toxicity. (C) 2003 American Cancer Society. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp Stat Ctr, Boston, MA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Northwestern Univ, Div Hematol Oncol, Chicago, IL 60611 USA. St Vincents Clin, Ctr Canc, New York, NY USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA 090001-27] NR 66 TC 171 Z9 173 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2003 VL 98 IS 3 BP 484 EP 495 DI 10.1002/cncr.11544 PG 12 WC Oncology SC Oncology GA 702VU UT WOS:000184246000005 PM 12879464 ER PT J AU Zeliadt, SB Penson, DF Albertsen, PC Concato, J Etzioni, RD AF Zeliadt, SB Penson, DF Albertsen, PC Concato, J Etzioni, RD TI Race independently predicts prostate specific antigen testing frequency following a prostate carcinoma diagnosis SO CANCER LA English DT Article DE prostate carcinoma; recurrence; prostate specific antigen testing; race; surveillance ID RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; RADIATION-THERAPY; CO-MORBIDITY; CANCER; SURVIVAL; CARE; MEN; RECURRENCE; PATTERNS AB BACKGROUND. The goals of the current study were to describe patterns of prostate specific antigen (PSA) surveillance for prostate carcinoma progression in a community-based cohort of patients and to identify independent clinical and socio-demographic factors that predict the frequency of surveillance. METHODS. Patients diagnosed with localized prostate carcinoma from October 1, 1991 to December 31, 1992 in New Haven and Hartford, Connecticut, were identified. Data were collected through standardized outpatient medical record review. Multivariate statistical methods were used to determine the factors that independently predicted the frequency of surveillance. RESULTS. Six hundred fifty-eight men with localized prostate carcinoma were included in the cohort. Forty-five percent of all patients were tested at least once annually, and 69% were tested at least once every 2 years. Multivariate models indicated that African American men were half as likely as Caucasian men to receive annual testing (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.24-0.97). Men diagnosed at age 70 years or older were 38% less likely to have annual testing than men diagnosed between the ages of 65 and 69 (OR, 0.62; 95% Cl, 0.41-0.94). A higher Gleason score and PSA at presentation also were associated independently with higher rates of annual PSA surveillance. CONCLUSIONS. Postdiagnosis PSA surveillance is common, although not universal. African American men were at significantly greater risk for receiving less frequent testing compared with Caucasian men. This disparity in access to care may explain, in part, previously observed racial differences in survival in prostate carcinoma. Further research is needed to identify the reasons for the racial disparity in PSA surveillance and to design interventions to lessen these differences. (C) 2003 American Cancer Society. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. Univ Connecticut, Sch Med, Urol Sect, Farmington, CT USA. Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Etzioni, RD (reprint author), Fred Hutchinson Canc Res Ctr, POB 19024,MP-665, Seattle, WA 98109 USA. FU NCI NIH HHS [CA-88160, CA-92408] NR 33 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2003 VL 98 IS 3 BP 496 EP 503 DI 10.1002/cncr.11492 PG 8 WC Oncology SC Oncology GA 702VU UT WOS:000184246000006 PM 12879465 ER PT J AU del Carmen, MG Hughes, KS Halpern, E Rafferty, E Kopans, D Parisky, YR Sardi, A Esserman, L Rust, S Michaelson, J AF del Carmen, MG Hughes, KS Halpern, E Rafferty, E Kopans, D Parisky, YR Sardi, A Esserman, L Rust, S Michaelson, J TI Racial differences in mammographic breast density SO CANCER LA English DT Article DE mammography; breast density; African American women; body mass index; racial differences ID HORMONE REPLACEMENT THERAPY; CANCER RISK; PARENCHYMAL PATTERNS; FAMILY-HISTORY; BLACK-WOMEN; ESTROGEN; FEATURES; CLASSIFICATION; CARCINOMA; SURVIVAL AB BACKGROUND. African American women have a lower incidence but a higher mortality from breast carcinoma than Caucasians. A proposed explanation for this discrepancy is the decreased efficacy of screening among African American women. Increased breast density in African American women may result in decreased sensitivity of mammography. The purpose of this article is to determine whether there is a difference in mammographic breast density between African American and Caucasian women. METHODS. A series of 769 women were recruited from 5 sites. Mammograms were reviewed centrally by seven reviewers using Breast Imaging Reporting and Data System categories converted to numeric values. The mean mammographic densities for Caucasian, African American, and Latina patients were compared using a two-way analysis of covariance. The mean values for each race were estimated adjusting for the reader as well as for each patient's age and body mass index (BMI). RESULTS. African American women had the lowest mean breast density. The reported density in this group was 2.43, compared with 2.69 among Caucasians and 2.65 among Latina patients. After adjusting for age and BMI as well as the reader, there was still an independent racial effect on breast density (P = 0.0050). CONCLUSIONS. Mammographic breast density was lower in African American women than in Caucasians and Latinas. This discrepancy may be an intrinsic racial difference due to undetermined causes. Factors, such as the growth rate of tumors and the incidence of calcifications, must be studied to confirm that other forces do not have a negative impact on the efficacy of screening mammograms in African American women. (C) 2003 American Cancer Society. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Gynecol Oncol Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. USC, Norris Canc Ctr, Los Angeles, CA USA. St Agnes Healthcare, Baltimore, MD USA. Mt Sinai Med Ctr, Miami, FL USA. Battelle Mem Inst, Columbus, OH 43201 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Hughes, KS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Surg Oncol, 100 Blossom St,Cox 626, Boston, MA 02114 USA. OI Hughes, Kevin/0000-0003-4084-6484; Sardi, Armando/0000-0003-4132-9489 NR 38 TC 25 Z9 25 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 1 PY 2003 VL 98 IS 3 BP 590 EP 596 DI 10.1002/cnr.11517 PG 7 WC Oncology SC Oncology GA 702VU UT WOS:000184246000018 PM 12879477 ER PT J AU Hsu, K Look, AT AF Hsu, K Look, AT TI Turning on a dimer: New insights into MLL chimeras SO CANCER CELL LA English DT Article ID ACUTE LEUKEMIAS; EXPRESSION; GENES; METHYLTRANSFERASE; FRAGMENTS; ALL-1 AB In this issue of Cancer Cell, So et al. (2003) demonstrate a novel mechanism for the oncogenic activity of MILL chimeric proteins. By providing coiled-coil or other dimerization domains, the cytoplasmic partners of MILL fusion proteins donate a platform for MILL homodimerization, allowing recruitment of accessory factors needed to activate the critical downstream targets, including selected subsets of the major HOX genes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hsu, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2003 VL 4 IS 2 BP 81 EP 83 DI 10.1016/S1535-6108(03)00192-2 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 716ZH UT WOS:000185060000001 PM 12957280 ER PT J AU Brugarolas, JB Vazquez, F Reddy, A Sellers, WR Kaelin, WG AF Brugarolas, JB Vazquez, F Reddy, A Sellers, WR Kaelin, WG TI TSC2 regulates VEGF through mTOR-dependent and -independent pathways SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HYPOXIA-INDUCIBLE FACTOR; TUMOR-SUPPRESSOR GENE; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; FACTOR 1-ALPHA HIF-1-ALPHA; HUMAN GLIOBLASTOMA CELLS; TUBEROUS SCLEROSIS GENE; MAMMALIAN TARGET; PHOSPHATIDYLINOSITOL 3-KINASE; EMBRYONIC LETHALITY AB Inactivation of the TSC2 tumor suppressor protein causes tuberous sclerosis complex (TSC), a disease characterized by highly vascular tumors. TSC2 has multiple functions including inhibition of mTOR (mammalian target of Rapamycin). We found that TSC2 regulates VEGF through mTOR-dependent and -independent pathways. TSC2 loss results in the accumulation of HIF-1alpha and increased expression of HIF-responsive genes including VEGF. Wild-type TSC2, but not a disease-associated TSC2 mutant, downregulates Hill Rapamycin normalizes HIF levels in TSC2(-/-) cells, indicating that TSC2 regulates HIF by inhibiting mTOR. In contrast, Rapamycin only partially downregulates VEGF in this setting, implying an mTOR-independent link between TSC2 loss and VEGF. This pathway may involve chromatin remodeling since the HDAC inhibitor Trichostatin A downregulates VEGF in TSC2(-/-) cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 87 TC 338 Z9 346 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2003 VL 4 IS 2 BP 147 EP 158 DI 10.1016/S1535-6108(03)00187-9 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 716ZH UT WOS:000185060000010 PM 12957289 ER PT J AU Cho, EY Spiegelman, D Hunter, DJ Chen, WY Zhang, SMM Colditz, GA Willett, WC AF Cho, EY Spiegelman, D Hunter, DJ Chen, WY Zhang, SMM Colditz, GA Willett, WC TI Premenopausal intakes of vitamins A, C, and E, folate, and carotenoids, and risk of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BETA-CAROTENE; DIETARY CAROTENOIDS; PROSPECTIVE COHORT; CIGARETTE-SMOKING; PLASMA; WOMEN; VEGETABLES; RETINOL; FRUITS; CONSUMPTION AB Intakes of vitamins A, C, and E, folate, and carotenoids have been hypothesized to reduce the risk of breast cancer. However, previous epidemiological studies on these nutrients and breast cancer risk have been inconclusive, and have included primarily postmenopausal women. We examined the intake of these nutrients in relation to breast cancer risk among 90,655 premenopausal women ages 26-46 years in 1991 in the Nurses' Health Study II. Nutrient intake was assessed with a validated food-frequency questionnaire at baseline in 1991 and in 1995. During 8 years of follow-up from 1991 to 1999, we documented 714 incident cases of invasive breast cancer. Overall, none of the vitamins and carotenoids was strongly related to a reduced risk of breast cancer. However, intake of vitamin A, including preformed vitamin A and carotenoids, was associated with a reduced risk of breast cancer among smokers; participants in the highest quintile of total vitamin A intake had a multivariate relative risk of 0.28 (95% confidence interval 0.12-0.62; P, test for trend <0.001; P, test for interaction <0.001) compared with those in the lowest quintile of intake. We found no evidence that higher intakes of vitamins C and E, and folate in early adult life reduce risk of breast cancer. However, intake of vitamin A may be related to a reduced risk of breast cancer among smokers. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Cho, EY (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385] NR 43 TC 70 Z9 71 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2003 VL 12 IS 8 BP 713 EP 720 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 711UD UT WOS:000184758700004 PM 12917201 ER PT J AU Ganis, G Kosslyn, SM Stose, S Thompson, WL Yurgelun-Todd, DA AF Ganis, G Kosslyn, SM Stose, S Thompson, WL Yurgelun-Todd, DA TI Neural correlates of different types of deception: An fMRI investigation SO CEREBRAL CORTEX LA English DT Article ID FUNCTIONAL MAGNETIC-RESONANCE; PREFRONTAL CORTEX ACTIVATION; ANTERIOR CINGULATE CORTEX; EVENT-RELATED FMRI; WORKING-MEMORY; RETRIEVAL; BRAIN; MRI; INFORMATION; RECOGNITION AB Deception is a complex cognitive activity, and different types of lies could arise from different neural systems. We investigated this possibility by first classifying lies according to two dimensions, whether they fit into a coherent story and whether they were previously memorized. fMRI revealed that well-rehearsed lies that fit into a coherent story elicit more activation in right anterior frontal cortices than spontaneous lies that do not fit into a story, whereas the opposite pattern occurs in the anterior cingulate and in posterior visual cortex. Furthermore, both types of lies elicited more activation than telling the truth in anterior prefrontal cortices (bilaterally), the parahippocampal gyrus (bilaterally), the right precuneus, and the left cerebellum. At least in part, distinct neural networks support different types of deception. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Martinos Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02142 USA. Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02478 USA. RP Ganis, G (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM ganis@wjh.harvard.edu NR 46 TC 202 Z9 209 U1 9 U2 34 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 AUG PY 2003 VL 13 IS 8 BP 830 EP 836 DI 10.1093/cercor/13.8.830 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 705MX UT WOS:000184399800004 PM 12853369 ER PT J AU Ye, B Cramer, DW Skates, SJ Gygi, SP Pratomo, V Fu, LF Horick, NK Licklider, LJ Schorge, JO Berkowitz, RS Mok, SC AF Ye, B Cramer, DW Skates, SJ Gygi, SP Pratomo, V Fu, LF Horick, NK Licklider, LJ Schorge, JO Berkowitz, RS Mok, SC TI Haptoglobin-alpha subunit as potential serum biomarker in ovarian cancer: Identification and characterization using proteomic profiling and mass spectrometry SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEINS; PATTERNS; CELLS; TECHNOLOGIES; DUPLICATION; CHAINS AB Purpose: The objective of this study was to identify and characterize new serum biomarkers in ovarian cancer patients using mass spectrometric protein profiling and specific immunological assays. Experimental Design: Serum samples from 80 cancer patients and 91 healthy women were analyzed by surface enhanced laser desorption and ionization-mass spectrometry (MS) profiling. A candidate biomarker was purified by affinity chromatography, and its sequence was determined by, liquid chromatography-tandem MS. An antibody was generated from the synthesized peptide for quantitative validation in the cases and controls. CA125 was determined and compared with the same set of specimens. Results: Using surface enhanced laser desorption and ionization, we found a serum biomarker at similar to11700 Da, which had peak intensity significantly higher in cases (1.366) compared with controls (0.208, P = 0.002), and subsequently identified this as the alpha chain of haptoglobin. EUSA indicated that Hp-alpha was less than or equal to2-fold higher in cancer serum compared with normal, benign tumor, and other gynecological cancers (P < 0.05) and had 64% sensitivity at 90% specificity alone and 91% sensitivity and 95% specificity if combined with CA125. Conclusions: Haptoglobin-derived alpha subunit is a potential marker for ovarian cancer that is complementary to CA125. MS-based protein profiling is a valuable tool for screening protein markers and useful to detect post-translational modification of tumor-associated proteins or abnormal metabolic products. However, confirmation of protein identity with specific antibodies is crucial for clinical application and functional studies. C1 Brigham & Womens Hosp, Lab Gynecol Oncol, Dept Obstet & Gynecol & Reprod Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Houston, TX 77030 USA. RP Ye, B (reprint author), Brigham & Womens Hosp, Lab Gynecol Oncol, Dept Obstet & Gynecol & Reprod Biol, 221 Longwood Ave,BLI-449, Boston, MA 02115 USA. FU NCI NIH HHS [UO1CA86381] NR 33 TC 192 Z9 217 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2003 VL 9 IS 8 BP 2904 EP 2911 PG 8 WC Oncology SC Oncology GA 710KW UT WOS:000184680200006 PM 12912935 ER PT J AU Gilbert, MR Supko, JG Batchelor, T Lesser, G Fisher, JD Piantadosi, S Grossman, S AF Gilbert, MR Supko, JG Batchelor, T Lesser, G Fisher, JD Piantadosi, S Grossman, S TI Phase I clinical and pharmacokinetic study of irinotecan in adults with recurrent malignant glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID CEREBROSPINAL-FLUID PHARMACOKINETICS; CAMPTOTHECIN DERIVATIVE IRINOTECAN; BLOOD-BRAIN-BARRIER; TOPOISOMERASE-I; P-GLYCOPROTEIN; CANCER-PATIENTS; METABOLITE SN-38; ACTIVE METABOLITE; ANALOG CPT-11; TOPOTECAN AB Purpose: A preliminary evaluation of the efficacy of irinotecan in patients with malignant glioma demonstrated modest activity. A markedly lower than expected incidence of drug-related toxicity was also noted. This Was consistent with pharmacokinetic data indicating that the total body clearance (CL) of irinotecan in this patient population was considerably greater than in colorectal cancer patients. Concomitant medications used chronically in brain cancer patients, especially glucocorticoids and anticonvulsants that induce hepatic enzymes involved in the metabolism or excretion of drugs, were believed to be the cause of the alteration in pharmacokinetic behavior. A Phase I study was therefore undertaken in patients with recurrent malignant gliomas to independently determine the maximum tolerated dose (MTD) of irinotecan in patients stratified according to the use of enzyme-inducing anticonvulsants (EIAs). Experimental Design: Patients with recurrent malignant gliomas received irinotecan as a weekly 90-min i.v. infusion for four consecutive weeks, with additional cycles of treatment repeated every 6 weeks. The starting dose was 125 mg/m(2)/week for both groups of patients (+/-EIA). Groups of greater than or equal to3 patients were evaluated at each dose level, and the modified continual reassessment method was used for dose adjustments. The plasma pharmacokinetics of irinotecan, its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), and the glucuronide conjugate of SN-38, SN-38 glucuronide, were determined in all patients during treatment with the first weekly dose. Results: Forty patients were enrolled into the study and treated with a total of 135 cycles of irinotecan. The MTD was determined to be 411 mg/m(2)/week in the +EIA cohort and 117 mg/m(2)/week in the -EIA cohort for the weekly X 4 every 6 weeks schedule. Pharmacokinetic studies showed that the CL of irinotecan was distinctly dose dependent in the patients receiving EIAs, decreasing from similar to50 liters/h/m(2) at the lower dose levels (125-238 mg/m(2)) to a mean SD value of 29.7 +/- 9.0 liters/h/m(2) (n = 7) at the MTD. The grand mean CL for a group of 13 patients who were not taking EIAs, 18.8+/-10.6 liters/h/m(2), was significantly different from the mean CL at the MTD of the +EIA cohort (P = 0.033). Mean values of the AUC of SN-38 (P = 0.4) and SN-38 glucuronide (P = 0.55) were not significantly different at the MTDs for the two cohorts of patients. Conclusions: The MTD of irinotecan was 3.5 times greater in patients with malignant glioma who were concurrently receiving EIAs than in those who were not. This study has also served to confirm that the concomitant administration of EIAs results in marked enhancement in the CL of irinotecan. These findings have important implications for subsequent clinical trials to further evaluate irinotecan in brain cancer patients and underscore the importance of assessing the potential for pharmacokinetic interactions between concurrent medications and chemotherapeutic agents. C1 Johns Hopkins Univ, NABTT Cent Off, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Fisher, JD (reprint author), Johns Hopkins Univ, NABTT Cent Off, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,Bunting Blaustein CRB G87, Baltimore, MD 21231 USA. RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU NCI NIH HHS [P30-CA0516, U01-CA62406]; PHS HHS [U01-CVA62475] NR 54 TC 79 Z9 80 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2003 VL 9 IS 8 BP 2940 EP 2949 PG 10 WC Oncology SC Oncology GA 710KW UT WOS:000184680200011 PM 12912940 ER PT J AU Shattuck, TM Kim, TS Costa, J Yandell, DW Imanishi, Y Palanisamy, N Gaz, RD Shoback, D Clark, OH Monchik, JM Wierman, ME Hollenberg, A Tojo, K Chaganti, RSK Arnold, A AF Shattuck, TM Kim, TS Costa, J Yandell, DW Imanishi, Y Palanisamy, N Gaz, RD Shoback, D Clark, OH Monchik, JM Wierman, ME Hollenberg, A Tojo, K Chaganti, RSK Arnold, A TI Mutational analyses of RB and BRCA2 as candidate tumour suppressor genes in parathyroid carcinoma SO CLINICAL ENDOCRINOLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; COMPARATIVE GENOMIC HYBRIDIZATION; CHRONIC-RENAL-FAILURE; CYCLIN D1; PRIMARY BREAST; MEN1 GENE; ADENOMAS; EXPRESSION; PROMOTER; PROTEIN AB OBJECTIVE Strong evidence indicates that at least one key tumour suppressor gene important for the development of malignant parathyroid tumours is located on chromosome 13, but the critical target gene remains unknown. Importantly, the region of acquired DNA loss includes two established tumour suppressor genes, the retinoblastoma gene, RB (RB1) and BRCA2. Resolution of whether RB or BRCA2 is the critical 13q tumour suppressor gene in parathyroid cancer requires analysis of these genes' sequences for intragenic inactivating mutations. Therefore, RB and BRCA2 were analysed in a group of parathyroid carcinomas in which mutations of these genes should be most readily detectable. PATIENTS AND DESIGN Six parathyroid carcinomas from four patients which showed loss of heterozygosity (LOH) at the RB locus and/or 13q loss by comparative genomic hybridazation (CGH) were selected from a CGH/LOH-screened panel of 16 carcinoma specimens from 10 patients. These tumours were examined for mutations by direct sequencing of the complete 27-exon coding region, intron-exon boundaries and promoter of RB. The 26 coding exons and intron-exon boundaries of BRCA2 were also directly sequenced in seven parathyrold carcinomas with loss in the BRCA2 region. RESULTS No microdeletions, insertions, or point mutations were detected in either RB or BRCA2 in any of the carcinomas. CONCLUSION The absence of tumour-specific somatic mutations in RB and BRCA2 suggests that they are unlikely to act as classic tumour suppressor genes in the pathogenesis of parathyroid carcinomas. While decreased expression of these genes might contribute to parathyroid carcinomatosis in a secondary fashion and 13q loss warrants further study as a diagnostic marker for parathyroid carcinoma, the putative 13q tumour suppressor awaits identification. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. Univ Vermont, Coll Med, Vermont Canc Ctr, Burlington, VT USA. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA. Univ Calif San Francisco, UCSF Mt Zion Med Ctr, Dept Surg, San Francisco, CA 94143 USA. Rhode Isl Hosp, Dept Surg, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Colorado, Vet Affairs Med Ctr, Div Endocrinol, Denver, CO 80202 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Jikei Univ, Sch Med, Dept Internal Med, Div Diabet & Endocrinol, Tokyo, Japan. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. OI Palanisamy, Nallasivam/0000-0002-0633-9772 NR 57 TC 35 Z9 37 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD AUG PY 2003 VL 59 IS 2 BP 180 EP 189 DI 10.1046/j.1365-2265.2003.01814.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705ZL UT WOS:000184427100006 PM 12864795 ER PT J AU Amorosa, VK Isaacs, SN AF Amorosa, VK Isaacs, SN TI Separate worlds set to collide: Smallpox, vaccinia virus vaccination, and human immunodeficiency virus and acquired immunodeficiency syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID METHYLISATIN BETA-THIOSEMICARBAZONE; COMPOUND 33T57; GAMMA-GLOBULIN; UNITED-STATES; HIV DISEASE; COMPLICATIONS; INFECTION; PROPHYLAXIS; GANGRENOSA; IMMUNITY AB Concerns about the possible release of smallpox by bioterrorists has led to policies that recommend smallpox vaccination of some health care providers, and, in the near future, the vaccine may become available to the general population on a voluntary basis. Both smallpox virus ( variola virus) and the smallpox vaccine ( vaccinia virus) will have a significant impact on people infected with human immunodeficiency virus (HIV). Given that populations with acquired immunodeficiency syndrome and populations with immunosuppressed conditions due to solid organ and bone marrow transplantation were not present in the days when smallpox was prevalent, we will speculate on how smallpox might present in immunodeficient patients, and we will review the adverse events expected from the smallpox vaccine in hosts with HIV infection. C1 Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Isaacs, SN (reprint author), Univ Penn, Dept Med, Div Infect Dis, 502 Johnson Pavil, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [R01 AI047237, AI47237, AI48487, U01 AI048487] NR 39 TC 16 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2003 VL 37 IS 3 BP 426 EP 432 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 705RE UT WOS:000184407900016 PM 12884168 ER PT J AU Giordano, TP Wright, JA Hasan, MQ White, AC Graviss, EA Visnegarwala, F AF Giordano, TP Wright, JA Hasan, MQ White, AC Graviss, EA Visnegarwala, F TI Do sex and race/ethnicity influence CD4 cell response in patients who achieve virologic suppression during antiretroviral therapy? SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN ID PROTEASE INHIBITOR; INFECTED PATIENTS; COUNTS; GENDER; PREDICTORS; INCREASES; WOMEN; RACE; RASH; RISK AB To determine whether CD4 cell count response to virus suppression during highly active antiretroviral therapy differs according to sex or race/ethnicity, we analyzed data in our observational cohort study for patients receiving their first antiretroviral regimen who experienced virus suppression by 6 months of therapy. In both univariate and multivariate analyses, women had greater CD4 cell count increases, compared with men, as did patients receiving a regimen that did not include a protease inhibitor. Race/ethnicity was not a factor. C1 Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Giordano, TP (reprint author), Houston VA Med Ctr 152, 2002 Holcombe Blvd,Ste 01Y, Houston, TX 77030 USA. OI White, A Clinton/0000-0002-9668-4632 FU NIAID NIH HHS [5 T32 AI07456-10]; NIMH NIH HHS [1 K23 MH67505-1] NR 24 TC 33 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD AUG 1 PY 2003 VL 37 IS 3 BP 433 EP 437 DI 10.1086/376638 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 705RE UT WOS:000184407900017 PM 12884169 ER PT J AU Temple, RO McBride, AM Horner, MD Taylor, RM AF Temple, RO McBride, AM Horner, MD Taylor, RM TI Personality characteristics of patients showing suboptimal cognitive effort SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article ID DIGIT RECOGNITION TEST; MILD HEAD TRAUMA; INJURY; MMPI-2; IMPAIRMENT; SEIZURES AB This study examined the relationship between performance on the Portland Digit Recognition Test (PDRT) and the MMPI-2 in a group of veterans who were suspected of having motivation to exaggerate cognitive and/or psychiatric symptoms. Number correct on "easy" trials on the PDRT correlated inversely with MMPI-2 measures of psychopathology, whereas number correct on "hard" trials positively correlated with the same scales. Some individuals performed poorly across both types of PDRT trials and had significant MMPI-2 elevations, whereas others performed poorly only on "hard" PDRT trials and had less extreme MMPI-2 elevations. This study reinforces the need to assess the validity of both cognitive and psychiatric symptom complaints. C1 Brown Univ, Rhode Isl Hosp, Providence, RI 02903 USA. James A Haley Vet Adm Med Ctr, Tampa, FL 33612 USA. Ralph H Johnson DVA Med Ctr, Charleston, SC USA. RP Temple, RO (reprint author), Brown Univ, Rhode Isl Hosp, 110 Lockwood St,Suite 430, Providence, RI 02903 USA. NR 19 TC 6 Z9 6 U1 3 U2 3 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD AUG PY 2003 VL 17 IS 3 BP 402 EP 409 DI 10.1076/clin.17.3.402.18080 PG 8 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 748DP UT WOS:000186847100012 PM 14704891 ER PT J AU Pollack, MH Allgulander, C Bandelow, B Cassano, GB Greist, JH Hollander, E Nutt, DJ Okasha, A Swinson, RP AF Pollack, MH Allgulander, C Bandelow, B Cassano, GB Greist, JH Hollander, E Nutt, DJ Okasha, A Swinson, RP TI WCA recommendations for the long-term treatment of panic disorder SO CNS SPECTRUMS LA English DT Article; Proceedings Paper CT Meeting of the World-Council-of-Anxiety CY SEP, 2000 CL PISA, ITALY SP World Council Anxiety ID PLACEBO-CONTROLLED TRIAL; COGNITIVE-BEHAVIORAL THERAPY; NATURALISTIC FOLLOW-UP; RANDOMIZED CONTROLLED TRIAL; MAINTENANCE DRUG-TREATMENT; DOUBLE-BLIND; MULTICENTER TRIAL; SUICIDE ATTEMPTS; SOCIAL PHOBIA; PSYCHOLOGICAL TREATMENT AB What are the symptoms of panic disorder and how is the disorder most effectively treated? One of the most commonly encountered anxiety disorders in the primary care setting, panic disorder is a chronic and debilitating illness. The core symptoms are recurrent panic attacks coupled with anticipatory anxiety and phobic avoidance, which together impair the patient's professional, social, and familial functioning. Patients with panic disorder have medically unexplained symptoms that lead to overutilization of healthcare services. Panic disorder is often comorbid with agoraphobia and major depression, and patients may be at increased risk of cardiovascular disease and, possibly, suicide. Research into the optimal treatment of this disorder has been undertaken in the past 2 decades, and numerous randomized, controlled trials have been published. Selective serotonin reuptake inhibitors have emerged as the most favorable treatment, as they have a beneficial side-effect profile, are relatively safe (even if taken in overdose), and do not produce physical dependency. High-potency benzo-diazepines, reversible monoamine oxidase inhibitors, and tricyclic antidepressants have also shown antipanic efficacy. In addition, cognitive-behavioral therapy has demonstrated efficacy in the acute and long-term treatment of panic disorder. An integrated treatment approach that combines pharmacotherapy with cognitive-behavioral therapy may provide the best treatment. Long term efficacy and ease of use are important considerations in treatment selection, as maintenance treatment is recommended far at least 12-24 months, and in some cases, indefinitely. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, Boston, MA 02114 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Related Disorders, WAC 812,15 Parkman St, Boston, MA 02114 USA. RI Bandelow, Borwin/E-7295-2011 OI Bandelow, Borwin/0000-0003-2511-3768 NR 140 TC 45 Z9 46 U1 2 U2 6 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTR JI CNS Spectr. PD AUG PY 2003 VL 8 IS 8 SU 1 BP 17 EP 30 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 715ZU UT WOS:000185005000003 PM 14767395 ER PT J AU Schettino, GPP Chatmongkolchart, S Hess, DR Kacmarek, RM AF Schettino, GPP Chatmongkolchart, S Hess, DR Kacmarek, RM TI Position of exhalation port and mask design affect CO2 rebreathing during noninvasive positive pressure ventilation SO CRITICAL CARE MEDICINE LA English DT Article DE noninvasive mechanical ventilation; mask; exhalation port; CO2 rebreathing; work of breathing ID ACUTE RESPIRATORY-FAILURE; SUPPORT VENTILATION; LUNG MODEL; DEVICES; TRIAL AB Objective. Noninvasive positive pressure ventilation may be considered a first line intervention to treat patients with hypercapnic respiratory failure. However, CO2 rebreathing from the ventilator circuit or mask may impair CO2 elimination and load the ventilatory muscles. This study was conducted to evaluate the effect of exhalation port location and mask design on CO, rebreathing during noninvasive positive pressure ventilation. Design: Lung model evaluation. Setting: Experimental laboratory of a large university-affiliated hospital. Subjects: A dual-chamber test lung was used to simulate the ventilatory mechanics of a patient with obstructive lung disease. Intervention. Hypercapnic respiratory failure (end-tidal CO2 of 75 mm Hg) and obstructive lung disease were simulated in a double-chamber lung model. A facial mask (inner volume of 165 mL) with exhalation port within the mask (Facial-MEP) or the same mask with exhalation port in the ventilator circuit (Facial-WS) and a total face mask with exhalation port within the mask (inner volume 875 mL, Total Face) were tested during continuous positive airway pressure and pressure support ventilation provided by a single-limb circuit ventilator at the same frequency and tidal volume. Measurements and Main Results. A capnometer and a flow transducer were placed in the lung model upper airway to measure the volume of CO2 rebreathed and tidal volume (VT). The inspiratory load was estimated from the pressure variation in the lung model driving chamber (P-DR). Volume of CO2 rebreathed was smaller during Facial-MEP compared with the other masks in all tested conditions (p < .001). The VT and PDR necessary to decrease end-tidal CO2 20% (from 75 to 60 mm Hg) was different among the tested masks (Facial-MEP, VT 701 +/- 9 mL, P-DR 8.1 +/- 0.1 cm H2O/sec; Facial-WS, VT 745 +/- 9 mL, P-DR 10.2 +/- 0.1 cm H2O/sec; Total Face, VT 790 +/- 12 mL, P-DR 11.4 +/- 0.2 cm H2O/sec, P < .001). Conclusion: Facial-MEP with its exhalation port within the mask and the smallest mask volume demonstrated less rebreathed CO2 and a lower PDR than either the Facial-WS or Total Face masks. Additional studies are necessary to confirm if mask design can clinically affect patient's inspiratory effort during noninvasive positive pressure ventilation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care & Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care & Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 17 TC 52 Z9 60 U1 0 U2 1 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 AUG PY 2003 VL 31 IS 8 BP 2178 EP 2182 DI 10.1097/01.CCM.0000081309.71887.E9 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 712KV UT WOS:000184797600015 PM 12973177 ER PT J AU Makino, CL Wen, XH Lem, J AF Makino, CL Wen, XH Lem, J TI Piecing together the timetable for visual transduction with transgenic animals SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID DOMINANT RETINITIS-PIGMENTOSA; GTPASE ACCELERATING PROTEIN; MOUSE ROD PHOTORECEPTORS; SINGLE-PHOTON RESPONSES; LIGHT-INDUCED APOPTOSIS; DEEP-SEA FISHES; IN-VIVO; RETINAL RODS; MICE LACKING; CGMP-PHOSPHODIESTERASE AB Transgenic mice bearing null or functional mutations are being used to define the roles of specific elements in phototransduction and also to time the molecular interactions. Genetic manipulation of the collision frequency between rhodopsin and transducin molecules identified this parameter as rate-limiting for the photoresponse onset. Genetic interference with rhodopsin phosphorylation and arrestin binding, transducin shut-off and calcium feedback has revealed their respective roles in shaping the response waveform. The timetable for all of these molecular events determines the amplitude, kinetics and reproducibility of the photoresponse. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Genet Program, Boston, MA 02111 USA. Tufts Univ, Sch Med, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. RP Makino, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. OI Makino, Clint/0000-0002-6005-9069 NR 63 TC 32 Z9 32 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD AUG PY 2003 VL 13 IS 4 BP 404 EP 412 DI 10.1016/S0959-4388(03)00091-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 722XH UT WOS:000185403000002 PM 12965286 ER PT J AU Hersch, SM AF Hersch, SM TI Huntington's disease: prospects for neuroprotective therapy 10 years after the discovery of the causative genetic mutation SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE Huntington's disease; neurodegeneration; neuroprotection; pathogenesis; clinical trials; therapy; review ID TRANSGENIC MOUSE MODEL; CELLULAR POLYGLUTAMINE TOXICITY; FETAL STRIATAL TRANSPLANTATION; KNOCK-IN MICE; NEURODEGENERATIVE DISEASES; TISSUE TRANSGLUTAMINASE; EXPANDED POLYGLUTAMINE; TRANSCRIPTION FACTORS; CALPAIN ACTIVATION; PROLONGS SURVIVAL AB Purpose of review Ten years of intensive research are now beginning to bring candidate neuroprotective therapies to clinical trials. This review describes recent progress in basic, preclinical, and clinical research that underlies current and potential neuroprotective trials. Recent findings Basic research continues to elucidate the proteolytic processing of huntingtin into toxic fragments and has examined the toxic potential of huntingtin monomers versus oligomers versus insoluble aggregates. Energy depletion has been reinvigorated as a therapeutic target by studies identifying very early mitochondrial alterations. Toxic interactions between mutant huntingtin and a variety of transcription factors have emerged as a major focus with a variety of studies suggesting transcriptional dysfunction to be a central mechanism in Huntington's disease. Progress in preclinical research included therapeutic leads identified by compound library screens, by designing polypeptides that can interact with huntingtin, and by testing compounds in transgenic mice with the potential for affecting some of the mechanisms thought to underlie neurodegeneration. While early results of neurotransplantation are generating increasing controversy, a variety of compounds discovered to benefit transgenic mice are working their way into clinical trials in symptomatic patients. Studies in presymptomatic individuals at risk for developing Huntington's disease are underway to enable the testing of agents with the potential for delaying or preventing onset of symptoms. Summary While laboratory research continues to advance and provide therapeutic leads, clinical trials are needed to test existing leads and guide further progress. With any luck, some of these tests will begin to identify treatments that make a difference for families with the disease. C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Hersch, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, MGH E,Bldg 114,Suite 2000,114 16th St, Charlestown, MA 02129 USA. FU NCCIH NIH HHS [AT00613]; NINDS NIH HHS [NS045242, NS35255] NR 64 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD AUG PY 2003 VL 16 IS 4 BP 501 EP 506 DI 10.1097/01.wco.0000084229.82329.03 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 710KF UT WOS:000184678800010 PM 12869810 ER PT J AU Aye, T Levitsky, LL AF Aye, T Levitsky, LL TI Type 2 diabetes: an epidemic disease in childhood SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE type 2 diabetes mellitus; obesity; children; adolescents; insulin; metformin ID INSULIN SENSITIVITY; GLUCOSE-TOLERANCE; AMERICAN CHILDREN; RESISTIN GENE; RISK-FACTORS; ADOLESCENTS; MELLITUS; OBESITY; POLYMORPHISM; PERSPECTIVE AB Type 2 diabetes mellitus in the pediatric population is now a public health problem. It represents 8 to 45% of all diabetes reported among children and adolescents. Concurrently, childhood obesity has become an epidemic in the United States. Epiderniologic risk factors and diagnostic criteria have largely been established: The incidence of type 2 diabetes increases with age and obesity. Children and adolescents diagnosed with type 2 diabetes usually have a first- or second-degree relative with the disorder. Familial clustering and twin studies have suggested a genetic component for type 2 diabetes. However, the molecular mechanisms that promote diabetes in susceptible individuals, the best treatment plans, and methods of prevention of this disorder are not yet established. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bartlett Hall,Extens 410, Boston, MA 02114 USA. NR 37 TC 31 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD AUG PY 2003 VL 15 IS 4 BP 411 EP 415 PG 5 WC Pediatrics SC Pediatrics GA 712MX UT WOS:000184802400010 PM 12891055 ER PT J AU Burton, K AF Burton, K TI An aperture-shifting light-microscopic method for rapidly quantifying positions of cells in 3D matrices SO CYTOMETRY PART A LA English DT Article DE microscopy; 3-dimensional; oblique illumination; brightfield; cell; gel; quantitative ID MIGRATION AB Background: Rapid measurements of large numbers of cells in 3D are often required for measurements of cell migration. A method is presented for quantifying the position of cells in three-dimensional gels using brightfield microscopy. Methods: Images were recorded using transmitted light with a closed condenser aperture diaphragm positioned off axis to produce oblique illumination. Two or more images, each at the same focal plane, were obtained with the aperture shifted equally to either side of the optical axis. All in-focus objects were at the same position in the two images, but out-of-focus objects were displaced parallel to the aperture movement. Results: The method was tested using gels containing 12-mum-diameter glass beads or cells that had migrated several hundred micrometers into the gel. The position in the image plane varied linearly with axial position, being reversed for objects above and below the focal plane. Beads and cells could be visualized up to a depth of >1 mm in gels. Conclusions: The method facilitates measurements of positions of cells in 3D matrices by eliminating the need to perform optical sectioning and can be used with any brightfield microscope. Supplementary material for this article can be found at http://www.interscience.wiley. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Burton, K (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [R24-CA-56591] NR 10 TC 5 Z9 6 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2003 VL 54A IS 2 BP 125 EP 131 DI 10.1002/cyto.a.10062 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 708BT UT WOS:000184547300006 PM 12879459 ER PT J AU Tannous, Z Torres, A Gonzalez, S AF Tannous, Z Torres, A Gonzalez, S TI In vivo real-time confocal reflectance microscopy: A noninvasive guide for mohs micrographic surgery facilitated by aluminum chloride, an excellent contrast enhancer SO DERMATOLOGIC SURGERY LA English DT Article ID SCANNING LASER MICROSCOPY; BASAL-CELL CARCINOMA; HUMAN SKIN; HISTOLOGY AB BACKGROUND. Mohs micrographic surgery (MMS) is based on microscopically controlled excision of cutaneous neoplasms and offers the highest cure rates with maximum tissue preservation. In vivo confocal microscopy (CM) allows noninvasive optical imaging of thin sections of living skin, in its native state, in real time, with high resolution and contrast. OBJECTIVE. To evaluate the feasibility of the use of in vivo CM as a surgical guide in MMS. METHODS. Five patients with a biopsy-proven basal cell carcinoma (BCC) were imaged by in vivo CM on one or two sites from the clinically visible skin cancer. The first Mohs layer was then excised, and the fresh-frozen sections were correlated with the CM findings. Aluminum chloride (AlCl) 20% was applied on the Mohs defect followed by in vivo CM on one site from each lesion. A second Mohs layer was subsequently excised, and fresh-frozen sections were correlated with CM findings. RESULTS. The findings of in vivo CM were confirmed by hematoxylin and eosin-stained frozen sections after excisions of the first and second Mohs layers. AlCl was found to provide an excellent contrast between BCC cells and the surrounding tissue, detected readily with both in vivo and ex vivo CM. The tumor cells with AlCl exhibited intensely bright nuclei with an excellent contrast as compared with the low-contrast dark nuclei without AlCl application. CONCLUSION. In vivo CM is a potential surgical guide for MMS, and AlCl provides an excellent exogenous agent to enhance tumor contrast for CM. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Bartlett Hall 814,55 Blossom St, Boston, MA 02114 USA. NR 21 TC 48 Z9 50 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD AUG PY 2003 VL 29 IS 8 BP 839 EP 846 DI 10.1046/j.1524-4725.2003.29219.x PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA 702AU UT WOS:000184203100009 PM 12859385 ER PT J AU Aspock, G Ruvkun, G Burglin, TR AF Aspock, G Ruvkun, G Burglin, TR TI The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3 pharynx motoneuron function SO DEVELOPMENT LA English DT Article DE Caenorhabditis elegans; homeobox; pharynx; ceh-2; empty spiracles; evolution; cross-species rescue ID EMPTY SPIRACLES; C-ELEGANS; CEREBRAL-CORTEX; NERVOUS-SYSTEM; AREA IDENTITY; CELL LINEAGE; EXPRESSION; DROSOPHILA; BRAIN; DEFECTS AB Several homeobox genes, for example those of the ems class, play important roles in animal head development. We report on the expression pattern and function of ceh-2, the Caenorhabditis elegans ems/Emx ortholog. CEH-2 protein is restricted to the nuclei of one type of small muscle cell, one type of epithelial cell, and three types of neurons in the anterior pharynx in the head. We have generated a deletion allele of ceh-2 that removes the homeobox. Animals homozygous for this deletion are viable and fertile, but grow slightly slower and lay fewer eggs than wild type. We assayed the function of two types of pharynx neurons that express ceh-2, the pairs M3 and NSM. M3 activity is substantially reduced in electropharyngeograms of ceh-2 deletion mutants; this defect can account for the observed retardation in larval development, as M3 activity is known to be necessary for effective feeding. NSM function and metabolism are normal based on the assays used. All cells that express ceh-2 in wild type are present in the ceh-2 mutant and have normal morphologies. Therefore, unlike other ems/Emx genes, ceh-2 seems to be important for a late differentiation step and not for neuron specification or regional patterning. Because the CEH-2 homeodomain is well conserved, we tested whether ceh-2 can rescue ems(-) brain defects in Drosophila, despite the apparent differences in biological roles. We found that the C elegans ems ortholog is able to substitute for fly ems in brain development, indicating that sequence conservation rather than conservation of biological function is important. C1 Univ Basel, Bioctr, Div Cell Biol, CH-4056 Basel, Switzerland. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Karolinska Inst, Novum, Dept Biosci, SE-14189 Huddinge, Sweden. Karolinska Inst, Ctr Genom & Bioinformat, SE-14189 Huddinge, Sweden. RP Univ Basel, Bioctr, Div Cell Biol, Klingelbergstr 70, CH-4056 Basel, Switzerland. EM thomas.burglin@biosci.ki.se RI Burglin, Thomas/A-3556-2013 NR 60 TC 23 Z9 29 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 EI 1477-9129 J9 DEVELOPMENT JI Development PD AUG PY 2003 VL 130 IS 15 BP 3369 EP 3378 DI 10.1242/dev.00551 PG 10 WC Developmental Biology SC Developmental Biology GA 713AA UT WOS:000184830700002 PM 12810585 ER PT J AU Mollinari, C Reynaud, C Martineau-Thuillier, S Monier, S Kieffer, S Garin, J Andreassen, PR Boulet, A Goud, B Kleman, JP Margolis, RL AF Mollinari, C Reynaud, C Martineau-Thuillier, S Monier, S Kieffer, S Garin, J Andreassen, PR Boulet, A Goud, B Kleman, JP Margolis, RL TI The mammalian passenger is an RCC1 family member protein TD-60 with an essential role in prometaphase to metaphase progression SO DEVELOPMENTAL CELL LA English DT Article ID XENOPUS EGG EXTRACTS; GTPASE-ACTIVATING PROTEIN; INNER CENTROMERE; MITOTIC SPINDLE; RAN GTPASE; CHROMOSOME SEGREGATION; CLEAVAGE FURROW; DNA-REPLICATION; BINDING PROTEIN; INCENP BINDS AB Passenger proteins migrate from inner centromeres to the spindle midzone during late mitosis, and those described to date are essential both for proper chromosome segregation and for completion of cell cleavage. We have purified and cloned the human passenger protein TD-60, and we here report that it is a member of the RCC1 family and that it binds preferentially the nucleotide-free form of the small G protein Rac1. Using siRNA, we further demonstrate that the absence of TD-60 substantially suppresses overall spindle assembly, blocks cells in prometaphase, and activates the spindle assembly checkpoint. These defects suggest TD-60 may have a role in global spindle assembly or may be specifically required to integrate kinetochores into the mitotic spindle. The latter is consistent with a TD-60 requirement for recruitment of the passenger proteins survivin and Aurora B, and suggests that like other passenger proteins, TD-60 is involved in regulation of cell cleavage. C1 Inst Biol Struct JP Ebel, CNRS, CEA, F-38027 Grenoble 1, France. Inst Curie, F-75248 Paris, France. CEA Grenoble, Dept Reponse & Dynam Cellulaires, F-38054 Grenoble 9, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margolis, RL (reprint author), Inst Biol Struct JP Ebel, CNRS, CEA, 41 Rue Jules Horowitz, F-38027 Grenoble 1, France. RI Kleman, Jean-Philippe/G-5107-2016; OI Kleman, Jean-Philippe/0000-0001-5648-5295; MOLLINARI, CRISTIANA/0000-0001-8112-5427 FU Fondazione Telethon NR 52 TC 70 Z9 75 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG PY 2003 VL 5 IS 2 BP 295 EP 307 DI 10.1016/S1534-5807(03)00205-3 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 713UR UT WOS:000184876800014 PM 12919680 ER PT J AU Kahan, BW Jacobson, LM Hullett, DA Ochoada, JM Oberley, TD Lang, KM Odorico, JS AF Kahan, BW Jacobson, LM Hullett, DA Ochoada, JM Oberley, TD Lang, KM Odorico, JS TI Pancreatic precursors and differentiated islet cell types from murine embryonic stem cells - An in vitro model to study islet differentiation SO DIABETES LA English DT Article ID TRANSCRIPTION FACTOR; MOUSE EMBRYOS; BETA-CELLS; INSULIN-II; B-CELL; EXPRESSION; GENE; PROGENITORS; MICE; PREPROINSULIN AB Embryonic stem (ES) cells differentiating in vitro reproduce many facets of early embryonic development, including the expression of developmentally regulated transcription factors and the differentiation of multipotent precursor cells. ES cells were evaluated for their ability to differentiate into pancreatic and islet lineage-restricted stages including pancreatic duodenal homeobox 1 (PDX1)-positive pancreatic precursor cells, early endocrine cell progenitors, and islet hormone-producing cells. Following growth and differentiation in nonselective medium containing serum, murine ES cells spontaneously differentiated into cells individually expressing each of the four major islet hormones: insulin, glucagon, somatostatin, and pancreatic polypeptide. PDX1 immunostaining cells appeared first, before hormone-positive cells had emerged. Hormone-positive cells appeared within focal clusters of cells coexpressing PDX1 and the nonclassical hormone markers peptide YY (YY) and islet amyloid polypeptide (IAPP) in combination with the definitive hormones, characteristic of endocrine cells appearing during early pancreaticogenesis. This system allows the investigation of many facets of islet development since it promotes the appearance of the complete range of islet phenotypes and reproduces important developmental stages of normal islet cytodifferentiation in differentiating ES cell cultures. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. WiCell Res Inst, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI 53792 USA. RP Odorico, JS (reprint author), Univ Wisconsin, Univ Wisconsin Hosp & Clin, Sch Med, Clin Sci Ctr H4 756, 600 Highland Ave, Madison, WI 53792 USA. NR 50 TC 99 Z9 111 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 AUG PY 2003 VL 52 IS 8 BP 2016 EP 2024 DI 10.2337/diabetes.52.8.2016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705UT UT WOS:000184414200018 PM 12882918 ER PT J AU Meigs, JB Wilson, PWF Nathan, DM D'Agostino, RB Williams, K Haffner, SM AF Meigs, JB Wilson, PWF Nathan, DM D'Agostino, RB Williams, K Haffner, SM TI Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies SO DIABETES LA English DT Article ID INSULIN-RESISTANCE SYNDROME; CARDIOVASCULAR RISK-FACTORS; BLOOD-GLUCOSE CONTROL; MIDDLE-AGED MEN; DIABETES-MELLITUS; SYNDROME PREDICTS; GENERAL-POPULATION; PROVISIONAL REPORT; MEXICAN-AMERICANS; DISEASE EVENTS AB The metabolic syndrome may be a common phenotype increasing risk for type 2 diabetes and cardiovascular disease. We assessed the prevalence and characteristics of the metabolic syndrome among population-based samples of 3,224 white subjects attending Framingham Offspring Study (FOS) exam 5 (1991-1995) and 1,081 non-Hispanic white and 1,656 Mexican-American subjects attending the San Antonio Heart Study (SAHS) phase II follow-up exam (1992-1996). Subjects were similar to50% women, aged 30-79 years, without diabetes, and classified with the metabolic syndrome according to criteria for obesity, dyslipidemia, hyperglycemia, and hypertension proposed by the Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) or the World Health Organization (WHO). We used regression models to estimate rates across ethnic groups and to assess the association of the metabolic syndrome with insulin resistance and predicted 10-year coronary heart disease (CHD) risk. Among FOS white subjects, the age- and sex-adjusted prevalence of the metabolic syndrome was 24% by both ATP III and WHO criteria; among SAHS non-Hispanic white subjects, 23 and 21%, respectively; and among SAHS Mexican-American subjects, 31 and 30%. Rates were highest among Mexican-American women (ATP III, 33%) and lowest among white women (21%). Subjects with the metabolic syndrome by ATP III criteria had higher age-, sex-, and ethnicity-adjusted levels of fasting insulin (11.3 muU/ml), homeostasis model assessment of insulin resistance (2.7), and predicted CHD risk (11.8%) than those without the syndrome (5.9 muU/ml, 1.3, and 6.4%, respectively; all P = 0.0001); differences were similar using WHO criteria. We conclude that the metabolic syndrome typically affects 20-30% of middle-aged adults in the U.S. By any criteria, subjects with the metabolic syndrome are more insulin resistant and at increased predicted risk for CHD versus those without the metabolic syndrome. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Dept Math Stat & Consulting Unit, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78284 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Div Gen Med, Dept Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL24799, N01-HC-38083, R01 HL36820] NR 47 TC 289 Z9 320 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2003 VL 52 IS 8 BP 2160 EP 2167 DI 10.2337/diabetes.52.8.2160 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705UT UT WOS:000184414200036 PM 12882936 ER PT J AU Kim, SH Ma, XW Klupa, T Powers, C Pezzolesi, M Warram, JH Rich, SS Krolewski, AS Doria, A AF Kim, SH Ma, XW Klupa, T Powers, C Pezzolesi, M Warram, JH Rich, SS Krolewski, AS Doria, A TI Genetic modifiers of the age at diagnosis of diabetes (MODY3) in carriers of hepatocyte nuclear factor-1 alpha mutations map to chromosomes 5p15, 9q22, and 14q24 SO DIABETES LA English DT Article ID LINKAGE ANALYSIS; ALPHA-GENE; C-ELEGANS; ONSET; MELLITUS; YOUNG; PHENOTYPES; TRAITS; LOCUS; SEL-1 AB Mutations in hepatocyte nuclear factor (HNF)-1alpha (MODY3) account for the largest proportion of maturity-onset diabetes of the young (MODY) cases in the U.S. This form of diabetes is characterized by impaired insulin secretion in response to glucose, but wide variability exists in the severity of hyperglycemia and in the age at which it becomes clinically manifest. We have previously shown that the age at onset of diabetes in MODY3 families is influenced by familial factors (including modifying genes) and exposure to diabetes in utero. To identify genes influencing the onset of MODY3, we conducted a genome scan in 13 extended MODY families in which diabetes segregates with an HNF-1alpha mutation. Linkage with age at onset of diabetes was assessed by genetic variance component analysis using SOLAR. The locus with the strongest evidence of linkage was on chromosome 14q24 (D14S588; logarithm of odds [LOD] = 2.58, P = 0.0004). This location overlaps with IDDM11 and includes SEL1L, a negative regulator of the Notch pathway that may control islet development. Linkage evidence also supported loci on 5p15 (D5S817; LOD = 2.44, P = 0.0004) and 9q22 (D9S910; LOD = 2.02, P = 0.0018). The latter matches a region linked to 2-h insulin levels in Pima Indians. Less strong linkage evidence was observed at three other regions: chromosomes 3p24 (LOD = 1.44), 7q21 (1.20), and 16q23 (1.51). Our data are consistent with the existence of multiple loci that contribute to the expression of the MODY3 phenotype. Identification of these genes will offer new insights into the pathophysiology of MODY that may, in turn, increase our understanding of the cellular events underlying more common forms of diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-47475, DK-55523, DK-36836] NR 25 TC 25 Z9 25 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 AUG PY 2003 VL 52 IS 8 BP 2182 EP 2186 DI 10.2337/diabetes.52.8.2182 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 705UT UT WOS:000184414200039 PM 12882939 ER PT J AU Grant, RW Hamrick, HE Sullivan, CM Dubey, AK Chueh, HC Cagliero, E Meigs, JB AF Grant, RW Hamrick, HE Sullivan, CM Dubey, AK Chueh, HC Cagliero, E Meigs, JB TI Impact of population management with direct physician feedback on care of patients with type 2 diabetes SO DIABETES CARE LA English DT Article ID DECISION-SUPPORT SYSTEMS; CLINICAL-PRACTICE; SELF-MANAGEMENT; RECOMMENDATIONS; PERFORMANCE; EXPERIENCE; MELLITUS; OUTCOMES; IMPROVE; QUALITY AB OBJECTIVE - Population-level strategies may improve primary care for diabetes. We designed a controlled study to assess the impact of population management versus usual care on metabolic risk factor testing and management in patients with type 2 diabetes. We also identified potential patient-related barriers to effective diabetes management. RESEARCH DESIGN AND METHODS - We used novel clinical software to rank 9 10 patients in a diabetes registry at a single primary care clinic and thereby identify the 149 patients with the highest HbA(1c) and cholesterol levels. After review of the medical records of these 149 patients, evidence-based guideline recommendations regarding metabolic testing and management were sent via e-mail to each intervention patient's primary care provider (PCP). Over a 3-month follow-up period, we assessed changes in the evidence-based management of intervention patients compared with a matched cohort of control patients receiving usual care at a second primary care clinic affiliated with the same academic medical center. RESULTS - in the intervention cohort, PCPs followed testing recommendations more often (78%) than therapeutic change recommendations (36%, P = 0.001). Compared with the usual care control cohort, population management resulted in a greater overall proportion of evidence-based guideline practices being followed (59 vs. 45%, P = 0.02). Most intervention patients (62%) had potential barriers to effective care, including depression (35%), substance abuse (26%), and prior nonadherence to care plans (18%). CONCLUSIONS - Population management with clinical recommendations sent to PCPs had a modest but statistically significant impact on the evidence-based management of diabetes compared with usual care. Depression and substance abuse are prevalent patient-level adherence barriers in patients with poor metabolic control. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Comp Sci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Revere HealthCare Ctr, Boston, MA 02114 USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. OI Grant, Richard/0000-0002-6164-8025 FU PHS HHS [2-T3211001-14] NR 25 TC 32 Z9 32 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 AUG PY 2003 VL 26 IS 8 BP 2275 EP 2280 DI 10.2337/diacare.26.8.2275 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720AQ UT WOS:000185238700008 PM 12882848 ER PT J AU Cox, DJ Penberthy, JK Zrebiec, J Weinger, K Aikens, JE Frier, B Stetson, B DeGroot, M Trief, P Schaechinger, H Hermanns, N Gonder-Frederick, L Clarke, W AF Cox, DJ Penberthy, JK Zrebiec, J Weinger, K Aikens, JE Frier, B Stetson, B DeGroot, M Trief, P Schaechinger, H Hermanns, N Gonder-Frederick, L Clarke, W TI Diabetes and driving mishaps - Frequency and correlations from a multinational survey SO DIABETES CARE LA English DT Article ID INSULIN; AWARENESS; ACCIDENTS; MELLITUS; ADULTS; RISK; COMPLICATIONS; PERFORMANCE; IDDM AB OBJECTIVE - The intensive treatment of diabetes to achieve strict glycemic control is a common clinical goal, but it is associated with an increased incidence of hypoglycemia. Becoming hypoglycemic while driving is a hazardous condition and may lead to a greater incidence of driving mishaps. This study investigated whether diabetes is associated with increased risk of driving mishaps and correlates of such a relationship. RESEARCH DESIGN AND METHODS - During routine visits to diabetes specialty clinics in seven U.S. and four European cities, consecutive adults with type I diabetes, type 2 diabetes, and nondiabetic spouse control subjects (n = 341, 332, and 363, respectively) completed an anonymous questionnaire concerning diabetes and driving. RESULTS - Type 1 diabetic drivers reported significantly more crashes, moving violations, episodes of hypoglycemic stupor, required assistance, and mild hypoglycemia while driving as compared with type 2 diabetic drivers or spouse control subjects (P < 0.01-0.001). Type 2 diabetic drivers had driving mishap rates similar to nondiabetic spouses, and the use of insulin or oral agents for treatment had no effect on the occurrence of driving mishaps. Crashes among type 1 diabetic drivers were associated with more frequent episodes of hypoglycemic stupor while driving, less frequent blood glucose monitoring before driving, and the use of insulin injection therapy as compared with pump therapy. One-half of the type 1 diabetic drivers and three-quarters of the type 2 diabetic drivers had never discussed hypoglycemia and driving with their physicians. CONCLUSIONS - Type 1 diabetic drivers are at increased risk for driving mishaps, but type 2 diabetic drivers, even on insulin, appear not to be at a higher risk than nondiabetic individuals. Clinical and treatment factors appear to increase risk, e.g., more frequent hypoglycemia while driving, method of insulin delivery, and infrequent self-testing before driving Physicians are encouraged to talk to their type I diabetic patients about hypoglycemia and driving. C1 Univ Virginia Hlth Syst, Charlottesville, VA 22908 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Chicago, Chicago, IL 60637 USA. Royal Infirm, Edinburgh, Midlothian, Scotland. Univ Louisville, Louisville, KY 40292 USA. Washington Univ, St Louis, MO USA. SUNY Upstate Med Univ, Syracuse, NY USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. Diabet Acad, Res Inst, Mergentheim, Germany. RP Cox, DJ (reprint author), Univ Virginia Hlth Syst, Box 800223, Charlottesville, VA 22908 USA. FU PHS HHS [5-P60-K20579-24, R01 28288] NR 21 TC 65 Z9 67 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 AUG PY 2003 VL 26 IS 8 BP 2329 EP 2334 DI 10.2337/diacare.26.8.2329 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720AQ UT WOS:000185238700017 PM 12882857 ER PT J AU Ryan, AS Berman, DM Nicklas, BJ Sinha, M Gingerich, RL Meneilly, GS Egan, JM Elahi, D AF Ryan, AS Berman, DM Nicklas, BJ Sinha, M Gingerich, RL Meneilly, GS Egan, JM Elahi, D TI Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity SO DIABETES CARE LA English DT Article ID ADIPOSE-SPECIFIC PROTEIN; INSULIN-RESISTANCE; FAT; SENSITIVITY; WEIGHT; GENE; HYPERINSULINEMIA; POLYMORPHISM; ASSOCIATION; EXPRESSION AB OBJECTIVE - The purpose of this study was to determine the relationships between plasma adiponectin and leptin levels, total and central obesity, and glucose utilization across the adult age span. RESEARCH DESIGN AND METHODS - We studied 148 women aged 18 - 81 years with a BMI range of 17.2-44.3 kg/m(2). Total percent body fat was determined by dual-energy X-ray absorptiometry and abdominal fat by computed tomography. Glucose tolerance in non-type 2 diabetic volunteers was determined with an oral glucose tolerance test. Glucose Utilization M was measured during the last 60 min of hyperinsulinemic-euglycemic clamps (240 pmol.m(-2).min(-1)). Plasma adiponectin levels were measured by radioimmunoassay. The women were separated into three age-groups: young, middle, and old (<40, 40-59, and 60 years, respectively), as well as by glucose tolerance status. RESULTS - Adiponectin concentrations did not differ by age-groups. There were significant age effects for BMI, percent body fat, visceral fat, subcutaneous abdominal fat, VO2max, and M. Adiponectin levels were lower in the prediabetic women (n = 18) than in the normal glucose-tolerant women (n = 108) and the women with type 2 diabetes (n = 22) (both P < 0.05). Univariate correlations revealed significant negative relationships between plasma adiponectin levels and MAL percent body fat, visceral fat, subcutaneous abdominal fat, fasting leptin, and fasting insulin and positive relationship with M (all P < 0.05). In a multiple stepwise regression model to predict adiponectin, only M remained in the model at P < 0.001. Multivariate analyses revealed a significant relation for M as a function of adiponectin, insulin, and VO2max. CONCLUSIONS - The data suggest that plasma adiponectin does not change with age but levels are negatively associated with percent body fat, visceral fat, subcutaneous abdominal fat 0 1 insulin, and leptin levels in women. Adiponectin is positively associated With M across the age span in women. C1 Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. VA Maryland Hlth Care Syst, Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD USA. Linco Res, St Charles, MO USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. NIA, Baltimore, MD 21224 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Ryan, AS (reprint author), Baltimore Vet Affairs Med Ctr, Div Gerontol, BT-18-GR,10 N Greene St, Baltimore, MD 21201 USA. FU NIA NIH HHS [K01-AG00685, K01-AG00747]; PHS HHS [R29-A614066] NR 25 TC 173 Z9 179 U1 0 U2 3 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 AUG PY 2003 VL 26 IS 8 BP 2383 EP 2388 DI 10.2337/diacare.26.8.2383 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720AQ UT WOS:000185238700026 PM 12882866 ER PT J AU Walter, U Toepfer, T Dittmar, KEJ Kretschmer, K Lauber, J Weiss, S Servos, G Lechner, O Scherbaum, WA Bornstein, SR von Boehmer, H Buer, J AF Walter, U Toepfer, T Dittmar, KEJ Kretschmer, K Lauber, J Weiss, S Servos, G Lechner, O Scherbaum, WA Bornstein, SR von Boehmer, H Buer, J TI Pancreatic NOD beta cells express MHC class II protein and the frequency of I-A(g7) mRNA-expressing beta cells strongly increases during progression to autoimmune diabetes SO DIABETOLOGIA LA English DT Article DE beta cell; MHC class II; NOD mice; Type-1-diabetes mellitus; single-cell multiplex RT PCR ID RESTRICTED CROSS-PRESENTATION; GLUTAMIC-ACID DECARBOXYLASE; TUMOR-NECROSIS-FACTOR; T-CELLS; INTERFERON-GAMMA; DENDRITIC CELLS; SELF-ANTIGENS; TH2 RESPONSES; ISLET CELLS; MICE AB Aims/hypothesis. In the NOD mouse model, attempts to show MHC class II expression by pancreatic beta cells were unsuccessful so far. We readdressed this question by analysing I-A(g7) expression in single pancreatic beta cells. Methods. Single-cell multiplex RT PCR and single-cell immunofluorescence were used to study MHC class II expression in NOD and NOD/SCID beta cells. Results. Pancreatic beta cells from NOD mice express the I-A(g7) protein as well as the corresponding mRNA. The frequency of MHC class II mRNA-expressing beta cells is drastically increased during the progression to overt diabetes. MHC class II protein is accumulated intracellularly, and invariant chain is co-expressed. Beta cells from 9- to 10-week-old NOD/SCID mice express MHC class II at the same low frequency as beta cells from 3-week-old NOD mice. Conclusion/interpretation. NOD beta cells express I-A(g7) and could be a direct target of autoreactive CD4+ T cells. This MHC class II expression is triggered by infiltrating lymphocytes. C1 German Res Ctr Biotechnol, Dept Cellbiol & Immunol, Braunschweig, Germany. German Res Ctr Biotechnol, Dept Mol Biotechnol, Braunschweig, Germany. Univ Dusseldorf, Dept Anat, D-4000 Dusseldorf, Germany. Univ Dusseldorf, Dept Endocrinol, D-4000 Dusseldorf, Germany. Inst Necker, INSERM, U373, Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hannover Med Sch, Inst Med Mikrobiol, D-3000 Hannover, Germany. RP Walter, U (reprint author), Univ Dusseldorf, German Diabet Res Inst, Hennekamp 65, D-40225 Dusseldorf, Germany. RI Kretschmer, Karsten/E-8174-2010 NR 46 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 IS 8 BP 1106 EP 1114 DI 10.1007/s00125-003-1164-y PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 709TT UT WOS:000184641000008 PM 12856083 ER PT J AU Aiello, LP Davis, MD Milton, RC Sheetz, MJ Arora, V Vignati, L AF Aiello, LP Davis, MD Milton, RC Sheetz, MJ Arora, V Vignati, L TI Initial results of the protein kinase C beta inhibitor Diabetic Macular Edema Study (PKC-DMES). SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Wisconsin, Madison, WI 53706 USA. EMMES Corp, Rockville, MD USA. Lilly Res Labs, Indianapolis, IN USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 113 BP A42 EP A42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100114 ER PT J AU Bates, SH Seifert, M Myers, MG AF Bates, SH Seifert, M Myers, MG TI The role of leptin receptor-STAT3 signalling in energy homeostasis, neuroendocrine function and glycaemic control. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Joslin Diabet Ctr, Sect Obes, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 648 BP A224 EP A225 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100648 ER PT J AU Carlson, CJ White, MF Rondinone, CM AF Carlson, CJ White, MF Rondinone, CM TI mTOR is a key player in the phosphorylation of IRS-1 at serine 307 SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Abbott Labs, Abbott Pk, IL 60064 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 614 BP A213 EP A213 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100614 ER PT J AU Geenen, V Brilot, F Hansenne, I Louis, C Martens, H Wucherpfennig, K Gorus, F AF Geenen, V Brilot, F Hansenne, I Louis, C Martens, H Wucherpfennig, K Gorus, F TI Thymus tolerance dysfunction in the development of the autoimmune diabetogenic response: a way for a novel type of vaccine/immunotherapy. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Liege, B-4000 Liege, Belgium. CHU Sart Tilman, Belgian NFSR, B-4000 Liege, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Free Univ Brussels, Belgian Registry Diabet, B-1050 Brussels, Belgium. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 22 BP A10 EP A10 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100023 ER PT J AU Genuth, S Zinman, B Cleary, P Orchard, T Jacobson, A Wong, N Detrano, R Backlund, JY AF Genuth, S Zinman, B Cleary, P Orchard, T Jacobson, A Wong, N Detrano, R Backlund, JY TI Coronary calcification in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Univ Calif Los Angeles, Harbor Med Ctr, Torrance, CA 90509 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 59 BP A23 EP A23 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100060 ER PT J AU Haffner, SM Zinman, B Kahn, SE Herman, WH Heise, MA O'Neill, MC Porter, LE AF Haffner, SM Zinman, B Kahn, SE Herman, WH Heise, MA O'Neill, MC Porter, LE CA ADOPT Study Grp TI Differences in the prevalence of the metabolic syndrome between ethnic groups in recently diagnosed Type 2 diabetes in the North American cohort of the ADOPT Study. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 406 BP A144 EP A144 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100406 ER PT J AU Hayashi, T Boyko, EJ McNeely, MJ Leonetti, DL Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ McNeely, MJ Leonetti, DL Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 399 BP A141 EP A141 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100399 ER PT J AU Holman, RR Kahn, SE Heise, MA Porter, LE Freed, MI AF Holman, RR Kahn, SE Heise, MA Porter, LE Freed, MI CA ADOPT Study Grp TI Levels of beta-cell dysfunction and insulin resistance differ between Europeans and North Americans with recently-diagnosed diabetes in the ADOPT study SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Oxford, Diabet Trials Unit, Oxford OX1 2JD, England. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 568 BP A198 EP A198 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100568 ER PT J AU Hull, RL Shen, Z Kodama, K Utzschneider, KM Carr, DB Wang, F Kahn, SE AF Hull, RL Shen, Z Kodama, K Utzschneider, KM Carr, DB Wang, F Kahn, SE TI Long term rosiglitazone and metformin treatment reduce the severity of islet amyloid deposition but do not prevent its formation. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 541 BP A188 EP A189 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100541 ER PT J AU Kulkarni, RN Ueki, K Okada, T AF Kulkarni, RN Ueki, K Okada, T TI Endogenous insulin is essential to prevent glucose-induced apoptosis in islet beta-cells. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 131 BP A48 EP A48 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100132 ER PT J AU Lipsky, BA Norden, C AF Lipsky, BA Norden, C TI Treating infected diabetic foot ulcers: Linezolid is clinically superior to amiopenicillin/beta-lactamase inhibitors (Amino/beta-LI). SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Washington, VA Puget Sound, Seattle, WA 98195 USA. Pharmacia Corp, Infect Dis, Peapack, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 8 BP A5 EP A5 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100009 ER PT J AU Malone, J Bautista, O Genuth, S Monnier, V Shamoon, H Nathan, D Service, FJ Kolterman, O Sivitz, W White, N McGill, J AF Malone, J Bautista, O Genuth, S Monnier, V Shamoon, H Nathan, D Service, FJ Kolterman, O Sivitz, W White, N McGill, J TI Advanced Glycation Endproducts (AGEs) predict worsening of diabetic retinopathy in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) participants. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ S Florida, Tampa, FL USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Iowa, Iowa City, IA 52242 USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 119 BP A43 EP A44 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100120 ER PT J AU Milton, RC Aiello, LP Davis, MD Sheetz, MJ Arora, V Vignati, L AF Milton, RC Aiello, LP Davis, MD Sheetz, MJ Arora, V Vignati, L TI Initial results of the protein kinase C beta inhibitor diabetic retinopathy study (PKC-DRS). SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 EMMES Corp, Rockville, MD USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Wisconsin, Madison, WI 53706 USA. Lilly Res Labs, Indianapolis, IN USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 114 BP A42 EP A42 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100115 ER PT J AU Ng, DPK Araki, SI Wyrwicz, L Rogus, JJ Canani, LH Makita, Y Haneda, M Warram, JH Krolewski, AS AF Ng, DPK Araki, SI Wyrwicz, L Rogus, JJ Canani, LH Makita, Y Haneda, M Warram, JH Krolewski, AS TI Protein kinase C beta-1 gene is a novel susceptibility locus for diabetic nephropathy in Type 1 diabetes mellitus. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th International-Diabetes-Federation Congress CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabet Federat C1 Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. Natl Univ Singapore, Dept Med 3, Singapore 117548, Singapore. Shiga Univ Med Sci, Sect Genet & Epidemiol, Otsu, Shiga 52021, Japan. Joslin Diabet Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Boston, MA 02115 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 87 BP A32 EP A33 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100088 ER PT J AU Veves, A Caselli, A Khaodhiar, L Horton, ES Economides, PA AF Veves, A Caselli, A Khaodhiar, L Horton, ES Economides, PA TI The effects of atorvastatin on the endothelial function in diabetic patients and subjects at risk for diabetes SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 1096 BP A378 EP A378 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242101095 ER PT J AU Vignati, L Aiello, LP Milton, RC Davis, MD Sheetz, MJ Arora, V AF Vignati, L Aiello, LP Milton, RC Davis, MD Sheetz, MJ Arora, V TI Diabetic retinopathy and diabetic macular edema progression rates in recent placebo-controlled clinical trials. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Lilly Res Labs, Indianapolis, IN USA. Joslin Diabet Ctr, Boston, MA 02215 USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 1141 BP A392 EP A392 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242101139 ER PT J AU Williams, K Ferrannini, E Bogardus, C DeFronzo, RA Hunt, KJ Garvey, W Reaven, GM Stern, MP AF Williams, K Ferrannini, E Bogardus, C DeFronzo, RA Hunt, KJ Garvey, W Reaven, GM Stern, MP TI A model to identify individuals likely to be insulin resistant. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Texas, Hlth Sci Ctr, Dept Med Clin Epidemiol, San Antonio, TX USA. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Univ Texas, Hlth Sci Ctr, Dept Med Diabet, San Antonio, TX USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Stanford Univ, Sch Med, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 555 BP A193 EP A194 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100555 ER PT J AU Yishak, AA Virella, G Zgibor, J Walsh, M Costacou, T Evans, RW Lopes-Virella, M Kagan, VE Orchard, T AF Yishak, AA Virella, G Zgibor, J Walsh, M Costacou, T Evans, RW Lopes-Virella, M Kagan, VE Orchard, T TI Role of immune complexes, oxidized LDL antibodies and total anti-oxidative reserve in diabetic nephropathy. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 84 BP A32 EP A32 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100085 ER PT J AU Zinman, B Kahn, SE Haffner, SM Herman, W Heise, MA O'Neill, MC AF Zinman, B Kahn, SE Haffner, SM Herman, W Heise, MA O'Neill, MC CA ADOPT Study Grp TI Prevalence and clinical significance of Glutamic Acid Decarboxylase (GAD) antibodies in recently diagnosed Type 2 diabetes in the ADOPT study cohort. SO DIABETOLOGIA LA English DT Meeting Abstract CT 18th Congress of the International-Diabetes-Federation CY AUG 24-29, 2003 CL PARIS, FRANCE SP Int Diabetes Fed C1 Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. GlaxoSmithKline, King Of Prussia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2003 VL 46 SU 2 MA 417 BP A148 EP A148 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 720BX UT WOS:000185242100417 ER PT J AU Dong, Q McKee, G Pitman, M Geisinger, K Tambouret, R AF Dong, Q McKee, G Pitman, M Geisinger, K Tambouret, R TI Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine-needle aspiration SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; epithelioid; cytology; CD117; c-Kit ID DIFFERENTIAL-DIAGNOSIS; CYTOLOGIC DIAGNOSIS; HEPATOCELLULAR-CARCINOMA; INTERSTITIAL-CELLS; BIOPSY DIAGNOSIS; MARKER; CD117; CAJAL; KIT AB Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and,from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclcar inclusions were frequent findings. Collagenous stroma it-as seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c-kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen. CD117 was positive in the c-kit-negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pathol, Winston Salem, NC 27103 USA. RP Tambouret, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 25 TC 21 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD AUG PY 2003 VL 29 IS 2 BP 55 EP 60 DI 10.1002/dc.10293 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 707FA UT WOS:000184498500001 PM 12889040 ER PT J AU Gopal, DV Lieberman, DA Magaret, N Fennerty, MB Sampliner, RE Garewal, HS Falk, GW Faigel, DO AF Gopal, DV Lieberman, DA Magaret, N Fennerty, MB Sampliner, RE Garewal, HS Falk, GW Faigel, DO TI Risk factors for dysplasia in patients with Barrett's esophagus (BE) - Results from a multicenter consortium SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association/Digestive Disease Week CY MAY 16-19, 1999 CL ORLANDO, FLORIDA SP Amer Gastroenterol Assoc DE Barrett's esophagus; COBE; cooperative study of Barrett's esophagus; age; length; prevalence; dysplasia ID COLUMNAR-LINED ESOPHAGUS; ENDOSCOPIC SURVEILLANCE; OBSERVER VARIATION; ADENOCARCINOMA; DIAGNOSIS; CANCER; PREVALENCE; THERAPY; EXTENT AB Studies show Barrett's esophagus prevalence increases with age, while mean length of Barrett's esophagus is unchanged. Few data are available about the relationship between age and length on the development of dysplasia. Our aim was to assess age and length as risk factors for dysplasia. Consecutive patients with Barrett's esophagus were enrolled in a multicenter study establishing a tissue bank of Barrett's esophagus patients 1994 and 1998. Demographics, length of Barrett's esophagus (centimeters), and histology were recorded. Risk factors for dysplasia were assessed, including patient age, gender, and length of Barrett's esophagus. Statistical analysis was performed comparing prevalence of dysplasia ( which included the presence of any carcinoma and high- or low-grade dysplasia) to age and length. In all, 309 patients were studied [ 278 (90%) male and 31 (10%) female]: 5 had adenocarcinoma of the esophagus, 11 had high- grade dysplasia, and 29 had low-grade dysplasia. Patients with Barrett's esophagus without dysplasia were younger than those with dysplasia [62 +/- 0.8 years vs 67 +/- 1.7 years (mean +/- SEM, P = 0.02)]. The risk of dysplasia increased by 3.3%/yr of age. Mean length of Barrett's esophagus in patients with Barrett's alone vs dysplasia was 4.0 +/- 0.2 cm vs 5.4 +/- 0.4 cm (P = 0.003). Patients with Barrett's esophagus length, 3 cm had a significantly greater prevalence of dysplasia compared to length < 3 cm ( 23% vs 9%, P = 0.0001). The risk of dysplasia increased by 14%/ cm of increased length. Multivariate analysis showed age and length to be independent risk factors. In conclusions; prevalence of dysplasia is strongly associated with age and length of Barrett's esophagus. These preliminary results can be used to develop a strategy for screening/surveillance based on age and length of Barrett's epithelium. C1 Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. So Arizona VA Healthcare Syst, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Faigel, DO (reprint author), Oregon Hlth & Sci Univ, Div Gastroenterol, PV-310,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Falk, Gary/0000-0002-7143-1436 NR 21 TC 70 Z9 73 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2003 VL 48 IS 8 BP 1537 EP 1541 DI 10.1023/A:1024715824149 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 700HB UT WOS:000184105600016 PM 12924649 ER PT J AU Lal, SK Pedrosa, M Orlander, J Klein, MA AF Lal, SK Pedrosa, M Orlander, J Klein, MA TI Primary biliary cirrhosis in an 86-year-old male SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article C1 VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston Med Ctr, Gastroenterol Sect, Boston, MA 02118 USA. VA Boston Healthcare Syst, Dept Internal Med, Boston, MA 02130 USA. Dept Vet Affairs Med Ctr, Dept Pathol & Lab Serv, Providence, RI USA. RP Pedrosa, M (reprint author), VA Boston Healthcare Syst, Gastroenterol Sect, 150 S Huntington Av 111-GI, Boston, MA 02130 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD AUG PY 2003 VL 48 IS 8 BP 1627 EP 1629 DI 10.1023/A:1024736411854 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 700HB UT WOS:000184105600027 PM 12924659 ER PT J AU Schipani, E AF Schipani, E TI Otoconin-22 and calcitonin: A novel modality of regulating calcium storages in lower vertebrates? SO ENDOCRINOLOGY LA English DT Editorial Material ID MAJOR PROTEIN; EMBRYOS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Schipani, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2003 VL 144 IS 8 BP 3285 EP 3286 DI 10.1210/en.2003-0473 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703AW UT WOS:000184258700003 PM 12865303 ER PT J AU Pissios, P Trombly, DJ Tzameli, I Maratos-Flier, E AF Pissios, P Trombly, DJ Tzameli, I Maratos-Flier, E TI Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; HORMONE MCH; MAP KINASE; GROWTH-FACTOR; MOLECULAR CHARACTERIZATION; SYNAPTIC PLASTICITY; MESSENGER-RNA; CELL-GROWTH; CYCLIC-AMP; RAT-BRAIN AB Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a key role in energy homeostasis. Like many neuropeptides, it signals through two G protein-coupled receptors. MCH receptor 1 (MCHR1) is the sole receptor expressed in rodents and couples to G(i) and G(q) proteins. Little is known about the intracellular pathways engaged by MCH and its receptor. Using HEK293 cells stably expressing MCHR1, we demonstrate that MCH, acting through MCHR1, antagonizes the action of forskolin, an adenylate cyclase activator that increases intracellular levels of cAMP. MCH also inhibits cAMP induction by the G(s)-coupled beta-adrenergic receptor. Activation of either the G(i)- or G(s)-dependent pathway typically results in ERK phosphorylation in HEK293 cells. In contrast to opposing actions on cAMP synthesis, simultaneous MCH and forskolin treatment results in synergistic activation of ERK. This synergy proceeds through pertussis toxin-independent pathways and requires several enzymatic activities such as protein kinase A, protein kinase C, phospholipase C, and Src kinase. Finally, we provide evidence that such positive interactions are not limited to cell lines but can also be observed in the brain. C1 Joslin Diabet Ctr, Div Res, Sect Obes, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Endocrinol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Div Res, Sect Obes, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-53978] NR 44 TC 46 Z9 48 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2003 VL 144 IS 8 BP 3514 EP 3523 DI 10.1210/en.2002-0004 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 703AW UT WOS:000184258700033 PM 12865333 ER PT J AU Van Stiegmann, G AF Van Stiegmann, G TI Update of endoscopic band ligation therapy for treatment of esophageal varices SO ENDOSCOPY LA English DT Article; Proceedings Paper CT 3rd International Workshop on Endoscopic Ultrasonography and Advanced Therapeutic Endoscopy CY MAR 07-09, 2003 CL SEOUL, SOUTH KOREA ID RANDOMIZED CLINICAL-TRIALS; METAANALYSIS; PREVENTION; SCLEROTHERAPY; CIRRHOSIS; PROPHYLAXIS; NADOLOL C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Denver Vet Affairs Hosp, Denver, CO 80262 USA. RP Van Stiegmann, G (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave,Box C-313, Denver, CO 80262 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD AUG PY 2003 VL 35 IS 8 BP S5 EP S8 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 712VQ UT WOS:000184819600026 PM 12929046 ER PT J AU Salinsky, TC Oken, BS Storzbach, T Dodrill, TB AF Salinsky, TC Oken, BS Storzbach, T Dodrill, TB TI Assessment of CNS effects of antiepileptic drugs by using quantitative EEG measures SO EPILEPSIA LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Epilepsy-Society CY DEC 03-05, 2001 CL PHILADELPHIA, PENNSYLVANIA SP Amer Epilepsy Soc DE antiepileptic drugs; electroencephalography; cognition; epilepsy ID EPILEPTIC PATIENTS; HEALTHY-ADULTS; CARBAMAZEPINE; PHENYTOIN; LAMOTRIGINE; PERFORMANCE; GABAPENTIN; FREQUENCY; VALPROATE; RELIABILITY AB Purpose: Antiepileptic drugs (AEDs) can be associated with adverse neurologic effects including cognitive dysfunction. Objective methods for recognizing AED effects on the brain could be valuable for long-term management. We compared quantitative EEG measures and cognitive tests in a group of patients beginning or ending AED therapy. Methods: Subjects included 20 patients beginning AED therapy (AEDon), 12 patients stopping AED therapy (AEDoff), 33 patient controls receiving stable AED therapy (AEDco), and 73 healthy controls (Nco). All subjects underwent structured EEG recording and a cognitive test battery before change in AED dose and again 12-16 weeks later, greater than or equal to4 weeks after the last dose change. Four occipital EEG measures (peak frequency, median frequency, relative theta and delta power) were analyzed. Cognitive test changes were scored by using test-retest regression equations based on the Nco subjects. Wilcoxon tests were used for two-group comparisons. Results: AEDons had a significant decrease, and AEDoffs, a significant increase in the peak frequency of the EEG rhythm, as compared with controls. Results for median frequency and theta power were similar. Change in the EEG peak frequency correlated with an aggregate cognitive change measure (r(2) = 0.71; p < 0.001), individual cognitive measures, and subjective complaints. Of the combined AEDon/AEDoff patients, 58% exceeded the 95% confidence interval for test-retest change in EEG peak frequency. Conclusions: Quantitative measures derived from the occipital EEG are sensitive to AEDs and correlate with AED-related cognitive effects and subjective complaints. Although this correlation does not indicate a direct relation, quantified EEG may be a practical measure of AED impact on the brain. C1 Oregon Hlth Sci Univ, Epilepsy Ctr, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Washington Univ, Epilepsy Ctr, Seattle, WA USA. RP Salinsky, TC (reprint author), Oregon Hlth Sci Univ, Epilepsy Ctr, 3181 SW Sam Jackson Pk Rd CDW 3, Portland, OR 97239 USA. NR 61 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD AUG PY 2003 VL 44 IS 8 BP 1042 EP 1050 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 708VG UT WOS:000184590000007 ER PT J AU Latini, R Wong, M Masson, S Staszewsky, L Maggioni, AP Anand, IS Cohn, JN AF Latini, R Wong, M Masson, S Staszewsky, L Maggioni, AP Anand, IS Cohn, JN CA Val HeFT Invest TI Brain natriuretic peptide, but not norepinephrine, predicts improvements in left-ventricular structure and function in patients with chronic heart failure enrolled to Val-HeFT SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Ist Ric Farmacol Mario Negri, Cardiovasc Res, Milan, Italy. VA Greater LA Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 34 EP 34 DI 10.1016/S0195-668X(03)93770-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800119 ER PT J AU Hamilton, GA Carroll, DL AF Hamilton, GA Carroll, DL TI Quality of life in implantable cardioverter defibrillator recipients: changes over the first two years after implantable cardioverter-defribrillator SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Univ Oslo, Oslo, Norway. Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 49 EP 49 DI 10.1016/S0195-668X(03)93828-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800177 ER PT J AU Burger, R Wagner, D AF Burger, R Wagner, D TI Soluble P-selectin, a marker of endothelial activation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Univ Basel Hosp, CH-4031 Basel, Switzerland. Ctr Blood Res Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 73 EP 73 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800272 ER PT J AU Wong, M Chiang, Y Glazer, R Cohn, JN AF Wong, M Chiang, Y Glazer, R Cohn, JN CA Val HeFT Investigators TI Signs and symptoms of heart failure as endpoints for assessing therapeutic response: Val-HeFT data SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 146 EP 146 DI 10.1016/S0195-668X(03)94194-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800543 ER PT J AU Takano, M Mac Neill, B Tearney, G Bouma, B DeJoseph, D Jang, IK AF Takano, M Mac Neill, B Tearney, G Bouma, B DeJoseph, D Jang, IK TI In-vivo coronary plaque characterization in diabetic patients by optical coherence tomography: comparison with non-diabetic patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Massachusetts Gen Hosp, Dept Cardiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 152 EP 152 DI 10.1016/S0195-668X(03)94217-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638800566 ER PT J AU Ammer, R Aretz, T Keane, D Ruskin, JN AF Ammer, R Aretz, T Keane, D Ruskin, JN TI Persistent atrial fibrillation induces apoptosis in atrial myocytes via p38 activation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Univ Klinikum Munster, Dept Cardiol, Munster, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 503 EP 503 DI 10.1016/S0195-668X(03)95492-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638801841 ER PT J AU Anand, IS Latini, R Wong, M Masson, S Maggioni, A Hester, A Aknay, N Cohn, JN AF Anand, IS Latini, R Wong, M Masson, S Maggioni, A Hester, A Aknay, N Cohn, JN CA Val HeFT investigators TI Relationship between changes in election fraction, brain natriuretic peptide and norepinephrine over time and the effect of valsartan in Val-HeFT SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 VA Med Ctr, Minneapolis, MN USA. Ist Mario Negri, Milan, Italy. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. Novartia Pharmaceut Corp, E Hanover, NJ USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 531 EP 531 DI 10.1016/S0195-668X(03)95589-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638801938 ER PT J AU Ropers, D Baum, U Anders, K Pohle, K Bautz, W Daniel, WG Achenbach, S AF Ropers, D Baum, U Anders, K Pohle, K Bautz, W Daniel, WG Achenbach, S TI Non-invasive investigation of coronary artery bypass grafts using multi-detector spiral computed tomography with sub-millimeter collimation SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. Univ Erlangen Nurnberg, Dept Diagnost Radiol, Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 568 EP 568 DI 10.1016/S0195-668X(03)95719-8 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638802068 ER PT J AU Nac Neill, B Takano, M DeJoseph, D Yabushita, H Tearney, G Bouam, B Jang, IK AF Nac Neill, B Takano, M DeJoseph, D Yabushita, H Tearney, G Bouam, B Jang, IK TI Stents with open cell design have a higher incidence of tissue prolapse compared to close cell design stents: evaluation by optical coherence tomography SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD AUG-SEP PY 2003 VL 24 SU S BP 638 EP 638 DI 10.1016/S0195-668X(03)95961-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727CM UT WOS:000185638802314 ER PT J AU Torp-Pedersen, C Rask-Madsen, C Gustafsson, I Gustafsson, F Kober, L AF Torp-Pedersen, C Rask-Madsen, C Gustafsson, I Gustafsson, F Kober, L TI Diabetes mellitus and cardiovascular risk: just another risk factor? SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT Meeting on the Mosaic of Cardiovascular Protection: Can We Find the Missing Piece CY NOV 09, 2002 CL VALLENTA, MALTA DE cardiovascular disease; hypertension; myocardial infarction; risk factors; type 2 diabetes mellitus ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; SCANDINAVIAN-SIMVASTATIN-SURVIVAL; END-POINT REDUCTION; ENDOTHELIAL DYSFUNCTION; INHIBITOR TRANDOLAPRIL; LOSARTAN INTERVENTION; CHOLESTEROL LEVELS; SUBGROUP-ANALYSES; RANDOMIZED TRIAL AB Patients with type 2 diabetes are at increased risk of developing cardiovascular disease. Also, individuals with cardiovascular disease have a poorer prognosis if they are diagnosed with type 2 diabetes. The coexistence of these two disorders increases the risk for morbidity and mortality from large- and small-vessel disease. The importance of dysfunctional glucose metabolism is apparent even at the earliest stages of vascular disease, with insulin resistance contributing to or arising from endothelial dysfunction. In the clinical setting, anti hypertensive treatment produces proportionally greater benefits in patients with type 2 diabetes than in non-diabetic individuals, and treatments that lower blood glucose reduce the risk of cardiovascular complications. As more becomes known about the inter-relationship of glycometabolic control and cardiovascular disease, the aetiology, pathology and treatment of the two diseases are becoming increasingly entwined. The present review summarizes the importance of type 2 diabetes in cardiovascular disease and discusses some of the therapeutic implications that arise from newly emerging data. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. C1 Bispebjerg Univ Hosp, Dept Cardiol, DK-2400 Copenhagen, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. Frederiksberg Univ Hosp, DK-2000 Copenhagen, Denmark. Univ Copenhagen Hosp, Rigshosp, Ctr Heart, DK-2100 Copenhagen, Denmark. RP Torp-Pedersen, C (reprint author), Bispebjerg Univ Hosp, Dept Cardiol, DK-2400 Copenhagen, Denmark. RI Torp-Pedersen, Christian/E-5931-2013 NR 39 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD AUG PY 2003 VL 5 IS F BP F26 EP F32 DI 10.1016/S1520-765X(03)90013-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 714UX UT WOS:000184932800005 ER PT J AU Behrens, EM Gadue, P Gong, SY Garrett, S Stein, PL Cohen, PL AF Behrens, EM Gadue, P Gong, SY Garrett, S Stein, PL Cohen, PL TI The mer receptor tyrosine kinase: expression and function suggest a role in innate immunity SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE apoptosis; phagocytosis; kinase; innate immunity; autoimmunity ID ANTIGEN-PRESENTING CELLS; KILLER T-CELLS; APOPTOTIC CELLS; ACTIVATION; PHAGOCYTOSIS; STIMULATION; CLEARANCE; MICE AB The mer receptor tyrosine kinase mediates phagocytosis of apoptotic cells and modulates cytokine production; it is also required for prevention of systemic autoimmune disease. Using a mer-specific antibody, we have confirmed the presence of mer on macrophages and now report its expression on NK cells, NKT cells, and dendritic cells (DC). We found that DC do not require mer for ingestion of apoptotic cells, as DC from mer-deficient mice phagocytose apoptotic cells normally. Mer was observed in splenic sections on cells outside follicular areas, probably representing DC and macrophages. Mer apparently participates in NKT-cell antigen-induced signaling, as NKT cells from mer-deficient mice evinced much lower cytokine production after in vivo alpha-galactosylceramide stimulation; this defect was intrinsic to the mer-deficient NKT cells. Taken together, these studies show mer expression on cells of the innate immune system. Mer, through its binding of lipid antigens, may not only mediate ingestion of apoptotic cells, but also signal events in NK cells, NKT cells, and DC. C1 Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Cohen, PL (reprint author), Univ Penn, 421 Curie Blvd,Room 757, Philadelphia, PA 19104 USA. NR 16 TC 49 Z9 52 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD AUG PY 2003 VL 33 IS 8 BP 2160 EP 2167 DI 10.1002/eji.200324076 PG 8 WC Immunology SC Immunology GA 709WC UT WOS:000184648700012 PM 12884290 ER PT J AU Befort, K Karchewski, L Lanoue, C Woolf, CJ AF Befort, K Karchewski, L Lanoue, C Woolf, CJ TI Selective up-regulation of the growth arrest DNA damage-inducible gene Gadd45 alpha in sensory and motor neurons after peripheral nerve injury SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE activating transcription factor 3; c-jun; dorsal root ganglion; Gadd45; rat; spinal cord ID MESSENGER-RNA EXPRESSION; DORSAL-ROOT GANGLION; P53-REGULATED PROTEIN GADD45; CELL-CYCLE CHECKPOINT; RAT-BRAIN; NEUROPATHIC PAIN; UV-IRRADIATION; SCIATIC-NERVE; AXONAL REGENERATION; ALZHEIMERS-DISEASE AB The growth arrest and DNA damage-inducible gene 45 alpha (Gadd45a) was one of 240 genes found previously by high density oligonucleotide microarray analysis to be regulated in the rat L4 and L5 dorsal root ganglia 3 days after transection of the sciatic nerve (>four-fold up-regulation). The Gadd45a mRNA expression profile investigated by northern blot, RNase protection assay and in situ hybridization in the rat shows negligible constitutive mRNA levels in embryonic, neonatal or adult intact dorsal root ganglia. Within 24 h of a sciatic nerve injury, a very large induction is found that persists for as long as regeneration of injured fibres is prevented by peripheral nerve ligation. When axons are allowed to regrow following sciatic nerve crush injury, Gadd45a expression is terminated at later time points, when levels of other markers of injury return towards normal. Colocalization with activating transcription factor 3-LI and c-jun mRNA implies that all peripherally injured primary sensory and motor neurons express Gadd45a mRNA. Injury to the central axons of dorsal root ganglion neurons produces only a minimal induction of Gadd45a while peripheral inflammation is without effect. Gadd45a is a specific marker of the presence of peripheral axonal injury in adult primary sensory and motor neurons. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Befort, K (reprint author), ULP, CNRS, INSERM, Inst Genet & Biol Mol & Cellulaire,UMR7104, Parc Innovat,1 Rue Laurent Fries BP 10142, F-67404 Illkirch Graffenstaden, CU Strasbourg, France. FU NICHD NIH HHS [HD 3853]; NINDS NIH HHS [NS 38253] NR 91 TC 32 Z9 36 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2003 VL 18 IS 4 BP 911 EP 922 DI 10.1046/j.1460.9568.2003.02827.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 717CZ UT WOS:000185069200019 PM 12925017 ER PT J AU Malecki, MT Klupa, T Moczulski, DK Rogus, JJ AF Malecki, MT Klupa, T Moczulski, DK Rogus, JJ TI The Ala45Thr polymorphism of BETA2/NeuroD1 gene and susceptibility to type 1 diabetes mellitus in Caucasians SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE Type 1 diabetes; BETA2/Neurod1 gene; genetic susceptibility ID NEUROD/BETA2 GENE; CANDIDATE GENES; INSULIN GENE; ASSOCIATION; LINKAGE; JAPANESE; ONSET AB It has recently been shown that mutations in BETA2/NeuroD1 are responsible for the development of type 2 diabetes mellitus (T2DM) in Caucasians. This gene is located near the IDDM7 region and one of its amino acid polymorphisms, Ala45Thr, has been associated with type 1 diabetes (T1DM) in Japanese and Danish populations. The aim of our study is to examine Ala45Thr for its role in T1DM in Caucasians. We used both population-based case-control analysis and family-based transmission/disequilibrium testing (TDT). Genotyping was carried out by the dot-blotting method using P32. Study subjects comprised 202 type 1 diabetes cases (mean age at diagnosis: 11.1 years, mean age at examination: 36.4 years) and 139 controls with normal fasting glucose. For the TDT study, allelic transmission was evaluated in 209 case family trios. The frequency of the Ala45 allele was 70.3% in cases and 62.9% in controls (p = 0.04), and 47.5% of cases were Ala45 homozygotes compared to 36.0% of controls (p = 0.03). The TDT component of the study did not achieve statistical significance. However, given the high frequency of this variant even among controls, exceptionally large data sets are needed to provide adequate power for this approach. Our case-control study suggests that the Ala45 variant of BETA2/NeuroD1 may be associated with T1DM in Caucasians (or in linkage disequilibrium with a causative variant). However, this finding should be confirmed by a much larger family-based study. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Jagiellonian Univ, Coll Med, Dept Metab Dis, Krakow, Poland. L Warynski Silesian Med Acad, Dept Internal Med, Zabrze, Poland. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rogus, JJ (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 20 TC 5 Z9 6 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD AUG PY 2003 VL 111 IS 5 BP 251 EP 254 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 715UU UT WOS:000184991300004 PM 12951629 ER PT J AU Pettus, BJ Bielawski, J Porcelli, AM Reames, DL Johnson, KR Morrow, J Chalfant, CE Obeid, LM Hannun, YA AF Pettus, BJ Bielawski, J Porcelli, AM Reames, DL Johnson, KR Morrow, J Chalfant, CE Obeid, LM Hannun, YA TI The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE(2) production in response to TNF-alpha SO FASEB JOURNAL LA English DT Article DE prostaglandin E-2; inflammation; ceramide; sphingosine; RNA interference; tumor necrosis factor ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; PROGRAMMED CELL-DEATH; FC-GAMMA-RI; EPITHELIAL-CELLS; SPHINGOLIPID METABOLISM; INTESTINAL POLYPOSIS; INHIBITS APOPTOSIS; PHOSPHOLIPASE A(2); ENDOTHELIAL-CELLS AB In this study we addressed the role of sphingolipid metabolism in the inflammatory response. In a L929 fibroblast model, tumor necrosis factor-alpha (TNF) induced prostaglandin E-2 (PGE(2)) production by 4 h and cyclooxygenase-2 (COX-2) induction as early as 2 h. This TNF-induced PGE(2) production was inhibited by NS398, a COX-2 selective inhibitor. GC-MS analysis revealed that only COX-2-generated prostanoids were produced in response to TNF, thus providing further evidence of COX-2 selectivity. As sphingolipids have been implicated in mediating several actions of TNF, their role in COX-2 induction and PGE(2) production was evaluated. Sphingosine-1-phosphate (S1P) induced both COX-2 and PGE(2) in a dose-responsive manner with an apparent ED50 of 100-300 nM. The related sphingolipid sphingosine also induced PGE(2), though with much less efficacy. TNF induced a 3.5-fold increase in sphingosine-1-phosphate levels at 10 min that rapidly returned to baseline by 40 min. Small interfering RNAs (siRNAs) directed against mouse SK1 decreased (typically by 80%) SK1 protein and inhibited TNF-induced SK activity. Treatment of cells with RNAi to SK1 but not SK2 almost completely abolished the ability of TNF to induce COX-2 or generate PGE(2). By contrast, cells treated with RNAi to S1P lyase or S1P phosphatase enhanced COX-2 induction leading to enhanced generation of PGE(2). Treatment with SK1 RNAi also abolished the effects of exogenous sphingosine and ceramide on PGE(2), revealing that the action of sphingosine and ceramide are due to intracellular metabolism into S1P. Collectively, these results provide novel evidence that SK1 and S1P are necessary for TNF to induce COX-2 and PGE(2) production. Based on these findings, this study indicates that SK1 and S1P could be implicated in pathological inflammatory disorders and cancer. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. Univ Bologna, Dept Biol, I-40126 Bologna, Italy. Vanderbilt Univ, Sch Med, Dept Med & Pharmacol, Nashville, TN 37212 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Room 501,Basic Sci Bldg,173 Ashley Ave,POB 250509, Charleston, SC 29425 USA. EM hannun@musc.edu FU NCI NIH HHS [CA87584, CA77839]; NHLBI NIH HHS [HL 07260]; NIDDK NIH HHS [DK48831]; NIGMS NIH HHS [GM08716, GM15431, GM43825, GM62887] NR 58 TC 211 Z9 226 U1 1 U2 7 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 AUG PY 2003 VL 17 IS 11 BP 1411 EP 1421 DI 10.1096/fj.02-1038com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 721YB UT WOS:000185345100033 PM 12890694 ER PT J AU Ellison, MA Hall, JE AF Ellison, MA Hall, JE TI Social stigma and compounded losses: quality-of-life issues for multiple-birth families SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Womens Health Research Conference CY OCT 09, 2002 CL BOSTON, MASSACHUSETTS DE multiple births; infertility; social stigma; qualitative research ID IN-VITRO FERTILIZATION; ASSISTED-REPRODUCTION TECHNIQUES; PRACTICE PATTERNS; OVULATION INDUCTION; UNITED-STATES; PREGNANCY; INACTION; CHILDREN; ADJUSTMENT; TWINS AB Objective: To determine the quality-of-life domains most impacted by multiple births. Design: Focus groups, qualitative research. Setting: Human volunteers in a medical research environment. Patient(s): Forty-three mothers, 29 raising multiple-birth children, 13 raising singletons, identified from random and convenience samples. Intervention(s): None. Main Outcome Measure(s): Maternal self-reports of the psychosocial sequelae of multiple or singleton births, based on qualitative data analysis of transcribed group discussions. Result(s): The quality-of-life domains that were most impacted by raising multiple birth children were social stigma, pregnancy loss, marital satisfaction, children's health, unmet family needs, parenting stress, maternal depression, and the infertility experience. Conclusion(s): Qualitative methods identified two novel quality-of-life domains in iatrogenic multiple birth families: social stigma and compounded losses. An unexpected finding was the potential for increased marital solidification as parents coped with the inordinate stresses of multiple births. As anticipated, children's health, unmet family needs, maternal depression, and parental stress were key areas of concern. In addition, the infertility experience had a lasting impact. These findings are significant, given that at least 38% of all assisted conceptions result in a multiple birth. This study lays the groundwork for further research on the impact of iatrogenic multiple births. (C) 2003 by American Society for Reproductive Medicine. C1 Harvard Univ, Reprod Endocrine Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Ellison, MA (reprint author), Harvard Univ, Reprod Endocrine Unit, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Bartlett Hall Ext 5, Boston, MA 02114 USA. FU NICHD NIH HHS [T32HD07396] NR 51 TC 45 Z9 48 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2003 VL 80 IS 2 BP 405 EP 414 DI 10.1016/S0015-0282(03)00659-0 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 709PZ UT WOS:000184634700029 PM 12909506 ER PT J AU Yang, H Shi, MJ Richardson, A Vijg, J Guo, ZM AF Yang, H Shi, MJ Richardson, A Vijg, J Guo, ZM TI Attenuation of leukocyte-endothelium interaction by antioxidant enzymes SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE catalase; superoxide dismutase; leukocyte adhesion; endothelial cells; free radicals ID HUMAN ATHEROSCLEROTIC PLAQUE; LOW-DENSITY-LIPOPROTEIN; NF-KAPPA-B; SUPEROXIDE-DISMUTASE; NITRIC-OXIDE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TRANSGENIC MICE; DROSOPHILA-MELANOGASTER; CELL-INTERACTIONS AB This report assessed the effect of overexpressing Cu,Zn superoxide dismutase (SOD) and/or catalase on the interaction of mononuclear cells (MNCs) and endothelial cells (ECs). ECs were obtained from the aorta of wild-type mice and transgenic mice overexpressing Cu,ZnSOD and/or catalase. MNCs were obtained from wild-type mice. Treatment of wild-type ECs with CuSO4-oxidized low-density lipoprotein (oxLDL) significantly elevated the expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and increased the adherence of MNCs. Overexpression of Cu,ZnSOD and/or catalase in ECs attenuated the adherence of MNCs and the expression of cell adhesion molecules induced by oxLDL. For example, ECs overexpressing Cu,ZnSOD and/or catalase showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than wild-type ECs. Moreover, ECs overexpressing Cu,ZnSOD and catalase in combination showed significantly less expression of VCAM-1 and ICAM-1 and less number of adherent MNCs than those overexpressing either Cu,ZnSOD or catalase alone. These results suggest that combinational overexpression of Cu,ZnSOD and catalase can reduce the expression of cell adhesion molecules and inhibit the adherence of leukocyte to ECs more efficiently than overexpression of Cu,ZnSOD or catalase alone. (C) 2003 Elsevier Inc. C1 Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37208 USA. Meharry Med Coll, Dept Internal Med, Nashville, TN 37208 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. RP Guo, ZM (reprint author), Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37208 USA. FU NCRR NIH HHS [RR03032]; NIA NIH HHS [P30 AG013319, P03 AG13319] NR 44 TC 25 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2003 VL 35 IS 3 BP 266 EP 276 DI 10.1016/S0891-5849(03)00277-6 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 703NG UT WOS:000184285600005 PM 12885588 ER PT J AU Savidge, TC Pan, WH Newman, P O'Brien, M Anton, PM Pothoulakis, C AF Savidge, TC Pan, WH Newman, P O'Brien, M Anton, PM Pothoulakis, C TI Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine SO GASTROENTEROLOGY LA English DT Article ID EPITHELIAL-CELLS; PSEUDOMEMBRANOUS COLITIS; INVASIVE BACTERIA; XENOGRAFT MODEL; RABBIT ILEUM; INFECTION; PROTECTION; DIARRHEA; INTERLEUKIN-8; EXPRESSION AB Background & Aims: Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis, diseases afflicting millions of people each year. Although C. difficile releases 2 structurally similar exotoxins, toxin A and toxin B, animal experiments suggest that only toxin A mediates diarrhea and enterocolitis. However, toxin A-negative/toxin B-positive strains of C. difficile recently were isolated from patients with antibiotic-associated diarrhea and colitis, indicating that toxin B also may be pathogenic in humans. Methods: Here we used subcutaneously transplanted human intestinal xenografts in immunodeficient mice to generate a chimeric animal model for C. difficile toxin-induced pathology of human intestine. Results: We found that intraluminal toxin B, like equivalent concentrations of toxin A, induced intestinal epithelial cell damage, increased mucosal permeability, stimulated interleukin (IL)-8 synthesis, and caused an acute inflammatory response characterized by neutrophil recruitment and tissue damage. Laser capture microdissection and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that intestinal epithelial cell-specific IL-8 gene expression also was increased significantly after luminal exposure to C. difficile toxins in vivo. Conclusions: We conclude that C. difficile toxin 13, like toxin A, is a potent inflammatory enterotoxin for human intestine. Future therapeutic or vaccine strategies for C. difficile infection therefore need to target both toxins. C1 Massachusetts Gen Hosp, Combined Dept Pediat Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, Lab Dev Gastroenterol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Anat Pathol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA USA. RP Savidge, TC (reprint author), Massachusetts Gen Hosp, Combined Dept Pediat Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, Lab Dev Gastroenterol, 114 16th St, Charlestown, MA 02129 USA. OI O'Brien, Michael J/0000-0003-1124-3537 FU NIDDK NIH HHS [DK33506, DK406561] NR 43 TC 119 Z9 120 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2003 VL 125 IS 2 BP 413 EP 420 DI 10.1016/S0016-5085(03)00902-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 707VU UT WOS:000184531200020 PM 12891543 ER PT J AU Jensen, DM AF Jensen, DM TI Current diagnosis and treatment of severe obscure GI hemorrhage SO GASTROINTESTINAL ENDOSCOPY LA English DT Review ID WIRELESS-CAPSULE ENDOSCOPY; SMALL-BOWEL ENDOSCOPY; PUSH-TYPE ENTEROSCOPY; TERM FOLLOW-UP; INTRAOPERATIVE ENTEROSCOPY; SMALL-INTESTINE; THERAPY; LESIONS; ORIGIN; YIELD C1 VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01-RR00865]; NIDDK NIH HHS [1K24 DK02650, DK41301] NR 63 TC 25 Z9 25 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD AUG PY 2003 VL 58 IS 2 BP 256 EP 266 DI 10.1067/mge.2003.332 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 707VZ UT WOS:000184531700021 PM 12872101 ER PT J AU Deisboeck, TS Wakimoto, H Nestler, U Louis, DN Sehgal, PK Simon, M Chiocca, EA Hochberg, FH AF Deisboeck, TS Wakimoto, H Nestler, U Louis, DN Sehgal, PK Simon, M Chiocca, EA Hochberg, FH TI Development of a novel non-human primate model for preclinical gene vector safety studies. Determining the effects of intracerebral HSV-1 inoculation in the common marmoset: a comparative study SO GENE THERAPY LA English DT Article DE herpes simplex virus-1; intracerebral inoculation; viral encephalitis; non-human primate model; owl monkey; common marmoset ID HERPES-SIMPLEX-VIRUS; AOTUS-TRIVIRGATUS; OWL MONKEY; INFECTIONS; TYPE-1; G207 AB The owl monkey (Aotus trivirgatus) has served as the standard non-human primate model of herpes simplex virus-1 (HSV-1) infection because it is highly susceptible to HSV-1 encephalitis. Owl monkeys, however, are expensive, difficult to obtain, and difficult to maintain in captivity, thus greatly hampering the efficiency of preclinical gene therapy trials for brain tumors using HSV-1-based vectors. We have therefore compared the susceptibility of the common marmoset (Callithrix Jacchus) with the owl monkey in a model of intracerebral inoculation of wildtype HSV-1 F-strain at increasing titers. The common marmosets consistently succumbed earlier to viral encephalitis than the owl monkeys. The histological evaluation of the common marmoset revealed extensive HSV-1 infection with a concomitant yet less marked inflammatory response compared to the owl monkeys. PCR for HSV-1 demonstrated a similar extra-CNS shedding route in both experimental models. Our findings show that the common marmoset is at least as susceptible to intracerebral HSV-infection as the owl monkey and that it can therefore serve as a valid and reliable experimental model for the important preclinical safety tests of HSV-based therapeutic viral vector constructs in the brain. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Neurosurg Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Mol Neurooncol Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, CS Kubik Lab Neuropathol, Charlestown, MA USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Collaborat Res Program, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Primate Pathol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Deisboeck, TS (reprint author), Massachusetts Gen Hosp East 6119, Mol Neurooncol Lab, Neurosurg Serv, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Nestler, Ulf/D-6503-2014 OI Nestler, Ulf/0000-0002-2963-4344 FU NCI NIH HHS [CA69246]; NCRR NIH HHS [P51RR00168-40] NR 15 TC 8 Z9 8 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD AUG PY 2003 VL 10 IS 15 BP 1225 EP 1233 DI 10.1038/sj.gt.3302003 PG 9 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 702CD UT WOS:000184207000004 PM 12858187 ER PT J AU Cortes, ML Bakkenist, CJ Di Maria, MV Kastan, MB Breakefield, XO AF Cortes, ML Bakkenist, CJ Di Maria, MV Kastan, MB Breakefield, XO TI HSV-1 amplicon vector-mediated expression of ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype SO GENE THERAPY LA English DT Article DE HSV-1 amplicon; ataxia-telangiectasia; irradiation; ATM ID SITE-SPECIFIC INTEGRATION; S-PHASE CHECKPOINT; ADENOASSOCIATED VIRUS; IONIZING IRRADIATION; BETA-GALACTOSIDASE; GENOTOXIC STRESS; GENE-EXPRESSION; DNA-DAMAGE; CELLS; PHOSPHORYLATION AB Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and radiation sensitivity. Previous research has shown that it is possible to correct the hereditary deficiency A-T by DNA transfection in cell culture, but the large size of the ATM cDNA (9 kb) limits the use of many vector types for gene replacement. HSV-1 amplicon vectors provide a means to deliver large genes to cells efficiently and without toxicity. In this study, the FLAG-tagged cDNA for human ATM was inserted into an HSV-1 amplicon under control of the CMV promoter (designated as HGC-ATM). FLAG-ATM expression was confirmed in 293T/17 cells and human A-T fibroblasts (GM9607) after transduction, by immunoprecipitation, Western analysis, and immunocytochemistry. Functional recovery was assessed by two independent assays. First, in vitro kinase assay showed that vector-derived ATM in GM9607 cells could successfully phosphorylate wt p53 using recombinant GST-p53(1-101). Second, in A-T cells infected with the HGC-ATM vector, the extent of accumulation in G(2)/M phase at 24 h postirradiation was similar to that observed in cells with wild-type endogenous ATM and lower than that observed in A-T cells infected with a control vector. Thus, these vectors provide a tool to test the feasibility of HSV-amplicons as gene therapy vectors for A - T. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mol Neurogenet Unit, Charlestown, MA 02129 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. RP Massachusetts Gen Hosp E, Dept Neurol, Mol Neurogenet Unit, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. OI Di Maria, Michael/0000-0003-0346-8517 FU NCI NIH HHS [CA21765, CA71387] NR 51 TC 12 Z9 13 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 EI 1476-5462 J9 GENE THER JI Gene Ther. PD AUG PY 2003 VL 10 IS 16 BP 1321 EP 1327 DI 10.1038/sj.gt.3301996 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 705ZT UT WOS:000184427700006 PM 12883528 ER PT J AU Robert, C Klein, C Cheng, G Kogan, A Mulligan, RC von Andrian, UH Kupper, TS AF Robert, C Klein, C Cheng, G Kogan, A Mulligan, RC von Andrian, UH Kupper, TS TI Gene therapy to target dendritic cells from blood to lymph nodes SO GENE THERAPY LA English DT Article DE dendritic cells; peripheral lymph nodes; selectin; retrovirus; targeting; immunotherapy ID ADHESION IN-VIVO; LEUKOCYTE ADHESION; T-CELLS; L-SELECTIN; MIGRATION; MELANOMA; VACCINATION; MECHANISMS; EFFICIENCY; CHEMOKINES AB Peripheral lymph nodes (PLN) are strategic microenvironments where antigen-presenting dendritic cells (DC), loaded with environmental antigens, and naive lymphocytes meet to initiate immune responses. The unique capacity of DC to induce primary immune responses has led to their use in clinical medicine; however, delivering DC to lymph nodes is problematic. Intravenously injected DC cannot access to PLN, while DC injected into tissue migrate inefficiently through lymphatics to PLN. We achieved DC targeting to T-cell areas of PLN by endowing DC with a novel receptor for peripheral node addressin (PNAd), an adhesion molecule present on the lymph node venular endothelium. This novel receptor is a chimeric E/L-selectin (ELS) that, we have previously shown, binds to PNAd. DC were genetically modified by retroviral transduction to express ELS. ELS expression was targeted to tips of microvilli, and mediated rolling of DC on PNAd both in vivo and in vitro. Such genetically engineered DC could extravasate directly from blood through the lymph node endothelium as opposed to nontransduced DC. This study provides evidence that the trafficking of DC can be modified using gene transfer technologies. More efficient delivery of DC to PLN should assist the development of improved vaccination strategies. C1 Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Kupper, TS (reprint author), Harvard Univ, Brigham & Womens Hosp, Skin Dis Res Ctr, Dept Dermatol, Av Louis Pasteur, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [P01 HL 56949, R01 HL54936, R01 HL62524]; NIAID NIH HHS [R01 AI41707, R37 AI25082]; NIAMS NIH HHS [P30 AR42689, R01 AR40124] NR 30 TC 17 Z9 19 U1 1 U2 5 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 AUG PY 2003 VL 10 IS 17 BP 1479 EP 1486 DI 10.1038/sj.gt.3302008 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 708EG UT WOS:000184553700011 PM 12900763 ER PT J AU An, JH Blackwell, TK AF An, JH Blackwell, TK TI SKN-1 links C-elegans mesendodermal specification to a conserved oxidative stress response SO GENES & DEVELOPMENT LA English DT Article DE oxidative stress; C. elegans; SKN-1; mesendoderm; intestine; lifespan ID UBIQUITIN-PROTEASOME PATHWAY; BZIP TRANSCRIPTION FACTOR; CAENORHABDITIS-ELEGANS; LIFE-SPAN; DNA-BINDING; INSULIN-RECEPTOR; GENE; NRF2; MICE; ENDODERM AB During the earliest stages of Caenorhabditis elegans embryogenesis, the transcription factor SKN-1 initiates development of the digestive system and other mesendodermal tissues. Postembryonic SKN-1 functions have not been elucidated. SKN-1 binds to DNA through a unique mechanism, but is distantly related to basic leucine-zipper proteins that orchestrate the major oxidative stress response in vertebrates and yeast. Here we show that despite its distinct mode of target gene recognition, SKN-1 functions similarly to resist oxidative stress in C. elegans. During postembryonic stages, SKN-1 regulates a key Phase II detoxification gene through constitutive and stress-inducible mechanisms in the ASI chemosensory neurons and intestine, respectively. SKN-1 is present in ASI nuclei under normal conditions, and accumulates in intestinal nuclei in response to oxidative stress. skn-1 mutants are sensitive to oxidative stress and have shortened lifespans. SKN-1 represents a connection between developmental specification of the digestive system and one of its most basic functions, resistance to oxidative and xenobiotic stress. This oxidative stress response thus appears to be both widely conserved and ancient, suggesting that the mesendodermal specification role of SKN-1 was predated by its function in these detoxification mechanisms. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM62891, R01 GM062891] NR 59 TC 299 Z9 323 U1 4 U2 29 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 2003 VL 17 IS 15 BP 1882 EP 1893 DI 10.1101/gad.1107803 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 707VX UT WOS:000184531500010 PM 12869585 ER PT J AU Hedrick, SC Sales, AEB Sullivan, JH Gray, SL Tornatore, J Curtis, M Zhou, XHA AF Hedrick, SC Sales, AEB Sullivan, JH Gray, SL Tornatore, J Curtis, M Zhou, XHA TI Resident outcomes of Medicaid-funded community residential care SO GERONTOLOGIST LA English DT Article; Proceedings Paper CT 54th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV, 2001 CL CHICAGO, ILLINOIS SP Gerontol Soc Amer DE long-term care; assisted living; health status ID HOME RESIDENTS; NURSING-HOMES; DEMENTIA; SERVICES; MEMORY AB Purpose: Washington State's initiatives to increase the availability and quality of community residential care presented an opportunity to describe clients entering adult family homes, adult residential care, and assisted living and to identify outcomes of care. Design and Methods: We enrolled 349 residents, 243 informal caregivers, and 299 providers in 219 settings. We conducted interviews at enrollment and 12 months later, and we collected data from state databases. Results: The average resident was a 78 year-old woman reporting dependence in two of six activities of daily living. Residents in adult family homes demonstrated significantly more disability. Seventy-eight percent of residents survived at the 12-month follow-up. In analyses that controlled for differences at enrollment, residents in the three types of settings were very similar in health outcomes at follow-up. Implications: State policies should reflect the wide range of needs of residents seeking care in these settings. Choices among type of setting can be based on the match of needs to individual preferences. C1 VA Puget Sound Hlth Care Syst, HSR&D, Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Calif Dept Hlth Serv, Epidemiol & Evaluat Sect, Maternal & Child Hlth Branch, Sacramento, CA USA. RP Hedrick, SC (reprint author), VA Puget Sound Hlth Care Syst, HSR&D, Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 30 TC 19 Z9 19 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2003 VL 43 IS 4 BP 473 EP 482 PG 10 WC Gerontology SC Geriatrics & Gerontology GA 715JE UT WOS:000184967700004 PM 12937326 ER PT J AU Klibanski, A AF Klibanski, A TI Growth hormone and cardiovascular risk markers SO GROWTH HORMONE & IGF RESEARCH LA English DT Article; Proceedings Paper CT 34th International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism CY OCT 25-26, 2002 CL BUDAPEST, HUNGARY DE C-reactive protein; cardiovascular risk markers; hypopituitarism; growth hormone deficiency; stroke; androgen deficiency ID C-REACTIVE PROTEIN; CORONARY HEART-DISEASE; ANTAGONIST PEGVISOMANT; HYPOPITUITARY ADULTS; PREMATURE MORTALITY; DEFICIENCY; WOMEN; ATHEROSCLEROSIS; HOMOCYSTEINE; MEN AB The association of hypopituitarism and growth hormone (GH) deficiency with increased cardiovascular mortality has become increasingly well established [1,2]. In GH-deficient adults, whether the onset of disease is in childhood or in adult life, a higher prevalence of atherosclerotic plaques and endothelial dysfunction has been described [3-5]. Of note, high-resolution ultrasonography has shown that patients with hypopituitarism have a higher prevalence of premature atherosclerosis even in the absence of clinical symptoms [6]. Specific anatomic abnormalities also have been described in adults with GH deficiency, including an increase in intimal-medial wall thickness [3]. The contribution of specific hormonal factors and prior irradiation to the development of vascular disease remains controversial [7]. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL457B, Boston, MA 02114 USA. NR 30 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD AUG PY 2003 VL 13 SU A BP S109 EP S115 DI 10.1016/S1096-6374(03)00065-0 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 726MZ UT WOS:000185604100022 PM 12914737 ER PT J AU Leidholdt, EM Williams, GE McGuire, EL AF Leidholdt, EM Williams, GE McGuire, EL TI A reassessment of radioactive material security in health care and biomedical research SO HEALTH PHYSICS LA English DT Article DE operational topic; radioactive materials; medical radiation; radiation protection AB The medical facilities of the U.S. Department of Veterans Affairs (VA) use radioactive material for health care and biomedical research. In the past, a single level of security for all radioactive material was generally deemed to be adequate. The events of 11 September 2001 prompted a reassessment of security. Based on site visits to VA facilities possessing a range of radioactive material typically used in health care and biomedical research, the VA National Health Physics Program has compiled recommendations for the security of radioactive material. A primary recommendation is to evaluate radioactive material from a risk perspective and use security measures commensurate with risk. The risk evaluation should consider activity, half-life, exposure rate constant, ALI, ease of removal/portability, and dispersibility. We concluded that current security measures are likely adequate for the risks associated with most nuclear medicine departments and biomedical research laboratories. However, for radioactive material of higher risk, particularly multicurie sources of long half-life, the radiation safely staff should consult with police/security experts to determine if additional security measures are warranted. This focus on risk should help optimize resource allocation. We also recommend that security evaluations consider both physical security and personnel security, training of staff with unescorted access to higher-risk radioactive material emphasize security issues, and disposal of higher-risk material not likely to be used. Finally, we note that the goals of security can be in conflict with hazard awareness and hazard communication. C1 US Dept Vet Affairs, VHA Natl Hlth Phys Program, Little Rock, AR 72114 USA. RP Leidholdt, EM (reprint author), US Dept Vet Affairs, VHA Natl Hlth Phys Program, 115HP-NLR,2200 Ft Roots Dr N, Little Rock, AR 72114 USA. EM edwin.leidholdt@med.va.gov NR 15 TC 4 Z9 4 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD AUG PY 2003 VL 85 IS 2 SU S BP S15 EP S19 DI 10.1097/00004032-200308001-00007 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 703WL UT WOS:000184304900004 PM 12865744 ER PT J AU Spettell, CM Wall, TC Allison, J Calhoun, J Kobylinski, R Fargason, R Kiefe, CI AF Spettell, CM Wall, TC Allison, J Calhoun, J Kobylinski, R Fargason, R Kiefe, CI TI Identifying physician-recognized depression from administrative data: Consequences for quality measurement SO HEALTH SERVICES RESEARCH LA English DT Article DE depression; HEDIS; quality of care; predictive value ID COOPERATIVE CARDIOVASCULAR PROJECT; ACUTE MYOCARDIAL-INFARCTION; PRIMARY-CARE; MEDICARE PATIENTS; MAJOR DEPRESSION; ACHIEVABLE BENCHMARKS; CHRONIC PAIN; OF-CARE; MANAGEMENT; ANTIDEPRESSANTS AB Background. Multiple factors limit identification of patients with depression from administrative data. However, administrative data drives many quality measurement systems, including the Health Plan Employer Data and Information Set (HEDIS(R)). Methods. We investigated two algorithms for identification of physician-recognized depression. The study sample was drawn from primary care physician member panels of a large managed care organization. All members were continuously enrolled between January I and December 31, 1997. Algorithm I required at least two criteria in any combination: (1) an outpatient diagnosis of depression or (2) a pharmacy claim for an antidepressant. Algorithm 2 included the same criteria as algorithm 1, but required a diagnosis of depression for all patients. With algorithm 1, we identified the medical records of a stratified, random subset of patients with and without depression (n = 465). We also identified patients of primary care physicians with a minimum of 10 depressed members by algorithm 1 (n = 32,819) and algorithm 2 (n = 6,837). Results. The sensitivity, specificity, and positive predictive values were: Algorithm 1: 95 percent, 65 percent, 49 percent; Algorithm 2: 52 percent, 88 percent, 60 percent. Compared to algorithm 1, profiles from algorithm 2 revealed higher rates of follow-up visits (43 percent, 55 percent) and appropriate antidepressant dosage acutely (82 percent, 90 percent) and chronically (83 percent, 91 percent) (p < 0.05 for all). Conclusions. Both algorithms had high false positive rates. Denominator construction (algorithm I versus 2) contributed significantly to variability in measured quality. Our findings raise concern about interpreting depression quality reports based upon administrative data. C1 USQA, Aetna Inc, Blue Bell, PA 19422 USA. Univ Alabama, Ctr Outcomes & Effect Res & Educ, Birmingham, AL USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Alabama, Dept Psychiat, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Spettell, CM (reprint author), USQA, Aetna Inc, 980 Jolly Rd,Mailstop U38A, Blue Bell, PA 19422 USA. OI Allison, Jeroan/0000-0003-4472-2112 FU AHRQ HHS [HS1112403, U18 HS009446, HS09446] NR 71 TC 45 Z9 45 U1 3 U2 7 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD AUG PY 2003 VL 38 IS 4 BP 1081 EP 1102 DI 10.1111/1475-6773.00164 PG 22 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 714ZL UT WOS:000184945500007 PM 12968818 ER PT J AU Rosen, HR Prieto, M Casanovas-Taltavull, T Cuervas-Mons, V Guckelberger, O Muiesan, P Strong, RW Bechstein, WO O'Grady, J Zaman, A Chan, B Berenguer, J Williams, R Heaton, N Neuhaus, P AF Rosen, HR Prieto, M Casanovas-Taltavull, T Cuervas-Mons, V Guckelberger, O Muiesan, P Strong, RW Bechstein, WO O'Grady, J Zaman, A Chan, B Berenguer, J Williams, R Heaton, N Neuhaus, P TI Validation and refinement of survival models for liver retransplantation SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 01-05, 2002 CL BOSTON, MA SP Amer Assoc Study Liver Dis ID HEPATIC RETRANSPLANTATION; RESOURCE UTILIZATION; PREDICT SURVIVAL; GRAFT CIRRHOSIS; TRANSPLANTATION; DISEASE; MELD; MORTALITY; EVOLUTION; FAILURE AB Orthotopic liver retransplantation (re-OLT) is highly controversial. The objectives of this study were to determine the validity of a recently developed United Network for Organ Sharing (UNOS) multivariate model using an independent cohort of patients undergoing re-OLT outside the United States, to determine whether incorporation of other variables that were incomplete in the UNOS registry would provide additional prognostic information, to develop new models combining data sets from both cohorts, and to evaluate the validity of the model for end-stage liver disease (MELD) in patients undergoing re-OLT. Two hundred eighty-one adult patients undergoing re-OLT (between 1986 and 1999) at 6 foreign transplant centers comprised the validation cohort. We found good agreement between actual survival and predicted survival in the validation cohort; 1-year patient survival rates in the low-, intermediate-, and high-risk groups (as assigned by the original UNOS model) were 72%, 68%, and 36%, respectively (P < .0001). In the patients for whom the international normalized ratio (INR) of prothrombin time was available, MELD correlated with outcome following re-OLT; the median MELD scores for patients surviving at least 90 days compared with those dying within 90 days were 20.75 versus 25.9, respectively (P = .004). Utilizing both patient cohorts (n = 979), a new model, based on recipient age, total serum bilirubin, creatinine, and interval to re-OLT, was constructed (whole model chi(2) = 105, P < .0001). Using the c-statistic with 30-day, 90-day, 1-year, and 3-year mortality as the end points, the area under the receiver operating characteristic (ROC) curves for 4 different models were compared. In conclusion, prospective validation and use of these models as adjuncts to clinical decision making in the management of patients being considered for re-OLT are warranted. C1 Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Biostat Clin Informat Anal & Decis Support Ctr, Portland, OR USA. Hosp La Fe, E-46009 Valencia, Spain. Ciudad Sanitaria & Univ Bellvitge, Unidad Trasplante Hepat, Barcelona, Spain. Univ Autonoma Madrid, Hosp Puerta Hierro, E-28049 Madrid, Spain. Free Univ Berlin, Klinikum Rudolf Virchow, D-1000 Berlin, Germany. Kings Coll London, London WC2R 2LS, England. Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. UCL, London, England. RP Rosen, HR (reprint author), Portland VA Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp,P3-GI, Portland, OR 97207 USA. EM hugo.rosen@medva.gov OI Muiesan, Paolo/0000-0002-7389-6691; Cuervas-Mons Martinez, Valentin/0000-0003-3086-9463 NR 28 TC 77 Z9 83 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2003 VL 38 IS 2 BP 460 EP 469 DI 10.1053/jhep.2003.50328 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 707VV UT WOS:000184531300022 PM 12883491 ER PT J AU McCluggage, WG Oliva, E Herrington, CS McBride, H Young, RH AF McCluggage, WG Oliva, E Herrington, CS McBride, H Young, RH TI CD10 and calretinin staining of endocervical glandular lesions, endocervical stroma and endometrioid adenocarcinomas of the uterine corpus: CD10 positivity is characteristic of, but not specific for, mesonephric lesions and is not specific for endometrial stroma SO HISTOPATHOLOGY LA English DT Article DE uterus; cervix; mesonephric lesions; adenocarcinoma; immunohistochemistry; CD10; calretinin ID ACUTE LYMPHOBLASTIC-LEUKEMIA; SMOOTH-MUSCLE TUMORS; RENAL-CELL CARCINOMA; DIFFERENTIAL-DIAGNOSIS; EXPRESSION; MARKER; CERVIX; NEOPLASMS; LYMPHOMA; SARCOMA AB Aims: In the female genital tract CD10 has been used to assist in the evaluation of mesenchymal tumours of the uterus and in determining whether endometrial stroma is present. CD10 positivity has also been shown in cervical mesonephric remnants and this antibody has been suggested as a useful immunohistochemical marker of mesonephric lesions in the female genital tract. Calretinin has also been shown to be positive in mesonephric lesions. In this study the specificity of these two antibodies in evaluating cervical and uterine glandular lesions and the value of CD10 in determining whether stroma is endometriotic or not were investigated. Methods and results: Cases of cervical tubo-endometrial metaplasia (TEM) (n=11), microglandular hyperplasia (MGH) (n=10), endometriosis (n=8), mesonephric remnants/hyperplasia (n=12), endocervical adenocarcinoma, usual type (n=15), mucinous variant of minimal deviation adenocarcinoma (MDA) (n=7) and mesonephric adenocarcinoma (n=3) were stained with antibodies against CD10 and calretinin. Nine cases of endometrial adenocarcinoma of endometrioid type were also stained. In all the cervical cases normal endocervical glands were negative with both antibodies except for one case with strong positive luminal staining with CD10. All cases of TEM, MGH and endometriosis were negative with CD10 and calretinin except for focal staining with CD10 in one case each of MGH (cytoplasmic staining) and endometriosis (luminal staining). Most usual endocervical adenocarcinomas were negative with both antibodies, although one exhibited focal cytoplasmic staining with calretinin and five exhibited limited luminal positivity with CD10. All MDAs were negative with both antibodies. Ten of 12 mesonephric remnants/hyperplasia showed luminal positivity with CD10 and one exhibited cytoplasmic and nuclear staining with calretinin. Two of three mesonephric adenocarcinomas showed luminal positivity with CD10 and nuclear and cytoplasmic positivity with calretinin. Seven of nine endometrial adenocarcinomas were positive with CD10 (four cytoplasmic, two membranous and cytoplasmic, one luminal and cytoplasmic) and three with calretinin (two cytoplasmic, one nuclear and cytoplasmic). Positive staining of endometriotic stroma with CD10 was present in all endometriosis cases but normal cervical stroma was also strongly positive, especially around glands. Endometriotic stroma and cervical stroma were negative with calretinin. Conclusions: We conclude that most endocervical glandular lesions, including mesonephric remnants/hyperplasia, are negative with calretinin. However, the focal nuclear and cytoplasmic positivity with calretinin in two of three mesonephric adenocarcinomas suggests that this may be a useful indicator of a mesonephric origin of a cervical adenocarcinoma. Most mesonephric remnants/hyperplasias exhibit luminal positivity with CD10, although this is not invariable and staining is usually focal. Positive luminal staining of a benign endocervical glandular lesion with CD10 may help confirm mesonephric remnants. Although positive staining with CD10 was found in two of three mesonephric adenocarcinomas, the observed immunoreactivity of several conventional cervical adenocarcinomas limits the diagnostic value of CD10 in confirming a mesonephric origin for an adenocarcinoma. Since all cervical MDAs were negative with CD10, positivity with this antibody may be of value in distinguishing mesonephric hyperplasia from MDA, although this distinction rarely necessitates immunohistochemistry. Most endometrial adenocarcinomas of endometrioid type stain with CD10 and thus positivity with this antibody is not specific for a mesonephric origin of an endometrial adenocarcinoma. Positivity of normal cervical stroma limits the value of CD10 staining in confirming a diagnosis of cervical endometriosis. C1 Royal Grp Hosp Trust, Dept Pathol, Belfast BT12 6BL, Antrim, North Ireland. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Harvard Med Sch, Boston, MA 02114 USA. Royal Liverpool Univ Hosp, Dept Pathol, Liverpool, Merseyside, England. RP McCluggage, WG (reprint author), Royal Grp Hosp Trust, Dept Pathol, Grosvenor Rd, Belfast BT12 6BL, Antrim, North Ireland. NR 29 TC 78 Z9 80 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD AUG PY 2003 VL 43 IS 2 BP 144 EP 150 DI 10.1046/j.1365-2559.2003.01684.x PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 705HY UT WOS:000184390700005 PM 12877729 ER PT J AU Hamamoto, Y Fujimoto, S Inada, A Takehiro, M Nabe, K Shimono, D Kajikawa, M Fujita, J Yamada, Y Seino, Y AF Hamamoto, Y Fujimoto, S Inada, A Takehiro, M Nabe, K Shimono, D Kajikawa, M Fujita, J Yamada, Y Seino, Y TI Beneficial effect of pretreatment of islets with fibronectin on glucose tolerance after islet transplantation SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE extracellular matrix; cell mass; DNA content; insulin content; insulin secretion ID CELL-MATRIX INTERACTIONS; PANCREATIC BETA-CELLS; EXTRACELLULAR-MATRIX; RAT ISLETS; INSULIN-SECRETION; IN-VITRO; APOPTOSIS; SURVIVAL; LANGERHANS; INTEGRIN AB The scarcity of available islets is an obstacle for clinically successful islet transplantation. One solution might be to increase the efficacy of the limited islets. Isolated islets are exposed to a variety of cellular stressors, and disruption of the cell-matrix connections damages islets. We examined the effect of fibronectin, a major component of the extracellular matrix, on islet viability, mass and function, and also examined whether fibronectin-treated islets improved the results of islet transplantation. Islets cultured with fibronectin for 48 hours maintained higher cell viability (0.146 +/- 0.010 vs. 0.173 +/- 0.007 by MTT assay), and also had a greater insulin and DNA content (86.8 +/- 3.6 vs. 72.8 +/- 3.2 ng/islet and 35.2 +/- 1.4 vs. 30.0 +/- 1.5 ng/islet, respectively) than islets cultured without fibronectin (control). Absolute values of insulin secretion were higher in fibronectin-treat-ed islets than in controls; however, the ratio of stimulated insulin secretion to basal secretion was not significantly different (206.9 +/- 23.3 vs. 191.7 +/- 20.2% when the insulin response to 16.7 mmol/l glucose was compared to that of 3.3 mmol/l glucose); the higher insulin secretion was thus mainly due to larger islet cell mass. The rats transplanted with fibronectin-treated islets had lower plasma glucose and higher plasma insulin levels within 2 weeks after transplantation, and had more favorable glucose tolerance 9 weeks after transplantation. These results indicate that cultivation with fibronectin might preserve islet cell viability, mass and insulin secretory function, which could improve glucose tolerance following islet transplantation. C1 Kyoto Univ, Grad Sch Med, Dept Metab & Clin Nutr, Kyoto, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Hamamoto, Y (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. NR 38 TC 10 Z9 10 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD AUG PY 2003 VL 35 IS 8 BP 460 EP 465 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724AY UT WOS:000185465200002 PM 12953162 ER PT J AU O'Neill, LP Randall, TE Lavender, J Spotswood, HT Lee, JT Turner, BM AF O'Neill, LP Randall, TE Lavender, J Spotswood, HT Lee, JT Turner, BM TI X-linked genes in female embryonic stem cells carry an epigenetic mark prior to the onset of X inactivation SO HUMAN MOLECULAR GENETICS LA English DT Article ID PREIMPLANTATION MOUSE EMBRYOS; HISTONE H4 ACETYLATION; CHROMOSOME INACTIVATION; XIST RNA; DOSAGE COMPENSATION; MUS MUSCULUS; EXPRESSION; H3; METHYLATION; DROSOPHILA AB We use chromatin immunoprecipitation to show that genes on the two active X chromosomes in undifferentiated, XX female embryonic stem cells (ES cells) are marked by hyperacetylation of all core histones, hyper(di)methylation of H3 lysine 4 and hypo(di)methylation of H3 lysine 9, compared with autosomal genes or genes on the single active X in XY male cells. The mark is found on both coding and promoter regions. On differentiation, and after the onset of X inactivation, the mark is reversed on the inactive X, whose genes show extreme hypoacetylation of all four core histones, hypo(di)methylation of H3K4 and hyper(di)methylation of H3K9. The mark is retained on the active X in female ES cells for at least several days of differentiation, but is not present in adult females. The selective marking of X-linked genes in female ES cells in a way that distinguishes them from the equivalent genes in males, is unprecedented. We suggest that the mark forms part of a chromatin-based mechanism that restricts X-inactivation to cells with more than one X chromosome. C1 Univ Birmingham, Sch Med, Dept Anat, Chromatin & Gene Express Grp, Birmingham B15 2TT, W Midlands, England. Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Turner, BM (reprint author), Univ Birmingham, Sch Med, Dept Anat, Chromatin & Gene Express Grp, Birmingham B15 2TT, W Midlands, England. NR 43 TC 23 Z9 24 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2003 VL 12 IS 15 BP 1783 EP 1790 DI 10.1093/hmg/ddg193 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 707WY UT WOS:000184533900001 PM 12874099 ER PT J AU Prettyman, TH Feldman, WC Ameduri, FP Barraclough, BL Cascio, EW Fuller, KR Funsten, HO Lawrence, DJ McKinney, GW Russell, CT Soldner, SA Storms, SA Szeles, C Tokar, RL AF Prettyman, TH Feldman, WC Ameduri, FP Barraclough, BL Cascio, EW Fuller, KR Funsten, HO Lawrence, DJ McKinney, GW Russell, CT Soldner, SA Storms, SA Szeles, C Tokar, RL TI Gamma-ray and neutron spectrometer for the dawn mission to 1 Ceres and 4 Vesta SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article; Proceedings Paper CT Nuclear Science Symposium (NSS)/Symposium on Nuclear Power Systems (SNPS) CY NOV 10-16, 2002 CL NORFOLK, VIRGINIA DE gamma-ray spectroscopy; planets; neutron spectroscopy; semiconductor device radiation effects ID RADIATION-DAMAGE; LUNAR PROSPECTOR; MARS ODYSSEY; DETECTORS; CDZNTE; PERFORMANCE; SPECTRA; SURFACE AB We present the design of the gamma-ray and neutron spectrometer (GR/NS) for Dawn, which is a NASA Discovery-class mission to explore two of the largest main-belt asteroids, 1 Ceres and 4 Vesta, who se accretion is believed to have been interrupted by the early formation of Jupiter. Dawn will determine the composition and structure of these protoplanetary bodies, providing context for a large number of primitive meteorites in our sample collection and a better understanding of processes occurring shortly after the onset of condensation of the solar nebula. The Dawn GR/NS design draws on experience from the successful Lunar Prospector and Mars Odyssey missions to enable accurate mapping of the surface composition and stratigraphy of major elements, radioactive elements, and hydrogen at both asteroids. Here, we describe the overall design of the GR/NS and compare the expected performance of the neutron spectrometer subsystem to the neutron spectrometer on Mars Odyssey. We also describe radiation damage studies carried out on CdZnTe detectors, which will be components of the primary gamma-ray spectrometer on Dawn. We conclude that provisions for annealing at moderate temperatures (40degreesC to 60degreesC) must be made to ensure that the spectrometer will function optimally over the nine-year mission. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Univ Calif Los Angeles, Inst Geophys & Planetary Phys, Los Angeles, CA 90024 USA. eV Prod, Saxonburg, PA 16056 USA. RP Prettyman, TH (reprint author), Los Alamos Natl Lab, POB 1663, Los Alamos, NM 87545 USA. RI Funsten, Herbert/A-5702-2015; Lawrence, David/E-7463-2015; OI Funsten, Herbert/0000-0002-6817-1039; Lawrence, David/0000-0002-7696-6667; Prettyman, Thomas/0000-0003-0072-2831; Russell, Christopher/0000-0003-1639-8298 NR 26 TC 28 Z9 28 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD AUG PY 2003 VL 50 IS 4 BP 1190 EP 1197 DI 10.1109/TNS.2003.815156 PN 1 PG 8 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 712GE UT WOS:000184789000076 ER PT J AU Chi, TH Wan, MM Lee, PP Akashi, K Metzger, D Chambon, P Wilson, CB Crabtree, GR AF Chi, TH Wan, MM Lee, PP Akashi, K Metzger, D Chambon, P Wilson, CB Crabtree, GR TI Sequential roles of Brg, the ATPase subunit of BAF chromatin remodeling complexes, in thymocyte development SO IMMUNITY LA English DT Article ID T-CELL DEVELOPMENT; MAMMALIAN SWI/SNF COMPLEXES; C-MYC EXPRESSION; BETA-CATENIN; PRE-TCR; LYMPHOCYTE DEVELOPMENT; IN-VIVO; RECEPTOR; GENE; DIFFERENTIATION AB T cells develop through distinct stages directed by a series of signals. We explored the roles of SWI/SNF-like BAF chromatin remodeling complexes in this process by progressive deletion of the ATPase subunit, Brg, through successive stages of early T cell development. Brg-deficient cells were blocked at each of the developmental transitions examined. Bcl-xL overexpression suppressed cell death without relieving the developmental blockades, leading to the accumulation of Brg-deleted cells that were unexpectedly cell cycle arrested. These defects resulted partly from the disruptions of pre-TCR and potentially Writ signaling pathways controlling the expression of genes such as c-Kit and c-Myc critical for continued development. Our studies indicate that BAF complexes dynamically remodel chromatin to propel sequential developmental transitions in response to external signals. C1 Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Dev Biol, Stanford, CA 94305 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. CU Strasbourg, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Crabtree, GR (reprint author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Pathol, Stanford, CA 94305 USA. FU NCI NIH HHS [CA39612]; NICHD NIH HHS [HD39454] NR 53 TC 108 Z9 111 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2003 VL 19 IS 2 BP 169 EP 182 DI 10.1016/S1074-7613(03)00199-7 PG 14 WC Immunology SC Immunology GA 714TF UT WOS:000184929000005 PM 12932351 ER PT J AU Mills, KD Ferguson, DO Alt, FW AF Mills, KD Ferguson, DO Alt, FW TI The role of DNA breaks in genomic instability and tumorigenesis SO IMMUNOLOGICAL REVIEWS LA English DT Review ID DEPENDENT PROTEIN-KINASE; DOUBLE-STRAND BREAKS; CLASS-SWITCH RECOMBINATION; ACUTE MYELOID-LEUKEMIA; HEAVY-CHAIN LOCUS; SEVERE COMBINED IMMUNODEFICIENCY; CYTIDINE DEAMINASE AID; B-CELL DEVELOPMENT; REPAIR GENE XRCC3; CHRONIC LYMPHOCYTIC-LEUKEMIA AB DNA double-strand breaks (DSBs) represent dangerous chromosomal lesions that can lead to mutation, neoplastic transformation, or cell death. DSBs can occur by extrinsic insult from environmental sources or may occur intrinsically as a result of cellular metabolism or a genetic program. Mammalian cells possess potent and efficient mechanisms to repair DSBs, and thus complete normal development as well as mitigate oncogenic potential and prevent cell death. When DSB repair (DSBR) fails, chromosomal instability results and can be associated with tumor formation or progression. Studies of mice deficient in various components of the non-homologous end joining pathway of DSBR have revealed key roles in both the developmental program of B and T lymphocytes as well as in the maintenance of general genome stability. Here, we review the current thinking about DSBs and DSBR in chromosomal instability and tumorigenesis, and we highlight the implications for understanding the karyotypic features associated with human tumors. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Enders Bldg,Mail Stop EN-334,320 Longwood Ave, Boston, MA 02115 USA. NR 198 TC 247 Z9 251 U1 1 U2 9 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 AUG PY 2003 VL 194 IS 1 BP 77 EP 95 DI 10.1034/j.1600-065X.2003.00060.x PG 19 WC Immunology SC Immunology GA 697YF UT WOS:000183970300008 PM 12846809 ER PT J AU Hideshima, T Richardson, P Anderson, KC AF Hideshima, T Richardson, P Anderson, KC TI Novel therapeutic approaches for multiple myeloma SO IMMUNOLOGICAL REVIEWS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; STEM-CELL TRANSPLANTATION; OVERCOMES DRUG-RESISTANCE; ACTIVATED PROTEIN-KINASE; HIGH-DOSE THERAPY; SOLUBLE INTERLEUKIN-6 RECEPTOR; PROTEASOME INHIBITOR PS-341; ALLOGENEIC BONE-MARROW AB Multiple myeloma (MM) affects 15 000 new patients annually in the US, with 50 000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM-host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS-341, can overcome classical drug resistance in preclinical and early clinical studies. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. FU PHS HHS [R0-150947, P0-178378] NR 148 TC 68 Z9 69 U1 0 U2 1 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 AUG PY 2003 VL 194 IS 1 BP 164 EP 176 DI 10.1034/j.1600-065X.2003.00053.x PG 13 WC Immunology SC Immunology GA 697YF UT WOS:000183970300013 PM 12846814 ER PT J AU Maldonado, A Game, BA Song, LX Huang, Y AF Maldonado, A Game, BA Song, LX Huang, Y TI Up-regulation of matrix metalloproteinase-1 expression in U937 cells by low-density lipoprotein-containing immune complexes requires the activator protein-1 and the Ets motifs in the distal and the proximal promoter regions SO IMMUNOLOGY LA English DT Article; Proceedings Paper CT 75th Annual Scientific Session of the American-Heart-Association CY NOV 17-20, 2002 CL CHICAGO, ILLINOIS SP Amer Heart Assoc ID BREAST-CANCER CELLS; OXIDIZED LDL; ATHEROSCLEROTIC PLAQUES; CIRCUMFERENTIAL STRESS; HUMAN MACROPHAGES; GENE-EXPRESSION; COLLAGENASE; RECEPTOR; TRANSCRIPTION; MECHANISMS AB We reported previously that low-density lipoprotein (LDL)-containing immune complexes (LDL-IC) stimulated matrix metalloproteinase-1 (MMP-1) expression in U937 histiocytes through Fc gamma receptor (FcgammaR)-mediated extracellular signal-regulated kinase pathway. The present study has explored the transcriptional mechanisms involved in the stimulation. Deletion analysis showed that LDL-IC stimulated MMP-1 promoter activity in cells transfected with the Construct 1 that contained a 4,334-bp MMP-1 promoter fragment, but had no effect in cells transfected with other constructs that had shorter MMP-1 promoter (2685-bp or less), suggesting that cis-acting elements located between -4334 and -2685 are required for the promoter stimulation. The mutation study further indicated that the activator protein-1 (AP-1) (-3471) or Ets (-3836) motifs in this distal region were essential for the LDL-IC-stimulated MMP-1 expression. Moreover, although above deletion analysis showed that LDL-IC did not stimulate MMP-1 promoter activity in cells transfected with constructs that contained the proximal AP-1 (-72) and Ets (-88) in the promoter fragments that are 2685-bp or less, the mutations of the -72 AP-1 or the -88 Ets motif in the construct 1 abolished the stimulation of MMP-1 expression by LDL-IC, suggesting that a long promoter sequence is required for the -72 AP-1 and -88 Ets motifs to be involved in the stimulation. Finally, electrophoretic mobility shift assay showed that LDL-IC stimulated the activities of transcription factors AP-1 and Ets. In conclusion, the present study shows that both the distal and proximal AP-1 and Ets motifs are required for LDL-IC-stimulated MMP-1 expression in U937 histiocytes. C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. NR 27 TC 7 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD AUG PY 2003 VL 109 IS 4 BP 572 EP 579 DI 10.1046/j.1365-2567.2003.01694.x PG 8 WC Immunology SC Immunology GA 710PM UT WOS:000184688700014 PM 12871225 ER PT J AU Qadri, F Ryan, ET Faruque, ASG Ahmed, F Khan, AI Islam, MM Akramuzzaman, SM Sack, DA Calderwood, SB AF Qadri, F Ryan, ET Faruque, ASG Ahmed, F Khan, AI Islam, MM Akramuzzaman, SM Sack, DA Calderwood, SB TI Antigen-specific immunoglobulin A antibodies secreted from circulating B cells are an effective marker for recent local immune responses in patients with cholera: Comparison to antibody-secreting cell responses and other immunological markers SO INFECTION AND IMMUNITY LA English DT Article ID MANNOSE-SENSITIVE HEMAGGLUTININ; HELICOBACTER-PYLORI UREASE; VIBRIO-CHOLERAE; ADULT VOLUNTEERS; VECTOR STRAINS; IN-VITRO; VACCINE; O139; IMMUNOGENICITY; LYMPHOCYTES AB Gut-derived lymphocytes transiently migrate through the peripheral circulation before homing back to mucosal sites and can be detected using an ELISPOT-based antibody secreting cell (ASC) assay. Alternatively, transiently circulating lymphocytes may be cultured in vitro, and culture supernatants may be assayed for antigen-specific responses (antibody in lymphocyte supernatant [ALS] assay). The ALS assay has not been validated extensively in natural mucosal infection, nor has the ALS response been compared to the ASC assay and other cholera-specific immunological responses. Accordingly, we examined immune responses in 30 adult patients with acute cholera in Bangladesh, compared with 10 healthy controls, measuring ALS-immunoglobulin A (IgA), ASC-IgA, and serum and fecal IgA responses to two potent Vibrio cholerae immunogens, the nontoxic B subunit of cholera toxin (CtxB) and lipopolysaccharide (LPS) and a weaker V. cholerae immunogen, the mannose-sensitive hemagglutinin (MSHA). We found significant increases of anti-CtxB, anti-LPS, and anti-MSHA IgA in supernatants of lymphocytes cultured 7 days after onset of cholera using the ALS assay. We found that ALS and ASC responses correlated extremely well; both had comparable sensitivities as the vibriocidal responses, and both procedures were more sensitive than fecal IgA measurements. An advantage of the ALS assay for studying mucosal immune responses is the ability to freeze antibodies in supernatants for subsequent evaluation; like the ASC assay, the ALS assay can distinguish recent from remote mucosal infection, a distinction that may be difficult to make in endemic settings using other procedures. C1 Int Ctr Diarrhoeal Dis Res, Ctr Hlth & Populat Res, Dhaka 1212, Bangladesh. Massachusetts Gen Hosp, Trop & Geog Med Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Qadri, F (reprint author), ICDDR B, Div Sci Lab, GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org FU FIC NIH HHS [D43 TW05572, D43 TW005572]; NIAID NIH HHS [AI40725, R01 AI040725]; NICHD NIH HHS [U01 HD039165, HD39165] NR 22 TC 53 Z9 57 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2003 VL 71 IS 8 BP 4808 EP 4814 DI 10.1128/IAI.71.8.4808-4814.2003 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 705JV UT WOS:000184392700069 PM 12874365 ER PT J AU Taneja, A Trehan, M Taylor, CR AF Taneja, A Trehan, M Taylor, CR TI 308-nm excimer laser for the treatment of localized vitiligo SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the Photomedicine-Society CY MAR 01, 2001 CL WASHINGTON, D.C. SP Photomed Soc ID REPIGMENTATION; PHOTOTHERAPY AB Background and Objective Vitiligo is commonly treated with PUVA, and more recently, narrow-band UVB (NBUVB) phototherapy. Given the proximity of the wavelengths of NBUVB (311 nm) and the excimer laser (308 nm), we undertook a clinical trial to test the efficacy of this device. Methods Twice-weekly 308-nm UV-B radiation was given to selected vitiligo lesions for a maximum of 60 treatments. These lesions had been unsuccessfully treated previously with at least one other method of treatment. Initial doses were 100 mJ/cm(2) with increments of 10-25%. Improvement was assessed on a visual scale via serial photographs. Results Subjects tolerated the treatment well. Improvement varied with body site. After 60 treatments, lesions on the hands and feet showed grade 2 improvement in 2/10 subjects and grade 1 in 8/10. For the axillae, there was grade 4 improvement in 1/3 subjects and grade 2 improvement in 2/3 by treatment 60. The face demonstrated the most rapid repigmentation with grade 4 repigmentation seen in 3/5 subjects by 40 treatments and grade 3 in 2/5 by 30 treatments. There were no adverse effects. Conclusions The user-friendly 308-nm excimer laser allows targeted treatments of localized vitiligo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. RP Trehan, M (reprint author), Bar 414,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 52 Z9 63 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD AUG PY 2003 VL 42 IS 8 BP 658 EP 662 DI 10.1046/j.1365-4362.2003.01997.x PG 5 WC Dermatology SC Dermatology GA 706RU UT WOS:000184468500020 PM 12890118 ER PT J AU Halpern, SD Asch, DA AF Halpern, SD Asch, DA TI Commentary: Improving response rates to mailed surveys: what do we learn from randomized controlled trials? SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID PHYSICIAN RESPONSE; QUESTIONNAIRES; INCENTIVES; SIZE C1 Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity & Promot, Philadelphia, PA USA. RP Asch, DA (reprint author), Univ Penn, Leonard Davis Inst Hlth Econ, 3641 Locust Walk, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 13 TC 16 Z9 17 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2003 VL 32 IS 4 BP 637 EP 638 DI 10.1093/ije/dyg184 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 712ED UT WOS:000184783500033 PM 12913043 ER PT J AU Chauhan, D Hideshima, T Anderson, KC AF Chauhan, D Hideshima, T Anderson, KC TI Apoptotic signaling in multiple myeloma: Therapeutic implications SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article DE multiple myeloma; apoptotic signaling; drug resistance ID MARROW STROMAL CELLS; FACTOR-KAPPA-B; MITOCHONDRIA-DERIVED ACTIVATOR; FARNESYL TRANSFERASE INHIBITOR; RESISTANT MYELOMA; CHROMATIN CONDENSATION; RETINOBLASTOMA PROTEIN; CASPASE ACTIVATION; MOLECULAR SEQUELAE; MEDIATED APOPTOSIS AB Fifteen thousand new cases of multiple myeloma (MM) will occur in the United States in 2003, and the disease remains incurable. Diverse classes of chemotherapeutic agents induce cell death or apoptosis, in MM cells; however, prolonged drug exposures ultimately induce chemoresistance. The mechanisms whereby MM cells resist drugs include alterations in intracellular signaling as well as adherence and cytokines in the bone marrow (BM) microenvironment. Novel agents that target the MM cell in its BM microenvironment are needed to both enhance anti-MM activity and prevent development of drug resistance. Delineation of cellular growth and apoptotic signaling pathways in MM cells may identify molecules that serve as novel therapeutic targets on the basis of interruption of MM cell growth or triggering of MM cell death. (C) 2003 The Japanese Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 78373]; PHS HHS [50947] NR 67 TC 17 Z9 17 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD AUG PY 2003 VL 78 IS 2 BP 114 EP 120 DI 10.1007/BF02983378 PG 7 WC Hematology SC Hematology GA 715NM UT WOS:000184978700003 PM 12953804 ER PT J AU Razzaque, MS Ahmed, BS Foster, CS Ahmed, AR AF Razzaque, MS Ahmed, BS Foster, CS Ahmed, AR TI Effects of IL-4 on conjunctival fibroblasts: Possible role in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID COLLAGEN-BINDING HEAT-SHOCK-PROTEIN-47; MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; INTERLEUKIN-4 TRANSGENIC MICE; COLONY-STIMULATING FACTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; MACROPHAGE PROLIFERATION; INCREASED EXPRESSION; PULMONARY-FIBROSIS; MOLECULAR EVENTS; IGA NEPHROPATHY AB PURPOSE. Increased stromal accumulation of macrophages and submucosal fibrosis due to excessive accumulation of collagens are central histologic features in ocular cicatricial pemphigoid (OCP). Interleukin (IL)-4 plays an important role in both the inflammatory and fibrotic events in several human and experimental diseases. In the present study, the possible role of IL-4 in the pathogenesis of OCP was investigated. METHODS. Biopsy specimens from the conjunctivae of 10 patients with OCP and 5 normal subjects were studied for the expression of IL-4 by immunohistochemistry. The expression level of IL-4 was also examined in conjunctival fibroblasts of normal control subjects and patients with OCP. The effects of IL-4 in the induction of inflammatory and fibrogenic molecules was studied in IL-4-treated conjunctival fibroblasts, and the expression levels of macrophage colony-stimulating factor (m-CSF), heat shock protein (HSP)-47 and type I Collagen was determined by quantitative real-time PCR. The level of IL-4 was also measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from patients with OCP during active stage and remission and were compared with the levels in control sera. RESULTS. Compared with the weak expression of IL-4 in the normal conjunctival sections, an increased expression of IL-4 was noted in conjunctival sections of patients with OCP. A similar increase in the expression of IL-4 was also detected in fibroblasts isolated from conjunctiva of patients with OCP, compared with control fibroblasts. Real-time PCR and ELISA detected a significantly increased level of m-CSF, at both the mRNA and protein levels in IL-4-stimulated cells. Similarly, IL-4 treatment resulted in the induction of type I Collagen and collagen-binding HSP47 by conjunctival fibroblasts, as detected by real-time PCR. However, no apparent changes in the levels of IL-4 were detected by ELISA in serum samples of patients with OCP and control subjects. CONCLUSIONS. Increased conjunctival expression of IL-4 may play an important role in the regulation of local accumulation of macrophages (by inducing m-CSF), and matrix accumulation (by inducing HSP47 and Collagen) during conjunctival scarring in patients with OCP. 114, therefore, may augment or enhance both conjunctival inflammatory and subsequent fibrotic re-sponses in patients with OCP. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol Immunol & Uveitis Serv, Boston, MA USA. RP Razzaque, MS (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY08379] NR 46 TC 16 Z9 17 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2003 VL 44 IS 8 BP 3417 EP 3423 DI 10.1167/iovs.02-1084 PG 7 WC Ophthalmology SC Ophthalmology GA 705EV UT WOS:000184383500024 PM 12882790 ER PT J AU Jensen, RJ Rizzo, JF Ziv, OR Grumet, A Wyatt, J AF Jensen, RJ Rizzo, JF Ziv, OR Grumet, A Wyatt, J TI Thresholds for activation of rabbit retinal, ganglion cells with an ultrafine, extracellular microelectrode SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ELECTRICAL-STIMULATION; RETINITIS-PIGMENTOSA; MORPHOMETRIC ANALYSIS; INNER RETINA; PHOTORECEPTORS; ABNORMALITIES; PRESERVATION; EXCITATION; ELECTRODES; NEURONS AB PURPOSE. To determine electrical thresholds required for extracellular activation of retinal ganglion cells as part of a project to develop an epiretinal prosthesis. METHODS. Retinal ganglion cells were recorded extracellularly in retinas isolated from adult New Zealand White rabbits. Electrical current pulses of 100-mus duration were delivered to the inner surface of the retina from a 5-mum long electrode. In about half of the cells, the point of lowest threshold was found by searching with anodal current pulses; in the other cells, cathodal current pulses were used. RESULTS. Threshold measurements were obtained near the cell bodies of 20 ganglion cells and near the axons of 19 ganglion cells. Both cathodal and anodal stimuli evoked a neural response in the ganglion cells that consisted of a single action potential of near-constant latency that persisted when retinal synaptic transmission was blocked with cadmium chloride. For cell bodies, but not axons, thresholds for both cathodal and anodal stimulation were dependent on the search method used to find the point of lowest threshold. With search and stimulation of matching polarity, cathodal stimuli evoked a ganglion cell response at lower currents (approximately one seventh to one tenth axonal threshold) than did anodal stimuli for both cell bodies and axons. With cathodal search and stimulation, cell body median thresholds were somewhat lower (approximately one halt) than the axonal median thresholds. With anodal search and stimulation, cell body median thresholds were approximately the same as axonal median thresholds. CONCLUSIONS. The results suggest that cathodal stimulation should produce lower thresholds, more localized stimulation, and somewhat better selectivity for cell bodies over axons than would anodal stimulation. C1 VA Med Ctr, Ctr Innovat Visual Rehabil, Boston, MA 02130 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Jensen, RJ (reprint author), VA Med Ctr, Ctr Innovat Visual Rehabil, Mail Stop 151E,150 S Huntington Ave, Boston, MA 02130 USA. NR 28 TC 100 Z9 101 U1 0 U2 5 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2003 VL 44 IS 8 BP 3533 EP 3543 DI 10.1167/iovs.02-1041 PG 11 WC Ophthalmology SC Ophthalmology GA 705EV UT WOS:000184383500038 PM 12882804 ER PT J AU Conigliaro, J Gordon, AJ McGinnis, KA Rabeneck, L Justice, AC AF Conigliaro, J Gordon, AJ McGinnis, KA Rabeneck, L Justice, AC CA Veterans Aging Cohort 3 Site Study TI How harmful is hazardous alcohol use and abuse in HIV infection: Do health care providers know who is at risk? SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE alcohol; AUDIT; binge drinking; HIV; AIDS; CD4 cell count; HIV-1 load; aspartate transaminase ID PROBLEM DRINKING; DISORDERS; QUESTIONS; ADHERENCE; VETERANS; DRINKERS; AUDIT AB We conducted a prospective cohort study to describe the association between alcohol use, HIV disease progression, and drug toxicity and to determine health care provider awareness of excessive alcohol use by recruiting 881 HIV-infected veterans (median age, 49 years; 99% male; 54% African American) from 3 VA HIV clinics. Twenty percent of patients were hazardous drinkers by the Alcohol Use Disorders Identification Test, 33% were binge drinkers, 32% had a chart ICD-9 alcohol diagnosis, and 12.5% and 66.7%, respectively, were described by their health care providers, as currently and ever drinking "too much." Hazardous/binge drinkers more often had detectable viral loads (P < 0.001). Patients with alcohol diagnoses more often had elevated alanine transaminase or aspartate transaminase levels (P < 0.02), anemia (P < 0.001), and elevated mean corpuscular volume (P < 0.001). Health care providers missed hazardous drinking in patients with undetectable viral loads (P = 0.01), patients without hepatitis C (P = 0.09), and patients with normal aspartate transaminase levels (P = 0.07) and missed alcohol diagnoses in patients without hepatitis and those with CD4 cell counts of >200/mL. We conclude that in HIV-positive veterans, hazardous drinking and alcohol diagnoses were common and associated with HIV disease progression and/or hepatic comorbidity and anemia. Health care providers more often missed alcohol problems in patients with less severe HIV infection and those without evidence of liver disease. Health care providers should routinely screen and counsel patients regarding alcohol problems as part of standard of care to minimize disease progression and bone marrow and hepatic toxicity. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Toronto, Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. RP Justice, AC (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,130-VACS, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [AG00826-03]; NIAAA NIH HHS [U01 AA 13566-02] NR 17 TC 77 Z9 78 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2003 VL 33 IS 4 BP 521 EP 525 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 703LA UT WOS:000184279800014 PM 12869842 ER PT J AU Chen, LX Eberhardt, R Enzenauer, RJ Horwitz, HM Luk, AJ Melnicoff, I Pepmuellar, PH Queen, KT Ramanujam, B Straka, PC Svara, C Travers, R Wallace, D Watanabe, W Weiss, T Schumacher, HR AF Chen, LX Eberhardt, R Enzenauer, RJ Horwitz, HM Luk, AJ Melnicoff, I Pepmuellar, PH Queen, KT Ramanujam, B Straka, PC Svara, C Travers, R Wallace, D Watanabe, W Weiss, T Schumacher, HR TI A look at rheumatology in China (2002) SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Editorial Material AB This report describes a visit by an international group interested in Rheumatology to the Rheumatology centers And traditional Chinese medicine units in the People's Republic of China. Differing disease patterns and treatment approaches offer opportunities for studies and collaborations. We can also learn from the traditional Chinese approach with individualization of therapy and attention to health maintenance. C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Presbyterian Med Ctr, Philadelphia, PA 19104 USA. Sheboygan Clin, Sheboygan, WI USA. Univ Tennessee, Coll Med, Ooltewah, TN USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Providence, RI 02912 USA. Univ Washington, Seattle, WA 98195 USA. VA Med Ctr, Seattle, WA USA. N Suburban Rheumatol Ltd, Des Plaines, IL USA. Lutheran Gen Advocate Hosp, Des Plaines, IL USA. St Louis Univ, St Louis, MO 63103 USA. Mt Med Associates, Waynesville, NC USA. Solo Practice, Santa Cruz, CA USA. Ctr DeReumatol DYK SA, Quito, Ecuador. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Raleigh Rheumatol Consultants, Raleigh, NC USA. Western Hosp, Melbourne, Vic, Australia. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Akita Univ, Sch Med, Akita 010, Japan. Arthrit Consultants Inc, St Louis, MO USA. RP Schumacher, HR (reprint author), Philadelphia VA Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 0 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2003 VL 9 IS 4 BP 228 EP 238 DI 10.1097/01.rhu.0000082156.86721.d8 PG 11 WC Rheumatology SC Rheumatology GA 758QC UT WOS:000187660800004 PM 17041463 ER PT J AU Sawalha, AH Lutz, BD Chaudhary, NA Kern, W Harley, JB Greenfield, RA AF Sawalha, AH Lutz, BD Chaudhary, NA Kern, W Harley, JB Greenfield, RA TI Panniculitis - A presenting manifestation of disseminated histoplasmosis in a patient with rheumatoid arthritis SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Article DE panniculitis; histoplasmosis; rheumatoid arthritis; infliximab ID IMMUNOSUPPRESSIVE THERAPY; INFLIXIMAB AB We report a case of histoplasma panniculitis in a patient with rheumatoid arthritis treated with multiple immunosuppressive agents including infliximab. The patient presented with erythematous, plaques involving the right upper anterior abdominal wall, the right flank and later extension to involve the left flank and the left axilla. The histopathologic examination of these lesions was consistent with lobular panniculitis and the cultures of these lesions and blood grew Histoplasma capsulatum. The clinical and histopathologic picture of histoplasma panniculitis and rheumatoid arthritis-associated panniculitis can be very similar, but the treatment is clearly different. Our case emphasizes the importance of considering rare manifestations of opportunistic infections in an era of widespread use of immunosuppressive medications in the field of rheumatology. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. RP Sawalha, AH (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Med, 825 NE 13th St,OMRF,Mail Stop 24, Oklahoma City, OK 73104 USA. NR 14 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD AUG PY 2003 VL 9 IS 4 BP 259 EP 262 DI 10.1097/01.rhu.0000083606.71931.79 PG 4 WC Rheumatology SC Rheumatology GA 758QC UT WOS:000187660800008 PM 17041467 ER PT J AU Bragdon, CR Jasty, M Muratoglu, OK O'Connor, DO Harris, WH AF Bragdon, CR Jasty, M Muratoglu, OK O'Connor, DO Harris, WH TI Third-body wear of highly cross-linked polyethylene in a hip simulator SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; polyethylene; crosslink; third-body; wear ID MOLECULAR-WEIGHT POLYETHYLENE; ACETABULAR CUPS; PROSTHESES; ARTHROPLASTY; DEBRIS AB The wear performance of a radiation cross-linked melted ultrahigh-molecular-weight polyethylene (UHMWPE) articulating against 28-mm cobalt chrome femoral heads in the presence of third-body particulate debris was investigated in a hip simulator and compared with the wear of conventional UHMWPE. Particles of aluminum oxide or bone cement containing barium sulfate were added to the serum. in the presence of aluminum oxide particles, the incremental wear rates of conventional UHMWPE averaged as high as 149 +/- 116 mg/million cycles compared with 37 +/- 38 mg/million cycles for the highly cross-linked components. The difference in the average weight loss was statistically significant at P < .01. With bone cement particles, the conventional UHMWPE components had an average incremental wear rate of 19 +/- 5mg/million cycles, and the wear rate of the highly cross-linked UHMWPE components was 0.5 +/- 0.7 mg/million cycles. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson Bldg 1126,Fruit St, Boston, MA 02114 USA. NR 26 TC 64 Z9 67 U1 1 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD AUG PY 2003 VL 18 IS 5 BP 553 EP 561 DI 10.1016/S0883-5403(03)00146-3 PG 9 WC Orthopedics SC Orthopedics GA 714GT UT WOS:000184905300003 PM 12934205 ER PT J AU Xing, YQ Musi, N Fujii, N Zou, LQ Luptak, I Hirshman, MF Goodyear, LJ Tian, R AF Xing, YQ Musi, N Fujii, N Zou, LQ Luptak, I Hirshman, MF Goodyear, LJ Tian, R TI Glucose metabolism and energy homeostasis in mouse hearts overexpressing dominant negative alpha 2 subunit of AMP-activated protein kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE; RAT-HEART; ISCHEMIA; GLYCOLYSIS; TRANSPORT; PHOSPHORYLATION; CONTRACTION; STIMULATION; SUBFAMILY; EXERCISE AB AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that plays a pivotal role in regulating cellular metabolism for sustaining energy homeostasis under stress conditions. Activation of AMPK has been observed in the heart during acute and chronic stresses, but its functional role has not been completely understood because of the lack of effective activators and inhibitors of this kinase in the heart. We generated transgenic mice (TG) with cardiac-specific overexpression of a dominant negative mutant of the AMPK alpha2 catalytic subunit to clarify the functional role of this kinase in myocardial ischemia. In isolated perfused hearts subjected to a 10-min ischemia, AMPK alpha2 activity in wild type (WT) increased substantially ( by 4.5-fold), whereas AMPK alpha2 activity in TG was similar to the level of WT at base line. Basal AMPK alpha1 activity was unchanged in TG and increased normally during ischemia. Ischemia stimulated a 2.5-fold increase in 2-deoxyglucose uptake over base line in WT, whereas the inactivation of AMPK alpha2 in TG significantly blunted this response. Using P-31 NMR spectroscopy, we found that ATP depletion was accelerated in TG hearts during no-flow ischemia, and these hearts developed left ventricular dysfunction manifested by an early and more rapid increase in left ventricular end-diastolic pressure. The exacerbated ATP depletion could not be attributed to impaired glycolytic ATP synthesis because TG hearts consumed slightly more glycogen during this period of no-flow ischemia. Thus, AMPK alpha2 is necessary for maintaining myocardial energy homeostasis during ischemia. It is likely that the functional role of AMPK in myocardial energy metabolism resides both in energy supply and utilization. C1 Brigham & Womens Hosp, Nucl Magnet Resonance Lab Physiol Chem, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Joslin Diabet Ctr, Dept Med, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tian, R (reprint author), NMR Lab Physiol Chem, 221 Longwood Ave,Rm 252, Boston, MA 02115 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 34 TC 148 Z9 160 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 AUG 1 PY 2003 VL 278 IS 31 BP 28372 EP 28377 DI 10.1074/jbc.M303521200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 705XC UT WOS:000184421100005 PM 12766162 ER PT J AU Wei, XL Yu, ZK Ramalingam, A Grossman, SR Yu, JH Bloch, DB Maki, CG AF Wei, XL Yu, ZK Ramalingam, A Grossman, SR Yu, JH Bloch, DB Maki, CG TI Physical and functional interactions between PML and MDM2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; NUCLEAR-BODY FORMATION; RING-FINGER DOMAIN; PROTEIN PML; RAR-ALPHA; PREMATURE SENESCENCE; ONCOGENIC RAS; P53; BODIES; BINDING AB The tumor suppressor protein PML and oncoprotein MDM2 have opposing effects on p53. PML stimulates p53 activity by recruiting it to nuclear foci termed PML nuclear bodies. In contrast, MDM2 inhibits p53 by promoting its degradation. To date, neither a physical nor functional relationship between PML and MDM2 has been described. In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent of p53. Two separate regions of PML are recognized which can interact with MDM2. The C-terminal half of PML, encoded by residues 300 - 633, can interact with the central region of MDM2 which includes the MDM2 acidic domain. In addition, PML amino acids 1 - 200, which encode the RING-finger and most of the B box zinc binding motifs, can interact with the C-terminal, RING-finger containing region of MDM2. Interestingly, PML mutants in which sumoylation at lysine 160 was inhibited displayed an increased association with MDM2, suggesting that sumoylation at this site may be a determinant of PML-MDM2 binding. Coexpression with MDM2 caused a redistribution of PML from the nucleus to the cytoplasm, and this required the PML N terminus and the MDM2 RING-finger domain. These results suggest that interaction between the PML N terminus and MDM2 C terminus can promote PML nuclear exclusion. Wild-type MDM2 inhibited the ability of PML to stimulate the transcriptional activity of a GAL4-CBP fusion protein. This inhibition required the central, acidic region of MDM2, but did not require the MDM2 C terminus. Taken together, these studies demonstrate that MDM2 and PML can interact through at least two separate protein regions, and that these interactions can have specific effects on the activity and/or localization of PML. C1 Univ Chicago, Dept Radiat Oncol, Chicago, IL 60637 USA. Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Maki, CG (reprint author), Univ Chicago, Dept Radiat Oncol, 5841 S Maryland Ave,MC 1105,Room G-06, Chicago, IL 60637 USA. FU NCI NIH HHS [1R01CA80918-01] NR 47 TC 51 Z9 55 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 AUG 1 PY 2003 VL 278 IS 31 BP 29288 EP 29297 DI 10.1074/jbc.M212215200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 705XC UT WOS:000184421100114 PM 12759344 ER PT J AU Hung, CC Ichimura, T Stevens, JL Bonventre, JV AF Hung, CC Ichimura, T Stevens, JL Bonventre, JV TI Protection of renal epithelial cells against oxidative injury by endoplasmic reticulum stress preconditioning is mediated by ERK1/2 activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UNFOLDED PROTEIN RESPONSE; INDUCED FUNCTIONAL INJURY; MAPK KINASE ACTIVATION; CYTOSOLIC-FREE CALCIUM; SIGNALING PATHWAYS; CELLULAR-RESPONSE; INDUCED APOPTOSIS; DEATH; SURVIVAL; CA2+ AB We investigated the role of the endoplasmic reticulum ( ER) stress response in intracellular Ca2+ regulation, MAPK activation, and cytoprotection in LLC-PK1 renal epithelial cells in an attempt to identify the mechanisms of protection afforded by ER stress. Cells preconditioned with trans-4,5-dihydroxy-1,2-dithiane, tunicamycin, thapsigargin, or A23187 expressed ER stress proteins and were resistant to subsequent H2O2-induced cell injury. In addition, ER stress preconditioning prevented the increase in intracellular Ca2+ concentration that normally follows H2O2 exposure. Stable transfection of cells with antisense RNA targeted against GRP78 (pkASgrp78 cells) prevented GRP78 induction, disabled the ER stress response, sensitized cells to H2O2-induced injury, and prevented the development of tolerance to H2O2 that normally occurs with preconditioning. ERK and JNK were transiently ( 30 - 60 min) phosphorylated in response to H2O2. ER stress-preconditioned cells had more ERK and less JNK phosphorylation than control cells in response to H2O2 exposure. Preincubation with a specific inhibitor of JNK activation or adenoviral infection with a construct that encodes constitutively active MEK1, the upstream activator of ERKs, also protected cells against H2O2 toxicity. In contrast, the pkASgrp78 cells had less ERK and more JNK phosphorylation upon H2O2 exposure. Expression of constitutively active ERK also conferred protection on native as well as pkASgrp78 cells. These results indicate that GRP78 plays an important role in the ER stress response and cytoprotection. ER stress preconditioning attenuates H2O2-induced cell injury in LLC-PK1 cells by preventing an increase in intracellular Ca2+ concentration, potentiating ERK activation, and decreasing JNK activation. Thus, the ER stress response modulates the balance between ERK and JNK signaling pathways to prevent cell death after oxidative injury. Furthermore, ERK activation is an important downstream effector mechanism for cellular protection by ER stress. C1 Brigham & Womens Hosp, Div Renal, Med Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Lilly Res Labs, Greenfield, IN 46146 USA. Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ichimura, T (reprint author), Brigham & Womens Hosp, Div Renal, Med Serv, Med Res Bldg,4th Floor,75 Francis St, Boston, MA 02115 USA. NR 64 TC 137 Z9 146 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 1 PY 2003 VL 278 IS 31 BP 29317 EP 29326 DI 10.1074/jbc.M302368200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 705XC UT WOS:000184421100117 PM 12738790 ER PT J AU Gaur, A Sinclair, M Caruso, E Peretti, G Zaleske, D AF Gaur, A Sinclair, M Caruso, E Peretti, G Zaleske, D TI Heterotopic ossification around the elbow following burns in children: Results after excision SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID BONE-FORMATION; INJURY AB Background: Major burn injuries close to joints alter the function of the musculoskeletal system through tissue loss and limitation of joint motion. In children with involvement of the hand, wrist, and forearm, restriction of elbow motion secondary to heterotopic ossification following a burn injury severely limits the function of the upper extremity. The purpose of this study was to review elbow function following excision of heterotopic ossification around the elbow in children. Methods: Eight children (ten elbows) from a population of 3245 consecutive patients who were admitted to our pediatric burn center were found to have severe heterotopic ossification of the elbow, leading to an inability to reach the mouth for feeding and the head and the perineum for self-care. Excision of the heterotopic ossification was undertaken if the patient had this limitation of function and if movement was restricted to a total arc of motion of <50degrees. Pain was not an indication for the operation. The procedure was performed at an average of 17.3 months following the injury. Results: Seven children (nine elbows) were available for follow-up at an average of fifty-six months after surgery. All nine elbows had an improved arc of motion (an average increase of 57degrees). Following excision, heterotopic ossification did not recur. All children were able to reach the face and the perineum following the operation. Conclusions: Excision of heterotopic ossification around the elbow following a burn injury in children can improve the arc of motion and improve the function of the extremity. A relatively simple operative and postoperative regimen can achieve satisfactory results. Level of Evidence: Therapeutic study, Level IV (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence. C1 Med Coll Penn & Hahnemann Univ, Dept Orthoped Surg, Philadelphia, PA 19102 USA. Altona Childrens Hosp, D-22763 Hamburg, Germany. Luigi Sacco Univ Hosp, Dept Orthopaed, Milan, Italy. Hosp San Raffaele, Dept Orthopaed, I-20132 Milan, Italy. Childrens Natl Med Ctr, Pediat Orthopaed Dept, Washington, DC 20010 USA. Massachusetts Gen Hosp, Boston, MA USA. Boston Shriners Hosp, Boston, MA USA. RP Gaur, A (reprint author), Med Coll Penn & Hahnemann Univ, Dept Orthoped Surg, Philadelphia, PA 19102 USA. OI Peretti, Giuseppe/0000-0001-9341-7187 NR 24 TC 27 Z9 28 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2003 VL 85A IS 8 BP 1538 EP 1543 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 708DP UT WOS:000184552100016 PM 12925635 ER PT J AU Iannotti, JP Ramsey, ML Williams, GR Warner, JJP AF Iannotti, JP Ramsey, ML Williams, GR Warner, JJP TI Nonprosthetic management of proximal humeral fractures SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OPERATIVE TREATMENT; INTERNAL-FIXATION; 4-PART FRACTURES; OPEN REDUCTION; 3-PART; CLASSIFICATION; HEAD; REPRODUCIBILITY; PLATE; PART C1 Cleveland Clin Fdn, Dept Orthopaed Surg A41, Cleveland, OH 44195 USA. Univ Penn, Presbyterian Hosp, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. Amer Acad Orthopaed Surg, Rosemont, IL USA. RP Iannotti, JP (reprint author), Cleveland Clin Fdn, Dept Orthopaed Surg A41, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 27 TC 8 Z9 11 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2003 VL 85A IS 8 BP 1578 EP 1593 PG 16 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 708DP UT WOS:000184552100022 ER PT J AU Bhandari, M Einhorn, TA Swiontkowski, MF Heckman, JD AF Bhandari, M Einhorn, TA Swiontkowski, MF Heckman, JD TI Who did what? (Mis)perceptions about authors' contributions to scientific articles based on order of authorship SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bhandari, M (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 15 Parkman St,ACC 503, Boston, MA 02114 USA. NR 10 TC 27 Z9 29 U1 1 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD AUG PY 2003 VL 85A IS 8 BP 1605 EP 1609 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 708DP UT WOS:000184552100024 PM 12925643 ER PT J AU Abboud, SL Ghosh-Choudhury, N Liu, C Shen, V Woodruff, K AF Abboud, SL Ghosh-Choudhury, N Liu, C Shen, V Woodruff, K TI Osteoblast-specific targeting of soluble colony-stimulating factor-1 increases cortical bone thickness in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 22-26, 2000 CL TORONTO, CANADA SP Amer Soc Bone & Mineral Res DE macrophage colony-stimulating factor; osteoclasts; osteoblasts; transgenic mice; bone remodeling ID AGED MALE RATS; OP/OP MICE; OSTEOCLAST FORMATION; MOLECULAR-CLONING; CANCELLOUS BONE; STROMAL CELLS; GROWTH-FACTOR; LONG-TERM; M-CSF; EXPRESSION AB The soluble and membrane-bound forms of CSF-1 are synthesized by osteoblasts and stromal cells in the bone microenvironment. Transgenic mice, generated to selectively express sCSF-1 in bone, showed increased cortical thickness in the femoral diaphysis caused by new bone formation along the endosteal surface. The ability of sCSF-1 to enhance bone cell activity in vivo is potentially relevant for increasing cortical bone in a variety of disorders. Introduction: The soluble form of colony-stimulating factor-1 (sCSF-1) and the membrane-bound form of CSF-1 (mCSF-1) have been shown to support osteoclastogenesis in vitro; however, the effect of each peptide on bone remodeling in vivo is unclear. To determine the effect of sCSF-1, selectively expressed in bone, the skeletal phenotype of transgenic mice harboring the human sCSF-1 cDNA under the control of the osteocalcin promoter was assessed. Methods: At 5 and 14 weeks, mice were analyzed for CSF-1 protein levels, weighed, and X-rayed, and femurs were removed for peripheral quantitative computed tomography, histology, and histomorphometry. Results: High levels of human sCSF-1 were detected in bone extracts and, to a lesser extent, in plasma. Adult transgenic mice showed normal body weight and increased circulating monocytic cells. At 5 weeks, the femoral diaphysis was similar in CSF-1T and wt/wt littermates. However, by 14 weeks, the femoral diaphysis in CSF-1T mice showed increased cortical thickness and bone mineral density. In contrast to the diaphysis, the femoral metaphysis of CSF-1T mice showed normal cancellous bone comparable with wt/wt littermates at each time point. Histological sections demonstrated increased woven bone along the endosteal surface of the diaphysis and intracortical remodeling. Fluorochrome-labeling analysis confirmed endocortical bone formation in CSF-1T, with a 3.1-fold increase in the percentage of double-labeled surfaces and a 3.6-fold increase in the bone formation rate compared with wt/wt mice. Although remodeling resulted in a slightly porous cortex, sCSF-1 preferentially stimulated endocortical bone formation, leading to increased cortical thickness. Conclusions: These findings indicate that sCSF-1 is a key determinant of bone cell activity in the corticoendosteal envelope. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Skeletech Inc, Bothell, WA USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Abboud, SL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [R01 AR042306, AR42306] NR 44 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2003 VL 18 IS 8 BP 1386 EP 1394 DI 10.1359/jbmr.2003.18.8.1386 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704CU UT WOS:000184320800002 PM 12929928 ER PT J AU Lopez, I Rodriguez, M Felsenfeld, AJ Estepa, JC Aguilera-Tejero, E AF Lopez, I Rodriguez, M Felsenfeld, AJ Estepa, JC Aguilera-Tejero, E TI Direct suppressive effect of acute metabolic and respiratory alkalosis on parathyroid hormone secretion in the dog SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE calcium; metabolic alkalosis; parathyroid hormone; pH; respiratory alkalosis ID IONIZED CALCIUM-CONCENTRATION; CHRONIC HYPERCALCEMIA; ALKALINE TIDE; HYPOCALCEMIA; BICARBONATE; ACIDOSIS; BONE; INVITRO; SEPSIS; SODIUM AB Acute alkalosis may directly affect PTH secretion. The effect of acute metabolic and respiratory alkalosis was studied in 20 dogs. PTH values were lower in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 +/- 0.6 pg/ml) alkalosis groups than in the control group (27 +/- 5 pg/ml). Acute alkalosis is an independent factor that decreases PTH values during normocalcemia and delays the PTH response to hypocalcemia. Introduction: We recently showed that acute metabolic and respiratory acidosis stimulated PTH secretion. This study was designed to evaluate whether acute metabolic and respiratory alkalosis suppressed parathyroid hormone (PTH) secretion. Materials and Methods: Three groups of 10 dogs were studied: control, acute metabolic alkalosis, and acute respiratory alkalosis. Metabolic alkalosis was induced with an infusion of sodium bicarbonate and respiratory alkalosis by hyperventilation. Calcium chloride was infused to prevent alkalosis-induced hypocalcemia during the first 60 minutes. During the next 30 minutes, disodium EDTA was infused to induce hypocalcemia and to evaluate the PTH response to hypocalcemia. Because the infusion of sodium bicarbonate resulted in hypernatremia, the effect of hypernatremia was studied in an additional group that received hypertonic saline. Results: After 60 minutes of a normocalcemic clamp, PTH values were less (p < 0.05) in the metabolic (5.6 +/- 0.8 pg/ml) and respiratory (1.8 0.6 pg/ml) alkalosis groups than in the control group (27 5 pg/ml); the respective blood pH values were 7.61 +/- 0.01, 7.59 +/- 0.02, and 7.39 +/- 0.02. The maximal PTH response to hypocalcemia was similar among the three groups. However, the maximal PTH response was observed after a decrease in ionized calcium of 0.20 mM in the control group but not until a decrease of 0.40 mM in the metabolic and respiratory alkalosis groups. In contrast to the metabolic alkalosis group, hypernatremia (157 +/- 2 mEq/liter) in the hypertonic saline group was associated with an increased PTH value (46 4 pg/ml). Finally, the half-life of intact PTH was not different among the control and two alkalosis groups. Conclusions: Acute metabolic and respiratory alkalosis markedly decreased PTH values during normocalcemia and delayed the PTH response to hypocalcemia. Whether acute metabolic and respiratory alkalosis affect PTH and calcium metabolism in such settings as the postprandial alkaline tide (metabolic alkalosis) and acute sepsis (respiratory alkalosis) deserves to be evaluated in future studies. C1 Univ Rabanales, Dept Med & Cirugia, Cordoba 14014, Spain. Univ Cordoba, Hosp Univ Reina Sofia, Dept Nefrol, Cordoba, Spain. Univ Cordoba, Hosp Reina Sofia, Unidad Invest, Cordoba, Spain. Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Cordoba, Dept Med & Ciurgia Anim, Cordoba, Spain. RP Aguilera-Tejero, E (reprint author), Univ Rabanales, Dept Med & Cirugia, Ctra Madrid Cadiz Km 396,Animal Campus, Cordoba 14014, Spain. RI Rodriguez, teresa/H-5452-2011 NR 29 TC 16 Z9 16 U1 0 U2 5 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2003 VL 18 IS 8 BP 1478 EP 1485 DI 10.1359/jbmr.2003.18.8.1478 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704CU UT WOS:000184320800011 PM 12929937 ER PT J AU Seton, M Choi, HK Hansen, MF Sebaldt, RJ Cooper, C AF Seton, M Choi, HK Hansen, MF Sebaldt, RJ Cooper, C TI Analysis of environmental factors in familial versus sporadic Paget's disease of bone - The New England Registry for Paget's disease of bone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE Paget's disease; registry; case series; epidemiology; familial ID MEASLES-VIRUS; EXPANSILE OSTEOLYSIS; OSTEOCLAST PRECURSORS; GENETIC-LINKAGE; CHROMOSOME 18Q; EPIDEMIOLOGY; TRANSCRIPTS; AGGREGATION; MUTATIONS; LOCI AB A registry for Paget's Disease (PD) was created to study the environmental and familial features of this disorder. This study examines the first 202 people enrolled. Those with a family history of PD (20%) suffered earlier deformity and fracture, and tended to have grandparents born abroad. These findings suggest heritage is important in PD; the role of environment remains unclear. Introduction: The New England Registry for Paget's Disease of Bone is a database that was created to explore the distribution and determinants of disease frequency. Methods: Using a case-series design, we explored the association of environmental factors in expression of the disease, comparing those patients with familial Paget's disease to those with sporadic Paget's disease (PD). Results and Conclusions: Analysis of the first 202 patients enrolled in the registry revealed a positive family history (FH) in 41 (20%). Significant findings in this cohort included an earlier age of onset (51 years FH+ versus 59 years FH- p < 0.05), a trend to a higher incidence of bone deformity (49% versus 33%, p < 0.1), and an increased fracture rate (27% versus 11%, p < 0.05). Persons with a FH of PD were less likely to record the United States or Canada as their grandparents' birthplace (p < 0.01), and sibships tended to be larger (p <0.05). A history of measles infection, childhood exposure to pets, milk ingestion, year of immigration to the United States, birth order, level of education, and functional status did not distinguish the two groups. The database confirms the high prevalence of familial PD and supports the theory that heritable factors are important in the pathogenesis of this focal disorder of bone metabolism. C1 Massachusetts Gen Hosp, Arthrit Unit, New England Registry Pagets Dis Bone, Boston, MA 02114 USA. RP Seton, M (reprint author), Massachusetts Gen Hosp, Arthrit Unit, New England Registry Pagets Dis Bone, Bulfinch 165, Boston, MA 02114 USA. NR 35 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD AUG PY 2003 VL 18 IS 8 BP 1519 EP 1524 DI 10.1359/jbmr.2003.18.8.1519 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 704CU UT WOS:000184320800016 PM 12929942 ER PT J AU Havranek, EP Krumholz, HM Dudley, RA Adams, K Gregory, D Lampert, S Lindenfeld, J Massie, BM Pina, I Restaino, S Rich, MW Konstam, MA AF Havranek, EP Krumholz, HM Dudley, RA Adams, K Gregory, D Lampert, S Lindenfeld, J Massie, BM Pina, I Restaino, S Rich, MW Konstam, MA TI Aligning quality and payment for heart failure care: Defining the challenges SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure management; reimbursement; quality of care AB Hospitals may not support programs that improve the quality of care delivered to heart failure patients because these programs lower readmission rates and empty beds, and therefore further diminish already-declining revenues. A conflict between the highest quality of care and financial solvency does not serve the interests of patients, physicians, hospitals, or payers. In principle, resolution of this conflict is simple: reimbursement systems should reward higher quality care. In practice, resolving the conflict is not simple. A recent roundtable discussion sponsored by the Heart Failure Society of America identified 4 major challenges to the design and implementation of reimbursement schemes that promote higher quality care for heart failure: defining quality, accounting for differences in disease severity, crafting novel payment mechanisms, and overcoming professional parochialism. This article describes each of these challenges in turn. C1 Denver Hlth Med Ctr, Dept Med, Div Cardiol, Denver, CO 80204 USA. Univ Colorado, HSC, Denver, CO 80202 USA. Yale Univ, Sch Med, Sect Cardiovasc Med,Sect Hlth Policy & Adm, Dept Internal Med,Dept Epidemiol & Publ Hlth, New Haven, CT USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Univ N Carolina, Div Cardiol, Dept Med, Dept Radiol, Chapel Hill, NC USA. Tufts New England Med Ctr, Boston, MA USA. Harvard Vanguard Med Assoc, Boston, MA USA. Univ Colorado, HSC, Dept Med, Div Cardiol, Denver, CO 80202 USA. Univ Calif San Francisco, Div Cardiol, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Case Western Reserve Univ, Sch Med, Dept Med, Div Cardiol, Cleveland, OH 44106 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Univ Washington, Sch Med, Div Cardiovasc, Dept Med, St Louis, MO USA. Tufts New England Med Ctr, Div Cardiol, Dept Med, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Havranek, EP (reprint author), Denver Hlth Med Ctr, Dept Med, Div Cardiol, 0960,777 Bannock St, Denver, CO 80204 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2003 VL 9 IS 4 BP 251 EP 254 DI 10.1054/jcaf.2003.30 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 715HP UT WOS:000184966000001 PM 13680543 ER PT J AU Anderson, JL Krause-Steinrauf, H Goldman, S Clemson, BS Domanski, MJ Hager, WD Murray, DR Mann, DL Massie, BM McNamara, DM Oren, R Rogers, WJ AF Anderson, JL Krause-Steinrauf, H Goldman, S Clemson, BS Domanski, MJ Hager, WD Murray, DR Mann, DL Massie, BM McNamara, DM Oren, R Rogers, WJ CA Beta Blocker Evaluation Survival T TI Failure of benefit and early hazard of bucindolol for Class IV heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE beta-blocker; bucindolol; heart failure; survival ID IDIOPATHIC DILATED CARDIOMYOPATHY; ADRENERGIC-RECEPTOR BLOCKADE; INTRINSIC SYMPATHOMIMETIC ACTIVITY; CONGESTIVE CARDIOMYOPATHY; RANDOMIZED TRIAL; SURVIVAL TRIAL; BETA-BLOCKADE; DOUBLE-BLIND; MERIT-HF; METOPROLOL AB Objectives: The risks and benefits of beta-blockade with bucindolol were assessed in heart failure (HF) patients with Class IV symptoms within the Beta-blocker Evaluation of Survival Trial (BEST). Background: beta-blockade is accepted therapy for mild to moderate HF, but its safety and efficacy in advanced HF have not been established. Methods: BEST recruited 2708 HF patients; of these, 226 with Class IV symptoms (n = 114 randomized to bucindolol, n = 112 to placebo) formed the basis of this study. All-cause death, HF hospitalization, and drug discontinuations occurring early during therapy (less than or equal to6 months) and overall during follow-up were assessed. Compared with Class III, Class IV patients were older and had higher plasma norepinephrine levels, prevalence of coronary disease, S3 gallops, and lower ejection fractions, but characteristics of the 2 Class IV treatment groups were similar. Results: During a mean of 1.6 years, 49% Class IV patients died, and 54% were hospitalized for HE Bucindolol increased the combined endpoint of death or HE hospitalization within the first 6 months (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1-2.7) and did not result in benefit overall (HR = 1.2, 95% CI = 0.9-1.6). HF hospitalization alone within 6 months was increased by bucindolol (HR = 1.7), and an early adverse trend for death was seen (HR = 1.6) with no benefit overall (HR = 1.1). Bucindolol was discontinued more frequently than placebo for worsening HF (11% versus 4%) and hypotension (3% versus 0%). Conclusions: Class IV HF patients in BEST were at high risk. Bucindolol did not reduce death or HF hospitalization and was associated with early hazard. C1 Univ Utah, Latter Day St Hosp, Sch Med, Div Cardiol, Salt Lake City, UT 84143 USA. NHLBI, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Tucson, AZ 85723 USA. Heart Care Midwest, Peoria, IL USA. Univ Connecticut, Farmington, CT USA. Vet Adm Med Ctr, San Antonio, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Iowa, Iowa City, IA USA. Univ Alabama, Tuscaloosa, AL 35487 USA. RP Anderson, JL (reprint author), Univ Utah, Latter Day St Hosp, Sch Med, Div Cardiol, 8th Ave & C St, Salt Lake City, UT 84143 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 29 TC 16 Z9 17 U1 1 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2003 VL 9 IS 4 BP 266 EP 277 DI 10.1054/jcaf.2003.42 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 715HP UT WOS:000184966000005 PM 13680547 ER PT J AU Bush, RL Lin, PH Lumsden, AB AF Bush, RL Lin, PH Lumsden, AB TI Endovascular management of abdominal aortic aneurysms SO JOURNAL OF CARDIOVASCULAR SURGERY LA English DT Article DE aortic aneurysm, abdominal, therapy; stents; blood vessel prosthesis implantation ID STENT GRAFT; CLINICAL-TRIAL; REPAIR; ENDOLEAK; DEVICE; EXPERIENCE; CONVERSION; DIAGNOSIS; MIGRATION; RUPTURE AB An estimated 1.5 Million people in the United States have abdominal aortic aneurysms (AAAs) with more than 200 000 American diagnosed each year. The natural history of AAAs is to expand and rupture, accounting for an estimated 15 000 deaths per year. Thus, the major impetus for AAA repair is for prophylaxis against aneurysm-related death. The standard open surgical repair of AAAs is a well-established and durable procedure. However, as with all other major abdominal surgical operations, associated significant morbidity and mortality exist, along with prolonged recovery and various late complications. Furthermore, both mortality and morbidity increase significantly with advanced patient age and associated co-morbid disease states. Endovascular AAA repair using covered stent-grafts offers a significantly less invasive alternative to conventional open-surgical repair. A considerable reduction in hospital stay has been demonstrated, with early return to preoperative levels of activity. Patients previously considered unsuitable for open repair can often receive treatment for aneurysms with endovascular techniques. Current estimates are that more than 1/2 all infrarenal AAAs will be repaired using endovascular approach in the future. Despite the minimally-invasiveness of this new treatment, there are unanswered questions as to the durability and efficacy of devices, which results in concerns about their ability to successfully protect the patient from subsequent rupture. Three devices are commercially available and have been extensively used for implantation in the United States with a 4(th) device recently receiving approval from the Food and Drug Administration (FDA). In this review article, endovascular management of AAAs with these devices is described, as are the design and deployment techniques of the currently available endografts. C1 Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. RP Bush, RL (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston VAMC,2002 Holcomb Blvd 112, Houston, TX 77030 USA. NR 29 TC 5 Z9 5 U1 0 U2 3 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0021-9509 J9 J CARDIOVASC SURG JI J. Cardiovasc. Surg. PD AUG PY 2003 VL 44 IS 4 BP 527 EP 534 PG 8 WC Cardiac & Cardiovascular Systems; Surgery; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Surgery GA 722TE UT WOS:000185392100005 PM 14627225 ER PT J AU Culver, JP Durduran, T Furuya, T Cheung, C Greenberg, JH Yodh, AG AF Culver, JP Durduran, T Furuya, T Cheung, C Greenberg, JH Yodh, AG TI Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE diffuse optical tomography; ischemia; cerebral blood flow; laser Doppler flowmetry; tissue oxygen saturation; cerebral metabolic rate of oxygen consumption ID CONSUMPTION FOLLOWING ACTIVATION; CORTICAL SPREADING DEPRESSION; NEAR-INFRARED ABSORPTION; ARTERY OCCLUSION; TURBID MEDIA; SPECTROSCOPIC ANALYSIS; FUNCTIONAL ACTIVATION; FOREPAW STIMULATION; BOUNDARY-CONDITIONS; TEMPORAL EVOLUTION AB Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto(2)), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo(2)). Temporary (60-minute) MCAO was pet-formed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 +/- 0.04, rCBV = 1.02 0.04, DeltaSto(2) = -11 +/- 2%, rOEF = 1.39 +/- 0.06 and rCMRo(2) 0.59 +/- 0.07. Although rOEF increased in response to decreased blood flow, rCMRo(2) decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature. C1 Univ Penn, Cerebrovasc Res Ctr, Dept Phys & Astron, Philadelphia, PA 19104 USA. Univ Penn, Cerebrovasc Res Ctr, Dept Neurol, Philadelphia, PA 19104 USA. RP Culver, JP (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Durduran, Turgut/N-7768-2015 OI Durduran, Turgut/0000-0001-5838-1027 FU NHLBI NIH HHS [HL-57835-04]; NINDS NIH HHS [K25 NS44339A01, NS33785] NR 68 TC 228 Z9 230 U1 2 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2003 VL 23 IS 8 BP 911 EP 924 DI 10.1097/01.WCB.0000076703.71231.BB PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 709BJ UT WOS:000184604600004 PM 12902835 ER PT J AU Holschneider, DP Maarek, JMI Yang, J Harimoto, J Scremin, OU AF Holschneider, DP Maarek, JMI Yang, J Harimoto, J Scremin, OU TI Functional brain mapping in freely moving rats during treadmill walking SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain mapping; cerebral blood flow; infusion pumps; autoradiography; cerebral cortex; motor activity ID CEREBRAL BLOOD-FLOW; MOTOR CORTEX; C-14 IODOANTIPYRINE; METABOLIC-ACTIVITY; FORELIMB MOVEMENT; VISUAL-SYSTEM; DIFFUSE LIGHT; STIMULATION; ORGANIZATION; EXERCISE AB A dilemma in functional neuroimaging is that immobilization of the subject, necessary to avoid movement artifact, extinguishes all but the simplest behaviors. Recently, we developed an implantable microbolus infusion pump (MIP) that allows bolus injection of radiotracers by remote activation in freely moving, nontethered animals. The MIP is examined as a tool for brain mapping in rats during a locomotor task. Cerebral blood flow-related tissue radioactivity (CBF-TR) was measured using [C-14]-iodoantipyrine with an indicator-fractionation method, followed by autoradiography. Rats exposed to walking on a treadmill, compared to quiescent controls, showed increases in CBF-TR in motor circuits (primary motor cortex, dorsolateral striatum, ventrolateral thalamus, midline cerebellum, copula pyramis, paramedian lobule), in primary somatosensory cortex mapping the forelimbs, hindlimbs and trunk, as well as in secondary visual cortex. These results support the use of implantable pumps as adjunct tools for functional neuroimaging of behaviors that cannot be elicited in restrained or tethered animals. C1 Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ So Calif, Sch Engn, Dept Biomed Engn, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, 1333 San Pablo St,BMT 401,MC 9112, Los Angeles, CA 90089 USA. FU NIBIB NIH HHS [R01 EB000300, R01 EB-00300-03] NR 44 TC 39 Z9 39 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD AUG PY 2003 VL 23 IS 8 BP 925 EP 932 DI 10.1097/01.WCB.0000072797.66873.6A PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 709BJ UT WOS:000184604600005 PM 12902836 ER PT J AU Fessler, MB Lepore, JJ Thompson, BT Semigran, MJ AF Fessler, MB Lepore, JJ Thompson, BT Semigran, MJ TI Right-to-left shunting through a patent foramen ovale in right ventricular infarction: Improvement of hypoxemia and hemodynamics with inhaled nitric oxide SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material DE right ventricular infarction; nitric oxide; patent foramen ovale; interatrial shunt ID END-EXPIRATORY PRESSURE; FLOW-THROUGH; HYPERTENSION; PERFUSION; SIZE AB Inhaled nitric oxide is a selective pulmonary vasodilator that has been used successfully to treat hemodynamic embarassment and right-to-left interatrial shunting in acute right heart failure. Previous reports have been in the setting of disorders causing elevated right heart afterload, such as pulmonary embolism, acute respiratory distress syndrome, and chronic obstructive pulmonary disease. Right ventricular infarction is a less common, but important cause of acute right heart failure with which the intensivist should be familiar. We report a Patient with night ventricular infarction for whom cardiogenic shock and refractory hypoxemia due to right-to-left interatrial shunting were, effectively treated with inhaled nitric oxide. The potential for broader application of inhaled nitric oxide as a therapy for right ventricular infarction is discussed. (C) 2003 by Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Med, Med Cardiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div,Pulm & Crit Care Unit, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Med Cardiol Div, 55 Fruit St,GRB 645, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL04021] NR 16 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD AUG PY 2003 VL 15 IS 5 BP 371 EP 374 DI 10.1016/S0952-8180(03)00053-9 PG 4 WC Anesthesiology SC Anesthesiology GA 726QT UT WOS:000185611100011 PM 14507565 ER PT J AU Grinspoon, SK Friedman, AJ Miller, KK Lippman, J Olson, WH Warren, MP AF Grinspoon, SK Friedman, AJ Miller, KK Lippman, J Olson, WH Warren, MP TI Effects of a triphasic combination oral contraceptive containing norgestimate/ethinyl estradiol on biochemical markers of bone metabolism in young women with osteopenia secondary to hypothalamic amenorrhea SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; REPLACEMENT THERAPY; DISTANCE RUNNERS; ANOREXIA-NERVOSA; TURNOVER; ESTROGEN; OSTEOPROTEGERIN; PREMENOPAUSAL AB This multicenter, double-blind, placebo-controlled, randomized study of 45 patients evaluated the short-term effects of an oral contraceptive [ Ortho Tri-Cyclen, 180-250 mug of norgestimate (NGM) and 35 mug of ethinyl estradiol (EE)] on biochemical markers of bone resorption, formation, and osteoprotegerin in young women (mean age +/- SD, 26.5 +/- 6.3 yr) with hypothalamic amenorrhea and osteopenia. Body fat, endocrine, and cognitive function were evaluated as secondary endpoints. Biomarkers of bone metabolism were measured at baseline and after three cycles of NGM/EE or placebo. There were significant decreases in mean values of N-telopeptide [mean (SD), -13.4 (13.4) vs. 1.2 (23.8) nmol bone collagen equivalents (BCE)/mmol creatinine (Cr); P = 0.001] and deoxypyridinoline [-1.2 (2.9) vs. -0.5 (1.5) nmol deoxypyridinoline/mmol Cr; P = 0.021] as well as significant decreases in bone specific alkaline phosphatase [-5.1 (3.5) vs. 0.4 (3.1) ng/ml; P < 0.001], osteocalcin [-5.9 (3.6) vs. -2.9 (3.7); P = 0.016], and procollagen of type I propeptide [-35.2 (44.6) vs. -0.2 (30.0) ng/ml; P = 0.025], but not osteoprotegerin [0.39 (1.46) vs. -0.2 (0.49) pmol/liter; P = 0.397] in the NGM/EE vs. placebo group. There were no significant differences between groups with respect to changes in cognitive function, mood, body weight, body mass index, body fat, percentage of body fat, and all endocrine levels except FSH, [-3.7 (3.8) vs. -0.6 (2.1) IU/liter; P < 0.001, NGM/EE vs. placebo]. No serious adverse events were reported in either group. These results suggest that NGM/EE decreases bone turnover in osteopenic premenopausal women with hypothalamic amenorrhea. Further studies are needed to determine whether estrogen will increase bone density in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Ortho Pharmaceut Corp, Raritan, NJ 08869 USA. Ethicon, Somerville, NJ 08876 USA. Ctr Menopause Hormonal Disorders & Womens Hlth, New York, NY 10022 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bul 457B,55 Fruit st, Boston, MA 02114 USA. EM Sgrinspoon@partners.org NR 40 TC 24 Z9 24 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2003 VL 88 IS 8 BP 3651 EP 3656 DI 10.1210/jc.2003-030033 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 711HH UT WOS:000184733200032 PM 12915650 ER PT J AU Misra, M Soyka, LA Miller, KK Herzog, DB Grinspoon, S de Chen, D Neubauer, G Klibanski, A AF Misra, M Soyka, LA Miller, KK Herzog, DB Grinspoon, S de Chen, D Neubauer, G Klibanski, A TI Serum osteoprotegerin in adolescent girls with anorexia nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID KAPPA-B LIGAND; POSTMENOPAUSAL WOMEN; BONE METABOLISM; RECEPTOR ACTIVATOR; LEPTIN; ESTROGEN; MARKERS; DENSITY; OSTEOPOROSIS; OSTEOPENIA AB Lowbone mineral density (BMD) in adolescents with anorexia nervosa ( AN) is associated with a low bone turnover state. Osteoprotegerin (OPG), a cytokine that acts as a decoy receptor for receptor activator of nuclear factor-kappaB ligand, decreases bone resorption by inhibiting differentiation of osteoclast precursors and activation of mature osteoclasts, and by stimulating osteoclast apoptosis. We compared OPG levels in 43 adolescent girls with AN with 38 controls and examined bone density, bone turnover, and hormonal parameters. Girls with AN had lower fat mass, lean body mass, lumbar BMD z-scores, and lumbar bone mineral apparent density than controls. OPG levels were higher in girls with AN than in controls (44.5 +/- 22.5 pg/ml vs. 34.5 +/- 12.7 pg/ml, P = 0.02). Osteocalcin, deoxypyridinoline, estradiol, free testosterone, IGF-I, and leptin were lower in AN than in healthy adolescents. OPG values correlated negatively with body mass index (r = -0.27, P = 0.02), percent fat mass (r = -0.35, P = 0.0002), leptin (r = -0.28, P = 0.02), lumbar BMD z-scores (r = -0.25, P = 0.03), and lumbar bone mineral apparent density (r = -0.26, P = 0.03). In conclusion, adolescent girls with AN have higher serum OPG values than controls. OPG values correlate negatively with markers of nutritional status and lumbar bone density z-scores and may be a compensatory response to the bone loss seen in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK-52625-05] NR 34 TC 49 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2003 VL 88 IS 8 BP 3816 EP 3822 DI 10.1210/jc.2003-030088 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 711HH UT WOS:000184733200056 PM 12915674 ER PT J AU Saab, S Wang, V AF Saab, S Wang, V TI Recurrent hepatitis C following liver transplant - Diagnosis, natural history, and therapeutic options SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE hepatitis C; liver transplantation ID PEGINTERFERON ALPHA-2A PEGASYS(R); RANDOMIZED MULTICENTER TRIAL; INTERFERON PLUS RIBAVIRIN; VIRUS-INFECTION; MYCOPHENOLATE-MOFETIL; PEGYLATED-INTERFERON; REJECTION EPISODES; VIRAL-HEPATITIS; GRAFT-SURVIVAL; DONOR AGE AB Hepatitis C virus (HCV) related cirrhosis is the most common indication for orthotopic liver transplantation (OLT). Updated data suggest Worse long-term outcomes for those transplanted with HCV than those transplanted for other indications. Re-infection With HCV post-OLT is universal, therefore diagnosis of recurrence should be based on histological findings in the setting of persistent viremia. Variables associated with worse outcome of recurrent disease include early recurrence, degree of immunosuppression, and donor age. Antiviral therapy has been used in the prevention and treatment of recurrent disease, and can be initiated prior to transplantation, prophylactically after transplantation, and during recurrence. Preliminary studies of pre-transplantation treatment demonstrate virological responses, but tolerance is common. Higher efficacy has been associated with combination therapy for recur-rent disease. Adverse effects limit its widespread use. C1 Univ Calif Los Angeles, Med Ctr, Div Dig Dis 44 138 CHS MC 168417, Dept Med, Los Angeles, CA 90095 USA. Dumont UCLA Transplant Ctr, Dept Surg, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Med Ctr, Div Dig Dis 44 138 CHS MC 168417, Dept Med, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 93 TC 13 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD AUG PY 2003 VL 37 IS 2 BP 155 EP 163 DI 10.1097/00004836-200308000-00013 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 702PW UT WOS:000184233100012 PM 12869888 ER PT J AU Wolfrum, C Shih, DQ Kuwajima, S Norris, AW Kahn, CR Stoffel, M AF Wolfrum, C Shih, DQ Kuwajima, S Norris, AW Kahn, CR Stoffel, M TI Role of Foxa-2 in adipocyte metabolism and differentiation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; BETA-CELL FUNCTION; GENE-EXPRESSION; TARGETED DISRUPTION; GLUCOSE-HOMEOSTASIS; GROWTH-HORMONE; IN-VIVO; OBESITY; PREF-1; HELIX AB Hepatocyte nuclear factors-3 (Foxa-1-3) are winged forkhead transcription factors that regulate gene expression in the liver and pancreatic islets and are required for normal metabolism. Here we show that Foxa-2 is expressed in preadipocytes and induced de novo in adipocytes of genetic and diet-induced rodent models of obesity. In preadipocytes Foxa-2 inhibits adipocyte differentiation by activating transcription of the Pref-1 gene. Foxa-2 and Pref-1 expression can be enhanced in primary preadipocytes by growth hormone, suggesting that the antiadipogenic activity of growth hormone is mediated by Foxa-2. In differentiated adipocytes Foxa-2 expression leads to induction of gene expression involved in glucose and fat metabolism, including glucose transporter-4, hexokinase-2, muscle-pyruvate kinase, hormone-sensitive lipase, and uncoupling proteins-2 and -3. Diet-induced obese mice with haploinsufficiency in Foxa-2 (Foxa-2(+/-)) develop increased adiposity compared with wild-type littermates as a result of decreased energy expenditure. Furthermore, adipocytes of these Foxa-2(+/-) mice exhibit defects in glucose uptake and metabolism. These data suggest that Foxa-2 plays an important role as a physiological regulator of adipocyte differentiation and metabolism. C1 Rockefeller Univ, Lab Metab Dis, New York, NY 10021 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Stoffel, M (reprint author), Rockefeller Univ, Lab Metab Dis, 1230 York Ave,Box 292, New York, NY 10021 USA. OI Norris, Andrew/0000-0001-8396-9543 FU NIDDK NIH HHS [R01 DK055033, R01 DK55033-04]; NIGMS NIH HHS [T32 GM007739, GM07739] NR 42 TC 79 Z9 82 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2003 VL 112 IS 3 BP 345 EP 356 DI 10.1172/JCI200318698 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 708LQ UT WOS:000184569100010 PM 12865419 ER PT J AU Norris, AW Chen, LH Fisher, SJ Szanto, I Ristow, M Jozsi, AC Hirshman, MF Rosen, ED Goodyear, LJ Gonzalez, FJ Spiegelman, BM Kahn, CR AF Norris, AW Chen, LH Fisher, SJ Szanto, I Ristow, M Jozsi, AC Hirshman, MF Rosen, ED Goodyear, LJ Gonzalez, FJ Spiegelman, BM Kahn, CR TI Muscle-specific PPAR gamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; GENE-EXPRESSION; RECEPTOR-ALPHA; ANTIDIABETIC THIAZOLIDINEDIONE; ADIPOCYTE DIFFERENTIATION; TROGLITAZONE ACTION; LIPID-METABOLISM; GLUCOSE; OBESITY AB Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by thiazolidinediones (TZDs) improves insulin resistance by increasing insulin-stimulated glucose disposal in skeletal muscle. it remains debatable whether the effect of TZDs on muscle is direct or indirect via adipose tissue. We therefore generated mice with muscle-specific PPARgamma knockout (MuPPARgammaKO) using Cre/laxP recombination. Interestingly, MuPPARgammaKO mice developed excess adiposity despite reduced dietary intake. Although insulin-stimulated glucose uptake in muscle was not impaired, MuPPARgammaKO mice had whole-body insulin resistance with a 36% reduction (P < 0.05) in the glucose infusion rate required to maintain euglycemia during hyperinsulinemic clamp, primarily due to dramatic impairment in hepatic insulin action. When placed on a high-fat diet, MuPPARgammaKO mice developed hyperinsulinemia and impaired glucose homeostasis identical to controls. Simultaneous treatment with TZD ameliorated these high fat-induced defects in MuPPARgammaKO mice to a degree identical to controls. There was also altered expression of several lipid metabolism genes in the muscle of MuPPARgammaKO mice. Thus, muscle PPARgamma is not required for the antidiabetic effects of TZDs, but has a hitherto unsuspected role for maintenance of normal adiposity, whole-body insulin sensitivity, and hepatic insulin action. The tissue crosstalk mediating these effects is perhaps due to altered lipid metabolism in muscle. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Beth Israel Med Ctr, Boston, MA USA. Natl Canc Inst, Mol Carcinogenesis Lab, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [R37 DK031036, DK31036, DK45935, P30 DK036836, R01 DK031036, R01 DK045935, T32 DK063702, T32-DK63702-01] NR 65 TC 265 Z9 273 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2003 VL 112 IS 4 BP 608 EP 618 DI 10.1172/JCI200317305 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 713BB UT WOS:000184833900020 PM 12925701 ER PT J AU Porteous, NB Grooters, AM Redding, SW Thompson, EH Rinaldi, MG De Hoog, GS Sutton, DA AF Porteous, NB Grooters, AM Redding, SW Thompson, EH Rinaldi, MG De Hoog, GS Sutton, DA TI Identification of Exophiala mesophila isolated from treated dental unit waterlines SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID DEMATIACEOUS FUNGI; MOLECULAR DIVERSITY; ATLANTIC SALMON; BLACK YEASTS; DERMATITIDIS; PHEOHYPHOMYCOSIS; INFECTION; HERPOTRICHIELLACEAE; JEANSELMEI; FUNGEMIA AB Members of the genus Exophiala are often difficult to identify to the species level because of their variable morphological appearances. This paper describes the methods used to identify Exophiala mesophila and provides salient differential features for distinguishing other mesophilic members of the genus. C1 Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Fungus Testing Lab, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Centraalbur Schimmelcultures, Utrecht, Netherlands. Louisiana State Univ, Sch Vet Med, Baton Rouge, LA USA. RP Porteous, NB (reprint author), Univ Texas, Hlth Sci Ctr, Dept Community Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 40 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2003 VL 41 IS 8 BP 3885 EP 3889 DI 10.1128/JCM.41.8.3885-3889.2003 PG 5 WC Microbiology SC Microbiology GA 711MW UT WOS:000184746500071 PM 12904410 ER PT J AU Burstein, HJ Harris, LN Marcom, PK Lambert-Falls, R Havlin, K Overmoyer, B Friedlander, RJ Gargiulo, J Strenger, R Vogel, CL Ryan, PD Ellis, MJ Nunes, RA Bunnell, CA Campos, SM Hallor, M Gelman, R Winer, EP AF Burstein, HJ Harris, LN Marcom, PK Lambert-Falls, R Havlin, K Overmoyer, B Friedlander, RJ Gargiulo, J Strenger, R Vogel, CL Ryan, PD Ellis, MJ Nunes, RA Bunnell, CA Campos, SM Hallor, M Gelman, R Winer, EP TI Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: Multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GENE AMPLIFICATION; HER2; CHEMOTHERAPY; PACLITAXEL; EFFICACY AB Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools. Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction greater than or equal to 50%. Serial testing for HER2 extracellular domain (ECD) was performed. Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression. Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC USA. S Carolina Oncol Associates, W Columbia, SC USA. Evanston Hosp Corp, Evanston, IL 60201 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. New Hampshire Oncol Hematol PA, Hooksett, NH USA. Capital Dist Hematol Oncol, Latham, NY USA. Miriam Hosp, Providence, RI 02906 USA. Rhode Isl Hosp, Providence, RI USA. Canc Res Network, Plantation, FL USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 221 Z9 226 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2003 VL 21 IS 15 BP 2889 EP 2895 DI 10.1200/JCO.2003.02.018 PG 7 WC Oncology SC Oncology GA 706PJ UT WOS:000184461800013 PM 12885806 ER PT J AU Ramanathan, RK Clark, JW Kemeny, NE Lenz, HJ Gococo, KO Haller, DG Mitchell, EP Kardinal, CG AF Ramanathan, RK Clark, JW Kemeny, NE Lenz, HJ Gococo, KO Haller, DG Mitchell, EP Kardinal, CG TI Safety and toxicity analysis of oxaliplatin combined with fluorouracil or as a single agent in patients with previously treated advanced colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol ID FIRST-LINE TREATMENT; RANDOMIZED TRIAL; LEUCOVORIN; IRINOTECAN; 1ST-LINE; FAILURE AB Purpose: Two consecutive compassionate use studies of oxaliplatin were conducted in the United States and Canada in more than 5,000 patients with locally advanced or metastatic colorectal carcinoma who had experienced treatment failure after at least one prior chemotherapy regimen. Patients and Methods: The main focus was safety. Patients were assigned to treatment with either single-agent oxaliplatin or oxaliplatin in combination with fluorouracil (FU) and with or without leucovorin (IV) in various regimens. Response data collection was not a trial objective, but time to treatment failure (TTF) was recorded in the first cohort (1,370 patients). Results: All treatment regimens were well tolerated, with an overall incidence of grade 3 or 4 hematologic toxicity of 23.2%, grade 3 or 4 treatment-related gastrointestinal toxicity of 26.4% (including diarrhea, vomiting, and mucositis), and grade 3 neurosensory toxicity 3.9%. Similar results were reported in the second cohort (3,806 patients), in which the eligibility criteria were much less restrictive. In the first cohort (in which 83% received prior irinotecan), median TTF was 14 weeks, and was similar for the five regimens combining oxaliplatin and FU with or without LV, but significantly shorter for the single-agent oxaliplatin arm. The overall dose-intensity of oxaliplatin was maintained at 85.5% (range, 80.6% to 94.3%) of that prescribed by protocol (average 36.7 mg/m(2)/wk). Conclusion: These data in a heavily pretreated patient population confirm that oxaliplatin is safe when used as a single agent or with a variety of FU-based regimens as salvage therapy in patients with advanced colorectal cancer. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Canc Ctr Carolinas, Greenville, NC USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. RP Ramanathan, RK (reprint author), UPMC, Canc Pavil,5150 Ctr Ave,562, Pittsburgh, PA 15232 USA. NR 17 TC 34 Z9 36 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2003 VL 21 IS 15 BP 2904 EP 2911 DI 10.1200/JCO.2003.11.045 PG 8 WC Oncology SC Oncology GA 706PJ UT WOS:000184461800015 PM 12885808 ER PT J AU Dalton, VK Rue, M Silverman, LB Gelber, RD Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, M Tarbell, NJ Sallan, SE Cohen, LE AF Dalton, VK Rue, M Silverman, LB Gelber, RD Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, M Tarbell, NJ Sallan, SE Cohen, LE TI Height and weight in children treated for acute lymphoblastic leukemia: Relationship to CNS treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOCYTIC-LEUKEMIA; LONG-TERM SURVIVORS; CRANIAL IRRADIATION; FINAL HEIGHT; DANA-FARBER; CHILDHOOD; GROWTH; OBESITY; ADULTS; GIRLS AB Purpose: We evaluated the long-term effects of treatment on height and weight in children with acute lymphoblastic leukemia (ALL) treated with one of the following three different CNS therapies: intrathecal therapy alone, intrathecal therapy with conventional cranial radiation, or intrathecal therapy with twice-daily radiation. Patients and Methods: Between 1987 and 1995, 618 children treated on two consecutive Dana-Farber Cancer Institute Consortium protocols for ALL were measured for height and weight at diagnosis, and approximately every 6 months thereafter. Patient height, weight, and body mass index (BMI) were converted to z scores for age and sex using the 2000 Centers for Disease Control and Prevention growth charts for the United States. Results: Children younger than 13 years at diagnosis had a statistically significant decrease in their height x scores and an increase in their BMI z scores, regardless of whether they had received cranial radiation. Young age at diagnosis and increased chemotherapy intensity were major risk factors. Unexpectedly, there was no significant difference in long-term height between children who received radiation and those who did not. Conclusion: Final height is compromised in survivors of ALL. The detrimental effects on height occur during therapy without the ability for long-term catch-up growth. Although patients became overweight for height, this seemed to be a result of relative height loss with normal weight gain rather than accelerated weight gain. The type of CNS treatment received did not affect changes in height, weight, or BMI. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Rochester, Med Ctr, Div Pediat Hematol Oncol, Rochester, NY 14642 USA. Div Pediat Oncol, San Juan, PR USA. Maine Med Ctr, Maine Childrens Canc Program, Dept Pediat Hematol Oncol, Portland, ME 04102 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Portland, ME 04102 USA. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. Hop St Justine, Div Hematol Oncol, Montreal, PQ H3T 1C5, Canada. Univ Laval, Ctr Hosp, Div Hematol Oncol, Quebec City, PQ, Canada. Tulane Med Sch, Sect Pediat Hematol Oncol, New Orleans, LA USA. RP Dalton, VK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Dana 355, Boston, MA 02115 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [CA 68484] NR 34 TC 63 Z9 64 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2003 VL 21 IS 15 BP 2953 EP 2960 DI 10.1200/JCO.2003.03.068 PG 8 WC Oncology SC Oncology GA 706PJ UT WOS:000184461800022 PM 12885815 ER PT J AU Oslin, DW Ten Have, TR Streim, JE Datto, CJ Weintraub, D DiFilippo, S Katz, IR AF Oslin, DW Ten Have, TR Streim, JE Datto, CJ Weintraub, D DiFilippo, S Katz, IR TI Probing the safety of medications in the frail elderly: Evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ADVERSE DRUG EVENTS; PHARMACOLOGICAL TREATMENT; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; RATING-SCALE; EARLY-ONSET; ANTIDEPRESSANTS; NORTRIPTYLINE; EFFICACY; DEMENTIA AB Background. In nursing home residents and other frail elderly patients, old age and potential drug-drug and drug-disease interactions may affect the relative safety and efficacy of medications. The purpose of this study was to examine the efficacy and tolerability of venlafaxine and sertraline for the treatment of depression among nursing home residents. Method. The study was a 10-week randomized, double-blind, controlled trial of venlafaxine (doses up to 150 mg/day) versus sertraline (doses up to 100 mg/day) among 52 elderly nursing home residents with a DSM-IV depressive disorder and, at most, moderate dementia. The primary measure of outcome was the Hamilton Rating Scale for Depression (HAM-D). Adverse events were monitored and recorded systematically during the trial. Results: Twelve subjects were discontinued due to serious adverse events (SAE), 5 were discontinued due to other significant side effects, and 2 withdrew consent. Tolerability estimated by the time to termination was lower for venlafaxine than sertraline for serious adverse events (log rank statistic = 5.28, p = .022), for serious adverse events or side effects (log rank statistic = 8.08, p = .005), or for serious adverse events, side effects, or withdrawal of consent (log rank statistic = 10.04, p = .002). Mean (SD) HAM-D scores at baseline were 20.2 (3.4) for sertraline and 20.3 (3.7) for venlafaxine; intent-to-treat endpoint HAM-D scores were 12.2 (5.1) and 15.7 (6.2) (F = 3.45; p = .069). There were no differences in categorical responses for the intent-to-treat sample or completers. Conclusion: In this frail elderly population, venlafaxine was less well tolerated and, possibly, less safe than sertraline without evidence for an increase in efficacy. This unexpected finding demonstrates the need for systematic research on the safety of drugs in the frail elderly. C1 Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Ctr Stydy Addict, Philadelphia, PA 19104 USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Katz, IR (reprint author), Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, 3535 Market St,Rm 3055, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [R37MH52147-09, P30MH52129, P30MH66270] NR 52 TC 67 Z9 68 U1 2 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD AUG PY 2003 VL 64 IS 8 BP 875 EP 882 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 714NM UT WOS:000184920400004 PM 12927001 ER PT J AU Fava, M McGrath, PJ Sheu, WP AF Fava, M McGrath, PJ Sheu, WP CA Reboxetine Study Grp TI Switching to reboxetine: An efficacy and safety study in patients with major depressive disorder unresponsive to fluoxetine SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID ONE ANTIDEPRESSANT FAILS; HEALTHY-VOLUNTEERS; RATING-SCALE; PSYCHIATRISTS; RELAPSE AB The aim of the present study was to evaluate the efficacy and safety of an immediate switch to reboxetine, a selective noradrenaline reuptake inhibitor (selective NRI), in patients with depression unresponsive to the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The study included 128 adult outpatients with DSM-IV major depressive disorder (MDD) who had not responded to at least 6 to 12 weeks of fluoxetine treatment, with at least 3 weeks of treatment on a minimum dose of 40 mg/d. Patients were switched, without a washout period, to reboxetine 4 mg twice daily, with the possibility of increasing the dose to 10 mg/d (given in divided doses) after 4 weeks of treatment. Efficacy was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-1) and Severity (CGI-S) scales. Safety was evaluated by recording spontaneously reported adverse events. A statistically significant (P < 0.001) improvement in the mean total HAM-D-17 score was seen from baseline by week 1 of treatment with reboxetine, and the improvement continue to week 8. CGI-I and CGI-S scores were similarly improved. The switch to reboxetine was well tolerated; the most common treatment-emergent adverse events were insomnia, headache, dry mouth, diaphoresis. and constipation, all of which were mild to moderate in severity and decreased in frequency as the study progressed. Immediate switching to reboxetine appears to be a safe and effective treatment for patients with depression who have failed to respond to an adequate dose of fluoxetine. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Pharmacia Corp, Toronto, ON, Canada. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. RI McGrath, Patrick/I-6410-2013 OI McGrath, Patrick/0000-0001-7217-7321 NR 29 TC 22 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2003 VL 23 IS 4 BP 365 EP 369 DI 10.1097/01.jcp.0000085409.08426.4c PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 708ET UT WOS:000184554700008 PM 12920412 ER PT J AU Baldessarini, RJ Hennen, J Wilson, M Calabrese, J Chengappa, R Keck, PE McElroy, SL Sachs, G Vieta, E Welge, JA Yatham, LN Zarate, CA Baker, RW Tohen, M AF Baldessarini, RJ Hennen, J Wilson, M Calabrese, J Chengappa, R Keck, PE McElroy, SL Sachs, G Vieta, E Welge, JA Yatham, LN Zarate, CA Baker, RW Tohen, M TI Olanzapine versus placebo in acute mania - Treatment responses in subgroups SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID BIPOLAR DISORDER; MAINTENANCE TREATMENT; PSYCHOTIC FEATURES; SCALE; EPISODES AB Two double-blind, placebo-controlled trials of olanzapine in acute mania showed significant overall antimanic efficacy, based on reductions in mania ratings. Their subject-level data were pooled to increase statistical power to test for differences in treatment responses among 10 subgroup pairs of interest using generalized estimating equations methods. Similar drug/placebo superiority and responsiveness to olanzapine was found in men versus women, psychotic versus nonpsychotic subjects, and those presenting in mania versus mixed states, and responses were independent of onset age, current age, or prior illness based on episodes, hospitalizations, recent rapid cycling, lifetime substance use, or previous antipsychotic treatment. Olanzapine and placebo responses paralleled closely (r(s) = 0.73). Patients were relatively more responsive to olanzapine who were younger at illness onset, lacked prior substance abuse, and had not previously received antipsychotic treatment (efficacy ratios 1.5-1.7, all P < 0.01). These well-powered comparisons of subgroups of interest indicate broad efficacy of olanzapine in the treatment of acute mania. C1 Harvard Univ, Sch Med, Dept Psychiat, Int Consortium Bipolar Diorder Res, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Int Consortium Bipolar Diorder Res, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA USA. Butler Univ, Dept Pharm & Hlth Sci, Indianapolis, IN 46208 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst, Dept Psychiat, Pittsburgh, PA USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Barcelona, Hosp Clin Barcelona, August Pi Sunyer Biomed Res Inst IDIBAPS, Barcelona, Spain. Univ British Columbia, Coll Med, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. NIMH, Bethesda, MD 20892 USA. Lilly Res Labs, Indianapolis, IN USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 NR 23 TC 47 Z9 50 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD AUG PY 2003 VL 23 IS 4 BP 370 EP 376 DI 10.1097/01.jcp.0000085410.08426.9a PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 708ET UT WOS:000184554700009 PM 12920413 ER PT J AU Valera, EM Berenbaum, H AF Valera, EM Berenbaum, H TI Brain injury in battered women SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY DEC 06-09, 2001 CL NEW ORLEANS, LOUISIANA SP Int Soc Traumat Stress Studies ID MINOR HEAD-INJURY; POSTTRAUMATIC-STRESS-DISORDER; VIOLENCE; RELIABILITY; CONCUSSION; DEPRESSION; SYMPTOMS; SCALES AB The goals of the present study were to examine (a) whether battered women in a sample of both shelter and nonshelter women are sustaining brain injuries from their partners and (b) if so, whether such brain injuries are associated with partner abuse severity, cognitive functioning, or psychopathology. Ninety-nine battered women were assessed using neuropsychological, psychopathology, and abuse history measures. Almost three quarters of the sample sustained at least I partner-related brain injury and half sustained multiple partner-related brain injuries. Further, in a subset of women (n = 57), brain injury severity was negatively associated with measures of memory, learning, and cognitive flexibility and was positively associated with partner abuse severity, general distress, anhedonic depression, worry, anxious arousal, and posttraurnatic stress disorder symptomatology. C1 Univ Illinois, Dept Psychol, Urbana, IL 61801 USA. RP Valera, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Bldg 149,9th Floor E,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [1 F31 MH11763-01A2] NR 53 TC 22 Z9 22 U1 3 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2003 VL 71 IS 4 BP 797 EP 804 DI 10.1037/0022-006X.71.4.797 PG 8 WC Psychology, Clinical SC Psychology GA 703QM UT WOS:000184292500018 PM 12924684 ER PT J AU Shapiro, NI Kociszewski, C Harrison, T Chang, YC Wedel, SK Thomas, SH AF Shapiro, NI Kociszewski, C Harrison, T Chang, YC Wedel, SK Thomas, SH TI Isolated prehospital hypotension after traumatic injuries: A predictor of mortality? SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE hypotension; prehospital; trauma; helicopter EMS; outcomes ID BLOOD-PRESSURE MEASUREMENTS; TRANSPORT; SCENE; HELICOPTER AB In patients with traumatic injuries, prehospital hypotension that resolves by Emergency Department (ED) arrival is of uncertain significance. We examined the impact of prehospital hypotension (PH) in normotensive ED patients with traumatic injuries on predicting mortality and chest/abdominal operative intervention. A retrospective cohort study was conducted of consecutive patients undergoing helicopter transport to two trauma centers between 1993 and 1997. Outcomes were mortality and chest or abdominal operative intervention. Of 545 scene transports, 55 (10.1%) patients were hypotensive on ED arrival, leaving 490 normotensive ED patients. Of 490 patients, 35 (7%) had PH and 455 (93%) had no PH. Multiple logistic regression showed the PH group to have a relative risk for death of 4.4 (95% CI: 1.2-16.6, p < 0.03) and for chest or abdominal operative intervention of 2.9 (1.1-7.6, p < 0.03). In this study of normotensive trauma center patients, prehospital hypotension was associated with increased risk of mortality and significant chest or abdominal injury. (C) 2003 Elsevier Inc. C1 Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Boston Medflight Crit Care Transport Serv, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Shapiro, NI (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 330 Brookline Ave,CC2-W, Boston, MA 02215 USA. RI Shapiro, Nathan/F-1718-2016 NR 14 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2003 VL 25 IS 2 BP 175 EP 179 DI 10.1016/S0736-4679(03)00167-7 PG 5 WC Emergency Medicine SC Emergency Medicine GA 707QE UT WOS:000184520700009 PM 12902005 ER PT J AU Mick, N Brown, DFM Nadel, ES AF Mick, N Brown, DFM Nadel, ES TI Pediatric altered mental status SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID HYPOGLYCEMIA C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD AUG PY 2003 VL 25 IS 2 BP 193 EP 196 DI 10.1016/S0736-4679(03)00176-8 PG 4 WC Emergency Medicine SC Emergency Medicine GA 707QE UT WOS:000184520700012 PM 12902008 ER PT J AU Mitsiades, CS Poulaki, V Mitsiades, N AF Mitsiades, CS Poulaki, V Mitsiades, N TI The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer SO JOURNAL OF ENDOCRINOLOGY LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; FAS-MEDIATED APOPTOSIS; INFLAMMATORY CYTOKINE REGULATION; INDUCED-PROXIMITY MODEL; EWINGS-SARCOMA FAMILY; BCL-2 PROTEIN FAMILY; CARCINOMA-CELL-LINES; FACTOR-KAPPA-B; FACTOR-ALPHA; IN-VIVO AB The tumor necrosis factor (TNF) family comprises several ligands, such as the prototype TNF-alpha, the Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL/Apo2L), which trigger apoptosis in susceptible cells by activating respective cell-surface receptors. The study of these cell death pathways has attracted significant attention in several fields, including that of thyroid cancer, because they participate in immune system function, as an arm of cell-mediated cytotoxicity, and because recombinant ligands are available for Pharmacological use. TNF-alpha is a pluripotent cytokine that induces both proapoptotic and anti-apoptotic effects on thyroid carcinoma cells. FasL triggers apoptosis in other tumor types, but thyroid carcinoma cells are resistant to this effect. On the other hand, TRAIL potently and selectively kills thyroid carcinoma cells. Consequently, TRAIL is the only member of the family with significant anticancer activity and an acceptable toxicity profile to be used as a novel therapy for thyroid cancer. The caspase inhibitor FLIP plays a significant role in negatively regulating receptor-induced apoptosis. Thelper 1-type cytokines, such as interferon-gamma, TNF-alpha and interleukin-1beta increase the sensitivity of both normal and neoplastic thyrocytes to FasL and TRAIL. On the other hand, IGF-I and other growth/ survival factors produced in the local tumor microenvironinent activate the phosphatidylinositol 3-kinase/Akt kinase pathway and exert an anti-apoptotic effect by upregulating several apoptosis inhibitors, including FLIP. Pharmacological modulation of apoptosis induced by FasL and TRAIL/Apo2L holds promise of therapeutic applications in human malignancies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. RP Mitsiades, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Mayer Bldg,Room M555,44 Binney St, Boston, MA 02115 USA. EM mitstades@netscape.net NR 111 TC 28 Z9 29 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD AUG PY 2003 VL 178 IS 2 BP 205 EP 216 DI 10.1677/joe.0.1780205 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 714GC UT WOS:000184903100004 PM 12904168 ER PT J AU Orlander, JD Fincke, BG AF Orlander, JD Fincke, BG TI Morbidity and mortality conference - A survey of academic internal medicine departments SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE graduate medical education; medical error; internal medicine training; survey ID ERROR AB This study sought to determine the prevalence and characteristics of morbidity and mortality conferences (M&MCs) in U.S. internal medicine training programs. Two hundred ninety-five of 416 (71%) surveys were returned. Ninety percent of programs have an M&MC. Most meet monthly, have a designated leader, and entail case discussions of 3 or fewer patients. Cases are selected on the basis of unexpected bad outcomes, teaching value, and to a lesser extent, suspected medical error. Two thirds of the sites use M&MCs to meet administrative requirements for quality assurance. M&MC, while prevalent in internal medicine training programs, has a heterogeneity of focus. Hence, the goals and role of the conference, as judged by this survey, do not appear to be well defined and may warrant further clarification. C1 Boston Univ, Boston Div,Sch Med,Evans Dept Med, Sect Gen Internal Med & Clin Epidemiol, VA Boston Hlth Care Syst, Boston, MA 02130 USA. Edith Nourse Rogers VA Med Ctr, Ctr Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Orlander, JD (reprint author), Boston Univ, Boston Div,Sch Med,Evans Dept Med, Sect Gen Internal Med & Clin Epidemiol, VA Boston Hlth Care Syst, 111PI,150 S Huntington Ave, Boston, MA 02130 USA. NR 10 TC 46 Z9 46 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2003 VL 18 IS 8 BP 656 EP 658 DI 10.1046/j.1525-1497.2003.20824.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 711CU UT WOS:000184722500010 PM 12911649 ER PT J AU Sankar, P Moran, S Merz, JF Jones, NL AF Sankar, P Moran, S Merz, JF Jones, NL TI Patient perspectives of medical confidentiality - A review of the literature SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE review; medical confidentiality; patient attitudes; privacy; biomedical ethics ID GENERAL-PRACTITIONER SERVICES; OVARIAN-CANCER SUSCEPTIBILITY; SEEK HEALTH-CARE; HIV-INFECTION; BREAST-CANCER; PATIENTS VIEW; THERAPEUTIC RELATIONSHIP; PARTNER NOTIFICATION; PATIENTS ATTITUDES; ADOLESCENT GIRLS AB OBJECTIVE: To lay the groundwork for a better understanding of patient views on medical confidentiality. DESIGN: Studies were found by searching medline, bioethicsline, and selected bibliographies. Articles concerning physician perspectives or implications of legal and administrative regulations were excluded. Only peer-reviewed journal articles reporting original research on patients' confidentiality views and conduct were included. MAIN RESULTS: Many patients are unaware of or misunderstand their legal or ethical right to medical confidentiality protections, which leads them to both over- and underestimate confidentiality protections. The possibility that medical information might be revealed, intentionally or not, to acquaintances in a clinic or other social community troubles patients as much as information release to insurers or employers. A significant minority of patients distrust confidentiality protections, leading some to report that they delay or forgo medical care. If doubtful that confidentiality will be upheld, patients will act independently to protect information. CONCLUSIONS: Our review found a wider variety of understandings and beliefs about medical confidentiality among patients than are often indicated in the writings of practitioners or legal experts. As medical confidentiality regulations evolve, these differences need to be recognized and accounted for in interactions between practitioners and patients. C1 Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Internal Med Unit, Boston, MA USA. RP Sankar, P (reprint author), Univ Penn, Ctr Bioeth, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. NR 124 TC 32 Z9 33 U1 7 U2 11 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2003 VL 18 IS 8 BP 659 EP 669 DI 10.1046/j.1525-1497.2003.20823.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 711CU UT WOS:000184722500011 PM 12911650 ER PT J AU Long, JA Polsky, D Asch, DA AF Long, JA Polsky, D Asch, DA TI Receipt of health services by low-income veterans SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article ID UNITED-STATES; CARE COVERAGE; OLDER-ADULTS; RISK-FACTORS; MORTALITY; INSURANCE; ACCESS; HOSPITALIZATION; DISPARITIES; PLUS C1 Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Long, JA (reprint author), Philadelphia Vet Affairs Ctr Hlth Equ Res & Promo, Philadelphia, PA USA. NR 30 TC 0 Z9 0 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2003 VL 14 IS 3 BP 305 EP 317 DI 10.1177/1049208903255439 PG 13 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 706XL UT WOS:000184480300001 PM 12955911 ER PT J AU Shacklett, BL Yang, O Hausner, MA Elliott, J Hultin, L Price, C Fuerst, M Matud, J Hultin, P Cox, C Ibarrondo, J Wong, JT Nixon, D Anton, PA Jamieson, BD AF Shacklett, BL Yang, O Hausner, MA Elliott, J Hultin, L Price, C Fuerst, M Matud, J Hultin, P Cox, C Ibarrondo, J Wong, JT Nixon, D Anton, PA Jamieson, BD TI Optimization of methods to assess human mucosal T-cell responses to HIV infection SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE mucosal immunity; ELISpot; T cells; tetramer; HIV; GALT ID IMMUNODEFICIENCY-VIRUS TYPE-1; INTESTINAL LAMINA PROPRIA; LINKED IMMUNOSPOT ASSAY; LYMPH-NODE IMMUNIZATION; PERIPHERAL-BLOOD; HIV-1-INFECTED SUBJECTS; MONOCLONAL-ANTIBODIES; VIRAL REPLICATION; IMMUNE-RESPONSES; FLOW-CYTOMETRY AB The majority of HIV-1 infections occur via sexual transmission at mucosal epithelia lining the vagina, cervix or rectum. Mucosal tissues also serve as viral reservoirs. However, our knowledge of human mucosal T-cell responses is limited. There is a need for reliable, sensitive, and reproducible methods for assessing mucosal immunity. Here we report on the collaborative efforts of two laboratories to optimize methods for processing, culturing, and analyzing mucosal lymphocytes. Rectal biopsy tissue was obtained by flexible sigmoidoscopy, which is rapid, minimally invasive, and well tolerated. Of the four methods compared for isolating mucosal mononuclear cells (MMC), collagenase digestion reproducibly yielded the most lymphocytes (4-7 x 10(6)). Furthermore, 0.5-1 x 10(6) MMC could be polyclonally expanded to yield 17 X 10(6) CD8+ T cells allowing mapping of responses to overlapping peptides spanning the HIV-1 genome using IFN-gamma enzyme-linked immunospot (ELISpot). Expansion also reduced the spontaneous IFN-gamma production normally detected in fresh MMC. Piperacillin-tazobactam and amphotericin B reduced contamination of MMC cultures to 4%. Taken together, these methods will be useful for studies of mucosal immunity to HIV-1 and other pathogens during natural infection and following vaccination. (C) 2003 Elsevier B.V All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Jamieson, BD (reprint author), Univ Calif Los Angeles, Med Ctr, Dept Med Hematol & Oncol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. RI Shacklett, Barbara/A-7288-2009; OI Shacklett, Barbara/0000-0002-7067-732X; Nixon, Douglas/0000-0002-2801-1786 FU NCI NIH HHS [CA16042]; NIAID NIH HHS [AI27763, AI01610, AI051596, AI28697, AI35040, AI37613, AI44595, AI50467] NR 52 TC 68 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD AUG PY 2003 VL 279 IS 1-2 BP 17 EP 31 DI 10.1016/S0022-1759(03)00255-2 PG 15 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 722ND UT WOS:000185381300002 PM 12969544 ER PT J AU Schattner, A Aviel-Ronen, S Mark, EJ AF Schattner, A Aviel-Ronen, S Mark, EJ TI Accelerated usual interstitial pneumonitis, anti-DNA antibodies and hypocomplementemia SO JOURNAL OF INTERNAL MEDICINE LA English DT Article DE anti-DNA antibodies; interstitial lung disease; systemic lupus erythematosus; usual interstitial pneumonitis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; IDIOPATHIC PULMONARY FIBROSIS; LUNG INVOLVEMENT; DISEASE AB A healthy 60-year-old patient presented with progressive dyspnoea. Clinical, radiographic and pathological features of interstitial lung disease were found and an open lung biopsy established the diagnosis of usual interstitial pneumonitis (UIP) (idiopathic pulmonary fibrosis). Despite treatment, the patient died 4 months later in respiratory failure. Although the patient had no extra-thoracic involvement at autopsy, his illness was associated with a very high titre of anti-double-stranded DNA antibodies, hypocomplementemia, hypergammaglobulinaemia and lymphoid hyperplasia. These features and a literature review, suggest immune-mediated lung damage in a subset of patients with UIP. C1 Kaplan Med Ctr, Dept Med, IL-76100 Rehovot, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel. Chaim Sheba Med Ctr, Dept Pathol, IL-52621 Tel Hashomer, Israel. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schattner, A (reprint author), Kaplan Med Ctr, Dept Med, IL-76100 Rehovot, Israel. NR 19 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD AUG PY 2003 VL 254 IS 2 BP 193 EP 196 DI 10.1046/j.1365-2796.2003.01144.x PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 699PR UT WOS:000184065600012 PM 12859701 ER PT J AU Gonzalez, S Astner, S An, W Goukassian, D Pathak, MA AF Gonzalez, S Astner, S An, W Goukassian, D Pathak, MA TI Dietary lutein/zeaxanthin decreases ultraviolet B-induced epidermal hyperproliferation and acute inflammation in hairless mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE antioxidants; carotenoids; lutein and zeaxanthin; oral photoprotection ID HUMAN-SKIN; BETA-CAROTENE; PROSTAGLANDIN SYNTHESIS; POLYPODIUM-LEUCOTOMOS; MACULAR DEGENERATION; LIPID-PEROXIDATION; ARACHIDONIC-ACID; CLINICAL-TRIAL; INDUCED DAMAGE; BASAL-CELL AB Lutein and zeaxanthin are carotenoids found in green leafy vegetables with interesting antioxidant properties. They are present in high concentrations in the fovea centralis of the human retina and their role in the prevention of age-related macula degeneration has been reported. We have investigated the effect of orally administered lutein and zeaxanthin in the cutaneous response to ultraviolet B irradiation. Female hairless SKh-1 mice receiving 0.4% and 0.04% lutein plus zeaxanthin-enriched diet for 2 wk were exposed to single doses of ultraviolet B radiation. Skin biopsies were taken at 24 and 48 h after irradiation and analyzed for the presence of apoptotic cells, proliferating cells, and expression of proliferating cell nuclear antigen. Our results show a clear ultraviolet-induced dose-dependent inflammatory response. Orally administered 0.4% lutein and zeaxanthin decreased significantly the edematous cutaneous response (p<0.01) as determined by the reduction of the UVB-induced increase of ear bifold thickening. Additionally, dietary carotenoids were efficient in reducing the ultraviolet B-induced increases in the percentage of proliferating cell nuclear antigen (p<0.05), bromodeoxyuridine (p<0.05), and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling-positive cells (p<0.01). These data demonstrate that oral supplementation of lutein and zeaxanthin diminishes the effects of ultraviolet B irradiation by reducing acute inflammatory responses and ultraviolet-induced hyperproliferative rebound. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. RP Gonzalez, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, 40 Blossom St,Bartlett Hall 814, Boston, MA 02114 USA. RI Barickman, Thomas/I-6993-2012 NR 46 TC 56 Z9 63 U1 2 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2003 VL 121 IS 2 BP 399 EP 405 DI 10.1046/j.1523-1747.2003.12355.x PG 7 WC Dermatology SC Dermatology GA 705JG UT WOS:000184391500025 PM 12880433 ER PT J AU Hamrah, P Huq, SO Liu, Y Zhang, Q Dana, MR AF Hamrah, P Huq, SO Liu, Y Zhang, Q Dana, MR TI Corneal immunity is mediated by heterogeneous population of antigen-presenting cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE corneal stroma; dendritic cells; macrophages; major histocompatibility complex; corneal transplantation ID EPIDERMAL LANGERHANS CELLS; NECROSIS-FACTOR-ALPHA; DENDRITIC CELLS; HLA-DR; TRANSPLANTATION; INTERLEUKIN-1; EXPRESSION; MIGRATION; REJECTION; ALLOGRAFTS AB Corneal antigen-presenting cells (APC), including dendritic cells (DC), were thought to reside exclusively in the peripheral cornea. Here, we present recent data from our group demonstrating that the central cornea is indeed endowed with a heterogeneous population of epithelial and stromal DC, which function as APC. Although the corneal periphery contains mature and immature resident bone marrow-derived CD11c(+) DC, the central cornea is endowed exclusively with immature and precursor DC, both in the epithelium and the stroma, wherein Langerhans cells and monocytic DC reside, respectively. During inflammation, a majority of resident DC undergo maturation by overexpressing major histocompatibility complex class II and B7 (CD80/CD86) costimulatory molecules. In addition to the DC, macrophages are present in the posterior corneal stroma. In transplantation, donor-derived DC are able to migrate to host cervical lymph nodes and activate host T cells via the direct pathway when allografts are placed in inflamed host beds. These data revise the tenet that the cornea is immune-privileged as a result of lack of resident lymphoreticular cells and suggest that the cornea is capable of diverse cellular mechanisms for antigen presentation. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Immunol Lab, 20 Staniford St, Boston, MA 02114 USA. NR 58 TC 113 Z9 118 U1 1 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2003 VL 74 IS 2 BP 172 EP 178 DI 10.1189/jlb.1102544 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FC UT WOS:000187392000005 PM 12885933 ER PT J AU Linseman, DA Cornejo, BJ Le, SS Meintzer, MK Laessig, TA Bouchard, RJ Heidenreich, KA AF Linseman, DA Cornejo, BJ Le, SS Meintzer, MK Laessig, TA Bouchard, RJ Heidenreich, KA TI A myocyte enhancer factor 2D (MEF2D) kinase activated during neuronal apoptosis is a novel target inhibited by lithium (vol 85, pg 1488, 2002) SO JOURNAL OF NEUROCHEMISTRY LA English DT Correction C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Linseman, DA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2003 VL 86 IS 4 BP 1055 EP 1055 DI 10.1046/j.1471-4159.2003.01999.x PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 706JW UT WOS:000184451400027 ER PT J AU Sanford, LD Tang, XD Xiao, JH Ross, RJ Morrison, AR AF Sanford, LD Tang, XD Xiao, JH Ross, RJ Morrison, AR TI GABAergic regulation of REM sleep in reticularis pontis oralis and caudalis in rats SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENT SLEEP; GIGANTOCELLULAR TEGMENTAL FIELD; GABA-A ANTAGONIST; PARADOXICAL SLEEP; MICROINJECTIONS; INDUCTION; CAT; BICUCULLINE; LESIONS; HYPOTHALAMUS AB The nucleus reticularis pontis oralis (RPO) and nucleus reticularis pontis caudalis (RPC) are implicated in the generation of rapid eye movement sleep (REM). Work in cats has indicated that GABA in RPO plays a role in the regulation of REM. We assessed REM after local microinjections into RPO and RPC of the gamma-aminobutyric acid-A (GABA(A)) agonist, muscimol (MUS), and the GABA(A) antagonist, bicuculline (BIC). Rats (90-day-old male Sprague-Dawley) were implanted with electrodes for recording electroencephalographs (EEG) and electromyographs (EMG). Guide cannulae were aimed into RPO (n = 9) and RPC (n = 8) for microinjecting MUS (200, 1,000.0 muM) and BIC (0.056, 0.333, 1.0, 1,000.0, and 10,000.0 muM). Animals received bilateral microinjections of saline, MUS, and BIC (0.2 mul microinjected at 0.1 mul/min) into each region followed by 6-h sleep recordings. In RPO, MUS (1,000.0 muM) suppressed REM and BIC (1,000.0 muM) enhanced REM. In RPC, MUS (200, 1,000.0 muM) suppressed REM, but BIC (1,000.0 muM and less) did not significantly affect REM. Higher concentrations of BIC (10,000.0 muM) injected into RPO (n = 9) and RPC (n = 4) produced wakefulness and escape behavior. The results indicate that GABA in RPO/RPC is involved in the regulation of REM and suggest site-specific differences in this regulation. C1 Eastern Virginia Med Sch, Sleep Res Lab, Dept Anat & Pathol, Norfolk, VA 23501 USA. Univ Penn, Lab Study Brain Sleep, Dept Biol Anim, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Sanford, LD (reprint author), Eastern Virginia Med Sch, Sleep Res Lab, Dept Anat & Pathol, POB 1980, Norfolk, VA 23501 USA. FU NINDS NIH HHS [NS-36694] NR 39 TC 61 Z9 62 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2003 VL 90 IS 2 BP 938 EP 945 DI 10.1152/jn.00993.2002 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 708KE UT WOS:000184565300042 PM 12672782 ER PT J AU Barker, FG Loeffler, JS Chapman, PH AF Barker, FG Loeffler, JS Chapman, PH TI Proton beam for arteriovenous malformations - Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2003 VL 99 IS 2 BP 223 EP 224 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 707TN UT WOS:000184526100009 ER PT J AU Barker, FG Butler, WE Lyons, S Cascio, E Ogilvy, CS Loeffler, JS Chapman, PH AF Barker, FG Butler, WE Lyons, S Cascio, E Ogilvy, CS Loeffler, JS Chapman, PH TI Dose-volume prediction of radiation-related complications after proton beam radiosurgery for cerebral arteriovenous malformations SO JOURNAL OF NEUROSURGERY LA English DT Article DE arteriovenous malformation; radiosurgery; complication ID GAMMA-KNIFE RADIOSURGERY; INTEGRATED LOGISTIC FORMULA; SURGERY; THERAPY; BRAIN; RISK; OBLITERATION; MANAGEMENT; ONCOLOGY; TUMORS AB Object. The use of radiosurgery for the treatment of cerebral arteriovenous malformations (AVMs) and other lesions demands an accurate understanding of the risk of radiation-related complications. Some commonly used formulas for predicting risk are based on extrapolation from small numbers of animal experiments, pilot human treatment series, and theoretical radiobiological considerations. The authors studied the incidence of complications after AVM radiosurgery in relation to dose, volume, and other factors in a large patient series. Methods. A retrospective review was conducted in 1329 patients with AVM treated by Dr. Raymond Kjellberg at the Harvard Cyclotron Laboratory (HCL) between 1965 and 1993. Dose and volume were obtained from HCL records, and information about patient follow up was derived from concurrent clinical records, questionnaires, and contact with referring physicians. Multivariate logistic regression with bootstrapped confidence intervals was used. Follow up was available in 1250 patients (94%); the median follow-up duration was 6.5 years. The median radiation dose was 10.5 Gy and the median treatment volume was 33.7 cm(3). Twenty-three percent of treated lesions were smaller than 10 cm(3). Fifty-one permanent radiation-related deficits occurred (4.1%). Of 1043 patients treated with a dose predicted by the Kjellberg isoeffective centile curve to have a less than 1% complication risk, 1.8% suffered radiation-related complications. Actual complication rates were 4.7% for 128 patients treated at Kjellberg risk centile doses of I to 1.8%, and 34% for 61 patients treated at risk centile doses of 2 to 2.5%. The fitted logistic model showed that complication risk was related to treatment dose and volume, thalamic or brainstem location, and patient age. Conclusions. The Kjellberg isoeffective risk centile curve significantly underpredicted actual risks of permanent complications after proton beam radiosurgery for AVMs. Actual risks were best predicted using a model that accounted for treatment dose and volume, lesion location, and patient age. C1 Massachusetts Gen Hosp, Neurosurg Serv, Proton Radiosurg Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Proton Radiosurg Grp, Cox 315,Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 39 TC 41 Z9 41 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2003 VL 99 IS 2 BP 254 EP 263 DI 10.3171/jns.2003.99.2.0254 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 707TN UT WOS:000184526100015 PM 12924697 ER PT J AU Li, XC Heckman, NE AF Li, XC Heckman, NE TI Local linear extrapolation SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE local linear estimation; prediction; bandwidth selection ID LEAST-SQUARES REGRESSION; NONPARAMETRIC REGRESSION; BANDWIDTH SELECTION; KERNEL REGRESSION; CROSS-VALIDATION; ERRORS AB A local linear estimator is proposed for extrapolating beyond the range of independent regression data. The asymptotic bias and variance of the local linear extrapolant are presented and used to calculate the asymptotic mean squared error. Three procedures are considered for choice of the bandwidth: a plug-in procedure. a forward cross-validation procedure and a procedure that combines the two. All of these are, in some sense. based on minimizing the asymptotic mean squared error. A simulation study shows that the forward cross-validation procedure outperforms the other two procedures both in terms of choosing a bandwidth and in terms of accurate extrapolation. The techniques are applied to two data sets. C1 Univ British Columbia, Dept Stat, Vancouver, BC V6T 1Z2, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Heckman, NE (reprint author), Univ British Columbia, Dept Stat, Vancouver, BC V6T 1Z2, Canada. EM nancy@stat.ubc.ca NR 25 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PD AUG-OCT PY 2003 VL 15 IS 4-5 BP 565 EP 578 DI 10.1080/10485250310001605432 PG 14 WC Statistics & Probability SC Mathematics GA 746QD UT WOS:000186756300013 ER PT J AU Fischman, AJ Thrall, JH AF Fischman, AJ Thrall, JH TI Who should read and interpret F-18-FDG PET studies? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 4 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2003 VL 44 IS 8 BP 1197 EP 1199 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 709XB UT WOS:000184650900006 PM 12902407 ER PT J AU Oaklander, AL Bowsher, D Galer, B Haanpaa, M Jensen, MP AF Oaklander, AL Bowsher, D Galer, B Haanpaa, M Jensen, MP TI Herpes zoster itch: Preliminary epidemiologic data SO JOURNAL OF PAIN LA English DT Article DE shingles; human nervous system; postherpetic neuralgia; pruritus ID TRIGEMINAL TROPHIC SYNDROME; POSTHERPETIC NEURALGIA; UNILATERAL PRURITUS; MOTOR INVOLVEMENT; HUMAN SKIN; PAIN; ALLODYNIA; ACYCLOVIR; SHINGLES; BRAIN AB The best-known complication of shingles (herpes zoster) is postherpetic neuralgia (PHN). PHN is commonly studied to investigate causes of and treatments for neuropathic pain. However, many patients with shingles experience neuropathic itch accompanying, or instead of, pain. Some report severe disabling postherpetic itch (PHI), and though it is rare, some patients injure themselves by scratching itchy skin that has lost protective sensation. To date, there is virtually no mention of PHI in the medical literature; neither epidemiologic, anatomic, physiologic, nor treatment studies. We analyzed 3 independent existing sets of data from 586 adults with shingles or PHN to glean epidemiologic information about pruritus during and after shingles. All data refer to itch localized to shingles-affected areas and initiated by shingles. They indicate that pruritus, usually mild or moderate, commonly accompanies both acute zoster and PHN. There was no significant difference in age between subjects with and without PHI. In one group, but not in another, there was an increased number of women with PHI. Subjects whose shingles affected the head, face, and neck were more likely to experience PHI than those whose shingles affected the torso. These findings indicate a need for research on zoster-associated itch, including prospective studies on frequency, impact, and treatment. (C) 2003 by the American Pain Society. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Nerve Injury Unit, Boston, MA 02114 USA. Univ Hosp Aintree, Pain Res Inst, Liverpool, Merseyside, England. Univ Washington, Sch Med, Med Ctr, Ctr Multidisciplinary Pain, Seattle, WA 98195 USA. Univ Helsinki Hosp, Pain Clin, Helsinki, Finland. Tampere Univ Hosp, Dept Neurol, Pain Unit, Tampere, Finland. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol,Nerve Injury Unit, 55 Fruit St,Clin 3, Boston, MA 02114 USA. FU NINDS NIH HHS [R01NS42866] NR 39 TC 65 Z9 68 U1 0 U2 7 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD AUG PY 2003 VL 4 IS 6 BP 338 EP 343 DI 10.1016/S1526-5900(03)00637-0 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 714GQ UT WOS:000184905000007 PM 14622691 ER PT J AU McLaughlin, ME Robson, CD Kieran, MW Jacks, T Pomeroy, SL Cameron, S AF McLaughlin, ME Robson, CD Kieran, MW Jacks, T Pomeroy, SL Cameron, S TI Marked regression of metastatic Pilocytic astrocytoma during treatment with imatinib mesylate (STI-571, Gleevec): A case report and laboratory investigation SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE astrocytoma; imatinib; platelet-derived growth factor receptors ID TYROSINE KINASE INHIBITOR; CHRONIC MYELOID-LEUKEMIA; LOW-GRADE ASTROCYTOMA; GROWTH-FACTOR-ALPHA; BCR-ABL; C-KIT; LEPTOMENINGEAL DISSEMINATION; OPTIC GLIOMA; EXPRESSION; RECEPTORS AB Pilocytic astrocytomas are the most common childhood glioma. Most children with pilocytic astrocytomas survive many years with their tumor, but alternative treatment approaches are needed for those with refractory or metastatic disease. Signaling by the platelet-derived growth factor tyrosine kinase receptor pathways have been postulated to contribute to the development of gliomas. The authors treated a single patient with refractory, metastatic pilocytic astrocytoma with the tyrosine kinase inhibitor imatinib mesylate and observed marked, transient regression of tumor during treatment. Immunohistochemistry was used to assess expression of reported target genes of imatinib mesylate in this patient's tumor tissue and of the PDGFR in pilocytic astrocytomas from 19 other patients. Immunohistochemistry showed that the patient's tumor cells did not express any of the reported target molecules inhibited by imatinib mesylate. PDGFR expression was detected in tumor vasculative in the panel of 20 tumors, and not in the tumor cells. The authors suggest that the PDGFR-signaling pathway postulated to contribute to the development of gliomas in adults might not contribute to pilocytic astrocytomas in children, and that treatment with imatinib mesylate should be considered in patients with refractory pilocytic astrocytoma. C1 Univ Texas, SW Med Ctr, Dept Pediat, Div Hematol Oncol, Dallas, TX 75019 USA. Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp,Div Neurosci, Boston, MA 02115 USA. RP Cameron, S (reprint author), Univ Texas, SW Med Ctr, Dept Pediat, Div Hematol Oncol, Dallas, TX 75019 USA. OI Robson, Caroline/0000-0001-5592-249X; Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [CA94678-02] NR 32 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG PY 2003 VL 25 IS 8 BP 644 EP 648 DI 10.1097/00043426-200308000-00012 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 708EC UT WOS:000184553300012 PM 12902920 ER PT J AU Fuchs, JR Terada, S Hannouche, D Ochoa, ER Vacanti, JP Fauza, DO AF Fuchs, JR Terada, S Hannouche, D Ochoa, ER Vacanti, JP Fauza, DO TI Fetal tissue engineering: Chest wall reconstruction SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Pediatrics CY OCT 19-25, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Pediat DE tissue engineering; cartilage; engineering; cartilage; fetal surgery; congenital anomalies; chest wall defects; transplantation ID ECTOPIA CORDIS; ULTRASONIC DIAGNOSIS; ARTICULAR-CARTILAGE; X COLLAGEN; IN-VITRO; CHONDROCYTES; REPAIR; CONSTRUCTS; CELLS; RAT AB Background/Purpose: This study was aimed at applying fetal tissue engineering to chest wall reconstruction. Methods: Fetal lambs underwent harvest of elastic and hyaline cartilage specimens. Once expanded in vitro, fetal chondrocytes were seeded onto synthetic scaffolds, which then were placed in a bioreactor. After birth, fetal cartilage constructs (n = 10) were implanted in autologous fashion into the ribs of all lambs (n = 6) along with identical, but acellular scaffolds, as controls (n = 6). Engineered and acellular specimens were harvested for analysis at 4 to 12 weeks postimplantation. Standard histology and matrix-specific staining were performed both before implantation and after harvest on all constructs. Results: Regardless of the source of chondrocytes, all fetal constructs resembled hyaline cartilage, both grossly and histologically, in vitro. In vivo, engineered implants retained hyaline characteristics for up to 10 weeks after implantation but remodeled into fibrocartilage by 12 weeks postoperatively. Mononuclear inflammatory infiltrates surrounding residual PGA/PLLA polymer fibers were noted in all specimens but most prominently in the acellular controls. Conclusions: Engineered fetal cartilage can provide structural replacement for at least up to 10 weeks after autologous, postnatal implantation in the chest wall. Fetal tissue engineering may prove useful for the treatment of severe congenital chest wall defects at birth. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Harvard Ctr Minimally Invas Surg, Boston, MA USA. Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. RP Fauza, DO (reprint author), Childrens Hosp, Fegan 3,300 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 14 Z9 15 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2003 VL 38 IS 8 BP 1188 EP 1193 DI 10.1016/S0022-3468(03)00265-3 PG 6 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 709WK UT WOS:000184649400011 PM 12891490 ER PT J AU Dasgupta, R Schnitzer, JJ Hendren, WH Donahoe, PK AF Dasgupta, R Schnitzer, JJ Hendren, WH Donahoe, PK TI Congenital adrenal hyperplasia: Surgical considerations required to repair a 46,XX patient raised as a boy SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE congenital adrenal hyperplasia; genital ambiguity ID STEROID 21-HYDROXYLASE DEFICIENCY; ADRENOGENITAL SYNDROME; DIAGNOSIS; CHILDREN; PROTEIN; BIRTH; HLA AB 21-hydroxylase deficiency (P450 CYP21) accounts for 90% of cases of congenital adrenal hyperplasia (CAH), which is associated with abnormally low cortisol and high production of androgen precursors and is the most common cause of ambiguous genitalia. Increased androgen causes in utero virilization of the fetus, consisting of clitoral enlargement, an urogenital sinus, and labioscrotal enlargement and fusion. This is the first case in an experience covering more than 30 years, of a 46,XX patient raised as a boy. The authors report a case of a Pakistani patient born of a consanguineous union, who came to medical attention at age 3 because of severe genital ambiguity; genetic analyses showed that the child was a compound heterozygote for CAH. The surgical management of this patient consisted of (1) staged hypospadias repairs preceded by testosterone therapy, (2) creation of a bladder graft neourethra, (3) removal of mullerian structures, (4) correction of bifid prepenile scrotum, and (5) insertion of testicular prostheses. The commitment to raise a 46,XX child as a boy is a very rare event. With a series of staged complex surgical procedures and careful steroid replacement, normal secondary sexual characteristics can be achieved in these children. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp Med Ctr, Dept Surg, Boston, MA USA. RP Donahoe, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Serv, Warren 11,55 Fruit St, Boston, MA 02114 USA. NR 31 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD AUG PY 2003 VL 38 IS 8 BP 1269 EP 1273 DI 10.1016/S0022-3468(03)00287-2 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 709WK UT WOS:000184649400033 PM 12891512 ER PT J AU Meltzner, GS Kobler, JB Hillman, RE AF Meltzner, GS Kobler, JB Hillman, RE TI Measuring the neck frequency response function of laryngectomy patients: Implications for the design of electrolarynx devices SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID VOCAL-TRACT; SPEECH; WAVE AB Measurements of the neck frequency response function (NFRF), defined as the ratio of the spectrum of the estimated volume velocity that excites the vocal tract to the spectrum of the acceleration delivered to the neck wall, were made at three different positions on the necks of nine laryngectomized subjects (five males and four females) and four normal laryngeal speakers (two males and two females). A minishaker driven by broadband noise provided excitation to the necks of subjects as they configured their vocal tracts to mimic the production of the vowels /a/, /ae/, and /I/. The sound pressure at the lips was measured with a microphone and an impedance head mounted on the shaker measured the acceleration. The neck wall passed low-frequency sound energy better than high-frequency sound energy, and thus the NFRF was accurately modeled as a low-pass filter. The NFRFs of the different subject groups (female laryngeal, male laryngeal speakers, laryngectomized males, and laryngectomized females) differed from each other in terms of corner frequency and gain, with both types of male subjects presenting NFRFs with larger overall gains. In addition, there was a notable amount of intersubject variability within groups. Because the NFRF is an estimate of how sound energy passes through the neck wall, these results should aid in the design of improved neck-type electrolarynx devices. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. MGH Inst Hlth Profess, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. EM geoff@mit.edu FU NIDCD NIH HHS [T32DC00038] NR 20 TC 16 Z9 17 U1 0 U2 1 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 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD AUG PY 2003 VL 114 IS 2 BP 1035 EP 1047 DI 10.1121/1.1582440 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 709RE UT WOS:000184637500043 PM 12942982 ER PT J AU Saxe, G Chawla, N Stoddard, F Kassam-Adams, N Courtney, D Cunningham, K Lopez, C Hall, E Sheridan, R King, D King, L AF Saxe, G Chawla, N Stoddard, F Kassam-Adams, N Courtney, D Cunningham, K Lopez, C Hall, E Sheridan, R King, D King, L TI Child stress disorders checklist: A measure of ASD and PTSD in children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Child Stress Disorders Checklist; posttraumatic stress; acute stress ID SCHOOL-AGE-CHILDREN; POSTTRAUMATIC-STRESS; FOLLOW-UP; ADOLESCENTS; INTERVIEW; SURVIVORS; VIOLENCE; DISASTER; SYMPTOMS AB Objective: To assess the psychometric properties of the Child Stress Disorders Checklist (CSDC), a 36-item observer-report instrument that measures acute stress and posttraumatic symptoms in children. Method: The CSDC Was administered to parents of 43 children with acute burns and 41 children who had experienced a traffic crash. This instrument was also administered to the burned children's primary nurse to estimate interrater reliability. The CSDC was completed again by parents of burned children, 2 days and 3 months later. Convergent validity was determined by correlating scores on the CSDC with scores on instruments of known validity for assessing posttraumatic stress disorder (PTSD) in children. Concurrent validity was determined through an examination of the relationship between CSDC scores and an index of trauma severity (percentage of body surface area burned). Discriminant validity was assessed by administering the Child Behavior Checklist (CBCL): it was hypothesized that PTSD symptoms would be more closely related to the PTSD scale of the CBCL than the Thought Problems scale of the CBCL. Results: The CSDC has reliable and valid psychometric properties. Conclusions: The CSDC, an observer-report instrument of ASD and PTSD in children, has important utility in clinical and research settings. C1 Boston Univ, Med Ctr, Dept Child & Adolescent Psychiat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Shriners Burns Hosp, Cambridge, MA 02138 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Saxe, G (reprint author), Boston Univ, Med Ctr, Dept Child & Adolescent Psychiat, Dowling 1 N,1 Boston Med Ctr Plaza, Boston, MA 02118 USA. RI Kassam-Adams, Nancy/C-4091-2009; OI Saxe, Glenn/0000-0002-4756-1169 FU CMHS SAMHSA HHS [U79 SM54305]; NIMH NIH HHS [R01 MH57370]; PHS HHS [R40 MC00138 03] NR 38 TC 31 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2003 VL 42 IS 8 BP 972 EP 978 DI 10.1097/01.CHI.0000046887.27264.F3 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 703VQ UT WOS:000184302700015 PM 12874500 ER PT J AU Redondo, P Sanchez-Carpintero, I Bauza, A Idoate, M Solano, T Mihm, MC AF Redondo, P Sanchez-Carpintero, I Bauza, A Idoate, M Solano, T Mihm, MC TI Immunologic escape and angiogenesis in human malignant melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-BETA; FACTOR VEGF; METASTATIC MELANOMA; FACTOR EXPRESSION; TUMOR-GROWTH; TRANSFORMING GROWTH-FACTOR-BETA-1; CYTOKINE PRODUCTION; GASTRIC-CARCINOMA; PROGNOSTIC VALUE AB Background: Melanoma escape mechanisms include immunosuppressive and angiogenic cytokine production. Objective. We sought to determine vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression by immunohistochemistry, and Soluble circulating plasma levels of VEGF, bFGF, IL-10, and transforming growth factor-beta2 in patients with different stages of melanoma. Methods: Biopsy specimens from 42 patients with primary melanoma and 9 with cutaneous metastases were Studied by immunohistochemistry. In another 46 patients with melanoma (8 stage I and II; 18, III; and 20, IV) and in 10 healthy control participants, bFGF, VEGF, IL-10, and transforming growth factor-beta2 circulating levels were analyzed. Results: bFGF was positive in 85% and VEGF in 47.5% of 42 primary melanomas. Of 10 patients with primary melanoma (Breslow depth 1.5-3 mm) 6 were VEGF positive and had metastases develop, whereas 4 were VEGF negative and had no metastases at 5 years of follow up VEGF, bFGF, and IL-10 plasma levels in patients with stages III and IV melanoma were higher than the control group (P < .05 and P < .01, respectively). An inverse relationship was found between VEGF and IL-10. Specifically, in 7 patients with IL-10 levels higher than 10 pg/mL, VEGF levels were less than 49 pg/mL (P < .05); in 9 patients with VEGF levels higher than 100 pg/mL, IL-10 levels were less than 6.7 pg/mL (P < .01). Conclusion: VEGF expression in 1.5- to 3.0-mm Breslow depth melanomas may be considered as an unfavorable prognostic factor. Immunosuppressive (IL-10, transforming growth factor-beta2) and proangiogenic (bFGF, VEGF) cytokines are increased in metastatic melanoma. Inverse plasma levels between IL-10 and VEGF in patients with metastatic melanoma are shown in vivo for the first time, the significance of which must be further investigated. C1 Univ Navarra Clin, Sch Med, Dept Dermatol, Pamplona 31080, Spain. Univ Navarra Clin, Sch Med, Dept Pathol, Pamplona 31080, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit, Boston, MA 02115 USA. RP Redondo, P (reprint author), Univ Navarra Clin, Sch Med, Dept Dermatol, POB 4209, Pamplona 31080, Spain. NR 49 TC 32 Z9 34 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD AUG PY 2003 VL 49 IS 2 BP 255 EP 263 DI 10.1067/S0190-9622(03)00921-6 PG 9 WC Dermatology SC Dermatology GA 708KN UT WOS:000184566100014 PM 12894074 ER PT J AU Simon, JA Hudes, ES Perez-Perez, GI AF Simon, JA Hudes, ES Perez-Perez, GI TI Relation of serum ascorbic acid to Helicobacter pylori serology in US adults: The Third National Health and Nutrition Examination Survey SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE ascorbic acid; Helicobacter pylori; vitamin C ID VITAMIN-C; GASTRIC-CANCER; UNITED-STATES; INFECTION; JUICE; RISK; CAGA; DETERMINANTS; ERADICATION; CARCINOMA AB Purpose: To examine the relation between serum ascorbic acid and Helicobacter pylori serology from a probability sample of US adults. Subjects and Methods: Data from 6,746 adults (ages 20 to 90 years) enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), 1988-1994 were analyzed. Multiple logistic regression models were examined taking into account sample weights and the complex survey design of NHANES III, and controlling for the effects of potential confounders. Because race appeared to modify the association between serum ascorbic acid and seropositivity to H. pylori, we conducted the analyses stratified by race. Results: A total of 2,189 adults (32%) had a positive serology for H. pylori, and, of these, 1,175 (54%) were positive for the CagA antigen. Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82-0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12-0.79, p < 0.05). Serum ascorbic acid levels were not significantly associated with H. pylori serology among non-whites (all p > 0.05). Conclusions: Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites. If these associations are related causally and are not the result of residual confounding by factors such as socioeconomic status, ascorbic acid may affect the risk of H. pylori infection and in turn, the risk for peptic ulcer disease and gastric cancer among white Americans. C1 San Francisco VA Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NYU, Sch Med, Dept Med, New York, NY USA. NYU, Sch Med, Dept Microbiol, New York, NY USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Med Serv, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL 53479] NR 41 TC 16 Z9 16 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD AUG PY 2003 VL 22 IS 4 BP 283 EP 289 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 707RR UT WOS:000184524100005 PM 12897042 ER PT J AU Finefrock, AE Bush, AI Doraiswamy, PM AF Finefrock, AE Bush, AI Doraiswamy, PM TI Current status of metals as therapeutic targets in Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Alzheimer's disease; clioquinol; copper; zinc; beta-amyloid ID AMYLOID-BETA-PEPTIDES; A-BETA; TRANSGENIC MICE; HYDROGEN-PEROXIDE; PLAQUE-FORMATION; FREE-RADICALS; ZINC; PROTEIN; COPPER; PATHOGENESIS AB There is accumulating evidence that interactions between beta-amyloid and copper, iron, and zinc are associated with the pathophysiology of Alzheimer's disease (AD). A significant dyshomeostasis of copper, iron, and zinc has been detected, and the mismanagement of these metals induces beta-amyloid precipitation and neurotoxicity. Chelating agents offer a potential therapeutic solution to the neurotoxicity induced by copper and iron dyshomeostasis. Currently, the copper and zinc chelating agent clioquinol represents a potential therapeutic route that may not only inhibit beta-amyloid neurotoxicity, but may also reverse the accumulation of neocortical beta-amyloid. A Phase II double-blind clinical trial of clioquinol with B-12 supplementation will be published soon, and the results are promising. This article summarizes the role of transition metals in amyloidgenesis and reviews the potential promise of chelation therapy as a treatment for AD. C1 Duke Univ, Med Ctr, Dept Psychiat, Div Biol Psychiat, Durham, NC 27710 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol Genet, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Aging Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Duke Univ, Med Ctr, Dept Geriatr Med, Durham, NC USA. Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Durham, NC 27710 USA. RP Doraiswamy, PM (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Div Biol Psychiat, Box 3018, Durham, NC 27710 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 43 TC 139 Z9 142 U1 1 U2 5 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 AUG PY 2003 VL 51 IS 8 BP 1143 EP 1148 DI 10.1046/j.1532-5415.2003.51368.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 706RT UT WOS:000184468400015 PM 12890080 ER PT J AU Playford, DA Levine, RA Picard, MH Handschumacher, MD AF Playford, DA Levine, RA Picard, MH Handschumacher, MD TI Illusion of contraction from out-of-plane translation: Can Doppler tissue velocities resolve it? SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR CONTRACTION; MYOCARDIAL VELOCITY; DOBUTAMINE STRESS; IMAGING TECHNIQUE; WALL-MOTION; ECHOCARDIOGRAPHY; GRADIENT; ABNORMALITIES; INDICATOR AB Background Assessment of wall motion is one of the most challenging aspects of echocardiography. Because of tapering cardiac shape, the impression of thickening can be produced by cardiac translation perpendicular to the image plane. Doppler tissue imaging (DTI) can potentially resolve this problem because in noncontracting myocardium, velocities (V) are uniform (V gradient [VG] = 0) and V measured by DTI should be unaffected by translation perpendicular to the imaging beam. Methods: A left ventricle-shaped phantom and a string model were translated at known angles to the ultrasound beam. Two-dimensional gray-scale, DTI, and M-mode images were acquired and analyzed. Results: During translation perpendicular to the image plane, 2-dimensional and M-mode images of the ventricular model showed apparent wall thickening, but analysis of the DTI images showed that V and VG across the walls were near 0 (V = 0.04 +/- 0.1 cm/s; VG = 0.02 +/- 0.02/s). Translation of both models at various angles relative to an M-mode beam also created the impression of wall thickening. However, DTI accurately measured the angle-corrected V component toward the transducer (r > 0.98, P < .0001), and VG corresponded to rigid body motion (0.003 0.02/s). Conclusions: M-mode and 2-dimensional echocardiography images are subject to the illusion of myocardial thickening resulting from out-of-plane translation. Analysis of tissue Doppler V avoids such error by accurately measuring V components and VG, and it has the potential to improve assessment of left ventricular function. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 19 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD AUG PY 2003 VL 16 IS 8 BP 832 EP 840 DI 10.1067/S0894-7317(03)00404-8 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709BG UT WOS:000184604400008 PM 12878992 ER PT J AU Hubchak, SC Runyan, CE Kreisberg, JI Schnaper, HW AF Hubchak, SC Runyan, CE Kreisberg, JI Schnaper, HW TI Cytoskeletal rearrangement and signal transduction in TGF-beta 1-stimulated mesangial cell collagen accumulation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR-BETA; FOCAL ADHESION PROTEINS; TGF-BETA; EXTRACELLULAR-MATRIX; TRANSFORMING GROWTH-FACTOR-BETA-1; EXPERIMENTAL GLOMERULONEPHRITIS; TRANSCRIPTIONAL ACTIVATION; EPITHELIAL-CELLS; CYTOCHALASIN-D; SMAD PROTEINS AB TGF-beta1 has been implicated in glomerular extracellular matrix accumulation, although the precise cellular mechanism(s) by which this occurs is not fully understood. The authors have previously shown that the Smad signaling pathway is present and functional in human glomerular mesangial cells and plays a role in activating type I collagen gene expression. It also was determined that TGF-beta1 activates ERK mitogen-activated protein kinase in mesangial cells to enhance Smad activation and collagen expression. Here, it was shown that TGF-beta1 rapidly induces cytoskeletal rearrangement in human mesangial cells, stimulating smooth muscle alpha-actin detection in stress fibers and promoting focal adhesion complex assembly and redistribution. Disrupting the actin cytoskeleton with cytochalasin D (Cyto D) selectively decreased basal and TGF-beta1-induced cell-layer collagen I and IV accumulation. The balance of matrix metalloproteinases (MMP) and inhibitors was altered by Cyto D or TGF-beta1 alone, increasing MMP activity, increasing MMP-1 expression, and decreasing tissue inhibitor of matrix metalloproteinase-2 expression. Cyto D also decreased basal and TGF-beta1-stimulated alpha1(1) collagen mRNA but did not inhibit TGF-beta-stimulated alpha1(IV) mRNA expression. A similar decrease in alpha1(I) mRNA expression caused by the actin polymerization inhibitor latrunculin B was partially blocked by the addition of jasplakinolide, which promotes actin assembly. The Rho-family GTPase inhibitor C. difficile toxin B or the Rho-associated kinase inhibitor Y-27632 also blocked TGF-beta1-stimulated alpha1(I) mRNA expression. Cytoskeletal disruption reduced Smad2 phosphorylation but had little effect on mRNA stability, TGF-beta receptor number, or receptor affinity. Thus, TGF-beta1-mediated collagen I accumulation is associated with cytoskeletal rearrangement and Rho-GTPase signaling. C1 Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Childrens Mem Inst Educ & Res, Chicago, IL USA. Univ Texas, Ctr Hlth Sci, Dept Surg, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. RP Hubchak, SC (reprint author), Northwestern Univ, Sch Med, Dept Pediat, W-140 Pediat,303 E Chicago Ave,Ward 12-112, Chicago, IL 60611 USA. FU NIDDK NIH HHS [DK49362, R01 DK049362] NR 48 TC 44 Z9 47 U1 0 U2 1 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 AUG PY 2003 VL 14 IS 8 BP 1969 EP 1980 DI 10.1097/01.ASN.0000076079.02452.92 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 704QZ UT WOS:000184352600002 PM 12874450 ER PT J AU Araki, SI Ng, DPK Krolewski, B Wyrwicz, L Rogus, JJ Canani, L Makita, Y Haneda, M Warram, JH Krolewski, AS AF Araki, SI Ng, DPK Krolewski, B Wyrwicz, L Rogus, JJ Canani, L Makita, Y Haneda, M Warram, JH Krolewski, AS TI Identification of a common risk haplotype for diabetic nephropathy at the protein kinase C-beta 1 (PRKCB1) gene locus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID C BETA-GENE; COMPLICATIONS; MELLITUS; EXPRESSION; ACTIVATION; RATS; AMELIORATION; INHIBITOR; GLOMERULI; LINKAGE AB Abnormal activation of protein kinase C-beta isoforms in the diabetic state has been implicated in the development of diabetic nephropathy. It is thus plausible that DNA sequence differences in the protein kinase C-beta1 gene (PRKCB1), which encodes both 01 and 011 isoforms, may influence susceptibility to nephropathy. Nine single-nucleotide polymorphisms (SNP) in PRKCB1 were tested for association with diabetic nephropathy in type I diabetes mellitus, by using both case-control and family-study designs. Allele and genotype distributions of two SNP in the promoter (-1504C/T and -546C/G) differed significantly between case patients and control patients (P < 0.05). These associations were particularly strong with diabetes mellitus duration of <24 yr (P = 0.002). The risk of diabetic nephropathy was higher among carriers of the T allele of the -1504C/T SNP, compared with noricarriers (odds ratio, 2.54; 95% confidence interval, 1.39 to 4.62), and among carriers of the G allele of the -546C/G SNP (odds ratio, 2.45; 95% confidence interval, 1.37 to 4.38). Among individuals with diabetes mellitus duration of greater than or equal to24 yr, these two SNP were not associated with diabetic nephropathy. These positive findings were confirmed by using the family-based transmission disequilibrium test. The T-G haplotype, with both risk alleles, was transmitted more frequently than expected from heterozygous parents to offspring who developed diabetic nephropathy during the first 24 yr of diabetes mellitus. It is concluded that DNA sequence differences in the promoter of PRKCB1 contribute to diabetic nephropathy susceptibility in type I diabetes mellitus. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Shiga Univ Med Sci, Dept Med 3, Otsu, Shiga, Japan. Natl Univ Singapore, Singapore, Singapore. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Room 368,1 Joslin Pl, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU NIDDK NIH HHS [DK53534, DK41526] NR 31 TC 26 Z9 28 U1 0 U2 1 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 AUG PY 2003 VL 14 IS 8 BP 2015 EP 2024 DI 10.1097/01.ASN.0000077347.27669.5C PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 704QZ UT WOS:000184352600007 PM 12874455 ER PT J AU Makhlouf, L Yamada, A Ito, T Abdi, R Ansari, MJI Khuong, CQ Winn, HJ Auchincloss, H Sayegh, MH AF Makhlouf, L Yamada, A Ito, T Abdi, R Ansari, MJI Khuong, CQ Winn, HJ Auchincloss, H Sayegh, MH TI Allorecognition and effector pathways of islet allograft rejection in normal versus nonobese diabetic mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID T-CELL; NOD MICE; AUTOIMMUNE DESTRUCTION; PANCREATIC-ISLETS; KIDNEY ALLOGRAFTS; GRAFT-REJECTION; DEFICIENT MICE; SURVIVAL; ANTIGEN; MOUSE AB Islet transplantation is becoming an accepted therapy to cure type I diabetes mellitus. The exact mechanisms of islet allograft rejection remain unclear, however. In vivo CD4(+) and CD8(+) T cell-depleting strategies and genetically altered mice that did not express MHC class I or class II antigens were used to study the allorecognition and effector pathways of islet allograft rejection in different strains of mice, including auto-immunity-prone nonobese diabetic (NOD) mice. In BALB/c mice, islet rejection depended on both CD4(+) and CD8(+) T cells. In C57BL/6 mice, CD8(+) T cells could eventually mediate islet rejection by themselves, but they produced rejection more efficiently with help from CD4(+) T cells stimulated through either the direct or indirect pathway. In C5713L/6 mice, CD4(+) T cells alone caused islet rejection when only the direct pathway was available but not when only the indirect pathway was available. In contrast, in NOD mice, CD4(+) T cells alone, with only the indirect pathway, could mediate islet and cardiac allograft rejection. These findings indicate that different mouse strains can make use of different pathways for T cell-mediated rejection of islet allografts. In addition, they demonstrate that NOD mice, which develop autoimmunity and are known to be resistant to tolerance induction, have an unusually powerful CD4(+) cell indirect mechanism that can cause rejection of both islet and cardiac allografts. These data shed light on the mechanisms of islet allograft rejection in different responder strains, including those with autoimmunity. C1 Brigham & Womens Hosp, Dept Med, Lab Immunogenet & Transplantat, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Transplant Lab, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Div Nephrol, Sch Med, Boston, MA 02115 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Dept Med, Lab Immunogenet & Transplantat, Div Renal, 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI41521] NR 45 TC 26 Z9 26 U1 0 U2 0 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 AUG PY 2003 VL 14 IS 8 BP 2168 EP 2175 DI 10.1097/01.ASN.0000079041.15707.A9 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 704QZ UT WOS:000184352600024 PM 12874472 ER PT J AU Kuroki, T Isshiki, K King, GL AF Kuroki, T Isshiki, K King, GL TI Oxidative stress: The lead or supporting actor in the pathogenesis of diabetic complications SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 4th Hyonam Kidney Laboratory International Diabetes Symposium CY JAN 18-19, 2003 CL SOON CHUN HYANG UNIV, SEOUL, SOUTH KOREA HO SOON CHUN HYANG UNIV ID PROTEIN-KINASE-C; ALPHA-LIPOIC ACID; ACTIVATED SIGNALING PATHWAYS; INDUCED INSULIN-RESISTANCE; VITAMIN-E SUPPLEMENTATION; BETA-CELL DYSFUNCTION; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; CONTROLLED TRIAL; MESANGIAL CELLS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Vascular Cell Biol & Complicat, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Vascular Cell Biol & Complicat, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY9178, NEY05110] NR 57 TC 46 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2003 VL 14 SU 3 BP S216 EP S220 DI 10.1097/01.ASN.0000077405.07888.07 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 706AT UT WOS:000184430000003 PM 12874434 ER PT J AU Lee, HB Ha, H King, GL AF Lee, HB Ha, H King, GL TI Reactive oxygen species and diabetic nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 Soon Chung Hyang Univ, Hyonam Kidney Lab, Seoul 140743, South Korea. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Lee, HB (reprint author), Soon Chung Hyang Univ, Hyonam Kidney Lab, 657 Hannam Dong, Seoul 140743, South Korea. NR 0 TC 3 Z9 4 U1 0 U2 1 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 AUG PY 2003 VL 14 SU 3 BP S209 EP S210 DI 10.1097/01.ASN.0000077403.06195.D2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 706AT UT WOS:000184430000001 ER PT J AU Grikscheit, T Ochoa, ER Srinivasan, A Gaissert, H Vacanti, JP AF Grikscheit, T Ochoa, ER Srinivasan, A Gaissert, H Vacanti, JP TI Tissue-engineered esophagus: Experimental substitution by onlay patch or interposition SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID COLON; REPLACEMENT AB Objectives: We proposed to fabricate a tissue-engineered esophagus and to use it for replacement of the abdominal esophagus. Methods: Esophagus organoid units, mesenchymal cores surrounded by epithelial cells, were isolated from neonatal or adult rats and paratopically transplanted on biodegradable polymer tubes, which were implanted in syngeneic hosts. Four weeks later, the tissue-engineered esophagus was either harvested or anastomosed as an onlay patch or total interposition graft. Green Fluorescent Protein labeling by means of viral infection of the organoid units was performed before implantation. Histology and immunohistochemical detection of the antigen a-actin smooth muscle were performed. Results: Tissue-engineered esophagus grows in sufficient quantity for interposition grafting. Histology reveals a complete esophageal wall, including mucosa, submucosa, and muscularis propria, which was confirmed by means of immunohistochemical staining for a-actin smooth muscle. Tissue-engineered esophagus architecture was maintained after interposition or use as a patch, and animals gained weight on a normal diet. Green Fluorescent Protein-labeled tissue-engineered esophagus preserved its fluorescent label, proving the donor origin of the tissue-engineered esophagus. Conclusions: Tissue-engineered esophagus resembles the native esophagus and maintains normal histology in anastomosis, with implications for therapy of long-segment esophageal tissue loss caused by congenital absence, surgical excision, or trauma. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 16 TC 75 Z9 83 U1 0 U2 6 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 AUG PY 2003 VL 126 IS 2 BP 537 EP 544 DI 10.1016/S0022-5223(03)00032-1 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 715UZ UT WOS:000184991800037 PM 12928655 ER PT J AU Hylek, EM AF Hylek, EM TI Trends in anticoagulation management across community-based practices in the United States: The Anticoagulation Consortium to Improve Outcomes Nationally (ACTION) study SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article; Proceedings Paper CT 7th National Conference on Anticoagulant Therapy CY MAY 08-10, 2003 CL SAN FRANCISCO, CALIFORNIA SP Anticoagulat Forum DE anticoagulation; warfarin; outcome; international normalized ratio ID RISK-FACTORS; BLEEDING COMPLICATIONS; THERAPY AB Randomized trials have demonstrated the effectiveness of warfarin in preventing thromboembolism. Translating the results of randomized trials into usual care is difficult, however, as trial patients are highly selected and closely monitored. The Anticoagulation Consortium to Improve Outcomes Nationally ( ACTION) study is a prospective observational assessment of anticoagulation care in 98 office-based practices and 3 hospital-based clinics in the United States. Site enrollment began in August 2000 and ended in February 2002 with 6761 patients recruited. The goals of this large prospective cohort study are ( 1) to gather data on complication rates associated with warfarin therapy across a broad range of patient ages and indications; ( 2) document trends in anticoagulation management and treatment practices; and ( 3) establish quality benchmarks for anticoagulation control and frequency of monitoring. This report describes the methodology and preliminary results. Analysis is ongoing, and full results will be reported in the future. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Hylek, EM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, 50 Staniford St,9th Floor Suite, Boston, MA 02114 USA. EM ehylek@partners.org NR 4 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD AUG-OCT PY 2003 VL 16 IS 1-2 BP 83 EP 86 DI 10.1023/B:THRO.0000014600.21367.7b PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 770HC UT WOS:000188716300016 PM 14760219 ER PT J AU Chang, LT Koutrakis, P Catalano, PJ Suh, HH AF Chang, LT Koutrakis, P Catalano, PJ Suh, HH TI Assessing the importance of different exposure metrics and time-activity data to predict 24-h personal PM2.5 exposures SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID PARTICULATE AIR-POLLUTION; INDOOR PARTICLE SOURCES; ENVIRONMENTAL TOBACCO-SMOKE; FINE PARTICLES; PULMONARY-FUNCTION; COARSE PARTICLES; UNITED-STATES; MORTALITY; BALTIMORE; CITIES AB Personal PM2.5 data from two recent exposure studies, the Scripted Activity Study and the Older Adults Study, were used to develop models predicting 24-h personal PM2.5 exposures. Both studies were conducted concurrently in the summer of 1998 and the winter of 1999 in Baltimore, MD. In the Scripted Activity Study, 1-h personal PM2.5 exposures were measured. Data were used to identify significant factors affecting personal exposures and to develop 1-h personal exposure models for five different micro-environments. By incorporating the time-activity diary data, these models were then combined to develop a time-weighted microenvironmental personal model (model M1AD) to predict the 24-h PM2.5 exposures measured for individuals in the Older Adults Study. Twenty-four-hour time-weighted models were also developed using 1-h ambient PM2.5 levels and time-activity data (model A1AD) or using 24-h ambient PM2.5 levels and time-activity data (model A24AD). The performance of these three models was compared to that using 24-h ambient concentrations alone (model A24). Results showed that factors affecting 1-h personal PM2.5 exposures included air conditioning status and the presence of environmental tobacco smoke (ETS) for indoor micro-environments, consistent with previous studies. ETS was identified as a significant contributor to measured 24-h personal PM2.5 exposures. Staying in an ETS-exposed microenvironment for 1 h elevated 24-h personal PM2.5 exposures by approximately 4 mug/m(3) on average. Cooking and washing activities were identified in the winter as significant contributors to 24-h personal exposures as well, increasing 4-h personal PM2.5 exposures by about 4 and 5 mug/m(3) per hour of activity, respectively. The ability of 3 microenvironmental personal exposure models to estimate 24-h personal PM2.5 exposures was generally comparable to and consistently greater than that of model A24. Results indicated that using time-activity data with 1-h exposure information, either as microenvironment-specific exposures (model M1AD) or as ambient concentrations (model A1AD), improves our ability to estimate 24-h personal PM2.5 exposure over the model using 24-h averaged ambient levels alone (model A24). Model performance was higher in the summer than in the winter season. in addition, higher crude R-2 values were reported for subjects participating in both seasons, where the R-2 values equated. 53,.55,.46, and.38 for models M1AD, A1AD, A24AD, and A24, respectively. The low predictive ability of the microenvironmental exposure models in the winter might, in part, be attributed to the narrow dynamic range of personal PM2.5 exposures. C1 Feng Chia Univ, Dept Environm Sci & Engn, Taichung 407, Taiwan. Harvard Univ, Sch Publ Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Chang, LT (reprint author), Feng Chia Univ, Dept Environm Sci & Engn, 100 Wenhwa Rd, Taichung 407, Taiwan. NR 43 TC 13 Z9 13 U1 1 U2 15 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD AUG-OCT PY 2003 VL 66 IS 16-19 BP 1825 EP 1846 DI 10.1080/15287390390212099 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 728YD UT WOS:000185743200023 PM 12959846 ER PT J AU Orcutt, HK King, LA King, DW AF Orcutt, HK King, LA King, DW TI Male-perpetrated violence among Vietnam veteran couples: Relationships with veteran's early life characteristics, trauma history, and PTSD symptomatology SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; Vietnam veterans; intimate partner violence; structural equation modeling ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL SAMPLE; FIT INDEXES; MODEL; VALIDITY; ANTECEDENTS; AGGRESSION; FAMILIES; EXPOSURE; PARTNERS AB Using structural equation modeling, we examined the impact of early-life stressors, war-zone stressors, and PTSD symptom severity on partner's reports of recent male-perpetrated intimate partner violence (IPV) among 376 Vietnam veteran couples. Results indicated that several variables demonstrated direct relationships with IPV, including relationship quality with mother, war-zone stressor variables, and PTSD symptom severity. Importantly, retrospective reports of a stressful early family life, childhood antisocial behavior, and war-zone stressors were indirectly associated with IPV via PTSD. One of our 2 war-zone stressor variables, perceived threat, had both direct and indirect (through PTSD) relationships with IPV. Experiencing PTSD symptoms as a result of previous trauma appears to increase an individual's risk for perpetrating IPV. Implications for research and treatment are discussed. C1 No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Orcutt, HK (reprint author), No Illinois Univ, Dept Psychol, De Kalb, IL 60115 USA. NR 56 TC 88 Z9 88 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2003 VL 16 IS 4 BP 381 EP 390 DI 10.1023/A:1024470103325 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 693QG UT WOS:000183729400010 PM 12895021 ER PT J AU Krinsley, KE Gallagher, JG Weathers, FW Kutter, CJ Kaloupek, DG AF Krinsley, KE Gallagher, JG Weathers, FW Kutter, CJ Kaloupek, DG TI Consistency of retrospective reporting about exposure to traumatic events SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the International-Society-of-Traumatic-Stress-Studies CY NOV 20-23, 1998 CL WASHINGTON, DC SP Int Soc Traumat Stress Studies DE trauma assessment; consistency of reporting; Evaluation of Lifetime Stressors; traumatic event characteristics; memory for traumatic events ID POSTTRAUMATIC-STRESS-DISORDER; ADMINISTERED PTSD SCALE; CHILDHOOD SEXUAL-ABUSE; RELIABILITY; VALIDITY; QUESTIONNAIRE; COMMUNITY; MEMORY; WOMEN; COMORBIDITY AB Lifetime exposure to traumatic events was assessed by means of a multimethod protocol applied to 76 male military veterans. Consistency of retrospective reporting was determined for physical and sexual assault and abuse, accidents, disasters, combat and warzone experiences, serious illness or injury, and hazardous duty. Findings demonstrate that respondents are generally consistent in reporting traumatic events, although the majority report more events upon reevaluation. Reporting about traumatic events shows some variation as a function of the life epoch in which events occurred, whether they were directly or indirectly experienced, and the type of trauma involved. Discussion addresses memory-related processes triggered by trauma evaluation or tied to characteristics of events themselves as potential sources of inconsistency. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Natl Ctr PTSD, Boston, MA 02118 USA. Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP Kaloupek, DG (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM danny.kaloupek@med.va.gov OI Kaloupek, Danny/0000-0002-0795-593X NR 44 TC 58 Z9 58 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD AUG PY 2003 VL 16 IS 4 BP 399 EP 409 DI 10.1023/A:1024474204233 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 693QG UT WOS:000183729400012 PM 12895023 ER PT J AU Lin, PH Bush, RL Lumsden, AB AF Lin, PH Bush, RL Lumsden, AB TI Proximal aortic stent-graft displacement with type I endoleak due to Heimlich maneuver SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID THROMBOSIS; ANEURYSM; COMPLICATIONS; REPAIR AB The Heimlich maneuver has saved countless lives by relieving foreign body obstruction from the respiratory tract. Complications related to this life-saving technique, particularly involving the abdominal aorta, are extremely rare. We report the case of a patient who underwent successful endovascular abdominal aortic aneurysm (AAA) repair, with AAA reduction at postoperative surveillance. Endograft displacement after performance of the Heimlich maneuver resulted in a proximal type I endoleak. This case underscores both the potential for aortic trauma from the Heimlich maneuver and the risk for clinical failure as a result of abdominal compression after successful endovascular AAA repair. C1 Baylor Coll Med, Houston VAMC, Michael E DrBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Houston VAMC, Michael E DrBakey Dept Surg, Div Vasc Surg & Endovasc Therapy, 2002 Holcomb Blvd, Houston, TX 77030 USA. NR 16 TC 5 Z9 5 U1 0 U2 1 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 AUG PY 2003 VL 38 IS 2 BP 380 EP 382 DI 10.1016/S0741-5214(03)00294-5 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 705RR UT WOS:000184409000026 PM 12891124 ER PT J AU DeBiasi, RL Clarke, P Meintzer, S Jotte, R Kleinschmidt-Demasters, BK Johnson, GL Tyler, KL AF DeBiasi, RL Clarke, P Meintzer, S Jotte, R Kleinschmidt-Demasters, BK Johnson, GL Tyler, KL TI Reovirus-induced alteration in expression of apoptosis and DNA repair genes with potential roles in viral pathogenesis SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; CASPASE RECRUITMENT DOMAIN; HEAT-SHOCK-PROTEIN-70 INHIBITS APOPTOSIS; SPINAL MUSCULAR-ATROPHY; CELL-CYCLE PROGRESSION; CENTRAL-NERVOUS-SYSTEM; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR; VIRUS-INFECTION; HOST-CELL AB Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-kappaB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo-T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Hematol & Oncol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Mol Signal Transduct, 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 B182, 4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 NR 98 TC 28 Z9 33 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 AUG PY 2003 VL 77 IS 16 BP 8934 EP 8947 DI 10.1128/JVI.77.16.8934-8947.2003 PG 14 WC Virology SC Virology GA 706PU UT WOS:000184462800033 PM 12885910 ER PT J AU Senthil, D Choudhury, GG Mclaurin, C Kasinath, BS AF Senthil, D Choudhury, GG Mclaurin, C Kasinath, BS TI Vascular endothelial growth factor induces protein synthesis in renal epithelial cells: A potential role in diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE renal hypertrophy; growth factors; protein translation ID PERMEABILITY FACTOR; RETINAL NEOVASCULARIZATION; SIGNALING PATHWAYS; MAMMALIAN TARGET; MESANGIAL CELLS; MESSENGER-RNA; FACTOR VEGF; FACTOR-BETA; KINASE-B; PHAS-I AB Background. Vascular endothelial growth factor (VEGF) is an important determinant of ocular complications of diabetes. Its potential role in diabetic renal disease has not been extensively studied. Methods. We employed mice with streptozotocin-induced type 1 diabetes and db/db mice with type 2 diabetes to study the regulation of renal VEGF. Studies of VEGF regulation of protein synthesis were performed using proximal tubular epithelial (MCT) cells in culture. Results. A nearly three-fold increase of VEGF165 expression in the renal cortex was seen, coinciding with renal hypertrophy in mice with either type 1 or type 2 diabetes. VEGF increased de novo protein synthesis and induced significant hypertrophy in MCT cells. VEGF stimulation of protein synthesis was dependent on tyrosine phosphorylation of the type 2 VEGF receptor and phosphatidylinositol 3-kinase (PI 3-kinase) activity. Activity of Akt was increased two- to three-fold by VEGF. Expression of dominant-negative Akt showed that Akt activation was also needed for VEGF-induced protein synthesis and cell hypertrophy. As PI 3-kinase-Akt axis regulates initial events in protein translation, these events were examined in the context of VEGF regulation of protein synthesis. VEGF stimulated eukaryotic initiation factor 4E-binding protein (4E-BP1) phosphorylation, which was dependent on activation of PI 3-kinase and Akt. Stable transfection with 4E-BP1 Thr(37,46) -Ala(37,46) mutant abolished the VEGF-induced de novo protein synthesis and cell hypertrophy. Conclusion. VEGF augments protein synthesis and induces hypertrophy in MCT cells in a PI 3-kinase- and Akt-dependent manner. Phosphorylation of Thr(37,46) in 4E-BP1 is required for VEGF-induced protein synthesis and hypertrophy in MCT cells. These data suggest a role for VEGF in the pathogenesis of diabetic renal disease. C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. GRECC, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDDK NIH HHS [DK55815] NR 48 TC 58 Z9 75 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 AUG PY 2003 VL 64 IS 2 BP 468 EP 479 DI 10.1046/j.1523-1755.2003.00135.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 697WP UT WOS:000183966500009 PM 12846742 ER PT J AU Seliger, SL Gillen, DL Longstreth, WT Kestenbaum, B Stehman-Breen, CO AF Seliger, SL Gillen, DL Longstreth, WT Kestenbaum, B Stehman-Breen, CO TI Elevated risk of stroke among patients with end-stage renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE end-stage renal disease; cerebrovascular accident; epidemiology ID MAINTENANCE HEMODIALYSIS; DIALYSIS PATIENTS; BLOOD-PRESSURE; ATHEROSCLEROSIS; FAILURE; ADULTS; CALCIFICATION; PREDICTORS; POPULATION; ARTERIES AB Background. Although end-stage renal disease (ESRD) has been associated with accelerated vascular disease of the cerebral circulation, there are no prior studies that have estimated the risk of hemorrhagic and ischemic stroke among the United States dialysis population relative to the general population. Methods. We performed a population-based cohort study to compare rates of hospitalized ischemic and hemorrhagic stroke among incident dialysis patients in the United States Renal System database and non-ESRD subjects from the general population identified in the National Hospital Discharge Survey. Results. After adjustment for age, gender, and race, estimated rates of hospitalized stroke were markedly higher for dialysis patients compared to the general population. The age-adjusted relative risk (RR) of stroke among dialysis patients compared to the general population was 6.1 [95% Confidence Interval (95% CI) 5.1, 7.1] for Caucasian males, 4.4 (95% CI 3.3, 5.5) for African American males, 9.7 (95%CI 8.2, 11.2) for Caucasians females and 6.2 (95%CI 4.8, 7.6) for African American females. When considered as separate outcomes, hospitalization rates for hemorrhagic and ischemic stroke were both markedly elevated for subjects treated with dialysis (ischemic, RR = 4.3 to 10.1; hemorrhagic, RR = 4.1 to 6.7). Conclusion. Incident dialysis patients are at markedly higher risk for hospitalized stroke when compared to the general population. Although prior public health initiatives have focused primarily on cardiac disease among patients treated with dialysis, our data suggest that new initiatives are needed to control the high risk of stroke in this population. C1 Univ Washington, Div Nephrol, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Div Nephrol, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), Univ Washington, Div Nephrol, Vet Affairs Puget Sound Hlth Care Syst, Mailstop 111A,1650 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK07721-6] NR 34 TC 198 Z9 211 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD AUG PY 2003 VL 64 IS 2 BP 603 EP 609 DI 10.1046/j.1523-1755.2003.00101.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 697WP UT WOS:000183966500023 PM 12846756 ER PT J AU Henderson, Z Ecker, JL AF Henderson, Z Ecker, JL TI Fetal scalp blood sampling - Limited role in contemporary obstetric practice: Part II SO LABORATORY MEDICINE LA English DT Editorial Material ID HEART-RATE PATTERNS; INTRAPARTUM ASSESSMENT; CONTROLLED TRIAL; PH; STIMULATION; LACTATE; MANAGEMENT; TESTS AB The intrapartum assessment of fetal well-being presents a challenge to obstetricians, especially given contemporary concern for rising rates of both cesarean delivery and malpractice litigation. Several techniques may be used to evaluate the fetus during labor including direct analysis of fetal blood obtained from via scalp sampling. Although blood specimens may be safely obtained from the fetal scalp during labor, the need for such sampling has been dramatically reduced in recent years by the use of other non-invasive tests such as fetal scalp stimulation or vibroacoustic stimulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02129 USA. RP Henderson, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02129 USA. NR 32 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD AUG PY 2003 VL 34 IS 8 BP 594 EP 600 DI 10.1309/GR5QVQWCJHYU370W PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 706VV UT WOS:000184476500016 ER PT J AU Barker, FG Carter, BS Ojemann, RG Jyung, RW Poe, DS McKenna, MJ AF Barker, FG Carter, BS Ojemann, RG Jyung, RW Poe, DS McKenna, MJ TI Surgical excision of acoustic neuroma: Patient outcome and provider caseload SO LARYNGOSCOPE LA English DT Article DE volume of care; acoustic neuroma; mortality; outcome ID VESTIBULAR SCHWANNOMA SURGERY; LEARNING-CURVE; HOSPITAL VOLUME; UNITED-STATES; CARE; MORTALITY; MANAGEMENT; REMOVAL; NUMBER AB Objectives/Hypothesis: For many complex surgical procedures, larger hospital or surgeon caseload is associated with better patient outcome. We examined the volume-outcome relationship for surgical excision of acoustic neuromas. Study Design: Retrospective cohort study. Methods: The Nationwide Inpatient Sample (1996 to 2000) was used. Multivariate regression analyses were adjusted for age, sex, race, payer, geographic region, procedure timing, admission type and source, medical comorbidities, and neurofibromatosis status. Results. At 265 hospitals, 2643 operations were performed by 352 identified primary surgeons. Outcome was measured on a four-level scale at hospital discharge: death (0.5%) and discharge to long-term care (1.2%), to short-term rehabilitation (4.4%), and directly to home (94%). Outcomes were significantly better after surgery at higher-volume hospitals (OR 0.47 for fivefold-larger caseload, P<.001) or by higher-volume surgeons (OR 0.46, P<.001). Of patients who had surgery at lowest-volume-quartile hospitals, 12.3% were not discharged directly home, compared with 4.1% at highest-volume-quartile hospitals. There was a trend toward lower mortality for higher-volume hospitals (P=.1) and surgeons (P=.06). Of patients who had surgery at lowest-caseload-quartile hospitals, 1.1% died, compared with 0.6% at highest-volume-quartile hospitals. Postoperative complications (including neurological complications, mechanical ventilation, facial palsy, and transfusion) were less likely with high-volume hospitals and surgeons. Length of stay was significantly shorter with high-volume hospitals (P=.01) and surgeons (P=.009). Hospital charges were lower for high-volume hospitals (by 6% [P=.006]) and surgeons (by 6% [P=.09]). Conclusion: For acoustic neuroma excision, higher-volume hospitals and surgeons provided superior short-term outcomes with shorter lengths of stay and lower charges. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. NR 45 TC 49 Z9 49 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 AUG PY 2003 VL 113 IS 8 BP 1332 EP 1343 DI 10.1097/00005537-200308000-00013 PG 12 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 712GX UT WOS:000184790900011 PM 12897555 ER PT J AU Takahashi, K Merchant, SN Miyazawa, T Yamaguchi, T McKenna, MJ Kouda, H Iino, Y Someya, T Tamagawa, Y Takiyama, Y Nakano, I Saito, K Boyer, P Kitamura, K AF Takahashi, K Merchant, SN Miyazawa, T Yamaguchi, T McKenna, MJ Kouda, H Iino, Y Someya, T Tamagawa, Y Takiyama, Y Nakano, I Saito, K Boyer, P Kitamura, K TI Temporal bone histopathological and quantitative analysis of mitochondrial DNA in MELAS SO LARYNGOSCOPE LA English DT Article ID TRANSFER RNA(LEU(UUR)) GENE; TRANSFER RNALEU(UUR) GENE; OXIDATIVE PHOSPHORYLATION; LACTIC-ACIDOSIS; POINT MUTATION; HEARING-LOSS; PATIENT; ENCEPHALOMYOPATHIES; ENCEPHALOPATHY; FUROSEMIDE AB Objectives/Hypothesis: Although hearing loss is common in MELAS (syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes), the histopathology of the temporal bone has not been reported. The majority of cases of MELAS are linked to a mitochondrial DNA (mtDNA) mutation at nucleotide 3243. In MELAS, normal mtDNA and mutant mtDNA coexist in a heteroplasmic manner. The purpose of the study was to report the otopathological findings from two patients with MELAS and quantitative mtDNA analysis in the inner ear of one of these patients. Study Design: Basic scientific histopathological examination and quantitative mtDNA analysis of the temporal bone. Methods: Temporal bones were embedded in celloidin and sectioned for light microscopic study. Graphic reconstruction of the cochlea was performed using the method described by Schuknecht. For quantitative mtDNA analysis, total DNA from the membranous part of the inner ear was collected, amplified by polymerase chain reaction, and digested with the restriction enzyme. The percentage of mutant/total mtDNA was measured by the ratio of fluorescence intensity. Results. Histopathological examination revealed severe degeneration of the stria vascularis and degenerative change of spiral ganglion cells in both patients. The quantitative DNA studies showed that the proportion of mutant to wild-type mtDNA was similar in both histologically affected and histologically unaffected tissues within the inner ear. Conclusion: Dysfunction of the stria vascularis and spiral ganglion cells causes sensorineural hearing loss in MELAS. C1 Tokyo Med & Dent Univ, Dept Otolaryngol, Bunkyo Ku, Tokyo 1138519, Japan. Gunma Univ, Dept Otolaryngol, Gunma, Japan. Jichi Med Sch, Dept Otolaryngol, Minami Kawachi, Tochigi 32904, Japan. Jichi Med Sch, Dept Neurol, Minami Kawachi, Tochigi 32904, Japan. Jichi Med Sch, Dept Pathol, Minami Kawachi, Tochigi 32904, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Teikyo Univ, Dept Otolaryngol, Itabashi Ku, Tokyo 173, Japan. Penn State Univ, Dept Pathol, Hershey, PA 17033 USA. BML Gen Lab, Kawagoe, Saitama, Japan. RP Kitamura, K (reprint author), Tokyo Med & Dent Univ, Dept Otolaryngol, Bunkyo Ku, Tokyo 1138519, Japan. NR 31 TC 22 Z9 22 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 AUG PY 2003 VL 113 IS 8 BP 1362 EP 1368 DI 10.1097/00005537-200308000-00018 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 712GX UT WOS:000184790900016 PM 12897560 ER PT J AU Paietta, E Neuberg, D Bennett, JM Dewald, G Rowe, JW Cassileth, PA Cripe, L Tallman, MS Wiernik, PH AF Paietta, E Neuberg, D Bennett, JM Dewald, G Rowe, JW Cassileth, PA Cripe, L Tallman, MS Wiernik, PH CA E Cooperative Oncology Grp TI Low expression of the myeloid differentiation antigen CD65s, a feature of poorly differentiated AML in older adults: study of 711 patients enrolled in ECOG trials SO LEUKEMIA LA English DT Article DE immunophenotype; AML in the elderly; CD65s ID ACUTE MYELOGENOUS LEUKEMIA; PREVIOUSLY UNRECOGNIZED FORM; ACUTE LYMPHOBLASTIC-LEUKEMIA; ONCOLOGY-GROUP EXPERIENCE; MINIMAL RESIDUAL DISEASE; CELL ACUTE-LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; DIAGNOSTIC-CRITERIA; ELDERLY-PATIENTS; BONE-MARROW AB CD65s appears when the progenitor antigen CD34 disappears, suggesting that this sialylated carbohydrate antigen marks a turning point in normal myeloid differentiation. We characterized acute myeloid leukemia (AML) with low CD65s expression ( CD65s(low) AML) in 711 patients entered on seven Eastern Cooperative Oncology Group AML treatment trials ( 1986 - 1999). Of those, 198 (28%) qualified as having CD65s(low) AML. Morphologically, CD65s(low) AML was more common in FAB subgroups with minimal differentiation, M0/M1 ( P = <0.0001). Early precursor antigens CD34, CD117 and terminal transferase were more frequent in CD65s(low) than CD65s(high) AML (P = <0.0001). Myeloperoxidase was present in fewer CD65s(low) myeloblasts, and the more mature myeloid antigens, CD15 and CD11b, were rarely detected (P = <0.0001). Yet, the two diagnoses did not differ in the distribution of cytogenetic prognostic groups or the occurrence of the multidrug-resistance mediator, P-glycoprotein. CD65s(low) AML patients were significantly older than CD65s(high) cases (P<0.0001). Furthermore, the incidence of CD65s low cases increased with age, from 20% in patients under the age of 50 years to 67% in patients older than 80 years ( P<0.0001). Overall, complete remission (CR) rate and overall survival were comparable in CD65s(low) and CD65s high AML. However, among patients 455 years of age, CD65s(low) AML had a decreased CR rate of 33 vs 44% in CD65s(high) AML ( P = 0.055). Thus, CD65s(low) AML represents immunophenotypically undifferentiated disease and occurs predominantly in older adults. Although not statistically significant, the observed association between low CD65s expression and decreased CR rate only in patients over the age of 55 is intriguing. C1 New York Med Coll, Immunol Lab, Our Lady Mercy Canc Ctr, Bronx, NY 10466 USA. Dana Farber Canc Inst, ECOG Stat Ctr, Boston, MA 02115 USA. Univ Rochester, Rochester, NY USA. Mayo Clin, Rochester, MN USA. Techn Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. Univ Miami, Coral Gables, FL 33124 USA. Indiana Univ, Bloomington, IN 47405 USA. Northwestern Univ, Sch Med, Feinberg Sch Med, Chicago, IL USA. Eastern Cooperat Oncol Grp, Boston, MA USA. RP Paietta, E (reprint author), New York Med Coll, Immunol Lab, Our Lady Mercy Canc Ctr, 600 E 233rd St, Bronx, NY 10466 USA. FU NCI NIH HHS [CA23318, CA11083, CA21115] NR 58 TC 12 Z9 12 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 AUG PY 2003 VL 17 IS 8 BP 1544 EP 1550 DI 10.1038/sj.leu.2402999 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 706DD UT WOS:000184436400013 PM 12886241 ER PT J AU Friedenberg, WR Graham, D Greipp, P Blood, E Winston, RD AF Friedenberg, WR Graham, D Greipp, P Blood, E Winston, RD TI The treatment of multiple myeloma with docetaxel (an ECOG study) SO LEUKEMIA RESEARCH LA English DT Article DE multiple myeloma; relapsing myeloma; docetaxel; refractory myeloma ID CLINICAL-TRIALS GROUP; PHASE-II TRIAL; TAXOL; TAXOTERE(TM); PACLITAXEL; RESISTANCE; CANCER; CELLS AB Background: Docetaxel has activity against multiple malignancies. In a previous ECOG study of untreated patients with multiple myeloma, paclitaxel was found to have mild activity, but had excessive toxicity. Docetaxel was evaluated in patients with relapsing or refractory multiple myeloma. Method: Well-documented patients with relapsing or refractory multiple myeloma, who had received no more than two prior combination chemotherapy regimens, were treated with docetaxel 75 mg m(-2) intravenously over 1h every 3 weeks. Patients were evaluated after two and four cycles of treatment. Standard ECOG criteria were used to evaluate for response and toxicity. Results: The study accrued 31 patients with 28 eligible for response and 30 for toxicity analysis. No objective responses (partial or complete) were found. One patient died due to pneumonia. The majority of patients (80%) developed grade 3-4 granulocytopenia and 23% experienced grade 3-4 thrombocytopenia. The median number of cycles was three. The median survival was 9.9 months. Conclusion: Docetaxel was inactive in patients with relapsing or refractory multiple myeloma. In addition, at 75 mg m(-2) every 3 weeks, there was extensive hematological toxicity. It is unlikely that a change in dose or a different schedule would significantly improve response, limit toxicity, and improve survival in patients with multiple myeloma. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Guthrie Clin, Dept Hematol Oncol, Sayre, PA 18840 USA. Carle Clin Assoc, Urbana, IL 61801 USA. Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Hubert H Canc Ctr, Coon Rapids, MN 55433 USA. RP Friedenberg, WR (reprint author), Guthrie Clin, Dept Hematol Oncol, 1 Guthrie Sq, Sayre, PA 18840 USA. FU NCI NIH HHS [CA 23318, CA 21115, CA 13650] NR 9 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD AUG PY 2003 VL 27 IS 8 BP 751 EP 754 DI 10.1016/S0145-2126(02)00344-2 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 692JZ UT WOS:000183659100012 PM 12801534 ER PT J AU Stone, ME AF Stone, ME TI The first Year (TM) - HIV: An essential guide for the newly diagnosed. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD AUG PY 2003 VL 128 IS 13 BP 119 EP 119 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 710VG UT WOS:000184703100253 ER PT J AU Mukohara, T Kudoh, S Yamauchi, S Kimura, T Yoshimura, N Kanazawa, H Hirata, K Wanibuchi, H Fukushima, S Inoue, K Yoshikawa, J AF Mukohara, T Kudoh, S Yamauchi, S Kimura, T Yoshimura, N Kanazawa, H Hirata, K Wanibuchi, H Fukushima, S Inoue, K Yoshikawa, J TI Expression of epidermal growth factor receptor (EGFR) and downstream-activated peptides in surgically excised non-small-cell lung cancer (NSCLC) SO LUNG CANCER LA English DT Article DE NSCLC; EGFR; ERK; Akt; STAT3; immunohistochemistry ID BREAST-CANCER; PROTEIN-KINASE; INDUCED APOPTOSIS; EPITHELIAL-CELLS; SURVIVAL; THERAPY; CARCINOMAS; TARGET AB Extracellular signal-regulated kinases (ERKs), Akt, and signal transducer and activator of transcription 3 (STAT3) are on signal transduction pathways triggered by epidermal growth factor receptor (EGFR). The purpose of this study was to evaluate the expressions of these peptides and to correlate the level of EGFR expression with downstream-activated peptide expression in non-small-cell lung cancer (NSCLC). A total of 60 specimens were studied by immunohistochemistry. EGFR overexpression was detected in 78% of specimens, but no significant relationship was found between it and any clinicopathological factors investigated. Phosphorylated (p)-ERK, p-Akt, and p-STAT3 expressions were observed in 28, 53, and 58% of specimens, respectively, and p-Akt and p-STAT3 expressions were correlated with well-differentiated tumor (P = 0.045 and 0.014, respectively). Half of the 60 specimens expressed two or three downstream-activated peptides. The level of EGFR expression was associated with expressions of p-ERK and p-Akt (P = 0.045 and 0.020, respectively). In a preliminary analysis, no peptides examined had an impact on relapse-free survival. In summary, various signal transduction pathways appeared frequently to participate in NSCLC, and the level of EGFR expression appeared to correlate with those of activated ERK and Akt, suggesting some role of receptor overexpression in more potent downstream activation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Osaka City Univ, Sch Med, Dept Internal Med 1, Abeno Ku, Osaka 5458585, Japan. Osaka City Univ, Sch Med, Dept Pathol, Abeno Ku, Osaka 5458585, Japan. Osaka City Univ, Sch Med, Dept Surg 2, Abeno Ku, Osaka 5458585, Japan. RP Mukohara, T (reprint author), Dana Farber Canc Inst, 44 Binney St,D820D, Boston, MA 02115 USA. NR 28 TC 86 Z9 99 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD AUG PY 2003 VL 41 IS 2 BP 123 EP 130 DI 10.1016/S0169-5002(03)00225-3 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 707TH UT WOS:000184525600001 PM 12871775 ER PT J AU Takahashi, K Takahashi, F Hirama, M Tanabe, KK Fukuchi, Y AF Takahashi, K Takahashi, F Hirama, M Tanabe, KK Fukuchi, Y TI Restoration of CD44S in non-small cell lung cancer cells enhanced their susceptibility to the macrophage cytotoxicity SO LUNG CANCER LA English DT Article DE CD44; osteopontin; lung cancer; macrophage; migration ID OSTEOPONTIN EXPRESSION; COLON CARCINOMAS; ENDOTHELIAL-CELLS; LYMPH-NODE; VARIANT; ADHESION; HYALURONATE; RECEPTOR; METASTASIS; ISOFORMS AB CD44 is a cell surface receptor for osteopontin (OPN) and hyaturonate. Transformation of normal tissue to a variety of cancers has been demonstrated to be associated with alterations of CD44 isoform expression. However, few reports have paid attention on differences in CD44S expression between non-small cell lung cancer (NSCLC) and adjacent normal lung tissue. In this study, we demonstrate that CD44S expression is down-regulated in NSCLC tissue when compared with paired normal Lung tissue. To investigate the role of CD44S down-regulation in NSCLC cells, we reintroduced the CD44S back into the NSCLC cell line, H322 cells, which originally Lack CD44S expression. The cytotoxicity by activated macrophage (RAW264.7 cells stimulated with lipopolysaccharide and interferon-gamma) against the H322 cells transfected with the CD44S gene (H322DeltaS) is more prominent than that against the H322 control transfectants (H322Deltaneo). The enhanced susceptibility of H322DeltaS cells to the activated macrophage cytotoxicity appears to be mediated by the interaction between CD44S expression on H322DeltaS cells and OPN produced by activated macrophages since it is completely blocked by either anti-OPN or anti-CD44 antibody. Moreover, H322DeltaS cells are attracted toward OPN produced by activated RAW264.7 cells to a much greater extent than H322Deltaneo cells. These findings suggest that CD44S down-regulation in NSCLC cells may confer a protective advantage of allowing escape from tumoricidal effector cells including activated macrophages of the host. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, Tokyo 1138421, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Takahashi, K (reprint author), Juntendo Univ, Sch Med, Dept Resp Med, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. NR 43 TC 17 Z9 22 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD AUG PY 2003 VL 41 IS 2 BP 145 EP 153 DI 10.1016/S0169-5002(03)00224-1 PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 707TH UT WOS:000184525600003 PM 12871777 ER PT J AU Soria, JC Johnson, BE Le Chevalier, T AF Soria, JC Johnson, BE Le Chevalier, T TI Imatinib in small cell lung cancer SO LUNG CANCER LA English DT Article; Proceedings Paper CT 1st IASLC/ASCO International Conference on Molecular Targeted Therapies in Lung Cancer CY JAN 15-19, 2003 CL MARBELLA, SPAIN SP IASLC, ASCO DE SCLC patients; Imatinib Mesylate; KIT; new targets; molecular targeted therapy ID TYROSINE KINASE INHIBITOR; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; C-KIT; CYTOGENETIC RESPONSES; PHASE-II; GROWTH; EXPRESSION AB Purpose: To evaluate the clinical efficacy of Imatinib Mesytate in untreated or sensitive relapsed small cell lung carcinoma patients. Secondary endpoints included assessment of the safety and tolerance of Imatinib, and an analysis of KIT expression in tumor samples. Patients and Methods: Patients with previously untreated small cell lung cancer (SCLC) or with a sensitive relapse (one prior regimen with a sustained response for over 60 days) were eligible. Imatinib was delivered at 600 mg on a daily basis. Response was evaluated at 6 weeks using SWOG criteria. Results: As planned in the study design, a total of 19 patients were included in the trial (9 chemonaive patients with extensive disease and 10 sensitive relapse SCLC patients). No objective responses were observed with most previously untreated patients staying on study for less than 30 days. The median time to progression was 1 and 1.2 month in the untreated and sensitive relapse groups, respectively. Only 4 out of 19 tumor samples (21%) stained for KIT by means of immunohistochemistry. Conclusions: No evidence of antitumor activity was observed in this small phase 11 trial including 19 SCLC patients treated with Imatinib Mesylate. KIT positivity in tumor samples appeared to be far less common than anticipated (21 vs. 70%). Future trials should include a screening procedure to evaluate KIT expression in SCLC samples. A better evaluation of KIT contribution to SCLC tumor progression needs to be achieved. (C) 2003 Elsevier Science Ireland Ltd and American Society of Clinical Oncology. Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Inst Gustave Roussy, Div Med, F-94805 Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Le Chevalier, T (reprint author), Inst Gustave Roussy, Div Med, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. NR 22 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD AUG PY 2003 VL 41 SU 1 BP S49 EP S53 DI 10.1016/S0169-5002(03)00142-9 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 712FY UT WOS:000184788100008 PM 12867062 ER PT J AU Clark, JA Bokhour, BG Inui, TS Silliman, RA Talcott, JA AF Clark, JA Bokhour, BG Inui, TS Silliman, RA Talcott, JA TI Measuring patients' perceptions of the outcomes of treatment for early prostate cancer SO MEDICAL CARE LA English DT Article DE prostate cancer; quality of life; treatment outcomes ID QUALITY-OF-LIFE; URINARY-INCONTINENCE; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; MEN; THERAPY; INSTRUMENT; RADIOTHERAPY; VALIDATION; SEXUALITY AB BACKGROUND. Compared with careful attention to the physical (eg, urinary, bowel, sexual) dysfunction that may follow treatment, little attention has been given to the behavioral, emotional, and interpersonal changes that the diagnosis of early prostate cancer and subsequent physical dysfunction may bring. OBJECTIVE. To construct patient-centered measures of the outcomes of treatment for early prostate cancer. RESEARCH DESIGN. Qualitative study followed by survey of early prostate cancer patients and group of comparable patients with no history of prostate cancer. Analysis of focus groups identified relevant domains of quality of life, which were represented by Likert scale items included in survey questionnaires. Psychometric analyses of survey data defined scales evaluated with respect to internal consistency and validity. RESULTS. Qualitative analysis identified three domains: urinary control, sexuality, and uncertainty about the cancer and its treatment. Psychometric analysis defined 11 scales. Seven were generically relevant to most older men: urinary control (eg, embarrassment with leakage), sexual intimacy (eg, anxiety about completing intercourse), sexual confidence (eg, comfort with sexuality), marital affection (eg, emotional distance from spouse/partner), masculine self esteem (eg, feeling oneself a whole man), health worry (eg, apprehensiveness about health changes), and PSA concern (eg, closely attending to one's PSA). Four scales were specific to the treatment experience: perceived cancer control, quality of treatment decision making, regret of treatment choice, and cancer-related outlook. CONCLUSION. The scales provide definition and metrics for patient-centered research in this area. They complement measures of physical dysfunction and bring into resolution outcomes of treatment that have gone unnoticed in previous studies. C1 Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02118 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Clark, JA (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Serv, 715 Albany St,T3-W, Boston, MA 02118 USA. NR 47 TC 71 Z9 71 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD AUG PY 2003 VL 41 IS 8 BP 923 EP 936 DI 10.1097/00005650-200308000-00006 PG 14 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 706WH UT WOS:000184477700006 PM 12886172 ER PT J AU Leaf, DA AF Leaf, DA TI The effect of physical exercise on reverse cholesterol transport SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; PHOSPHOLIPID TRANSFER PROTEIN; CORONARY-ARTERY DISEASE; PLASMA HDL-CHOLESTEROL; MIDDLE-AGED MEN; HEPATIC LIPASE; MYOCARDIAL-INFARCTION; PROLONGED EXERCISE AB High-density lipoproteins (HDL) are recognized for their role in coronary artery disease (CAD) risk reduction. Plasma HDL plays a pivotal role in the reverse cholesterol transport (RCT) process. Physical exercise is well recognized as a modality that affects HDL metabolism. The purpose of this discussion is to describe the effects of physical exercise on RCT. (C) 2003 Elsevier Inc. All rights reserved. C1 Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Leaf, DA (reprint author), Greater Los Angeles VA Healthcare Syst, Div Gen Internal Med, Dept Med, 111G,Wilshire & Sawtelle Blvd, Los Angeles, CA 90073 USA. NR 95 TC 27 Z9 28 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2003 VL 52 IS 8 BP 950 EP 957 DI 10.1016/S0026-0495(03)00147-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716EF UT WOS:000185015300002 PM 12898457 ER PT J AU Murray, SS Duarte, MEL Brochmann, EJ AF Murray, SS Duarte, MEL Brochmann, EJ TI The effects of dietary restriction on humeral and mandibular bone in SENCAR, C57BL/6, and DBA/2 mice SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 20-24, 2002 CL SAN ANTONIO, TEXAS SP American-Soc-Bone-Mineral-Res ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; CALORIE RESTRICTION; TUMOR PROMOTION; CALCIUM-REPLETE; INBRED STRAINS; INDUCED OBESE; B6C3F1 MICE; DNA DAMAGE; HIGH-FAT AB Dietary restriction (DR) increases the life span and retards the development of age-related disorders. However, the low body mass that accompanies DR is associated with risk factors for fracture that may outweigh the beneficial effects of DR on cellular aging that are mediated, in part, by limiting free radical generation and oxidative damage. We tested the effects of DR in murine models that differ in free radical generation capacity (SENCAR > C57 > DBA). Male mice of each strain were killed at 10 weeks of age (t(0); time zero) or randomized to an ad libitum-fed (AL-fed) or 30% DR feeding regimen for 6 months. The food consumption of AL-fed mice was measured daily. DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. The DR diet was normalized with respect to calcium (Ca), phosphorus (P), and micronutrients. Lean body mass (LBM), bone mineral density (BMD), and bone mineral content (BMC) in the humerus and mandible were determined by PIXImus densitometry. The length and midshaft width of the humerus were determined by direct measurement. There were highly strain- and diet/time-dependent effects on LBM, humerus length, mandibular and humeral BMD, and humeral BMC. The interaction between diet/time and strain was more significant in the humerus than the mandible. All 30% DR mice had lower humeral BMDs and BMCs than their respective AL-fed controls. However, 30% DR C57 and DBA (but not SENCAR) mice had higher humeral BMD and BMC than their respective to controls. There was a linear relationship between LBM and humeral BMD and BMC in both AL-fed and 30% DR mice, suggesting that the lower BMD and BMC in 30% DR mice, relative to AL-fed controls, reflects a physiologic adaptation to lower biomechanical loading. Mandibular BMC in 30% DR C57 (but not DBA or SENCAR) mice was lower than that observed in their AL-fed controls. Mandibular BMD and BMC increased versus t(0) values in 30% DR mice of all strains. (C) 2003 Elsevier Inc. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, GRECC 11E, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA 91343 USA. Fed Univ Rio De Janeiro, Dept Histol & Embryol, Rio De Janeiro, Brazil. Fed Univ Rio De Janeiro, PABCAM HUCFF, Rio De Janeiro, Brazil. RP Murray, SS (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11E, Sepulveda Ambulatory Care Ctr & Nursing Home, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 36 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD AUG PY 2003 VL 52 IS 8 BP 970 EP 977 DI 10.1016/S002600495(03)00164-1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 716EF UT WOS:000185015300005 PM 12898460 ER PT J AU Pearson, AM Baksa, K Ramet, M Protas, M McKee, M Brown, D Ezekowitz, RAB AF Pearson, AM Baksa, K Ramet, M Protas, M McKee, M Brown, D Ezekowitz, RAB TI Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila SO MICROBES AND INFECTION LA English DT Article DE cytoskeleton; Drosophila; innate immunity; phagocytosis ID PEPTIDOGLYCAN RECOGNITION PROTEIN; ALDRICH-SYNDROME PROTEIN; ACTIN-FILAMENTS; ARP2/3 COMPLEX; MEDIATED PHAGOCYTOSIS; IMMUNE-RESPONSES; APOPTOTIC CELLS; WASP; RECEPTOR; MACROPHAGES AB Phagocytosis is a complex and apparently evolutionarily conserved process that plays a central role in the immune response to infection. By ultrastructural and functional criteria, Drosophila hemocyte (macrophage) phagocytosis resembles mammalian phagocytosis. Using a non-saturated forward genetic screen for larval hemocyte phagocytosis mutants, D-SCAR and profilin were identified as important regulators of phagocytosis in Drosophila. In both hemocytes ex vivo and the macrophage-like S2 cell line, lack of D-SCAR significantly decreased phagocytosis of Escherichia coli and Staphylococcus aureus. In contrast, profilin mutant hemocytes exhibited increased phagocytic activity. Analysis of double mutants suggests that D-SCAR and profilin interact during phagocytosis. Finally, RNA interference studies in S2 cells indicated that the D-SCAR homolog D-WASp also participates in phagocytosis. This study demonstrates that Drosophila provides a viable model system in which to dissect the complex interactions that regulate phagocytosis. (C) 2003 Published by Editions scientifiques et medicales Elsevier SAS. C1 Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Jackson 1402,MGH 55 Fruit St, Boston, MA 02114 USA. EM Aezekowitz@partners.org FU NIAID NIH HHS [5PO1 AI44220]; NICHD NIH HHS [HD 40793]; NIDDK NIH HHS [DK 57521, DK 38452, DK 43351] NR 39 TC 80 Z9 83 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 EI 1769-714X J9 MICROBES INFECT JI Microbes Infect. PD AUG PY 2003 VL 5 IS 10 BP 815 EP 824 DI 10.1016/S1286-4579(03)00157-6 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 717JP UT WOS:000185085600001 PM 12919849 ER PT J AU Deziel, E Lepine, F Milot, S Villemur, R AF Deziel, E Lepine, F Milot, S Villemur, R TI rhlA is required for the production of a novel biosurfactant promoting swarming motility in Pseudomonas aeruginosa: 3-(3-hydroxyalkanoyloxy)alkanoic acids (HAAs), the precursors of rhamnolipids SO MICROBIOLOGY-SGM LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; SERRATIA-LIQUEFACIENS MG1; BACILLUS-SUBTILIS; TWITCHING MOTILITIES; CONTINUOUS CULTURE; ESCHERICHIA-COLI; GENE-EXPRESSION; STRAIN 57RP; BIOSYNTHESIS; RHAMNOSE AB Pseudomonas aeruginosa produces extracellular glycolipids composed of L-rhamnose and 3-hydroxyalkanoic acid called rhamnolipids. Although these compounds are usually regarded as biosurfactants or haemolysins, their exact physiological function is not well understood. Rhamnolipids are synthesized by a rhannnosyltransferase, encoded by the rhlAB operon, which catalyses the transfer of TDP-L-rhamnose to 3-(3-hydroxyalkanoyloxy)alkanoic acid (HAA) moieties of various lengths. RhlB is the catalytic protein of the rhamnosyltransferase. rhlA is indispensable for rhamnolipid synthesis, but its function is unknown. Using a liquid chromatography/mass spectrometry method, the production of extracellular HAAs by P. aeruginosa was detected previously and it was demonstrated that they are the actual precursors of rhamnolipid biosynthesis. In this report, evidence is presented indicating that rhlA is required for production of HAAs and that these HAAs display potent surface-active properties. P. aeruginosa can colonize surfaces by swarming motility, a form of organized translocation requiring the production of wetting agents. Using rhlA and rhlB mutants it was observed that swarming requires the expression of the rhlA gene but does not necessitate rhamnolipid production, as HAAs act as surfactants. Finally, it was shown that the use of ammonium instead of nitrate as source of nitrogen and an excess of available iron both decrease rhlA expression and swarming motility. C1 INRS, Inst Armand Frappier, Laval, PQ H7V 1B7, Canada. RP Deziel, E (reprint author), Massachusetts Gen Hosp, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA. RI Deziel, Eric/A-7678-2008; OI Deziel, Eric/0000-0002-4609-0115; Villemur, Richard/0000-0001-9768-8937 NR 55 TC 201 Z9 208 U1 2 U2 30 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD AUG PY 2003 VL 149 BP 2005 EP 2013 DI 10.1099/mic.0.26154-0 PN 8 PG 9 WC Microbiology SC Microbiology GA 713FK UT WOS:000184846300007 PM 12904540 ER PT J AU Takahashi, C Bronson, RT Socolovsky, M Contreras, B Lee, KY Jacks, T Noda, M Kucherlapati, R Ewen, ME AF Takahashi, C Bronson, RT Socolovsky, M Contreras, B Lee, KY Jacks, T Noda, M Kucherlapati, R Ewen, ME TI Rb and N-ras function together to control differentiation in the mouse SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR NF-IL6; ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE CELLS; RETINOBLASTOMA PROTEIN; ADIPOCYTE DIFFERENTIATION; GENE-EXPRESSION; H-RAS; K-RAS; GLUCOCORTICOID RECEPTOR; CAENORHABDITIS-ELEGANS AB The product of the retinoblastoma tumor suppressor gene (Rb) can control cell proliferation and promote differentiation. Murine embryos nullizygous for Rb die midgestation with defects in cell cycle regulation, control of apoptosis, and terminal differentiation of several tissues, including skeletal muscle, nervous system, and lens. Previous cell culture-based experiments have suggested that the retinoblastoma protein (pRb) and Ras operate in a common pathway to control cellular differentiation. Here we have tested the hypothesis that the proto-oncogene N-ras participates in Rb-dependent regulation of differentiation by generating and characterizing murine embryos deficient in both N-ras and Rb. We show that deletion of N-ras rescues a unique subset of the developmental defects associated with nullizygosity of Rb, resulting in a significant extension of life span. Rb-/-; N-ras(-/-) skeletal muscle has normal fiber density, myotube length and thickness, in contrast to Rb-deficient embryos. Additionally, Rb-/-; N-ras(-/-) muscle shows a restoration in the expression of the late muscle-specific gene MCK, and this correlates with a significant potentiation of MyoD transcriptional activity in Rb-/-; N-ras(-/-), compared to Rb-/- myoblasts in culture. The improved differentiation of skeletal muscle in Rb-/-; N-ras(-/-) embryos occurs despite evidence of deregulated proliferation and apoptosis, as seen in Rb-deficient animals. Our findings suggest that the control of differentiation and proliferation by Rb are genetically separable. C1 Dana Farber Canc Inst, Dept Med Oncol & Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Rodent Histopathol Core, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Kyoto Univ, Grad Sch Med, Dept Mol Oncol, Sakyo Ku, Kyoto 6068501, Japan. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Dept Med Oncol & Med, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA065842, CA 65842] NR 71 TC 40 Z9 41 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 AUG PY 2003 VL 23 IS 15 BP 5256 EP 5268 DI 10.1128/MCB.23.15.5256-5268.2003 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 703MP UT WOS:000184283700014 PM 12861012 ER PT J AU Chen, TP Ueda, Y Dodge, JE Wang, ZJ Li, E AF Chen, TP Ueda, Y Dodge, JE Wang, ZJ Li, E TI Establishment and maintenance of genomic methylation patterns in mouse embryonic stem cells by Dnmt3a and Dnmt3b SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DE-NOVO METHYLATION; HUMAN CANCER-CELLS; DNA CYTOSINE-5 METHYLTRANSFERASES; MAMMALIAN DEVELOPMENT; CPG METHYLATION; GENE; EXPRESSION; FAMILY; OVEREXPRESSION; CLONING AB We have previously shown that the DNA methyltransferases Dnmt3a and Dnmt3b carry out de novo, methylation of the mouse genome during early postimplantation development and of maternally imprinted genes in the oocyte. In the present study, we demonstrate that Dnmt3a and Dnmt3b are also essential for the stable inheritance, or "maintenance," of DNA methylation patterns. Inactivation of both Dnmt3a and Dnmt3b in embryonic stem (ES) cells results in progressive loss of methylation in various repeats and single-copy genes. Interestingly, introduction of the Dnmt3a, Dnmt3a2, and Dnmt3b1 isoforms back into highly demethylated mutant ES cells restores genomic methylation patterns; these isoforms appear to have both common and distinct DNA targets, but they all fail to restore the maternal methylation imprints. In contrast, overexpression of Dnmt1 and Dnmt3b3 failed to restore DNA methylation patterns due to their inability to catalyze de novo, methylation in vivo. We also show that hypermethylation of genomic DNA by Dnmt3a and Dnmt3b is necessary for ES cells to form teratomas in nude mice. These results indicate that genomic methylation patterns are determined partly through differential expression of different Dnmt3a and Dnmt3b isoforms. C1 Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Cardiovasc Res Ctr, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Cutaneous Biol Res Ctr, Sch Med, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. OI Ueda, Yoshihide/0000-0003-3196-3494 FU NCI NIH HHS [CA82389, R01 CA082389]; NIGMS NIH HHS [GM52106] NR 49 TC 395 Z9 404 U1 4 U2 17 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 AUG PY 2003 VL 23 IS 16 BP 5594 EP 5605 DI 10.1128/MCB.23.16.5594-5605.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 707TZ UT WOS:000184527100010 PM 12897133 ER PT J AU Rossi, S Graner, E Febbo, P Weinstein, L Bhattacharya, N Onody, T Bubley, G Balk, S Loda, M AF Rossi, S Graner, E Febbo, P Weinstein, L Bhattacharya, N Onody, T Bubley, G Balk, S Loda, M TI Fatty acid synthase molecular signatures expression defines distinct in prostate cancer SO MOLECULAR CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; MEDIATED APOPTOSIS; APOLIPOPROTEIN-E; LIGAND TRAIL; E-CADHERIN; CELLS; PROGRESSION; ACTIVATION; OVEREXPRESSION; PATHWAY AB The androgen-regulated enzyme fatty acid synthase (FAS), required for de novo lipogenesis, is overexpressed in several cancers including prostate carcinoma and has been associated with aggressive disease. FAS expression was assessed in 81 prostate carcinomas, both by immunohistochemistry in tissue microarrays and by Affymetrix Hu95Av2 oligonucleotide arrays. Both FAS mRNA and protein were significantly overexpressed in prostate carcinomas compared with the corresponding normal tissue. FAS mRNA and protein expression increased substantially from normal to prostatic intraepithelial neoplasia, to low grade, to high grade, and to androgen-independent bone metastases. A significant correlation between FAS mRNA and protein expression was found in two thirds of the cases. In 17% of the cases, FAS protein levels were high despite low mRNA levels, and these tumors exhibited a distinct molecular signature when compared with tumors that did not express FAS protein. Whereas the latter group of tumors expressed some proapoptotic genes, tumors with high FAS levels overexpressed, among other genes, its transcriptional regulator, steroid regulator binding protein, and apolipoprotein E. These data demonstrate (1) the consistent overexpression of FAS in prostate carcinoma compared with the adjacent normal tissue, (2) a strong association between FAS and prostate tumor initiation and progression, (3) the highest FAS expression occurring in androgen-independent bone metastases, (4) the transcriptional and posttranscriptional regulation of FAS in the majority and in a subset of prostate cancers, respectively, and (5) most importantly, the identification by FAS expression of prostate tumors with unique molecular signatures and potentially diverse biologic behavior. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Regina Elena Inst Canc Res, Rome, Italy. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, D-740B,44 Binney St, Boston, MA 02115 USA. RI Graner, Edgard/K-4411-2012; OI Rossi, Sabrina/0000-0001-9122-1308 FU NCI NIH HHS [P01 CA89021-02, CA84995-04, CA90381-01A1] NR 45 TC 160 Z9 170 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2003 VL 1 IS 10 BP 707 EP 715 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 714MG UT WOS:000184917600002 PM 12939396 ER PT J AU Li, YQ Yu, WH Ren, J Chen, W Huang, L Kharbanda, S Loda, M Kufe, D AF Li, YQ Yu, WH Ren, J Chen, W Huang, L Kharbanda, S Loda, M Kufe, D TI Heregulin targets gamma-catenin to the nucleolus by a mechanism dependent on the DF3/MUC1 oncoprotein SO MOLECULAR CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; EPIDERMAL-GROWTH-FACTOR; BETA-CATENIN; BREAST-CANCER; NUCLEAR-LOCALIZATION; FACTOR RECEPTOR; SIGNALING NETWORK; EPITHELIAL-CELLS; TYROSINE KINASE; ERBB RECEPTORS AB The DF3/MUC1 transmembrane oncoprotein is aberrantly overexpressed in most human breast carcinomas and interacts with the Wnt effector,gamma-catenin. Here, we demonstrate that MUC1 associates constitutively with ErbB2 in human breast cancer cells and that treatment with heregulin/neuregulin-1 (HRG) increases the formation of MUC1-ErbB2 complexes. The importance of the MUC1-ErbB2 interaction is supported by the demonstration that HRG induces binding of MUC1 and gamma-catenin and targeting of the MUC1-gamma-catenin complex to the nucleolus. Significantly, nucleolar localization of gamma-catenin in response to HRG is dependent on MUC1 expression. Moreover, mutation of a RRK motif in the MUC1 cytoplasmic domain abrogates HRG-induced nucleolar localization of MUC1 and gamma-catenin. In concert with these results, we show nucleolar localization of MUC1 and gamma-catenin in human breast carcinomas but not in normal mammary ductal epithelium. These findings demonstrate that MUC1 functions in cross talk between ErbB2 and Writ pathways by acting as a shuttle for HRG-induced nucleolar targeting of gamma-catenin. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. ILEX Prod Inc, Boston, MA USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Yu, Wei-Hsuan/0000-0002-1782-3738 FU NCI NIH HHS [CA97098] NR 48 TC 75 Z9 82 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD AUG PY 2003 VL 1 IS 10 BP 765 EP 775 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 714MG UT WOS:000184917600008 PM 12939402 ER PT J AU Frolov, A Chahwan, S Ochs, M Arnoletti, JP Pan, ZZ Favorova, O Fletcher, J von Mehren, M Eisenberg, B Godwin, AK AF Frolov, A Chahwan, S Ochs, M Arnoletti, JP Pan, ZZ Favorova, O Fletcher, J von Mehren, M Eisenberg, B Godwin, AK TI Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumors SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TYROSINE KINASE INHIBITOR; CHRONIC MYELOGENOUS LEUKEMIA; C-KIT; CYTOGENETIC RESPONSES; GENE-EXPRESSION; IMATINIB MESYLATE; MUSCLE ATROPHY; CELL-SURVIVAL; MUTATIONS; PHOSPHODIESTERASE AB Gastrointestinal stromal tumors (GISTs), defined by the presence of constitutively activated KIT, are the most common gastrointestinal mesenchymal malignancies. This observation has been successfully exploited in clinical trials of Gleevec (also known as imatinib mesylate, STI-571) for patients with unresectable and/ or metastatic GISTs. The biological mechanisms of Gleevec as well as its downstream molecular effects are generally unknown. We used a DNA microarray-based approach to identify gene expression patterns and signaling pathways that were altered in response to Gleevec in GIST cells. We identified a total of 148 genes or expressed sequence tags (of 10,367) that were differentially regulated; 7 known genes displayed a durable response after treatment. The significantly down-regulated genes were SPRY4A, FZD8, PDE2A, RTP801, FLJ201398, and ARHGEF2. The only upregulated gene was MAFbx. On a functional level, we demonstrated that imatinib inhibited phosphorylation of KIT, AKT, and extracellular signal-regulated kinase 1/2 without affecting the total level of these proteins and that differential expression of these response genes involved activation of mitogen-activated protein kinase-dependent and -independent pathways. In an attempt to correlate these in vitro findings to clinical data, we examined GIST needle biopsy specimens taken from patients before and after Gleevec administration according to the CST1571-B2222 Phase II trial and demonstrated that expression levels of the two gene transcripts evaluated correlated well with clinical response. This study emphasizes the potential value of an in vitro cell model to investigate GIST response to imatinib in vivo, for the purpose of identifying important genetic markers of clinical response, mechanisms of drug action, and possible therapeutic targets. C1 Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Bioinformat, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Informat Sci & Technol, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Russian State Med Univ, Dept Mol Biol & Biotechnol, Grad Program, Moscow 117869, Russia. RP Godwin, AK (reprint author), Fox Chase Canc Ctr, Dept Med Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI Pan, Zhong-Zong/B-6964-2012 FU NCI NIH HHS [3 U10 CA21661-27, P50 CA83638] NR 41 TC 75 Z9 84 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD AUG PY 2003 VL 2 IS 8 BP 699 EP 709 PG 11 WC Oncology SC Oncology GA 714MK UT WOS:000184917900001 PM 12939459 ER PT J AU Shamji, AF Nghiem, P Schreiber, SL AF Shamji, AF Nghiem, P Schreiber, SL TI Integration of growth factor and nutrient signaling: Implications for cancer biology SO MOLECULAR CELL LA English DT Review ID P70 S6 KINASE; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; TUMOR-SUPPRESSOR PROTEINS; COMPLEX GENE-PRODUCTS; TUBEROUS SCLEROSIS; CELL-GROWTH; MAMMALIAN TARGET; FKBP12-RAPAMYCIN-ASSOCIATED PROTEIN; TRANSLATION INITIATION; AKT PHOSPHORYLATION AB Signaling networks that promote cell growth are frequently dysregulated in cancer. One regulatory network, which converges on effectors such as 4EBP1 and S6K1, leads to growth by promoting protein synthesis. Here, we discuss how this network is regulated by both extracellular signals, such as growth factors, and intracellular signals, such as nutrients. We discuss how mutations amplifying either type of signal can lead to tumor formation. In particular, we focus on the recent discovery that a tumor suppressor complex whose function is lost in tuberous sclerosis patients regulates the nutrient signal carried by the critical signaling protein TOR to the effectors 4EBP1 and S6K1. Finally, we describe how the small molecule rapamycin, which inhibits TOR and thereby the activation of these effectors, could be useful to treat tumors that have become dependent upon this pathway for growth. C1 Harvard Univ, Harvard Biophys Program, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02115 USA. RP Schreiber, SL (reprint author), Harvard Univ, Harvard Biophys Program, 12 Oxford St, Cambridge, MA 02138 USA. RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X FU NIAMS NIH HHS [K08-AR02087]; NIGMS NIH HHS [GM38627] NR 79 TC 143 Z9 163 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG PY 2003 VL 12 IS 2 BP 271 EP 280 DI 10.1016/j.molcel.2003.08.016 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 716VJ UT WOS:000185050000001 PM 14536067 ER PT J AU Clatworthy, AE Valencia, MA Haber, JE Oettinger, MA AF Clatworthy, AE Valencia, MA Haber, JE Oettinger, MA TI V(D)J recombination and RAG-mediated transposition in yeast SO MOLECULAR CELL LA English DT Article ID STRAND BREAK REPAIR; SACCHAROMYCES-CEREVISIAE; IN-VITRO; DNA TRANSPOSITION; PROTEINS; CLEAVAGE; GENE; MUTANTS; COMPLEX; ENDS AB Antigen receptor genes are assembled during lymphoid development by a specialized recombination reaction normally observed only in cells of the vertebrate immune system. Here, we show that expression in Saccharomyces cerevisiae of murine RAG1 and RAG2, the lymphoid-specific components of the V(D)J recombinase, is sufficient to induce V(D)J cleavage and rejoining in this lower eukaryote. The RAG proteins cleave recombination substrates introduced into yeast cells, generating signal ends that can be joined to form signal joints. These signal joints are precise, as in mammalian cells, and their formation is dependent on a yeast nonhomologous end-joining protein, the XRCC4 homolog LIF1. Moreover, joining of Smal-generated blunt ends is generally imprecise in the yeast strain used here, suggesting that the RAG proteins influence signal-end joining. Cleaved signal ends are also transposed into new sites in DNA, allowing RAG-induced transposition to be studied in vivo. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Ctr, Waltham, MA 02454 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Haber, James/0000-0002-1878-0610 FU NIGMS NIH HHS [GM48026, GM20056] NR 47 TC 35 Z9 36 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD AUG PY 2003 VL 12 IS 2 BP 489 EP 499 DI 10.1016/S1097-2765(03)00305-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 716VJ UT WOS:000185050000021 PM 14536087 ER PT J AU Matsunaga, J Barocchi, MA Croda, J Young, TA Sanchez, Y Siqueira, I Bolin, CA Reis, MG Riley, LW Haake, DA Albert, KI AF Matsunaga, J Barocchi, MA Croda, J Young, TA Sanchez, Y Siqueira, I Bolin, CA Reis, MG Riley, LW Haake, DA Albert, KI TI Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily SO MOLECULAR MICROBIOLOGY LA English DT Article ID INTERROGANS SEROVAR COPENHAGENI; MESSENGER-RNA STABILITY; OUTER-MEMBRANE PROTEIN; MAMMALIAN INFECTION; MOLECULAR ANALYSIS; SEQUENCE-ANALYSIS; BINDING PROTEIN; CELLS; LIPOPROTEIN; CLONING AB Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two fig genes, designated ligA and ligB, and one pseudogene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The fig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Immun, Berkeley, CA 94720 USA. Brazilian Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Salvador, BA, Brazil. Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. Cornell Univ, Weill Med Coll, Div Internal Med & Infect Dis, New York, NY USA. RP Haake, DA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RI Ko, Albert/P-2343-2015 FU FIC NIH HHS [D43 TW000905, D43 TW000919, TW-00905, TW-00919]; NIAID NIH HHS [AI-01605, AI-34431, R01 AI034431, R21 AI034431, R29 AI034431] NR 56 TC 151 Z9 158 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 2003 VL 49 IS 4 BP 929 EP 945 DI 10.1046/j.1365-2958.2003.03619.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 714WJ UT WOS:000184936200007 PM 12890019 ER PT J AU Reginato, MJ Mills, KR Paulus, JK Lynch, DK Sgroi, DC Debnath, J Muthuswamy, SK Brugge, JS AF Reginato, MJ Mills, KR Paulus, JK Lynch, DK Sgroi, DC Debnath, J Muthuswamy, SK Brugge, JS TI Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis SO NATURE CELL BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; BCL-2 FAMILY; CELL-DEATH; PROAPOPTOTIC ACTIVITY; BH3-ONLY PROTEINS; EPITHELIAL-CELLS; DOWN-REGULATION; MOTOR COMPLEX; SURVIVAL; KINASE AB Epithelial cells must adhere to the extracellular matrix (ECM) for survival, as detachment from matrix triggers apoptosis or anoikis(1). Integrins are major mediators of adhesion between cells and ECM proteins, and transduce signals required for cell survival(2). Recent evidence suggests that integrin receptors are coupled to growth factor receptors in the regulation of multiple biological functions(2); however, mechanisms involved in coordinate regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we identify the pro-apoptotic protein Bim as a critical mediator of anoikis in epithelial cells. Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis. Detachment-induced expression of Bim requires a lack of beta(1)-integrin engagement, downregulation of EGF receptor (EGFR) expression and inhibition of Erk signalling. Overexpressed EGFR was uncoupled from integrin regulation, resulting in the maintenance of Erk activation in suspension, and a block in Bim expression and anoikis. Thus, Bim functions as a key sensor of integrin and growth factor signals to the Erk pathway, and loss of such coordinate regulation may contribute to tumour progression. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RI Reginato, Mauricio/I-6155-2013 OI Reginato, Mauricio/0000-0002-7541-4094 NR 35 TC 321 Z9 329 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2003 VL 5 IS 8 BP 733 EP 740 DI 10.1038/ncb1026 PG 8 WC Cell Biology SC Cell Biology GA 710NX UT WOS:000184687300015 PM 12844146 ER PT J AU Otto, EA Schermer, B Obara, T O'Toole, JF Hiller, KS Mueller, AM Ruf, RG Hoefele, J Beekmann, F Landau, D Foreman, JW Goodship, JA Strachan, T Kispert, A Wolf, MT Gagnadoux, MF Nivet, H Antignac, C Walz, G Drummond, IA Benzing, T Hildebrandt, F AF Otto, EA Schermer, B Obara, T O'Toole, JF Hiller, KS Mueller, AM Ruf, RG Hoefele, J Beekmann, F Landau, D Foreman, JW Goodship, JA Strachan, T Kispert, A Wolf, MT Gagnadoux, MF Nivet, H Antignac, C Walz, G Drummond, IA Benzing, T Hildebrandt, F TI Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination SO NATURE GENETICS LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; POLARIZED EPITHELIAL-CELLS; ADOLESCENT NEPHRONOPHTHISIS; JUVENILE NEPHRONOPHTHISIS; CAENORHABDITIS-ELEGANS; SITUS-INVERSUS; CANDIDATE GENE; PCY MICE; PROTEIN; NEPHROCYSTIN AB Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. C1 Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. Univ Hosp Freiburg, Div Renal, Freiburg, Germany. Univ Hosp Freiburg, Clin Res Ctr, Freiburg, Germany. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Soroka Med Ctr, Dept Pediat, IL-84101 Beer Sheva, Israel. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Univ Newcastle Upon Tyne, Int Ctr Life, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Hannover Med Sch, Inst Mol Biol, Hannover, Germany. Univ Paris 05, Necker Hosp, Dept Pediat Nephrol, Paris, France. Univ Paris 05, Necker Hosp, INSERM, U574, Paris, France. CHU Tours, Chambray Les Tours, France. Inst Reg Sante, Chambray Les Tours, France. Univ Paris 05, Necker Hosp, Dept Genet, Paris, France. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Hildebrandt, F (reprint author), Univ Michigan, Dept Pediat, 8220C MSRB 3,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Schermer, Bernhard/E-9972-2014; OI Schermer, Bernhard/0000-0002-5194-9000; Otto, Edgar/0000-0002-2387-9973 FU NIDDK NIH HHS [R01 DK078209, R21 DK069604] NR 49 TC 369 Z9 383 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2003 VL 34 IS 4 BP 413 EP 420 DI 10.1038/ng1217 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 706TE UT WOS:000184470500019 PM 12872123 ER PT J AU Hrachovinova, I Cambien, B Hafezi-Moghadam, A Kappelmayer, J Camphausen, RT Widom, A Xia, LJ Kazazian, HH Schaub, RG McEver, RP Wagner, DD AF Hrachovinova, I Cambien, B Hafezi-Moghadam, A Kappelmayer, J Camphausen, RT Widom, A Xia, LJ Kazazian, HH Schaub, RG McEver, RP Wagner, DD TI Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A SO NATURE MEDICINE LA English DT Article ID TISSUE FACTOR; IN-VIVO; VENOUS THROMBOSIS; TYROSINE PHOSPHORYLATION; GLYCOPROTEIN LIGAND-1; SOLUBLE FORM; FACTOR-VIII; PLATELETS; EXPRESSION; LEUKOCYTES AB High plasma levels of soluble P-selectin are associated with thrombotic disorders and may predict future cardiovascular events. Mice with high levels of soluble P-selectin have more microparticles in their plasma than do normal mice. Here we show that chimeras of P-selectin and immunoglobulin (P-sel-Ig) induced formation of procoagulant microparticles in human blood through P-selectin glycoprotein ligand-1 (PSGL-1; encoded by the Psgl1 gene, officially known as Selpl). In addition, Psgl1(-/-) mice produced fewer microparticles after P-sel-Ig infusion and did not spontaneously increase their microparticle count in old age as do wild-type mice. Injected microparticles specifically bound to thrombi and thus could be involved in thrombin generation at sites of injury. Infusion of P-sel-Ig into hemophilia A mice produced a 20-fold increase over control immunoglobulin in microparticles containing tissue factor. This significantly improved the kinetics of fibrin formation in the hemophilia A mice and normalized their tail-bleeding time. P-sel-Ig treatment could become a new approach to sustained control of bleeding in hemophilia. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Oklahoma Med Res Fdn, Cardiovasc Biol Res Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Med Glycobiol, Dept Biochem & Mol Biol, Oklahoma City, OK 73104 USA. Wyeth Res, Cambridge, MA 02140 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU NHLBI NIH HHS [R01 HL053756, HL 54502, HL56949, P01 HL056949]; PHS HHS [53756] NR 45 TC 206 Z9 214 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2003 VL 9 IS 8 BP 1020 EP 1025 DI 10.1038/nm899 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 706ZL UT WOS:000184484900025 PM 12858167 ER PT J AU Greka, A Navarro, B Oancea, E Duggan, A Clapham, DE AF Greka, A Navarro, B Oancea, E Duggan, A Clapham, DE TI TRPC5 is a regulator of hippocampal neurite length and growth cone morphology SO NATURE NEUROSCIENCE LA English DT Article ID CALCIUM TRANSIENTS; CATION CHANNEL; FUNCTIONAL-CHARACTERIZATION; NEURONAL DIFFERENTIATION; SYNAPTIC VESICLE; STATHMIN FAMILY; NERVOUS-SYSTEM; PROTEIN; CORTACTIN; RECEPTOR AB Growth cone motility is regulated by both fast voltage-dependent Ca2+ channels and by unknown receptor-operated Ca2+ entry mechanisms. Transient receptor potential (TRP) homomeric TRPC5 ion channels are receptor-operated, Ca2+-permeable channels predominantly expressed in the brain. Here we show that TRPC5 is expressed in growth cones of young rat hippocampal neurons. Our results indicate that TRPC5 channel subunits interact with the growth cone-enriched protein stathmin 2, are packaged into vesicles and are carried to newly forming growth cones and synapses. Once in the growth cone, TRPC5 channels regulate neurite extension and growth-cone morphology. Dominant-negative TRPC5 expression allowed significantly longer neurites and filopodia to form. We conclude that TRPC5 channels are important components of the mechanism controlling neurite extension and growth cone morphology. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard MIT Div Hlth Sci & Technol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Clapham, DE (reprint author), Childrens Hosp, Howard Hughes Med Inst, Enders 1309,320 Longwood Ave, Boston, MA 02115 USA. NR 42 TC 232 Z9 247 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2003 VL 6 IS 8 BP 837 EP 845 DI 10.1038/nn1092 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 705UP UT WOS:000184413700013 PM 12858178 ER PT J AU Chin, L AF Chin, L TI The genetics of malignant melanoma: Lessons from mouse and man SO NATURE REVIEWS CANCER LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; MELANOCORTIN-1 RECEPTOR VARIANTS; PRIMARY CUTANEOUS MELANOMA; CELL-CYCLE ARREST; ULTRAVIOLET-RADIATION; GERMLINE MUTATIONS; RED HAIR; C-MET AB Therapeutic resistance and proclivity for metastasis are hallmarks of malignant melanoma. Genetic, epidemiological and genomic investigations are uncovering the spectrum of stereotypical mutations that are associated with melanoma and how these mutations relate to risk factors such as ultraviolet exposure. The ability to validate the pathogenetic relevance of these mutations in the mouse, coupled with advances in rational drug design, has generated optimism for the development of effective prevention programmes, diagnostic measures and targeted therapeutics in the near future. C1 Harvard Univ, Sch Med, Dept Dermatol, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. NR 163 TC 177 Z9 177 U1 3 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD AUG PY 2003 VL 3 IS 8 BP 559 EP 570 DI 10.1038/nrc1145 PG 12 WC Oncology SC Oncology GA 708EK UT WOS:000184554000012 PM 12894244 ER PT J AU Knight, EL Stampfer, MJ Rimm, EB Hankinson, SE Curhan, GC AF Knight, EL Stampfer, MJ Rimm, EB Hankinson, SE Curhan, GC TI Moderate alcohol intake and renal function decline in women: a prospective study SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE alcohol; creatinine clearance; glomerular filtration rate; renal function; renal insufficiency ID GLOMERULAR-FILTRATION RATE; CREATININE CLEARANCE; SERUM CREATININE; RISK; CONSUMPTION; DISEASE; PREDICTION AB Background. The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue. Methods. In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr). Results. Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a greater than or equal to25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a greater than or equal to25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day. Conclusions. Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period. C1 Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA 02115 USA. RP Knight, EL (reprint author), Channing Labs, Nurses Hlth Study, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA87969]; NHLBI NIH HHS [HL34594]; NIDDK NIH HHS [T32DK0740, DK52866, T32DK07791] NR 20 TC 35 Z9 37 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD AUG PY 2003 VL 18 IS 8 BP 1549 EP 1554 DI 10.1093/ndt/gfg228 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 707FN UT WOS:000184500000021 PM 12897093 ER PT J AU Lorenzl, S Albers, DS Relkin, N Ngyuen, T Hilgenberg, SL Chirichigno, J Cudkowicz, ME Beal, MF AF Lorenzl, S Albers, DS Relkin, N Ngyuen, T Hilgenberg, SL Chirichigno, J Cudkowicz, ME Beal, MF TI Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Alzheimer's disease; Parkinson's disease; matrix metalloproteinases; amyotrophic lateral sclerosis; tissue inhibitors of metalloproteinases ID AMYOTROPHIC-LATERAL-SCLEROSIS; AMYLOID PROTEIN-PRECURSOR; BLOOD-BRAIN-BARRIER; TISSUE INHIBITORS; GELATINASE-B; CEREBROSPINAL-FLUID; CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; MATRIX-METALLOPROTEINASE-9; MMP-9 AB Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) are elevated in postmortem brain tissue of AD patients. MMPs and TIMPs are found in neurons, microglia, vascular endothelial cells and leukocytes. The aim of this study was to determine whether circulating levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 are elevated in the plasma of AD patients. We compared AD patients to age- and gender-matched controls as well as to Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) patients. There was constitutive expression of gelatinase A (MMP-2), and gelatinase B (MMP-9), in all the samples as shown by zymographic analysis. Levels of MMP-9 were significantly (P = 0.003) elevated in the plasma of AD patients as compared to controls. Plasma levels of MMP-2, TIMP-1 and TIMP-2 were unchanged. There were no significant changes of MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in PD and ALS samples. TIMP-1 and TIMP-2 were significantly correlated with MMP-9 in the AD patients. ApoE genotyping of plasma samples showed that levels of MMP-2, TIMP-1 and TIMP-2 and MMP-9 were not significantly different between the ApoE subgroups. These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St,Room F-610, New York, NY 10021 USA. NR 34 TC 123 Z9 128 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD AUG PY 2003 VL 43 IS 3 BP 191 EP 196 DI 10.1016/S0197-0186(03)00004-4 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 679BD UT WOS:000182900400002 PM 12689599 ER PT J AU Simon, DK Friedman, J Breakefield, XO Jankovic, J Brin, MF Provias, J Bressman, SB Charness, ME Tarsy, D Johns, DR Tarnopolsky, MA AF Simon, DK Friedman, J Breakefield, XO Jankovic, J Brin, MF Provias, J Bressman, SB Charness, ME Tarsy, D Johns, DR Tarnopolsky, MA TI A heteroplasmic mitochondrial complex I gene mutation in adult-onset dystonia SO NEUROGENETICS LA English DT Article DE genetics; mitochondria; haplogroup; ND1 ID HEREDITARY OPTIC NEUROPATHY; NO PATHOGENIC MUTATIONS; 3-NITROPROPIONIC ACID; MULTIPLE-SCLEROSIS; DNA; DISORDERS; DEAFNESS; PLUS; EPIDEMIOLOGY; PARKINSONISM AB Mitochondrial DNA (mtDNA) mutations can cause rare forms of dystonia, but the role of mtDNA mutations in other types of dystonia is not well understood. We now report identification by sequencing, restriction endonuclease analyses, and clonal analyses of a heteroplasmic missense A to G base pair substitution at nucleotide position 3796 (A3796G) in the gene encoding the ND1 subunit of mitochondrial complex I in a patient with adult-onset dystonia, spasticity, and core-type myopathy. The mutation converts a highly conserved threonine to an alanine. The same mutation subsequently was identified in 2 of 74 additional unrelated adult-onset dystonia patients. A muscle biopsy was obtained from 1 of these 2 subjects and this revealed abnormalities of electron transport chain (ETC) activities. The mutation was absent in 64 subjects with early onset dystonia, 82 normal controls, and 65 subjects with Parkinson's disease or multiple system atrophy. The A3796G mutation previously has been reported in 3 of 226 subjects from mitochondrial haplogroup H. Each of the 3 subjects in our study harboring the A3796G mutation was also from haplogroup H. However, a subgroup analysis of haplogroup H subjects from our study indicates that the A3796G mutation is significantly overrepresented among haplogroup H adult-onset dystonia subjects compared with haplogroup H controls (P<0.01). This difference remains significant even after excluding the index patient (P=0.04). These data suggest that, among haplogroup H subjects, the presence of the A3796G mutation increases the risk of developing adult-onset dystonia. C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Allergan Pharmaceut Inc, Irvine, CA 92623 USA. McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. Beth Israel Deaconess Med Ctr, New York, NY USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Boston, MA 02215 USA. McMaster Univ, Hamilton, ON, Canada. RP Simon, DK (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Harvard Inst Med, Room 856,4 Blackfan Circle, Boston, MA 02115 USA. OI Charness, Michael/0000-0002-3301-8966 NR 42 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD AUG PY 2003 VL 4 IS 4 BP 199 EP 205 DI 10.1007/s10048-003-0150-3 PG 7 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 715QU UT WOS:000184984400007 PM 12756609 ER PT J AU Nieto-Castanon, A Ghosh, SS Tourville, JA Guenther, FH AF Nieto-Castanon, A Ghosh, SS Tourville, JA Guenther, FH TI Region of interest based analysis of functional imaging data SO NEUROIMAGE LA English DT Article DE fMRI; MRI; methods; region of interest; anatomical variability; multivariate analysis ID HUMAN NEOCORTEX; FMRI DATA; BRAIN; ABNORMALITIES; INFERENCE; PET AB fMRI analysis techniques are presented that test functional hypotheses at the region of interest (ROI) level. An SPM-compatible Matlab toolbox has been developed that allows the creation of subject-specific ROI masks based on anatomical markers and the testing of functional hypotheses on the regional response using multivariate time-series analysis techniques. The combined application of subject-specific ROI definition and region-level functional analysis is shown to appropriately compensate for intersubject anatomical variability, offering finer localization and increased sensitivity to task-related effects than standard techniques based on whole-brain normalization and voxel or cluster-level functional analysis, while providing a more direct link between discrete brain region hypotheses and the statistical analyses used to test them. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA 02129 USA. MIT, Res Lab Elect, Speech Commun Grp, Cambridge, MA 02139 USA. RP Nieto-Castanon, A (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. OI Ghosh, Satrajit/0000-0002-5312-6729 FU NIDCD NIH HHS [R29 DC 02852] NR 18 TC 92 Z9 94 U1 2 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2003 VL 19 IS 4 BP 1303 EP 1316 DI 10.1016/S1053-8119(03)00188-5 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 717GK UT WOS:000185079000004 PM 12948689 ER PT J AU Weber, AL AF Weber, AL TI Imaging of the mandible, maxilla, and pharynx - Preface SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2003 VL 13 IS 3 BP XIII EP XIV DI 10.1016/S1052-5149(03)00062-5 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600001 ER PT J AU Weber, AL Rahemtullah, A Ferry, JA AF Weber, AL Rahemtullah, A Ferry, JA TI Hodgkin and non-Hodgkin lymphoma of the head and neck: clinical, pathologic, and imaging evaluation SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY MALIGNANT-LYMPHOMA; PRIMARY THYROID LYMPHOMA; NERVOUS-SYSTEM LYMPHOMA; SKELETAL-MUSCLE LYMPHOMA; EXTRANODAL LYMPHOMAS; BURKITTS-LYMPHOMA; CANCER STATISTICS; PARANASAL SINUSES; ORAL CAVITY; DISEASE AB Lymphomas comprise a heterogeneous group of malignancies that can arise in different nodal and extranodal sites in the head and neck [1-7]. They constitute approximately 3% to 5% of all malignancies and are generally divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) [8-10]. Cervical lymph nodes can be involved by lymphomas of almost any type and are discussed in the section on nodal lymphomas. Among extranodal head and neck sites, the Waldeyer ring is the most common site of involvement, accounting for more than half of extranodal head and neck lymphomas reported in most series. This site is followed, in descending order of frequency, by the ocular adnexa (orbit, lacrimal gland, conjunctiva, and eyelids), the sinonasal area, salivary glands, oral cavity, and larynx. The thyroid gland and eye are other head and neck sites where lymphomas arise. Lymphomas are currently classified based on morphology, immunophenotype, genetic features, and clinical syndromes. Various schemes have been developed to classify lymphomas over the years, and the one currently in use by pathologists and hemato-oncologists is the World Health Organization (WHO) classification, which is based on the principles defined in the Revised European-American Classification of Lymphoid Neoplasms (REAL). Both the WHO and REAL classifications subdivide lymphomas primarily based on cell of origin: B-cell lymphomas, T-cell and natural killer- (NK-) cell lymphomas, and HL [9,11, 12]. HL is a lymphoma. that arises primarily in nodal sites and is discussed later. The remaining neoplasms are referred to as NHLs and comprise the subtypes summarized in Box 1. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 64 TC 58 Z9 65 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 AUG PY 2003 VL 13 IS 3 BP 371 EP + DI 10.1016/S1052-5149(03)00039-X PG 23 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600002 PM 14631680 ER PT J AU Caruso, PA Rincon, S Weber, AL AF Caruso, PA Rincon, S Weber, AL TI Lesions of the maxilla: crossroads of lthe head and neck SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID AUTOSOMAL RECESSIVE OSTEOPETROSIS; ODONTOGENIC KERATOCYST; SINUS ASPERGILLOSIS; FIBROUS DYSPLASIA; OROANTRAL FISTULA; NASOPALATINE CYST; PARANASAL SINUSES; NASAL POLYPS; CT; NEUROBLASTOMA AB The maxilla has an intimate relationship with various adjacent spaces of the head and neck. Because of its central location, lesions of the maxilla may involve the oral cavity, dentition, nasal cavity, masticator space, and orbit. Likewise, lesions originating within these spaces may involve the maxilla. Recognition of this relationship is important in the diagnosis and treatment of maxillofacial pathology. This article illustrates the role of the maxilla as a crossroad of pathology in the head and neck. C1 Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Caruso, PA (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 71 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2003 VL 13 IS 3 BP 411 EP + DI 10.1016/S1052-5149(03)00046-7 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600004 PM 14631682 ER PT J AU Weber, AL Romo, L Hashmi, S AF Weber, AL Romo, L Hashmi, S TI Malignant tumors of the oral cavity and oropharynx: clinical, pathologic, and radiologic evaluation SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID SQUAMOUS-CELL CARCINOMA; ADENOID CYSTIC CARCINOMA; POSITRON-EMISSION-TOMOGRAPHY; SALIVARY-GLAND TUMORS; PLEOMORPHIC ADENOMA; NECK TUMORS; MR FINDINGS; GD-DTPA; MUCOEPIDERMOID CARCINOMA; EPIDERMOID CARCINOMA AB Malignant tumors of the oral cavity and oropharynx represent squamous cell carcinomas in 90% of cases. These tumors affect different anatomic sites, and patients' prognosis is related to tumor location, locoregional extent, lymph node involvement in the neck, and distant metastases. CT, MR imaging, and positron emission tomography scanning are the most important diagnostic modalities used in assessing these clinical parameters. Furthermore, these imaging modalities constitute an integral part in the staging of these malignancies. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Atlanta Med Ctr, Atlanta, GA USA. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 111 TC 16 Z9 17 U1 3 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 AUG PY 2003 VL 13 IS 3 BP 443 EP + DI 10.1016/S1052-5149(03)00037-6 PG 23 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600006 PM 14631684 ER PT J AU Weber, AL Al Arayedh, S Rashid, A AF Weber, AL Al Arayedh, S Rashid, A TI Nasopharynx: clinical, pathologic, and radiologic assessment SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; RESONANCE-IMAGING FINDINGS; SKULL BASE EROSION; COMPUTED-TOMOGRAPHY; RETROPHARYNGEAL LYMPHADENOPATHY; MR CHARACTERISTICS; NERVE INVOLVEMENT; EXTRAMEDULLARY PLASMACYTOMA; CHOROID METASTASIS; DISTANT METASTASES AB Malignant tumors of the nasopharynx most commonly represent nonkeratinizing squamous cell carcinomas, of which the undifferentiated carcinoma is the most common type. The most prevalent clinical finding is a mass in the neck. Infiltrating tumors in the nasopharynx defy recognition clinically, including endoscopy For diagnosis and staging, CT and MR imaging are the most important imaging modalities. For recurrent nasopharyngeal cancer, MR imaging and positron emission tomography scanning are the preferred imaging modalities. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. Harvard Univ, Sch Publ Hlth, Atlanta Med Ctr, Atlanta, GA USA. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. NR 111 TC 14 Z9 18 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2003 VL 13 IS 3 BP 465 EP + DI 10.1016/S1052-5149(03)00041-8 PG 20 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600007 PM 14631685 ER PT J AU Yoshiura, K Weber, AL Runnels, S Scrivani, SJ AF Yoshiura, K Weber, AL Runnels, S Scrivani, SJ TI Cystic lesions of the mandible and maxilla SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CALCIFYING ODONTOGENIC CYST; ANEURYSMAL BONE-CYSTS; CEMENTO-OSSEOUS DYSPLASIA; COMPUTED-TOMOGRAPHY; KERATOCYSTS; JAWS; CT; AMELOBLASTOMAS; CLASSIFICATION; DIAGNOSIS AB Cystic lesions appearing in the maxilla and mandible are demonstrated with their typical radiographic features. This article presents radiographic techniques used for diagnosis. Cysts of the jaws are classified into two categories: odontogenic and nonodontogenic. Key characteristics to differentiate among these radiographic features are discussed. In addition, the article discusses the differentiation of jaw cysts from benign tumors that appear in the jaws. C1 Kyushu Univ, Fac Dent Sci, Dept Oral Radiol, Higashi Ku, Fukuoka 8128582, Japan. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Columbia Presbyterian Med Ctr, Div Oral & Maxillofacial Surg, New York, NY 10032 USA. Columbia Presbyterian Med Ctr, Ctr Oral Facial & Head Pain, New York, NY USA. RP Yoshiura, K (reprint author), Kyushu Univ, Fac Dent Sci, Dept Oral Radiol, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan. NR 38 TC 8 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2003 VL 13 IS 3 BP 485 EP + DI 10.1016/S1052-5149(03)00035-2 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600008 PM 14631686 ER PT J AU Weber, AL Bui, C Kaneda, T AF Weber, AL Bui, C Kaneda, T TI Malignant tumors of the mandible and maxilla SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PRIMARY INTRAOSSEOUS CARCINOMA; OSTEOGENIC-SARCOMA; MULTIPLE-MYELOMA; CHONDROMYXOID FIBROMA; MUCOEPIDERMOID CARCINOMA; AGGRESSIVE FIBROMATOSIS; AMELOBLASTIC CARCINOMA; RADIOLOGIC FEATURES; FACIAL BONES AB Malignant lesions of the mandible represent a diverse group of entities divided into lesions that originate within the mandible or affect the mandible secondarily. These lesions are investigated initially with conventional films, especially Panorex radiograph. For detailed assessment, including staging and before surgery or radiation therapy, CT and MR imaging are indicated. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Univ N Carolina, Dept Orthodont, Chapel Hill, NC 27599 USA. Nihon Univ, Sch Dent, Dept Radiol, Matsudo, Chiba 2718587, Japan. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 85 TC 9 Z9 9 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 AUG PY 2003 VL 13 IS 3 BP 509 EP + DI 10.1016/S1052-5149(03)00042-X PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600010 PM 14631688 ER PT J AU Caruso, PA Harris, GJ Padwa, BL AF Caruso, PA Harris, GJ Padwa, BL TI CT imaging of craniofacial malformations SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID TREACHER-COLLINS-SYNDROME; GROWTH-FACTOR RECEPTOR-2; CLEFT FACE SYNDROME; CROUZON-SYNDROME; APERT-SYNDROME; MANDIBULOFACIAL DYSOSTOSIS; HEMIFACIAL MICROSOMIA; ACROFACIAL DYSOSTOSIS; BIRTH PREVALENCE; SONIC HEDGEHOG AB Cross-sectional medical imaging techniques, including x-ray CT and MR imaging, frequently are employed in the evaluation of patients with craniofacial malformations. Because of its superior visualization of bone, CT is an important tool in the preoperative assessment and postoperative follow-up of patients with craniofacial deformities. This article explores the role of CT in the diagnosis and presurgical evaluation of craniofacial malformations. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Imaging Serv 3D, Boston, MA USA. Harvard Univ, Sch Dent Med, Childrens Hosp, Div Plast & Oral Surg, Boston, MA USA. RP Caruso, PA (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 147 TC 4 Z9 4 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 AUG PY 2003 VL 13 IS 3 BP 541 EP + DI 10.1016/S1052-5149(03)00061-3 PG 33 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600012 PM 14631690 ER PT J AU DaSilva, AFM Shaefer, J Keith, DA AF DaSilva, AFM Shaefer, J Keith, DA TI The temporomandibular joint: clinical and surgical, aspects SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID COMPUTED-TOMOGRAPHY; DIAGNOSTIC SUBGROUP; MANDIBULAR CONDYLE; DISC DISPLACEMENT; DISORDERS; POSITION; TMJ; MR; ARTHROGRAPHY; PAIN AB Temporomandibular joint (TMJ) disorders include different types of pathologic processes affecting each of the joint components: mandibular condyle, glenoid fossa, and articular disc. This article describes the various pathologies found in the TMJ and discusses the imaging techniques that provide additional information about these conditions. In addition, the article discusses the advantages and disadvantages of these techniques and demonstrates their application to the diagnosis and surgical treatment planning of temporomandibular disorders. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Keith, DA (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Wang 1201,55 Fruit St, Boston, MA 02114 USA. NR 38 TC 5 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD AUG PY 2003 VL 13 IS 3 BP 573 EP + DI 10.1016/S1052-5149(03)00043-1 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 714LK UT WOS:000184915600013 PM 14631691 ER PT J AU Ganis, G Thompson, WL Mast, FW Kosslyn, SM AF Ganis, G Thompson, WL Mast, FW Kosslyn, SM TI Visual imagery in cerebral visual dysfunction SO NEUROLOGIC CLINICS LA English DT Article ID MENTAL-IMAGERY; CORTICAL BLINDNESS; UNILATERAL NEGLECT; FORM AGNOSIA; MINDS EYE; GENERATION; LESIONS; NEUROPSYCHOLOGY; DISSOCIATION; PERCEPTION AB Many sorts of deficits in imagery follow brain damage, but the relation between the site of damage and the type, of deficit is not simple or straightforward. The dissociations in performance after brain damage provide hints regarding the processing system underlying imagery, but difficulties in interpretation urge caution in mapping these findings to theoretical models. Neuroimaging techniques, such as PET and fMRI, open a window into the working brain and offer valuable information not easily accessible through the study of patients who may have deficits beyond those observable and may rely on compensation and neural reorganization. As we come to understand the mental imagery system more fully, such issues as the laterality of image generation are likely to prove too coarse and vague. The brain is an enormously intricate organ, and even within a circumscribed domain such as imagery it seems to process information in complex and subtle ways. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Univ Zurich, Inst Psychol, CH-8006 Zurich, Switzerland. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ganis, G (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. RI Mast, Fred/B-5058-2013; OI Ganis, Giorgio/0000-0001-6175-2618 NR 63 TC 14 Z9 15 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD AUG PY 2003 VL 21 IS 3 BP 631 EP + AR PII S0733-8619(02)00097-X DI 10.1016/S0733-8619(02)00097-X PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 696GR UT WOS:000183879700004 PM 13677816 ER PT J AU Richtand, NM Welge, JA Levant, B Logue, AD Hayes, S Pritchard, LM Geracioti, TD Coolen, LM Berger, SP AF Richtand, NM Welge, JA Levant, B Logue, AD Hayes, S Pritchard, LM Geracioti, TD Coolen, LM Berger, SP TI Altered behavioral response to dopamine D(3) receptor agonists 7-OH-DPAT and PD 128907 following repetitive amphetamine administration SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE dopamine D3 receptor; behavioral sensitization; amphetamine; 7-OH-DPAT; PD 128907; locomotion ID VENTRAL TEGMENTAL AREA; HUMAN COCAINE FATALITIES; NUCLEUS-ACCUMBENS; RAT-BRAIN; LOCOMOTOR-ACTIVITY; MESSENGER-RNA; AUTORECEPTOR SUBSENSITIVITY; EXTRACELLULAR DOPAMINE; INDIVIDUAL-DIFFERENCES; ENVIRONMENTAL STIMULI AB Behavioral sensitization, the progressive and enduring enhancement of certain behaviors following repetitive drug use, is mediated in part by dopaminergic pathways. Increased locomotor response to drug treatment, a sensitizable behavior, is modulated by an opposing balance of dopamine receptor subtypes, with D1/D2 dopamine receptor stimulation increasing and D3 dopamine receptor activation inhibiting amphetamine-induced locomotion. We hypothesize that tolerance of D3 receptor locomotor inhibition contributes to behavioral sensitization. In order to test the hypothesis that expression of behavioral sensitization results in part from release of D3 receptor-mediated inhibition, thereby resulting in decreased response to D3 receptor agonists, we examined the effect of repetitive amphetamine administration on the behavioral response to the D3 receptor preferring agonists 7-OH-DPAT and PD 128907. D3-selective effects have recently been described for both drugs at a low dose. At 1 week following completion of a repetitive treatment regimen, amphetamine-pretreated rats displayed a decreased response to D3-selective doses of both 7-OH-DPAT and PD 128907, when compared to animals receiving saline pretreatment. Moreover, in addition to the quantitative alteration in response, there was a change in the inter-relation between response to amphetamine and D3 agonist. A highly significant inverse relation between locomotor inhibitory response to PD 128907 and the locomotor-stimulant response to amphetamine was observed prior to amphetamine treatment. In contrast, 10 days following repetitive amphetamine treatment, the relation between response to PD 128907 and amphetamine was not detected. The observed behavioral alteration could not be accounted for by changes in D3 receptor binding in ventral striatum. These findings suggest a persistent release of D3 receptor-mediated inhibitory influence contributes to the expression of behavioral sensitization to amphetamine. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Cincinnati Vet Affairs Med Ctr, Dept Psychiat 5116A, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Ctr Biostat Serv, Cincinnati, OH 45267 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH 45267 USA. Portland VA Med Ctr, Mental Hlth & Neurosci Div, Portland, OR 97201 USA. RP Richtand, NM (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 231 Albert Sabin Way,Ml0559, Cincinnati, OH 45267 USA. EM neil.richtand@uc.edu NR 81 TC 24 Z9 24 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2003 VL 28 IS 8 BP 1422 EP 1432 DI 10.1038/sj.npp.1300182 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 704DD UT WOS:000184321700004 PM 12700693 ER PT J AU Oslin, DW Berrettini, W Kranzler, HR Pettinati, H Gelernter, J Volpicelli, JR O'Brien, CP AF Oslin, DW Berrettini, W Kranzler, HR Pettinati, H Gelernter, J Volpicelli, JR O'Brien, CP TI A functional polymorphism of the mu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcoholism; naltrexone; genetics; treatment; pharmacology ID ADDICTION SEVERITY INDEX; PLACEBO-CONTROLLED TRIAL; SUBSTANCE DEPENDENCE; RELAPSE PREVENTION; BETA-ENDORPHIN; ABUSE; OPRM1; THERAPY; RISK; SENSITIVITY AB This study examined the association between two specific polymorphisms of the gene encoding the m-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A(+118)G (Asn40Asp) and C+17T (Ala6Val) SNPs in the gene encoding the m-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p = 0.044) and a longer time to return to heavy drinking (p = 0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p = 0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a m-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone. C1 Univ Penn, Dept Psychiat, Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, MIRECC, Philadelphia, PA USA. Univ Penn, Dept Psychiat, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Univ Connecticut, Sch Med, Dept Psychiat, Alcohol Res Ctr, Storrs, CT 06269 USA. VA Connecticut Healthcare Syst, Psychiat Serv, New Haven, CT USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. RP Oslin, DW (reprint author), Univ Penn, Dept Psychiat, Ctr Study Addict, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [RR 06192]; NIAAA NIH HHS [AA 03510, AA 07517, AA 11062, AA 11330, AA 13736]; NIDA NIH HHS [DA 001586, DA 11385, DA 14008]; NIMH NIH HHS [MH 01599] NR 50 TC 380 Z9 395 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2003 VL 28 IS 8 BP 1546 EP 1552 DI 10.1038/sj.npp.1300219 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 704DD UT WOS:000184321700019 PM 12813472 ER PT J AU Chiocca, EA AF Chiocca, EA TI Gene therapy: A primer for neurosurgeons SO NEUROSURGERY LA English DT Article DE cerebral ischemia; gene therapy; gliomas; Parkinson's disease; spinal fusion ID AMINO-ACID DECARBOXYLASE; EXPRESSING TYROSINE-HYDROXYLASE; ADENOASSOCIATED VIRUS VECTORS; NITRIC-OXIDE SYNTHASE; RAT PARKINSON MODEL; SEVERE COMBINED IMMUNODEFICIENCY; PROTECTS STRIATAL NEURONS; TYPE-1 THYMIDINE KINASE; FOCAL CEREBRAL-ISCHEMIA; MALIGNANT BRAIN-TUMORS AB GENE THERAPY INVOLVES the transfer of genes into cells with therapeutic intent. Although several methods can accomplish this, vectors based on viruses still provide the most efficient approach. For neurosurgical purposes, preclinical and clinical applications in the areas of glioma therapy, spinal neurosurgery, and neuroprotection for treatment of Parkinson's disease and cerebral ischemia are reviewed. In general, therapies applied in the neurosurgical realm have proven relatively safe, despite occasional, well-publicized cases of morbidity and death in non-neurosurgical trials. However, continued clinical and preclinical research in this area is critical, to fully elucidate potential toxicities and to generate truly effective treatments that can be applied in neurological diseases. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Neurosurg Serv, Brain Tumor Serv, Boston, MA 02114 USA. RP Chiocca, EA (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, Neurosurg Serv, Brain Tumor Serv, Cox 315, Boston, MA 02114 USA. NR 94 TC 14 Z9 15 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD AUG PY 2003 VL 53 IS 2 BP 364 EP 373 DI 10.1227/01.NEU.0000073532.05714.2B PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 707LY UT WOS:000184513200037 PM 12925253 ER PT J AU Winickoff, JP Pbert, L Klein, JD Lando, HA Carroll, BC Mermelstein, R Moolchan, ET Prokhorov, AV Ossip-Klein, D AF Winickoff, JP Pbert, L Klein, JD Lando, HA Carroll, BC Mermelstein, R Moolchan, ET Prokhorov, AV Ossip-Klein, D TI Youth tobacco control research and activities in the United States: The current national landscape SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID ADOLESCENT SMOKING; CIGARETTES AB This paper highlights the increasing level of collaboration, resource sharing, and consensus building in youth tobacco control taking place in the United States. Better knowledge of the current research, activities, and collaborations in this area will help in the planning of activities and the rational allocation of funds for tobacco control programs, research, advocacy, and counter-advertising initiatives. We defined three general classifications for organizations that had national youth tobacco control activities: Government centers and institutes, nongovernment organizations, and bridging organizations. We asked national experts in our own organization and at all other included organizations to suggest additional groups for inclusion. After gathering available public information on each organization from Web sites and printed materials, we then solicited additional information by personal communication with individuals in leadership positions for youth tobacco control within each group. We developed a uniform framework to present a clear picture of each group in the areas of institutional conception, general goals, youth tobacco control research, and youth tobacco control activities. We identified 16 organizations that met the selection criteria. This paper contains an overview of each institution and its youth tobacco control research and activities. The tables provide a helpful reference guide presenting the institutional conception, goals, funding for research, activities, and Web sites for the institutions and organizations discussed here. Many groups have current youth tobacco control priorities in the United States. This synthesis of current research, funding sources, programmatic activities, and collaborations in the United States will be a valuable resource for clinicians, tobacco control advocates, researchers, and program planners. C1 Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, Div Gen Pediat, MGH, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Div Prevent & Behav Med, Worcester, MA 01605 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Illinois, Hlth Res & Policy Ctr, Dept Psychol & Publ Hlth, Chicago, IL 60680 USA. NIDA, Teen Tobacco Addict Treatment Res Ctr, NIH, Baltimore, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp, Ctr Child & Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. NR 17 TC 3 Z9 3 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD AUG PY 2003 VL 5 IS 4 BP 435 EP 454 DI 10.1080/1462220031000118612 PG 20 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 718LM UT WOS:000185147700001 PM 12959780 ER PT J AU Prokhorov, AV Warneke, C de Moor, C Emmons, KM Jones, MM Rosenblum, C Hudmon, KS Gritz, ER AF Prokhorov, AV Warneke, C de Moor, C Emmons, KM Jones, MM Rosenblum, C Hudmon, KS Gritz, ER TI Self-reported health status, health vulnerability, and smoking behavior in college students: Implications for intervention SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID HIGH-SCHOOL-STUDENTS; CESSATION; PERCEPTIONS; SMOKERS AB Health-related factors, including prevalence of respiratory symptoms and perceived health status, were analyzed by smoking status and by stages of change for quitting to evaluate their potential use as motivators for tobacco cessation. Data were obtained from a survey of 1,283 Houston-area community college students. Respiratory symptoms were most frequent among current smokers and least frequent among never smokers. A higher prevalence of reported respiratory symptoms was associated with being in later stages of readiness to change. An "optimism bias" regarding smoking-related health was evident among smokers; over half of the current smokers believed that their health was better than the average same-age smoker's health, and 19% believed that their health was better than that of the same-age nonsmoker. Furthermore, virtually all of the smokers perceived that their health was either not at all or only slightly affected by smoking, and almost half of smokers thought that quitting would bring either no benefit or only minor benefit to their health. Of the smokers, 45% believed that continuing to smoke would have only minor or no impact on their health. Differences in perceived health vulnerability were observed across the various stages of readiness to quit; precontemplators reported the lowest perceptions of health vulnerability related to smoking, and those in the preparation stage reported the highest perceptions of vulnerability. Smoking cessation counselors should consider measuring and demonstrating the early tobacco-attributable health problems to young smokers to possibly enhance motivation to quit. C1 Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Prokhorov, AV (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, 1515 Holcombe Blvd,Box 243, Houston, TX 77030 USA. FU NCI NIH HHS [R01 CA69425-01A1] NR 20 TC 39 Z9 42 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD AUG PY 2003 VL 5 IS 4 BP 545 EP 552 DI 10.1080/1462220031000118649 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 718LM UT WOS:000185147700011 PM 12959792 ER PT J AU Saxon, AJ Baer, JS Davis, TM Sloan, KL Malte, CA Fitzgibbons, K Kivlahan, DR AF Saxon, AJ Baer, JS Davis, TM Sloan, KL Malte, CA Fitzgibbons, K Kivlahan, DR TI Smoking cessation treatment among dually diagnosed individuals: Preliminary evaluation of different pharmacotherapies SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NICOTINE DEPENDENCE TREATMENT; SUSTAINED-RELEASE BUPROPION; PSYCHIATRIC-DISORDERS; REPLACEMENT THERAPY; INTERVENTION TRIAL; CIGARETTE-SMOKING; UNITED-STATES; DRUG-ABUSE; ALCOHOL; TOBACCO AB This descriptive, observational pilot study evaluated a smoking cessation intervention using open-label bupropion and nicotine replacement within an addiction treatment center for patients with high rates of comorbid psychiatric diagnoses. Participants were 115 veterans receiving substance abuse treatment at a Veterans Administration outpatient program who voluntarily sought smoking cessation treatment. Three fourths of participants had a psychiatric diagnosis in addition to substance dependence (i.e., dual diagnosis). The intervention consisted of a weekly smoking cessation therapy group and pharmacotherapy as determined by participant and clinician preference (none, nicotine replacement only, bupropion only, or combined nicotine and bupropion). A total of 47 participants (40.9%) completed four group smoking cessation sessions, and 17 (14.8%) completed eight sessions. Of these participants, 27 (23.5%) had breath carbon monoxide (CO) levels <9ppm (indicating short-term abstinence) at session 4, and nine (7.8%) had CO levels <9 ppm at session 8. Participants who received nicotine replacement alone or with bupropion attended more sessions than did subjects who did not receive nicotine replacement. Participants receiving combined medications had greater reductions in CO levels at session 4 than did the other participants. There was no evidence of increased use of other substances during smoking cessation treatment. These findings indicate that many dually diagnosed individuals are willing to attempt smoking cessation with appropriate pharmacotherapy and achieve reductions in CO measures, but only minimal success was observed with respect to cessation. Additional research is needed to assess medication effects in randomized trials, to explore effects of more intensive treatments, and to assess possible harm reduction from smoking interventions within this population. C1 Univ Washington, Ctr Excellence Subst Abuse Treatment & Educ, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Saxon, AJ (reprint author), VA Med Ctr, S-116-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 38 TC 16 Z9 18 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD AUG PY 2003 VL 5 IS 4 BP 589 EP 596 DI 10.1080/1462220031000118702 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 718LM UT WOS:000185147700017 PM 12959797 ER PT J AU Tritos, NA Mun, E Bertkau, A Grayson, R Maratos-Flier, E Goldfine, A AF Tritos, NA Mun, E Bertkau, A Grayson, R Maratos-Flier, E Goldfine, A TI Serum ghrelin levels in response to glucose load in obese subjects post-gastric bypass surgery SO OBESITY RESEARCH LA English DT Article DE gastric bypass surgery; ghrelin ID GROWTH-HORMONE SECRETAGOGUE; WEIGHT-LOSS; DIAGNOSTIC-CRITERIA; CIRCULATING GHRELIN; OREXIGENIC PEPTIDE; FOOD-INTAKE; STOMACH; SECRETION; RECEPTOR; HUMANS AB Objective: We sought to elucidate further the mechanisms leading to weight loss after gastric bypass (GBP) surgery in morbidly obese individuals. Ghrelin is a gastroenteric appetite-stimulating peptide hormone, fasting levels of which decrease with increasing adiposity and increase with diet-induced weight loss. In addition, ghrelin levels rapidly decline postprandially. Research Methods and Procedures: We measured serum ghrelin responses to a 75-g oral glucose tolerance test (OGTT) in 6 subjects who had undergone GBP surgery 1.5 +/- 0.7 years before-testing and compared these responses with 6 obese subjects about to undergo GBP surgery, 6 obese nonsurgical subjects (matched for BMI to the post-GBP surgical group), and 5 lean subjects. Results: Despite weight loss induced by the GBP surgery, fasting serum ghrelin levels were significantly lower in the post-GBP surgery group than in the lean subject (by 57%) or pre-GBP surgery (by 45%) group. Serum ghrelin levels during the OGTT were significantly lower in postoperative than in lean, obese pre-GBP surgical, or obese nonsurgical subjects. The magnitude of the decline in serum ghrelin levels between 0 and 120 minutes post-OGTT was significantly smaller in postoperative (by 62%), obese pre-GBP surgical (by 80%), or obese nonsurgical (by 69%) subjects in comparison with lean subjects. Discussion: Serum ghrelin levels in response to OGTT are lower in subjects post-GBP surgery than, in either lean or obese subjects. Tonically low serum ghrelin levels may be involved in the mechanisms inducing sustained weight loss after GBP surgery. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goldfine, A (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [M01 RR 01032]; NIDDK NIH HHS [DK 53978, DK 56113, DK 56116, K23 DK 02795] NR 31 TC 76 Z9 77 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD AUG PY 2003 VL 11 IS 8 BP 919 EP 924 DI 10.1038/oby.2003.126 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 711QR UT WOS:000184753000001 PM 12917494 ER PT J AU Pian, D Ferrucci, S Anderson, SF Wu, C AF Pian, D Ferrucci, S Anderson, SF Wu, C TI Paramacular coloboma SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE albinitic nevus; coloboma; congenital; embryology; macula; paramacular coloboma; torpedo maculopathy ID RETINAL-PIGMENT EPITHELIUM; EYE DEVELOPMENT; HUMAN FOVEA; MACULOPATHY AB Background. Paramacular coloboma (plural: colobomata) is a solitary oval football or torpedo-shaped chorioretinal lesion located temporal to the fovea in one or both eyes. Previous case reports have speculated varying etiology, but few have justified its pathognomonic shape and location. We believe it to be congenital in nature and caused by incomplete differentiation of the arcuate bundles along the horizontal raphe in development of the macular architecture. Associated ocular findings may include blepharophimosis, situs inversus, or other anomalous retinal vascular patterns. Case Reports. Three cases of asymptomatic unilateral paramacular colobomata are presented. In each case, a single oval chorioretinal lesion temporal to the macula was found during routine examination. Visual acuity and Humphrey threshold visual field testing were normal with no other associated congenital, systemic, or ocular abnormalities. Because the lesion is nonprogressive, these patients can be followed on an annual basis. Conclusion. Due to their anatomical origin, paramacular colobomata are always located temporal to the macula and have an oval football-shaped appearance. Visual acuity and visual field testing are usually normal, although highly observant patients may be aware of a mild scotoma. Differential diagnosis is important because the clinical appearance can be similar to acquired conditions, most notably age-related macular degeneration and presumed ocular histoplasmosis syndrome. C1 Sepulveda VA Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA. Santa Barbara Community Based Outpatient Clin, VA Greater Los Angeles Healthcare Syst, Santa Barbara, CA USA. Nursing Home, Sepulveda, CA USA. So Calif Coll Optometry, Fullerton, CA USA. Baltimore VA Med Ctr, VA Maryland Healthcare Syst, Baltimore, MD USA. SUNY Coll Optometry, New York, NY 10010 USA. Kaiser Permanente, Thousand Oaks, CA USA. RP Ferrucci, S (reprint author), Sepulveda VA Ambulatory Care Ctr, VA Greater Los Angeles Healthcare Syst, 16111 Plummer St,112E, Sepulveda, CA 91343 USA. NR 40 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD AUG PY 2003 VL 80 IS 8 BP 556 EP 563 DI 10.1097/00006324-200308000-00008 PG 8 WC Ophthalmology SC Ophthalmology GA 714CA UT WOS:000184893700003 PM 12917574 ER PT J AU Kesavalu, L Holt, SC Ebersole, JL AF Kesavalu, L Holt, SC Ebersole, JL TI In vitro environmental regulation of Porphyromonas gingivalis growth and virulence SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Porphyromonas gingivalis; hemin; iron; growth; virulence ID MICROBIAL IRON TRANSPORT; OUTER-MEMBRANE PROTEINS; MURINE LESION MODEL; BACTEROIDES-GINGIVALIS; HEMIN-BINDING; COORDINATE REGULATION; PERIODONTAL-DISEASE; BACTERIAL VIRULENCE; HEMOLYTIC-ACTIVITY; PROTOPORPHYRIN-IX AB Porphyromonas gingivalis appears to be a major contributor to periodontal disease, especially soft tissue destruction, which is reflected by the ability to cause invasive, spreading lesions, and tissue inflammation in a murine abscess model. This study investigated the role of hemin on the regulation of growth and virulence of P. gingivalis strains. P. gingivalis strains W50, A7A1-28, 3079, 381, W50/BEI, and NG4B19 were grown in broth and on blood agar plates. P. gingivalis cells grown under iron-depleted conditions for multiple passages showed significantly decreased lesion size in mice, in contrast to cells grown under iron-normal (5 mug/ml) and iron-elevated conditions. Statistically significant (P < 0.01) decreases in gingipain enzyme activity were found among the strains grown under iron-depleted conditions. P. gingivalis grown in the presence of blood induced significantly different lesion type, lesion size, lesion onset, and mortality. Elevated hemin resulted in increased cell-associated iron in P. gingivalis , which increased the capacity of the microorganism to survive at times of iron deprivation. These results indicate that hemin or iron availability regulates multiple aspects related to P. gingivalis virulence, including growth, survival, gingipain levels, and iron accumulation. C1 Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY 40536 USA. Forsyth Inst, Boston, MA USA. RP Kesavalu, L (reprint author), Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, 159 HSRB, Lexington, KY 40536 USA. FU NIDCR NIH HHS [DE-11368] NR 57 TC 26 Z9 28 U1 3 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD AUG PY 2003 VL 18 IS 4 BP 226 EP 233 DI 10.1034/j.1399-302X.2003.00071.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 694VE UT WOS:000183795200005 PM 12823798 ER PT J AU Smith, DJ Lam, A Barnes, LA King, WF Peacock, Z Wise, DL Trantolo, DJ Taubman, MA AF Smith, DJ Lam, A Barnes, LA King, WF Peacock, Z Wise, DL Trantolo, DJ Taubman, MA TI Remote glucosyltransferase-microparticle vaccine delivery induces protective immunity in the oral cavity SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE GTF; IGA; rectal; dental caries ID STREPTOCOCCUS-MUTANS ANTIGEN; BACTERIAL PROTEIN ANTIGEN; SALMONELLA-TYPHI TY21A; TOXIN-B-SUBUNIT; CHOLERA-TOXIN; INTRANASAL IMMUNIZATION; IMMUNOGLOBULIN-A; SOBRINUS GLUCOSYLTRANSFERASE; PARENTERAL IMMUNIZATION; RECTAL IMMUNIZATIONS AB Intranasally administered dental caries vaccines show significant promise for human application. Alternate mucosal routes may be required, however, to induce caries-protective salivary IgA antibody in children with respiratory diseases. Since rectal mucosa contains inductive lymphoid tissue, we hypothesized that the rectal route could be used to induce salivary immunity to mutans streptococcal glucosyltransferase (GTF), resulting in protective immunity to experimental dental caries. We first explored the ability of glucosyltransferase, incorporated into polylactide-co-glycolide (PLGA) microparticles (MP), and administered rectally together with mucosal adjuvant, to induce a salivary IgA antibody response. Groups of Sprague-Dawley rats (6/group) were immunized rectally on days 0, 7, 14 and 21 with a) GTF-MP alone, b) GTF-MP with cholera toxin, c) GTF-MP with detoxified mutant Escherichia coli toxin (dLT), or d) sham immunized with PLGA and cholera toxin. An additional group was immunized intranasally with GTF-MP alone. Saliva and nasal washes of all intranasally immunized rats contained IgA antibody to glucosyltransferase on day 28. Salivary IgA antibody was also detected in 7/12 rats rectally immunized with GTF-MP and cholera toxin or dLT, although responses were lower than those obtained by intranasal immunization. Most fecal extracts from rectally delivered GTF-MP plus cholera toxin or dLT rats contained IgA antibody to GTF-MP. Low levels of fecal IgA antibody were detected in 3/6 intranasally immunized rats and 2/6 rats rectally immunized with GTF-MP alone. We then examined the extent to which salivary IgA antibody induced by the rectal route could be protective. At 25, 31 and 38 days of age, two groups of female Sprague-Dawley rats (13/group) were rectally immunized with GTF-MP and cholera toxin or with empty microparticles and cholera toxin (sham group). A third group was intranasally immunized with GTF-MP alone. After demonstrating salivary IgA responses to GTF in most GTF-immunized rats, all animals were infected with streptomycin-resistant Streptococcus sobrinus and placed on diet 2000. After 79 days of infection, total caries on molar surfaces were lower in both rectally (7.9 +/- 1.0) and intranasally (7.1 +/- 0.9; P < 0.0.03) immunized groups compared with the sham-immunized group (11.9 +/- 1.6). Smooth surface caries were significantly lower (P < 0.05) in both rectally and intranasally immunized groups. These results support the interconnectedness of the mucosal immune system and indicate that rectal immunization with GTF-MP, together with adjuvant, or intranasal immunization with GTF-MP alone, can induce protective levels of salivary antibody in rats. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Cambridge Sci Inc, Cambridge, MA USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04733, DE-12434, DE-06153] NR 42 TC 8 Z9 9 U1 1 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD AUG PY 2003 VL 18 IS 4 BP 240 EP 248 DI 10.1034/j.1399-302X.2003.00074.x PG 9 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 694VE UT WOS:000183795200007 PM 12823800 ER PT J AU Chang, C Lauffenburger, DA Morales, TI AF Chang, C Lauffenburger, DA Morales, TI TI Motile chondrocytes from newborn calf: migration properties and synthesis of collagen II SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE chondrocytes; cell migration; fibronectin; insulin-like growth factor-I ID SMOOTH-MUSCLE ACTIN; GROWTH-FACTOR REGULATION; ARTICULAR-CARTILAGE; CELL-MIGRATION; PROTEOGLYCAN SYNTHESIS; RETINOIC ACID; NITRIC-OXIDE; IN-VITRO; FIBRONECTIN; ADHESION AB Objective: To determine whether differentiated chondrocytes are motile. Design: Calf articular chondrocytes isolated from six animals were cultured in spinner flasks and removed on days 3 and 7. Boyden chamber assays and time-lapse videornicroscopy were performed to monitor and quantify cell migration. A novel method for selectively harvesting and metabolically labeling the migrated cells was developed, based on cell movement to the underside of the Boyden chamber membranes. The 3 H-collagen synthesized by these cells was purified and analyzed by SDS-PAGE and autoradiography either before or after cyanogen bromide cleavage. Results: In Boyden chambers, locomotion of day 3 chondrocytes on fibronectin-coated membranes was similar to3-fold higher than on bovine serum albumin-coated controls (39+/-15 vs 12+/-8 cells/mm(2), respectively (P=0.005)). Insulin-like growth factor-1 (IGF-1, 10 ng/ml) was chemotactic, increasing motility to 87 +/- 16 cells/mm(-) (difference from fibronectin alone: P=0.0003). A similar response was observed for day 7 cells, but IGF-1 activation was not as pronounced (P=0.055). The collagen patterns produced by the migrated cells closely resembled those of standard collagen type II, without any evidence of collagen 1 production. In videotracking experiments, motile cells attached on fibronectin exhibited typical lamellipodia and filopodia, and -30% of attached cells were motile (speed >1 mum/h and directional persistence >1 h). Typical cell path lengths were 3G-50 pm, substantially greater than a full cell length displacement. Conclusion: A population of well-differentiated chondrocytes capable of matrix (COL II) synthesis are motile in vitro. This original finding opens new avenues to study the potential of motile cells for cartilage repair. (C) 2003 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. MIT, Div Biol Engn, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Jackson 1223,55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR 47000] NR 47 TC 50 Z9 50 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD AUG PY 2003 VL 11 IS 8 BP 603 EP 612 DI 10.1016/S1063-4584(03)00087-6 PG 10 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 707ZC UT WOS:000184539000007 PM 12880583 ER PT J AU Nayak, LM Deschler, DG AF Nayak, LM Deschler, DG TI Lymphomas SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID NON-HODGKINS-LYMPHOMA; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; CHRONIC LYMPHOCYTIC-LEUKEMIA; MALIGNANT-LYMPHOMAS; PROGNOSTIC FACTORS; BURKITTS-LYMPHOMA; SALIVARY-GLANDS; EXTRANODAL HEAD; NATURAL-HISTORY; NECK AB Lymphomas are the most common nonepithelial tumors of the head and neck [1], and otolaryngologists are frequently involved in their diagnosis. Lymphomas represent an important cause of morbidity and mortality in the United States, with an estimated new-case incidence of 60,900 (31,900 men, 29,000 women) for 2002. Estimated lymphoma-related deaths for 2002 are 25,800 (13,500 men, 12,300 women) [2]. This article reviews the presentation, diagnosis, staging, and treatment of non-Hodgkin's and Hodgkin's lymphomas. Chronic lymphocytic leukemia and posttransplant lymphoproliferative disorder, both closely related to lymphoma, are also discussed. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 86 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2003 VL 36 IS 4 BP 625 EP + DI 10.1016/S0030-6665(03)00033-1 PG 23 WC Otorhinolaryngology SC Otorhinolaryngology GA 702DH UT WOS:000184209600007 PM 14567057 ER PT J AU Gubbels, SP Barkhuizen, A Hwang, PH AF Gubbels, SP Barkhuizen, A Hwang, PH TI Head and neck manifestations of Wegener's granulomatosis SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODY; QUALITY-OF-LIFE; SUBGLOTTIC STENOSIS; CYCLOPHOSPHAMIDE THERAPY; OTOLOGIC MANIFESTATIONS; SYSTEMIC VASCULITIS; DISEASE-ACTIVITY; EAR; METHOTREXATE; INVOLVEMENT AB Although Wegener's granulomatosis classically affects the kidneys, lungs, and respiratory tract, head and neck manifestations are common. A broad range of head and neck manifestations has been reported in this patient population. The otolaryngologist plays an important role in the diagnosis and management of Wegener's granulomatosis. This article reviews the multiple head and neck manifestations that have been reported in patients with Wegener's granulomatosis. The diagnostic work up and therapeutic approach to the patient with Wegener's granulomatosis, both medical and surgical, are also discussed. C1 Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Arthrit & Rheumat Dis, Portland, OR 97239 USA. Portland VA Med Ctr, Rheumatol Sect, Portland, OR 97239 USA. RP Hwang, PH (reprint author), Oregon Hlth & Sci Univ, Dept Otolaryngol Head & Neck Surg, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 88 TC 34 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 2003 VL 36 IS 4 BP 685 EP + DI 10.1016/S0030-665(03)00023-9 PG 22 WC Otorhinolaryngology SC Otorhinolaryngology GA 702DH UT WOS:000184209600010 PM 14567060 ER PT J AU Lu, L Baldeon, ME Savidge, T Pothoulakis, C Walker, WA AF Lu, L Baldeon, ME Savidge, T Pothoulakis, C Walker, WA TI Development of microbial-human Enterocyte interaction: Cholera toxin SO PEDIATRIC RESEARCH LA English DT Article ID RAT SMALL-INTESTINE; CYCLIC ADENOSINE-MONOPHOSPHATE; ADENYLATE-CYCLASE; INCREASED SENSITIVITY; DIARRHEAL DISEASE; FLUID SECRETION; INVOLVEMENT; TRANSPORT; MODEL AB Diarrhea in infants and children is a major health hazard worldwide. Certain toxigenic diarrheas occur more commonly and are manifested more severely during the neonatal period. We have previously studied the regulation of cholera toxin-induced secretion in animal models during development. In those studies we have shown that cholera toxin stimulates a much greater secretion by immature compared with mature small intestine, and the mechanism appears to be an up-regulation of postreceptor signal transduction molecules (adenyl cyclase and G(salpha)) leading to an elevated cAMP level. In this study, using experimental models of human intestinal development (fetal cell lines, a micro-Ussing chamber, organ cultures, and fetal intestinal xenograft transplants), we provide preliminary evidence that cholera toxin induces an enhanced secretion mediated in part by a developmental up-regulation of the cAMP response in immature versus mature human small intestine. Additional studies are needed, however, to further define whether other developmental events (e.g. receptor expression) also regulate cholera toxin-enterocyte-enhanced interaction. Nonetheless, this approach to determining the role of development in the pathophysiology of cholera in infants may help in strategies to prevent and treat this condition and other age-related intestinal infectious diseases. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02129 USA. Univ San Francisco Quito, Programa Alimentos & Nutr, Circulo Cumbaya, Quito, Ecuador. RP Walker, WA (reprint author), Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, 114 16th St 114-3503, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01-HD31852, R37-HD12437]; NIDDK NIH HHS [P01-DK33506, T32-DK07477, P30-DK40561] NR 31 TC 9 Z9 9 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD AUG PY 2003 VL 54 IS 2 BP 212 EP 218 DI 10.1203/01.PDR.0000074974.21797.83 PG 7 WC Pediatrics SC Pediatrics GA 705RC UT WOS:000184407700011 PM 12736381 ER PT J AU Wagner, CA Lukewille, U Valles, P Breton, S Brown, D Giebisch, GH Geibel, JP AF Wagner, CA Lukewille, U Valles, P Breton, S Brown, D Giebisch, GH Geibel, JP TI A rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE mouse kidney; isolated renal tubules; pH measurement; vacuolar H+-ATPase; collecting duct ID VACUOLAR H+-ATPASE; PROXIMAL CONVOLUTED TUBULE; CORTICAL COLLECTING DUCT; RENAL INTERCALATED CELLS; RAT-KIDNEY; INTRACELLULAR PH; EPITHELIAL-CELLS; TRANSGENIC MICE; EXPRESSION; SUSPENSION AB The increasing number of available genetically manipulated mice makes it necessary to develop tools and techniques for examining the phenotypes of these animals. We have developed a straightforward and rapid method for the isolation of large quantities of single tubule fragments from the mouse kidney. Immunohistochemistry, electron microscopy, and fluorescence microscopy were used to evaluate the viability, functional characteristics, and morphology of proximal tubules (PT), and collecting ducts from cortex (CCD) and inner stripe of the outer medulla (ISOMCD). Tubules were isolated using a modified collagenase digestion technique, and selected under light microscopy for experimentation. Electron microscopy and trypan blue exclusion showed that a large portion of unselected proximal tubules were damaged by the digestion procedure. The selected tubules, however, all excluded trypan blue, indicating that the plasma membrane had remained intact. Immunocytochemistry on isolated CCD showed normal distribution of H+-ATPase, pendrin, and anion exchanger-1 (AE-1) staining. The pH-sensitive dye 2',7'-bis(2-carboxylethyl)-5(6)-carboxyfluorescein (BCECF) was used to measure Na+-dependent and -independent intracellular pH (pH(i)) recovery rates in PT, and in single intercalated cells of CCD and ISOMCD fragments. Na+-dependent pH(i)-recovery was 0.144+/-0.008 (PT), 0.182+/-0.013 (CCD), and 0.112+/-0.010 pH units/min. (ISOMCD). Na+-independent pH(i) recovery was found in all three segments (PT: 0.021+/-0.002, CCD: 0.037+/-0.002, ISOMCD: 0.033+/-0.002 pH units/min) and was sensitive to concanamycin. In summary, we have developed a new technique for rapid and straightforward preparation of large quantities of defined tubule fragments from mouse kidney. Using this technique, the first measurements of plasma membrane vacuolar H+-ATPase activities in mouse PT and collecting duct were made. This technique will facilitate further characterization of kidney function in normal and genetically manipulated animals. C1 Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Univ Nacl Cuyo, Fac Med, Catedra Fisiopatol, RA-5500 Mendoza, Argentina. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. RP Wagner, CA (reprint author), Univ Zurich, Inst Physiol, Winterthurerstr 190, CH-8057 Zurich, Switzerland. EM Wagnerca@access.unizh.ch FU NIDDK NIH HHS [DK 17433, DK 32573, DK 38452, DK 42956, DK 43351, DK 50230, DK 57521] NR 55 TC 28 Z9 28 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 EI 1432-2013 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD AUG PY 2003 VL 446 IS 5 BP 623 EP 632 DI 10.1007/s00424-003-1082-3 PG 10 WC Physiology SC Physiology GA 711VQ UT WOS:000184762100017 PM 12748863 ER PT J AU Gillies, R Moyal, D Forestier, S Kollias, N AF Gillies, R Moyal, D Forestier, S Kollias, N TI Non-invasive in vivo determination of UVA efficacy of sunscreens using diffuse reflectance spectroscopy SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE assessment; avobenzone; efficacy; in-vivo; oxybenzone; sunscreen; UVA ID PIGMENT DARKENING PPD; PROTECTION FACTORS; ANIMAL-MODEL; MOUSE MODEL; HUMAN-SKIN; RADIATION; SPECTRUM; PHOTOPROTECTION; EXPOSURE; INVIVO AB Background: Evaluation of sunscreen efficacy is most relevant when measured on the surface it is meant to protect, namely on human skin in vivo . Application of any material to the surface of the skin alters its optical properties. Diffuse reflectance spectroscopy (DRS) is a non-invasive technique to measure changes in the optical properties of the skin decoupled from its biological responses following sunscreen application. Methods: This study compared measurements of UVA efficacy of oxybenzone and avobenzone at different concentrations (0-5%) using DRS, human phototest and an in vitro technique. Twenty subjects were enrolled for each product measured by DRS and 10 different subjects were enrolled for each product measured by human phototest. Six areas 5 cm x 10 cm were outlined on each subject's back. DRS measurements were performed on four subsites within each area before and 20 min after sunscreen application. UVA efficacy for each concentration of product was calculated from the measured transmission spectrum of a given product convoluted with the spectrum of a Xenon light source adequately filtered to obtain the UVA spectrum from 320 to 400 nm and the erythema action spectrum. Phototesting was performed using the same light source and persistent pigment darkening as the biological endpoint. Measurements were made with sunscreen coverage of 2 mg/cm(2) . In vitro measurements were performed using an Optometrics instrument. Results: All three techniques showed a linear response between calculated UVA efficacy and product concentration. Conclusions: This study showed that DRS is a rapid and reproducible method to calculate UVA efficacy of sunscreen materials and that its results correlate closely with those obtained by human phototesting. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. LOreal Rech, Clichy, France. RP Kollias, N (reprint author), Johnson & Johnson Consumer Prod Worldwide, 199 Grandview Rd, Skillman, NJ 08558 USA. NR 26 TC 9 Z9 11 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD AUG PY 2003 VL 19 IS 4 BP 190 EP 194 DI 10.1046/j.0905-4383.2003.00022.x PG 5 WC Dermatology SC Dermatology GA 708NR UT WOS:000184575000005 PM 12925190 ER PT J AU Grikscheit, TC AF Grikscheit, TC TI Tissue engineering of the gastrointestinal tract for surgical replacement: a nutrition tool of the future? SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT Symposium on Intestinal Failure CY SEP 04, 2002 CL GLASGOW, SCOTLAND DE tissue engineering; gastrointestinal tract replacement; animal models ID HEPATOCELLULAR TRANSPLANTATION; ESOPHAGEAL SUBSTITUTE; SMALL-INTESTINE; GENE-THERAPY; SMALL-BOWEL; SHORT-GUT; LIVER; COLON; INTERPOSITION; FAILURE AB Optimal nutrition depends on the multiple complex functions performed by the gastrointestinal tract, which range from basic functions such as storage, conduit and mechanical processing to more finely regulated capabilities such as vectorial transport, immune defence and cell signalling. Surgical strategies to supply lacking gastrointestinal tract tissues have relied on either replacement by proxy (surgical substitution) or the introduction of prostheses. Tissue engineering seeks to replace missing tissues with engineered tissues that more accurately reproduce the native physiological and anatomical milieu. It is now possible to engineer several areas of the gastrointestinal tract with high fidelity, and to employ tissue-engineered bowel in replacement in animal models. These replacement models have reflected excellent anatomical and physiological recapitulation of native bowel by the tissue-engineered constructs in vivo. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grikscheit, TC (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 47 TC 6 Z9 6 U1 0 U2 2 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD AUG PY 2003 VL 62 IS 3 BP 739 EP 743 DI 10.1079/PNS2003289 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 724KV UT WOS:000185487500019 PM 14692609 ER PT J AU Molinari, V Karel, M Jones, S Zeiss, A Cooley, SG Wray, L Brown, E Gallagher-Thompson, D AF Molinari, V Karel, M Jones, S Zeiss, A Cooley, SG Wray, L Brown, E Gallagher-Thompson, D TI Recommendations about the knowledge and skills required of psychologists working with older adults SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID MENTAL-HEALTH AB This article is an initial attempt to furnish recommendations for the skills and knowledge psychologists need to work competently with older adults. We use two levels of competence across seven broad areas that are most relevant for professional practice. The first competence level is that required of general psychologists who provide some professional services to older adults; the second level is that needed by more specialized experts in the field for practice and training. This article is not fashioned as a "how to" document and is not intended to disenfranchise anyone. Recommendations are proposed that delineate the types of competence needed for specific geropsychology activities that are relevant to a variety of settings providing mental health services to older adults. C1 Vet Affairs Boston Healthcare Syst, Boston, MA USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Perry Point Vet Affairs Med Ctr, Perry Point, MD USA. Vet Affairs Palo Alto Hlth Care Syst, Psychol Serv, Palo Alto, CA USA. Dept Vet Affairs, Geriatr & Extended Care Strateg Healthcare Grp, Washington, DC USA. Vet Affairs Western New York Healthcare Syst, Buffalo, NY USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Molinari, V (reprint author), Univ S Florida, Dept Aging & Mental Hlth, MHC 1440, Louis de la Parte Florida Mental Hlth Inst, 13301 Bruce B Downs Blvd, Tampa, FL 33612 USA. NR 26 TC 15 Z9 15 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD AUG PY 2003 VL 34 IS 4 BP 435 EP 443 DI 10.1037/0735-7028.34.4.435 PG 9 WC Psychology, Multidisciplinary SC Psychology GA 705NR UT WOS:000184401600013 ER PT J AU Tager, AM Luster, AD AF Tager, AM Luster, AD TI BLT1 and BLT2: the leukotriene B-4 receptors SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ENDOTHELIAL-CELLS; IN-VITRO; HUMAN-NEUTROPHILS; CHEMOATTRACTANT RECEPTOR; PHARMACOLOGICAL ACTIVITY; CHEMOTACTIC RESPONSE; ANTAGONIST LY293111; MOLECULAR-CLONING; CANCER CELLS AB Two receptors for leukotriene B-4 (LTB4) have been molecularly identified: BLT1 and BLT2. Both receptors are G protein-coupled seven transmembrane domain receptors, whose genes are located in very close proximity to each other in the human and mouse genomes. The two receptors differ in their affinity and specificity for LTB4: BLT1 is a high-affinity receptor specific for LTB4, whereas BLT2 is a low-affinity receptor that also binds other eicosanoids. The two receptors also differ in their pattern of expression with BLT1 being expressed primarily in leukocytes, whereas BLT2 is expressed more ubiquitously. By mediating the activities of LTB4, these receptors participate both in host immune responses and in the pathogenesis of inflammatory diseases. Reduced disease severity in animal inflammatory models seen with LTB4 receptor antagonists and in mice with targeted deletion of BLT1 have revealed important roles for LTB4 and its receptors in regulating pathologic inflammation. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammat Dis, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Sch Med, Boston, MA 02114 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammat Dis, Bldg 149-8301,13th St, Charlestown, MA 02129 USA. NR 95 TC 197 Z9 205 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG-SEP PY 2003 VL 69 IS 2-3 BP 123 EP 134 DI 10.1016/S0952-3278(03)00073-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 712WT UT WOS:000184822600006 PM 12895595 ER PT J AU Craft, S Asthana, S Cook, DG Baker, LD Cherrier, M Purganan, K Wait, C Petrova, A Latendresse, S Watson, GS Newcomer, JW Schellenberg, GD Krohn, AJ AF Craft, S Asthana, S Cook, DG Baker, LD Cherrier, M Purganan, K Wait, C Petrova, A Latendresse, S Watson, GS Newcomer, JW Schellenberg, GD Krohn, AJ TI Insulin dose-response effects on memory and plasma amyloid precursor protein in Alzheimer's disease: interactions with apolipoprotein E genotype SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE MESH terms; amyloid beta-protein precursor; insulin resistance; apolipoproteins e; energy metabolism; diabetes ID MILD SENILE DEMENTIA; DEGRADING ENZYME; EXTRACELLULAR LEVELS; CEREBROSPINAL-FLUID; DIABETES-MELLITUS; BETA-PROTEIN; ZUCKER RATS; GLUCOSE; RECEPTOR; HYPERINSULINEMIA AB In previous studies, adults with Alzheimer's disease (AD) showed memory enhancement when plasma insulin levels were raised to 85 muU/ml, whereas normal adults' memory was unchanged. Degree of memory enhancement was also related to apolipoprotein E (apoE) genotype status for AD patients. Response differences between normal and AD groups could reflect dose-response differences for insulin. To examine this question, 22 adults with AD and 15 normal adults received five doses of insulin on separate days in counterbalanced order, resulting in five plasma insulin levels (10, 25 35, 85 and 135 muU/ml), while plasma glucose levels of similar to100 mg/dl were maintained. Cognitive performance and plasma APP levels were measured after 120 min of infusion. Relative to baseline, AD patients who were not apoE-epsilon4 homozygotes had improved memory at higher insulin levels of 35 and 85 muU/ml, whereas normal adults and AD patients who were epsilon4 homozygotes showed improved memory at insulin levels of 25 muU/ml. Normal adults' memory was also improved at insulin levels of 85 muU/ml. Plasma APP was lowered for adults with AD without the epsilon4 allele at higher levels (85 muU/ml) than for normal adults and epsilon4 homozygotes, who showed decreased APP at the 35 muU/ml level. AD patients with a single epsilon4 allele showed a different pattern of insulin effects on APP than did other subjects. In general, few effects of insulin were seen at the highest dose for any subject group. These results support a role for insulin in normal memory and APP modulation that follows a curvilinear response pattern, and suggest that AD patients who are not epsilon4 homozygotes have reduced sensitivity to insulin that may interfere with such modulation. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Washington Univ, Dept Psychiat, St Louis, MO 63105 USA. RP Craft, S (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG-05136, AG-10880] NR 36 TC 151 Z9 158 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 2003 VL 28 IS 6 BP 809 EP 822 DI 10.1016/S0306-4530(02)00087-2 PG 14 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 695TY UT WOS:000183847500007 PM 12812866 ER PT J AU Goldberg, SN Charboneau, JW Dodd, GD Dupuy, DE Gervais, DA Gillams, AR Kane, RA Lee, FT Livraghi, T McGahan, JP Rhim, H Silverman, SG Solbiati, L Vogl, TJ Wood, BJ AF Goldberg, SN Charboneau, JW Dodd, GD Dupuy, DE Gervais, DA Gillams, AR Kane, RA Lee, FT Livraghi, T McGahan, JP Rhim, H Silverman, SG Solbiati, L Vogl, TJ Wood, BJ CA Int Working Grp Image-Guided Tumor TI Image-guided tumor ablation: Proposal for standardization of terms and reporting criteria SO RADIOLOGY LA English DT Article DE radiofrequency (RF) ablation; radiology and radiologists; review ID PERCUTANEOUS RADIOFREQUENCY ABLATION; SMALL HEPATOCELLULAR-CARCINOMA; LASER-INDUCED THERMOTHERAPY; QUALITY IMPROVEMENT GUIDELINES; MICROWAVE COAGULATION THERAPY; RENAL-CELL CARCINOMA; THERMAL ABLATION; HEPATIC-TUMORS; LIVER METASTASES; TISSUE ABLATION AB The field of image-guided tumor ablation requires standardization of terms and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments with different technologies, such as chemical ablation (ethanol or acetic acid) and thermal therapies, such as radiofrequency, laser, microwave, ultrasound, and cryoablation. On the basis of this premise, a working committee was established with the goal of producing a proposal on such standardization. The intent of the Working Group is to provide a framework that will facilitate the clearest communication between investigators and will provide the greatest flexibility in comparisons between the many new, exciting, and emerging technologies. The members of the Working Group now propose a vehicle for reporting the various aspects of image-guided ablation therapy, including classifications of therapies and procedures, appropriate descriptors of image guidance, and terms to define imaging and pathologic findings. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's hope and intention that adherence to the recommendations of this proposal will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and ultimately to improved patient outcomes. (C) RSNA, 2003. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Univ Texas, Rhode Isl Hosp, Hlth Sci Ctr, Providence, RI USA. Massachusetts Gen Hosp, Boston, MA USA. Middlesex Hosp, London, England. Univ Wisconsin, Madison, WI USA. Osped Civile, Virnercate, Italy. Univ Calif Davis, Ctr Med, Sacramento, CA 95817 USA. Hanyang Univ Hosp, Seoul 133791, South Korea. Brigham & Womens Hosp, Boston, MA 02115 USA. Osped Gen, Busto Arsizio, Italy. Univ Klinikum, Frankfurt, Germany. Imaging Sci Program, NIH, Bethesda, MD USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. OI Dupuy, Damian/0000-0003-0524-5982; Solbiati, Luigi/0000-0002-3109-1449 NR 89 TC 259 Z9 291 U1 3 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2003 VL 228 IS 2 BP 335 EP 345 DI 10.1148/radiol.2282021787 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 705DU UT WOS:000184381100009 PM 12893895 ER PT J AU Bluemke, DA Weber, TM Rubin, D de Lange, EE Semelka, R Redvanly, RD Chezmar, J Outwater, E Carlos, R Saini, S Holland, GA Mammone, JF Brown, JJ Milestone, B Javitt, MC Jacobs, P AF Bluemke, DA Weber, TM Rubin, D de Lange, EE Semelka, R Redvanly, RD Chezmar, J Outwater, E Carlos, R Saini, S Holland, GA Mammone, JF Brown, JJ Milestone, B Javitt, MC Jacobs, P TI Hepatic MR imaging with ferumoxides: Multicenter study of safety and effectiveness of direct injection protocol SO RADIOLOGY LA English DT Article DE contrast media; iron; liver neoplasms, diagnosis; liver neoplasms, MR ID FOCAL LIVER-LESIONS; PREOPERATIVE DETECTION; ARTERIAL PORTOGRAPHY; HELICAL CT; SPIRAL CT; METASTASES; EFFICACY; SPIO AB PURPOSE: To compare the Safety and effectiveness of an undiluted direct injection of fetumoxides with those of a diluted slow infusion of ferumoxides during 30 minutes in patients with known liver lesions or in those suspected of having them. MATERIALS AND METHODS: Two hundred thirty-three patients at 16 institutions were randomized to receive either an undiluted direct injection of 0.56 mg of iron per kilogram of body weight of ferumoxides administered during 2 minutes (2 mL/min) or a diluted slow infusion administered during 30 minutes. Safety was assessed with monitoring for adverse events and laboratory tests. For sensitivity, specificity, and accuracy analysis, two independent blinded observers identified and classified lesions as benign or malignant with precontrast images and with pre- and postcontrast images combined., RESULTS: There was no statistically significant difference in adverse events in the, group with direct injection compared with those in the group with infusion (21 [18%] of 114 patients vs 19 [17%] of 112 patients, respectively). No serious adverse events were observed. The most common adverse events in the group with direct injection versus the group with infusion were headache (five [4%] of 114 vs three [3%] of 112, respectively) and back, pain (five [4%] of 114 vs three [3%] of 112, respectively). Overall, in 68 (62%) of 109 patients with direct injection and 71 (66%) of 108 patients with infusion, additional magnetic resonance (MR) imaging information was obtained after, ferumoxides administration (P = .67). Sensitivity, i specificity, and accuracy for the diagnosis of malignancy were significantly improved by adding images obtained after ferumoxides administration to the images obtained before contrast agent administration (P < .05 for all comparisons). CONCLUSION: Direct injection of ferumoxides has safety and effectiveness profiles similar to those of slow infusion of the agent. Further findings indicate that the addition of ferumoxides increases-the sensitivity and specificity of hepatic MR evaluation when compared with unenhanced MR imaging. (C) RSNA, 2003. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. Univ Alabama, Birmingham, AL USA. Good Samaritan Hosp, San Jose, CA USA. Univ Virginia, Charlottesville, VA USA. Scatliff MRI, UNC Hosp, Chapel Hill, NC USA. Thomas Jefferson Univ Hosp, Philadelphia, PA USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Coll Penn Tenet, Philadelphia, PA USA. Univ Camden, Cooper Hosp, Med Ctr, Camden, NJ USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. George Washington Univ, Ctr Med, Washington, DC USA. Adv Magnet, Cambridge, MA USA. RP Bluemke, DA (reprint author), Johns Hopkins Univ, Sch Med, 600 N Wolfe St, Baltimore, MD 21287 USA. OI Bluemke, David/0000-0002-8323-8086 NR 17 TC 25 Z9 27 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD AUG PY 2003 VL 228 IS 2 BP 457 EP 464 DI 10.1148/radiol.2282012061 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 705DU UT WOS:000184381100025 PM 12893904 ER PT J AU McMahon, PM Araki, SS Sandberg, EA Neumann, PJ Gazelle, GS AF McMahon, PM Araki, SS Sandberg, EA Neumann, PJ Gazelle, GS TI Cost-effectiveness of PET in the diagnosis of Alzheimer disease SO RADIOLOGY LA English DT Article DE Alzheimer disease; brain, PET; cost-effectiveness; dementia; positron emission tomography (PET) ID POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-DIAGNOSIS; UTILITY SCORES; UNITED-STATES; DEMENTIA; DONEPEZIL; QUALITY; CARE; MILD AB PURPOSE: To evaluate the cost-effectiveness of positron emission tomography (PET) in the diagnosis of Alzheimer disease (AD) in community-dwelling patients with mild or moderate dementia who present to specialized AD centers. MATERIALS AND METHODS: A decision-analytic model was used to compare costs and quality-adjusted life years (QALYs) associated with strategies involving single photon emission computed tomography (SPECT), dynamic susceptibility-weighted contrast material-enhanced magnetic resonance (MR) imaging, and PET as functional imaging adjuncts to the standard clinical work-up. Sensitivity analyses were performed to examine changes in test characteristics, health-related quality-of-life survey instruments, therapeutic effectiveness, and treatment rules. RESULTS: The use of PET to confirm the results of the standard clinical work-up cost more but yielded fewer benefits than a strategy in which dynamic susceptibility-weighted contrast-enhanced MR imaging was substituted for the typically performed structural computed tomography. This relationship remained stable in scenarios in which standard diagnostic work-up accuracy, drug treatment effectiveness, and version of the Health Utilities Index were altered. Dynamic susceptibility-weighted contrast enhanced MR imaging cost $598,800 per QALY gained (range, $74,400 to $1.9 million per QALY), compared with the cost of the standard diagnostic work-up. Treating all patients with dementia was the dominant imaging strategy, except when side effects in patients with non-AD-related dementia were modeled. In all scenarios, SPECT yielded fewer benefits than other strategies at a higher cost. CONCLUSION: PET may have high diagnostic accuracy, but adding it to the standard diagnostic regimen at AD clinics would yield limited, if any, benefits at very high costs. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Doctoral Program Hlth Policy, Cambridge, MA 02138 USA. Harvard Univ, Ctr Risk Anal, Program Econ Evaluat Med Technol, Cambridge, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. FU NCI NIH HHS [1 R25 CA92203-01A1, R25 CA092203]; NLM NIH HHS [5 T-15 LM07092] NR 42 TC 37 Z9 37 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 AUG PY 2003 VL 228 IS 2 BP 515 EP 522 DI 10.1148/radiol.2282020915 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 705DU UT WOS:000184381100033 PM 12802006 ER PT J AU Reddy, R Keshavan, M Yao, JK AF Reddy, R Keshavan, M Yao, JK TI Reduced plasma antioxidants in first-episode patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE plasma antioxidants; albumin; uric acid; bilirubin; gender; psychosis; cigarette smoking; neuroleptic-naive ID FUNCTIONAL LIFE-SPAN; ACUTE-PHASE PROTEINS; OXIDATIVE DAMAGE; SERUM-ALBUMIN; URIC-ACID; CAPACITY; SEVERITY; SCALE AB Recent findings suggest that free radical-mediated pathological processes may underlie membrane deficits that have been observed in schizophrenia. We have previously demonstrated that both total antioxidant status (TAS) and individual antioxidants were significantly reduced in plasma of chronic schizophrenic patients, on and off haloperidol. To test whether reductions in plasma antioxidants are independent of treatment or illness progression, levels of plasma antioxidants were evaluated in 43 patients at first-episode of psychosis, 31 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder (reconfirmed after 6 months) and 12 patients with primary mood (bipolar or depressive (BP/D)) disorder, at neuroleptic-naive baseline as well as 40 age- and sex-matched normal controls (NC). The major plasma antioxidants albumin, uric acid and bilirubin were all significantly lower in the first-episode schizophrenic, but not in the BP/D patients, than in normal controls. Factors that can affect these antioxidants-age, gender, diet and smoking-were examined. Body mass index (BMI) was significantly lower in patients, but was not correlated with plasma albumin and bilirubin; there was a trend for a correlation with uric acid in schizophrenic patients. Lower antioxidant levels were independent of smoking status of patients. The present data suggest that a defect in the antioxidant defense system (AODS), which may lead to oxidative damage, occurs early in the course of illness and is independent of treatment effect. (C) 2003 Elsevier Science B.V. All rights reserved. C1 VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Bldg 13,7180 Highland Dr, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH45203, MH58141] NR 33 TC 101 Z9 107 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG 1 PY 2003 VL 62 IS 3 BP 205 EP 212 DI 10.1016/S0920-9964(02)00407-3 PG 8 WC Psychiatry SC Psychiatry GA 699ML UT WOS:000184060500002 PM 12837516 ER PT J AU Messamore, E Hoffman, WF Janowsky, A AF Messamore, E Hoffman, WF Janowsky, A TI The niacin skin flush abnormality in schizophrenia: a quantitative dose - response study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; niacin; laser Doppler flowmetry; prostaglandins; skin flush ID LASER-DOPPLER FLOWMETRY; CUTANEOUS BLOOD-FLOW; NICOTINIC-ACID; PROSTAGLANDIN ACTIVITY; INFLAMMATION; SPECTROSCOPY; RELEASE; HUMANS AB Niacin dilates cutaneous blood vessels, resulting in a pronounced skin flush in most people. The flush response to niacin is attenuated in schizophrenia, but the quantification and physiological mechanism of this abnormality have not been described in detail. It is not clear whether the mechanism involves changes in the pharmacological sensitivity to niacin, or whether there is a reduced ability of the vasculature to dilate adequately in subjects with schizophrenia. We address this question in the present study by characterizing the dose-response relationship between topically applied alpha-methylnicotinate (AMN) and cutaneous blood flow changes, which were quantified by laser Doppler flowmetry. The dose-response curve was shifted to the right in subjects with schizophrenia. The EC50 value of AMN was significantly increased in the schizophrenia group (mean: 1.66 mM; 95% confidence interval: 1.04-2.65 mM) as compared to the control group (mean: 0.38 mM; 95% confidence interval: 0.263-0.547 mM). The blood flow responses to higher ANM doses were lower in the schizophrenics; however, there was no statistically significant difference in the extrapolated maximal blood flow response value (F-max) between the two groups. The results suggest that the skin flush abnormality in schizophrenia primarily reflects reduced pharmacological sensitivity to niacin rather than an inadequate cutaneous vasodilatory response to the stimulus. Since vasodilatation in response to niacin requires the release of prostaglandins, the data from this study suggest that schizophrenia is associated with abnormalities in enzymes, receptors, or signal transduction mechanisms that affect the synthesis, release, or response to vasodilatory prostaglandins. Published by Elsevier Science B.V. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97201 USA. Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Messamore, E (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, P35C,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIMH NIH HHS [R01 MH43586] NR 28 TC 48 Z9 49 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG 1 PY 2003 VL 62 IS 3 BP 251 EP 258 DI 10.1016/S0920-9964(02)00311-0 PG 8 WC Psychiatry SC Psychiatry GA 699ML UT WOS:000184060500008 PM 12837522 ER PT J AU Fuchs, CS AF Fuchs, CS TI Current and ongoing trials with irinotecan in the United States SO SEMINARS IN ONCOLOGY LA English DT Review ID METASTATIC COLORECTAL-CANCER; PHASE-II TRIAL; RANDOMIZED TRIAL; FLUOROURACIL; LEUCOVORIN; MULTICENTER; CARCINOMA; CPT-11 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 5 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2003 VL 30 IS 4 SU 12 BP 9 EP 17 DI 10.1016/S0093-7754(03)00329-4 PG 9 WC Oncology SC Oncology GA 720XK UT WOS:000185287700003 PM 14508722 ER PT J AU Hoff, PM Fuchs, CS AF Hoff, PM Fuchs, CS TI The experience with oxaliplatin in the treatment of upper gastrointestinal carcinomas SO SEMINARS IN ONCOLOGY LA English DT Review ID ADVANCED GASTRIC-CANCER; RANDOMIZED PHASE-III; DATA-BASE REPORT; ESOPHAGEAL CANCER; COLORECTAL-CANCER; CLINICAL ACTIVITY; TRIAL; CHEMOTHERAPY; CISPLATIN; THERAPY C1 Albert Einstein Hosp, Ctr Clin Studies Canc, Sao Paulo, Brazil. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept GI Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 36 TC 15 Z9 15 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2003 VL 30 IS 4 SU 15 BP 54 EP 61 DI 10.1053/S0093-7754(03)00406-8 PG 8 WC Oncology SC Oncology GA 731RL UT WOS:000185900200009 PM 14523796 ER PT J AU Chawla, AK Kachnic, LA Clark, JW Willett, CG AF Chawla, AK Kachnic, LA Clark, JW Willett, CG TI Combined modality therapy for rectal and colon cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID POSTOPERATIVE RADIATION-THERAPY; LOCALLY ADVANCED PRIMARY; TERM FOLLOW-UP; PROTRACTED-INFUSION FLUOROURACIL; THYMIDYLATE SYNTHASE EXPRESSION; RECURRENT COLORECTAL-CANCER; EXTERNAL-BEAM IRRADIATION; TOTAL MESORECTAL EXCISION; SURGICAL ADJUVANT BREAST; HIGH-DOSE LEUCOVORIN C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Med Sch, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA. NR 72 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2003 VL 30 IS 4 SU 9 BP 101 EP 112 DI 10.1016/S0093-7754(03)00276-8 PG 12 WC Oncology SC Oncology GA 713EY UT WOS:000184845200011 PM 12908141 ER PT J AU Jakupcak, M Salters, K Gratz, KL Roemer, L AF Jakupcak, M Salters, K Gratz, KL Roemer, L TI Masculinity and emotionality: An investigation of men's primary and secondary emotional responding SO SEX ROLES LA English DT Article DE masculinity; affect intensity; fear of emotions ID AFFECT INTENSITY MEASURE; GENDER-ROLE STRESS; NEGATIVE AFFECT; CHILD CONVERSATIONS; MEASUREMENT MODEL; SEX-DIFFERENCES; APPRAISAL; EXPRESSION; STEREOTYPES; FREQUENCY AB In this study, we investigated the role of masculinity in men's affect intensity and men's fear of emotions. Men's masculine ideology and self-reported masculine gender role stress were assessed as cognitive and experiential factors of adherence to traditional masculine gender norms. Masculine ideology was negatively related to men's global affect intensity. However, on a 3-factor model of affect intensity, only negative reactivity was significantly related to masculine ideology. Both masculine ideology and masculine gender role stress were positively related to men's fear of emotions. Results are discussed in the context of theories of gender differences in emotion. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Massachusetts, Boston, MA 02125 USA. RP Jakupcak, M (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way 116 MHC, Seattle, WA 98108 USA. NR 52 TC 27 Z9 28 U1 0 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-0025 J9 SEX ROLES JI Sex Roles PD AUG PY 2003 VL 49 IS 3-4 BP 111 EP 120 DI 10.1023/A:1024452728902 PG 10 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA 692EH UT WOS:000183647500002 ER PT J AU McLean, CA Kohl, K Baker, MA Sinclair, MF Ciesielski, CA Markowitz, LE AF McLean, CA Kohl, K Baker, MA Sinclair, MF Ciesielski, CA Markowitz, LE TI The syphilis reactor grid: Help or hindrance for syphilis surveillance? SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID UNITED-STATES; EPIDEMIOLOGY; ADULTS AB Background: Health departments use reactor grids (sex, age, and serologic test for syphilis [STS] titer criteria) to determine which persons to evaluate for untreated syphilis. Goal: The goal of the study was to assess reactor grid performance in Chicago and reactor grid use nationally in 1999 to 2000. Study Design: We reviewed Chicago health department records to identify characteristics of persons with a reactive STS excluded from evaluation by reactor grid criteria and syphilis cases not meeting evaluation criteria. We surveyed health departments regarding reactor grid use. Results: Of persons with a reactive STS, 46% did not meet criteria for health department evaluation, including 62% of men, 29% of women, and 21% with titers greater than or equal to1:8. The reactor grid would have excluded 17% of primary syphilis cases. Overall, 82% of health departments use reactor grids. Conclusions: Reactor grids are widely used and may exclude persons with infectious syphilis from health department evaluation, especially men. The impact of reactor grid use on syphilis control and surveillance in the United States should be evaluated. C1 Natl Ctr HIV STD & TB Prevent, Div Sexually Transmitted Dis Prevent, Epidemilol & Surveillance Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Immunizat Safety Branch, Atlanta, GA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA USA. Chicago Dept Publ Hlth, Chicago, IL USA. RP McLean, CA (reprint author), Natl Ctr HIV STD & TB Prevent, Div Sexually Transmitted Dis Prevent, Epidemilol & Surveillance Branch, Mailstop E-02,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 2003 VL 30 IS 8 BP 650 EP 653 DI 10.1097/01.OLQ.0000085945.93505.61 PG 4 WC Infectious Diseases SC Infectious Diseases GA 709GV UT WOS:000184618200010 PM 12897688 ER PT J AU Catalano, OA Dal Pozzo, F Grifi, DN Menchi, I Rosenthal, DI AF Catalano, OA Dal Pozzo, F Grifi, DN Menchi, I Rosenthal, DI TI Paraffinoma of the knee SO SKELETAL RADIOLOGY LA English DT Article DE paraffinoma; knee; foreign body granuloma; radiographs; MRI ID BREAST; COMPLICATION AB We present the case of a 90-year-old man with a swollen, painful knee and a history of paraffin injections. Radiography showed soft tissue streaky and nodular calcifications without erosions. MR imaging showed globular areas of low signal intensity on T1- and T2-weighted images which became even more hypointense on STIR sequences, and an infiltrative hypointense region containing areas of high signal on T1-weighted, T2-weighted and STIR images. Biopsy confirmed soft tissue foreign body granulomata, fibrous reaction and areas of inflammation. We believe this to be the first report of MR imaging of paraffinoma outside the breast. C1 AO Rummo, Serv Radiol, Benevento, Italy. PO Santa Maria Nuova, Serv Radiol, Florence, Italy. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Catalano, OA (reprint author), Via Prov 93, I-82010 Beltiglio Ceppaloni, BN, Italy. NR 14 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD AUG PY 2003 VL 32 IS 8 BP 485 EP 488 DI 10.1007/s00256-003-0640-2 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 711TB UT WOS:000184756200009 PM 12768243 ER PT J AU Maggard, MA O'Connell, JB Liu, JH Etzioni, DA Ko, CY AF Maggard, MA O'Connell, JB Liu, JH Etzioni, DA Ko, CY TI Sample size calculations in surgery: Are they done correctly? SO SURGERY LA English DT Article; Proceedings Paper CT 64th Annual Meeting of the Society-of-University-Surgeons CY FEB 12-15, 2003 CL HOUSTON, TEXAS SP Soc Univ Surg ID RANDOMIZED CONTROLLED TRIALS; STATISTICAL POWER; CLINICAL-TRIALS; QUALITY AB Background. Randomized controlled trials (RCTs) are considered the gold standard for evidence-based clinical research, but Prior work has suggested that there may be poor reporting of sample sizes in the surgical literature. Sample size calculations are essential for planning a study to minimize both type I and type II errors. We hypothesized that sample size calculations may not be performed consistently in surgery studies and, therefore, many studies may be "undetpowered." To address this issue, we reviewed RCTs published in the surgical literature to determine how often sample size calculations were reported and to analyze each study's ability to detect varying degrees of differences in outcomes. Methods. A comprehensive MEDLINE search identified RCTs published in Annals of Surgery, Archives of Surgery, and Surgery between 1999 and 2002. Each study was evaluated by two independent reviewers. Sample size calculations were performed to determine whether they had 80% power to detect differences between treatment groups of 50% (large) and 20% (small), with one-sided test, alpha = 0.05. For the underpowered studies, the degree to which sample size would need to be increased was determined. Results. One hundred twenty-seven RCT articles were identified; of these, 48 (38%) reported sample size calculations. Eighty-six (68%) studies reported positive treatment effect, whereas 41 (32%)found negative results. Sixty-three (50%) of the studies were appropriately powered to detect a 50% effect change, whereas 24 (19%) had the power to detect a 20% difference. Of the studies that were underpowered, more than half needed to increase sample size by more than 10-fold. Conclusions. The reporting of sample size calculations was not provided in more than 60% of recently published surgical RCTs. Moreover, only half of studies had sample sizes appropriate to detect large, differences between treatment groups. C1 Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, Sch Med, Dept Surg, 10833 Conte Ave,CHS,Rm 72-215, Los Angeles, CA 90095 USA. NR 12 TC 31 Z9 32 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 2003 VL 134 IS 2 BP 275 EP 279 DI 10.1067/msy.2003.235 PG 5 WC Surgery SC Surgery GA 719BZ UT WOS:000185184900024 PM 12947329 ER PT J AU Fihn, SD Gadisseur, AAP Pasterkamp, E van der Meer, FJM Breukink-Engbers, WGM Geven-Boere, LM van Meegen, E de Vries-Goldschmeding, H Antheunissn-Anneveld, I van't Hoff, R Harderman, D Smink, M Rosendaal, FR AF Fihn, SD Gadisseur, AAP Pasterkamp, E van der Meer, FJM Breukink-Engbers, WGM Geven-Boere, LM van Meegen, E de Vries-Goldschmeding, H Antheunissn-Anneveld, I van't Hoff, R Harderman, D Smink, M Rosendaal, FR TI Comparison of control and stability of oral anticoagulant therapy using acenocoumarol versus. phenprocoumon SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE anticoagulation; international normalised ratio; phenprocoumon; acenocoumarol ID RISK-FACTORS; WARFARIN ANTICOAGULATION; BLEEDING COMPLICATIONS; VITAMIN-K; REVERSAL; PHYTONADIONE; OUTPATIENTS; INFARCTION; QUALITY AB Variability in the control of oral anticoagulant therapy has been associated with a heightened risk of complications. We compared, control of anticoagulation between two commonly used coumarins, phenprocournon and acenocoumarol, and among anticoagulation clinics. All qualifying patients were managed at six regional anticoagulation clinics in the Netherlands. This retrospective cohort study compiled data during a three-year period from a computerised dosing and management system. Anticoagulation control was expressed as the percent of time within the therapeutic range and stability expressed as the time-weighted variance in the international normalised ratio (INR). Data were available for 22,178 patients of whom 72% were treated with acenocoumarol. INRs of patients who received phenprocoumon were within the therapeutic range 50% of the time compared with 43% for acenocoumarol (OR 1.32,95% Cl 1.24-1.41). Moreover, patients on phenprocoumon required 15% fewer monitoring visits and had more stable INR values. These observations were consistent for all six clinics. There were also sizable differences between the clinics with respect to control and stability of anticoagulation that were stable from year-to-year and were unrelated to the drug used. With its longer half-life of three to five days, phenprocoumon produces more stable anticoagulation than acenocoumarol and should generally be the drug of choice when these are the available choices. The differences observed among clinics suggest that certain clinics employ policies and practices resulting in better control of anti coagulation. C1 Vet Affairs Puget Sound Hlth Care Syst, NW Hlth Serv Res Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Leiden Univ, Med Ctr, Dept Clin Epidemiol & Hemostasis, NL-2300 RA Leiden, Netherlands. Leiden Univ, Med Ctr, Thrombosis Ctr, NL-2300 RA Leiden, Netherlands. Oostgelderland Anticoagulat Clin, Lichtenvoorde, Netherlands. Leeuwarden Anticoagulat Clin, Leeuwarden, Netherlands. Anticoagulat Clin Hague, The Hague, Netherlands. Dutch Red Cross, Utrecht Div, Thrombosis Ctr, Utrecht, Netherlands. Schiedam Anticoagulat Clin, Schiedam, Netherlands. Anticoagulat Clin Midden Brabant, Brabant, Netherlands. Anticoagulat Serv Alkmaar, Alkmaar, Netherlands. RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, NW VA Hlth Serv Res & Dev Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 29 TC 55 Z9 56 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 2003 VL 90 IS 2 BP 260 EP 266 DI 10.1160/TH02-10-0179 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 712AV UT WOS:000184774000012 PM 12888873 ER PT J AU Medeiros, BC Kogel, KE Kane, MA AF Medeiros, BC Kogel, KE Kane, MA TI Transfusion-related acute lung injury (TRALI) following platelet transfusion in a patient receiving high-dose Interleukin-2 for treatment of metastatic renal cell carcinoma SO TRANSFUSION AND APHERESIS SCIENCE LA English DT Article DE Interleukin-2; platelet; renal cell carcinoma; transfusion-related acute lung injury (TRALI) AB Transfusion-related acute lung injury (TRALI) is an uncommon life-threatening complication of hemotherapy. It is hypothesized to be the result of two independent insults: the first related to the clinical status of the patient and the second to the infusion of biologic response modifiers within blood components. We present a case of TRALI in a patient who received high-dose Interleukin-2 (IL-2) as treatment for metastatic renal cell carcinoma, where IL-2 is speculated to have been the first insult and transfusion of platelet concentrate the second. This is the first reported case of TRALI complicating treatment with high-dose immunotherapy. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Med Oncol Hematol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Sch Med Oncol, Denver, CO 80220 USA. RP Medeiros, BC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med Oncol Hematol, 4200 E 9th Ave, Denver, CO 80262 USA. NR 11 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1473-0502 J9 TRANSFUS APHER SCI JI Transfus. Apher. Sci. PD AUG PY 2003 VL 29 IS 1 BP 25 EP 27 DI 10.1016/S1473-0502(03)00094-6 PG 3 WC Hematology SC Hematology GA 711YP UT WOS:000184768900007 PM 12877889 ER PT J AU Frank, LM Brown, EN AF Frank, LM Brown, EN TI Persistent activity and memory in the entorhinal cortex SO TRENDS IN NEUROSCIENCES LA English DT Article ID HIPPOCAMPUS; DIRECTION; NEURONS AB The entorhinal cortex (EC) is an essential component of the medial temporal lobe long-term-memory system. Recently, Egorov et A demonstrated that neurons in layer 5 of the EC show graded persistent activity: each neuron could maintain a constant rate firing over several minutes, even in the absence of input from other neurons. These findings suggest that layer-5 EC neurons could play a central role in the formation of associations among stimuli that occur at different times. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Frank, LM (reprint author), Univ Calif San Francisco, Dept Physiol, Box 0444, San Francisco, CA 94143 USA. OI Frank, Loren/0000-0002-1752-5677 NR 15 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD AUG PY 2003 VL 26 IS 8 BP 400 EP 401 DI 10.1016/S0166-2236(03)00176-0 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 713WF UT WOS:000184880400004 PM 12900167 ER PT J AU Zorrilla, EP Tache, Y Koob, GF AF Zorrilla, EP Tache, Y Koob, GF TI Nibbling at CRF receptor control of feeding and gastrocolonic motility SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; HUMAN UROCORTIN-II; ANXIETY-LIKE BEHAVIOR; COMPETITIVE ANTAGONISTS; PHARMACOLOGICAL CHARACTERIZATION; RAT-BRAIN; GASTROINTESTINAL-TRACT; NONPEPTIDE ANTAGONIST; PERIPHERAL UROCORTIN; TYPE-1 RECEPTOR AB Inadequate pharmacological tools, until recently, hindered the understanding of the roles of corticotropin-releasing factor (CRF) receptor subtypes in appetite regulation and gastrocolonic motor function. Now, novel ligands that are selective for CRF1 or CRF2 receptors are helping to uncover the specific functions of CRF receptor subtypes. Central or peripheral CRF2 receptor activation suppresses feeding independently of CRF1 receptors. In the rat, central administration of CRF2 receptor agonists promotes satiation without eliciting the malaise, behavioral arousal or anxiogenesis associated with CRF, receptor agonists. Conversely, central administration of CRF1 receptor agonists elicits short-onset anorexia independently of CRF2 receptor activation. With respect to gastrointestinal motor function, stress inhibits gastric motility through CRF2 receptor-dependent central autonomic and peripheral myenteric systems. By contrast, stress stimulates colonic motility via CRF, receptor-dependent sacral parasympathetic and colonic myenteric mechanisms. These findings have important physiological implications and suggest targeted approaches for the pharmacotherapy of obesity and stress-related functional gastrointestinal and eating disorders. C1 Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, CURE, Digest Dis Res Ctr, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. RP Zorrilla, EP (reprint author), Scripps Res Inst, Dept Neuropharmacol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI koob, george/P-8791-2016 FU NIDDK NIH HHS [DK26741, DK33061, DK57238] NR 60 TC 92 Z9 94 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 2003 VL 24 IS 8 BP 421 EP 427 DI 10.1016/S0165-6147(03)00177-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 714TP UT WOS:000184929800008 PM 12915052 ER PT J AU Smith, RP Devine, P Jones, H DeNittis, A Whittington, R Metz, JM AF Smith, RP Devine, P Jones, H DeNittis, A Whittington, R Metz, JM TI Internet use by patients with prostate cancer undergoing radiotherapy SO UROLOGY LA English DT Article ID HEALTH INFORMATION; ONCOLOGY; QUALITY AB Objectives. To analyze the amount of Internet use, type of Internet use, and factors that predict Internet use by patients with prostate cancer. Methods. A questionnaire evaluating the use of the Internet was given to 295 patients undergoing radiotherapy for prostate cancer in three different settings: an academic center (AC), a Veterans Affairs center (VA), and a community hospital. The study included 171 AC patients (58%), 104 VA patients (35%), and 20 community hospital patients (7%). Results. The response rate to the questionnaire was greater than 99%. Overall, 128 (43%) of 295 patients had a home computer. This differed among the institutions, with 64% of AC patients and only 5% of VA patients having a home computer (P < 0.0001). Overall, 94 (32%) of 295 patients used the Internet to access cancer information, with 48% of AC patients and 8% of VA patients using the Internet (P < 0.0001). Seventeen percent of black patients (n = 113) had a home computer compared with 62% of white patients (n = 175; P < 0.0001). Equal access to computers did not influence Internet use because, among those patients who had access to computers, black patients used the Internet less than did white patients (32% versus 61%, P < 0.0001). Men 65 years of age or younger were more likely to use the Internet (45%) than those older than 65 years (28%; P = 0.004). Patients used many sites to access different types of information. Conclusions. A significant number of patients with prostate cancer access the Internet to obtain cancer information. Urologists and radiation oncologists should be familiar with this important resource to help patients access appropriate material. C1 Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA USA. W Jersey Canc Ctr, Voorhees, NJ USA. RP Smith, RP (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St,2 Donner, Philadelphia, PA 19104 USA. NR 19 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 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2003 VL 62 IS 2 BP 273 EP 277 DI 10.1016/S0090-4295(03)00251-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 708FU UT WOS:000184557200016 PM 12893334 ER PT J AU Bhayani, SB Ong, A Oh, WK Kantoff, PW Kavoussi, LR AF Bhayani, SB Ong, A Oh, WK Kantoff, PW Kavoussi, LR TI Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer: A long-term update SO UROLOGY LA English DT Article ID TESTIS CANCER; MANAGEMENT; LYMPHADENECTOMY; EXPERIENCE; CARCINOMA; TUMORS AB Objectives. To assess retrospectively the long-term cancer control in patients undergoing laparoscopic retroperitoneal lymph node dissection (RPLND) in the management of clinical Stage I nonseminomatous germ cell testicular tumors. Methods. A retrospective review of 29 patients undergoing laparoscopic RPLND was performed. All patients had clinical Stage I nonseminomatous germ cell testicular tumor, with vascular invasion and/or embryonal carcinoma in the orchiectomy specimen. A modified template dissection was performed. Patients with retroperitoneal metastases were offered two cycles of chemotherapy. A modified follow-up schedule was used in patients with pathologically negative nodes. Results. Lymph nodes were negative in 17 of 29 patients. Of these 17 patients, 15 had no recurrence and were free of disease with 5.8 years of follow-up. Two patients had recurrence, one in the chest, and one biochemically, and both were free of disease after chemotherapy. Twelve of 29 patients had lymph nodes with metastatic testicular cancer. Ten of these patients underwent adjuvant chemotherapy and were free of disease with 6.3 years of follow-up. One patient had a biochemical recurrence after positive RPLND and was salvaged with chemotherapy. One patient was observed after positive RPLND and was free of disease with 4.9 years of follow-up. The only long-term complication was retrograde ejaculation in I patient. Conclusions. Laparoscopic RPLND is a safe, minimally invasive treatment option in patients with clinical Stage I nonseminomatous germ cell testicular tumor. The cancer control appears to be similar, with minimal morbidity compared with the open procedure. C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kavoussi, LR (reprint author), Johns Hopkins Univ Hosp, Dept Urol, 600 N Wolfe St,Suite 161,Jefferson St Bldg, Baltimore, MD 21287 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 12 TC 49 Z9 55 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 AUG PY 2003 VL 62 IS 2 BP 324 EP 327 DI 10.1016/S0090-4295(03)00324-8 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 708FU UT WOS:000184557200026 PM 12893344 ER PT J AU Loughlin, KR Hawtrey, CE AF Loughlin, KR Hawtrey, CE TI Moses Swick, the father of intravenous urography SO UROLOGY LA English DT Biographical-Item C1 Brigham & Womens Hosp, Div Urol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Univ Iowa, Coll Med, Dept Urol, Iowa City, IA 52242 USA. RP Loughlin, KR (reprint author), Brigham & Womens Hosp, Div Urol, 75 Francis St, Boston, MA 02115 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 0090-4295 J9 UROLOGY JI Urology PD AUG PY 2003 VL 62 IS 2 BP 385 EP 389 DI 10.1016/S0090-4295(02)02286-0 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 708FU UT WOS:000184557200041 PM 12893369 ER PT J AU Buckley, KA Li, PL Khimani, AH Hofmann-Lehmann, R Liska, V Anderson, DC McClure, HM Ruprecht, RM AF Buckley, KA Li, PL Khimani, AH Hofmann-Lehmann, R Liska, V Anderson, DC McClure, HM Ruprecht, RM TI Convergent evolution of SIV env after independent inoculation of rhesus macaques with infectious proviral DNA SO VIROLOGY LA English DT Article DE SIV env evolution; intramuscular inoculation with proviral DNA; infectious SIV DNA ID SIMIAN IMMUNODEFICIENCY VIRUS; POLYMERASE CHAIN-REACTION; ATTENUATED SIV; MONOCLONAL-ANTIBODIES; ADULT MACAQUES; LIVE; MONKEYS; NEUTRALIZATION; PROTECTION; DISEASE AB The env gene of three simian immunodeficiency virus (SIV) variants developed convergent mutations during disease progression in six rhesus macaques. The monkeys had been inoculated with supercoiled plasmids encoding infectious proviruses of SIVmac239 (a pathogenic, wild-type strain), SIVDelta3 (the live attenuated vaccine strain derived from SIVmac239), or SIVDelta3+ (a pathogenic progeny virus that had evolved from SIVDelta3). All six monkeys developed immunodeficiency and progressed to fatal disease. Although many divergent mutations arose in env among the different hosts, three regions consistently mutated in all monkeys studied; these similar mutations developed independently even though the animals had received only a single infectious molecular clone rather than standard viral inocula that contain viral quasispecies. Together, these data indicate that the env genes of SIVmac239, SIVDelta3, and SIVDelta3+, in the context of different proviral backbones, evolve similarly in different hosts during disease progression. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Res Resources, Atlanta, GA 30329 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol, Atlanta, GA 30329 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Immunol, Atlanta, GA 30329 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB-809, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NCIRD CDC HHS [IP30 28691]; NCRR NIH HHS [RR-00165, RR-14180] NR 27 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 2003 VL 312 IS 2 BP 470 EP 480 DI 10.1016/S0042-6822(03)00262-9 PG 11 WC Virology SC Virology GA 715AH UT WOS:000184948000021 PM 12919751 ER PT J AU Meltzer, PC Blundell, P Zona, T Yang, LH Huang, H Bonab, AA Livni, E Fischman, A Madras, BK AF Meltzer, PC Blundell, P Zona, T Yang, LH Huang, H Bonab, AA Livni, E Fischman, A Madras, BK TI A second-generation (99m)technetium single photon emission computed tomography agent that provides in vivo images of the dopamine transporter in primate brain SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECOGNITION SITES; ACID METHYL-ESTERS; DEFICIT HYPERACTIVITY DISORDER; HIGH-AFFINITY; PARKINSONS-DISEASE; IMAGING AGENTS; BETA-CIT; TC-99M-LABELED TROPANES; RECEPTOR-BINDING; RAT STRIATUM AB The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for Parkinson's disease (Pd) and attention deficit hyperactivity disorder (ADHD). In ADHD, DAT density levels are elevated, while in Pd these levels are depleted. The depletion of DAT levels also corresponds with the loss of dopamine. We now describe the design, synthesis, biology, and SPECT imaging in nonhuman primates of second-generation (99m)technetium-based tropane ligands that bind potently and selectively to the DAT. We demonstrate that improved selectivity and biological stability allows sufficient agent to enter the brain and label the DAT in vivo to provide a quantitative measure of DAT density in nonhuman primates. We introduce FLUORATEC (N-[(2-((3'-N-propyl-(1"R)-3"alpha-(4-fluorophenyl)tropane-2"beta-1-propanoyl)(2-mercaptoethyl)amino)acetyl)-2-aminoethanethiolato]technetium(V) oxide), a DAT imaging agent that has emerged from these studies and is now in phase 1 clinical trials in the U.S. C1 Organix Inc, Woburn, MA 01801 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Southborough, MA 01772 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Meltzer, PC (reprint author), Organix Inc, 240 Salem St, Woburn, MA 01801 USA. EM meltzer@organixinc.com FU NCRR NIH HHS [RR 00168]; NIDA NIH HHS [DA 48309, DA 06303, DA 09462] NR 54 TC 8 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 31 PY 2003 VL 46 IS 16 BP 3483 EP 3496 DI 10.1021/jm0301484 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 705RM UT WOS:000184408600010 PM 12877586 ER PT J AU Bedecarrats, GY Linher, KD Janovick, JA Beranova, M Kada, F Seminara, SB Conn, PM Kaiser, UB AF Bedecarrats, GY Linher, KD Janovick, JA Beranova, M Kada, F Seminara, SB Conn, PM Kaiser, UB TI Four naturally occurring mutations in the human GnRH receptor affect ligand binding and receptor function SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE GnRH; GnRH receptor; gonadotrope; signal transduction ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; PROTEIN-COUPLED RECEPTORS; MOLECULAR-MECHANISMS; HOMOZYGOUS MUTATION; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; KINASE-C; ACTIVATION; LH AB In the present study, we performed functional analyses of four mutations in the human GnRH receptor (GnRHR) gene, identified in patients with idiopathic hypogonadotropic hypogonadism. These mutations result in amino acid substitutions in the extracellular N-terminal domain (Thr321Ile), second extracellular loop (Cys200Tyr), third intracellular loop (Leu266Arg) and sixth transinembrane helix (Cys279Tyr). Immunocytochemical analysis of cells transfected with HA-tagged GnRHR constructs revealed that all four mutant receptors were present on the cell surface. However, all four mutant receptors failed to exhibit measurable specific GnRH binding and, except for Thr32Ile, any significant inositol phosphate accumulation after GnRH stimulation. In addition, Leu266Arg and Cys279Tyr receptors were unable to stimulate gonadotropin subunit or GnRHR gene promoter activity in response to GnRH. Interestingly, the Cys200Tyr mutant was able to stimulate gonadotropin subunit and GnRHR promoter activity, albeit with a higher EC(50) and a markedly reduced maximal response compared to wild type receptor. The Tht-32Ile mutant was also able to stimulate gonadotropin subunit and GnRHR promoters, but with a further significant increase in EC(50). Similarly, this mutant partially retained the ability to activate extracellular signal-regulated kinase 1 and stimulate CRE-luciferase activity with an identical shift in EC50. Taken together, the studies suggest that the Thr32Ile mutation reduces hGnRHR function primarily by reducing ligand binding affinity, and the Cys200Tyr mutation reduces cell surface receptor expression. All four amino acid substitutions interfered with ligand binding, and affected signal transduction and stimulation of gonadotropin and GnRHR gene expression in response to GnRH. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Oregon Hlth & Sci Univ, Beaverton, OR 97006 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 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 FIC NIH HHS [TW00668]; NICHD NIH HHS [R01HD19938, HD19899, U54 HD281328] NR 44 TC 35 Z9 37 U1 2 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL 31 PY 2003 VL 205 IS 1-2 BP 51 EP 64 DI 10.1016/S0303-7207(03)00201-6 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 711GT UT WOS:000184731800006 PM 12890567 ER PT J AU Neumann, CA Krause, DS Carman, CV Das, S Dubey, DP Abraham, JL Bronson, RT Fujiwara, Y Orkin, SH Van Etten, RA AF Neumann, CA Krause, DS Carman, CV Das, S Dubey, DP Abraham, JL Bronson, RT Fujiwara, Y Orkin, SH Van Etten, RA TI Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression SO NATURE LA English DT Article ID ABL TYROSINE KINASE; PAG GENE-PRODUCT; PHYSIOLOGICAL INHIBITOR; OXIDATIVE STRESS; LIFE-SPAN; CELLS; MICE; CLONING; PROTEIN; EXPRESSION AB Reactive oxygen species are involved in many cellular metabolic and signalling processes(1) and are thought to have a role in disease, particularly in carcinogenesis and ageing(2). We have generated mice with targeted inactivation of Prdx1, a member of the peroxiredoxin family of antioxidant enzymes(3). Here we show that mice lacking Prdx1 are viable and fertile but have a shortened lifespan owing to the development beginning at about 9 months of severe haemolytic anaemia and several malignant cancers, both of which are also observed at increased frequency in heterozygotes. The haemolytic anaemia is characterized by an increase in erythrocyte reactive oxygen species, leading to protein oxidation, haemoglobin instability, Heinz body formation and decreased erythrocyte lifespan. The malignancies include lymphomas, sarcomas and carcinomas, and are frequently associated with loss of Prdx1 expression in heterozygotes, which suggests that this protein functions as a tumour suppressor. Prdx1-deficient fibroblasts show decreased proliferation and increased sensitivity to oxidative DNA damage, whereas Prdx1-null mice have abnormalities in numbers, phenotype and function of natural killer cells. Our results implicate Prdx1 as an important defence against oxidants in ageing mice. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. RP Van Etten, RA (reprint author), Tufts New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NIEHS NIH HHS [F32 ES011586] NR 31 TC 435 Z9 456 U1 6 U2 33 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 31 PY 2003 VL 424 IS 6948 BP 561 EP 565 DI 10.1038/nature01819 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 706LG UT WOS:000184454700045 PM 12891360 ER PT J AU Tsao, DY Vanduffel, W Sasaki, Y Fize, D Knutsen, TA Mandeville, JB Wald, LL Dale, AM Rosen, BR Van Essen, DC Livingstone, MS Orban, GA Tootell, RBH AF Tsao, DY Vanduffel, W Sasaki, Y Fize, D Knutsen, TA Mandeville, JB Wald, LL Dale, AM Rosen, BR Van Essen, DC Livingstone, MS Orban, GA Tootell, RBH TI Stereopsis activates V3A and caudal intraparietal areas in macaques and humans SO NEURON LA English DT Article ID HUMAN VISUAL-CORTEX; DISPARITY-SELECTIVE NEURONS; LATERAL OCCIPITAL COMPLEX; VERGENCE EYE-MOVEMENTS; SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; BINOCULAR INTERACTION; 3-DIMENSIONAL SPACE; STEREOSCOPIC DEPTH; SPATIAL ATTENTION AB Stereopsis, the perception of depth from small differences between the images in the two eyes, provides a rich model for investigating the cortical construction of surfaces and space. Although disparity-tuned cells have been found in a large number of areas in macaque visual cortex, stereoscopic processing in these areas has never been systematically compared using the same stimuli and analysis methods. In order to examine the global architecture of stereoscopic processing in primate visual cortex, we studied fMRI activity in alert, fixating human and macaque subjects. In macaques, we found strongest activation to near/far compared to zero disparity in areas V3, V3A, and CIPS. In humans, we found strongest activation to the same stimuli in areas V3A, V7, the V4d topolog (V4d-topo), and a caudal parietal disparity region (CPDR). Thus, in both primate species a small cluster of areas at the parieto-occipital junction appears to be specialized for stereopsis. C1 Massachusetts Gen Hosp, NMR Ctr, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Katholieke Univ Leuven, Fac Med, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Tsao, DY (reprint author), Massachusetts Gen Hosp, NMR Ctr, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. EM doris@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Fize, Denis/F-4525-2011; Wald, Lawrence/D-4151-2009 FU NEI NIH HHS [R01 EY016187-01A2, R01 EY013135-04]; NIBIB NIH HHS [1R01EB00790]; NIMH NIH HHS [1R01MH67529] NR 75 TC 181 Z9 185 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD JUL 31 PY 2003 VL 39 IS 3 BP 555 EP 568 DI 10.1016/S0896-6273(03)00459-8 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 709LC UT WOS:000184625800016 PM 12895427 ER PT J AU George, DJ Kaelin, WG AF George, DJ Kaelin, WG TI The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP George, DJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 3 TC 84 Z9 89 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 31 PY 2003 VL 349 IS 5 BP 419 EP 421 DI 10.1056/NEJMp030061 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 706FV UT WOS:000184443700001 PM 12890838 ER PT J AU Teng, M Wolf, M Lowrie, E Ofsthun, N Lazarus, JM Thadhani, R AF Teng, M Wolf, M Lowrie, E Ofsthun, N Lazarus, JM Thadhani, R TI Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAGE RENAL-DISEASE; VITAMIN-D-RECEPTOR; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; ARTERY CALCIFICATION; DIALYSIS PATIENTS; MORTALITY RISK; ADYNAMIC BONE; YOUNG-ADULTS; CORONARY AB BACKGROUND: Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D. METHODS: We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated. RESULTS: The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) among those receiving calcitriol (P<0.001). The difference in survival was significant at 12 months and increased with time (P<0.001). In the adjusted analysis, the mortality rate was 16 percent lower (95 percent confidence interval, 10 to 21 percent) among paricalcitol-treated patients than among calcitriol-treated patients. A significant survival benefit was evident in 28 of 42 strata examined, and in no stratum was calcitriol favored. At 12 months, calcium and phosphorus levels had increased by 6.7 and 11.9 percent, respectively, in the paricalcitol group, as compared with 8.2 and 13.9 percent, respectively, in the calcitriol group (P<0.001). The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent, as compared with 64 percent among those who switched from paricalcitol to calcitriol (P=0.04). CONCLUSIONS: Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Fresenius Med Care N Amer, Lexington, MA USA. RP Thadhani, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. NR 42 TC 654 Z9 684 U1 0 U2 14 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 31 PY 2003 VL 349 IS 5 BP 446 EP 456 DI 10.1056/NEJMoa022536 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 706FV UT WOS:000184443700006 PM 12890843 ER PT J AU McGee, DM Connolly, SA Young, RH Scully, RE Harris, NL AF McGee, DM Connolly, SA Young, RH Scully, RE Harris, NL TI A 10-year-old girl with recurrent bouts of abdominal pain - Massive edema of the ovary with torsion. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHILDREN; MASSES; ADOLESCENCE; CHILDHOOD C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, 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 Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP McGee, DM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 21 TC 2 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 31 PY 2003 VL 349 IS 5 BP 486 EP 494 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 706FV UT WOS:000184443700011 PM 12890848 ER PT J AU Armstrong, K Weber, B FitzGerald, G Hershey, JC Pauly, MV Lemaire, J Subramanian, K Asch, DA AF Armstrong, K Weber, B FitzGerald, G Hershey, JC Pauly, MV Lemaire, J Subramanian, K Asch, DA TI Life insurance and breast cancer risk assessment: Adverse selection, genetic testing decisions, and discrimination SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE insurance selection bias; genetic screening; BRCA1 ID OVARIAN-CANCER; MUTATION; IDENTIFICATION; INFORMATION; WOMEN; BRCA1 AB Life insurance industry access to genetic information is controversial. Consumer groups argue that access will increase discrimination in life insurance premiums and discourage individuals from undergoing genetic testing that may provide health benefits. Conversely, life insurers argue that without access to risk information available to individuals, they face substantial financial risk from adverse selection. Given this controversy, we conducted a retrospective cohort study to evaluate the impact of breast cancer risk information on life insurance purchasing, the impact of concerns about life insurance discrimination on use of BRCA1/2 testing, and the incidence of life insurance discrimination following participation in breast cancer risk assessment and BRCA1/2 testing. Study participants were 636 women who participated in genetic counseling and/or genetic testing at a University based clinic offering breast cancer risk assessment, genetic counseling, and BRCA1/2 testing between January 1995 and May 2000. Twenty-seven women (4%) had increased and six (1%) had decreased their life insurance since participation in breast cancer risk assessment. The decision to increase life insurance coverage was associated with predicted breast cancer risk (adjusted OR 1.03 for each 1% absolute increase in risk, 95% CI 1.01-1.10) and being found to carry a mutation in BRCA1/2 (OR 5.10, 95% CI 1.90-13.66). Concern about life insurance discrimination was inversely associated with the decision to undergo BRCA1/2 testing (RR 0.67, 95% Cl 0.52-0.85). No respondent reported having life insurance denied or canceled. In this cohort of women, these results indicate that information about increased breast cancer risk is associated with increase in life insurance purchasing, raising the possibility of adverse selection. Although fear of insurance discrimination is associated with the decision not to undergo BRCA1/2 testing, there was no evidence of actual insurance discrimination from BRCA1/2 testing. (C) 2003 Wiley-Liss, Inc. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Temple Univ, Philadelphia, PA 19122 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X FU NCI NIH HHS [R01-CA82393, CA57601] NR 24 TC 39 Z9 42 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL 30 PY 2003 VL 120A IS 3 BP 359 EP 364 DI 10.1002/ajmg.a.20025 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 698AE UT WOS:000183974800009 PM 12838555 ER PT J AU Vaish, NK Larralde, R Fraley, AW Szostak, JW McLaughlin, LW AF Vaish, NK Larralde, R Fraley, AW Szostak, JW McLaughlin, LW TI A novel, modification-dependent ATP-binding aptamer selected from an RNA library incorporating a cationic functionality SO BIOCHEMISTRY LA English DT Article ID IN-VITRO SELECTION; EXPONENTIAL ENRICHMENT; SYSTEMATIC EVOLUTION; NUCLEIC-ACID; CATALYTIC REPERTOIRE; DNA ENZYME; LIGANDS; NUCLEOTIDE; RIBOZYMES; ADENOSINE AB An analogue of uridine triphosphate containing a cationic functional group was incorporated into a degenerate RNA library by enzymatic polymerization. In vitro selection experiments using this library yielded a novel receptor that binds ATP under physiological pH and salt conditions in a manner completely dependent on the presence of the cationic functionality. The consensus sequence and a secondary structure model for the ATP binding site were obtained by the analysis of functional sequences selected from a partially randomized pool based on the minimal parental sequence. Mutational studies of this receptor indicated that several of the modified uridines are critical for ATP binding. Analysis of the binding of ATP analogues revealed that the modified RNA receptor makes numerous contacts with ATP, including interactions with the triphosphate group. In contrast, the aptamer repeatedly isolated from natural RNA libraries does not interact with the triphosphate group of ATP. The incorporation of a cationic amine into nucleic acids clearly allows novel interactions to occur during the molecular recognition of ligands, which carries interesting implications for the RNA world hypothesis. In addition, new materials generated from such functionalized nucleic acids could be useful tools in research and diagnostics. C1 Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. 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), Boston Coll, Dept Chem, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM vaishn@sirna.com; fraley@bioorga.u-strasbg.fr; szostak@molbio.mgh.harvard.edu; larry.mclaughlin@bc.edu FU NIGMS NIH HHS [GM-53936] NR 65 TC 35 Z9 36 U1 2 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 29 PY 2003 VL 42 IS 29 BP 8842 EP 8851 DI 10.1021/bi027354i PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 705HX UT WOS:000184390600022 PM 12873145 ER PT J AU Feldman, RB Rhew, DC Wong, JY Charles, RA Goetz, MB AF Feldman, RB Rhew, DC Wong, JY Charles, RA Goetz, MB TI Azithromycin monotherapy for patients hospitalized with community-acquired pneumonia - A 3(1)/(2)-year experience from a veterans affairs hospital SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; MACROLIDE RESISTANCE; ANTIMICROBIAL RESISTANCE; ELDERLY PATIENTS; THERAPY; ERYTHROMYCIN; EPIDEMIOLOGY; MANAGEMENT; CLARITHROMYCIN; SUSCEPTIBILITY AB Background: Current American Thoracic Society (ATS) community-acquired pneumonia treatment guidelines recommend azithromycin monotherapy for a limited subset of hospitalized patients. We evaluated the effectiveness of azithromycin monotherapy in a more generalized population of patients hospitalized with mild-to-moderate community-acquired pneumonia. Methods: We reviewed medical records from a Veterans Affairs facility for patients admitted with community-acquired pneumonia between December 1, 1997, and June 30, 2001, comparing those receiving azithromycin monotherapy, other ATS-recommended antibiotics, and non-ATS-recommended antibiotics. We excluded patients with immunosuppression, metastatic cancer, or hospital-acquired pneumonia. Outcome measures included times to stability, meeting criteria for change to oral therapy, and eligibility for discharge; length of stay; intensive care unit transfer; and mortality. Outcomes were adjusted for pneumonia severity, skilled nursing facility status, and processes of care. Results: A total of 442 patients were eligible for the study (221 in the azithromycin monotherapy group, 129 in the ATS group, and 92 in the non-ATS group). Times to clinical stability and to fulfilling early switch criteria were not statistically significantly different among the 3 groups. Mean time to fulfilling early discharge criteria was 2.48 days for patients receiving azithromycin monotherapy vs 2.84 days for those receiving ATS antibiotics (P=.008) and 2.58 days for those receiving non-ATS antibiotics (P=.64). Overall mean length of stay was shorter in the azithromycin monotherapy group (4.35 days) vs the ATS (5.73 days) (P=.002) and non-ATS (6.21 days) (P<.001) groups. Mortality, intensive care unit transfer, and readmission rates were similar across the groups. Conclusion: Azithromycin monotherapy is equally as efficacious as other ATS-recommended regimens for treating hospitalized patients with mild-to-moderate community-acquired pneumonia. C1 Zynx Hlth Inc, Cedars Sinai Hlth Syst, Dept Hlth Serv Res, Beverly Hills, CA 90212 USA. VA Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Rhew, DC (reprint author), Zynx Hlth Inc, Cedars Sinai Hlth Syst, Dept Hlth Serv Res, 9100 Wilshire Blvd,Suite 655E, Beverly Hills, CA 90212 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 39 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 28 PY 2003 VL 163 IS 14 BP 1718 EP 1726 DI 10.1001/archinte.163.14.1718 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 704YQ UT WOS:000184369900012 PM 12885688 ER PT J AU Natarajan, S Liao, YL Cao, GC Lipsitz, SR McGee, DL AF Natarajan, S Liao, YL Cao, GC Lipsitz, SR McGee, DL TI Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID IMPAIRED FASTING GLUCOSE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; US ADULTS; WOMEN; MELLITUS; IMPACT; PREVALENCE; SURVIVAL; INSULIN AB Background: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. Methods: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. Results: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% Cl, 0.72-0.75) in men and -0.65 (95% Cl, -0.68 to -0.63) in women. Conclusions: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk. C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Florida State Univ, Dept Stat, Tallahassee, FL 32306 USA. RP Natarajan, S (reprint author), 423 E 23rd St,Room 11101-S, New York, NY 10010 USA. FU NHLBI NIH HHS [HL52329, HL67460, HL68900]; NIDDK NIH HHS [DK52329] NR 38 TC 95 Z9 96 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 28 PY 2003 VL 163 IS 14 BP 1735 EP 1740 DI 10.1001/archinte.163.14.1735 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 704YQ UT WOS:000184369900014 PM 12885690 ER PT J AU Ruprecht, RM Ferrantelli, F Kitabwalla, M Xu, WD McClure, HM AF Ruprecht, RM Ferrantelli, F Kitabwalla, M Xu, WD McClure, HM TI Antibody protection: passive immunization dof neonates against oral AIDS virus challenge SO VACCINE LA English DT Article; Proceedings Paper CT International Symposium on Protection of Newborns through Maternal Immunization CY DEC 08-11, 2002 CL VEYRIER DU LAC, FRANCE SP Fdn Merieux, WHO DE neutralizing monoclonal antibodies; passive immunization and correlates of immune protection; HIV transmission through breastfeeding ID HUMAN MONOCLONAL-ANTIBODIES; RHESUS-MONKEYS; CLADE-B; NEUTRALIZATION; COMBINATION; PREVENTION; MACAQUES; DISEASE; VACCINE; INFECTION AB We have established models for intrapartum and milk-borne HIV transmission by orally challenging neonatal macaques with chimeric simian-human immunodeficiency viruses (SHIVs). This allowed us to test safety and efficacy of passive immunization with human neutralizing monoclonal antibodies (nmAbs), which had been isolated from HIV clade B-infected individuals and which target conserved, functionally important epitopes. The nmAbs studied were F105 or IgG1b12, b12 for short (directed against the CD4 binding site), 2G12 (anti-gp120), 2F5 and 4E10 (both anti-gp41). Out of 16 newborn macaques challenged orally with different SHIV strains, 11 were completely protected by triple or quadruple nmAb combinations, even by post-exposure prophylaxis. In vitro, the combination of b12, 2G12, 2175 and 4E10 potently neutralized primary HIV isolates of clades A, B, C, and D. Our data suggest that passive immunization with currently available anti-HIV clade B nmAbs could play a role in preventing transmission of non-clade B isolates through breastfeeding. We furthermore conclude that the epitopes recognized by the nmAbs in our successful passive immunization studies are important determinants for protection and provide targets for developing neutralizing antibody-response-based, active AIDS vaccines. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA. RP Ruprecht, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [P01 AI48240, R01 AI34226] NR 15 TC 59 Z9 60 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 28 PY 2003 VL 21 IS 24 BP 3370 EP 3373 DI 10.1016/S0264-410X(03)00335-9 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 705NZ UT WOS:000184402300006 PM 12850342 ER PT J AU King, A Andersson, A Strand, BL Lau, J Skjak-Braek, G Sandler, S AF King, A Andersson, A Strand, BL Lau, J Skjak-Braek, G Sandler, S TI The role of capsule composition and biologic responses in the function of transplanted microencapsulated islets of Langerhans SO TRANSPLANTATION LA English DT Editorial Material ID ALGINATE-POLYLYSINE MICROCAPSULES; RAT PANCREATIC-ISLETS; L-LYSINE MICROCAPSULES; IN-VITRO; POLYCATION MICROCAPSULES; HUMAN MACROPHAGES; OXYGEN-TENSION; HOST-REACTION; MEMBRANE; INSULIN C1 Uppsala Univ, Biomed Ctr, Dept Med Cell Biol, Uppsala, Sweden. Norwegian Univ Sci & Technol, Dept Biotechnol, Trondheim, Norway. RP King, A (reprint author), Joslin Diabet Ctr, Sect Islet Transplant & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. RI King, Aileen/I-5935-2013; Strand, Berit Lokensgard/O-3999-2015 OI King, Aileen/0000-0001-5759-7985; Strand, Berit Lokensgard/0000-0002-9951-0355 NR 51 TC 18 Z9 19 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2003 VL 76 IS 2 BP 275 EP 279 DI 10.1097/01.TP.0000078625.29988.0A PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 706GH UT WOS:000184445400001 PM 12883179 ER PT J AU Mapara, MY Kim, YM Marx, J Sykes, M AF Mapara, MY Kim, YM Marx, J Sykes, M TI Donor lymphocyte infusion-mediated graft-versus-leukemia effects in mixed chimeras established with a nonmyeloablative conditioning regimen: Extinction of graft-versus-leukemia effects after conversion to full donor chimerism SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; HOST DISEASE; T-CELLS; MYELOABLATIVE THERAPY; TOLERANCE; MODEL; IRRADIATION; INDUCTION; FATE AB Background. We investigated an approach to separating graft-versus-lymphoma (GVL) effects from graft-versus-host disease (GVHD) in mice receiving a nonmyeloablative conditioning regimen allowing establishment of mixed hematopoietic chimerism. Methods. We evaluated the ability of donor lymphocyte infusions (DLI) to mediate GVL effects without GVHD in mixed chimeras prepared with cyclophosphamide, anti-T-cell antibodies, and thymic irradiation. To examine the fate of GVH-reactive donor CD8(+) T cells, we used the 2C T-cell receptor (TCR) transgenic mouse strain, which carries an L-d-specific transgenic TCR on the B6 background. Results. Administration of DLI on day 35 post-BMT led to conversion from mixed to full donor chimerism and mediated a powerful GVL effect with complete protection (100% survival) against mortality induced by a host-type lymphoma (EL4) administered 7 days later (100% mortality in non-DLI controls; P<0.001). No GVHD occurred in DLI recipients. Rechallenging the surviving DLI recipients, which had converted to full chimerism, with the same tumor dose 17 weeks later led to rapid tumor mortality. Long-term DLI recipients had anti-host proliferative responses, but not CTL responses in vitro. When given as DLI together with wild-type spleen cells, marked expansion of GVH-reactive 2C CD8(+) T cells was observed on day 10, followed by a marked decline in their numbers by week 10 post-DLI. Conclusions. Nonmyeloablative induction of mixed chimerism followed by administration of DLI can mediate powerful GVL effects. The late loss of DLI-mediated GVL effects may reflect the eventual loss of donor-derived GVH-reactive CTL, which occurs in association with conversion to full donor chimerism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplant Biol Res, Boston, MA 12129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplantat Sect,Transplant Biol Res, MGH-E,Bldg 149-5102,13th St, Boston, MA 12129 USA. RI mapara, markus/A-2134-2013 FU NCI NIH HHS [R01 CA 79989] NR 24 TC 53 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 27 PY 2003 VL 76 IS 2 BP 297 EP 305 DI 10.1097/01.TP.0000072014.83469.2D PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 706GH UT WOS:000184445400005 PM 12883182 ER PT J AU Redinbaugh, EM Sullivan, AM Block, SD Gadmer, NM Lakoma, M Mitchell, AM Seltzer, D Wolford, J Arnold, RM AF Redinbaugh, EM Sullivan, AM Block, SD Gadmer, NM Lakoma, M Mitchell, AM Seltzer, D Wolford, J Arnold, RM TI Doctors' emotional reactions to recent death of a patient: cross sectional study of hospital doctors SO BRITISH MEDICAL JOURNAL LA English DT Article ID JUNIOR HOUSE OFFICERS; STRESS; PHYSICIANS; MEDICINE; CARE AB Objectives To describe doctors' emotional reactions to the recent death of an "average" patient and to explore the effects of level of training on doctors' reactions. Design Cross sectional study using quantitative data. Setting Two academic teaching hospitals in the United States. Participants 188 doctors (attending physicians (equivalent to UK consultants), residents (equivalent to UK senior house officers), and interns (equivalent to UK junior house officers)) who cared for 68 patients who died in the hospital. Main outcome measures Doctors' experiences in providing care, their emotional reactions to the patient's death, and their use of coping and social resources to manage their emotions. Results Most doctors (139/188, 74%) reported satisfying experiences in caring for a dying patient. Doctors reported moderate levels of emotional impact (mean 4.7 (SD 2.4) on a 0-10 scale) from the death. Women and those doctors who had cared for the patient for a longer time experienced stronger emotional reactions. Level of training was not related to emotional reactions, but interns reported needing significantly more emotional support than attending physicians. Although most junior doctors discussed the patient's death with an attending physician, less than a quarter of interns and residents found senior teaching staff (attending physicians) to be the most helpful source of support. Conclusions Doctors who spend a longer time caring for their patients get to know them better but this also makes them more vulnerable to feelings of loss when these patients die. Medical teams may benefit from debriefing within the department to give junior doctors an opportunity to share emotional responses and reflect on the patient's death. C1 Univ Pittsburgh, Inst Canc, Dept Behav Med & Oncol, Pittsburgh, PA 15232 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA USA. RP Redinbaugh, EM (reprint author), Univ Pittsburgh, Inst Canc, Dept Behav Med & Oncol, 5150 Ctr Ave 445, Pittsburgh, PA 15232 USA. NR 22 TC 113 Z9 115 U1 0 U2 12 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JUL 26 PY 2003 VL 327 IS 7408 BP 185 EP 189 DI 10.1136/bmj.327.7408.185 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 706DL UT WOS:000184437300013 PM 12881257 ER PT J AU Meyerson, M AF Meyerson, M TI Human genetic variation and disease SO LANCET LA English DT Editorial Material ID DNA-SEQUENCES; ASSOCIATION C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 NR 11 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 26 PY 2003 VL 362 IS 9380 BP 259 EP 260 DI 10.1016/S0140-6736(03)14002-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 705UL UT WOS:000184413400003 PM 12892951 ER PT J AU Porcellini, S Vallanti, G Nozza, S Poli, G Lazzarin, A Tambussi, G Siccardi, AG Grassi, F AF Porcellini, S Vallanti, G Nozza, S Poli, G Lazzarin, A Tambussi, G Siccardi, AG Grassi, F TI Improved thymopoietic potential in aviremic HIV infected individuals treated with HAART by intermittent IL-2 administration SO AIDS LA English DT Article DE HIV-1; interleukin-2; immune reconstitution; thymus; T cell development; foetal thymic organ cultures; T cell receptor excision circles ID HUMAN IMMUNODEFICIENCY VIRUS-1; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MARROW TRANSPLANTATION; DECREASED THYMIC OUTPUT; T-CELL HOMEOSTASIS; PERIPHERAL-BLOOD; IN-VITRO; IMMUNE RECONSTITUTION; HUMAN STROMA; HUMAN ADULT AB Objective: In HIV-positive individuals administration of intermittent interleukin (IL)-2 in addition to highly active antiretroviral therapy (HAART) induces expansion of the peripheral T cell pool with dilution of signal joint T cell receptor excision circles (sjTREC) that cannot be used to measure thymic output. We analysed whether in vitro thymopoiesis could be used to predict in vivo thymic output in IL-2 treated subjects. Design and methods: We correlated the relative variation of peripheral CD4 T cells over 12 months in HIV-positive subjects on HAART or HAART + IL-2 with the mean levels of both sjTREC and T cells developed in chimeric murine foetal thymic organ cultures (FTOC) reconstituted with circulating progenitors. Results: In contrast with HAART treated individuals in which these values were directly correlated, in subjects receiving HAART + IL-2 the increase of CD4 T cells in vivo was correlated to neither sjTREC number nor to reconstitution of FTOC, probably reflecting a main effect of IL-2 in the expansion of the peripheral T cell pool. Nevertheless, addition of IL-2 to HAART determined a significant increase of in vitro thymopoietic potential in individuals with undetectable viraemia. Conclusions: The increased T cell development in vitro after addition of IL-2 to HAART suggests that intermittent IL-2 administration may exert a positive influence on lymphopoiesis. In two subjects with positive viraemia treated with IL-2 we observed reduced in vitro development of T cell precursors suggesting that the positive influence of IL-2 on thymopoiesis could be secondary to the control of viral replication by HAART. These observations provide novel evidence in support of the potential beneficial use of IL-2 in HAART treated individuals. (C) 2003 Lippincott Williams Wilkins. C1 San Raffaele Sci Inst, Dept Immunol & Infect Dis, AIDS Immunopathogenesis Unit, Milan, Italy. Univ Milan, Dipartimento Biol & Genet Sci Med, Milan, Italy. San Raffaele Sci Inst, Div Infect Dis, Dept Immunol & Infect Dis, I-20132 Milan, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. RP Grassi, F (reprint author), Biomed Res Inst, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. OI Nozza, Silvia/0000-0002-2673-2731 NR 40 TC 2 Z9 2 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 25 PY 2003 VL 17 IS 11 BP 1621 EP 1630 DI 10.1097/01.aids.0000060393 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 710BW UT WOS:000184661800006 PM 12853744 ER PT J AU Ioannidis, JPA Contopoulos-Ioannidis, DG Rosenberg, PS Goedert, JJ De Rossi, A Espanol, T Frenkel, L Mayaux, MJ Newell, ML Pahwa, SG Rousseau, C Scarlatti, G Sei, S Sen, L O'Brien, TR AF Ioannidis, JPA Contopoulos-Ioannidis, DG Rosenberg, PS Goedert, JJ De Rossi, A Espanol, T Frenkel, L Mayaux, MJ Newell, ML Pahwa, SG Rousseau, C Scarlatti, G Sei, S Sen, L O'Brien, TR CA HIV Host Genetics Int Meta Anal TI Effects of CCR5-Delta 32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis SO AIDS LA English DT Article DE CCR5-Delta 32; CCR2-64I; death; disease progression; HIV-1; perinatal transmission ID INDIVIDUAL-PATIENT DATA; PEDIATRIC HIV-1 INFECTION; CHEMOKINE GENE VARIANT; CORECEPTOR USAGE; VIRAL PHENOTYPE; CCR5; TRANSMISSION; POLYMORPHISMS; RISK; PATHOGENESIS AB Objective: Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-Delta32 and CCR2-641 in an international meta-analysis. Methods: Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. Results: There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-Delta32 and CCR2-641 showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (0) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-Delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P = 0.01 for the time-dependent model). For CCR2-641, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P < 0.01 for the time-dependent model). CCR5-Delta32 and CCR2-641 offered no clear protection after clinical AIDS had developed. Conclusion: The CCR5-Delta32 and CCR2-641 alelles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life. (C) 2003 Lippincott Williams Wilkins. C1 Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. Univ Ioannina, Dept Pediat, Sch Med, GR-45110 Ioannina, Greece. Fdn Res & Technol Hellas, Inst Biomed Res, Ioannina, Greece. Tufts Univ, New England Med Ctr, Dept Med, Boston, MA 02111 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Univ Padua, AIDS Reference Ctr, Oncol Sect, Dept Oncol & Surg Sci, I-35100 Padua, Italy. Hosp Gen Valle Hebron, Immunol Unit, Barcelona, Spain. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Div Pediat Infect Dis,Dept Pediat, Seattle, WA 98195 USA. INSERM, Paris, France. UCL, Inst Child Hlth, Ctr Paediat Epidemiol, London WC1E 6BT, England. NYU, Sch Med, N Shore Univ Hosp, Div Immunol,Dept Pediat, Manhasset, NY USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. DIBIT San Raffaele Sci Inst, Viral Evolut & Transmiss Unit, Milan, Italy. NCI, HIV Clin Interface Lab, NIH, Frederick, MD 21701 USA. Hosp Pediat JP Garrahan, Lab Biol Celular & Retrovirus, Buenos Aires, DF, Argentina. RP Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Clin & Mol Epidemiol Unit, GR-45110 Ioannina, Greece. EM jioannid@cc.uoi.gr RI Ioannidis, John/G-9836-2011; De Rossi, Anita/L-3128-2015 OI De Rossi, Anita/0000-0001-6435-7509 NR 39 TC 37 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD JUL 25 PY 2003 VL 17 IS 11 BP 1631 EP 1638 DI 10.1097/01.aids.0000060411.18106.0f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 710BW UT WOS:000184661800007 PM 12853745 ER PT J AU Gould, GG Mehta, AK Frazer, A Ticku, MK AF Gould, GG Mehta, AK Frazer, A Ticku, MK TI Quantitative autoradiographic analysis of the new radioligand [H-3](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([H-3]NCS-382) at gamma-hydroxybutyric acid (GHB) binding sites in rat brain SO BRAIN RESEARCH LA English DT Article DE gamma-hydroxybutyric acid; [H-3]NCS-382; autoradiography; GABA receptors; GHB receptor; GHB antagonist ID RECEPTOR ANTAGONIST; GABA(B) RECEPTOR; NCS-382; SYSTEM; CORTEX AB (2E)-(5-Hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid (NCS-382) is an antagonist for gamma-hydroxybutyric acid (GHB) at GHB receptor sites. Advantages of using [H-3]NCS-382 over [H-3]GHB in radioligand binding studies are that unlike GHB, NCS-382 does not appear to bind to, activate, or interfere with the functioning of GABA(B) or GABA(A) receptors, either directly or indirectly. Herein we establish a protocol for use of [H-3]NCS-382 by quantitative autoradiography. GHB was used to define non-specific binding, since it displaced [H-3]NCS-382 to an extent equivalent to NCS-382. Among many areas of brain examined, two regions in which high specific binding of [H-3]NCS-382 occurred were the hippocampus and cerebral cortex. Areas such as the striatum and nucleus accumbens exhibited intermediate levels of specific binding. No or very low binding was observed in other areas such as the cerebellum and dorsal raphe nucleus. The distribution of GHB binding sites as defined by [H-3]NCS-382 suggests that GHB may play a role in neuromodulation or neurotransmission in frontal brain areas. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol 7764, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Gould, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol 7764, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI Gould, Georgianna/0000-0002-5470-8763 FU NIDA NIH HHS [DA14986]; NIMH NIH HHS [MH57001] NR 24 TC 28 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 25 PY 2003 VL 979 IS 1-2 BP 51 EP 56 DI 10.1016/S0006-8993(03)02865-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 705LT UT WOS:000184397100007 PM 12850570 ER PT J AU Choe, H Li, WH Wright, PL Vasilieva, N Venturi, M Huang, CC Grundner, C Dorfman, T Zwick, MB Wang, LP Rosenberg, ES Kwong, PD Burton, DR Robinson, JE Sodroski, JG Farzan, M AF Choe, H Li, WH Wright, PL Vasilieva, N Venturi, M Huang, CC Grundner, C Dorfman, T Zwick, MB Wang, LP Rosenberg, ES Kwong, PD Burton, DR Robinson, JE Sodroski, JG Farzan, M TI Tyrosine sulfation of human antibodies contributes to recognition of the CCR5 binding region of HIV-1 gp120 SO CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; AMINO-TERMINAL DOMAIN; ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTORS; CORECEPTOR USAGE; DISTINCT CCR5; N-TERMINUS; ENTRY; NEUTRALIZATION AB Sulfated tyrosines at the amino terminus of the principal HIV-1 coreceptor CCR5 play a critical role in its ability to bind the HIV-1 envelope glycoprotein gp120 and mediate HIV-1 infection. Here, we show that a number of human antibodies directed against gp120 are tyrosine sulfated at their antigen binding sites. Like that of CCR5, antibody association with gp120 is dependent on sulfate moieties, enhanced by CD4, and inhibited by sulfated CCR5-derived peptides. Most of these antibodies preferentially associate with gp120 molecules of CCR5-utilizing (R5) isolates and neutralize primary R5 isolates more efficiently than laboratory-adapted isolates. These studies identify a distinct subset of CD4-induced HIV-1 neutralizing antibodies that closely emulate CCR5 and demonstrate that tyrosine sulfation can contribute to the potency and diversity of the human humoral response. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Microbiol & Mol Genet,Div AIDS, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div AIDS, Boston, MA 02115 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Farzan, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med Microbiol & Mol Genet,Div AIDS, Boston, MA 02115 USA. OI Li, Wenhui/0000-0003-1305-7404 FU NIAID NIH HHS [R01 AI043891] NR 55 TC 126 Z9 129 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 25 PY 2003 VL 114 IS 2 BP 161 EP 170 DI 10.1016/S0092-8674(03)00508-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705CN UT WOS:000184378700006 PM 12887918 ER PT J AU Masutomi, K Yu, EY Khurts, S Ben-Porath, I Currier, JL Metz, GB Brooks, MW Kaneko, S Murakami, S DeCaprio, JA Weinberg, RA Stewart, SA Hahn, WC AF Masutomi, K Yu, EY Khurts, S Ben-Porath, I Currier, JL Metz, GB Brooks, MW Kaneko, S Murakami, S DeCaprio, JA Weinberg, RA Stewart, SA Hahn, WC TI Telomerase maintains telomere structure in normal human cells SO CELL LA English DT Article ID REVERSE-TRANSCRIPTASE HTERT; HUMAN-DIPLOID FIBROBLASTS; CATALYTIC SUBUNIT; LIFE-SPAN; G-STRAND; SACCHAROMYCES-CEREVISIAE; HUMAN-LYMPHOCYTES; IMMORTAL CELLS; RNA COMPONENT; MOUSE CELLS AB In normal human cells, telomeres shorten with successive rounds of cell division, and immortalization correlates with stabilization of telomere length. These observations suggest that human cancer cells achieve immortalization in large part through the illegitimate activation of telomerase expression. Here, we demonstrate that the rate-limiting telomerase catalytic subunit hTERT is expressed in cycling primary presenescent human fibroblasts, previously believed to lack hTERT expression and telomerase activity. Disruption of telomerase activity in normal human cells slows cell proliferation, restricts cell lifespan, and alters the maintenance of the 3' single-stranded telomeric overhang without changing the rate of overall telomere shortening. Together, these observations support the view that telomerase and telomere structure are dynamically regulated in normal human cells and that telomere length alone is unlikely to trigger entry into replicative senescence. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Kanazawa Univ, Canc Res Inst, Dept Mol Oncol, Kanazawa, Ishikawa 9200934, Japan. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Kanazawa Univ, Grad Sch Med, Dept Gastroenterol, Kanazawa, Ishikawa 9208641, Japan. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Stewart, Sheila/C-5213-2012 FU NCI NIH HHS [F32 CA93033, K01 CA94223, R01 CA78461] NR 60 TC 496 Z9 555 U1 10 U2 47 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 25 PY 2003 VL 114 IS 2 BP 241 EP 253 DI 10.1016/S0092-8674(03)00550-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705CN UT WOS:000184378700013 PM 12887925 ER PT J AU Javanbakht, H Halwani, R Cen, S Saadatmand, J Musier-Forsyth, K Gottlinger, H Kleiman, L AF Javanbakht, H Halwani, R Cen, S Saadatmand, J Musier-Forsyth, K Gottlinger, H Kleiman, L TI The interaction between HIV-1 Gag and human lysyl-tRNA synthetase during viral assembly SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMER TRANSFER-RNAS; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; CAPSID PROTEIN; WILD-TYPE; PARTICLES; BINDING; PR160GAG-POL AB Human lysyl-tRNA synthetase (LysRS) is a tRNA-binding protein that is selectively packaged into HIV-1 along with its cognate tRNA(Lys) isoacceptors. Evidence exists that Gag alone is sufficient for the incorporation of LysRS into virions. Herein, using both in vitro and in vivo methods, we begin to map regions in Gag and LysRS that are required for this interaction. In vitro reactions between wild-type and truncated HIV-1 Gag and human LysRS were monitored using GST-tagged molecules and glutathione-agarose chromatography. Gag/LysRS interaction in vivo was detected in 293FT cells cotransfected with plasmids coding for wild-type or mutant HIV-1 Gag and LysRS, either by monitoring Gag.LysRS complexes immunoprecipitated from cell lysate with anti-LysRS or by measuring the ability of LysRS to be packaged into budded Gag viral-like particles. Based on these studies, we conclude that the Gag/LysRS interaction depends upon Gag sequences within the C-terminal domain of capsid (the last 54 amino acids) and amino acids 208-259 of LysRS. The latter domain includes the class II amino-acyl-tRNA synthetase consensus sequence known as motif 1. Both regions have been implicated in homodimerization of capsid and LysRS, respectively. Sequences falling outside these amino acid stretches can be deleted from either molecule without affecting the Gag/LysRS interaction, further supporting the observation that LysRS is incorporated into Gag viral-like particles independent of its ability to bind tRNA(Lys). C1 Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. Jewish Gen Hosp, McGill AIDS Ctr, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Med, Montreal, PQ H3T 1E2, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3T 1E2, Canada. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Kleiman, L (reprint author), Jewish Gen Hosp, Lady Davis Inst Med Res, 3755 Cote St Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 38 TC 67 Z9 69 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 JUL 25 PY 2003 VL 278 IS 30 BP 27644 EP 27651 DI 10.1074/jbc.M301840200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 702UL UT WOS:000184242700040 PM 12756246 ER PT J AU Cheng, EHY Sheiko, TV Fisher, JK Craigen, WJ Korsmeyer, SJ AF Cheng, EHY Sheiko, TV Fisher, JK Craigen, WJ Korsmeyer, SJ TI VDAC2 inhibits BAK activation and mitochondrial apoptosis SO SCIENCE LA English DT Article ID DEPENDENT ANION CHANNEL; BCL-X-L; CYTOCHROME-C; PERMEABILITY TRANSITION; PROTEIN; FAMILY; DEATH; RELEASE; DYSFUNCTION; RESPIRATION AB The multidomain proapoptotic molecules BAK or BAX are required to initiate the mitochondrial pathway of apoptosis. How cells maintain the potentially lethal proapoptotic effector BAK in a monomeric inactive conformation at mitochondria is unknown. In viable cells, we found BAK complexed with mitochondrial outer-membrane protein VDAC2, a VDAC isoform present in low abundance that interacts specifically with the inactive conformer of BAK. Cells deficient in VDAC2, but not cells lacking the more abundant VDAC1, exhibited enhanced BAK oligomerization and were more susceptible to apoptotic death. Conversely, overexpression of VDAC2 selectively prevented BAK activation and inhibited the mitochondrial apoptotic pathway. Death signals activate "BH3-only" molecules such as tBID, BIM, or BAD, which displace VDAC2 from BAK, enabling homo-oligomerization of BAK and apoptosis. Thus, VDAC2, an isoform restricted to mammals, regulates the activity of BAK and provides a connection between mitochondrial physiology and the core apoptotic pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R37CA50239]; NINDS NIH HHS [NS42319] NR 29 TC 468 Z9 490 U1 2 U2 16 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 25 PY 2003 VL 301 IS 5632 BP 513 EP 517 DI 10.1126/science.1083995 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 704LE UT WOS:000184340500042 PM 12881569 ER PT J AU Punglia, RS D'Amico, AV Catalona, WJ Roehl, KA Kuntz, KM AF Punglia, RS D'Amico, AV Catalona, WJ Roehl, KA Kuntz, KM TI Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RADICAL PROSTATECTOMY; REFERENCE RANGES; BIOPSY STRATEGY; 4.0 NG/ML; FREE PSA; MEN; POPULATION; DISEASE; AGE; HYPERPLASIA AB Background: The sensitivity and specificity of a screening test are biased when disease status is not verified in all subjects and when the likelihood of confirmation depends on the test result itself. We assessed the screening characteristics of the prostate-specific antigen (PSA) measurement after correction for verification bias. Methods: Between 1995 and 2001, 6691 men underwent PSA-based screening for prostate cancer. Of these men, 705 (11 percent) subsequently underwent biopsy of the prostate. Under the assumption that the chance of undergoing a biopsy depends only on the PSA-test result and other observed clinical variables, we used a mathematical model to estimate adjusted receiver-operating-characteristic (ROC) curves. Results: Adjusting for verification bias significantly increased the area under the ROC curve (i.e., the overall diagnostic performance) of the PSA test, as compared with an unadjusted analysis (0.86 vs. 0.69, P<0.001, for men less than 60 years of age; 0.72 vs. 0.62, P=0.008, for men 60 years of age or older). If the threshold PSA value for undergoing biopsy were set at 4.1 ng per milliliter, 82 percent of cancers in younger men and 65 percent of cancers in older men would be missed. A digital rectal examination that is abnormal but not suspicious for cancer does not affect the overall performance characteristics of the test. Conclusions: A lower threshold level of PSA for recommending prostate biopsy, particularly in younger men, may improve the clinical value of the PSA test. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO USA. Northwestern Univ, Fineberg Sch Med, Dept Urol, Chicago, IL USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Kuntz, KM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, 718 Huntington Ave, Boston, MA 02115 USA. FU AHRQ HHS [T32 HS00020-16] NR 28 TC 206 Z9 221 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 24 PY 2003 VL 349 IS 4 BP 335 EP 342 DI 10.1056/NEJMoa021659 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 703ZH UT WOS:000184312800006 PM 12878740 ER PT J AU Ahmed, AR Kelly, JL Avram, MM McCluskey, RT Ryan, DP Duncan, LM AF Ahmed, AR Kelly, JL Avram, MM McCluskey, RT Ryan, DP Duncan, LM TI A 79-year-old woman with gastric lymphoma and erosive mucosal and cutaneous lesions - Paraneoplastic pemphigus associated with gastric marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID STEVENS-JOHNSON SYNDROME; ERYTHEMA MULTIFORME; RITUXIMAB; NEOPLASIA C1 New England Baptist Hosp, Dept Oral Med, Boston, MA 02120 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), New England Baptist Hosp, Dept Oral Med, Boston, MA 02120 USA. RI Duncan, Lyn/E-9878-2013 NR 21 TC 26 Z9 29 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 24 PY 2003 VL 349 IS 4 BP 382 EP 391 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 703ZH UT WOS:000184312800013 PM 12878746 ER PT J AU Syken, J Macian, F Agarwal, S Rao, A Munger, K AF Syken, J Macian, F Agarwal, S Rao, A Munger, K TI TID1, a mammalian homologue of the drosophila tumor suppressor lethal(2) tumorous imaginal discs, regulates activation-induced cell death in Th2 cells SO ONCOGENE LA English DT Article DE tumor suppressor; apoptosis; DnaJ protein; T cells ID ESCHERICHIA-COLI DNAJ; T-CELL; CD95 LIGAND; MOLECULAR CHAPERONES; MEDIATED APOPTOSIS; ATPASE ACTIVITY; UP-REGULATION; EXPRESSION; GENE; PROTEIN AB We previously described two human DnaJ proteins, hTid-1(L) and hTid-1(S), which are derived from alternative splicing of the TID1 gene, the human homologue of the Drosophila tumor suppressor lethal(2) tumorous imaginal discs, and showed that hTid-1(L) promoted while hTid-1(S) antagonized apoptosis. There are two subsets of helper T cells, Th1 and Th2, of which Th2 cells are significantly less prone to apoptosis induced by stimulation through the T-cell receptor. This apoptotic process is known as activation-induced cell death (AICD). The molecular basis for the differential susceptibility of Th1 and Th2 cells to AICD is not known. Here we show that the antiapoptotic variant, Tid-1(S), is selectively induced in murine Th2 cells following activation. Expression of a dominant-negative mutant of hTid-1(S) in a Th2 cell line strikingly enhanced activation of caspase 3 in response to CD3 stimulation, and caused the cells to become sensitive to AICD. Hence, the accumulation of Tid-1(S) in Th2 cells following activation represents a novel mechanism that may contribute to the induction of apoptosis resistance during the activation of Th2 cells. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Munger, K (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave,D2-544A, Boston, MA 02115 USA. OI Munger, Karl/0000-0003-3288-9935; Macian, Fernando/0000-0003-2666-035X NR 41 TC 18 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 24 PY 2003 VL 22 IS 30 BP 4636 EP 4641 DI 10.1038/sj.onc.1206569 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 701FF UT WOS:000184157000003 PM 12879007 ER PT J AU Soejima, K Fang, WZ Rollins, BJ AF Soejima, K Fang, WZ Rollins, BJ TI DNA methyltransferase 3b contributes to oncogenic transformation induced by SV40T antigen and activated Ras SO ONCOGENE LA English DT Article DE DNA methyltransferase; tumor suppressor; lung cancer ID TUMOR-SUPPRESSOR GENE; HISTONE DEACETYLASE COMPLEX; HUMAN CANCER-CELLS; CYTOSINE-5 METHYLTRANSFERASES; RENAL-CARCINOMA; LUNG-CANCER; IMMUNODEFICIENCY SYNDROME; HUMAN FIBROBLASTS; CPG METHYLATION; STEM-CELLS AB Transcriptional silencing of tumor suppressor genes in association with DNA methylation contributes to malignant transformation. However, the specific DNA methyltransferases that initiate this process are unknown. Here we show that a de novo DNA methyltransferase, DNMT3b, substantially contributes to the oncogenic phenotype in a lung cancer model. Normal human bronchial epithelial (NHBE) cells expressing telomerase, SV40 large T antigen, and activated Ras were immortal, formed colonies in soft agar, and expressed DNMT3b. Antisense suppression of DNMT3b prevented soft agar growth. Furthermore, mouse embryo fibroblasts expressing T antigen and Ras formed soft agar colonies and large tumors, but fibroblasts from Dnmt3b(-/-) mice did not grow in soft agar and were much less tumorigenic in vivo. The tumor suppressor genes, FHIT, TSLC1, and RASSF1A were downregulated in transformed NHBE cells, and antisense DNMT3b treatment resulted in re-expression of FHIT and TSLC1. While expression of TSCL1 correlated with methylation of CpG dinucleotides in its promoter region, the expression of FHIT did not, suggesting that DNMT3b may silence genes by several mechanisms including direct DNA methylation or recruitment of proteins that modify chromatin. Regardless of mechanism, our data indicate that DNMT3b plays an important role in transformation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, M430,44 Binney St, Boston, MA 02115 USA. NR 57 TC 73 Z9 80 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 24 PY 2003 VL 22 IS 30 BP 4723 EP 4733 DI 10.1038/sj.onc.1206510 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 701FF UT WOS:000184157000013 PM 12879017 ER PT J AU Krzyzanowska, MK Pintilie, M Tannock, IF AF Krzyzanowska, MK Pintilie, M Tannock, IF TI Factors associated with failure to publish large randomized trials presented at an oncology meeting SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FLORIDA SP Amer Soc Clin Oncol ID PUBLICATION BIAS; CLINICAL-TRIALS; ABSTRACTS; METAANALYSIS; COHORT; FATE; TIME AB Context Large clinical trials are the criterion standard for making treatment decisions, and nonpublication of the results of such trials can lead to bias in the literature and contribute to inappropriate medical decisions. Objectives To determine the rate of full publication of large randomized trials presented at annual meetings of the American Society of Clinical Oncology (ASCO), quantify bias against publishing nonsignificant results, and identify factors associated with time to publication. Design Survey of 510 abstracts from large (sample size, greater than or equal to200), phase 3, randomized controlled trials presented at ASCO meetings between 1989 and 1998. Trial results were classified as significant (Pless than or equal to.05 for the primary outcome measure) or nonsignificant (P>.05 or not reported), and the type of presentation and sponsorship were identified. Subsequent full publication was,identified using a search of MEDLINE and EMBASE, completed November 1, 2001; the search was updated in November 2002, using the Cochrane Register of Controlled Trials. Authors were contacted if the searches did not find evidence of publication. Main Outcome Measures Publication rate at 5 years; time from presentation to full publication. Results Of 510 randomized trials, 26% were not published in full within 5 years after presentation at the meeting. Eighty-one percent of the studies with significant results had been published by this time compared with 68% of the studies with nonsignificant results (P<.001). Studies with oral or plenary presentation were published sooner than those not presented (P=.002), and studies with pharmaceutical sponsorship were published sooner than studies with cooperative group sponsorship or studies for which sponsorship was not specified (P=.02). These factors remained significant in a multivariable model. The most frequent reason cited by authors for not publishing was lack of time, funds, or other resources. Conclusions A substantial number of large phase 3 trials presented at an international oncology meeting remain unpublished 5 years after presentation. Bias against publishing nonsignificant results is a problem even for large randomized trials. Non-publication breaks the contract that investigators make with trial participants, funding agencies, and ethics boards. C1 Univ Toronto, Princess Margaret Hosp, Dept Med Oncol, Toronto, ON M5G 2M9, Canada. Dana Farber Canc Inst, Dept Adult Oncol, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Princess Margaret Hosp, Dept Biostat, Toronto, ON M4X 1K9, Canada. RP Tannock, IF (reprint author), Univ Toronto, Princess Margaret Hosp, Dept Med Oncol, 610 Univ Ave,Room 5-208, Toronto, ON M5G 2M9, Canada. NR 28 TC 195 Z9 197 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 23 PY 2003 VL 290 IS 4 BP 495 EP 501 DI 10.1001/jama.290.4.495 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 703JB UT WOS:000184275300021 PM 12876092 ER PT J AU Neimark, MA Andermann, ML Hopfield, JJ Moore, CI AF Neimark, MA Andermann, ML Hopfield, JJ Moore, CI TI Vibrissa resonance as a transduction mechanism for tactile encoding SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vibrissa; whisker; somatosensory; resonance; rat; frequency ID CERCAL SENSORY SYSTEM; RAT; CORTEX; DISCRIMINATION; NEURONS; MOUSE AB We present evidence that resonance properties of rat vibrissae differentially amplify high-frequency and complex tactile signals. Consistent with a model of vibrissa mechanics, optical measurements of vibrissae revealed that their first mechanical resonance frequencies systematically varied from low ( 60 - 100 Hz) in longer, posterior vibrissae to high ( similar to 750 Hz) in shorter, anterior vibrissae. Resonance amplification of tactile input was observed in vivo and ex vivo, and in a variety of boundary conditions that are likely to occur during perception, including stimulation of the vibrissa with moving complex natural stimuli such as sandpaper. Vibrissae were underdamped, allowing for sharp tuning to resonance frequencies. Vibrissa resonance constitutes a potentially useful mechanism for perception of high-frequency and complex tactile signals. Amplification of small amplitude signals by resonance could facilitate detection of stimuli that would otherwise fail to drive neural activity. The systematic map of frequency sensitivity across the face could facilitate texture discrimination through somatotopic encoding of frequency content. These findings suggest strong parallels between vibrissa tactile processing and auditory encoding, in which the cochlea also uses resonance to amplify low-amplitude signals and to generate a spatial map of frequency sensitivity. C1 Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Martinos Ctr, Charlestown, MA 02129 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Moore, CI (reprint author), MIT, McGovern Inst, E25-436,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Moore, Christopher/C-5588-2009 NR 36 TC 104 Z9 107 U1 0 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL 23 PY 2003 VL 23 IS 16 BP 6499 EP 6509 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 704DX UT WOS:000184323900013 PM 12878691 ER PT J AU Morrow, DA Braunwald, E AF Morrow, DA Braunwald, E TI Future of biomarkers in acute coronary syndromes - Moving toward a multimarker strategy SO CIRCULATION LA English DT Editorial Material ID BRAIN NATRIURETIC PEPTIDE; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION; RISK STRATIFICATION; RENAL-INSUFFICIENCY; PROGNOSTIC VALUE; UNSTABLE ANGINA; TROPONIN-I; TACTICS-TIMI-18; INFLAMMATION C1 TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 24 TC 142 Z9 157 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 22 PY 2003 VL 108 IS 3 BP 250 EP 252 DI 10.1161/01.CIR.0000078080.37974.D2 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 703MB UT WOS:000184282200004 PM 12876133 ER PT J AU Gillessen, S Naumov, YN Nieuwenhuis, EES Exley, MA Lee, FS Mach, N Luster, AD Blumberg, RS Taniguchi, M Balk, SP Strominger, JL Dranoff, G Wilson, SB AF Gillessen, S Naumov, YN Nieuwenhuis, EES Exley, MA Lee, FS Mach, N Luster, AD Blumberg, RS Taniguchi, M Balk, SP Strominger, JL Dranoff, G Wilson, SB TI CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID V(ALPHA)14 NKT CELLS; RESPONSES IN-VIVO; ALPHA-GALACTOSYLCERAMIDE; CUTTING EDGE; ANTIGEN PRESENTATION; IL-4 PRODUCTION; ACTIVATION; MICE; EXPRESSION; COMPLEX AB CD1d-restricted T cells contribute to tumor protection, but their precise roles remain unclear. Here we show that tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor induce the expansion of CD1d-restricted T cells through a mechanism that involves CD1d and macrophage inflammatory protein 2 expression by CD8alpha(-), CD11c(+) dendritic cells (DCs). The antitumor immunity stimulated by vaccination with irradiated, granulocyte-macrophage colony-stimulating factor-secreting tumor cells was abrogated in CD1d- and Jalpha281-deficient mice, revealing a critical role for CD1d-restricted T cells in this response. The loss of antitumor immunity was associated with impaired tumor-induced T helper 2 cytokine production, although IFN-gamma secretion and cytotoxicity were preserved. DCs from immunized CD1d-deficient mice showed compromised maturation and function. Together, these results delineate a role for CD1d-restricted T cell-DC cross talk in the shaping of antitumor immunity. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Gastrointestinal Div, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02115 USA. Massachusetts Gen Hosp E, Dept Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Chiba Univ, Core Res Evolut Sci & Technol Project, Chiba 2608670, Japan. Chiba Univ, Dept Mol Immunol, Chiba 2608670, Japan. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Diabet Res Labs, Cambridge, MA 02138 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Taniguchi, Masaru/N-7932-2015 OI Taniguchi, Masaru/0000-0001-7821-7179 FU NCI NIH HHS [R01 CA074886]; NIAID NIH HHS [R01 AI045051] NR 56 TC 61 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 2003 VL 100 IS 15 BP 8874 EP 8879 DI 10.1073/pnas.1033098100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 704ZC UT WOS:000184371000052 PM 12847287 ER PT J AU Klein, L Khazaie, K von Boehmer, H AF Klein, L Khazaie, K von Boehmer, H TI In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYMIC SELECTION; SELF-PEPTIDE; TOLERANCE; CD25(+); ANERGY; AUTOIMMUNITY; RESPONSES; IL-2; REQUIREMENTS; SUPPRESSION AB Adoptive transfer of antigen-specific CD25(+)CD4(+) regulatory T cells was used to analyze the stability of their phenotype, their behavior after immunization, and their mode of suppressing cotransferred naive T cells in vivo. We found that regulatory T cells maintained their phenotype in the absence of antigen, were not anergic in vivo, and proliferated as extensively as naive CD4(+) T cells after immunization without losing their suppressive function in vivo and in vitro. In vivo, the expansion of cotransferred naive T cells was suppressed relatively late in the response such that regulatory T cells expressing mostly IL-10 but not IL-2 or IFN-gamma represented the dominant subset of cells. Our results reveal properties of regulatory T cells that were not predicted from in vitro studies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 FU NIAID NIH HHS [R37 AI053102, 1R01AI53102] NR 34 TC 305 Z9 315 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 2003 VL 100 IS 15 BP 8886 EP 8891 DI 10.1073/pnas.1533365100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 704ZC UT WOS:000184371000054 PM 12857946 ER PT J AU St-Pierre, J Lin, J Krauss, S Tarr, PT Yang, RJ Newgard, CB Spiegelman, BM AF St-Pierre, J Lin, J Krauss, S Tarr, PT Yang, RJ Newgard, CB Spiegelman, BM TI Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1 alpha and 1 beta (PGC-1 alpha and PGC-1 beta) in muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL INNER MEMBRANE; UNCOUPLING PROTEIN HOMOLOG; PROTON LEAK; INDUCIBLE COACTIVATOR; METABOLIC DEPRESSION; LIVER-MITOCHONDRIA; THYROID-HORMONE; MAMMALIAN-CELLS; THERMOGENESIS; RESPIRATION AB Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha is a coactivator of nuclear receptors and other transcription factors that regulates several components of energy metabolism, particularly certain aspects of adaptive thermogenesis in brown fat and skeletal muscle, hepatic gluconeogenesis, and fiber type switching in skeletal muscle. PGC-1alpha has been shown to induce mitochondrial biogenesis when expressed in muscle cells, and preliminary analysis has suggested that this molecule may specifically increase the fraction of uncoupled versus coupled respiration. In this paper, we have performed detailed bioenergetic analyses of the function of PGC-1alpha and its homolog PGC-1beta in muscle cells by monitoring simultaneously oxygen consumption and membrane potential. Cells expressing PGC-1alpha or PGC-1beta display higher proton leak rates at any given membrane potential than control cells. However, cells expressing PGC-1alpha have a higher proportion of their mitochondrial respiration linked to proton leak than cells expressing PGC-1beta. Although these two proteins cause a similar increase in the expression of many mitochondrial genes, PGC-1beta preferentially induces certain genes involved in the removal of reactive oxygen species, recently recognized as activators of uncoupling proteins. Together, these data indicate that PGC-1alpha and PGC-1beta profoundly alter mitochondrial metabolism and suggest that these proteins are likely to play different physiological functions. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Sarah W Stedman Ctr Nutr Studies, Durham, NC 27710 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way,SM958, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK54477] NR 35 TC 324 Z9 339 U1 1 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 18 PY 2003 VL 278 IS 29 BP 26597 EP 26603 DI 10.1074/jbc.M301850200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701ER UT WOS:000184155700041 PM 12734177 ER PT J AU Park, KM Byun, JY Kramers, C Kim, JI Huang, PL Bonventre, JV AF Park, KM Byun, JY Kramers, C Kim, JI Huang, PL Bonventre, JV TI Inducible nitric-oxide synthase is an important contributor to prolonged protective effects of ischemic preconditioning in the mouse kidney SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE-RENAL-FAILURE; INDUCED FUNCTIONAL INJURY; MAPK KINASE ACTIVATION; HEAT-SHOCK PROTEINS; L-ARGININE; CELL INJURY; URETERAL OBSTRUCTION; REPERFUSION INJURY; CONSCIOUS RABBITS; CARDIAC MYOCYTES AB Ischemic preconditioning renders the mouse kidney resistant to subsequent ischemia. Understanding the mechanisms responsible for ischemic preconditioning is important for formulating therapeutic strategies aimed at mimicking protective mechanisms. We report that the resistance afforded by 30 min of bilateral kidney ischemia persists for 12 weeks after preconditioning. The protection is reflected by improved postischemic renal function, reduced leukocyte infiltration, reduced postischemic disruption of the actin cytoskeleton, and reduced postischemic expression of kidney injury molecule-1 (Kim-1). The protection is observed in both BALB/c and C57BL/6J strains of mice. Thirty minutes of prior ischemia increases the expression of inducible nitric-oxide synthase ( iNOS) and endothelial NOS ( eNOS) and the expression of heat shock protein (HSP)-25 and is associated with increased interstitial expression of alpha-smooth muscle actin (alpha-SMA), an indication of long term postischemic sequelae. Treatment with Nomega-nitro-L-arginine (L-NNA), an inhibitor of NO synthesis, increases kidney susceptibility to ischemia. Gene deletion of iNOS increases kidney susceptibility to ischemia, whereas gene deletion of eNOS has no effect. Pharmacological inhibition of NOS by L-NNA or L-N6-(1-iminoethyl) lysine (L-NIL, a specific inhibitor of iNOS) mitigates the kidney protection afforded by 30 min of ischemic preconditioning. Fifteen minutes of prior ischemic preconditioning, which does not result in the disruption of the actin cytoskeleton, impairment of renal function, increased interstitial alpha-SMA, or increased iNOS or eNOS expression, but does increase HSP-25 expression, partially protects the kidney from ischemia on day 8 via a mechanism that is not abolished by L-NIL treatment. Thus, iNOS is responsible for a significant component of the long term protection afforded the kidney by ischemic preconditioning, which results in persistent renal interstitial disease, but does not explain the preconditioning seen with shorter periods of ischemia. C1 Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Med Serv, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Bonventre, JV (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, MRB4,75 Francis St, Boston, MA 02115 USA. RI Kramers, C./L-4458-2015 FU NIDDK NIH HHS [DK 38452, DK 39773]; NINDS NIH HHS [NS 10828] NR 55 TC 134 Z9 140 U1 1 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 JUL 18 PY 2003 VL 278 IS 29 BP 27256 EP 27266 DI 10.1074/jbc.M301778200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701ER UT WOS:000184155700122 PM 12682064 ER PT J AU Tsui, CP Sung, JJY Leung, FW AF Tsui, CP Sung, JJY Leung, FW TI Role of acute elevation of portal venous pressure by exogenous glucagon on gastric mucosal injury in rats with portal hypertension SO LIFE SCIENCES LA English DT Review DE portal hypertension; gastric mucosal injury; portal venous pressure; glucagon; somatostatin ID NITRIC-OXIDE SYNTHASE; ENDOSCOPIC VARICEAL LIGATION; ENDOTHELIAL GROWTH-FACTOR; BLOOD-FLOW DISTRIBUTION; CIRRHOTIC-PATIENTS; CONGESTIVE GASTROPATHY; ACID-SECRETION; HYPERDYNAMIC CIRCULATION; HELICOBACTER-PYLORI; SOMATOSTATIN ANALOG AB Time-course studies revealed the increased susceptibility of the gastric mucosa to noxious injury in portal hypertension correlates with the level of elevated portal venous pressure and hyperglucagonemia. Whether acute elevation of portal venous pressure by exogenous glucagon aggravates such injury is not known. We tested the hypothesis that glucagon in a dose sufficient to acutely elevate portal venous pressure aggravates noxious injury of the gastric mucosa in rats with portal hypertension. Infusion of a portal hypotensive dose of somatostatin should reverse these changes. In anesthetized rats with portal vein ligation, glucagon, somatostatin or the combination was administered intravenously in a randomized, coded fashion. Acidified ethanol-induced gastric mucosal injury was determined. Portal venous pressure and gastric mucosal perfusion and oxygenation (reflectance spectrophotometry) were monitored to confirm the effects of the respective intravenous treatments. Exogenous glucagon exacerbated acidified ethanol-induced gastric mucosal injury. The exacerbation was attenuated by somatostatin. These changes paralleled the portal hypertensive and hypotensive effects. of glucagon and somatostatin, respectively. Our data suggest that a unique mechanism is triggered with the onset of portal hypertension. In an antagonistic manner, glucagon and somatostatin modulate this novel mechanism that controls portal venous pressure and susceptibility of the gastric mucosa to noxious injury. Published by Elsevier Science Inc. C1 W Los Angeles Vet Affairs Med Ctr, Med Res Serv, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ, Sepulveda, CA 91343 USA. RP Leung, FW (reprint author), W Los Angeles Vet Affairs Med Ctr, Med Res Serv, Sepulveda Ambulatory Care Ctr, Sepulveda, CA 91343 USA. RI Hossain, Sarah /C-7332-2009 OI Hossain, Sarah /0000-0003-1355-0979 NR 136 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD JUL 18 PY 2003 VL 73 IS 9 BP 1115 EP 1129 DI 10.1016/S0024-3205(03)00413-2 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 694RK UT WOS:000183787900003 PM 12818720 ER PT J AU Jasmin, L Rabkin, SD Granato, A Boudah, A Ohara, PT AF Jasmin, L Rabkin, SD Granato, A Boudah, A Ohara, PT TI Analgesia and hyperalgesia from GABA-mediated modulation of the cerebral cortex SO NATURE LA English DT Article AB It is known that pain perception can be altered by mood, attention and cognition, or by direct stimulation of the cerebral cortex(1), but we know little of the neural mechanisms underlying the cortical modulation of pain. One of the few cortical areas consistently activated by painful stimuli is the rostral agranular insular cortex (RAIC) where, as in other parts of the cortex, the neurotransmitter gamma-aminobutyric acid (GABA) robustly inhibits neuronal activity. Here we show that changes in GABA neurotransmission in the RAIC can raise or lower the pain threshold-producing analgesia or hyperalgesia, respectively-in freely moving rats. Locally increasing GABA, by using an enzyme inhibitor or gene transfer mediated by a viral vector, produces lasting analgesia by enhancing the descending inhibition of spinal nociceptive neurons. Selectively activating GABA(B)-receptor-bearing RAIC neurons produces hyperalgesia through projections to the amygdala, an area involved in pain and fear. Whereas most studies focus on the role of the cerebral cortex as the end point of nociceptive processing, we suggest that cerebral cortex activity can change the set-point of pain threshold in a top-down manner. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02129 USA. Catholic Univ, Dept Psychol, I-20123 Milan, Italy. RP Jasmin, L (reprint author), Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; GRANATO, Alberto/0000-0003-3755-1036 NR 30 TC 185 Z9 189 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 17 PY 2003 VL 424 IS 6946 BP 316 EP 320 DI 10.1038/nature01808 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 701RZ UT WOS:000184183900043 PM 12867983 ER PT J AU Devor, A Dunn, AK Andermann, ML Ulbert, I Boas, DA Dale, AM AF Devor, A Dunn, AK Andermann, ML Ulbert, I Boas, DA Dale, AM TI Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex SO NEURON LA English DT Article ID CURRENT SOURCE-DENSITY; CEREBRAL-BLOOD-FLOW; EVENT-RELATED FMRI; ACTIVITY-DEPENDENT INCREASES; NEURONAL-ACTIVITY; BARREL CORTEX; EVOKED-POTENTIALS; BRAIN ACTIVITY; IMAGING SPECTROSCOPY; SENSORY STIMULATION AB Recent advances in brain imaging techniques, including functional magnetic resonance imaging (fMRI), offer great promise for noninvasive mapping of brain function. However, the indirect nature of the imaging signals to the underlying neural activity limits the interpretation of the resulting maps. The present report represents the first systematic study with sufficient statistical power to quantitatively characterize the relationship between changes in blood oxygen content and the neural spiking and synaptic activity. Using two-dimensional optical measurements of hemodynamic signals, simultaneous recordings of neural activity, and an event-related stimulus paradigm, we demonstrate that (1) there is a strongly nonlinear relationship between electrophysiological measures of neuronal activity and the hemodynamic response, (2) the hemodynamic response continues to grow beyond the saturation of electrical activity, and (3) the initial increase in deoxyhemogloblin that precedes an increase in blood volume is counterbalanced by an equal initial decrease in oxyhemoglobin. C1 Massachusetts Gen Hosp, NMR Ctr, Harvard Med Sch, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Biophys, Boston, MA 02115 USA. Hungarian Acad Sci, Inst Psychol, H-1068 Budapest, Hungary. RP Devor, A (reprint author), Massachusetts Gen Hosp, NMR Ctr, Harvard Med Sch, Charlestown, MA 02129 USA. RI Ulbert, Istvan/F-2213-2010; Dale, Anders/A-5180-2010; Dunn, Andrew/I-9527-2014 FU NCRR NIH HHS [P41 RR14075, R01 RR13609]; NIBIB NIH HHS [R01 EB000790, R01 EB00790-01A2]; NINDS NIH HHS [R01 NS044623] NR 52 TC 235 Z9 237 U1 0 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 17 PY 2003 VL 39 IS 2 BP 353 EP 359 DI 10.1016/S0896-6273(03)00403-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 703AC UT WOS:000184256800014 PM 12873390 ER PT J AU Fihn, SD AF Fihn, SD TI Acute uncomplicated urinary tract infection in women SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SPERMICIDE-COATED CONDOMS; RISK-FACTORS; TRIMETHOPRIM-SULFAMETHOXAZOLE; POSTMENOPAUSAL WOMEN; ESCHERICHIA-COLI; YOUNG-WOMEN; RANDOMIZED TRIAL; ANTIMICROBIAL RESISTANCE; ACUTE CYSTITIS; DOUBLE-BLIND C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Fihn, SD (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, 152,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [2-R01-DK431341-07] NR 54 TC 103 Z9 119 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 17 PY 2003 VL 349 IS 3 BP 259 EP 266 DI 10.1056/NEJMcp030027 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 701KA UT WOS:000184165700011 PM 12867610 ER PT J AU Daily, JP Waldron, MA Harris, NL Brown, DF AF Daily, JP Waldron, MA Harris, NL Brown, DF TI Case 22-2003: A 22-year-old man with chills and fever after a stay in South America - Plasmodium vivax malaria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AMEBIC LIVER-ABSCESS; FALCIPARUM-MALARIA; RETURNED TRAVELER; BARTONELLOSIS; CHLOROQUINE; MICROSCOPY; RESISTANCE; DIAGNOSIS; PARASITES; OUTBREAK C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Clin Microbiol labs, Parasitol Sect, Boston, MA 02114 USA. RP Daily, JP (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 36 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 17 PY 2003 VL 349 IS 3 BP 287 EP 295 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 701KA UT WOS:000184165700014 PM 12867613 ER PT J AU Cho, EY Spiegelinan, D Hunter, DJ Chen, WY Stampfer, MJ Colditz, GA Willett, WC AF Cho, EY Spiegelinan, D Hunter, DJ Chen, WY Stampfer, MJ Colditz, GA Willett, WC TI Premenopausal fat intake and risk of breast cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HORMONE-RECEPTOR STATUS; SERUM ESTROGEN-LEVELS; DIETARY-FAT; FOOD-CONSUMPTION; POOLED ANALYSIS; POSTMENOPAUSAL WOMEN; NORWEGIAN WOMEN; DAIRY-PRODUCTS; COHORT; METAANALYSIS AB Background: International comparisons and case-control studies have suggested a positive relation between dietary fat intake and breast cancer risk, but prospective studies, most of them involving postmenopausal women, have not supported this association. We conducted a prospective analysis of the relation between dietary fat intake and breast cancer risk among premenopausal women enrolled in the Nurses' Health Study II. Methods: Dietary fat intake and breast cancer risk were assessed among 90 655 premenopausal women aged 26 to 46 years in 1991. Fat intake was assessed with a food-frequency questionnaire at baseline in 1991 and again in 1995. Breast cancers were self-reported and confirmed by review of pathology reports. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. Results: During 8 years of follow-up, 714 women developed incident invasive breast cancer. Relative to women in the lowest quintile of fat intake, women in the highest quintile of intake had a slight increased risk of breast cancer (RR = 1.25, 95% CI = 0.98 to 1.59; P-trend = .06). The increase was associated with intake of animal fat but not vegetable fat; RRs for the increasing quintiles of animal fat intake were 1.00 (referent), 1.28, 1.37, 1.54, and 1.33 (95% Cl = 1.02 to 1.73; P-trend = .002). Intakes of both saturated and monounsaturated fat were related to modestly elevated breast cancer risk. Among food groups contributing to animal fat, red meat and high-fat dairy foods were each associated with an increased risk of breast cancer. Conclusions: Intake of animal fat, mainly from red meat and high-fat dairy foods, during premenopausal years is associated with an increased risk of breast cancer. C1 Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, 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. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Cho, EY (reprint author), Harvard Univ, Sch Med, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM eunyoung.cho@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385] NR 36 TC 142 Z9 146 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUL 16 PY 2003 VL 95 IS 14 BP 1079 EP 1085 PG 7 WC Oncology SC Oncology GA 703QB UT WOS:000184291500014 PM 12865454 ER PT J AU Plomondon, ME Rumsfeld, JS Humble, CG Meterko, M McDonald, GO Grover, FL Perlin, JB Shroyer, ALW AF Plomondon, ME Rumsfeld, JS Humble, CG Meterko, M McDonald, GO Grover, FL Perlin, JB Shroyer, ALW TI Factors influencing risk-adjusted patient satisfaction after coronary artery bypass grafting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-SURGERY; HOSPITAL-CARE; QUALITY C1 Denver VA Med Ctr, Denver, CO 80220 USA. Performance Anal Ctr Excellence, Morrisville, NC USA. HSR&D Management Decis & Res Ctr, Boston, MA USA. VA Off Patient Care Serv, Washington, DC USA. Veterans Hlth Adm, Washington, DC USA. RP Plomondon, ME (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80220 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 15 PY 2003 VL 92 IS 2 BP 206 EP 208 DI 10.1016/S0002-9149(03)00540-X PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 701HW UT WOS:000184163000017 PM 12860226 ER PT J AU Levine, GN Kem, MJ Berger, PB Brown, DL Klein, LW Kereiakes, DJ Sanborn, TA Jacobs, AK AF Levine, GN Kem, MJ Berger, PB Brown, DL Klein, LW Kereiakes, DJ Sanborn, TA Jacobs, AK CA American Heart Assoc Diagnostic In TI Management of patients undergoing percutaneous coronary revascularization SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID PLATELET GLYCOPROTEIN-IIB/IIIA; PRACTICE GUIDELINES COMMITTEE; AMERICAN-HEART-ASSOCIATION; PERIPHERAL VASCULAR COMPLICATIONS; ACCESS SITE COMPLICATIONS; IODINATED CONTRAST-MEDIA; PLACEBO-CONTROLLED TRIAL; ADVERSE CARDIAC EVENTS; ACUTE-RENAL-FAILURE; RADIOCONTRAST-INDUCED NEPHROPATHY AB While performance of percutaneous coronary intervention (PCl) remains the domain of specialized cardiologists, patients undergoing PCl are cared for by noninvasive cardiologists, internists, and primary care physicians. Therefore, patient care is optimized when the entire patient care team understands procedural risks and complications as well as optimum patient management before, during, and after PCl. Before PCl, patients with contrast dye allergies should be identified and pretreated with steroids and an H,-blocker. Hydration should be initiated and maintained before and after the procedure to minimize the risks for contrast nephropathy. Periprocedure, patients should be monitored clinically for evidence of ischemia. In patients with significant groin, flank, abdominal, or back pain, as well as those with decrease in hematocrit or unexplained hypotension, the diagnosis of groin or retroperitoneal hematoma should be considered and promptly evaluated. Groin tenderness, pulsatile mass, or bruit should prompt evaluation for possible femoral pseudoaneurysm or arteriovenous fistulae. After the procedure, all patients treated with coronary stents should receive aspirin plus clopidogrel. Patients who develop typical anginal symptoms between the 1st and 6th to 8th months after PCl are likely to have restenosis and can be evaluated by an imaging study or repeated catheterization. C1 Baylor Coll Med, Houston, TX 77030 USA. St Louis Univ, St Louis, MO 63103 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Rush Med Coll, Chicago, IL 60612 USA. Lindner Res Ctr, Cincinnati, OH USA. Ohio Heart Hlth Ctr, Cincinnati, OH USA. Evanston NW Healthcare, Evanston, IL USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Levine, GN (reprint author), Houston Vet Affairs Med Ctr, Cardiol Sect, 3C-330,111-B,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 181 TC 58 Z9 60 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 2003 VL 139 IS 2 BP 123 EP 136 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 701HX UT WOS:000184163100006 PM 12859162 ER PT J AU Takayama, K Hayes, B Vestling, MM Massey, RJ AF Takayama, K Hayes, B Vestling, MM Massey, RJ TI Transposon-5 mutagenesis transforms Corynebacterium matruchotii to synthesize novel hybrid fatty acids that functionally replace corynomycolic acid SO BIOCHEMICAL JOURNAL LA English DT Article DE Claisen-type condensation; corynomycolic acid; electrospray MS; electron-impact MS; transposon-5 mutagenesis; ultrathin section electron microscopy ID CELL-FREE SYSTEM; MYCOBACTERIUM-TUBERCULOSIS; MYCOLIC ACIDS; BACTERIONEMA-MATRUCHOTII; BIOSYNTHESIS; TREHALOSE; WALL; IDENTIFICATION; DIPHTHERIAE; VIRULENCE AB Enzymes within the biosynthetic pathway of mycolic acid (C-60- C-90 alpha-alkyl, beta-hydroxyl fatty acid) in Mycobacterium tuberculosis are attractive targets for developing new anti-tuberculosis drugs. We have turned to the simple model system of Corynebacterium matruchotii to study the terminal steps in the anabol pathway of a C-32 mycolic acid called corynomycolic acid. By transposon-5 mutagenesis. we transformed C. matruchotii into a mutant that is unable to synthesize corynomycolic acid. Instead, it synthesized two related series of novel fatty acids that were released by saponification front the cell wall fraction and from two chloroform/methanol-extractable glycolipids presumed to be analogues of trehalose mono- and di-corynomycolate. By chemical analyses and MS, we determined the general structure of the two series to be 2.4.6,8, 10-penta-alkyl decanoic acid for the larger series (C-70-C-77) and 2.4,6,8 -tetra-alkyl octanoic acid for the smaller series (C-52-C-64), both containing multiple keto groups, hydroxy groups and double bonds. The mutant was temperaturesensitive, aggregated extensively, grew very slowly relative to the wild type, and was resistant to the presence of lysozyme. We suggest that a regulatory protein that normally prevents the transfer of the condensation product back to P-ketoacyl synthase in the corynomycolate synthase system of the wild type was inactivated in the mutant. This will result in multiple Claisen-type condensation and the formation of two similar series of these complex hybrid fatty acids. A similar protein in M. tuberculosis would be an attractive target for new drug discovery. C1 William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. Univ Wisconsin, Dept Chem, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Electron Microscope Facil, Madison, WI 53706 USA. RP Takayama, K (reprint author), William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 31 TC 5 Z9 5 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 2003 VL 373 BP 465 EP 474 DI 10.1042/BJ20030248 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 705HR UT WOS:000184390100015 PM 12879902 ER PT J AU Allsopp, RC Morin, GB DePinho, R Harley, CB Weissman, IL AF Allsopp, RC Morin, GB DePinho, R Harley, CB Weissman, IL TI Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; IN-VIVO; MICE; LENGTH; MARROW; CANCER; RNA AB Telomere shortening ultimately limits the replicative life span of cultured human somatic cells. Telomeres also shorten during replicative aging in vivo in hematopoietic cells, including early hematopoietic progenitors and hematopoietic stem cells (HSCs), from humans and mice, despite readily detectable levels of telomerase in these cells. To assess the relevance of telomerase to the long-term replicative capacity of HSCs in vivo, we serially transplanted HSCs from wild-type and telomerase-deficient mice until exhaustion and monitored telomere length in HSCs during this process. Telomerase-deficient HSCs could be serially transplanted for only 2 rounds, whereas wild-type HSCs could be serially transplanted for at least 4 rounds. Furthermore, the rate of telomere shortening was increased approximately 2-fold during serial transplantation of telomerase-deficient HSCs. These findings suggest that one role for telomerase in the HSC is to partially counter the rate of telomere shortening during division of HSCs, thereby preventing premature loss of telomere function and providing added replicative capacity. (C) 2003 by The American Society of Hematology. C1 Stanford Univ, Sch Med, Dept Pathol, Beckman Ctr, Stanford, CA 94305 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Geron, Menlo Pk, CA USA. RP Allsopp, RC (reprint author), Stanford Univ, Sch Med, Dept Pathol, Beckman Ctr, Rm B259, Stanford, CA 94305 USA. RI Tang, Macy/B-9798-2014; Morin, Gregg/E-9123-2012 OI Morin, Gregg/0000-0001-8949-4374 FU NCI NIH HHS [CA 42551]; NIDDK NIH HHS [DK 53074] NR 23 TC 189 Z9 210 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2003 VL 102 IS 2 BP 517 EP 520 DI 10.1182/blood-2002-07-2334 PG 4 WC Hematology SC Hematology GA 699XY UT WOS:000184083500024 PM 12663456 ER PT J AU Fischbach, MA Settleman, J AF Fischbach, MA Settleman, J TI Specific biochemical inactivation of oncogenic Ras proteins by nucleoside diphosphate kinase SO CANCER RESEARCH LA English DT Article ID METASTASIS SUPPRESSOR NM23; TUMOR-METASTASIS; 3-DIMENSIONAL STRUCTURES; SIGNAL-TRANSDUCTION; GTP; MECHANISM; CANCER; MUTANTS; ACTIVATION; BETA AB Activating mutations of Ras have been implicated in similar to30% of human cancers. In every case, the biochemical consequence of such mutations is to disrupt the GTPase activity of Ras and to render Ras resistant to the actions of GTPase activating proteins. Consequently, oncogenic Ras mutants are "locked" in a GTP-bound active state. We detected a potent activity in Escherichia coli extract that can efficiently convert mutationally activated GTP-bound Ras to the inactive GDP-bound form. Purification of the protein responsible for this activity led to the identification of the enzyme nucleoside diphosphate kinase (Ndk). The human orthologue of Ndk is the NM23 metastasis suppressor, which we found to exhibit a similar activity. Purified Ndk effectively inactivates several of the oncogenic forms of Ras that are seen frequently in human cancers, including RasD12, the most commonly detected Ras mutation. Significantly, Ndk does not detectably affect wild-type Ras or an activated form of the Ras-related Rho GTPase. These results demonstrate that it is possible, through biochemical means, to specifically inactivate oncogenic Ras as a potential therapeutic approach to tumors that harbor Ras mutations. Moreover, the results suggest that the loss of NM23 expression that is commonly observed during tumor progression could lead to increased potency of oncogenic Ras proteins. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. NR 29 TC 11 Z9 13 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2003 VL 63 IS 14 BP 4089 EP 4094 PG 6 WC Oncology SC Oncology GA 705DE UT WOS:000184379800041 PM 12874011 ER PT J AU Buckhaults, P Zhang, Z Chen, YC Wang, TL St Croix, B Saba, S Bardelli, A Morin, PJ Polyak, K Hruban, RH Velculescu, VE Shih, IM AF Buckhaults, P Zhang, Z Chen, YC Wang, TL St Croix, B Saba, S Bardelli, A Morin, PJ Polyak, K Hruban, RH Velculescu, VE Shih, IM TI Identifying tumor origin using a gene expression-based classification map SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER ANTIGEN; MOLECULAR CLASSIFICATION; SERIAL ANALYSIS; IDENTIFICATION; PREDICTION; DIAGNOSIS; CA125; MUC16; MUCIN AB Identifying the primary site in cases of metastatic carcinoma of unknown origin has profound clinical importance in managing cancer patients. Although transcriptional profiling promises molecular solutions to this clinical challenge, simpler and more reliable methods for this purpose are needed. A training set of 11 serial analysis of gene expression (SAGE) libraries was analyzed using a combination of supervised and unsupervised computational methods to select a small group of candidate genes with maximal power to discriminate carcinomas of different tissue origins. Quantitative real-time PCR was used to measure their expression levels in an independent validation set of 62 samples of ovarian, breast, colon, and pancreatic adenocarcinomas and normal ovarian surface epithelial controls. The diagnostic power of this set of genes was evaluated using unsupervised cluster analysis methods. From the training set of 21,321 unique SAGE transcript tags derived from 11 libraries, five genes were identified with expression patterns that distinguished four types of adenocarcinomas. Quantitative real-time PCR expression data obtained from the validation set clustered tumor samples in an unsupervised manner, generating a self-organized map with distinctive tumor site-specific domains. Eighty-one percent (50 of 62) of the carcinomas were correctly allocated in their corresponding diagnostic regions. Metastases clustered tightly with their corresponding primary tumors. A classification map diagnostic of tumor types was generated based on expression patterns of five genes selected from the SAGE database. This expression map analysis may provide a reliable and practical approach to determine tumor type in cases of metastatic carcinoma of clinically unknown origin. C1 Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21231 USA. NCI, Frederick, MD 21701 USA. NIA, Baltimore, MD 21224 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shih, IM (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 418 N Bond St,B-315, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA97527, P50-CA62924] NR 26 TC 68 Z9 69 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2003 VL 63 IS 14 BP 4144 EP 4149 PG 6 WC Oncology SC Oncology GA 705DE UT WOS:000184379800049 PM 12874019 ER PT J AU Nabors, LLB Suswam, E Huang, YY Yang, XH Johnson, MJ King, PH AF Nabors, LLB Suswam, E Huang, YY Yang, XH Johnson, MJ King, PH TI Tumor necrosis factor a induces angiogenic factor up-regulation in malignant glioma cells: A role for RNA stabilization and HuR SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BINDING PROTEIN HUR; LYMPHOKINE MESSENGER-RNA; 3' UNTRANSLATED REGION; URIDINE-RICH ELEMENTS; FACTOR-ALPHA; BRAIN-TUMORS; 3'-UNTRANSLATED REGION; STABILITY FACTOR; MAMMALIAN-CELLS AB Malignant glioma (MG) cells up-regulate angiogenic factor expression in response to different extracellular signals such as hypoxia and cytokines. This up-regulation in turn promotes angiogenesis and tumor progression. Posttranscriptional gene regulation has been implicated as one mechanism for this tumor response, and we have previously shown that HuR, a protein associated with RNA stabilization, is overexpressed in MGs (L. B. Nabors et al., Cancer Res., 61: 2154-2161, 2001). Here, we demonstrate a marked up-regulation (RNA and protein) of tumor necrosis factor alpha (TNF-alpha), interleukin 8, and, to a lesser extent, vascular endothelial growth factor in U251 glioma cells after stimulation with TNF-alpha. RNA kinetic studies indicated that TNF-alpha induced the stabilization of all three transcripts. Using a luciferase reporter assay, we demonstrate that the AU-rich elements (AREs) in the 3'-untranslated region of these genes significantly contribute to this posttranscriptional regulation. UV cross-linking and immunoprecipitation with glioma extracts indicate that HuR binds to all three ARFs. When HuR is overexpressed in glioma cells, there is enhanced RNA stabilization of all three angiogenic factor transcripts with a concomitant increase in mRNA and protein expression (up to 7-fold). These findings indicate that TNF-alpha up-regulates angiogenic factor expression in MG cells and that RNA stabilization, via the AREs in the 3'-untranslated region, contributes to this up-regulation. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. Univ Alabama, Dept Clin Pharmacol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP King, PH (reprint author), Univ Alabama, Dept Neurol, 1235 Jefferson Tower,625 S 19th St, Birmingham, AL 35294 USA. NR 46 TC 89 Z9 102 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2003 VL 63 IS 14 BP 4181 EP 4187 PG 7 WC Oncology SC Oncology GA 705DE UT WOS:000184379800054 PM 12874024 ER PT J AU Jin, SH Mao, H Schnepp, RW Sykes, SM Silva, AC D'Andrea, AD Hua, XX AF Jin, SH Mao, H Schnepp, RW Sykes, SM Silva, AC D'Andrea, AD Hua, XX TI Menin associates with FANCD2, a protein involved in repair of DNA damage SO CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; FANCONI-ANEMIA PROTEINS; NUCLEAR-MATRIX; POSITIONAL CLONING; EPITHELIAL-CELLS; S-PHASE; GENE; TYPE-1; TRANSCRIPTION; CHROMATIN AB Multiple endocrine neoplasia type I (MEN1) is an inherited tumor syndrome characterized by tumors in multiple endocrine organs including the parathyroids, pancreatic islets, and the pituitary. The gene mutated in MEN1 patients, Men1, encodes a protein of 610 amino acid residues, menin, and mutations in the Men1 gene lead to the MEN1 syndrome. Although the chromosomal instability in the peripheral lymphocytes from the MEN1 patients has been reported previously, it is not clear whether menin is involved in repair of DNA damage. Here we show that menin specifically interacts with FANCD2, a protein encoded by a gene involved in DNA repair and mutated in patients with an inherited cancer-prone syndrome, Fanconi anemia. The interaction between menin and FANCD2 is enhanced by gamma-irradiation. Moreover, loss of menin expression in mouse embryonic fibroblasts leads to increased sensitivity to DNA damage. Furthermore, menin is localized to chromatin and nuclear matrix, and the association with nuclear matrix is enhanced by gamma-irradiation. Together, these results suggest that menin plays a critical role in repair of DNA damage in concert with FANCD2. C1 Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Dept Canc Biol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Hua, XX (reprint author), Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Dept Canc Biol, 412 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [K01 CA078592-06, 1K01CA78592] NR 54 TC 107 Z9 113 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2003 VL 63 IS 14 BP 4204 EP 4210 PG 7 WC Oncology SC Oncology GA 705DE UT WOS:000184379800057 PM 12874027 ER PT J AU Bozkurt, B Mann, DL AF Bozkurt, B Mann, DL TI Shortness of breath SO CIRCULATION LA English DT Article C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. RP Bozkurt, B (reprint author), Houston VA Med Ctr, 4C211,2002 Holocombe Blvd, Houston, TX 77030 USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 15 PY 2003 VL 108 IS 2 BP E11 EP E13 DI 10.1161/01.CIR.000007595.36340.78 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 701DL UT WOS:000184152900001 PM 12860894 ER PT J AU Parodi, S Lechner, A Osih, R Vespa, P Pegues, D AF Parodi, S Lechner, A Osih, R Vespa, P Pegues, D TI Nosocomial enterobacter meningitis: Risk factors, management, and treatment outcomes SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NEGATIVE BACILLARY MENINGITIS; EXTERNAL VENTRICULAR DRAINS; INTRACRANIAL-PRESSURE MONITORS; INTENSIVE-CARE UNIT; BACTERIAL-MENINGITIS; MOLECULAR EPIDEMIOLOGY; NEUROSURGICAL PATIENTS; TRIMETHOPRIM-SULFAMETHOXAZOLE; 3RD-GENERATION CEPHALOSPORINS; RESISTANT ENTEROBACTER AB Enterobacter species are increasingly a cause of nosocomial meningitis among neurosurgery patients, but risk factors for these infections are not well defined. A review of all adult patients hospitalized at the University of California-Los Angeles (UCLA) Medical Center during an 8-year period identified 15 postneurosurgical cases of Enterobacter meningitis (EM). Cure was achieved in 14 cases (93%), and efficacy was similar for carbapenem- and cephalosporin-based treatment. A matched case-control study comparing 26 controls with 13 case patients hospitalized exclusively at the UCLA Medical Center found that external cerebrospinal fluid (CSF) drainage devices (odds ratio [OR], 21.8; P=.001), isolation of Enterobacter species from a non-CSF culture (OR, 24.6; P=.002), and prolonged administration of antimicrobial drugs before the diagnosis of meningitis that were inactive in vitro against Enterobacter species (OR, 13.3; P=.008) were independent risk factors for EM. Despite favorable treatment outcomes, EM is a serious infection associated with Enterobacter species colonization or infection at other surgical sites, with selective antimicrobial pressure, and with invasive CNS devices. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 32 178, Dept Med,Div Infect Dis, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Infect Dis, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Div Lab Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Div Neurosurg, Los Angeles, CA 90095 USA. RP Pegues, D (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Hlth Sci 32 178, Dept Med,Div Infect Dis, Los Angeles, CA 90095 USA. NR 46 TC 13 Z9 16 U1 2 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 JUL 15 PY 2003 VL 37 IS 2 BP 159 EP 166 DI 10.1086/375596 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 700DZ UT WOS:000184098500001 PM 12856206 ER PT J AU Neuzil, KM Maynard, C Griffin, MR Heagerty, P AF Neuzil, KM Maynard, C Griffin, MR Heagerty, P TI Winter respiratory viruses and health care use: A population-based study in the Northwest United States SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CHRONIC LUNG-DISEASE; SYNCYTIAL VIRUS; INFLUENZA EPIDEMICS; YOUNG-CHILDREN; PARAINFLUENZA VIRUS; OUTPATIENT VISITS; ELDERLY PERSONS; IMPACT; MORTALITY; INFECTIONS AB To quantify health care use among adults during influenza and respiratory syncytial virus (RSV) seasons, we identified a cohort of veterans aged greater than or equal to18 years who used Department of Veterans Affairs (VA) facilities in Oregon and Washington states as their source of health care. During 1998-2000, veterans accrued 237,159 person-years of follow-up. Using VA data sources, we measured acute cardiopulmonary hospitalizations and primary care and urgent care visits. Differences between rates of study events when influenza and/or RSV were circulating and event rates when neither virus was circulating were used to calculate winter virus attributable morbidity. Inpatient and outpatient event rates were consistently higher during winter virus season, compared with non-winter virus season. Annual rates of cardiopulmonary hospitalizations attributable to influenza or RSV infection ranged from 0.8 (95% confidence interval [CI], 0.1-1.5) per 1000 low-risk individuals aged 18-49 years, to 10.6 (95% CI, 7.5-13.6) per 1000 high-risk individuals aged greater than or equal to65 years. Each year, circulation of influenza and RSV coincide with predictable increases in medical care use. C1 Univ Washington, Sch Med, Dept Med, Med Serv 111ID, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vet Affairs Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. RP Neuzil, KM (reprint author), Univ Washington, Sch Med, Dept Med, Med Serv 111ID, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 41 TC 28 Z9 29 U1 1 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 JUL 15 PY 2003 VL 37 IS 2 BP 201 EP 207 DI 10.1086/375604 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 700DZ UT WOS:000184098500007 PM 12856212 ER PT J AU Lehnertz, B Ueda, Y Derijck, AAHA Braunschweig, U Perez-Burgos, L Kubicek, S Chen, TP Li, E Jenuwein, T Peters, AHFM AF Lehnertz, B Ueda, Y Derijck, AAHA Braunschweig, U Perez-Burgos, L Kubicek, S Chen, TP Li, E Jenuwein, T Peters, AHFM TI Suv39h-mediated histone H3 lysine 9 methylation directs DNA methylation to major satellite repeats at pericentric heterochromatin SO CURRENT BIOLOGY LA English DT Article ID BINDING PROTEIN MECP2; DE-NOVO METHYLATION; METHYLTRANSFERASE GENE; LOCALIZATION; EXPRESSION; COMPLEX; CANCER; DNMT3A; CELLS; MAINTENANCE AB Background: Histone H3 lysine 9 (H3-K9) methylation and DNA methylation are characteristic hallmarks of mammalian heterochromatin. H3-K9 methylation was recently shown to be a prerequisite for DNA methylation in Neurospora crassa and Arabidopsis thaliana. Currently, it is unknown whether a similar dependence exists in mammalian organisms. Results: Here, we demonstrate a physical and functional link between the Suv39h-HP1 histone methylation system and DNA methyltransferase 3b (Dnmt3b) in mammals. Whereas in wild-type cells Dnmt3b interacts with HP1alpha and is concentrated at heterochromatic foci, it fails to localize to these regions in Suv39h double null (dn) mouse embryonic stem (ES) cells. Consistently, the Suv39h dn ES cells display an altered DNA methylation profile at pericentric satellite repeats, but not at other repeat sequences. In contrast, H3-K9 trimethylation at pericentric heterochromatin is not impaired in Dnmt1 single- or Dnmt3a/Dnmt3b double-deficient ES cells. We also show that pericentric heterochromatin is not transcriptionally inert and can give rise to transcripts spanning the major satellite repeats. Conclusions: These data demonstrate an evolutionarily conserved pathway between histone H3-K9 methylation and DNA methylation in mammals. While the Suv39h HMTases are required to direct H3-K9 trimethylation and Dnmt3b-dependent DNA methylation at pericentric repeats, DNA methylation at centromeric repeats occurs independent of Suv39h function. Thus, our data also indicate a more complex interrelatedness between histone and DNA methylation systems in mammals. Both methylation systems are likely to be important in reinforcing the stability of heterochromatic subdomains and thereby in protecting genome integrity. C1 Vienna Bioctr, Res Inst Mol Pathol, A-1030 Vienna, Austria. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Jenuwein, T (reprint author), Vienna Bioctr, Res Inst Mol Pathol, Dr Bohrgasse 7, A-1030 Vienna, Austria. RI Kubicek, Stefan/C-2089-2017; OI Kubicek, Stefan/0000-0003-0855-8343; Braunschweig, Ulrich/0000-0001-6653-0926; Ueda, Yoshihide/0000-0003-3196-3494 FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 41 TC 681 Z9 710 U1 3 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 15 PY 2003 VL 13 IS 14 BP 1192 EP 1200 DI 10.1016/S0960-9822(03)00432-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 702VE UT WOS:000184244600020 PM 12867029 ER PT J AU D'Andrea, A AF D'Andrea, A TI Fanconi anemia SO CURRENT BIOLOGY LA English DT Editorial Material ID BRCA2 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Andrea, A (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 3 TC 10 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 15 PY 2003 VL 13 IS 14 BP R546 EP R546 DI 10.1016/S0960-9822(03)00467-6 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 702VE UT WOS:000184244600005 PM 12867043 ER PT J AU Ossipova, ON Green, JBA AF Ossipova, ON Green, JBA TI Par-1 and Par-4 (XEEK1, LKB1) function in Xenopus embryos. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Med, Dept Genet, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Green, Jeremy/F-3630-2010 OI Green, Jeremy/0000-0002-6102-2620 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 80 BP 462 EP 463 PG 2 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300087 ER PT J AU Wang, J Chan, J Roberts, T AF Wang, J Chan, J Roberts, T TI IGF-I receptor signaling in zebrafish development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 82 BP 463 EP 463 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300089 ER PT J AU Levin, M AF Levin, M TI Electric embryos: Endogenous ion fluxes and voltage gradients in left-right asymmetry SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Forsyth Inst, Cambridge, MA 02138 USA. NR 0 TC 6 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 169 BP 482 EP 482 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300166 ER PT J AU Payne-Ferreira, TL Yelick, PC AF Payne-Ferreira, TL Yelick, PC TI The role of alk8 in zebrafish development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 237 BP 497 EP 497 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300226 ER PT J AU Jurynec, MJ Hoshijima, K Bahary, N Grunwald, DJ AF Jurynec, MJ Hoshijima, K Bahary, N Grunwald, DJ TI Genomic characterization and cloning of the zebrafish neural crest mutant, alyron. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Univ Utah, Dept Human Genet, SLC, Salt Lake City, UT 84112 USA. Harvard Univ, Dept Hematol Oncol, Childrens Hosp, DFCI, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 246 BP 499 EP 499 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300232 ER PT J AU Peterson, C Patel, R Carney, G Taylor, B White, K AF Peterson, C Patel, R Carney, G Taylor, B White, K TI The role of reaper and sickle in developmental apoptosis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Cambridge, MA 02138 USA. Oregon State Univ, Dept Zool, Corvallis, OR 97331 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 351 BP 520 EP 520 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300316 ER PT J AU Thirumangalathu, S Loeken, MR AF Thirumangalathu, S Loeken, MR TI Regulation of cell death by Pax-3 during neural tube development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Joslin Diabet Ctr, Cambridge, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 352 BP 520 EP 520 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300317 ER PT J AU Owen, M Bulte, J Cicchetti, F Chen, I Owen, C Wang, XK Yu, MX Jokivarsi, K Brownell, AL AF Owen, M Bulte, J Cicchetti, F Chen, I Owen, C Wang, XK Yu, MX Jokivarsi, K Brownell, AL TI Development of in vivo imaging techniques for trafficking of subventricular zone neural stem cells (SVZSC). SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Simmons Coll, Dept Biol, Boston, MA 02115 USA. Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA. CHUL, Unit 233, Quebec City, PQ, Canada. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RI Bulte, Jeff/A-3240-2008 OI Bulte, Jeff/0000-0003-1202-1610 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 404 BP 532 EP 532 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300363 ER PT J AU Chan, J Bayliss, PE Whitehead, G Keating, M Wood, JM Roberts, TM AF Chan, J Bayliss, PE Whitehead, G Keating, M Wood, JM Roberts, TM TI Zebrafish fin regeneration as a model system for adult angiogenesis and anti-angiogenic therapy. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 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. Harvard Univ, Sch Med, Childrens Hosp,Dept Cell Biol, Howard Hughes Med Inst,Dept Cardiol, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 415 BP 534 EP 534 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300372 ER PT J AU Goldstein, AM Doyle, AM Williams, JA Roberts, DJ AF Goldstein, AM Doyle, AM Williams, JA Roberts, DJ TI BMP4 is essential for normal development of the enteric nervous system. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 457 BP 544 EP 544 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300412 ER PT J AU Provot, S Murtaugh, LC Kempf, H Chung, UI Kronenberg, H Lassar, AB AF Provot, S Murtaugh, LC Kempf, H Chung, UI Kronenberg, H Lassar, AB TI Regulation of chondrocyte maturation by the transcription factor Nkx3.2/Bapx1. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Med, BCMP Dept, Boston, MA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RI Kempf, Herve/F-1171-2011 OI Kempf, Herve/0000-0003-1818-2327 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 571 BP 570 EP 570 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300514 ER PT J AU Albertson, RC Payne-Ferreira, TL Yelick, PC AF Albertson, RC Payne-Ferreira, TL Yelick, PC TI Activin receptors IIa and IIb exhibit distinct roles in craniofacial development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Dent Med, Dept Cytokine Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 615 BP 579 EP 579 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300552 ER PT J AU Gamer, L Nove, J Rosen, V AF Gamer, L Nove, J Rosen, V TI Functional analysis of BMP3 in mice and frogs. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Forsyth Inst, Boston, MA USA. HSDM, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 630 BP 583 EP 583 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300566 ER PT J AU Nogi, T Levin, M AF Nogi, T Levin, M TI Electrical controls of regeneration in planaria. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Forsyth Inst, Boston, MA USA. RI Nogi, Taisaku/C-7657-2009; Nogi, Taisaku/F-4675-2017 NR 0 TC 2 Z9 2 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 644 BP 586 EP 586 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300579 ER PT J AU Ogawa, Y Lee, JT AF Ogawa, Y Lee, JT TI Xite, X-inactivation Intergenic transcription elements that regulate the probability of choice. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-for-Development-Biology CY JUL 30-AUG 02, 2003 CL BOSTON, MASSACHUSETTS SP Soc Dev Biol C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2003 VL 259 IS 2 MA 712 BP 601 EP 601 PG 1 WC Developmental Biology SC Developmental Biology GA 705AD UT WOS:000184373300638 ER PT J AU Schacht, V Ramirez, MI Hong, YK Hirakawa, S Feng, D Harvey, N Williams, M Dvorak, AM Dvorak, HF Oliver, G Detmar, M AF Schacht, V Ramirez, MI Hong, YK Hirakawa, S Feng, D Harvey, N Williams, M Dvorak, AM Dvorak, HF Oliver, G Detmar, M TI T1 alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema SO EMBO JOURNAL LA English DT Article DE angiogenesis; lymphangiogenesis; podoplanin; Prox1; T1 alpha ID MUCIN-TYPE GLYCOPROTEIN; ENDOTHELIAL-CELLS; I CELLS; MEMBRANE-PROTEIN; PLASMA-MEMBRANE; CLONING; SYSTEM; GENE; ANGIOGENESIS; ANTIGEN AB Within the vascular system, the mucin-type transmembrane glycoprotein T1alpha/podoplanin is predominantly expressed by lymphatic endothelium, and recent studies have shown that it is regulated by the lymphatic-specific homeobox gene Prox1. In this study, we examined the role of T1alpha/podoplanin in vascular development and the effects of gene disruption in mice. T1alpha/podoplanin is first expressed at around E11.0 in Prox1-positive lymphatic progenitor cells, with predominant localization in the luminal plasma membrane of lymphatic endothelial cells during later development. T1alpha/podoplanin(-/-) mice die at birth due to respiratory failure and have defects in lymphatic, but not blood vessel pattern formation. These defects are associated with diminished lymphatic transport, congenital lymphedema and dilation of lymphatic vessels. T1alpha/podoplanin is also expressed in the basal epidermis of newborn wild-type mice, but gene disruption did not alter epidermal differentiation. Studies in cultured endothelial cells indicate that T1alpha/podoplanin promotes cell adhesion, migration and tube formation, whereas small interfering RNA-mediated inhibition of T1alpha/podoplanin expression decreased lymphatic endothelial cell adhesion. These data identify T1alpha/podoplanin as a novel critical player that regulates different key aspects of lymphatic vasculature formation. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu FU NCI NIH HHS [CA86410, CA69184, CA92644, P01 CA092644, R01 CA069184, R01 CA086410]; NHLBI NIH HHS [HL47049, P01 HL047049]; NIAID NIH HHS [AI33372, AI44066, R01 AI033372] NR 36 TC 402 Z9 420 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 15 PY 2003 VL 22 IS 14 BP 3546 EP 3556 DI 10.1093/emboj/cdg342 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705FU UT WOS:000184385700009 PM 12853470 ER PT J AU Yan, C Martinez-Quiles, N Eden, S Shibata, T Takeshima, F Shinkura, R Fujiwara, Y Bronson, R Snapper, SB Kirschner, MW Geha, R Rosen, FS Alt, FW AF Yan, C Martinez-Quiles, N Eden, S Shibata, T Takeshima, F Shinkura, R Fujiwara, Y Bronson, R Snapper, SB Kirschner, MW Geha, R Rosen, FS Alt, FW TI WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility SO EMBO JOURNAL LA English DT Article DE actin polymerization; lamellipodium; Rho GTPase; WASP-related protein; WAVE ID WISKOTT-ALDRICH-SYNDROME; WASP-RELATED PROTEIN; ARP2/3 COMPLEX; N-WASP; EPITHELIAL-CELLS; FAMILY PROTEINS; SCAR; LAMELLIPODIA; ACTIVATION; MICE AB The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement. C1 Ctr Blood Res, Boston, MA 02115 USA. Howard Hughes Med Inst, Div Immunol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit Med Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. RP Alt, FW (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 44 TC 125 Z9 126 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 15 PY 2003 VL 22 IS 14 BP 3602 EP 3612 DI 10.1093/emboj/cdg350 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705FU UT WOS:000184385700014 PM 12853475 ER PT J AU Suntharalingam, M Moughan, J Coia, LR Krasna, MJ Kachnic, L Haller, DG Willett, CG John, MJ Minsky, BD Owen, JB AF Suntharalingam, M Moughan, J Coia, LR Krasna, MJ Kachnic, L Haller, DG Willett, CG John, MJ Minsky, BD Owen, JB TI The national practice for patients receiving radiation therapy for carcinoma of the esophagus: Results of the 1996-1999 patterns of care study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE esophageal carcinoma; patterns of care; evaluation; management ID COMBINED-MODALITY THERAPY; ENDOSCOPIC ULTRASONOGRAPHY; RANDOMIZED TRIAL; CANCER; SURGERY; CHEMORADIOTHERAPY; CHEMOTHERAPY; CHEMORADIATION; RADIOTHERAPY AB Purpose: A Patterns of Care Study (PCs) was conducted to evaluate the standards of practice for patients receiving radiation therapy for esophageal cancer from 1996 to 1999. This study examined the evaluation and treatment schemes used during this time and compared these results to the PCS data obtained between 1992 and 1994 to identify any fundamental changes in national practice. Methods: A national survey was conducted using a two-stage cluster sampling technique. Specific information was collected on 414 patients with esophageal cancer who received radiotherapy (RT) as part of definitive or adjuvant management at 59 institutions. Patients were staged according to the 1983 AJCC. Eligibility criteria for case review included RT between 1996 and 1999, no evidence of distant metastasis (including CT evidence of either supraclavicular or celiac nodes >1 cm), squamous cell or adenocarcinoma histology, Karnofsky performance status >60, tumors in the thoracic esophagus with <2 cm extension into the stomach, and no prior malignancies within the last 5 years. Statistical analysis was performed on the database using SUDAAN software to accurately reflect the type of sampling technique used by PCs. For the purpose of this analysis, institutions were stratified as either large or small based on the number of new cases seen each year. For the purposes of comparison, the 1992-1994 PCS esophageal survey results were subjected to the same statistical procedures and tests. Results: The median age of patients was 64 years. Seventy-seven percent were male, and 23% were female. Karnofsky performance status was greater than or equal to80% in 85% of patients. The racial profile mirrors the previous survey with 75% Caucasian, 21% African-American, 3% Asian, and <1% Hispanic. A review of the histology revealed a nearly 50:50 split between squamous cell and adenocarcinoma. Sixteen percent were clinical Stage I, 39% clinical Stage II, and 33% clinical Stage III according to the 1983 AJCC system. Workup included endoscopy (96%), CT of the chest (87%), CT of the abdomen (75%), and esophagram (64%). Endoscopic ultrasound (EUS) was used in 18% of cases as compared to <2% in the original survey (p < 0.0001). Patients treated at large centers were more likely to undergo EUS than those treated at small centers (23% vs. 12%, p = 0.047). Fifty-six percent of patients received concurrent chemoradiation as definitive treatment. There was a significant increase in the use of concurrent chemoradiation before planned surgical resection as compared to the original survey (27% vs. 10%, p = 0.007). Other schemes included RT alone (10%), postoperative RT (1%), and postoperative chemoradiation (5%). Forty-six percent of patients with adenocarcinoma underwent trimodality therapy as compared to 19% with squamous cell carcinomas (p = 0.0002). Patients undergoing preoperative chemoradiation were more likely to have had an EUS. The median total dose of external RT was 50.4 Gy, and the median dose per fraction was 1.8 Gy. Brachytherapy was used in 6% of cases. The chemotherapy agents most commonly used included 5-fluorouracil (82%), cisplatin (67%), and paclitaxel (22%). Paclitaxel was more commonly employed as part of a preoperative chemoradiation regimen than in the setting of definitive chemoradiation (46% vs. 12%, p = 0.03). Compared to the original survey, paclitaxel use significantly increased between 1996 and 1999 (0.2% vs. 22%, p = 0.001). Conclusions: The Patterns of Care Survey confirms the use of concurrent chemoradiation as part of the national standards of practice for the management of esophageal cancer patients. A comparison with the previous study documents the significant rise in the use of EUS, preoperative chemoradiation followed by surgery, and the increasing use of paclitaxel as part of a combined modality regimen. (C) 2003 Elsevier Inc. C1 Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. Amer Coll Radiol, Philadelphia, PA USA. Community Med Ctr, Dept Radiat Oncol, Toms River, NJ USA. Boston Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02118 USA. Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Canc Ctr St Agnes, Fresno, CA USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Suntharalingam, M (reprint author), Univ Maryland, Sch Med, Dept Radiat Oncol, Gudelsky Bldg,22 S Greene St, Baltimore, MD 21201 USA. FU NCI NIH HHS [CA65435] NR 20 TC 45 Z9 57 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2003 VL 56 IS 4 BP 981 EP 987 DI 10.1016/S0360-3016(03)00256-6 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 697HX UT WOS:000183937500011 PM 12829133 ER PT J AU DeLaney, TF Spiro, IJ Suit, HD Gebhardt, MC Hornicek, FJ Mankin, HJ Rosenberg, AL Rosenthal, DI Miryousefi, F Ancukiewicz, M Harmon, DC AF DeLaney, TF Spiro, IJ Suit, HD Gebhardt, MC Hornicek, FJ Mankin, HJ Rosenberg, AL Rosenthal, DI Miryousefi, F Ancukiewicz, M Harmon, DC TI Neoadjuvant chemotherapy and radiotherapy for large extremity soft-tissue sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE soft tissue sarcoma; adjuvant therapy ID LIMB-SPARING SURGERY; ADJUVANT CHEMOTHERAPY; POSTOPERATIVE RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED TRIAL; LOCAL-CONTROL; ADULTS; CARE AB Purpose: Treatment of extremity soft-tissue sarcomas yields excellent local control, but distant failure is common with large, high-grade tumors. A regimen of preoperative chemotherapy consisting of mesna, adriamycin, ifosfamide, and dacarbazine (MAID) interdigitated with radiotherapy followed by resection and postoperative chemotherapy with or without radiotherapy was designed to improve treatment outcome. We report the mature outcome data on 48 treated patients and compare them with the data of an historical matched control patient population. Methods and Materials: Adult patients with high-grade extremity soft-tissue sarcomas greater than or equal to8 cm were treated with three cycles-of preoperative chemotherapy combined with 44 Gy of radiotherapy followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy was delivered postoperatively. Results: All 48 patients (MO) received the MAID protocol treatment, and their outcome was superior to that of the historical control patients. The 5-year actuarial local control, freedom from distant metastasis, disease-free survival, and overall survival rate was 92% and 86% (p = 0.1155), 75% and 44% (p = 0.0016), 70% and 42% (p = 0.0002), and 87% and 58% (p = 0.0003) for the MAID and control patient groups, respectively. Acute hematologic toxicity in the MAID group included febrile neutropenia in 12 patients (25%). Wound healing complications occurred in 14 (29%) of 48 MAID patients. One MAID patient developed late fatal myelodysplasia. Conclusion: After aggressive chemoradiation and surgery, these patients showed a significant reduction in distant metastases, with a highly significant gain in disease-free and overall survival compared with a historical control group. On the basis of this experience, the Radiation Therapy Oncology Group conducted a multi-institutional trial. (C) 2003 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Diagnost Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 18 TC 136 Z9 144 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 15 PY 2003 VL 56 IS 4 BP 1117 EP 1127 DI 10.1016/S0360-3016(03)00186-X PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 697HX UT WOS:000183937500028 PM 12829150 ER PT J AU Hile, DD Kirker-Head, C Doherty, SA Kowaleski, MP McCool, J Wise, DL Trantolo, DJ AF Hile, DD Kirker-Head, C Doherty, SA Kowaleski, MP McCool, J Wise, DL Trantolo, DJ TI Mechanical evaluation of a porous bone graft substitute based on poly(propylene glycol-co-fumaric acid) SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE bioresorbable bone graft substitute; porous biomaterials; biocompatibility; poly(propylene glycol-co-fumaric acid); mechanics of bone substitutes ID ALLOGRAFTS; FRACTURES; INFECTION; STRENGTH; EXTENDER AB A porous, resorbable polymer composite based on poly(propylene glycol-co-fumaric acid) (PPF) was mechanically evaluated in vitro for use as a bone graft substitute and fracture fixative. The test material created a dynamic system capable of initially providing mechanical integrity to bony voids and a degradative mechanism for ingrowth by native bone. The unsaturated polymer, PPF, was crosslinked in the presence of effervescent agents to yield a porous microstructure upon curing. An in vitro degradation study first assessed the temporal mechanical properties of the test material. This research was followed by an ex vivo study using a long-bone osteotomy model to characterize the mechanics of fixation. Results showed the initial compressive strength of the cross-linked PPF system was comparable to cancellous bone. The rate of strength loss was commensurate with the predicted mechanical recovery of healing bone with analogous results in a composite that comprised also 25% (by weight) autograft. Mechanical testing in the long-bone model demonstrated that PPF-based bone-graft substitute increased the flexural strength of K-wire stabilized osteotomies. These results suggest that this type of bone graft substitute may have clinical utility in the stabilization of complex tubular bone fractures. (C) 2003 Wiley Periodicals, Inc. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Tufts Univ, Sch Vet Med, Orthopaed Res Lab, North Grafton, MA 01536 USA. RP Hile, DD (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [1 R43 AR46970]; PHS HHS [1 R43 46130] NR 24 TC 7 Z9 7 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD JUL 15 PY 2003 VL 66B IS 1 BP 311 EP 317 DI 10.1002/jbm.b.10011 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 697CB UT WOS:000183923700004 PM 12808589 ER PT J AU Taplin, ME Rajeshkumar, B Halabi, S Werner, CP Woda, BA Picus, J Stadler, W Hayes, DF Kantoff, PW Vogelzang, NJ Small, EJ AF Taplin, ME Rajeshkumar, B Halabi, S Werner, CP Woda, BA Picus, J Stadler, W Hayes, DF Kantoff, PW Vogelzang, NJ Small, EJ TI Androgen receptor mutations in androgen-in dependent prostate cancer: Cancer and Leukemia Group B Study 9663 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GENE-MUTATIONS; HORMONAL-THERAPY; BINDING DOMAIN; FLUTAMIDE; CELLS AB Purpose : The mechanisms responsible for prostate cancer androgen independence are diverse. Mutations of the androgen receptor (AR) gene that broaden ligand specificity have been implicated. Bone marrow specimens containing prostate tumor were obtained from men undergoing antiandrogen withdrawal for AR sequence analysis and clinical correlation. Materials and Methods: Eligible men enrolled on a trial of antiandrogen withdrawal had a minimum prostate-specific antigen (PSA) level of 5 ng/dL that was increasing on castration therapy including an antiandrogen. With informed consent, marrow biopsies were obtained to collect prostate tumor. Additional samples were obtained from men enrolled on chemotherapy trials. AR cDNA or DNA was polymerase chain reaction-amplified, cloned, and sequenced. The AR CAG repeat length was recorded. Results: One hundred eighty-four bone marrow biopsies were obtained, and 48 had prostate tumor detected by light microscopy. The ARs from these 48 samples were sequenced. Overall, five (10%) of 48 tumors had mutated ARs. AR point mutations were detected in the hormone-binding domain involved in transcription factor binding. Three mutations were novel in prostate cancer. One tumor sample had a CAG repeat length of 21, compared with germline length of 22 repeats. There was no association between detectability of AR mutations and antiandrogen withdrawal response or survival. Conclusion: These data suggest that AR mutations are present in approximately 10% of patients with prostate cancer who experience treatment failure with hormone therapy that included an antiandrogen. Mutations in the AR likely confer a growth advantage for a subset of progressive prostate cancers. Correlation of AR mutation with antiandrogen withdrawal response or survival could not be made. (C) 2003 by American Society of Clinical Oncology. C1 Univ Massachusetts, Mem Hlth Ctr, Dept Oncol, Worcester, MA 01655 USA. Dana Farber Canc Inst, Boston, MA USA. Canc & Leukemia Grp, B Stat Ctr, Durham, NC USA. Washington Univ, Barnes Hosp, St Louis, MO USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Taplin, ME (reprint author), Univ Massachusetts, Mem Hlth Ctr, Dept Oncol, 55 Lake Ave, Worcester, MA 01655 USA. FU NCI NIH HHS [U10CA31946, U10CA78967] NR 29 TC 255 Z9 268 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2003 VL 21 IS 14 BP 2673 EP 2678 DI 10.1200/JCO.2003.11.102 PG 6 WC Oncology SC Oncology GA 702JB UT WOS:000184219800009 PM 12860943 ER PT J AU Lee, CK Barlogie, B Munshi, N Zangari, M Fassas, A Jacobson, J van Rhee, F Cottler-Fox, M Muwalla, F Tricot, G AF Lee, CK Barlogie, B Munshi, N Zangari, M Fassas, A Jacobson, J van Rhee, F Cottler-Fox, M Muwalla, F Tricot, G TI DTPACE: An effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REFRACTORY MULTIPLE-MYELOMA; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HIGH-DOSE MELPHALAN; PREVIOUSLY UNTREATED MYELOMA; RANDOMIZED TRIAL; THERAPY; DOXORUBICIN; MANAGEMENT; CANCER AB Purpose : To improve outcome in previously treated patients (at least two cycles of standard therapy) with multiple myeloma, tholidomide was combined with cytotoxic chemotherapy as induction therapy. Patients and Methods: The regimen consisted of 4-days of oral dexamethasone, daily thalidomide, and 4 days of continuous-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide (DTPACE). Response to two cycles of DTPACE for induction was evaluated in 236 patients. Before being treated with DTPACE, 148 patients (63%) had shown progressive disease while receiving standard chemotherapy, and 55 patients (23%) had chromosome 13 abnormalities. Results : The partial remission rate (PR) after two cycles of DTPACE was 32%, with 16% attaining a complete remission (CR) or near-CR (nCR; defined as only immunofixation electrophoresis-positive). Patients with high lactate dehydrogenase (LDH; n = 98) showed a better response than those with normal LDH (n = 138): PR or better, 43% v 27% (P = .01); CR + nCR, 25% v 11% (P = .01). Patients with chromosome 13 abnormalities (n = 55) responded equally well as the other patients (n = 181): PR or better, 35% v33% (P = .84); CR + nCR, 17% v 15% (P = .73). Patients who received 100% dose of DTPACE for two cycles (n = 115) achieved higher response rates than those with less than 100% dose (n = 121): PR or better, 49% v 17% (P < .0001); CR + nCR, 27% v 6% (P < .0001). Conclusion: Combination therapy of oral dexamethasone and thalidomide with infusional chemotherapy is effective as induction therapy before autotransplantation, especially in patients with high-risk features. (C) 2003 by American Society of Clinical Oncology. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Canc Res & Biostat, Seattle, WA USA. RP Lee, CK (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Slot 776,4301 W Markham, Little Rock, AR 72205 USA. NR 25 TC 104 Z9 108 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 15 PY 2003 VL 21 IS 14 BP 2732 EP 2739 DI 10.1200/JCO.2003.01.055 PG 8 WC Oncology SC Oncology GA 702JB UT WOS:000184219800018 PM 12860952 ER PT J AU Wong, JS Wang, XS Witte, T Nie, LH Carvou, N Kern, P Chang, HC AF Wong, JS Wang, XS Witte, T Nie, LH Carvou, N Kern, P Chang, HC TI Stalk region of beta-chain enhances the coreceptor function of CD8 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; T-CELL RECEPTOR; MHC CLASS-I; ALPHA-3 DOMAIN; LYMPHOCYTES-T; INTRAEPITHELIAL LYMPHOCYTES; DIFFERENTIAL EXPRESSION; SURFACE EXPRESSION; CRYSTAL-STRUCTURE; CD8-BETA CHAINS AB CD8 glycoproteins are expressed as either alphaalpha homodimers or alphabeta heterodimers on the surface of T cells. CD8alphabeta is a more efficient coreceptor than the CD8alphaalpha for peptide Ag recognition by TCR. Each CD8 subunit is composed of four structural domains, namely, Ig-like domain, stalk region, transmembrane region, and cytoplasmic domain. In an attempt to understand why CD8alphabeta is a better coreceptor than CD8alphaalpha, we engineered, expressed, and functionally tested a chimeric CD8alpha protein whose stalk region is replaced with that of CD8beta. We found that the beta stalk region enhances the coreceptor function of chimeric CD8alphaalpha to a level similar to that of CD8alphabeta. Surprisingly, the beta stalk region also restored functional activity to an inactive CD8alpha variant, carrying an Ala mutation at Are (R8A), to a level similar to that of wild-type CD8alphabeta. Using the R8A variant of CD8alpha, a panel of anti-CD8alpha Abs, and three MHC class I (MHCI) variants differing in key residues known to be involved in CD8alpha interaction, we show that the introduction of the CD8beta stalk leads to a different topology of the CD8alpha-MHCI complex without altering the overall structure of the Ig-like domain of CD8alpha or causing the MHCI to employ different residues to interact with the CD8alpha Ig domain. Our results show that the stalk region of CD8beta is capable of fine-tuning the coreceptor function of CD8 proteins as a coreceptor, possibly due to its distinct protein structure, smaller physical size and the unique glycan adducts associated with this region. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Chang, HC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Witte, Torsten/B-5783-2016 FU NIAID NIH HHS [AI45789] NR 48 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2003 VL 171 IS 2 BP 867 EP 874 PG 8 WC Immunology SC Immunology GA 700BY UT WOS:000184093800047 PM 12847256 ER PT J AU Hellman, J Tehan, MM Warren, HS AF Hellman, J Tehan, MM Warren, HS TI Murein lipoprotein, peptidoglycan-associated lipoprotein, and outer membrane protein A are present in purified rough and smooth lipopolysaccharides SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ESCHERICHIA-COLI; ENDOTOXIN; ANTISERUM; BACTERIA; SHOCK; GENE AB Purified lipopolysaccharides (LPSs) have been used for many decades to gain insight into processes that occur during sepsis. Previous studies indicate that purified LPSs often contain trace protein contaminants. To identify protein contaminants of LPSs, we performed immunoblotting using, as antigen, purified LPS from various species of bacteria and, as primary antibodies, anti-murein lipoprotein (MLP), peptidoglycan-associated lipoprotein ( PAL), and outer membrane protein A ( OmpA). MLP, PAL, and/or OmpA were detected in 10 of the 13 LPS preparations and were present in LPS from rough and smooth bacteria. PAL and MLP have been reported to stimulate inflammation. The studies indicate that PAL and MLP are common contaminants of purified LPS and raise the possibility that these contaminants may influence results of studies performed using purified LPS. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI 01722]; NIGMS NIH HHS [GM 59694] NR 15 TC 24 Z9 24 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2003 VL 188 IS 2 BP 286 EP 289 DI 10.1086/376453 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 699HT UT WOS:000184051500014 PM 12854085 ER PT J AU Bush, AI AF Bush, AI TI Beta-amyloid cuproprotein: A therapeutic target for Alzheimer's disease SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Meeting Abstract CT 11th International Conference on Biological Inorganic Chemistry CY JUL 19-23, 2003 CL CAIMS, AUSTRALIA C1 Univ Melbourne, Parkville, Vic 3052, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD JUL 15 PY 2003 VL 96 IS 1 BP 43 EP 43 DI 10.1016/S0162-0134(03)80478-6 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 698QG UT WOS:000184009800067 ER PT J AU Bonne, O Brandes, D Segman, R Pitman, RK Yehuda, R Shalev, AY AF Bonne, O Brandes, D Segman, R Pitman, RK Yehuda, R Shalev, AY TI Prospective evaluation of plasma cortisol in recent trauma survivors with posttraumatic stress disorder SO PSYCHIATRY RESEARCH LA English DT Article DE hypothalamic-pituitary-adrenal axis; prognosis; longitudinal ID MOTOR-VEHICLE ACCIDENTS; ADRENOCORTICAL ACTIVITY; SALIVARY CORTISOL; PTSD; INDIVIDUALS; SYMPTOMS; HEALTH; CYCLE; PHASE AB Hypothalamic pituitary adrenal axis abnormalities have been described in posttraumatic stress disorder (PTSD), and among the recently traumatized. Plasma cortisol and continuous measures of PTSD symptoms were obtained from 21 survivors, at 1 week and 6 months after traumatic events. Eight survivors met Clinician Administered PTSD Scale criteria for PTSD at 6 months. Cortisol levels at 1 week did not predict subsequent PTSD. Survivors with and without PTSD had similar mean levels of cortisol at both time points. Cortisol levels at 6 months negatively correlated with self-reported PTSD symptoms within PTSD subjects. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Hadassah Univ Hosp, Ctr Traumat Stress, IL-91120 Jerusalem, Israel. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Dept Vet Affairs Med Ctr, Dept Psychiat, Posttraumat Stress Disorder Program, Bronx, NY 10468 USA. RP Bonne, O (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr,Room 200, Bethesda, MD 20892 USA. FU NIMH NIH HHS [MH 50379] NR 24 TC 36 Z9 36 U1 3 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL 15 PY 2003 VL 119 IS 1-2 BP 171 EP 175 DI 10.1016/S0165-1781(03)00098-2 PG 5 WC Psychiatry SC Psychiatry GA 704FX UT WOS:000184329300018 PM 12860372 ER PT J AU Maemura, T Shin, M Sato, M Mochizuki, H Vacanti, JP AF Maemura, T Shin, M Sato, M Mochizuki, H Vacanti, JP TI A tissue-engineered stomach as a replacement of the native stomach SO TRANSPLANTATION LA English DT Article ID EPITHELIAL ORGANOID UNITS; REGENERATIVE SIGNALS; TOTAL GASTRECTOMY; SMALL-INTESTINE; INTERPOSITION; SCAFFOLDS; POUCH; GENE; GUT AB Background. Despite recent advances in reconstruction techniques, total gastrectomy is still accompanied by various complications. As an alternative treatment, we propose a tissue-engineered stomach that replaces the mechanical and metabolic functions of a normal stomach. The objective of this study was to demonstrate the function of a tissue-engineered stomach as a replacement of the native stomach. Methods. Tissue-engineered stomachs were formed in recipient rats from stomach epithelium organoid units isolated from neonatal donor rats. After 12 weeks, the animals underwent a second operation for replacement of the native stomachs. Results. Tissue-engineered stomachs were successfully used as a substitute of the native stomach in a rat model. An upper gastrointestinal tract study revealed no evidence of bowel stenosis or obstruction at both anastomosis sites. Histologically, the tissue-engineered stomachs had well-developed vascularized tissue with a neomucosa continuously lining the lumen and stratified smooth muscle layers. Immunohistochemical staining for a-actin smooth muscle showed that the smooth muscle layers were arranged in a regular fashion. Scanning electron microscopy showed that the surface topography of the tissue-engineered stomachs resembled that of native stomachs. Conclusions. It has been demonstrated that a tissue-engineered stomach can replace a native stomach in a rat model. Replacement of the native stomach by a tissue-engineered stomach had beneficial effects on the formation of neomucosa and smooth muscle layers in the tissue-engineered stomach. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 21 Z9 22 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL 15 PY 2003 VL 76 IS 1 BP 61 EP 65 DI 10.1097/01.TP.000006803.63554.1B PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 703BW UT WOS:000184261000011 PM 12865787 ER PT J AU Nash, IS Mosca, L Blumenthal, RS Davidson, MH Smith, SC Pasternak, RC AF Nash, IS Mosca, L Blumenthal, RS Davidson, MH Smith, SC Pasternak, RC TI Contemporary awareness and understanding of cholesterol as a risk factor - Results of an American heart association national survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 51st Annual Scientific Session of the American-College-of-Cardiology CY MAR 17-20, 2002 CL ATLANTA, GEORGIA SP Amer Coll Cardiol ID EDUCATION-PROGRAM; KNOWLEDGE; DISEASE; BEHAVIOR AB Background: Public awareness and understanding of risk factors for atherosclerotic vascular disease are essential for successful primary and secondary prevention. The American Heart Association is committed to reducing cardiovascular disease. Methods: A professional market survey company conducted a structured national telephone survey of English-speaking adults 40 years and older on behalf of the American Heart Association. Regional and sex quotas were imposed on the sample, and responses were weighted to match the 1999 census projections for region of the country, age, sex, and race. Results: Interviews were completed with 1163 adults 40 years and older. A national probability sample of 1114 was created. Of the final sample, 28.5% were 65 years or older, 56.1% were women, and 86.5% were white. Although 91.2% of respondents stated that it was "important to them personally to have a healthy cholesterol level" (77.6% extremely or very important), 51% did not know their own level. Only 40.2% were aware of national guidelines for cholesterol management, and 53.1% either did not know or overestimated the correct desirable total cholesterol level for a healthy adult. When asked what sources of information they rely on the most, 66.8% identified physicians, while only 3.7% rely primarily on the Internet. Conclusions: Public understanding of cholesterol management is suboptimal. Physicians have a unique opportunity, on the basis of public attitudes and access, to improve cholesterol education. C1 Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. Columbia Univ, New York Presbyterian Hosp, Dept Med, Div Cardiol, New York, NY USA. Cornell Univ, New York Presbyterian Hosp, Dept Med, Div Cardiol, New York, NY USA. Johns Hopkins Med Inst, John Hopkins Ciccarone Ctr Prevent Heart Dis, Baltimore, MD 21205 USA. Rush Med Coll, Rush Heart Inst, Chicago, IL 60612 USA. Univ N Carolina, Dept Med, Div Cardiol, Chapel Hill, NC USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Nash, IS (reprint author), Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, Box 1030,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 12 TC 37 Z9 37 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 14 PY 2003 VL 163 IS 13 BP 1597 EP 1600 DI 10.1001/archinte.163.13.1597 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 701HL UT WOS:000184162100014 PM 12860584 ER PT J AU Meigs, JB AF Meigs, JB TI The metabolic syndrome - May be a guidepost or detour to preventing type 2 diabetes and cardiovascular disease SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID INSULIN-RESISTANCE; LIFE-STYLE; MELLITUS; RISK C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 12 TC 37 Z9 45 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD JUL 12 PY 2003 VL 327 IS 7406 BP 61 EP 62 DI 10.1136/bmj.327.7406.61 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 702NF UT WOS:000184229400001 PM 12855493 ER PT J AU Gozani, O Karuman, P Jones, DR Ivanov, D Cha, J Lugovskoy, AA Baird, CL Zhu, H Field, SJ Lessnick, SL Villasenor, J Mehrotra, B Chen, J Rao, VR Brugge, JS Ferguson, CG Payrastre, B Myszka, DG Cantley, LC Wagner, G Divecha, N Prestwich, GD Yuan, JY AF Gozani, O Karuman, P Jones, DR Ivanov, D Cha, J Lugovskoy, AA Baird, CL Zhu, H Field, SJ Lessnick, SL Villasenor, J Mehrotra, B Chen, J Rao, VR Brugge, JS Ferguson, CG Payrastre, B Myszka, DG Cantley, LC Wagner, G Divecha, N Prestwich, GD Yuan, JY TI The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor SO CELL LA English DT Article ID CANDIDATE TUMOR-SUPPRESSOR; PLECKSTRIN-HOMOLOGY-DOMAIN; PHOSPHATIDYLINOSITOL 3-PHOSPHATE; MAMMALIAN-CELLS; BINDING DOMAINS; FYVE FINGER; ZINC-FINGER; COMPLEX; DNA; IDENTIFICATION AB Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Utah, Ctr Biomol Interact Anal, Salt Lake City, UT 84132 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Echelon Biosci Inc, Salt Lake City, UT 84108 USA. Hop Purpan, INSERM, U563, Dept Oncogenesis,IFR30, F-31059 Toulouse, France. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RI Ivanov, Dmitri/B-4600-2011; Baird, Cheryl/F-6569-2011; Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIA NIH HHS [KO8AG19245, AG16674]; NIGMS NIH HHS [GM36624, GM57705]; NINDS NIH HHS [NS29632] NR 56 TC 326 Z9 336 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 11 PY 2003 VL 114 IS 1 BP 99 EP 111 DI 10.1016/S0092-8674(03)00480-X PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 702JC UT WOS:000184219900009 PM 12859901 ER PT J AU Cai, DS Dhe-Paganon, S Melendez, PA Lee, JS Shoelson, SE AF Cai, DS Dhe-Paganon, S Melendez, PA Lee, JS Shoelson, SE TI Two new substrates in insulin signaling, IRS5/DOK4 and IRS6/DOK5 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASE; DOCKING PROTEIN; NEGATIVE REGULATION; PTB DOMAIN; DOK-R; FAMILY; IRS-1; ACTIVATION; P62(DOK); GROWTH AB We have identified two new human genes that encode proteins with tandem pleckstrin homology-phosphotyrosine binding (PH-PTB) domains at their amino termini. Because the other known PH-PTB proteins ( insulin receptor substrates: IRS-1, IRS-2, IRS-3, and IRS-4, and the downstream of kinases: DOK-1, DOK-2, and DOK-3) are substrates of insulin and insulin-like growth factor (IGF)-1 receptors, we asked whether these new proteins, termed IRS5/DOK4 and IRS6/DOK5, might also have roles in insulin and IGF-1 signaling. Northern analyses indicate that IRS5/DOK4 is ubiquitously expressed but most abundant in kidney and liver. IRS6/DOK5 expression is highest in skeletal muscle. Both proteins are tyrosine-phosphorylated in response to insulin and IGF-1 in transfected cells, although the kinetics differ. Insulin receptor-phosphorylated IRS5/DOK4 associates with RasGAP, Crk, Src, and Fyn, but not phosphatidylinositol 3-kinase p85, Grb2, SHP-2, Nck, or phospholipase Cgamma Src homology 2 domains, and activates MAPK in cells. IRS6/DOK5 neither associates with these Src homology 2 domains nor activates MAPK. IRS5/DOK4 and IRS6/DOK5 represent two new signaling proteins with potential roles in insulin and IGF-1 action. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK43123, DK36836, F32 DK61187] NR 36 TC 105 Z9 110 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 JUL 11 PY 2003 VL 278 IS 28 BP 25323 EP 25330 DI 10.1074/jbc.M212430200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 697AN UT WOS:000183920200010 PM 12730241 ER PT J AU Castrillon, DH Miao, LL Kollipara, R Horner, JW DePinho, RA AF Castrillon, DH Miao, LL Kollipara, R Horner, JW DePinho, RA TI Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; MOUSE; GROWTH; FAILURE; IDENTIFICATION; OOCYTES; PATHWAY; AGE-1; GENES; FKHR AB Foxo transcription factors have been implicated in diverse biological processes, including metabolism, cellular stress responses, and aging. Here, we show that Foxo3a(-/-) female mice exhibit a distinctive ovarian phenotype of global follicular activation leading to oocyte death, early depletion of functional ovarian follicles, and secondary infertility. Foxo3a thus functions at the earliest stages of follicular growth as a suppressor of follicular activation. In addition to providing a molecular entry point for studying the regulation of follicular growth, these results raise the possibility that accelerated follicular initiation plays a role in premature ovarian failure, a common cause of infertility and premature aging in women. C1 Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Womens & Perinatal Pathol Div, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. FU PHS HHS [K08] NR 23 TC 444 Z9 460 U1 3 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUL 11 PY 2003 VL 301 IS 5630 BP 215 EP 218 DI 10.1126/science.1086336 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 699KN UT WOS:000184056200044 PM 12855809 ER PT J AU Ronthal, M Gonzalez, RG Smith, RN Frosch, MP AF Ronthal, M Gonzalez, RG Smith, RN Frosch, MP TI A man with repetitive strokes in the posterior circulation - Giant-cell arteritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; WEGENERS-GRANULOMATOSIS; DISEASE; AORTITIS; TUBERCULOSIS; VASCULITIS; PATIENT; MANIFESTATIONS C1 Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ronthal, M (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. NR 39 TC 25 Z9 26 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 10 PY 2003 VL 349 IS 2 BP 170 EP 180 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 698XH UT WOS:000184024400012 PM 12853591 ER PT J AU Zhuang, SG Ouedraogo, GD Kochevar, IE AF Zhuang, SG Ouedraogo, GD Kochevar, IE TI Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases SO ONCOGENE LA English DT Article DE apoptosis; epidermal growth factor receptor; caspase; keratinocyte; protein phosphatase; singlet oxygen ID RABBIT SKELETAL-MUSCLE; CATHEPSIN-B; REVERSIBLE INACTIVATION; TYROSINE PHOSPHATASES; ULTRAVIOLET-LIGHT; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; PLASMA-MEMBRANE; CELL APOPTOSIS; UVA RADIATION AB Downregulation of survival signaling pathways contributes to the cytotoxicity of reactive oxygen species (ROS) and may underlie certain therapies for hyperproliferative diseases. We have investigated the role of singlet oxygen, an ROS formed by photosensitization, in the regulation of survival signaling via the epidermal growth factor receptor (EGFR). Exposure of human keratinocytes to singlet oxygen resulted in rapid loss of EGFR, which was not blocked by either inhibition of receptor internalization or by interrupting the major proteolytic pathways (proteasome, lysosome or calpain). However, pretreatment with a caspase-3 inhibitor, DEVD-FMK, inhibited EGFR degradation. Caspase-3 cleavage was detected as early as 5 min after singlet oxygen treatment, and recombinant active caspase-3 completely cleaved EGFR in a keratinocyte membrane fraction. The singlet oxygen-induced loss of EGFR was accompanied by dephosphorylation of EGFR as well as of Akt and extracellular signal-regulated kinase 1/2 (ERK)1/2. Singlet oxygen-induced protein dephosphorylation was not dependent on activation of caspase-3. In contrast, inhibition of protein phosphatases (PPs) with okadaic acid completely blocked dephosphorylation of EGFR, ERK1/2 and Akt as well as degradation of EGFR. These results indicate that the oxidative stress produced by singlet oxygen rapidly disrupts EGFR-mediated signaling by decreasing both the protein level and its phosphorylation. These responses depended on intertwined activation of caspase-3 and PPs. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp, WEL-224,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM 30755] NR 60 TC 35 Z9 37 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL 10 PY 2003 VL 22 IS 28 BP 4413 EP 4424 DI 10.1038/sj.onc.1206604 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 698BZ UT WOS:000183978900011 PM 12853978 ER PT J AU Ruo, B Rumsfeld, JS Hlatky, MA Liu, HY Browner, WS Whooley, MA AF Ruo, B Rumsfeld, JS Hlatky, MA Liu, HY Browner, WS Whooley, MA TI Depressive symptoms and health-related quality of life - The heart and soul study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-ARTERY DISEASE; ACTIVITY STATUS INDEX; SELF-RATED HEALTH; FUNCTIONAL STATUS; BYPASS-SURGERY; PRIMARY-CARE; MYOCARDIAL-INFARCTION/; PERCEIVED HEALTH; FOLLOW-UP; PRIME-MD AB Context Little is known regarding the extent to which patient-reported health status, including symptom burden, physical limitation, and quality of life, is determined by psychosocial vs physiological factors among patients with chronic disease. Objective To compare the contributions of depressive symptoms and measures of cardiac function to the health status of patients with coronary artery disease. Design, Setting, and Participants Cross-sectional study of 1024 adults with stable coronary artery disease recruited from outpatient clinics in the San Francisco Bay Area between September 2000 and December 2002. Main Measures Measurement of depressive symptoms using the Patient Health Questionnaire (PHQ); assessment of cardiac function by measuring left ventricular ejection fraction on echocardiography, exercise capacity on treadmill testing, and ischemia on stress echocardiography; and measurement of a range of health status outcomes, including symptom burden, physical limitation, and quality of life, using the Seattle Angina Questionnaire. Participants were also asked to rate their overall health as excellent, very good, good, fair, or poor. Results Of the 1024 participants, 201 (20%) had depressive symptoms (PHQ score :10). Participants with depressive symptoms were more likely than those without depressive symptoms to report at least mild symptom burden (60% vs 33%; P<.001), mild physical limitation (73% vs 40%; P<.001), mildly diminished quality of life (67% vs 31%; P<.001), and fair or poor overall health (66% vs 30%; P<.001). In multivariate analyses adjusting for measures of cardiac function and other patient characteristics, depressive symptoms were strongly associated with greater symptom burden (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.3-2.7; P=.002), greater physical limitation (OR, 3.1; 95% Cl, 2.1-4.6; P<.001), worse quality of life (OR, 3.1; 95% Cl, 2.2-4.6; P<.001), and worse overall health (OR, 2.0; 95% Cl, 1.3-2.9; P<.001). Although decreased exercise capacity was associated with worse health status, left ventricular ejection fraction and ischemia were not. Conclusions Among patients with coronary disease, depressive symptoms are strongly associated with patient-reported health status, including symptom burden, physical limitation, quality of life, and overall health. Conversely, 2 traditional measures of cardiac function-ejection fraction and ischemia-are not. Efforts to improve health status should include assessment and treatment of depressive symptoms. C1 Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Denver Vet Affairs Med Ctr, Cardiol & Hlth Serv Res, Denver, CO USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Whooley, MA (reprint author), Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [R01 HL079235, R01 HL079235-01A1] NR 57 TC 431 Z9 442 U1 1 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 JUL 9 PY 2003 VL 290 IS 2 BP 215 EP 221 DI 10.1001/jama.290.2.215 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 698GH UT WOS:000183989800026 PM 12851276 ER PT J AU Wang, TJ Larson, MG Levy, D Benjamin, EJ Corey, D Leip, EP Vasan, RS AF Wang, TJ Larson, MG Levy, D Benjamin, EJ Corey, D Leip, EP Vasan, RS TI Heritability and genetic linkage of plasma natriuretic peptide levels SO CIRCULATION LA English DT Article DE natriuretic peptides; genetics; epidemiology; atrial natriuretic factor ID BLOOD-PRESSURE; HYPERTENSION; PHENOTYPES; DISEASE AB Background-Natriuretic peptides play a critical role in the maintenance of salt and water homeostasis and regulation of vascular tone. Thus, interindividual variation in plasma natriuretic peptide levels may contribute to variation in susceptibility to volume overload and hypertension. It is unknown to what extent genetic factors contribute to variation in plasma natriuretic peptide levels. Methods and Results-We studied 1914 Framingham Study participants (mean age 57 years, 53% women) who underwent routine echocardiography and testing for plasma N-terminal proatrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP). We estimated sex-specific multivariable models and used variance-components methods, implemented in SOLAR (Sequential Oligogenic Linkage Analysis Routines), to estimate heritability. Multipoint linkage analyses were performed using data from a 10-cM-density genome scan. Age, clinical, and echocardiographic variables accounted for 42% and 40% of the variation in log N-ANP and log BNP levels, respectively, in men. Corresponding values in women were 27% and 21%. Multivariable-adjusted heritabilities were 0.44 for log N-ANP and 0.35 for log BNP (P<0.0001). Genome-wide linkage analyses, based on 1142 participants from the 314 largest families, revealed 2 regions of suggestive linkage for log N-ANP and log BNP on chromosomes 2p25 (log-of-odds score 2.40) and 12p13 (log-of-odds score 2.13), respectively. Conclusions-In this community-based sample, a substantial proportion of the unexplained variation in plasma natriuretic peptide levels was attributable to additive genetic effects. Additional studies using candidate gene approaches may provide insight into the genetic loci that regulate plasma natriuretic peptide levels in humans. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1U01-HL-66582, K24-HL-04334, N01-HC-25195] NR 19 TC 59 Z9 63 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 JUL 8 PY 2003 VL 108 IS 1 BP 13 EP 16 DI 10.1161/01.CIR.0000081657.83724.A7 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 698GZ UT WOS:000183991600015 PM 12821537 ER PT J AU Patti, ME Butte, AJ Crunkhorn, S Cusi, K Berria, R Kashyap, S Miyazaki, Y Kohane, I Costello, M Saccone, R Landaker, EJ Goldfine, AB Mun, E DeFronzo, R Finlayson, J Kahn, CR Mandarino, LJ AF Patti, ME Butte, AJ Crunkhorn, S Cusi, K Berria, R Kashyap, S Miyazaki, Y Kohane, I Costello, M Saccone, R Landaker, EJ Goldfine, AB Mun, E DeFronzo, R Finlayson, J Kahn, CR Mandarino, LJ TI Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; GAMMA COACTIVATOR-1; EXPRESSION PROFILE; MICROARRAY DATA; OBESE PATIENTS; LIPID-CONTENT; PIMA-INDIANS; FATTY-ACIDS; MELLITUS AB Type 2 diabetes mellitus (DM) is characterized by insulin resistance and pancreatic beta cell dysfunction. in high-risk subjects, the earliest detectable abnormality is insulin resistance in skeletal muscle. Impaired insulin-mediated signaling, gene expression, glycogen synthesis, and accumulation of intramyocellular triglycerides have all been linked with insulin resistance, but no specific defect responsible for insulin resistance and DM has been identified in humans. To identify genes potentially important in the pathogenesis of DM, we analyzed gene expression in skeletal muscle from healthy metabolically characterized nondiabetic (family history negative and positive for DM) and diabetic Mexican-American subjects. We demonstrate that insulin resistance and DM associate with reduced expression of multiple nuclear respiratory factor-1 (NRF-1)-dependent genes encoding key enzymes in oxidative metabolism and mitochondrial function. Although NRF-1 expression is decreased only in diabetic subjects, expression of both PPARgamma coactivator 1-alpha and-beta (PGC1-alpha/PPARGC1 and PGC1-beta/PERC), coactivators of NRF-1 and PPARgamma-dependent transcription, is decreased in both diabetic subjects and family history-positive nondiabetic subjects. Decreased PGC1 expression may be responsible for decreased expression of NRF-dependent genes, leading to the metabolic disturbances characteristic of insulin resistance and DM. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Childrens Hosp, Div Informat & Endocrinol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NCRR NIH HHS [RR-01346, M01 RR001346]; NHGRI NIH HHS [P01HG01323]; NHLBI NIH HHS [HL066582, U01 HL066582]; NIDDK NIH HHS [DK02526, DK06087, DK063696, DK24092, DK47936, K12 DK063696, R01 DK024092, R01 DK047936, R01 DK060837, R56 DK024092, U24 DK058739] NR 52 TC 1137 Z9 1164 U1 7 U2 57 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 2003 VL 100 IS 14 BP 8466 EP 8471 DI 10.1073/pnas.1032913100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 702KF UT WOS:000184222500077 PM 12832613 ER PT J AU Hang, L John, M Asaduzzaman, M Bridges, EA Vanderspurt, C Kirn, TJ Taylor, RK Hillman, JD Progulske-Fox, A Handfield, M Ryan, ET Calderwood, SB AF Hang, L John, M Asaduzzaman, M Bridges, EA Vanderspurt, C Kirn, TJ Taylor, RK Hillman, JD Progulske-Fox, A Handfield, M Ryan, ET Calderwood, SB TI Use of in vivo-induced antigen technology (IVIAT) to identify genes uniquely expressed during human infection with Vibrio cholerae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOXIN-COREGULATED PILI; MANNOSE-SENSITIVE HEMAGGLUTININ; EL-TOR BIOTYPES; PSEUDOMONAS-AERUGINOSA; BACTERIAL VIRULENCE; ENDEMIC CHOLERA; IDENTIFICATION; COLONIZATION; PROTECTION; O139 AB In vivo-induced antigen technology is a method to identify proteins expressed by pathogenic bacteria during human infection. Sera from 10 patients convalescing from cholera infection in Bangladesh were pooled, adsorbed against in vitro-grown El Tor Vibrio cholerae 01, and used to probe a genomic expression library in Escherichia coli constructed from El Tor V. cholerae 01 strain N16961. We identified 38 positive clones in the screen, encoding pili (PilA and TcpA), cell membrane proteins (PilQ, MshO, MshP, and CapK), methyl-accepting chemotaxis proteins, chemotaxis and motility proteins (CheA and CheR), a quorum-sensing protein (LuxP), and four hypothetical proteins. Analysis of immune responses to purified PilA and TcpA in individual patients demonstrated that the majority seroconverted to these proteins, confirming results with pooled sera. These results suggest that PilA and its outer membrane secretin, PilQ, are expressed during human infection and may be involved in colonization of the gastrointestinal tract. These results also demonstrate substantial immune responses to TcpA in patients infected with El Tor V. cholerae O1. In vivo-induced antigen technology provides a simple method for identifying microbial proteins expressed during human infection, but not during in vitro growth. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. Dartmouth Coll, Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. Univ Florida, Coll Dent, Ctr Mol Microbiol, Gainesville, FL 32610 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. FU FIC NIH HHS [D43 TW005572, D43 TW05572]; NIAID NIH HHS [R01 AI025096, R01 AI040725, R01 AI25096, R01 AI40725, R01 AI44487]; NICHD NIH HHS [U01 HD039165, UO1 HD39165]; NIDCR NIH HHS [R01 DE013523, R01 DE13523] NR 35 TC 84 Z9 99 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 8 PY 2003 VL 100 IS 14 BP 8508 EP 8513 DI 10.1073/pnas.1431769100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 702KF UT WOS:000184222500084 PM 12826608 ER PT J AU Ansari, MJI Salama, AD Chitnis, T Smith, RN Yagita, H Akiba, H Yamazaki, T Azuma, M Iwai, H Khoury, SJ Auchincloss, H Sayegh, MH AF Ansari, MJI Salama, AD Chitnis, T Smith, RN Yagita, H Akiba, H Yamazaki, T Azuma, M Iwai, H Khoury, SJ Auchincloss, H Sayegh, MH TI The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE diabetes mellitus, insulin-dependent; mice, inbred NOD; autoimmunity; self-tolerance; programmed cell death protein 1 ID B7 FAMILY; T-CELLS; MONOCLONAL-ANTIBODY; IMMUNE-SYSTEM; EXPRESSION; LYMPHOCYTES; MOLECULE; MEMBER; MOUSE; ONSET AB Programmed death-1 (PD-1) receptor, an inhibitory costimulatory molecule found on activated T cells, has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in the development of autoimmune diabetes. PD-1 or PD-L1 but not PD-L2 blockade rapidly precipitated diabetes in prediabetic female nonobese diabetic (NOD) mice regardless of age (from 1 to 10-wk-old), although it was most pronounced in the older mice. By contrast, cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) blockade induced disease only in neonates. Male NOD mice also developed diabetes after PD-1-PD-L1 pathway blockade, but NOR mice, congenic to NOD but resistant to the development of diabetes, did not. Insulitis scores were significantly higher and frequency of interferon gamma-producing GAD-reactive splenocytes was increased after PD-1-PD-L1 pathway blockade compared with controls. Interestingly, PD-L1 but not PD-L2 was found to be expressed on inflamed islets of NOD mice. These data demonstrate a central role for PD-1 PD-L1 interaction in the regulation of induction and progression of autoimmune diabetes in the NOD mouse and provide the rationale to develop new therapies to target this costimulatory pathway in this disease. C1 Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg & Pathol, Boston, MA 02115 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 1138421, Japan. Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo 1138549, Japan. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010; OI khoury, samia/0000-0003-3198-6063 FU NIAID NIH HHS [P01 AI-41521, P01 AI041521] NR 29 TC 356 Z9 378 U1 3 U2 20 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 7 PY 2003 VL 198 IS 1 BP 63 EP 69 DI 10.1084/jem.20022125 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 700VP UT WOS:000184132100007 PM 12847137 ER PT J AU Christmas, P Carlesso, N Shang, HB Cheng, SM Weber, BM Preffer, FI Scadden, DT Soberman, RJ AF Christmas, P Carlesso, N Shang, HB Cheng, SM Weber, BM Preffer, FI Scadden, DT Soberman, RJ TI Myeloid expression of cytochrome P4504F3 is determined by a lineage-specific alternative promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; B-4 OMEGA-HYDROXYLASE; LEUKOTRIENE B-4; TRANSCRIPTION FACTORS; COREPRESSOR CTBP; HUMAN MONOCYTE; DNA-BINDING; CYP4F3 GENE; IN-VITRO; ACTIVATION AB The cytochrome P450 4F3 (CYP4F3) gene encodes two functionally distinct enzymes that differ only by the selection of exon 4 (CYP4F3A) or exon 3 (CYP4F3B). CYP4F3A inactivates leukotriene B-4, a reaction that has significance for controlling inflammation. CYP4F3B converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a potent activator of protein kinase C. We have previously shown that mRNAs coding for CYP4F3A and CYP4F3B are generated from distinct transcription start sites in neutrophils and liver. We therefore investigated mechanisms that regulate the cell-specific expression of these two isoforms. Initially, we analyzed the distribution of CYP4F3 in human leukocytes and determined a lineage-specific pattern of isoform expression. CYP4F3A is expressed in myeloid cells and is coordinate with myeloid differentiation markers such as CD11b and myeloperoxidase during development in the bone marrow. In contrast, CYP4F3B expression is restricted to a small population of CD3+ T lymphocytes. We identified distinct transcriptional features in myeloid, lymphoid, and hepatic cells that indicate the presence of multiple promoters in the CYP4F3 gene. The hepatic promoter depends on a cluster of hepatocyte nuclear factor sites 123-155 bp upstream of the initiator ATG codon. The myeloid promoter spans 400 bp in a region 468-872 bp upstream of the ATG codon; it is associated with clusters of CACCT sites and can be activated by ZEB-2, a factor primarily characterized as a transcriptional repressor in cells that include lymphocytes. ZEB-2 interacts with C-terminal binding protein and Smads, and this would provide opportunities for integrating environmental signals in myelopoiesis and inflammation. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Christmas, P (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 Navy Yard,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL68256, HL55718]; NIDDK NIH HHS [DK52234, DK59991]; NIGMS NIH HHS [GM-61823] NR 46 TC 15 Z9 18 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 JUL 4 PY 2003 VL 278 IS 27 BP 25133 EP 25142 DI 10.1074/jbc.M302106200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 695HJ UT WOS:000183824800107 PM 12709424 ER PT J AU Haughn, L Hawley, RG Morrison, DK von Boehmer, H Hockenbery, DM AF Haughn, L Hawley, RG Morrison, DK von Boehmer, H Hockenbery, DM TI BCL-2 and BCL-X-L restrict lineage choice during hematopoietic differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-DEFICIENT MICE; CELL-DEATH; MEDIATED ACTIVATION; GROWTH-FACTORS; EXPRESSION; APOPTOSIS; PROTEIN; FAMILY; INHIBITION; RAF-1 AB Differentiation of hematopoietic cells from multipotential progenitors is regulated by multiple growth factors and cytokines. A prominent feature of these soluble factors is promotion of cell survival, in part mediated by expression of either of the anti-apoptotic proteins, BCL-2 and BCL-X-L. The complex expression pattern of these frequently redundant survival factors during hematopoiesis may indicate a role in lineage determination. To investigate the latter possibility, we analyzed factor-dependent cell-Patersen (FDCP)-Mix multipotent progenitor cells in which we stably expressed BCL-2 or BCL-X-L. Each factor maintained complete survival of interleukin-3 (IL-3)-deprived FDCP-Mix cells but, unexpectedly, directed FDCP-Mix cells along restricted and divergent differentiation pathways. Thus, IL-3-deprived FDCP-Mix BCL-2 cells differentiated exclusively to granulocytes and monocytes/macrophages, whereas FDCP-Mix BCL-X-L cells became erythroid. FDCP-Mix BCL-2 cells grown in IL-3 were distinguished from FDCP-Mix and FDCP-Mix BCL-X-L cells by a striking reduction in cellular levels of Raf-1 protein. Replacement of the BCL-2 BH4 domain with the related BCL-X-L BH4 sequence resulted in a switch of FDCP-Mix BCL-2 cells to erythroid fate accompanied by persistence of Raf-1 protein expression. Moreover, enforced expression of Raf-1 redirected FDCP-Mix BCL-2 cells to an erythroid fate, and prohibited generation of myeloid cells. These results identify novel roles for BCL-2 and BCL-X-L in cell fate decisions beyond cell survival. These effects are associated with differential regulation of Raf-1 expression, perhaps involving the previously identified interaction between BCL-2-BH4 and the catalytic domain of Raf-1. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Seattle, WA 98109 USA. Amer Red Cross, Hematopoiesis Dept, Jerome H Holland Lab, Rockville, MD 20855 USA. NCI, Cellular Growth Mechanisms Sect, Frederick Canc Res & Dev Ctr, NIH, Ft Detrick, MD 21702 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hockenbery, DM (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Mailstop D2-190,1100 Fairview Ave N, Seattle, WA 98109 USA. FU NHLBI NIH HHS [IP50HL54881] NR 48 TC 34 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 4 PY 2003 VL 278 IS 27 BP 25158 EP 25165 DI 10.1074/jbc.M212849200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 695HJ UT WOS:000183824800110 PM 12721288 ER PT J AU Pineda, P Kanter, A McIvor, RS Benkovic, SJ Rosowsky, A Wagner, CR AF Pineda, P Kanter, A McIvor, RS Benkovic, SJ Rosowsky, A Wagner, CR TI Dihydrofolate reductase mutant with exceptional resistance to methotrexate but not to trimetrexate SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SUBSTITUTIONS; VARIANTS AB Two double (F31A/F34A, 160A/L67G) and one quadruple (F31A/F34A/I60A/L67G) mutant murine dihydrofolate reductases were constructed and evaluated for their ability to impart antifolate resistance. Both 160A/L67G and F31A/F34A/I60A/L67G were found to be unstable and devoid of catalytic activity. The K-i values for F31A/F34A, methotrexate (MTX), bis-MTX, and PT-523 were found to be 10100-, 4410-, and 617-fold higher than the wild-type enzyme, respectively, but only 13.5-fold higher for trimetrexate (TMTX). These findings suggest that F31A/F34A could be used for gene therapy to render normal cells resistant to MTX but sensitive to TMTX. C1 Univ Minnesota, Dept Med Chem, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Genet & Dev, Minneapolis, MN 55455 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 USA. Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wagner, CR (reprint author), Univ Minnesota, Dept Med Chem, 8-101 Weaver Densford Hall,308 Harvard St, Minneapolis, MN 55455 USA. FU NCI NIH HHS [CA60803] NR 12 TC 7 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 3 PY 2003 VL 46 IS 14 BP 2816 EP 2818 DI 10.1021/jm034057i PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 695HF UT WOS:000183824500003 PM 12825924 ER PT J AU Mora, JR Bono, MR Manjunath, N Weninger, W Cavanagh, LL Rosemblatt, M von Andrian, UH AF Mora, JR Bono, MR Manjunath, N Weninger, W Cavanagh, LL Rosemblatt, M von Andrian, UH TI Selective imprinting of gut-homing T cells by Peyer's patch dendritic cells SO NATURE LA English DT Article ID CHEMOKINE RECEPTOR; IN-VIVO; LYMPHOCYTE; TISSUE; DIFFERENTIATION; LOCALIZATION; MIGRATION; INTEGRINS; EFFECTOR; ACQUISITION AB Whereas naive T cells migrate only to secondary lymphoid organs(1,2), activation by antigen confers to T cells the ability to home to non-lymphoid sites(3,4). Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered(5-7). Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Chile, Fdn Ciencias Vida, Fac Ciencias, Lab Inmunol, Santiago 6842301, Chile. Millennium Inst Fundamental & Appl Biol, Santiago 6842301, Chile. RP von Andrian, UH (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008; Bono, Maria/G-7461-2014; OI Weninger, Wolfgang/0000-0003-3133-8699 NR 30 TC 675 Z9 702 U1 6 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 3 PY 2003 VL 424 IS 6944 BP 88 EP 93 DI 10.1038/nature01726 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 696XL UT WOS:000183912800046 PM 12840763 ER PT J AU Ross, SE Greenberg, ME Stiles, CD AF Ross, SE Greenberg, ME Stiles, CD TI Basic helix-loop-helix factors in cortical development SO NEURON LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; BHLH TRANSCRIPTION FACTORS; MAMMALIAN ACHAETE-SCUTE; NEURAL PROGENITOR CELLS; STEM-CELLS; NEURONAL DIFFERENTIATION; OLIGODENDROCYTE DIFFERENTIATION; SUBTYPE SPECIFICATION; TARGETED DISRUPTION; DETERMINATION GENES AB Transcription factors with bHLH motifs modulate critical events in the development of the mammalian neocortex. Multipotent cortical progenitors are maintained in a proliferative state by bHLH factors from the Id and Hes families. The transition from proliferation to neurogenesis involves a coordinate increase in the activity of proneural bHLH factors (Mash1, Neurogenin1,, and Neurogenin2) and a decrease in the activity of Hes and Id factors. As development proceeds, inhibition of proneural bHLH factors in cortical progenitors promotes the formation of astrocytes. Finally, the formation of oligodendrocytes is triggered by an increase in the activity of bHLH factors Olig1 and Olig2 that may be coupled with a decrease in Id activity. Thus, bHLH factors have key roles in corticogenesis, affecting the timing of differentiation and the specification of cell fate. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurobiol,Div Neurosci, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Microbiol & Mol Genet, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24926] NR 110 TC 399 Z9 419 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUL 3 PY 2003 VL 39 IS 1 BP 13 EP 25 DI 10.1016/S0896-6273(03)00365-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 699LB UT WOS:000184057400006 PM 12848929 ER PT J AU Tallman, MS Gray, R Robert, NJ LeMaistre, CF Osborne, CK Vaughan, WP Gradishar, WJ Pisansky, TM Fetting, J Paietta, E Lazarus, HM AF Tallman, MS Gray, R Robert, NJ LeMaistre, CF Osborne, CK Vaughan, WP Gradishar, WJ Pisansky, TM Fetting, J Paietta, E Lazarus, HM TI Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW; MYELODYSPLASTIC SYNDROME; RANDOMIZED-TRIAL; AXILLARY NODES; THERAPY; SUPPORT; CYCLOPHOSPHAMIDE; METHOTREXATE; RESCUE AB BACKGROUND: The prognosis for women with primary breast cancer and 10 or more involved axillary lymph nodes is poor. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation has been reported to be effective in the adjuvant setting for patients at high risk for relapse. METHODS: We randomly assigned 540 female patients with primary breast cancer and at least 10 involved ipsilateral axillary lymph nodes to receive either six cycles of adjuvant chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) or the same adjuvant chemotherapy followed by high-dose chemotherapy with cyclophosphamide and thiotepa and autologous hematopoietic stem-cell transplantation. RESULTS: Among the 511 eligible patients, there was no significant difference in disease-free survival, overall survival, or the time to recurrence between those who received CAF alone and those who received CAF plus high-dose chemotherapy and stem-cell transplantation. Among 417 patients fulfilling strict eligibility criteria, the time to recurrence was longer for patients who underwent stem-cell transplantation than for those who received CAF alone. In the transplantation group, nine patients died of transplantation-related complications and a myelodysplastic syndrome or acute myeloid leukemia developed in nine. CONCLUSIONS: The addition of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation to six cycles of adjuvant chemotherapy with CAF may reduce the risk of relapse but does not improve the outcome among patients with primary breast cancer and at least 10 involved axillary lymph nodes. Conventional-dose adjuvant chemotherapy remains the standard of care for such patients. C1 Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inova Fairfax Hosp, Falls Church, VA USA. Texas Transplant Inst, San Antonio, TX USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Univ Alabama, Birmingham, AL USA. Mayo Clin, Div Radiat Oncol, Rochester, MN USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. Case Western Reserve Univ, Sch Med, Ireland Canc Ctr, Cleveland, OH USA. RP Tallman, MS (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. FU NCI NIH HHS [CA13650, CA16116, CA17145, CA21115, CA23318, CA28926, CA32102, CA66636] NR 37 TC 118 Z9 122 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 3 PY 2003 VL 349 IS 1 BP 17 EP 26 DI 10.1056/NEJMoa030684 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 696PW UT WOS:000183896100004 PM 12840088 ER PT J AU Lamont, EB Christakis, NA AF Lamont, EB Christakis, NA TI Complexities in prognostication in advanced cancer - "To help them live their lives the way they want to" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; CELL LUNG-CANCER; KARNOFSKY PERFORMANCE STATUS; RANDOMIZED CONTROLLED TRIAL; METASTATIC BREAST-CANCER; TERMINALLY ILL PATIENTS; SUPPORTIVE CARE BSC; BREAKING BAD-NEWS; HEPATOCELLULAR-CARCINOMA; CHEMOTHERAPY PLUS C1 Univ Chicago, Med Ctr, Dept Med, Gen Internal Med Sect, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Lamont, EB (reprint author), Univ Chicago, Med Ctr, Dept Med, Gen Internal Med Sect, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA. RI Christakis, Nicholas/B-6690-2008; Christakis, Nicholas/C-3205-2009 FU NCI NIH HHS [K07 CA-93892, K07 CA093892] NR 72 TC 107 Z9 107 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 2 PY 2003 VL 290 IS 1 BP 98 EP 104 DI 10.1001/jama.290.1.98 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 696CR UT WOS:000183868600025 PM 12837717 ER PT J AU Gibson, CM Karha, J Murphy, SA James, D Morrow, DA Cannon, CP Glugliano, RP Antman, EM Braunwald, E AF Gibson, CM Karha, J Murphy, SA James, D Morrow, DA Cannon, CP Glugliano, RP Antman, EM Braunwald, E CA TIMI Study Grp TI Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the thrombolysis in myocardial infarction trials SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; CORONARY INTERVENTION; THROMBIN INHIBITION; RANDOMIZED TRIAL; INTRAVENOUS NPA; TIMI 4; THERAPY; ANGIOPLASTY; ALTEPLASE; IMMEDIATE AB OBJECTIVES We hypothesized that early recurrent myocardial infarction (MI) following fibrinolytic administration would be assessed with higher mortality at both 30 days and 2 years. BACKGROUND Although early recurrent MI after fibrinolytic therapy has been associated with increased early mortality in the acute MI setting, its relation to long-term mortality has not been fully explored. METHODS Mortality data were ascertained in 20,101 patients enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 4, 9, and 10B and Intravenous NPA for the Treatment of Infarcting Myocardium Early (InTIME-II) acute MI trials. RESULTS The frequency of symptomatic recurrent MI during the index hospitalization was 4.2% (836/20,101). Recurrent MI during the index hospital period was associated with increased 30-day mortality (16.4% [137/836] vs. 6.2% [1,188/19,260], p < 0.001). Likewise, recurrent MI was associated with a sustained increase in mortality up to two years, even after adjustments were made for covariates known to be associated with mortality and recurrent MI (hazard ratio 2.11, p < 0.001). However, this higher mortality at 2 years was due to an early divergence in mortality by 30 days and was not due to a significant increase in late mortality between 30 days and 2 years (4.38% [31/707] vs. 3.76% [685/18,206], p = NS). Percutaneous coronary intervention during the index hospitalization was associated with a lower rate of in-hospital recurrent MI (1.6% vs. 4.5%, p < 0.001) and lower two-year mortality (5.6% vs. 11.6%, p < 0.001). Performance of coronary artery bypass graft surgery was also associated with a lower recurrent rate of MI (0.7% vs. 4.3%, p < 0.001) and lower two-year mortality rate (7.95% vs. 10.6%, p = 0.0008). CONCLUSIONS Early recurrent MI is associated with increased mortality up to two years. However, most deaths occur early, and the risk of additional deaths between the index hospital period and two years was not significantly increased among patients with recurrent MI. Percutaneous coronary intervention during the index hospitalization was associated with a lower risk of recurrent MI and a lower risk of two-year mortality. (C) 2003 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Gibson, CM (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 25 TC 106 Z9 113 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 2 PY 2003 VL 42 IS 1 BP 7 EP 16 DI 10.1016/S0735-1097(03)00506-0 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 695HQ UT WOS:000183825400002 PM 12849652 ER PT J AU Kabrhel, C Binder, W AF Kabrhel, C Binder, W TI Clinical pearls: A 37-year-old man with a rash... SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID CRUSTED SCABIES; IVERMECTIN C1 Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Emergency Med, Boston, MA 02114 USA. RP Kabrhel, C (reprint author), Brigham & Womens Hosp, Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, 55 Fruit St, Boston, MA 02114 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2003 VL 10 IS 7 BP 776 EP 779 DI 10.1111/j.1553-2712.2003.tb00072.x PG 4 WC Emergency Medicine SC Emergency Medicine GA 697WR UT WOS:000183966700011 PM 12837652 ER PT J AU Kasman, DL Fryer-Edwards, K Braddock, CH AF Kasman, DL Fryer-Edwards, K Braddock, CH TI Educating for professionalism: Trainees' emotional experiences on IM and pediatrics inpatient wards SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Society-of-Teachers-of-Family-Medicine CY APR, 2001 CL DENVER, COLORADO SP Natl Soc Tearchers Family Med ID US MEDICAL-SCHOOLS; PATIENT SATISFACTION; MOOD STATES; STUDENTS; PHYSICIAN; STRESS; FACULTY; CARE; RESIDENCY; CURRICULUM AB Purpose. To assess day-to-day emotions and the experiences that trigger these emotions for medical trainees in hospital settings. The overarching goal was to illuminate training experiences that affect professional behaviors of physicians. Method. This qualitative study, conducted April-June 2000, used semistructured, open-ended interviews, observations by a non-participant, and a self-report task at two inpatient services (internal medicine and pediatrics) at different hospitals within a single academic institution in the northwestern United States. Twelve team members, including medical students, interns, residents, and attendings, were invited to participate. Ten completed all aspects of the study. Interviews were conducted before and after a one-week period of non-participant observations and self-report tasks. The authors grouped emotional experiences into "positive" or "difficult" emotions. Data were analyzed for coherent themes using grounded theory and content analysis. Results. Positive emotions included gratitude, happiness, compassion, pride, and relief, and were triggered by connections with patients and colleagues, receiving recognition for one's labors, learning, being a part of modern medicine, and receiving emotional support from others. Difficult emotions included anxiety, guilt, sadness, anger, and shame and were triggered by uncertainty, powerlessness, responsibility, liability, lack of respect, and a difference in values. Tragedy and patients' suffering was the only trigger to elicit both positive (compassion) and difficult (sadness) emotions. Conclusion. This study identified common and important emotions experienced by medical trainees and the common triggers for these emotions. Understanding trainees' experiences of uncertainty, powerlessness, differing values, and lack of respect can guide education program designs and reforms to create an environment that fosters professional growth. C1 US Dept Vet Affairs, Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Dept Med Hist & Eth, Sch Med, Seattle, WA USA. Univ Washington, Dept Med, Sch Med, Seattle, WA USA. NR 81 TC 42 Z9 43 U1 1 U2 7 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2003 VL 78 IS 7 BP 730 EP 741 DI 10.1097/00001888-200307000-00017 PG 12 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 711LG UT WOS:000184741600011 PM 12857696 ER PT J AU Nielsen, GP O'Connell, JX Wehrli, BM Rosenberg, AE AF Nielsen, GP O'Connell, JX Wehrli, BM Rosenberg, AE TI Collagen-rich tumors of soft tissues: An overview SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE collagen; soft tissue tumor; fibrous; fibroblast; myofibroblast; spindle cell ID SOLITARY FIBROUS TUMOR; GRADE FIBROMYXOID SARCOMA; SPINDLE-CELL LIPOMA; INFLAMMATORY MYOFIBROBLASTIC TUMOR; NUCHAL-TYPE FIBROMA; SCLEROSING EPITHELIOID FIBROSARCOMA; UPPER RESPIRATORY-TRACT; DESMOPLASTIC FIBROBLASTOMA; TENDON SHEATH; PLEOMORPHIC FIBROMA AB Although relatively common, soft tissue tumors frequently present diagnostic problems for practicing pathologists. Immunohistochemistry has facilitated the diagnosis of many mesenchymal tumors; however, there is considerable overlap in the staining profiles among cells demonstrating fibroblastic and myofibroblastic differentiation. It has been our experience that soft tissue tumors associated with abundant extracellular collagen deposition commonly cause problems in classification. One reason for this is that tumors displaying this morphology include representatives from different histogenetic families. Specifically, tumors exhibiting fibroblastic, myofibroblastic and even lipomatous differentiation may manifest as a densely collagenous mass. It is the purpose of this review to highlight these collagen-rich soft tissue tumors. C1 Surrey Mem Hosp, Dept Pathol, Surrey, BC V3V 1Z2, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. London Hlth Sci Ctr, Dept Pathol, London, ON, Canada. RP O'Connell, JX (reprint author), Surrey Mem Hosp, Dept Pathol, 13750 96th Ave, Surrey, BC V3V 1Z2, Canada. NR 165 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD JUL PY 2003 VL 10 IS 4 BP 179 EP 199 DI 10.1097/00125480-200307000-00001 PG 21 WC Pathology SC Pathology GA 697YT UT WOS:000183971400001 PM 12826824 ER PT J AU Hung, AM Chertow, GA Young, BS Carey, S Johansen, KL AF Hung, AM Chertow, GA Young, BS Carey, S Johansen, KL TI Inflammatory markers are unrelated to physical activity, performance, and functioning in hemodialysis SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Society-of-Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Nephrol ID CHRONIC-RENAL-FAILURE; C-REACTIVE PROTEIN; INTERLEUKIN-1 RECEPTOR ANTAGONIST; RECOMBINANT-HUMAN-ERYTHROPOIETIN; MAINTENANCE DIALYSIS PATIENTS; PERITONEAL-DIALYSIS; ENERGY-EXPENDITURE; NUTRITIONAL-STATUS; PLASMA-FIBRINOGEN; HEART-FAILURE AB Objective: To determine the associations among dietary intake and inflammatory cytokines with physical activity, function, and performance in maintenance dialysis patients. Design: Cross-sectional analysis of cohort study. Setting: University-affiliated dialysis units, general clinical research center. Subjects: Multiethnic cohort of maintenance hemodialysis patients. Main Outcome Measures: Physical activity by accelerometry; physical performance by gait speed, stair climbing, and chair raising; physical functioning by the Medical Outcomes Study Short Form 36-item questionnaire subscale scores; and maximal and adjusted activity scores of human activity profile. Results: Levels of inflammatory cytokines were uniformly high. Tumor necrosis factor-a was directly correlated with dietary protein and energy intake; no other cytokines were directly or inversely correlated with intake. Dietary intake was associated with physical activity, as expected, and not significantly associated with performance or function (with the exception of gait speed). There were no significant associations among inflammatory cytokines and physical activity, performance, or function. Conclusion: Although dietary intake and inflammation may independently influence traditional proxies of nutritional status, this analysis provides no evidence for a link between cytokines and physical activity, performance, or function in hemodialysis patients. More research is required to understand the role of cytokines in protein energy malnutrition and the mechanisms of wasting and functional decline in the dialysis population. (C) 2003 by the National Kidney Foundation, Inc. C1 San Francisco VA Med Ctr, Div Nephrol 111J, San Francisco, CA 94121 USA. Univ Calif San Francisco, Mt Zion Med Ctr, San Francisco, CA 94120 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Hung, AM (reprint author), San Francisco VA Med Ctr, Div Nephrol 111J, 4150 Clement St, San Francisco, CA 94121 USA. FU NCRR NIH HHS [RR-00083] NR 56 TC 9 Z9 9 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 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD JUL PY 2003 VL 10 IS 3 BP 232 EP 240 DI 10.1053/j.arrt.2003.10.002 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 760FE UT WOS:000187800300010 PM 14708079 ER PT J AU Anton, R Randall, C Latham, P Ciraulo, D LoCastro, J Donovan, D Kivlahan, D Saxon, A Johnson, B Roache, J Mason, B Salvato, F Williams, L Mattson, M Miller, W Westerberg, V Tonigan, JS O'Malley, S Petrakis, I Krystal, J Pettinati, H Flannery, B Swift, R Longabaugh, R Weiss, R Gastfriend, D Greenfield, S Zweben, A Cisler, R Fleming, M Hosking, J Garbutt, J Couper, D AF Anton, R Randall, C Latham, P Ciraulo, D LoCastro, J Donovan, D Kivlahan, D Saxon, A Johnson, B Roache, J Mason, B Salvato, F Williams, L Mattson, M Miller, W Westerberg, V Tonigan, JS O'Malley, S Petrakis, I Krystal, J Pettinati, H Flannery, B Swift, R Longabaugh, R Weiss, R Gastfriend, D Greenfield, S Zweben, A Cisler, R Fleming, M Hosking, J Garbutt, J Couper, D CA COMBINE Study Res Grp TI Testing combined pharmacotherapies and behavioral interventions in alcohol dependence: Rationale and methods SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE alcohol-dependence; pharmacotherapy; behavioral-intervention; methodology ID PLACEBO-CONTROLLED TRIAL; COMPULSIVE DRINKING SCALE; DOUBLE-BLIND; ETHANOL-CONSUMPTION; DOPAMINE RELEASE; CLINICAL-TRIALS; HEAVY DRINKERS; PROJECT MATCH; USE DISORDERS; NALTREXONE AB Increasing knowledge about effective therapies for alcohol dependence calls for new research designs to examine treatment interactions between pharmacotherapies and behavioral interventions. In 1997, the National Institute on Alcohol Abuse and Alcoholism recruited 11 sites and a coordinating center for a large-scale (1,375 subjects), randomized placebo controlled trial to test 16 weeks of active treatment using naltrexone and acamprosate alone and in combination. Most participants receive 9 brief sessions delivered by medically trained providers to promote sobriety and enhance medication adherence (Medical Management, MM). Half the participants are also randomized to individualized psychotherapy (up to 20 sessions of Combined Behavioral Intervention, CBI), integrating elements of the successful behavioral interventions from Project MATCH. COMBINE seeks to evaluate the efficacy of the two most promising medications (naltrexone and acamprosate) both singly and together, when combined with different intensities of behavioral therapies. COMBINE incorporates a number of innovative design aspects, including a no-pill psychotherapy-alone condition, behavioral interventions that are both manual-guided and individualized, and pharmacotherapy dosing that is greater than in some previous, trials. Two COMBINE pilot studies demonstrate the safety and acceptability of the combination pharmacotherapy dosing, and the feasibility of implementing the manualized behavioral interventions. This paper introduces COMBINE's goals, methods and analytic strategies, and their potential to improve multimodal treatment selection. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Boston Univ, Boston Univ Vet Adm Sch Med, Boston, MA 02215 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Addict Treatment Ctr, Seattle, WA 98195 USA. Univ Texas, SW Texas Addict Res & Technol Ctr, San Antonio, TX 78285 USA. Univ Miami, Sch Med, Miami, FL 33101 USA. NIAAA, Bethesda, MD USA. Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. Yale Univ, Sch Med, Subst Abuse Treatment Unit, New Haven, CT 06510 USA. Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Brown Univ, Providence, RI 02912 USA. Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Belmont, MA 02178 USA. Univ Wisconsin, Ctr Addict & Behav Hlth Res, Milwaukee, WI 53201 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27599 USA. RP Gastfriend, D (reprint author), Massachusetts Gen Hosp Back Bay, 388 Commonwealth Ave,Lower Level, Boston, MA 02215 USA. EM dgastfriend@partners.org RI Mason, Barbara/P-6604-2016 NR 111 TC 67 Z9 69 U1 5 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2003 VL 27 IS 7 BP 1107 EP 1122 DI 10.1097/01.alc.0000086765.46408.64 PG 16 WC Substance Abuse SC Substance Abuse GA 704RV UT WOS:000184354500010 ER PT J AU Anton, R Randall, C Latham, P Ciraulo, D LoCastro, J Donovan, D Kivlahan, D Saxon, A Johnson, B Roache, J Tiouririne, NAD Mason, B Salvato, F Williams, L Mattson, M Miller, W Westerberg, V Tonigan, JS O'Malley, S Petrakis, I Krystal, J Pettinati, H Flannery, B Swift, R Longabaugh, R Weiss, R Gastfriend, D Greenfield, S Zweben, A Cisler, R Fleming, M Hosking, J Garbutt, J Couper, D AF Anton, R Randall, C Latham, P Ciraulo, D LoCastro, J Donovan, D Kivlahan, D Saxon, A Johnson, B Roache, J Tiouririne, NAD Mason, B Salvato, F Williams, L Mattson, M Miller, W Westerberg, V Tonigan, JS O'Malley, S Petrakis, I Krystal, J Pettinati, H Flannery, B Swift, R Longabaugh, R Weiss, R Gastfriend, D Greenfield, S Zweben, A Cisler, R Fleming, M Hosking, J Garbutt, J Couper, D CA COMBINE Study Res Grp TI Testing combined pharmacotherapies and behavioral interventions for alcohol dependence (The COMBINE study): A pilot feasibility study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcoholism; pharmacotherapy; behavioral therapy; naltrexone; acamprosate ID PLACEBO-CONTROLLED TRIAL; NALTREXONE; ACAMPROSATE; DRINKING; THERAPY; SAFETY AB Background: Medications (such as naltrexone and acamprosate) as well as behavioral therapies have been previously reported to be effective in the reduction of alcohol intake and to prevent relapse drinking. However, the efficacy of using several medications alone or together in combination with behavioral therapies has not been widely investigated. The purpose of this study was to evaluate the feasibility of this combined therapy approach to apply it to a larger scale multisite clinical trial. Outcome focused on recruitment, retention, adherence to study parameters and medication, physical complaints, and physiologic toxicity. Methods: At 11 sites, 108 individuals with alcohol dependence were randomized in a double blind fashion to receive placebo, naltrexone, or acamprosate alone or in combination. In addition, some individuals were randomized to receive Medical Management (MM) provided by a health care practitioner alone or in combination with an enhanced behavioral intervention, Combined Behavioral Intervention (CBI), delivered by a trained therapist. A final group received CBI alone without pills. All participants were treated and assessed for a maximum of 16 weeks. Results: The attendance at therapy and research visits, and medication adherence and tolerability were good with no statistical differences between the medication or behavioral intervention groups. Over 75% of participants completed the week-16, end of study, assessment and the average medication adherence (percent of total pills taken) was about 65%. The level and types of physical complaints were not unexpected and similar among the medication and placebo groups. There were no group differences in liver or kidney toxicity. Importantly, the combination of naltrexone and acamprosate did not present significantly more physical complaints than either alone. Conclusions: Sufficient numbers of alcohol dependent participants can be recruited and retained in a relatively sophisticated outpatient trial combining medications and behavioral interventions. Participant adherence to the trial protocol including medication regimens was at acceptable levels. Physical complaints and organ toxicity were within expected and acceptable levels. Based on these results a larger scale study utilizing these methodologies appears feasible. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Boston Univ, Boston Univ Vet Adm Sch Med, Boston, MA 02215 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Addict Treatment Ctr, Seattle, WA 98195 USA. Univ Texas, SW Texas Addict Res & Technol Ctr, San Antonio, TX 78285 USA. Univ Miami, Sch Med, Miami, FL USA. NIAAA, Bethesda, MD USA. Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. Yale Univ, Sch Med, Subst Abuse Treatment Unit, New Haven, CT USA. Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Brown Univ, Providence, RI 02912 USA. Harvard Univ, McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Belmont, MA USA. Univ Wisconsin, Ctr Addict & Behav Hlth Res, Milwaukee, WI 53201 USA. Univ N Carolina, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA. RP Anton, R (reprint author), Med Univ S Carolina, 67 President St, Charleston, SC 29425 USA. EM antonr@musc.edu RI Mason, Barbara/P-6604-2016 NR 22 TC 37 Z9 37 U1 4 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2003 VL 27 IS 7 BP 1123 EP 1131 DI 10.1097/01.ALC.0000078020.92938.0B PG 9 WC Substance Abuse SC Substance Abuse GA 704RV UT WOS:000184354500011 ER PT J AU Krahn, D Freese, J Hauser, R Barry, K Goodman, B AF Krahn, D Freese, J Hauser, R Barry, K Goodman, B TI Alcohol use and cognition at mid-life: The importance of adjusting for baseline cognitive ability and educational attainment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE cognition; alcohol; IQ; education; consumption ID CONSUMPTION; DRINKING; PERFORMANCE; SMOKING; COMMUNITY; COHORT; SAMPLE; WINE; MEN AB Background: The nature of the relationship between cognition and alcohol consumption remains controversial. Studies have reported negative, positive, and nonsignificant effects of alcohol consumption on cognition. Problematic throughout the literature is that baseline cognitive ability has not been adequately controlled in previous studies, and even educational attainment is only sometimes controlled. Because such variables may be associated with both alcohol intake and later-life cognition, we hypothesize that the observed relationship between alcohol intake and cognition may change when these variables or other conditions in early life have been controlled. Methods: We examined the relationship of alcohol intake and cognition at age 53 using the Wisconsin Longitudinal Study, which has followed Wisconsin high school graduates from 1957 to 1992. Our measures include cognitive ability test scores from the freshman and junior years of high school, educational attainment, an abstract reasoning test score at age 53, alcohol intake at age 53, and other measures. Results: When no controls were used, both men and women with low levels of alcohol consumption at 53 (i.e., 0-1 drink per day) had better scores on the abstract reasoning subtest of the Wechsler Adult Intelligence Scale (WAIS-R) at age 53 than subjects who never drank or currently did not drink. However, after adjusting for adolescent-measured cognitive ability and educational attainment, men with low levels of consumption no longer had higher abstract reasoning scores than nondrinking men, but they still did have higher abstract reasoning scores than men who drank more than one drink per day. For women, adjusting for cognitive ability and educational attainment eliminated all significant effects of alcohol on cognition, and reversed the nonsignificant result that women with higher consumption had the highest cognition scores. These results demonstrate the importance of adjusting for baseline cognitive ability when attempting to study the effect of long-term alcohol use patterns on cognition, and that educational attainment cannot be considered a valid substitute for baseline cognition scores. Conclusions: Much of the apparent benefit of moderate alcohol intake on cognition in our society may well be explained by differential rates of alcohol consumption among subjects with differing baseline cognitive ability scores. Neither is there evidence that moderate alcohol intake reduces cognitive functioning. C1 William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Madison, WI USA. Univ Wisconsin, Dept Sociol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Demog Hlth & Aging, Madison, WI 53706 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Krahn, D (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [R01-AG09775-10, P01-AG21079-01] NR 22 TC 19 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUL PY 2003 VL 27 IS 7 BP 1162 EP 1166 DI 10.1097/01.ALC.0000078060.18662.C1 PG 5 WC Substance Abuse SC Substance Abuse GA 704RV UT WOS:000184354500016 PM 12878923 ER PT J AU Breitner, JCS AF Breitner, JCS TI Alzheimer disease in Turkey too SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, GRECC S182, Seattle, WA 98108 USA. RP Breitner, JCS (reprint author), VA Puget Sound Hlth Care Syst, GRECC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JUL-SEP PY 2003 VL 17 IS 3 BP 137 EP 138 DI 10.1097/00002093-200307000-00002 PG 2 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 728HP UT WOS:000185712000001 PM 14512825 ER PT J AU Atiya, M Hyman, BT Albert, MS Killiany, R AF Atiya, M Hyman, BT Albert, MS Killiany, R TI Structural magnetic resonance imaging in established and prodromal Alzheimer disease: A review SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Review ID MILD COGNITIVE IMPAIRMENT; APOLIPOPROTEIN-E GENOTYPE; MEDIAL TEMPORAL-LOBE; E EPSILON-4 ALLELE; ENTORHINAL CORTEX ATROPHY; VOXEL-BASED MORPHOMETRY; REGISTERED SERIAL MRI; WHOLE-BRAIN ATROPHY; ADRDA WORK GROUP; HIPPOCAMPAL VOLUME C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Boston Univ, Dept Anat & Neurobiol, Boston, MA 02215 USA. RP Albert, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. NR 153 TC 51 Z9 57 U1 1 U2 4 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 JUL-SEP PY 2003 VL 17 IS 3 BP 177 EP 195 DI 10.1097/00002093-200307000-00010 PG 19 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 728HP UT WOS:000185712000008 PM 14512832 ER PT J AU Perrin, JM Homer, CJ AF Perrin, JM Homer, CJ TI Leadership by example: The institute of Medicine's view of how federal health care programs can improve quality of care SO AMBULATORY PEDIATRICS LA English DT Editorial Material DE Institute of Medicine; medicaid; policy; quality C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Initiat Child Healthcare Qual, Boston, MA 02114 USA. RP Perrin, JM (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St 901, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD JUL-AUG PY 2003 VL 3 IS 4 BP 162 EP 163 DI 10.1367/1539-4409(2003)003<0162:LBETIO>2.0.CO;2 PG 2 WC Pediatrics SC Pediatrics GA 704VH UT WOS:000184361000001 PM 12882591 ER PT J AU Murphy, SA Dauterman, K de Lemos, JA Kermgard, S Antman, EM Braunwald, E Gibson, CM AF Murphy, SA Dauterman, K de Lemos, JA Kermgard, S Antman, EM Braunwald, E Gibson, CM CA TIMI 14 Investigators TI Angiographic and clinical characteristics associated with the development of Q-wave and non-Q-wave myocardial infarction in the Thrombolysis In Myocardial Infarction (TIMI) 14 trial SO AMERICAN HEART JOURNAL LA English DT Article ID PROGNOSIS; POPULATION; FLOW AB Background in the absence of thrombolytic therapy, patients with non-Q-wave myocardial infarction (MI) have previously been shown to have lower long-term mortality rates than patients with Q-wave MI. The goal of our study was to examine the angiographic and clinical differences between non-Q-wave MI and Q-wave MI in patients with ST elevation MI (STEMI) in the era of thrombolytic and combination therapy of thrombolytics plus glycoprotein IIb/IIIa inhibitors. Methods Angiography was performed 90 minutes after thrombolytic administration in the Thrombolysis in Myocardial Infarction (TIMI) 14 trial. The development of a non-Q-wave MI was assessed on electrocardiogram performed at the time of hospital discharge. Angiographic findings were assessed at an angiographic core: laboratory by blinded investigators. Results The qualifying episode of ST elevation developed into a non-Q-wave MI in 36% of patients (315/878) and into,a Q-wave MI in 64% of patients (563/878). In patients in whom non-Q-wave MI developed, the rate of TIMI grade 3 flow was higher, peak creatine kinase level was lower, mean left ventricular ejection fraction was greater, corrected TIMI frame counts (CTFCs) were lower (ie, faster blood flow), and chest pain duration after, thrombolytic administration was shorter. Patients in whom non-Q-wave MI developed less frequently underwent a percutaneous coronary intervention (PCI), and when they did, they had faster post-PCI CTFCs and higher rates of post-PCI TIMI grade 3 flow. Patients in whom a non-Q-wave MI developed had lower rates of severe recurrent ischemia. There were no differences in 30-day or in-hospital mortality rates or recurrent MI between patients with Q-wave MI and patients with non-Q-wave MI. Conclusion After thrombolytic therapy in STEMI with or without abciximab, ejection fractions were higher, the duration of ischemia was shorter, and coronary blood flow at both 90 minutes and after PCI was faster in patients who sustained non-Q-wave MI than in patients who sustained Q-wave MI. No differences in mortality or recurrent MI rates were detected in patients who sustained a Q-wave MI and patients in whom a Q-wave MI did not evolve in the modern thrombolytic era. C1 TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Harvard Med Sch, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. RP Gibson, CM (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 20 TC 2 Z9 3 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 JUL PY 2003 VL 146 IS 1 BP 42 EP 47 DI 10.1016/S0002-8703(03)00145-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 703PV UT WOS:000184290900006 PM 12851606 ER PT J AU Ansari, M Alexander, M Tutar, A Massie, BM AF Ansari, M Alexander, M Tutar, A Massie, BM TI Incident cases of heart failure in a community cohort: Importance and outcomes of patients with preserved systolic function SO AMERICAN HEART JOURNAL LA English DT Article ID EJECTION FRACTION; PREVALENCE; PERFORMANCE; MORTALITY AB Background The clinical presentation and outcomes of patients with heart failure and preserved systolic function have not been well characterized in the outpatient setting. Methods This was a retrospective cohort study of 403 patients with new-onset heart failure in a large regional health maintenance organization between July 1996 and December 1996. The clinical characteristics and treatment of patients with preserved ejection fractions (PrEF; >45%) were compared with those of patients with with reduced left ventricular function (Low EF) after excluding patients with terminal comorbidities. The main outcome measure was the combination of death, cardiovascular (CV) hospitalization, or both, which was assessed for as long as 24 months (mean, 22 months) with proportional hazards models. Results Sixty-five patients (16%) did not have an assessment of left ventricular (LV) function. Of the remaining 338 patients, 191 (57%) had an EF <45% (Low EF group) and 147 (44%) had preserved LV function (PrEF group). Patients with PrEF tended to be older, more frequently women, have less coronary disease and myocardial infarction, and have more atria[ fibrillation and other comorbid conditions. They had higher systolic blood pressures and pulse pressures and slower heart rates than the patients with reduced LV function on initial presentation. Overall, mortality and CV hospitalization rates were similar in the 2 groups; however, on multivariate analysis, which took into account baseline differences between groups, low EF was a significant independent predictor of the combined end point (hazard ratio, 1.9; 95% Cl, 1.3-2.9). Conclusions Patients with preserved LV function constitute a significant portion of incident outpatient patients with heart failure and carry a better prognosis than patients with reduced LV function. C1 San Francisco VAMC, Cardiol Div 111C, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Calif San Francisco, Med Effectiveness Res Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. RP Massie, BM (reprint author), San Francisco VAMC, Cardiol Div 111C, 4150 Clement St, San Francisco, CA 94121 USA. NR 14 TC 17 Z9 18 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 JUL PY 2003 VL 146 IS 1 BP 115 EP 120 DI 10.1016/S0002-8703(03)00123-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 703PV UT WOS:000184290900018 PM 12851618 ER PT J AU Duggan, C Bechard, L Donovan, K Vangel, M O'Leary, A Holmes, C Lehmann, L Guinan, E AF Duggan, C Bechard, L Donovan, K Vangel, M O'Leary, A Holmes, C Lehmann, L Guinan, E TI Changes in resting energy expenditure among children undergoing allogeneic stem cell transplantation SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy expenditure; pediatrics; stem cell transplantation; supportive care ID BONE-MARROW TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL PARENTERAL-NUTRITION; VITAMIN-E; CHILDHOOD; WEIGHT; CHEMOTHERAPY; DISEASE; THERAPY; SUPPORT AB Background: Because of the effects of chemotherapy and radiotherapy, patients undergoing stem cell transplantation (SCT) are commonly provided nutritional support with parenteral nutrition. The energy and nutrient needs of these patients have not been well studied. Objective: The objective was to measure resting energy expenditure (REE), dietary intake, and biochemical and anthropometric changes in children before and after allogeneic SCT. Design: This was a prospective cohort study of 37 children aged 9.1 +/- 6.4 y ((x) over bar +/- SD) undergoing SCT who were enrolled in an open-label trial of a unique supportive care intervention that included the routine use of oral leucovorin, vitamin E, and ursodeoxycholic acid. Parenteral nutrition was provided to match 100% of measured or estimated REE. REE was measured weekly via indirect calorimetry. Results: Baseline REE was 95% of the predicted age- and sex-matched norms and was significantly correlated with midarm muscle area (r = 0.82, P < 0.001). REE fell to a nadir of approximate to80% of the predicted levels by week 3 after SCT, with a gradual increase in weeks 4 and 5. Arm anthropometric measurements showed no change in triceps skinfold thickness but significant declines in midarm muscle area after SCT. Serum vitamin E remained in the normal range. Conclusions: Children undergoing SCT show significant declines in REE after transplantation. These changes may be due to alterations in lean body mass. Standard nutritional regimens may lead to overfeeding. C1 Childrens Hosp, Div GI Nutr, Clin Nutr Serv, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Duggan, C (reprint author), Childrens Hosp, Div GI Nutr, Clin Nutr Serv, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [5P30CA06516]; NIDDK NIH HHS [5-T32-DK07477] NR 32 TC 16 Z9 17 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 JUL PY 2003 VL 78 IS 1 BP 104 EP 109 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 692KP UT WOS:000183660500015 PM 12816778 ER PT J AU Eloubeidi, MA Mason, AC Desmond, RA El-Serag, HB AF Eloubeidi, MA Mason, AC Desmond, RA El-Serag, HB TI Temporal trends (1973-1997) in survival of patients with Esophageal adenocarcinoma in the United States: A glimmer of hope? SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID BARRETTS-ESOPHAGUS; RISING INCIDENCE; GASTRIC CARDIA; PATTERNS; CANCER; MEN AB OBJECTIVE: The incidence and mortality related to esophageal adenocarcinoma (EAC) has been rising in the United States. Meanwhile, the number of diagnostic and therapeutic procedures has increased in number and improved technologically. However, the impact of these advances on the survival of EAC in clinical practice remains unknown. METHODS: Patients with histologically proven EAC between 1973 and 1997 were identified in registries of the Surveillance, Epidemiology, and End Results database, and analyzed in 5-yr time periods. The observed and relative survival rates were calculated. The joint influence of the time of diagnosis, stage and grade of cancer, demographic features. surgical therapy, and radiotherapy were assessed in Cox proportional hazard survival analyses. RESULTS: Between 1973 and 1997, we identified 4835 patients with EAC. The 1-yr and 5-yr observed survival rates increased from 34% and 5% during 1973-1977 to 44% and 13% during 1993-1997 (p < 0.05). In the Cox survival analysis. the more recent year of diagnosis, early stage of tumor, younger age at presentation, receiving radiotherapy or surgery were independent predictors of reduced risk of mortality. The proportion of patients with in situ EAC and those with local spread increased progressively from 0.3% and 17.7% in 1973-1977 to 2.3% and 25.3%, respectively, in 1993-1997 (p < 0.05). The proportion of patients receiving radiation therapy either before or after surgery has increased from 7% in 1973-1977 to 16% in 1993-1997 (p < 0.05). CONCLUSIONS: The short- and long-term survival of patients with EAC has improved slightly in the United States over the past 25 yr. Some of the improvement may be related to an increase in the number of younger patients, and in cases with in situ and localized cancers. However, the overall survival of patients with EAC remains dismal. (C) 2003 by Am. Coll. of Gastroenterology. C1 Houston Vet Affairs Med Ctr 152, Sect Gastroenterol & Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Alabama, Gastroenterol Sect, Med Stat Sect, Birmingham, AL USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL USA. Albuquerque Vet Affairs Med Ctr, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, Sect Gastroenterol & Hlth Serv Res, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 137 Z9 139 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUL PY 2003 VL 98 IS 7 BP 1627 EP 1633 DI 10.1016/S0002-9270(03)00228-4 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 702GP UT WOS:000184216400029 PM 12873590 ER PT J AU Schneider, LS Katz, IR Park, S Napolitano, J Martinez, RA Azen, SP AF Schneider, LS Katz, IR Park, S Napolitano, J Martinez, RA Azen, SP TI Psychosis of Alzheimer disease - Validity of the construct and response to risperidone SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article AB Objective: The authors evaluated the efficacy of risperidone in reducing psychotic and aggressive symptoms in a subgroup of patients who fulfilled operationalized criteria for psychosis of dementia. Methods: Authors conducted a subgroup analysis of patients in the risperidone database arising from a previous double-blind, randomized, placebo-controlled study. In the primary study, patients age 55 or older, with a DSH-IV diagnosis of Alzheimer disease and/or vascular dementia were randomized to placebo or 0.5 mg, 1.0 mg, or 2.0 mg/day of risperidone. For this analysis, patients were selected who fulfilled operationalized criteria for psychosis of dementia. These criteria were then validated. The primary outcome measures were the newly developed Psychosis and Aggression Severity Indices, derived from Parts 1 and 2 of the BEHAVE-AD rating scale. Results: At Week 12 and endpoint, patients with psychosis of dementia receiving 1 mg or 2 mg/day of risperidone showed significantly more improvement on the Psychosis Severity and Aggressiveness Severity Indices than those receiving placebo. Conclusions: The construct of psychosis of dementia was validated, and the severity of both psychosis and aggressiveness was reduced with risperidone treatment in a robust and dose-related way, with a continuing response over the 12-week trial period. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Psychiat, Los Angeles, CA 90033 USA. Univ Penn, Dept Psychiat, Mental Illness Res Educ & Clin Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Janssen Res Fdn, Titusville, NJ USA. RP Azen, SP (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP-218, Los Angeles, CA 90033 USA. FU NIA NIH HHS [5 P50 AG5142]; NIMH NIH HHS [1 MH90001] NR 10 TC 30 Z9 30 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL-AUG PY 2003 VL 11 IS 4 BP 414 EP 425 DI 10.1176/appi.ajgp.11.4.414 PG 12 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 702GM UT WOS:000184216200004 PM 12837670 ER PT J AU Wong-Beringer, A Liao, C Nguyen, M Pallares, J AF Wong-Beringer, A Liao, C Nguyen, M Pallares, J TI Applying patient selection criteria for drotrecogin alfa therapy in practice SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID ACTIVATED PROTEIN-C; SEVERE SEPSIS; SYSTEM C1 Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. Huntington Mem Hosp, Serv Pharm, Pasadena, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Western Univ, Coll Pharm, Pomona, CA USA. RP Wong-Beringer, A (reprint author), Univ So Calif, Sch Pharm, 1985 Zonal Ave, Los Angeles, CA 90089 USA. NR 10 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 2003 VL 60 IS 13 BP 1345 EP 1352 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699GB UT WOS:000184047400013 PM 12901037 ER PT J AU Cannon, JP Silverman, RM AF Cannon, JP Silverman, RM TI A pharmacist-driven antimicrobial approval program at a Veterans Affairs hospital SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT ASHP Midyear Clinical Meeting CY DEC 03-05, 2001 CL NEW ORLEANS, LOUISIANA SP ASHP ID OUTCOMES; EXPENDITURES AB Management Case Studies describe approaches to real-life management problems in health systems. Each installment is a brief description of a problem and how it was dealt with. The cases are intended to help readers deal with similar experiences in their own work sites. Problem solving, not hypothesis testing, is emphasized. Successful resolution of the management issue is not a criterion for publication-important lessons can be learned from failures, too. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Pharm Serv 119, Dept Pharm Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Informat Management Serv, Hines, IL 60141 USA. RP Cannon, JP (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Pharm Serv 119, Dept Pharm Serv, Bldg 1,Room B106, Hines, IL 60141 USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUL 1 PY 2003 VL 60 IS 13 BP 1358 EP 1362 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699GB UT WOS:000184047400015 PM 12901039 ER PT J AU Lewis, CM Levinson, DF Wise, LH DeLisi, LE Straub, RE Hovatta, I Williams, NM Schwab, SG Pulver, AE Faraone, SV Brzustowicz, LM Kaufmann, CA Garver, DL Gurling, HMD Lindholm, E Coon, H Moises, HW Byerley, W Shaw, SH Mesen, A Sherrington, R O'Neill, FA Walsh, D Kendler, KS Ekelund, J Paunio, T Lonnqvist, J Peltonen, L O'Donovan, MC Owen, MJ Wildenauer, DB Maier, W Nestadt, G Blouin, JL Antonarakis, SE Mowry, BJ Silverman, JM Crowe, RR Cloninger, CR Tsuang, MT Malaspina, D Harkavy-Friedman, JM Svrakic, DM Bassett, AS Holcomb, J Kalsi, G McQuillin, A Brynjolfson, J Sigmundsson, T Petursson, H Jazin, E Zoega, T Helgason, T AF Lewis, CM Levinson, DF Wise, LH DeLisi, LE Straub, RE Hovatta, I Williams, NM Schwab, SG Pulver, AE Faraone, SV Brzustowicz, LM Kaufmann, CA Garver, DL Gurling, HMD Lindholm, E Coon, H Moises, HW Byerley, W Shaw, SH Mesen, A Sherrington, R O'Neill, FA Walsh, D Kendler, KS Ekelund, J Paunio, T Lonnqvist, J Peltonen, L O'Donovan, MC Owen, MJ Wildenauer, DB Maier, W Nestadt, G Blouin, JL Antonarakis, SE Mowry, BJ Silverman, JM Crowe, RR Cloninger, CR Tsuang, MT Malaspina, D Harkavy-Friedman, JM Svrakic, DM Bassett, AS Holcomb, J Kalsi, G McQuillin, A Brynjolfson, J Sigmundsson, T Petursson, H Jazin, E Zoega, T Helgason, T TI Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY LOCUS; LINKAGE ANALYSIS; WIDE SCAN; VULNERABILITY LOCUS; GENETIC-LINKAGE; SIBLING PAIRS; SCHIZOAFFECTIVE DISORDER; CHROMOSOME 8P; FOLLOW-UP; FAMILIES AB Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R-avg) and then weighted for sample size (rootN[affected cases]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P-AvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P-ord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (P-AvgRnk <.000417). Two aggregate criteria for linkage were also met ( clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P-AvgRnk and P-ord <.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations. C1 Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Guys Kings & St Thomas Sch Med, Div Genet & Dev, London, England. UCL, Royal Free & Univ Coll Med Sch, Dept Psychiat & Behav Sci, London WC1E 6BT, England. NYU, Med Ctr, New York, NY 10016 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NIMH, Clin Brain Disorders Branch, Intramural Res Program, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Biomedicum, Dept Mol Med, Helsinki, Finland. Natl Publ Hlth Inst, Dept Mental Hlth, Helsinki, Finland. Univ Helsinki, Dept Med Genet, Biomedicum, Helsinki, Finland. Cardiff Univ, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Rutgers State Univ, Dept Genet, Piscataway, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ 08854 USA. Univ Louisville, Sch Med, Dept Psychiat & Behav Sci, Louisville, KY 40292 USA. Louisville Vet Affairs Med Ctr, Louisville, KY USA. Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden. Univ Utah, Salt Lake City, UT USA. Univ Hosp Schleswig Holstein, Dept Psychiat & Psychotherapy, Genet Mol Lab, Kiel, Germany. Univ Calif Irvine, Dept Psychiat, Irvine, CA 92717 USA. DNA Sci, Fremont, CA USA. Hosp Nacl Psiquitr, San Jose, Costa Rica. Xenon Genet, Burnaby, BC, Canada. Queens Univ Belfast, Belfast, Antrim, North Ireland. Hlth Res Board, Dublin, Ireland. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA USA. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. Univ Geneva, Sch Med, Ctr Med Univ Geneva, Dept Med Genet, CH-1211 Geneva, Switzerland. Wolston Pk Hosp, Queensland Ctr Schizophrenia Res, Wacol, Australia. Univ Queensland, Dept Psychiat, Brisbane, Qld, Australia. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Mental Hlth Clin Res Ctr, Iowa City, IA 52242 USA. Washington Univ, Dept Psychiat, St Louis, MO USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Gen Hosp, Dept Psychiat, Reykjavik, Iceland. Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland. RP Levinson, DF (reprint author), Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, 3535 Market St,Room 4006, Philadelphia, PA 19104 USA. EM DFL@mail.med.upenn.edu RI O'Neill, Francis/C-5582-2008; Lewis, Cathryn/A-5225-2010; turton, miranda/F-4682-2011; Hovatta, Iiris/D-6871-2012; Cloninger, Claude/F-5357-2012; Ekelund, Jesper/D-6655-2013; Gurling, Hugh/A-5029-2010; Antonarakis, Stylianos/N-8866-2014; McQuillin, Andrew/C-1623-2008; OI O'Neill, Francis Anthony/0000-0002-7531-7657; Faraone, Stephen/0000-0002-9217-3982; Harkavy-Friedman, Jill/0000-0002-1449-0667; Lewis, Cathryn/0000-0002-8249-8476; Hovatta, Iiris/0000-0002-5990-7892; Cloninger, Claude/0000-0003-3096-4807; Antonarakis, Stylianos/0000-0001-8907-5823; McQuillin, Andrew/0000-0003-1567-2240; Moises, Hans/0000-0003-1522-3226; O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council [G9309834, G9810900]; NIMH NIH HHS [1R01 MH 41874-01, 1R37 MH 43518, 5U01 MH 46318, K02 MH 01089, K08 MH 01392, K24 MH 64197, K24 MH064197, R01 MH 41953, R01 MH 42643, R01 MH 44245, R01 MH 45097, R01 MH 45390, R01 MH 4558, R01 MH 52537, R01 MH 56098, R01 MH 61602, R01 MH 62440, R01 MH041953, R01 MH044292, R01 MH062440, R37 MH043518, U01 MH 44292, U01 MH 46276, U01 MH 46289, U01 MH046276, U01 MH046289, U01 MH046318]; PHS HHS [K02 01207] NR 62 TC 817 Z9 844 U1 5 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2003 VL 73 IS 1 BP 34 EP 48 DI 10.1086/376549 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 696UA UT WOS:000183904900004 PM 12802786 ER PT J AU Giallourakis, C Stoll, M Miller, K Hampe, J Lander, ES Daly, MJ Schreiber, S Rioux, JD AF Giallourakis, C Stoll, M Miller, K Hampe, J Lander, ES Daly, MJ Schreiber, S Rioux, JD TI IBD5 is a general risk factor for inflammatory bowel disease: Replication of association with Crohn disease and identification of a novel association with ulcerative colitis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HAPLOTYPE STRUCTURE; GENETIC-VARIATION; NOD2 GENE; SUSCEPTIBILITY; GENOTYPE; CLASSIFICATION; POPULATION; MUTATIONS AB Inflammatory bowel disease (IBD) refers to complex chronic relapsing autoimmune disorders of the gastrointestinal tract that have been traditionally classified into Crohn disease ( CD) and ulcerative colitis (UC). We have previously reported that genetic variation within a 250-kb haplotype (IBD5) in the 5q31 cytokine gene cluster confers susceptibility to CD in a Canadian population. In the current study, we first replicated this association by examining 368 German trios with CD and demonstrating, by transmission/ disequilibrium testing (TDT), that the same haplotype is associated with CD (chi(2) = 5.97; P = .007). Our original association study focused on the role of IBD5 in CD; we next explored the potential contribution of this locus to UC susceptibility in 187 German trios. Given the TDT results in the present cohort with UC, IBD5 may also act as a susceptibility locus for UC (chi(2) = 8.10; P = .002). We then examined locus-locus interactions between IBD5 and CARD15, a locus reported elsewhere to confer risk exclusively to CD. Our current results indicate that the two loci act independently to confer risk to CD but that these two loci may behave in an epistatic fashion to promote the development of UC. Moreover, IBD5 was not associated with particular clinical manifestations upon phenotypic stratification in the current cohort with CD. Taken together, our results suggest that IBD5 may act as a general risk factor for IBD, with loci such as CARD15 modifying the clinical characteristics of disease. C1 Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Kiel, Dept Internal Med, Kiel, Germany. RP Rioux, JD (reprint author), Whitehead Inst, Ctr Genome Res, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. RI Schreiber, Stefan/B-6748-2008; Hampe, Jochen/A-2555-2010; Rioux, John/A-9599-2015 OI Schreiber, Stefan/0000-0003-2254-7771; Hampe, Jochen/0000-0002-2421-6127; Rioux, John/0000-0001-7560-8326 NR 21 TC 122 Z9 124 U1 0 U2 0 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 JUL PY 2003 VL 73 IS 1 BP 205 EP 211 DI 10.1086/376417 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 696UA UT WOS:000183904900018 PM 12776251 ER PT J AU Ploth, DW Shepp, PH Counts, C Hutchison, F AF Ploth, DW Shepp, PH Counts, C Hutchison, F TI Prospective analysis of global costs for maintenance of patients with ESRD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE costs of end-stage renal disease (ESRD); hemodialysis (HD); outcomes; hospital resource utilization ID STAGE RENAL-DISEASE; KIDNEY-DISEASE; HEMODIALYSIS; MORBIDITY; CARE AB Background. The prevalence of end-stage renal disease (ESRD) has doubled in the past decade, with total costs projected to exceed $16.5 billion by the end of 2002. Methods: The purpose of this prospective study is to determine all costs related to inpatient and outpatient health care utilization incurred by 76 patients with ESRD in an outpatient hemodialysis setting for 1 year. Costs were derived from a computer-based cost-allocation process that distributed cost components and overhead to designated revenue-producing departments. Results: During the 1-year study period, these patients had 1,459 total inpatient and outpatient hospital visits (mean, 19.2 visits/patient; range, 0 to 84 visits/patient). There were 149 general inpatient hospital admissions. Of 238 total emergency room visits, 89 visits resulted in admission to the hospital (37%). Conclusion: Total hospital costs for all patients for the year were $1,831,880 (actual charges, $2,929,147). As expected, the greatest hospital cost expenditures were attributed to inpatient hospital admissions ($1,419,022; 77.5% of total). Of total hospital costs, inpatient bed costs were the single highest expenditure. The cost for outpatient hemodialysis therapy was $33,784/patient-year, consisting of facility costs of $17,200, outpatient pharmacy costs of $14,100, and outpatient professional costs of $2,500/patient-year. Average costs for hospital facility and/or professional fees were $42,730/patient-year, whereas average costs for outpatient dialysis facility and/or professional fees were $33,784, for an estimated global cost of $76,515/patient-year. Our cost estimate for care of this unique inner-city population substantially exceeds those reported earlier by others. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, MUSC Transplant Ctr, Charleston, SC 29425 USA. Dialysis Clin Inc, Charleston, SC USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Ploth, DW (reprint author), Med Univ S Carolina, Div Nephrol, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. NR 15 TC 28 Z9 29 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2003 VL 42 IS 1 BP 12 EP 21 DI 10.1016/S0272-6386(03)00404-9 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 696MK UT WOS:000183890500003 PM 12830452 ER PT J AU Takahashi, S Cui, YH Kojima, T Han, YH Zhou, RL Kamioka, M Yu, SY Matsuura, M Matsushima, E Wilcox, M Arinami, T Shen, YC Faraone, SV Tsuang, MT AF Takahashi, S Cui, YH Kojima, T Han, YH Zhou, RL Kamioka, M Yu, SY Matsuura, M Matsushima, E Wilcox, M Arinami, T Shen, YC Faraone, SV Tsuang, MT TI Family-based association study of markers on chromosome 22 in schizophrenia using African-American, European-American, and Chinese families SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE schizophrenia; chromosome 22; D22S683; family-based association study; FBAT ID CARDIO-FACIAL SYNDROME; GENOME-WIDE SEARCH; SUSCEPTIBILITY LOCUS; TRANSMISSION DISEQUILIBRIUM; MILLENNIUM-CONSORTIUM; UNIFIED APPROACH; LINKAGE ANALYSIS; GENES; D22S278; TESTS AB Several studies suggest that loci at chromosome 22q11.2-q13 might be linked to susceptibility to schizophrenia. Here we performed family-based association studies on chromosome 22q using 12 DNA microsatellite markers in African-American, European-American, and Chinese pedigrees. The marker D22S683 showed significant linkage and association with schizophrenia in not only the European-American sample but also in a combined sample (European-American and Chinese samples). Notably, D22S683 is located nearby and between D22S278 and D22S283, which have shown linkage and association to schizophrenia in prior reports. However, we found no significant association for the African-American sample. In conclusion, our data provide further support for the idea that the region around D22S683 contains a susceptibility gene for schizophrenia. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Nihon Univ, Sch Med, Dept Neuropsychiat, Tokyo, Japan. Beijing Med Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. Univ Tsukuba, Inst Basic Med Sci, Dept Med Genet, Tsukuba, Ibaraki 305, Japan. Tokyo Med & Dent Univ, Fac Med, Dept Neuropsychiat, Tokyo 113, Japan. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R37MH43518, 1 R01MH41874-01, 5 UO1MH46318, R01MH43518, R01MH44292, R01MH59624, R01MH60485, R25MH60485, UO1MH46276, UO1MH46298] NR 29 TC 24 Z9 25 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 1 PY 2003 VL 120B IS 1 BP 11 EP 17 DI 10.1002/ajmg.b.20031 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 693HM UT WOS:000183711300002 PM 12815732 ER PT J AU Ngo-Metzger, Q McCarthy, EP Burns, RB Davis, RB Li, FP Phillips, RS AF Ngo-Metzger, Q McCarthy, EP Burns, RB Davis, RB Li, FP Phillips, RS TI Older Asian Americans and Pacific Islanders dying of cancer use hospice less frequently than older white patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OF-LIFE CARE; BREAST-CANCER; DECISION-MAKING; UNITED-STATES; WOMEN; ETHNICITY; ATTITUDES; SERVICES; BARRIERS; END AB PURPOSE: Cancer is the leading cause of death among Asian Americans, yet little is known about their use of hospice care. We examined hospice use by Asian patients compared with white patients, and assessed whether utilization differs among those born in the United States or abroad. METHODS: We studied Asian and white Medicare beneficiaries registered in the Surveillance, Epidemiology, and End Results (SEER) Program who died of primary lung, colorectal, prostate, breast, gastric, or liver cancer between 1988 and 1998. We used logistic regression to determine the effects of race/ ethnicity and birthplace on hospice use, adjusting for demographic characteristics, managed care insurance, year of diagnosis, tumor stage at diagnosis, and tumor registry. RESULTS: Of the 184,081 patients, 5% (n = 8614) were Asian Americans, of whom 45% (n = 3847) were foreign born. Compared with whites, Asian Americans were more likely to be male, married, and enrolled in managed care. Compared with U.S.-born Asian Americans, foreign-born Asian Americans were more likely to reside in low-income areas. After adjustment, patients who were Asian American (odds ratio [OR] = 0.67; 95% confidence interval [CI]: 0.62 to 0.73) and born abroad (OR = 0.90; 95% CI 0.86 to 0.94) were less likely to use hospice care than were white patients. These results were consistent across the six cancer diagnoses that were examined. CONCLUSION: Older Asian Americans dying of cancer, especially those who are born abroad, are less likely than white patients to use hospice care at the end of life. Additional research is needed to understand the reasons for these differences and to eliminate potential barriers to hospice care. (C) 2003 by Excerpta Medica Inc. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02115 USA. RP Ngo-Metzger, Q (reprint author), Hlth Policy Res, 100 Theory,Suite 110, Irvine, CA 92697 USA. FU NCI NIH HHS [U01 CA86322, 5R29 CA79052, U01 CA086322-01] NR 63 TC 44 Z9 44 U1 4 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2003 VL 115 IS 1 BP 47 EP 53 DI 10.1016/S0002-9343(03)00258-4 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 700WV UT WOS:000184134900008 PM 12867234 ER PT J AU Thadhani, R Wolf, M Hsu-Blatman, K Sandler, L Nathan, D Ecker, JL AF Thadhani, R Wolf, M Hsu-Blatman, K Sandler, L Nathan, D Ecker, JL TI First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE gestational diabetes mellitus; insulin resistance; sex hormone binding globulin ID RANDOMIZED CONTROLLED TRIAL; POLYCYSTIC-OVARY-SYNDROME; GLUCOSE-TOLERANCE; INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; PREGNANCY; MANAGEMENT; POPULATION; HYPERINSULINEMIA; DETERMINANTS AB OBJECTIVE: We sought to examine the association between early pregnancy levels of sex hormone binding globulin and subsequent gestational diabetes mellitus, an association that has not been studied previously. STUDY DESIGN: We conducted a nested case-control study of 44 patients with gestational diabetes mellitus and 94 women with negative third-trimester screening for gestational diabetes mellitus. Sex hormone binding globulin levels were measured from serum samples that had been collected in the first trimester, and clinical data were ascertained from prospectively collected electronic medical records. RESULTS: Compared with women without gestational diabetes mellitus, first-trimester sex hormone binding globulin levels were lower among women in whom gestational diabetes mellitus subsequently developed (187 +/- 82 nmol/L vs 233 +/- 92 nmol/L, P < .01). In logistic regression analysis that was adjusted for body mass index, age, race, smoking, blood pressure, serum testosterone and estradiol levels, and gestational age at serum collection, sex hormone binding globulin levels remained independently associated with subsequent gestational diabetes mellitus. For every 50-nmol/L increase in sex hormone binding globulin, the odds of gestational diabetes mellitus fell by 31% (odds ratio, 0.69; 95% CI: 0.48, 0.99). CONCLUSION: Sex hormone binding globulin offers a potential early marker to target women who are at risk for gestational diabetes mellitus. C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Med, Founders 036,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03804]; NICHD NIH HHS [HD39223] NR 35 TC 50 Z9 55 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2003 VL 189 IS 1 BP 171 EP 176 DI 10.1067/mob.2003.343 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 703TE UT WOS:000184296400030 PM 12861158 ER PT J AU Dietrich, AJ Williams, JW Ciotti, MC Schulkin, J Stotland, N Rost, K Baram, D Cornell, J AF Dietrich, AJ Williams, JW Ciotti, MC Schulkin, J Stotland, N Rost, K Baram, D Cornell, J TI Depression care attitudes and practices of newer obstetrician-gynecologists: A national survey SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE depressive disorders; depression, postpartum; education, medical, graduate; obstetrics, gynecology ID RANDOMIZED CONTROLLED-TRIAL; PHYSICIANS; RESIDENTS AB OBJECTIVE: The study was undertaken to assess attitudes and behavior of newer obstetricians/gynecologists in depression care. STUDY DESIGN: One thousand randomly selected physicians in their final year of training or recent practice received a survey about depression: training; related attitudes, responsibility, confidence; and self-reported care for the last depressed patient. RESULTS: Of those eligible, 437 (64%) returned the survey Current residents reported more didactic mental health training, but practice patterns were similar to recent graduates. Overall, 94% felt responsible for recognition, whereas about half indicated asking about substance abuse, sexual abuse, or physical abuse, 37% expressed confidence in their ability to treat with medications, and 22% felt confident in their ability to manage depression overall. CONCLUSION: Residents are receiving more didactic mental health training, yet changes in training are not yet reflected in reported practice patterns or confidence. The use of antidepressant medications and assessment of contributing conditions such as abuse deserve more emphasis in training. C1 Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH 03755 USA. Duke Univ, Ctr Hlth Serv Res Primary Care, Durham, NC 27706 USA. Duke Univ, Durham Vet Affairs Med Ctr, Durham, NC 27706 USA. Duke Univ, Dept Med, Durham, NC 27706 USA. Univ Calif Davis, Dept Obstet & Gynecol, Davis, CA 95616 USA. Rush Med Coll, Amer Coll Obstetricians & Gynecologists, Chicago, IL 60612 USA. Rush Med Coll, Dept Psychiat, Chicago, IL 60612 USA. Rush Med Coll, Dept Obstet & Gynecol, Chicago, IL 60612 USA. Univ Colorado, Ctr Hlth Sci, Dept Family Med, Boulder, CO 80309 USA. HealthPartners Med Grp, Dept Obstet & Gynecol, San Antonio, TX USA. San Antonio Ctr Excellence Hlth Serv Res, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Div Geriatr, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX USA. RP Dietrich, AJ (reprint author), Dartmouth Coll Sch Med, Dept Community & Family Med, 7250 Strasenburgh Hall, Hanover, NH 03755 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 21 TC 28 Z9 28 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2003 VL 189 IS 1 BP 267 EP 273 DI 10.1067/mob.2003.410 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 703TE UT WOS:000184296400047 PM 12861173 ER PT J AU Aiello, LM AF Aiello, LM TI Perspectives on diabetic retinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; PANRETINAL PHOTO-COAGULATION; VASCULAR-PERMEABILITY FACTOR; BLOOD-GLUCOSE CONTROL; SEVERE VISUAL-LOSS; MACULAR EDEMA; RETINAL NEOVASCULARIZATION; COMPLICATIONS TRIAL; PANCREATIC EXTRACTS; PIGMENT EPITHELIUM AB PURPOSE: To review the evolution of the understanding of diabetic retinopathy (DR) and methods of treating DR, the present clinically relevant practice for eye disease in patients with diabetes mellitus, and trends in clinical patient care over the next 3 to 5 years. DESIGN: Tabular review and presentation of clinical trials contributing to the understanding and treatment of DR and the author's philosophy of care for the patient with diabetes. RESULTS: Diabetic retinopathy is a microvascular complication of diabetes mellitus that is a significant cause of new,onset blindness. The Diabetic Retinopathy Study was the first multicentered, randomized, clinical trial in ophthalmology. This study provided the scientific evidence for treatment of DR with scatter (panretinal) photocoagulation, and led to the funding of other multicentered clinical trials, including the Early Treatment Diabetic Retinopathy Study, which greatly elucidated the natural history of DR and firmly established laser photocoagulation as treatment for proliferative diabetic retinopathy (PDR) and diabetic macular edema. The Diabetes Control and Complications Trial and United Kingdom Prospective Diabetes Study established the value of intensive glycemic control in reducing the risk of onset and progression of DR and other microvascualr complications of diabetes. CONCLUSIONS: Severe vision loss and moderate vision loss from diabetes are essentially preventable with timely detection and treatments, careful long,term follow-up and comprehensive diabetes mellitus care firmly based on clinical evidence. Future treatments, as outgrowths of further understanding of the biochemical basis of the disease, will aim at curing or preventing retinal complications from diabetes. (Am J Ophthalmol 2003;136: 122-135. (C) 2003 by Elsevier Inc. All rights reserved.). C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LM (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. EM Lloyd.M.Aiello@joslin.harvard.edu NR 99 TC 115 Z9 126 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL PY 2003 VL 136 IS 1 BP 122 EP 135 DI 10.1016/S0002-9394(03)00219-8 PG 14 WC Ophthalmology SC Ophthalmology GA 694LY UT WOS:000183777100018 PM 12834680 ER PT J AU Hamrah, P Chen, L Zhang, Q Dana, MR AF Hamrah, P Chen, L Zhang, Q Dana, MR TI Novel expression of vascular endothelial growth factor receptor (VEGFR)-3 and VEGF-C on corneal dendritic cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DRAINING LYMPH-NODES; ANGIOGENESIS IN-VIVO; TYROSINE KINASES; CONTACT HYPERSENSITIVITY; PERMEABILITY FACTOR; CANCER METASTASIS; TUMOR-CELLS; LYMPHANGIOGENESIS; MOUSE; INDUCTION AB Vascular endothelial growth factor-3 (VEGFR-3) plays a critical role in embryonic cardiovascular development and is thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on adult vascular endothelium. Recent evidence also suggests expression of VEGFR-3 on some tumor-associated macrophages. We have studied the expression of VEGFR-3, its ligand VEGF-C and the co-receptor neuropilin-2, in normal and inflamed corneas and characterized the phenotype and distribution of VEGFR-3(+) cells. Our data demonstrate, for the first time, the expression of VEGFR-3 on corneal dendritic cells (DC) and its up-regulation in inflammation. VEGFR-3(+) DC are CD11c(+)CD45(+)CD11b(+), and are mostly major histocompatibility (MHC) class II(-)CD80(-)CD86(-), indicating immature DC of a monocytic lineage. During inflammation, there is rapid increase in the number of VEGFR-3(+) DC in the cornea associated with heightened membranous expression as compared to a mostly intracellular expression in uninflamed tissue. VEGFR-3(+) DC in normal corneas are VEGF-C- neuropilin-2(-), but express VEGF-C in inflammation. interestingly, similar cells are absent both in the normal and inflamed skin. These data demonstrate. for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel potential relationship between lymphangiogenesis and leukocyte trafficking in the eye. C1 Schepens Eye Res Inst, Immunol Lab, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Hamrah, P (reprint author), Univ Louisville, Dept Ophthalmol & Visual Sci, 301 E Mohammed Ali Blvd, Louisville, KY 40202 USA. EM pedram.hamrah@louisville.edu FU NEI NIH HHS [EY-12963, R01 EY012963] NR 89 TC 76 Z9 85 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2003 VL 163 IS 1 BP 57 EP 68 DI 10.1016/S0002-9440(10)63630-9 PG 12 WC Pathology SC Pathology GA 695KP UT WOS:000183829900007 PM 12819011 ER PT J AU Yamashiro, K Tsujikawa, A Ishida, S Usui, T Kaji, Y Honda, Y Ogura, Y Adamis, AP AF Yamashiro, K Tsujikawa, A Ishida, S Usui, T Kaji, Y Honda, Y Ogura, Y Adamis, AP TI Platelets accumulate in the diabetic retinal vasculature following endothelial death and suppress blood-retinal barrier breakdown SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; IN-VIVO EVALUATION; GROWTH-FACTOR; RETINOPATHY; CELLS; EXPRESSION; CD40; ADHESIVENESS; AGGREGATION; CYTOKINES AB Platelet microthrombi are present in the diabetic retinal vasculature of humans and rodents; however, the mechanisms and consequences of their presence have not been defined. The current study demonstrates that platelet containing microthrombi accumulate in the retinal vasculature of the rat within 2 weeks of experimental diabetes, a timepoint at which leukocyte-mediated endothelial cell injury and death are known to occur. Platelet accumulation increased with the duration of diabetes, and crossover experiments revealed that maximal platelet accumulation required both diabetic platelets and a diabetic endothelium. Platelet accumulation also coincided with the expression of Fas and FasL in the diabetic retina. When endothelial cell apoptosis was inhibited with an anti-FasL neutralizing antibody, platelet accumulation was effectively suppressed. When platelets were depleted from the systemic circulation with an antiplatelet antibody, blood-retinal barrier breakdown worsened in the diabetic animals. These findings suggest that platelet accumulation in the diabetic retinal vasculature is secondary to endothelial cell death and serves, in part, to suppress blood-retinal barrier breakdown. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Retina Res Lab, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan. Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. Univ Tokyo, Fac Med, Dept Ophthalmol, Tokyo, Japan. Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 467, Japan. Eyetech Res Ctr, Woburn, MA 01801 USA. RP Adamis, AP (reprint author), Eyetech Res Ctr, 42 Cummings Pk, Woburn, MA 01801 USA. RI ISHIDA, SUSUMU/D-7067-2012 FU NEI NIH HHS [EY11627, EY12611] NR 33 TC 33 Z9 35 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2003 VL 163 IS 1 BP 253 EP 259 DI 10.1016/S0002-9440(10)63648-6 PG 7 WC Pathology SC Pathology GA 695KP UT WOS:000183829900025 PM 12819029 ER PT J AU Du, JY Miller, AJ Widlund, HR Horstmann, MA Ramaswamy, S Fisher, DE AF Du, JY Miller, AJ Widlund, HR Horstmann, MA Ramaswamy, S Fisher, DE TI MLANA/MART1 and SlLV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; MICROPHTHALMIA GENE-PRODUCT; SILVER LOCUS PROTEIN; WAARDENBURG-SYNDROME; IN-VIVO; MELAN-A/MART-1 ANTIGEN; TIETZ-SYNDROME; T-LYMPHOCYTES; FACTOR FAMILY; S100 PROTEIN AB The clinically important melanoma diagnostic antibodies HMB-45, melan-A, and MITF (D5) recognize gene products of the melanocyte-lineage genes SIELV/PMEL17/GP100, MLANA/MART1, and MITF, respectively. MITF encodes a transcription factor that is essential for normal melanocyte development and appears to regulate expression of several pigmentation genes. In this report, the possibility was examined that MITF might additionally regulate expression of the SILV and MLANA genes. Both genes contain conserved MITF consensus DNA sequences that were bound by MITF in vitro and in vivo, based on electrophoretic mobility shift assay and chromatin-immunoprecipitation. In addition, WIT regulated their promoter/enhancer regions in reporter assays, and up- or down-regulation of MITF produced corresponding modulation of endogenous SILV and MLANA in melanoma cells. Expression patterns were compared with these factors in a series of melanoma cell lines whose mutational status of the proto-oncogene BRAF was also known. SILV and MLANA expression correlated with MITF, while no clear correlation was seen relative to BRAF mutation. Finally, mRNA expression array analysis of primary human melanomas demonstrated a tight correlation in their expression levels in clinical tumor specimens. Collectively, this study links three important melanoma antigens into a common transcriptional pathway regulated by MITF. C1 Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Dana Farber Canc Inst & Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Dept Pediat Hematol Oncol, Dana Farber Canc Inst & Childrens Hosp, 44 Binney St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR43369, R01 AR043369] NR 76 TC 152 Z9 159 U1 1 U2 6 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2003 VL 163 IS 1 BP 333 EP 343 DI 10.1016/S0002-9440(10)63657-7 PG 11 WC Pathology SC Pathology GA 695KP UT WOS:000183829900034 PM 12819038 ER PT J AU Jain, FA Zhao, LH Selig, MK Kradin, RL AF Jain, FA Zhao, LH Selig, MK Kradin, RL TI Epinephrine promotes pulmonary angiitis: evidence for a beta(1)-adrenoreceptor-mediated mechanism SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung; vessels; airways; immunity; lymphocytes ID TUMOR-NECROSIS-FACTOR; CONGESTIVE-HEART-FAILURE; FACTOR-ALPHA; CELLS; RECEPTOR; STRESS; EXPRESSION; EXERCISE; AUGMENTS; ANTIGEN AB Epinephrine (Epi) increases lymphocyte traffic to lung. We investigated whether Epi also modulates pulmonary cell-mediated immune responses in vivo. C57BL/6 mice were immunized with hen-egg lysozyme (HEL) on day 0, challenged with HEL intratracheally at day 12, and killed at day 15. Mice received Epi (0.5 mg/kg) subcutaneously during the sensitization phase, days 1-7 (Epi-SP), or the effector phase, days 12-14 (Epi-EP); controls received saline subcutaneously. Epi-SP mice showed increased airway inflammation (P<0.03) and pulmonary angiitis (P<0.04) characterized by endothelialitis and subendothelial fibrin deposition. Macrophages and granulocytes were increased in perivascular cuffs in situ (P<0.001). CD3(+) lymphocytes increased in the bronchoalveolar lavage fluid, whereas NK1.1(+) and CD4(+)CD25(+) lymphocytes decreased (all P<0.05). Atenolol, a selective beta(1)-adrenoreceptor (AR) antagonist, inhibited the increased vascular and airway inflammation and the reduction in CD4(+)CD25(+) lymphocytes (all P<0.05) yielded by Epi, whereas all α/β-AR blockers inhibited airway inflammation. We conclude that Epi-EP selectively promotes vascular inflammation in vivo via a β(1)-receptor-mediated mechanism. C1 Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Immunopathol Unit, Warren 5, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI-39054] NR 28 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 2003 VL 285 IS 1 BP L232 EP L239 DI 10.1152/ajplung.00248.2002 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 686HB UT WOS:000183314400025 PM 12730078 ER PT J AU Nanthakumar, NN Klopcic, CE Fernandez, I Walker, WA AF Nanthakumar, NN Klopcic, CE Fernandez, I Walker, WA TI Normal and glucocorticoid-induced development of the human small intestinal xenograft SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week/101st Annual Meeting of the American-Gastroenterological-Association CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Gastroenterol Assoc DE sucrase; lactase; trehalase; intestinal ontogeny; hormonal regulation ID EPIDERMAL GROWTH-FACTOR; HUMAN-FETAL JEJUNUM; NECROTIZING ENTEROCOLITIS; ORGAN-CULTURE; GASTROINTESTINAL-TRACT; CORTICOSTEROID-THERAPY; SUCRASE-ISOMALTASE; DIFFERENTIATION; EXPRESSION; HYDROCORTISONE AB The aim of this study was to determine whether intestinal xenografts could recapitulate human in utero development by using disaccharidases as markers. Twenty-week-old fetal intestine was transplanted into immunocompromised mice and was followed. At 20-wk of gestation, the fetal human intestine was morphologically developed with high sucrase and trehalase but had low lactase activities. By 9-wk posttransplantation, jejunal xenografts were morphologically and functionally developed and were then monitored for less than or equal to6 mo. Both sucrase and trehalase activities remained unchanged, but lactase activity increased in a manner similar to that described in in utero development. Changes in sucrase and lactase activities were paralleled by protein levels. Cortisone acetate treatment at 20-wk posttransplantation accelerated the ontogeny of lactase but did not alter sucrase and trehalase activities. Biopsies from 1- and 2-yr-old infant intestine showed that all activities, except trehalase in the proximal intestine, corresponded to the levels found in jejunal xenografts at 24 wk posttransplantation. These studies suggest that 20-wk-old fetal intestine has the extrauterine developmental potential to follow normal intrauterine ontogeny as a xenograft. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Med Sch, Dept Pediat, Charlestown, MA 02129 USA. RP Nanthakumar, NN (reprint author), Massachusetts Gen Hosp E, Dev Gastroenterol Lab, 114 16th St,Rm 3650, Charlestown, MA 02129 USA. OI Chumpitazi, Corrie/0000-0001-5323-2743 FU NICHD NIH HHS [R01-HD-31852, R37-HD-12437]; NIDDK NIH HHS [P30-DK-043351, P01-DK-33506, P30-DK-40561] NR 48 TC 21 Z9 21 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 JUL PY 2003 VL 285 IS 1 BP R162 EP R170 DI 10.1152/ajpregu.00721.2001 PG 9 WC Physiology SC Physiology GA 687AW UT WOS:000183354500025 PM 12560204 ER PT J AU Wetzel, RK Sweadner, KJ AF Wetzel, RK Sweadner, KJ TI Phospholemman expression in extraglomerular mesangium and afferent arteriole of the juxtaglomerular apparatus SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glomerulus; renin; macula densa; Na,K-ATPase; FXYD ID NA-K-ATPASE; PROTEIN-KINASE-C; NA,K-ATPASE GAMMA-SUBUNIT; IMMUNOCYTOCHEMICAL LOCALIZATION; ALPHA-SUBUNIT; RAT-KIDNEY; MONOCLONAL-ANTIBODY; RENAL NA,K-ATPASE; GENE-EXPRESSION; BETA-3 SUBUNIT AB The molecular mechanisms with which the juxtaglomerular apparatus accomplishes its twin functions, acute regulation of glomerular blood flow and secretion of renin, are still not clearly understood. Least understood is the role of the extraglomerular mesangial (EM) cells, also known as lacis or Goormaghtigh cells, which lie sandwiched between the macula densa and the afferent and efferent arterioles. Here, we report that immunoreactivity for phospholemman (FXYD1), a singlespan membrane protein homologous to the gamma (gamma) subunit of the Na,K-ATPase, is found in the kidney in EM cells with the Na,K-ATPase beta(2)-subunit and in cortical blood vessels and the afferent arteriole with Na, K-ATPase alpha(2) and beta(2). Phospholemman's distribution in EM cells is distinct from that of the Na, K-ATPase gamma-subunit, which is found on the basolateral surface of macula densa cells with Na, K-ATPase alpha(1) and beta(1). Phospholemman is a major kinase target, and its location in the juxtaglomerular apparatus suggests that it is involved in tubuloglomerular feedback. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, 149-6118,149 13th St, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01-HL-36271] NR 51 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2003 VL 285 IS 1 BP F121 EP F129 DI 10.1152/ajprenal.00241.2002 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 686HC UT WOS:000183314500014 PM 12657562 ER PT J AU Natarajan, S Glick, H Criqui, M Horowitz, D Lipsitz, SR Kinosian, B AF Natarajan, S Glick, H Criqui, M Horowitz, D Lipsitz, SR Kinosian, B TI Cholesterol measures to identify and treat individuals at risk for coronary heart disease SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; PRIMARY PREVENTION TRIAL; MYOCARDIAL-INFARCTION; HDL-CHOLESTEROL; PREDICTING RISKS; ARTERY DISEASE; MEN; THERAPY; TRIGLYCERIDE; PRAVASTATIN AB Background: Low-density lipoprotein (LDL)-based guidelines are currently used to initiate and monitor cholesterol-lowering therapy. Methods: Using stratified analyses, data from the Framingham Heart Study and the Coronary Primary Prevention Trial were evaluated to determine whether (1) cholesterol levels total cholesterol [TC] or LDL [low-density lipoprotein]) better discriminated risk for coronary heart disease (CHD) than cholesterol ratios (LDL/HDL [high-density lipoprotein] or TC/HDL); and (2) whether changes in ratios better predicted risk reduction than changes in levels. Results: Individuals with similar LDL/HDL ratios had similar risks for CHD regardless of whether they had high LDL levels or low LDL levels (23% vs 23% for the CPPT, 13.8% vs 14% for FHS men, and 8.6% vs 10.9% for FHS women). Among men with similar initial LDL/HDL ratios and similar changes in LDL/HDL ratios, risks for CHD did not differ (20.3% compared with 21.0%; p =0.96) between those with the largest and smallest reductions in LDL levels (21.3% compared with 6.5%). Among men with similar initial LDL levels and similar LDL reductions, a 20% reduction in risk for CHD was seen (19.5% compared with 24.5%; p =0.005) between those with the largest and smallest reductions in LDL/HDL ratios (23% compared with 4.6%). TC/HDL had predictive ability similar to LDL/HDL. Conclusions: Cholesterol levels do not provide incremental predictive value over cholesterol ratios in identifying people at risk for CHD. Changes in ratios are better predictors of successful CHD risk reduction than changes in levels. Future guidelines should consider incorporating ratios in initiating and monitoring successful lipid-lowering therapy. C1 NYU, Sch Med, New York, NY USA. VA New York Harbor Healthcare Syst, Dept Med, New York, NY USA. Univ Penn, Med Ctr, Div Gen Internal Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Natarajan, S (reprint author), 423 E 23rd St,Room 11101-S, New York, NY 10010 USA. FU NHLBI NIH HHS [HL61769]; NIA NIH HHS [R-29-AG09837] NR 36 TC 81 Z9 81 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2003 VL 25 IS 1 BP 50 EP 57 DI 10.1016/S0749-3797(03)00092-8 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 693GM UT WOS:000183708800008 PM 12818310 ER PT J AU Grossman, R Yehuda, R New, A Schmeidler, J Silverman, J Mitropoulou, V Maria, NS Golier, J Siever, L AF Grossman, R Yehuda, R New, A Schmeidler, J Silverman, J Mitropoulou, V Maria, NS Golier, J Siever, L TI Dexamethasone suppression test findings in subjects with personality disorders: Associations with posttraumatic stress disorder and major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CORTISOL EXCRETION; PLASMA-CORTISOL; PHYSICAL ABUSE; GLUCOCORTICOID-RECEPTORS; BORDERLINE PATIENTS; BASAL CORTISOL; 17-OHCS LEVELS; CHILDHOOD; WOMEN; ILLNESS AB Objective: Previous studies using the 1.0-mg dexamethasone suppression test (DST) in subjects with personality disorders have produced mixed results. However, these studies focused on major depression and did not consider the possible effects of the comorbidity of posttraumatic stress disorder (PTSD). PTSD has been shown to be associated with increased cortisol suppression. To investigate the effect of PTSD, the authors conducted a 0.5-mg DST, which is more sensitive than the 1.0-mg DST for detection of increased cortisol suppression, in a group of subjects with personality disorders. Method: Subjects with personality disorders (N=52) ingested 0.5 mg of dexamethasone. Pre- and postfasting blood samples were drawn for measurement of cortisol levels. A three-way analysis of covariance was used to test for the main effects of major depression, PTSD, and gender on percent cortisol suppression, with plasma dexamethasone concentration as a covariate. Secondary analyses assessed for main and interaction effects of age at which trauma(s) occurred and a diagnosis of borderline personality disorder. Results: Neither major depression nor gender had a significant effect on percent cortisol suppression. Subjects with PTSD had significantly higher percent cortisol suppression than subjects with major depression. Age at which trauma(s) occurred and a borderline personality disorder diagnosis had no significant main or interaction effects on cortisol suppression. Conclusions: A high level of cortisol suppression was associated with PTSD in subjects with personality disorder. This finding is similar to published findings for PTSD subjects without personality disorders. Major depression, gender, age when trauma(s) occurred, and a diagnosis of borderline personality disorder did not have significant main or interaction effects on cortisol suppression. C1 CUNY, Mt Sinai Med Ctr, Dept Psychiat, New York, NY 10029 USA. CUNY, Mt Sinai Med Ctr, Dept Biomath Sci, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. Univ Pittsburgh, Dept Psychol, Med Ctr, Pittsburgh, PA USA. RP Grossman, R (reprint author), CUNY, Mt Sinai Med Ctr, Dept Psychiat, Box 1230, New York, NY 10029 USA. FU NCRR NIH HHS [5-M01-RR-0071]; NIMH NIH HHS [MH-49555, MH-58697-01] NR 44 TC 46 Z9 46 U1 1 U2 5 PU AMER PSYCHIATRIC PRESS, 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 JUL PY 2003 VL 160 IS 7 BP 1291 EP 1297 DI 10.1176/appi.ajp.160.7.1291 PG 7 WC Psychiatry SC Psychiatry GA 697RN UT WOS:000183957200014 PM 12832244 ER PT J AU Schurhoff, F Szoke, A Meary, A Bellivier, F Rouillon, F Pauls, D Leboyer, M AF Schurhoff, F Szoke, A Meary, A Bellivier, F Rouillon, F Pauls, D Leboyer, M TI Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NORMAL CONTROL PROBANDS; SCHIZOAFFECTIVE DISORDER; PERCEPTUAL ABERRATION; PSYCHOSIS PRONENESS; NEGATIVE SYMPTOMS; ROSCOMMON FAMILY; SCHIZOTYPY; RELATIVES; PREVALENCE; INDICATORS AB Objective: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. Method: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. Results: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. Conclusions: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies. C1 Hop Albert Chenevier, Serv Psychiat Adulte Pr Rouillon, F-94000 Creteil, France. Hop Henri Mondor, Inst Natl Saute & Rech Med, Unite 513, Creteil, France. Harvard Univ, Sch Med, Psychiat & Neurodev Genet Unit, Massachusetts Gen Hosp, Charlestown, MA USA. RP Schurhoff, F (reprint author), Hop Albert Chenevier, Serv Psychiat Adulte Pr Rouillon, 40 Rue Mesly, F-94000 Creteil, France. RI BELLIVIER, FRANK/H-5197-2012 NR 41 TC 52 Z9 52 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, 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 JUL PY 2003 VL 160 IS 7 BP 1313 EP 1319 DI 10.1176/appi.ajp.160.7.1313 PG 7 WC Psychiatry SC Psychiatry GA 697RN UT WOS:000183957200017 PM 12832247 ER PT J AU Weiss, RD Griffin, ML Mazurick, C Berkman, B Gastfriend, DR Frank, A Barber, JP Blaine, J Salloum, I Moras, K AF Weiss, RD Griffin, ML Mazurick, C Berkman, B Gastfriend, DR Frank, A Barber, JP Blaine, J Salloum, I Moras, K TI The relationship between cocaine craving, psychosocial treatment, and subsequent cocaine use SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 17-20, 2000 CL SAN JUAN, PUERTO RICO SP Coll Problems Drug Dependence ID COMPULSIVE DRINKING SCALE; NATIONAL-INSTITUTE; DRUG-USE; DEPENDENCE; ABSTINENCE; ALCOHOL; ABUSERS AB Objective: Regular measurement of craving during treatment for cocaine dependence can monitor patients' clinical status and potentially assess their risk for drug use in the near future. Effective treatment can reduce the correlation between craving and subsequent drug use by helping patients abstain despite high craving. This study examined the relationship between cocaine craving, psychosocial treatment, and cocaine use in the ensuing week. Method: In the National Institute on Drug Abuse Collaborative Cocaine Treatment Study, which compared four psychosocial treatments for cocaine dependence, a three-item craving questionnaire was administered weekly to 449 patients to see whether it predicted cocaine use in the ensuing week. Cocaine use was assessed with self-reports and urine screening. Results: With control for the previous week's cocaine use, a higher composite score on the craving questionnaire was associated with greater likelihood of cocaine use in the subsequent week; each 1-point increase on the composite score of the craving questionnaire increased the likelihood of cocaine use in the ensuing week by 10%. However, among patients who received individual plus group drug counseling, the treatment condition with the best overall cocaine use outcome, increased craving scores were not associated with greater likelihood of cocaine use in the subsequent week. Conclusions: A three-item cocaine craving questionnaire predicted the relative likelihood of cocaine use during the subsequent week. Moreover, the relationship between craving and subsequent cocaine use varied by treatment condition, suggesting that the most effective treatment in the study might have weakened the link between craving and subsequent use. C1 McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Penn, Ctr Psychotherapy Res, Dept Psychiat, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Drug Abuse, Bethesda, MD USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. RP Weiss, RD (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. FU NIDA NIH HHS [DA-07693, DA-00326, DA-07085, DA-07090, DA-07663, DA-07673]; NIMH NIH HHS [MH-45178] NR 33 TC 66 Z9 68 U1 5 U2 8 PU AMER PSYCHIATRIC PRESS, 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 JUL PY 2003 VL 160 IS 7 BP 1320 EP 1325 DI 10.1176/appi.ajp.160.7.1320 PG 6 WC Psychiatry SC Psychiatry GA 697RN UT WOS:000183957200018 PM 12832248 ER PT J AU Calsyn, DA DeMarco, FJ Saxon, AJ Sloan, KL Gibbon, KE AF Calsyn, DA DeMarco, FJ Saxon, AJ Sloan, KL Gibbon, KE TI Evaluation of a minimal services treatment track for noncompliant patients in opioid substitution treatment SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID METHADONE-MAINTENANCE TREATMENT C1 VA Puget Sound HCS, Addict Treatment Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. RP Calsyn, DA (reprint author), VA Puget Sound HCS, Addict Treatment Ctr, MS-116DDTP,1660 S Columbian Way, Seattle, WA 98108 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2003 VL 93 IS 7 BP 1086 EP 1088 DI 10.2105/AJPH.93.7.1086 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 695JK UT WOS:000183827200030 PM 12835190 ER PT J AU Titton, RL Gervais, DA Boland, GW Maher, MM Mueller, PR AF Titton, RL Gervais, DA Boland, GW Maher, MM Mueller, PR TI Sonography and sonographically guided fine-needle aspiration biopsy of the thyroid gland: Indications and techniques, pearls and pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CORE BIOPSY; FOLLOW-UP; NODULES; DIAGNOSIS; CARCINOMA; LESIONS; ULTRASONOGRAPHY; ADEQUACY C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 26 TC 27 Z9 29 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 2003 VL 181 IS 1 BP 267 EP 271 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 692DG UT WOS:000183644800050 PM 12818871 ER PT J AU Gill, TJ DeFrate, LE Wang, C Carey, CT Zayontz, S Zarins, B Li, GA AF Gill, TJ DeFrate, LE Wang, C Carey, CT Zayontz, S Zarins, B Li, GA TI The biomechanical effect of posterior cruciate ligament reconstruction on knee joint function - Kinematic response to simulated muscle loads SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID TERM FOLLOW-UP; IN-VITRO; ANTERIOR-POSTERIOR; SURGICAL REPAIR; GRAFT PLACEMENT; DEFICIENT KNEE; ACUTE TEARS; INJURIES; STABILITY; FIXATION AB Background: The effectiveness of posterior cruciate ligament reconstruction in restoring normal kinematics under physiologic loading is unknown. Hypothesis: Posterior cruciate ligament reconstruction does not restore normal knee kinematics under muscle loading. Study Design: In vitro biomechanical study. Methods: Kinematics of knees with an intact, resected, and reconstructed posterior cruciate ligament were measured by a robotic testing system under simulated muscle loads. Anteroposterior tibial translation and internal-external tibial rotation were measured at 0degrees, 30degrees, 60degrees, 90degrees, and 120degrees of flexion under posterior drawer loading, quadriceps muscle loading, and combined quadriceps and hamstring muscle loading. Results: Reconstruction reduced the additional posterior tibial translation caused by ligament deficiency at all flexion angles tested under posterior drawer loading. Ligament deficiency increased external rotation and posterior translation at angles higher than 60degrees of flexion when simulated muscle loading was applied. Posterior cruciate ligament reconstruction reduced the posterior translation and external rotation observed in posterior cruciate ligament-deficient knees at higher flexion angles, but differences were not significant. Conclusion: Under physiologic loading conditions, posterior cruciate ligament reconstruction does not restore six degree of freedom knee kinematics. Clinical Relevance: Abnormal knee kinematics may lead to development of long-term knee arthrosis. (C) 2003 American Orthopaedic Society for Sports Medicine. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. RP Li, GA (reprint author), Bioengn Res Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. NR 41 TC 48 Z9 53 U1 1 U2 4 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUL-AUG PY 2003 VL 31 IS 4 BP 530 EP 536 PG 7 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 702RQ UT WOS:000184237600009 PM 12860540 ER PT J AU Fishman, JA AF Fishman, JA TI Smallpox and live-virus vaccination in transplant recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE bioterrorism; chickenpox; immunocompromised host; organ transplant; smallpox; vaccine; vaccinia; varicella; variola; virus ID HUMAN DENDRITIC CELLS; UNITED STATES 1963; VACCINIA VIRUS; VARICELLA VACCINE; COMPLICATIONS; IMMUNIZATION; MANAGEMENT; EXPERIENCE; CHILDREN; ISRAEL AB Recent bioterrorism raises the specter of reemergence of smallpox as a clinical entity. The mortality of variola major infection ('typical smallpox') was approximately 30% in past outbreaks. Programs for smallpox immunization for healthcare workers have been proposed. Atypical forms of smallpox presenting with flat or hemorrhagic skin lesions are most common in individuals with immune deficits with historic mortality approaching 100%. Smallpox vaccination, even after exposure, is highly effective. Smallpox vaccine contains a highly immunogenic live virus, vaccinia. Few data exist for the impact of variola or safety of vaccinia in immunocompromised hosts. Both disseminated infection by vaccinia and person-to-person spread after vaccination are uncommon. When it occurs, secondary vaccinia has usually affected individuals with pre-existing skin conditions (atopic dermatitis or eczema) or with other underlying immune deficits. Historically, disseminated vaccinia infection was uncommon but often fatal even in the absence of the most severe form of disease, 'progressive vaccinia'. Some responded to vaccinia immune globulin. Smallpox exposure would be likely to cause significant mortality among immunocompromised hosts. In the absence of documented smallpox expoures, immunocompromised hosts should not be vaccinated against smallpox. Planning for bioterrorist events must include consideration of uniquely susceptible hosts. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02115 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Div Infect Dis, Transplant Infect Dis & Compromised Host Program, Boston, MA 02115 USA. NR 55 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2003 VL 3 IS 7 BP 786 EP 793 DI 10.1034/j.1600-6143.2003.00145.x PG 8 WC Surgery; Transplantation SC Surgery; Transplantation GA 698ZZ UT WOS:000184032600004 PM 12814470 ER PT J AU Kurtz, J Lie, A Griffith, M Eysaman, S Shaffer, J Anosova, N Turka, L Benichou, G Sykes, M AF Kurtz, J Lie, A Griffith, M Eysaman, S Shaffer, J Anosova, N Turka, L Benichou, G Sykes, M TI Lack of role for CsA-sensitive or Fas pathways in the tolerization of CD4 T cells via BMT and anti-CD40L SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE AICD; apoptosis; bone marrow; CD154; CD40L; cyclosporine; deletion; tolerance; transplantation ID BONE-MARROW-TRANSPLANTATION; DONOR-SPECIFIC TOLERANCE; VERSUS-HOST-DISEASE; COSTIMULATORY BLOCKADE; MONOCLONAL-ANTIBODY; CLONAL DELETION; CYCLOSPORINE-A; HEMATOPOIETIC CHIMERISM; ALLOGRAFT TOLERANCE; MIXED CHIMERISM AB Anti-CD40L mAb plus bone marrow transplantation (BMT) and recipient CD8 T-cell depletion permits long-term mixed hematopoietic chimerism and systemic donor-specific tolerance to be achieved across full MHC barriers. Initial tolerance is characterized by peripheral deletion of donor-reactive CD4 cells. In regimens using costimulatory blockade without BMT to achieve allograft survival, cyclosporine inhibited graft survival, suggesting that the combination may not be clinically applicable. We assessed the role of cyclosporine-sensitive mechanisms and the mechanisms of T-cell apoptosis involved in the induction of early peripheral CD4(+) T-cell tolerance by BMT with anti-CD40L. Neither a short course of cyclosporine (14days) nor the absence of FAS-mediated activation-induced cell death (AICD) blocked the induction or maintenance of donor-specific tolerance. IL-2 production was not associated with tolerance induction, consistent with the lack of a role for Fas-mediated AICD. Mice in which passive T-cell death was impaired because of constitutive expression of a Bcl-XL transgene did not develop tolerance with this protocol. These data confirm that deletion of donor-reactive T cells is critical for the induction of mixed chimerism and tolerance. However, the mechanisms involved may differ from those involved in costimulatory blockade regimens that do not include BMT. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Sch Med,Bone Marrow Transplantat Sect, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CMI Lab, Boston, MA 02115 USA. Univ Penn, Dept Med, Hlth Syst, Philadelphia, PA 19104 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Sch Med,Bone Marrow Transplantat Sect, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL49915]; PHS HHS [IT32-07529] NR 51 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2003 VL 3 IS 7 BP 804 EP 816 DI 10.1034/j.1600-6143.2003.00128.x PG 13 WC Surgery; Transplantation SC Surgery; Transplantation GA 698ZZ UT WOS:000184032600006 PM 12814472 ER PT J AU Matas, AJ Bartlett, ST Leichtman, AB Delmonico, FL AF Matas, AJ Bartlett, ST Leichtman, AB Delmonico, FL TI Morbidity and mortality after living kidney donation, 1999-2001: Survey of United States Transplant Centers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney donor; morbidity; mortality ID LAPAROSCOPIC DONOR NEPHRECTOMY; SURVIVAL; DIALYSIS; RATES AB There have been two recent trends in living kidney donation: increased acceptance of living donors and increased acceptance of laparoscopic nephrectomy (L-N). We surveyed 234 UNOS-listed kidney transplant programs to determine current living donor morbidity and mortality for open nephrectomy, hand-assisted LN, and non-hand-assisted LN. Of the 234 centers, 171 (73%) responded. Between 1/1/1999 and 7/1/2001, these centers carried out 10828 living donor nephrectomies: 52.3% open, 20.7% hand-assisted LN, and 27% non-hand-assisted LN. Two donors (0.02%) died from surgical complications and one is in a persistent vegetative state (all after LN). Reoperation was necessary in 22 (0.4%) open, 23 (1.0%) hand-assisted LN, and 21 (0.9%) non-hand-assisted LN cases (p=0.001). Complications not requiring reoperation were reported for 19 (0.3%) open, 22 (1.0%) hand-assisted LN, and 24 (0.8%) non-hand-assisted LN cases (p=0.02). Readmission rate was higher for LN (1.6%) vs. open (0.6%) donors (p<0.001), almost entirely as a result of an increase in gastrointestinal complications in LN donors. Morbidity and mortality for living donor nephrectomy at transplant centers in the United States remain low. We provide current data from which comprehensive informed consent can be obtained from donors. C1 Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. Univ Maryland, Dept Surg, College Pk, MD 20742 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Matas, AJ (reprint author), Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. NR 19 TC 220 Z9 234 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2003 VL 3 IS 7 BP 830 EP 834 DI 10.1034/j.1600-6143.2003.00126.x PG 5 WC Surgery; Transplantation SC Surgery; Transplantation GA 698ZZ UT WOS:000184032600008 PM 12814474 ER PT J AU Srinivasa, V Gerner, P Haderer, A Abdi, S Jarolim, P Wang, GK AF Srinivasa, V Gerner, P Haderer, A Abdi, S Jarolim, P Wang, GK TI The relative toxicity of amitriptyline, bupivacaine, and levobupivacaine administered as rapid infusions in rats SO ANESTHESIA AND ANALGESIA LA English DT Article ID ROPIVACAINE AB Intravascular injection of local anesthetics carries the risk of cardiovascular (CV) and central nervous system (CNS) toxicity. Amitriptyline, a tricyclic antidepressant, has local anesthetic potency that is more than that of bupivacaine. In this study, we compared the CV and CNS toxicity of the local anesthetics bupivacaine and levobupivacaine with that of amitriptyline. Twenty-nine Sprague-Dawley rats had their right external jugular vein and carotid artery cannulated under general anesthesia. On Day 2, rats were sedated with midazolam (0.375 mg/kg intraperitoneally) and received rapid infusions of either 1) bupivacaine, levobupivacaine, or amitriptyline at 2 mg . kg(-1) . min(-1) (5 mg/mL concentration) or 2) normal saline (400 muL . kg(-1) . min(-1)) through an external jugular vein cannula. Electrocardiogram and arterial blood pressure were measured until the dose to cause impending death was reached (heart rate 50 bpm/asystole or apnea for >30 s). The mean dose required to cause apnea and impending death wag significantly larger for amitriptyline (74.0 +/- 21 mg/kg and 74.5 +/- 21 mg/kg, respectively) than for levobupivacaine (32.2 +/- 20 mg/kg and 33.9 +/- 22 mg/kg, respectively) or bupivacaine (21.5 +/- 7 mg/kg and 22.7 +/- 7 mg/kg, respectively) (P < 0.05). A significantly larger dose of amitriptyline, given by rapid infusion, is required to cause CV and CNS toxicity in rats, when compared with bupivacaine and levobupivacaine. C1 Harvard Univ, Dept Anesthesiol Peroperat & Pain Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Intens Care, Boston, MA 02115 USA. RP Gerner, P (reprint author), Harvard Univ, Dept Anesthesiol Peroperat & Pain Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM064051, GM48090] NR 22 TC 14 Z9 14 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 JUL PY 2003 VL 97 IS 1 BP 91 EP 95 DI 10.1213/01.ANE.0000065600.15574.AB PG 5 WC Anesthesiology SC Anesthesiology GA 695CZ UT WOS:000183814700018 PM 12818949 ER PT J AU Kobierski, LA Abdi, S DiLorenzo, L Feroz, N Borsook, D AF Kobierski, LA Abdi, S DiLorenzo, L Feroz, N Borsook, D TI A single intravenous injection of KRN5500 (antibiotic spicamycin) produces long-term decreases in multiple sensory hypersensitivities in neuropathic pain SO ANESTHESIA AND ANALGESIA LA English DT Article ID NERVE INJURY; PERIPHERAL MONONEUROPATHY; MECHANICAL ALLODYNIA; RAT MODEL; HYPERALGESIA; PLASTICITY; DISORDERS; ANALOGS AB Neuropathic pain is a significant clinical problem. Currently, there are no drugs that produce complete amelioration of this type of pain. We have previously shown that KRN5500, a derivative of the antibiotic spicamycin, produces a prolonged (7-day), and significant reduction in neuropathic pain, but not nociceptive pain. Herein, we provide further evidence for the efficacy of this drug in inhibiting pain after IV injection in a spared nerve injury model of neuropathic pain. A single IV dose of the drug produces an increase in pain thresholds to punctuate mechanical stimuli and to cold stimuli over a period of 7 days, whereas IV injection of the vehicle is without any effect. No change in pain threshold was observed in the contralateral foot. In addition, a significant antiallodynic effect to mechanical stimuli was observed at 1, 2, 4, and 6 wk. The drug may be a potential candidate for cancer-related neuropathic pain as well as a marker for discovery of effective analgesics for neuropathic pain. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Funct Pain Neuroimaging & Therapy Res, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Ctr Funct Pain Neuroimaging & Therapy Res, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Ctr Funct Pain Neuroimaging & Therapy Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Borsook, D (reprint author), Ctr Funct Pain Neuroimaging & Therapy Res, MGH NMR Ctr, Dept Radiol, Rm 2316, Charlestown, MA 02129 USA. NR 24 TC 8 Z9 9 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 JUL PY 2003 VL 97 IS 1 BP 174 EP 182 DI 10.1213/01.ANE.0000066359.83348.F1 PG 9 WC Anesthesiology SC Anesthesiology GA 695CZ UT WOS:000183814700031 PM 12818962 ER PT J AU Pollack, CV Hollander, JE O'Neil, BJ Neumar, RW Summers, R Camargo, CA Younger, JG Callaway, CW Gallagher, EJ Kellermann, AL Krause, GS Schafermeyer, RW Sloan, E Stern, S AF Pollack, CV Hollander, JE O'Neil, BJ Neumar, RW Summers, R Camargo, CA Younger, JG Callaway, CW Gallagher, EJ Kellermann, AL Krause, GS Schafermeyer, RW Sloan, E Stern, S CA ACEP Res Comm TI Status report: Development of emergency medicine research since the Macy Report SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID OTTAWA KNEE RULE; RISK STRATIFICATION; CAREER; SATISFACTION; RADIOGRAPHY; FUTURE; PAIN AB In Williamsburg, VA, April 17 to 20, 1994, the Josiah Macy, Jr. Foundation sponsored a conference entitled "The Role of Emergency Medicine in the Future of American Medical Care," a report on which was published in Annals in 1995. This report promulgated recommendations for the development and enhancement of academic departments of emergency medicine and a conference to develop an agenda for research in emergency medicine. The American College of Emergency Physicians' Research Committee, along with several ad hoc members, presents updates in several of the areas addressed by the Macy Report and subsequent conferences, as a status report for the development of emergency medicine research as a whole, as of late 2002. C1 Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Wayne State Univ, Detroit, MI USA. Univ Mississippi, Jackson, MS 39216 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Ctr Med, Pittsburgh, PA USA. Emory Univ, Sch Med, Atlanta, GA USA. Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Univ Illinois, Chicago, IL USA. RP Pollack, CV (reprint author), Penn Hosp, Dept Emergency Med, 800 Spruce St, Philadelphia, PA 19107 USA. OI Callaway, Clifton/0000-0002-3309-1573; Younger, John/0000-0002-0820-0635; Hollander, Judd/0000-0002-1318-2785 NR 28 TC 11 Z9 11 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JUL PY 2003 VL 42 IS 1 BP 66 EP 80 DI 10.1067/mem.2003.237 PG 15 WC Emergency Medicine SC Emergency Medicine GA 697XF UT WOS:000183968000011 PM 12827125 ER PT J AU Irizarry, MC AF Irizarry, MC TI A turn of the sulfatide in Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID CEREBROSPINAL-FLUID; CSF; DEMENTIA; MYELIN C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Dis Res Unit, Charlestown, MA USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Dis Res Unit, Charlestown, MA USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2003 VL 54 IS 1 BP 7 EP 8 DI 10.1002/ana.10642 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 695DC UT WOS:000183815000003 PM 12838515 ER PT J AU Al-Chalabi, A Scheffler, MD Smith, BN Parton, MJ Cudkowicz, ME Andersen, PM Hayden, DL Hansen, VK Turner, MR Shaw, CE Leigh, PN Brown, RH AF Al-Chalabi, A Scheffler, MD Smith, BN Parton, MJ Cudkowicz, ME Andersen, PM Hayden, DL Hansen, VK Turner, MR Shaw, CE Leigh, PN Brown, RH TI Ciliary neurotrophic factor genotype does not influence clinical phenotype in amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID MOTOR-NEURON DISEASE; CNTF GENE; NULL MUTATION; DEGENERATION; RECEPTOR; RHCNTF; TRIAL AB Ciliary neurotrophic factor (CNTF) maintains survival of adult motor neurons. Mice lacking the CNTF gene develop mild, progressive motor neuron loss. In the normal human population, 1 to 2.3% are homozygous for a null allele, and reports suggest this mutant is associated with a younger onset of amyotrophic lateral sclerosis (ALS). We have tested this hypothesis in a study of 400 subjects with ALS and 236 controls. There was no difference in age of onset, clinical presentation, rate of progression, or disease duration for those with one or two copies of the null allele, excluding CNTF as a major disease modifier in ALS. C1 Inst Psychiat, Acad Neurosci Ctr, Dept Neurol, London SE5 8AF, England. MGH East, Day Neuromuscular Res Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Neurol Clin Trials Unit, Boston, MA 02114 USA. Umea Univ, Dept Neurol, Umea, Sweden. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Guys Kings & St Thomas Sch Med, Dept Neurol, London, England. Guys Kings & St Thomas Sch Med, Dept Med & Mol Genet, London, England. Univ London Kings Coll, Inst Psychiat, London WC2R 2LS, England. RP Al-Chalabi, A (reprint author), Inst Psychiat, Acad Neurosci Ctr, Dept Neurol, DO41,De Crespigny Pk, London SE5 8AF, England. RI Al-Chalabi, Ammar/E-5361-2010; Turner, Martin/F-7240-2011; Smith, Bradley/H-6107-2013; OI Al-Chalabi, Ammar/0000-0002-4924-7712; Turner, Martin/0000-0003-0267-3180 NR 20 TC 23 Z9 24 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2003 VL 54 IS 1 BP 130 EP 134 DI 10.1002/ana.10638 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 695DC UT WOS:000183815000019 PM 12838531 ER PT J AU Piccart, M Parker, LM Pritchard, KI AF Piccart, M Parker, LM Pritchard, KI TI Oestrogen receptor downregulation: an opportunity for extending the window of endocrine therapy in advanced breast cancer SO ANNALS OF ONCOLOGY LA English DT Review DE advanced breast cancer; estrogen receptor downregulation; 'Faslodex'; fulvestrant; postmenopausal; sequencing ID FIRST-LINE THERAPY; SELECTIVE AROMATASE INHIBITOR; RANDOMIZED DOUBLE-BLIND; PHASE-III TRIALS; POSTMENOPAUSAL WOMEN; MEGESTROL-ACETATE; PURE ANTIESTROGEN; HORMONAL-THERAPY; TAMOXIFEN; ANASTROZOLE AB Background: Advanced breast cancer is largely incurable and current treatment modalities are aimed towards restricting tumour growth, prolonging survival, palliating symptoms and maintaining quality of life (QoL). The development of breast cancer is strongly influenced by endogenous oestrogens (and other growth factors), leading to a strong focus on the development of antioestrogenic compounds for the treatment of hormone-sensitive advanced disease. Design: This is a review of current endocrine therapies available for postmenopausal women with advanced breast cancer, examining the likely impact of newer agents on treatment strategies. Results: In postmenopausal women, current treatment options include tamoxifen, aromatase inhibitors (AIs) and megestrol acetate. Fulvestrant ('Faslodex') is a new, well-tolerated, oestrogen receptor antagonist that has no known agonist effect and is at least as effective as the At anastrozole for the treatment of postmenopausal patients with metastatic or advanced breast cancer who have progressed on prior endocrine therapy. Fulvestrant maintains QoL throughout successful treatment. Conclusions: Fulvestrant represents a new treatment option for postmenopausal women with advanced disease. New agents that appear to lack cross-resistance with existing treatments may be used to extend the time period during which endocrine therapy may be employed before the need for cytotoxic chemotherapy. C1 Inst Jules Bordet, Chemotherapy Unit, B-1000 Brussels, Belgium. Dana Farber Canc Inst, Boston, MA 02115 USA. Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. RP Piccart, M (reprint author), Inst Jules Bordet, Chemotherapy Unit, 1 Rue Heger Bordet,Blvd Waterloo 125, B-1000 Brussels, Belgium. NR 85 TC 12 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUL PY 2003 VL 14 IS 7 BP 1017 EP 1025 DI 10.1093/annone/mdg290 PG 9 WC Oncology SC Oncology GA 705EH UT WOS:000184382400009 PM 12853342 ER PT J AU Grant, RW Devita, NG Singer, DE Meigs, JB AF Grant, RW Devita, NG Singer, DE Meigs, JB TI Improving adherence and reducing medication discrepancies in patients with diabetes SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GEORGIA SP Soc Gen Internal Med DE adherence; randomized controlled trial; type 2 diabetes mellitus ID CARE; INTERVENTIONS; MANAGEMENT; PRESCRIPTIONS; TRIAL; SCALE AB Objective. To improve medication adherence by reducing self-reported adherence barriers, and to identify medication discrepancies by comparing physician-prescribed and patient-reported medical regimens. Design: Prospective, randomized, controlled trial. Setting and Participants: A single academically affiliated community health center. Eligible patients had type 2 diabetes, had undergone laboratory testing in the year preceding the study, and had visited the clinic in the 6 months preceding the study. Intervention: A pharmacist administered detailed questionnaires, provided tailored education regarding medication use and help with appointment referrals, and created a summary of adherence barriers and medication discrepancies that was entered into the medical record and electronically forwarded to the primary care provider. Measurements: Changes in self-reported adherence rates and barriers were compared 3 months after the initial interview. Intervention patients with medication discrepancies at baseline were assessed for resolution of discrepancies at 3 months. Results: Rates of self-reported medication adherence were very high and did not improve further at 3 months (6.9 of 7 d, with all medicines taken as prescribed; p=0.3). Medical regimen discrepancies were identified in 44% of intervention patients, involving 45 doses of medicines. At 3-month follow-up, 60% of discrepancies were resolved by corrections in the medical record, while only 7% reflected corrections by patients. Conclusions: In this community cohort, patients reported few adherence barriers and very high medication adherence rates. Our patient-tailored intervention did not further reduce these barriers or improve self-reported adherence. The high prevalence of medication discrepancies appeared to mostly reflect inaccuracies in the medical record rather than patient errors. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Partners Community HealthCare Inc, Needham, MA USA. RP Grant, RW (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St, Boston, MA 02114 USA. OI Grant, Richard/0000-0002-6164-8025 FU PHS HHS [2-T3211001-14] NR 25 TC 50 Z9 52 U1 1 U2 10 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 2003 VL 37 IS 7-8 BP 962 EP 969 DI 10.1345/aph.1C452 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699VC UT WOS:000184075800004 PM 12841801 ER PT J AU Gray, SL Hedrick, SC Rhinard, EE Sales, AE Sullivan, JH AF Gray, SL Hedrick, SC Rhinard, EE Sales, AE Sullivan, JH TI Potentially inappropriate medication use in community residential care facilities SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE community residential care; drug utilization; elderly ID DRUG-USE; EXPLICIT CRITERIA; BOARD AB Objective: To describe the prevalence of potentially inappropriate medication use in community residential care (CRC) facilities at baseline, describe exposure to potentially inappropriate drugs during the 1-year follow-up, and examine characteristics associated with potentially inappropriate use. Design: A cohort study was conducted using 282 individuals aged greater than or equal to65 years entering a CRC facility in a 3-county area in the Puget Sound region of Washington State between April 1998 and December 1998 on Medicaid funding. Main Outcome Measure: Use of potentially inappropriate medications as defined by explicit criteria (e.g., drugs that should generally be avoided in the elderly because potential risks outweigh any potential benefits). Results: Sixty-two (22%) residents took a total of 75 potentially inappropriate medications at baseline. The most common agents used at baseline were oxybutynin (3.5%) and amitriptyline (3.5%). The incidence of new use of potentially inappropriate medications was 0.1/100 person-days during the follow-up period. Potentially inappropriate use was related to self-reported fair or poor health (adjusted OR 1.42; 95% CI 1.05 to 1.92) and number of prescription drugs (adjusted OR 1.12; 95% CI 1.05 to 1.19). In the Cox proportional hazard model, no characteristics predicted new potentially inappropriate medication use during the follow-up. Conclusions: Potentially inappropriate medication use is common among residents in CRC facilities. A comprehensive periodic review may be beneficial for reducing potentially inappropriate use, especially for patients taking multiple drugs. C1 Univ Washington, Sch Pharm, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Box 357630, Seattle, WA 98195 USA. OI Sales, Anne/0000-0001-9360-3334 FU NIA NIH HHS [KO8AG00808-01] NR 25 TC 23 Z9 24 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 2003 VL 37 IS 7-8 BP 988 EP 993 DI 10.1345/aph.1C365 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699VC UT WOS:000184075800008 PM 12841805 ER PT J AU Grikscheit, TC Ochoa, ER Ramsanahie, A Alsberg, E Mooney, D Whang, EE Vacanti, JP AF Grikscheit, TC Ochoa, ER Ramsanahie, A Alsberg, E Mooney, D Whang, EE Vacanti, JP TI Tissue-engineered large intestine resembles native colon with appropriate in vitro physiology and architecture SO ANNALS OF SURGERY LA English DT Article ID POUCH-ANAL ANASTOMOSIS; ULCERATIVE-COLITIS; ILEAL RESERVOIR AB Objective: Novel production and in vitro characterization of tissue engineered colon. Summary Background Data: The colon provides important functions of short chain fatty acid production, sodium and water absorption, and storage. We report the first instance of tissue-engineered colon (TEC) production from autologous cells and its in vitro characterization. Methods: Organoid units, mesenchymal cell cores surrounded by a polarized epithelia derived from full thickness sigmoid colon dissection from neonatal Lewis rats, adult rats, and tissue engineered colon itself, were implanted on a polymer scaffold into the omentum of syngeneic hosts. TEC was either anastomosed at 4 weeks or excised for Ussing chamber studies or histology, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling assay. Results: TEC was generated by 100% of all animals without regard to tissue source, the first instance of engineered intestine from adult cells or an engineered tissue. TEC architecture is identical to native with muscularis propria staining for actin, acetylcholinesterase detected in a linear distribution in the lamina propria, S100-positive cells, ganglion cells, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling assay similar to native colon. Ussing chamber data indicated in vitro function consistent with mature colonocytes, and a positive short circuit current response to theophylline indicating intact ion transfer. TEM showed normal microarchitecture. Colon architecture was maintained in anastomosis with gross visualization of fluid uptake. Conclusions: TEC can be successfully produced with fidelity to native architecture and in vitro function from neonatal syngeneic tissue, adult tissue, and TEC itself. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Integrat Med & Innovat Technol, Boston, MA USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. RI Liu, Yifei/L-7828-2014 OI Liu, Yifei/0000-0002-1087-9827 NR 13 TC 68 Z9 69 U1 1 U2 7 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 JUL PY 2003 VL 238 IS 1 BP 35 EP 41 DI 10.1097/01.SLA.0000074964.77367.4a PG 7 WC Surgery SC Surgery GA 730MQ UT WOS:000185834900005 PM 12832963 ER PT J AU Mullen, JT Tanabe, KK AF Mullen, JT Tanabe, KK TI Viral oncolysis for malignant liver tumors SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE oncolysis; replication-conditional viruses; gene therapy; clinical trials; liver tumors ID HERPES-SIMPLEX-VIRUS; REPLICATION-SELECTIVE ADENOVIRUS; RECOMBINANT VACCINIA VIRUS; MONKEY AOTUS-TRIVIRGATUS; NEWCASTLE-DISEASE VIRUS; PROSTATE-CANCER CELLS; DIRECTED GENE-THERAPY; GIBBON HYLOBATES-LAR; PHASE-II TRIAL; THYMIDINE KINASE AB Viral oncolysis represents a unique strategy to exploit the natural process of viral replication to kill tumor cells. Although this concept dates back nearly a century, recent advances in the fields of molecular biology and virology have enabled investigators to genetically engineer viruses with greater potency and tumor specificity. In this article we review the general mechanisms by which oncolytic viruses achieve their antineoplastic efficacy and specificity. We focus on the development of several classes of oncolytic viruses for the treatment of malignant liver tumors, including adenoviruses, vaccinia viruses, and herpes simplex viruses, and discuss the results of clinical trials for these viruses. We also describe results from our laboratory research program, which is focused on developing effective, liver tumor-specific Herpes simplex virus 1 mutants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Tanabe, KK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, 100 Blossom St,Cox Bldg 626, Boston, MA 02114 USA. NR 79 TC 15 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUL PY 2003 VL 10 IS 6 BP 596 EP 605 DI 10.1245/ASO.2003.07.020 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 698AJ UT WOS:000183975200004 PM 12839843 ER PT J AU Lee, D Friend, D Gurish, M Mathis, D Benoist, C Brenner, M AF Lee, D Friend, D Gurish, M Mathis, D Benoist, C Brenner, M TI Autoantibody effector mechanisms in inflammatory arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 18, 2003 CL LISBON, PORTUGAL C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2003 VL 62 SU 1 BP 8 EP 8 PG 1 WC Rheumatology SC Rheumatology GA 863HG UT WOS:000224551400023 ER PT J AU Allan, JS AF Allan, JS TI Prognostic significance of CD44v5 expression in human thymic epithelial neoplasms - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, 55 Fruit St,Blake 1570, 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2003 VL 76 IS 1 BP 218 EP 218 AR PII S0003-4975(03)00575-7 DI 10.1016/S0003-4975(03)00575-7 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 697XK UT WOS:000183968400048 ER PT J AU Pisick, E Skarin, AT Salgia, R AF Pisick, E Skarin, AT Salgia, R TI Recent advances in the molecular biology, diagnosis and novel therapies for various small blue cell tumors SO ANTICANCER RESEARCH LA English DT Review DE small blue cell tumors; SCLC; non-Hodgkins lymphoma; Ewing's sarcoma; rhabdomyosarcoma; Merkel carcinoma; neuroblastoma; carcinoid; diagnosis; therapy; review ID NON-HODGKINS-LYMPHOMA; ANTI-CD20 MONOCLONAL-ANTIBODY; PHASE-II TRIAL; COMPARATIVE GENOMIC HYBRIDIZATION; METASTATIC CARCINOID-TUMORS; COLONY-STIMULATING FACTOR; HUMAN NEURO-BLASTOMA; C-KIT PROTOONCOGENE; LUNG-CANCER CELLS; EWINGS-SARCOMA TRANSLOCATION AB Small blue cell tumors are a group of tumors that share a common histologic characteristic with H&E staining. This makes differentiation from one another difficult as they all appear small, blue and round. Even though they all appear the same, they are vastly different from each other. Several different techniques have been developed to help further delineate and classify these tumors which include: small cell lung cancer (SCLC); non-Hodgkin's lymphoma (NHL); Ewing's sarcoma; rhabdomyosarcoma; Merkel carcinoma; neuroblastoma; carcinoid tumors; and intra-abdominal desmpolastic small round cell tumor. Using immunoperoxidase staining, reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization techniques, these tumors have been successfully differentiated from one another. This separation makes staging and treatment of these tumors more effective, as not all of these tumors respond to the same modality of treatment. The following review summarizes some of the recent findings in the various small blue cell tumors and with the potential of novel therapies. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Thorac Oncol Program,Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Salgia, R (reprint author), 5841S Maryland Ave, Chicago, IL 60637 USA. NR 265 TC 13 Z9 13 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 2003 VL 23 IS 4 BP 3379 EP 3396 PG 18 WC Oncology SC Oncology GA 711DD UT WOS:000184723600037 PM 12926079 ER PT J AU Wang, MG Tran, JH Jacoby, GA Zhang, YY Wang, F Hooper, DC AF Wang, MG Tran, JH Jacoby, GA Zhang, YY Wang, F Hooper, DC TI Plasmid-mediated quinolone resistance in clinical isolates of Escherichia coli from Shanghai, China SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLASS-1 INTEGRON; FLUOROQUINOLONE RESISTANCE; ANTIBIOTIC-RESISTANCE; NALIDIXIC-ACID; MECHANISMS; BLA(CTX-M-2); CASSETTES; STRAINS; ORF513; GENE AB Although quinolone resistance usually results from chromosomal mutations, recent studies indicate that quinolone resistance can also be plasmid mediated. The gene responsible, qnr, is distinct from the known quinolone resistance genes and in previous studies seemed to be restricted to Klebsiella pneumoniae and Escherichia coli isolates from the University of Alabama in Birmingham, where this resistance was discovered. In Shanghai, the frequency of ciprofloxacin resistance in E. coli has exceeded 50% since 1993. Seventy-eight unique ciprofloxacin-resistant clinical isolates of E. coli from Shanghai hospitals were screened for the qnr gene by colony blotting and Southern hybridization of plasmid DNA. Conjugation experiments were done with azide-resistant E. coli J53 as a recipient with selection for plasmid-encoded antimicrobial resistance (chloramphenicol, gentamicin, or tetracycline) and azide counterselection. qnr genes were sequenced, and the structure of the plasmid DNA adjacent to qnr was analyzed by primer walking with a sequential series of outward-facing sequencing primers with plasmid DNA templates purified from transconjugants. Six (7.7%) of 78 strains gave a reproducible hybridization signal with a qnr gene probe on colony blots and yielded strong signals on plasmid DNA preparations. Quinolone resistance was transferred from all six probe-positive strains. Transconjugants had 16- to 250-fold increases in the MICs of ciprofloxacin relative to that of the recipient. All six strains contained qnr with a nucleotide sequence identical to that originally reported, except for a single nucleotide change (CT (A) under bar -->CT (G) under bar at position 537) encoding the same amino acid. qnr was located in complex In4 family class 1 integrons. Two completely sequenced integrons were designated In36 and In37. Transferable plasmid-mediated quinolone resistance associated with qnr is thus prevalent in quinolone-resistant clinical strains of E. coli from Shanghai and may contribute to the rapid increase in bacterial resistance to quinolones in China. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200040, Peoples R China. Lahey Clin Fdn, Dept Infect Dis, Burlington, MA 01805 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. OI Wang, Minggui/0000-0001-7682-5859 FU NIAID NIH HHS [AI43312, R01 AI057576, R37 AI023988, R01 AI023988, AI23988, R01 AI043312] NR 28 TC 283 Z9 366 U1 6 U2 28 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 JUL PY 2003 VL 47 IS 7 BP 2242 EP 2248 DI 10.1128/AAC.47.7.2242-2248.2003 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 694RA UT WOS:000183786700028 PM 12821475 ER PT J AU Pennick, GJ Clark, M Sutton, DA Rinaldi, MG AF Pennick, GJ Clark, M Sutton, DA Rinaldi, MG TI Development and validation of a high-performance liquid chromatography assay for voriconazole SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PLASMA AB An analytical method for the determination of voriconazole (UK-109,496; Pfizer) in plasma was developed and validated. The method utilizes solid-phase extraction technology and high-performance liquid chromatography. The lower limit of quantitation is 0.2 mug/ml, and the range of linearity tested was 0.2 to 10 mug/ml. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. RP Pennick, GJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 6 TC 94 Z9 98 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2003 VL 47 IS 7 BP 2348 EP 2350 DI 10.1128/AAC.47.7.2348-2350.2003 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 694RA UT WOS:000183786700049 PM 12821496 ER PT J AU Garcia, AM Szasz, N Trippel, SB Morales, TI Grodzinsky, AJ Frank, EH AF Garcia, AM Szasz, N Trippel, SB Morales, TI Grodzinsky, AJ Frank, EH TI Transport and binding of insulin-like growth factor I through articular cartilage SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID DYNAMIC COMPRESSION; IGF-I; BIOSYNTHETIC RESPONSE; ELECTRICAL MIGRATION; INCREASED EXPRESSION; FLUID-FLOW; PROTEINS; EXPLANTS; PROTEOGLYCAN; CHONDROCYTES AB This study focused on the role of insulin-like growth factor (IGF) binding proteins (IGFBPs) in cartilage on the transport and binding of IGF-I within the tissue. We have developed experimental and theoretical modeling techniques to quantify and contrast the roles of diffusion, binding, fluid convection, and electrical migration on the transport of IGF-I within cartilage tissue. Bovine articular cartilage disks were equilibrated in buffer containing I-125-IGF-I and graded levels of unlabeled IGF-I. Equilibrium binding, as measured by the uptake ratio of I-125-IGF-I in the tissue (free plus bound) to the concentration of labeled species in the buffer, was found to be consistent with a first-order reversible binding model involving one dominant family of binding sites within the matrix. Western ligand blots revealed a major IGF binding doublet around 23 kDa, which has been previously shown to coincide with IGFBP-6. Diffusive transport of I-125-IGF-I through cartilage was measured and found to be consistent with a diffusion-limited reaction theoretical model incorporating first-order reversible binding. Addition of excess amounts of unlabeled IGF-I during steady state transport of I-125-IGF-I resulted in release of bound I-125-IGF-I from the tissue, as predicted by the diffusion-reaction model. In contrast, addition of the low-affinity Des(1-3)IGF-I analog did not result in release of bound I-125-IGF-I. Application of electric current was used to augment transport of IGF-I through cartilage via electroosmosis and electrophoresis. Taken together, our results suggest that a single dominant substrate family, the high-affinity IGFBPs, is responsible for much of the observed binding of IGF-I within cartilage. The data suggest that intratissue fluid flow, such as that induced by mechanical loading of cartilage in vivo may be expected to enhance IGF transport by an order of magnitude and that this increment may help to counterbalance the restrictions encountered by the immobilization of IGFs by the binding proteins. (C) 2003 Elsevier Science (USA). All rights reserved. C1 MIT, Dept Elect Engn & Comp Sci, Ctr Biomed Engn, Continuum Electromech Grp, Cambridge, MA 02139 USA. Indiana Univ, Dept Orthopaed, Bloomington, IN 47405 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Frank, EH (reprint author), MIT, Dept Elect Engn & Comp Sci, Ctr Biomed Engn, Continuum Electromech Grp, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ehfrank@mit.edu FU NIAMS NIH HHS [AR33236] NR 44 TC 44 Z9 45 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL 1 PY 2003 VL 415 IS 1 BP 69 EP 79 DI 10.1016/S0003-9861(03)00215-7 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 694QE UT WOS:000183784800009 PM 12801514 ER PT J AU Waner, M North, PE Scherer, KA Frieden, IJ Waner, A Mihm, MC AF Waner, M North, PE Scherer, KA Frieden, IJ Waner, A Mihm, MC TI The nonrandom distribution of facial hemangiomas SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 13th International Workshop on Vascular Anomalies CY MAY 10-13, 2000 CL MONTREAL, CANADA ID JUVENILE HEMANGIOMAS; MALFORMATIONS; INFANTS AB Objective: To map sites of occurrence of facial infantile hemangiomas and correlate these with pattern of tumor growth, clinical complications, and proximity to structural and developmental landmarks. Design: A retrospective medical record review of 205 patients diagnosed with facial infantile hemangioma. Setting: Arkansas Children's Hospital, Little Rock, a 250-bed teaching hospital affiliated with the University of Arkansas for Medical Sciences. Patients: Based on their clinical photographs, 232 of the hemangiomas were mapped on a facial schematic. Each lesion was encoded with a number reflective of its location, and this number was shared by other lesions occurring at the same site. Frequencies of complicating ulceration and airway obstruction were determined by medical record review. Results: Two patterns of tumor growth were evident among the hemangiomas analyzed: focal (177 lesions [76.3%]) and diffuse (55 lesions [23.7%]). The focal hemangiomas mapped to 22 sites of occurrence, all near lines of mesenchymal or mesenchymal-ectodermal embryonic fusion. The 55 diffuse hemangiomas showed a segmental tissue distribution and thus were designated as frontonasal (15 lesions [27%]), maxillary (19 lesions [35%]), or mandibular (21 lesions [38%]). Ulceration was 3 times more common in patients with diffuse hemangiomas (21 [51%] of 41) than in patients with focal hemangiomas (28 [17%] of 164). Airway obstruction was characteristic of diffuse mandibular hemangiomas. Conclusions: Facial infantile hemangiomas occurred in 2 distinct patterns of tissue involvement: a focal type with a tumorlike appearance and a less common diffuse type with a plaquelike appearance. The diffuse lesions were more likely to be complicated by ulceration or airway obstruction and showed a strikingly segmental distribution pattern. Focal hemangiomas, in contrast, showed a predilection for regions of embryological fusion. C1 Arkansas Childrens Hosp, Dept Pediat Otolaryngol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Otolaryngol Head & Neck Surg, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Regensburg, Dept Dermatol, D-8400 Regensburg, Germany. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Waner, M (reprint author), Arkansas Childrens Hosp, Dept Pediat Otolaryngol, 800 Marshall St, Little Rock, AR 72202 USA. OI Frieden, Ilona/0000-0001-7305-5940 NR 15 TC 125 Z9 131 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2003 VL 139 IS 7 BP 869 EP 875 DI 10.1001/archderm.139.7.869 PG 7 WC Dermatology SC Dermatology GA 700GP UT WOS:000184104500004 PM 12873881 ER PT J AU Fukumoto, H Tennis, M Locascio, JJ Hyman, BT Growdon, JH Irizarry, MC AF Fukumoto, H Tennis, M Locascio, JJ Hyman, BT Growdon, JH Irizarry, MC TI Age but not diagnosis is the main predictor of plasma amyloid beta-protein levels SO ARCHIVES OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE PEDIGREES; CEREBROSPINAL-FLUID LEVELS; APOLIPOPROTEIN-E GENOTYPE; CLINICAL-DIAGNOSIS; DOWN-SYNDROME; MOUSE MODEL; A-BETA; DEMENTIA; PEPTIDE; BRAIN AB Background: Plasma amyloid beta-protein Abeta42 levels are increased in patients with familial Alzheimer disease (AD) mutations, and high levels reportedly identify individuals at risk to develop AD. Objectives: To determine whether there are characteristic changes in plasma Abeta40 and Abeta42 levels in sporadic AD, and to examine the relationship of plasma Abeta measures with clinical, demographic, and genetic variables in a prospectively characterized outpatient clinic population. Patients: A total of 371 outpatients with sporadic AD (n = 146), mild cognitive impairment (n = 37), or Parkinson disease (n = 96) and nondemented control cases (n = 92). Methods: We collected plasma samples and determined Abeta40 and Abeta42 levels by sandwich enzyme-linked immunosorbent assay with the use of the capture antibody BNT77 (anti-Abeta11-28) and the detector anti-bodies horseradish peroxidase-linked BA27 (anti-Abeta40) and BC05 (anti-Abeta42). Results: Mean Abeta40 and Abeta42 levels increased significantly with age in each diagnostic group. When covaried for age, mean plasma levels of Abeta40 and Abeta42 did not differ significantly among the 4 diagnostic groups. Within the mild cognitive impairment and AD groups, Abeta40 and Abeta42 levels did not correlate with duration of memory impairment or with cognitive test scores. The Abeta measures were not influenced by family history of AD, apolipoprotein E genotype, or current medication use of cholinesterase inhibitors, vitamin E, statins, nonsteroidal anti-inflammatory drugs, or estrogen. Conclusions: Plasma Abeta measures increase with age, but, in contrast to reports on familial AD, plasma Abeta measures were neither sensitive nor specific for the clinical diagnosis of mild cognitive impairment or sporadic AD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Alzheimer Dis Res Unit, B114-2010,11416th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG00793] NR 40 TC 171 Z9 177 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2003 VL 60 IS 7 BP 958 EP 964 DI 10.1001/archneur.60.7.958 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 699PH UT WOS:000184064800007 PM 12873852 ER PT J AU Witt, WP Riley, AW Coiro, MJ AF Witt, WP Riley, AW Coiro, MJ TI Childhood functional status, family stressors, and psychosocial adjustment among school-aged children with disabilities in the United States SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PEDIATRIC PHYSICAL DISORDERS; CHRONIC HEALTH CONDITIONS; PSYCHOLOGICAL ADJUSTMENT; CHRONIC ILLNESS; SOCIAL SUPPORT; INDEPENDENCE MEASURE; BEHAVIORAL-PROBLEMS; MENTAL-RETARDATION; RESISTANCE FACTORS; LIVING SYSTEMS AB Background: During the last 30 years, several studies have indicated that children with disabilities are at increased risk for emotional and behavioral morbidity. Population-based studies are needed to understand the relationship between functional status, family stressors, and the psychosocial adjustment of children with disabilities. Methods: Using data from the 1994 and 1995 National Health Interview Surveys, Disability Supplement, this study examines the associations between children's function l status, family stressors, and the psychosocial adjustment of school-aged children with disabilities. Results: Regression analyses indicate that children's functional impairments in the areas of communication or learning, poor maternal health and mental health, family burden, and poverty are significantly and positively associated with psychosocial maladjustment among children with disabilities. Conclusions: Children's functional activity limitations and family stressors are significant correlates of psychosocial adjustment among children with disabilities. These data indicate a need for routine screening for mental health problems among children with disabilities, as well as a family-oriented approach to their medical care. C1 Harvard Univ, Sch Med, Harvard Pediat Hlth Serv, Res Fellowship Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. RP Witt, WP (reprint author), Northwestern Univ, Ctr Healthcare Studies, 676 N St Clair St,Suite 200, Chicago, IL 60611 USA. FU AHRQ HHS [R03 HS11254-01, T32HS00063] NR 79 TC 60 Z9 62 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUL PY 2003 VL 157 IS 7 BP 687 EP 695 DI 10.1001/archpedi.157.7.687 PG 9 WC Pediatrics SC Pediatrics GA 699EZ UT WOS:000184044800014 PM 12860792 ER PT J AU Kelly, PJ Furie, KL Shafqat, S Rallis, N Chang, YC Stein, J AF Kelly, PJ Furie, KL Shafqat, S Rallis, N Chang, YC Stein, J TI Functional recovery following rehabilitation after hemorrhagic and ischemic stroke SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cerebral hemorrhage; rehabilitation; stroke; treatment outcome ID PERTH-COMMUNITY-STROKE; PROGNOSTIC FACTORS; INTRACEREBRAL HEMORRHAGE; INPATIENT REHABILITATION; COPENHAGEN STROKE; SURVIVAL; INFARCTION; HEMATOMAS; SEVERITY AB Objectives: To quantify recovery after rehabilitation therapy and to identify factors that predicted functional outcome in survivors of intracerebral hemorrhage (ICH) compared with cerebral infarction. Design: Retrospective study of consecutive ICH and cerebral infarction admissions to a rehabilitation hospital over a 4-year period. Setting: Free-standing urban rehabilitation hospital. Participants: A total of 1064 cases met the inclusion criteria (545 women, 519 men; 871 with cerebral infarction, 193 with ICH). Interventions: Not applicable. Main Outcome Measures: Functional status was measured using the FIM(TM) instrument, recorded at admission and discharge. Recovery was quantified by the change in FIM total score (DeltaFIM total score). Outcome measures were total discharge FIM score and DeltaFIM total score. Univariate and multivariate analyses were performed. Results: Total admission FIM score was higher in patients with cerebral infarction than in patients with ICH (59 vs 51, P=.0001). No difference in total discharge FIM score was present. Patients with ICH made a significantly greater recovery than those with cerebral infarction (DeltaFIM total score, 28 vs 23.3; P=.002). On multivariate analysis, younger age, longer length of stay, and admission FIM cognitive subscore independently predicted total discharge FIM and DeltaFIM total score. The severity of disability at admission, indicated by total admission FIM score, independently predicted total discharge FIM score, but not DeltaFIM total score. The ICH patients with the most severely disabling strokes had significantly greater recovery than cerebral infarction patients with stroke of similar severity. Conclusions: The patients with ICH had greater functional impairment than the cerebral infarction patients at admission, but made greater gains. Patients with the most severely disabling ICH improved more than those with cerebral infarction of comparable severity. Initial severity of disability, age, and duration of therapy best predicted functional outcome after rehabilitation. C1 Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Stein, J (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. NR 30 TC 83 Z9 85 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JUL PY 2003 VL 84 IS 7 BP 968 EP 972 DI 10.1016/S0003-9993(03)00040-6 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 699PK UT WOS:000184065000005 PM 12881818 ER PT J AU Levin, M AF Levin, M TI Bioelectromagnetics in morphogenesis SO BIOELECTROMAGNETICS LA English DT Review DE electromagnetic fields; embryology; development; regeneration; cancer; ultraweak photons; self-assembly ID APPLIED ELECTRIC-FIELD; ULTRAWEAK PHOTON-EMISSION; WEAK ELECTROMAGNETIC-FIELDS; JUNCTIONAL INTERCELLULAR COMMUNICATION; EMBRYONIC MUSCLE-CELL; STATIC MAGNETIC-FIELD; HUMAN BREAST-CANCER; PARTIAL LIMB REGENERATION; CORNEAL EPITHELIAL-CELLS; LONGIFLORUM POLLEN TUBES AB Understanding the factors that allow biological systems to reliably self-assemble consistent, highly complex, four dimensional patterns on many scales is crucial for the biomedicine of cancer, regeneration, and birth defects. The role of chemical signaling factors in controlling embryonic morphogenesis has been a central focus in modem developmental biology. While the role of tensile forces is also beginning to be appreciated, another major aspect of physics remains largely neglected by molecular embryology: electromagnetic fields and radiations. The continued progress of molecular approaches to understanding biological form and function in the post genome era now requires the merging of genetics with functional understanding of biophysics and physiology in vivo. The literature contains much data hinting at an important role for bioelectromagnetic phenomena as a mediator of morphogenetic information in many contexts relevant to embryonic development. This review attempts to highlight briefly some of the most promising (and often underappreciated) findings that are of high relevance for understanding the biophysical factors mediating morphogenetic signals in biological systems. These data originate from contexts including embryonic development, neoplasm, and regeneration. (C) 2003 Wiley-Liss, Inc. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. NR 423 TC 74 Z9 79 U1 1 U2 18 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PD JUL PY 2003 VL 24 IS 5 BP 295 EP 315 DI 10.1002/bem.10104 PG 21 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA 695EM UT WOS:000183818200001 PM 12820288 ER PT J AU Xu, RH Li, XC AF Xu, RH Li, XC TI A comparison of parametric versus permutation methods with applications to general and temporal microarray gene expression data SO BIOINFORMATICS LA English DT Article AB Motivation: In analyses of microarray data with a design of different biological conditions, ranking genes by their differential 'importance' is often desired so that biologists can focus research on a small subset of genes that are most likely related to the experiment conditions. Permutation methods are often recommended and used, in place of their parametric counterparts, due to the small sample sizes of microarray experiments and possible non-normality of the data. The recommendations, however, are based on classical knowledge in the hypothesis test setting. Results: We explore the relationship between hypothesis testing and gene ranking. We indicate that the permutation method does not provide a metric for the distance between two underlying distributions. In our simulation studies permutation methods tend to be equally or less accurate than parametric methods in ranking genes. This is partially due to the discreteness of the permutation distributions, as well as the non-metric property. In data analysis the variability in ranking genes can be assessed by bootstrap. It turns out that the variability is much lower for permutation than parametric methods, which agrees with the known robustness of permutation methods to individual outliers in the data. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Xu, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 13 TC 23 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUL 1 PY 2003 VL 19 IS 10 BP 1284 EP 1289 DI 10.1093/bioinformatics/btg155 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 701BG UT WOS:000184145200015 PM 12835273 ER PT J AU Wilens, TE Biederman, J Wozniak, J Gunawardene, S Wong, J Monuteaux, M AF Wilens, TE Biederman, J Wozniak, J Gunawardene, S Wong, J Monuteaux, M TI Can adults with attention-deficit/hyperactivity disorder be distinguished from those with comorbid bipolar disorder? Findings from a sample of clinically referred adults SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; ADHD; adults; comorbidity ID DEFICIT HYPERACTIVITY DISORDER; UTAH RATING-SCALE; PSYCHIATRIC COMORBIDITY; CONDUCT DISORDER; JUVENILE MANIA; UNITED-STATES; ADHD CHILDREN; LATENT CLASS; FOLLOW-UP; SYMPTOMS AB Background: Despite data describing the overlap of attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) in youth, little is known about adults with these co-occurring disorders. We now evaluate the clinical characteristics of referred adults with (n = 24) and without BPD (n = 27). Methods: Referred adults to clinical trials of ADHD were evaluated by psychiatric evaluation using DSM-IV criteria. Structured psychiatric interviews were used to systematically assess adult and childhood disorders. Results: The vast majority of patients with ADHD plus BPD had bipolar H disorder (88%). Adults with ADHD plus BPD had higher rates of the combined subtype of ADHD compared to ADHD without BPD (x(2) = 8.7, p =.003), a greater number of DSM-IV ADHD symptoms (14.8 +/- 2.9 and 11.4 +/- 4.0; t = -3.4, p <.01), more attentional symptoms of ADHD (8.1 +/- 1.4 and 6.8 +/- 2.1; t = -2.5, p <.02; trend), poorer global functioning (47 +/- 5.9 and 52 +/- 7.4, t = 2.6, p <.02; trend), and additional comorbid psychiatric disorders (3.7 +/- 2.5 and 2.0 +/- 1.9; t = -2.9, p <.01). Conclusions: These results suggest that adults with ADHD plus BPD have prototypic symptoms of both disorders, suggesting that both disorders are present and are distinguishable clinically. Biol Psychiatry 2003;54: 1-8 (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Pediat Psychopharmacol Clin, Sch Med, Massachusetts Gen Hosp,Clin Res Program Pediat Ps, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Pediat Psychopharmacol Clin, Sch Med, Massachusetts Gen Hosp,Clin Res Program Pediat Ps, 15 Parkman St,ACC 725, Boston, MA 02114 USA. FU NIDA NIH HHS [R01 DA12945] NR 50 TC 58 Z9 61 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2003 VL 54 IS 1 BP 1 EP 8 DI 10.1016/S0006-3223(03)01666-9 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 696BT UT WOS:000183866000001 PM 12842302 ER PT J AU Wilens, TE Prince, JB Spencer, T Van Patten, SL Doyle, R Girard, K Hammerness, P Goldman, S Brown, S Biederman, J AF Wilens, TE Prince, JB Spencer, T Van Patten, SL Doyle, R Girard, K Hammerness, P Goldman, S Brown, S Biederman, J TI An open trial of bupropion for the treatment of adults with attention-deficit/hyperactivity disorder and bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 155th Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Psychiat Assoc DE ADHD; pharmacotherapy; adults; bipolar disorder ID DEFICIT HYPERACTIVITY DISORDER; CONTROLLED CLINICAL-TRIAL; DOUBLE-BLIND TRIAL; UTAH RATING-SCALE; PREPUBERTAL CHILDREN; ADHD CHILDREN; II PATIENTS; DEPRESSION; ONSET; METHYLPHENIDATE AB Background: Despite the increasing recognition of co-morbid attention-deficit/hyperactivity disorder (ADHD), and bipolar disorder (BPD) in adults, there are no prospective trials of pharmacological agents to treat ADHD in these patients. Given the efficacy of bupropion for ADHD in adults, as well as its use in the management of bipolar depression, we studied the tolerability and efficacy of sustained-release (SR) bupropion in adults with ADHD plus BPD. Methods: This was an open, prospective, 6-week trial of bupropion SR (up to 200 mg b.i.d.) in adults with DSM-IV ADHD plus historical bipolar I disorder (BPD I) (10%) or bipolar II disorder (BPD II) (90%). Adults receiving adjunct antimanic agents (mood stabilizers and antipsychotics) at baseline were included in the study. We used standardized psychiatric instruments for diagnosis and outcome. Efficacy was based primarily on the Clinical Global Impression Scale (CGI) for ADHD and the ADHD symptom checklist. Results: Of 36 patients entered (75% male, mean age 34 years), 30 patients (83%) completed the protocol. At end point (last observation carried forward [LOCF]) compared to baseline, treatment with bupropion SR resulted in significant reductions in the ADHD symptom checklist (-55%, z = 5.63, p <.001) and CGI severity of ADHD (-40%, z = 6.285, p <.001). Bupropion was associated with reductions in ratings of mania and depression. Conclusions: The results from this open study of adults with ADHD plus BPD suggest that sustained-release bupropion may be effective in treating ADHD in the context of a lifetime diagnosis of BPD, without significant activation of mania. Further controlled trials are warranted. Biol Psychiatry 2003;54:9-16 (C) 2003 Society of Biological Psychiatry. C1 Harvard Univ, Pediat Psychopharmacol Clin, Massachusetts Gen Hosp, Sch Med,Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Pediat Psychopharmacol Clin, Massachusetts Gen Hosp, Sch Med,Clin Res Program Pediat Psychopharmacol, 15 Parkman St,ACC 725, Boston, MA 02114 USA. FU NIDA NIH HHS [R01 DA12945] NR 65 TC 43 Z9 45 U1 2 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 JUL 1 PY 2003 VL 54 IS 1 BP 9 EP 16 DI 10.1016/S0006-3223(03)01664-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 696BT UT WOS:000183866000002 PM 12842303 ER PT J AU Doney, K Hagglund, H Leisenring, W Chauncey, T Appelbaum, FR Storb, R AF Doney, K Hagglund, H Leisenring, W Chauncey, T Appelbaum, FR Storb, R TI Predictive factors for outcome of allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE acute lymphoblastic leukemia; hematopoietic cell transplantation; adults; Philadelphia chromosome ID BONE-MARROW-TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; HOST-DISEASE; CYTOGENETIC ABNORMALITIES; FOLLOW-UP; REMISSION; CANCER; IMMUNOPHENOTYPE; CHEMOTHERAPY; SURVIVAL AB Between January 1990 and December 1997, 182 adults with acute lymphoblastic leukemia (ALL) received allogeneic hematopoietic cell transplants according to Fred Hutchinson Cancer Research Center protocols. Patients eligible for transplantation included those in first remission, especially those at high risk of relapse (n = 41), and any patient in second or later remissions (n = 46) or in relapse (n = 95). The median patient age was 29.4 years (range, 18.0-57.6 years), and the median duration of disease was 13.3 months (range, 2.4-221.9 months). Fifty-six patients had Philadelphia chromosome-positive ALL. Most patients (n = 169) received a conditioning regimen of cyclophosphamide 120 mg/kg plus 12.0 to 15.75 Gy of total body irradiation and a combination of cyclosporine and methotrexate as graft-versus-host disease (GVHD) prophylaxis. One hundred twenty-one patients received stem cells from HLA-identical donors (88 related donors and 33 unrelated donors), and 61 received stem cells from HLA-mismatched donors (26 related donors and 35 unrelated donors). Actuarial disease-free survival at 5 years was 21% for all patients, 43% for patients in first remission, 24% for patients in second or later remissions, and 9% for patients in relapse. Univariate and multivariate Cox regression analyses were performed to identify factors associated with survival, relapse, nonrelapse mortality, and disease-free survival. Factors significantly associated (P <.01) with improved survival and disease-free survival included younger age and being in first remission. Lower disease-free survival was associated with receiving cyclosporine alone as GVHD prophylaxis (P <.01). Risk of relapse correlated only with disease status at transplantation: patients who underwent transplantation in relapse had a 9-fold increased risk compared with patients who underwent transplantation in first remission. Acute or chronic GVHD had no significant effect on relapse. Increased nonrelapse mortality was associated with HLA-mismatched donors, a positive cytomegalovirus serology before transplantation, and GVHD prophylaxis with only cyclosporine. Patients with Philadelphia chromosome-positive ALL had survival and relapse rates similar to patients with normal cytogenetics. (C) 2003 American Society fir Blood and Marrow Transplantation. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Med Ctr, Seattle, WA 98109 USA. Huddinge Univ Hosp, Stockholm, Sweden. Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Doney, K (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Med Ctr, 1100 Fairview Ave N,D5-280,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [CA 18029, CA 15704, CA 18221] NR 34 TC 46 Z9 51 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2003 VL 9 IS 7 BP 472 EP 481 DI 10.1016/S1083-8791(03)00149-6 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 708AR UT WOS:000184544600007 PM 12869961 ER PT J AU Sethi, RK Neavyn, MJ Rubash, HE Shanbhag, AS AF Sethi, RK Neavyn, MJ Rubash, HE Shanbhag, AS TI Macrophage response to cross-linked and conventional UHMWPE SO BIOMATERIALS LA English DT Article DE cross-linked UHMWPE; total joint replacement; inflammation; macrophages; cytokines ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP REPLACEMENTS; TUMOR-NECROSIS-FACTOR; OSTEOBLAST-LIKE CELLS; TITANIUM SURFACE-ROUGHNESS; VANADIUM ALLOY PARTICLES; GENERATED IN-VIVO; OSTEOCLAST DIFFERENTIATION; WEAR PARTICLES; HUMAN MONOCYTES AB To prevent wear debris-induced osteolysis and aseptic loosening, cross-linked ultra-high molecular weight polyethylene's (UHMWPE) with improved wear resistance have been developed. Hip simulator studies have demonstrated very low wear rates with these new materials leading to their widespread clinical use. However, the biocompatibility of this material is not known. We studied the macrophage response to cross-linked UHMWPE (XLPE) and compared it to conventional UHMWPE (CPE) as well as other clinically used orthopaedic materials such as titanium-alloy (TiAlV) and cobalt-chrome alloy (CoCr). Human peripheral blood monocytes and murine macrophages, as surrogates for cells mediating peri-implant inflammation, were cultured onto custom designed lipped disks fabricated from the test materials to isolate cells. Culture supernatants were collected at 24 and 48 h and analyzed for cytokines such as IL-1alpha, IL-1beta, TNF-alpha and IL-6. Total RNA was extracted from adherent cells and gene expression was analyzed using qualitative RT-PCR. In both in vitro models, macrophages cultured on cross-linked and conventional polyethylene released similar levels of cytokines, which were also similar to levels on control tissue culture dishes. Macrophages cultured on TiAlV and CoCr-alloy released significantly higher levels of cytokines. Human monocytes from all donors varied in the magnitude of cytokines released when cultured on identical surfaces. The variability in individual donor responses to TiAlV and CoCr surfaces may reflect how individuals respond differently to similar stimuli and perhaps reveal a predisposed sensitivity to particular materials. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Biomat Lab, Boston, MA 02114 USA. RP Shanbhag, AS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Biomat Lab, GRJ 1115 55 Fruit St, Boston, MA 02114 USA. NR 98 TC 57 Z9 59 U1 1 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUL PY 2003 VL 24 IS 15 BP 2561 EP 2573 DI 10.1016/S0142-9612(03)00056-5 PG 13 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 677DD UT WOS:000182790900001 PM 12726710 ER PT J AU Lees, S AF Lees, S TI Mineralization of type I collagen SO BIOPHYSICAL JOURNAL LA English DT Article ID TURKEY LEG TENDON; VOLTAGE ELECTRON-MICROSCOPY; GENERALIZED PACKING MODEL; X-RAY-DIFFRACTION; TISSUES; BONE AB It was previously found that the lateral spacing of the collagen molecules in wet mineralized tissues is exactly proportional to the inverse wet density. Several properties were investigated and the same type of relationship was observed each time. A possible explanation is offered. It is hypothesized that mineral is deposited initially in the extrafibrillar space so as to isolate the fibrils. Further deposition reduces the net free fibril volume thereby decreasing the spacing between collagen molecules. The linear relationship is derived from density considerations together with limitations on the collagen packing structure described as the generalized packing model. Three experimental situations were studied: lateral spacing wet tissue versus density; lateral spacing dry tissue versus density; and lateral spacing versus water content. The observed variations of the spacing can be attributed to a structure where the mass of the tissue remains constant but the volume decreases linearly with increasing mineral content. C1 Forsyth Inst, Boston, MA 02115 USA. RP Lees, S (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. NR 15 TC 35 Z9 36 U1 0 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2003 VL 85 IS 1 BP 204 EP 207 PG 4 WC Biophysics SC Biophysics GA 695FN UT WOS:000183820600019 PM 12829476 ER PT J AU Davidov, O Zelen, M AF Davidov, O Zelen, M TI The theory of case-control studies for early detection programs SO BIOSTATISTICS LA English DT Article DE case-control studies; early detection programs; odds ratio; screening ID NATURAL-HISTORY; LEAD TIME; SCREENING DATA; CANCER; BIAS; DISEASE; PREVENTION; TRIALS; STATE AB Although case-control studies are widely used for evaluating the benefit of early detection programs I the theoretical basis underlying this application has not been well developed. In this paper the properties of chronic disease case-control studies for evaluating early detection programs are investigated. An idealized case-control study is analyzed and the theoretical expression for the odds ratio associated with the benefit of screening is derived. The odds ratio is related to the natural history of disease and the screening program. Our results indicate that case-control studies result in odds ratios that are surprisingly close to unity and consequently have low power. C1 Univ Haifa, Dept Stat, IL-31905 Haifa, Israel. Harvard Univ, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Davidov, O (reprint author), Univ Haifa, Dept Stat, Mt Carmel, IL-31905 Haifa, Israel. FU NCI NIH HHS [CA-78607] NR 31 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2003 VL 4 IS 3 BP 411 EP 421 DI 10.1093/biostatistics/4.3.411 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 700EZ UT WOS:000184100800008 PM 12925508 ER PT J AU D'Andrea, A AF D'Andrea, A TI New insights from Fanconi anemia SO BLOOD LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP D'Andrea, A (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 JUL 1 PY 2003 VL 102 IS 1 BP 1 EP 1 DI 10.1182/blood-2003-05-1447 PG 1 WC Hematology SC Hematology GA 695FK UT WOS:000183820300001 ER PT J AU Xia, YP Li, BS Hylton, D Detmar, M Yancopoulos, GD Rudge, JS AF Xia, YP Li, BS Hylton, D Detmar, M Yancopoulos, GD Rudge, JS TI Transgenic delivery of VEGF to mouse skin leads to an inflammatory condition resembling human psoriasis SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; TUMOR-NECROSIS-FACTOR; SOLUBLE E-SELECTIN; DISEASE-ACTIVITY; OVEREXPRESSING ANGIOPOIETIN-1; RHEUMATOID-ARTHRITIS; RECEPTOR FLT-1; NUCLEAR-FACTOR; MICE AB Gene therapy approaches involving vascular endothelial growth factor (VEGF) to promote therapeutic angiogenesis are under consideration for conditions ranging from ischemic heart disease to nonhealing skin ulcers. Here we make the surprising observation that the transgenic delivery of VEGF to the skin results in a profound inflammatory skin condition with many of the cellular and molecular features of psoriasis, including the characteristic vascular changes, epidermal alterations, and inflammatory infiltrates. Even longstanding psoriatic disease remains dependent on the transgenic VEGF in this model because it can be effectively reversed by the addition of VEGF Trap, a potent VEGF antagonist. Previous attempts to faithfully replicate the psoriatic phenotype through the transgenic delivery of epidermal keratinocyte growth factors or inflammatory mediators generated phenotypes with only partial resemblance to human psoriasis, leaving unanswered questions about the etiology of this disease. The ability of transgenic VEGF to induce a psoriasiform phenotype suggests a new etiology and treatment approach for this disease and further substantiates emerging concerns about possible proinflammatory adverse effects that might be associated with therapeutic attempts to deliver VEGF. (C) 2003 by The American Society of Hematology. C1 Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Xia, YP (reprint author), Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA. FU NCI NIH HHS [CA 69184, CA 86410] NR 56 TC 211 Z9 236 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2003 VL 102 IS 1 BP 161 EP 168 DI 10.1182/blood-2002-12-3793 PG 8 WC Hematology SC Hematology GA 695FK UT WOS:000183820300032 PM 12649136 ER PT J AU Ferrando, AA Armstrong, SA Neuberg, DS Sallan, SE Silverman, LB Korsmeyer, SJ Look, AT AF Ferrando, AA Armstrong, SA Neuberg, DS Sallan, SE Silverman, LB Korsmeyer, SJ Look, AT TI Gene expression signatures in MLL-rearranged T-lineage and B-precursor acute leukemias: dominance of HOX dysregulation SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BONE-MARROW-CELLS; UNIQUE LEUKEMIA; POOR-PROGNOSIS; FETAL LIVER; FUSION; THYMOCYTES; DIFFERENTIATION; LEUKEMOGENESIS AB Rearrangements of the MLL locus, located on human chromosome 11q23, are frequent in both infant and therapy-related leukemias..Gene expression analysis of MLL-rearranged B-precursor acute lymphoblastic leukemias (MLL B-ALLs) has identified these cases as a unique subtype of leukemia, characterized by the expression of genes associated with both lymphoid and myeloid hematopoietic lineages. Here we show that MLL fusions also generate a distinct genetic subtype of T-lineage ALL (MLL T-ALL), in which leukemic cells are characterized by an early arrest in thymocyte differentiation, with suggestive evidence of commitment to the gammadelta lineage. Interestingly, multiple genes linked to cell proliferation (eg, PCNA, MYC, CDK2, and POLA) were down-regulated in MLL-fusion samples, relative to those transformed by other T-ALL oncogenes (P < .000 001, Fisher exact test). Overall, MLL T-ALL cases consistently demonstrated increased levels of expression of a subset of major HOX genes-HOXA9, HOXA10, and HOXC6-and the MEIS1 HOX coregulator (P < .008, one-sided Wilcoxon test), a pattern of gene expression that was reiterated in MLL B-ALLS. However, expression of myeloid lineage genes, previously reported in MLL B-ALLs, was not identified in T-lineage cases with this abnormality, suggesting that myeloid gene dysregulation is dispensable in leukemic transformation mediated by MLL fusion proteins. Our findings implicate dysregulation of HOX gene family members as a dominant mechanism of leukemic transformation induced by chimeric MLL oncogenes. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Dept Biostat Sci Canc Immunol & AIDS, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dept Biostat Sci Canc Immunol & AIDS, 44 Binney St,Mayer 630, Boston, MA 02115 USA. FU NCI NIH HHS [CA 21765, CA 68484, CA 92551] NR 52 TC 202 Z9 202 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2003 VL 102 IS 1 BP 262 EP 268 DI 10.1182/blood-2002-10-3221 PG 7 WC Hematology SC Hematology GA 695FK UT WOS:000183820300045 PM 12637319 ER PT J AU Sattler, M Quinnan, LR Pride, YB Gramlich, JL Chu, SC Even, GC Kraeft, SK Chen, LB Salgia, R AF Sattler, M Quinnan, LR Pride, YB Gramlich, JL Chu, SC Even, GC Kraeft, SK Chen, LB Salgia, R TI 2-methoxyestradiol alters cell motility, migration, and adhesion SO BLOOD LA English DT Article ID ENDOGENOUS MAMMALIAN METABOLITE; INHIBITS TUBULIN POLYMERIZATION; ABL-RELATED GENE; TYROSINE KINASE; ESTROGEN METABOLITE; MYELOID-LEUKEMIA; SIGNAL-TRANSDUCTION; HYDROGEN-PEROXIDE; TUMOR-GROWTH; FUSION AB The effect of 2-methoxyestradiol, 2ME2, an endogenous metabolite of 17beta-estradiol (E2), on cell growth and cytoskeletal functions in a BCR-ABL-transformed cell line model was investigated. We determined the interaction of 2ME2 with ST1571 (Gleevec, imatinib mesylate) in ST1571 drug-sensitive and -resistant cell lines. In cells expressing BCR-ABL, ST1571 cooperated with 2ME2 in reducing cell growth, and ST1571 -resistant cells were sensitive to 2ME2 treatment. 2ME2 also inhibited growth of several cancer cell lines by a mechanism independent of BCR-ABL. BCR-ABL transformation leads to altered motility, increased adhesion, and spontaneous migration in different in vitro model systems. 2ME2 was found to specifically inhibit the spontaneous motility of BCR-ABL-transformed Ba/F3 cells and to change the morphology and volume of treated cells. Cells attached to fibronectin-coated surfaces showed a reduced number of filipodia and lamellipodia. In addition, 2ME2 significantly reduced BCR-ABL-mediated adhesion to fibronectin. The spontaneous migration of BCR-ABL-transformed cells through a transwell membrane also was found to be significantly decreased by 2ME2. Cytoskeletal changes were accompanied by alteration of tubulin formation, distinct from paciltaxel treatment. These results demonstrate that 2ME2 treatment of transformed cells strongly reduces cytoskeletal functions and may also be useful for the treatment of cancers with high metastatic potential. Combination of 2ME2 with other anticancer drugs may be beneficial to treatment of drug-resistant cancers. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 53 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2003 VL 102 IS 1 BP 289 EP 296 DI 10.1182/blood-2002-03-0729 PG 8 WC Hematology SC Hematology GA 695FK UT WOS:000183820300049 PM 12637335 ER PT J AU Turner, J Holmes, M Czolij, R Gaensler, K Yang, HD Fujiwara, Y Chong, B Koh, P Perkins, A Orkin, S Crossley, M AF Turner, J Holmes, M Czolij, R Gaensler, K Yang, HD Fujiwara, Y Chong, B Koh, P Perkins, A Orkin, S Crossley, M TI Basic Kruppel-like factor recruits multiple co-repressors to silence gene expression. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 13th Conference on Hemoglobin Switching CY SEP 26-30, 2002 CL OXFORD, ENGLAND C1 Univ Sydney, Sch Mol & Microbial Biosci, Sydney, NSW 2006, Australia. Univ New S Wales, Sch Pathol, Ctr Thrombosis & Vasc Res, Sydney, NSW 2052, Australia. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Monash Univ, Dept Physiol, Clayton, Vic 3800, Australia. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Crossley, Maxwell/C-5285-2014; Perkins, Andrew/M-3216-2014 OI Crossley, Maxwell/0000-0001-9851-033X; Perkins, Andrew/0000-0003-3644-7093 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2003 VL 31 IS 1 BP 135 EP 136 PG 2 WC Hematology SC Hematology GA 700FF UT WOS:000184101400050 ER PT J AU Mahajan, NC Narlikar, G Boyapaty, G Weissman, SM AF Mahajan, NC Narlikar, G Boyapaty, G Weissman, SM TI Purification of SWI/SNF like chromatin remodeling activity of beta globin LCR by DNA-affinity chromatography. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 13th Conference on Hemoglobin Switching CY SEP 26-30, 2002 CL OXFORD, ENGLAND C1 Yale Univ, Sch Med, Boyer Ctr Mol Med, New Haven, CT 06510 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2003 VL 31 IS 1 BP 154 EP 155 PG 2 WC Hematology SC Hematology GA 700FF UT WOS:000184101400110 ER PT J AU Orkin, SH AF Orkin, SH TI Transcriptional control of erythroid development. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 13th Conference on Hemoglobin Switching CY SEP 26-30, 2002 CL OXFORD, ENGLAND C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2003 VL 31 IS 1 BP 157 EP 157 PG 1 WC Hematology SC Hematology GA 700FF UT WOS:000184101400121 ER PT J AU Tufarelli, C Stanley, JAS Garrick, D Sharpe, JA Ayyub, H Chen, TP Li, E Wood, WG Higgs, DR AF Tufarelli, C Stanley, JAS Garrick, D Sharpe, JA Ayyub, H Chen, TP Li, E Wood, WG Higgs, DR TI RNA mediated silencing and methylation of a non imprinted autosomal gene. SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 13th Conference on Hemoglobin Switching CY SEP 26-30, 2002 CL OXFORD, ENGLAND C1 MRC, Mol Haematol Unit, WIMM, Oxford, England. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD JUL-AUG PY 2003 VL 31 IS 1 BP 167 EP 167 PG 1 WC Hematology SC Hematology GA 700FF UT WOS:000184101400154 ER PT J AU Wraga, M Thompson, WL Alpert, NM Kosslyn, SM AF Wraga, M Thompson, WL Alpert, NM Kosslyn, SM TI Implicit transfer of motor strategies in mental rotation SO BRAIN AND COGNITION LA English DT Article DE mental imagery; mental rotation; motor learning; PET ID POSITRON-EMISSION-TOMOGRAPHY; NEURAL MECHANISMS; CORTICAL ACTIVITY; TRANSFORMATIONS; PET; OBJECTS; REPRESENTATIONS; STIMULATION; ACTIVATION; IMAGERY AB Recent research indicates that motor areas are activated in some types of mental rotation. Many of these studies have required participants to perform egocentric transformations of body parts or whole bodies; however, motor activation also has been found with nonbody objects when participants explicitly relate the objects to their hands. The current study used positron emission tomography (PET) to examine whether such egocentric motor strategies can be transferred implicitly from one type of mental rotation to another. Two groups of participants were tested. In the Hand-Object group, participants performed imaginal rotations of pictures of hands; following this, they then made similar judgments of pictures of Shepard-Metzler objects. The Object-Object group performed the rotation task for two sets of Shepard-Metzler objects only. When the second condition in each group (which always required rotating Shepard-Metzler objects) was compared, motor areas (Area 6 and M I) were found to be activated only in the Hand-Object group. These findings suggest that motor strategies can be covertly transferred to imaginal transformations of nonbody objects. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Smith Coll, Dept Psychol, Northampton, MA 01063 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wraga, M (reprint author), Smith Coll, Dept Psychol, Northampton, MA 01063 USA. FU NIMH NIH HHS [MH60734-01] NR 34 TC 78 Z9 83 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD JUL PY 2003 VL 52 IS 2 BP 135 EP 143 DI 10.1016/S0278-2626(03)00033-2 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 696TF UT WOS:000183902800001 PM 12821095 ER PT J AU Thannickal, TC Siegel, JM Nienhuis, R Moore, RY AF Thannickal, TC Siegel, JM Nienhuis, R Moore, RY TI Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy SO BRAIN PATHOLOGY LA English DT Article ID HISTAMINE-CONTAINING NEURONS; RAT-BRAIN; LOCUS-COERULEUS; MUSCLE TONE; HYPOTHALAMUS; RECEPTOR; PEPTIDES; WAKEFULNESS; CATAPLEXY; MUTATION AB Human narcolepsy is correlated with a greatly reduced number of hypocretin (orexin) containing neurons and axons, and an elevated level of hypothalamic gliosis. We now report that the percentage loss of Hcrt cells and percentage elevation of GFAP staining are variable across forebrain and brain-stem nuclei, and are maximal in the posterior and tuberomammillary hypothalamic region. Regional gliosis and percent loss of hypocretin axons in narcoleptics are not correlated with regional hypocretin cell soma density in normals or with regional percent soma loss in narcoleptics. Rather they are independently and strongly correlated with the regional density of hypocretin axons and the message density for hypocretin receptor 2, as quantified in the rat. These results are consistent with the hypotheses that the loss of hypocretin function in narcolepsy results from a cytotoxic or immunologically mediated attack focused on hypocretin receptor 2 or an antigen anatomically linked to hypocretin receptor 2, and that this process is intensified in regions of high axonal density. C1 Univ Calif Los Angeles, Dept Psychiat, North Hills, CA 91343 USA. VA Greater Los Angeles Healthcare Syst, Neurobiol Res, North Hills, CA 91343 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, North Hills, CA 91343 USA. EM jsiegel@ucla.edu FU NHLBI NIH HHS [HL41370]; NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610] NR 54 TC 77 Z9 80 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JUL PY 2003 VL 13 IS 3 BP 340 EP 351 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 744EC UT WOS:000186614100010 PM 12946023 ER PT J AU Chou, RC Langan, TJ AF Chou, RC Langan, TJ TI In vitro synchronization of mammalian astrocytic cultures by serum deprivation SO BRAIN RESEARCH PROTOCOLS LA English DT Article DE astrocyte; cell cycle; glioma; synchronization; serum deprivation ID CELL-CYCLE SYNCHRONIZATION; HELA CELLS; PROLIFERATION; INHIBITOR; DIVISION; DENSITY; GROWTH; ADULT; FETAL; G1 AB The study of the regulation of cell division cycle in vitro requires cell cultures growing in the same phase of the cycle. The procedure by which cells are arrested in specific phases of the cell cycle is termed synchronization. Synchronization is particularly important in the study of astrocyte biology, as its application allows astrocytes to re-enter the cell cycle from a state of quiescence (G(0)), and, under carefully defined experimental conditions, move together into subsequent phases such as the G(1) and S phases. A number of methods have been established to synchronize mammalian cell cultures, including centrifugal elutriation, mitotic shake-off, and chemically induced cell cycle arrest. Yet there are intrinsic limitations associated with these methods. In the present protocol, we describe a simple, reliable, and reversible procedure to synchronize astrocytic cultures from newborn rat brains by serum deprivation. This protocol consists essentially of two parts: (I) proliferation of astrocytes under optimal conditions in vitro until reaching desired confluence; and (2) synchronization of cultures by serum down-shift and arrested in the G(0) phase of the cell cycle. This procedure has recently been extended toward the study of cell cycle control in astroglioma cells and astrocytes from injured adult brains. Since it was also employed in recent precursor cloning studies in developmental biology, this procedure will certainly find increasing use in future research. (C) 2003 Elsevier Science B.V. All rights reserved. C1 SUNY Buffalo, Dept Neurol, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Pediat, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. SUNY Buffalo, Dept Physiol & Biophys, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. RP Chou, RC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Div Rheumatol Allergy & Clin Immunol, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. NR 26 TC 17 Z9 23 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1385-299X J9 BRAIN RES PROTOC JI Brain Res. Protoc. PD JUL PY 2003 VL 11 IS 3 BP 162 EP 167 DI 10.1016/S1385-299X(03)00043-6 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 704HK UT WOS:000184333800003 PM 12842221 ER PT J AU Strauss, SJ Liu, W Maharaj, L Shringarpure, R Anderson, C Schenkein, D Lister, TA Joel, SP AF Strauss, SJ Liu, W Maharaj, L Shringarpure, R Anderson, C Schenkein, D Lister, TA Joel, SP TI The effect of proteasome inhibition with bortezomib(Velcade (TM)) in B cell lymphoma cell lines SO BRITISH JOURNAL OF CANCER LA English DT Meeting Abstract CT British Cancer Research Meeting 2003 CY JUL 02-05, 2003 CL BOURNEMOUTH, ENGLAND C1 St Bartholomews Hosp, Dept Med Oncol, London, England. Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Millennium Pharmaceut, Boston, MA USA. RI Liu, Wai/B-7877-2008 OI Liu, Wai/0000-0001-7099-7510 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 2003 VL 88 SU 1 BP S65 EP S65 PG 1 WC Oncology SC Oncology GA 699ED UT WOS:000184042200251 ER PT J AU Radin, AI Kim, HT Grant, BW Bennett, JM Kirkwood, JM Stewart, JA Hahn, RG Dutcher, JP Wiernik, PH Oken, MM AF Radin, AI Kim, HT Grant, BW Bennett, JM Kirkwood, JM Stewart, JA Hahn, RG Dutcher, JP Wiernik, PH Oken, MM TI Phase II study of alpha 2 interferon in the treatment of the chronic myeloproliferative disorders (E5487) - A trial of the eastern cooperative oncology group SO CANCER LA English DT Article DE myeloproliterative disease; essential thrombocythemia; polycythemia rubra vera; agnogenic myeloid metaplasia; myelofibrosis; interferon ID CHRONIC MYELOGENOUS LEUKEMIA; HAIRY-CELL LEUKEMIA; HUMAN-LEUKOCYTE INTERFERON; LONG-TERM TREATMENT; ESSENTIAL THROMBOCYTHEMIA; ALPHA-INTERFERON; POLYCYTHEMIA-VERA; BONE-MARROW; MYELOID METAPLASIA; HUMAN-FIBROBLASTS AB BACKGROUND. in vitro and clinical data suggest a therapeutic role for alpha2 interferon (IFN) in the treatment of the chronic myeloproliferative disorders. Accordingly, a multiinstitutional, Phase II trial of IFN in patients with agnogenic myeloid metaplasia (AMM), essential thrombocythernia (ET), and polycythemia rubra vera (PRV) in the spent phase was initiated. The objectives of this study were 1) to investigate the response rates that may be achieved with IFN in the treatment of patients with these disorders, 2) to estimate the durability of the responses, and 3) to assess the toxicities of IFN in these populations. METHODS. Enrollment was limited to patients with AMM, ET, or PRV who already had developed 1) anemia or transfusion dependency, 2) thrombocytosis uncontrolled by standard therapy, 3) hemostatic complications, or 4) symptomatic splenomegaly. Initially, patients were started on IFN at a dose of 5 MU/m(2) per day as a subcutaneous injection. After the first 16 patients had been treated, the starting dose of IFN was reduced to 2 MU/m(2) per day because of unexpected toxicities. RESULTS. IFN demonstrated different levels of efficacy and toxicity in each of the three diseases studied. The overall response rates achieved among the evaluable patients in each category were as follows: ET, 88.2% (n = 17 patients; 1 complete response and 14 partial responses); PRV, 41.7% (n = 12 patients; I complete response and 4 partial responses); and AMM, 3.2% (n 31 patients; 0 complete responses and I partial response). Thrombocytosis and leukocytosis were controlled in nearly all patients, with reversal of splenomegaly and resorption of myelofibrosis achieved in fewer patients. The toxicities attributed to IFN differed notably among the three disease groups: patients who had AMM suffered systemic and neurologic toxicities more frequently than patients who had PRV or ET; whereas patients who had ET experienced a greater than expected incidence of most typically transient elevations of serum amino acid hepatic abnormalities, transaminase levels. CONCLUSIONS. The current study demonstrated the safety and efficacy of IFN in patients with ET, PRV, and AMM. Objective responses and/or disease stabilization were obtained in patients with all three disease entities, including the reversal of splenomegaly and resorption of myelofibrosis in some patients. Cancer 2003;98: 100-9. (C) 2003 American Cancer Society. C1 Cornell Univ, Med Ctr, Div Hematol Oncol, Dept Internal Med, New York, NY 10021 USA. Dana Farber Canc Inst, Dept BIostat Sci, Boston, MA 02115 USA. Univ Vermont, Vermont Reg Canc Ctr, Div Hematol, Dept Med, Burlington, VT 05401 USA. Univ Rochester, Ctr Canc, Div Pathol & Lab Med, Rochester, NY USA. Univ Pittsburgh, Dept Med, Div Med Oncol, Pittsburgh, PA 15260 USA. Univ Wisconsin, Sect Med Oncol, Madison, WI 53706 USA. Mayo Clin & Mayo Fdn, Dept Med, Rochester, MN 55905 USA. Our Lady Mercy Med Ctr, Dept Med, Div Med Oncol, New York, NY USA. Virginia Piper Canc Inst, Div Hematol Oncol, Dept Med, Minneapolis, MN USA. RP Radin, AI (reprint author), 41 5th Ave, New York, NY 10003 USA. FU NCI NIH HHS [CA21115, CA11083, CA13650, CA16116, CA20176, CA23318, CA66636] NR 59 TC 28 Z9 29 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2003 VL 98 IS 1 BP 100 EP 109 DI 10.1002/cncr.11486 PG 10 WC Oncology SC Oncology GA 692QE UT WOS:000183671100015 PM 12833462 ER PT J AU Huang, CI Neuberg, D Johnson, BE Wei, JY Christiani, DC AF Huang, CI Neuberg, D Johnson, BE Wei, JY Christiani, DC TI Expression of bcl-2 protein is associated with shorter survival in nonsmall cell lung carcinoma SO CANCER LA English DT Article DE nonsmall cell lung carcinoma (NSCLC); lung cancer; bcl-2; uninvolved lung; Western blot; survival ID MITOCHONDRIAL-MEMBRANES; ENDOPLASMIC-RETICULUM; PROGNOSTIC VALUE; CANCER CELLS; APOPTOSIS; P53; LOCALIZATION; DEATH; PROGRESSION; ONCOPROTEIN AB BACKGROUND. The aim of this study was to assess the relationship between the expression of the 27-kilodalton (kD) bcl-2 protein and survival among nonsmall cell lung carcinoma (NSCLC) patients. METHODS. Paired tissue samples of histologically confirmed tumor and uninvolved lung of 91 randomly selected NSCLC patients were used in this study. The expression of 27-kD bcl-2 proteins in uninvolved lung and tumor tissue specimens was analyzed using Western blot analysis. Overall survival was estimated using the Kaplan-Meier method. The relation between patient survival and expression of the 27-kD bcl-2 protein in uninvolved lung, tumor, and in uninvolved lung and/or tumor tissue specimens was assessed using log-rank tests and Cox proportional hazards multiple regression. RESULTS. The 27-kD bcl-2 protein was expressed in 54% of the uninvolved lung tissue specimens, in 53% of the tumor tissue specimens, and in 70% of the uninvolved lung and/or tumor tissue specimens. When NSCLC patient survival was considered with respect to the expression of the 27-kD bcl-2 protein, a statistically significant shorter survival was observed for patients whose tissue samples expressed the 27-kD bcl-2 protein in the uninvolved lung and in the uninvolved lung and/or tumor (log-rank test, P = 0.008 and P = 0.001, respectively). Cox proportional hazards multiple regression models also showed statistically significant associations between shorter survival and positive 27-kD protein expression in the uninvolved lung (hazard ratio of 2.27; P = 0.05) and in the uninvolved lung and/or tumor (hazard ratio of 5.58, P = 0.008) after controlling for tumor size, stage, the type of surgery received, smoking status, age, and cell type. CONCLUSIONS. In the current study, patients with nonsmall cell lung carcinoma with positive expression of the 27-kD protein bcl-2, either in the uninvolved lung or in uninvolved lung and/or tumor, were found to have significantly poorer postresection survival. Cancer 2003;98:135-43. (C) 2003 American Cancer Society. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Arkansas Med Sci, Dept Geriatr, Reynolds Ctr Aging, Little Rock, AR 72205 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Bldg 1,Room 1407, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74386]; NIEHS NIH HHS [ES 00002, T32 ES 07069] NR 45 TC 7 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2003 VL 98 IS 1 BP 135 EP 143 DI 10.1002/cncr.11461 PG 9 WC Oncology SC Oncology GA 692QE UT WOS:000183671100019 PM 12833466 ER PT J AU Kufe, D Weichselbaum, R AF Kufe, D Weichselbaum, R TI Radiation therapy - Activation of gene transcription and the development of genetic radiotherapy - Therapeutic strategies in oncology SO CANCER BIOLOGY & THERAPY LA English DT Review DE ionizing radiation; gene transcription; EGR-1; TNF-alpha; gene therapy; adenovector; genetic radiotherapy ID TUMOR-NECROSIS-FACTOR; IONIZING-RADIATION; FACTOR-ALPHA; EGR-1 PROMOTER; INDUCIBLE PROMOTER; INTERFERON-GAMMA; TYROSINE KINASE; PHASE-I; CELLS; EXPRESSION AB Radiotherapy is a widely used local and regional modality for the treatment of cancer. Despite improved methods of radiation delivery, local recurrence accounts for treatment failure in most patients. Radiosensitizers have been studied as one approach for improving the effectiveness of radiotherapy. Few agents, however, have been shown to selectively increase the anti-tumor effects of radiation. Advances in our understanding of how cells respond molecularly to ionizing radiation have provided opportunities for the development of new approaches that selectively enhance radiotherapy of tumors. Cells respond to ionizing radiation with the activation of specific early and later response genes. These findings led us to the concept that promoters from these genes could be used to drive therapeutic transgenes introduced into irradiated tumor cells. In this strategy, designated genetic radiotherapy, radiation is combined with gene therapy, another local/regional modality, to spatially and temporally control transgene expression in the irradiated field. Tumor necrosis factor-alpha (TNF-alpha) was selected as the transgenic protein for its potent anti-tumor activity and synergistic interactions with ionizing radiation. The radio-inducible elements from the early growth response-1 (EGR-1) gene promoter have been inserted upstream to a cDNA encoding TNF-alpha and integrated into a replication-defective adenovirus (Ad. EGR-TNF). Preclinical studies have shown that tumors infected with Ad. EGR-TNF respond to radiation with induction of TNF-alpha expression and substantial increases in anti-tumor activity. Importantly, local production of TNF-alpha is not associated with the limiting toxicities encountered when this cytokine was administered systemically. Based on these findings, radiation in combination with intratumoral administration of a second generation Ad. EGR-TNF (TNFerade) has completed Phase I evaluation and has entered Phase II clinical trials. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Sch Med, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 37 TC 53 Z9 72 U1 1 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2003 VL 2 IS 4 BP 326 EP 329 PG 4 WC Oncology SC Oncology GA 726WJ UT WOS:000185624300003 PM 14508100 ER PT J AU Fanzo, JC Lynch, MP Phee, H Hyer, M Cremesti, A Grassme, H Norris, JS Coggeshall, KM Rueda, BR Pernis, AB Kolesnick, R Gulbins, E AF Fanzo, JC Lynch, MP Phee, H Hyer, M Cremesti, A Grassme, H Norris, JS Coggeshall, KM Rueda, BR Pernis, AB Kolesnick, R Gulbins, E TI CD95 rapidly clusters in cells of diverse origins SO CANCER BIOLOGY & THERAPY LA English DT Article DE receptor aggregation; apoptosis; acid sphingomyelinase; ceramide; rafts ID RICH MEMBRANE RAFTS; DEATH AB We have shown that CD95-mediated cell death requires a clustering of the receptor in distinct sphingolipid-rich domains of the cell membrane (Grassme et al., 2000, Cremesti et al., 2000). These domains form in response to acid sphingomyelinase (ASM)-induced ceramide generation. However, recent studies challenged the finding of early CD95 clustering (Algeciras-Schimnich et al., 2002). Here, six independent groups tested clustering of CD95 in diverse cell type including primary cells ex vivo and established cell lines. The studies show clustering of CD95 within seconds to minutes in all cell types tested by the different groups. In addition, clustering of CD95 was detected after stimulation of cells using three agonistic anti-CD95 antibodies (CH11, APO-1-3 and JO2), CD95 ligand and stimuli that induce an upregulation and activation of the endogenous CD95/CD95 ligand system. The data confirm our previous studies and suggest rapid, i.e., within seconds to minutes, CD95 clustering as a general phenomenon occurring in many cell types. C1 Univ Essen Gesamthsch, Dept Mol Biol, D-45122 Essen, Germany. Columbia Univ, Dept Med, New York, NY USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. RP Gulbins, E (reprint author), Univ Essen Gesamthsch, Dept Mol Biol, Hufelandstr 55, D-45122 Essen, Germany. EM erich.gulbins@uni-essen.de RI Gulbins, Erich/L-6989-2014 OI Gulbins, Erich/0000-0002-3117-1342 FU NCI NIH HHS [CA 64268, CA 21765, CA 69596, CA 85704]; NHLBI NIH HHS [HL 6225]; NICHD NIH HHS [HD 35934] NR 13 TC 37 Z9 37 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2003 VL 2 IS 4 BP 392 EP 395 PG 4 WC Oncology SC Oncology GA 726WJ UT WOS:000185624300014 PM 14508111 ER PT J AU Kaelin, WG AF Kaelin, WG TI E2F1 as a target - Promoter-driven suicide and small molecule modulators SO CANCER BIOLOGY & THERAPY LA English DT Review DE E2F; retinoblastoma; cell cycle; apoptosis; chemotherapy; oncolytic virus ID CELL-CYCLE ARREST; S-PHASE ENTRY; RETINOBLASTOMA TUMOR-SUPPRESSOR; TRANSCRIPTION FACTOR E2F-1; EFFICIENTLY INDUCES APOPTOSIS; DEPENDENT KINASE INHIBITORS; DNA-BINDING ACTIVITY; GENE-TRANSFER; IN-VIVO; CANCER-CELLS AB Decreased requirements for mitogens and diminished sensitivity to antiproliferative signals are among the hallmarks of human cancer. These attributes are due, at least partly, to mutations that directly or indirectly compromise the function of the retinoblastoma tumor suppressor protein (pRB), which is a negative regulator of a family of cell-cycle regulatory transcription factors referred to generically as E2F. Activation of E2F target genes is sufficient to induce unscheduled cellular proliferation but, under certain circumstances, can also lead to programmed cell death (apoptosis). This chapter will review the role of E2F in cancer and outline opportunities for the development of anticancer agents based on E2F biology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 107 TC 20 Z9 20 U1 2 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL-AUG PY 2003 VL 2 IS 4 SU 1 BP S48 EP S54 PG 7 WC Oncology SC Oncology GA 754RQ UT WOS:000187345600007 PM 14508080 ER PT J AU Plaskon, LA Penson, DF Vaughan, TL Stanford, JL AF Plaskon, LA Penson, DF Vaughan, TL Stanford, JL TI Cigarette smoking and risk of prostate cancer in middle-aged men SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEALTHY MEDICAL-STUDENTS; EPSTEIN-BARR-VIRUS; BREAST-CANCER; PSYCHOLOGICAL DISTRESS; NEGATIVE AFFECTIVITY; OVARIAN-CANCER; DNA-REPAIR; STRESS; PSYCHONEUROIMMUNOLOGY; WOMEN AB Cigarette smoking may increase the risk of prostate cancer by affecting circulating hormone levels or through exposure to carcinogens. Although there are plausible mechanisms that could explain an association between smoking and prostate cancer, previous studies are inconsistent. The goal of this population-based case-control study was to assess this association in middle-aged men. Cases (n = 753) were men ages 40-64 years diagnosed with prostate cancer from 1993 to 1996 identified using the Seattle-Puget Sound Cancer Registry. Age-matched controls without prostate cancer from the same region (n = 703) were identified using random digit dialing. Participants completed detailed in-person interviews. Logistic regression was used to compute adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to assess the prostate cancer-cigarette smoking relationship. Current smokers had an increased risk (OR = 1.4, 95% CI 1.0-2.0) relative to nonsmokers. A dose-response relationship was noted between number of pack-years smoked and prostate cancer risk (trend P = 0.03). The OR = 1.6 (95% CI 1.1-2.2) for men with >40 pack-years of smoking, with a stronger association observed in men with more aggressive disease (OR = 2.0, 95% CI 1.3-3.1). Smoking cessation resulted in a decline in risk (trend P = 0.02). Smoking is associated with a moderately increased relative risk of prostate cancer. Furthermore, a dose-response relationship exists between number of pack-years smoked and cancer risk. Given that smoking cessation seems to reduce these risks, results from this study have public health ramifications and suggest that prostate cancer should be added to the list of tumors for which cigarette smoking is a risk factor. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1100 Fairview Ave N,MW-814, Seattle, WA 98109 USA. FU NCI NIH HHS [N01-CN-05230, CA56678]; NIDDK NIH HHS [T32 DK007721] NR 37 TC 54 Z9 56 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2003 VL 12 IS 7 BP 604 EP 617 PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 703YW UT WOS:000184311700004 PM 12869398 ER PT J AU Nahta, R Trent, S Yang, CW Schmidt, EV AF Nahta, R Trent, S Yang, CW Schmidt, EV TI Epidermal growth factor receptor expression is a candidate target of the synergistic combination of trastuzumab and flavopiridol in breast cancer SO CANCER RESEARCH LA English DT Article ID RNA-POLYMERASE-II; CYCLIN D1; P-TEFB; ANTIBODY; TRANSFORMATION; APOPTOSIS; THERAPY; CELLS; HER2; NEU AB ErbB2 and cyclin D1 are interacting oncogenes that are particularly important in breast cancer. We demonstrated previously synergy between two drugs that separately address each oncogene, trastuzumab and flavopiridol. Here we examine the cellular basis for this interaction. Although both drugs are thought to alter cell cycle progression, the combination of trastuzumab and flavopiridol had little effect on G, progression or retinoblastoma protein phosphorylation. Instead, trastuzumab-flavopiridol synergistically enhanced apoptosis. Recent data have suggested that transcription elongation mediated by Cdk9 in P-TEFb is a more sensitive flavopiridol target than Cdk4. Supporting this view, we found synergy between 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole riboside and trastuzumab, but not between inhibitors of Cdk4 and trastuzumab. Similarly, a signature set of mRNAs that included the epidermal growth factor receptor (EGFR) responded to the combination of trastuzumab-flavopiridol in a gene expression array analysis. Three lines of evidence confirmed the EGFR is a potential target of flavopiridol-trastuzumab synergy: (a) EGFR protein expression was rapidly and completely lost after combination treatment; (b) a cell line that expresses amplified levels of both erbB2 and the EGFR was resistant to the combined drugs; and (c) treatment with epidermal growth factor prevented any therapeutic effects of flavopiridol and trastuzumab, singly or in combination. Taken together, our results suggest that synergy between flavopiridol and trastuzumab can result from enhanced apoptosis, and that combination effects on EGFR expression are involved in the interaction. C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Charlottetown, PE 02129, Canada. RP Schmidt, EV (reprint author), Massachusetts Gen Hosp, Serv Pediat, Fruit Serv, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA69069, P50 CA89393] NR 25 TC 25 Z9 28 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2003 VL 63 IS 13 BP 3626 EP 3631 PG 6 WC Oncology SC Oncology GA 697KL UT WOS:000183941800029 PM 12839951 ER PT J AU Abdollahi, A Lipson, KE Han, XH Krempien, R Trinh, T Weber, KJ Hahnfeldt, P Hlatky, L Debus, J Howlett, AR Huber, PE AF Abdollahi, A Lipson, KE Han, XH Krempien, R Trinh, T Weber, KJ Hahnfeldt, P Hlatky, L Debus, J Howlett, AR Huber, PE TI SU5416 and SU6668 attenuate the angiogenic effects of radiation-induced tumor cell growth factor production and amplify the direct anti-endothelial action of radiation in vitro SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL-CELLS; IONIZING-RADIATION; CANCER; RADIOTHERAPY; APOPTOSIS; INHIBITOR; EXPRESSION; PROTECTION; FLK-1/KDR; SURVIVAL AB In recent decades, radiation research has concentrated primarily on the cancer cell compartment. Much less is known about the effect of ionizing radiation on the endothelial cell compartment and the complex interaction between tumor cells and their microenvironment. Here we report that ionizing radiation is a potent antiangiogenic agent that inhibits endothelial cell survival, proliferation, tube formation and invasion. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor were able to reduce the radiosensitivity of endothelial cells. Yet, it is also found that radiation induces angiogenic factor production by tumor cells that can be abrogated by the addition of antiangiogenic agents. Receptor tyrosine kinase inhibitors of Flk-1/KDR/VEGFR2, FGFR1 and PDGFRbeta, SU5416, and SU6668 enhanced the antiangiogenic effects of direct radiation of the endothelial cells. In a coculture system of PC3 prostate cancer cells and endothelial cells, isolated irradiation of the PC3 cells enhanced endothelial cell invasiveness through a Matrigel matrix, which was inhibited by SU5416 and SU6668. Furthermore, ionizing radiation up-regulated VEGF and basic fibroblast growth factor in PC3 cells and VEGFR2 in endothelial cells. Together these findings suggest a radiation-inducible protective role for tumor cells in the support of their associated vasculature that may be down-regulated by coadministration of angiogenesis inhibitors., These results rationalize concurrent administration of angiogenesis inhibitors and radiotherapy in cancer treatment. C1 German Canc Res Ctr, Dept Radiat Oncol, D-69120 Heidelberg, Germany. SUGEN Inc, San Francisco, CA 94080 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Univ Heidelberg, Sch Med, Dept Radiat Oncol, D-69120 Heidelberg, Germany. RP Huber, PE (reprint author), German Canc Res Ctr, Dept Radiat Oncol, 280 Neuenheimer Feld, D-69120 Heidelberg, Germany. NR 30 TC 126 Z9 133 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2003 VL 63 IS 13 BP 3755 EP 3763 PG 9 WC Oncology SC Oncology GA 697KL UT WOS:000183941800049 PM 12839971 ER PT J AU Barbara, PD Van den Brink, GR Roberts, DJ AF Barbara, PD Van den Brink, GR Roberts, DJ TI Development and differentiation of the intestinal epithelium SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE visceral endoderm; intestinal epithelium; signaling pathways; BMP; Hh; HOX; Sox; Wnt/beta-catenin; epithelial-mesenchymal interaction ID BONE MORPHOGENETIC PROTEIN; REGION-SPECIFIC EXPRESSION; TGF-BETA SUPERFAMILY; SONIC HEDGEHOG; ENDODERM FORMATION; HOX GENES; JUVENILE POLYPOSIS; DIGESTIVE-TRACT; GUT ENDODERM; GASTROINTESTINAL-TRACT AB The gastrointestinal tract develops from a simple tube to a complex organ with patterns of differentiation along four axes of asymmetry. The organ is composed of all three germ layers signaling to each other during development to form the adult structure. The gut epithelium is a constitutively developing tissue, constantly differentiating from a stem cell in a progenitor pool throughout the life of the organism. Signals from the adjacent mesoderm and between epithelial cells are required for normal orderly development/differentiation, homeostasis, and apoptosis. Embryonically important patterning factors are used during adult stages for these processes. Such critical pathways as the hedgehog, bone morphogenetic protein, Notch, Sox, and Writ systems are used both in embryologic and adult times of gut development. We focus on and review the roles of these factors in gut epithelial cell development and differentiation. C1 CNRS, UPR 1142, Inst Genet Humaine, F-34396 Montpellier, France. Univ Amsterdam, Acad Med Ctr, Lab Expt Intenal Med, NL-1105 AZ Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02114 USA. RP Barbara, PD (reprint author), CNRS, UPR 1142, Inst Genet Humaine, 141 Rue Cardonille, F-34396 Montpellier, France. EM desanta@igh.cnrs.fr NR 110 TC 135 Z9 135 U1 1 U2 13 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD JUL PY 2003 VL 60 IS 7 BP 1322 EP 1332 DI 10.1007/s00018-003-2289-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 707YL UT WOS:000184537500005 ER PT J AU Gould, KL Carabello, BA AF Gould, KL Carabello, BA TI Why angina in aortic stenosis with normal coronary arteriograms? SO CIRCULATION LA English DT Editorial Material DE editorials; stenosis; angina; myocardium; hypertrophy ID LEFT-VENTRICULAR HYPERTROPHY; BLOOD-FLOW; VALVE REPLACEMENT; PECTORIS; ARTERIES; MECHANISMS; REGRESSION; PERFUSION; PRESSURE; ISCHEMIA C1 Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Med, Med Serv 111, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Internal Med, Div Cardiol, Houston, TX USA. RP Carabello, BA (reprint author), Baylor Coll Med, Houston Vet Affairs Med Ctr, Dept Med, Med Serv 111, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 18 TC 38 Z9 39 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 JUL 1 PY 2003 VL 107 IS 25 BP 3121 EP 3123 DI 10.1161/01.CIR.0000074243.02378.80 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 696KY UT WOS:000183887100002 PM 12835405 ER PT J AU Reddy, VY Wrobleski, D Houghtaling, C Josephson, ME Ruskin, JN AF Reddy, VY Wrobleski, D Houghtaling, C Josephson, ME Ruskin, JN TI Combined epicardial and endocardial electroanatomic mapping in a porcine model of healed myocardial infarction SO CIRCULATION LA English DT Article; Proceedings Paper CT 23rd Annual Scientific Sessions of the North-American-Society-of-Pacing-and-Electrophysiology CY MAY 08-11, 2002 CL SAN DIEGO, CALIFORNIA SP N Amer Soc Pacing Electrophysiol DE ablation; electrophysiology; mapping; myocardial infarction; pericardium ID RECURRENT VENTRICULAR-TACHYCARDIA; CATHETER ABLATION; SINUS RHYTHM; DISEASE; HEART AB Background-Substrate mapping of post-myocardial infarction ventricular tachycardia involves electroanatomic delineation of scarred tissue on the basis of electrogram characteristics during sinus rhythm. A percutaneous transthoracic technique was recently described that allows catheter mapping of the epicardial surface of the heart. This study sought to determine whether the epicardial extent of a myocardial infarct could be defined during sinus rhythm. Methods and Results-In a porcine model of healed anterior wall myocardial infarction (n=13 animals), detailed in vivo left ventricular endocardial and ventricular epicardial electroanatomic mapping was performed. Catheter access to the pericardial space was achieved by subxyphoid puncture under fluoroscopic guidance. Bipolar electrogram amplitude and duration characteristics of normal tissue were established on the basis of in vivo epicardial mapping data in 8 additional normal animals. With the use of these criteria, radiofrequency lesions (4 to 11 per animal) were placed along the endocardial and epicardial scar borders as defined by the electroanatomic map. The area of epicardial scar defined by abnormal bipolar voltage correlated well with the dimensions measured on pathological examination. The size and location also correlated well with the scar dimensions defined by electrogram duration criteria. Late potentials were noted in the border zones of both surfaces of the scar. During pathological examination, the radiofrequency lesions were situated at the borders of the epicardial scar. Conclusions-A 3-dimensional construct of the infarcted myocardium can be rendered by combined epicardial and endocardial electroanatomic mapping. This experimental protocol is propaedeutic to future clinical studies incorporating endocardial and epicardial substrate mapping into catheter ablation strategies to treat post-myocardial infarction ventricular tachycardia. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Cardiac Arrhythmia Serv, Boston, MA 02215 USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. FU NHLBI NIH HHS [K23 HL68064-01A1] NR 16 TC 55 Z9 56 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 JUL 1 PY 2003 VL 107 IS 25 BP 3236 EP 3242 DI 10.1161/01.CIR.0000074280.62478.E1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 696KY UT WOS:000183887100021 PM 12796129 ER PT J AU Fifer, MA Yoerger, DM Picard, MH Vlahakes, GJ Palacios, IF AF Fifer, MA Yoerger, DM Picard, MH Vlahakes, GJ Palacios, IF TI Covered stent septal ablation for hypertrophic obstructive cardiomyopathy - Initial success but ultimate failure resulting from collateral formation SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fifer, MA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, WACC 478,15 Parkman St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 0 TC 11 Z9 12 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 JUL 1 PY 2003 VL 107 IS 25 BP 3248 EP 3249 DI 10.1161/01.CIR.0000068035.52761.71 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 696KY UT WOS:000183887100024 PM 12835408 ER PT J AU Virella, G Lopes-Virella, MF AF Virella, G Lopes-Virella, MF TI Lipoprotein autoantibodies: Measurement and significance SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; CONTAINING IMMUNE-COMPLEXES; ADVANCED GLYCATION ENDPRODUCTS; MONOCYTE-DERIVED MACROPHAGES; DEPENDENT DIABETES-MELLITUS; MODIFIED LDL ANTIBODIES; OXIDIZED LDL; CAROTID ATHEROSCLEROSIS; HEART-DISEASE C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Metab Nutr, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Virella, G (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, 173 Ashley Ave,POB 250504, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-55782, P01 HL055782] NR 75 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 2003 VL 10 IS 4 BP 499 EP 505 DI 10.1128/CDLI.10.4.499-505.2003 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 703MU UT WOS:000184284100001 PM 12853376 ER PT J AU Malik, SN Siu, LL Rowinsky, EK DeGraffenried, L Hammond, LA Rizzo, L Bacus, S Brattain, MG Kreisberg, JI Hidalgo, M AF Malik, SN Siu, LL Rowinsky, EK DeGraffenried, L Hammond, LA Rizzo, L Bacus, S Brattain, MG Kreisberg, JI Hidalgo, M TI Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol ID EGF RECEPTOR; TYROSINE KINASE; ANTIBODY C225; PHASE-I; FAMILY; CP-358,774; CISPLATIN; THERAPY AB Background: OSI-774 is an inhibitor of the epidermal growth factor receptor tyrosine kinase (EGFR-TK) currently in clinical development. In preclinical models, the antitumor activity of OSI-774 was directly related to its ability to inhibit the EGFR-TK. On the basis of these data, we hypothesized that inhibition of the EGFR-TK will be required for this agent to be effective in the clinic. This study evaluated the pharmacodynamic effects of OSI-774 in normal skin tissues collected from patients treated with the agent in a Phase I study. Methods: Patients with advanced cancer who were treated in a Phase I study of OSI-774 underwent a biopsy of normal skin epidermis at baseline and after the last dose of drug in the first course of treatment. The expression and activation of the EGFR, downstream signaling extracyto-plasmatic-regulated kinase (Erk), and cell cycle regulator p27 were determined in paraffin-embedded skin tissues using an immunohistochemical method (IHC). The IHC data were analyzed using both a semiquantitative scoring system and an automatic absorbance quantitative IHC method. The number of cells with nuclear staining of p27 per 500 cells was determined. Plasma samples were collected to quantitate OSI-774 plasma concentrations. Results: A total of 56 skin specimens was collected from 28 patients treated with OSI-774 at doses ranging from 25 to 200 mg/day. There was a significant decrease in phospho-EGFR (Tyr 1173) expression as determined semiquantitatively with OSI-774 treatment [2.75 +/- 0.51 (mean +/- SD) pretreatment versus 2.36 +/- 0.76 after treatment, pair comparison P = 0.01]. The quantitative ratio [(phopho-EGFR/ EGFR) x 100] of phospho-EGFR (Tyr1173) decreased from 64.16 +/- 36.58 pretreatment to 48.87 +/- 35.37 post-treatment (pair comparison, P = 0.02). No significant differences were observed in phospho-Erk (Thr202/Tyr2O4) expression. The mean number of cells with nuclear staining for p27 increased from 185 +/- 101 (mean +/- SD) pretreatment to 253 +/- 111 post-treatment (pair comparison P = 0.02). A total of 12 (42.8%), 7 (25%), and 14 (50%) patients had >25% variation in the ratio of phospho-EGFR (Tyr1173), phospho-Erk (Thr202/Tyr2O4), and p27 expression, respectively. Only changes in p27 expression were related to the administered dose of OSI-774. Conclusions: OSI-774 exerted pharmacodynamic effects in skin tissues of 30-50% of patients treated with the agent. Up-regulation of p27, which is a downstream effect of EGFR inhibition, was dose related. Although there was a significant decrement in phospho-EGFR (Tyr1173), it was not related to the administered dose of OSI-774. On the basis of these findings and the relatively simple and reliable method to measure p27 expression, this biomarker appears to be the most promising and is being evaluated in Phase II studies as a predictor of clinical outcome. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78285 USA. Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78229 USA. Ventana QDL Inc, Chicago, IL USA. RP Hidalgo, M (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, 1650 Orleans St,Room 1M88, Baltimore, MD 21231 USA. RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 NR 20 TC 96 Z9 106 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2003 VL 9 IS 7 BP 2478 EP 2486 PG 9 WC Oncology SC Oncology GA 700JK UT WOS:000184108700014 PM 12855621 ER PT J AU Duan, ZF Duan, YF Lamendola, DE Yusuf, RZ Naeem, R Penson, RT Seiden, MV AF Duan, ZF Duan, YF Lamendola, DE Yusuf, RZ Naeem, R Penson, RT Seiden, MV TI Overexpression of MAGE/GAGE genes in paclitaxel/doxorubicin-resistant human cancer cell lines SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; MAGE GENE; PACLITAXEL RESISTANCE; DRUG-RESISTANCE; REACTION ASSAY; EXPRESSION; ANTIGENS; FAMILY AB Previous studies directed at identifying paclitaxel resistance genes in a paclitaxel-resistant subclone of the human ovarian cancer cell line SKOV-3 identified a novel cancer testis antigen, Taxol resistance-associated gene 3 (TRAG-3). Because investigation suggested that TRAG-3, located on chromosome Xq28, does not directly participate in the paclitaxel-resistant phenotype, it was hypothesized that TRAG-3 might be linked to a neighboring gene that is directly involved in the drug-resistant phenotype, or alternatively, overexpression of TRAG-3 might be attributable to coregulation with other cancer testis antigens. To distinguish between these two hypotheses, expression of the genes that flank TRAG-3 was evaluated, namely the Centrin 2 gene and several members of the MAGE gene cluster. Northern analysis demonstrates overexpression of MAGE2 but not Centrin 2. Extension of this analysis to other neighboring and non-neighboring representative cancer testis antigens reveals overexpression of MAGE3, MAGE6, MAGE11, and MAGE12, as well as GAGE-2, GAGE-4, GAGE-5, GAGE-6, and GAGE-7 (clustered on Xp11) in SKOV-3(TR), as compared with SKOV-3. In addition, Affymetrix-based analysis of gene expression in SKOV-3 subclones with variable paclitaxel resistance demonstrates MAGE gene overexpression occurs early in the development of the paclitaxel-resistant phenotype, whereas GAGE gene overexpression occurs somewhat later. Evaluation of additional breast and ovarian cancer cell lines reveals MAGE/GAGE overexpression in both paclitaxel- and doxorubicin-resistant cell lines, whereas gemcitabine-resistant subclones of several ovarian cancer cell lines, including SKOV-3(GR), reveals no change in MAGE/GAGE expression. To determine whether MAGE gene overexpression contributes directly to the drug-resistant phenotype, MAGE2 or MAGE6, cDNA was introduced into the paclitaxel-sensitive human ovarian cancer cell line OVCAR8. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cytotoxicity analysis of both MAGE2 and MAGE6 transfectants demonstrates a 4-fold increase in resistance to paclitaxel and 2-fold increase in resistance to doxorubicin but not to other drugs, such as topotecan and cisplatin, through a nonmultidrug resistance-1 mechanism. MAGE2 or MAGE6 overexpression also induces a growth advantage in OVCAR8-transfected cells. These studies suggest that the in vitro acquisition of paclitaxel and doxorubicin resistance can be associated with increased expression of a variety of both neighboring and non-neighboring cancer testis antigens genes. This does not appear to be a consequence of random genetic instability or genomic amplification of the X chromosome. These antigens, because of limited expression in normal tissues, may be suitable targets for immunotherapy and novel therapeutic strategies in the treatment of chemotherapy-resistant epithelial tumors. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640, Boston, MA 02114 USA. NR 44 TC 94 Z9 100 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL PY 2003 VL 9 IS 7 BP 2778 EP 2785 PG 8 WC Oncology SC Oncology GA 700JK UT WOS:000184108700051 PM 12855658 ER PT J AU Ioannou, GN Kowdley, KV AF Ioannou, George N. Kowdley, Kris V. TI Iron, HFE Mutations, and Hepatocellular Carcinoma: Is Hepatic Iron a Carcinogen? SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID HEREDITARY HEMOCHROMATOSIS; H63D MUTATIONS; CANCER RISK; LIVER IRON; CIRRHOSIS; POPULATION; C282Y; GENE; PREVALENCE; OVERLOAD C1 [Ioannou, George N.; Kowdley, Kris V.] Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. [Ioannou, George N.] Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Ioannou, GN (reprint author), Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. NR 24 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2003 VL 1 IS 4 BP 246 EP 248 DI 10.1016/S1542-3565(03)00126-5 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KJ UT WOS:000208071000002 PM 15017663 ER PT J AU Hirsch, MS Brun-Vezinet, F Clotet, B Conway, B Kuritzkes, DR D'Aquila, RT Demeter, LM Hammer, SM Johnson, VA Loveday, C Mellors, JW Jacobsen, DM Richman, DD AF Hirsch, MS Brun-Vezinet, F Clotet, B Conway, B Kuritzkes, DR D'Aquila, RT Demeter, LM Hammer, SM Johnson, VA Loveday, C Mellors, JW Jacobsen, DM Richman, DD TI Antiretroviral drug resistance testing in adults infected with human immunodeficiency virus type 1: 2003 recommendations of an international AIDS Society-USA panel SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HIV-1 REVERSE-TRANSCRIPTASE; HIGH-LEVEL RESISTANCE; INHIBITOR-CONTAINING REGIMEN; GENOTYPIC RESISTANCE; PROTEASE INHIBITORS; TREATMENT INTERRUPTIONS; ZIDOVUDINE RESISTANCE; VERTICAL TRANSMISSION; DISEASE PROGRESSION; CROSS-RESISTANCE AB New information about the benefits and limitations of testing for resistance to human immunodeficiency virus (HIV) type 1 (HIV-1) drugs has emerged. The International AIDS Society-USA convened a panel of physicians and scientists with expertise in antiretroviral drug management, HIV-1 drug resistance, and patient care to provide updated recommendations for HIV-1 resistance testing. Published data and presentations at scientific conferences, as well as strength of the evidence, were considered. Properly used resistance testing can improve virological outcome among HIV-infected individuals. Resistance testing is recommended in cases of acute or recent HIV infection, for certain patients who have been infected as long as 2 years or more prior to initiating therapy, in cases of antiretroviral failure, and during pregnancy. Limitations of resistance testing remain, and more study is needed to refine optimal use and interpretation. C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Rochester, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Vet Affairs Med Ctr, Pittsburgh, PA USA. Int AIDS Soc USA, San Francisco, CA USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. Hop Bichat Claude Bernard, F-75877 Paris 18, France. Hosp Univ Germans Trias & Pujol, HIV Unit, Barcelona, Spain. Hosp Univ Germans Trias & Pujol, Fdn IrsiCAIXA, Barcelona, Spain. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Hirsch, MS (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 65 Landsdowne St,Rm 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org NR 169 TC 391 Z9 407 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2003 VL 37 IS 1 BP 113 EP 128 DI 10.1086/375597 PG 16 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 695JE UT WOS:000183826700016 PM 12830416 ER PT J AU Sam, R Chebrolu, B Reyes, CV Pierce, KL Molnar, Z Dhand, R Ing, TS AF Sam, R Chebrolu, B Reyes, CV Pierce, KL Molnar, Z Dhand, R Ing, TS TI Transjugular renal biopsy in an unconscious patient maintained on mechanical ventilation SO CLINICAL NEPHROLOGY LA English DT Article DE transjugular renal biopsy; unconsciousness; mechanical ventilation ID LIVER-DISEASE; EXPERIENCE AB Aim: Transjugular renal biopsy is a relatively new technique that has often been applied to patients with concomitant renal and liver diseases. It is believed that with this particular biopsy approach, one can avoid the high risk of conventional renal biopsy-related bleeding in patients who also often suffer from coagulopathy. However, other indications for this procedure have not been clearly defined. Herein, we describe an unconscious patient afflicted with acute renal failure and maintained on mechanical ventilation in whom the performance of a renal biopsy was deemed necessary. Methods: The transjugular renal biopsy technique was carried out because this unconscious patient could not follow breathing instructions for a conventional biopsy to be performed. Also, it would have been difficult for the patient to lay prone during the conventional biopsy procedure. Results: A total of 7 glomeruli were obtained and a diagnosis of vasculitis-related necrotizing glomerulonephritis and acute tubular necrosis was made. Subsequently, the patient was treated successfully with steroid therapy. Conclusion: Transjugular kidney biopsy should be considered in unconscious renal biopsy-requiring patients maintained on mechanical ventilation. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Radiol, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Pathol, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Cook Cty Hosp, Chicago, IL 60612 USA. RP Ing, TS (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD JUL PY 2003 VL 60 IS 1 BP 53 EP 57 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 696KU UT WOS:000183886700009 PM 12872859 ER PT J AU George, MS Nahas, Z Kozel, FA Li, XB Yamanaka, K Mishory, A Bohning, DE AF George, MS Nahas, Z Kozel, FA Li, XB Yamanaka, K Mishory, A Bohning, DE TI Mechanisms and the current state of transcranial magnetic stimulation SO CNS SPECTRUMS LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; LEFT PREFRONTAL CORTEX; HUMAN CEREBRAL-CORTEX; LONG-TERM DEPRESSION; MAJOR DEPRESSION; MOTOR CORTEX; SLEEP-DEPRIVATION; ELECTROCONVULSIVE-THERAPY; DOUBLE-BLIND AB Transcranial magnetic stimulation (TMS) is unique among the current brain stimulation techniques because it is relatively non-invasive. TMS markedly differs from vagus nerve stimulation, deep brain stimulation and magnetic seizure therapy, all of which require either an implanted prosthesis or general anesthesia, or both. Since its rebirth in its modern form in 1985, TMS has already shown potential usefulness in at least three important domains-as a basic neuroscience research instrument, as a potential clinical diagnostic tool, and as a therapy for several different neuropsychiatric conditions. The TMS scientific literature has now expanded beyond what a single summary article can adequately cover. This review highlights several new developments in combining TMS with functional brain imaging, using TMS as a psychiatric therapy, potentially using TMS to enhance performance, and finally recent advances in the core technology of TMS. TMS' ability to non-invasively and focally stimulate the brain of an awake human is proving to be a most important development for neuroscience in general, and neuropsychiatry in particular. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Psychiat, 502 N IOP,67 President St, Charleston, SC 29425 USA. RI Kozel, Frank/I-5366-2012 FU NIA NIH HHS [R01-AG40956] NR 151 TC 59 Z9 62 U1 3 U2 7 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTR JI CNS Spectr. PD JUL PY 2003 VL 8 IS 7 BP 496 EP + PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 710MM UT WOS:000184684000014 PM 12894031 ER PT J AU Keck, PE McElroy, SL Havens, JR Altshuler, LL Nolen, WA Frye, MA Suppes, T Denicoff, KD Kupka, R Leverich, GS Rush, AJ Post, RM AF Keck, PE McElroy, SL Havens, JR Altshuler, LL Nolen, WA Frye, MA Suppes, T Denicoff, KD Kupka, R Leverich, GS Rush, AJ Post, RM TI Psychosis in bipolar disorder: Phenomenology and impact on morbidity and course of illness SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID FOLLOW-UP; MOOD-CONGRUENT; SYMPTOMS; UNIPOLAR; MANIA; SCHIZOPHRENIA; FAMILY; PREDICTION; DIAGNOSIS; FEATURES AB Although psychosis is common in bipolar disorder, few studies have examined the prognostic significance of psychotic features. In addition, some studies suggest that the presence of mood-incongruent psychosis, in particular, is associated with poorer outcome compared with mood-congruent psychosis. We assesses the phenomenology and prevalence of mood-congruent and mood-incongruent psychotic symptoms in 352 patients with bipolar I disorder participating in the Stanley Foundation Bipolar Treatment Network. We compared the demographic and clinical features, and measures of psychosocial and vocational functioning in patients with and without a history of psychosis. The phenomenology of psychosis in this cohort of patients with bipolar disorder was similar to that reported in earlier studies and supported the lack of diagnostic specificity of any one type of psychotic symptom. There were no significant differences between patients with and without a history of psychosis on any demographic, psychosocial, vocational, or course of illness variables. Only family history of bipolar disorder was significantly more common in patients with nonpsychotic bipolar disorder compared to patients with a history of psychosis. Among bipolar patients with a history of psychosis, only the proportion of women and lifetime prevalence rates of anxiety disorders occurred significantly more in patients with mood-incongruent delusions. In this large cohort of outpatients with bipolar I disorder, neither a history of psychosis nor of mood-incongruent psychosis had prognostic significance at entry into the Network. The lack of observable prognostic impact may have been, in part, due to the relatively high morbidity and poor functional outcome of a substantial portion of the total cohort. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH 45267 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. SW Med Ctr, Dallas, TX USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Utrecht, Ctr Med, Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. RP Keck, PE (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, 231 Albert Sabin Way,ML 559, Cincinnati, OH 45267 USA. RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [R01 MH079261] NR 34 TC 81 Z9 85 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 2003 VL 44 IS 4 BP 263 EP 269 DI 10.1016/S0010-440X(03)00089-0 PG 7 WC Psychiatry SC Psychiatry GA 703YV UT WOS:000184311600001 PM 12923703 ER PT J AU Dudenhoefer, EJ Nouri, M Gipson, IK Baratz, KH Tisdale, AS Dryja, TP Abad, JC Dohlman, CH AF Dudenhoefer, EJ Nouri, M Gipson, IK Baratz, KH Tisdale, AS Dryja, TP Abad, JC Dohlman, CH TI Histopathology of explanted collar button keratoprostheses: A clinicopathologic correlation SO CORNEA LA English DT Article DE keratoprosthesis; cornea; corneal pathology; ocular pemphigoid; graft failure AB Purpose. To compare the histopathology of three PMMA collar button type keratoprosthesis (KPro)/corneal specimens, explanted due to various complications, with that from one KPro/corneal specimen taken postmortem from an otherwise "healthy" enucleated eye. Methods. Patient I (chemical injury) had no problems for 3 years after KPro placement; the entire eye was obtained postmortem. Patient 2 (repeated graft failures, nonautoimmune disease) developed an "unlaserable" retroprosthesis membrane 4 months after KPro placement. A new KPro was placed. Patient 3 [ocular cicatricial pemphigoid (OCP)] developed tissue melt at the KPro-cornea interface 7 months after KPro placement, and the KPro was replaced. Patient 4 (OCP) developed progressive corneal melt around the KPro 3.5 years after placement resulting in replacement. All KPro/cornea specimens were processed and sectioned for histology with the KPro in place. Results. All patients exhibited growth of corneal or conjunctival derived epithelium under the KPro front plate. In patients 1 and 2, no epithelial down-growth was noted and the keratocyte density appeared normal with few inflammatory cells present. Dense fibrous tissue was present behind the KPro in patient 2. Patients 3 and 4 showed massive inflammatory cell infiltration and tissue necrosis with "melt" adjacent to the stem resulting in epithelial downgrowth. Conclusions. Corneal inflammation and degradation after KPro placement correlate well with the preoperative diagnostic category. Patients with immune-related corneal surface disease can exhibit marked inflammatory responses leading to necrosis, stromal melting, and the formation of an epithelial fistula. In contrast, patients without autoimmune corneal disease demonstrate a remarkably noninflamed cornea with intact keratocytes and without epithelial ingrowth, commensurate with their clinical appearance. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. RP Dohlman, CH (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 28 Z9 28 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2003 VL 22 IS 5 BP 424 EP 428 DI 10.1097/00003226-200307000-00007 PG 5 WC Ophthalmology SC Ophthalmology GA 696EN UT WOS:000183873700007 PM 12827047 ER PT J AU Ambati, BK Joussen, AM Kuziel, WA Adamis, AP Ambati, J AF Ambati, BK Joussen, AM Kuziel, WA Adamis, AP Ambati, J TI Inhibition of corneal neovascularization by genetic ablation of CCR2 SO CORNEA LA English DT Article DE angiogenesis; neovascularization; cornea; CCR2; inhibition ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FUNCTIONAL-RESPONSE; ENDOTHELIAL-CELLS; GROWTH-FACTOR; IN-VIVO; ANGIOGENESIS; INFLAMMATION; EXPRESSION; MCP-1; DIFFERENTIATION AB Purpose. To determine if genetic ablation of the chemokine receptor CCR2 (involved in leukocyte and endothelial chemotaxis) inhibits the development of corneal neovascularization. Methods. Wild-type C57BL/6J mice, as well as species-specific counterparts with targeted homozygous disruption of the CCR2. underwent chemical and mechanical denudation of corneal and limbal epithelium. Corneas were harvested 2 weeks after injury. Neovascularization was quantified by CD31 immunostaining. Results. The mean percentages of neovascularized corneal area in control mice and CCR2-deficient mice 2 weeks after denudation were 58.3% and 38.8% (P = 0.047), respectively. Conclusions. Development of corneal neovascularization is inhibited in CCR2-deficient mice. C1 Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30907 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, D-50931 Cologne, Germany. Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. Eyetech Pharmaceut, Woburn, MA 01801 USA. Univ Kentucky, Dept Ophthalmol, Lexington, KY 40536 USA. RP Ambati, BK (reprint author), Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30907 USA. NR 32 TC 30 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 2003 VL 22 IS 5 BP 465 EP 467 DI 10.1097/00003226-200307000-00013 PG 3 WC Ophthalmology SC Ophthalmology GA 696EN UT WOS:000183873700013 PM 12827053 ER PT J AU Alston, TA AF Alston, TA TI Nuclear fallout in sepsis SO CRITICAL CARE MEDICINE LA English DT Editorial Material ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; CIRCULATING NUCLEOSOMES; APOPTOSIS; SERUM; ANTIBODIES; DISEASES; PLASMA; CELL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2003 VL 31 IS 7 BP 2076 EP 2077 DI 10.1097/01.CCM.0000074723.94644.C7 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 702HT UT WOS:000184219000030 PM 12847409 ER PT J AU Wennerberg, K Forget, MA Ellerbroek, SM Arthur, WT Burridge, K Settleman, J Der, CJ Hansen, SH AF Wennerberg, K Forget, MA Ellerbroek, SM Arthur, WT Burridge, K Settleman, J Der, CJ Hansen, SH TI Rnd proteins function as RhoA antagonists by activating p190 RhoGAP SO CURRENT BIOLOGY LA English DT Article ID ACTIN STRESS FIBERS; BINDING PROTEIN; CELL-ADHESION; ESCHERICHIA-COLI; REGULATES CELL; GTPASE; RAC; MECHANISM; FAMILY; CYTOSKELETON AB Background: The Rnd proteins Rnd1, Rnd2, and Rnd3 (RhoE) comprise a unique branch of Rho-family G-proteins that lack intrinsic GTPase activity and consequently remain constitutively "active." Prior studies have suggested that Rnd proteins play pivotal roles in cell regulation by counteracting the biological functions of the RhoAGTPase, but the molecular basis for this antagonism is unknown. Possible mechanisms by which Rnd proteins could function as RhoA antagonists include sequestration of RhoA effector molecules, inhibition of guanine nucleotide exchange factors, and activation of GTPase-activating proteins (GAPS) for RhoA. However, effector molecules of Rnd proteins with such properties have not been identified. Results: Here we identify p190 RhoGAP (p190), the most abundant GAP for RhoA in cells, as an interactor with Find proteins and show that this interaction is mediated by a p190 region that is distinct from the GAP domain. Using Rnd3-RhoA chimeras and Rnd3 mutants defective in p190 binding, as well as p190-deficient cells, we demonstrate that the cellular effects of Rnd expression are mediated by p190. We moreover show that Rnd proteins increase the GAP activity of p190 toward GTP bound RhoA and, finally, demonstrate that expression of Rnd3 leads to reduced cellular levels of RhoA-GTP by a p190-dependent mechanism. Conclusions: Our results identify p190 RhoGAPs as effectors of Rnd proteins and demonstrate a novel mechanism by which Rnd proteins function as antagonists of RhoA. C1 Boston Biomed Res Inst, Watertown, MA 02472 USA. Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Hansen, SH (reprint author), Boston Biomed Res Inst, Watertown, MA 02472 USA. EM hansen@bbri.org OI Wennerberg, Krister/0000-0002-1352-4220 FU NCI NIH HHS [R01 CA63071, R01 CA092354, R01 CA62142]; NIGMS NIH HHS [R01 GM29860] NR 44 TC 136 Z9 137 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUL 1 PY 2003 VL 13 IS 13 BP 1106 EP 1115 DI 10.1016/S0960-9822(03)00418-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 698JP UT WOS:000183995700020 PM 12842009 ER PT J AU Silverman, LB Sallan, SE AF Silverman, LB Sallan, SE TI Newly diagnosed childhood acute lymphoblastic leukemia: update on prognostic factors and treatment SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE childhood acute lymphoblastic leukemia; minimal residual disease; gene expression profiling; pharmacogenomics; late effects ID MINIMAL RESIDUAL DISEASE; CHILDRENS CANCER GROUP; LONG-TERM SURVIVORS; PEDIATRIC-ONCOLOGY-GROUP; ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE LYMPHOID LEUKEMIA; NEONATAL BLOOD SPOTS; CRANIAL IRRADIATION; DANA-FARBER AB The development of effective therapy for children with acute lymphoblastic leukemia is one of the great successes of clinical hematology andoncology. Fifty years ago, childhood acute lymphoblastic leukemia was universally fatal, but current long-term event-free survival rates are nearly 80%. Despite this improved outcome, there are still many challenges facing investigators today. In some recent clinical trials, the outcome of "high-risk" patients has approached that of "lower risk" patients, suggesting that currently applied clinical factors, such as age and presenting leukocyte count, no longer identify the 20% of newly diagnosed patients who ultimately will relapse. Additionally, therapy remains nonspecific, toxic, and sometimes lethal. As more children with acute lymphoblastic leukemia survive into adolescence and adulthood, there is a need to address the late sequelae of current therapy and to develop more leukemia-specific treatments, Promising avenues of research, which may identify biologically distinctive subsets of acute lymphoblastic leukemia and potential targets for novel therapies, include studies of minimal residual disease, lymphoblast genetics (including genetic profiling studies), and host-related pharmacogenomics. C1 Dana Farber Canc Inst, Dept Paediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Dept Paediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 83 TC 24 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2003 VL 10 IS 4 BP 290 EP 296 DI 10.1097/00062752-200307000-00007 PG 7 WC Hematology SC Hematology GA 694FF UT WOS:000183762600007 PM 12799535 ER PT J AU Rizouli, V Gribben, JG AF Rizouli, V Gribben, JG TI Role of autologous stem cell transplantation in chronic lymphocytic leukemia SO CURRENT OPINION IN HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; HIGH-DOSE THERAPY; MYELODYSPLASTIC SYNDROME; MULTIPLE-MYELOMA; CD38 EXPRESSION; LYMPHOPROLIFERATIVE MALIGNANCIES; GENOMIC ABERRATIONS; PBSC MOBILIZATION; SALVAGE TREATMENT AB Autologous hematopoietic stem sell transplantation is increasingly considered for treatment of patients with high-risk chronic lymphocytic leukemia. Patients not eligible for allogeneic hematopoietic stem cell transplantation with poor prognosis disease, documented chemosensitivity, and a minimal tumor burden at the time of hematopoietic stem cell transplantation can be treated with autologous hematopoietic stem cell transplantation currently using peripheral blood stem cells. Different purging methods to obtain sources of stem cells free of tumor contamination are currently being evaluated. Major concerns are judicious selection of which patients may benefit from this approach, the subsequent risk of relapse of disease, and the long-term risk of development of secondary malignancies, including myelodysplastic syndrome and acute myelogenous leukemia. Recognizing and reducing the risk factors that contribute to relapse and complications of the procedure should improve outcome after autologous hematopoietic stem cell transplantation. With the increasing use, increasing effectiveness, and low treatment-related mortality associated with nonmyeloablative conditioning regimens, the question of whether a patient should be offered autologous or allogeneic hematopoietic stem sell transplantation can be a difficult one. Defining salvage settings for relapse and implementing a tandem autologous/allogeneic hematopoietic stem cell transplantation approach may provide a method to improve outcome for selected patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Rizouli, V (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 518, Boston, MA 02115 USA. NR 62 TC 3 Z9 3 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JUL PY 2003 VL 10 IS 4 BP 306 EP 311 DI 10.1097/00062752-200307000-00009 PG 6 WC Hematology SC Hematology GA 694FF UT WOS:000183762600009 PM 12799537 ER PT J AU Freytes, CO AF Freytes, CO TI Thromboembolic complications related to indwelling central venous catheters in children SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE catheterization; central venous; catheter; indwelling; child; neoplasm; thrombosis ID CANCER-PATIENTS; VEIN-THROMBOSIS; WARFARIN; PROPHYLAXIS; PREVALENCE; TRIAL AB Purpose of review Thrombosis is one of the most frequent complications of indwelling central venous catheters. During the past year, new information has emerged regarding the incidence and predisposing factors of thromboembolic complications of indwelling central venous catheters. Because indwelling central venous catheters are widely used, it is important to be aware of new information regarding thromboembolic complications of these devices. Recent findings Recent studies have better defined the risks of thromboembolic complications in patients with cancer with indwelling central venous catheters. Acquired hypercoagulable disorders such as heparin-induced thrombocytopenia, antiphospholipid syndrome, and therapy with asparaginase are associated with thromboembolic disorders in patients with indwelling central venous catheters. Studies analyzing the association between inherited hypercoagulable disorders and thrombosis have shown conflicting results. Preliminary studies suggest that low molecular weight heparins could have a role in the prevention of catheter-related thromboembolic disorders. Nevertheless, larger prospective studies will be necessary to determine the role of anticoagulants in the prevention of thromboembolic disorders in patients with cancer with indwelling central venous catheters. Summary Recent reports will facilitate the evaluation and risk assessment of children with cancer who have indwelling central venous catheters. Despite these advances, large, controlled studies focusing on specific populations of patients, such as children, should be undertaken to determine the true performance and optimal use of indwelling central venous catheters. Future studies should also address better ways to prevent catheter-related thrombosis and infection. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Freytes, CO (reprint author), Univ Texas, Hlth Sci Ctr, Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 14 TC 19 Z9 19 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD JUL PY 2003 VL 15 IS 4 BP 289 EP 292 DI 10.1097/00001622-200307000-00002 PG 4 WC Oncology SC Oncology GA 712ME UT WOS:000184800800002 PM 12874506 ER PT J AU Gupta, SN Palceski, D AF Gupta, SN Palceski, D TI Lichen planopilaris presenting as truncal alopecia: A case presentation and review of the literature SO CUTIS LA English DT Review ID HUMAN HAIR FOLLICLE; FACE AB Lichen planopilaris is an inflammatory condition of unknown etiology, characterized by violaceous folliculocentric papules and hair loss. Some clinicians consider lichen planopilaris to be a variant of lichen planus, but others believe it to be a separate disease entity. Many treatment modalities have been utilized, with varying degrees of success. We describe the case of a 63-year-old man who presented with widespread alopecia of the trunk and extremities and was subsequently diagnosed with lichen planopilaris. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Cuyahoga Falls Hosp, Summa Hlth Syst, Dept Dermatol, Cuyahoga Falls, OH USA. RP Palceski, D (reprint author), TriCty Dermatol, 421 Graham Rd, Cuyahoga Falls, OH 44221 USA. NR 26 TC 7 Z9 8 U1 0 U2 1 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD JUL PY 2003 VL 72 IS 1 BP 63 EP 66 PG 4 WC Dermatology SC Dermatology GA 701XX UT WOS:000184195200009 PM 12889717 ER PT J AU Bashirullah, A Pasquinelli, AE Kiger, AA Perrimon, N Ruvkun, G Thummel, CS AF Bashirullah, A Pasquinelli, AE Kiger, AA Perrimon, N Ruvkun, G Thummel, CS TI Coordinate regulation of small temporal RNAs at the onset of Drosophila metamorphosis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE timing; heterochronic genes; ecdysone; transcription; gene regulation ID CAENORHABDITIS-ELEGANS; LARVAL DEVELOPMENT; MANDUCA-SEXTA; ECDYSONE; GENE; EXPRESSION; TRANSCRIPTION; INTERFERENCE; MELANOGASTER; IDENTIFICATION AB The lin-4 and let-7 small temporal RNAs play a central role in controlling the timing of Caenorhabditis elegans cell fate decisions. let-7 has been conserved through evolution, and its expression correlates with adult development in bilateral animals, including Drosophila [Nature 408 (2000), 86]. The best match for lin-4 in Drosophila, miR-125, is also expressed during pupal and adult stages of Drosophila development [Curr. Biol. 12 (2002), 735]. Here, we ask whether the steroid hormone ecdysone induces let-7 or miR-125 expression at the onset of metamorphosis, attempting to link a known temporal regulator in Drosophila with the heterochronic pathway defined in C elegans. We find that let-7 and miR-125 are coordinately expressed in late larvae and prepupae, in synchrony with the high titer ecdysone pulses that initiate metamorphosis. Unexpectedly, however, their expression is neither dependent on the EcR ecdysone receptor nor inducible by ecdysone in cultured larval organs. Although let-7 and miR-125 can be induced by ecdysone in Kc tissue culture cells, their expression is significantly delayed relative to that seen in the animal. let-7 and miR-125 are encoded adjacent to one another in the genome, and their induction correlates with the transient appearance of an similar to500-nt RNA transcribed from this region, providing a mechanism to explain their precise coordinate regulation. We conclude that a common precursor RNA containing both let-7 and miR-125 is induced independently of ecdysone in Drosophila, raising the possibility of a temporal signal that is distinct from the well-characterized ecdysone-EcR pathway. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Utah, Howard Hughes Med Inst, Dept Human Genet, Salt Lake City, UT 84112 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Thummel, CS (reprint author), Univ Utah, Howard Hughes Med Inst, Dept Human Genet, 15 N 2030 E Room 5100, Salt Lake City, UT 84112 USA. FU NIGMS NIH HHS [R01 GM078176] NR 41 TC 85 Z9 91 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2003 VL 259 IS 1 BP 1 EP 8 DI 10.1016/S0012-1606(03)00063-0 PG 8 WC Developmental Biology SC Developmental Biology GA 694UB UT WOS:000183791900001 PM 12812783 ER PT J AU Yoon, JC Xu, G Deeney, JT Yang, SN Rhee, J Puigserver, P Levens, AR Yang, RJ Zhang, CY Lowell, BB Berggren, PO Newgard, CB Bonner-Weir, S Weir, G Spiegelman, BM AF Yoon, JC Xu, G Deeney, JT Yang, SN Rhee, J Puigserver, P Levens, AR Yang, RJ Zhang, CY Lowell, BB Berggren, PO Newgard, CB Bonner-Weir, S Weir, G Spiegelman, BM TI Suppression of beta cell energy metabolism and insulin release by PGC-1 alpha SO DEVELOPMENTAL CELL LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1; DEPENDENT DIABETES-MELLITUS; PANCREATIC-ISLETS; HEPATIC GLUCONEOGENESIS; MITOCHONDRIAL BIOGENESIS; GENE-EXPRESSION; GLUCOSE; SECRETION; GLUCOKINASE; DYSFUNCTION AB beta cell dysfunction is an important component of type 2 diabetes, but the molecular basis for this defect is poorly understood. The transcriptional coactivator PGC-1alpha mRNA and protein levels are significantly elevated in islets from multiple animal models of diabetes; adenovirus-mediated expression of PGC-1alpha to levels similar to those present in diabetic rodents produces a marked inhibition of glucose-stimulated insulin secretion from islets in culture and in live mice. This inhibition coincides with changes in metabolic gene expression associated with impaired P cell function, including the induction of glucose-8-phosphatase and suppression of GLUT2, glucokinase, and glycerol-3-phosphate dehydrogenase. These changes result in blunting of the glucose-induced rise in cellular ATP levels and membrane electrical activity responsible for Ca2+ influx and insulin exocytosis. These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Obes Res Ctr, Boston, MA 02118 USA. Karolinska Inst, Dept Mol Med, Rolf Luft Ctr Diabet Res, SE-17176 Stockholm, Sweden. Duke Univ, Med Ctr, Sarah W Stedman Ctr Nutr Studies, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK58508, DK61562] NR 44 TC 95 Z9 103 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUL PY 2003 VL 5 IS 1 BP 73 EP 83 DI 10.1016/S1534-5807(03)00170-9 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 700MB UT WOS:000184114800011 PM 12852853 ER PT J AU Noguchi, H Kaneto, H Weir, GC Bonner-Weir, S AF Noguchi, H Kaneto, H Weir, GC Bonner-Weir, S TI PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells SO DIABETES LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; INSULIN GENE; HOMEOBOX FACTOR; EXPRESSION; DELIVERY; DIFFERENTIATION; HYPERGLYCEMIA; DUODENUM; ELEMENTS; GLUCOSE AB The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK61251, DK36836, DK44523] NR 23 TC 153 Z9 162 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 JUL PY 2003 VL 52 IS 7 BP 1732 EP 1737 DI 10.2337/diabetes.52.7.1732 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 695PF UT WOS:000183838900021 PM 12829640 ER PT J AU Nelson, KM Boyko, EJ AF Nelson, KM Boyko, EJ TI Predicting impaired glucose tolerance using common clinical information - Data from the Third National Health and Nutrition Examination Survey SO DIABETES CARE LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Diabetes-Association CY JUN 13-17, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Diabetes Assoc ID DIABETES-MELLITUS; FASTING GLUCOSE; CARDIOVASCULAR-DISEASE; RISK-FACTOR; LIFE-STYLE; US ADULTS; INDIVIDUALS; PREVENTION; PREVALENCE; OBESITY AB OBJECTIVE - To develop a score to predict impaired glucose tolerance (IGT) using common clinical data. RESEARCH DESIGN AND METHODS - We analyzed data from the Third National Health and Nutrition Examination Survey (NHANES 111) for 2,746 individuals aged 40-74 years who completed an oral glucose tolerance test. IGT was defined as a 2-h postchallenge glucose greater than or equal to140 mg/dl (7.7 mmol/l). We performed bivariate and multivariate analyses to describe the association of IGT with commonly available clinical information. A numerical score to predict IGT was derived from the results of the multivariate logistic regression models. RESULTS - Fasting glucose levels between 101 and 109 mg/dl (5.6 and 6.0 mmol/l) or between 110 and 125 mg/dl (6.1 and 6.9 mmol/l) were associated with IGT (odds ratio 1.8 and 6.2, respectively; P < 0.05). BMI greater than or equal to25 kg/m(2), Mexican-American ethnicity, age between 60 and 74 years, hypertension, and triglyceride level greater than or equal to150 mg/dl (1.69 mmol/l) were also associated with IGT. The area under the receiver operating characteristic curve for an 8-point scale derive from the multivariate analysis was 0.74 (95% CI 0.72-0.76). Setting a low cut point of 2 on this scale resulted in high sensitivity (86%), whereas a high cut point of 6 yielded high specificity (97%) for the detection of IGT. CONCLUSIONS - A numerical score based on common clinical data can identify individuals with a low or high likelihood of having IGT. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 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 98108 USA. NR 26 TC 28 Z9 29 U1 0 U2 0 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 JUL PY 2003 VL 26 IS 7 BP 2058 EP 2062 DI 10.2337/diacare.26.7.2058 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729RK UT WOS:000185787600019 PM 12832313 ER PT J AU Hamdy, O Ledbury, S Mullooly, C Jarema, C Porter, S Ovalle, K Moussa, A Caselli, A Caballero, AE Economides, PA Veves, A Horton, ES AF Hamdy, O Ledbury, S Mullooly, C Jarema, C Porter, S Ovalle, K Moussa, A Caselli, A Caballero, AE Economides, PA Veves, A Horton, ES TI Lifestyle modification improves endothelial function in obese subjects with the insulin resistance syndrome SO DIABETES CARE LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; WEIGHT-LOSS; METABOLIC SYNDROME; DIABETES-MELLITUS; EXERCISE; DISEASE; ARTERY; MEN; VASODILATION; RISK AB OBJECTIVE - Endothelial. dysfunction has been reported in type 2 diabetic patients and in obese subjects with insulin resistance syndrome (IRS). This study evaluates the effects of weight reduction and exercise on vascular reactivity of the macro- and the microcirculation in obese subjects with IRS. RESEARCH DESIGN AND METHODS - We studied 24 obese subjects (9 men and 15 women, age 49.3 +/- 1.9 years, BMI 36.7 +/- 0.94 kg/m(2), mean +/- SEM) with IRS at baseline and after 6 months of weight reduction and exercise. Brachial artery flow-mediated dilation (FMD) and response to sublingual glyceryltrinitrate (GTN) were assessed by high-resolution ultrasound. Microvascular reactivity was evaluated by the laser-Doppler perfusion imaging after iontophoresis of acetylcholine and sodium nitroprusside. We also measured plasma levels of soluble intercellular adhesion molecule (sICAM), vascular adhesion molecule, voir Willebrand factor, plasminogen activator inhibitor-1 (PAI-1) antigen, and tissue plasminogen activator antigen. RESULTS - This intervention resulted in 6.6 +/- 1% reduction in body weight (P < 0.001) and significant improvement of insulin sensitivity index (2.9 +/- 0.36 vs. 1.9 +/- 0.33 if [10(-4) . min(-1) . (muU ml(-1))], P < 0.001). FMD significantly improved (12.9 +/- 1.2% vs. 7.9 +/- 1.0%, P < 0.001), whereas response to GTN and microvascular reactivity did not change. Similar observations were seen when the subjects were subclassified according to their glucose tolerance to normal glucose tolerance, impaired glucose tolerance, and type 2 diabetes. sICAM and PAI-1 significantly decreased (251.3 +/- 7.7 vs. 265.6 +/- 9.3 ng/ml,P = 0.018 and 36.2 +/- 3.6 vs. 48.6 +/- 3.9 ng/ml, P = 0.001, respectively). The relationship between percentage weight reduction and improved FMD was linear (R-2 = 0.47, P = 0.001). CONCLUSIONS - We conclude that 6 months of weight reduction and exercise improve macrovascular endothelial function and reduces selective markers of endothelial activation and coagulation in obese subjects with IRS regardless of the degree of glucose tolerance. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Clin Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Microcirculat Lab, Boston, MA USA. RP Hamdy, O (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Clin Res Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [RR-01032] NR 33 TC 195 Z9 200 U1 1 U2 9 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 JUL PY 2003 VL 26 IS 7 BP 2119 EP 2125 DI 10.2337/diacare.26.7.2119 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 729RK UT WOS:000185787600029 PM 12832323 ER PT J AU Carvalho, E AF Carvalho, E TI EFSD/Eli Lilly research fellowship in diabetes & metabolism SO DIABETOLOGIA LA English DT Article ID ADIPOSE-TISSUE; INSULIN-RESISTANCE; OBESITY; MELLITUS; MUSCLE; MICE; GENE C1 BIDMC, Boston, MA USA. Harvard Med Sch, Boston, MA USA. RP Carvalho, E (reprint author), BIDMC, Boston, MA USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JUL PY 2003 VL 46 IS 7 BP R43 EP R45 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 709VB UT WOS:000184644300001 ER PT J AU Hur, C Nishioka, NS Gazelle, GS AF Hur, C Nishioka, NS Gazelle, GS TI Cost-effectiveness of photodynamic therapy for treatment of Barrett's esophagus with high grade dysplasia SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Barrett's esophagus; esophageal adenocarcinoma; endoscopy/photodynamic therapy; esophagectomy; cost-benefit analysis; clinical decision support systems ID GASTROESOPHAGEAL REFLUX; HOSPITAL VOLUME; UNITED-STATES; FOLLOW-UP; CANCER; ADENOCARCINOMA; ESOPHAGECTOMY; SURVEILLANCE; MANAGEMENT; CARCINOMA AB The purpose of this study was to compare the effectiveness and cost-effectiveness of photodynamic therapy (PDT) versus surgical esophagectomy and intensive endoscopic surveillance for patients with Barrett's esophagus and high-grade dysplasia (HGD) who are operative candidates. The results of our Markov Monte Carlo model show that PDT increased life expectancy by 1.8 years and quality-adjusted life expectancy (QALE) by 1.65 years when compared to the surveillance strategy. Relative to the esophagectomy strategy, PDT resulted in a greater life expectancy by 0.8 years and 2.17 additional quality-adjusted life years (QALYs). Although PDT cost $20,400 and $7,100 more than surveillance and esophagectomy respectively, the resulting incremental cost-effective ratios (ICERs) of $12,400/QALY and $3,300/QALY are within commonly accepted values. These findings were sensitive to the value assigned to the quality of life after PDT, but only at unrealistic values. In conclusion, PDT increases life expectancy and is cost-effective when compared to endoscopic surveillance and surgical esophagectomy. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Hur, C (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 0 Emerson Pl,Suite 2H, Boston, MA 02114 USA. NR 41 TC 51 Z9 53 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUL PY 2003 VL 48 IS 7 BP 1273 EP 1283 DI 10.1023/A:1024146823549 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 689DK UT WOS:000183476200011 PM 12870783 ER PT J AU Cuevas, BD Abell, AN Witowsky, JA Yujiri, T Johnson, NL Kesavan, K Ware, M Jones, PL Weed, SA DeBiasi, RL Oka, Y Tyler, KL Johnson, GL AF Cuevas, BD Abell, AN Witowsky, JA Yujiri, T Johnson, NL Kesavan, K Ware, M Jones, PL Weed, SA DeBiasi, RL Oka, Y Tyler, KL Johnson, GL TI MEKK1 regulates calpain-dependent proteolysis of focal adhesion proteins for rear-end detachment of migrating fibroblasts SO EMBO JOURNAL LA English DT Article DE calpain; MEKK1; rear-end detachment ID EPIDERMAL-GROWTH-FACTOR; CELL-MIGRATION; GENE DISRUPTION; ERK/MAP KINASE; ACTIVATION; ACTIN; CYTOSKELETON; FIBRONECTIN; INTERACTS; CLEAVAGE AB Herein, we define how MEKK1, a MAPK kinase kinase, regulates cell migration. MEKK1 is associated with actin fibers and focal adhesions, localizing MEKK1 to sites critical in the control of cell adhesion and migration. EGF-induced ERK1/2 activation and chemotaxis are inhibited in MEKK1-/- fibroblasts. MEKK1 deficiency causes loss of vinculin in focal adhesions of migrating cells, increased cell adhesion and impeded rear-end detachment. MEKK1 is required for activation of the cysteine protease calpain and cleavage of spectrin and talin, proteins linking focal adhesions to the cytoskeleton. Inhibition of ERK1/2 or calpain, but not of JNK, mimics MEKK1 deficiency. Therefore, MEKK1 regulates calpain-mediated substratum release of migrating fibroblasts. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Cell & Struct Biol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Craniofacial Biol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Yamaguchi Univ Med, Dept Internal Med 3, Yamaguchi, Japan. RP Cuevas, BD (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 38 TC 86 Z9 90 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 1 PY 2003 VL 22 IS 13 BP 3346 EP 3355 DI 10.1093/emboj/cdg322 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 697QD UT WOS:000183954000014 PM 12839996 ER PT J AU Yildiz, A Sachs, GS Turgay, A AF Yildiz, A Sachs, GS Turgay, A TI Pharmacological management of agitation in emergency settings SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID DOUBLE-BLIND; RAPID TRANQUILIZATION; INTRAMUSCULAR HALOPERIDOL; PSYCHOTIC AGITATION; LORAZEPAM; EFFICACY; OLANZAPINE; SYMPTOMS; PATIENT; SCHIZOPHRENIA AB Objective: To review, firstly, published studies comparing classic antipsychotics, benzodiazepines, and/or combination of both; and secondly, available data on the use of atypical antipsychotic medications in controlling agitation and aggressive behaviour seen in psychiatric patients in emergency. Method: In the first review, studies comparing antipsychotics, benzodiazepines, and combination of both; and in the second review, efficacy trials of atypical antipsychotics that include an active and/or inactive comparator for the treatment of acute agitation were identified and reviewed. Data from clinical trials meeting the inclusion criteria were summarised by recording improvement rates, definition of improvement, and timing of defined improvement for individual studies. Results: In the first review, 11 trials were identified meeting the inclusion criteria, eight with a blind design. The total number of subjects was 701. These studies taken together suggest that combination treatment may be superior to the either agent alone with higher improvement rates and lower incidence of extrapyramidal side effects. In the review of atypical antipsychotic agents as acute antiagitation compounds, five studies were identified, three with a blind design. The total number of subjects was 711, of which 15% (104) was assigned to the placebo arm. This review found atypical antipsychotics to be as effective as the classic ones and more advantageous in many aspects. Conclusion: Atypical antipsychotics such as risperidone, ziprasidone, and olanzapine with or without benzodiazepines should be considered first in the treatment of acute agitation. If these agents are not available the combination of a classic antipsychotic and a benzodiazepine would be a reasonable alternative. An oral treatment should always be offered first for building up an alliance with the patient and suggesting an internal rather than external locus of control. C1 Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Program, Boston, MA USA. Univ Toronto, Scarborough Hosp, Toronto, ON, Canada. RP Yildiz, A (reprint author), 9109 Sokak No 12-6 Halil Nevzat Sen,Apt PK35370, Izmir, Turkey. NR 42 TC 51 Z9 54 U1 2 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 J9 EMERG MED J JI Emerg. Med. J. PD JUL PY 2003 VL 20 IS 4 BP 339 EP 346 DI 10.1136/emj.20.4.339 PG 8 WC Emergency Medicine SC Emergency Medicine GA 696JK UT WOS:000183883700010 PM 12835344 ER PT J AU Puchalski, SS Green, JN Rasmussen, DD AF Puchalski, SS Green, JN Rasmussen, DD TI Melatonin effect on rat body weight regulation in response to high-fat diet at middle age SO ENDOCRINE LA English DT Article DE melatonin; high-fat diet; body weight; leptin; insulin; visceral fat ID PLASMA LEPTIN; VISCERAL FAT; FOOD-INTAKE; INSULIN; ADIPOSITY; ADIPOCYTES; HUMANS AB We previously demonstrated that daily melatonin administration to middle-aged rats to restore youthful plasma melatonin levels also decreased body weight, visceral fat, plasma leptin, and plasma insulin to more youthful levels, without detectable changes in consumption of chow diet. We now evaluate: (a) whether melatonin alters consumption of a more precisely quantifiable liquid diet similar in high-fat content to the typical American diet; (b) differences between melatonin-induced endocrine responses in the fasted vs fed state; and (c) time course of these responses. Ten-month-old male Sprague-Dawley rats received liquid diet containing either 0.2 mug/mL melatonin (MELATONIN) or vehicle (CONTROL) (n = 14/treatment); the diet was available throughout each night, but was removed for the final 10 h of each daytime. MELATONIN rats gained 4% body weight during the first 2 wk and then stabilized, whereas CONTROL rats continued to gain for an additional week, achieving 8% gain (p < 0.05 vs MELATONIN). During the first 3 wk, afternoon tail-blood leptin, but not insulin, levels decreased in melatonin-treated rats (p < 0.05 vs CONTROL). After 8 wk, half of the rats were killed at the midpoint of the dark period (NIGHT; fed) and half at the end of the light period (DAYTIME; fasted). NIGHT but not DAYTIME plasma leptin levels were decreased in MELATONIN rats, whereas DAYTIME but not NIGHT plasma insulin levels were decreased (p < 0.05 vs CONTROL). Melatonin treatment did not alter cumulative food consumption. Thus, melatonin decreased weight gain in response to high-fat diet, decreased plasma leptin levels within 3 wk-before decreasing plasma insulin-and exerted these metabolic effects independent of total food consumption. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res, Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res, Educ & Clin Ctr, S-116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [AA10567] NR 24 TC 35 Z9 35 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD JUL PY 2003 VL 21 IS 2 BP 163 EP 167 DI 10.1385/ENDO:21:2:163 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 707QN UT WOS:000184521500010 PM 12897381 ER PT J AU Puchalski, SS Green, JN Rasmussen, DD AF Puchalski, SS Green, JN Rasmussen, DD TI Melatonin effects on metabolism independent of gonad function SO ENDOCRINE LA English DT Article DE melatonin; testosterone; gonadal steroids; visceral fat; leptin; insulin ID IODOMELATONIN BINDING-SITES; FEMALE RAT-BRAIN; PLASMA LEPTIN; LONG-TERM; SECRETION; INSULIN; IMPACT; WEIGHT; FAT; MEN AB We previously demonstrated that daily melatonin administration to middle-aged rats, restoring nocturnal plasma melatonin to young adult levels, decreased body weight and suppressed visceral fat and plasma leptin. In some species, metabolic and some neuronal responses to melatonin are mediated or dependent at least in part on gonadal steroid levels. Thus, melatonin-induced changes in gonadal steroid secretion may have mediated the aging-dependent melatonin-induced metabolic responses in our previous studies. To address this issue, melatonin (0.4 mug/mL) or vehicle (0.01% ethanol) was administered for 10 wk in the drinking water of both castrate and sham-operated Sprague-Dawley male rats, starting 1 mo after surgery at 9 mo of age. Melatonin treatment decreased (p < 0.05) body weight in sham-operated rats by 7 +/- 2% relative to control (n = 7/treatment), comparable to our previous results; melatonin likewise decreased (p < 0.05) body weight in castrate rats by 6 2% relative to control (n = 7/treatment). Melatonin treatment also decreased both intraabdominal fat and plasma leptin levels in both intact and castrate rats, with no significant differences of percentage suppression in the intact versus castrate rats. These results demonstrate that suppression of body weight, visceral adiposity, and plasma leptin levels by daily melatonin administration to middle-aged rats was independent of gonadal function. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat, Seattle, WA USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [AA10567] NR 27 TC 9 Z9 9 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD JUL PY 2003 VL 21 IS 2 BP 169 EP 173 DI 10.1385/ENDO:21:2:169 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 707QN UT WOS:000184521500011 PM 12897382 ER PT J AU Williams, DL Cummings, DE Grill, HJ Kaplan, JM AF Williams, DL Cummings, DE Grill, HJ Kaplan, JM TI Meal-related ghrelin suppression requires postgastric feedback SO ENDOCRINOLOGY LA English DT Article ID ACYLATED PEPTIDE; STOMACH; SECRETION; HUMANS; CELLS; RATS AB Plasma ghrelin levels are rapidly suppressed by ingestion or gastric delivery of nutrients. Given that the majority of circulating ghrelin appears to be of gastric origin, we addressed the contribution of gastric distention or nutrient sensitivity to this response. Awake, unrestrained rats received intragastric infusions of glucose or water (1 ml/min for 12 min) with gastric emptying either proceeding normally or prevented by inflation of a pyloric cuff. When emptying was permitted, glucose infusion reduced ghrelin level by approximately 50%, and, in agreement with previous data, water infusions were without effect. Ghrelin level was not affected by either infusate when gastric emptying was prevented, thereby discounting a role for gastric distention in the meal-related ghrelin response. That glucose and water infusions were similarly ineffective when the pylorus was occluded shows, further, that gastric chemosensation is not a sufficient trigger for the ghrelin response. We conclude that the meal-related suppression of plasma ghrelin requires postgastric (pre- or postabsorptive) stimulation. C1 Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Williams, DL (reprint author), Univ Penn, Dept Psychol, 3815 Walnut St, Philadelphia, PA 19104 USA. RI Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK 21397, DK 42284, DK 61516] NR 16 TC 131 Z9 132 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2003 VL 144 IS 7 BP 2765 EP 2767 DI 10.1210/en.2003-0381 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 690KL UT WOS:000183547800003 PM 12810528 ER PT J AU Leupen, SM Tobet, SA Crowley, WF Kaila, K AF Leupen, SM Tobet, SA Crowley, WF Kaila, K TI Heterogeneous expression of the potassium-chloride cotransporter KCC2 in gonadotropin-releasing hormone neurons of the adult mouse SO ENDOCRINOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; K-CL COTRANSPORTER; GNRH NEURONS; GENE-EXPRESSION; NERVOUS-SYSTEM; FEMALE RATS; AMINO-ACIDS; GABA; SECRETION; MATURATION AB In mature central neurons, chloride extrusion mediated by the K-Cl cotransporter KCC2 appears to be largely responsible for the Cl- driving force that allows gamma-aminobutyric acid(A) (GABA(A)) receptor activation to trigger a hyperpolarization. In its absence, GABA's effect is typically depolarizing and often excitatory. We examined the colocalization of KCC2 and GnRH in adult male and female mice using a combined in situ hybridization-immunofluorescence procedure. We found that KCC2 was localized to approximately 34% of GnRH neurons. This proportion was similar in females and males. However, females exhibited a marked rostrocaudal gradient of colocalization that was not seen in males. By contrast, KCC2 was localized to nearly all vasopressin neurons of the supraoptic nucleus. These results indicate that a substantial fraction of GnRH neurons may be depolarized and excited by GABA(A) receptor activation throughout life, supporting the existence of functionally heterogeneous subpopulations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Biochem, Boston, MA 02114 USA. Univ Helsinki, Dept Biosci, SF-00014 Helsinki, Finland. RP Leupen, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, BHX-519,55 Fruit St, Boston, MA 02114 USA. RI Kaila, Kai/R-8528-2016; OI Kaila, Kai/0000-0003-0668-5955; Tobet, Stuart/0000-0002-1615-7331 FU NICHD NIH HHS [HD 08630-02, HD 33441]; NIMH NIH HHS [MH 57748] NR 40 TC 26 Z9 26 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2003 VL 144 IS 7 BP 3031 EP 3036 DI 10.1210/en.2002-220995 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 690KL UT WOS:000183547800036 PM 12810559 ER PT J AU Duty, SM Singh, NP Silva, MJ Barr, DB Brock, JW Ryan, L Herrick, RF Christiani, DC Hauser, R AF Duty, SM Singh, NP Silva, MJ Barr, DB Brock, JW Ryan, L Herrick, RF Christiani, DC Hauser, R TI The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE comet assay; DNA damage; environmental; human sperm; phthalates; urinary metabolites ID HUMAN REFERENCE POPULATION; GEL-ELECTROPHORESIS ASSAY; CHROMATIN STRUCTURE ASSAY; DOUBLE-STRAND BREAKS; MUCOSAL CELLS; IN-VITRO; GENOTOXICITY; METABOLITES; ESTERS; REPRODUCIBILITY AB Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry;, data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 mum [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 mum (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Rm 1405,665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 OI Ryan, Louise/0000-0001-5957-2490; FU NIEHS NIH HHS [T32 ES07069, ES00002, ES09718] NR 47 TC 164 Z9 177 U1 3 U2 29 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 JUL PY 2003 VL 111 IS 9 BP 1164 EP 1169 DI 10.1289/ehp.5756 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 715VH UT WOS:000184992700025 PM 12842768 ER PT J AU Bucurescu, G Stieritz, DD AF Bucurescu, G Stieritz, DD TI Evidence of an association between Chlamydia pneumoniae and cerebrovascular accidents SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE cerebrovascular accidents; Chlamydia pneumoniae; stroke ID CAROTID-ARTERY; DISEASE; ANTIBODIES; STROKE; RISK; INFECTION; ASSAYS AB The authors report results of a retrospective pilot study showing a strong association between patients with stroke/TIA and the presence of circulating IgG and IgA antibodies to Chlamydia pneumoniae. These results support the hypothesis that chronic active or persistent infection may play a role in the mechanism of thrombosis. The risk for stroke associated with Chlamydial circulating antibodies appeared to be independent of other risk factors such as diabetes and hypercholesterolemia. C1 Vet Affairs Med Ctr, Neurol Serv, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Pathol & Lab Med Serv, Philadelphia, PA 19104 USA. RP Bucurescu, G (reprint author), Vet Affairs Med Ctr, Neurol Serv, Woodland & Univ Ave, Philadelphia, PA 19104 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2003 VL 10 IS 4 BP 449 EP 452 DI 10.1046/j.1468-1331.2003.00605.x PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 692YD UT WOS:000183687100017 PM 12823500 ER PT J AU Pasquinelli, AE McCoy, A Jimenez, E Salo, E Ruvkun, G Martindale, MQ Baguna, J AF Pasquinelli, AE McCoy, A Jimenez, E Salo, E Ruvkun, G Martindale, MQ Baguna, J TI Expression of the 22 nucleotide let-7 heterochronic RNA throughout the Metazoa: a role in life history evolution? SO EVOLUTION & DEVELOPMENT LA English DT Article ID 18S RDNA SEQUENCES; REGULATORY RNA; CAENORHABDITIS-ELEGANS/; DEVELOPMENTAL PROGRAM; HOX GENES; PLATYHELMINTHES; MORPHOLOGY; MICRORNAS; IDENTIFICATION; CHAETOGNATHA AB The 22 nucleotide let-7 small temporal RNA has been found consistently in samples from diverse bilateria but not from sponge or cnidarians. Here we further examine the phylogenetic distribution of this regulatory RNA by sampling representatives of diverse metazoan lineages. The 22 nucleotide let-7 RNA is detectable in triclad and polyclad platyhelminths, nemertean, and chaetognath but not ctenophore or acoel metazoans. These results support recent arguments that acoels are distinct from other acoelomate platyhelminths. We argue that let-7 is not a bilaterian or triploblast synapomorphy but instead evolved later in metazoan evolution, perhaps in association with complex life history traits. C1 Univ Calif San Diego, Div Biol 0368, Mol Biol Sect, La Jolla, CA 92093 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Biol Lab, Cambridge, MA 02138 USA. Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Spain. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Hawaii, Kewalo Marine Lab, Honolulu, HI 96813 USA. RP Pasquinelli, AE (reprint author), Univ Calif San Diego, Div Biol 0368, Mol Biol Sect, 9500 Gilman Dr,Bonner Hall,Room 2214, La Jolla, CA 92093 USA. RI Salo, Emili/M-3928-2014; OI Salo, Emili/0000-0001-5460-9223; jimenez-guri, eva/0000-0002-9592-1077 NR 37 TC 73 Z9 76 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1520-541X J9 EVOL DEV JI Evol. Dev. PD JUL-AUG PY 2003 VL 5 IS 4 BP 372 EP 378 DI 10.1046/j.1525-142X.2003.03044.x PG 7 WC Evolutionary Biology; Developmental Biology; Genetics & Heredity SC Evolutionary Biology; Developmental Biology; Genetics & Heredity GA 694VY UT WOS:000183796900005 PM 12823453 ER PT J AU Van Remmen, H Hamilton, ML Richardson, A AF Van Remmen, H Hamilton, ML Richardson, A TI Oxidative damage to DNA and aging SO EXERCISE AND SPORT SCIENCES REVIEWS LA English DT Review DE mitochondrial DNA; nuclear DNA; exercise; dietary restriction; oxidative stress ID CALORIC RESTRICTION; 8-HYDROXYDEOXYGUANOSINE; EXERCISE; NUCLEAR; STRESS; REPAIR AB Oxidative damage to DNA increases with age in several tissues and animal models, and mitochondrial DNA has a higher level of oxidative damage than nuclear DNA. Dietary restriction extends lifespan and is associated with reduced levels of damage to mitochondrial and nuclear DNA. The effect of exercise on DNA damage appears to be related to the intensity of the exercise. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Van Remmen, H (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, GRECC 182, 7400 Merton Mintoe Blvd, San Antonio, TX 78229 USA. FU NIA NIH HHS [1PO1-AG20591, 1PO1-AG14674] NR 15 TC 33 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0091-6331 J9 EXERC SPORT SCI REV JI Exerc. Sport Sci. Rev. PD JUL PY 2003 VL 31 IS 3 BP 149 EP 153 DI 10.1097/00003677-200307000-00009 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 702KD UT WOS:000184222300009 PM 12882482 ER PT J AU Morioka, H Morii, T Vogel, T Hornicek, FJ Weissbach, L AF Morioka, H Morii, T Vogel, T Hornicek, FJ Weissbach, L TI Interaction of plasminogen-related protein B with endothelial and smooth muscle cells in vitro SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE plasminogen-related protein B; antiangiogenesis; endothelial cell; mural cell; basic fibroblast growth factor ID BLOOD-VESSEL FORMATION; P38 MAP KINASE; GROWTH-FACTOR; TUMOR-GROWTH; CELLULAR INVASION; FOCAL ADHESIONS; CANCER-CELLS; TGF-BETA; ANGIOGENESIS; ANGIOSTATIN AB Plasminogen-related protein B (PRP-B) closely resembles the N-terminal plasminogen activation peptide, which is released from plasminogen during conversion to plasmin. We have previously demonstrated that the steady-state level of mRNA encoding PRP-B is increased within tumor tissues, and that recombinant PRP-B antagonizes neoplastic growth when administered systemically to mice harboring tumors, but no insights into the cell targets of PRP-B have been presented. Employing serum-free medium optimized for culturing human endothelial or smooth muscle cells, we show that recombinant PRP-B inhibits basic fibroblast growth factor-dependent cell migration for both cell types, as well as tube formation of endothelial cells. Comparison with the angiogenesis inhibitors angiostatin and endostatin revealed similar results. Recombinant PRP-B is effective in promoting cell attachment of endothelial and smooth muscle cells, and antibody interference experiments reveal that the interaction of recombinant PRP-B with endothelial cells is mediated at least in part by alpha(v)-containing integrins. Inhibition of angiogenesis in vivo by PRP-B was demonstrated in the chicken chorioallantoic membrane assay. PRP-B and other antiangiogenic molecules may elicit metabolic perturbations in endothelial cells as well as perivascular mesenchymal cells such as smooth muscle cells and pericytes. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Kiryat Weizmann, Biotechnol Gen, IL-76326 Rehovot, Israel. RP Weissbach, L (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, GRJ 1124,55 Fruit St, Boston, MA 02114 USA. EM Lweissbach@partners.org NR 68 TC 5 Z9 6 U1 0 U2 4 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2003 VL 287 IS 1 BP 166 EP 177 DI 10.1016/S0014-4827(03)00137-X PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 692XC UT WOS:000183684700017 PM 12799192 ER PT J AU Kishi, S Uchiyama, J Baughman, AM Goto, T Lin, MC Tsai, SB AF Kishi, S Uchiyama, J Baughman, AM Goto, T Lin, MC Tsai, SB TI The zebrafish as a vertebrate model of functional aging and very gradual senescence SO EXPERIMENTAL GERONTOLOGY LA English DT Article; Proceedings Paper CT 2nd Symposium on Organisms with Slow Aging (SOSA-2) CY JAN 17-18, 2003 CL UNIV SOUTHERN CALIFRONIA, LOS ANGELES, CALIFORNIA HO UNIV SOUTHERN CALIFRONIA DE zebrafish; aging; senescence; stress; indeterminate growth; telomerase; telomere ID GUPPY POECILIA-RETICULATA; SIAMESE FIGHTING FISH; TELOMERASE ACTIVITY; LEBISTES-RETICULATUS; PROTEIN OXIDATION; ORYZIAS-LATIPES; IN-VIVO; LIPID-PEROXIDATION; BETTA-SPLENDENS; DNA-DAMAGE AB The zebratish (Danio rerio) has been developed as a powerful model for genetic studies in developmental biology, which also gives insights into several diseases of adult humans such as cardiovascular disease and cancer. Because aging processes affect these and many other human diseases, it is important to compare zebrafish and other mammalian aging. However, the aging process of zebrafish remains largely unexplored, and little is known about its functional aging and senescence. In a survey of aging in zebrafish, we detected senescence-associated beta-galactosidase activity in skin and oxidized protein accumulation in muscle. However, we did not observe lipofuscin granules ('aging pigments'), which commonly accumulate in postmitotic cells of other vertebrates. This absence of lipofuscins may be consistent with the existence of continuously proliferating myocytes that incorporated BrdU in muscle tissues of aged zebrafish. Moreover, we demonstrated that zebrafish have constitutively abundant telomerase activity in somatic tissues from embryos to aged adults. Although some stress-associated markers are upregulated and minor histological changes are observed during the aging process of zebrafish, our studies together with other evidence of remarkable reproductive and regenerative abilities suggest that zebrafish show very gradual or sub-negligible senescence in vivo. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kishi, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 72 TC 91 Z9 93 U1 0 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL PY 2003 VL 38 IS 7 BP 777 EP 786 DI 10.1016/S0531-5565(03)00108-6 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 706KG UT WOS:000184452400013 PM 12855287 ER EF