FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bilezikian, JP Potts, JT AF Bilezikian, JP Potts, JT TI Asymptomatic primary hyperparathyroidism: New issues and new questions - Bridging the past with the future SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Asymptomatic Primary Hyperparathyroidism CY APR 08-09, 2002 CL NIH, BETHESDA, MARYLAND HO NIH ID BONE-MINERAL DENSITY; MILD PRIMARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE 1-34; POSTMENOPAUSAL WOMEN; FOLLOW-UP; SERUM-CALCIUM; CARDIAC ABNORMALITIES; LONGITUDINAL CHANGES; MENOPAUSAL WOMEN; HEALTH SURVEY C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bilezikian, JP (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. FU NIDDK NIH HHS [R01 DK032333] NR 89 TC 40 Z9 41 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 NOV PY 2002 VL 17 SU 2 BP N57 EP N67 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500010 PM 12412779 ER PT J AU Bilezikian, JP Potts, JT AF Bilezikian, JP Potts, JT TI Niddk Workshop Program Asymptomatic Primary Hyperparathyroidism - A Perspective for the 21(st) Century - Natcher Conference Center - NIH, Bethesda, Maryland, April 8-9, 2002 - Introduction SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bilezikian, JP (reprint author), Columbia Univ Coll Phys & Surg, 630 W 168th St, New York, NY 10032 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2002 VL 17 SU 2 BP N1 EP N1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500001 ER PT J AU Bilezikian, JP Potts, JT El-Hajj Fuleihan, G Kleerekoper, M Neer, R Peacock, M Rastad, J Silverberg, SJ Udelsman, R Wells, SA AF Bilezikian, JP Potts, JT El-Hajj Fuleihan, G Kleerekoper, M Neer, R Peacock, M Rastad, J Silverberg, SJ Udelsman, R Wells, SA TI Summary statement from a Workshop on Asymptomatic Primary Hyperparathyroidism: A perspective for the 21st century SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Editorial Material C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Amer Univ Beirut, Med Ctr, Dept Med, Beirut, Lebanon. Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Univ Hosp, Dept Surg, Uppsala, Sweden. Yale Univ, Sch Med, Yale New Haven Hosp, Dept Surg, New Haven, CT USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA. FU NIDDK NIH HHS [R01 DK032333] NR 0 TC 135 Z9 140 U1 0 U2 1 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2002 VL 17 SU 2 BP N2 EP N11 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500002 PM 12412771 ER PT J AU Juppner, H Potts, JT AF Juppner, H Potts, JT TI Immunoassays for the detection of parathyroid hormone SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Asymptomatic Primary Hyperparathyroidism CY APR 08-09, 2002 CL NIH, BETHESDA, MARYLAND HO NIH ID CARBOXYL-TERMINAL REGION; IMMUNORADIOMETRIC ASSAY; RENAL-FAILURE; BONE-DISEASE; PTH; FRAGMENTS; BINDING; CELLS; SPECIFICITY; PTH-(1-84) AB Biologically active parathyroid hormone (PTH) in humans with normal renal function circulates predominantly as an 84 amino acid peptide. PTH fragments of varying length arise either from metabolism of the intact hormone within the parathyroid glands or in peripheral tissues, such as liver, and the resulting carboxyl-terminal peptides are eliminated mainly by glomerular filtration and subsequent tubular degradation. Most of the initially raised anti-PTH antisera were directed against epitopes within the mid- or carboxyl-terminal regions of the hormone. These antibodies were used for the development of conventional, displacement-type radioimmunoassays, but provided only an index of the biologically active PTH(1-84) in the circulation. Subsequently developed immunometric assays use two distinct antibodies, a capture antibody usually directed against a carboxyl-terminal portion of PTH(1-84) and a radio- or enzyme-labeled detection antibody usually directed against the amino-terminal portion of the hormone. Such assays were thought to detect largely, if not exclusively, intact PTH, thus providing the concentration of biologically active hormone in blood, which is especially important for establishing the diagnosis of hyperparathyroidism. However, serum samples from normal subjects and patients with primary or secondary hyperparathyroidism have demonstrated that most immunometric two-site sandwich assays detect, besides PTH(1-84), one or more recently discovered large carboxyl-terminal PTH fragments that lack a portion of the amino-terminal end of the molecule. Some of these amino-terminally truncated PTH molecules [ntPTH(1-84)] exhibit an elution profile on high performance liquid chromatography (HPLC) that is indistinguishable from that of synthetic PTH(784). Such peptides were previously thought to be of minimal if any biological activity, but recent studies have shown that synthetic PTH(7-84) has hypocalcemic properties in vivo and that it inhibits osteoclastic bone resorption and the formation of mature osteoclasts in vitro. It is currently unclear whether important differences in disease states can be revealed by comparing results obtained with older immunometric assays that measure the full-length hormone and ntPTH(1-84) versus newer assays that measure only PTH(1-84). Therefore, whereas most immunometric PTH assay systems are appropriate for the diagnosis of primary hyperparathyroidism, it is possible that immunometric assays designed to detect only PTH(1-84) will be more useful in certain diagnostic studies, for intraoperative PTH monitoring and for assessing the pulsatility of PTH secretion. In addition, the ability to distinguish between the relative concentrations of ntPTH(1-84) versus PTH(1-84) may reveal previously unsuspected roles for the ntPTH(1-84) fragments in the pathophysiology of patients with end-stage renal disease and/or other disorders involving parathyroid hormone. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. NR 32 TC 21 Z9 24 U1 0 U2 3 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 NOV PY 2002 VL 17 SU 2 BP N81 EP N86 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 609BV UT WOS:000178883500013 PM 12412782 ER PT J AU Gatinel, DM Hoang-Xuan, T Azar, DT AF Gatinel, DM Hoang-Xuan, T Azar, DT TI Three-dimensional representation and qualitative comparisons of the amount of tissue ablation to treat mixed and compound astigmatism SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IN-SITU KERATOMILEUSIS; EC-5000 EXCIMER-LASER; HYPEROPIC ASTIGMATISM; PHOTOREFRACTIVE KERATECTOMY AB Purpose: To compare the shape and volume of the lenticules of corneal tissue ablated for the correction of spherical, cylindrical, and spherocylindrical refractive errors using Boolean operations of theoretical 3-dimensional (3-D) surfaces. Setting. Department of Ophthalmology, Rothschild Foundation, Paris, France. Methods: Digital modeling software was used to perform graphic representations of ablated lenticules on 3-D virtual surfaces. Various Boolean operations were performed between different preoperative and postoperative surfaces, and the additional and subtractive properties of ablated theoretical lenticules were analyzed to determine profiles of ablated lenticules for mixed and compound myopic and hyperopic astigmatism. Results: Negative-cylindrical treatment, used to treat simple myopic astigmatism, was equivalent to the combination of a positive-cylindrical and a negative-spherical treatment of the same magnitude. Combining a pure negative-cylindrical and a positive-spherical treatment in a sequential strategy when treating compound astigmatism resulted in redundant ablation (piano lenticule), leading to an unnecessary increase in the amount of tissue ablation. Conclusions: Negative-cylindrical treatments result in greater tissue ablation than corresponding positive-cylindrical treatments. For any given compound astigmatic error, the strategy using the greater magnitude of positive cylinder incurs the minimal amount of tissue ablation. (C) 2002 ASCRS and ESCRS. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Rothschild Fdn, Paris, France. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2002 VL 28 IS 11 BP 2026 EP 2034 AR PII S0886-3350(02)01379-2 DI 10.1016/S0886-3350(02)01379-2 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 615WX UT WOS:000179271300029 PM 12457680 ER PT J AU Takagi, Y Harada, J Chiarugi, A Moskowitz, MA AF Takagi, Y Harada, J Chiarugi, A Moskowitz, MA TI STAT1 is activated in neurons after ischemia and contributes to ischemic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE STAT1; ischemia; neuron; Akt; caspase-3 ID FOCAL CEREBRAL-ISCHEMIA; IFN-GAMMA; SIGNALING PATHWAY; TARGETED DISRUPTION; INDUCED APOPTOSIS; JAK/STAT PATHWAY; EXPRESSION; SURVIVAL; MICE; PHOSPHORYLATION AB Signal transducers and activators of transcription (STAT) proteins are a family of transcription factors that play a crucial role in growth and differentiation in a variety of cell types. Among them, STAT1, which is expressed in the brain and directly activated by reactive oxygen species, participates in the regulation of cytokine-signaling and cellular responses, particularly to interferon-gamma. Very little, however, is known about the importance of STAT1 during brain injury. The authors found that STAT1 was phosphorylated at tyrosine(701) and serine(727) and translocated into neuronal nuclei within hours after middle cerebral artery occlusion. At later time points, STAT1 immunoreactivity colocalized with TUNEL-positive neurons, thereby suggesting a role in cell death. In mice genetically deficient in STAT1 expression, the volume of ischemic brain injury was reduced, neurologic deficits were less severe, and TUNEL-positive neurons were also less numerous compared with wild-type mice. STAT1-knockout mice showed increased phosphorylated Akt and decreased procaspase-3 cleavage. Major strain differences in phosphorylated STAT3 or cyclooxygenase-2 protein expression were not found after ischemia. These results indicate that STAT1 is activated and translocated within ischemic neurons and may contribute to brain injury by regulating transcription and phosphorylation of proteins related to apoptosis and cell death. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat,Neurosci C, Boston, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Stroke & Neurovasc Regulat,Neurosci C, 149 13th St,Room 6403, Boston, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [5 P50 NS10828] NR 39 TC 58 Z9 69 U1 0 U2 0 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 NOV PY 2002 VL 22 IS 11 BP 1311 EP 1318 DI 10.1097/01.WCB.0000034148.72481.F4 PG 8 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 611XK UT WOS:000179043000004 PM 12439288 ER PT J AU El-Serag, HB AF El-Serag, HB TI Hepatocellular carcinoma - An epidemiologic view SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT Yale University Workshop on Hepatocellular Carcinoma CY MAR 15-16, 2002 CL NEW HAVEN, CONNECTICUT SP Yale Sch Med DE hepatocellular carcinoma; epidemiology; hepatitis ID PRIMARY LIVER-CANCER; CHRONIC HEPATITIS-C; UNITED-STATES; DIABETES-MELLITUS; RISK-FACTORS; B VIRUS; CIRRHOSIS; PREVALENCE; ETIOLOGY; SURVIVAL AB Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and is estimated to cause approximately half a million deaths annually. Because of its high fatality rates, the incidence and mortality rates are almost equal. The major risk factors for HCC are chronic hepatitis B virus infection, chronic hepatitis C virus (HCV) infection, and alcoholic cirrhosis. The epidemiology of HCC is characterized by marked demographic (age, gender; race/ethnicity) and geographic variations. Hepatitis B virus infection, with and without aflatoxin exposure, is responsible for most cases in developing countries; better control of these risk factors has resulted in a recent decline in HCC in some places like Taiwan and China. Recently, however, a trend of rising rates of HCC has been reported from several developed countries in Europe and North America. These new trends are associated with ''new'' risk factors such as HCV and, possibly, diabetes. In the United States, the incidence of HCC has approximately doubled over the past 3 decades. White individuals are two to three times less often affected than African Americans, who in turn are two to three times less often affected than Asians, Pacific Islanders, or Native Americans. Men are two to three times more often affected than women. Concomitant with the rising rates of HCC, there has been a shift of incidence from typically elderly patients to relatively younger patients between ages of 40 to 60 years. An increase in HCV-related HCC accounts for at least half of the witnessed increase in HCC in the United States. Hepatocellular carcinoma continues to carry an overall dismal survival rate (close to 5%); very few patients qualify for and receive potentially curative therapy. The future incidence trends of HCC will be determined to a large extent by the clinical course of HCV-infected people. C1 Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr 152, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr 152, Gastroenterol Sect, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 38 TC 360 Z9 373 U1 1 U2 16 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 NOV-DEC PY 2002 VL 35 IS 5 SU 2 BP S72 EP S78 DI 10.1097/00004836-200211002-00002 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 614AT UT WOS:000179165200002 PM 12394209 ER PT J AU Lee, SK Xu, Z Lieberman, J Shankar, P AF Lee, SK Xu, Z Lieberman, J Shankar, P TI The functional CD8 T cell response to HIV becomes type-specific in progressive disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; PRIMARY IMMUNE-RESPONSE; LYMPHOCYTE RESPONSES; GENETIC-VARIATION; IMPAIRED FUNCTION; PLASMA VIREMIA; NEF PROTEIN; ESCAPE; RECOGNITION; CD4(+) AB High levels of HIV-specific CD8 T cells are demonstrable throughout HIV disease using laboratory assays that measure responses to consensus epitopes. in acute infection, the dynamics of the antiviral CD8 T cell response correlate well with the decline in viremia. However in chronic infection, although responses are detected against a broader spectrum of epitopes, virus-specific CD8 T cells are apparently unable to control viral replication. To investigate whether CD8 T cells responding to consensus epitopes may have lost their in vivo relevance in the chronic phase because of viral evolution driven by immune pressure, we compared the CD8 T cell response to CD4 T cell targets infected with either lab-adapted HIVIIIB or the patient's own virus. The magnitude of the IFN-gamma response declined with disease progression, especially to autologous virus. T cell receptor (TCR) clonotypes of HIVIIIB and autologous virus-responding cells were determined by sequencing TCR beta chain variable (TCRBV) genes. In two of three asymptomatic donors, the dominant clonotypes overlapped, whereas in five symptomatic patients, the TCR clonotypes responding to HIVIIIB virus were completely different from those responding to autologous virus. Moreover, in cytolytic assays, T cell lines derived from IFN-gamma(+) cells responding to lab-adapted or autologous virus cross-recognized target cells infected with either virus in asymptomatic subjects with shared TCR clonotypes but not in progressors with differing clonotypes. Therefore, in advanced-stage patients, viral-specific CD8 T cells recognizing consensus epitopes persist from an earlier response but no longer effectively recognize autologous virus. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Shankar, P (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-45306, AI-49792] NR 51 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2002 VL 110 IS 9 BP 1339 EP 1347 DI 10.1172/JCI200216028 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 612HW UT WOS:000179069500017 PM 12417573 ER PT J AU Manire, CA Rhinehart, HL Sutton, DA Thompson, EH Rinaldi, MG Buck, JD Jacobson, E AF Manire, CA Rhinehart, HL Sutton, DA Thompson, EH Rinaldi, MG Buck, JD Jacobson, E TI Disseminated mycotic infection caused by Colletotrichum acutatum in a Kemp's ridley sea turtle (Lepidochelys kempi) SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SUBCUTANEOUS ABSCESS; DRUG-INTERACTIONS; ITRACONAZOLE; RIFAMPIN; GLOEOSPORIOIDES; IDENTIFICATION; BREAKTHROUGH; ANTHRACNOSE; PROPHYLAXIS; FLORIDA AB Colletotrichum acutatum is a cosmopolitan plant pathogen with a wide host range. While the organism's phytopathogenic potential has been well documented, it has never been reported as an etiologic agent of disease in either animals or humans. In this case, a juvenile Kemp's ridley sea turtle, Lepidochelys kempi, probably with immune compromise following cold stunning (extended hypothermia), developed a disseminated mycotic infection in the lungs and kidneys. Prophylactic treatment with oral itraconazole did not prevent or cure the infection. This report of a Colletotrichum acutatum infection in an animal extends the range of disease caused by this organism beyond that of a phytopathogen. C1 Sea Turtle Rehabil Hosp, Mote Marine Lab & Aquarium, Sarasota, FL 34236 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Florida, Coll Vet Med, Dept Small Anim Clin Sci, Gainesville, FL 32610 USA. RP Manire, CA (reprint author), Sea Turtle Rehabil Hosp, Mote Marine Lab & Aquarium, 1600 Ken Thompson Pkwy, Sarasota, FL 34236 USA. NR 41 TC 19 Z9 21 U1 1 U2 3 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 NOV PY 2002 VL 40 IS 11 BP 4273 EP 4280 DI 10.1128/JCM.40.11.4273-4280.2002 PG 8 WC Microbiology SC Microbiology GA 612BH UT WOS:000179053200063 PM 12409409 ER PT J AU Rauck, PK Muriel, AC Cassem, NH AF Rauck, PK Muriel, AC Cassem, NH TI Parents with cancer: Who's looking after the children? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Rauck, PK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WACC 725,15 Parkman St, Boston, MA 02114 USA. NR 1 TC 24 Z9 24 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 NOV 1 PY 2002 VL 20 IS 21 BP 4399 EP 4402 PG 4 WC Oncology SC Oncology GA 610NP UT WOS:000178967000020 PM 12409342 ER PT J AU Noble, VE Nadel, ES Brown, DFM AF Noble, VE Nadel, ES Brown, DFM TI Change in mental status SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID EPILEPSY; PSYCHOSIS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 7 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 NOV PY 2002 VL 23 IS 4 BP 401 EP 403 AR PII S0736-4679(02)00602-9 DI 10.1016/S0736-4679(02)00602-9 PG 3 WC Emergency Medicine SC Emergency Medicine GA 624LP UT WOS:000179761400017 PM 12480023 ER PT J AU Orlander, JD Fincke, BG Hermanns, D Johnson, GA AF Orlander, JD Fincke, BG Hermanns, D Johnson, GA TI Medical residents' first clearly remembered experiences of giving bad news SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE doctor-patient communication; graduate medical education; survey research ID CANCER-PATIENTS; EDUCATION; UNDERGRADUATE; STUDENTS; BARRIERS; DELIVERY AB CONTEXT: Communication of bad news to patients or families is a difficult task that requires skill and sensitivity. Little is known about doctors' formative experiences in giving bad news, what guidance they receive, or what lessons they learn in the process. OBJECTIVE: To learn the circumstances in which medical residents first delivered bad news to patients or families, the nature of their experience, and their opinions about how best to develop the needed skills. DESIGN: Confidential mailed survey. SETTING AND SUBJECTS: All medicine house officers at 2 urban, university-based residency programs in Boston. MAIN OUTCOME MEASURES: Details of medical residents' first clearly remembered experiences of giving bad news to a patient or family member; year in training; familiarity with the patient; information about any planning prior to, observation of, or discussion after their first experience; and the usefulness of such discussions. We also asked general questions about delivering bad news, such as how often this was done, as well as asking for opinions about actual and desired training. RESULTS: One hundred twenty-nine of two hundred thirteen surveys (61%) were returned. Most (73%) trainees first delivered bad news while a medical student or intern. For this first experience, most (61%) knew the patient for just hours or days. Only 59% engaged in any planning for the encounter. An attending physician was present in 6 (5%) instances, and a more-senior trainee in 14 (11%) others. Sixty-five percent of subjects debriefed with at least 1 other person after the encounter, frequently with a lesser-trained physician or a member of their own family. Debriefing focused on the reaction of those who were given the bad news and the reaction of the trainee. When there were discussions with more-senior physicians, before or after the encounter, these were judged to be helpful approximately 80% of the time. Most subjects had given bad news between 5 and 20 times, yet 10% had never been observed doing so. Only 81 of 128 (63%) had ever observed an attending delivering bad news, but those who did found it helpful 96% of the time. On 7-point scales, subjects rated the importance of skills in delivering bad news highly, (mean 6.8), believed such skill can be improved (mean 6.6), and thought that more guidance should be offered to them during such activity (mean 5.8). CONCLUSION: Medical students and residents frequently deliver bad news to patients and families. This responsibility begins early in training. In spite of their inexperience, many do not appear to receive adequate guidance or support during their earliest formative experiences. C1 VA Boston Healthcare Syst, Sect Gen Internal Med & Clin Epidemiol, Boston Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Evans Dept Med, Boston Med Ctr,Sect Gen Internal Med, Boston, MA 02118 USA. Edith Nourse Rogers VA Med Ctr, Ctr Qual Outcomes & Econ Res, Bedford, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Orlander, JD (reprint author), VA Boston Healthcare Syst, Sect Gen Internal Med & Clin Epidemiol, Boston Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 33 TC 32 Z9 33 U1 1 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 NOV PY 2002 VL 17 IS 11 BP 825 EP 840 DI 10.1046/j.1525-1497.2002.10915.x PG 16 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 614NU UT WOS:000179196900002 PM 12406353 ER PT J AU Forlow, SB White, EJ Thomas, KL Bagby, GJ Foley, PL Ley, K AF Forlow, SB White, EJ Thomas, KL Bagby, GJ Foley, PL Ley, K TI T cell requirement for development of chronic ulcerative dermatitis in E- and P-selectin-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY DISEASE; ATOPIC-DERMATITIS; IMMUNE-RESPONSES; NULL MICE; RECRUITMENT; CHEMOKINE; CYTOKINES; ADHESION; IL-17; SUSCEPTIBILITY AB C57BL/6 mice deficient in E- and P-selectin (E-/-P-/-) kept under specific pathogen-free barrier conditions have high circulating neutrophil counts and develop hypercellular cervical lymph nodes with substantial plasma cell infiltrates, severe ulcerative dermatitis, conjunctivitis, and lung pathology, which eventually lead to premature death. To test the hypothesis that the pathology in E-/-P-/- mice may be caused by dysfunctional lymphocyte activity, we crossed E-/-P-/- mice with recombination activation gene (Rag)-1(-/-) mice to generate E(-/-)P(-/-)Rag-1(-/-) mice lacking mature T and B lymphocytes. E(-/-)P(-/-)Rag-1(-/-) mice had circulating neutrophil counts and plasma G-CSF levels similar to E-/-P-/- mice. Remarkably, none of the E(-/-)P(-/-)Rag-1(-/-) mice developed conjunctivitis or ulcerative dermatitis typical of E-/-P-/- mice. These mice were overall healthier in appearance than E-/-P-/- mice, and histopathologic changes in the lung were reduced. Cervical lymph nodes in E(-/-)P(-/-)Rag-1(-/-) mice were much smaller than those of E-/-P-/- mice, containing few mononuclear cells and no plasma cells. These data show that the severe disease phenotype of E-/-P-/- mice depends on lymphocyte function. We conclude that a dysregulated immune response in E-/-P-/- mice causes disease development, but is not necessary for elevated neutrophil counts. C1 Univ Virginia, Cardiovasc Res Ctr, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22908 USA. Univ Virginia, Ctr Comparat Med, Charlottesville, VA 22908 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA. RP Ley, K (reprint author), Univ Virginia, Cardiovasc Res Ctr, Hlth Syst Box 801394, Charlottesville, VA 22908 USA. OI Foley, Patricia/0000-0001-5735-9485 FU NHLBI NIH HHS [HL54136, HL10447] NR 23 TC 13 Z9 13 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 NOV 1 PY 2002 VL 169 IS 9 BP 4797 EP 4804 PG 8 WC Immunology SC Immunology GA 607DY UT WOS:000178777400015 PM 12391189 ER PT J AU Ito, Y Arai, S van Oers, NSC Aifantis, I von Boehmer, H Miyazaki, T AF Ito, Y Arai, S van Oers, NSC Aifantis, I von Boehmer, H Miyazaki, T TI Positive selection by the pre-TCR yields mature CD8(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LINEAGE COMMITMENT; ALPHA-BETA; THYMOCYTE DEVELOPMENT; ANTIGEN RECEPTOR; THYMIC SELECTION; SIGNAL STRENGTH; MUTANT MICE; DELTA; GENE; SURFACE AB It has been of much interest whether there is functional redundancy between the constitutively signaling pre-Talpha/TCRbeta (pre-TCR) and ligated TCRalphabeta complexes, which independently operate the two distinct checkpoints during thymocyte development, i.e., the pre-TCR involved in beta-selection at the CD4(-)CD8(-) double-negative stage and the TCRalphabeta being crucial for positive/negative selection at the CD4(+)CD8(+) double-positive stage. We found that the pre-TCR expressed on double-positive cells in TCRalpha-deficient (TCRalpha(-/-)) mice produced a small number of mature CD8(+) T cells. Surprisingly, when pre-Talpha was overexpressed, resulting in augmentation of pre-TCR expression, there was a striking increase of the CD8(+) T cells. In addition, even in the absence of up-regulation of pre-TCR expression, a similar increase of CD8(+) T cells was also observed in TCRalpha(-/-) mice overexpressing Egr-1, which lowers the threshold of signal strength required for positive selection. In sharp contrast, the CD8(+) T cells drastically decreased in the absence of pre-Talpha on a TCRalpha(-/-) background. Thus, the pre-TCR appears to functionally promote positive selection of CD8(+) T cells. The biased production of CD8(+) T cells via the pre-TCR might also support the potential involvement of signal strength in CD4/CD8 lineage commitment. C1 Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75390 USA. Univ Tokyo, Dept Appl Biol Chem, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Miyazaki, T (reprint author), Univ Texas, SW Med Ctr, Ctr Immunol, 6000 Harry Hines Blvd,NA 7200, Dallas, TX 75390 USA. FU NIAID NIH HHS [R01AI42953]; PHS HHS [R01A14728, R01A145846] NR 39 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2002 VL 169 IS 9 BP 4913 EP 4919 PG 7 WC Immunology SC Immunology GA 607DY UT WOS:000178777400029 PM 12391203 ER PT J AU Belmares, MP Busch, R Wucherpfennig, KW McConnell, HM Mellins, ED AF Belmares, MP Busch, R Wucherpfennig, KW McConnell, HM Mellins, ED TI Structural factors contributing to DM susceptibility of MHC class II/Peptide complexes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HLA-DR MOLECULES; CLASS-II MHC; MYELIN BASIC-PROTEIN; IMMATURE DENDRITIC CELLS; CRYSTAL-STRUCTURE; INVARIANT CHAIN; RHEUMATOID-ARTHRITIS; PEPTIDE EXCHANGE; HYDROGEN-BONDS; BINDING AB Peptide loading of MHC class 11 (MHCII) molecules is assisted by HLA-DM, which releases invariant chain peptides from newly synthesized MHCII and edits the peptide repertoire. Determinants of susceptibility of peptide/MHCII complexes to DM remain controversial, however. Here we have measured peptide dissociation in the presence and the absence of DM for 36 different complexes of varying intrinsic stability. We found large variations in DM susceptibility for different complexes using either soluble or full-length HLA-DM. The DM effect was significantly less for unstable complexes than for stable ones, although this correlation was modest. Peptide sequence- and allelle-dependent interactions along the entire length of the Ag binding groove influenced DM susceptibility. We also observed differences in DM susceptibility during peptide association. Thus, the peptide repertoire displayed to CD4(+) T cells is the result of a mechanistically complicated editing process and cannot be simply predicted from the intrinsic stability of the complexes in the absence of DM. C1 Stanford Univ, Med Ctr, Dept Pediat, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Mellins, ED (reprint author), Stanford Univ, Med Ctr, Dept Pediat, Sch Med, Stanford, CA 94305 USA. FU NIAID NIH HHS [1F32AI10298-01, AI07290-15, AI13587, AI28809] NR 60 TC 50 Z9 50 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2002 VL 169 IS 9 BP 5109 EP 5117 PG 9 WC Immunology SC Immunology GA 607DY UT WOS:000178777400053 PM 12391227 ER PT J AU Gurney, KB Yang, OO Wilson, SB Uittenbogaart, CH AF Gurney, KB Yang, OO Wilson, SB Uittenbogaart, CH TI TCR gamma delta(+) and CD161(+) thymocytes express HIV-1 in the SCID-hu mouse, potentially contributing to immune dysfunction in HIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELTA T-CELLS; ACQUIRED IMMUNODEFICIENCY SYNDROME; PERIPHERAL-BLOOD; DENDRITIC CELLS; HUMAN THYMUS; NKT CELLS; PRODUCTIVE INFECTION; DIFFERENTIAL TROPISM; MOLECULAR ANALYSIS; FETAL DEVELOPMENT AB The vast diversity of the T cell repertoire renders the adaptive immune response capable of recognizing a broad spectrum of potential antigenic peptides. However, certain T cell rearrangements are conserved for recognition of specific pathogens, as is the case for TCRgammadelta cells. In addition, an immunoregulatory class of T cells expressing the NK receptor protein 1A (CD161) responds to nonpeptide Ags presented on the MHC-like CD1d molecule. The effect of HIV-1 infection on these specialized T cells in the thymus was studied using the SCID-hu mouse model. We were able to identify CD161-expressing CD3(+) cells but not the CD1d-restricted invariant Valpha24/Vbeta11/CD161(+) NK T cells in the thymus. A subset of TCRgammadelta cells and CD161-expressing thymocytes express CD4, CXCR4, and CCR5 during development in the thymus and are susceptible to HIV-1 infection. TCRgammadelta thymocytes were productively infectable by both X4 and R5 virus, and thymic HIV-1 infection induced depletion of CD4(+) TCRgammadelta cells. Similarly, CD4(+)CD161(+) thymocytes were depleted by thymic HIV-1 infection, leading to enrichment of CD4(-)CD161(+) thymocytes. Furthermore, compared with the general CD4-negative thymocyte population, CD4(-)CD161(+) NK T thymocytes exhibited as much as a 27-fold lower frequency of virus-expressing cells. We conclude that HIV-1 infection and/or disruption of cells important in both innate and acquired immunity may contribute to the overall immune dysfunction seen in HIV-1 disease. C1 Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, AIDS Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Infect Dis, Los Angeles, CA 90095 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Uittenbogaart, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI 32440]; NICHD NIH HHS [HD 29341, HD 37597] NR 77 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2002 VL 169 IS 9 BP 5338 EP 5346 PG 9 WC Immunology SC Immunology GA 607DY UT WOS:000178777400081 PM 12391255 ER PT J AU Waisbren, SE Read, CY Ampola, M Brewster, TG Demmer, L Greenstein, R Ingham, CL Korson, M Msall, M Pueschel, S Seashore, M Shih, VE Levy, HL AF Waisbren, SE Read, CY Ampola, M Brewster, TG Demmer, L Greenstein, R Ingham, CL Korson, M Msall, M Pueschel, S Seashore, M Shih, VE Levy, HL CA New England Consortium Metabolic TI Newborn screening compared to clinical identification of biochemical genetic disorders SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article AB A group of 28 patients with inherited metabolic disease (homocystinuria galactosaemia, maple syrup urine disease and biotinidase deficiency) diagnosed by screening were compared with a group of 17 similar patients identified clinically. The rate of hospitalization was similar for the two groups. The patients diagnosed clinically showed a higher incidence of mental retardation and their parents experienced greater stress and found greater difficulty in meeting their child's needs. C1 Childrens Hosp, Inborn Errors Metab Clin, Boston, MA 02115 USA. Boston Coll, Sch Nursing, Chestnut Hill, MA 02167 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Maine Med Ctr, Portland, ME 04102 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Vermont Dept Hlth, Burlington, VT 05402 USA. Rhode Isl Hosp, Providence, RI USA. Yale Univ, Sch Med, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waisbren, SE (reprint author), Childrens Hosp, Inborn Errors Metab Clin, IC Smith 108, Boston, MA 02115 USA. EM susan.waisbren@tch.harvard.edu FU NINR NIH HHS [1 F31 NR07400-01A2] NR 2 TC 7 Z9 7 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD JAN PY 2002 VL 25 IS 7 BP 599 EP 600 DI 10.1023/A:1022003726224 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 638GB UT WOS:000180562300009 PM 12638945 ER PT J AU Miles, SA Testa, M Huang, J Wade, M Carden, J Scadden, DT AF Miles, SA Testa, M Huang, J Wade, M Carden, J Scadden, DT TI Lack of antitumor activity and intolerance of interleukin-4 in patients with advanced HIV disease and Kaposi's sarcoma SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN IL-6; RECEPTOR EXPRESSION; CELL-GROWTH; KS CELLS; AIDS; CYTOKINE; GP130 AB Kaposi's sarcoma (KS), the most common malignancy associated with HIV infection, is caused by the Kaposi sarcoma herpesvirus (KSHV). Exacerbations of KSHV are associated with increased human interleukin-6 (HuIL-6), and elevated IL-6 could be related to the development of KS. IL-4, a cytokine with pleiotropic effects, suppresses IL-6 in vivo and modestly inhibits AIDS-KS-derived cells in vitro. Suppression of IL-6 by exogenous IL-4 could result in antitumor activity. We report the results of a clinical trial to test this hypothesis. A phase I/II dose escalation safety, tolerance, and efficacy trial was conducted in patients with biopsy-proven AIDS-related KS, at two university medical centers. Patients were scheduled to receive IL-4 (0.5, 1.5, 3.0, or 4.0 mug/kg/day) administered subcutaneously (s.c.) in sequential cohorts. Patients were continued on study as long as the drug was tolerated or the disease progressed. Patients were followed for antitumor activity, effects on viral replication, immune status, and clinical and laboratory toxicity. Seventeen patients were enrolled at two sites over a 21-month period. There were 15 males and 2 females, and 1 patient was Hispanic. All patients had a Karnofsky score >70. Patients enrolled only into the two lower dose cohorts (0.5 and 1.5 mug/kg/day). Both groups had similar baseline characteristics. The median time on treatment was only 7.4 and 8.4 weeks for the 0.5 and 1.5 mug/kg/day dose levels, respectively. There was significant neutropenia, with 6 patients having grade 3 or greater toxicity requiring granulocyte colony-stimulating factor (G-CSF). Three patients on a dose of 1.5 mug/kg/day stopped treatment due to protocol-defined toxicity. There were no appreciable effects on CD4/CD8 counts. HIV viral RNA did not significantly change over time. However, in several people, it appeared to decline with treatment and rebound with discontinuation of treatment. Corresponding changes were noted in the HIV immunocomplex dissociated (ICD) p24 antigen. One patient had a partial response, 11 patients had stable disease, and 5 patients had disease progression during the short period of treatment. The maximum tolerated dose for IL-4 in patients with advanced AIDS-related KS is 1. 5 mug/kg/day. At this dose level, IL-4 is poorly tolerated and is not an effective KS treatment. Treatment of the majority of patients is discontinued because of drug-related toxicity or because of disease progression. Future studies of IL-4 should be confined to studies of cytokine manipulation of the underlying HIV infection, as there appears to be little antitumor activity. C1 Univ Calif Los Angeles, CARE Clin, Los Angeles, CA 90095 USA. Harvard Univ, Sch Publ Hlth, Adult Div, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Miles, SA (reprint author), Univ Calif Los Angeles, CARE Clin, Room BH412 CHS,Campus Code 179320, Los Angeles, CA 90095 USA. NR 19 TC 3 Z9 4 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD NOV PY 2002 VL 22 IS 11 BP 1143 EP 1148 DI 10.1089/10799900260442575 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 625JH UT WOS:000179813000009 PM 12513914 ER PT J AU Komers, R Tian, W Lindsley, JN Oyama, TT Cohen, DM Anderson, S AF Komers, R Tian, W Lindsley, JN Oyama, TT Cohen, DM Anderson, S TI Effects of cyclooxygenase-2 (COX-2) inhibition on plasma and renal renin in diabetes SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article; Proceedings Paper CT World Congress of Nephrology CY OCT 10-17, 2001 CL SAN FRANCISCO, CALIFORNIA SP ASN, ISN ID MACULA DENSA; RENOVASCULAR HYPERTENSION; BLOOD-FLOW; RAT-KIDNEY; EXPRESSION; PRESSURE; MICE; SUPPRESSION; NEPHROPATHY; SECRETION AB COX-2-derived prostaglandins (PG) have been suggested to be important modulators of renin release and expression. However, the role of COX-2 in various high-renin states is still being debated. In the present studies we explored the role of COX-2-derived PG on basal and angiotensin converting enzyme inhibitor (ACEI)-stimulated plasma and renal renin concentrations (PRC and RRC, RIA), and mRNA expression (RmRNA, RNAse protection assay) in experimental diabetes (DM). Groups of moderately hyperglycemic (n = 5, similar to350 mg/dl), streptozotocin-diabetic rats (D) after 3 weeks of DM were treated with a selective COX-2 inhibitor, MF-tricyclic (MF, 5 mg/kg/day for 10 days in food), the combination of MF and the ACEI enalapril (3 mg/kg/day), enalapril alone, or vehicle (MF-free chow), for 10 days. Non-diabetic control rats, fed MF-free chow, were also studied. All groups of diabetic rats demonstrated similar glycemic control. Treatment with ACEI resulted in significant elevations in PRC, RRC and RmRNA as compared to non-ACEI treated groups of diabetic and control rats. A similar rise in these parameters was observed in the rats treated with the combination of ACEI and MF. Furthermore, in diabetic rats treated with MF alone, PRC and RRC were similar to vehicle-treated animals. Diabetic rats demonstrated higher urinary PG as compared to controls. MF-treated rats demonstrated a significant reduction in urinary PG excretion. In summary, selective COX-2 inhibition influenced neither basal renin status nor ACEI-induced renin release and expression in diabetic rats. These findings do not support a significant role for COX-2 in mediating renin status in diabetes. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Mol Med, Dept Med, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Cell & Dev Biol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIA NIH HHS [AG 14699]; NIDDK NIH HHS [DK 52494] NR 31 TC 9 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD NOV PY 2002 VL 140 IS 5 BP 351 EP 357 DI 10.1067/mlc.2002.128551 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 618XJ UT WOS:000179442600008 PM 12434137 ER PT J AU Beal, MW Simmonds, K AF Beal, MW Simmonds, K TI Clinical uses of mifepristone: An update for women's health practitioners SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Article ID PROGESTERONE-RECEPTOR MODULATORS; EARLY MEDICAL ABORTION; VAGINAL MISOPROSTOL; EARLY-PREGNANCY; UNITED-STATES; BREAST-CANCER; RU-486; TERMINATION; EXPRESSION; EFFICACY AB In September 2000, the U.S. Food and Drug Administration (FDA) approved the use of mifepristone for the provision of medical abortion. Although mifepristone was developed and marketed because of its potential to effect early first-trimester medical abortion, it has additional applications to health care, including the treatment of gynecologic conditions, cancer, and Cushing's disease. The controversial nature of abortion has dominated the publicity about mifepristone. The evidence for the safety and efficacy of mifepristone in medical abortion has been overshadowed, and many clinicians are unaware of the other potential uses of the drug. This article provides a discussion of background information on the pharmacology, development of, and research on mifepristone and an update on current and potential uses in health care today. Information on the FDA-approved regimen and alternative protocols for management of mifepristone in its use in abortion care are presented. (C) 2002 by the American College of Nurse-Midwives. C1 Yale Univ, Sch Nursing, New Haven, CT 06536 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Planned Parenthood, Boston, MA USA. Martha Eliot Hlth Ctr, Jamaica Plain, MA USA. RP Beal, MW (reprint author), Yale Univ, Sch Nursing, 100 Church St S,POB 9740, New Haven, CT 06536 USA. NR 66 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD NOV-DEC PY 2002 VL 47 IS 6 BP 451 EP 460 AR PII S1526-9523(02)00331-8 DI 10.1016/S1526-9523(02)00331-8 PG 10 WC Nursing SC Nursing GA 620PR UT WOS:000179542200008 PM 12484667 ER PT J AU Ogino, S Wilson, RB AF Ogino, S Wilson, RB TI Quantification of PCR bias caused by a single nucleotide polymorphism in SMN gene dosage analysis SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID SPINAL MUSCULAR-ATROPHY; IDENTIFICATION; AMPLIFICATION; CARRIERS; MUTATIONS; ALLELES; PRODUCT; DNA AB Approximately 94% of patients with spinal muscular atrophy lack both copies of SMN1 exon 7, and most carriers have only one copy of SMN1 exon 7. We described previously the effect of SMN1/SMN2 hetero-duplex formation on SMN gene dosage analysis, which is a multiplex quantitative PCR assay to determine the copy numbers of SMN1 and SMN2 using DraI digestion to differentiate SMN2 from SMN1. We describe herein the quantification of PCR bias between SMN1 exon 7 and SMN2 exon 7, which differ by only one nucleotide that is not present in either primer binding site. Using samples from 272 individuals with various SMN genotypes, we found that the amplification efficiency of SMN2 was consistent only approximately 80% that of SMN1. Thus, even a single nucleotide polymorphism, not in primer binding sites, can cause reproducible PCR bias. The precision and accuracy of our SMN gene dosage analysis are high because our assay design and controls take advantage of the consistency of the PCR bias. As additional clinically significant single nucleotide polymorphisms (SNPs) are discovered, assessment of PCR bias, and judicious selection of standards and controls, will be increasingly important for quantitative PCR assays. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3rd Floor, Boston, MA 02115 USA. NR 25 TC 13 Z9 14 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2002 VL 4 IS 4 BP 185 EP 190 DI 10.1016/S1525-1578(10)60702-7 PG 6 WC Pathology SC Pathology GA 613HD UT WOS:000179126100002 PM 12411585 ER PT J AU Morihara, T Chu, T Ubeda, O Beech, W Cole, GM AF Morihara, T Chu, T Ubeda, O Beech, W Cole, GM TI Selective inhibition of A beta 42 production by NSAID R-enantiomers SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; beta-amyloid; non-steroidal anti-inflammatory drugs (NSAIDs); nuclear factor-kappa B (NF-kappa B); R-flurbiprofen; R-ibuprofen ID NF-KAPPA-B; ALZHEIMERS-DISEASE; FLURBIPROFEN ENANTIOMERS; CYCLOOXYGENASE; INFLAMMATION; IBUPROFEN; RELEASE; DOMAIN AB Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with reduced risk for Alzheimer's disease (AD) and selected NSAIDs racemates suppress beta-amyloid (Abeta) accumulation in vivo and Abeta42 production in vitro. Clinical use of NSAIDs for preventing or treating AD has been hampered by dose-limiting toxicity believed to be due to cyclooxygenase (COX)-inhibition that is reportedly not essential for selective Abeta42 reduction. Profens have racemates and R-enantiomers were supposed to be inactive forms. Here we demonstrate that R-ibuprofen and R-flurbiprofen, with poor COX-inhibiting activity, reduce Abeta42 production by human cells. Although these R-enantiomers inhibit nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB can selectively regulate Abeta42, Abetab42 reduction is not mediated by inhibition of NF-kappaB activation. Because of its efficacy at lowering Abeta42 production and low toxicity profile, R-flurbiprofen is a strong candidate for clinical development. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles VA Healthcare Syst, GRECC, Sepulveda, CA USA. RP Cole, GM (reprint author), Univ Calif Los Angeles, Dept Med, Greater Los Angeles VA Healthcare Syst GRECC11E, 16111 Plummer St, Sepulveda, CA 91343 USA. FU NIA NIH HHS [AG13471] NR 22 TC 125 Z9 129 U1 0 U2 4 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 NOV PY 2002 VL 83 IS 4 BP 1009 EP 1012 DI 10.1046/j.1471-4159.2002.01195.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 611YR UT WOS:000179046200029 PM 12421374 ER PT J AU Linseman, DA Phelps, RA Bouchard, RJ Le, SS Laessig, TA McClure, ML Heidenreich, KA AF Linseman, DA Phelps, RA Bouchard, RJ Le, SS Laessig, TA McClure, ML Heidenreich, KA TI Insulin-like growth factor-I blocks Bcl-2 interacting mediator of cell death (Bim) induction and intrinsic death signaling in cerebellar granule neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE insulin-like growth factor; cerebellar granule neuron; apoptosis; mitochondria; Bim; forkhead transcription factor ID FORKHEAD TRANSCRIPTION FACTOR; CENTRAL-NERVOUS-SYSTEM; CYTOCHROME-C RELEASE; IGF-I; MITOCHONDRIAL DEPOLARIZATION; CASPASE ACTIVATION; FAMILY MEMBERS; PURKINJE-CELLS; MESSENGER-RNA; APOPTOSIS AB Cerebellar granule neurons depend on insulin-like growth factor-I (IGF-I) for their survival. However, the mechanism underlying the neuroprotective effects of IGF-I is presently unclear. Here we show that IGF-I protects granule neurons by suppressing key elements of the intrinsic (mitochondrial) death pathway. IGF-I blocked activation of the executioner caspase-3 and the intrinsic initiator caspase-9 in primary cerebellar granule neurons deprived of serum and depolarizing potassium. IGF-I inhibited cytochrome c release from mitochondria and prevented its redistribution to neuronal processes. The effects of IGF-I on cytochrome c release were not mediated by blockade of the mitochondrial permeability transition pore, because IGF-I failed to inhibit mitochondrial swelling or depolarization. In contrast, IGF-I blocked induction of the BH3- only Bcl-2 family member, Bim (Bcl-2 interacting mediator of cell death), a mediator of Bax-dependent cytochrome c release. The suppression of Bim expression by IGF-I did not involve inhibition of the c-Jun transcription factor. Instead, IGF-I prevented activation of the forkhead family member, FKHRL1, another transcriptional regulator of Bim. Finally, adenoviral-mediated expression of dominant-negative AKT activated FKHRL1 and induced expression of Bim. These data suggest that IGF-I signaling via AKT promotes survival of cerebellar granule neurons by blocking the FKHRL1-dependent transcription of Bim, a principal effector of the intrinsic death-signaling cascade. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol C236, 4200 E 9th Ave, Denver, CO 80262 USA. FU NINDS NIH HHS [NS38619-01A1] NR 55 TC 116 Z9 125 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2002 VL 22 IS 21 BP 9287 EP 9297 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 611RM UT WOS:000179031600019 PM 12417654 ER PT J AU Teter, B Ashford, JW AF Teter, B Ashford, JW TI Neuroplasticity in Alzheimer's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Review DE neuroplasticity; Alzheimer's; genetics; apo-lipoprotein E; therapeutics; pharmacogenetics ID AMYLOID PRECURSOR PROTEIN; NERVE GROWTH-FACTOR; LONG-TERM POTENTIATION; APOLIPOPROTEIN-E GENOTYPE; E-DEFICIENT MICE; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; DENSITY-LIPOPROTEIN RECEPTOR; ESTROGEN REPLACEMENT THERAPY; HIPPOCAMPAL ORGANOTYPIC CULTURES AB Ramon y Cajal proclaimed in 1928 that "once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers the nerve paths are something fixed, ended and immutable. Everything must die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree." (Ramon y Cajal, 1928). In large part, despite the extensive knowledge gained since then, the latter directive has not yet been achieved by 'modern' science. Although we know now that Ramon y Cajal's observation on CNS plasticity is largely true (for lower brain and primary cortical structures), there are mechanisms for recovery from CNS injury. These mechanisms, however, may contribute to the vulnerability to neurodegenerative disease. They may also be exploited therapeutically to help alleviate the suffering from neurodegenerative conditions. Published 2002 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, VA Med Ctr, Dept Med, Sepulveda, CA 91343 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Kentucky, Dept Psychiat, Lexington, KY USA. Univ Kentucky, Dept Neurol, Lexington, KY USA. Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. Vet Affairs Med Ctr, Lexington, KY USA. RP Teter, B (reprint author), Univ Calif Los Angeles, VA Med Ctr, Dept Med, MC151,16111 Plummer St, Sepulveda, CA 91343 USA. FU NIA NIH HHS [K01 AG000962] NR 698 TC 63 Z9 64 U1 6 U2 17 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2002 VL 70 IS 3 BP 402 EP 437 DI 10.1002/jnr.10441 PG 36 WC Neurosciences SC Neurosciences & Neurology GA 608EL UT WOS:000178832200021 PM 12391603 ER PT J AU Mariolis, T Picard, C AF Mariolis, T Picard, C TI The quality of life and Wellness program: Alternative to traditional psychiatric nursing clinical placements SO JOURNAL OF NURSING EDUCATION LA English DT Article C1 Fitchburg State Coll, Dept Nursing, Fitchburg, MA 01420 USA. Massachusetts Gen Hosp, Grad Sch Nursing, Inst Hlth Profess, Boston, MA 02114 USA. RP Mariolis, T (reprint author), Fitchburg State Coll, Dept Nursing, 160 Pearl St, Fitchburg, MA 01420 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0148-4834 J9 J NURS EDUC JI J. Nurs. Educ. PD NOV PY 2002 VL 41 IS 11 BP 501 EP 503 PG 3 WC Nursing SC Nursing GA 613FZ UT WOS:000179123300009 PM 12437057 ER PT J AU Thurmuller, P Troulis, MJ Rosenberg, A Kaban, LB AF Thurmuller, P Troulis, MJ Rosenberg, A Kaban, LB TI Changes in the condyle and disc in response to distraction osteogenesis of the minipig mandible SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP, 2001 CL ORLANDO, FLORIDA SP Amer Assoc Oral Maxillofac Surg ID TEMPOROMANDIBULAR-JOINT; MACACA-MULATTA; OSTEOTOMY; ADVANCEMENT; ATROPHY; SHEEP; MODEL AB Purpose: Distraction osteogenesis (DO) is a commonly used technique for mandibular lengthening, but changes in the temporomandibular joint have not been well documented. The purpose of this study was to evaluate the effect of DO, at varying rates, on the mandibular condyle and articular disc. Materials and Methods: Semiburied distractors were placed via submandibular incisions in 15 minipigs. Two unoperated animals served as controls. The protocol consisted of 0 day latency and rates of 1, 2, or 4 mm/d for a 12-mm gap. After the animals were killed (0, 24, or 90 days), ipsilateral and contralateral condyles and discs were harvested and evaluated to determine changes in 1) condylar form and size, 2) condylar surface, and 3) the articular disc. Results: Articular surfaces of the condyles in control animals were smooth, with no irregularities or erosions. In animals undergoing distraction, ipsilateral condyles showed increasing changes in morphology and AP dimension, and surface contour irregularities as the DO rate increased. These changes were present, but to a lesser degree, in the contralateral condyles. Articular discs of both ipsilateral and contralateral sides showed variable thinning at the medial aspect at end DO. After 90 days, changes in the condyles and discs were reduced by remodeling except in the 4 mm/d DO groups. Conclusions: Results of this preliminary study indicate that gross changes occur in condyles and discs after unilateral mandibular DO. These changes are more severe at faster distraction rates (4 mm/d) and tend to resolve during neutral fixation when a rate of 1 mm/d is used. (C) 2002 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med,Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Oral & Maxillofacial Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Sch Dent Med,Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Oral & Maxillofacial Surg Serv, Fruit St,Warren Bldg 1201, Boston, MA 02114 USA. NR 30 TC 32 Z9 35 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2002 VL 60 IS 11 BP 1327 EP 1333 DI 10.1053/joms.2002.35733 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 611KV UT WOS:000179017000018 PM 12420269 ER PT J AU Behnam, K Murray, SS Whitelegge, JP Brochmann, EJ AF Behnam, K Murray, SS Whitelegge, JP Brochmann, EJ TI Identification of the molecular chaperone alpha B-crystallin in demineralized bone powder and osteoblast-like cells SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE heat shock protein; osteoblast; crystallin; bone; proteomics; chaperone ID HEAT-SHOCK PROTEINS; MASS-SPECTROMETRY; BETA-CRYSTALLIN; MOUSE EMBRYO; IN-VITRO; STRESS; EXPRESSION; HEAT-SHOCK-PROTEIN-27; CYTOSKELETON; LOCALIZATION AB Bone is subjected to a variety of physiological, as well as cell-deforming biomechanical stresses, including hydrostatic compression and fluid flow. However, little is known about the molecular mechanisms that protect bone cells from mechanical, ischemic, or oxidative damage. Crystallins are 20 kD heat shock proteins that function as molecular chaperones. We tested the hypothesis that alpha B-crystallin (alphaB-crystallin), the most widely expressed vertebrate crystallin, is present in bone and osteoblast-like cells. Noncollagenous proteins (NCPs) were extracted from human demineralized bone matrix with 4 NI guanidine HCl containing 0.5 M CaCl2 and protease inhibitors, defatted, dialyzed against 0.2%, (v/v) Triton X-100 in 100 mM Tris-HCl (pH 7.2) and water, centrifuged, and lyophilized. The NCPs were separated by 2D IEF/SDS-PAGE. The two most abundant 20 kD spots, with apparent pis of 7.85 and 7.42 in urea gels, were excised, subjected to matrix-assisted laser desorption ionization/time-of-flight mass spectrometry, and identified as alphaB-crystallins. Indirect immunofluorescence localized alphaB-crystallin to the interphase nucleus, cytoskeleton and cytoplasm of proliferating MC3T3-El mouse osteoblast-like cells, as well as the cytoskeleton and cytoplasm of confluent cells. In conclusion, alphaB-crystallin is present in bone and osteoblast-like cells. We hypothesize that alphaB-crystallin may play a role in protecting the osteoblast cytoskeleton from mechanical stress and may be important in modulating nuclear or cellular functions, such as transcription or apoptosis, as observed in other tissues. Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society. C1 VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Pasarow Mass Spectrometry Lab, Chem & Biochem & Neuropsychiat Inst, Los Angeles, CA 90095 USA. RP VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. EM murrayes@ucla.edu FU NIAID NIH HHS [AI 12601]; NINDS NIH HHS [NS 31271, NS 07171] NR 38 TC 8 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0736-0266 EI 1554-527X J9 J ORTHOP RES JI J. Orthop. Res. PD NOV PY 2002 VL 20 IS 6 BP 1190 EP 1196 AR PII S0736-0266(02)00071-2 DI 10.1016/S0736-0266(02)00071-2 PG 7 WC Orthopedics SC Orthopedics GA 618CP UT WOS:000179400800009 PM 12472228 ER PT J AU Casarett, D Karlawish, J Sankar, P Hirschman, KB Asch, DA AF Casarett, D Karlawish, J Sankar, P Hirschman, KB Asch, DA TI Obtaining informed consent for cancer pain research: Do patients with advanced cancer and patients with chronic pain have different concerns? SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE pain; research ethics; human subjects; informed consent ID RANDOMIZED CONTROLLED TRIAL; QUALITY-OF-LIFE; PALLIATIVE CARE RESEARCH; TRANSDERMAL FENTANYL; SYMPTOM ASSESSMENT; BREAKTHROUGH PAIN; ORAL MORPHINE; MANAGEMENT; SATISFACTION; GUIDELINES AB To explore the factors that patients with malignant tend nonmalignant pain consider when deciding whether to enroll in pain research studies, determine whether their views are different, and determine whether willingness to enroll in research is associated with pain. severity, semi-structured interviews were conducted with 80 patients (cancer pain: n = 40; chronic nonmalignant pain: n = 40). The risks and potential benefits that were important to patients with cancer were the same as those that were important to patients with chronic pain. Willingness to enroll in, research was associated with pain severity (Spearman p = 0.33; P = 0.041) in patients with chronic pain, but not in patients with cancer pain. Patients with cancer pain do not have different concerns than chronic pain patients do. Although chronic pain patients' willingness to enroll in research was related to pain severity and a desire, for better pain management, cancer patients' willingness to enroll was not. J Pain Symptom Manage 2002;24:506-516. (C) U.S. Cancer Pain Relief Committee, 2002. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Leonard Davis Inst Hlth Econ, Wilmington, DE USA. Univ Penn, Sch Social Work, Philadelphia, PA USA. RP Casarett, D (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 47 TC 5 Z9 5 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2002 VL 24 IS 5 BP 506 EP 516 AR PII S0885-3924(02)00527-4 DI 10.1016/S0885-3924(02)00527-4 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 629PY UT WOS:000180059100008 PM 12547050 ER PT J AU Steinkamp, M Geva, A Joffe, S Lapp, CN Neufeld, EJ AF Steinkamp, M Geva, A Joffe, S Lapp, CN Neufeld, EJ TI Chronic disseminated intravascular coagulation and childhood-onset skin necrosis resulting from homozygosity for a protein C Gla domain mutation, Arg15Trp SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE chromogenic assay; disseminated intravascular coagulation; factor V inactivation; Gla domain; hypercoagulable states; Protein C ID DEFICIENCY; GENE AB A toddler of Haitian descent presented with an 18-month history of chronic consumption coagulopathy, followed by catastrophic skin necrosis. Protein C deficiency (1% to 3% of control) was noted by functional assay; chromogenic assay and antigen levels were 30% of control. Plasma infusion abrogated the disseminated intravascular coagulation-like state. The authors identified a homozygous mutation, C1432T, resulting in a missense, Arg15Trp, in the gamma-carboxyglutamate domain of the protein. Chronic consumption coagulopathy without purpura fulminans or venous thrombosis is a rare presentation of defective protein C pathway. The result of this mutation is a mixed type I (low antigen) and type 11 (low function) phenotype. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol, 300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; OI Steinkamp, Mara/0000-0003-1226-9325; Joffe, Steven/0000-0002-0667-7384 NR 9 TC 5 Z9 6 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 NOV PY 2002 VL 24 IS 8 BP 685 EP 688 DI 10.1097/00043426-200211000-00018 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 614JF UT WOS:000179184300018 PM 12439046 ER PT J AU Nishimura, K Rasool, F Ferguson, MB Sobel, M Niederman, R AF Nishimura, K Rasool, F Ferguson, MB Sobel, M Niederman, R TI Benchmarking the clinical prosthetic dental literature on MEDLINE SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; HEALTH; SEARCHES; MEDICINE; PAPER; CARE; READ AB Statement of problem. The utility of evidence-based clinical prosthetic dental decision making is, in part, predicated on the availability of high-quality clinical trials and the use of current best evidence. With literature or outcomes continually evolving, it is difficult to know how much information is available, how fast it changes, or where it is located. Purpose. This study identified and quantified the availability of high-quality prosthetic dental clinical trials, determined the dynamics of literature increase, and identified the location of relevant literature published within a specific decade. Material and methods. A search strategy based on the Medical Subject Headings (MeSH) vocabulary for prosthetic dentistry was developed to examine MEDLINE with use of the Ovid Web Gateway search engine between the years 1990-1999. Specific and sensitive methodologic search filters identified 4 categories of information: etiology, diagnosis, therapy, and prognosis. The identified studies were limited to human subjects and to articles written in English. The results were subdivided by year to identify trends and location of the literature. This evaluation did not include the following: (1) other databases or languages or (2) an evaluation of the validity or clinical applicability of the literature. The first factor would increase the estimated number of relevant articles, whereas the second factor would decrease it. Results. Between 1990 and 1999, MEDLINE identified 10,258 articles published in English on human prosthodontic issues. When subdivided by clinical category, the number of articles per year (mean +/- SD) for specific and sensitive searches, respectively, was as follows: etiology, 10 +/- 6 and 95 +/- 27; diagnosis, 11 +/- 5 and 77 +/- 21; therapy, 6 +/- 2 and 153 +/- 52; and prognosis, 13 +/- 6 and 91 +/- 27. For sensitive searches, this amounted to approximately 416 articles per year. The time-course analysis indicated that the number of articles in each category increased by approximately 7% per year. The articles were published in more than 60 different journals: approximately 50% of the articles were published in 14 journals, whereas the remaining articles were published in 46 journals. Conclusion. There appears to be substantial clinical prosthetic dental literature upon which to base clinical decisions. With the sensitive search strategy used as an estimate, to stay current, one would need to read and absorb approximately 8 articles per week, 52 weeks per year, across 60 different journals. Increases in the volume of literature each year make access even more difficult. These trends suggest the need for computer-based clinical knowledge systems. C1 Forsyth Inst, Ctr Evidence Based Dent, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Restorat Dent, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Off Dent Educ, Boston, MA 02115 USA. RP Niederman, R (reprint author), Forsyth Inst, Ctr Evidence Based Dent, 140 Fenway, Boston, MA 02115 USA. OI niederman, richard/0000-0001-6674-1774 FU NIDCD NIH HHS [NIDCR T35 04581] NR 19 TC 8 Z9 8 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD NOV PY 2002 VL 88 IS 5 BP 533 EP 541 DI 10.1067/mpr.2002.129301 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 628QX UT WOS:000180008800013 PM 12474005 ER PT J AU Seidel, B Krebs, DE AF Seidel, B Krebs, DE TI Base of support is not wider in chronic ataxic and unsteady patients SO JOURNAL OF REHABILITATION MEDICINE LA English DT Article DE stride width; gait; vestibular; cerebellar ID GAIT; POSTUROGRAPHY; PERFORMANCE; STABILITY; BALANCE; AGE AB "Wide-based gait" is considered indicative of imbalance. No quantitative gait analyses, however, have related base of support to steadiness during gait. To determine whether patients with cerebellar or vestibular disorders had a wider base of support than matched healthy individuals, we analyzed 102 balance-impaired patients and healthy subjects during free and paced gait. Kinematic data were collected using a high-precision optoelectronic system. There were no significant differences in the base of support between unsteady and healthy subjects, nor between patients with vestibular and cerebellar diagnoses. The base of support correlated with the body mass index and waist circumference in all subject groups. These data suggest that base of support during gait fails to identify balance-impaired subjects and is related more to biomechanical than to neurological factors. Therefore, "wide-based gait" should no longer be considered the sine qua non of ataxic or unsteady gait. Clinicians should not focus on decreasing base of support as a therapeutic goal for chronic, unsteady patients. C1 MGH Inst Hlth Profess, Massachusetts Gen Hosp Biomot Lab, Charlestown, MA 02129 USA. RP Krebs, DE (reprint author), MGH Inst Hlth Profess, Massachusetts Gen Hosp Biomot Lab, 36 1st Ave,Room 223, Charlestown, MA 02129 USA. FU NCCIH NIH HHS [R21AT00553]; NIA NIH HHS [R01AG11255] NR 21 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1650-1977 J9 J REHABIL MED JI J. Rehabil. Med. PD NOV 1 PY 2002 VL 34 IS 6 BP 288 EP 292 DI 10.1080/165019702760390392 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 606PL UT WOS:000178742300008 PM 12440804 ER PT J AU O'Connor, TJ Fitzgerald, SG Cooper, RA Thorman, TA Boninger, ML AF O'Connor, TJ Fitzgerald, SG Cooper, RA Thorman, TA Boninger, ML TI Kinetic and physiological analysis of the GAME(wheels) system SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cardiovascular fitness; computer games; exercise; wheelchair ID SPINAL-CORD INJURIES; WHEELCHAIR PROPULSION; PUSHRIM FORCES; COMPUTER GAMES; VIDEO-GAME AB For individuals with a spinal cord injury or dysfunction (SCI/D), opportunities to exercise are limited and are usually not highly motivating experiences. Exercise programs or extracurricular activities may help increase or maintain the cardiovascular fitness level of individuals with SCI/D. The GAME(Wheels) system, an interface between a portable roller system and a computer, enables an individual to control a video game by propelling his or her wheelchair. The purpose of this study was to investigate whether the propulsive forces used during video play, both with and without the GAME(Wheels) system, were different. A secondary purpose was to examine differences in metabolic parameters during exercise under these two conditions. Ten manual wheelchair users exercised on the GAME(Wheels) system with and without controlling a video game. Physiological and kinetic data were collected six times during two exercise trials. Kinetic data were recorded with the SMART(Wheel) and used to investigate propulsion forces. No significant differences were found in the resultant force, rate of rise, or number of hand contacts with the pushrims. This study showed that propulsion pattern did not change significantly when wheelchair users exercised while playing a computer video game. Oxygen consumption, ventilation, and heart rate were significantly different (p < 0.05) between the two groups during the last three exercise intervals and cooldown. Playing a video game while exercising may help to motivate manual wheelchair users to exercise longer and regularly, something that was reported by this study's subjects; likewise, exercising while playing a video game may not be associated with higher pushrim forces and stroke frequencies. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. Houston VA Med Ctr, Houston, TX USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr 151R-1, Pittsburgh, PA 15206 USA. FU NICHD NIH HHS [P01 HD33989-04, P01-HD33989-0151, K08 HD01122-01] NR 22 TC 8 Z9 8 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD NOV-DEC PY 2002 VL 39 IS 6 BP 627 EP 634 PG 8 WC Rehabilitation SC Rehabilitation GA 667UV UT WOS:000182253200003 PM 17943665 ER PT J AU McGibbon, CA Krebs, DE AF McGibbon, CA Krebs, DE TI Compensatory gait mechanics in patients with unilateral knee arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE gait; elderly; unilateral arthritis; knee; power flow; energy transfer ID ENERGY-EXPENDITURE PROBLEM; SUPERVISED FITNESS WALKING; FRACTIONS APPROACH; PHYSICAL THERAPY; ADDUCTION MOMENT; CONTROLLED TRIAL; DISABLED ELDERS; LINK SYSTEM; OSTEOARTHRITIS; EXERCISE AB Objective. Few studies exist on gait adaptation caused by knee osteoarthritis (OA), and those have only explored adaptations of the kinematics and kinetics of the knee joint itself. We characterize ankle, knee, hip, and low back mechanical energy expenditures (MEE) and compensations (MEC) during gait in patients with knee OA. Methods. Thirteen elderly patients with unilateral knee OA and 10 matched healthy elderly controls were studied during preferred and paced speed gait. Gait speed, step length, and lower extremity and low back joint MEE and MEC were compared between groups. Results. Patients with knee OA had lower, but not significantly different, walking speed and step length compared to the controls, and had significantly different joint kinetic profiles. Patients had reduced ankle power at terminal stance, lacked a second positive peak in knee power, and had increased power absorption at the hip. Abnormal knee kinematics were exaggerated when walking at a paced speed, but hip kinetics normalized among patients with OA. Conclusion. Reduced ankle plantar-flexion power in patients with knee OA was probably due to disrupted transfer of energy through the knee. Lack of concentric knee power supports prior studies' conclusions that patients with knee OA avoid using their quadriceps to stabilize the knee, probably to reduce articular loads. Patients with knee OA increase eccentric hip power due to increased hip extension caused by abnormal knee kinematics, potentially increasing hip articular forces. This passive mechanism, however, may assist in the advancement of the leg into swing phase. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Phys Therapy, Biomot Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Phys Therapy & Clin Invest, Biomot Lab, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Phys Therapy, Biomot Lab, RSL 010,40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [R01 AG12561]; NIAMS NIH HHS [R01 AR45278] NR 45 TC 59 Z9 64 U1 1 U2 11 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2002 VL 29 IS 11 BP 2410 EP 2419 PG 10 WC Rheumatology SC Rheumatology GA 611XL UT WOS:000179043100028 PM 12415602 ER PT J AU Ritsher, JB McKellar, JD Finney, JW Otilingam, PG Moos, RH AF Ritsher, JB McKellar, JD Finney, JW Otilingam, PG Moos, RH TI Psychiatric comorbidity, continuing care and mutual help as predictors of five-year remission from substance use disorders SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; ABUSE TREATMENT; TREATMENT OUTCOMES; 1-YEAR OUTCOMES; 12-STEP; INVOLVEMENT; ALCOHOLICS AB Objective: In a cohort of 2,595 male patients in VA intensive treatment programs for substance use disorders (SUD), we tested whether psychiatric comorbidity, outpatient care and mutual help group attendance during the first two follow-up years predicted remission status at Year 5, controlling for covariates. Method: Logistic regression modeling of longitudinal data was used to test the hypotheses. Results: Dual diagnosis patients were less likely to be in remission at Year 5 than SUD only patients. Outpatient care was at best only weakly related to Year 5 remission status. By contrast, mutual help involvement substantially improved the chances of substance use remission at Year 5 for both SUD only and dual diagnosis patients. Mutual help involvement did not, however, offset the poorer prognosis for dual diagnosis patients. Conclusions: Because mutual help groups specifically targeted to individuals with comorbid substance use and psychiatric disorders are currently rare, further research is recommended to investigate whether they are more effective than standard SUD mutual help groups in facilitating the recovery of persons with dual diagnoses. C1 Ctr Hlth Care Evaluat, Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. RP Ritsher, JB (reprint author), San Francisco VAMC, No Calif Inst Res & Educ, 4150 Clement St,116A, San Francisco, CA 94121 USA. FU NIAAA NIH HHS [AA12718] NR 31 TC 60 Z9 60 U1 4 U2 7 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 2002 VL 63 IS 6 BP 709 EP 715 PG 7 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 631ET UT WOS:000180155700009 PM 12529071 ER PT J AU Chan, BP Kochevar, IE Redmond, RW AF Chan, BP Kochevar, IE Redmond, RW TI Enhancement of porcine skin graft adherence using a light-activated process SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the European-Society-for-Photobiology CY SEP 03-11, 2001 CL LILLEHAMMER, NORWAY SP European Soc Photobiol DE skin; graft; adherence; light-activation ID TISSUE ADHESIVES; CYANOACRYLATE; TEMPERATURE AB Background. Skin grafts are widely used in plastic surgery, and burn and ulcer wound management. Rapid and sustained adherence, the ability to resist shear stress, and a void-free surface-to-surface contact are critical to the success of graft survival. Mechanical and adhesive fixation aids are currently used to achieve graft adherence and they are not free of problems. Photochemical tissue bonding (PTB) is an emerging laser technique with numerous applications in surgical specialties. In the current study, PTB was investigated as a means to bond and enhance the adherence of skin grafts. Methods. In this study, ex vivo porcine skin grafts treated with a photosensitizing dye, rose bengal (RB), were approximated dermis-to-dermis and irradiated with visible light from an argon laser at 514 nm. The adherence of the skin grafts was measured immediately after irradiation. Dose-response relationships between the light and the dye with adherence of the grafts were established. The surface temperature of the skin under irradiation was monitored and the viability of the skin cells in the grafts was also measured. Results. Results showed that the skin graft adherence was RB dose-dependent in a statistically significant manner with the concentration of RB reaching a plateau value of 0.1% (w/v) of RB. Graft adhesion also increased with laser fluence up to 504 J/cm(2) in the presence of 0.1% RB. No fluence dependence was observed in the absence of RB. Thermogram results showed that the maximal surface temperature during irradiation was less than 40degreesC. Histological investigation and trypan blue exclusion assays demonstrated that skin grafts retained cell viability and collagen organization after PTB. Conclusion. This ex vivo study demonstrates that PTB using argon laser irradiation and RB enhances skin graft adherence by forming dermal-dermal bonding. The increase in adherence is a function of the concentration of RB and the laser fluence. The results also suggest that the PTB is a potentially safe procedure because it is nonthermal in nature and does not significantly affect the skin cell viability. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 17 TC 51 Z9 54 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 2002 VL 108 IS 1 BP 77 EP 84 DI 10.1006/jsre.2002.6516 PG 8 WC Surgery SC Surgery GA 620HM UT WOS:000179528000011 PM 12443718 ER PT J AU Trehan, M Taylor, CR AF Trehan, M Taylor, CR TI Medium-dose 308-nm excimer laser for the treatment of psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID T-CELLS; PUVA; PHOTOTHERAPY; METHOXSALEN; CLEARANCE; RADIATION; REMISSION; LIGHT AB Background: The excimer laser delivers targeted ultraviolet B 308-nm radiation. Objective: This investigation evaluated the efficacy of multiple, medium-dose excimer 308-nm laser treatments for psoriasis. Methods: Twenty volunteers with plaque psoriasis were enrolled. Six plaques received treatment 3 times per week for tip to 8 weeks; another plaque served as a control. As in standard phototherapy, a flexible close escalation scheme was implemented during the course of treatment. Modified Psoriasis Area and Severity index scores were rendered throughout the study with follow-tips at 1, 2, 4, and 6 months. Results: Fifteen subjects completed the study without complications. The mean number of treatments to achieve >95% clearance was 10.6. The mean cumulative UV radiation close was 6.1 J/cm(2), and the mean remission tithe was 3.5 months. Conclusion: A thrice-weekly, medium-dose irradiation schedule with the 308-nm laser can effectively clear localized plaque-type psoriasis in fewer treatments with an overall lower cumulative close, compared with standard phototherapy. This innovative UV device allows specific targeting of affected sites without needless exposure of unaffected skin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed,Gange Photomed Res Ctr, Boston, MA 02114 USA. RP Trehan, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Wellman Labs Photomed,Gange Photomed Res Ctr, 55 Fruit St,Bartlett 622, Boston, MA 02114 USA. NR 16 TC 50 Z9 52 U1 0 U2 0 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 NOV PY 2002 VL 47 IS 5 BP 701 EP 708 DI 10.1067/mjd.2002.125075 PG 8 WC Dermatology SC Dermatology GA 609FM UT WOS:000178893000007 PM 12399761 ER PT J AU Friedlander, AH Garrett, NR Norman, DC AF Friedlander, AH Garrett, NR Norman, DC TI The prevalence of calcified carotid artery atheromas on the panoramic radiographs of patients with type 2 diabetes mellitus SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID INSULIN-RESISTANCE ATHEROSCLEROSIS; IMPAIRED GLUCOSE-TOLERANCE; RISK-FACTORS; CARDIOVASCULAR RISK; CIGARETTE-SMOKING; ISCHEMIC-STROKE; COMPLICATIONS; HYPERTENSION; DISEASE; MORTALITY AB Background. People with type 2 diabetes mellitus are disproportionately at risk of experiencing stroke, because hyper-glycemia and other risk factors associated with diabetes accelerate development of cervical carotid artery atheromas. Removal of these atheromas may reduce the incidence of stroke. The authors conducted a study to ascertain if those treated without insulin (noninsulin-treated, or NIT) would have a lower prevalence of atheromas on their radiographs and a lower prevalence of risk factors than those treated with insulin (insulin-treated, or IT). Methods. The authors evaluated the panoramic radiographs and medical records of 46 neurologically asymtomatic men (n=34) and women (n=12) (age range 62-77 years, mean age 68.5 years) with type 2 diabetes. They used Fisher exact test to perform a statistical comparison of the prevalence of atherogenic atheromas and risk factors between groups. Results. The radiographs showed that 24 percent of the NIT patients had atheromas; this difference was not statistically significant (P=.52). The groups had similar risk factors-that is, high levels of glycsylated hemoglobin A, or HbA(1c); smoking, hyper-tension and obesity (P>.05). When compared with the 4 percent atheroma prevalence rate among healthy people of similar age, the rates were significantly higher in both the NIT (P=.02) and IT (P=.0006) patients. Conclusion. These results demonstrate that people with type 2 diabetes, irrespective of treatment modality, have high rates of atheromas as visualised on their panoramic radiographs. Clinical Implications. Dentists treating patients with type 2 diabetes mellitus must review their panoramic radiographs carefully for evidence of atheroma formation. Patients with atheromatous lesions must be referred to their physicians for further evaluation and treatment because the modification of atherogenic risk factors and the surgical removal of atheromas in certain people have been shown to reduce the likelihood of stroke. C1 Dept Vet Affairs Greater Los Angeles Healthcare S, Oral Biol Res Lab, Los Angeles, CA USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Weintraub Ctr Reconstruct Biotechnol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@med.va.gov FU NIDCR NIH HHS [DE 09085] NR 56 TC 24 Z9 25 U1 0 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2002 VL 133 IS 11 BP 1516 EP 1523 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 618CD UT WOS:000179399800016 PM 12462696 ER PT J AU Abbara, S Bowles, J Yamashita, S Machi, J AF Abbara, S Bowles, J Yamashita, S Machi, J TI Small bowel perforation with minor trauma: A rare complication of an ovarian cystic teratoma SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, Boston, MA 02114 USA. Univ Hawaii, John A Burns Sch Med, Surg Residency Program, Honolulu, HI 96822 USA. Georgetown Univ Hosp, Dept Radiol, Washington, DC 20007 USA. RP Abbara, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Integrat Med & Innovat Technol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2002 VL 53 IS 5 BP 990 EP 992 DI 10.1097/01.TA.0000033753.65011.67 PG 3 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 618DV UT WOS:000179403900032 PM 12435956 ER PT J AU Latini, DM Penson, DF Colwell, HH Lubeck, DP Mehta, SS Henning, JM Lue, TF AF Latini, DM Penson, DF Colwell, HH Lubeck, DP Mehta, SS Henning, JM Lue, TF TI Psychological impact of erectile dysfunction: Validation of a new health related quality of life measure for patients with erectile dysfunction SO JOURNAL OF UROLOGY LA English DT Article DE penis; impotence; questionnaires; quality of life; psychology, medical ID OF-LIFE; MEN AB Purpose: Male erectile dysfunction has a substantial impact on health related quality of life. We examined the psychometric properties of 2 new scales created to measure the psychological impact of erectile dysfunction. Materials and Methods: Patients enrolled in a long-term study of men with erectile dysfunction completed clinical and health related quality of life information at baseline and at 3 followup points. The questionnaire incorporated a number of standard scales of psychosocial characteristics as well as questions developed from comments made during focus groups of men with erectile dysfunction and of their female partners. Principal components analysis was used to identify underlying constructs in response to the new questions. Results: A total of 168 men completed the baseline quality of life questionnaire. The principal components analysis of the psychological impact of erectile dysfunction questions resulted in 2 new scales. Reliability was good with an internal consistency reliability of 0.91 for scale 1 and 0.72 for scale 2. Test-retest reliability was 0.76 and 0.66, respectively. Men reporting a greater psychological impact of erectile dysfunction also reported greater impairment in functional status, lower sexual self-efficacy, greater depression and anxiety at the last intercourse. Each new scale significantly differentiated men with mild/moderate versus severe erectile dysfunction. Conclusions: We developed 2 new scales to measure the psychological impact of erectile dysfunction and they showed good reliability and validity. These new scales, named the Psychological Impact of Erectile Dysfunction instrument, comprehensively capture the psychological effect of erectile dysfunction on health related quality of life, which is not adequately assessed by existing patient centered measures of erectile function. C1 Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Urol Outcomes Res Grp, San Francisco, CA 94143 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Urol, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. TAP Pharmaceut Prod, Lake Forest, IL USA. RP Latini, DM (reprint author), Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. OI Latini, David/0000-0002-6161-4861 NR 18 TC 48 Z9 49 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2002 VL 168 IS 5 BP 2086 EP 2091 DI 10.1097/01.ju.0000034365.57110.b7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 603LX UT WOS:000178562100052 PM 12394715 ER PT J AU Nugent, HM Groothuis, A Seifert, P Guerraro, JL Nedelman, M Mohanakumar, T Edelman, ER AF Nugent, HM Groothuis, A Seifert, P Guerraro, JL Nedelman, M Mohanakumar, T Edelman, ER TI Perivascular endothelial implants inhibit intimal hyperplasia in a model of arteriovenous fistulae: A safety and efficacy study in the pig SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE anastomosis; perivascular; endothelial implants; endothelium; intimal hyperplasia; arteriovenous fistula ID HEMODIALYSIS-PATIENTS; VENOUS STENOSES; VASCULAR ACCESS; ANGIOPLASTY; INJURY; VEIN; RECONSTRUCTION; RESTENOSIS; GROWTH AB Vascular access complications are a major problem in hemodialysis patients. Native arteriovenous fistulae, historically the preferred mode of access, have a patency rate of only 60% at 1 year. The most common mode of failure is due to progressive stenosis at the anastomotic site. We have previously demonstrated that perivascular endothelial cell implants inhibit intimal thickening following acute balloon injury in pigs and now seek to determine if these implants provide a similar benefit in the chronic and more complex injury model of arteriovenous anastomoses. Side-to-side femoral artery-femoral vein anastomoses were created in 24 domestic swine and the toxicological, biological and immunological responses to allogeneic endothelial cell implants were investigated 3 days and 1 and 2 months postoperatively. The anastomoses were wrapped with polymer matrices containing confluent porcine aortic endothelial cells (PAE; n = 14) or control matrices without cells (n = 10). PAE implants significantly reduced intimal hyperplasia at the anastomotic sites compared to controls by 68% (p < 0.05) at 2 months. The beneficial effects of the PAE implants were not due to differences in the rates of reendothelialization between the groups. No significant immunological response to the allogeneic endothelial cells that impacted on efficacy was detected in any of the pigs. No apparent toxicity was observed in any of the animals treated with endothelial implants. These data suggest that perivascular endothelial cell implants are safe and reduce early intimal hyperplasia in a porcine model of arteriovenous anastomoses. Copyright (C) 2002 S. Karger AG, Basel. C1 MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Charles River Labs, Pharmacol & Surg, Worcester, MA USA. Washington Univ Med, Dept Surg, St Louis, MO USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP Edelman, ER (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Bldg 16,Room 343, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL 60407]; NIGMS NIH HHS [GM/HL 49039] NR 27 TC 40 Z9 40 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD NOV-DEC PY 2002 VL 39 IS 6 BP 524 EP 533 DI 10.1159/000067207 PG 10 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 644HV UT WOS:000180912600007 PM 12566978 ER PT J AU Limon, A Devroe, E Lu, R Ghory, HZ Silver, PA Engelman, A AF Limon, A Devroe, E Lu, R Ghory, HZ Silver, PA Engelman, A TI Nuclear localization of human immunodeficiency virus type 1 preintegration complexes (PICs): V165A and R166A are pleiotropic integrase mutants primarily defective for integration, not PIC nuclear import SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURE-BASED MUTAGENESIS; RETROVIRAL DNA INTEGRATION; AMINO-ACID-RESIDUES; REAL-TIME PCR; IN-VIVO; MOLECULAR CLONE; PROTEIN; REPLICATION; CELLS; IDENTIFICATION AB Retroviral replication requires the integration of reverse-transcribed viral cDNA into a cell chromosome. A key barrier to forming the integrated provirus is the nuclear envelope, and numerous regions in human immunodeficiency virus type 1 (HIV-1) have been shown to aid the nuclear localization of viral preintegration complexes (PICs) in infected cells. One region in integrase (IN), composed of Val-165 and Arg-166, was reportedly essential for HIV-1 replication and nuclear localization in all cell types. In this study we confirmed that HIV-1(V165A) and HIV-1(R166A) were replication defective and that less mutant viral cDNA localized to infected cell nuclei. However, we present three lines of evidence that argue against a specific role for Val-165 and Arg-166 in PIC nuclear import. First, results of transient transfections revealed that V165A FLAG-tagged IN and green fluorescent protein-IN fusions carrying either V165A or R166A predominantly localized to cell nuclei. Second, two different strains of previously described class II IN mutant viruses displayed similar nuclear entry profiles to those observed for HIV-1(V165A) and HIV-1(R166A), suggesting that defective nuclear import may be a common phenotype of replication-defective IN mutant viruses. Third, V165A and R166A mutants were defective for in vitro integration activity, when assayed both as PICs isolated from infected T-cells and as recombinant IN proteins purified from Escherichia coli. Based on these results, we conclude that HIV-1(V165A) and HIV-1(R166A) are pleiotropic mutants primarily defective for IN catalysis and that Val-165 and Arg-166 do not play a specific role in the nuclear localization of HIV-1 PICs in infected cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [P30 AI028691, AI28691, AI39394, AI45313, R01 AI039394, R37 AI039394]; NIGMS NIH HHS [GM36373, R01 GM036373, R37 GM036373] NR 57 TC 71 Z9 73 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 NOV PY 2002 VL 76 IS 21 BP 10598 EP 10607 DI 10.1128/JVI.76.21.10598-10607.2002 PG 10 WC Virology SC Virology GA 602NX UT WOS:000178512300003 PM 12368302 ER PT J AU Basmaciogullari, S Babcock, GJ Van Ryk, D Wojtowicz, W Sodroski, J AF Basmaciogullari, S Babcock, GJ Van Ryk, D Wojtowicz, W Sodroski, J TI Identification of conserved and variable structures in the human immunodeficiency virus gp120 glycoprotein of importance for CXCR4 binding SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-TERMINAL DOMAIN; ENVELOPE V3 LOOP; HIV TYPE-1 GLYCOPROTEIN-120; HUMAN MONOCLONAL-ANTIBODY; MACROPHAGE-TROPIC HIV-1; HUMAN LYMPHOID-TISSUE; CHEMOKINE RECEPTORS; PARAMAGNETIC PROTEOLIPOSOMES; CORECEPTOR UTILIZATION; SURFACE GLYCOPROTEIN AB CD4 and the chemokine receptors, CXCR4 and CCR5, serve as receptors for human immunodeficiency virus type 1 (HIV-1). Binding of the HIV-1 gp120 envelope glycoprotein to the chemokine receptors normally requires prior interaction with CD4. Mapping the determinants on gp120 for the low-affinity interaction with CXCR4 has been difficult due to the nonspecific binding of this viral glycoprotein to cell surfaces. Here we examine the binding of a panel of gp120 mutants to paramagnetic proteoliposomes displaying CXCR4 on their surfaces. We show that the gp120 beta19 strand and third variable (V3) loop contain residues important for CXCR4 interaction. Basic residues from both elements, as well as a conserved hydrophobic residue at the V3 tip, contribute to CXCR4 binding. Removal of the gp120 V1/V2 variable loops allows the envelope glycoprotein to bind CXCR4 in a CD4-independent manner. These results indicate that although some variable gp120 residues contribute to the specific binding to CCR5 or CXCR4, gp120 elements common to CXCR4- or CCR5-using strains are involved in the interaction with both coreceptors. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Univ Penn, Sch Med, Stellar Chance Labs, Philadelphia, PA 19104 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Jimmy Fund Bldg,Room 824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31783, AI42848, R01 AI024030, R01 AI041851, AI24030, AI24755, AI41851, P30 AI042848, R01 AI031783, R37 AI024755] NR 80 TC 66 Z9 67 U1 0 U2 5 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 NOV PY 2002 VL 76 IS 21 BP 10791 EP 10800 DI 10.1128/JVI.76.21.10791-10800.2002 PG 10 WC Virology SC Virology GA 602NX UT WOS:000178512300023 PM 12368322 ER PT J AU Hegde, NR Tomazin, RA Wisner, TW Dunn, C Boname, JM Lewinsohn, DM Johnson, DC AF Hegde, NR Tomazin, RA Wisner, TW Dunn, C Boname, JM Lewinsohn, DM Johnson, DC TI Inhibition of HLA-DR assembly, transport, and loading by human cytomegalovirus glycoprotein US3: a novel mechanism for evading major histocompatibility complex class II antigen presentation SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER-CELLS; ENDOPLASMIC-RETICULUM; INVARIANT CHAIN; PEPTIDE TRANSLOCATION; GENE-PRODUCT; HEAVY-CHAINS; INTRACELLULAR-TRANSPORT; SURFACE EXPRESSION; T-CELLS; MOLECULES AB Human cytomegalovirus (HCMV) establishes persistent lifelong infections and replicates slowly. To withstand robust immunity, HCMV utilizes numerous immune evasion strategies. The HCW gene cassette encoding US2 to US11 encodes four homologous glycoproteins, US2, US3, US6, and US11, that inhibit the major histocompatibility complex class I (MHC-I) antigen presentation pathway, probably inhibiting recognition by CD8(+) T lymphocytes. US2 also inhibits the MHC-II antigen presentation pathway, causing degradation of human leukocyte antigen (HLA)-DR-alpha and -DM-alpha and preventing recognition by CD4(+) T cells. We investigated the effects of seven of the US2 to US11 glycoproteins on the MHC-II pathway. Each of the glycoproteins was expressed by using replication-defective adenovirus vectors. In addition to US2, US3 inhibited recognition of antigen by CD4(+) T cells by a novel mechanism. US3 bound to class II alpha/beta complexes in the endoplasmic reticulum (ER), reducing their association with Ii. Class II molecules moved normally from the ER to the Golgi apparatus in US3-expressing cells but were not sorted efficiently to the class II loading compartment. As a consequence, formation of peptide-loaded class II complexes was reduced. We concluded that US3 and US2 can collaborate to inhibit class II-mediated presentation of endogenous HCMV antigens to CD4(+) T cells, allowing virus-infected cells to resist recognition by CD4(+) T cells. C1 Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England. Portland Vet Affairs Med Ctr, Div Pulm & Crit Care Med, Portland, OR 97207 USA. RP Johnson, DC (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Mail Code L-220,Rm 6383 BCs, Portland, OR 97239 USA. RI Hegde, Nagendra/J-5920-2014; Lewinsohn, David/I-4936-2013; OI Hegde, Nagendra/0000-0001-5260-2159; Lewinsohn, David/0000-0001-9906-9494; Boname, Jessica/0000-0002-5149-5934 FU NEI NIH HHS [EY11245, R01 EY011245] NR 65 TC 67 Z9 72 U1 1 U2 7 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 NOV PY 2002 VL 76 IS 21 BP 10929 EP 10941 DI 10.1128/JVI.76.21.10929-10941.2002 PG 13 WC Virology SC Virology GA 602NX UT WOS:000178512300037 PM 12368336 ER PT J AU Madani, N Millette, R Platt, EJ Marin, M Kozak, SL Bloch, DB Kabat, D AF Madani, N Millette, R Platt, EJ Marin, M Kozak, SL Bloch, DB Kabat, D TI Implication of the lymphocyte-specific nuclear body protein Sp140 in an innate response to human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID VIF PROTEIN; SUBCELLULAR-LOCALIZATION; REVERSE TRANSCRIPTION; RESTRICTIVE CELLS; LEUKEMIA PROTEIN; SP100 PROTEINS; DNA-SYNTHESIS; EARLY STEPS; PML; BODIES AB The viral infectivity factor (Vif) of human immunodeficiency virus type 1 (HIV-1) neutralizes an unidentified antiviral pathway that occurs only in nonpermissive (NP) cells. Using a yeast two-hybrid screen of a human lymphocyte cDNA library, we identified several potential Vif partners. One, the nuclear body protein Sp140, was found specifically in all NP cells (n=12 cell lines tested; Pless than or equal to0.001), and HIV-1 infection induced its partial dispersal from nuclear bodies into cytosolic colocalization with Vif. Our results implicate Sp140 in a response to HIV-1 that may be related to or coordinated with the pathway that inactivates HIV-1 lacking vif. C1 Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Kabat, D (reprint author), Oregon Hlth Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. FU NIAID NIH HHS [AI49729, R01 AI049729, R21 AI049729] NR 57 TC 39 Z9 40 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 21 BP 11133 EP 11138 DI 10.1128/JVI.76.21.11133-11138.2002 PG 6 WC Virology SC Virology GA 602NX UT WOS:000178512300057 PM 12368356 ER PT J AU Kominsky, DJ Bickel, RJ Tyler, KL AF Kominsky, DJ Bickel, RJ Tyler, KL TI Reovirus-induced apoptosis requires mitochondrial release of Smac/DIABLO and involves reduction of cellular inhibitor of apoptosis protein levels SO JOURNAL OF VIROLOGY LA English DT Article ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; INFLUENZA-A VIRUS; LYMPHOCYTE APOPTOSIS; MEDIATED APOPTOSIS; FAMILY PROTEINS; MEASLES-VIRUS; T-CELLS; DEATH; IAP AB Many viruses belonging to diverse viral families with differing structure and replication strategies induce apoptosis both in cultured cells in vitro and in tissues in vivo. Despite this fact, little is known about the specific cellular apoptotic pathways induced during viral infection. We have previously shown that reovirus-induced apoptosis of HEK cells is initiated by death receptor activation but requires augmentation by mitochondrial apoptotic pathways for its maximal expression. We now show that reovirus infection of HEK cells is associated with selective cytosollic release of the mitochondrial proapoptotic factors cytochrome c and Smac/DLABLO, but not the release of apoptosis-inducing factor. Release of these factors is not associated with loss of mitochondrial transmembrane potential and is blocked by overexpression of Bcl-2. Stable expression of caspase-9b, a dominant-negative form of caspase-9, blocks reovirus-induced caspase-9 activation but fails to significantly reduce activation of the key effector caspase, caspase-3. Smac/DIABLO enhances apoptosis through its action on cellular inhibitor of apoptosis proteins (IAPs). Reovirus infection is associated with selective downregulation of cellular IAPs, including c-LAP1, XIAP, and survivin, effects that are blocked by Bcl-2 expression, establishing the dependence of IAP down-regulation on mitochondriall events. Taken together, these results are consistent with a model in which Smac/DLABLO-mediated inhibition of 1APs, rather than cytochrome c-mediated activation of caspase-9, is the key event responsible for mitochondrial augmentation of reovirus-induced apoptosis. These studies provide the first evidence for the association of Smac/DIABLO with virus-induced apoptosis. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1R01AG14071]; NINDS NIH HHS [T32NS07321, T32 NS007321] NR 63 TC 50 Z9 55 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2002 VL 76 IS 22 BP 11414 EP 11424 DI 10.1128/JVI.76.22.11414-11424.2002 PG 11 WC Virology SC Virology GA 608AF UT WOS:000178822400026 PM 12388702 ER PT J AU Roman, GC Erkinjuntti, T Wallin, A Pantoni, L Chui, HC AF Roman, GC Erkinjuntti, T Wallin, A Pantoni, L Chui, HC TI Subcortical ischaemic vascular dementia SO LANCET NEUROLOGY LA English DT Review ID WHITE-MATTER LESIONS; AUTOSOMAL-DOMINANT ARTERIOPATHY; CHRONIC CEREBRAL HYPOPERFUSION; ENCEPHALOPATHY BINSWANGERS DISEASE; EXECUTIVE COGNITIVE IMPAIRMENT; CORONARY-ARTERY BYPASS; BRAIN-BARRIER FUNCTION; VISUAL RATING-SCALES; AMYLOID ANGIOPATHY; RISK-FACTORS AB Vascular dementia is the second most common type of dementia. The subcortical ischaemic form (SIVD) frequently causes cognitive impairment and dementia in elderly people. SIVD results from small-vessel disease, which produces either arteriolar occlusion and lacunes or widespread incomplete infarction of white matter due to critical stenosis of medullary arterioles and hypoperfusion (Binswanger's disease). Symptoms include motor and cognitive dysexecutive slowing, forgetfulness, dysarthria, mood changes, urinary symptoms, and short-stepped gait. These manifestations probably result from ischaemic interruption of parallel circuits from the prefrontal cortex to the basal ganglia and corresponding thalamocortical connections. Brain imaging (computed tomography and magnetic resonance imaging) is essential for correct diagnosis. The main risk factors are advanced age, hypertension, diabetes, smoking, hyperhomocysteinaemia, hyperfibrinogenaemia, and other conditions that can cause brain hypoperfusion such as obstructive sleep apnoea, congestive heart failure, cardiac arrhythmias, and orthostatic hypotension. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) and some forms of cerebral amyloid angiopathy have a genetic basis. Treatment is symptomatic and prevention requires control of treatable risk factors. C1 Univ Texas, HSC, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Gothenburg, Molndal, Sweden. Sahlgrens Univ Hosp, Molndal, Sweden. Univ Florence, Florence, Italy. Univ So Calif, Los Angeles, CA USA. Rancho Los Amigos Natl Rehabil Ctr, Downey, CA USA. RP Roman, GC (reprint author), Univ Texas, HSC, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [P01 AG12435] NR 152 TC 504 Z9 555 U1 4 U2 44 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2002 VL 1 IS 7 BP 426 EP 436 DI 10.1016/S1474-4422(02)00190-4 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 606KC UT WOS:000178732300020 PM 12849365 ER PT J AU Joensuu, H Fletcher, C Dimitrijevic, S Silberman, S Roberts, P Demetri, G AF Joensuu, H Fletcher, C Dimitrijevic, S Silberman, S Roberts, P Demetri, G TI Management of malignant gastrointestinal stromal tumours SO LANCET ONCOLOGY LA English DT Review ID TYROSINE KINASE INHIBITOR; SMOOTH-MUSCLE TUMORS; SOFT-TISSUE SARCOMAS; C-KIT PROTOONCOGENE; STEM-CELL FACTOR; INTERSTITIAL-CELLS; PROGNOSTIC FACTORS; GERMLINE MUTATION; BCR-ABL; DIFFERENTIAL-DIAGNOSIS AB Gastrointestinal stromal tumours (GISTs) are the most common form of mesenchymal tumour of the gastrointestinal tract. Clinically, they range from small indolent tumours curable with surgery alone to aggressive cancers. Making a distinction between an indolent and a malignant GIST is unreliable with conventional histopathological techniques. The presence of metastases at the time of diagnosis confirms malignancy, but all GISTs should be regarded as having malignant potential. GISTs characteristically express the KIT protein, a transmembrane tyrosine kinase receptor for stem-cell factor. Most GISTs have a mutation in the KIT proto-oncogene that translates into a gain-of-function constitutive activation of the KIT kinase. KIT activation seems to be an early tumour-promoting event in pathogenesis. Commonly, malignant GISTs show high-level primary resistance to conventional chemotherapy. Imatinib mesylate is an orally administered selective inhibitor of certain tyrosine kinases including KIT. Most patients with advanced malignant GISTs achieve clinical benefit and significant antitumour responses with imatinib mesylate. Responses have been durable, and most patients tolerate the drug well at clinically effective doses. Imatinib mesylate is the first effective systemic therapy for advanced GIST. C1 Univ Helsinki, Cent Hosp, Dept Radiotherapy & Oncol, Helsinki, Finland. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Novortis Oncol, Basel, Switzerland. Turku Univ, Cent Hosp, Dept Surg, FIN-20520 Turku, Finland. Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Dept Med Oncol, Boston, MA 02115 USA. RP Joensuu, H (reprint author), Univ Helsinki, Cent Hosp, Dept Oncol, Haartmaninkatu 4,POB 180, FIN-00029 Helsinki, Finland. NR 80 TC 331 Z9 377 U1 1 U2 9 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2002 VL 3 IS 11 BP 655 EP 664 DI 10.1016/S1470-2045(02)00899-9 PG 10 WC Oncology SC Oncology GA 612QK UT WOS:000179086800018 PM 12424067 ER PT J AU Weichselbaum, RR Kufe, DW Hellman, S Rasmussen, HS King, CR Fischer, PH Mauceri, HJ AF Weichselbaum, RR Kufe, DW Hellman, S Rasmussen, HS King, CR Fischer, PH Mauceri, HJ TI Radiation-induced tumour necrosis factor-alpha expression: clinical application of transcriptional and physical targeting of gene therapy SO LANCET ONCOLOGY LA English DT Review ID VASCULAR ENDOTHELIAL-CELLS; FIBROBLAST GROWTH-FACTOR; PROTEIN-KINASE-C; IONIZING-RADIATION; EGR-1 PROMOTER; IN-VIVO; FACTOR CACHECTIN; MESSENGER-RNA; FACTOR TNF; ANGIOSTATIN AB Promising data are emerging on a new anticancer agent, Ad.EGR-TNF, an adenoviral vector, which contains radio-inducible DNA sequences from the early growth response (EGR1) gene promoter and cDNA for the gene encoding human tumour necrosis factor-alpha. Ad.EGR-TNF combines the well-documented broad-spectrum anticancer activity of TNFalpha with the proven clinical usefulness of radiotherapy. Systemic delivery of the TNFalpha protein has had limited success clinically because of severe dose-limiting toxic effects. This limitation has been overcome by the use of a gene delivery approach, combined with a radiation-inducible promoter to express the TNFalpha protein in the irradiated tumour tissue. Preclinical and early phase I clinical testing indicates that effective concentrations of TNFalpha can be delivered to the tumour site without significant systemic exposure or toxic effects. The combination of radiation and TNFalpha gene delivery has produced striking antitumour effects in model systems in animals. In the clinical setting, potent anticancer activity has been observed with a high rate of complete and partial objective tumour responses. A novel mechanism of destruction of the tumour vasculature seems to be central to this distinct antitumour activity. This review summarises the rationale, mechanistic basis, preclinical data, and preliminary clinical findings for this new treatment model. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Harvard Univ, Dana Farber Canc Inst, Expt Therapuet Program, Boston, MA 02115 USA. GenVec Inc, Gaithersburg, MD USA. RP Weichselbaum, RR (reprint author), Duchossois Ctr Adv Med, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. NR 75 TC 68 Z9 77 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2002 VL 3 IS 11 BP 665 EP 671 DI 10.1016/S1470-2045(02)00900-2 PG 7 WC Oncology SC Oncology GA 612QK UT WOS:000179086800019 PM 12424068 ER PT J AU Fechner, FP Faquin, WC Pilch, BZ AF Fechner, FP Faquin, WC Pilch, BZ TI Wegener's granulomatosis of the orbit: A clinicopathological study of 15 patients SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the Triological-Society CY MAY 12-14, 2002 CL BOCA RATON, FLORIDA SP Triol Soc ID NASAL BIOPSY; C-ANCA; EXPERIENCE AB Objectives. Wegener's granulomatosis is a granulomatous and necrotizing vasculitis that classically involves the respiratory and renal systems. The goal of the study was to define clinical and pathological characteristics in a subgroup of patients with the changes of Wegener's granulomatosis involving the orbit. Study Design. Retrospective study. Methods. A database search identified 15 patients with the histological changes of Wegener's granulomatosis of the orbit presenting over a 23-year period. A review of the histological specimens, radiological studies, and patient charts was performed. Additional follow-up data were obtained through patient interviews. Results. Of 15 patients (median age, 54 y) with Wegener's granulomatosis of the orbit identified, the disease was limited to the orbit in 12 patients; 3 patients had additional sinonasal involvement. All patients underwent various surgical procedures followed by medical treatment (cyclophosphamide and prednisone). Specimens showed characteristic histopathological features of Wegener's granulomatosis. Follow-up data were available for 12 patients with a median period of 5 years. In the group with only orbital involvement, none of the patients developed systemic progression of Wegener's granulomatosis. Only one patient had multiple local recurrences and later developed contralateral orbital Wegener's granulomatosis. Conclusions. Wegener's granulomatosis limited to the orbit is a localized form of the disease without systemic progression. Diagnostic surgical procedures followed by aggressive medical treatment results in good outcome, although local recurrence may occur. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02144 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Fechner, FP (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02144 USA. NR 20 TC 34 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2002 VL 112 IS 11 BP 1945 EP 1950 DI 10.1097/00005537-200211000-00007 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 614ME UT WOS:000179193300007 PM 12439160 ER PT J AU Hur, K Kim, JI Choi, SI Choi, EK Carp, RI Kim, YS AF Hur, K Kim, JI Choi, SI Choi, EK Carp, RI Kim, YS TI The pathogenic mechanisms of prion diseases SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE transmissible spongiform encephalopathies (TSEs) or prion diseases; prion protein (PrPC, PrPSc); pathogenic mechanisms; neurodegeneration; oxidative stress ID SCRAPIE-INFECTED MICE; CREUTZFELDT-JAKOB-DISEASE; CALCIUM-BINDING PROTEIN; OXIDATIVE STRESS; NEURODEGENERATIVE DISEASES; INCREASED EXPRESSION; NERVOUS-SYSTEM; SPONGIFORM ENCEPHALOPATHIES; PREFERENTIALLY INTERACTS; GENE-EXPRESSION AB Transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative diseases of humans and animals, including bovine spongiform encephalopathy (BSE) of cattle, scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans. Prion diseases have become an important issue in public health and in the scientific world not only due to the possible relationship between BSE and new variant CJD (nvCJD) but also due to the unique biological features of the infectious agent. Although the nature of the infectious agent and the pathogenic mechanisms of prion diseases are not fully understood, considerable evidence suggests that an abnormal form (PrPSc) of a host prion protein (PrPC) may compose substantial parts of the infectious agent and that various factors such as oxidative stress and calcium cytotoxicity are associated with the pathogenesis of prion diseases. Here, we briefly review and discuss the pathogenic mechanisms of prion diseases. These advances in understandings of fundamental biology of prion diseases may open the possibilities for the prevention and treatment of these unusual diseases and also suggest applications in more common neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Hallym Univ, Hallym Acad Sci, Ilsong Inst Life Sci, Dongan Gu 431060, Anyang, South Korea. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Kim, YS (reprint author), Hallym Univ, Hallym Acad Sci, Ilsong Inst Life Sci, Ilsong Bldg,Kwanyang Dong 1605-4, Dongan Gu 431060, Anyang, South Korea. NR 75 TC 33 Z9 33 U1 0 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV PY 2002 VL 123 IS 12 BP 1637 EP 1647 AR PII S0047-6374(02)00099-4 DI 10.1016/S0047-6374(02)00099-4 PG 11 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 627HL UT WOS:000179927700012 PM 12470901 ER PT J AU Hauser-Kara, DA Bartel, DL AF Hauser-Kara, DA Bartel, DL TI Periprosthetic modelling of femoral component fit using computed tomography data for total hip arthroplasty: a feasibility study SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE total hip arthroplasty; joint replacement; optimisation; implant design ID PROSTHESIS; BONE AB The aim of the work was to create a new three-dimensional periprosthetic multi-criteria optimisation technique to identify the best six degrees of freedom transform to position a porous-coated anatomic cementless femoral component for three factors, including: first, maximisation of the degree of contact achieved between designated bone ingrowth surfaces and the periprosthetic bone; secondly, minimisation of the bone mass to be removed to accommodate the component and thirdly, the extreme constraint of the component to be positioned so that it does not project beyond the periosteum. Discrete integrals were computed over regions of interest derived from the polyhedral component mesh in transaxial CT scan planes, using a polygon scan-conversion algorithm. A new biomedical imaging volume rendering technique utilising dynamic virtual textures was developed to visualise the design trade-offs. Pareto-optima were identified for four femora that matched an average-sized component. The non-linear, multi-modal fit metric was quadratic near minima, with a narrow trough of equivalent fit values within 3 mm of translation and 3 degrees of rotation with respect to the canal axis, and possessed a dependence most pronounced for distal-directed insertion against varus/valgus rotation. The study gives previously unavailable data on the three-dimensional femoral component fit and is the first report that demonstrates that fitting the implant using several design criteria in a multi-criteria optimisation scheme is feasible. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Cornell Univ, Hosp Special Surg, Program Biomech Engn, Ithaca, NY USA. RP Hauser-Kara, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU PETER PEREGRINUS LTD PI HERTS PA MICHAEL FARADAY HOUSE, SIX HILLS WAY, STEVANAGE, HERTS SG1 2AY, ENGLAND SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD NOV PY 2002 VL 40 IS 6 BP 641 EP 646 DI 10.1007/BF02345302 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 632JF UT WOS:000180219600005 PM 12507314 ER PT J AU Tierney, WM Weinberger, M Ashton, CM McHorney, CA AF Tierney, WM Weinberger, M Ashton, CM McHorney, CA TI A remarkable legacy of science review of AHRQ-funded articles published in Medical Care during John Eisenberg's directorship of AHRQ SO MEDICAL CARE LA English DT Editorial Material ID QUALITY-OF-LIFE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED TRIAL; PHYSICIAN JOB-SATISFACTION; SELF-MANAGEMENT PROGRAM; OUTCOMES RESEARCH TEAMS; NURSING-HOME RESIDENTS; HEALTH-STATUS; INTRAINDIVIDUAL CHANGES; EDUCATIONAL-PROGRAM C1 Richard L Roudebush VA Med Ctr, HSR&D Serv, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Regenstrief Inst Hlth Care, Indianapolis, IN 46204 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27515 USA. Durham VA Med Ctr, Durham, NC USA. Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Tierney, WM (reprint author), Richard L Roudebush VA Med Ctr, HSR&D Serv, 11H,1481 W 10th St, Indianapolis, IN 46202 USA. NR 84 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2002 VL 40 IS 11 BP 1003 EP 1011 DI 10.1097/01.MLR.0000032180.23171.01 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 611DP UT WOS:000179001400001 PM 12409845 ER PT J AU Polsky, D Keating, NL Weeks, JC Schulman, KA AF Polsky, D Keating, NL Weeks, JC Schulman, KA TI Patient choice of breast cancer treatment - Impact on health state preferences SO MEDICAL CARE LA English DT Article DE choice; patient participation; breast cancer; health state preferences ID COMPARING TOTAL MASTECTOMY; SURGICAL-TREATMENT; DECISION-MAKING; CLINICAL-TRIAL; WOMEN; OUTCOMES; CARE; PARTICIPATION; INVOLVEMENT; LUMPECTOMY AB BACKGROUND. Multiple treatment options exist for many medical conditions. The extent to which physicians should involve the patient in the choice the treatment to be delivered is not well understood. OBJECTIVE. To test the impact of breast cancer treatment choice on patients' health state preferences. DESIGN AND SETTING. A cohort from 29 hospitals (primarily referral centers) in Massachusetts, Texas, Washington DC, and New York. Subjects were surveyed at 5 months, 1 year, and 2 years following surgery and asked whether they had a choice in the type of treatment received. SUBJECTS. Women age 67 or older treated in 1996 to 1997 for localized breast cancer (n = 683). MEASURES. Patient preferences for current health state, assessed with patient valuations using the visual analogue scale WAS) from the EuroQol instrument and with general public valuations using the Health Utilities Index (HUI), and 1-year medical costs. RESULTS. For the adjusted analysis at 5 months, the adjusted mean VAS score was 78.7 for women who reported a choice and 75.3 for women who reported no choice, a difference of 3.4 (P = 0.03). The difference in the HUI score was 3.6 (P = 0.10) and the difference in the 1-year medical costs was -$4363 (P = 0.01). There were no statistically significant differences at the 1-year and 2-year interviews. CONCLUSIONS. A woman's perception of choice of surgical treatment for breast cancer is associated with a short-term benefit on her preference of health state, suggesting choice helps with recovery, but does not provide long-term benefits. C1 Univ Penn Hlth Syst, Div Gen Internal Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn Hlth Syst, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Div Gen Internal Med, Sect Hlth Serv & Policy Res, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC 27706 USA. RP Polsky, D (reprint author), Univ Penn Hlth Syst, Div Gen Internal Med, Dept Med, Blockley Hall Rm 1212, Philadelphia, PA 19104 USA. FU AHRQ HHS [HS08395] NR 35 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2002 VL 40 IS 11 BP 1068 EP 1079 DI 10.1097/01.MLR.0000032188.93444.20 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 611DP UT WOS:000179001400008 PM 12409852 ER PT J AU Kovacs, TOG Jensen, DM AF Kovacs, TOG Jensen, DM TI Recent advances in the endoscopic diagnosis and therapy of upper gastrointestinal, small intestinal, and colonic bleeding SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID PROSPECTIVE RANDOMIZED TRIAL; ACUTE VARICEAL HEMORRHAGE; CONTROLLED CLINICAL-TRIAL; ESOPHAGEAL-VARICES; PEPTIC-ULCERS; INJECTION SCLEROTHERAPY; COMPARING SOMATOSTATIN; PORTAL-HYPERTENSION; HEATER PROBE; DOUBLE-BLIND AB Endoscopy has evolved as the first and primary modality to evaluate patients with severe gastrointestinal hemorrhage. Panendoscopy, push enteroscopy, and colonoscopy provide vital diagnostic and prognostic information and the opportunity for therapeutic intervention. Experienced endoscopists who use standardized endoscopic hemostatic techniques can arrest active bleeding from gastrointestinal lesions and improve patient outcome. This article reviews recent advances in the endoscopic diagnosis and treatment of severe gastrointestinal hemorrhage that have resulted in improved patient care. C1 VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA. RP Kovacs, TOG (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Sch Med, Bldg 115,Room 212,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [M01-RR00865]; NIDDK NIH HHS [1K24 DK 02650, DK 41301, R01-DK 33273] NR 110 TC 36 Z9 38 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 2002 VL 86 IS 6 BP 1319 EP + AR PII S0025-7125(02)00079-2 DI 10.1016/S0025-7125(02)00079-2 PG 40 WC Medicine, General & Internal SC General & Internal Medicine GA 647UF UT WOS:000181111900006 PM 12510456 ER PT J AU Metlay, JP Shea, JA Asch, DA AF Metlay, JP Shea, JA Asch, DA TI Antibiotic prescribing decisions of generalists and infectious disease specialists: Thresholds for adopting new drug therapies SO MEDICAL DECISION MAKING LA English DT Article DE antibiotics; medical decision making; attitudes of health personnel ID COMMUNITY-ACQUIRED PNEUMONIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; PRIMARY-CARE PHYSICIANS; ANTIMICROBIAL RESISTANCE; UNITED-STATES; PNEUMOCOCCAL PNEUMONIA; RESPONSE RATES; ADULT PATIENTS; MAIL SURVEYS; MANAGEMENT AB The objective of this study was to examine whether physicians are willing to continue to use older antibiotics in the face of drug resistance in order to preserve newer antibiotics for future use. The study was a national sample of 398 generalist physicians and 429 infectious disease (ID) specialists. Clinical vignettes prompted respondents to select the level of resistance to a hypothetical older antibiotic at which they would prefer a newer antibiotic without any current resistance in the treatment of a patient with pneumococcal pneumonia. Vignettes varied in the site of care of the patient as a proxy for variation in disease severity. Respondents significantly reduced their threshold for switching to a newer antibiotic as disease severity increased. Generalists were more responsive to disease severity than ID specialists. Thus, the adoption of recommendations to limit overuse of newer antibiotics maybe variable across clinical settings and providers, reducing the impact of these recommendations on emerging resistance. C1 Univ Penn, Sch Med, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, Philadelphia, PA 19104 USA. Univ Penn, Div Gen Internal Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Metlay, JP (reprint author), Univ Penn, Sch Med, Ctr Hlth Equ Res & Promot, Dept Vet Affairs, 712 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 35 TC 10 Z9 10 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2002 VL 22 IS 6 BP 498 EP 505 DI 10.1177/0272989X02238297 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 615RQ UT WOS:000179260800005 PM 12458980 ER PT J AU Holmes, WC AF Holmes, WC TI HIV/AIDS, utilities, and cost-effectiveness analysis: Stepping toward the future SO MEDICAL DECISION MAKING LA English DT Editorial Material ID QUALITY-OF-LIFE C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2002 VL 22 IS 6 BP 522 EP 525 DI 10.1177/0272989X02238584 PG 4 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 615RQ UT WOS:000179260800008 PM 12458983 ER PT J AU Joffe, H Hall, JE Soares, CN Hennen, J Reilly, CJ Carlson, K Cohen, LS AF Joffe, H Hall, JE Soares, CN Hennen, J Reilly, CJ Carlson, K Cohen, LS TI Vasomotor symptoms are associated with depression in perimenopausal women seeking primary care SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE depression; women; perimenopause; hot flushes; night sweats; vasomotor symptoms; sleep ID COMMUNITY SAMPLE; HOT FLUSHES; ESTROGEN; SEROTONIN; PREVALENCE; DISORDERS; MOOD AB Objective: To compare the relationship between vasomotor symptoms (hot flushes and night sweats) and depression in perimenopausal women with that in postmenopausal and older premenopausal women. Design: Questionnaire data assessing current depressive symptoms (Center for Epidemiologic Studies Depression Scale), hot flushes, night sweats, menopausal status, depression history, hormonal therapy use, and demographic characteristics were collected from women aged 40 to 60 years seeking primary care. Multivariable logistic regression models were used to examine the relationship between vasomotor symptoms and depression. \ Results: Depression (defined by a Center for Epidemiologic Studies Depression Scale score 25) was observed in 14.9% of 141 perimenopausal women, 13.9% of 151 postmenopausal women, and 7.6% of 184 older premenopausal women. Recent vasomotor symptoms were reported by 53.9% of perimenopausal women, 43.7% of postmenopausal women, and 20.7% of older premenopausal women. Perimenopausal women with vasomotor symptoms were 4.39 times more likely to be depressed than those without vasomotor symptoms (95% Cl, 1.40-13.83), an association that did not change after controlling for depression history. In contrast with perimenopausal women, postmenopausal and older premenopausal women with vasomotor symptoms did not have a significantly greater risk for depression than women of the same menopausal status without vasomotor symptoms (adjusted odds ratios, 1.28 and 1.77; 95% Cl, 0.47-3.46 and 0.53-5.89, respectively). Conclusions: Hot flushes and night sweats are associated with depression in perimenopausal women. Further investigation is warranted to elucidate the mechanism by which hot flushes may be associated with depression in perimenopausal women and not in postmenopausal or older premenopausal women. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. McLean Hosp, Biostat Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Womens Hlth Associates, Boston, MA 02114 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Program, 15 Parkman St,WACC 815, Boston, MA 02114 USA. NR 22 TC 112 Z9 119 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2002 VL 9 IS 6 BP 392 EP 398 DI 10.1097/01.GME.0000033599.12580.A3 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 614JN UT WOS:000179185100003 PM 12439097 ER PT J AU Kokkotou, E Marafelia, P Mantzos, EI Tritos, NA AF Kokkotou, E Marafelia, P Mantzos, EI Tritos, NA TI Serum monocyte chemoattractant protein-1 is increased in chronic autoimmune thyroiditis SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID HASHIMOTOS-THYROIDITIS; GRAVES-DISEASE; MESSENGER-RNA; CHEMOKINES; EXPRESSION; RECRUITMENT; PATHOLOGY; CYTOLYSIS; RECEPTOR; ABSENCE AB Chemokines are a large family of cytokines, which may be involved in the pathogenesis of a wide variety of inflammatory or autoimmune conditions. The role of chemokines in chronic autoimmune thyroiditis is unknown. We sought to examine the role of CC chemokines in chronic autoimmune thyroiditis. We measured serum levels of CC chemokines, including monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1a and 1b (MIP-1a and MIP-1b) in 32 women with chronic autoimmune thyroiditis in comparison with 2 control groups (33 apparently healthy women and 43 women with benign cold thyroid nodules) by enzyme-linked immunosorbent assay (ELISA). We found a 45% increase in serum MCP-1 levels in women with chronic autoimmune thyroiditis compared with either of the 2 control groups (P = .01). There was no difference in either serum MIP-1a (P = .69) or MIP-1b (P = .81) levels between women with chronic autoimmune thyroiditis and controls. Among women with chronic autoimmune thyroiditis, women with a family history of hypothyroidism had a 59% increase in serum MCPA levels compared with women with no family history of hypothyroidism (P = .02). Serum MCP-1 levels were associated with serum levels of antithyroid peroxidase (r = .2, P = .03) (anti-TPO Ab) and antithyroglobulin (r = .2, P = .04) antibodies (anti-TG Ab). There was no association between serum MCPA levels and serum free thyroxine index (P = .57), triiodothyronine (T-3) (P = .47) or thyroid-stimulating hormone (TSH) (P = .47) levels. Serum MCP-1 is increased in women with chronic autoimmune thyroiditis, especially in the presence of a family history of hypothyroidism, indicating a possible pathogenetic role for MCP-1 in this condition. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med,Div Expt Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med,Div Endocrinol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Univ Athens, Sch Med, Evgenid Hosp, Endocrine Unit, Athens, Greece. RP Tritos, NA (reprint author), Joslin Diabet Ctr, 1 Joslin Pl 653, Boston, MA 02215 USA. NR 30 TC 14 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2002 VL 51 IS 11 BP 1489 EP 1493 DI 10.1053/meta.2002.34717 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 611CM UT WOS:000178998900022 PM 12404203 ER PT J AU Nadeau, WJ Pistole, TG McCormick, BA AF Nadeau, WJ Pistole, TG McCormick, BA TI Polymorphonuclear leukocyte migration across model intestinal epithelia enhances Salmonella typhimurium killing via the epithelial derived cytokine, IL-6 SO MICROBES AND INFECTION LA English DT Article DE Salmonella typhimurium; polymorphonuclear leukocytes; epithelial cells; IL-6 ID CELLS; MACROPHAGES; NEUTROPHILS; SECRETION; LIPOPOLYSACCHARIDE; PHAGOCYTOSIS; ATTACHMENT; MONOLAYERS; ADHERENCE AB The host response to Salmonella typhimurium involves movement of polymorphonuclear leukocytes (PMN) across the epithelium and into the intestinal lumen. Following their arrival in the lumen, the PMN attempt to combat bacterial infection by activating antimicrobial defenses such as granule release, oxidative burst, phagocytosis, and cell signaling. We sought to examine PMN-S. typhimurium interaction following PMN arrival in the lumenal compartment. Here, for the first time, we demonstrate that PMN that have transmigrated across model intestinal epithelia have an enhanced ability to kill S. typhimurium. Our data provide evidence to indicate that the extracellular release of the primary and secondary granules of PMN, myeloperoxidase and lactoferrin, respectively, is correlated with enhanced bacterial killing. Furthermore, epithelial cells, during PMN transmigration, release the cytokine IL-6. IL-6 is known to increase intracellular stores of Ca2+, and we have determined that this epithelial released cytokine is not only responsible for priming the PMN to release their granules, but also stimulating the PMN to kill S. typhimurium. These results substantiate the pathway in which PMN transmigration activates the epithelial release of IL-6, which in turn increases intracellular Ca2+ storage. Our results, herein, extend this pathway to include an enhanced PMN granule release and an enhanced killing of S. typhimurium. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Harvard Univ, Sch Med,Mucosal Immunol Lab, Dept Pediat Gastroenterol & Nutr, Massachusetts Gen Hosp, Boston, MA 02129 USA. Univ New Hampshire, Dept Microbiol, Durham, NH 03824 USA. RP McCormick, BA (reprint author), Harvard Univ, Sch Med,Mucosal Immunol Lab, Dept Pediat Gastroenterol & Nutr, Massachusetts Gen Hosp, 114 16th St,114-3503, Boston, MA 02129 USA. FU NIAID NIH HHS [AI-47412]; NIDDK NIH HHS [DK-56754, DK-33506] NR 29 TC 21 Z9 22 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD NOV PY 2002 VL 4 IS 14 BP 1379 EP 1387 AR PII S1286-4579(02)00020-5 DI 10.1016/S1286-4579(02)00020-5 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 632VJ UT WOS:000180243900001 PM 12475628 ER PT J AU Dobashi, K Singh, I Orak, JK Asayama, K Singh, AK AF Dobashi, K Singh, I Orak, JK Asayama, K Singh, AK TI Combination therapy of N-acetylcysteine, sodium nitroprusside and phosphoramidon attenuates ischemia-reperfusion injury in rat kidney SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE N-acetylcysteine; nitric oxide; endothelin; ischemia-reperfusion injury; antioxidant enzymes; free radicals ID ACUTE-RENAL-FAILURE; NITRIC-OXIDE; SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; FREE-RADICALS; TUBULAR-NECROSIS; PROXIMAL TUBULE; RELAXING FACTOR; TISSUE-INJURY; ENDOTHELIUM AB Renal ischemia is of clinical interest because of its role in renal failure and also renal graft rejection. To evaluate the effect of the combination of N-acetylcysteine (NAC), a potent antioxidant, sodium nitroprusside (SNP), a nitric oxide donor, and phosphoramidon (P), an endothelin converting enzyme inhibitor, on tissue protection against ischemia-reperfusion injury, we studied the biochemical and morphological changes due to 90 min of renal ischemia-reperfusion in the rat model. Ninety min of ischemia caused very severe injury and the animals could not survive after 4 days without any treatment. Whereas, animals in the treated groups survived i.e. the NAC group (25%), NAC + SNP group (43%) and in the NAC + SNP + P group (100%), 2 weeks after 90 min of ischemia. A significant increase in the serum levels of creatinine and urea nitrogen was shown in the untreated group and to a much lesser extent in the treated group, especially in the NAC + SNP + P group. The protective effect was also supported by light microscopic studies on renal tissue sections. We also measured the activities of antioxidant enzymes in tissue homogenates. With the exception of Mn-superoxide dismutase, the activities of antioxidant enzymes (catalase, glutathione peroxidase, CuZn-superoxide dismutase) were decreased in the untreated kidney. The administration of NAC alone and NAC + SNP protected against the loss of activities. Treatment with a combination of NAC, SNP and P showed a synergistic effect as evidenced by the best protection. These results suggest that pre-administration of a combination of antioxidant (NAC) with endothelin derived vasodilators (sodium nitroprusside and Phosphoramidon) attenuates renal ischemia-reperfusion injury, e. g. in donor kidney for transplantation, by protecting cells against free radical damage. C1 Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat & Pathol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pathol & Lab Med, 171 Ashley Ave,316 CSB, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-34741, NS-40810, NS-37766, NS-22576] NR 48 TC 27 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2002 VL 240 IS 1-2 BP 9 EP 17 DI 10.1023/A:1020629020443 PG 9 WC Cell Biology SC Cell Biology GA 603EH UT WOS:000178545500002 PM 12487367 ER PT J AU Kuwata, T Gongora, C Kanno, Y Sakaguchi, K Tamura, T Kanno, T Basrur, V Martinez, R Appella, E Golub, T Ozato, K AF Kuwata, T Gongora, C Kanno, Y Sakaguchi, K Tamura, T Kanno, T Basrur, V Martinez, R Appella, E Golub, T Ozato, K TI Gamma interferon triggers interaction between ICSBP (IRF-8) and TEL, recruiting the histone deacetylase HDAC3 to the interferon-responsive element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR PU.1; REGULATORY FACTORS; IN-VIVO; GENE; EXPRESSION; MACROPHAGES; COMPLEX; FAMILY; DNA AB ICSBP (IRF-8) is a transcription factor of the IRF family expressed only in the immune system. It is induced in macrophages by gamma interferon (IFN-gamma) and contributes to macrophage functions. By interacting with Ets family protein PU.1, ICSBP binds to the IRF/Ets composite element and stimulates transcription. ICSBP binds to another DNA element, the IFN-stimulated response element (ISRE), a common target of the IRF family. Limited knowledge as to how ICSBP and other IRF proteins regulate ISRE-dependent transcription in WN-y-activated macrophages is available. By mass-spectrometric analysis of ISRE-bound proteins in macrophages, we identified TEL, another Ets member, as a factor recruited to the element in an IFN-y-dependent manner. In vitro analysis with recombinant proteins indicated that this recruitment is due to a direct interaction between ICSBP and TEL, which is enhanced by the presence of ISRE. Significantly, the interaction with TEL in turn resulted in the recruitment of the histone deacetytase HDAC3 to the ISRE, causing increased repression of IFN-y-mediated reporter activity through the ISRE. This repression may provide a negative-feedback mechanism operating after the initial transcriptional activation by IFN-y. By associating with two different Ets family proteins, ICSBP exerts a dual function in IFN-y-dependent gene regulation in an immune system-specific manner. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01,6 Ctr Dr,MSC-2753, Bethesda, MD 20892 USA. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 61 TC 37 Z9 38 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 NOV PY 2002 VL 22 IS 21 BP 7439 EP 7448 DI 10.1128/MCB.22.21.7439-7448.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603XQ UT WOS:000178586900008 PM 12370291 ER PT J AU Wu, L Sun, T Kobayashi, K Gao, P Griffin, JD AF Wu, L Sun, T Kobayashi, K Gao, P Griffin, JD TI Identification of a family of mastermind-like transcriptional coactivators for mammalian notch receptors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CONDITION CAUSING STROKE; DROSOPHILA MASTERMIND; HUMAN HOMOLOG; SIGNAL-TRANSDUCTION; PROTEIN; PATHWAY; DIFFERENTIATION; DELTA; GENE; ACTIVATOR AB The molecular mechanisms by which Notch receptors induce diverse biological responses are not fully understood. We recently cloned a mammalian homologue of the Mastermind gene of Drosophila melanogaster, MAML1 (Mastermind-like-1 molecule) and determined that it functions as a transcriptional coactivator for Notch receptors. In this report, we characterize two additional genes in this Mastermind-like gene family: MAML2 and MAML3. The three MAML genes are widely expressed in adult tissues but exhibit distinct expression patterns in mouse early spinal cord development. All MAML proteins localize to nuclear bodies, share a conserved basic domain in their N termini that binds to the ankyrin repeat domain of Notch, and contain a transcriptional activation domain in their C termini. Moreover, as determined by using coimmunoprecipitation assays, each MAML protein was found to be capable of forming a multiprotein complex with the intracellular domain of each Notch receptor (ICN1 to -4) and CSL in vivo. However, MAML3 bound less efficiently to the ankyrin repeat domain of Notch1. Also, in U20S cells, whereas MAML1 and MAML2 functioned efficiently as coactivators with each of the Notch receptors to transactivate a Notch target HES1 promoter construct, MAML3 functioned more efficiently with ICN4 than with other forms of ICN. Similarly, MAML1 and MAML2 amplified Notch ligand (both Jagged2 and Delta1)-induced transcription of the HES-1 gene, whereas MAML3 displayed little effect. Thus, MAML proteins may modify Notch signaling in different cell types based on their own expression levels and differential activities and thereby contribute to the diversity of the biological effects resulting from Notch activation. C1 Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM james-griffin@dfci.harvard.edu FU NCI NIH HHS [R01CA36167, R01 CA036167] NR 58 TC 135 Z9 152 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2002 VL 22 IS 21 BP 7688 EP 7700 DI 10.1128/MCB.22.21.7688-7700.2002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 603XQ UT WOS:000178586900032 PM 12370315 ER PT J AU King, IFG Francis, NJ Kingston, RE AF King, IFG Francis, NJ Kingston, RE TI Native and recombinant polycomb group complexes establish a selective block to template accessibility to repress transcription in vitro SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE ACETYLTRANSFERASE COMPLEXES; POSITION-EFFECT VARIEGATION; DOSAGE-DEPENDENT MODIFIERS; TRITHORAX GROUP PROTEINS; RNA-POLYMERASE-II; CHROMATIN STRUCTURE; HOMEOTIC GENE; LYSINE 9; IN-VITRO; DROSOPHILA AB Polycomb group (PcG) proteins are responsible for stable repression of homeotic gene expression during Drosophila melanogaster development. They are thought to stabilize chromatin structure to prevent transcription, though how they do this is unknown. We have established an in vitro system in which the PcG complex PRC1 and a recombinant PRC1 core complex (PCC) containing only PcG proteins are able to repress transcription by both RNA polymerase 11 and by T7 RNA polymerase. We find that assembly of the template into nucleosomes enhances repression by PRC1 and PCC. The subunit Psc is able to inhibit transcription on its own. PRC1- and PCC-repressed templates remain accessible to Gal4-VP16 binding, and incubation of the template with HeLa nuclear extract before the addition of PCC eliminates PCC repression. These results suggest that PcG proteins do not merely prohibit all transcription machinery from binding the template but instead likely inhibit specific steps in the transcription reaction. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 62 TC 72 Z9 76 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2002 VL 22 IS 22 BP 7919 EP 7928 DI 10.1128/MCB.22.22.7919-7928.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 610HB UT WOS:000178953700018 PM 12391159 ER PT J AU McMillan, DR Christians, E Forster, M Xiao, XZ Connell, P Plumier, JC Zuo, XX Richardson, J Morgan, S Benjamin, IJ AF McMillan, DR Christians, E Forster, M Xiao, XZ Connell, P Plumier, JC Zuo, XX Richardson, J Morgan, S Benjamin, IJ TI Heat shock transcription factor 2 is not essential for embryonic development, fertility, or adult cognitive and psychomotor function in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HSP70 GENE-TRANSCRIPTION; CELLULAR-LOCALIZATION; ERYTHROLEUKEMIA-CELLS; TARGETED DISRUPTION; FACTOR FAMILY; INDUCE HSP70; FACTOR-II; MOUSE; EXPRESSION; ACTIVATION AB Members of the heat shock factor (HSF) family are evolutionarily conserved regulators that share a highly homologous DNA-binding domain. In mammals, Hsf1 is the main factor controlling the stress-inducible expression of Hsp genes while the functions of Hsf2 and Hsf4 are less clear. Based on its developmental profile of expression, it was hypothesized that Hsf2 may play an essential role in brain and heart development, spermatogenesis, and erythroid differentiation. To directly assess this hypothesis and better understand the underlying mechanisms that require Hsf2, we generated Hsf2 knockout mice. Here, we report that Hsf2(-/-) mice are viable and fertile and exhibit normal life span and behavioral functions. We conclude that Hsf2, most probably because its physiological roles are integrated into a redundant network of gene regulation and function, is dispensable for normal development, fertility, and postnatal psychomotor function. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Div Cell & Mol Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ N Texas, Dept Pharmacol, Hlth Sci Ctr, Ft Worth, TX 76107 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Unit, Charlestown, MA 02129 USA. RP Benjamin, IJ (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. FU NHLBI NIH HHS [R01-HL60667-03]; PHS HHS [K14] NR 48 TC 48 Z9 51 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 NOV PY 2002 VL 22 IS 22 BP 8005 EP 8014 DI 10.1128/MCB.22.22.8005-8014.2002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 610HB UT WOS:000178953700025 PM 12391166 ER PT J AU Pellman, D Sagot, I Rodal, A Mosely, J Goode, B AF Pellman, D Sagot, I Rodal, A Mosely, J Goode, B TI A novel actin nucleation mechanism mediated by the formin Bni1p and profilin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 34 BP 7A EP 7A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100035 ER PT J AU Sun, Y AF Sun, Y TI Cytochrome c release mediated apoptosis pathway and tumor metastasis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 114 BP 21A EP 21A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100114 ER PT J AU Sheeman, BM Pellman, D AF Sheeman, BM Pellman, D TI Localization and regulation of dynein in Saccharomyces cerevisiae SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 227 BP 41A EP 41A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100227 ER PT J AU Feng, Y Walsh, CA AF Feng, Y Walsh, CA TI Oligomerization of a mitotic phosphoprotein mNudE is essential for microtubule dynamics during cell division SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 245 BP 44A EP 44A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100245 ER PT J AU Beauchamp, RL AF Beauchamp, RL TI The TSC1 tumor suppressor hamartin interacts with neurofilament-L and possibly functions as a novel integrator of the neuronal cytoskeleton SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 345 BP 61A EP 62A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100345 ER PT J AU Lennon, NJ Kho, A Brown, RH AF Lennon, NJ Kho, A Brown, RH TI Examination of age, muscle group and species specific gene expression changes in dysferlin-deficient mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA USA. Childrens Hosp, Childrens Hosp Informat Program, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 587 BP 105A EP 105A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100587 ER PT J AU Hemler, ME Kazarov, AR Kolesnikova, TV Yang, X Stipp, CS AF Hemler, ME Kazarov, AR Kolesnikova, TV Yang, X Stipp, CS TI Modulation of integrin-dependent functions by associated tetraspanin molecules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Dept Immunol AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 796 BP 142A EP 143A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100795 ER PT J AU Jauliac, SJ Lopez-Rodriguez, C Shaw, LM Brown, LF Rao, A Toker, A AF Jauliac, SJ Lopez-Rodriguez, C Shaw, LM Brown, LF Rao, A Toker, A TI The role of NFAT transcription factors in integrin-mediated carcinoma invasion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Lopez-Rodriguez, C/G-4482-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 824 BP 147A EP 147A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100823 ER PT J AU White, K Yokokura, T Krieser, R Huseinovic, N Patel, R AF White, K Yokokura, T Krieser, R Huseinovic, N Patel, R TI The regulation and execution of apoptosis in Drosophila SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Charlestown, MA USA. RI White, Kristin/D-7936-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 822 BP 147A EP 147A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100821 ER PT J AU Primo, VC Alonso, JL Goldmann, WH Sharma, CP AF Primo, VC Alonso, JL Goldmann, WH Sharma, CP TI Free fatty acids and sterols in Saw Palmetto Berry Extract (SPBE) inhibit cell growth in prostate cancer cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Boston Bioprod Inc, Ashland, MA USA. RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 893 BP 159A EP 160A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100892 ER PT J AU Shiraishi, I Melendez, J Welch, S Gaines, L Schaefer, E Walsh, K Sussman, MA Rosenzweig, A AF Shiraishi, I Melendez, J Welch, S Gaines, L Schaefer, E Walsh, K Sussman, MA Rosenzweig, A TI Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Kyoto Prefectural Univ Med, Childrens Res Hosp, Div Pediat, Kyoto, Japan. Biosource Int, Hopkinton, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Program Cardiovasc Gene, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 915 BP 163A EP 163A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100914 ER PT J AU Linseman, DA Bartley, CM Meintzer, MK Le, SS Laessig, TA Bouchard, RJ Heidenreich, KA AF Linseman, DA Bartley, CM Meintzer, MK Le, SS Laessig, TA Bouchard, RJ Heidenreich, KA TI Ca2+/calmodulin-dependent protein kinase II promotes neuronal survival by inhibiting HDAC repression of MEF2D SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver VAMC, Denver, CO USA. RI Bartley, Christopher/G-4226-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 923 BP 165A EP 165A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100922 ER PT J AU Huang, S Jagadeeswaran, R Liu, ES Cho, HT Benz, EJ AF Huang, S Jagadeeswaran, R Liu, ES Cho, HT Benz, EJ TI Mitotic reorganization of protein 4.1R involves phosphorylation by cdc2 kinase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Jagadeeswaran, Ramasamy/C-9987-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 932 BP 166A EP 166A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569100931 ER PT J AU de Carvalho, PCS Pellman, D AF de Carvalho, PCS Pellman, D TI Microtubule plus-end dynamics and attachment to the kinetochore in budding yeast SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Porto, ICBAS, P-4100 Oporto, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1056 BP 188A EP 188A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101055 ER PT J AU Yu, W Stamenkovic, I Merton, B AF Yu, W Stamenkovic, I Merton, B TI MMP-7 mediated shedding of syndecan-1 and nucleus trafficking of cytotail syndecan-1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1188 BP 211A EP 212A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101187 ER PT J AU Yu, W Woessner, FJ McNeish, JD Stamenkovic, I AF Yu, W Woessner, FJ McNeish, JD Stamenkovic, I TI CD44HSPG trans-activating erbB4 mediated by proHB-EGF proteolytic processing by MMP-7 during the female reproductive organs remodeling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1187 BP 211A EP 211A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101186 ER PT J AU Laprise, P Viel, A Rivard, N AF Laprise, P Viel, A Rivard, N TI The hDlg-dependent recruitment of p85/PI-3K to adherens junction is regulated by phosphorylation of hDlg on both serine/threonine and tyrosine residues SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1230 BP 219A EP 219A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101229 ER PT J AU Dreier, L Burbea, M Dittman, J Grunwald, M Kaplan, J AF Dreier, L Burbea, M Dittman, J Grunwald, M Kaplan, J TI Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C-elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1464 BP 260A EP 260A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101463 ER PT J AU Allport, JR Tang, Y Snyder, EY Weissleder, R AF Allport, JR Tang, Y Snyder, EY Weissleder, R TI Murine progenitor cells are preferentially recruited to tumor vasculature via an alpha(4)-integrin independent mechanism SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1533 BP 272A EP 272A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101532 ER PT J AU Sachs, RK Vazquez, M Javier, A Hahnfeldt, P Hlatky, L AF Sachs, RK Vazquez, M Javier, A Hahnfeldt, P Hlatky, L TI Searching for fingerprints of densely-ionizing radiation in evolution SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Univ Calif Berkeley, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1557 BP 276A EP 277A PG 2 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101556 ER PT J AU Yang, J Liu, X Adamian, M Bulgakov, O Li, T AF Yang, J Liu, X Adamian, M Bulgakov, O Li, T TI Rootletin is the structural component of the vertebrate ciliary rootlet SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Eye & Ear Infirm, Berman Gund Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1845 BP 328A EP 328A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101844 ER PT J AU Kim, MJ Cotman, SL Halfter, W Cole, GJ AF Kim, MJ Cotman, SL Halfter, W Cole, GJ TI Modulation of laminin- and FGF-mediated neurite outgrowth by agrin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 N Carolina State Univ, Raleigh, NC 27695 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 1920 BP 341A EP 341A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569101919 ER PT J AU Srinivasan, DG Fisk, RM Xu, H van den Heuvel, SJ AF Srinivasan, DG Fisk, RM Xu, H van den Heuvel, SJ TI Developmental control of mitotic spindle position and cleavage plane specification in C-elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, MGH Canc Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RI van den Heuvel, Sander/B-8892-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 2393 BP 425A EP 425A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569102392 ER PT J AU Allport, JR Weissleder, R AF Allport, JR Weissleder, R TI Isolation, characterization and in vitro culture of murine Lewis Lung Carcinoma tumor-derived endothelium; an in vitro tumor model SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3084 BP 547A EP 547A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103083 ER PT J AU Russo, AL Albadawi, H Patton, GM Watkins, MT AF Russo, AL Albadawi, H Patton, GM Watkins, MT TI Cyclooxygenase mRNA expression in human microvascular endothelium SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract CT 42nd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2002 VL 13 MA 3099 BP 550A EP 550A PG 1 WC Cell Biology SC Cell Biology GA 621BR UT WOS:000179569103098 ER PT J AU Ellisen, LW Ramsayer, KD Johannessen, CM Yang, A Beppu, H Minda, K Oliner, JD McKeon, F Haber, DA AF Ellisen, LW Ramsayer, KD Johannessen, CM Yang, A Beppu, H Minda, K Oliner, JD McKeon, F Haber, DA TI REDD1, a developmentally regulated transcriptional target of p63 and p53, links p63 to regulation of reactive oxygen species SO MOLECULAR CELL LA English DT Article ID KINASE C-ABL; DNA-DAMAGE; CELL-CYCLE; P53-INDUCED APOPTOSIS; HUMAN KERATINOCYTES; HYDROGEN-PEROXIDE; BINDING-SITE; INDUCTION; P73; FAMILY AB We identified REDD1 as a novel transcriptional target of p53 induced following DNA damage. During embryogenesis, REDD1 expression mirrors the tissuespecific pattern of the p53 family member p63, and TP63 null embryos show virtually no expression of REDDI, which is restored in mouse embryo fibroblasts following p63 expression. In differentiating primary keratinocytes, TP63 and REDD1 expression are coordinately downregulated, and ectopic expression of either gene inhibits in vitro differentiation. REDD1 appears to function in the regulation of reactive oxygen species (ROS); we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress, which are both increased following ectopic expression of either TP63 or REDD1. Thus, REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Affymetrix Corp, Santa Clara, CA 95051 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 84066, CA 82831, R01 CA122589] NR 43 TC 254 Z9 264 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2002 VL 10 IS 5 BP 995 EP 1005 DI 10.1016/S1097-2765(02)00706-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619AJ UT WOS:000179450600009 PM 12453409 ER PT J AU Baksh, S Widlund, HR Frazer-Abel, AA Du, JY Fosmire, S Fisher, DE DeCaprio, JA Modiano, JF Burakoff, SJ AF Baksh, S Widlund, HR Frazer-Abel, AA Du, JY Fosmire, S Fisher, DE DeCaprio, JA Modiano, JF Burakoff, SJ TI NFATc2-mediated repression of cyclin-dependent kinase 4 expression SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; T-CELLS; NUCLEAR IMPORT; CALCINEURIN; ACTIVATION; PROTEIN; HYPERTROPHY; PROGRESSION; INHIBITION; CHROMATIN AB The calcineurin-regulated transcription factor, nuclear factor of activated T cells (NFAT), controls many aspects of T cell function. Here, we demonstrate that the calcineurin/NFAT pathway negatively regulates the expression of cyclin-dependent kinase 4 (CDK4). A canonical NFAT binding site was identified and found to be sensitive to calcium signals, FK506/CsA, and histone deacetylase activity and to not require AP-1. Ectopic expression of NFATc2 inhibited the basal activity of the human CDK4 promoter. Additionally, both calcineurin Aalpha(-/-) and NFATc2(-/-) mice had elevated protein levels of CDK4, confirming a negative regulatory role for the calcineurin/NFAT pathway. This pathway may thus regulate the expression of CDK4 at the transcriptional level and control how cells re-enter a resting, nonproliferative state. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. AMC Canc Res Ctr, Denver, CO 80214 USA. Donald Monk Canc Res Fdn, Denver, CO 80214 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA. RP Burakoff, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. OI Modiano, Jaime/0000-0001-6398-7648 FU NCI NIH HHS [CA 86432, R01 CA 70758]; NHLBI NIH HHS [HL 01310] NR 40 TC 133 Z9 135 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2002 VL 10 IS 5 BP 1071 EP 1081 DI 10.1016/S1097-2765(02)00701-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619AJ UT WOS:000179450600015 PM 12453415 ER PT J AU Chi, YI Frantz, JD Oh, BC Hansen, L Dhe-Paganon, S Shoelson, SE AF Chi, YI Frantz, JD Oh, BC Hansen, L Dhe-Paganon, S Shoelson, SE TI Diabetes mutations delineate an atypical POU domain in HNF-1 alpha SO MOLECULAR CELL LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; I ALPHA-GENE; HOMEODOMAIN-DNA COMPLEX; EARLY-ONSET NIDDM; TRANSCRIPTION FACTOR; JAPANESE SUBJECTS; MODY3 MUTATIONS; DIMERIZATION DOMAIN; CRYSTAL-STRUCTURE; BINDING AB Mutations in Hnf-1alpha are the most common Mendelian cause of diabetes mellitus. To elucidate the molecular function of a mutational hotspot, we cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules are bound to the promoter. Each contains a homeodomain and a second domain structurally similar to POU-specific domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains create a stable interface that further distinguishes HNF-1alpha from other flexible POU-homeodomain proteins. The numerous diabetes causing mutations in HNF-1alpha thus identified a previously unrecognized POU domain which was used as a search model to identify additional POU domain proteins in sequence databases. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM steven.shoelson@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK 43123] NR 52 TC 48 Z9 49 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2002 VL 10 IS 5 BP 1129 EP 1137 DI 10.1016/S1097-2765(02)00704-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 619AJ UT WOS:000179450600020 PM 12453420 ER PT J AU Liu, YY Brent, GA AF Liu, YY Brent, GA TI A complex deoxyribonucleic acid response element in the rat Ca2+/calmodulin-dependent protein kinase IV gene 5 '-flanking region mediates thyroid hormone induction and chicken ovalbumin upstream promoter transcription factor 1 repression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; COUP-TF; BINDING PROTEIN; NEURONAL DIFFERENTIATION; SIGNALING PATHWAY; BRAIN-DEVELOPMENT; LATE-PHASE; EXPRESSION; ACTIVATION; CALCIUM AB Ca2+/Calmodulin-dependent protein kinase IV (CaMKIV) is regulated by T-3 in a time- and concentration-dependent manner in the developing rat brain and plays an important role in neuronal-specific gene regulation. T-3 treatment, but not retinoic acid (RA), stimulated endogenous CaMKIV mRNA 5-fold in mouse embryonic stem (ES) cells differentiated into neurons. We localized a region -750 to -700 in the CaMKIV gene 5'-flanking region that conferred T-3 responsiveness and bound thyroid hormone receptor (TR), retinoic acid receptor (RAR), and chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TF1). T-3 and RA treatment stimulated the CaMKIV hormone response element. Cotransfection of a COUP-TF1 expression vector repressed the T-3 response and augmented the RA response. Mutational analysis identified three half-sites arranged in a direct repeat (AB) and overlapping inverted repeat (BC), required for functional induction and receptor binding. TR and RAR bound predominantly to the BC portion of the element and COUP-TF1 to the AB region, with a close correlation of binding and functional studies. COUP-TF1 binding did not influence TR/retinoid X receptor binding but modestly augmented RAR/retinoid X receptor binding. A single element confers T-3 and COUP-TF1 regulation of CaMKIV expression. C1 Univ Calif Los Angeles, Mol Endocrinol Lab, Sch Med,Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Mol Endocrinol Lab, Sch Med,Dept Physiol, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, Mol Endocrinol Lab, Sch Med,Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01-CA-89364] NR 70 TC 16 Z9 16 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 2002 VL 16 IS 11 BP 2439 EP 2451 DI 10.1210/me.2001-0324 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 610HG UT WOS:000178954200003 PM 12403833 ER PT J AU Wilkemeyer, MF Menkari, CE Charness, ME AF Wilkemeyer, MF Menkari, CE Charness, ME TI Novel antagonists of alcohol inhibition of L1-mediated cell adhesion: Multiple mechanisms of action SO MOLECULAR PHARMACOLOGY LA English DT Article ID GLYCINE RECEPTOR FUNCTION; PROTEIN-KINASE-C; L1 KNOCKOUT MICE; ANESTHETIC ACTION; ETHANOL ACTIONS; ION CHANNELS; ENHANCEMENT; MOLECULES; PHOSPHORYLATION; HYPOPLASIA AB 1-Octanol antagonizes ethanol inhibition of L1-mediated cell adhesion and prevents ethanol teratogenesis in mouse whole embryo culture. Herein, we identify a new series of alcohol antagonists and study their mechanism of action. Cell aggregation assays were carried out in ethanol-sensitive, human L1-transfected NIH/3T3 cells in the absence and presence of 100 mM ethanol or 2 mM 1-butanol and candidate antagonists. Antagonist potency for 1-alcohols increased progressively over 5 log orders from 1-pentanol (C5) to 1-dodecanol (C12). Antagonist potency declined from 1-dodecanol (C12) to 1-tridecanol (C13), and 1-tetradecanol (C14) and 1-pentadecanol (C15) were inactive. The presence and position of a double bond in the 1-butanol molecule determined whether a compound was a full agonist (1-butanol), a mixed agonist-antagonist (2-buten-1-ol), or an antagonist (3-buten-1-ol). Increasing the concentration of agonist (1-butanol or ethanol) overcame the antagonism of 3-buten-1-ol, benzyl alcohol, cyclopentanol, and 3-pentanol, but not that of 4-methyl-1-pentanol, 2-methyl-2-pentanol, 1-pentanol, 2-pentanol, 1-octanol, and 2,6-di-isopropylphenol (propofol), suggesting that the mechanisms of antagonism may differ between these groups of compounds. These findings suggest that selective straight, branched, and cyclic alcohols may act at multiple, discrete sites to antagonize the actions of ethanol and 1-butanol on L1-mediated cell-cell adhesion. C1 Harvard Univ, VA Boston Healthcare Syst, Dept Neurol, Sch Med,Neurol Serv, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Charness, ME (reprint author), Harvard Univ, VA Boston Healthcare Syst, Dept Neurol, Sch Med,Neurol Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIAAA NIH HHS [AA11297, AA12974] NR 42 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2002 VL 62 IS 5 BP 1053 EP 1060 DI 10.1124/mol.62.5.1053 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606QR UT WOS:000178745100011 PM 12391267 ER PT J AU Pranzatelli, MR Tate, ED Kinsbourne, M Caviness, VS Mishra, B AF Pranzatelli, MR Tate, ED Kinsbourne, M Caviness, VS Mishra, B TI Forty-one-year follow-up of childhood-onset opsoclonus-myoclonus-ataxia: Cerebellar atrophy, multiphasic relapses, and response to IVIG SO MOVEMENT DISORDERS LA English DT Article DE ACTH; cerebellar ataxia; dancing eyes; IVIG; Kinsbourne syndrome; myoclonus ID NEUROBLASTOMA; ENCEPHALOPATHY; CHILDREN AB We report on an adult with opsoclonus-myoclonusataxia syndrome experiencing widely spaced neurological relapses, who was followed for 41 years. His responses to treatment are described. (C) 2002 Movement Disorder Society. C1 So Illinois Univ, Natl Pediat Myoclonus Ctr, Sch Med, Dept Neurol, Springfield, IL 62702 USA. So Illinois Univ, Natl Pediat Myoclonus Ctr, Sch Med, Dept Pediat, Springfield, IL USA. New Sch Univ, Winchester, MA USA. Tufts Univ, Winchester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Temple Univ, Philadelphia, PA 19122 USA. RP Pranzatelli, MR (reprint author), So Illinois Univ, Natl Pediat Myoclonus Ctr, Sch Med, Dept Neurol, POB 19658, Springfield, IL 62702 USA. NR 20 TC 17 Z9 18 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2002 VL 17 IS 6 BP 1387 EP 1390 DI 10.1002/mds.10283 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 618FV UT WOS:000179408800043 PM 12465092 ER PT J AU Yildiran, ST Fothergill, AW Sutton, DA Rinaldi, MG AF Yildiran, ST Fothergill, AW Sutton, DA Rinaldi, MG TI In vitro susceptibilities of cerebrospinal fluid isolates of Cryptococcus neoformans collected during a ten-year period against fluconazole, voriconazole and posaconazole (SCH56592) SO MYCOSES LA English DT Article DE Cryptococcus neoformans; cerebrospinal fluid; antifungal susceptibility; fluconazole; voriconazole; posaconazole ID IN-VITRO; DIMORPHIC FUNGI; AMPHOTERICIN-B; MENINGITIS; AIDS; ITRACONAZOLE; RESISTANCE; FAILURE; RELAPSE AB We investigated the in vitro susceptibilities of 213 cerebrospinal fluid isolates of Cryptococcus neoformans isolated from 192 patients through a 10-year period, 1990-99, against fluconazole, voriconazole and posaconazole (SCH56592) by using the NCCLS (National Committee for Clinical Laboratory Standards) macrodilution method, M27-A. The overall MICs50 and MICs90 of fluconazole, voriconazole and posaconazole were found to be 2 and 8 mug ml(-1) less than or equal to0.125 mug ml(-1) (both), and less than or equal to 0.015 and 0.06 mug ml(-1), respectively. The MIC ranges, MICs50, and MICs90 of three triazoles were also determined according to the defined year category (1990-94, 1995, 1996, 1997 and 1998-99). The MICs50 and MICs90 of each triazole remained almost unchanged and did not exhibit any sign of an upward shift during a decade (1990-99). However, a tendency for development of possible cross-resistance between the three triazoles was observed only in 1996. Meanwhile, the individual relapsing isolates (n:21) from 20 patients exhibited same, higher or, suprisingly, lower MICs, particularly against fluconazole and posaconazole. C1 Gulhane Mil Med Acad, Div Med Mycol, Dept Microbiol & Clin Microbiol, TR-06018 Ankara, Turkey. Sch Med, TR-06018 Ankara, Turkey. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Yildiran, ST (reprint author), Gulhane Mil Med Acad, Div Med Mycol, Dept Microbiol & Clin Microbiol, TR-06018 Ankara, Turkey. NR 24 TC 26 Z9 28 U1 0 U2 0 PU BLACKWELL VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 57, D-10707 BERLIN, GERMANY SN 0933-7407 J9 MYCOSES JI Mycoses PD NOV PY 2002 VL 45 IS 9-10 BP 378 EP 383 DI 10.1046/j.1439-0507.2002.00765.x PG 6 WC Dermatology; Mycology SC Dermatology; Mycology GA 621WH UT WOS:000179613700007 PM 12421285 ER PT J AU Sax, JK Fei, PW Murphy, ME Bernhard, E Korsmeyer, SJ El-Deiry, WS AF Sax, JK Fei, PW Murphy, ME Bernhard, E Korsmeyer, SJ El-Deiry, WS TI BID regulation by p53 contributes to chemosensitivity SO NATURE CELL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; CYTOCHROME-C RELEASE; APOPTOSIS IN-VIVO; P53-DEPENDENT APOPTOSIS; POTENTIAL MEDIATOR; DEATH RECEPTOR; CANCER-CELLS; BINDING-SITE; BCL-2 FAMILY; GENE AB The role of the p53 protein (encoded by TP53) in tumour suppression relies partly on the ability of p53 to regulate the transcription of genes that are important in cell-cycle arrest and in apoptosis. But the apoptotic pathway mediated by p53 is not fully understood. Here we show that BID, a member of the pro-apoptotic Bcl-2 family of proteins, is regulated by p53. BID mRNA is increased in a p53-dependent manner in vitro and in vivo, with strong expression in the splenic red pulp and colonic epithelium of gamma-irradiated mice. Both the human and the mouse BID genomic loci contain p53-binding DNA response elements that bind p53 and mediate p53-dependent transactivation of a reporter gene. In addition, BID-null mouse embryonic fibroblasts are more resistant than are wild-type fibroblasts to the DNA damaging agent adriamycin and the nucleotide analogue 5-fluorouracil, both of which stabilize endogenous p53. Our results indicate that BID is a p53-responsive 'chemosensitivity gene' that may enhance the cell death response to chemotherapy. C1 Univ Penn, Sch Med, Dept Med,Howard Hughes Med Inst, Lab Mol Oncol & Cell Cycle Regulat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Howard Hughes Med Inst,Lab Mol Oncol & Cell Cycle, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Genet, Howard Hughes Med Inst,Lab Mol Oncol & Cell Cycle, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Dept Pharmacol, Philadelphia, PA 19111 USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Howard Hughes Med Inst, Boston, MA 02115 USA. RP Sax, JK (reprint author), Univ Penn, Sch Med, Dept Med,Howard Hughes Med Inst, Lab Mol Oncol & Cell Cycle Regulat, Philadelphia, PA 19104 USA. NR 50 TC 265 Z9 274 U1 0 U2 6 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 NOV PY 2002 VL 4 IS 11 BP 842 EP 849 DI 10.1038/ncb866 PG 8 WC Cell Biology SC Cell Biology GA 613NE UT WOS:000179137700012 PM 12402042 ER PT J AU Wang, YQ Cui, HJ Schroering, A Ding, JL Lane, WS McGill, G Fisher, DE Ding, HF AF Wang, YQ Cui, HJ Schroering, A Ding, JL Lane, WS McGill, G Fisher, DE Ding, HF TI NF-kappa B2 p100 is a pro-apoptotic protein with anti-oncogenic function SO NATURE CELL BIOLOGY LA English DT Article ID NF-KAPPA-B; CELL-DEATH; SPLENIC MICROARCHITECTURE; CANCER; ALPHA; ACTIVATION; GENE; INHIBITION; RECEPTORS; RESPONSES AB Nuclear factor-kappaB (NIF-kappaB) promotes cell survival by upregulating expression of anti-apoptotic genes, a process that is antagonized by inhibitors of kappaB (IkappaB) factors(1) The only NF-kappaB family member known to be mutated in human cancer is NF-kappaB2 p100 (ref. 2), a factor with IkappaB activity. Here, we report the isolation from irradiated mouse tumour cells of a complex that induces caspase-8 activity in cell-free assays and identify p100 as an essential component of this complex. Expression of p100 profoundly sensitizes cells to death-receptor-mediated apoptosis through a pathway that is independent of IkappaB-like activity. The carboxyl terminus of p100 contains a death domain(3) that is absent from all known tumour-derived mutants. This death domain mediates recruitment of p100 into death machinery complexes after ligand stimulation and is essential for p100's pro-apoptotic activity. p100 also sensitizes NIH3T3 cells to apoptosis triggered by oncogenic Ras, resulting in a marked inhibition of transformation that is rescued by suppression of endogenous caspase-8. These observations thus identify an IkappaB-independent apoptotic activity of NF-kappaB2 p100 and help explain its unique tumour suppressor role. C1 Med Coll Ohio, Dept Biochem & Mol Biol, Toledo, OH 43614 USA. Harvard Univ, Harvard Microchem & Proteom Anal Facil, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Wang, YQ (reprint author), Med Coll Ohio, Dept Biochem & Mol Biol, 3035 Arlington Ave, Toledo, OH 43614 USA. NR 29 TC 47 Z9 51 U1 0 U2 1 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 NOV PY 2002 VL 4 IS 11 BP 888 EP 893 DI 10.1038/ncb872 PG 6 WC Cell Biology SC Cell Biology GA 613NE UT WOS:000179137700018 PM 12389034 ER PT J AU Cowles, CR Hirschhorn, JN Altshuler, D Lander, ES AF Cowles, CR Hirschhorn, JN Altshuler, D Lander, ES TI Detection of regulatory variation in mouse genes SO NATURE GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GILBERTS-SYNDROME; CANDIDATE GENES; EXPRESSION; DNA; DIVERSITY; REGIONS; ASSAY AB Functional polymorphism in genes can be classified as coding variation, altering the amino-acid sequence of the encoded protein, or regulatory variation, affecting the level or pattern of expression of the gene. Coding variation can be recognized directly from DNA sequence, and consequently its frequency and characteristics have been extensively described. By contrast, virtually nothing is known about the extent to which gene regulation varies in populations. Yet it is likely that regulatory variants are important in modulating gene function: alterations in gene regulation have been proposed to influence disease susceptibility and to have been the primary substrate for the evolution of species(1). Here, we report a systematic study to assess the extent of cis-acting regulatory variation in 69 genes across four inbred mouse strains. We find that at least four of these genes show allelic differences in expression level of 1.5-fold or greater, and that some of these differences are tissue specific. The results show that the impact of regulatory variants can be detected at a significant frequency in a genomic survey and suggest that such variation may have important consequences for organismal phenotype and evolution. The results indicate that larger-scale surveys in both mouse and human could identify a substantial number of genes with common regulatory variation. C1 Whitehead Inst, Cambridge, MA 02142 USA. MIT, Ctr Genome Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA USA. RP Lander, ES (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM lander@wi.mit.edu RI Altshuler, David/A-4476-2009; Phelps, Steve/H-2263-2011 OI Altshuler, David/0000-0002-7250-4107; NR 23 TC 259 Z9 268 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2002 VL 32 IS 3 BP 432 EP 437 DI 10.1038/ng992 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 611TX UT WOS:000179034800022 PM 12410233 ER PT J AU Finger, EB Bluestone, JA AF Finger, EB Bluestone, JA TI When ligand becomes receptor - tolerance via B7 signaling on DCs SO NATURE IMMUNOLOGY LA English DT Editorial Material ID EXPRESSING INDOLEAMINE 2,3-DIOXYGENASE; T-CELL COSTIMULATION; TRYPTOPHAN CATABOLISM; DENDRITIC CELLS; CTLA-4; CD28/B7; MICE AB CTLA-4-Ig is used to block the costimulation of T cells to interfere with their activation. This reagent may actually be working by provoking DCs to catabolize tryptophan, thereby depriving T cells and contributing to their demise. C1 Univ Calif San Francisco, Ctr Diabet, Sch Med, San Francisco, CA 94143 USA. RP Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM jbluest@diabetes.ucsf.edu NR 13 TC 78 Z9 83 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 EI 1529-2916 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2002 VL 3 IS 11 BP 1056 EP 1057 DI 10.1038/ni1102-1056 PG 2 WC Immunology SC Immunology GA 612KE UT WOS:000179073000011 PM 12407416 ER PT J AU Sharp, R Recio, JA Jhappan, C Otsuka, T Liu, SQ Yu, YL Liu, WJ Anver, M Navid, F Helman, LJ DePinho, RA Merlino, G AF Sharp, R Recio, JA Jhappan, C Otsuka, T Liu, SQ Yu, YL Liu, WJ Anver, M Navid, F Helman, LJ DePinho, RA Merlino, G TI Synergism between INK4a/ARF inactivation and aberrant HGF/SF signaling in rhabdomyosarcomagenesis SO NATURE MEDICINE LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; SKELETAL-MUSCLE DIFFERENTIATION; BHLH PROTEIN TWIST; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR; SATELLITE CELLS; MYOGENIC DIFFERENTIATION; GENE-EXPRESSION; MET AB Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet molecular events associated with the genesis and progression of this potentially fatal disease are largely unknown. For the molecules and pathways that have been implicated, genetic validation has been impeded by lack of a mouse model of RMS. Here we show that simultaneous loss of Ink4a/Arf function and disruption of c-Met signaling in Ink4a/Arf(-/-) mice transgenic for hepatocyte growth factor/scatter factor (HGF/SF) induces RMS with extremely high penetrance and short latency. In cultured myoblasts, c-Met activation and Ink4a/Arf loss suppress myogenesis in an additive fashion. Our data indicate that human c-MET and INK4a/ARF, situated at the nexus of pathways regulating myogenic growth and differentiation, represent critical targets in RMS pathogenesis. The marked synergism in mice between aberrant c-Met signaling and Ink4a/Arf inactivation, lesions individually implicated in human RMS, suggests a therapeutic combination to combat this devastating childhood cancer. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Ctr, SAIC, Pathol Histotechnol Lab, Frederick, MD USA. NCI, Pediat Branch, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol Med & Genet, Boston, MA 02115 USA. RP Merlino, G (reprint author), NCI, Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA. OI Recio, Juan Angel/0000-0002-7320-3832 FU NCI NIH HHS [U01CA84313-04] NR 39 TC 112 Z9 114 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2002 VL 8 IS 11 BP 1276 EP 1280 DI 10.1038/nm787 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 614ZK UT WOS:000179221200034 PM 12368906 ER PT J AU Scholz, J Woolf, CJ AF Scholz, J Woolf, CJ TI Can we conquer pain? SO NATURE NEUROSCIENCE LA English DT Review ID MOLECULAR MECHANISMS; NEUROPATHIC PAIN; ACTIVATION; MANAGEMENT; INHIBITION; ANALGESIA; THERAPY AB Pain can be an adaptive sensation, an early warning to protect the body from tissue injury. By the introduction of hypersensitivity to normally innocuous stimuli, pain may also aid in repair after tissue damage. Pain can also be maladaptive, reflecting pathological function of the nervous system. Multiple molecular and cellular mechanisms operate alone and in combination within the peripheral and central nervous systems to produce the different forms of pain. Elucidation of these mechanisms is key to the development of treatments that specifically target underlying causes rather than just symptoms. This new approach promises to revolutionize pain diagnosis and management. C1 Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Neural Plast Res Grp, Boston, MA 02129 USA. NR 24 TC 451 Z9 470 U1 1 U2 65 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2002 VL 5 SU S BP 1062 EP 1067 DI 10.1038/nn942 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 611WT UT WOS:000179041300015 PM 12403987 ER PT J AU Gilbertson, MW Shenton, ME Ciszewski, A Kasai, K Lasko, NB Orr, SP Pitman, RK AF Gilbertson, MW Shenton, ME Ciszewski, A Kasai, K Lasko, NB Orr, SP Pitman, RK TI Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma SO NATURE NEUROSCIENCE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; ERA TWIN REGISTRY; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; SEXUAL ABUSE; PTSD; BRAIN; MRI; DAMAGE; SIZE AB In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients' trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs-both the trauma-exposed and unexposed members-had significantly smaller hippocampi than non-PTSD pairs. C1 Vet Adm Med Ctr, Res Serv, Manchester, NH 03104 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Vet Adm Boston Healthcare Syst, Psychiat Serv, Brockton, MA 02301 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. RP Gilbertson, MW (reprint author), Vet Adm Med Ctr, Res Serv, 718 Smyth Rd, Manchester, NH 03104 USA. FU NIMH NIH HHS [R01 MH054636, K02 MH001110, K02 MH001110-10, K02-MH01110, R01-MH54636] NR 50 TC 708 Z9 725 U1 9 U2 99 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2002 VL 5 IS 11 BP 1242 EP 1247 DI 10.1038/nn958 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 609CG UT WOS:000178884600029 PM 12379862 ER PT J AU Ichikawa, T Hogemann, D Saeki, Y Tyminski, E Terada, K Weissleder, R Chiocca, EA Basilion, JP AF Ichikawa, T Hogemann, D Saeki, Y Tyminski, E Terada, K Weissleder, R Chiocca, EA Basilion, JP TI MRI of transgene expression: Correlation to therapeutic gene expression SO NEOPLASIA LA English DT Article DE CLIO; ETR; transgene; amplicon; MRI ID CONFERS ENHANCED TUMORIGENICITY; BACTERIAL ARTIFICIAL CHROMOSOME; TRANSFERRIN RECEPTOR; MALIGNANT GLIOMA; IN-VIVO; ESCHERICHIA-COLI; AMPLICON VECTORS; CELLS; MUTANT; TUMOR AB Magnetic resonance imaging (MRI) can provide high-resolution 3D maps of structural and functional information, yet its use of mapping in vivo gene expression has only recently been explored. A potential application for this technology is to noninvasively image transgene expression. The current study explores the latter using a nonregulatable internalizing engineered transferrin receptor (ETR) whose expression can be probed for with a superparamagnetic Tf-CLIO probe. Using an HSV-based amplicon vector system for transgene delivery, we demonstrate that: 1) ETR is a sensitive MR marker gene; 2) several transgenes can be efficiently expressed from a single amplicon; 3) expression of each transgene results in functional gene product; and 4) ETR gene expression correlates with expression of therapeutic genes when the latter are contained within the same amplicon. These data, taken together, suggest that MRI of ETR expression can serve as a surrogate for measuring therapeutic transgene expression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NFCR,Ctr Mol Anal & Imaging,Dept Radiol, Boston, MA 02129 USA. RP Basilion, JP (reprint author), Massachusetts Gen Hosp E, Ctr Mol Imaging Res, Bldg 149,13th St,5406, Charlestown, MA 02129 USA. NR 37 TC 75 Z9 82 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD NOV-DEC PY 2002 VL 4 IS 6 BP 523 EP 530 DI 10.1038/sj.neo.7900266 PG 8 WC Oncology SC Oncology GA 612WN UT WOS:000179098600008 PM 12407446 ER PT J AU Bush, AI AF Bush, AI TI Metal complexing agents as therapies for Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article; Proceedings Paper CT Symposium on Emerging Alzheimers Disease Therapies CY NOV 07, 2001 CL UNIV PENN, PHILADELPHIA, PENNSYLVANIA SP Ctr Neurodegenerat Disease Res HO UNIV PENN DE amyloid; Alzheimer's disease; copper; zinc; oxidation; hydrogen peroxide; superoxide dismutase ID AMYLOID PRECURSOR PROTEIN; RECEPTOR-RELATED PROTEIN; A-BETA; NEUROFIBRILLARY TANGLES; SUPEROXIDE-DISMUTASE; CEREBROSPINAL-FLUID; SYNAPTIC VESICLES; OXIDATIVE DAMAGE; TRANSGENIC MICE; CEREBRAL-CORTEX AB Modern research approaches into drug development for Alzheimer's disease (AD) target beta-amyloid (Abeta) accumulation in the brain. The main approaches attempt to prevent Abeta production (secretase inhibitors) or to clear Abeta (vaccine). However, there is now compelling evidence that Abeta does not spontaneously aggregate, but that there is an age-dependent reaction with excess brain metal (copper, iron and zinc), which induces the protein to precipitate into metal-enriched masses (plaques). The abnormal combination of Abeta with Cu or Fe induces the production of hydrogen peroxide, which may mediate the conspicuous oxidative damage to the brain in AD. We have developed metal-binding compounds that inhibit the in vitro generation of hydrogen peroxide by Abeta, as well as reverse the aggregation of the peptide in vitro and from human brain post-mortem specimens. Most recently, one of the compounds, clioquinol (CQ; a USP antibiotic) was given orally for 9 weeks to amyloid-bearing transgenic mice, and succeeded in markedly inhibiting Abeta accumulation. On the basis of these results, CQ is being tested in clinical trials. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Melbourne, Mental Hlth Res Inst Victoria, Oxidat Disorders Res Unit, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 78 TC 221 Z9 232 U1 4 U2 35 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2002 VL 23 IS 6 BP 1031 EP 1038 AR PII S0197-4580(02)00120-3 DI 10.1016/S0197-4580(02)00120-3 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 630CH UT WOS:000180089600007 PM 12470799 ER PT J AU Berger, MA Barros, VG Sarchi, MI Tarazi, FI Antonelli, MC AF Berger, MA Barros, VG Sarchi, MI Tarazi, FI Antonelli, MC TI Long-term effects of prenatal stress on dopamine and glutamate receptors in adult rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE autoradiography; corticostriatal projections; dopamine D-2-like receptors; group III metabotropic glutamate receptors; NMDA glutamate receptors; prenatal restraint stress ID NUCLEUS-ACCUMBENS-SEPTI; MATERNAL STRESS; BASAL GANGLIA; IMMUNOCYTOCHEMICAL LOCALIZATION; GLUCOCORTICOID SECRETION; POSTNATAL-DEVELOPMENT; PARKINSONS-DISEASE; CEREBRAL-CORTEX; CAUDATE-PUTAMEN; D4 DOPAMINE AB Prenatal stress greatly influences the ability of an individual to manage stressful events in adulthood. Such vulnerability may result from abnormalities in the development and integration of forebrain dopaminergic and glutamatergic projections during the prenatal period. In this study, we assessed the effects of prenatal stress on the expression of selective dopamine and glutamate receptor subtypes in the adult offsprings of rats subjected to repeated restraint stress during the last week of pregnancy. Dopamine D-2-like receptors increased in dorsal frontal cortex (DFC), medial prefrontal cortex (MPC), hippocampal CA(1) region and core region of nucleus accumbens (NAc) of prenatally stressed rats compared to control subjects. Glutamate NMDA receptors increased in MPC, DFC, hippocampal CA1, medial caudate-putamen, as well as in shell and core regions of NAc. Group III metabotropic glutamate receptors increased in MPC and DFC of prenatally stressed rats, but remained unchanged in all other regions examined. These results indicate that stress suffered during the gestational period has long lasting effects that extend into the adulthood of prenatally stressed offsprings. Changes in dopamine and glutamate receptor subtype levels in different forebrain regions of adult rats suggest that the development and formation of the corticostriatal and corticolimbic pathways may be permanently altered as a result of stress suffered prenatally. Maldevelopment of these pathways may provide a neurobiological substrate for the development of schizophrenia and other idiopathic psychotic disorders. C1 Univ Buenos Aires, Fac Farm & Bioquim, IQUIFIB, CONICET, RA-1113 Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicomatemat, RA-1053 Buenos Aires, DF, Argentina. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. RP Antonelli, MC (reprint author), Univ Buenos Aires, Fac Farm & Bioquim, IQUIFIB, CONICET, Junin 956, RA-1113 Buenos Aires, DF, Argentina. NR 53 TC 99 Z9 100 U1 0 U2 8 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2002 VL 27 IS 11 BP 1525 EP 1533 DI 10.1023/A:1021656607278 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 625JC UT WOS:000179812500027 PM 12512957 ER PT J AU Halgren, E Dhond, RP Christensen, N Van Petten, C Marinkovic, K Lewine, JD Dale, AM AF Halgren, E Dhond, RP Christensen, N Van Petten, C Marinkovic, K Lewine, JD Dale, AM TI N400-like magnetoencephalography responses modulated by semantic context, word frequency, and lexical class in sentences SO NEUROIMAGE LA English DT Article DE reading; sentences; semantic context; lexicon; magnetoencephalography; temporal lobe; prefrontal cortex; language; perirhinal cortex ID EVENT-RELATED POTENTIALS; MEDIAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; SURFACE-BASED ANALYSIS; CLOSED-CLASS WORDS; BRAIN POTENTIALS; CORTICAL SURFACE; RECOGNITION MEMORY; SPATIOTEMPORAL STAGES; COORDINATE SYSTEM AB Words have been found to elicit a negative potential at the scalp peaking at similar to400 ms that is strongly modulated by semantic context. The current study used whole-head magnetoencephalography (MEG) as male subjects read sentences ending with semantically congruous or incongruous words. Compared with congruous words, sentence-terminal incongruous words consistently evoked a large magnetic field over the left hemisphere, peaking at similar to450 ms. Source modeling at this latency with conventional equivalent current dipoles (ECDs) placed the N400m generator in or near the left superior temporal sulcus. A distributed solution constrained to the cortical surface suggested a sequence of differential activation, beginning in Wernicke's area at similar to250 ms, spreading to anterior temporal sites at similar to270 ms, to Broca's area by similar to300 ms, to dorsolateral prefrontal cortices by similar to320 ms, and to anterior orbital and frontopolar cortices by similar to370 ms. Differential activity was exclusively left-sided until >370 ms, and then involved right anterior temporal and orbital cortices. At the peak of the N400m, activation in the left hemisphere was estimated to be widespread in the anterior temporal, perisylvian, orbital, frontopolar, and dorsolateral prefrontal cortices. In the right hemisphere, the orbital, as well as, weakly, the right anterior temporal cortices were activated. Similar but weaker field patterns were evoked by intermediate words in the sentences, especially to low-frequency words occurring in early sentence positions where there is little preceding context. The locations of the N400m sources identified with the distributed solution correspond well with those previously demonstrated with direct intracranial recordings, and suggested by functional magnetic resonance imaging (fMRI). These results help identify a distributed cortical network that supports online semantic processing. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, MGH NMR Ctr, Boston, MA 02115 USA. INSERM, E9926, F-13258 Marseille, France. Univ Utah, Dept Radiol, Salt Lake City, UT USA. Univ Utah, Program Neurosci, Salt Lake City, UT USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Halgren, E (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NINDS NIH HHS [NS18741, R01 NS018741] NR 66 TC 250 Z9 262 U1 0 U2 28 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 NOV PY 2002 VL 17 IS 3 BP 1101 EP 1116 DI 10.1006/nimg.2002.1268 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 611JG UT WOS:000179012800002 PM 12414253 ER PT J AU Schellingerhout, D Bogdanov, AA AF Schellingerhout, D Bogdanov, AA TI Viral imaging in gene therapy - Noninvasive demonstration of gene delivery and expression SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; KINASE ENZYME-ACTIVITY; IN-VIVO; TRANSGENE EXPRESSION; LIVING ANIMALS; MEMBRANE-PROTEINS; REPORTER GENE; BRAIN-TUMORS; LOCALIZATION; RECEPTOR AB Gene therapy is a rapidly developing modality of treatment, with applications in acquired and inherited disorders. Gene delivery vehicles ("vectors") are the main impediment in the evolution of gene therapy into a clinically acceptable mainstream therapy. Vectors based on viral particles are the most commonly used vehicles to carry genes to the organs and tissues of interest. Despite initial promise and substantial progress in the development of experimental gene therapy protocols, human gene therapy still is based on technologies that so far do not allow for routine clinical use. Recent progress in viral vector production and better understanding of molecular aspects of vector delivery and targeting issues has created the need for imaging techniques that would be useful in addressing the problems and opportunities inherent in viral gene therapy development. Two integral components of gene therapy monitoring, the imaging of gene delivery and the imaging of resultant exogenous; gene expression, are recognized. These molecular imaging components provide a realistic means for assessment of safety and efficacy of preclinical and clinical development of gene therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Schellingerhout, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Room 5403,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 49 TC 8 Z9 10 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 NOV PY 2002 VL 12 IS 4 BP 571 EP + AR PII S1052-5149(02)00034-5 DI 10.1016/S1052-5149(02)00034-5 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 671XW UT WOS:000182491400007 PM 12687912 ER PT J AU Booij, L Van der Does, W Benkelfat, C Bremner, D Cowen, PJ Fava, M Gillin, C Leyton, M Moore, P Smith, KA Van der Kloot, WA AF Booij, L Van der Does, W Benkelfat, C Bremner, D Cowen, PJ Fava, M Gillin, C Leyton, M Moore, P Smith, KA Van der Kloot, WA TI Predictors of mood response to acute tryptophan depletion: A reanalysis SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE tryptophan depletion; serotonin; amino acids; depression; mood; Hamilton depression rating scale ID ANTIDEPRESSANT ACTION; RAPID DEPLETION; HEALTHY-VOLUNTEERS; SEROTONIN FUNCTION; MAJOR DEPRESSION; BULIMIA-NERVOSA; HUMAN BRAIN; FOLLOW-UP; RELAPSE; MALES AB Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors Of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled ('mega-analysis') in order to investigate the mdiating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors Of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Leiden Univ, Dept Psychol, NL-2333 AK Leiden, Netherlands. Leiden Univ, Dept Psychiat, NL-2333 AK Leiden, Netherlands. McGill Univ, Dept Psychiat, Montreal, PQ, Canada. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. Univ Oxford, Dept Psychiat, Oxford, England. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. VA San Diego Healthcare Syst, San Diego, CA USA. RP Van der Does, W (reprint author), Leiden Univ, Dept Psychol, Wassenaarseweg 52, NL-2333 AK Leiden, Netherlands. RI Van der Does, Willem/B-1465-2008 OI Van der Does, Willem/0000-0002-9753-2454 NR 44 TC 121 Z9 122 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2002 VL 27 IS 5 BP 852 EP 861 AR PII S0893-133X(02)00361-5 DI 10.1016/S0893-133X(02)00361-5 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604DG UT WOS:000178600100016 PM 12431859 ER PT J AU Kahkonen, S Ahveninen, J Pennanen, S Liesivuori, J Ilmoniemi, RJ Jaaskelainen, IP AF Kahkonen, S Ahveninen, J Pennanen, S Liesivuori, J Ilmoniemi, RJ Jaaskelainen, IP TI Serotonin modulates early cortical auditory processing in healthy subjects. Evidence from MEG with acute tryptophan depletion SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE auditory; event-related magnetic field; magnetoencephalography (MEG); middle-latency auditory magnetic field (MAEF); serotonin; tryptophan depletion ID EVOKED MAGNETIC-FIELDS; MIDDLE-LATENCY; 5-HYDROXYINDOLEACETIC ACID; BRAIN TRYPTOPHAN; MONOAMINERGIC INNERVATION; INTENSITY DEPENDENCE; CEREBROSPINAL-FLUID; PLASMA TRYPTOPHAN; NORMAL VOLUNTEERS; AMINO-ACIDS AB We studied the effects of acute tryptophan depletion (ATD) on early cortical auditory processing. Middle-latency auditory evoked fields (MAEF) were investigated in 14 healthy subjects after 5 h of ATD or control mixture ingestion in a randomized, double-blinded, controlled crossover design study. MAEFs to monaural click stimuli (0.1 ms duration) were recorded with a 122-channel neuromagnetometer. Total plasma tryptophan (Trp), free Trp, and large neutral amino acid (LNAA) concentrations were determined by using high-performance liquid chromatography. ATD lowered the total plasma Trp levels by 75%,free Trp level by 47%, and the ratio Trpl./SigmaLNAA by 92%. The control mixture increased total Trp level by 45% andfree Trp by 32%, and decreased the ratio Trp/SigmaLNAA by 35%. The ratio tyrosine/SigmaLNAA did not differ between ATD and control experiment. ATD resulted in a significant main effect on Pam latencies and a nea-rsignificant main effect on Pam amplitudes. A significant Mixture ingestion X Sex interaction on Nbm amplitude and a significant Mixture ingestion X Sex X Hemisphere interaction on Pam latency were observed. ATD did not affect the MAEF source dipoles. The Pam latencies in both hemispheres had a significant negative relationship with the extent of ATD. The results suggest that the neurotransmitter serotonin is involved in early auditory cortical processing. Further, the serotonin modulation may be different in males and females. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, FIN-00029 Helsinki, Finland. Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, SF-00100 Helsinki, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Kahkonen, S (reprint author), Univ Helsinki, Cent Hosp, BioMag Lab, Ctr Engn, POB 340, FIN-00029 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013; Ilmoniemi, Risto/E-9704-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618 NR 44 TC 22 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2002 VL 27 IS 5 BP 862 EP 868 AR PII S0893-133X(02)00357-3 DI 10.1016/S0893-133X(02)00357-3 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 604DG UT WOS:000178600100017 PM 12431860 ER PT J AU Kim, KJ Sisterson, JM Englert, PAJ Caffee, MW Reedy, RC Vincent, J Castaneda, C AF Kim, KJ Sisterson, JM Englert, PAJ Caffee, MW Reedy, RC Vincent, J Castaneda, C TI Experimental cross-sections for the production of Be-10 from natural carbon targets with 40.6 to 500 MeV protons SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE proton cross-sections; Be-10; cosmogenic nuclides ID NUCLIDE PRODUCTION; COSMOGENIC BE-10; ENERGY PROTONS; COSMIC-RAY; AL-26; NUCLEI; METEORITES; HYDROGEN; C-14; MG AB Cross-sections for the production of Be-10 from natural carbon targets were measured for proton energies ranging from 40.6 to 500 MeV. The yield of Be-10 in each target was determined using accelerator mass spectrometry. The values of these new cross-sections ranged from 0.164 to 2.75 mb and confirmed previously published data in this energy range. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Victoria Univ Wellington, Fac Sci, Wellington, New Zealand. Inst Geol & Nucl Sci Ltd, Lower Hutt, New Zealand. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Purdue Univ, PRIME Lab, W Lafayette, IN 47907 USA. Los Alamos Natl Lab, Grp NIS 2, Los Alamos, NM 87545 USA. Univ British Columbia, TRIUMF, Vancouver, BC V6T 2A3, Canada. Univ Calif Davis, Crocker Nucl Lab, Davis, CA 95616 USA. RP Englert, PAJ (reprint author), Victoria Univ Wellington, Fac Sci, POB 600, Wellington, New Zealand. RI Caffee, Marc/K-7025-2015; OI Caffee, Marc/0000-0002-6846-8967; Kim, Kyeong J/0000-0001-6220-8411; Reedy, Robert/0000-0002-2189-1303 NR 25 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD NOV PY 2002 VL 196 IS 3-4 BP 239 EP 244 AR PII S0168-583X(02)01297-1 DI 10.1016/S0168-583X(02)01297-1 PG 6 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 616JH UT WOS:000179300300004 ER PT J AU Pirl, WF Mello, J AF Pirl, WF Mello, J TI Psychological complications of prostate cancer SO ONCOLOGY-NEW YORK LA English DT Article ID QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; HOT FLASHES; DEPRESSION; ANXIETY; MEN; ONCOLOGISTS; RECOGNITION; MEDICATION; INVENTORY AB Over the past decade, interest has been growing in. the quality of life of men with prostate cancer. Traditionally considered a group with few psychological complications, 10% to 20% of men with prostate cancer are found to have clinically significant levels of psychological distress. This article reviews the prevalence of psychiatric symptomatology among prostate cancer patients, the psychological challenges of coping with the disease, and general guidelines for treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 34 TC 15 Z9 15 U1 0 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2002 VL 16 IS 11 BP 1448 EP 1453 PG 6 WC Oncology SC Oncology GA 620VR UT WOS:000179553800004 PM 12469925 ER PT J AU Hatton, MP Thakker, MM Ray, S AF Hatton, MP Thakker, MM Ray, S TI Orbital and adnexal trauma associated with open-globe injuries SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID PENETRATING OCULAR INJURIES; EYE INJURIES; PROGNOSTIC FACTORS; SYSTEM-REGISTRY; SURVIVAL; CHILDREN AB Purpose: To describe the incidence and patterns of orbital and adnexal injuries in patients with open-globe injuries. Methods: Charts of 300 consecutive patients with open-globe injuries presenting to the Massachusetts Eye and Ear Infirmary were retrospectively reviewed. The data were analyzed with respect to the type of open globe (penetrating, perforating, or rupture) and location (zone) of globe injury. Each of these subgroups was then evaluated for the absence (group 1) or presence (group 2) of coexisting orbital and/or adnexal injury. Visual acuity at presentation was compared between the two groups. Results: Orbital and adnexal injuries were present in 25.7% of patients with open globes. The most common concurrent injuries were lacerations of the eyelid, orbital fracture, and retrobulbar hemorrhage. The mechanisms of globe injury differed significantly between groups 1 and 2. Penetrating injuries accounted for 82.1% of group 1 but only 49.3% of group 2 patients, whereas rupture occurred more frequently in group 2 (48.1%) than in group 1 (17.0%) patients. Orbital and adnexal injuries were associated with poorer visual acuity at presentation, probably because of the high incidence of posterior globe injuries in these patients. Conclusions: Orbital and adnexal injuries were observed in 25.7% of patients who sustained trauma that resulted in open globes. Concurrent injury to these extraocular structures is associated with worse visual acuity at presentation and an increased likelihood of posterior globe injuries. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Trauma Serv, Boston, MA 02114 USA. RP Hatton, MP (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Trauma Serv, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD NOV PY 2002 VL 18 IS 6 BP 458 EP 461 DI 10.1097/01.IOP.0000029716.95047.86 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 617PC UT WOS:000179369200015 PM 12439061 ER PT J AU Hatton, MP Remulla, HD Tolentino, MJ Rubin, PAD AF Hatton, MP Remulla, HD Tolentino, MJ Rubin, PAD TI Clinical applications of color Doppler Imaging in the management of orbital lesions SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 24-27, 1999 CL ORLANDO, FLORIDA SP Amer Acad Ophthalmol ID ULTRASONOGRAPHY; EYE AB Purpose: To present the clinical applications of color Doppler imaging (CDI) as an adjunctive study in the diagnosis and treatment of orbital lesions. Methods: Retrospective noncomparative case series. Medical records of 17 patients with orbital lesions who underwent orbital CDT were reviewed, and their orbital CDT results, diagnosis, and treatment were studied. The main outcome measures were detection of abnormal orbital vascular flow and presence or absence of blood flow within orbital lesions by CDT. Results: Absence of intralesional flow was associated with an orbital lesion considered benign. Tumors in which flow was present were more frequently malignant or had malignant potential. Reversal of flow in the superior ophthalmic vein was observed in patients with carotid-cavernous fistula and orbital varix. Conclusions: CDT is a useful adjunctive imaging study for evaluating the vascularity of orbital tumors. The absence or presence of intratumoral blood flow, as demonstrated by CDT can help determine the nature of the orbital mass and can assist with surgical planning. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD NOV PY 2002 VL 18 IS 6 BP 462 EP 465 DI 10.1097/01.IOP.0000029718.48146.56 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 617PC UT WOS:000179369200016 PM 12439062 ER PT J AU To, KW Thirkill, CE Jakobiec, FA Lessell, S Berson, EL AF To, KW Thirkill, CE Jakobiec, FA Lessell, S Berson, EL TI Lymphoma-associated retinopathy SO OPHTHALMOLOGY LA English DT Article ID CANCER-ASSOCIATED RETINOPATHY; MELANOMA-ASSOCIATED RETINOPATHY; SMALL-CELL-CARCINOMA; CUTANEOUS MALIGNANT-MELANOMA; CALCIUM-BINDING PROTEIN; PARANEOPLASTIC RETINOPATHY; LUNG-CARCINOMA; PHOTORECEPTOR DEGENERATION; ENDOMETRIAL CANCER; RECOVERIN AB Objective: To describe the clinical, electrophysiologic, and serologic findings in a patient with retinal degeneration associated with Hodgkin's lymphoma. Design: Case report with ancillary immunohistochemical studies. Methods: A 24-year-old woman experienced night blindness and fundus abnormalities 1 week after initiation of chemotherapy for Hodgkin's lymphoma. Visual fields and full-field electroretinograms (ERGs) were monitored over a 10-year period. Serum antibodies were studied on Western blot reactions on a solubilized extract of bovine retina. Serum antibodies were also evaluated through indirect immunohistochemistry on rhesus monkey retina. Results: Visual field and ERG amplitudes, initially abnormal, became reduced further over 10 years. Serum antibodies were identified that reacted to a retinal protein or proteins approximating 65 kd; these antibodies showed immunologic activity against photoreceptors. Conclusions: A progressive paraneoplastic retinopathy can occur in association with Hodgkin's lymphoma. The pathogenesis of the retinal degeneration appears to be related to a serum antibody that is reacting to a retinal protein or proteins of approximately 65 kd. (C) 2002 by the American Academy of Ophthalmology, Inc. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab,Dept Ophthalmol, Boston, MA 02114 USA. Univ Calif Davis, Sacramento, CA 95817 USA. RP To, KW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [1 P30 EY12576-01] NR 41 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2002 VL 109 IS 11 BP 2149 EP 2153 AR PII S0161-6420(02)01261-7 DI 10.1016/S0161-6420(02)01261-7 PG 5 WC Ophthalmology SC Ophthalmology GA 607EL UT WOS:000178778600052 PM 12414431 ER PT J AU Mankarious, LA Cherukupally, SR Adams, AB AF Mankarious, LA Cherukupally, SR Adams, AB TI Gross and histologic changes in the developing rabbit subglottis in response to a controlled depth of injury SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Combined Otolaryngological Spring Meeting CY MAY 09, 2001-MAY 12, 2011 CL PALM DESERT, CALIFORNIA ID STENOSIS; PROLIFERATION; GROWTH; TRAUMA AB OBJECTIVE: Our goal was to determine the effects of both perichondrial and intracartilaginous injury in the developing rabbit subglottis versus normal development. DESIGN: We conducted a descriptive, pilot study of changes in the shape and histology of the subglottis after a controlled depth of injury in 27 New Zealand White rabbits, ages 4 weeks, 8 weeks, and 1(1)/(2) years. INTERVENTION: Within each age group, 3 animals underwent no surgery, 3 underwent perichondrial injury, and 3 underwent intracartilaginous injury. RESULTS: Perichondrially injured animals in the 4-week age group developed a marked abnormality in the shape of the cricoid cartilage in the injured region. Cartilage of the perichondriallly injured animals in the 8-week and 1(1)/(2)-year groups became histologically consistent with fibrous tissue: The cartilage of all animals that underwent intracartilaginous injury was replaced with fibrous tissue. CONCLUSION: In this observational study, we identified 3 relevant findings. First, the responses of the cartilage to a perichondrial injury suggest that the luminal soft tissues may exert some morphologic control in developmentally young animals. Second, only the 4-week-old group's cartilage was tolerant of a perichondrial injury with continued growth of the ring. Third, no animal's cartilage could withstand an intracartilaginous injury regardless of age. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2002 VL 127 IS 5 BP 442 EP 447 DI 10.1067/mhn.2002.128895 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 620PT UT WOS:000179542300012 PM 12447239 ER PT J AU Cecorsterd, I Allchorne, A Woolf, CJ AF Cecorsterd, I Allchorne, A Woolf, CJ TI Progressive tactile hypersensitivity after a peripheral nerve crush: non-noxious mechanical stimulus-induced neuropathic pain SO PAIN LA English DT Article DE tactile hypersensitivity; nerve crush; neuropathic pain; nerve injury; animal model ID PRIMARY SENSORY NEURONS; PRIMARY AFFERENT-FIBERS; DORSAL-ROOT GANGLIA; RAT SPINAL-CORD; NEUROTROPHIC FACTOR; SCIATIC-NERVE; GRACILE NUCLEI; NEUROPEPTIDE-Y; INJURY; HYPERALGESIA AB Neuropathic pain syndromes are characterized by spontaneous pain and by stimulus-evoked allodynia and hyperalgesia. Stimulus-induced pain, i.e. the capacity of external stimuli to alter sensory processing so as to generate a pain hypersensitivity that outlasts the initiating stimulus, is usually present only after intense activation of nociceptors. In abnormal pain states, however, such as after capsaicin injection or inflammation, a stimulus-induced incremental pain can be generated by repetitive light touch, termed progressive tactile hypersensitivity (PTH). In the present study, we have examined whether PTH also occurs in two experimental models of neuropathic pain: a crush injury of the sciatic nerve and the spared nerve injury (SNI) model. When applied during the first weeks after injury to the territory of the injured crushed nerve, repeated low-intensity mechanical stimulation did not change the mechanical withdrawal threshold response. However, 10 weeks and after, the same repeated stimulation induced a progressive tactile hypersensitivity that persisted after discontinuation of the tactile stimulation. Following SNI, repeated stimulation of the hypersensitive skin territory, corresponding to the intact spared sural nerve, never induced PTH. Tactile stimulation of regenerating afferents but not spared non-injured afferents, can induce, therefore, PTH and such a stimulus-induced alteration in pain processing may contribute to clinical neuropathic pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 CHU Vaudois, Dept Anesthesiol, Anesthesiol Pain Res Grp, CH-1011 Lausanne, Switzerland. CHU Vaudois, Dept Expt Surg, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plastic Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cecorsterd, I (reprint author), CHU Vaudois, Dept Anesthesiol, Anesthesiol Pain Res Grp, CH-1011 Lausanne, Switzerland. NR 59 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2002 VL 100 IS 1-2 BP 155 EP 162 AR PII S0304-3959(02)00275-0 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 622TW UT WOS:000179664000017 ER PT J AU Sander, LM Deisboeck, TS AF Sander, LM Deisboeck, TS TI Growth patterns of microscopic brain tumors SO PHYSICAL REVIEW E LA English DT Article ID SCATTER FACTOR EXPRESSION; SELF-ORGANIZATION; FACTOR RECEPTOR; SPHEROID MODEL; CELL MOTILITY; HUMAN GLIOMAS; PROLIFERATION; MIGRATION; GENES AB Highly malignant brain tumors such as glioblastoma multiforme form complex growth patterns in vitro in which invasive cells organize in tenuous branches. Here, we formulate a chemotaxis model for this sort of growth. A key element controlling the pattern is homotype attraction, i.e., the tendency for invasive cells to follow pathways previously explored. We investigate this in two ways: we show that there is an intrinsic instability in the model, which leads to branch formation. We also give a discrete description for the expansion of the invasive zone, and a continuum model for the nutrient supply. The results indicate that both strong heterotype chemotaxis and strong homotype chemoattraction are required for branch formation within the invasive zone. Our model thus can give a way to assess the importance of the various processes, and a way to explore and analyze transitions between different growth regimes. C1 Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA. Univ Michigan, Michigan Ctr Theoret Phys, Ann Arbor, MI 48109 USA. MIT, HSt Biomed Engn Ctr, Harvard MIT HST Athinoula A Martinos Ctr Biomed I, Complex Biosyst Modeling Lab, Cambridge, MA 02139 USA. MIT, Ctr Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Sander, LM (reprint author), Univ Michigan, Dept Phys, Ann Arbor, MI 48109 USA. NR 25 TC 71 Z9 71 U1 0 U2 8 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD NOV PY 2002 VL 66 IS 5 AR 051901 DI 10.1103/PhysRevE.66.051901 PG 7 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 622DG UT WOS:000179630800065 PM 12513517 ER PT J AU Cheng, WH Endo, A Zhou, L Penney, J Chen, HC Arroyo, A Leon, P Nambara, E Asami, T Seo, M Koshiba, T Sheen, J AF Cheng, WH Endo, A Zhou, L Penney, J Chen, HC Arroyo, A Leon, P Nambara, E Asami, T Seo, M Koshiba, T Sheen, J TI A unique short-chain dehydrogenase/reductase in Arabidopsis glucose signaling and abscisic acid biosynthesis and functions SO PLANT CELL LA English DT Article ID GENE-EXPRESSION; 9-CIS-EPOXYCAROTENOID DIOXYGENASE; ALDEHYDE OXIDASE; ZEAXANTHIN EPOXIDASE; DEVELOPMENTAL ARREST; INSENSITIVE MUTANTS; HIGHER-PLANTS; WATER-STRESS; SDR ENZYMES; ETHYLENE AB Glc has hormone-like functions and controls many vital processes through mostly unknown mechanisms in plants. We report here on the molecular cloning of GLUCOSE INSENSITIVE1 (GIN1) and ABSCISIC ACID DEFICIENT2 (ABA2) which encodes a unique Arabidopsis short-chain dehydrogenase/reductase (SDR1) that functions as a molecular link between nutrient signaling and plant hormone biosynthesis. SDR1 is related to SDR superfamily members involved in retinoid and steroid hormone biosynthesis in mammals and sex determination in maize. Glc antagonizes ethylene signaling by activating ABA2/GIN1 and other abscisic acid (ABA) biosynthesis and signaling genes, which requires Glc and ABA synergistically. Analyses of aba2/gin1 null mutants define dual functions of endogenous ABA in inhibiting the post-germination developmental switch modulated by distinct Glc and osmotic signals and in promoting organ and body size and fertility in the absence of severe stress. SDR1 is sufficient for the multistep conversion of plastid- and carotenoid-derived xanthoxin to abscisic aldehyde in the cytosol. The surprisingly restricted spatial and temporal expression of SDR1 suggests the dynamic mobilization of ABA precursors and/or ABA. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Acad Sinica, Inst Bot, Taipei 11529, Taiwan. Tokyo Metropolitan Univ, Dept Biol Sci, Hachioji, Tokyo 1920397, Japan. Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Biol Mol Plantas, Cuernavaca 62271, Morelos, Mexico. RIKEN, Inst Phys & Chem Res, Plant Sci Ctr, Wako, Saitama 3510198, Japan. RIKEN, Inst Phys & Chem Res, Plant Funct Lab, Wako, Saitama 3510198, Japan. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Endo, Akira/O-5537-2014; Seo, Mitsunori/N-9603-2015 FU NIGMS NIH HHS [GM60493, R01 GM060493] NR 79 TC 391 Z9 426 U1 6 U2 64 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD NOV PY 2002 VL 14 IS 11 BP 2723 EP 2743 DI 10.1105/tpc.006494 PG 21 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 615UF UT WOS:000179264700007 PM 12417697 ER PT J AU Smith, BL AF Smith, BL TI Mammography at a crossroad - How do physicians reconcile conflicting study results with the biologic truths of breast cancer? SO POSTGRADUATE MEDICINE LA English DT Editorial Material ID DEATH RATES C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, 100 Blossom St,Cox 120, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD NOV PY 2002 VL 112 IS 5 BP 11 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 835RW UT WOS:000222504200001 PM 12462182 ER PT J AU Kashork, CD Sutton, VR Allen, JSF Schmidt, DE Likhite, ML Potocki, L O'Brien, WE Shaffer, LG AF Kashork, CD Sutton, VR Allen, JSF Schmidt, DE Likhite, ML Potocki, L O'Brien, WE Shaffer, LG TI Low or absent unconjugated estriol in pregnancy: an indicator for steroid sulfatase deficiency detectable by fluorescence in situ hybridization and biochemical analysis SO PRENATAL DIAGNOSIS LA English DT Article DE unconjugated estriol (uE3); steroid sulfatase (STS); contiguous gene deletion syndrome; microdeletion; ichthyosis; laboratory diagnostics; genetic testing ID X-LINKED ICHTHYOSIS; DISTAL SHORT ARM; PRENATAL-DIAGNOSIS; FREQUENT DELETIONS; CHROMOSOME; GENE; HETEROGENEITY AB It has been previously reported that a low or absent maternal serum unconjugated estriol (uE3) level is associated with placental steroid sulfatase (STS) deficiency. Here we report a correlation between patients who present with a very low or absent maternal serum uE3 and a deletion of the STS gene as assessed by fluorescence in situ hybridization (FISH). We studied nine prenatal cases that presented to the clinical laboratory with an abnormal triple screen, specifically low or absent maternal serum uE3 and a 46,XY karyotype. FISH analysis showed complete deletion of a probe containing the STS gene in six cases and one case had a partial deletion (reduced but not absent signal). The remaining two cases were not deleted for the STS probe. All mothers tested whose fetus showed a deletion were shown to be STS deletion carriers using FISH. Biochemical analysis was performed on 7/9 prenatal specimens. All fetuses deleted for the STS probe were also found to be deficient for STS by biochemical analysis of cultured amniotic fluid (5/5). Of the two fetuses not deleted for the STS probe, one was deficient for STS activity, while the other had a normal result. The abnormal result of enzyme deficiency by biochemical analysis in a non-deletion case likely represents a mutation in the STS gene, not detectable by this FISH assay. Postnatal FISH confirmation of the STS deletion was performed in 1/7 cases. Clinical follow-up was available for 4/9 cases following birth. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Kleberg Cytogenet Lab, Houston, TX 77030 USA. Baylor Coll Med, Biochem Genet Lab, Houston, TX 77030 USA. Ctr Maternal Fetal Med & Reprod Genet, Rockville, MD USA. Queens Med Ctr, Honolulu, HI USA. Massachusetts Gen Hosp, Partners Genet Clin, Boston, MA 02114 USA. RP Shaffer, LG (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza,Room S801, Houston, TX 77030 USA. NR 19 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD NOV PY 2002 VL 22 IS 11 BP 1028 EP 1032 DI 10.1002/pd.466 PG 5 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 617ZE UT WOS:000179390400015 PM 12424769 ER PT J AU Stryker, JE AF Stryker, JE TI Reporting medical information: Effects of press releases and newsworthiness on medical journal articles' visibility in the news media SO PREVENTIVE MEDICINE LA English DT Article DE journalism; medical; information dissemination; mass media; United States ID BREAST-CANCER; PUBLIC DISSEMINATION; SCIENCE COVERAGE; INGELFINGER RULE; POPULAR PRESS; ACCURACY; SCIENTISTS; NEWSPAPERS; RISK; MEDICINES AB Background. Characteristics defining newsworthiness of journal articles appearing in JAMA and NEJM were examined to determine if they affect visibility in the news media. It was also hypothesized that press releases affected the amount of news coverage of a journal article due to the fact that the most newsworthy journal articles are selected for press releases. Methods. Journal articles (N = 95) were coded for characteristics believed to describe the "newsworthiness" of journal articles. Quantity of news coverage of the journal articles was estimated using the LEXIS-NEXIS database. Bivariate associations were examined using one-way analysis of variance, and multivariate analyses utilized OLS regression. Results. Characteristics of the newsworthiness of medical journal articles predicted their visibility in newspapers. The issuing of press releases also predicted newspaper coverage. However, press releases predicted newspaper coverage largely because more newsworthy journal articles had accompanying press releases rather than because the press release itself was influential. Conclusion. Journalists report on medical information that is topical, stratifies risk based on demographic and lifestyle variables, and has lifestyle rather than medical implications. Medical journals issue press releases for articles that possess the characteristics journalists are looking for, thereby further highlighting their importance. (C) 2002 American Health Foundation and Elsevier Science (USA). C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Stryker, JE (reprint author), Dana Farber Canc Inst, 44 Binney St,Smith 262, Boston, MA 02115 USA. NR 51 TC 44 Z9 46 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 2002 VL 35 IS 5 BP 519 EP 530 DI 10.1006/pmed.2002.1102 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 613CK UT WOS:000179113900013 PM 12431901 ER PT J AU Pirl, WF Siegel, GI Goode, MJ Smith, MR AF Pirl, WF Siegel, GI Goode, MJ Smith, MR TI Depression in men receiving androgen deprivation therapy for prostate cancer: A pilot study SO PSYCHO-ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; DISORDERS; SURVIVAL; MOOD AB Purpose: Prostate cancer is the most common malignancy in men and one of the leading causes of cancer death in men internationally. Treatment for prostate cancer frequently includes androgen deprivation therapy (ADT). Reports of depressive symptoms arising during ADT are emerging. This study examines the prevalence rates and risk factors associated with major depression in this population. Method: 45 men with prostate cancer receiving ADT at the MGH Cancer Center were surveyed for depression with the SCID for Axis I disorders for DSM-IV and the Beck Depression Inventory. Results: Major depressive disorder was prevalent in 12.8% of the men with prostate cancer receiving ADT, eight times the national rate of depression in men, 32 times the rate in men over 65 years old. Major depression was not associated with worsening disease, medical response to ADT, receiving chemotherapy, or the type of ADT. Past history of depression was associated with current depression in this population (p < 0.000). No first onset cases of depression occurred on ADT in this sample. Conclusion: This data suggests a significant rate of major depression in men with prostate cancer receiving ADT and that men with past histories of depression may be at particular risk for recurrence of their depression while undergoing this treatment. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pirl, WF (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 1220,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 85 Z9 85 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD NOV-DEC PY 2002 VL 11 IS 6 BP 518 EP 523 DI 10.1002/pon.592 PG 6 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 628LD UT WOS:000179995600006 PM 12476433 ER PT J AU Patenaude, AF AF Patenaude, AF TI Beyond a shadow of doubt: Assessing the psychological impact of predictive genetic testing for multiple endocrine neoplasia type 2. SO PSYCHO-ONCOLOGY LA English DT Book Review C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD NOV-DEC PY 2002 VL 11 IS 6 BP 543 EP 544 DI 10.1002/pon.610 PG 2 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 628LD UT WOS:000179995600011 ER PT J AU Hyams, KC Scott, K AF Hyams, KC Scott, K TI Adding to our understanding of Gulf War health issues SO PSYCHOLOGICAL MEDICINE LA English DT Editorial Material ID VETERANS C1 US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, VA Cent Off, Washington, DC 20420 USA. Canadian Forces Med Grp Headquarters, Ottawa, ON K1A 0K6, Canada. RP Hyams, KC (reprint author), US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, VA Cent Off, 810 Vermont Ave NW, Washington, DC 20420 USA. NR 6 TC 2 Z9 2 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2002 VL 32 IS 8 BP 1335 EP 1337 DI 10.1017/S0033291702006669 PG 3 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 621AD UT WOS:000179565600001 PM 12455931 ER PT J AU Frankle, WG Perlis, RH Deckersbach, T Grandin, LD Gray, SM Sachs, GS Nierenberg, AA AF Frankle, WG Perlis, RH Deckersbach, T Grandin, LD Gray, SM Sachs, GS Nierenberg, AA TI Bipolar depression: relationship between episode length and antidepressant treatment SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DOUBLE-BLIND; IMIPRAMINE; DISORDER; MANIA; PLACEBO; ILLNESS AB Background. The role of antidepressant medications in bipolar depression remains controversial, mainly due to a lack of research in this area. In this study the authors examined the episode length in bipolar depression and the relationship between antidepressant therapy and episode length. Method. A retrospective chart review of 165 subjects identified 50 (30%) with bipolar illness who experienced a major depressive episode between I January 1998 and 15 December 2000. Data gathered utilized a structured instrument completed by the clinician at each visit. This instrument includes modified SCID mood modules as well as continuous ratings for each associated symptom of depression and mood elevation. Survival analysis was employed to calculate the median length of the depressive episodes for the entire group. Further survival analysis compared the episode length for subjects treated with antidepressants during the depression (N = 33) with those who did not receive antidepressants (N = 17). The rate of switch into elevated mood states was compared for the two groups. Results. The survival analysis for the entire sample demonstrated 25%, 50% and 75% probability of recovery at 33 (S.E. 8.7), 66 (S.E. 17.9) and 215 (S.E. 109.9) days, respectively. Comparing those who received (N = 33) and those who did not receive (N = 17) antidepressants during the episode did not reveal any difference in the length of the depressive episode. Switch rates were not significantly different between those receiving antidepressants and those not taking these medications (15.2% v. 17.6%, respectively). Conclusions. Over the past 20 years little progress has been made in reducing the length of depressive episodes in those with bipolar illness. This is despite increasing pharmacological options available for treating depression. Clinicians treating bipolar depression should discuss with their patients the likelihood that the episode will last between 2-3 months. Our results also suggest that antidepressant treatment may not reduce the length of depressive episodes, neither did it appear to contribute to affective switch in our sample. C1 Columbia Univ, NYSPI, Dept Psychiat, Unit 2, New York, NY 10032 USA. Massachusetts Gen Hosp, Partners Bipolar Treatment Ctr, Dept Psychiat, Boston, MA 02114 USA. RP Frankle, WG (reprint author), Columbia Univ, NYSPI, Dept Psychiat, Unit 2, 1051 Riverside Dr, New York, NY 10032 USA. OI Frankle, William/0000-0003-0356-4197 NR 19 TC 24 Z9 24 U1 2 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2002 VL 32 IS 8 BP 1417 EP 1423 DI 10.1017/S0033291702006165 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 621AD UT WOS:000179565600010 PM 12455940 ER PT J AU Kahkonen, S Jaaskelainen, IP Pennanen, S Liesivuori, J Ahveninen, J AF Kahkonen, S Jaaskelainen, IP Pennanen, S Liesivuori, J Ahveninen, J TI Acute trytophan depletion decreases intensity dependence of auditory evoked magnetic N1/P2 dipole source activity SO PSYCHOPHARMACOLOGY LA English DT Article DE auditory; electroencephalography (EEG); magnetoencephalography (MEG); serotonin; tryptophan depletion ID CENTRAL SEROTONERGIC NEUROTRANSMISSION; EVENT-RELATED POTENTIALS; TRYPTOPHAN DEPLETION; STIMULUS-INTENSITY; HUMAN BRAIN; MONOAMINERGIC INNERVATION; SENSATION SEEKING; TYROSINE; CORTEX; MONKEY AB Rationale: Intensity dependence of the N1/P2 components may be regulated by serotonergic neurons in the primary auditory cortex, where low activity leads to a high intensity dependence and vice versa. Depletion of tryptophan (TRP), a precursor for serotonin has been described to reduce serotonin content in brain of animals and humans. Objective: We investigated the intensity dependence of magnetic and electric N1/P2 components in ten subjects in a double-blind, controlled, cross-over design study after oral mixture of amino-acids leading to acute tryptophan depletion (ATD) and control. Methods: Auditory evoked magnetic fields (AEF) and potentials (AEP) were recorded with 122-channel magnetoencephalography simultaneously with 64-channel EEG 5 h after ingestion of mixtures. The AEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole. The amplitudes and latencies of N1 and P2 recorded with EEG were analyzed at frontal electrode site. Results: TRP depletion decreased the total and free TRP levels by 76 and 45% and control mixture increased it by 48 and 28%. ANOVA showed that ATD had a significant main effect on the N1m/P2m dipole moments at the contralateral (P=0.02), but failed significantly to influence the ipsilateral responses. A significant mixture ingestion-by-stimulus intensity interaction was observed on the N1m/P2m dipole moments at the contralateral hemisphere (P=0.01). The N1/P2 slope for intensity dependence function was decreased following ATD compared with the control experiment (P=0.01) at the contralateral hemisphere. For EEG, a significant mixture ingestion-by-stimulus intensity interaction on the N1 latencies at the Fz electrode position was observed (P=0.01). Conclusion: ATD decreased the intensity dependence of N1m/P2m source dipole moments in the primary auditory cortex at the hemisphere contralateral to the ear stimulated. These results suggest that serotonin participates in the regulation of intensity of auditory stimulation. C1 Univ Helsinki, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Engn Ctr, Helsinki 00029, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Univ Helsinki, Dept Psychol, Appercept & Cort Dynam Res Team, Helsinki, Finland. Kuopio Reg Inst Occupat Hlth, Lab Environm Microbiol, Kuopio, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, Kuopio, Finland. Univ Helsinki, Dept Neurol, Helsinki, Finland. RP Kahkonen, S (reprint author), Univ Helsinki, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. EM Seppo.Kahkonen@helsinki.fi RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013 OI Jaaskelainen, Iiro/0000-0001-6001-6950; NR 44 TC 31 Z9 31 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2002 VL 164 IS 2 BP 221 EP 227 DI 10.1007/s00213-002-1194-z PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 620LM UT WOS:000179534900013 PM 12404086 ER PT J AU Goldstein, A Spencer, KM Donchin, E AF Goldstein, A Spencer, KM Donchin, E TI The influence of stimulus deviance and novelty on the P300 and Novelty P3 SO PSYCHOPHYSIOLOGY LA English DT Article DE P300; Novelty P3; stimulus deviance; novelty; principal components analysis ID EVENT-RELATED POTENTIALS; INVOLUNTARY ATTENTION; BRAIN POTENTIALS; DISTRACTIBILITY; INHIBITION; COMPONENTS; TASK; PROBABILITY; PARADIGM; ODDBALL AB This study examined the relationship between ERP components elicited by deviant stimuli by disentangling the P300 and Novelty P3 components. using spatiotemporal principal components analysis and a dense electrode array. The three-tone paradigm was used and the pitch attributes of the tones were systematically manipulated so as to map the amplitude of the ERP components on the stimulus context. A comparison was made between the components elicited by events in the three-stimulus, classical oddball, and novelty oddball paradigms, Responses to deviant stimuli consisted of independent and dissociable ERP components in the 400-600-ms time range: A parietal component (P300) that was larger for targets than rare nontargets and was affected by the difficulty of discrimination, a fronto-central component (Novelty P3) that was larger for novel tones and for rare nontargets in the difficult discrimination condition, and an additional anterior negative component responded similarly to all types of deviant stimuli. C1 Bar Ilan Univ, Dept Psychol, Ramat Gan, Israel. Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA USA. Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. Univ Illinois, Beckman Inst, Champaign, IL 61820 USA. RP Donchin, E (reprint author), Univ S Florida, Dept Psychol, 4202 Fowler Ave, Tampa, FL 33620 USA. OI Spencer, Kevin/0000-0002-5500-7627; Goldstein, Abraham/0000-0002-9349-0621 FU NIMH NIH HHS [MH016259, MH11516] NR 42 TC 116 Z9 123 U1 2 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2002 VL 39 IS 6 BP 781 EP 790 DI 10.1017/S004857720201048X PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 628MA UT WOS:000179998200009 PM 12462506 ER PT J AU Sitnikova, T Salisbury, DF Kuperberg, G Holcomb, PJ AF Sitnikova, T Salisbury, DF Kuperberg, G Holcomb, PJ TI Electrophysiological insights into language processing in schizophrenia SO PSYCHOPHYSIOLOGY LA English DT Article DE schizophrenia; language; context-irrelevant semantic associations; event-related potentials; N400 ID THOUGHT-DISORDER; WORD PRONUNCIATION; LEXICAL AMBIGUITY; BRAIN POTENTIALS; REACTION-TIMES; CONTEXT; NORMS; N400; RECOGNITION; ACTIVATION AB Deficits in language comprehension in schizophrenia were examined using event-related potentials (ERPs). Schizophrenic and healthy participants read sentences in which the first clause ended with a homograph, and the second clause started with a tat-get word that was semantically related to the homograph's dominant meaning (e.g., 1. Diving was forbidden front the bridge because the river had rocks in it, or 2. The guests played bridge because the river had rocks in it.). Processing of the targets (e.g.. "river") was expected to be primarily influenced by the preceding overall sentence context (congruent in 1 incongruent in 2) in healthy participants, but to be inappropriately affected by the dominant meaning of homographs (e.g.. the "structure" meaning of "bridge") in sentences like 2 in schizophrenic patients. The N400 ERP component that is known to be sensitive to contextual effects during language processing confirmed these predictions. This showed that language abnormalities in schizophrenia may be related to deficient processing of context-irrelevant semantic representations of words from the discourse. C1 Tufts Univ, Dept Psychol, Medford, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Inst Psychiat, Dept Med Psychol, London, England. RP Sitnikova, T (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02115 USA. FU NIMH NIH HHS [R01 MH058704] NR 60 TC 56 Z9 57 U1 2 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2002 VL 39 IS 6 BP 851 EP 860 DI 10.1017/S0048577202010466 PG 10 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 628MA UT WOS:000179998200015 PM 12462512 ER PT J AU Cohen, LM Dobscha, SK Hails, KC Pekow, PS Chochinov, HM AF Cohen, LM Dobscha, SK Hails, KC Pekow, PS Chochinov, HM TI Depression and suicidal ideation in patients who discontinue the life-support treatment of dialysis SO PSYCHOSOMATIC MEDICINE LA English DT Article ID TERMINALLY ILL; MAJOR DEPRESSION; ASSISTED SUICIDE; RISK-FACTORS; DEATH; DIAGNOSIS; CARE; DECISION; ATTITUDES; WITHDRAWN AB Objective: The objective of this study was to determine the prevalence of major depression and suicidal ideation in patients who stop the life-support treatment of dialysis. Methods: The authors prospectively studied 79 subjects who discontinued maintenance dialysis at eight facilities in North America. Structured interviews were conducted with 23 patients and 76 families. Results: The prevalence of major depression in the sample was between 5% and 25%, and only 1 of 22 patients considered himself to have the illness of depression. Approximately 12% of the respondents were unsure or believed that discontinuing dialysis was the equivalent of suicide. This belief did not correlate with measures of depression. In comparison with the general population there seemed to be an increased prevalence of past suicide attempts. Conclusions: Most patients who decide to stop dialysis do not seem to be influenced by major depression or ordinary suicidal ideation. Although the sample size was small, these results highlight the need to further examine the theoretical framework and terminology of depression and suicide in the context of terminal illness. Key words: dialysis, depression, suicide, life support. C1 Baystate Med Ctr, Dept Psychiat, Springfield, MA 01199 USA. Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. Albert Einstein Med Ctr, Dept Psychiat, Philadelphia, PA 19141 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Univ Manitoba, Dept Psychiat & Family Med, Winnipeg, MB, Canada. CancerCare Manitoba, Winnipeg, MB, Canada. RP Cohen, LM (reprint author), Baystate Med Ctr, Dept Psychiat, S2669, Springfield, MA 01199 USA. NR 51 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2002 VL 64 IS 6 BP 889 EP 896 DI 10.1097/01.PSY.0000028828.64279.84 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 622AB UT WOS:000179622900006 PM 12461194 ER PT J AU Safren, SA Radomsky, AS Otto, MW Salomon, E AF Safren, SA Radomsky, AS Otto, MW Salomon, E TI Predictors of psychological well-being in a diverse sample of HIV-positive patients receiving highly active antiretroviral therapy SO PSYCHOSOMATICS LA English DT Article ID THEORETICALLY BASED APPROACH; PROTEASE INHIBITORS; SOCIAL SUPPORT; DYSFUNCTIONAL ATTITUDES; ADHERENCE; DEPRESSION; AIDS; RECOMMENDATIONS; STRATEGIES; MEDICATION AB The purpose of the present study was to identify variables relevant to psychological well-being in HIV patients receiving highly active antiretroviral therapy (HAART). Multiple stressors accompany living with HIV while managing a HAART regimen. However, a variety of cognitive and behavioral variables can protect against or augment the deleterious effects of stress in this population. The authors hypothesized that satisfaction with social support, coping styles, and maladaptive attributions about HIV would explain more variance in psychological well-being than stressful life events per se. Participants were individuals with HIV receiving antiretroviral therapy-either starting a new HAART regimen or having difficulties adhering to their current regimen. Satisfaction with social support, coping styles, and punishment beliefs about HIV were uniquely associated with depression, quality of life, and self-esteem over and above the effects of stressful life events. These results provide support for continued psychosocial interventions that target these variables among patients with HIV. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fenway Community Hlth, Boston, MA USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 812,15 Parkman St, Boston, MA 02114 USA. OI Radomsky, Adam/0000-0003-2807-184X NR 35 TC 41 Z9 42 U1 0 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2002 VL 43 IS 6 BP 478 EP 485 DI 10.1176/appi.psy.43.6.478 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 614DW UT WOS:000179173900007 PM 12444231 ER PT J AU Bohne, A Keuthen, NJ Wilhelm, S Deckersbach, T Jenike, MA AF Bohne, A Keuthen, NJ Wilhelm, S Deckersbach, T Jenike, MA TI Prevalence of symptoms of body dysmorphic disorder and its correlates: A cross-cultural comparison SO PSYCHOSOMATICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; BECK DEPRESSION INVENTORY; UNITED-STATES; SELF-ESTEEM; PHYSICAL ATTRACTIVENESS; PSYCHOMETRIC PROPERTIES; STUDENTS; PREFERENCES; APPEARANCE; POPULATION AB The authors investigated the prevalence of body image concerns, body dysmorphic disorder, and related psychiatric symptoms in a group of 101 American students. Results were compared with data from a group of 133 German students. Survey data were collected on body image concerns, self-esteem, depression, anxiety, obsessive-compulsive symptoms, and skin picking. A total of 74.3% of the American students endorsed body image concerns, and 28.7% were preoccupied by them; 4.0% appeared to meet DSM-IV criteria for body dysmorphic disorder. Body esteem was significantly correlated with self-esteem and depressive, anxiety, and obsessive-compulsive symptoms. Body image concerns and preoccupation were significantly greater in American than in German students, although the prevalence of probable body dysmorphic disorder was not. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp E, OCD Clin, 149 13th St, Charlestown, MA 02129 USA. NR 32 TC 60 Z9 63 U1 2 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2002 VL 43 IS 6 BP 486 EP 490 DI 10.1176/appi.psy.43.6.486 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 614DW UT WOS:000179173900008 PM 12444232 ER PT J AU Sachs, RK Arsuaga, J Vazquez, M Hlatky, L Hahnfeldt, P AF Sachs, RK Arsuaga, J Vazquez, M Hlatky, L Hahnfeldt, P TI Using graph theory to describe and model chromosome aberrations SO RADIATION RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; IONIZING-RADIATION; FISH; EXCHANGES; REARRANGEMENTS; LYMPHOCYTES; RESOLUTION; ORIGIN; REPAIR; MFISH AB A comprehensive description of chromosome aberrations is introduced that is suitable for all cytogenetic protocols (e.g. solid staining, banding, FISH, mFISH, SKY, bar coding) and for mathematical analyses. "Aberration multigraphs" systematically characterize and interrelate three basic aberration elements: (1) the initial configuration of chromosome breaks; (2) the exchange process, whose cycle structure helps to describe aberration complexity; and (3) the final configuration of rearranged chromosomes, which determines the observed pattern but may contain cryptic misrejoinings in addition. New aberration classification methods and a far-reaching generalization of mPAINT descriptors, applicable to any protocol, emerge. The difficult problem of trying to infer actual exchange processes from cytogenetically observed final patterns is analyzed using computer algorithms, adaptations of known theorems on cubic graphs, and some new graph-theoretical constructs. Results include the following: (1) For a painting protocol, unambiguously inferring the occurrence of a high-order cycle requires a corresponding number of different colors; (2) cycle structure can be computed by a simple trick directly from mPAINT descriptors if the initial configuration has no more than one break per homologue pair; and (3) higher-order cycles are more frequent than the obligate cycle structure specifies. Aberration multigraphs are a powerful new way to describe, classify and quantitatively analyze radiation-induced chromosome aberrations. They pinpoint (but do not eliminate) the problem that, with present cytogenetic techniques, one observed pattern corresponds to many possible initial configurations and exchange processes. (C) 2002 by Radiation Research Society. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Evans Hall, Berkeley, CA 94720 USA. FU NCI NIH HHS [CA86823]; NIGMS NIH HHS [GM 57245] NR 39 TC 10 Z9 10 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2002 VL 158 IS 5 BP 556 EP 567 DI 10.1667/0033-7587(2002)158[0556:UGTTDA]2.0.CO;2 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 612RR UT WOS:000179089700002 PM 12385633 ER PT J AU Harisinghani, MG Gervais, DA Hahn, PE Cho, CH Jhaveri, K Varghese, J Mueller, PR AF Harisinghani, MG Gervais, DA Hahn, PE Cho, CH Jhaveri, K Varghese, J Mueller, PR TI CT-guided transgluteal drainage of deep pelvic abscesses: Indications, technique, procedure-related complications, and clinical outcome SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2001 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE abscess, percutaneous drainage; computed tomography (CT), guidance; pelvic organs, abscess; pelvic organs, interventional procedures ID TRANSRECTAL DRAINAGE AB Deep pelvic abscesses may present a unique challenge for percutaneous drainage because of numerous overlying structures, which preclude safe percutaneous access. These structures include the pelvic bones, intestine, bladder, iliac vessels, and gynecologic organs. Use of the transgluteal approach to drain these abscesses can circumvent these obstacles and provide a useful surgical alternative or a temporizing measure. The transgluteal approach requires a thorough understanding of the anatomy of the sciatic foramen region and associated anatomic structures. The ideal approach for transgluteal. access is to insert the catheter as close to the sacrum as possible, at the level of the sacrospinous ligament. Transgluteal drainage can be performed with the tandem-trocar technique or the Seldinger technique. Modifications of the procedure are needle aspiration not followed by catheter placement, use of the angled gantry technique, bilateral transgluteal drainage, combined anterior and posterior drainage, and drainage of necrotic pelvic masses. The transgluteal approach is a useful option in pediatric patients. Daily catheter care is essential for successful percutaneous catheter therapy. Although pain has been cited as a common complication of the technique, this complication can be minimized with judicious use of analgesia and a meticulous technique. Other complications are hemorrhage and catheter malposition. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 45 Z9 48 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2002 VL 22 IS 6 BP 1353 EP 1367 DI 10.1148/rg.226025039 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 613MT UT WOS:000179136600004 PM 12432107 ER PT J AU Bosch, JL Kaufman, JA Beinfeld, MT Adriaensen, MEAPM Brewster, DC Gazelle, GS AF Bosch, JL Kaufman, JA Beinfeld, MT Adriaensen, MEAPM Brewster, DC Gazelle, GS TI Abdominal aortic aneurysms: Cost-effectiveness of elective endovascular and open surgical repair SO RADIOLOGY LA English DT Article DE aneurysm, abdominal, 981.73; aorta, grafts and prostheses, 981.1286; aorta, interventional procedures, 981.1286; cost-effectiveness; economics, medical ID QUALITY-OF-LIFE; STENT-GRAFT; HEALTH; COMPLICATIONS; EXPERIENCE; MULTICENTER; MANAGEMENT; OUTCOMES; DISEASE; SURGERY AB PURPOSE: To evaluate :the cost-effectiveness of elective enclovascular and open surgical repair of infrarenal abdominal aortic aneurysms (AAAs) by taking into account short- and long-term outcomes. MATERIALS AND METHODS: A Markov decision model was developed to evaluate quality-adjusted life-years (QALYs) and lifetime costs of enclovascular and open surgical repair. The incremental cost-effectiveness ratio (CER) was calculated for enclovascular repair relative to open surgery in a cohort of 70-year-old men with an AAA between 5 and 6 m in diameter. Clinically effectiveness data were derived from the literature. Cost data were derived from Medicare reimbursement rates, the literature. One- and multiple-way sensitivity analyses were performed on. uncertain model parameters. Costs were converted to year 2000 U.S. dollars; future costs band outcomes were discounted at 3%. RESULTS: The incremental CER of enclovascular repair was $9,905 per QALY. QALYs and lifetime costs were higher for enclovascular repair than for open surgery (6.74 vs 6.52 and $39,785 vs $37;606,- respectively). In sensitivity analyses, the incremental CER was insensitive to immediate conversion rate and procedure mortality rate. The incremental CER was sensitive (ie, more than $75,000 per QALY or enclovascular repair was ruled out by dominance) to systemic-remote complications, long-term failures, and ruptures. CONCLUSION: The, results suggest that enclovascular repair is a cost-effective alternative compared with open surgery for the elective repair of AAA. The benefits and cost-effectiveness are highly dependent on uncertain outcomes, however, particularly long-term, failure and rupture rates. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Med Ctr, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Dotter Intervent Inst, Portland, OR USA. RP Bosch, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 0 Emerson Pl,Suite 2H, Boston, MA 02114 USA. NR 68 TC 37 Z9 38 U1 1 U2 3 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 NOV PY 2002 VL 225 IS 2 BP 337 EP 344 DI 10.1148/radiol.2252011687 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500006 PM 12409564 ER PT J AU Prasad, SR Jhaveri, KS Saini, S Hahn, PF Halpern, EF Sumner, JE AF Prasad, SR Jhaveri, KS Saini, S Hahn, PF Halpern, EF Sumner, JE TI CT tumor measurement for therapeutic response assessment: Comparison of unidimensional, bidimensional, and volumetric techniques - Initial observations SO RADIOLOGY LA English DT Article DE breast neoplasms, metastases; liver neoplasms, CT; liver neoplasms, secondary; liver neoplasms, staging; liver neoplasms, therapy ID HELICAL SPIRAL CT; CANCER-TREATMENT; SIZE; TRIALS AB PURPOSE: To compare unidimensional, bidimensional, and volumetric techniques for evaluation of treatment response in patients with liver metastases from breast cancer in a phase III clinical trial. MATERIALS AND METHODS: Helical computed tomographic (CT) studies in 38 patients with liver metastases from breast cancer who were enrolled in a phase III clinical trial were evaluated before treatment and at 6 months after treatment. Two subspecialty radiologists measured all lesions on transverse CT scans with use of electronic calipers according to both unidimensional and bidimensional criteria. Volumetric measurements were made by tracing individual lesions. Measurements of individual lesions were summed to obtain patient response, which was categorized as complete response, disappearance of lesions; partial response, greater than 30% decrease in tumor diameter (unidimensional), greater than 50% reduction in tumor area (bidimensional), or greater than 65% reduction in tumor volume (volumetric); disease progression, greater than 20% increase in tumor diameter, greater than 25% increase in tumor area, or greater than 73% increase in tumor volume: or stable disease (size response other than that of complete response, partial response, or disease progression). RESULTS: In 37 patients, there was concordant treatment response with use of unidimensional and bidimensional techniques. Volumetric measurement produced results different from those of the unidimensional and bidimensional techniques in 12 and 13 patients, respectively. In six patients with partial response per unidimensional and bidimensional criteria, the response based on the volumetric technique was stable disease. In two patients with stable disease per bidimensional and unidimensional criteria, the response was partial response by volumetric measurement. In four patients with disease progression per bidimensional and unidimensional criteria, the response was stable disease per volumetric criteria. CONCLUSION: Volumetric measurement of tumor burden gives different results for treatment response compared with that of the unidimensional or bidimensional technique in a considerable proportion of patients. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. WorldCare, Cambridge, MA USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,White 270-E, Boston, MA 02114 USA. NR 15 TC 140 Z9 143 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2002 VL 225 IS 2 BP 416 EP 419 DI 10.1148/radiol.2252011604 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500016 PM 12409574 ER PT J AU Garg, K Keith, RL Byers, T Kelly, K Kerzner, AL Lynch, DA Miller, YE AF Garg, K Keith, RL Byers, T Kelly, K Kerzner, AL Lynch, DA Miller, YE TI Randomized controlled trial with low-dose spiral CT for lung cancer screening: Feasibility study and preliminary results SO RADIOLOGY LA English DT Article DE cancer screening; lung neoplasms, CT; lung neoplasms, diagnosis ID COMPUTED-TOMOGRAPHY; OBSTRUCTION; PULMONARY; SPUTUM; CELLS; RISK AB PURPOSE: To assess the feasibility of conducting a randomized controlled trial for lung cancer screening. MATERIALS AND METHODS: Subjects are being recruited into a randomized controlled trial to undergo either low-dose spiral computed tomography (CT) or observation. Subjects are from a high-risk group with known chronic obstructive pulmonary disease and sputum atypia and a moderate-risk group randomly selected from the general population of a Veterans Affairs Medical Center. All subjects must be 50-80 years of age with 30 or more pack-years of cigarette smoking and must not have undergone chest CT during the previous 3 years. Baseline screening CT is performed with 50 mA, 120 kVp, 5-mm collimation, and a pitch of 2. CT scan interpretation and management of nodules is based on Society of Thoracic Radiology guidelines. The chi(2) test for categoric data was used for statistical analysis. RESULTS: To date, 304 eligible subjects have been contacted, and 239 (79%) have agreed to participate in the trial. One hundred nineteen (88%) of the 136 subjects in the high-risk group and 120 (71%) of the 168 subjects in the moderate-risk group agreed to randomization (P < .001). To date, 190 subjects have been randomized. Of the first 92 subjects examined with CT, 22 (40%) of 55 in the high-risk group and eight (22%) of 37 in the moderate-risk group had one to six noncalcified nodules that required follow-up (P = .07). In all but three subjects, nodules were smaller than 5 mm. Two of the three larger nodules were malignancies. CONCLUSION: Findings of this study indicate that a randomized controlled trial of CT to screen for lung cancer is feasible. (C) RSNA, 2002. C1 Univ Colorado, Ctr Comprehens Canc, Dept Oncol, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Biostat & Epidemiol, Denver, CO USA. Univ Colorado, Denver Vet Affairs Med Ctr, Div Pulm Med, Denver, CO 80202 USA. Univ Colorado, Denver Vet Affairs Med Ctr, Dept Radiol, Denver, CO 80202 USA. RP Garg, K (reprint author), Univ Colorado Hosp, Dept Radiol, Anchutz Outpatient Pavillon,1635 N Ursula St,Camp, Aurora, CO 80010 USA. NR 27 TC 50 Z9 57 U1 0 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 NOV PY 2002 VL 225 IS 2 BP 506 EP 510 DI 10.1148/radiol.2252011851 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 608AG UT WOS:000178822500028 PM 12409588 ER PT J AU Chaidarun, SS Klibanski, A AF Chaidarun, SS Klibanski, A TI Gonadotropinomas SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE gonadotrope adenoma; gonadotropins; clinically nonfunctioning tumor; null cell adenoma ID HUMAN PITUITARY-ADENOMAS; FOLLICLE-STIMULATING-HORMONE; TUMOR-TRANSFORMING GENE; THYROTROPIN-RELEASING-HORMONE; MESSENGER-RNA EXPRESSION; GAMMA-KNIFE RADIOSURGERY; ESTROGEN-RECEPTOR-BETA; NULL-CELL ADENOMAS; GROWTH-FACTOR; IN-VITRO AB Advances in immunocytochemistry, electron microscopy, cell culture, and molecular techniques have demonstrated that 80 to 90% of the clinically nonfunctioning pituitary adenomas are gonadotrope-derived and recently recognized as gonadotropinomas, which account for as many as 40 to 50% of all pituitary macroadenomas. Patients usually present with mass effects including visual field loss and headache, hypogonadism, and hypopituitarism. Commonly, the tumor is found incidentally. Recently, a few patients with gonadotropinomas were reported to have hormonal hypersecretion syndromes such as ovarian hyperstimulation, testicular enlargement, and precocious puberty. The tumors can be divided into two broad categories: functioning gonadotropinomas with positive immunostaining for follicle-stimulating hormone, leutinizing hormone, and/or their sub-units; and nonfunctioning gonadotropinomas or null cell tumors with negative immunostaining for all pituitary hormones but positive nuclear immunostaining for steroid factor-1 or DAX-1 characteristic of gonadotrope differentiation, with evidence of gonadotropin production or gene expression at the mRNA level. Gonadotropinomas are monoclonal in origin but the pathogenesis of these tumors is unknown and factors that stimulate clonal proliferation not yet determined. A new pituitary oncogene, pituitary tumor transforming gene, has recently been found to be overexpressed in about two thirds of these tumors but it is also detected in all other pituitary tumor subtypes. Alterations of tumor hormone receptors and local growth factors may also play a role in the tumor development and/or progression. Transphenoidal surgery remains the principal therapy for the macroadenomas. Radiosurgery using gamma knife, the linear accelerator, or proton beam therapy showed promising results, especially for controlling the residual or recurrent tumors. Medical therapy with somatostatin analogs, dopamine agonists, and gonadotropin-releasing hormone agonists and antagonists are rarely effective in reducing tumor size. Experimental therapy with intraoperative local chemotherapy or potential gene therapy requires further investigation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02115 USA. NR 88 TC 24 Z9 26 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD NOV PY 2002 VL 20 IS 4 BP 339 EP 348 DI 10.1055/s-2002-36708 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 632AM UT WOS:000180200800005 PM 12536357 ER PT J AU Caviness, VS Makris, N Montinaro, E Sahin, NT Bates, JF Schwamm, L Caplan, D Kennedy, DN AF Caviness, VS Makris, N Montinaro, E Sahin, NT Bates, JF Schwamm, L Caplan, D Kennedy, DN TI Anatomy of stroke, Part I - An MRI-based topographic and volumetric system of analysis SO STROKE LA English DT Article DE embolism; image processing, computer assisted; magnetic resonance imaging; stroke, cardioembolic ID CEREBRAL WHITE-MATTER; ISCHEMIC STROKE; HUMAN NEOCORTEX; DIFFUSION; PERFUSION; PARCELLATION; INFARCTIONS; BRAIN; CIRCULATION; THRESHOLDS AB Background and Purpose-The clinical diagnosis and treatment of stroke, as well as investigations into the underlying pathophysiology of the disease, hinge on inferences from the anatomy of the stroke lesion. We describe an MRI-based system of topographic and volumetric analysis that considers distribution of infarct with respect to neuroanatomic structures, superficial and deep perfusion compartments, and gray and white matter tissue types. Methods-MRI-based 3-dimensional topographic and volumetric analysis of presumed MCA embolic stroke was performed months after the acute event in 21 subjects ranging in age from 34 to 75 years. Results-The topography of infarction was greatly variable, with virtually all regions of the MCA territory involved in at least I stroke in the series. In 14, there was involvement of the M I as well as the M2 through M4 territories; in 6, there was involvement of only the M2 through M4 territories; and in 2, there was involvement of only the M1 territory. The volumes varied from 3.1 to 256 cm(3), corresponding approximately to a range of 1% to 90% of the total MCA territory. Conclusions-The system of topographic and volumetric analysis is generally applicable to all strokes in the forebrain where the infarct is visualized in MRI, independent of vascular territory, clinical correlates, and interval between stroke and MRI. The results emphasize the variety of topographic patterns and lesion volumes of strokes. Intended long-range applications include correlation of outcome of stroke with predictions from acute-phase diffusion-. and perfusion-weighted imaging and investigations of the potential benefit of therapeutic agents. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Univ Roma La Sapienza, Dept Neurol, Rome, Italy. RP Kennedy, DN (reprint author), Ctr Morphometr Anal, MGH E, Bldg 149,13th St, Boston, MA 02129 USA. RI Kennedy, David/H-3627-2012; OI Schwamm, Lee/0000-0003-0592-9145 FU NIDA NIH HHS [DA 09467]; NINDS NIH HHS [P01 NS27950, NS34189] NR 41 TC 38 Z9 39 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2002 VL 33 IS 11 BP 2549 EP 2556 DI 10.1161/01.STR.0000036083.90045.08 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 612LE UT WOS:000179076100005 PM 12411641 ER PT J AU Caviness, VS Makris, N Montinaro, E Sahin, NT Bates, JF Schwamm, L Caplan, D Kennedy, DN AF Caviness, VS Makris, N Montinaro, E Sahin, NT Bates, JF Schwamm, L Caplan, D Kennedy, DN TI Anatomy of stroke, Part II - Volumetric characteristics with implications for the local architecture of the cerebral perfusion system SO STROKE LA English DT Article DE embolism; image processing, computer assisted; magnetic resonance imaging; stroke, cardioembolic ID CAROTID-ARTERY OCCLUSION; ACUTE ISCHEMIC STROKE; MRI; INFARCTIONS; THRESHOLDS; FEATURES; MATTER AB Background and Purpose-The margin of a stroke is assumed to approximate a trace of the isobar of the perfusion threshold for infarction at the time that infarction occurred. Working from this hypothesis, we have analyzed stroke topography and volume in MR images obtained at a time remote from the stroke event. We have derived parameters from these images that may give information on local perfusion competence and microvascular architecture because they influenced the contour of stroke at the time infarction occurred. Methods-MR images were obtained months after presumed embolic middle cerebral artery stroke in 21 subjects. Volumetric analyses of image data were undertaken with respect to the tissue shape of stroke and scaling ratios of anatomic partitions involved in stroke. Results-For stroke confined to a single volume, the 3-dimensional form conforms to a parabola in which the height-to-width ratios are variable. The ratio for cortex is greater than that for underlying white matter. Scaling ratios indicate a close correlation between volume of cortex and radiata destroyed and total volume of stroke, but the relative proportions vary as a function of location within the M4 territory. Conclusions-Scaling ratios for cortex and radiata to stroke volume are consistent with vascular studies that depict a modular microvascular perfusion architecture for the cortex and underlying white matter. The stroke descriptors are inferred to be related to the competence of collateral perfusion at the time that stroke occurred. This inference may be tested by serial volumetric analysis of the perfusion-diffusion examination mismatch immediately and over the longer-term evolution of stroke. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Univ Roma La Sapienza, Dept Neurol, Rome, Italy. RP Kennedy, DN (reprint author), Massachusetts Gen Hosp E, Ctr Morphometr Anal, Bldg 149,13th St, Boston, MA 02129 USA. RI Kennedy, David/H-3627-2012; OI Schwamm, Lee/0000-0003-0592-9145 FU NIDA NIH HHS [DA 09467]; NINDS NIH HHS [NS34189, P01 NS27950] NR 26 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2002 VL 33 IS 11 BP 2557 EP 2564 DI 10.1161/01.STR.0000036084.82955.C7 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 612LE UT WOS:000179076100006 PM 12411642 ER PT J AU Aoki, T Sumii, T Mori, T Wang, XY Lo, EH AF Aoki, T Sumii, T Mori, T Wang, XY Lo, EH TI Blood-brain barrier disruption and matrix metalloproteinase-9 expression during, reperfusion injury - Mechanical versus embolic focal ischemia in spontaneously hypertensive rats SO STROKE LA English DT Article DE brain edema; metalloproteinases; neuroprotection; stroke; tissue plasminogen activator ID CEREBRAL-ARTERY OCCLUSION; GENE KNOCK-OUT; PLASMINOGEN-ACTIVATOR; MATRIX-METALLOPROTEINASE-9; STROKE; THROMBOLYSIS; INHIBITION; INFARCTION; EVOLUTION; DYNAMICS AB Background and Purpose-Most experimental models of cerebral ischemia use mechanical methods of occlusion and reperfusion. However, differences between mechanical reperfusion versus clot thrombolysis may influence reperfusion injury profiles. In this study we compared blood flow recovery, blood-brain barrier (BBB) permeability, and matrix metalloproteinase-9 (MMP-9) expression in cortex after mechanical versus thrombolytic reperfusion in rat focal ischemia. Methods-Male spontaneously hypertensive rats were used. Mechanical ischemia/reperfusion was achieved with the use of an intraluminal filament to occlude the middle cerebral artery for 2 hours. Thrombolytic reperfusion was achieved by administering tissue plasminogen activator at 2 hours after embolic focal ischemia. Regional cortical blood flow was monitored by laser-Doppler flowmetry. BBB permeability in cortex was measured by Evans blue dye leakage. Cortical MMP-9 levels were assessed with zymography and immunohistochemistry. Results-Blood flow recovery during mechanical reperfusion was complete in both central and peripheral areas of ischemic cortex. However, after thrombolysis, reperfusion was incomplete, with moderate recovery in the periphery only. BBB permeability was mainly increased in the central regions of the ischemic cortex after mechanical reperfusion but was increased in both central and peripheral areas after thrombolysis. Overall, MMP-9 levels were higher after embolic versus mechanical ischemia/reperfusion, even though ischemic injury was similar in both models at 24 hours. Conclusions-There are significant differences in the profiles of blood flow recovery, BBB leakage, and MMP-9 upregulation in mechanical versus thrombolytic reperfusion after focal ischemia. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, E 149-2401, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS37074, R01-NS38731, R01-NS40529] NR 35 TC 142 Z9 154 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2002 VL 33 IS 11 BP 2711 EP 2717 DI 10.1161/01.STR.0000033932.34467.97 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 612LE UT WOS:000179076100030 PM 12411666 ER PT J AU Grunberg, SM Srivastava, A Grunberg, KJ Weeks, J AF Grunberg, SM Srivastava, A Grunberg, KJ Weeks, J TI Intensity of chemotherapy-induced emesis and overall survival as determinants of a global utility score SO SUPPORTIVE CARE IN CANCER LA English DT Article DE nausea and vomiting; utility; standard gamble; patient preference ID QUALITY-OF-LIFE; CANCER-CHEMOTHERAPY; PROSTATE-CANCER; RECEIVING END; HEALTH; COST; PREFERENCES; THERAPY AB Cost-utility analysis is appropriate for supportive care interventions, since both quality of life and duration of survival are taken into account. However, utility scores, which reflect quality of life, have not been objectively defined for parameters such as emesis. The Standard Gamble technique identifies utility by determining patient preference for retaining a fixed intermediate health state or taking a gamble with perfect health and death as possible outcomes (the odds of the two gamble outcomes can be varied). If death is not a reasonable negative anchor (for example, with transient symptoms of treatment), then a surrogate negative anchor that is itself defined according to a perfect health/death gamble may be used. We explored use of the Standard Gamble to define a reasonable surrogate negative anchor for evaluation of the impact of emesis. Ten normal volunteers performed a Standard Gamble exercise in which the fixed health state was a year of chemotherapy followed by survival in good health and the gamble had possible outcomes of perfect health or immediate death. The amount of nausea/vomiting during chemotherapy (continuous or none) and the duration of overall survival (6 years or 2 years) were varied to produce four unique health states. All subjects completed the exercise and demonstrated construct validity. Mean utility scores ranged from 0.89 for 6-year survival/no emesis to 0.46 for 2-year survival/continuous emesis. Presence of emesis significantly affected utility (0.565 vs 0.88), while shorter survival had a lesser effect (0.67 vs 0.78). The Standard Gamble technique can be used to evaluate nausea and vomiting. The fixed health state of I year of chemotherapy with continuous nausea and vomiting followed by I year of good health defines a utility score of 0.46. This is a reasonable negative surrogate anchor and is being used in a current Cancer and Leukemia Group B (CALGB) study. C1 Univ Vermont, Div Hematol Oncol, Fletcher Allen HealthCare, Burlington, VT 05401 USA. Dana Farber Canc Inst, Ctr Hlth Outcomes, Boston, MA 02115 USA. RP Grunberg, SM (reprint author), Univ Vermont, Div Hematol Oncol, Fletcher Allen HealthCare, UHC Campus St Joseph 3400,1 S Prospect St, Burlington, VT 05401 USA. NR 20 TC 12 Z9 12 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD NOV PY 2002 VL 10 IS 8 BP 624 EP 629 DI 10.1007/s00520-002-0381-0 PG 6 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 624MQ UT WOS:000179763800007 PM 12436221 ER PT J AU Moller-Hartmann, W Krings, T Coenen, VA Mayfrank, L Weidemann, J Kranzlein, H Thron, A Cosgrove, GR Kikinis, R AF Moller-Hartmann, W Krings, T Coenen, VA Mayfrank, L Weidemann, J Kranzlein, H Thron, A Cosgrove, GR Kikinis, R TI Preoperative assessment of motor cortex and pyramidal tracts in central cavernoma employing functional and diffusion-weighted magnetic resonance imaging SO SURGICAL NEUROLOGY LA English DT Article DE functional MRI; diffusion weighted imaging; fiber tracts; presurgical planning; motor cortex ID HUMAN BRAIN; SYSTEM; TUMORS; MRI AB BACKGROUND Functional MRI (fMRI) combines anatomic with functional information and has therefore been widely used for preoperative planning of patients with mass lesions affecting functionally important brain regions. However, the courses of functionally important fiber tracts are not visualized. We therefore propose to combine fMRI with diffusion-weighted MRI (DWI) that allows visualization of large fiber tracts and to implement this data in a neuronavigation system. METHODS DWI was successfully performed at a field strength of 1.5 Tesla, employing a spin-echo sequence with gradient sensitivity in six noncollinear directions to visualize the course of the pyramidal tracts, and was combined with echo-planar T2* fMRI during a hand motor task in a patient with central cavernoma. RESULTS Fusion of both data sets allowed visualization of the displacement of both the primary sensorimotor area (M1) and its large descending fiber tracts. Intraoperatively, these data were used to aid in neuronavigation. Confirmation was obtained by intraoperative electrical stimulation. Postoperative MRI revealed an undisrupted pyramidal tract in the neurologically intact patient. CONCLUSION The combination of fMRI with DWI allows for assessment of functionally important cortical areas and additional visualization of large fiber tracts, Information about the orientation of fiber tracts in normal appearing white matter in patients with tumors within the cortical motor system cannot be obtained by other functional or conventional imaging methods and is vital for reducing operative morbidity as the information about functional cortex. This technique might, therefore, have the prospect of guiding neurosurgical interventions, especially when linked to a neuronavigation system. (C) 2002 by Elsevier Science Inc. C1 Univ Technol, Dept Neuroradiol, Univ Hosp, D-52057 Aachen, Germany. Univ Technol, Dept Neurosurg, Univ Hosp, D-52057 Aachen, Germany. Univ Technol, Interdisciplinary Ctr Clin Res Cent Nervous Syst, Univ Hosp, D-52057 Aachen, Germany. Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Krings, T (reprint author), Univ Technol, Dept Neuroradiol, Univ Hosp, Pauwelsstr 30, D-52057 Aachen, Germany. NR 14 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD NOV PY 2002 VL 58 IS 5 BP 302 EP 308 AR PII S0090-3019(02)00869-8 DI 10.1016/S0090-3019(02)00869-8 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 630JJ UT WOS:000180103500003 PM 12504288 ER PT J AU Stuber, GD Evans, SB Higgins, MS Pu, YP Figlewicz, DP AF Stuber, GD Evans, SB Higgins, MS Pu, YP Figlewicz, DP TI Food restriction modulates amphetamine-conditioned place preference and nucleus accumbens dopamine release in the rat SO SYNAPSE LA English DT Article ID 6-HYDROXYDOPAMINE LESIONS; INTRAVENOUS COCAINE; LOCOMOTOR-ACTIVITY; MESSENGER-RNA; DEPRIVATION; INCREASES; LEPTIN; REWARD; TRANSPORTER; MORPHINE AB Food restriction has been shown to increase self-administration of psychostimulants, including cocaine and amphetamine (AMPH). Consistent with this, food-restricted rats are more sensitized to the rewarding effects of cocaine as measured by conditioned place preference (CPP). This study investigated whether moderate food restriction in rats (15 g/day) results in an increased CPP, relative to ad libitum-fed controls, to a second psychostimulant, AMPH. Conditioning trials consisted of six alternating injections of i.p. AMPH (0.425-6.8 mg/kg) and i.p. saline, paired with distinct environments. On Day 7, a drug-free 20-min choice test for environment was carried out to assess CPP. 0.85 mg/kg AMPH significantly increased CPP in food-restricted vs. ad libitum-fed rats. At 1.7 and 3.4 mg/kg AMPH, food-restricted rats showed decreased CPP, but increased locomotor activity, relative to ad libitum fed controls. To evaluate whether an alteration in extracellular fluid DA levels in the nucleus accumbens (NAc) core could account for these behavioral alterations, DA release was measured by microdialysis. DA release to a single acute i.p. injection of either 0.85 or 1.7 mg/kg AMPH was comparable in food-restricted and ad libitum fed rats. However, ad libitum fed rats demonstrated conditioned DA release after an AMPH conditioning paradigm analogous to the CPP paradigm, whereas food-restricted rats demonstrated no conditioned DA release. In conclusion, altered DA release in the nucleus accumbens core is not a primary effect of moderate food restriction and cannot completely account for either the altered CPP behavior or enhanced locomotor activity observed in this study. Published 2002 Wiley-Liss, Inc.(dagger). C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Endocrinol Metab 151,1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu RI Stuber, Garret/E-1160-2011 FU NINDS NIH HHS [T32 NS007431, T32 NS/MH 07431]; PHS HHS [R0140963] NR 48 TC 44 Z9 46 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD NOV PY 2002 VL 46 IS 2 BP 83 EP 90 DI 10.1002/syn.10120 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 600WA UT WOS:000178413700006 PM 12211086 ER PT J AU Holmes, LB AF Holmes, LB TI Untitled SO TERATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 2002 VL 66 IS 5 BP 201 EP 201 DI 10.1002/tera.10051 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 611BX UT WOS:000178997500001 ER PT J AU Peyvandi, F De Cristofaro, R Akhavan, S Carew, JA Landolfi, R Bauer, KA Mannucci, PM AF Peyvandi, F De Cristofaro, R Akhavan, S Carew, JA Landolfi, R Bauer, KA Mannucci, PM TI Two naturally occurring mutations on FVII gene (S3631-W364C) altering intrinsic catalytic activity SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE factor VII; extrinsic coagulation; tissue factor ID FACTOR-VII DEFICIENCY; TISSUE FACTOR-BINDING; GROWTH-FACTOR DOMAIN; COAGULATION-FACTOR; CRYSTAL-STRUCTURE; FACTOR-X; ACTIVATION; SITE; SUBSTITUTION; SECRETION AB Factor VII (FVII) requires the cleavage of an internal peptide bond and the association with tissue factor (TF) to attain its fully active FVIIa conformation. This event alone leaves FVIIa in a zymogen-like state of relatively low specific activity. The TF-induced allosteric enhancement of FVIIa's activity contributes to the procoagulant activity of the complex. We have characterized two naturally occurring mutations (S363I - W364C) on FVII gene. Both homozygous patients for each mutation have a normal FVII:Ag level associated to an undetectable FVII coagulant activity. The patient carrying the allele 364C had a more severe hemorrhagic diathesis than the S363I mutant. To understand the mechanism of these deficiency, in vitro expression analysis with further biochemical characterization of recombinant proteins of both mutants FVII-363I, FVII-364C and wild type (WTFVII) FVII constructs were done. The results recapitulated the patients' plasma data with normal Ag level and no detectable coagulant activity. The D-F-Pip-R-pNA and CH3SO2-D-CHA-A-But-R chromogenic substrates were used to evaluate the amidolytic activity of WT and mutant FVII in presence and absence of recombinant tissue factor (rTF). Binding of FVII to rTF by a solid phase binding assay was done using recombinant human rTF. The results of amidolytic assays showed that rTF enhances 28 fold the value of the specificity of constant (kcat/K-m) in WT but no activity was detectable in either mutant constructs under any condition. The equilibrium dissociation constant of rTF-FVIIa interaction showed Kd equal to 4.4 +/- 0.2nM, 4.9 +/- 0.5nM and 6 +/- 0.9 of WT, 3631 and 364C FVII forms, respectively. The Kd values of the non activated forms were equal to 24.7 +/- 3.3, 24.4 +/- 3.1 and 20.6 +/- 4nM, respectively. These data demonstrate that, compared to the WT form, FVII-363I and FVII-364C have no significant affinity change for TF and that the detrimental effect of these two mutations is attributable to the loss of an efficient catalytic machinery in the FVII molecule causing a severe deficiency of coagulant activities. C1 IRCCS, Maggiore Hosp, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Fondaz Luigi Villa, I-20122 Milan, Italy. Catholic Univ Sch Med, Hemostasis Res Ctr, Rome, Italy. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Med,Hematol Sect, Boston, MA USA. RP Peyvandi, F (reprint author), Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Via Pace 9, I-20122 Milan, Italy. EM flora.peyvandi@unimi.it RI Mannucci, Pier/C-3102-2014; OI Peyvandi, Flora/0000-0001-7423-9864 NR 29 TC 4 Z9 5 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 NOV PY 2002 VL 88 IS 5 BP 750 EP 755 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 615LD UT WOS:000179245900010 PM 12428089 ER PT J AU Gushiken, FC Le, A Arnett, FC Thiagarajan, P AF Gushiken, FC Le, A Arnett, FC Thiagarajan, P TI Polymorphisms beta 2-glycoprotein I: phospholipid binding and multimeric structure SO THROMBOSIS RESEARCH LA English DT Article DE beta 2-glycoprotein I; anionic phospholipid; vesicle aggregation ID AMINO-ACID-SEQUENCE; BETA(2)-GLYCOPROTEIN I; PARTICLES; VESICLES AB beta2-glycoprotein I is a phospholipid-binding protein of 326 amino acids and is found in plasma at a concentration of similar to 200 mug/ml. It has a sequence of positively charged amino acids located at the carboxy terminus that mediates anionic phospholipid binding. Two polyrnorphisms (306Cys --> Gly and 316Trp --> Set) located at the phospholipid-binding site have been described. Homozygous state for either mutation and a compound heterozygous state show no phospholipid binding. Interestingly, heterozygotes for either 306Cys-->Gly or 316Trp-->Ser mutation have normal cardiolipin binding suggesting that beta2-glycoprotein I may circulate as a multimeric structure where wild-type subunits compensate the defective binding of the mutant ones. We investigated the effect of these mutations on quaternary structure of beta2-glycoprotein I and phospholipid binding. As previously reported, under native conditions, beta2-glycoprotein I shows an apparent molecular weight of similar to 320 kDa and it can be dissociated into subunits of lower molecular weight by boiling in 6 M urea. We show that the multimeric structure is not affected by the presence of mutations in the phospholipid-binding domain. beta2-glycoprotein I induces aggregation of anionic phospholipid vesicles suggesting again a multivalent interaction where at least two binding sites are required to bridge adjacent vesicles. beta2-glycoprotein I-induced aggregation does not cause vesicle fusion or damage as demonstrated by fluorescence resonance energy transfer (FRET) or encapsulated calcein release. In conclusion, the normal cardiolipin binding in heterozygous state for mutations at phospholipid-binding domain may be due to the multimeric structure of beta2-glycoprotein I. (C) 2002 Published by Elsevier Science Ltd. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Thrombosis Res, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Baylor Coll Med, Dept Pathol, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Rheumatol, Houston, TX USA. RP Thiagarajan, P (reprint author), VA Med Ctr, Mail 113,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 65096] NR 18 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD NOV 1 PY 2002 VL 108 IS 2-3 BP 175 EP 180 DI 10.1016/S0049-3848(02)00392-4 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 657DZ UT WOS:000181651300012 PM 12590955 ER PT J AU Randolph, GW Daniels, GH AF Randolph, GW Daniels, GH TI Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid SO THYROID LA English DT Article ID SERUM THYROGLOBULIN; FOLLOW-UP; RISK-FACTORS; CANCER; RADIOIODINE; MANAGEMENT; PAPILLARY; I-131; TISSUE; DIAGNOSIS AB We performed a retrospective record review of patients who received large lobar remnant ablation after surgery for well-differentiated thyroid carcinoma including 30 with papillary carcinoma, 14 with follicular carcinoma, and 6 with Hurthle cell carcinoma. We compared these 50 patients to a group of patients who underwent total or near-total thyroidectomy for well-differentiated thyroid carcinoma. The ablation group was treated with single outpatient doses of 29.9 MCi I-131 to prepare for whole-body radioiodine scanning. Subsequent serum thyrotropin (TSH) concentration during thyroid hormone withdrawal was greater than 25 muU/mL in 94% of patients. The mean TSH in this population (76 muU/mL) was not statistically different from a group of 50 patients who underwent total or near-total thyroidectomy (mean, TSH 71 muU/ml p = 0.84). Twenty-four hour radioiodine uptake post-29.9 mCi I-131 ablation was less than 1% in 80% of patients. The mean radioiodine uptake (0.8%) in the lobe ablation population was significantly lower than in patients treated with total thyroidectomy (mean, 2.4 %, p < 0.001). There was minimal morbidity after 29.9 mCi I-131 ablation of large lobar remnants. Outpatient 29.9 mCi I-131 ablation is a safe, effective, and less costly alternative to completion thyroidectomy in selected patients. Although we included patients with both papillary and follicular carcinoma in our review, we recommend this method for patients with minimally invasive follicular carcinoma requiring whole body scanning, even with large postsurgical remnants in place. C1 Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit, ACC 730,Fruit St, Boston, MA 02114 USA. NR 64 TC 31 Z9 36 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2002 VL 12 IS 11 BP 989 EP 996 DI 10.1089/105072502320908321 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620MZ UT WOS:000179538300008 PM 12490076 ER PT J AU Koyama, I Fuchinoue, S Urashima, Y Kato, Y Tsuji, K Kawase, T Murakami, T Tojimbara, T Nakajima, I Teraoka, S AF Koyama, I Fuchinoue, S Urashima, Y Kato, Y Tsuji, K Kawase, T Murakami, T Tojimbara, T Nakajima, I Teraoka, S TI Living related liver transplantation for polycystic liver disease SO TRANSPLANT INTERNATIONAL LA English DT Article DE liver transplantation; polycystic liver disease ID EXPERIENCE AB Polycystic liver disease (PCLD) is a rare inherited disorder, often associated with polycystic disease of the kidney. Although liver failure is unusual, some patients suffer from hepatic enlargement associated with severe complications such as abdominal distention, cachexia and dyspnea. Until recently, many surgical attempts had been made to reduce hepatic size, however, results have been unsatisfactory [3, 9 10]. Today, liver transplantation is recommended as a therapeutic option, and excellent outcome has been demonstrated [1, 2, 4, 5, 6. 8. 11]. In this paper, we present the first case study of total hepatectomy and partial liver transplantation for PCLD, from a living, related donor. The patient is a 38-year-old man with PCLD who underwent living related liver transplantation (LRLT). He is alive and well 21 months after the operation, with complete resolution of the symptoms. He has returned to his previous job, with a marked improvement in his quality of life. Our experience demonstrates that LRLT can be an option for treatment of PCLD. C1 Tokyo Womens Med Univ, Kidney Ctr, Dept Surg, Shinjuku Ku, Tokyo, Japan. RP Koyama, I (reprint author), Massachusetts Gen Hosp, Dept Surg, White 546,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD NOV PY 2002 VL 15 IS 11 BP 578 EP 580 DI 10.1007/s00147-002-0459-0 PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 628FX UT WOS:000179983200010 PM 12461664 ER PT J AU Teranishi, K Alwayn, IPJ Buhler, L Gollackner, B Knosalla, C Correa, L Down, JD White-Scharf, ME Sachs, DH Duthaler, R Katopodis, A Awwad, M Cooper, DKC AF Teranishi, K Alwayn, IPJ Buhler, L Gollackner, B Knosalla, C Correa, L Down, JD White-Scharf, ME Sachs, DH Duthaler, R Katopodis, A Awwad, M Cooper, DKC TI Depletion of natural anti-pig antibodies by the continuous infusion of oligosaccharides in a pig-to-baboon model SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 6th Congress of the International-Society-for-Organ-Sharing CY JUL 24-27, 2001 CL NAGOYA, JAPAN SP Int Soc Organ Sharing ID CELL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. Novartis Pharma AG, Transplantat Res, Basel, Switzerland. Immerge BioTherapeut, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD NOV PY 2002 VL 34 IS 7 BP 2757 EP 2758 AR PII S0041-1345(02)03398-5 DI 10.1016/S0041-1345(02)03398-5 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 613ZP UT WOS:000179162200094 PM 12431597 ER PT J AU Pardee, AB AF Pardee, AB TI PaJaMas in Paris SO TRENDS IN GENETICS LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 7 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 2002 VL 18 IS 11 BP 585 EP 587 AR PII S0168-9525(02)02780-4 DI 10.1016/S0168-9525(02)02780-4 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 607MX UT WOS:000178796300009 PM 12414189 ER PT J AU Burgio, KL AF Burgio, KL TI Influence of behavior modification on overactive bladder SO UROLOGY LA English DT Article; Proceedings Paper CT Symposium on New Perspectives on the Overactive Bladder CY MAR 08-09, 2002 CL CAMBRIDGE, MASSACHUSETTS ID URINARY-INCONTINENCE; DETRUSOR INSTABILITY; CONTROLLED TRIAL; OLDER WOMEN; BIOFEEDBACK; DRILL AB Behavioral interventions have been used for decades to treat urge incontinence and other symptoms of overactive bladder. Perhaps the earliest form of treatment was the bladder drill, an intensive intervention designed to increase the interval between voids to establish a normal frequency of urination and normalization of bladder function. Bladder training is a modification of bladder drill that is conducted more gradually on an outpatient basis and has resulted in significant reduction of incontinence in older, community-dwelling women. Multicomponent behavioral training is another form of behavioral treatment that includes pelvic floor muscle training and exercise. This intervention focuses less on voiding habits and more on altering the physiologic responses of the bladder and pelvic floor muscles. Using biofeedback or other teaching methods, patients learn strategies to inhibit bladder contraction using pelvic floor muscle contraction and other urge suppression strategies. Although behavioral and drug therapies are known to be highly effective for reducing urge incontinence, few patients are cured with either treatment alone. Thus, future research should explore ways to enhance the effectiveness of these conservative therapies. Although the mechanisms by which behavioral treatments work have not been established, there is some evidence that behavioral and drug interventions may operate by different mechanisms, suggesting that they may have additive effects and that combining them may result in better outcomes. Future research needs to examine the mechanisms by which these therapies reduce incontinence and whether combining behavioral and drug treatment will result in better outcomes than either therapy alone. (C) 2002, Elsevier Science Inc. C1 Dept Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, GRECC, 11G,700 19th St S, Birmingham, AL 35233 USA. NR 23 TC 30 Z9 32 U1 2 U2 4 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 NOV PY 2002 VL 60 IS 5A SU S BP 72 EP 76 AR PII S0090-4295(02)01800-9 DI 10.1016/S0090-4295(02)01800-9 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 626UY UT WOS:000179893100020 PM 12493360 ER PT J AU Dahl, DM L'esperance, JO Trainer, AF Jiang, Z Gallagher, K Litwin, DEM Blute, RD AF Dahl, DM L'esperance, JO Trainer, AF Jiang, Z Gallagher, K Litwin, DEM Blute, RD TI Laparoscopic radical prostatectomy: Initial 70 cases at a US university medical center SO UROLOGY LA English DT Article ID RETROPUBIC PROSTATECTOMY; EXPERIENCE; CONTINENCE AB Objectives. To report our experience with the first 70 cases of laparoscopic radical prostatectomy. Radical retropubic prostatectomy is an accepted therapy for the management of locally confined prostate cancer. Recently, laparoscopic prostatectomy has been introduced as a minimally invasive alternative to open radical prostatectomy. Several published series from Europe have demonstrated that laparoscopic radical prostatectomy is a safe and feasible approach to the management of localized prostate cancer. Methods. From May 2000 to May 2001, transperitoneal laparoscopic radical prostatectomy was performed on 70 men, aged 40 to 76 years, who were appropriate candidates for radical retropubic prostatectomy. Patient characteristics, surgical statistics, and pathologic results were prospectively collected. Results. The mean preoperative prostate-specific antigen level was 6.6 ng/mL (range 1.5 to 20.7). The preoperative Gleason sum was 6 in 53 patients (75.7%), 7 in 16 (22.9%), and 8 in 1 patient (1.4%). The mean operating time was 274 minutes (range 165 to 495). The estimated blood loss averaged 449 mL (range 50 to 2750), and 4 patients (5.7%) required blood transfusions. In I case, we converted to a standard retropubic approach. Two intraoperative (2.9%) and 14 (20%) overall postoperative complications occurred. Positive surgical margins were reported in 8 specimens (11.4%). At a minimum of 3 months' follow-up, 85% reported use of 0 or 1 pad per day. The operative times, amount of blood loss, and complication rate decreased dramatically with experience. Conclusions. Laparoscopic radical prostatectomy is a technically demanding procedure that is a feasible option for the surgical treatment of localized prostate cancer. The morbidity of this operation is significantly less than that of radical retropubic prostatectomy. The laparoscopic approach shows significant promise for reducing surgical morbidity and improving the anatomic radical prostatectomy. (C) 2002, Elsevier Science Inc. C1 Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Div Urol, Worcester, MA 01605 USA. Univ Massachusetts, Dept Surg, Worcester, MA 01605 USA. Univ Massachusetts, Dept Pathol, Worcester, MA 01605 USA. RP Dahl, DM (reprint author), Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,GrB 1102, Boston, MA 02114 USA. NR 13 TC 48 Z9 51 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 NOV PY 2002 VL 60 IS 5 BP 859 EP 863 AR PII S0090-4295(02)01953-2 DI 10.1016/S0090-4295(02)01953-2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 614KU UT WOS:000179188700031 PM 12429316 ER PT J AU Klausner, AP Galea, J Vapnek, JM AF Klausner, AP Galea, J Vapnek, JM TI Effect of catheter size on urodynamic assessment of bladder outlet obstruction SO UROLOGY LA English DT Article ID PRESSURE-FLOW; URETHRAL INSTRUMENTATION AB Objectives. To examine the effect of cross-sectional catheter diameter on urodynamic measurement of bladder outlet obstruction as predicted by the Abrams-Griffiths nomogram. Methods. Thirty-one patients with symptomatic benign prostatic hyperplasia underwent free flow measurements followed by pressure-flow urodynamic evaluation using 5F and I OF urethral catheters in randomly assigned order. The measurements of voided volume, maximal flow rate (Qmax), postvoid residual volume, and detrusor pressure at maximal flow (PdetQmax) were compared. Data points were then plotted on the Abrams-Griffiths nomogram, and categorization of bladder outlet obstruction was assigned for each catheter size. Results. The use of I OF catheters resulted in both a significant decrease in Omax and increase in PdetQmax compared with the use of 5F catheters. Of 31 patients, 10 (32%) were incorrectly categorized as obstructed according to the Abrams-Griffiths nomogram when the larger sized catheter was used, and 17 (55%) experienced migration from a less obstructed to a more obstructed category. Conclusions. The use of 5F catheters allows for more accurate diagnosis of bladder outlet obstruction. In urodynamic evaluations, the larger size I OF catheters should be avoided, especially in patients with borderline symptoms. (C) 2002, Elsevier Science Inc. C1 Mt Sinai Med Ctr, Dept Urol, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Vapnek, JM (reprint author), Mt Sinai Med Ctr, Dept Urol, Box 1272,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 14 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 2002 VL 60 IS 5 BP 875 EP 880 AR PII S0090-4295(02)01873-3 DI 10.1016/S0090-4295(02)01873-3 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 614KU UT WOS:000179188700034 PM 12429319 ER PT J AU Amendola, A Tanzi, E Zappa, A Colzani, D Boschini, A Musher, DM Zanetti, AR AF Amendola, A Tanzi, E Zappa, A Colzani, D Boschini, A Musher, DM Zanetti, AR TI Safety and immunogenicity of 23-valent pneumococcal polysaccharide vaccine in HIV-1 infected former drug users SO VACCINE LA English DT Article DE pneumococcal polysaccharide vaccine; HIV-1 load; CD4+counts ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDES; ANTIBODY-RESPONSES; DISEASE; IMMUNIZATION; INFLUENZA; ADULTS; IMPACT AB The immunogenicity of 23-valent pneumococcal polysaccharide vaccine was assessed in 57 HIV-1 infected former intravenous drug users and in 20 HIV-1 negative controls. The effect of vaccination on HIV-1 infection was studied in a subgroup of 38 patients, 60% of whom under highly active antiretroviral therapy (HAART). Antibody to capsular polysaccharides from Streptococcus pneumoniae serotypes 3, 4, 6B, 19F, 23F, and changes in CD4+ count, HIV-1 RNA, proviral DNA and HIV-1 phenotype were measured in pre- and post-vaccination samples. Vaccinations were well-tolerated. The rate of responders was higher (P < 0.05) in HIV-1 negative than in HIV-1 infected individuals. No difference in antibody response was found within HIV-1 infected patients stratified according to CD4+ counts. Post-vaccination antibody geometric mean concentrations (GMCs) to the five antigens were higher (P < 0.05) than baseline in HIV-1 negative subjects, but not in HIV-1 positive individuals. Those with CD4+ >500 cells/mm(3) showed a significant increase of antibody against type 3 only. Immunisation caused no significant changes in CD4+ counts and in either plasma HIV-1 RNA nor proviral DNA levels. Pneumococcal vaccination does not induce virological or immunological deterioration in HIV infected patients, but the antibody response to a single dose of vaccine is poor. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Milan, Inst Virol, I-20133 Milan, Italy. San Patrignano Community, Rimini, Italy. Houston Dept Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX USA. RP Zanetti, AR (reprint author), Univ Milan, Inst Virol, Via Pascal 38, I-20133 Milan, Italy. RI Amendola, Antonella/M-8980-2016; Tanzi, Elisabetta/M-9066-2016 OI Amendola, Antonella/0000-0002-0499-8977; Tanzi, Elisabetta/0000-0002-4119-701X NR 24 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 1 PY 2002 VL 20 IS 31-32 BP 3720 EP 3724 AR PII S0264-410X(02)00357-2 DI 10.1016/S0264-410X(02)00357-2 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 619RA UT WOS:000179489000015 PM 12399200 ER PT J AU Cheng, J Glaser, RM Kruger-Grey, H White-Scharf, ME Cooper, DKC Thall, AD AF Cheng, J Glaser, RM Kruger-Grey, H White-Scharf, ME Cooper, DKC Thall, AD TI Promotion of xenogeneic hematopoietic chimerism in rodents by mononuclear phagocyte depletion SO XENOTRANSPLANTATION LA English DT Article DE liposomes; medronate; mice; mononuclear phagocytes; pigs; xenotransplantation ID MIXED ALLOGENEIC CHIMERISM; TOLERANCE INDUCTION; PREPARATIVE REGIMEN; B-CELLS; MACROPHAGES; LIPOSOMES; MICE; TRANSPLANTATION; RECONSTITUTION; CLODRONATE AB The successful establishment of tolerance toward pig tissues in primates through hematopoietic progenitor cell engraftment is restricted by the rapid disappearance of these cells in the recipient following infusion. We developed and tested the hypothesis that phagocytes of the reticuloendothelial system are responsible for the rapid clearance of infused pig hematopoietic cells using a mouse model. Mice received non-myeloablative conditioning and, on various days, were injected with medronate-encapsulated liposomes (M-L) or control blank liposomes, followed by the intravenous infusion of miniature swine hematopoietic cells. M-L were well-tolerated in mice (n=100) at levels that deplete mononuclear phagocytes. Depletion of mononuclear phagocytes in normal Balb/c mice as well as in severe combined immune deficient mice increased the accumulation of pig hematopoietic cells in the bone marrow (BM) by 10-fold when measured 24 h after the infusion of the cells. Colony-forming unit analysis showed an increased accumulation of pig hematopoietic progenitors in the BM of mice that were infused with medronate-liposomes. We conclude that depletion of mononuclear phagocytes by M-L has the potential to lower the barrier to the establishment of mixed chimerism and tolerance induction in xenotransplantation. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. BioTransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH-E,Bldg 149,13th St, Boston, MA 02129 USA. NR 31 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2002 VL 9 IS 6 BP 402 EP 409 DI 10.1034/j.1399-3089.2002.01112.x PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 601YP UT WOS:000178477200008 PM 12371936 ER PT J AU Szostak, JW AF Szostak, JW TI Molecular biology - RNA gets a grip on translation SO NATURE LA English DT Editorial Material ID EXPRESSION C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. NR 8 TC 5 Z9 6 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 2002 VL 419 IS 6910 BP 890 EP 891 DI 10.1038/419890a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 609MN UT WOS:000178909700027 PM 12410294 ER PT J AU Yu, MX Airaksinen, AJ Gee, AD Lotjonen, S Kuikka, JT Vepsalainen, JJ Hiltunen, J Bergstrom, KA AF Yu, MX Airaksinen, AJ Gee, AD Lotjonen, S Kuikka, JT Vepsalainen, JJ Hiltunen, J Bergstrom, KA TI Radiosynthesis of [I-123]N-(3-iodoprop-(2E)-enyl)-2 alpha-(imino-methyl)-3 beta-(3 ',4 '-dichlorophenyl) nortropane as a potential SPET tracer for dopamine transporter SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE KUC-25019; dopamine transporter; tropane analog; SPET; I-123 ID BETA-CIT-FP; C-11; AFFINITY; ANALOGS; FE AB The radiosynthesis of a novel tropane derivative [I-123]KUC-25019, [[I-123] N-(3-iodoprop-(2E)-enyl)-2alpha-(imino-methyl)-3beta-(3',4'-dichlorophenyl)nortropane], a potential inhibitor of the dopamine transporter is reported. The synthetic routes include the preparation of standard reference, the stannyl precursor and the I-123-labeling synthesis. The no-carrier-added I-123-labeling has about 20% yield, the specific activity of [I-123]KUC-25019 is > 107 GBq/ mumol and the radiochemical purity of [I-123] KUC-25019 is >95%. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Niuvanniemi Hosp, FIN-70240 Kuopio, Finland. MAP Med Technol Oy, FIN-41160 Tikkakoski, Finland. Aarhus Univ Hosp, PET Ctr, D-8000 Aarhus, Denmark. Univ Kuopio, Dept Chem, FIN-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-70210 Kuopio, Finland. RP Yu, MX (reprint author), Massachusetts Gen Hosp, Dept Radiol, Barlett Hall 500R, Boston, MA 02114 USA. EM ymeixiang@partners.org RI Airaksinen, Anu/N-9070-2014 OI Airaksinen, Anu/0000-0002-5943-3105 NR 11 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD OCT 30 PY 2002 VL 45 IS 12 BP 1011 EP 1017 DI 10.1002/jlcr.619 PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 617XT UT WOS:000179386800003 ER PT J AU Pratt, SJ Drejer, A Foott, H Barut, B Brownlie, A Postlethwait, J Kato, Y Yamamoto, M Zon, LI AF Pratt, SJ Drejer, A Foott, H Barut, B Brownlie, A Postlethwait, J Kato, Y Yamamoto, M Zon, LI TI Isolation and characterization of zebrafish NFE2 SO PHYSIOLOGICAL GENOMICS LA English DT Article DE hematopoiesis; transcription factors; erythroid lineage; sauternes mutant ID TRANSCRIPTION FACTOR NF-E2; GLOBIN GENE-EXPRESSION; AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; LEUCINE ZIPPER PROTEIN; SMALL MAF PROTEINS; FUNCTIONAL-CHARACTERIZATION; POSITIONAL CLONING; MICE LACKING; VERTEBRATE; ERYTHROPOIESIS AB Vertebrate hematopoiesis is regulated by distinct cell-specific transcription factors such as GATA-1 and SCL. Mammalian p45-NFE2 was characterized for its ability to bind the hypersensitive sites of the globin locus control region. NFE2 is a member of a cap'n'collar (CNC) and basic zipper (BZIP) superfamily that regulates gene transcription. It has been implicated in diverse processes such as globin gene expression, oxidative stress, and platelet lineage differentiation. Here, we have isolated the zebrafish ortholog of NFE2. The gene is highly homologous, particularly in the DNA-binding domain. Mapping the zebrafish NFE2 to linkage group 23 establishes a region of chromosomal synteny with human chromosome 12, further suggesting evolutionary conservation. During embryogenesis, the zebrafish gene is expressed specifically in erythroid cells and also in the developing ear. NFE2 expression is lacking in zebrafish mutants that have no hematopoietic cells. An analysis of the sauternes mutant, which carries a mutation in the ALAS-2 gene and thus has defective heme synthesis, demonstrates higher levels of NFE2 expression than normal. This further establishes the block to erythroid differentiation in the sauternes mutant. Our studies demonstrate conservation of the vertebrate genetic program for the erythroid lineage. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Univ Tsukuba, Ctr Tsukuba Adv Res Alliance, Tsukuba, Ibaraki 3058577, Japan. RP Zon, LI (reprint author), Childrens Hosp, Howard Hughes Med Inst, Enders 7,300 Longwood Ave, Boston, MA 02115 USA. RI Yamamoto, Masayuki/A-4873-2010 FU NHLBI NIH HHS [R01-HL-48801-11]; NIDDK NIH HHS [R01-DK-55381, P50-DK-49216] NR 43 TC 17 Z9 17 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT 29 PY 2002 VL 11 IS 2 BP 91 EP 98 DI 10.1152/physiolgenomics.00112.2001 PG 8 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 609FK UT WOS:000178892800007 PM 12388799 ER PT J AU Urbanc, B Cruz, L Le, R Sanders, J Ashe, KH Duff, K Stanley, HE Irizarry, MC Hyman, BT AF Urbanc, B Cruz, L Le, R Sanders, J Ashe, KH Duff, K Stanley, HE Irizarry, MC Hyman, BT TI Neurotoxic effects of thioflavin S-positive amyloid deposits in transgenic mice and Alzheimer's disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID A-BETA DEPOSITION; NEURONAL LOSS; PRECURSOR PROTEIN; MUTANT PRESENILIN-1; NEUROFIBRILLARY TANGLES; NEUROPIL CHANGES; SENILE PLAQUES; PEPTIDE; CORTEX; ABNORMALITIES AB Despite extensive deposition of putatively neurotoxic amyloid-beta (Abeta) protein in the brain, it has not been possible to demonstrate an association of Abeta deposits with neuronal loss in Alzheimer's disease (AD), and neuronal loss is minimal in transgenic mouse models of AD. Using triple immunostaining confocal microscopy and analyzing the images with the cross-correlation density map method from statistical physics, we directly compared Abeta deposition, Abeta morphology, and neuronal architecture. We found dramatic, focal neuronal toxicity associated primarily with thioflavin S-positive fibrillar Abeta deposits in both AD and PSAPP mice. These results, along with computer simulations, suggest that Abeta develops neurotoxic properties in vivo when it adopts a fibrillar beta-pleated sheet conformation. C1 Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02219 USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Urbanc, B (reprint author), Boston Univ, Ctr Polymer Studies, Boston, MA 02215 USA. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013 OI Urbanc, Brigita/0000-0001-9159-7698; FU NCRR NIH HHS [P41 RR013622, P41 RR13622]; NIA NIH HHS [AG00793, AG08487, AG15379, AG15453, AG17216, P01 AG015379, P01 AG015453, P01 AG017216, R01 AG008487] NR 39 TC 137 Z9 141 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 29 PY 2002 VL 99 IS 22 BP 13990 EP 13995 DI 10.1073/pnas.222433299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400007 PM 12374847 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Fanourakis, G Gu, XS Bailey, C Joseph, M Libermann, TA Treon, SP Munshi, NC Richardson, PG Hideshima, T Anderson, KC AF Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Fanourakis, G Gu, XS Bailey, C Joseph, M Libermann, TA Treon, SP Munshi, NC Richardson, PG Hideshima, T Anderson, KC TI Molecular sequelae of proteasome inhibition in human multiple myeloma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KAPPA-B ACTIVITY; OVERCOMES DRUG-RESISTANCE; BREAST-CANCER CELLS; INDUCED APOPTOSIS; INTERFERON-GAMMA; CDNA CLONING; C-MYC; FUNCTIONAL-ANALYSIS; 26S PROTEASOME; T-CELLS AB The proteasome inhibitor PS-341 inhibits lkappaB degradation, prevents NF-kappaB activation, and induces apoptosis in several types of cancer cells, including chemoresistant multiple myeloma (MM) cells. PS-341 has marked clinical activity even in the setting of relapsed refractory MM. However, PS-341-induced apoptotic cascade(s) are not yet fully defined. By using gene expression profiling, we characterized the molecular sequelae of PS-341 treatment in MM cells and further focused on molecular pathways responsible for the anticancer actions of this promising agent. The transcriptional profile of PS-341-treated cells involved down-regulation of growth/survival signaling pathways, and up-regulation of molecules implicated in proapoptotic cascades (which are both consistent with the proapoptotic effect of proteasome inhibition), as well as up-regulation of heat-shock proteins and ubiquitin/proteasome pathway members (which can correspond to stress responses against proteasome inhibition). Further studies on these pathways showed that PS-341 decreases the levels of several antiapoptotic proteins and triggers a dual apoptotic pathway of mitochondrial cytochrome c release and caspase-9 activation, as well as activation of Jun kinase and a Fas/caspase-8-dependent apoptotic pathway [which is inhibited by a dominant negative (decoy) Fas construct]. Stimulation with IGF-1, as well as overexpression of Bcl-2 or constitutively active Akt in MM cells also modestly attenuates PS-341-induced cell death, whereas inhibitors of the BH3 domain of Bcl-2 family members or the heat-shock protein 90 enhance tumor cell sensitivity to proteasome inhibition. These data provide both insight into the molecular mechanisms of antitumor activity of PS-341 and the rationale for future clinical trials of PS-341, in combination with conventional and novel therapies, to improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Jerome Lipper Multiple Myeloma C, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Genom Ctr, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Jerome Lipper Multiple Myeloma C, Boston, MA 02115 USA. RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU NIDDK NIH HHS [R24 DK58739]; PHS HHS [P0-1 78378, R0-1 50947] NR 61 TC 509 Z9 532 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 29 PY 2002 VL 99 IS 22 BP 14374 EP 14379 DI 10.1073/pnas.202445099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400074 PM 12391322 ER PT J AU Dauer, W Kholodilov, N Vila, M Trillat, AC Goodchild, R Larsen, KE Staal, R Tieu, K Schmitz, Y Yuan, CA Rocha, M Jackson-Lewis, V Hersch, S Sulzer, D Przedborski, S Burke, R Hen, R AF Dauer, W Kholodilov, N Vila, M Trillat, AC Goodchild, R Larsen, KE Staal, R Tieu, K Schmitz, Y Yuan, CA Rocha, M Jackson-Lewis, V Hersch, S Sulzer, D Przedborski, S Burke, R Hen, R TI Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEURONS IN-VITRO; METABOLIC INHIBITION; DOPAMINE RELEASE; BODY FORMATION; RAT STRIATUM; DISEASE; TOXICITY; GENE; MPP+; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AB Parkinson's disease (PD) is most commonly a sporadic illness, and is characterized by degeneration of substantia nigra dopamine (DA) neurons and abnormal cytoplasmic aggregates of alpha-synuclein. Rarely, PD may be caused by missense mutations in alpha-synuclein. MPTP, a neurotoxin that inhibits mitochondrial complex I, is a prototype for an environmental cause of PD because it produces a pattern of DA neurodegeneration that closely resembles the neuropathology of PD. Here we show that alpha-synuclein null mice display striking resistance to MPTP-induced degeneration of DA neurons and DA release, and this resistance appears to result from an inability of the toxin to inhibit complex I. Contrary to predictions from in vitro data, this resistance is not due to abnormalities of the DA transporter, which appears to function normally in alpha-synuclein null mice. Our results suggest that some genetic and environmental factors that increase susceptibility to PD may interact with a common molecular pathway, and represent the first demonstration that normal alpha-synuclein function may be important to DA neuron viability. C1 Columbia Univ, Dept Neurol, New York, NY 10027 USA. Columbia Univ, Dept Pathol, New York, NY 10027 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. Columbia Univ, Dept Pharmacol, New York, NY 10027 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10027 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Dauer, W (reprint author), Columbia Univ, Dept Neurol, New York, NY 10027 USA. RI Tieu, Kim/F-5426-2012; Schmitz, Yvonne/L-6183-2013 OI Tieu, Kim/0000-0001-6606-4371; NR 37 TC 355 Z9 371 U1 0 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 29 PY 2002 VL 99 IS 22 BP 14524 EP 14529 DI 10.1073/pnas.172514599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 610NT UT WOS:000178967400099 PM 12376616 ER PT J AU Cornforth, MN Greulich-Bode, KM Loucas, BD Arsuaga, J Vazquez, M Sachs, RK Bruckner, M Molls, M Hahnfeldt, P Hlatky, L Brenner, DJ AF Cornforth, MN Greulich-Bode, KM Loucas, BD Arsuaga, J Vazquez, M Sachs, RK Bruckner, M Molls, M Hahnfeldt, P Hlatky, L Brenner, DJ TI Chromosomes are predominantly located randomly with respect to each other in interphase human cells SO JOURNAL OF CELL BIOLOGY LA English DT Article DE nuclear organization; human chromosome clustering; multiplex FISH; chromosome aberrations; proximity ID EXCHANGE ABERRATIONS; NUCLEAR ARCHITECTURE; HUMAN-LYMPHOCYTES; GAMMA-RAYS; RADIATION; DAMAGE; PROXIMITY; ORGANIZATION; CENTROMERES; TERRITORIES AB To test quantitatively whether there are systematic chromosome-chromosome associations within human interphase nuclei, interchanges between all possible heterologous pairs of chromosomes were measured with 24-color whole-chromosome painting (multiplex FISH), after damage to interphase lymphocytes by sparsely ionizing radiation in vitro. An excess of interchanges for a specific chromosome pair would indicate spatial proximity between the chromosomes comprising that pair. The experimental design was such that quite small deviations from randomness (extra pairwise interchanges within a group of chromosomes) would be detectable. The only statistically significant chromosome cluster was a group of five chromosomes previously observed to be preferentially located near the center of the nucleus. However, quantitatively, the overall deviation from randomness within the whole genome was small. Thus, whereas some chromosome-chromosome associations are clearly present, at the whole-chromosomal level, the predominant overall pattern appears to be spatially random. C1 Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. Univ Texas, Med Branch, Dept Radiat Oncol, Galveston, TX 77555 USA. German Canc Res Ctr, Dept Skin Carcinogenesis, D-69120 Heidelberg, Germany. Tech Univ Munich, Dept Radiat Oncol, D-81675 Munich, Germany. Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Brenner, DJ (reprint author), Columbia Univ, Ctr Radiol Res, 630 W 168th St, New York, NY 10032 USA. FU NCI NIH HHS [CA 49062, CA 86823, CA76260, P01 CA049062]; NCRR NIH HHS [RR 11623] NR 38 TC 66 Z9 69 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 28 PY 2002 VL 159 IS 2 BP 237 EP 244 DI 10.1083/jcb.200206009 PG 8 WC Cell Biology SC Cell Biology GA 612AQ UT WOS:000179051500005 PM 12403811 ER PT J AU Mishra-Gorur, K Rand, MD Perez-Villamil, B Artavanis-Tsakonas, S AF Mishra-Gorur, K Rand, MD Perez-Villamil, B Artavanis-Tsakonas, S TI Down-regulation of Delta by proteolytic processing SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Delta; Kuzbanian; Notch; cleavage; down-regulation ID DOMINANT-NEGATIVE FORMS; CELL FATE; DROSOPHILA DEVELOPMENT; NOTCH ACTIVATION; SERRATE; LIGAND; RECEPTOR; PROTEIN; CHOICE; PATHWAY AB Notch signaling regulates cell fate decisions during development through local cell interactions. Signaling is triggered by the interaction of the Notch receptor with its transmembrane ligands expressed on adjacent cells. Recent studies suggest that Delta is cleaved to release an extracellular fragment, DIEC, by a mechanism that involves the activity of the metalloprotease Kuzbanian; however, the functional significance of that cleavage remains controversial. Using independent functional assays in vitro and in vivo, we examined the biological activity of purified soluble Delta forms and conclude that Delta cleavage is an important down-regulating event in Notch signaling. The data support a model whereby Delta inactivation is essential for providing the critical ligand/receptor expression differential between neighboring cells in order to distinguish the signaling versus the receiving partner. C1 Harvard Univ, Ctr Canc, Dept Cell Biol, Massachusetts Gen Hosp,Sch Med, Charlestown, MA 02129 USA. Univ Vermont, Coll Med, Dept Anat & Neurobiol, Burlington, VT 05405 USA. Coll France, F-75231 Paris, France. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Ctr Canc, Dept Cell Biol, Massachusetts Gen Hosp,Sch Med, Room 7308,Bldg 149, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P20 RR 16435, P20 RR016435]; NIGMS NIH HHS [R01 GM062931, R01 GM 62931]; NINDS NIH HHS [R01 NS 26084, R01 NS026084] NR 66 TC 83 Z9 85 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 28 PY 2002 VL 159 IS 2 BP 313 EP 324 DI 10.1083/jcb.200203117 PG 12 WC Cell Biology SC Cell Biology GA 612AQ UT WOS:000179051500012 PM 12403816 ER PT J AU Tan, KM Duquette, M Liu, JH Dong, YC Zhang, RG Joachimiak, A Lawler, J Wang, JH AF Tan, KM Duquette, M Liu, JH Dong, YC Zhang, RG Joachimiak, A Lawler, J Wang, JH TI Crystal structure of the TSP-1 type 1 repeats: a novel layered fold and its biological implication SO JOURNAL OF CELL BIOLOGY LA English DT Article DE thrombospondin; TSR domain; X-ray structure; angiogenesis; GAG binding ID HEPARIN-BINDING; GROWTH-FACTOR; RECEPTOR COMPLEX; CELL-ADHESION; F-SPONDIN; IN-VITRO; THROMBOSPONDIN-1; PROTEIN; PEPTIDES; DOMAIN AB Thrombospondin-1 (TSP-1) contains three type 1 repeats (TSRs), which mediate cell attachment, glycosaminoglycan binding, inhibition of angiogenesis, activation of TGFbeta, and inhibition of matrix metalloproteinases. The crystal structure of the TSRs reported in this article reveals a novel, antiparallel, three-stranded fold that consists of alternating stacked layers of tryptophan and arginine residues from respective strands, capped by disulfide bonds on each end. The front face of the TSR contains a right-handed spiral, positively charged groove that might be the "recognition" face, mediating interactions with various ligands. This is the first high-resolution crystal structure of a TSR domain that provides a prototypic architecture for structural and functional exploration of the diverse members of the TSR superfamily. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,Room SM-1036, Boston, MA 02115 USA. FU NCI NIH HHS [CA 92644, P01 CA092644]; NHLBI NIH HHS [HL 49081, HL 68003, R01 HL049081, R01 HL068003]; NIGMS NIH HHS [GM 56008] NR 49 TC 135 Z9 139 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 28 PY 2002 VL 159 IS 2 BP 373 EP 382 DI 10.1083/jcb.200206062 PG 10 WC Cell Biology SC Cell Biology GA 612AQ UT WOS:000179051500017 PM 12391027 ER PT J AU Buhler, L Kurilla-Mahon, B Chang, Q Abraham, S Alwayn, IPJ Appel, JZ Newman, D Awwad, M White-Scharf, ME Sackstein, R Sachs, DH Cooper, DKC Down, JD AF Buhler, L Kurilla-Mahon, B Chang, Q Abraham, S Alwayn, IPJ Appel, JZ Newman, D Awwad, M White-Scharf, ME Sackstein, R Sachs, DH Cooper, DKC Down, JD TI Cryopreservation and mycophenolate therapy are detrimental to hematopoietic progenitor cells SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; NONLETHAL PREPARATIVE REGIMEN; MIXED CHIMERISM; STEM-CELLS; HEMATOLOGIC MALIGNANCIES; ALLOGRAFT TOLERANCE; FREQUENCY-ANALYSIS; MOFETIL; INDUCTION AB Background. The aim of the present study was to determine whether certain components of nonmyeloablative regimens for hematopoietic cell transplantation might compromise the growth of hematopoietic progenitors. Methods. Porcine peripheral blood progenitor cells (PBPC) were cytokine-mobilized, collected by leukapheresis, and cryopreserved using 5% dimethyl sulfoxide and 6% hydroxyethyl starch. The influence of cryopreservation on PBPC was tested in vitro by enumeration of colony-forming units (CFUs) in methylcellulose and cobblestone area-forming cell (CAFC) subsets in stromal-associated long-term cultures on fresh and frozen PBPC. The effects of mycophenolate mofetil (MMF) on porcine PBPC and baboon and human bone marrow (BM) were tested in vitro by adding varying doses of MMF to the CFU assays. One baboon was treated with increasing doses of MMF (100-500 mg/kg per day continuously intravenous), and sequential BM aspirations were tested for CFU content. Results. Fresh cytokine-mobilized PBPC had similar frequencies of progenitor cells when compared with porcine BM. Freezing-thawing of PBPC had no effect on porcine CFUs but reduced the recovery of CAFCs by more than 90%. In vitro, MMF completely inhibited the development of porcine and human CFUs at a concentration of 1 mug/mL and of baboon CFUs at levels between 10 and 100 mug/mL. Plasma-free mycophenolic acid levels of 10 to 30 mug/mL were associated with decreased CFUs in the BM. Conclusions. Cryopreservation and MMF potentially prevent engraftment of porcine PBPC by reducing the content or development of progenitor cells. These results indicate that the use of fresh PBPC might improve the induction of mixed hematopoietic chimerism and raise the possibility that use of high doses of MMF in the poststem cell transplant may compromise engraftment. C1 BioTransplant Inc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Down, JD (reprint author), BioTransplant Inc, Bldg 75,3rd Ave, Charlestown, MA 02129 USA. FU NIAID NIH HHS [5P01 AI 39755, 1P01 AI 45897] NR 35 TC 6 Z9 6 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 OCT 27 PY 2002 VL 74 IS 8 BP 1159 EP 1166 DI 10.1097/01.TP.0000031947.81048.DA PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 609RM UT WOS:000178918400018 PM 12438964 ER PT J AU Basile, JN AF Basile, JN TI Systolic blood pressure - It is time to focus on systolic hypertension - especially in older people SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID PULSE PRESSURE C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Charleston, SC 29401 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Div Gen Internal Med Geriatr, Charleston, SC 29401 USA. NR 12 TC 9 Z9 9 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD OCT 26 PY 2002 VL 325 IS 7370 BP 917 EP 918 DI 10.1136/bmj.325.7370.917 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 610XB UT WOS:000178986300005 PM 12399325 ER PT J AU Costigan, M Befort, K Karchewski, L Griffin, RS D'Urso, D Allchorne, A Sitarski, J Mannion, JW Pratt, RE Woolf, CJ AF Costigan, Michael Befort, Katia Karchewski, Laurie Griffin, Robert S. D'Urso, Donatella Allchorne, Andrew Sitarski, Joanne Mannion, James W. Pratt, Richard E. Woolf, Clifford J. TI Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. SO BMC NEUROSCIENCE LA English DT Article AB Background: Rat oligonucleotide microarrays were used to detect changes in gene expression in the dorsal root ganglion (DRG) 3 days following sciatic nerve transection (axotomy). Two comparisons were made using two sets of triplicate microarrays, naive versus naive and naive versus axotomy. Results: Microarray variability was assessed using the naive versus naive comparison. These results support use of a P < 0.05 significance threshold for detecting regulated genes, despite the large number of hypothesis tests required. For the naive versus axotomy comparison, a 2-fold cut off alone led to an estimated error rate of 16%; combining a > 1.5-fold expression change and P < 0.05 significance reduced the estimated error to 5%. The 2-fold cut off identified 178 genes while the combined >1.5-fold and P < 0.05 criteria generated 240 putatively regulated genes, which we have listed. Many of these have not been described as regulated in the DRG by axotomy. Northern blot, quantitative slot blots and in situ hybridization verified the expression of 24 transcripts. These data showed an 83% concordance rate with the arrays; most mismatches represent genes with low expression levels reflecting limits of array sensitivity. A significant correlation was found between actual mRNA differences and relative changes between microarrays (r(2) = 0.8567). Temporal patterns of individual genes regulation varied. Conclusions: We identify parameters for microarray analysis which reduce error while identifying many putatively regulated genes. Functional classification of these genes suggest reorganization of cell structural components, activation of genes expressed by immune and inflammatory cells and down-regulation of genes involved in neurotransmission. C1 [Costigan, Michael; Befort, Katia; Karchewski, Laurie; Griffin, Robert S.; Allchorne, Andrew; Sitarski, Joanne; Mannion, James W.; Woolf, Clifford J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. [Costigan, Michael; Befort, Katia; Karchewski, Laurie; Griffin, Robert S.; Allchorne, Andrew; Sitarski, Joanne; Mannion, James W.; Woolf, Clifford J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [D'Urso, Donatella] Bayer AG, D-5600 Wuppertal, Germany. [Pratt, Richard E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM costigan@helix.mgh.harvard.edu; befort@titus.u-strasbg.fr; lkarch@titus.ustrasbg.fr; robert_griffin@student.hms.harvard.edu; donatella.durso.dd@bayer-ag.de; aallchorne@partners.org; joannesitarski@hotmail.com; mannionjames@hotmail.com; repratt@bics.bwh.harvard.edu; woolf.clifford@mgh.harvard.edu FU NIH [NS38253, HD38533] FX We thank Bayer AG and the NIH (NS38253, HD38533) for financial support. NR 138 TC 325 Z9 331 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD OCT 25 PY 2002 VL 3 AR 16 DI 10.1186/1471-2202-3-16 PG 18 WC Neurosciences SC Neurosciences & Neurology GA V11KQ UT WOS:000207530900001 PM 12401135 ER PT J AU Opazo, C Huang, XD Cherny, RA Moir, RD Roher, AE White, AR Cappai, R Masters, CL Tanzi, RE Inestrosa, NC Bush, AI AF Opazo, C Huang, XD Cherny, RA Moir, RD Roher, AE White, AR Cappai, R Masters, CL Tanzi, RE Inestrosa, NC Bush, AI TI Metalloenzyme-like activity of Alzheimer's disease beta-amyloid - Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H2O2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID A-BETA; OXIDATIVE STRESS; TRANSGENIC MICE; NEUROFIBRILLARY TANGLES; SUPEROXIDE-DISMUTASE; SENILE PLAQUES; ZINC; PROTEIN; NEURONS; COPPER AB beta-Amyloid (Abeta) 1-42, implicated in the pathogenesis of Alzheimer's disease, forms an oligomeric complex that binds copper at a CuZn superoxide dismutase-like binding site. Abeta.Cu complexes generate neurotoxic H2O2 from O-2 through Cu2+ reduction, but the reaction mechanism has been unclear. We now report that Abeta1-42, when binding up to 2 eq of Cu2+, generates the H2O2 catalytically by recruiting biological reducing agents as substrates under conditions where the Cu2+ or reducing agents will not form H2O2 themselves. Cholesterol is an important substrate for this activity, as are vitamin C, L-DOPA, and dopamine (V-max for dopamine = 34.5 nM/min, K-m = 8.9 muM). The activity was inhibited by anti-Abeta antibodies, Cu2+ chelators, and Zn2+. Toxicity of Abeta in neuronal culture was consistent with catalytic H2O2 production. All was not toxic in cell cultures in the absence of Cu2+, and dopamine (5 pm) markedly exaggerated the neurotoxicity of 200 rim Abeta1-42.Cu. Therefore, microregional catalytic H2O2 production, combined with the exhaustion of reducing agents, may mediate the neurotoxicity of Abeta in Alzheimer's disease, and inhibitors of this novel activity may be of therapeutic value. C1 Sun Hlth Res Inst, Haldeman Lab Alzheimer Dis Res, Sun City, AZ 85351 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Mental Hlth Res Inst, Oxidat Disorders Lab, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Pontificia Univ Catolica Chile, Fac Ciencias Biol, Dept Biol Celular & Mol, Ctr Regulac Celular & Patol, Santiago 114D, Chile. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Lab Oxidat Biol, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016 OI Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891 FU NIA NIH HHS [2R01 AG 12685]; NIMH NIH HHS [1K01 MH 02001] NR 47 TC 398 Z9 421 U1 8 U2 57 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 OCT 25 PY 2002 VL 277 IS 43 BP 40302 EP 40308 DI 10.1074/jbc.M206428200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 607KU UT WOS:000178791400021 PM 12192006 ER PT J AU Sabeti, PC Reich, DE Higgins, JM Levine, HZP Richter, DJ Schaffner, SF Gabriel, SB Platko, JV Patterson, NJ McDonald, GJ Ackerman, HC Campbell, SJ Altshuler, D Cooper, R Kwiatkowski, D Ward, R Lander, ES AF Sabeti, PC Reich, DE Higgins, JM Levine, HZP Richter, DJ Schaffner, SF Gabriel, SB Platko, JV Patterson, NJ McDonald, GJ Ackerman, HC Campbell, SJ Altshuler, D Cooper, R Kwiatkowski, D Ward, R Lander, ES TI Detecting recent positive selection in the human genome from haplotype structure SO NATURE LA English DT Article ID LINKAGE DISEQUILIBRIUM; EVOLUTION; RECOMBINATION; RESISTANCE; ALLELE; ORIGIN AB The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD(1) and CD40 ligand(2). At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection. C1 Whitehead Inst MIT Ctr Genome Res, Cambridge, MA 02142 USA. Univ Oxford, Inst Biol Anthropol, Oxford OX2 6QS, England. Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Loyola Univ, Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60143 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lander, ES (reprint author), Whitehead Inst MIT Ctr Genome Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; OI Altshuler, David/0000-0002-7250-4107; Kwiatkowski, Dominic/0000-0002-5023-0176 NR 26 TC 980 Z9 1007 U1 13 U2 155 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 24 PY 2002 VL 419 IS 6909 BP 832 EP 837 DI 10.1038/nature01140 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 607BD UT WOS:000178769800045 PM 12397357 ER PT J AU Nathan, DM AF Nathan, DM TI Initial management of glycemia in type 2 diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; IMPAIRED GLUCOSE-TOLERANCE; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; INSULIN-TREATMENT; CONTROLLED TRIAL; FASTING GLUCOSE; CLINICAL-TRIAL; NPH INSULIN C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA. NR 59 TC 180 Z9 186 U1 0 U2 7 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 OCT 24 PY 2002 VL 347 IS 17 BP 1342 EP 1349 DI 10.1056/NEJMcp021106 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 607FK UT WOS:000178781300007 PM 12397193 ER PT J AU Kitabwalla, M Ruprecht, RM AF Kitabwalla, M Ruprecht, RM TI RNA interference - A new weapon against HIV and beyond SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMID DNA; RECEPTOR; GENE; HEPATOCYTES; INDIVIDUALS; RESISTANCE; INFECTION; CELLS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kitabwalla, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCRR NIH HHS [R01 RR14180] NR 25 TC 49 Z9 58 U1 0 U2 7 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 OCT 24 PY 2002 VL 347 IS 17 BP 1364 EP 1367 DI 10.1056/NEJMcibr022294 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 607FK UT WOS:000178781300012 PM 12397198 ER PT J AU Nathan, DG Weatherall, DJ AF Nathan, DG Weatherall, DJ TI Academic freedom in clinical research SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IRON-CHELATION-THERAPY; THALASSEMIA MAJOR; BETA-THALASSEMIA; ORAL DEFERIPRONE; OVERLOAD; DEFEROXAMINE; TOXICITY; EFFICACY; RAT; L1 C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Oxford, Oxford OX3 9DS, England. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL54785-07] NR 30 TC 51 Z9 51 U1 2 U2 3 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 OCT 24 PY 2002 VL 347 IS 17 BP 1368 EP 1371 DI 10.1056/NEJMsb020394 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 607FK UT WOS:000178781300013 PM 12397199 ER PT J AU Okamoto, Y Obeid, LM Hannun, YA AF Okamoto, Y Obeid, LM Hannun, YA TI Bcl-xL interrupts oxidative activation of neutral sphingomyelinase SO FEBS LETTERS LA English DT Article DE Bcl-xL; neutral sphingomyelinase; glutathione; ceramide ID RADIATION-INDUCED APOPTOSIS; BREAST-CARCINOMA CELLS; CERAMIDE FORMATION; GLIOMA-CELLS; HL-60 CELLS; GLUTATHIONE; PATHWAY; DEATH; INHIBITION; GENERATION AB Recent studies demonstrate a role for intracellular oxidation in the regulation of neutral sphingomyelinase (N-SMase). Glutathione (GSH) has been shown to regulate N-SMase in vitro and in cells. However, it has not been established whether the effects of GSH in cells are due to direct action on N-SMase. In this study, treatment of human mammary carcinoma MCF-7 cells with diamide, a thiol-depleting agent, caused a decrease in intracellular GSH and degradation of sphingomyelin (SM) to ceramide. The SM pool hydrolyzed in response to diamide belonged to the bacterial SMase-resistant pool of SM. Importantly, pretreatment of MCF-7 cells with GSH, N-acetylcysteine, an antioxidant, or GW69A, a specific N-SMase inhibitor, prevented diamide-induced degradation of SM to ceramide, suggesting that intracellular levels of GSH regulate the extent to which SM is degraded to ceramide and that this probably involves a GW69A-sensitive N-SMase. Unexpectedly, expression of Bcl-xL prevented tumor necrosis factor-alpha-induced SM hydrolysis and ceramide accumulation but not the decrease in intracellular GSH. Furthermore, Bcl-xL inhibited diamide-induced SM hydrolysis and ceramide accumulation but not the decrease in intracellular GSH. These results suggest that the site of action of Bcl-xL is downstream of GSH depletion and upstream of ceramide accumulation, and that GSH probably does not exert direct physiologic effects on N-SMase. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave, Charleston, SC 29425 USA. RI OKAMOTO, Yasuo/J-8438-2015; OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583]; NIDDK NIH HHS [DK59340]; NIGMS NIH HHS [GM-43825] NR 49 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 23 PY 2002 VL 530 IS 1-3 BP 104 EP 108 AR PII S0014-5793(02)03435-X DI 10.1016/S0014-5793(02)03435-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 608PZ UT WOS:000178856900020 PM 12387875 ER PT J AU Vagin, O Denevich, S Munson, K Sachs, G AF Vagin, O Denevich, S Munson, K Sachs, G TI SCH28080, a K+-competitive inhibitor of the gastric H,K-ATPase, binds near the M5-6 luminal loop, preventing K+ access to the ion binding domain SO BIOCHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; SARCOPLASMIC-RETICULUM; ALPHA-SUBUNIT; TRANSMEMBRANE DOMAINS; MEMBRANE TOPOLOGY; H+/K+-ATPASE; BETA-SUBUNIT; H+,K+-ATPASE; NA,K-ATPASE; IDENTIFICATION AB Inhibition of the gastric H,K-ATPase by the imidazo[1,2-alpha]pyridine, SCH28080, is strictly competitive with respect to K+ or its surrogate, NH4+. The inhibitory kinetics [V-max, K-m,K-app(NH4+), K-i(SCH28080), and competitive, mixed, or noncompetitive] of mutants can define the inhibitor binding domain and the route to the ion binding region within M4-6. While mutations Y799F, Y802F, I803L, S806N, V807I (M5), L811V (M5-6), Y928H (M8), and Q905N (M7-8) had no effect on inhibitor kinetics, mutations P798C, Y802L, P810A, P810G, C813A or -S, I814V or -F, F818C, T823V (M5, M5-6, and M6), E914Q, F917Y, G918E, T929L, and F932L (M7-8 and M8) reduced the affinity for SCH28080 up to 10-fold without affecting the nature of the kinetics. In contrast, the L809F substitution in the loop between M5 and M6 resulted in an similar to100-fold decrease in inhibitor affinity, and substitutions L809V, I816L, Y925F, and M937V (M5-6, M6, and M8) reduced the inhibitor affinity by 10-fold, all resulting in noncompetitive kinetics. The mutants L81 IF, Y922I, and I940A also reduced the inhibitor affinity up to 10-fold but resulted in mixed inhibition. The mutations I819L, Q923V, and Y925A also gave mixed inhibition but without a change in inhibitor affinity. These data, and the 9-fold loss of SCH28080 affinity in the C813T mutant, suggest that the binding domain for SCH28080 contains the surface between L809 in the M5-6 loop and C813 at the luminal end of M6, approximately two helical turns down from the ion binding region, where it blocks the normal ion access pathway. On the basis of a model of the Ca-ATPase in the E-2 conformation (PDB entry 1kju), the mutants that change the nature of the kinetics are arranged on one side of M8 and on the adjacent side of the M5-6 loop and M6 itself. This suggests that mutations in this region modify the enzyme structure so that K+ can access the ion binding domain, even with SCH28080 bound. C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA 90073 USA. RP VAGLAHS W LA, Bldg 113,Room 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu FU NIDDK NIH HHS [DK46917]; PHS HHS [53462, 17294, 41301] NR 32 TC 50 Z9 50 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 22 PY 2002 VL 41 IS 42 BP 12755 EP 12762 DI 10.1021/bi025921w PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605TW UT WOS:000178694000021 PM 12379118 ER PT J AU Luo, Y Li, B Yang, GA Gergely, J Tao, T AF Luo, Y Li, B Yang, GA Gergely, J Tao, T TI Cross-linking between the regulatory regions of troponin-I and troponin-C abolishes the inhibitory function of troponin SO BIOCHEMISTRY LA English DT Article ID SKELETAL-MUSCLE CONTRACTION; THIN FILAMENT PROTEINS; BIOLOGICAL-ACTIVITY; CONFORMATIONAL TRANSITION; PROXIMITY RELATIONSHIPS; PROTEOLYTIC FRAGMENTS; CA-2+-SPECIFIC SITES; ACTIN-TROPOMYOSIN; RABBIT; BINDING AB We reported previously that both residues 48 and 82 on opposite sides of troponin-C's (TnC's) N-terminal regulatory hydrophobic cleft photo-cross-linked to Met121 of troponin-I (TnI) [Luo, Y., Leszyk, J., Qian, Y., Gergely, J., and Tao, T. (1999) Biochemistry 38, 6678-6688]. Here we report that the Ca2+-absent inhibitory activity of troponin (Tn) was progressively lost as the extent of photo-cross-linking increased. To extend these studies, we constructed a mutant TnI with a single cysteine at residue 121 (TnI121). In Tn complexes containing TnI121 and mutant TnCs with a single cysteine at positions 12, 48, 82, 98, or 125 (TnC12, TnC48 etc.), TnI121 formed disulfide cross-links primarily with TnC48 and TnC82 when Ca2+ was present, and with only TnC48 when Ca2+ was absent. These results indicate that TnI Met121 is situated within the N-domain hydrophobic cleft of TnC in the presence of Ca2+, and that it moves out of the cleft upon Ca2+ removal but remains within the vicinity of TnC. Activity assays revealed that the Met121 to Cys mutation in TnI121 reduced the Ca2+-present activation of Tn, indicating that Met121 is important in hydrophobic interactions between this TnI region and TnC's N-domain cleft. The formation of a disulfide cross-link between TnI121 and TnC48 or TnC82 abolished the Ca2+-absent inhibitory activity of Tn, indicating that the movement of the Met 121 region of TnI out of TnC's N-domain cleft is essential for the occurrence of further events in the inhibitory process of skeletal muscle contraction. On the basis of these and other results, a simple mechanism for Ca2+ regulation of skeletal muscle contraction is presented and discussed. C1 Boston Biomed Res Inst, Muscle & Motil Grp, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA. RP Tao, T (reprint author), Boston Biomed Res Inst, Muscle & Motil Grp, 64 Grove St, Watertown, MA 02472 USA. FU NIAMS NIH HHS [AR21673] NR 52 TC 2 Z9 2 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 22 PY 2002 VL 41 IS 42 BP 12891 EP 12898 DI 10.1021/bi020396m PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605TW UT WOS:000178694000036 PM 12379133 ER PT J AU Doheny, D Danisi, F Smith, C Morrison, C Velickovic, M de Leon, D Bressman, SB Leung, J Ozelius, L Klein, C Breakefield, XO Brin, MF Silverman, JM AF Doheny, D Danisi, F Smith, C Morrison, C Velickovic, M de Leon, D Bressman, SB Leung, J Ozelius, L Klein, C Breakefield, XO Brin, MF Silverman, JM TI Clinical findings of a myoclonus-dystonia family with two distinct mutations SO NEUROLOGY LA English DT Article ID CHROMOSOME 7Q; MAJOR LOCUS; GENE AB Myoclonus-dystonia has recently been associated with mutations in the epsilon-sarcoglycan gene (SCGE) on 7q21. Previously, the authors reported a patient with myoclonus-dystonia and an 18-bp deletion in the DYT1 gene on 9q34. The authors have now re-evaluated the patient harboring this deletion for mutations in the SGCE gene and identified a missense change. In the current study, the authors describe the clinical details of this family carrying mutations in two different dystonia genes. Further analysis of these mutations separately and together in cell culture and in animal models should clarify their functional consequences. C1 Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Med Univ Lubeck, Dept Neurol, Lubeck, Germany. RP Doheny, D (reprint author), Mt Sinai Sch Med, Dept Neurol, Annenberg 14-51A,Box 1052, New York, NY 10029 USA. FU NINDS NIH HHS [NS28384, NS37409] NR 10 TC 35 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 22 PY 2002 VL 59 IS 8 BP 1244 EP 1246 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 606GR UT WOS:000178726700022 PM 12391355 ER PT J AU Ishida, M Iwai, Y Tanaka, Y Okazaki, T Freeman, GJ Minato, N Honjo, T AF Ishida, M Iwai, Y Tanaka, Y Okazaki, T Freeman, GJ Minato, N Honjo, T TI Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues SO IMMUNOLOGY LETTERS LA English DT Article DE PD-1; PD-L1; PD-L2; T-cell; inhibitory receptor; negative signal ID CTLA-4; MICE; IMMUNORECEPTOR; ACTIVATION; MOTIF; ENGAGEMENT; DEFICIENT; SURFACE; ABSENCE AB PD-1 is a member of the immunoglobulin superfamily expressed on immune cells, including T and B cells, and is involved in the delivery of inhibitory signal upon engagement of its ligands, PD-L1 and PD-L2. While the expression profile of PD-1 has been well documented, the analysis of PD-L1 and PD-L2 distributions on a protein basis has not been carried out because of the lack of available monoclonal antibodies specific for the molecules. In this study, we established two monoclonal antibodies, 1-111A and 122, specific for marine PD-L1 and PD-L2, respectively, and examined their expression profiles. Based on flow cytometric analyses, the expression of PD-L1 was detected in a variety of lymphohematopoietic cell types, including a minor proportion of T and B cells in the spleen, majority of pre-B cells and myeloid cells in bone marrow and subsets of thymocytes, while the expression of PD-L2 was not observed in the lymphohematopoietic cells at all. Notably, a significant proportion of the most immature lineage-marker-negative and c-Kit-positive bone marrow cells containing stem cells did express PD-L1. Following mitogenic stimulation, essentially all lymphocytes expressed PD-L1. Furthermore, a variety of leukemic lines also expressed PD-L1, while none of them did PD-L2. Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Biostudies, Lab Immunol & Cell Biol, Kyoto 6068501, Japan. Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Honjo, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Yoshidakonoe Cho, Kyoto 6068501, Japan. RI Honjo, Tasuku/N-4470-2016 NR 17 TC 123 Z9 144 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD OCT 21 PY 2002 VL 84 IS 1 BP 57 EP 62 AR PII S0165-2478(02)00142-6 DI 10.1016/S0165-2478(02)00142-6 PG 6 WC Immunology SC Immunology GA 608MR UT WOS:000178850500008 PM 12161284 ER PT J AU Muller, J Hart, CM Francis, NJ Vargas, ML Sengupta, A Wild, B Miller, EL O'Connor, MB Kingston, RE Simon, JA AF Muller, J Hart, CM Francis, NJ Vargas, ML Sengupta, A Wild, B Miller, EL O'Connor, MB Kingston, RE Simon, JA TI Histone methyltransferase activity of a Drosophila polycomb group repressor complex SO CELL LA English DT Article ID GROUP GENE ENHANCER; GROUP PROTEIN; HOMEOTIC GENE; CAENORHABDITIS-ELEGANS; DEACETYLASE RPD3; CHROMATIN STRUCTURE; LYSINE 9; ZESTE; TRITHORAX; ARABIDOPSIS AB Polycomb group (PcG) proteins maintain transcriptional repression during development, likely by creating repressive chromatin states. The Extra Sex Combs (ESC) and Enhancer of Zeste [E(Z)] proteins are partners in an essential PcG complex, but its full composition and biochemical activities are not known. A SET domain in E(Z) suggests this complex might methylate histones. We purified an ESC-E(Z) complex from Drosophila embryos and found four major subunits: ESC, E(Z), NURF-55, and the PcG repressor, SU(Z)12. A recombinant complex reconstituted from these four subunits methylates lysine-27 of histone H3. Mutations in the E(Z) SET domain disrupt methyltransferase activity in vitro and HOX gene repression in vivo. These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing. C1 European Mol Biol Lab, Gene Express Programme, D-69117 Heidelberg, Germany. Max Planck Inst Entwicklungsbiol, D-72076 Tubingen, Germany. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Muller, J (reprint author), European Mol Biol Lab, Gene Express Programme, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI Hart, Craig/B-4832-2016; OI Hart, Craig/0000-0002-9870-991X; O'Connor, Michael/0000-0002-3067-5506 NR 61 TC 874 Z9 905 U1 5 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 2002 VL 111 IS 2 BP 197 EP 208 DI 10.1016/S0092-8674(02)00976-5 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 606UX UT WOS:000178753500009 PM 12408864 ER PT J AU Bailly, V Zhang, ZW Meier, W Cate, R Sanicola, M Bonventre, JV AF Bailly, V Zhang, ZW Meier, W Cate, R Sanicola, M Bonventre, JV TI Shedding of kidney injury molecule-1, a putative adhesion protein involved in renal regeneration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CELL INTERACTIONS; HEPATITIS-A VIRUS; SIALOMUCIN COMPLEX; MEDIATED RELEASE; EPITHELIAL-CELLS; EPISIALIN MUC1; TNF-ALPHA; MATRIX; ECTODOMAIN; IDENTIFICATION AB KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury. The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins. Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions. In this study, we report that the KIM-1b transcript is expressed predominantly in adult human kidney. We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein. We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage. A monoclonal antibody that binds at or close to the proteolytic site can partially block the shedding of KIM-1. Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase. We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer. C1 Harvard Univ, Sch Med,Div Hlth Serv & Technol, Dept Med,Harvard Massachusetts Inst Technol, Massachusetts Gen Hosp,Med Serv, Charlestown, MA 02129 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Bailly, V (reprint author), 14th Cambridge Ctr, Cambridge, MA 02142 USA. NR 46 TC 172 Z9 193 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 OCT 18 PY 2002 VL 277 IS 42 BP 39739 EP 39748 DI 10.1074/jbc.M200562200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605EA UT WOS:000178662500088 PM 12138159 ER PT J AU Yang, FM Liu, XB Quinones, M Melby, PC Ghio, A Haile, DJ AF Yang, FM Liu, XB Quinones, M Melby, PC Ghio, A Haile, DJ TI Regulation of reticuloendothelial iron transporter MTP1 (Slc11a3) by inflammation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; RECOMBINANT HUMAN INTERLEUKIN-6; CANCER-PATIENTS; STORAGE IRON; SERUM IRON; TNF-ALPHA; ANEMIA; MICE; METABOLISM AB Acute and chronic inflammation cause many changes in total body iron metabolism including the sequestration of iron in phagocytic cells of the reticuloendothelial system. This change in iron metabolism contributes to the development of the anemia of inflammation. MTP1, the duodenal enterocyte basolateral iron exporter, is also expressed in the cells of the reticuloendothelial system (RES) and is likely to be involved in iron recycling of these cells. In this study, we use a lipopolysaccharide model of the acute inflammation in the mouse and demonstrate that MTP1 expression in RES cells of the spleen, liver, and bone marrow is down-regulated by inflammation. The down-regulation of splenic expression of MTP1 by inflammation was also observed in a Leishmania donovani model of chronic infection. The response of MTP1 to lipopolysaccharide (LPS) requires signaling through the LPS receptor, Toll-like receptor 4 (TLR4). In mice lacking TLR4, MTP1 expression is not altered in response to LPS. In addition, mice lacking tumor necrosis factor-receptor 1a respond appropriately to LPS with down-regulation of MTP1, despite hyporesponsiveness to tumor necrosis factor-alpha signaling, suggesting that this cytokine may not be required for the LPS effect. We hypothesize that the iron sequestration in the RES system that accompanies inflammation is because of down-regulation of MTP1. C1 S Texas Vet Hlth Syst, Audie L Murphy Mem Vet Affairs Med Ctr, San Antonio, TX 78229 USA. US EPA, Natl Hlth & Environm Effect Res Lab, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Haile, DJ (reprint author), S Texas Vet Hlth Syst, Audie L Murphy Mem Vet Affairs Med Ctr, San Antonio, TX 78229 USA. FU NIDDK NIH HHS [R01DK53079] NR 45 TC 141 Z9 145 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 OCT 18 PY 2002 VL 277 IS 42 BP 39786 EP 39791 DI 10.1074/jbc.M201485200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 605EA UT WOS:000178662500093 PM 12161425 ER PT J AU Leung, FW Iwata, F Kao, J Seno, K Itoh, M Leung, JWC AF Leung, FW Iwata, F Kao, J Seno, K Itoh, M Leung, JWC TI Ruthenium red-sensitive cation channels, but not calcitonin gene-related peptide or substance P-mediated mechanisms, protect duodenal villi against acid-induced damage SO LIFE SCIENCES LA English DT Article DE CGRP; substance P; ruthenium red; acid-induced duodenal villous injury ID ALKALINE SECRETION; RABBIT DUODENUM; RAT DUODENUM; BLOOD-FLOW; MESENTERIC HYPEREMIA; SENSORY NEURONS; CAPSAICIN; ANTAGONIST; INJURY; RECEPTOR AB Intestinal mucosal capsaicin-sensitive afferent nerves mediate, in part, the protective mesenteric hyperemia after intraduodenal acidification, Mechanisms associated the sensory neuropeptides, e.g. calcitonin gene-related peptide (CGRP), substance P, and ruthenium red-sensitive cation channels contribute to acid-induced mesenteric hyperemia, but whether they play a role in protection against acid-induced duodenal villous damage is not known. We tested the hypothesis that in doses that attenuate acid-induced hyperemia, inhibitors of these mechanisms will exacerbate acid-induced duodenal villous damage. Intravenous vehicle, specific receptor antagonists of CGRP (CGRP(8-37)), substance P (CP 96345), intraduodenal ruthenium red or vehicle was administered, followed by intraduodenal perfusion with 0.1 N HCl. Duodenal tissue was processed for hematoxylin and eosin staining. Villous damage was scored by blinded observers. Deep villous injury was significantly increased after treatment with ruthenium red, but not with CGRP(8-37) or CP 96345. These findings support the hypothesis that ruthenium red-sensitive cation channels, but not neuropeptides associated with intestinal mucosal afferent nerves, are involved in the acid-sensing mechanism which mediates the protection against acid-induced duodenal villous damage. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA 91343 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Sepulveda Ambulatory Care Ctr & Nursing Home, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Ctr Ulcer Res & Educ, Los Angeles, CA 90024 USA. Nagoya City Univ, Sch Med, Dept Internal Med 1, Nagoya, Aichi 467, Japan. Univ Calif Davis, Med Ctr, Div Gastroenterol, Sacramento, CA 95817 USA. Univ Calif Davis, Med Ctr, Vet Affairs No Calif Syst Clin, Sacramento Vet Affairs Med Ctr,Res Serv, Sacramento, CA 95817 USA. Univ Calif Davis, Med Ctr, Vet Affairs No Calif Syst Clin, Sacramento Vet Affairs Med Ctr,Med Serv, Sacramento, CA 95817 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Div GI 111G, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 28 TC 2 Z9 2 U1 0 U2 1 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 OCT 18 PY 2002 VL 71 IS 22 BP 2617 EP 2624 AR PII S0024-3205(02)02106-9 DI 10.1016/S0024-3205(02)02106-9 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 603YR UT WOS:000178589300004 PM 12354580 ER PT J AU Rajagopol, J Shepard, JAO Mark, EJ Malhotra, A AF Rajagopol, J Shepard, JAO Mark, EJ Malhotra, A TI A 58-year-old man with interstitial pulmonary disease. Eosinophilic granuloma, late (burned-out) stage. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LANGERHANS CELL HISTIOCYTOSIS; LUNG; FEATURES; ADULT; RESOLUTION; CARCINOMA; LESIONS; THERAPY C1 Massachusetts Gen Hosp, Pulm & Crit Care Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Dept Cellular & Mol Biol, Cambridge, MA 02138 USA. RP Rajagopol, J (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Dept, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 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 OCT 17 PY 2002 VL 347 IS 16 BP 1262 EP 1268 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 604CP UT WOS:000178598300009 PM 12393825 ER PT J AU Weinstein, DF AF Weinstein, DF TI Duty hours for resident physicians - Tough choices for teaching hospitals SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weinstein, DF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 7 TC 85 Z9 87 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 OCT 17 PY 2002 VL 347 IS 16 BP 1275 EP 1278 DI 10.1056/NEJMsb022065 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 604CP UT WOS:000178598300013 PM 12393829 ER PT J AU Gilon, D Cape, EG Handschumacher, MD Song, JK Solheim, J VanAuker, M King, MEE Levine, RA AF Gilon, D Cape, EG Handschumacher, MD Song, JK Solheim, J VanAuker, M King, MEE Levine, RA TI Effect of three-dimensional valve shape on the hemodynamics of aortic stenosis: Three-dimensional echocardiographic stereolithography and patient studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR VOLUME; IN-VIVO VALIDATION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; GORLIN FORMULA; MITRAL-VALVE; 2-DIMENSIONAL ECHOCARDIOGRAPHY; DOBUTAMINE ECHOCARDIOGRAPHY; PRESSURE RECOVERY; SEPTAL-DEFECTS; AREA AB OBJECTIVES This study tested the hypothesis that the impact of a stenotic aortic valve depends not only on the cross-sectional area of its limiting orifice but also on three-dimensional (3D) valve geometry. BACKGROUND Valve shape can potentially affect the hemodynamic impact of aortic stenosis by altering the ratio of effective to anatomic orifice area (the coefficient of orifice contraction [Cc]). For a given flow rate and anatomic area, a lower Cc increases velocity and pressure gradient. This effect has been recognized in mitral stenosis but assumed to be absent in aortic stenosis (constant Cc of 1 in the Gorlin equation). METHODS In order to study this effect with actual valve shapes in patients, 3D echocardiography was used to reconstruct a typical spectrum of stenotic aortic valve geometrics from doming to flat. Three different shapes were reproduced as actual models by stereolithography (computerized laser polymerization) with orifice areas of 0.5, 0.75, and 1.0 cm(2) (total of nine valves) and studied with physiologic flows. To determine whether valve shape actually influences hemodynamics in the clinical setting, we also related Cc (= continuity/planimeter areas) to stenotic aortic valve shape in 35 patients with high-quality echocardiograms. RESULTS In the patient-derived 3D models, Cc varied prominently with valve shape, and was largest for long, tapered domes that allow more gradual flow convergence compared with more steeply converging flat valves (0.85 to 0.90 vs. 0.71 to 0.76). These variations translated into differences of up to 40% in pressure drop for the same anatomic area and flow rate, with corresponding variations in Gorlin (effective) area relative to anatomic values. In patients, Cc was significantly lower for flat versus doming bicuspid valves (0.73 +/- 0.14 vs. 0.94 +/- 0.14, p < 0.0001) with 40 +/- 5% higher gradients (p < 0.0001). CONCLUSIONS Three-dimensional valve shape is an important determinant of pressure loss in patients with aortic stenosis, with smaller effective areas and higher pressure gradients for flatter valves. This effect can translate into clinically important differences between planimeter and effective valve areas (continuity or Gorlin). Therefore, valve shape provides additional information beyond the planimeter orifice area in determining the impact of valvular aortic stenosis on patient hemodynamics. (J Am Coll Cardiol 2002-,40:1479-86). (C) 2002 by the American College of Cardiology Foundation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med & Engn, Childrens Hosp, Pittsburgh, PA USA. Santin Engn, Peabody, MA USA. RP Gilon, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK508,32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL38176, K24 HL64697, R01 HL53702] NR 48 TC 58 Z9 59 U1 0 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 OCT 16 PY 2002 VL 40 IS 8 BP 1479 EP 1486 AR PII S0735-1097(02)02269-6 DI 10.1016/S0735-1097(02)02269-6 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 604DF UT WOS:000178600000017 PM 12392840 ER PT J AU Scirica, BM Cannon, CP McCabe, CH Murphy, SA Anderson, HV Rogers, WJ Stone, PH Braunwald, E AF Scirica, BM Cannon, CP McCabe, CH Murphy, SA Anderson, HV Rogers, WJ Stone, PH Braunwald, E CA Thrombosis Myocardial Ischemia III TI Prognosis in the Thrombolysis in Myocardial Ischemia III Registry according to the Braunwald unstable angina pectoris classification SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; CLINICAL PRESENTATION; TROPONIN-I; RISK; STRATIFICATION; MANAGEMENT; INFARCTION; MORPHOLOGY; TIROFIBAN AB The unstable angina pectoris (UAP) classification proposed by Braunwald in 1989, although often used, has never been validated in a large, prospective multicenter study in which all subgroups of patients were included. Patients with UAP or non-ST-elevation myocardial infarction (NSTEMI) were enrolled in the Thrombolysis In Myocardial Ischemia III Registry and classified according to the Braunwald classification for UAP. Clinical end points were compared at 6 weeks and 1 year. Of 3,318 patients, those with primary UAP had lower rates of recurrent myocardial infarction (MI) or death when compared with patients with secondary UAP and post-MI UAP at 6 weeks (4.1% vs 6.4% vs 13.4%, respectively; p <0.001) and 1 year (9.7% vs 16.7% vs 19.7%; p <0.001). Recurrent ischemia at 6 weeks followed the same gradient (13.2% vs 18.5% vs 20.8%; p<0.001). Patients with secondary UAP had similar extent of disease at angiography as primary UAP. Patients with nonresting UAP had lower rates of death or MI than patients with UAP at rest (3.0% vs 5.6%, p = 0.011 at 6 weeks, and 8.2% vs 12.5%, p = 0.004 at 1 year). Patients with ST-segment deviation and those who had received prior antianginal medical treatment also had worse outcomes. Thus, the Braunwald classification of UAP predicts prognosis with secondary UAP, post-MI UAP, and patients with pain at rest who have a higher risk for death or recurrent cardiac events. Given their high risk for adverse events, patients with secondary UAP should be treated aggressively. (C) 2002 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Clin Res Inst, Boston, MA USA. Texas Heart Inst, Houston, TX 77025 USA. Univ Texas, Houston, TX USA. Univ Alabama, Div Cardiovasc, Birmingham, AL USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 9 Z9 11 U1 0 U2 2 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 OCT 15 PY 2002 VL 90 IS 8 BP 821 EP 826 AR PII S0002-9149(02)02701-7 DI 10.1016/S0002-9149(02)02701-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 603NF UT WOS:000178565400001 PM 12372567 ER PT J AU Morshedi-Meibodi, A Larson, MG Levy, D O'Donnell, CJ Vasan, RS AF Morshedi-Meibodi, A Larson, MG Levy, D O'Donnell, CJ Vasan, RS TI Heart rate recovery after treadmill exercise testing and risk of cardiovascular disease events (the Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RATE-VARIABILITY; MYOCARDIAL-INFARCTION; MORTALITY; COHORT; ASSOCIATION; POPULATION; PREDICTORS; ECG AB A delayed heart rate (HR) recovery after graded exercise testing has been associated with increased all-cause mortality in clinic-based samples. No prior study has examined the association of HR recovery after exercise with the incidence of coronary heart disease (CHD) and cardiovascular disease (CVD) events. We evaluated 2,967 Framingham study subjects (1,400 men, mean age 43 years) who were free of CVD and underwent a treadmill exercise test (Bruce protocol) at a routine examination. We examined the relations of HR recovery indexes (decrease in HR from peak exercise) to the incidence of a first CHD or CVD event and all-cause mortality, adjusting for established CVD risk factors. During follow-up (mean 15 years), 214 subjects experienced a CHD event (156 men), 312 developed a CVD event (207 men), and 167 died (105 men). In multivariable models, continuous HR recovery indexes were not associated with the incidence of CHD or CVD events, or with all-cause mortality. However, in models evaluating quintile-based cut points, the top quintile of HR recovery (greatest decline in HR) at 1-minute after exercise was associated with a lower risk of CHD (hazards ratio vs bottom 4 quintiles 0.54, 95% confidence interval [CI], 0.32 to 0.93) and CVD (hazards ratio 0.61, 95% CI 0.41 to 0.93), but not all-cause mortality (hazards ratio 0.99, 95% CI 0.60 to 1.62). In our community-based sample, HR recovery indexes were not associated with all-cause mortality. A very rapid HR recovery immediately after exercise was associated with lower risk of CHD and CVD events. These findings should be confirmed in other settings. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol & Clin Epidemiol,Beth Israel Hosp, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [K24-HL 04334-01A1, N01-HC-25195] NR 21 TC 104 Z9 111 U1 0 U2 7 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 OCT 15 PY 2002 VL 90 IS 8 BP 848 EP 852 AR PII S0002-9149(02)02706-6 DI 10.1016/S0002-9149(02)02706-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 603NF UT WOS:000178565400006 PM 12372572 ER PT J AU Holmes, LB AF Holmes, LB TI Teratogen-induced limb defects SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE teratogens; limb deficiency; vascular disruption ID FETAL-HYDANTOIN SYNDROME; VALPROIC ACID; PRENATAL EXPOSURE; ANTICONVULSANT DRUGS; WARFARIN EMBRYOPATHY; CONGENITAL-ANOMALIES; ALCOHOL SYNDROME; FIRST-TRIMESTER; SPINA-BIFIDA; PREGNANCY AB Limb abnormalities are one of the most common and visible phenotypic effects of several human teratogens. The specific effects are different for most teratogens and include effects on limb morphogenesis (thalidomide, warfarin, phenytoin, valproic acid) and the effect of vascular disruption on a limb that had formed normally (misoprostol, chorionic villus sampling, and phenytoin). Either duplication (preaxial polydactyly of hands and feet) or deficiency (absence of thumb) is a common effect of thalidomide; no other human teratogen identified to date has this effect on the developing limb. Procedures during pregnancy, including chorionic villus sampling and dilation and curettage, produce defects of vascular disruption. For common exposures, such as alcohol and cocaine, it has been difficult to confirm objectively the exposure during embryogenesis and to ascribe specific limb defects that are produced. The molecular basis for the limb defects produced by the recognized human teratogens remains unknown. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. NR 72 TC 51 Z9 52 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 15 PY 2002 VL 112 IS 3 BP 297 EP 303 DI 10.1002/ajmg.10781 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 599DH UT WOS:000178318500010 PM 12357474 ER PT J AU Nallamothu, BK Mehta, RH Saint, S Llovet, A Bossone, E Cooper, JV Sechtem, U Isselbacher, EM Nienaber, CA Eagle, KA Evangelista, A AF Nallamothu, BK Mehta, RH Saint, S Llovet, A Bossone, E Cooper, JV Sechtem, U Isselbacher, EM Nienaber, CA Eagle, KA Evangelista, A TI Syncope in acute aortic dissection: Diagnostic, prognostic, and clinical implications SO AMERICAN JOURNAL OF MEDICINE LA English DT Article AB BACKGROUND: Syncope is a well-recognized symptom of acute aortic dissection, often indicating the development of dangerous complications such as cardiac tamponade. SUBJECTS AND METHODS: We identified consecutive patients with acute aortic dissection at 18 referral centers in six countries. Data on key clinical findings and outcomes were collected via extensive questionnaires. Multiple logistic regression models were used to determine the association between syncope and in-hospital mortality, adjusting for demographic characteristics, dissection type, comorbid conditions, and complications (e.g., cardiac tamponade). RESULTS: Syncope was reported in 96 (13%) of 728 patients. Patients with syncope were more likely to die in the hospital (34% [n = 33 deaths]) than were those without syncope (23% [ 144/632], P = 0.01). They were also more likely to have cardiac tamponade (28% [n = 27] vs. 8% [n = 49], P <0.001), stroke (18% [n = 17] vs. 4% [n = 27], P <0.001), and other neurologic deficits (25% [n = 24] vs. 14% [n = 88], P = 0.005). After multivariate adjustment, clinical factors independently associated with the occurrence of syncope included a proximal dissection (odds ratio [OR] = 5.5; 95% confidence interval [Cl]: 2.5 to 12; P <0.001), cardiac tamponade (OR = 3.1; 95% Cl: 1.7 to 5.4; P <0.001), and stroke (OR = 3.5; 95% CI: 1.7 to 7.2; P = 0.001). There was a significant association between in-hospital death and syncope after adjustment for demographic characteristics alone (OR = 2.0; 95% CI: 1.2 to 3.5; P = 0.01), but not after adjustment for dissection type, comorbid conditions, and complications. CONCLUSION: Patients with dissections complicated by cardiac tamponade or stroke are significantly more likely to present with syncope. If these complications are excluded, syncope alone does not appear to increase the risk of death independently. C1 Univ Michigan, Sch Med, Ann Arbor, MI USA. Ann Arbor VA Med Ctr, Ann Arbor, MI USA. Hosp Univ 12 Octubre, Madrid, Spain. Ist Policlin San Donato, San Donato Milanese, Italy. Robert Bosch Krankenhaus, Stuttgart, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, Rostock, Germany. Hosp Gen Univ Vall Hebron, Barcelona, Spain. RP Eagle, KA (reprint author), Dept Internal Med, 3910 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 11 TC 42 Z9 49 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2002 VL 113 IS 6 BP 468 EP 471 AR PII S0002-9343(02)01254-8 DI 10.1016/S0002-9343(02)01254-8 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 613TY UT WOS:000179148600004 PM 12427495 ER PT J AU Jacobs, BP Dennehy, C Ramirez, G Sapp, J Lawrence, VA AF Jacobs, BP Dennehy, C Ramirez, G Sapp, J Lawrence, VA TI Milk thistle for the treatment of liver disease: A systematic review and meta-analysis SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID CHRONIC HEPATITIS-C; SILYBUM-MARIANUM L; DOUBLE-BLIND; INITIAL TREATMENT; CONTROLLED TRIAL; VIRAL-HEPATITIS; SILYMARIN; CIRRHOSIS; THERAPY; INTERFERON-ALPHA-2B AB PURPOSE: Milk thistle, an herbal compound, is the dietary supplement taken most frequently by patients with chronic liver disease. We performed a systematic review of the literature to determine the efficacy and safety of this herb for the treatment of liver disease. METHODS: We searched English and non-English reports through July 1999 using thirteen databases and reference lists, and contacting manufacturers and technical experts. Reviewers independently screened all reports to identify randomized placebo-controlled trials that evaluated milk thistle for the treatment of liver disease. Outcomes of primary interest included mortality, histological findings on liver biopsy specimens, serum aminotransferase and albumin levels, and prothrombin times. RESULTS: Fourteen trials met inclusion criteria. Four trials reported outcomes for mortality among 433 participants. The overall summary odds ratio for mortality in the milk thistle group compared with placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.5; P = 0.6). Three trials assessed histology on liver biopsy; study quality was inversely associated with the likelihood of histological benefit for milk thistle compared with placebo. There were no differences in serum alanine aminotransferase, aspartate aminotransferase, or albumin levels, or prothrombin times, among participants assigned to milk thistle compared with those assigned to placebo. The only statistically significant difference was a greater reduction in alanine aminotransferase levels among patients with chronic liver disease assigned to milk thistle (- 9 IU/L, 95% CI: - 18 to - I IU/L; P = 0.05), but this reduction was of negligible clinical importance and no longer statistically significant after limiting analyses to studies of longer duration or of higher quality. The frequency of adverse effects was low and, in clinical trials, indistinguishable from placebo. CONCLUSION: Treatment with milk thistle appears to be safe and well tolerated. We found no reduction in mortality, in improvements in histology at liver biopsy, or in biochemical markers of liver function among patients with chronic liver disease. Data are too limited to exclude a substantial benefit or harm of milk thistle on mortality, and also to support recommending this herbal compound for the treatment of liver disease. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Osher Ctr, Dept Clin Pharm, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio Evidence Based Practice Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Disseminat & Implementat Ctr, San Antonio, TX USA. RP Jacobs, BP (reprint author), Univ Calif San Francisco, Osher Ctr Integrat Med, Box 1726, San Francisco, CA 94143 USA. NR 84 TC 117 Z9 121 U1 4 U2 17 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 OCT 15 PY 2002 VL 113 IS 6 BP 506 EP 515 AR PII S0002-9343(02)01244-5 DI 10.1016/S0002-9343(02)01244-5 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 613TY UT WOS:000179148600010 PM 12427501 ER PT J AU Yao, JK Stanley, JA Reddy, RD Keshavan, MS Pettegrew, JW AF Yao, JK Stanley, JA Reddy, RD Keshavan, MS Pettegrew, JW TI Correlations between peripheral polyunsaturated fatty acid content and in vivo membrane phospholipid metabolites SO BIOLOGICAL PSYCHIATRY LA English DT Article DE red blood cell; polyunsaturated fatty acids; membranes; in vivo P-31 magnetic resonance spectroscopy; phosphomonoesters; prefrontal; schizophrenia ID MAGNETIC-RESONANCE SPECTROSCOPY; DOCOSAHEXAENOIC ACID; SCHIZOPHRENIC-PATIENTS; EICOSAPENTAENOIC ACID; ERYTHROCYTE-MEMBRANES; ARACHIDONIC-ACID; BRAIN; DEFICIENCY; SUPPLEMENTATION; TURNOVER AB Background: There is evidence for membrane abnormalities in schizophrenia. It is unclear whether the observed membrane deficits in peripheral cells parallel central membrane phospholipid metabolism. To address this question we examined the relations between red blood cell polyunsaturated fatty acids and brain phospholipid metabolites from different regions of interest in schizophrenia and healthy subjects. Methods: Red blood cell membrane fatty acids were measured by capillary gas chromatography and in vivo brain phospholipid metabolite levels were measured using a multi-voxel P-31 Magnetic Resonance Spectroscopy technique on 11 first-episode, neuroleptic-naive schizophrenic subjects and 11 normal control subjects. Results: Both the total polyunsaturated fatty acids and the individual 20:4(n-6) contents were significantly correlated with the freely-mobile phosphomonoester [PME(s-tau(c))] levels (r =.5643, p =.0062 and r =.6729, p =.0006, respectively). The 18:2(n-6) polyunsaturated fatty acids content correlated positively with freely-mobile phosphodiester [PDE(s-tau(c))] levels (r =.5573, p =.0071). The above correlations were present in the combined right and left prefrontal region of the brain, while other regions including the basal ganglia, occipital, inferior parietal, superior temporal and centrum semiovale yielded no significant correlations. Conclusions: Our preliminary data support the association between the decreased red blood cell membrane phospholipid polyunsaturated fatty acids content and the decreased building blocks [PME(s-tau(c))] and breakdown products [PDE(s-tau(c))] of membrane phospholipids in the prefrontal region of first-episode, neuroleptic-naive schizophrenic subjects. Biol Psychiatry 2002;52: 823-830 (C) 2002 Society of Biological Psychiatry. C1 VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH 45203, MH 46614, MH 58141] NR 35 TC 61 Z9 62 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2002 VL 52 IS 8 BP 823 EP 830 AR PII S0006-3223(02)01397-5 DI 10.1016/S0006-3223(02)01397-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 601BE UT WOS:000178425600007 PM 12372654 ER PT J AU Sieff, C Nathan, D AF Sieff, C Nathan, D TI Novel treatment for Diamond-Blackfan anemia? SO BLOOD LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Sieff, C (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 OCT 15 PY 2002 VL 100 IS 8 BP 2685 EP 2685 DI 10.1182/blood-2002-07-2220 PG 1 WC Hematology SC Hematology GA 602RW UT WOS:000178519100001 ER PT J AU Lee, SJ Zahrieh, D Alyea, EP Weller, E Ho, VT Antin, JH Soiffer, RJ AF Lee, SJ Zahrieh, D Alyea, EP Weller, E Ho, VT Antin, JH Soiffer, RJ TI Comparison of T-cell-depleted and non-T-cell-depleted unrelated donor transplantation for hematologic diseases: clinical outcomes, quality of life, and costs SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; GRAFT; PROPHYLAXIS; PROGRAM; IMPACT AB T-cell depletion (TCD) and immunosuppressive medications (ISTs) are 2 methods used for graft-versus-host disease (GVHD) prophylaxis in unrelated donor (URD) transplantation. However, comparisons of the clinical outcomes including quality of life and direct medical costs associated with each type of procedure have not been reported. We reviewed 48 TCD and 98 IST procedures performed from 1/1/97 to 12/31/99 at the Dana-Farber Cancer Institute, Boston, MA. With a median follow-up of 1.6 years for survivors, no differences were seen in relapse, acute GVHD, and overall survival between TCD and IST patients. Multivariable Cox modeling showed that age of 56 years or less (P = .002) and low-risk disease (P = .001) predicted survival, but method of GVHD prophylaxis (P = .6) and degree of human leukocyte antigen (HLA) matching (P = .8) did not. A subset of patients (53%) completed quality of life surveys prior to and at 6 and 12 months after transplantation; participation in the quality of life study was not associated with clinical characteristics and outcomes.. No differences were seen in quality of life scores prior to transplantation, and changes over time were similar between groups. Costs ($113 000 vs $155 000, P < .0001) and total hospital days (34 vs 46, P = .0006) were significantly lower for patients undergoing TCD procedures. As prospective, randomized studies comparing methods of GVHD prophylaxis are performed, assessment of quality of life and costs should be included to fully understand the overall impact of each intervention. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75267]; NIAID NIH HHS [AI29530] NR 21 TC 29 Z9 30 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2002 VL 100 IS 8 BP 2697 EP 2702 DI 10.1182/blood-2002-03-0984 PG 6 WC Hematology SC Hematology GA 602RW UT WOS:000178519100007 PM 12351374 ER PT J AU Lutskiy, MI Sasahara, Y Kenney, DM Rosen, FS Remold-O'Donnell, E AF Lutskiy, MI Sasahara, Y Kenney, DM Rosen, FS Remold-O'Donnell, E TI Wiskott-Aldrich syndrome in a female SO BLOOD LA English DT Article ID X-CHROMOSOME INACTIVATION; SYNDROME PROTEIN; CARRIER DETECTION; GENE; THROMBOCYTOPENIA; LYMPHOCYTES; PLATELETS; GIRL; IDENTIFICATION; SPLENECTOMY AB Wiskott-Aldrich syndrome (WAS) is an X-linked disease characterized by thrombocytopenia, eczema, and various degrees of immune deficiency. Carriers of mutated WASP have nonrandom X chromosome inactivation in their blood cells and are disease-free. We report data on a 14-month-old girl with a history of WAS in her family who presented with thrombocytopenia, small platelets, and immunologic dysfunction. Sequencing of the WASP gene showed that the patient was heterozygous for the splice site mutation previously found in one of her relatives with WAS. Sequencing of all WASP exons revealed no other mutation. Levels of WASP in blood mononuclear cells were 60% of normal. Flow cytometry after intracellular staining of peripheral blood mononuclear cells with WASP monoclonal antibody revealed both WASP(bright) and WASP(dim) populations. X chromosome inactivation in the patient's blood cells was found to be random, demonstrating that both maternal and paternal active X chromosomes are present. These findings indicate that the female patient has a defect in the mechanisms that lead in disease-free WAS carriers to preferential survival/proliferation of cells bearing the active wild-type X chromosome. Whereas the patient's lymphocytes are skewed toward WASP(bright) cells, about 65% of her monocytes and the majority of her B cells (CD19(+)) are WASP(dim). Her naive T cells (CD3(+)CD45RA(+)) include WASP(bright) and WASP(dim) populations, but her memory T cells (CD3(+)CD45RA(-)) are all WASP(bright). After activation in vitro of T cells, all cells exhibited CD3+CD45RA- phenotype and most were WASP(bright) with active paternal (wild-type) X chromosome, suggesting selection against the mutated WASP allele during terminal T-cell maturation/differentiation. C1 Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR02172]; NHLBI NIH HHS [HL 59561]; NIAID NIH HHS [AI39574] NR 44 TC 28 Z9 31 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2002 VL 100 IS 8 BP 2763 EP 2768 DI 10.1182/blood-2002-02-0388 PG 6 WC Hematology SC Hematology GA 602RW UT WOS:000178519100016 PM 12351383 ER PT J AU Balasubramanian, V Grabowski, E Bini, A Nemerson, Y AF Balasubramanian, V Grabowski, E Bini, A Nemerson, Y TI Platelets, circulating tissue factor, and fibrin colocalize in ex vivo thrombi: real-time fluorescence images of thrombus formation and propagation under defined flow conditions SO BLOOD LA English DT Article ID SHED MEMBRANE MICROPARTICLES; MONOCLONAL-ANTIBODY; PROCOAGULANT ACTIVITY; FACTOR PATHWAY; FACTOR ANTIGEN; BLOOD; EXPRESSION; LEUKOCYTES; CELLS; COAGULATION AB Although it is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of tissue factor (TF) to blood, there is still little agreement about the mechanisms of thrombus propagation and the identities of the molecular species participating in this process. In this study, we characterized the thrombotic process in real-time and under defined flow conditions to determine the relative contribution and spatial distribution of 3 components of the thrombi: circulating or blood-borne TF (cTF), fibrin, and platelets. For this purpose, we used high-sensitivity, multicolor immunofluorescence microscopy coupled with a laminar flow chamber. Freshly drawn blood, labeled with mepacrine (marker for platelets and white cells), anti-hTF1(Alexa.568) (marker for tissue factor), and anti-T(2)G(1)(Cy-5) (marker for fibrin) was perfused over collagen-coated glass slides at wall shear rates of 100 and 650 s(-1). A motorized filter cube selector facilitated imaging every 5 seconds at 1 of 3 different wavelengths, corresponding to optimal wavelengths for the 3 markers above. Real-time video recordings obtained during each of 10 discrete experiments show rapid deposition of platelets and fibrin onto collagen-coated glass. Overlay images of fluorescent markers corresponding to platelets, fibrin, and cTF clearly demonstrate colocalization of these 3 components in growing thrombi. These data further support our earlier observations that, in addition to TF present in the vessel wall, there is a pool of TF in circulating blood that contributes to the propagation of thrombosis at a site of vascular injury. C1 Mt Sinai Sch Med, Div Thrombosis Res, New York, NY 10029 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York Blood Ctr, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Thrombosis Lab, Boston, MA USA. RP Nemerson, Y (reprint author), Mt Sinai Sch Med, Div Thrombosis Res, Box 1269,Annenberg 24-92,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NHLBI NIH HHS [HL 33095, 5 P50 HL54469, 5 P01HL29019] NR 24 TC 91 Z9 96 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2002 VL 100 IS 8 BP 2787 EP 2792 DI 10.1182/blood-2002-03-0902 PG 6 WC Hematology SC Hematology GA 602RW UT WOS:000178519100019 PM 12351386 ER PT J AU Howie, D Okamoto, S Rietdijk, S Clarke, K Wang, NH Gullo, C Bruggeman, JP Manning, S Coyle, AJ Greenfield, E Kuchroo, V Terhorst, C AF Howie, D Okamoto, S Rietdijk, S Clarke, K Wang, NH Gullo, C Bruggeman, JP Manning, S Coyle, AJ Greenfield, E Kuchroo, V Terhorst, C TI The role of SAP in murine CD150 (SLAM)-mediated T-cell proliferation and interferon gamma production SO BLOOD LA English DT Article ID LYMPHOCYTIC ACTIVATION MOLECULE; LINKED LYMPHOPROLIFERATIVE-DISEASE; MEASLES-VIRUS RECEPTOR; HUMAN B-LYMPHOCYTES; GENE-PRODUCT; CYTOKINE PRODUCTION; DENDRITIC CELLS; SH2 DOMAIN; COSTIMULATORY SIGNAL; UP-REGULATION AB CD150 (signaling lymphocyte activation molecule [SLAM]) is a self-ligand cell surface glycoprotein expressed on T cells, B cells, macrophages, and dendritic cells. To further explore the role of CD150 signaling in costimulation and T(H)1 priming we have generated a panel of rat anti-mouse CD150 monoclonal antibodies. CD150 cell surface expression is upregulated with rapid kinetics in activated T cells and lipopolysaccharide/interferon gamma (IFN-gamma)-activated macrophages. Anti-CD150 triggering induces strong costimulation of T cells triggered through CD3. DNA synthesis of murine T cells induced by anti-CD150 is not dependent on SLAM-associated protein (SAP, SH2D1A), because anti-CD150 induces similar levels of DNA synthesis in SAP(-/-) T cells. Antibodies to CD150 also enhance IFN-gamma production both in wild-type and SAP(-/-) T cells during primary stimulation. The level of IFN-gamma production is higher in SAP(-/-) T cells than in wild-type T cells. Anti-CD150 antibodies also synergize with interleukin 12 (IL-12) treatment in up-regulation of IL-12 receptor beta(2) mRNA during T(H)1 priming, and inhibit primary T(H)2 polarization in an IFN-gamma-dependent fashion. Crosslinking CD150 on CD4 T cells induces rapid serine phosphorylation of Akt/PKB. We speculate that this is an important pathway contributing to CD150-mediated T-cell proliferation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Howie, D (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, RE-204,330 Brookline Ave, Boston, MA 02215 USA. NR 56 TC 57 Z9 59 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 OCT 15 PY 2002 VL 100 IS 8 BP 2899 EP 2907 DI 10.1182/blood-2002-02-0445 PG 9 WC Hematology SC Hematology GA 602RW UT WOS:000178519100034 PM 12351401 ER PT J AU Beckerman, J Cheung, J Keane, D Ruskin, J AF Beckerman, J Cheung, J Keane, D Ruskin, J TI Drug-induced bradyarrhythmias are an increasing indication for permanent pacemaker implantation SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P55 BP E86 EP E86 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600069 ER PT J AU Labresh, KA MacDonald, C Liljestrand, JS Schwamm, LH AF Labresh, KA MacDonald, C Liljestrand, JS Schwamm, LH TI Secondary prevention in hospitalized stroke patients SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 MassPRO, Waltham, MA USA. Outcome Sci Inc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P62 BP E87 EP E87 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600075 ER PT J AU Maron, DJ Weintraub, WS Hartigan, PM Casperson, P Murphy, A Potter, K Teo, KK Knudtson, ML Kostuk, WJ Boden, WE O'Rourke, RA AF Maron, DJ Weintraub, WS Hartigan, PM Casperson, P Murphy, A Potter, K Teo, KK Knudtson, ML Kostuk, WJ Boden, WE O'Rourke, RA TI Achieving AHA/ACC secondary prevention goals in a clinical trial SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Emory Univ Hosp, Atlanta, GA 30322 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Hartford Hosp, Hartford, CT 06115 USA. McMaster Univ, Med Ctr, Hamilton, ON, Canada. Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada. London Hlth Sci Ctr, London, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P31 BP E82 EP E82 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600047 ER PT J AU Petersen, LA McNeil, BJ Normand, SLT AF Petersen, LA McNeil, BJ Normand, SLT TI Effect of adjustment for center in multi-center comparisons of AMI quality of care SO CIRCULATION LA English DT Meeting Abstract CT 4th Scientific Forum on Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke CY OCT 13-14, 2002 CL WASHINGTON, D.C. SP Amer Heart Assoc Councils Cardiovasc Dis Young, Cardiovasc Nursing, Cardio Thorac & Vasc Surg, Amer Coll Cardiol Fdn, Dept Vet Affairs C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Harvard Med Sch, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 2002 VL 106 IS 16 MA P229 BP E116 EP E116 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 605NH UT WOS:000178683600218 ER PT J AU Beall, B Besser, J Bisno, A Chuang, IL Craig, AS Facklam, R Fetter, J Gerber, MA Gray, G Hill, H Lepine, L Levine, O McGeer, A Moore, M Pearson, M O'Brien, K Schuchat, A Sewell, M Shulman, S Siegel, J Stevens, DL Strausbaugh, L Van Beneden, C AF Beall, B Besser, J Bisno, A Chuang, IL Craig, AS Facklam, R Fetter, J Gerber, MA Gray, G Hill, H Lepine, L Levine, O McGeer, A Moore, M Pearson, M O'Brien, K Schuchat, A Sewell, M Shulman, S Siegel, J Stevens, DL Strausbaugh, L Van Beneden, C CA Prevention Invasive Grp A Streptoc TI Prevention of invasive group A streptococcal disease among household contacts of case patients and among postpartum and postsurgical patients: Recommendations from the Centers for Disease Control and Prevention SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GROUP-A STREPTOCOCCUS; SURGICAL-WOUND INFECTIONS; HEALTH-CARE WORKERS; PHARYNGEAL CARRIAGE; ERADICATE GROUP; PENICILLIN; OUTBREAK; STRAINS; FAMILY; SUSCEPTIBILITY AB The Centers for Disease Control and Prevention hosted a workshop to formulate recommendations for the control of invasive group A streptococcal (GAS) disease among household contacts of persons with invasive GAS infections and for responding to postpartum and postsurgical invasive GAS infections. Experts reviewed data on the risk of subsequent invasive GAS infection among household contacts of case patients, the effectiveness of chemoprophylactic regimens for eradicating GAS carriage, and the epidemiology of postpartum and postsurgical GAS infection clusters. For household contacts of index patients, routine screening for and chemoprophylaxis against GAS are not recommended. Providers and public health officials may choose to offer chemoprophylaxis to household contacts who are at an increased risk of sporadic disease or mortality due to GAS. One nosocomial postpartum or postsurgical invasive GAS infection should prompt enhanced surveillance and isolate storage, whereas greater than or equal to2 cases caused by the same strain should prompt an epidemiological investigation that includes the culture of specimens from epidemiologically linked health care workers. C1 Ctr Dis Control & Prevent, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Minnesota Dept Hlth, Minneapolis, MN USA. Miami Vet Affairs Med Ctr, Miami, FL USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. CDC, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Tennessee Dept Hlth, Nashville, TN USA. CDC, Resp Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Act Bacterial Core Surveillance Program, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Northside Hosp, Atlanta, GA USA. Assoc Profess Infect Control & Epidemiol, Washington, DC 20005 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Amer Acad Pediat, Elk Grove Village, IL 60007 USA. Univ Iowa, Coll Publ Hlth, Iowa City, IA USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Emory Univ, Sch Med, Atlanta, GA USA. NIAID, Bethesda, MD 20892 USA. Univ Toronto, Lab Med & Publ Hlth Sci, Toronto, ON, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. CDC, Epidem Intelligence Serv Program, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. CDC, Epidem Intelligence Serv Program, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. CDC, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. New Mexico Dept Hlth, Santa Fe, NM USA. Council State & Terr Epidemiologists, Atlanta, GA 30341 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Northwestern Univ, Dept Pediat, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Boise VA Med Ctr, Boise, ID USA. Univ Washington, Sch Med, Seattle, WA USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR USA. Infect Dis Soc Amer, Alexandria, VA 22314 USA. RP Moore, M (reprint author), Ctr Dis Control & Prevent, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd,Mailstop D-63, Atlanta, GA 30333 USA. RI mcgeer, allison /H-7747-2014 OI mcgeer, allison /0000-0001-5647-6137 NR 60 TC 65 Z9 68 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 OCT 15 PY 2002 VL 35 IS 8 BP 950 EP 959 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YC UT WOS:000178303800006 ER PT J AU Muder, RR Yu, VL AF Muder, RR Yu, VL TI Infection due to Legionella species other than L-pneumophila SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PITTSBURGH PNEUMONIA AGENT; NOSOCOMIAL LEGIONNAIRES-DISEASE; COMMUNITY-ACQUIRED PNEUMONIA; PROSTHETIC-VALVE ENDOCARDITIS; SP-NOV; MICDADEI PNEUMONIA; TRANSPLANT RECIPIENT; PONTIAC FEVER; BOZEMANII PNEUMONIA; GENUS LEGIONELLA AB In addition to Legionella pneumophila, 19 Legionella species have been documented as human pathogens on the basis of their isolation from clinical material. Like L. pneumophila, other Legionella species are inhabitants of natural and man-made aqueous environments. The major clinical manifestation of infection due to Legionella species is pneumonia, although nonpneumonic legionellosis (Pontiac fever) and extrapulmonary infection may occur. The majority of confirmed infections involving non-pneumophila Legionella species have occurred in immunosuppressed patients. Definitive diagnosis requires culture on selective media. Fluoroquinolones and newer macrolides are effective therapy. A number of nosocomial cases have occurred in association with colonization of hospital water systems; elimination of Legionella species from such systems prevents their transmission to susceptible patients. It is likely that many cases of both community-acquired and nosocomial Legionella infection remain undiagnosed. Application of appropriate culture methodology to the etiologic diagnosis of pneumonia is needed to further define the role of these organisms in disease in humans. C1 VA Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 116 TC 137 Z9 143 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2002 VL 35 IS 8 BP 990 EP 998 DI 10.1086/342884 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YC UT WOS:000178303800011 PM 12355387 ER PT J AU Goruppi, S Bonventre, JV Kyriakis, JM AF Goruppi, S Bonventre, JV Kyriakis, JM TI Signaling pathways and late-onset gene induction associated with renal mesangial cell hypertrophy SO EMBO JOURNAL LA English DT Article DE diabetic renal hypertrophy; p8; RNAi; signal transduction; transcriptional profiling ID PROTEIN-KINASE-B; DNA-BINDING ACTIVITY; INDUCED CARDIOMYOCYTE HYPERTROPHY; GLYCOGEN-SYNTHASE KINASE-3; CARDIAC-HYPERTROPHY; TRANSCRIPTION FACTORS; PANCREATIC-CANCER; RNA INTERFERENCE; HUMAN P8; STRESS AB In chronic diseases such as diabetes mellitus, continuous stress stimuli trigger a persistent, self-reinforcing reprogramming of cellular function and gene expression that culminates in the pathological state. Late-onset, stable changes in gene expression hold the key to understanding the molecular basis of chronic diseases. Renal failure is a common, but poorly understood complication of diabetes. Diabetic nephropathy begins with mesangial cell hypertrophy and hyperplasia, combined with excess matrix deposition. The vasoactive peptide endothelin promotes the mesangial cell hypertophy characteristic of diabetic nephropathy. In this study, we examined the signaling pathways and changes in gene expression required for endothelin-induced mesangial cell hypertrophy. Transcriptional profiling identified seven genes induced with slow kinetics by endothelin. Of these, p8, which encodes a small basic helix-loop-helix protein, was most strongly and stably induced. p8 is also induced in diabetic kidney. Mesangial cell hypertrophy and p8 induction both require activation of the ERK, JNK/SAPK and PI-3-K pathways. Small interfering RNA (siRNA)-mediated RNA interference indicates that p8 is required for endothelin-induced hypertrophy. Thus, p8 is a novel marker for diabetic renal hypertrophy. C1 Massachusetts Gen Hosp, Dept Med, Diabet Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Renal Unit, Charlestown, MA 02129 USA. RP Kyriakis, JM (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Dept Med,Mol Cardiol Res Inst, Boston, MA 02111 USA. FU NIDDK NIH HHS [R01-DK41513] NR 63 TC 51 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 2002 VL 21 IS 20 BP 5427 EP 5436 DI 10.1093/emboj/cdf535 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 607QK UT WOS:000178802100012 PM 12374743 ER PT J AU Quinn, LS Anderson, BG Drivdahl, RH Alvarez, B Argiles, JM AF Quinn, LS Anderson, BG Drivdahl, RH Alvarez, B Argiles, JM TI Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: Implications for treatment of muscle wasting disorders SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE skeletal muscle; interleukin-15; cachexia; muscle hypertrophy; muscle atrophy; protein synthesis; protein degradation; cytokines ID GROWTH-FACTOR-I; SATELLITE CELL-ACTIVITY; IGF-I; PROTEIN-SYNTHESIS; BODY-COMPOSITION; CANCER CACHEXIA; INSULIN; EXPRESSION; HORMONE; RATS AB Interleukin-15 (IL-15) is a novel anabolic factor for skeletal muscle which inhibits muscle wasting associated with cancer (cachexia) in a rat model. To develop a cell culture system in which the mechanism of the anabolic action of IL-15 on skeletal muscle could be examined, the mouse C2 skeletal myogenic cell line was transduced with a retroviral expression vector for IL-15 and compared to sister cells transduced with a control vector. Overexpression of IL-15 induced fivefold higher levels of sarcomeric myosin heavy chain and a-actin accumulation in differentiated myotubes. Secreted factors from IL-15-overexpressing myogenic cells, but not from control cells, induced increased myofibrillar protein accumulation in cocultured control myotubes. IL-15 overexpression induced a hypertrophic myotube morphology similar to that described for cultured myotubes which overexpressed the well-characterized anabolic factor insulin-like growth factor-I (IGF-I). However, in contrast to IGF-I, the hypertrophic action of IL-15 on skeletal myogenic cells did not involve stimulation of skeletal myoblast proliferation or differentiation. IL-15 induced myotube hypertrophy at both low and high IGF-I concentrations. Furthermore, in contrast to IGF-I, which stimulated only protein synthesis under these culture conditions, IL-15 both stimulated protein synthesis and inhibited protein degradation in cultured skeletal myotubes. These findings indicate that IL-15 action on skeletal myogenic cells is distinct from that of IGF-I. Due to the ability of IGF-I to stimulate cell division and its association with several forms of cancer, controversy exists concerning the advisability of treating cachexia or age-associated muscle wasting with IGF-I. Administration of IL-15 or modulation of the IL-15 signaling pathway may represent an alternative strategy for maintaining skeletal muscle mass under these conditions. (C) 2002 Elsevier Science (USA). C1 VA Puget Sound Hlth Care Syst, Amer Lake Div 151, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. VA Puget Sound Hlth Care Syst, Res Serv, Tacoma, WA 98493 USA. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div 151, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. NR 51 TC 94 Z9 100 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 15 PY 2002 VL 280 IS 1 BP 55 EP 63 DI 10.1006/excr.2002.5624 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 603VR UT WOS:000178582000006 PM 12372339 ER PT J AU Cotman, SL Vrbanac, V Lebel, LA Lee, RL Johnson, KA Donahue, LR Teed, AM Antonellis, K Bronson, RT Lerner, TJ MacDonald, ME AF Cotman, SL Vrbanac, V Lebel, LA Lee, RL Johnson, KA Donahue, LR Teed, AM Antonellis, K Bronson, RT Lerner, TJ MacDonald, ME TI Cln3(Delta ex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; MITOCHONDRIAL ATP SYNTHASE; BATTEN-DISEASE; SUBUNIT-C; GENE KNOCKOUT; MOUSE; PROTEIN; MODEL; CLN3; EXPRESSION AB Juvenile-onset neuronal ceroid lipofuscinosis (JNCL; Batten. disease) features hallmark membrane deposits and loss of central nervous system (CNS) neurons: Most cases of the disease are due to recessive inheritance of an similar to1 kb deletion in the CLN3 gene, encoding battenin. To investigate the common JNCL mutation, we have introduced an identical genomic DNA deletion into the murine CLN3 homologue (Cln3) to create Cln3(Deltaex7/8) knock-in mice. The Cln3(Deltaex7/8) allele produced alternatively spliced mRNAs, including a variant predicting non-truncated protein, as well as mutant battenin that was detected in the cytoplasm of cells in the periphery and CNS. Moreover, Cln3(Deltaex7/8) homozygotes exhibited accrual of JNCL-like membrane deposits from before birth, in proportion to battenin levels, which were high in liver and select neuronal populations. However, liver enzymes and CNS development were normal. Instead, Cln3(Deltaex7/8) mice displayed recessively inherited degenerative changes in retina, cerebral cortex and cerebellum, as well as neurological deficits and premature death. Thus, the harmful impact of the common JNCL mutation on the CNS was not well correlated with membrane deposition per se, suggesting instead a specific battenin activity that is essential for the survival of CNS neurons. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 32099, NS 33648, R01 NS033648] NR 30 TC 80 Z9 81 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 OCT 15 PY 2002 VL 11 IS 22 BP 2709 EP 2721 DI 10.1093/hmg/11.22.2709 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 607AR UT WOS:000178768700003 PM 12374761 ER PT J AU Yang, KK Dorner, BG Merkel, U Ryffel, B Schutt, C Golenbock, D Freeman, MW Jack, RS AF Yang, KK Dorner, BG Merkel, U Ryffel, B Schutt, C Golenbock, D Freeman, MW Jack, RS TI Neutrophil influx in response to a peritoneal infection with Salmonella is delayed in lipopolysaccharide-binding protein or CD14-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACUTE SEPTIC PERITONITIS; BACTERIAL CLEARANCE; CELL ACTIVATION; INNATE IMMUNITY; MAST-CELLS; RECEPTOR; LPS; LIPOPROTEINS; RECOGNITION; PROTECTION AB The induction of an adaptive immune response to a previously unencountered pathogen is a time-consuming process and initially the infection must be held in check by the innate immune system. In the case of an i.p. infection with Salmonella typhimurium, survival requires both CD14 and LPS-binding protein (LBP) which, together with Toll-like receptor 4 and myeloid differentiation protein 2, provide a sensitive means to detect bacterial LPS. In this study, we show that in the first hours after i.p. infection with Salmonella a local inflammatory response is evident and that concomitantly neutrophils flood into the peritoneum. This rapid neutrophil influx is dependent on TNF since it is 1) abolished in TNF KO mice and 2) can be induced by i.p. injection of TNF in uninfected animals. Neutrophil influx is not strictly dependent on the presence of either LBP or CD14. However, in their absence, no local inflammatory response is evident, neutrophil migration is delayed, and the mice succumb to the infection. Using confocal microscopy, we show that the neutrophils which accumulate in CD14 and LBP null mice, albeit with delayed kinetics, are nevertheless fully capable of ingesting the bacteria. We suggest that the short delay in neutrophil influx gives the pathogen a decisive advantage in this infection model. C1 Univ Klinikum Greifswald, Inst Immunol & Transfus Med, D-17489 Greifswald, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. Univ Massachusetts, Div Infect Dis, Worcester, MA 01655 USA. Inst Transgenose, CNRS, Orleans, France. RP Jack, RS (reprint author), Univ Klinikum Greifswald, Inst Immunol & Transfus Med, Sauerbruchstr, D-17489 Greifswald, Germany. FU NCRR NIH HHS [RR 14466]; NIDDK NIH HHS [DK 50305] NR 26 TC 66 Z9 67 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2002 VL 169 IS 8 BP 4475 EP 4480 PG 6 WC Immunology SC Immunology GA 602NU UT WOS:000178512000053 PM 12370383 ER PT J AU Ghigo, E Capo, C Tung, CH Raoult, D Gorvel, JP Mege, JL AF Ghigo, E Capo, C Tung, CH Raoult, D Gorvel, JP Mege, JL TI Coxiella burnettii survival in THP-1 monocytes involves the impairment of phagosome maturation: IFN-gamma mediates its restoration and bacterial killing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TYPHIMURIUM-CONTAINING VACUOLES; AVIUM-CONTAINING PHAGOSOMES; TUMOR-NECROSIS-FACTOR; SALMONELLA-TYPHIMURIUM; Q-FEVER; MYCOBACTERIUM-AVIUM; MURINE MACROPHAGES; CELLS; PHAGOLYSOSOMES; ACIDIFICATION AB The subversion of microbicidal functions of macrophages by intracellular pathogens is critical for their survival and pathogenicity. The replication of Coxiella burnetii, the agent of Q fever, in acidic phagolysosomes of nonphagocytic cells has been considered as a paradigm of intracellular life of bacteria. We show in this study that C. burnetii survival in THP-1 monocytes was not related to phagosomal pH because bacterial vacuoles were acidic independently of C. burnetii virulence. In contrast, virulent C. burnetii escapes killing in resting THP-1 cells by preventing phagosome maturation. Indeed, C. burnetii vacuoles did not fuse with lysosomes because they were devoid of cathepsin D, and did not accumulate lysosomal trackers; the acquisition of markers of late endosomes and late endosomes-early lysosomes was conserved. In contrast, avirulent variants of C. burnetii were eliminated by monocytes and their vacuoles accumulated late endosomal and lysosomal markers. The fate of virulent C. burnetii in THP-1 monocytes depends on cell activation. Monocyte activation by IFN-gamma restored C. burnetii killing and phagosome maturation as assessed by colocalization of C. buruetii with active cathepsin D. In addition, when IFN-gamma was added before cell infection, it was able to stimulate C. burnetii killing but it also induced vacuolar alkalinization. These findings suggest that IFN-gamma mediates C. burnetii killing via two distinct mechanisms, phagosome maturation, and phagosome alkalinization. Thus, the tuning of vacuole biogenesis is likely a key part of C. burnetii survival and the pathophysiology of Q fever. C1 Inst Federatif Rech, CNRS UMR 6020, Unite Rickettsies, F-13385 Marseille 5, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Ctr Immunol Marseille Luminy, Marseille, France. RP Mege, JL (reprint author), Inst Federatif Rech, CNRS UMR 6020, Unite Rickettsies, 27 Blvd Jean Moulin, F-13385 Marseille 5, France. RI Eric, Ghigo/N-9427-2016; MEGE, JEAN-LOUIS/O-6063-2016 NR 33 TC 86 Z9 91 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2002 VL 169 IS 8 BP 4488 EP 4495 PG 8 WC Immunology SC Immunology GA 602NU UT WOS:000178512000055 PM 12370385 ER PT J AU Kohler, H Rodrigues, SP Maurelli, AT McCormick, BA AF Kohler, H Rodrigues, SP Maurelli, AT McCormick, BA TI Inhibition of Salmonella typhimurium enteropathogenicity by piperidine, a metabolite of the polyamine cadaverine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MODEL INTESTINAL EPITHELIUM; PROTEIN KINASE-C; NEUTROPHIL MIGRATION; BACTERIAL FLAGELLIN; IMMUNE-RESPONSE; CELLS; SECRETION; MEMBRANE; PATHOGENICITY; REQUIREMENT AB Piperidine is a 1-ring heterocyclic compound formed from the polyamine cadaverine in the human intestine. Because heterocyclic compounds are routinely used in the promotion of antimicrobial treatment strategies, it was considered whether piperidine could be used against infection with enteric pathogens. This study demonstrates that piperidine treatment prevented the invasion of Salmonella typhimurium into model intestinal epithelium by nearly 95%. In vivo studies also revealed that it increased mouse survival and reduced S. typhimurium translocation into and colonization of various organs and tissues. Initial evaluations demonstrated that piperidine reduced the S. typhimurium-induced polymorphonuclear leukocyte transepithelial migration response in vitro by inhibiting activation of protein kinase C. Piperidine did not affect the ability of S. typhimurium to elicit interleukin-8 secretion by epithelial cells or to activate extracellular-regulated kinase signal transduction pathways. These results show that piperidine does not exhibit paninhibitory activity and suggest that piperidine may be useful in down-regulating active inflammation at mucosal surfaces. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunil Lab, 114 16th St 114-3503, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 33506, DK 56754] NR 40 TC 9 Z9 10 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2002 VL 186 IS 8 BP 1122 EP 1130 DI 10.1086/344236 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 598YK UT WOS:000178304800010 PM 12355363 ER PT J AU Dedeoglu, A Kubilus, JK Jeitner, TM Matson, SA Bogdanov, M Kowall, NW Matson, WR Cooper, AJL Ratan, RR Beal, MF Hersch, SM Ferrante, RJ AF Dedeoglu, A Kubilus, JK Jeitner, TM Matson, SA Bogdanov, M Kowall, NW Matson, WR Cooper, AJL Ratan, RR Beal, MF Hersch, SM Ferrante, RJ TI Therapeutic effects of cystamine in a murine model of Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; cystamine; transglutaminase; glutamyl lysine; neuroprotection; transgenic R6/2 mice ID NEURONAL INTRANUCLEAR INCLUSIONS; TRANSGENIC MOUSE MODEL; AGGREGATES IN-VITRO; TISSUE TRANSGLUTAMINASE; POLYGLUTAMINE DOMAINS; GLUTAMINE REPEATS; NEURODEGENERATIVE DISEASES; EXPANDED POLYGLUTAMINE; CEREBROSPINAL-FLUID; NERVOUS-SYSTEM AB The precise cause of neuronal death in Huntington's disease (HD) is unknown. Proteolytic products of the huntingtin protein can contribute to toxic cellular aggregates that may be formed in part by tissue transglutaminase (Tgase). Tgase activity is increased in HD brain. Treatment in R6/2 transgenic HD mice, using the transglutaminase inhibitor cystamine, significantly extended survival, improved body weight and motor performance, and delayed the neuropathological sequela. Tgase activity and N-Sigma-(gamma-L-glutamyl)-L-lysine (GGEL) levels were significantly altered in HD mice. Free GGEL, a specific biochemical marker of Tgase activity, was markedly elevated in the neocortex and caudate nucleus in HD patients. Both Tgase and GGEL immunoreactivities colocalized to huntingtin aggregates. Cystamine treatment normalized transglutaminase and GGEL levels in R6/2 mice. These findings are consistent with the hypothesis that transglutaminase activity may play a role in the pathogenesis of HD, and they identify cystamine as a potential therapeutic strategy for treating HD patients. C1 Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Unit 182B, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. ESA Labs Inc, Chelmsford, MA 01824 USA. Cornell Univ, Presbyterian Hosp, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. Cornell Univ, Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurol Serv, Ctr Aging Genet & Neurodegenerat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Ferrante, RJ (reprint author), Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. RI Kowall, Neil/G-6364-2012; Cooper, Arthur/H-5171-2016 OI Kowall, Neil/0000-0002-6624-0213; FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG13846, AG 14930, AG12992]; NINDS NIH HHS [NS 38180, NS 39258, NS35255, NS37102] NR 56 TC 216 Z9 223 U1 1 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 OCT 15 PY 2002 VL 22 IS 20 BP 8942 EP 8950 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 605PQ UT WOS:000178686600019 PM 12388601 ER PT J AU Liu, HY Buenafe, AC Matejuk, A Ito, A Zamora, A Dwyer, J Vandenbark, AA Offner, H AF Liu, HY Buenafe, AC Matejuk, A Ito, A Zamora, A Dwyer, J Vandenbark, AA Offner, H TI Estrogen inhibition of EAE involves effects on dendritic cell function SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE EAE; estrogen; dendritic cells ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; BONE-MARROW CULTURES; IN-VIVO; IFN-GAMMA; MULTIPLE-SCLEROSIS; LARGE NUMBERS; FEMALE MICE; T-CELLS; MATURATION AB Estrogen has been found to have suppressive effects on the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. We have investigated the effects of 17beta-estradiol (E2) treatment on dendritic cells (DCs) in two different mouse models of EAE. The frequency of CD11b(+)/CD11c(+) DCs was significantly decreased in the brain of mice protected from EAE induction by E2 treatment. In addition, the frequency of CD11c(+)/CD8alpha(+) DCs producing tumor necrosis factor (TNF)alpha and interferon (IFN)gamma in the spleen of E2-treated mice was dramatically decreased compared to that in control mice with EAE, demonstrating an effect of E2 on DC function. In order to examine E2 effects on DCs in more detail, splenic DCs were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 to promote maturation. E2 pretreatment was found to suppress the ability of cultured DCs bearing a mature phenotype to present Ag to myelin basic protein (MBP)-specific T cells. Analysis of cytokine production demonstrated that E2 decreased TNFalpha, IFNgamma and IL-12 production in mature DCs. In addition, MBP-specific T cells cocultured with E2-pretreated mature DCs in the presence of antigen demonstrated a shift towards production of Th2 cytokines IL-4 and IL-10 and a concomitant decrease in the production of Th1 cytokines TNFa and IFNgamma. Thus, E2 treatment appears to have multiple effects on the DC population, which may contribute to a down-regulation or block in the activation of Th1 cells involved in the induction of EAE. (C) 2002 Wiley-Liss, Inc. C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW US Vets Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 40 TC 102 Z9 106 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD OCT 15 PY 2002 VL 70 IS 2 BP 238 EP 248 DI 10.1002/jnr.10409 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 600NG UT WOS:000178396700012 PM 12271473 ER PT J AU Stone, ME AF Stone, ME TI Anemia in women: Self-help and treatment. 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 OCT 15 PY 2002 VL 127 IS 17 BP 88 EP 88 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 602ZF UT WOS:000178533800148 ER PT J AU Ivan, M Haberberger, T Gervasi, DC Michelson, KS Gunzler, V Kondo, K Yang, HF Sorokina, I Conaway, RC Conaway, JW Kaelin, WG AF Ivan, M Haberberger, T Gervasi, DC Michelson, KS Gunzler, V Kondo, K Yang, HF Sorokina, I Conaway, RC Conaway, JW Kaelin, WG TI Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; FACTOR-RESPONSIVE GENE; PROLINE HYDROXYLATION; SMOOTH-MUSCLE; HIF-ALPHA; IN-VITRO; 4-HYDROXYLASE; BINDING; VHL; COMPLEX AB The product of the von Hippel-Lindau gene, pVHL, targets the alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF) for polyubiquitination in the presence of oxygen. The binding of pVHL to HIF is governed by the enzymatic hydroxylation of conserved prolyl residues within peptidic motifs present in the HIFalpha family members. By using a biochemical purification strategy, we have identified a human homolog of Caenorhabditis elegans Egl9 as a HIF prolyl hydroxylase. In addition, we studied the activity of a structurally diverse collection of low molecular weight inhibitors of procollagen prolyl 4-hydroxylase as potential inhibitors of the HIF hydroxylase. A model compound of this series stabilized HIF in a variety of cells, leading to the increased production of its downstream target, vascular endothelial growth factor. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02116 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02116 USA. FibroGen Inc, San Francisco, CA 94080 USA. Stowers Res Inst, Kansas City, MO 64110 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02116 USA. RI Ivan, Mircea/A-8109-2012; OI Conaway, Joan/0000-0002-2786-0663 NR 39 TC 370 Z9 381 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 2002 VL 99 IS 21 BP 13459 EP 13464 DI 10.1073/pnas.192342099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700023 PM 12351678 ER PT J AU Boyson, JE Rybalov, B Koopman, LA Exley, M Balk, SP Racke, FK Schatz, F Masch, R Wilson, SB Strominger, JL AF Boyson, JE Rybalov, B Koopman, LA Exley, M Balk, SP Racke, FK Schatz, F Masch, R Wilson, SB Strominger, JL TI CD1d and invariant NKT cells at the human maternal-fetal interface SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KILLER T-CELLS; COLONY-STIMULATING FACTOR; X DBA/2 MICE; PERIPHERAL-BLOOD; EXTRAVILLOUS TROPHOBLAST; TRYPTOPHAN CATABOLISM; SYSTEMIC TOLERANCE; MESSENGER-RNA; HLA-G; EXPRESSION AB Invariant CD1d-restricted natural killer T (iNKT) cells comprise a small, but significant, immunoregulatory T cell subset. Here, the presence of these cells and their CD1d ligand at the human maternal-fetal interface was investigated. Immunohistochemical staining of human decidua revealed the expression of CD1d on both villous and extravillous trophoblasts, the fetal cells that invade the maternal decidua. Decidual iNKT cells comprised 0.48% of the decidual CD3+ T cell population, a frequency 10 times greater than that seen in peripheral blood. Interestingly, decidual CID4+ iNKT cells exhibited a striking Th1-like bias (IFN-gamma production), whereas peripheral blood CD4+ iNKT clones exhibited a Th2-like bias (1L-4 production). Moreover, compared to their peripheral blood counterparts, decidual iNKT clones were strongly polarized toward granulocyte/macrophage colony-stimulating factor production. The demonstration of CD1d expression on fetal trophoblasts together with the differential pattern of cytokine expression by decidual iNKT cells suggests that maternal iNKT cell interactions with CD1d expressed on invading fetal cells may play an immunoregulatory role at the maternal-fetal interface. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. NYU, Med Ctr, Dept Obstet & Gynecol, New York, NY 10016 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Strominger, JL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. FU NCI NIH HHS [CA-47554]; NIAID NIH HHS [AI-50207, R01 AI050207]; NICHD NIH HHS [F32 HD008515, F32 HD008515-01, F32 HD008515-02, F32 HD008515-03] NR 50 TC 101 Z9 107 U1 1 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 OCT 15 PY 2002 VL 99 IS 21 BP 13741 EP 13746 DI 10.1073/pnas.162491699 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700073 PM 12368486 ER PT J AU Girnun, GD Smith, WM Drori, S Sarraf, P Mueller, E Eng, C Nambiar, P Rosenberg, DW Bronson, RT Edelmann, W Kucherlapati, R Gonzalez, FJ Spiegelman, BM AF Girnun, GD Smith, WM Drori, S Sarraf, P Mueller, E Eng, C Nambiar, P Rosenberg, DW Bronson, RT Edelmann, W Kucherlapati, R Gonzalez, FJ Spiegelman, BM TI APIC-dependent suppression of colon carcinogenesis by PPAR gamma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; FAMILIAL ADENOMATOUS POLYPOSIS; COLORECTAL-CANCER; BETA-CATENIN; SEQUENCE VARIANTS; DIABETES-MELLITUS; PROTEIN-KINASE; MOUSE MODEL; APC; EXPRESSION AB Activation of PPARgamma by synthetic ligands, such as thiazoliclinediones, stimulates adipogenesis and improves insulin sensitivity. Although thiazolidinediones represent a major therapy for type 2 diabetes, conflicting studies showing that these agents can increase or decrease colonic tumors in mice have raised concerns about the role of PPARgamma in colon cancer. To analyze critically the role of this receptor, we have used mice heterozygous for Ppargamma with both chemical and genetic models of this malignancy. Heterozygous loss of PPARgamma causes an increase in beta-catenin levels and a greater incidence of colon cancer when animals are treated with azoxymethane. However, mice with preexisting damage to Apc, a regulator of beta-catenin, develop tumors in a manner insensitive to the status of PPARgamma. These data show that PPARgamma can suppress beta-catenin levels and colon carcinogenesis but only before damage to the APC/beta-catenin pathway. This finding suggests a potentially important use for PPARgamma ligands as chemopreventative agents in colon cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06117 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Harvard Partners Ctr Genet & Genomics, Boston, MA 02115 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. FU NIDDK NIH HHS [F32 DK061313, R01 DK 57670, R01 DK057670, F32 DK 61313] NR 48 TC 168 Z9 175 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 2002 VL 99 IS 21 BP 13771 EP 13776 DI 10.1073/pnas.162480299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 604RW UT WOS:000178635700078 PM 12370429 ER PT J AU Cohen, SP Larkin, T Fant, GV Oberfoell, R Stojanovic, M AF Cohen, SP Larkin, T Fant, GV Oberfoell, R Stojanovic, M TI Does needle insertion site affect diskography results? A retrospective analysis SO SPINE LA English DT Article DE diskography; low back pain; lumbar disc ID INTERNAL DISC DISRUPTION; LOW-BACK-PAIN; ASYMPTOMATIC SUBJECTS; LUMBAR DISCOGRAPHY; SYMPTOMS; FUSION AB Study Design. A retrospective clinical data analysis was performed. Objectives. To determine the effect of needle insertion site on provocative diskography results, and to ascertain whether performing diskography ipsilaterally to a patient's reported pain leads to a higher rate of false-positives. Summary of Background Data. In certain groups of patients, provocative diskography is associated with a significant false-positive rate, which can lead to misdiagnosis and inappropriate treatment. Although purported by some to be a cause of false-positive diskogram results, the effect of needle insertion site on diskography results has yet to be determined. Methods. The charts of 127 patients who underwent diskography were evaluated to determine the relationship between the location of pain, needle insertion site, and diskography results. Results. Performing diskography on the side ipsilateral to a patient's pain did not result in a higher incidence of positive diskogram results. Conclusion. False-positive diskography results are unlikely to result from performing the procedure on the same side as a patient's reported pain. C1 NYU, Sch Med, Dept Anesthesiol, New York, NY 10016 USA. Walter Reed Army Med Ctr, Pain Management Ctr, Dept Anesthesia, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Clin Invest, Washington, DC 20307 USA. Massachusetts Gen Hosp, MGH Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Cohen, SP (reprint author), NYU, Sch Med, Dept Anesthesia, 550 1St Ave, New York, NY 10016 USA. NR 21 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 15 PY 2002 VL 27 IS 20 BP 2279 EP 2282 DI 10.1097/01.BRS.0000029259.85120.42 PG 4 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 605VH UT WOS:000178697400016 PM 12394907 ER PT J AU Lawrence, VA Hilsenbeck, SG Noveck, H Poses, RM Carson, JL AF Lawrence, VA Hilsenbeck, SG Noveck, H Poses, RM Carson, JL TI Medical complications and outcomes after hip fracture repair SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DISPLACED SUBCAPITAL FRACTURES; MULTIFACTORIAL RISK INDEX; MAJOR NONCARDIAC SURGERY; FEMORAL-NECK; INTERNAL-FIXATION; PULMONARY COMPLICATIONS; FEMUR; HEMIARTHROPLASTY; ARTHROPLASTY; OSTEOSYNTHESIS AB Background: Most evidence guiding perioperative medical risk management of patients undergoing hip fracture repair focuses on cardiac and thromboembolic risk. Little is known of the relative clinical importance of other complications. Objective: To systematically map incidence and outcomes of a broad spectrum of medical complications after hip fracture repair. Methods: Retrospective cohort study of patients 60 years or older in 20 academic, community, and Veterans Affairs hospitals. Data on complications and mortality were abstracted from medical records by trained abstractors using standardized, pretested forms or the National Death Index. Results: Of 8930 patients, 1737 (19%) had postoperative medical complications. Cardiac and pulmonary complications were most frequent (8% and 4% of patients, respectively). Similar numbers of patients had serious cardiac or pulmonary complications (2% and 3%, respectively). Other complications were gastrointestinal tract bleeding (2%), combined cardiopulmonary complications (1%), venous thromboembolism (1%), and transient ischemic attack or stroke (1%). Renal failure and septic shock were rare. After the index complication, 416 patients had 587 additional complications. Mortality was similar for serious cardiac or pulmonary complications (30 day: 22% and 17%, respectively; 1 year: 36% and 44%, respectively) and highest for patients with multiple complications (30 day: 29%-38%; 1 year: 43%-62%). Complications and death occurred significantly earlier for serious cardiac than for serious pulmonary complications (1 vs 4 days, 2 vs 8 days, P<.001); length of stay for patients surviving these complications was similar. Conclusions: Most patients had no medical complications after hip fracture repair. Serious cardiac and pulmonary complications were equally important in frequency, mortality, and survivors' length of stay. Patients with multiple complications had especially poor prognosis. C1 UTHSCSA, Dept Med, Div Gen Med, San Antonio, TX 78229 USA. UTHSCSA, S Texas Vet Hlth Care Syst, Div Gen Med, Audie L Murphy Div, San Antonio, TX 78229 USA. UTHSCSA, Div Med Oncol, San Antonio, TX 78229 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, Dept Med, New Brunswick, NJ USA. Brown Univ, Sch Med, Dept Med, Div Gen Internal Med, Providence, RI USA. Mem Hosp Rhode Isl, Pawtucket, RI USA. RP Lawrence, VA (reprint author), UTHSCSA, Dept Med, Div Gen Med, 7703 Floyd Curl Dr,Mail Code 7879, San Antonio, TX 78229 USA. FU AHRQ HHS [R01HSO7322] NR 62 TC 111 Z9 138 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 14 PY 2002 VL 162 IS 18 BP 2053 EP 2057 DI 10.1001/archinte.162.18.2053 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 603EP UT WOS:000178546100004 PM 12374513 ER PT J AU El-Serag, HB Graham, DY Richardson, P Inadomi, JM AF El-Serag, HB Graham, DY Richardson, P Inadomi, JM TI Prevention of complicated ulcer disease among chronic users of nonsteroidal anti-inflammatory drugs - The use of a nomogram in cost-effectiveness analysis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UPPER GASTROINTESTINAL TOXICITY; ANTIINFLAMMATORY DRUGS; PEPTIC-ULCER; RHEUMATOID-ARTHRITIS; HELICOBACTER-PYLORI; CONTROLLED TRIAL; DUODENAL-ULCERS; ELDERLY PERSONS; HIGH-RISK; MISOPROSTOL AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of clinical upper gastrointestinal tract (UGI) events, namely, symptomatic ulcer, perforation, bleeding, and obstruction. Our objective in this study was to compare the cost-effectiveness of several strategies aimed at reducing the risk of clinical UGI events in NSAID users. Methods: A decision tree model was used for patients requiring long-term treatment with NSAIDs to compare conventional NSAID therapy alone with 7 other treatment strategies to reduce the risk of NSAID-related clinical UGI events (cotherapy with proton-pump inhibitor, cotherapy with misoprostol, cyclooxygenase [COX]-2-selective NSAID therapy, or Helicobacter pylori treatment followed by each of the previous strategies, including conventional NSAID treatment, respectively). The outcome measure is the incremental cost per clinical UGI event prevented compared with conventional NSAID treatment over 1 year. Results: The use of a COX-2-selective NSAID and cotherapy with proton-pump inhibitors were the 2 most cost-effective strategies. However, the incremental cost associated with these strategies was high (>$35000) in persons with a low risk of clinical UGI event with conventional NSAIDs (eg, 2.5% per year). If the baseline risk of clinical UGI events is moderately high (eg, 6.5%), using a COX-2-selective NSAID becomes the most effective and least costly (dominant) treatment strategy, followed closely by cotherapy with a daily proton-pump inhibitor. Because small changes in costs or assumed efficacy of these drugs could change the conclusions, the incremental cost-effectiveness ratios between any 2 strategies were presented in a nomogram that allows the flexible use of a wide range of values for costs and rates of clinical UGI events. Conclusions: The risk of clinical UGI events in NSAID users depends on their baseline risk, the added risk associated with the individual NSAID, and the protection conferred by cotherapy. A nomogram can be used to incorporate these factors and derive estimates regarding cost-effectiveness of competing strategies aimed at reducing the risk of clinical UGI events. C1 Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res Sect, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Ann Arbor, MI USA. Hlth Serv Res & Dev Serv, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP El-Serag, HB (reprint author), Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res Sect, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. RI Inadomi, John/A-6221-2014 OI Inadomi, John/0000-0001-6776-8661 NR 32 TC 34 Z9 35 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 OCT 14 PY 2002 VL 162 IS 18 BP 2105 EP 2110 DI 10.1001/archinte.162.18.2105 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 603EP UT WOS:000178546100010 PM 12374519 ER PT J AU Takano, H Gusella, JF AF Takano, Hiroki Gusella, James F. TI The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor SO BMC NEUROSCIENCE LA English DT Article AB Background: Huntington's disease (HD) pathogenesis is due to an expanded polyglutamine tract in huntingtin, but the specificity of neuronal loss compared with other polyglutamine disorders also implies a role for the protein's unknown inherent function. Huntingtin is moderately conserved, with 10 HEAT repeats reported in its amino-terminal half. HD orthologues are evident in vertebrates and Drosophila, but not in Saccharomyces cerevisiae, Caenorhabditis elegans or Arabidopsis thaliana, a phylogenetic profile similar to the NF-kB/Rel/dorsal family transcription factors, suggesting a potential functional relationship. Results: We initially tested the potential for a relationship between huntingtin and dorsal by overexpression experiments in Drosophila S2 cells. Drosophila huntingtin complexes via its carboxyl-terminal region with dorsal, and the two enter the nucleus concomitantly, partly in a lipopolysaccharide (LPS)-and Nup88-dependent manner. Similarly, in HeLa cell extracts, human huntingtin co-immunoprecipitates with NF-kB p50 but not with p105. By cross-species comparative analysis, we find that the carboxyl-terminal segment of huntingtin that mediates the association with dorsal possesses numerous HEAT-like sequences related to those in the amino-terminal segment. Thus, Drosophila and vertebrate huntingtins are composed predominantly of 28 to 36 degenerate HEAT-like repeats that span the entire protein. Conclusion: Like other HEAT-repeat filled proteins, huntingtin is made up largely of degenerate HEAT-like sequences, suggesting that it may play a scaffolding role in the formation of particular protein-protein complexes. While many proteins have been implicated in complexes with the amino-terminal region of huntingtin, the NF-kB/Rel/dorsal family transcription factors merit further examination as direct or indirect interactors with huntingtin's carboxyl-terminal segment. C1 [Gusella, James F.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Dept Genet, Sch Med, Charlestown, MA 02129 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, MGH E Bldg 149,13th St, Charlestown, MA 02129 USA. EM hiroki@bri.niigata-u.ac.jp; gusella@helix.mgh.harvard.edu FU Wills Foundation; Huntington's Disease Society of America's Coalition for the Cure; [NS16367] FX We thank Robert J. Lake, Naoto Ito, Noriko Ito, Tadashi Uemura, Marcy E. MacDonald, Francesca Persichetti, and Paige Hilditch-Maguire for useful discussions and instruction and Peter A. Piepenhagen, and Spyros Artavanis- Tsakonas for help with confocal microscopy. H. T. was supported by a postdoctoral fellowship from the Wills Foundation. This work was also supported by NS16367 and the Huntington's Disease Society of America's Coalition for the Cure. NR 48 TC 73 Z9 75 U1 0 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2202 J9 BMC NEUROSCI JI BMC Neurosci. PD OCT 14 PY 2002 VL 3 AR 15 DI 10.1186/1471-2202-3-15 PG 13 WC Neurosciences SC Neurosciences & Neurology GA V11KP UT WOS:000207530800001 PM 12379151 ER PT J AU Maresca, KP Shoup, TM Femia, FJ Burker, MA Fischman, A Babich, JW Zubieta, J AF Maresca, KP Shoup, TM Femia, FJ Burker, MA Fischman, A Babich, JW Zubieta, J TI Synthesis, characterization, and biodistribution of a Technetium-99m '3+1' fatty acid derivative. The crystal and molecular structures of a series of oxorhenium model complexes SO INORGANICA CHIMICA ACTA LA English DT Article DE rhenium(V)-oxo core; fatty acids; heart imaging; metal-oxo complexes; rhenium-thiolate complexes ID PALMITIC ACID; METABOLISM; TOMOGRAPHY; C-11; MYOCARDIUM; KINETICS; INVIVO; TRACER; I-123 AB The '3 + 1' design of complexes of the {(ReO)-O-nu)(3+) core was exploited in the preparation of two series of compounds incorporating fatty acid components. In one case, the fatty acid subunit is attached to the monodentate ligand '1' of the [ReO(tridentate)(monodentate)] complex, with the tridentate component consisting of the sulfido-dithiolate donor, (SCH2CH2)(2)S}(2-), and represented by the complexes [ReO{eta(3)-(SCH2CH2)(2)S}{eta(1)-S(CH2)(4)CO2H}] (1) and [ReO{eta(3)-(SCH2CH2)(2)S} {eta(1)-S(CH2)(10)CO2H}] (2). The second series exhibits the fatty acid attachment at the tridentate site, {(SCH2CH2)(2)NR}(2-), in the complexes of the general type [ReO{eta(3)-(SCH2CH2)(2)NR}{eta(1)-SCH2C6H4X}] (4: R=-(CH2)(7)CH3, X= -Cl; 5: R=-(CH2)(7)CH3, X = -Br; 6: R = -(CH2)(7)CH3, X = -OCH3) and [ReO{eta(3)-(SCH2CH2)(2){eta1-SCH2C6H4X}] (7: R = -(CH2)(7)CH3, X = Cl; 8: R = -(CH2)(15)CH3, X = -H). Compounds I and 2 exhibit square-pyramidal geometry, while 4-8 approach more closely the trigonal bipyramidal prototype. The Tc-99m analogue [(TcO)-Tc-99m{eta(3) -(SCH2CH2)(2)N(CH2)(15)CO2H} {eta(1)-SCH2C6H5}] (9) was also prepared. Preliminary biodistribution studies in rats indicate poor heart-to-blood ratios (less than 1.0), suggesting that the complex is not a useful reagent for heart imaging. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Biostream Inc, Cambridge, MA 02142 USA. Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Babich, JW (reprint author), Biostream Inc, 160 2nd St, Cambridge, MA 02142 USA. NR 28 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0020-1693 J9 INORG CHIM ACTA JI Inorg. Chim. Acta PD OCT 14 PY 2002 VL 338 BP 149 EP 156 AR PII S0020-1693(02)01015-0 DI 10.1016/S0020-1693(02)01015-0 PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 607JA UT WOS:000178787400020 ER PT J AU Cichewicz, RH Lim, KC McKerrow, JH Nair, MG AF Cichewicz, RH Lim, KC McKerrow, JH Nair, MG TI Kwanzoquinones A-G and other constituents of Hemerocallis fulva 'Kwanzo' roots and their activity against the human pathogenic trematode Schistosoma mansoni SO TETRAHEDRON LA English DT Article DE anthraquinones; Hemerocallis fulva 'Kwanzo'; natural products; schistosomiasis ID ANTHRAQUINONES; PRAZIQUANTEL AB Schistosomiasis is a debilitating disease caused by parasitic trematodes of the genus Schistosoma that afflicts 200 million people worldwide. Daylilies (Hemerocallis spp.) have been used in Asia for the treatment of schistosomiasis; however, the active principles have not been fully characterized. In our studies of Hemerocallis fulva 'Kwanzo' Kaempfer roots, we have isolated seven new anthraquinones, kwanzoquinones A (1), B (2), C (4), D (5), E (6), F (7), and G (9), two known anthraquinones, 2-hydroxychry sophanol (3) and rhein (8), one new naphthalene glycoside, 5-hydroxydianellin (11), one known naphthalene glycoside, dianellin (10), one known flavone, 6-methylluteolin (12), and a-tocopherol. The structures of the compounds were elucidated by spectroscopic and chemical methods. Compounds 1-11 and the monoacetates of kwanzoquinones A and B, 1a and 2a, respectively, were tested for their activity against multiple life-stages of Schistosoma mansoni. Compound 3 immobilized all cercariae within 15 s at 3.1 mug/mL. However, upon removal of the compound, 20% of the immobilized cercariae recovered after 24 h. In contrast, compound 6 immobilized cercariae within 12-14 min at 25 mug/mL. Following removal of the compound, all cercariae died within 24 h. The adult worms were also immobilized within 16 h by compounds 3 and 6 at 50 mug/mL. None of the compounds had an effect on the schistosomula stage. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Michigan State Univ, Dept Hort, Bioact Nat Prod & Phytoceut, E Lansing, MI 48824 USA. Michigan State Univ, Natl Food Safety & Toxicol Ctr, E Lansing, MI 48824 USA. Univ Calif San Francisco, Dept Pathol & Cell & Mol Pharmacol, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Nair, MG (reprint author), Michigan State Univ, Dept Hort, Bioact Nat Prod & Phytoceut, E Lansing, MI 48824 USA. EM nairm@msu.edu RI Jansen, Nils/G-1835-2011 NR 28 TC 34 Z9 34 U1 1 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD OCT 14 PY 2002 VL 58 IS 42 BP 8597 EP 8606 AR PII S0040-4020(02)00802-5 DI 10.1016/S0040-4020(02)00802-5 PG 10 WC Chemistry, Organic SC Chemistry GA 604MF UT WOS:000178624700027 ER PT J AU Raychowdhury, R Fleming, JV McLaughlin, JT Bulitta, CJ Wang, TC AF Raychowdhury, R Fleming, JV McLaughlin, JT Bulitta, CJ Wang, TC TI Identification and characterization of a third gastrin response element (GAS-RE3) in the human histidine decarboxylase gene promoter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE histidine decarboxylase; gastrin response elements; transcription factors ID PHORBOL 12-MYRISTATE 13-ACETATE; CANCER CELLS; ACTIVATION; EXPRESSION; HISTAMINE; MESSENGER AB In human gastric cancer cells the human histidine decarboxylase gene is regulated by gastrin through two overlapping cis-acting elements known as gastrin response elements 1&2 (GAS-RE1, GAS-RE2) [J. Biol. Chem. 274 (1999) 20961]. Here, we report the identification and characterization of a third element GAS-RE3 that was localized to a region +28 to +48 downstream of the transcriptional start site (+1). Gastrin stimulation induced a rapid increase in binding to the element of a novel nuclear factor named gastrin response element-binding protein 3 (GAS-REBP3). Block mutations in the GAS-RE3 sequence ((+38)GTGCG(+42) to (+38)TAAGT(+42)) led to reduced promoter activity and decreased binding in EMSA. UV cross-linking studies and Southwestern blot analysis with wildtype and mutant GAS-RE3 showed that GAS-REBP3 was a similar to110 kDa protein. Thus, gastrin-mediated regulation of HDC gene expression appears to be mediated by a complex cis-acting element, which binds at least three distinct nuclear factors. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Wang, TC (reprint author), Univ Massachusetts, Med Ctr, Div Gastroenterol, LRB 208,364 Plantat St, Worcester, MA 01605 USA. OI McLaughlin, John/0000-0001-6158-5135 FU NIDDK NIH HHS [5 R01 DK48077-06] NR 25 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 11 PY 2002 VL 297 IS 5 BP 1089 EP 1095 AR PII S0006-291X(02)02345-8 DI 10.1016/S0006-291X(02)02345-8 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 605TH UT WOS:000178692800004 PM 12372397 ER PT J AU Nelson, RM Green, AR Hainsworth, AH AF Nelson, RM Green, AR Hainsworth, AH TI Electrophysiological actions of gamma-aminobutyric acid and clomethiazole on recombinant GABA(A) receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE GABA(A) receptor; GABA (gamma-aminobutyric acid)-mimetic; clomethiazole; neuroprotective agent; bicuculline ID ACUTE ISCHEMIC STROKE; INDUCED GLUTAMATE; RAT-BRAIN; IN-VITRO; CHLORMETHIAZOLE; CHANNEL; COMPLEX; PHARMACOLOGY; MODULATION; SUBTYPES AB Clomethiazole is a gamma-aminobutyric acid (GABA)-mimetic agent with anticonvulsant, sedative and neuroprotective properties. The pharmacological actions of clomethiazole that underlie its functional profile have not been fully explored, but are known to result from an interaction with the GABA(A) receptor. Here, we present a quantitative electrophysiological study of clomethiazole action at human recombinant GABA(A) receptors. Whole-cell currents were recorded from murine L(tk-) cells stably transfected with either alpha1, beta1 and gamma2 or alpha1, beta2 and gamma2 GABA(A) receptor subunits. Clomethiazole directly activated GABA(A) currents in alpha1/beta1/gamma2- and alpha1/beta2/gamma2-containing cells, with EC50 values of 0.3 and 1.5 mM, respectively. A low concentration of clomethiazole (30 muM) also potentiated the action of GABA in both cell types, equivalent to a 3-fold increase in potency and up to 1.8-fold increase in maximal current. Both direct activation and gamma-aminobutyric acid potentiation are likely to contribute to the in vivo profile of clomethiazole. (C) 2002 Elsevier Science B.V. All rights reserved. C1 De Montfort Univ, Sch Pharm, Pharmacol Res Grp, Leicester LE1 9BH, Leics, England. AstraZeneca R&D Charnwood, Loughborough LE11 5RH, Leics, England. RP Hainsworth, AH (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Room 6402,149 13th St, Charlestown, MA 02129 USA. NR 40 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 11 PY 2002 VL 452 IS 3 BP 255 EP 262 AR PII S0014-2999(02)02233-1 DI 10.1016/S0014-2999(02)02233-1 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 602XQ UT WOS:000178530100001 PM 12359265 ER PT J AU Dhe-Paganon, S Duda, K Iwamoto, M Chi, YI Shoelson, SE AF Dhe-Paganon, S Duda, K Iwamoto, M Chi, YI Shoelson, SE TI Crystal structure of the HNF4 alpha ligand binding domain in complex with endogenous fatty acid ligand SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROMOLECULAR STRUCTURES; NUCLEAR RECEPTORS; RETINOIC ACID; MUTATIONS; YOUNG; GENE; DIFFRACTION; MODY1; GAMMA; RAR AB HNF4alpha is an orphan member of the nuclear receptor family with prominent functions in liver, gut, kidney and pancreatic beta cells. We have solved the x-ray crystal structure of the HNF4alpha ligand binding domain, which adopts a canonical fold. Two conformational states are present within each homodimer: an open form with a helix 12 (alpha12) extended and collinear with alpha10 and a closed form with alpha12 folded against the body of the domain. Although the protein was crystallized without added ligands, the ligand binding pockets of both closed and open forms contain fatty acids. The carboxylic acid headgroup of the fatty acid ion pairs with the guanidinium group of Arg(226) at one end of the ligand binding pocket, while the aliphatic chain fills a long, narrow channel that is lined with hydrophobic residues. These findings suggest that fatty acids are endogenous ligands for HNF4alpha and establish a framework for understanding how HNF4alpha activity is enhanced by ligand binding and diminished by MODY1 mutations. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK43123, T32 DK07260] NR 24 TC 177 Z9 180 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 11 PY 2002 VL 277 IS 41 BP 37973 EP 37976 DI 10.1074/jbc.C200420200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602XK UT WOS:000178529600002 PM 12193589 ER PT J AU Chen, TP Ueda, Y Xie, SP Li, E AF Chen, TP Ueda, Y Xie, SP Li, E TI A novel Dnmt3a isoform produced from an alternative promoter localizes to euchromatin and its expression correlates with active de novo methylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA CYTOSINE-5 METHYLTRANSFERASES; EMBRYONIC STEM-CELLS; DE-NOVO; MAMMALIAN DEVELOPMENT; GERM-LINE; GENE; LETHALITY; MUTATION; CLONING; DOMAIN AB Previous studies have shown that the Dnmt3b gene encodes multiple variants via alternative splicing. However, only one form of Dnmt3a has been identified to date. We report here the discovery of a small form of Dnmt3a, denoted Dnmt3a2, from both human and mouse. The transcript encoding Dnmt3a2 is initiated from a downstream intronic promoter. As a result, the Dnmt3a2 protein lacks the N-terminal 223 (human) or 219 (mouse) amino acid residues of the full-length Dnmt3a. Recombinant Dnmt3a2 protein displayed similar cytosine methyltransferase activity as Dnmt3a in vitro. However, Dnmt3a and Dnmt3a2 exhibited strikingly different subcellular localization patterns. Unlike Dnmt3a, which was concentrated on heterochromatin, Dnmt3a2 displayed a localization pattern suggestive of euchromatin association. Dnmt3a2 is the predominant form in embryonic stem cells and embryonal carcinoma cells and can also be detected from testis, ovary, thymus, and spleen, whereas Dnmt3a is expressed at low levels ubiquitously. Comparison of human embryonal carcinoma cell lines with breast/ovarian cancer cell lines indicates that DNMT3A2 expression correlates with high de novo methylation activity. These findings suggest that Dnmt3a and Dnmt3a2 may have distinct DNA targets and different functions in development. C1 Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. OI Ueda, Yoshihide/0000-0003-3196-3494 FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 28 TC 183 Z9 193 U1 1 U2 13 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 OCT 11 PY 2002 VL 277 IS 41 BP 38746 EP 38754 DI 10.1074/jbc.M205312200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 602XK UT WOS:000178529600094 PM 12138111 ER PT J AU Mazarati, AM Wasterlain, CG AF Mazarati, AM Wasterlain, CG TI Anticonvulsant effects of four neuropeptides in the rat hippocampus during self-sustaining status epilepticus SO NEUROSCIENCE LETTERS LA English DT Article DE dynorphin A (1-13); galanin; neuropeptide Y; somatostatin; neuropeptide; hippocampus; status epilepticus ID TEMPORAL-LOBE EPILEPSY; ACID-TREATED RATS; SOMATOSTATIN; RELEASE; RECEPTORS; MODELS AB We compared the anticonvulsant actions of dynorphin A (1-13), galanin, neuropeptide Y and somatostatin in a model of self-sustaining status epilepticus (SSSE). SSSE was induced in adult Wistar rats by 30 min intermittent perforant path stimulation. Peptides or saline were injected into the hilus of the dentate gyrus 10 min after the end of perforant path stimulation. EEG was analyzed using Harmonie software (Stellate systems). While all neuropeptides showed significant seizureprotecting effects, their anticonvulsant profiles followed different patterns: somatostatin and NPY induced strong, but transient suppression of spikes and seizures, while seizure suppression by dynorphin and galanin was more profound and irreversible. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Adm Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Adm Med Ctr, Brain Res Inst, Los Angeles, CA 90073 USA. RP Mazarati, AM (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Adm Med Ctr, Dept Neurol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS 13515] NR 20 TC 46 Z9 48 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 11 PY 2002 VL 331 IS 2 BP 123 EP 127 AR PII S0304-3940(02)00847-9 DI 10.1016/S0304-3940(02)00847-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 605UW UT WOS:000178696300014 PM 12361856 ER PT J AU Hajjar, RJ MacRae, CA AF Hajjar, RJ MacRae, CA TI Adrenergic-receptor polymorphisms and heart failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 16 TC 18 Z9 19 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 OCT 10 PY 2002 VL 347 IS 15 BP 1196 EP 1199 DI 10.1056/NEJMe020105 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 601TW UT WOS:000178465100011 PM 12374881 ER PT J AU Lieberman, J AF Lieberman, J TI Defying death - HIV mutation to evade cytotoxic T lymphocytes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VARIANTS C1 Ctr Blood Res, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 5 TC 9 Z9 9 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 10 PY 2002 VL 347 IS 15 BP 1203 EP 1204 DI 10.1056/NEJMcibr022067 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 601TW UT WOS:000178465100014 PM 12374884 ER PT J AU Altshuler, L Mintz, J Leight, K AF Altshuler, L Mintz, J Leight, K TI The Life Functioning Questionnaire (LFQ): a brief, gender-neutral scale assessing functional outcome SO PSYCHIATRY RESEARCH LA English DT Article DE role function; functional impairment; bipolar disorder; assessment; quality of life ID CHRONICALLY MENTALLY-ILL; RELIABILITY; VALIDITY; ADJUSTMENT; REHABILITATION; SCHIZOPHRENIA; SCHEDULE; ILLNESS; WORK AB The Life Functioning Questionnaire (LFQ) is a 5-min, 14-item, gender-neutral self-report questionnaire designed to assess role function over the preceding month in four domains: workplace, duties at home, leisure time with family and leisure time with friends. To validate the LFQ for use as an instrument assessing functional outcome in patients with a mood disorder, the LFQ was administered to three different samples of patients (N=87). Fifty-nine concurrently completed the self-report version of the Social Adjustment Scale (SAS-SR) and 32 concurrently had a Clinical Global Impression Scale for Bipolar Disorder (CGI-BP) assessment. The LFQ proved to have high internal consistency reliability, high test-retest reliability, excellent concurrent validity with the SAS-SR, and high validity as a measurement of severity of illness when compared with the CGI-BP The LFQ provides a reliable, consistent and valid assessment of function at work and home in both male and female patients with a mood disorder. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mood Disorders Res Program, Los Angeles, CA 90095 USA. Vet Adm Med Ctr, W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. RP Altshuler, L (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Mood Disorders Res Program, 300 UCLA Med Plaza, Los Angeles, CA 90095 USA. NR 32 TC 38 Z9 38 U1 0 U2 2 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 OCT 10 PY 2002 VL 112 IS 2 BP 161 EP 182 AR PII S0165-1781(02)00180-4 DI 10.1016/S0165-1781(02)00180-4 PG 22 WC Psychiatry SC Psychiatry GA 624PC UT WOS:000179767500007 PM 12429362 ER PT J AU Petryshen, T McInnis, M Tahl, T Aldinger, A Daly, M DePaulo, R Lander, ES Sklar, P AF Petryshen, T McInnis, M Tahl, T Aldinger, A Daly, M DePaulo, R Lander, ES Sklar, P TI Linkage disequilibrium mapping of positional candidate genes in bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O5 BP 713 EP 714 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400048 ER PT J AU Sklar, P Smoller, J Freedman, M Daly, M Tahl, A McInnis, MG Bennett, P Lim, YM Kirov, G Jones, I Owen, M Rosenbaum, J Sachs, G Craddock, N DePaulo, JR Lander, ES AF Sklar, P Smoller, J Freedman, M Daly, M Tahl, A McInnis, MG Bennett, P Lim, YM Kirov, G Jones, I Owen, M Rosenbaum, J Sachs, G Craddock, N DePaulo, JR Lander, ES TI Family-based and case-control studies identify BDNF as a risk locus for bipolar disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Birmingham, Queen Elizabeth Psychiat Hosp, Birmingham B15 2TT, W Midlands, England. Columbia Univ, New York, NY USA. Univ Wales Coll Med, Cardiff CF4 4XN, S Glam, Wales. RI Jones, Ian/B-4925-2009; McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O40 BP 727 EP 727 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400083 ER PT J AU Van der Meulen, EM Bakker, SC Sandkuijl, LA Pauls, DL Monsuur, AJ Van 't Slot, R Minderaa, RB Gunning, WB Wijmenga, C Pearson, PL Buitelaar, JK Sinke, RJ AF Van der Meulen, EM Bakker, SC Sandkuijl, LA Pauls, DL Monsuur, AJ Van 't Slot, R Minderaa, RB Gunning, WB Wijmenga, C Pearson, PL Buitelaar, JK Sinke, RJ TI A genome wide scan of 166 Dutch sibpairs with attention-deficit hyperactivity disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. Massachusetts Gen Hosp, Unit Psychiat & Neurodev Genet, Boston, MA 02114 USA. Univ Ctr Child & Adolescent Psychiat, Groningen, Netherlands. Univ Ctr Child & Adolescent Psychiat, Amsterdam, Netherlands. Leiden Univ, Dept Med Stat, Med Ctr, NL-2300 RA Leiden, Netherlands. RI Buitelaar, Jan/E-4584-2012; Wijmenga, Cisca/D-2173-2009 OI Buitelaar, Jan/0000-0001-8288-7757; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O62 BP 735 EP 736 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400105 ER PT J AU Flores-Villanueva, PO Palha, JA McAlister, C Dobesova, LM Belmonte-de-Abreu, P Ruano, D Macedo, A Dourado, A Soares, M Valente, J Azevedo, MH Yunis, E Faraone, SV Tsuang, MT Goodman, AB AF Flores-Villanueva, PO Palha, JA McAlister, C Dobesova, LM Belmonte-de-Abreu, P Ruano, D Macedo, A Dourado, A Soares, M Valente, J Azevedo, MH Yunis, E Faraone, SV Tsuang, MT Goodman, AB TI SNP of retinoid X receptor (RXR) B at chromosome 6p21.3 associated with schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Biol Mol & Celular, Oporto, Portugal. Univ Fed Rio Grande Sul, Dept Psychiat, Porto Alegre, RS, Brazil. Univ Coimbra, Dept Psychiat, Coll Med, P-3000 Coimbra, Portugal. RI Belmonte-de-Abreu, Paulo/C-6634-2011; macedo santos, antonio/M-5737-2013 OI Belmonte-de-Abreu, Paulo/0000-0002-2853-2004; macedo santos, antonio/0000-0003-2180-2718 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O76 BP 741 EP 741 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400119 ER PT J AU Smoller, JW Rosenbaum, JF Biederman, J Kennedy, J Dai, D Racette, S Laird, N Tsuang, MT Slaugenhaupt, SA AF Smoller, JW Rosenbaum, JF Biederman, J Kennedy, J Dai, D Racette, S Laird, N Tsuang, MT Slaugenhaupt, SA TI Association of a marker at the corticotropin releasing hormone locus with behavioral inhibition SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Med Sch, Harvard Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O90 BP 746 EP 747 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400133 ER PT J AU Leonard, S Gault, J Logel, J Short, M Berger, R Drebing, C Olincy, A Ross, RG Adler, LE Freedman, R AF Leonard, S Gault, J Logel, J Short, M Berger, R Drebing, C Olincy, A Ross, RG Adler, LE Freedman, R TI Promoter mutations in the alpha 7 nicotinic acetylcholine receptor subunit gene are associated with an inhibitory deficit found in schizophrenia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA O96 BP 749 EP 749 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400139 ER PT J AU van der Meulen, EM Pauls, DL Faraone, SV Rogers, JT van de Giessen, EM Buitelaar, JK AF van der Meulen, EM Pauls, DL Faraone, SV Rogers, JT van de Giessen, EM Buitelaar, JK TI A genetic iron metabolism defect may be involved in the etiology of attention-deficit hyperactivity disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Utrecht, Netherlands. Massachusetts Gen Hosp, Unit Psychiat & Neurodev Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Aging Unit, Dept Psychiat Neurosci, Boston, MA 02114 USA. RI Buitelaar, Jan/E-4584-2012 OI Buitelaar, Jan/0000-0001-8288-7757 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA P193 BP 823 EP 824 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400344 ER PT J AU Medina, R Escamilla, M Dassori, A Contreras, S Levinson, D Raventos, H Montero, P Balderas, T Ontiveros, A Nicolini, H Mendoza, R Camacho, A Delgado, A AF Medina, R Escamilla, M Dassori, A Contreras, S Levinson, D Raventos, H Montero, P Balderas, T Ontiveros, A Nicolini, H Mendoza, R Camacho, A Delgado, A TI Cluster analysis of schizophrenia patients using lifetime dimensions of psychosis SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract CT 10th World Congress of Psychiatric Genetics CY OCT 09-13, 2002 CL BRUSSELS, BELGIUM C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, San Antonio, TX USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Costa Rica, San Jose, Costa Rica. Univ Nuevo Leon, Monterrey, Mexico. Inst Nacl Psiquiatria, Mexico City, DF, Mexico. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 2002 VL 114 IS 7 MA P292 BP 859 EP 859 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 600WH UT WOS:000178414400443 ER PT J AU Lu-Yao, G Albertsen, PC Stanford, JL Stukel, TA Walker-Corkery, ES Barry, MJ AF Lu-Yao, G Albertsen, PC Stanford, JL Stukel, TA Walker-Corkery, ES Barry, MJ TI Natural experiment examining impact of aggressive screening and treatment on prostate cancer mortality in two fixed cohorts from Seattle area and Connecticut SO BRITISH MEDICAL JOURNAL LA English DT Article ID SURVEILLANCE SERIES; INTERPRETING TRENDS; DEATH CERTIFICATES; RECENT DECLINES; SURVIVAL RATES; REGRESSION AB Objective To determine whether the more intensive screening and treatment for prostate cancer in the Seattle-Puget Sound area in 1987-90 led to lower mortality from prostate cancer than in Connecticut. Design Natural experiment comparing two fixed cohorts from 1987 to 1997. Setting Seattle-Puget Sound and Connecticut surveillance, epidemiology, and end results areas. Participants Population based cohorts of male Medicare beneficiaries aged 65-79 drawn from the Seattle (n=94 900) and Connecticut (n=1 20 62 1) areas. Main outcome measures Rates of screening for prostate cancer, treatment with radical prostatectomy and external beam radiotherapy, and prostate cancer specific mortality. Results The prostate specific antigen testing rate in Seattle was 5.39 (95% confidence interval 4.76 to 6.11) times that of Connecticut, and the prostate biopsy rate was 2.20 (1.81 to 2.68) times that of Connecticut during 1987-90. The 10 year cumulative incidences of radical prostatectomy and external beam radiotherapy tip to 1996 were 2.7% and 3.9% for Seattle cohort members compared with 0.5% and 3.1% for Connecticut cohort members. The adjusted rate ratio of prostate cancer mortality up to 1997 was 1.03 (0.95 to 1.11) in Seattle compared with Connecticut. Conclusion More intensive screening for prostate cancer and treatment with radical prostatectomy and external beam radiotherapy among Medicare beneficiaries in the Seattle area than in the Connecticut area was not associated with lower prostate cancer specific mortality over 11 years of follow up. C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. HealthStat, Princeton, NJ 08543 USA. Univ Connecticut, Ctr Hlth, Dept Surg, Div Urol, Farmington, CT 06030 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Program Prostate Canc Res, Seattle, WA 98109 USA. Dartmouth Coll, Sch Med, Ctr Evaluat Clin Sci, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. FU AHRQ HHS [R01 HS008397, R01 HS010278] NR 16 TC 139 Z9 142 U1 0 U2 4 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 OCT 5 PY 2002 VL 325 IS 7367 BP 740 EP 743 DI 10.1136/bmj.325.7367.740 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 603AU UT WOS:000178537300014 PM 12364300 ER PT J AU Noel, PH Pugh, JA AF Noel, PH Pugh, JA TI Management of overweight and obese adults SO BRITISH MEDICAL JOURNAL LA English DT Review ID PRIMARY-CARE; WEIGHT AB New treatment strategies have failed to control the global increase in obesity. Here two scientists discuss common barriers that need to be overcome by both healthcare professionals and patients if weight reduction is to be achieved and maintained. C1 S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr Excellence, San Antonio, TX 78229 USA. RP Noel, PH (reprint author), S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr Excellence, San Antonio, TX 78229 USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 30 TC 35 Z9 37 U1 0 U2 1 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 OCT 5 PY 2002 VL 325 IS 7367 BP 757 EP 761 DI 10.1136/bmj.325.7367.757 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 603AU UT WOS:000178537300021 PM 12364306 ER PT J AU Komatsuzaki, K Dalvin, S Kinane, TB AF Komatsuzaki, K Dalvin, S Kinane, TB TI Modulation of G(i alpha 2) signaling by the axonal guidance molecule UNC5H2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE G protein; signaling; G(i alpha 2); UNC5H2; MAPK ID GTPASE-ACTIVATING PROTEINS; HETEROTRIMERIC G-PROTEINS; SOMATOSTATIN RECEPTOR; TRANSITION-STATE; ADENYLYL-CYCLASE; ANTISENSE RNA; C-ELEGANS; IN-VIVO; FAMILY; GROWTH AB The G protein, G(ialpha2), regulates a number of cellular functions including cell migration, proliferation, and differentiation. The transduction of signal depends on the ability of the alpha subunit to cycle between a GDP bound and an active GTP bound state capable of interacting with intracellular enzymes. Here, we now report the novel interaction of gip2 (constitutively activated G(ialpha2)) with the cytoplasmic domain of UNC5H2. Like G(ialpha2), we found that UNC5H2 is widely expressed particularly in cells which migrate. UNC5H2 binds G(ialpha), when it is charged with GTP. The interaction of G(ialpha2) and UNC5H2 liberated adenylyl cyclase from G(ialpha2) inhibition. Thus, by sequestering the alpha subunit, UNC5H2 is a novel inhibitor of G(ialpha2) thereby increasing intracellular cAMP levels. The expression of UNC5H2 in the brain and immune system suggests that this novel inhibitor of G protein signaling may have broad significance for axonal guidance and chemotaxis. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Pulm Unit, Boston, MA 02114 USA. RP Kinane, TB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Pulm Unit, Jackson 14-GRJ 1416,55 Fruit St, Boston, MA 02114 USA. OI Dalvin, Sussie/0000-0002-6092-4710 NR 32 TC 16 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 4 PY 2002 VL 297 IS 4 BP 898 EP 905 AR PII S0006-291X(02)02277-5 DI 10.1016/S0006-291X(02)02277-5 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 603PY UT WOS:000178569700030 PM 12359238 ER PT J AU Levin, M Thorlin, T Robinson, KR Nogi, T Mercola, M AF Levin, M Thorlin, T Robinson, KR Nogi, T Mercola, M TI Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning SO CELL LA English DT Article ID MESSENGER-RNA LOCALIZATION; RIGHT AXIS FORMATION; CHICK-EMBRYO; DROSOPHILA OOCYTES; INTRACELLULAR PH; PRIMITIVE STREAK; XENOPUS EMBRYOS; BUDDING YEAST; GAP-JUNCTIONS; ALPHA-SUBUNIT AB A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Forsyth Inst, Cytokine Biol Dept, Boston, MA 02115 USA. Sahlgrens Univ Hosp, Inst Clin Neurosci, SE-41345 Gothenburg, Sweden. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP Mercola, M (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Nogi, Taisaku/C-7657-2009; Nogi, Taisaku/F-4675-2017 FU NHLBI NIH HHS [R01 HL63271] NR 85 TC 253 Z9 257 U1 3 U2 26 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 4 PY 2002 VL 111 IS 1 BP 77 EP 89 DI 10.1016/S0092-8674(02)00939-X PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 601RQ UT WOS:000178461900010 PM 12372302 ER PT J AU Shiojima, I Yefremashvili, M Luo, ZY Kureishi, Y Takahashi, A Tao, JZ Rosenzweig, A Kahn, CR Abel, ED Walsh, K AF Shiojima, I Yefremashvili, M Luo, ZY Kureishi, Y Takahashi, A Tao, JZ Rosenzweig, A Kahn, CR Abel, ED Walsh, K TI Akt signaling mediates postnatal heart growth in response to insulin and nutritional status SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEFT-VENTRICULAR MASS; REGULATE CARDIAC-HYPERTROPHY; PROTEIN-KINASE-B; P70 S6 KINASE; PHOSPHOINOSITIDE 3-KINASE; CELL-GROWTH; IN-VIVO; CARDIOMYOCYTE HYPERTROPHY; TRANSLATION INITIATION; MOLECULAR MECHANISMS AB Akt is a serine-threonine kinase that mediates a variety of cellular responses to external stimuli. During postnatal development, Akt signaling in the heart was up-regulated when the heart was rapidly growing and was down-regulated by caloric restriction, suggesting a role of Akt in nutrient-dependent regulation of cardiac growth. Consistent with this notion, reductions in Akt, 70-kDa S6 kinase 1, and eukaryotic initiation factor 4E-binding protein 1 phosphorylation were observed in mice with cardiac-specific deletion of insulin receptor gene, which exhibit a small heart phenotype. In contrast to wild type animals, caloric restriction in these mice had little effect on Akt phosphorylation in the heart. Furthermore, forced expression of Akt1 in these hearts restored 70-kDa S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1 phosphorylation to normal levels and rescued the small heart phenotype. Collectively, these results indicate that Akt signaling mediates insulin-dependent physiological heart growth during postnatal development and suggest a mechanism by which heart size is coordinated with overall body size as the nutritional status of the organism is varied. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. St Elizabeths Med Ctr, Div Cardiovasc Res, Boston, MA 02135 USA. Univ Utah, Sch Med, Program Human Biol & Genet, Salt Lake City, UT 84112 USA. Massachusetts Gen Hosp E, Program Cardiovasc Gene Therapy, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Walsh, K (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 715 Albany St, Boston, MA 02118 USA. RI Bando, Yasuko/M-4831-2014 FU NHLBI NIH HHS [HL59521, HL50692, HL61557, HL62886, HL66957]; NIA NIH HHS [AG15052, AG17241]; NIAMS NIH HHS [AR40197]; NIDDK NIH HHS [DK58073, R01 DK092065] NR 68 TC 133 Z9 138 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 4 PY 2002 VL 277 IS 40 BP 37670 EP 37677 DI 10.1074/jbc.M204572200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LH UT WOS:000178447100098 PM 12163490 ER PT J AU Zago, L Tzourio-Mazoyer, N AF Zago, L Tzourio-Mazoyer, N TI Distinguishing visuospatial working memory and complex mental calculation areas within the parietal lobes SO NEUROSCIENCE LETTERS LA English DT Article DE positron emission tomography; superior parietal cortex; calculation; supramarginal gyrus; angular gyrus; left hemisphere; visuospatial working memory ID PET; CORTEX; BRAIN AB The present study was aimed at differentiate, within the parietal cortex, the areas underlying visuospatial working memory/attentionnal processes and those devoted to arithmetic processing. We compared, using positron emission tomography, the cerebral networks activated in two groups of subjects, one solving two-by-two digit numbers multiplications and the other performing a visuospatial non-numerical N-Back task. Both tasks were compared to a resting state and a control condition. During both tasks, activation was observed, bilaterally, in superior parietal areas reflecting visuospatial working memory and attentionnal processes shared by both tasks. The calculation task elicited more activation in the left inferior parietal lobule and the left precuneus. These areas could subtend numerical representation, numbers storage and retrieval processes. These results added some strong support for a special role of the left inferior parietal areas in arithmetic processing. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Caen, Grp Imagerie Neurofonct, UMR 6095, CNRS,CEA,GIP Cyceron, F-14032 Caen, France. RP Zago, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, NMR Ctr, Dept Radiol,Sch Med, 149 13th St, Charlestown, MA 02129 USA. RI Tzourio-Mazoyer, Nathalie/B-5598-2008; Zago, Laure/B-7124-2008; GINSPAN, All/B-8714-2008 OI Tzourio-Mazoyer, Nathalie/0000-0002-6236-4390; NR 19 TC 53 Z9 59 U1 2 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 4 PY 2002 VL 331 IS 1 BP 45 EP 49 AR PII S0304-3940(02)00833-9 DI 10.1016/S0304-3940(02)00833-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 604XN UT WOS:000178646500012 PM 12359320 ER PT J AU Freed, LA Benjamin, EJ Levy, D Larson, MG Evans, JC Fuller, DL Lehman, B Levine, RA AF Freed, LA Benjamin, EJ Levy, D Larson, MG Evans, JC Fuller, DL Lehman, B Levine, RA TI Mitral valve prolapse in the general population - The benign nature of echocardiographic features in the Framingham Heart Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PAPILLARY-MUSCLE TRACTION; TERM FOLLOW-UP; HYPERTROPHIC CARDIOMYOPATHY; DIMENSIONAL ECHOCARDIOGRAPHY; CLINICAL-FEATURES; REQUIRING SURGERY; YOUNG-WOMEN; REGURGITATION; PREVALENCE; MOTION AB OBJECTIVES The aim of this study was to examine the echocardiographic features and associations of mitral valve prolapse (MVP) diagnosed by current two-dimensional echocardiographic criteria in an unselected outpatient sample. BACKGROUND Previous studies of patients with MVP have emphasized the frequent occurrence of echocardiographic abnormalities such as significant mitral regurgitation (MR) and left atrial (LA) enlargement that are associated with clinical complications. These studies, however, have been limited by the use of hospital-based or referral series. METHODS We quantitatively studied all 150 subjects with possible MVP by echocardiography and 150 age- and gender-matched subjects without MVP from the 3,491 subjects in the Framingham Heart Study. Based on leaflet morphology, subjects were classified as having classic (n = 46), nonclassic (n = 37), or no MVP: RESULTS Leaflet length, MR degree, and LA and left ventricular size were significantly but mildly increased in MVP (p < 0.0001 to 0.004), with mean values typically within normal range. Average MR jet area was 15.1 +/- 1.4% (mild) in classic MVP and 8.9 +/- 1.5% (trace) in nonclassic MVP; MR was severe In only 3 of 46 (6.5%) subjects with classic MVP, and LA volume was increased in only 8.7% of those with classic MVP and 2.7% of those with nonclassic MVP. CONCLUSIONS Although the echocardiographic characteristics of subjects with MVP in the Framingham Heart Study differ from those without MVP, they display a far more benign profile of associated valvular, atrial, and ventricular abnormalities than previously reported in hospital-or referral-based series. Therefore, these findings may influence the perception of and approach to the outpatient with MVP. (C) 2002 by the American College of Cardiology Foundation. C1 Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Med, Cardiac Unit, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Dept Med, Cardiac Unit, 55 Fruit St,VBK 508, Boston, MA 02114 USA. OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038, HL38176, HL53702, K24 HL67434]; NINDS NIH HHS [5-R01-NS-17950-16] NR 74 TC 85 Z9 98 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 2 PY 2002 VL 40 IS 7 BP 1298 EP 1304 AR PII S0735-1097(02)02161-7 DI 10.1016/S0735-1097(02)02161-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 599FX UT WOS:000178324400014 PM 12383578 ER PT J AU Orlander, JD Barber, TW Fincke, BG AF Orlander, JD Barber, TW Fincke, BG TI The morbidity and mortality conference: The delicate nature of learning from error SO ACADEMIC MEDICINE LA English DT Article ID QUALITY ASSURANCE; MISTAKES; FALLIBILITY; PHYSICIANS; MEDICINE; IMPACT; CARE AB The morbidity and mortality conference (M&MC) appears to have sprung from the efforts of physicians to improve practice through the examination of medical errors and bad outcomes. The modern M&MC has had limited examination (and almost none outside surgery and anesthesia), but may be straying from the precepts from which it evolved. Learning from one's errors is important, but confronting them is difficult and is particularly delicate when done in conference. If the effort is successful, it can serve as a model. If unsuccessful, it can instead convey the lesson that attempting to learn from error is at best unproductive and at worst unpleasant. Thus, the M&MC is a double-edged sword, and particular attention should be given to the way that it is conducted. The authors review the historical roots and current literature on the M&MC, discusses relevant literature on medical error, and offers a definition, guiding principles, and a set of guidelines for a modern internal medicine M&MC. The ideas are presented not as a blueprint, but rather to stimulate a debate on the merits of establishing a framework for a working model, in order to refocus on the tradition of self-analysis and critical thinking in a manner that is productive for all participants. C1 Boston Univ, VA Boston Hlth Care Syst, Residency Program, Sect Gen Internal Med & Epidemiol, Boston, MA 02130 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Orlander, JD (reprint author), Boston Univ, VA Boston Hlth Care Syst, Residency Program, Sect Gen Internal Med & Epidemiol, 150 S Huntington Ave, Boston, MA 02130 USA. NR 27 TC 108 Z9 108 U1 1 U2 9 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 OCT PY 2002 VL 77 IS 10 BP 1001 EP 1006 DI 10.1097/00001888-200210000-00011 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 617MP UT WOS:000179365700010 PM 12377674 ER PT J AU Palevsky, PM Bunchman, T Tetta, C AF Palevsky, PM Bunchman, T Tetta, C TI The Acute Dialysis Quality Initiative - Part V: Operational characteristics of CRRT SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE hemofiltration; hemodialysis; continuous renal replacement therapy ID ACUTE-RENAL-FAILURE; CONTINUOUS VENOVENOUS HEMOFILTRATION; PLATELET-ACTIVATING-FACTOR; CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; CONTINUOUS HEMODIALYSIS; CYTOKINE REMOVAL; DETERMINANTS; CLEARANCE; HEMODIAFILTRATION; INFLAMMATION AB This report represents the consensus statement of the ADQI workgroup addressing the operational characteristics of continuous renal replacement therapy (CRRT). Issues addressed included the specific operational characteristics of continuous hemofiltration (HF), continuous hemodialysis (HD), and continuous hemodiafiltration (HDF) and the impact of these different modalities on solute removal. The relative roles of arteriovenous (AV) and venovenous (VV) modalities of therapy were also evaluated. The workgroup also addressed the optimal components of a CRRT system from an operational standpoint. (C) 2002 by the National Kidney Foundation, Inc. C1 VA Pittsburgh Healthcare Syst, Renal Sect 111FU, Univ Dr Div, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, US Vet Adm, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Alabama, Med Ctr, Dept Pediat Nephrol, Birmingham, AL 35294 USA. Bellco SpA, Clin & Lab Res Dept, Mirandola, Italy. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect 111FU, Univ Dr Div, Pittsburgh, PA 15240 USA. NR 24 TC 7 Z9 7 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 OCT PY 2002 VL 9 IS 4 BP 268 EP 272 DI 10.1053/jarr.2002.35567 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 672HV UT WOS:000182515900009 PM 12382230 ER PT J AU Geiben-Lynn, R AF Geiben-Lynn, R TI Anti-human immunodeficiency virus noncytolytic CD8(+) T-cell response: A review SO AIDS PATIENT CARE AND STDS LA English DT Article ID LONG TERMINAL REPEAT; LEUKEMIA INHIBITORY FACTOR; REVERSE TRANSCRIPTION; HIV-1 INFECTION; CHEMOKINE RECEPTORS; HUMAN THIOREDOXIN; GENE-EXPRESSION; MEDIATED SUPPRESSION; PRIMARY MACROPHAGES; BETA-CHEMOKINES AB The CD8(+) T-cell immune response for human immunodeficiency virus (HIV) is divided into a cytolytic and noncytolytic mechanism. The mechanism of cell-mediated cytotoxic immunity for the partial control of human immunodeficiency virus type 1 (HIV-1) replication in infected individuals is well-characterized, and the direct killing of virus-infected cells by antigen-specific cytotoxic T-lymphocytes (CTL) is widely correlated with disease outcome. However, the mechanism of the noncytolytic component is not well understood. In part, this is because the main inhibitory factor or factors called CD8(+) T-cell antiviral factor (CAF), have not yet been purified. In addition, results between the investigators are difficult to compare because of technical differences between laboratories, including the use of different in vitro cell expansion and stimulation methods for the CD8(+) T cells, the necessity of sequential biochemical purification steps with restricted amounts of material, the complex analysis and interpretation of gene expression arrays, the use of different HIV strains, and the use of different short- or long-term inhibition assays using primary or immortalized target cells. Nevertheless, the diminishing efficacy of highly active antiretroviral therapy (HAART) because of the development of resistant HIV and the persistence of latent HIV provides a strong rationale for an immune therapy approach using antiviral factor(s) of the CD8(+) T-cell noncytolytic immune response. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Geiben-Lynn, R (reprint author), 25 Hawthorne St,2, Watertown, MA 02472 USA. FU PHS HHS [A130914] NR 62 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT PY 2002 VL 16 IS 10 BP 471 EP 477 DI 10.1089/10872910260351249 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 607AV UT WOS:000178769000002 PM 12437858 ER PT J AU Rukstalis, MR Lynch, KG Oslin, DW Pettinati, HM Anderson, SM Volpicelli, JR Anton, RF AF Rukstalis, MR Lynch, KG Oslin, DW Pettinati, HM Anderson, SM Volpicelli, JR Anton, RF TI Carbohydrate-deficient transferrin levels reflect heavy drinking in alcohol-dependent women seeking treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE carbohydrate-deficient transferrin; gender; estradiol; alcohol dependence ID GAMMA-GLUTAMYL-TRANSFERASE; ADDICTION SEVERITY INDEX; PERCENT-CDT-TIA; OUTPATIENT ALCOHOLICS; BIOLOGICAL MARKERS; CONSUMPTION; POPULATION; SERUM; NALTREXONE; INDICATOR AB Background: Carbohydrate-deficient transferrin (CDT) is a biochemical marker that has been shown to be sensitive in detecting heavy drinking in men, but studies examining CDT in women have been inconsistent because of small sample sizes and failure to consider hormonal status. In healthy female subjects, CDT levels are significantly higher in premenopausal women with higher estradiol (E2) levels (>30 pg/ml) and those taking exogenous estrogens (oral contraceptives, hormone replacement therapy) compared with men and postmenopausal women. This study examined the relationship between drinking behavior and CDT levels in a large sample of alcohol-dependent women and contrasted findings in a comparison group of alcohol-dependent men. The study also examined the extent that E2 levels mediated the relationship between CDT levels and heavy drinking in the alcohol-dependent women. Methods: This study examined the association between CDT level at treatment entry and alcohol consumption the month before initiating treatment in 96 women with a DSM-III-R diagnosis of alcohol dependence, as compared with similar data in 123 male alcoholics. To explore the relationship between E2 and CDT, E2 was measured in women at the time of CDT sampling. Linear regression was used to examine whether patterns of alcohol consumption in the 28 days before the CDT blood sampling predicted the CDT level in women and men presenting for treatment for alcohol dependence. Results: CDT levels were higher in women than men and were related to quantitative alcohol consumption (total standard drinks, percentage of days drinking, percentage of days of heavy drinking) in the month before initiating treatment, irrespective of E2 levels in women. Conclusions: These results suggest that in a larger sample of female alcoholics, the amount of alcohol consumed predicted CDT, similar to what has been reported in male alcoholics. The E2 status did not seem to mediate these results. C1 Univ Penn, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Med Ctr Vet Affairs, Philadelphia, PA USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Rukstalis, MR (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [R01AA-09544, R01AA-07517, K23AA-00251]; NIMH NIH HHS [R01-MH55454, K08MH01599-01] NR 37 TC 2 Z9 3 U1 0 U2 0 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 OCT PY 2002 VL 26 IS 10 BP 1539 EP 1544 DI 10.1097/01.ALC.0000034155.71497.17 PG 6 WC Substance Abuse SC Substance Abuse GA 605AJ UT WOS:000178653000011 PM 12394287 ER PT J AU Angeja, BG de Lemos, J Murphy, SA Marble, SJ Antman, EM Cannon, CP Braunwald, E Gibson, CM AF Angeja, BG de Lemos, J Murphy, SA Marble, SJ Antman, EM Cannon, CP Braunwald, E Gibson, CM CA TIMI Study Grp TI Impact of diabetes mellitus on epicardial and microvascular flow after fibrinolytic therapy SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT ELEVATION; TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; CORONARY VASODILATION; STRONG PREDICTOR; MORTALITY; TRIAL; REPERFUSION; ANGIOPLASTY AB Background Patients with diabetes are at increased risk of death after acute myocardial infarction, independent of other baseline risk factors and more severe coronary artery disease. We studied the angiographic and electrocardiographic responses to thrombolytic agents in patients with diabetes; in particular ST-segment resolution as a measure of microvascular flow. Methods Angiography was performed in 2588 patients at 90 minutes after thrombolytic agent administration as well as after percutaneous coronary. intervention (PCI) in the Thrombolysis In Myocardial Infarction (TIMI) 4, 10A, 10B, and 14 trials. Electrocardiographic parameters were assessed at baseline and at 90 minutes in the TIMI 14 trial. Results compared with those without diabetes, patients with diabetes (347/2588 [13.4%]) were older, more often female, heavier, and less often smokers, and they had higher systolic blood pressure on admission. At angiography, they. more frequently had 3-vessel disease, well-developed collateral vessels, more distal culprit lesions; and smaller reference segment diameters. In the infarct-related artery, there was no relationship between diabetes and TIMI 3 flow at 90 minutes (55.4% vs 59.0% without diabetes) or after PCI, (83.7% vs 84.2%, both P = NS). Corrected TIMI frame counts were also similar at both time points. However, there was less frequent complete ST-segment resolution among diabetic patients, after thrombolysis (38.6% vs 49.2%, adjusted P = .04). Conclusion Thrombolysis and adjunctive/rescue PCI achieved equal rates of epicardial flow in patients with and without diabetes. However, diabetic patients had less complete ST-segment resolution, suggesting impaired microvascular flow. Abnormal microvascular flow may contribute at least in part to the poorer outcomes observed in patients with diabetes and acute myocardial infarction. C1 Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA 94143 USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX USA. Harvard Univ, Clin Res Inst, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Angeja, BG (reprint author), Univ Calif San Francisco, Dept Med, Div Cardiovasc, 505 Parnassus Ave,Moffitt M1182,Box 0124, San Francisco, CA 94143 USA. NR 35 TC 34 Z9 36 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 OCT PY 2002 VL 144 IS 4 BP 649 EP 656 DI 10.1067/mhj.2002.124869 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 600GU UT WOS:000178382900014 PM 12360161 ER PT J AU Walsh, CR Cupples, LA Levy, D Kiel, DP Hannan, M Wilson, PWF O'Donnell, CJ AF Walsh, CR Cupples, LA Levy, D Kiel, DP Hannan, M Wilson, PWF O'Donnell, CJ TI Abdominal aortic calcific deposits are associated with increased risk for congestive, heart failure: The Framingham Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY DISEASE; CONVERTING-ENZYME INHIBITOR; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; POPULATION; PROGRESSION; MORTALITY; PRESSURE; ULTRASOUND AB Objectives We sought to determine the association of aortic atherosclerosis, detected by calcific deposits in the abdominal aorta seen on lateral lumbar radiographs, with risk for congestive heart failure (CHF). Background Although the association between atherosclerotic coronary heart disease (CHID) and CHIF has been extensively studied, there are limited prospective data regarding the association of extracoronary atherosclerosis with CHF. Methods Lateral lumbar radiographs were obtained in 2467 Framingham Heart Study participants (1030 males and 1437 females) free of CHF in 1968. An abdominal aortic calcium (AAC) score was calculated for each subject based on the extent of calcium in the abdominal aorta. Proportional hazards models were used to test for associations between AAC score and CHF risk. Results There were 141 cases of CHF in men and 169 cases in women. In men, the multivariable-adjusted risk for CHF was increased for the second (hazards ratio [HR] 1.5, 95% CI 0.9-2.5) and third (HR 2.2, 95% CI 1.3-3.7) tertiles compared with the lowest tertile. Similarly, in women, the multivariable-adjusted risk for CHF was increased for the second (HR 1.8, 95% CI 1.1-2.9) and third (HR 3.2, 95% CI 2.0-5.1) tertiles compared with the lowest tertile. After further adjustment for CHID occurring prior to the onset of CHF, risk remained significantly increased for both men and women. Conclusions Atherosclerosis of the abdominal aorta is an important risk factor for CHF, independent of CHD and other risk factors. Noninvasive detection and quantification of atherosclerosis may be useful in identifying high-risk individuals likely to benefit from strategies aimed at preventing CHF. The possibility of a link between AAC and vascular compliance deserves further study. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Boston Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Hebrew Rehabil Ctr Aged, Sch Med, Res & Training Inst,Div Aging, Boston, MA 02215 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. OI Hannan, Marian/0000-0002-9586-6928; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038] NR 44 TC 66 Z9 68 U1 1 U2 2 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 OCT PY 2002 VL 144 IS 4 BP 733 EP 739 DI 10.1067/mhj.2002.124404 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 600GU UT WOS:000178382900025 PM 12360172 ER PT J AU Murphy, SA Chen, C Cannon, CP Antman, EM Gibson, CM AF Murphy, SA Chen, C Cannon, CP Antman, EM Gibson, CM CA TIMI Study Grp TI Impact of gender on angiographic and clinical outcomes after fibrinolytic therapy in acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; TRIAL; SEX; ABCIXIMAB; MORTALITY; WOMEN AB Although this study of 2,596 patients enrolled in the Thrombolysis In Myocardial Infarction angiographic trials showed that women are at higher risk for adverse outcomes after thrombolytic administration, differences in angiographic or electrocardiographic measures of reperfusion success before and after percutaneous coronary intervention do not appear to account for. the discrepancy. Both identified confounders such as differences in baseline characteristics, and unidentified confounders likely account for the poorer clinical outcomes among women. C1 Brigham & Womens Hosp, TIMI Study Grp, Dept Med, Boston, MA 02215 USA. Beth Israel Med Ctr, Boston, MA USA. RP Gibson, CM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Dept Med, 333 Longwood Ave, Boston, MA 02215 USA. NR 19 TC 10 Z9 10 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 OCT 1 PY 2002 VL 90 IS 7 BP 766 EP + AR PII S0002-9149(02)02608-5 DI 10.1016/S0002-9149(02)02608-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 601KE UT WOS:000178444200017 PM 12356395 ER PT J AU Bindra, PS Ruskin, JN Keane, D AF Bindra, PS Ruskin, JN Keane, D TI Usefulness of predischarge defibrillation testing after defibrillator implantation in hospitalized patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVERTER-DEFIBRILLATORS AB Keeping patients in the hospital to complete predischarge defibrillation testing after implantation of implantable cardiac defibrillator may be unnecessary because this study showed a 0% rate of defibrillation failure. All patients were successfully defibrillated after induction of ventricular fibrillation at predischarge testing with no significant change in the defibrillation energy requirement at implantation or predischarge. C1 Massachusetts Gen Hosp, Cardiac Unit, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Keane, D (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. NR 15 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 OCT 1 PY 2002 VL 90 IS 7 BP 798 EP + AR PII S0002-9149(02)02618-8 DI 10.1016/S0002-9149(02)02618-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 601KE UT WOS:000178444200028 PM 12356406 ER PT J AU Limprasert, P Murray, IVJ Tsuang, DW Leverenz, JB Lee, VMY Trojanowski, JQ La Spada, AR AF Limprasert, P Murray, IVJ Tsuang, DW Leverenz, JB Lee, VMY Trojanowski, JQ La Spada, AR TI Beta-synuclein transgenic mice show significant reductions in alpha-synuclein protein expression levels. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 0 TC 1 Z9 1 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 OCT PY 2002 VL 71 IS 4 SU S MA 11 BP 165 EP 165 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800012 ER PT J AU Wheeler, VC Lebel, LA Vrbanac, V Riele, HT MacDonald, ME AF Wheeler, VC Lebel, LA Vrbanac, V Riele, HT MacDonald, ME TI Mismatch repair gene Msh2 is a genetic modifier of CAG repeat instability and striatal-specific disease in HdhQ111 knock-in mice. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Netherlands Canc Inst, Div Mol Carcinogenesis, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 103 BP 184 EP 184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800105 ER PT J AU Bond, J Roberts, E Mochida, GH Askham, JM Walsh, CA Woods, CG AF Bond, J Roberts, E Mochida, GH Askham, JM Walsh, CA Woods, CG TI Identification of the MCPH5 gene suggests an evolutionary mechanism in the control of brain size. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 St Jamess Univ Hosp, Mol Med Unit, Leeds, W Yorkshire, England. Harvard Univ, Sch Med, Div Neurogenet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. St James Univ Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. RI woods, christopher/A-1361-2010 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 123 BP 188 EP 188 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800125 ER PT J AU Leach, NT Michaud, S Quade, BJ Ligon, AH Michelson, AM Maas, RL Korf, BR Herrick, SR Ferguson, HL Morton, CC AF Leach, NT Michaud, S Quade, BJ Ligon, AH Michelson, AM Maas, RL Korf, BR Herrick, SR Ferguson, HL Morton, CC TI Characterization of a t(X;2)(pl 1.2;q37) de novo associated with congenital anomalies: Positional identification of disrupted genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 179 BP 199 EP 199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800181 ER PT J AU Wade-Martins, R Innoue, R Asadi-Moghaddam, K Ranasinghe, M Chiocca, EA Saeki, Y AF Wade-Martins, R Innoue, R Asadi-Moghaddam, K Ranasinghe, M Chiocca, EA Saeki, Y TI The iBAC: an efficient high capacity genomic DNA expression system. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 193 BP 202 EP 202 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800195 ER PT J AU Gabriel, SB Schaffner, SF Reich, DE Sabeti, P Freedman, M Daly, MJ Altshuler, D AF Gabriel, SB Schaffner, SF Reich, DE Sabeti, P Freedman, M Daly, MJ Altshuler, D TI An extended analysis of haplotype structure in the human genome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Whitehead Inst, Inst Genome Res, Cambridge, MA 02142 USA. RI Schaffner, Stephen/D-1189-2011; Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 1 Z9 1 U1 0 U2 2 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 OCT PY 2002 VL 71 IS 4 SU S MA 206 BP 205 EP 205 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800207 ER PT J AU Reich, DE Gabriel, SB Goldstein, DB McDonald, GM Wilson, JF Sabeti, PC Thomas, MG Bradman, N Ward, R Ferrell, R Linares, AR Pearce, L Henderson, B Jorde, LB Altshuler, D Lander, ES AF Reich, DE Gabriel, SB Goldstein, DB McDonald, GM Wilson, JF Sabeti, PC Thomas, MG Bradman, N Ward, R Ferrell, R Linares, AR Pearce, L Henderson, B Jorde, LB Altshuler, D Lander, ES TI Haplotype structure and linkage disequilibrium in 26 worldwide populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MD SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Utah, Salt Lake City, UT USA. USC, Los Angeles, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Oxford, Oxford OX1 2JD, England. UCL, London WC1E 6BT, England. Whitehead Inst, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009; Thomas, Mark/A-2219-2012 OI Altshuler, David/0000-0002-7250-4107; Thomas, Mark/0000-0002-2452-981X NR 0 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2002 VL 71 IS 4 SU S MA 207 BP 205 EP 205 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800210 ER PT J AU Howlett, NG Taniguchi, T Olson, S Cox, B Waisfisz, Q de Die-Smulders, C Persky, N Grompe, M Joenje, H Pals, G Ikeda, H Fox, EA D'Andrea, AD AF Howlett, NG Taniguchi, T Olson, S Cox, B Waisfisz, Q de Die-Smulders, C Persky, N Grompe, M Joenje, H Pals, G Ikeda, H Fox, EA D'Andrea, AD TI Biallelic inactivation of BRCA2 in Fanconi Anemia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR USA. Free Univ Amsterdam, Dept Clin Genet & Human Genet, Ctr Med, Amsterdam, Netherlands. Acad Hosp Maastricht, Dept Clin Genet, Maastricht, Netherlands. Sapporo Med Univ, Sch Med, Dept Pathol, Sapporo, Hokkaido, Japan. RI Pals, Gerard/A-5198-2011 NR 0 TC 0 Z9 0 U1 1 U2 2 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 OCT PY 2002 VL 71 IS 4 SU S MA 379 BP 237 EP 237 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800382 ER PT J AU Brose, MS Volpe, P Kumar, M Rishi, I Einhorn, E Gerrero, R Herlyn, M Minna, J Wooster, R Stratton, MR F'utreal, PA AF Brose, MS Volpe, P Kumar, M Rishi, I Einhorn, E Gerrero, R Herlyn, M Minna, J Wooster, R Stratton, MR F'utreal, PA TI BRAF and RAS mutations inhuman lung cancer and melanoma SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Hosp Univ Penn, Dept Haematol & Med Oncol, Philadelphia, PA USA. Abramson Family Canc Res Inst, Philadelphia, PA USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. Wellcome Trust Sanger Inst, Hinxton, England. NR 0 TC 1 Z9 1 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 OCT PY 2002 VL 71 IS 4 SU S MA 432 BP 246 EP 246 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800433 ER PT J AU Herrick, SR Bosco, AF Bruns, GAP Eisenman, R Farra, C Ferguson, HL Gusella, JF Higgins, AW Korf, BR Ligon, AX Leach, NT Lemyre, E Kim, HG Maas, RL MacDonald, ME Michaud, S Michelson, AM Quade, BJ Williamson, RE Morton, CC AF Herrick, SR Bosco, AF Bruns, GAP Eisenman, R Farra, C Ferguson, HL Gusella, JF Higgins, AW Korf, BR Ligon, AX Leach, NT Lemyre, E Kim, HG Maas, RL MacDonald, ME Michaud, S Michelson, AM Quade, BJ Williamson, RE Morton, CC TI Developmental Genome Anatomy Project (DGAP): Mapping genes that cause congenital anomalies SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Hosp, Boston, MA 02115 USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Montreal, Montreal, PQ H3C 3J7, Canada. NR 0 TC 1 Z9 1 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 OCT PY 2002 VL 71 IS 4 SU S MA 730 BP 297 EP 297 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800731 ER PT J AU Sicinska, E Thomas, A Miron, PM AF Sicinska, E Thomas, A Miron, PM TI Chromosome specific aneuploidy rates in pregnancy loss: Use in development of FISH protocols when tissue culture fails. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 773 BP 304 EP 304 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800776 ER PT J AU Miron, PM Herrick, S Morton, CC Stoler, J Wikins-Haug, L Weremowicz, S AF Miron, PM Herrick, S Morton, CC Stoler, J Wikins-Haug, L Weremowicz, S TI Custom probes for PGD of acrocentric chromosome rearrangements: Use of the BAC resource consortium. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 805 BP 309 EP 309 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800807 ER PT J AU Chen, ZY Morton, CC Corey, DP AF Chen, ZY Morton, CC Corey, DP TI Expression profile of the human inner ear genes and the identification of candidate genes for genetic deafness. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 809 BP 311 EP 311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800811 ER PT J AU Caton, MM Jose, S Agular, PDC Hewett, J Breakefield, XO Ozelius, L AF Caton, MM Jose, S Agular, PDC Hewett, J Breakefield, XO Ozelius, L TI Characterization of torsin related proteins (Tor2A/Tor3A) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Albert Einstein Coll Med, Dept Mol Genet, Charlestown, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 865 BP 320 EP 320 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800865 ER PT J AU Folias, A Matkovic, M Bruun, D Reid, S Hejna, J Grompe, M D'Andrea, A Moses, R AF Folias, A Matkovic, M Bruun, D Reid, S Hejna, J Grompe, M D'Andrea, A Moses, R TI Direct interaction between the breast cancer tumor suppressor protein, BRCA1, and the Fanconi anemia protein, FANCA. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 876 BP 322 EP 322 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800879 ER PT J AU Korey, CA MacDonald, ME AF Korey, CA MacDonald, ME TI Palmitoyl-protein thioesterase 1 (PPT1) function in Drosophila: Towards a molecular understanding of infantile neuronal ceroid lipofuscinosis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 936 BP 332 EP 332 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800939 ER PT J AU Schneider, KA Brown, T Nancarrow, CM Recklitis, C Diller, L AF Schneider, KA Brown, T Nancarrow, CM Recklitis, C Diller, L TI Genetic counseling in a pediatric cancer clinic: Results of a pilot program. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 996 BP 342 EP 342 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025800992 ER PT J AU Stanton, VP Hahn, WC Wojcicki, W Olson, J Jasani, S Kwok, PY Surti, U AF Stanton, VP Hahn, WC Wojcicki, W Olson, J Jasani, S Kwok, PY Surti, U TI Derivation of immortal cell lines from monospermic complete hydatidiform moles: A new resource for haplotype discovery SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Variagenics, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. Magee Womens Res Inst, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1086 BP 358 EP 358 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801082 ER PT J AU DeMeo, DL Weiss, ST Drazen, JM Chapman, HA Reilly, JJ Ginns, LC Speizer, FE Silverman, EK AF DeMeo, DL Weiss, ST Drazen, JM Chapman, HA Reilly, JJ Ginns, LC Speizer, FE Silverman, EK TI Genetic epidemiology of severe, early-onset chronic obstructive pulmonary disease: Risk to relatives for sensitive spirometric phenotypes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Channing Labs, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 OCT PY 2002 VL 71 IS 4 SU S MA 1176 BP 373 EP 373 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801172 ER PT J AU Pezzolesi, MG Nam, M Nagase, T Klupa, T Dunn, JS Rich, SS Warram, JH Krolewski, AS AF Pezzolesi, MG Nam, M Nagase, T Klupa, T Dunn, JS Rich, SS Warram, JH Krolewski, AS TI Examination of candidate chromosomal regions for type 2 diabetes (T2DM) reveals evidence for a new susceptibility locus and potential epistatic effects. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1519 BP 430 EP 430 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801512 ER PT J AU Perry, RT Hill, WD Wiener, H Harrell, L Gearhart, DA Blacker, D Tanzi, RE McInnis, MG Bassett, SS Go, RCP Kutlar, F Kutlar, A AF Perry, RT Hill, WD Wiener, H Harrell, L Gearhart, DA Blacker, D Tanzi, RE McInnis, MG Bassett, SS Go, RCP Kutlar, F Kutlar, A TI A strong association of the XmnI promoter polymorphism of the gamma globin gene (HBG2) to Alzheimers Disease in the NIMH sibling dataset. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. VAMC, Augusta, GA USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Alabama, Birmingham, AL USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1540 BP 434 EP 434 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801537 ER PT J AU Moore, JM Blumenstiel, B DeFelice, M Roy, J Nguyen, H Hattangadi, N Lochner, A Daly, MJ Altshuler, D Gabriel, SB AF Moore, JM Blumenstiel, B DeFelice, M Roy, J Nguyen, H Hattangadi, N Lochner, A Daly, MJ Altshuler, D Gabriel, SB TI Implementation of high throughput SNP genotyping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Whitehead Inst, Ctr Genome Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1604 BP 444 EP 444 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801599 ER PT J AU Hutcheson, HB Olson, LM Bradford, Y Folstein, SE Santangelo, SL Sutcliffe, J Haines, JL AF Hutcheson, HB Olson, LM Bradford, Y Folstein, SE Santangelo, SL Sutcliffe, J Haines, JL TI Examination of candidate genes on chromosome 7 in autism. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Program Human Genet, Nashville, TN USA. Tufts Univ, New England Med Ctr Hosp, Sch Med, Dept Psychiat, Boston, MA 02111 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1613 BP 446 EP 446 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801607 ER PT J AU Ng, DPK Rogus, JJ Antonellis, A Canani, LH Makita, Y Moczulski, D Nam, M Walker, WH Smiles, A Warram, JH Krolewski, AS AF Ng, DPK Rogus, JJ Antonellis, A Canani, LH Makita, Y Moczulski, D Nam, M Walker, WH Smiles, A Warram, JH Krolewski, AS TI Investigation of human chromosome 3q for a major susceptibility gene for diabetic nephropathy using linkage disequilibrium mapping. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 NR 0 TC 1 Z9 1 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 OCT PY 2002 VL 71 IS 4 SU S MA 1615 BP 446 EP 446 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801608 ER PT J AU Li, YJ Pericak-Vance, MA Haines, JL Siddique, N McKenna-Yasek, D Martin, ER Hung, WY Sapp, P Allen, CI Chen, W Hosler, B Saunders, AM Dellefave, L Brown, RH Siddique, T AF Li, YJ Pericak-Vance, MA Haines, JL Siddique, N McKenna-Yasek, D Martin, ER Hung, WY Sapp, P Allen, CI Chen, W Hosler, B Saunders, AM Dellefave, L Brown, RH Siddique, T TI APOE promoter region is associated with age at onset of amyotrophic lateral sclerosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Day Neuromuscular Lab, Boston, MA 02114 USA. Vanderbilt Univ, Program Human Genet, Nashville, TN USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1636 BP 450 EP 450 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801639 ER PT J AU Allinghaml, RR Wiggs, JL Hauser, ER Hauser, MA Graham, FL LaRocque, KR Broomer, BW del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA AF Allinghaml, RR Wiggs, JL Hauser, ER Hauser, MA Graham, FL LaRocque, KR Broomer, BW del Bono, EA Shi, JR Haines, JL Pericak-Vance, MA TI Ordered subset analysis in primary open-angle glaucoma (POAG): Evidence for linkage to chromosomes 14 and 15. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1655 BP 453 EP 453 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801655 ER PT J AU Ramos, PS Kelly, JA Meyer, CM Leiran, AN Ortmann, WA Harley, JB Moser, KL AF Ramos, PS Kelly, JA Meyer, CM Leiran, AN Ortmann, WA Harley, JB Moser, KL TI A genome scan for lupus-related autoimmunity genes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Univ Minnesota, Dept Med, Div Rheumat & Autoimmune Dis, Minneapolis, MN 55455 USA. Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1673 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801673 ER PT J AU Rana, BK Gabriel, SB Schaffer, SF Daly, MJ Altshuler, D Schork, NJ AF Rana, BK Gabriel, SB Schaffer, SF Daly, MJ Altshuler, D Schork, NJ TI The power of genome-wide haplotype analyses for complex traits. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Univ Calif San Diego, Dept Psychiat, Polymorphism Res Lab, La Jolla, CA 92093 USA. MIT, Whitehead Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1671 BP 456 EP 456 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801672 ER PT J AU Malecki, MT Klupa, T Walus, M Czogala, W Bochenski, J Greenlaw, P Sieradzki, J AF Malecki, MT Klupa, T Walus, M Czogala, W Bochenski, J Greenlaw, P Sieradzki, J TI A role of hereditary hemochromatosis HFE gene mutations in susceptibility to type 2 diabetes mellitus in a Polish population. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Jagiellonian Univ, Dept Metab Dis, Krakow, Poland. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1803 BP 478 EP 478 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801803 ER PT J AU Larocque, KR Hauser, MA Wiggs, JL Broomer, B del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL Allingham, RR AF Larocque, KR Hauser, MA Wiggs, JL Broomer, B del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL Allingham, RR TI Primary open-angle glaucoma (POAG) candidate gene analysis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1821 BP 481 EP 481 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801821 ER PT J AU Bochenski, JP Wolkow, PP Canani, LH Smiles, A Pezzolesi, MG Warram, JH Krolewski, AS AF Bochenski, JP Wolkow, PP Canani, LH Smiles, A Pezzolesi, MG Warram, JH Krolewski, AS TI A polymorphism in ENPP-1 that is associated with ectopic ossification is also associated with diabetic end-stage renal disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, 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 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 OCT PY 2002 VL 71 IS 4 SU S MA 1854 BP 486 EP 486 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801855 ER PT J AU Chen, H Huo, Y Wang, N MacKinnon, DF Potash, JB Sklar, P DePaulo, R Ross, CA McInnis, MG AF Chen, H Huo, Y Wang, N MacKinnon, DF Potash, JB Sklar, P DePaulo, R Ross, CA McInnis, MG TI The expression pattern of 119 genes from the region of 18q21-22 that has shown linkage to bipolar disorder. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McInnis, Melvin/F-6963-2012 OI McInnis, Melvin/0000-0002-0375-6247 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 1855 BP 487 EP 487 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801856 ER PT J AU Walter, JW Allingham, RR Flor, JD LaRocque, KR Graham, FL Broomer, B del Bono, EA Haines, JL Pericak-Vance, MA Hauser, MA Wiggs, JL AF Walter, JW Allingham, RR Flor, JD LaRocque, KR Graham, FL Broomer, B del Bono, EA Haines, JL Pericak-Vance, MA Hauser, MA Wiggs, JL TI Optineurin sequence variants do not predispose to primary open angle glaucoma. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2002 VL 71 IS 4 SU S MA 1872 BP 489 EP 489 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801873 ER PT J AU Liu, XZ Ouyang, XM Xia, XJ Zheng, J Fang, L Pandya, A Du, LL Corey, D Katherine, KO Petit, C Smith, RJH Arnos, KS Dallos, P Balkany, T Nance, WE Chen, ZY AF Liu, XZ Ouyang, XM Xia, XJ Zheng, J Fang, L Pandya, A Du, LL Corey, D Katherine, KO Petit, C Smith, RJH Arnos, KS Dallos, P Balkany, T Nance, WE Chen, ZY TI Prestin, a cochlear motor protein, is defective in non-syndromic recessive deafness. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Univ Miami, Dept Otolaryngol D 48, Miami, FL 33152 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. Northwestern Univ, Auditory Physiol Lab, Dept Commun Sci & Disorders, Evanston, IL USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Gallaudet Univ, Dept Biol, Washington, DC 20002 USA. Inst Pasteur, CNRS URA 1968, Unit Gnt Dficits Senoriels, F-75724 Paris, France. Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. RI Zheng, Jing/F-5273-2017 NR 0 TC 0 Z9 0 U1 0 U2 2 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 OCT PY 2002 VL 71 IS 4 SU S MA 1991 BP 510 EP 510 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025801990 ER PT J AU Teixeira, CAF Espinola, JE Bessa, CJP Guimares, A Miranda, MCS Mcdonald, ME Ribeiro, MG Boustany, RMN AF Teixeira, CAF Espinola, JE Bessa, CJP Guimares, A Miranda, MCS Mcdonald, ME Ribeiro, MG Boustany, RMN TI Spectrum of mutations in the CLN6 gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Duke Univ, Durham, NC USA. Univ Porto, Dept Neurobiol Genet, Inst Mol & Cellular Biol, P-4100 Oporto, Portugal. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Hosp Geral Santo Antnio, Unidade Neuropatol, Oporto, Portugal. Univ Porto, Inst Cincias Biomdicas Abel Salazar, Dept Patol & Imunol, Oporto, Portugal. Inst Genet Med Porto, Unidade Enzimol, Oporto, Portugal. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 2221 BP 548 EP 548 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025802219 ER PT J AU Freedman, MF Reich, DE Gabriel, SB Sklar, PM Hirschhom, JN Altshuler, D AF Freedman, MF Reich, DE Gabriel, SB Sklar, PM Hirschhom, JN Altshuler, D TI The impact of population stratification in case-control studies. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Human-Genetics CY OCT 15-19, 2002 CL BALTIMORE, MARYLAND SP Amer Soc Human Genet, NICHHD, NCI, NIMH, Affymetrix Inc, Gentra Syst, NIDCD C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Whitehead Inst, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 71 IS 4 SU S MA 2353 BP 571 EP 571 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 594AC UT WOS:000178025802339 ER PT J AU Dabora, SL Roberts, P Nieto, A Perez, R Jozwiak, S Franz, D Bissler, J Thiele, EA Sims, K Kwiatkowski, DJ AF Dabora, SL Roberts, P Nieto, A Perez, R Jozwiak, S Franz, D Bissler, J Thiele, EA Sims, K Kwiatkowski, DJ TI Association between a high-expressing interferon-gamma allele and a lower frequency of kidney angiomyolipomas in TSC2 patients SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TUBEROUS SCLEROSIS COMPLEX; RENAL-CELL CARCINOMA; FIRST INTRON; GENE; DISEASE; POLYMORPHISM; REPEAT; LYMPHANGIOLEIOMYOMATOSIS; DISEQUILIBRIUM; PATHOGENESIS AB Tuberous sclerosis complex (TSC) is a familial hamartoma syndrome in which renal involvement is common and, at times, life threatening. We have investigated the potential effect of a non-TSC gene on renal disease in a cohort of 172 TSC patients with TSC2 mutations. Patients were genotyped for an interferon-gamma (IFN-gamma) microsatellite polymorphism, within intron 1, for which one common allele (allele 2, with 12 CA repeats) has been shown to have a higher expression of IFN-gamma. A chi(2) analysis was used to examine the association between IFN-gamma allele 2 and the development of kidney angiomyolipomas (KAMLs) in this TSC2 cohort. Because of the age-dependent development of KAMLs in TSC, we initially focused on the 127 patients who were >5 years old. Additional subgroup analyses were done to investigate the influence of age and gender. The transmission/disequilibrium test (TDT) was also performed in a subset of this cohort (46 probands) for whom parent and/or sibling samples were available for analysis. Both chi(2) analysis and TDT suggested an association between IFN-gamma allele 2 and the absence of KAMLs in patients who have known TSC2 mutations. Among the 127 patients who were >5 years old, KAMLs were present in 95 (75%) and were absent in 32 (25%). In the group with KAML present, the frequency of IFN-gamma allele 2 was 56%; in the group with KAML absent, the frequency of IFN-gamma allele 2 was significantly higher, at 78% (P = .02, by chi(2) analysis). The family-based TDT analysis gave similar results, with a TDT statistic (TDT chi(2) = 5.45) corresponding to a P value of .02. Subgroup analyses show that both age and gender may influence the impact of this association. Although these results should be replicated in other populations with TSC, the present study suggests that modifier genes play a role in the variable expression of TSC and also suggests a potential therapy for KAMLs in patients with TSC. C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Childrens Hosp, Div Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurogenet Lab, Boston, MA 02114 USA. Childrens Mem Hosp, Dept Child Neurol, Warsaw, Poland. Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. RP Dabora, SL (reprint author), Brigham & Womens Hosp, Div Hematol, 221 Longwood Ave,LMRC 301, Boston, MA 02115 USA. FU NCI NIH HHS [CA86248, R21 CA086248, R33 CA086248]; NINDS NIH HHS [R37 NS031535, NS31535, R01 NS031535] NR 38 TC 35 Z9 38 U1 0 U2 9 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 OCT PY 2002 VL 71 IS 4 BP 750 EP 758 DI 10.1086/342718 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 604HT UT WOS:000178613800005 PM 12192641 ER PT J AU Hand, CK Khoris, J Salachas, F Gros-Louis, F Lopes, AAS Mayeux-Portas, V Brewer, CG Brown, RH Meininger, V Camu, W Rouleau, GA AF Hand, CK Khoris, J Salachas, F Gros-Louis, F Lopes, AAS Mayeux-Portas, V Brewer, CG Brown, RH Meininger, V Camu, W Rouleau, GA TI A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q (vol 70, pg 251, 2001) SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Correction C1 McGill Univ, Ctr Res Neurosci, Montreal, PQ H3A 2T5, Canada. Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. McGill Univ, Montreal Genome Ctr, Ctr Hlth, Montreal, PQ H3A 2T5, Canada. Hop Gui De Chauliac, UNCD, Mol Unit, INSERM,Inst Biol, Montpellier, France. Hop Gui De Chauliac, Dept Neurol, Montpellier, France. Hop La Pitie Salpetriere, Serv Neurol, Div Mazarin, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hand, CK (reprint author), McGill Univ, Ctr Res Neurosci, Montreal, PQ H3A 2T5, Canada. NR 1 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2002 VL 71 IS 4 BP 1007 EP 1007 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 604HT UT WOS:000178613800032 ER PT J AU Weber, EJ Silverman, RA Callaham, ML Pollack, CV Woodruff, PG Clark, S Camargo, CA AF Weber, EJ Silverman, RA Callaham, ML Pollack, CV Woodruff, PG Clark, S Camargo, CA TI A prospective multicenter study of factors associated with hospital admission among adults with acute asthma SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACUTE BRONCHIAL-ASTHMA; MANAGEMENT; EMERGENCY; PERCEPTION; SEVERITY; GUIDELINES; PHYSICIANS; RELAPSE AB PURPOSE: We sought to determine patient characteristics associated with hospital admission after emergency, treatment for asthma, and whether disposition guidelines are followed. SUBJECTS AND METHODS: We performed a prospective multicenter cohort study involving 64 emergency departments in the United States and Canada. Consecutive adult patients with asthma exacerbations were interviewed, and their charts were reviewed using standardized protocols. Telephone follow-up at 2 weeks determined relapse. RESULTS: Of 1805 patients, 363 (20%; 95% confidence interval [CI]: 18% to 22%) were hospitalized. Among patients with severe exacerbations (final peak flow <50% of predicted), 122 (49%; 95% CI: 43% to 55%) were hospitalized. Admission was associated with final peak flow, female sex, nonwhite race, severity of chronic illness, and severity of exacerbation. Admission predictors were similar regardless of hospital funding, re-gion, or size. Among patients with mild or moderate exacerbations of asthma (peak flow greater than or equal to50% predicted), the likelihood of admission was associated significantly with the number of predefined risk factors for death from asthma. Of patients who were discharged from the emergency department, 62 (5%; 95% Cl: 4% to 6%) relapsed within 72 hours. Relapse was not associated with final peak flow (P = 0.39). CONCLUSION: Associations between patient characteristics and disposition were similar across sites. Despite guidelines to the contrary, half of patients with final peak flow <50% were discharged. After emergency department treatment and discharge, short-term relapse was uncommon among patients with asthma, suggesting that strict peak flow cutoffs may be unnecessary if risk factors in patients with mild or moderate exacerbations are considered. (C) 2002 by Excerpta Medica, Inc. C1 Univ Calif San Francisco, Emergency Dept, Div Emergency Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Pulm & Crit Care, San Francisco, CA 94143 USA. Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Pk, NY 11042 USA. Penn Hosp, Dept Emergency Med, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. RP Weber, EJ (reprint author), Univ Calif San Francisco, Emergency Dept, Div Emergency Med, Box 0208, San Francisco, CA 94143 USA. OI Callaham, Michael/0000-0003-2284-256X; Weber, Ellen/0000-0002-0094-1973 FU NHLBI NIH HHS [HL-03533, HL-63253] NR 31 TC 54 Z9 57 U1 2 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2002 VL 113 IS 5 BP 371 EP 378 AR PII S0002-9343(02)01242-1 DI 10.1016/S0002-9343(02)01242-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 607PF UT WOS:000178799400003 PM 12401531 ER PT J AU Wu, J Viguera, A Riley, L Cohen, L Ecker, J AF Wu, J Viguera, A Riley, L Cohen, L Ecker, J TI Mood disturbance in pregnancy and the mode of delivery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 14-19, 2002 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med DE pregnancy; depression; mode of delivery ID DEPRESSIVE SYMPTOMS; SOCIAL SUPPORT; PREVALENCE; PREDICTORS; OUTCOMES; ANXIETY; LABOR; RISK AB OBJECTIVE: In prior studies, mood disturbance has been associated with poor obstetric outcomes. The purpose of this study was to determine whether depression during pregnancy is associated with a higher frequency of cesarean or assisted vaginal delivery. STUDY DESIGN: A mood disorders questionnaire, which included the standardized Center for Epidemiologic Studies Depression Scale (CES-D), was offered to all antenatal patients in their early third trimester from January 1996 to December 1999 at the Massachusetts General Hospital. Maternal demographics and pregnancy outcome data were collected from a computerized database on 1697 patients who completed the surveys. A CES-D score of 16 or higher was considered to indicate significant depressive symptoms, Rates of cesarean section and assisted vaginal delivery in women with and without scores of 16 or higher were compared by using the chi(2) test. RESULTS: Of the study population, 264 women (15.6%) had CES-D scores of 16 or higher, Among all subjects, the cesarean section rate was 24.0%, and the assisted vaginal delivery rate was 10,0%. There was no statistically significant difference between the rate of cesarean section (26.5% vs 23.6%) or assisted vaginal delivery (8.0% vs 10.4%) in women with and without elevated CES-D scores (P =.34). These findings did not change when nulliparous and multiparous patients were analyzed separately, when the definition of patients at risk for depression was expanded to include women who indicated current or past use of antidepressants or when the cutoff CES-D score criteria was increased to 19 or 25. With our sample size, an alpha =.05 and a beta =.2, we had the power to detect a 7.5% difference between our two groups. CONCLUSION: Data from this study did not support a relationship between depressive symptoms during pregnancy and mode of delivery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Perinatal & Reprod Psychiat, Boston, MA USA. RP Wu, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 21 TC 44 Z9 45 U1 1 U2 4 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 OCT PY 2002 VL 187 IS 4 BP 864 EP 867 DI 10.1067/mob.2002.127126 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 606AJ UT WOS:000178709300010 PM 12388965 ER PT J AU Yu, EN Foster, CS AF Yu, EN Foster, CS TI Chronic postoperative endophthalmitis due to Pseudomonas oryzihabitans SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FLAVIMONAS-ORYZIHABITANS AB PURPOSE: To report a case of chronic postoperative endophthalmitis caused by the gram negative bacterium Pseudomonas oryzihabitans. DESIGN: Interventional case report. METHODS: A 77-year-old man was referred to our service for nonpainful uveitis in the right eye accompanied by increased intraocular pressure of 2 years' duration with onset 4 months after uncomplicated extracapsular cataract extraction and posterior chamber intraocular lens implantation. The uveitis partially responded to topical corticosteroid therapy but was recurrent with tapering of steroids. An anterior chamber tap and vitreous biopsies sent for cultures were negative. Owing to the persistence of inflammation despite intraocular vancomycin injection, the lens implant and capsule were removed and culture of the latter revealed the bacterium P. oryzihabitans. RESULTS: There was no recurrence of inflammation after removal of the lens implant and capsule. CONCLUSIONS: Unlike other gram-negative organisms, which are associated with poor outcomes, P. oryzihabitans may masquerade as chronic uveitis because of its low virulence. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 11 Z9 11 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 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2002 VL 134 IS 4 BP 613 EP 614 DI 10.1016/S0002-9394(02)01586-6 PG 2 WC Ophthalmology SC Ophthalmology GA 601KY UT WOS:000178446100021 PM 12383826 ER PT J AU Chen, MC Solomon, TE Salazar, EP Kui, R Rozengurt, E Soll, AH AF Chen, MC Solomon, TE Salazar, EP Kui, R Rozengurt, E Soll, AH TI Secretin regulates paracellular permeability in canine gastric monolayers by a Src kinase-dependent pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE secretin receptors; epidermal growth factor receptors; gastric mucosal defense; paracellular pathway; regulation of paracellular pathway; apical epidermal growth factor receptors; PP2; tyrosine kinases ID CHIEF CELL MONOLAYERS; GROWTH-FACTOR-ALPHA; TIGHT JUNCTIONS; TYROSINE PHOSPHORYLATION; PEPSINOGEN SECRETION; FAMILY KINASES; PROTECTION; EXPRESSION; RECEPTOR; CULTURE AB Previous studies found that epidermal growth factor (EGF) decreased paracellular permeability in gastric mucosa, but the other physiological regulators and the molecular mechanisms mediating these responses remain undefined. We investigated the role of secretin and Src in regulating paracellular permeability because secretin regulates gastric chief cell function and Src mediates events involving the cytoskeletal-membrane interface, respectively. Confluent monolayers were formed from canine gastric epithelial cells in short-term culture on Transwell filter inserts. Resistance was monitored in the presence of secretin with or without specific kinase inhibitors. Tyrosine phosphorylation of Src at Tyr(416) was measured with a site-specific phosphotyrosine antibody. Basolateral, but not apical, secretin at concentrations from 1 to 100 nM dose dependently increased resistance; this response was rapid and sustained over hours. PP2 (10 muM), a selective Src tyrosine kinase inhibitor, but not the inactive isomer PP3, abolished the increase in resistance by secretin but only modestly attenuated apical EGF effects. AG-1478 (100 nM), a specific EGF receptor tyrosine kinase inhibitor, attenuated the resistance increase to EGF but not secretin. Secretin, but not EGF, induced tyrosine phosphorylation of Src at Tyr(416) in a dose-dependent fashion, with the maximal response observed at 1 min. PP2, but not PP3, dramatically inhibited this tyrosine phosphorylation. Secretin increases paracellular resistance in gastric mucosa through a Src-mediated pathway, while the effect of EGF is Src independent. Src appears to mediate the physiological effects of this G(s)-coupled receptor in primary epithelial cells. C1 Univ Calif Los Angeles, Sch Med, CURE, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Inst Mol Biol, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Hlth Care Syst, Med Serv, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Hlth Care Syst, Res Serv, Los Angeles, CA USA. RP Soll, AH (reprint author), Vet Adm Wadsworth Hosp Ctr, Bldg 115,Rm 215,11301 Wilshire Blvd, Los Angeles, CA USA. FU NIDDK NIH HHS [DK-19984] NR 36 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2002 VL 283 IS 4 BP G893 EP G899 DI 10.1152/ajpgi.00429.2001 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 592BJ UT WOS:000177916600009 PM 12223349 ER PT J AU Holschneider, DP Maarek, JMI Harimoto, J Yang, J Scremin, OU AF Holschneider, DP Maarek, JMI Harimoto, J Yang, J Scremin, OU TI An implantable bolus infusion pump for use in freely moving, nontethered rats SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE drug delivery; functional neuroimaging; cerebral blood flow; iodo-antipyrine; autoradiography ID CEREBRAL BLOOD-FLOW; STRESS AB One of the current constraints on functional neuroimaging in animals is that to avoid movement artifacts during data acquisition, subjects need to be immobilized, sedated, or anesthetized. Such measures limit the behaviors that can be examined, and introduce the additional variables of stress or anesthetic agents that may confound meaningful interpretation. This study provides a description of the design and characteristics of a self-contained, implantable microbolus infusion pump (MIP) that allows triggering of a bolus injection at a distance in conscious, behaving rats that are not restrained or tethered. The MIP is externally triggered by a pulse of infrared light and allows in vivo bolus drug delivery. We describe application of this technology to the intravenous bolus delivery of iodo[C-14]antipyrine in a freely moving animal, followed immediately by lethal injection, rapid removal of the brain, and analysis of regional cerebral blood flow tissue radioactivity with the use of autoradiography. The ability to investigate changes in brain activation in nonrestrained animals makes the MIP a powerful tool for evaluation of complex behaviors. C1 Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Engn, Dept Biomed Engn, Los Angeles, CA 90089 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, LAC USC Hosp, Dept Psychiat, 1200 N State St,Rm 10-621, Los Angeles, CA 90033 USA. RI Kipke, Daryl/A-2167-2009 FU NIBIB NIH HHS [R01 EB000300] NR 18 TC 25 Z9 25 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2002 VL 283 IS 4 BP H1713 EP H1719 DI 10.1152/ajpheart.00362.2002 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 594DY UT WOS:000178034500052 PM 12234827 ER PT J AU Matthay, MA Bhattacharya, S Gaver, D Ware, LB Lim, LHK Syrkina, O Eyal, F Hubmayr, R AF Matthay, MA Bhattacharya, S Gaver, D Ware, LB Lim, LHK Syrkina, O Eyal, F Hubmayr, R TI Ventilator-induced lung injury: in vivo and in vitro mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE acute lung injury; macrophages; neutrophils ID RESPIRATORY-DISTRESS SYNDROME AB A lung-protective ventilator strategy significantly reduces mortality in patients with acute lung injury. Substantial progress has been made in understanding how mechanical stress can injure the lung, both in terms of alterations in barrier properties of the pulmonary endothelium and epithelium as well as in stimulating proinflammatory responses of macrophages and neutrophils. C1 Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, San Francisco, CA 94115 USA. Univ Calif San Francisco, Inst Cardiovasc Res, Dept Anesthesia, San Francisco, CA 94115 USA. Columbia Univ, Lung Biol Lab, New York, NY 10019 USA. Tulane Univ, Dept Biomed Engn, New Orleans, LA 70118 USA. Vanderbilt Univ, Dept Pulm & Crit Care Med, Nashville, TN 37232 USA. Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. Univ S Alabama, Dept Pediat, Mobile, AL 36604 USA. Mayo Clin & Mayo Fdn, Div Pulm & Crit Care, Rochester, MN 55905 USA. RP Matthay, MA (reprint author), Univ Calif San Francisco, Inst Cardiovasc Res, Dept Med, 505 Parnassus Ave,M-917, San Francisco, CA 94115 USA. RI Gaver, Donald/G-5347-2010 NR 15 TC 69 Z9 73 U1 0 U2 4 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 OCT PY 2002 VL 283 IS 4 BP L678 EP L682 DI 10.1152/ajplung.00154.2002 PG 5 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 592UD UT WOS:000177954500003 PM 12225942 ER PT J AU Bagby, SP LeBard, LS Luo, ZM Ogden, BE Corless, C McPherson, ED Speth, RC AF Bagby, SP LeBard, LS Luo, ZM Ogden, BE Corless, C McPherson, ED Speth, RC TI ANG II AT(1) and AT(2) receptors in developing kidney of normal microswine SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE developing kidney; AT(1); AT(2); quantitative autoradiography; swine ID ANGIOTENSIN TYPE-2 RECEPTOR; RAT-KIDNEY; BLOOD-PRESSURE; RENAL-CORTEX; SUBTYPE 2; EXPRESSION; TISSUES; RENIN; FETAL AB To identify an appropriate model of human renin-angiotensin system (RAS) involvement in fetal origins of adult disease, we quantitated renal ANG II AT(1) and AT(2) receptors (AT1R and AT2R, respectively) in fetal (90-day gestation, n = 14), neonatal (3-wk, n = 5), and adult (6-mo, n = 8) microswine by autoradiography ((125)I-labeled [Sar(1)Ile(8)]ANG II+cold CGP-42112 for AT1R, (125)I-CGP-42112 for AT2R) and by whole kidney radioligand binding. The developmental pattern of renal AT1R in microswine, like many species, exhibited a 10-fold increase postnatally (P < 0.001), with maximal postnatal density in glomeruli and lower density AT1R in extraglomerular cortical and outer medullary sites. With aging, postnatal AT1R glomerular profiles increased in size (P < 0.001) and fractional area occupied (P < 0.04), with no change in the number per unit area. Cortical levels of AT2R by autoradiography fell with age from congruent to 5,000 fmol/g in fetal kidneys to congruent to 60 and 20% of fetal levels in neonatal and adult cortex, respectively (P < 0.0001). The pattern of AT2R binding in postnatal pig kidney mimicked that described in human and simian, but not rodent, species: dense AT2R confined to discrete cortical structures, including pre- and juxtaglomerular, but not intraglomerular, vasculature. Our results provide a quantitative assessment of ANG II receptors in developing pig kidney and document the concordance of pigs and primates in developmental regulation of renal AT1R and AT2R. C1 Oregon Hlth Sci Univ, Div Nephrol, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Comparat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Washington State Univ, Sch Vet Med, Dept Vet & Comparat Anat, Pullman, WA 99164 USA. Washington State Univ, Sch Vet Med, Dept Physiol & Pharmacol, Pullman, WA 99164 USA. RP Bagby, SP (reprint author), Oregon Hlth Sci Univ, Div Nephrol, Dept Med, Suite 262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM bagbys@ohsu.edu FU NICHD NIH HHS [P01-HD-34430] NR 34 TC 17 Z9 19 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 OCT PY 2002 VL 283 IS 4 BP F755 EP F764 DI 10.1152/ajprenal.00313.2001 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 591HH UT WOS:000177873300019 PM 12217867 ER PT J AU Hendrick, V Altshuler, L AF Hendrick, V Altshuler, L TI Management of major depression during pregnancy SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HUMAN BREAST-MILK; MOTHER-INFANT PAIRS; LOW-BIRTH-WEIGHT; POSTNATAL DEPRESSION; COGNITIVE-DEVELOPMENT; MATERNAL STRESS; NURSING INFANTS; PEDIATRIC PSYCHOPHARMACOLOGY; INTERPERSONAL PSYCHOTHERAPY; POSTPARTUM DEPRESSION C1 W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Hendrick, V (reprint author), Univ Calif Los Angeles, Mood Disorders Res Program, Neuropsychiat Inst & Hosp, UCLA Med Plaza,Bldg 300,Suite 2345, Los Angeles, CA 90095 USA. NR 79 TC 22 Z9 22 U1 3 U2 10 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2002 VL 159 IS 10 BP 1667 EP 1673 DI 10.1176/appi.ajp.159.10.1667 PG 7 WC Psychiatry SC Psychiatry GA 600GR UT WOS:000178382700008 PM 12359670 ER PT J AU Golier, JA Yehuda, R Lupien, SJ Harvey, PD Grossman, R Elkin, A AF Golier, JA Yehuda, R Lupien, SJ Harvey, PD Grossman, R Elkin, A TI Memory performance in Holocaust survivors with posttraumatic stress disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHILDHOOD SEXUAL ABUSE; HIPPOCAMPAL VOLUME; COMBAT VETERANS; EXPLICIT MEMORY; CORTISOL-LEVELS; DEFICITS; DISSOCIATION; IMPLICIT; ATROPHY; PTSD AB Objective: The authors evaluated memory performance in Holocaust survivors and its association with posttraumatic stress disorder (PTSD) and age. Method: Memory performance was measured in Holocaust survivors with PTSD (N= 31) and without PTSD (N=16) and healthy Jewish adults not exposed to the Holocaust (N=35). Explicit and implicit memory were measured by paired-associate recall and word stem completion, respectively. Results: The groups did not differ by age or gender, but the survivors with PTSD had significantly fewer years of education and had lower estimated IQs than the survivors without PTSD and the nonexposed group. There was a significant overall group effect for paired-associate recall but not word stem completion. The survivors with PTSD recalled fewer semantically unrelated words than did the survivors without PTSD and the nonexposed group and fewer semantically related words than the nonexposed group. Of the survivors with PTSD, 36% performed at a level indicative of frank cognitive impairment. older age was significantly associated with poorer paired-associate recall in the survivors with PTSD but not in the other two groups. Conclusions: Markedly poorer explicit but not implicit memory was found in Holocaust survivors with PTSD, which may be a consequence of or a risk factor for chronic PTSD. Accelerated memory decline is one of several explanations for the significantly greater association of older age with poorer explicit memory in survivors with PTSD, which, if present, could increase the cognitive burden of this illness with aging. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. McGill Univ, Douglas Hosp, Res Ctr, Verdun, PQ, Canada. RP Golier, JA (reprint author), Bronx VAMC, Dept Psychiat 116A, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIMH NIH HHS [MH 49555] NR 42 TC 87 Z9 88 U1 1 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2002 VL 159 IS 10 BP 1682 EP 1688 DI 10.1176/appi.ajp.159.10.1682 PG 7 WC Psychiatry SC Psychiatry GA 600GR UT WOS:000178382700011 PM 12359673 ER PT J AU Deckersbach, T Savage, CR Curran, T Bohne, A Wilhelm, S Baer, L Jenike, MA Rauch, SL AF Deckersbach, T Savage, CR Curran, T Bohne, A Wilhelm, S Baer, L Jenike, MA Rauch, SL TI A study of parallel implicit and explicit information processing in patients with obsessive-compulsive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 11-14, 1999 CL TORONTO, CANADA SP Assoc Adv Behav Therapy AB Objective: This study examined implicit sequence learning in patients with obsessive-compulsive disorder (OCD) under dual-task conditions. Frontal-striatal networks support implicit learning and are implicated in the pathophysiology of OCD. Neuroimaging data suggest that during implicit learning, OCD patients use neural systems normally active during explicit learning to compensate for striatal dysfunction. Method: The authors examined implicit sequence learning in 25 OCD patients and 25 healthy comparison subjects using a dual-task paradigm, with subjects simultaneously engaged in an explicit memory task and an implicit learning task. They predicted that implicit learning in OCD subjects would be disrupted because concurrent explicit information-processing demands would prevent use of compensatory processes. Results: OCD patients failed to show evidence of implicit learning and exhibited a significant deficit in comparison with healthy subjects. Conclusions: These results are consistent with the hypothesis that concurrent explicit and implicit information-processing demands interfere with implicit learning in OCD patients. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 149-9102,Bldg 149,13th St,9th Floor, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH 60219] NR 7 TC 51 Z9 53 U1 3 U2 8 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2002 VL 159 IS 10 BP 1780 EP 1782 DI 10.1176/appi.ajp.159.10.1780 PG 3 WC Psychiatry SC Psychiatry GA 600GR UT WOS:000178382700026 PM 12359688 ER PT J AU Kuna, ST Brennick, MJ AF Kuna, ST Brennick, MJ TI Effects of pharyngeal muscle activation on airway pressure-area relationships SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE hypoglossus nerve; glossopharyngeus nerve; vagus nerve; velopharynx; oropharynx ID OBSTRUCTIVE SLEEP-APNEA; HYPOGLOSSAL NERVE-STIMULATION; ELECTRICAL-STIMULATION; FLOW MECHANICS; VOLUME BEHAVIOR; PATENCY; RAT AB Fiberoptic imaging in an isolated, sealed upper airway was performed in 10 decerebrate cats to determine the effect of pharyngeal muscle activation on airway pressure-area relationships. Bilateral cuff electrodes stimulated the distal cut ends of the following nerves: medial and lateral hypoglossus, glossopharyngeus, and pharyngeal branch of vagus. At given intraluminal pressures ranging from +6 to -6 cm H2O, cross-sectional area was measured in the rostral oropharynx, velopharynx, and caudal oropharynx, with and without nerve stimulation. A mixed model analysis of variance indicated a relatively constant increase in area across the pressure range with glossopharyngeal stimulation at any given level. Significant interactions between pressure and stimulation were present in the rostral oropharynx with medial hypoglossus stimulation and in the caudal oropharynx with independent and combined hypoglossal branch stimulation and pharyngeal branch of vagus stimulation. With stimulation of the hypoglossal nerves, greater increases in area in these regions occurred in the lower pressure ranges. Stimulation of the pharyngeal branch of the vagus caused a greater decrease in area at the higher pressure ranges in the caudal oropharynx and velopharynx. The results indicate that the mechanical effects of pharyngeal muscle activation depend not only on the region and muscles activated but also on the intraluminal pressure. C1 Philadelphia Vet Affairs Med Ctr, Primary Care & Consultat Med Serv, Philadelphia, PA 19104 USA. Univ Penn, Pulm Allergy & Crit Care Div, Dept Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA. RP Kuna, ST (reprint author), Philadelphia Vet Affairs Med Ctr, Primary Care & Consultat Med Serv, 111P,Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL-27520] NR 24 TC 27 Z9 29 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2002 VL 166 IS 7 BP 972 EP 977 DI 10.1164/rccm.200203-214OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 599YJ UT WOS:000178362600016 PM 12359656 ER PT J AU Eichhorn, JH Young, RH Clement, PB Scully, RE AF Eichhorn, JH Young, RH Clement, PB Scully, RE TI Mesodermal (Mifflerian) adenosarcoma of the ovary - A clinicopathologic analysis of 40 cases and a review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-27, 1999 CL SAN FRANCISCO, CALIFORNIA SP US & Canadian Acad Pathol DE adenosarcoma; mesodermal mixed tumor; ovary ID EXTRAUTERINE MULLERIAN ADENOSARCOMA; ENDOLYMPHATIC STROMAL MYOSIS; SARCOMATOUS OVERGROWTH; ENDOMETRIOSIS; UTERUS; TUMORS; CHEMOTHERAPY; PERITONEUM; RECURRENCE; ESTROGEN AB Forty cases of mesodermal adenosarcoma of the ovary occurred in women 30-84 years of age (mean 54 years). Abdominal discomfort and distension were the usual complaints. All the patients were treated with an oophorectomy, which was accompanied by a hysterectomy in 85%, a contralateral oophorectomy in 65%, and nonsurgical therapy in 28%. Tumor rupture occurred at or before the operation in 67% of the cases. Twenty-six tumors were stage 1, 11 stage 11, and 3 stage III. The tumors were unilateral in 97.5% of the cases and 5.5-50 cm (mean 14 cm) in greatest dimension; most of the tumors were predominantly solid but contained numerous small cysts. Microscopic examination revealed sarcomatous overgrowth in 12 tumors. Sex cord-like elements were present in six tumors (including four with sarcomatous overgrowth) and heterologous elements in five (including two with sarcomatous overgrowth). The highest mitotic index of the sarcomatous component was 1-25 (mean 6) mitotic figures per 10 high power fields. Only 6 of 26 women (23%) who were followed postoperatively for greater than or equal to5 years were free of tumor. In the other 20 patients recurrent tumor appeared at 0.4-6.6 years (mean 2.6 years) after operation as pure sarcoma (low grade or high grade) or adenosarcoma (with or without sarcomatous overgrowth). Eight women had additional recurrences, and four women had blood-borne metastases. One patient was alive at 15.7 years after the excision of pulmonary metastases. The 5-, 10-, and 15-year survival rates were 64%, 46%, and 30%, respectively. Age <53 years, tumor rupture, a high grade, and the presence of high-grade sarcomatons overgrowth appeared to be associated with recurrence or extraovarian spread. Ovarian adenosarcomas have a worse prognosis than uterine adenosarcomas, presumably because of the greater ease of peritoneal spread. Many of the tumors caused problems in differential diagnosis. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vancouver Gen Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Eichhorn, JH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, 32 Fruit St,Warren 105C, Boston, MA 02114 USA. NR 55 TC 54 Z9 58 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2002 VL 26 IS 10 BP 1243 EP 1258 DI 10.1097/01/PAS.0000029066.53683.4B PG 16 WC Pathology; Surgery SC Pathology; Surgery GA 599VT UT WOS:000178356400001 PM 12360039 ER PT J AU Delmonico, FL Murray, J AF Delmonico, FL Murray, J TI Interview with Dr Joseph Murray SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID DEATH; TRANSPLANTATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 15 TC 6 Z9 6 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 OCT PY 2002 VL 2 IS 9 BP 803 EP 806 DI 10.1034/j.1600-6143.2002.20901.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 603ZK UT WOS:000178591000001 ER PT J AU Lin, PH Kulbaski, MJ Terramani, TT Bush, RL Brinkman, WT Chen, CY Conklin, B Lumsden, AB AF Lin, PH Kulbaski, MJ Terramani, TT Bush, RL Brinkman, WT Chen, CY Conklin, B Lumsden, AB TI The regained referral ground and clinical practice of vena cava filter placement in vascular surgery SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southeastern-Surgical-Congress CY FEB 01-05, 2002 CL NASHVILLE, TENNESSEE ID INSERTION; PATTERNS; TRAUMA AB Interventional. radiologist rather than vascular surgeons have become the predominant clinicians placing inferior vena cava (IVC) filters since the percutaneous device was introduced more than a decade ago. We conducted a retrospective analysis of 592 patients treated at a single institution between 1987 and 2000 to determine the indications, referral pattern, and clinical outcome of IVC filter placement between the radiologist and surgeon groups. Before 1989 all filters were placed by surgeons in the operating room. The adoption of the percutaneous delivery method by radiologists in 1989 led to a dramatic increase in its practice volume accounting for 99 per cent of all filters placed from 1991 to 1993 (P < 0.001). The development of an endovascular program by the vascular surgeons in 1994 led to a steady increase in its IVC filter practice annually (P < 0.05) and accounted for 42 per cent of all filter placements in 2000. A distinct referral pattern also emerged as 74 per cent of all filter placements by surgeons were referred by surgical services. The proportion of filter placement for strict indications remained constant over time between the two groups (P = 0.86). The complications and survival rates were not significantly different between the two groups (P = 0.24). Percutaneous devices have dramatically increased the clinical volume of IVC filter placement by interventional radiologists. Vascular surgeons with endovascular interest are well suited to perform the procedure and can regain referral ground of IVC filter placement. C1 Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Michael E DeBakey Dept Surg, Houston, TX 77030 USA. Emory Univ, Sch Med, Dept Surg, Div Vasc Surg, Atlanta, GA 30322 USA. RP Lin, PH (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, 2002 Holcomb Blvd,112-OCL, Houston, TX 77030 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2002 VL 68 IS 10 BP 865 EP 870 PG 6 WC Surgery SC Surgery GA 605TG UT WOS:000178692700009 PM 12412712 ER PT J AU Ho, PM Rumsfeld, JS Lyons, E Every, NR Magid, DJ AF Ho, PM Rumsfeld, JS Lyons, E Every, NR Magid, DJ TI Lack of an association between medicare supplemental insurance and delay in seeking emergency care for patients with myocardial infarction SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 20-23, 1999 CL BOSTON, MASSACHUSETTS SP Soc Amer Emergency Med ID PRIVATE HEALTH-INSURANCE; THROMBOLYTIC THERAPY; COVERAGE; SERVICES; ACCESS; DEFIBRILLATION; ENROLLEES; AMERICANS; IMPACT; TRIAGE AB Study objective: Previous studies have shown that Medicare patients without supplemental insurance are less likely to receive preventive services, such as mammography. The effect of supplemental insurance on the appropriate use of emergency services is unknown. We sought to determine whether the absence of supplemental Medicare coverage is associated with increased delay in seeking care for acute myocardial infarction. Methods: In this retrospective cohort study, we compared the time from symptom onset to hospital arrival (the time-delay interval) in Medicare patients with and without supplemental insurance coverage who presented with an acute myocardial infarction to 1 of 19 hospitals in King County, WA, from 1989 to 1993. There were 1,373 patients with Medicare-only coverage and 2,050 patients with Medicare plus supplemental insurance coverage. Results: The age-, sex-, and race-adjusted median time delay was 135 minutes for the Medicare-only group and 130 minutes for the Medicare plus supplemental insurance group (P=.34; 95% confidence interval for median time-delay difference in minutes -5 to 10). There was no significant association between the presence of Medicare supplemental insurance coverage and time delay in Cox regression models, which also adjusted for event year, income, education, past cardiac history, and clinical symptoms. Conclusion: For this cohort of Medicare patients, the absence of supplemental insurance coverage did not lead to significantly increased delays in seeking care for myocardial infarction. Lack of supplemental insurance for Medicare patients might not have as great an effect on the use of emergency services as it has on other health care services. C1 Denver VA Med Ctr, Cardiol & Hlth Serv Res, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO USA. Colorado Permanente Med Grp, Clin Res Unit, Denver, CO USA. Univ Washington, Cardiovasc Outcomes Res Ctr, Seattle, WA 98195 USA. VA Puget Sound Healtcare Syst, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO USA. RP Ho, PM (reprint author), 1055 Clermont St 111B, Denver, CO 80220 USA. NR 23 TC 3 Z9 3 U1 1 U2 4 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 OCT PY 2002 VL 40 IS 4 BP 381 EP 387 DI 10.1067/mem.2002.125717 PG 7 WC Emergency Medicine SC Emergency Medicine GA 596ZP UT WOS:000178197400001 PM 12239492 ER PT J AU Cowper, DC Kubal, JD Maynard, C Hynes, DM AF Cowper, DC Kubal, JD Maynard, C Hynes, DM TI A primer and comparative review of major US mortality databases SO ANNALS OF EPIDEMIOLOGY LA English DT Review DE MeSH headings; databases; mortality; vital statistics; veterans ID NATIONAL-DEATH-INDEX; VETERAN POPULATION; VITAL STATUS; ASCERTAINMENT AB PURPOSE: Mortality data are important tools for research requiring vital status information. We reviewed the major mortality databases and mortality ascertainment services available in the United States, including the National Death Index (NDI), the Social Security Administration (SSA) files, and the Department of Veterans Affairs databases. METHODS: The content, reliability, and accuracy of mortality sources are described and compared. We also describe how investigators can gain access to these resources and provide further contact information. RESULTS: We reviewed the accuracy of major mortality sources. The sensitivity (i.e., the proportion of the true number of deaths) of the NDI ranged from 87.0% to 97.9%, whereas the sensitivity for the VA Beneficiary Identification and Records Locator System (BIRLS) ranged between 80.0% and 94.5%. The sensitivity of SSA files ranged between 83.0% and 83.6%. Sensitivity for the VA Patient Treatment File (PTF) was 33%. CONCLUSIONS: While several national mortality ascertainment services are available for vital status (i.e., death) analyses, the NDI information demonstrated the highest sensitivity and, currently, it is the only source at the national level with a cause of death field useful for research purposes. Researchers must consider methods used to ascertain vital status as well as the quality of the information in mortality databases. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Hines VA Hosp, VA Informat Resource Ctr, VIReC 578 151V, Dept Vet Affairs Hlth Serv Res, Hines, IL 60141 USA. Hines VA Hosp, Dev Serv Resource Ctr, Hines, IL 60141 USA. Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Hlth Serv Res & Dev Serv Ctr Excellence, Hines, IL USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Epidemiol Res & Informat Ctr, Seattle, WA USA. NW Ctr Outcomes Res Older Adults, Seattle, WA USA. Loyola Univ, Dept Med, Maywood, IL 60153 USA. RP Cowper, DC (reprint author), Hines VA Hosp, VA Informat Resource Ctr, VIReC 578 151V, Dept Vet Affairs Hlth Serv Res, POB 5000, Hines, IL 60141 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 16 TC 304 Z9 305 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2002 VL 12 IS 7 BP 462 EP 468 AR PII S1047-2797(01)00285-X DI 10.1016/S1047-2797(01)00285-X PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 594GN UT WOS:000178041400004 PM 12377423 ER PT J AU Abbruzzese, C Porrini, SC Mariani, B Gould, FK Mcabney, JP Monckton, DG Ashizawa, T Giacanelli, M AF Abbruzzese, C Porrini, SC Mariani, B Gould, FK Mcabney, JP Monckton, DG Ashizawa, T Giacanelli, M TI Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1 SO ANNALS OF NEUROLOGY LA English DT Article ID CTG REPEAT; SOMATIC INSTABILITY; CAG REPEAT; EXPANSIONS; MOSAICISM; HETEROGENEITY; STABILITY; MUSCLE; EVENTS; GENE AB Myotonic dystrophy type I (DM1) is caused by the expansion of an unstable CTG repeat in the DMPK gene on chromosome 19q13.3. We present two siblings with DM1 who each inherited a premutation allele, (CTG)(43), stably transmitted from the mother and a full-mutation allele, either (CTG)(500) or (CTG)(180), derived from a paternal protomutation allele, (CTG)(52). Small-pool polymerase chain reaction analysis showed that the (CTG)(52) repeat allele was relatively stable in somatic tissues but was highly unstable in the male germline and extremely biased toward further expansion, consistent with the high levels of anticipation observed in DM1 families. The (CTG)(43) allele showed subtle somatic instability in the mother, with maximum additions of two repeats and deletions of one repeat. Conversely, in the younger affected siblings the (CTG)(43) allele showed a high degree of somatic instability (approximately 70% mutation load), resulting in deletions reverting to the high end of the normal range (down to [CTG](33)) and additions up to the proto-mutation range (up to [CTG](64)). The difference in the somatic stability of the (CTG)(43) allele between the mother and her offspring suggests that interallelic interactions or other mechanisms in trans regulate the stability of the (CTG)(43) premutation allele. C1 Univ Texas, Dept Neurol, Med Branch, Galveston, TX 77555 USA. Azienda Osped San Camillo Forlanini, Dipartimento Medicochirurg Neurosci, Lab Istopatol Neurogenet Mol, Rome, Italy. Univ Glasgow, Inst Biomed & Life Sci, Glasgow, Lanark, Scotland. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. RP Ashizawa, T (reprint author), Univ Texas, Dept Neurol, Med Branch, 301 Univ Blvd, Galveston, TX 77555 USA. NR 23 TC 13 Z9 13 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2002 VL 52 IS 4 BP 435 EP 441 DI 10.1002/ana.10304 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 600GG UT WOS:000178381800008 PM 12325072 ER PT J AU Poorkaj, P Muma, NA Zhukareva, V Cochran, EJ Shannon, KM Hurtig, H Koller, WC Bird, TD Trojanowski, JQ Lee, VMY Schellenberg, GD AF Poorkaj, P Muma, NA Zhukareva, V Cochran, EJ Shannon, KM Hurtig, H Koller, WC Bird, TD Trojanowski, JQ Lee, VMY Schellenberg, GD TI An (R)5(L) tau mutation in a subject with a progressive supranuclear palsy phenotype SO ANNALS OF NEUROLOGY LA English DT Article ID NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; PRESENILE-DEMENTIA; GENE; ISOFORMS; PATHOLOGY; MISSENSE; CRITERIA; FTDP-17; EXON-10 AB MAPT, the gene encoding tau, was screened for mutations in 96 progressive supranuclear palsy subjects. A point mutation ((R)5(L)) was identified in a single progressive supranuclear palsy subject that was not in the other progressive supranuclear palsy subjects or in 96 controls. Functionally, this mutation alters the ability of tau to promote microtubule assembly. Analysis of soluble tau from different brain regions indicates that the mutation does not affect the ratio of tau isoforms synthesized. Aggregated insoluble tau from subcortical regions was predominantly four-repeat tau with no or one amino terminal insert (0N4R and 1N4R). Insoluble tau from cortical regions also contained 1N3R tau. Thus, the (R)5(L) mutation causes a progressive supranuclear palsy phenotype, presumably by a gain-of-function mechanism. C1 GRECC, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98195 USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Loyola Univ, Med Ctr, Dept Pharmacol, Maywood, IL 60153 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Rush Presbyterian St Lukes Med Ctr, Dept Pathol, Chicago, IL 60612 USA. Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Miami, Dept Neurol, Miami, FL 33152 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. RP Schellenberg, GD (reprint author), GRECC, Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 182-B,1660 S Columbian Way, Seattle, WA 98195 USA. OI Muma, Nancy/0000-0001-8272-3138 FU NIA NIH HHS [AG10124, AG17583, AG11762] NR 20 TC 110 Z9 115 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2002 VL 52 IS 4 BP 511 EP 516 DI 10.1002/ana.10340 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 600GG UT WOS:000178381800019 PM 12325083 ER PT J AU Inagi, K Connor, NP Suzuki, T Ford, CN Bless, DM Nakajima, M AF Inagi, K Connor, NP Suzuki, T Ford, CN Bless, DM Nakajima, M TI Glottal configuration, acoustic, and aerodynamic changes induced by variation in suture direction in arytenoid adduction procedures SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY MAY 14-16, 2001 CL PALM DESERT, CALIFORNIA SP Amer Broncho Esophagol Assoc DE arytenoid adduction; lateral cricoarytenoid muscle; thyroarytenoid muscle ID VIVO CANINE MODEL; VOCAL CORD PARALYSIS; MEDIALIZATION; BIOMECHANICS; FOLD AB Arytenoid adduction is a phonosurgical procedure in which the arytenoid cartilages are approximated to reduce posterior glottal gap size and improve voice. Voice outcomes following arytenoid adduction are not always optimal. The goal of this study was to systematically vary suture direction and force of pull on the arytenoid cartilages in a human excised laryngeal model to determine the optimal combination of factors for reducing glottal gap and improving voice. Several factors demonstrated significant effects. Changes in suture direction and force of pull affected glottal configuration in both the horizontal and vertical planes. Increased force of pull on the muscular process resulted in increased adduction of the vocal process for all suture directions. Changes in suture direction and force of pull also affected acoustic and aerodynamic measures of induced voice. Therefore, voice outcomes can be optimized with arytenoid adduction if the vocal fold plane is accurately adjusted. C1 Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg,Sch Med, Madison, WI 53792 USA. Kitasato Inst, Med Ctr Hosp, Dept Otolaryngol Head & Neck Surg, Saitama, Japan. William S Middleton Mem Vet Adm Med Ctr, Surg Serv, Madison, WI USA. RP Connor, NP (reprint author), Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg,Sch Med, Room K4-711,600 Highland Ave, Madison, WI 53792 USA. FU NIDCD NIH HHS [P6DC000976] NR 19 TC 12 Z9 12 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2002 VL 111 IS 10 BP 861 EP 870 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 604GR UT WOS:000178609200001 PM 12389852 ER PT J AU Cambria, RP Clouse, WD Davison, JK Dunn, PF Corey, M Dorer, D AF Cambria, RP Clouse, WD Davison, JK Dunn, PF Corey, M Dorer, D TI Thoracoabdominal aneurysm repair: Results with 337 operations performed over a 15-year interval SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Surgical-Association CY APR 24-27, 2002 CL HOT SPRINGS, VIRGINIA SP Amer Surg Assoc ID SPINAL-CORD PROTECTION; ACUTE-RENAL-FAILURE; LEFT-HEART BYPASS; AORTIC-ANEURYSM; NEUROLOGIC DEFICIT; DEEP HYPOTHERMIA; RISK FACTOR; SURGERY; PARAPLEGIA; EXPERIENCE AB Objective To review perioperative results and late survival after thoracoabdominal aneurysm repair (TAA), in particular to assess the impact over time of epidural cooling (EC) on spinal cord ischemic complications (SCI). Summary Background Data A variety of operative approaches and protective adjuncts have been used in TAA to minimize the major complications of perioperative death and SCI. There is no consensus with respect to the optimal approach. Methods From January 1987 to November 2001, 337 consecutive TAA repairs were performed by a single surgeon. Clinical features included prior aortic grafts in 97 (28.8%) and emergent operation in 82 (24.6%), including rupture in 46 (13.6%) and dissection in 63 (19%). Operative management consisted of a clamp/sew technique with adjuncts in 93%. EC (since July 1993) to prevent SCI was used in 194 (57.6%) repairs. Variables associated with the end points of operative mortality and postoperative SCI were assessed with the Fisher exact test and logistic regression; late survival was estimated with the Kaplan-Meier method. Results Operative mortality was 8.3% and was associated with non-elective operation, intraoperative hypotension, total transfusion requirement, and the postoperative complications of paraplegia, renal failure, and pulmonary insufficiency. Postoperative renal failure and transfusion requirement were independent correlates of mortality. SCI of any severity occurred in 38 of 334 (11.4%) operative survivors, with 22/38 (6.6% of cohort) sustaining total paraplegia. EC reduced the risk of SCI in patients with types I-III TAA (10.6% vs. 19.8%, P =.04). Independent correlates of SCI over the entire study interval included types I/II TAA, rupture, cross-clamp duration, sacrifice of T9-L1 intercostal vessels, and intraoperative hypotension. Late survival rates at 2 and 5 years were 81.2 +/- 3% and 67.2 +/- 5%. Conclusions EC has decreased the risk of SCI after TAA repair. Decreasing the substantial proportion (nearly 25%) of patients requiring nonelective operation will improve results. Late survival is equal to that after routine AAA repair, indicating that the considerable resource expenditure required for TAA repair is worthwhile. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Vasc Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Thorac Aort Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Anesthesia Serv, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St WAC 458, Boston, MA 02114 USA. NR 45 TC 213 Z9 225 U1 0 U2 2 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 OCT PY 2002 VL 236 IS 4 BP 471 EP 479 DI 10.1097/01.SLA.0000031240.26001.E2 PG 9 WC Surgery SC Surgery GA 599JB UT WOS:000178329700010 PM 12368676 ER PT J AU Stylopoulos, N Gazelle, GS Rattner, DW AF Stylopoulos, N Gazelle, GS Rattner, DW TI Paraesophageal hernias: Operation or observation? SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Surgical-Association CY APR 24-27, 2002 CL HOT SPRINGS, VIRGINIA SP Amer Surg Assoc ID DAM HEALTH OUTCOMES; LAPAROSCOPIC REPAIR; HIATAL-HERNIA; INTRATHORACIC STOMACH; SURGICAL-MANAGEMENT; DECISION-ANALYSIS; GASTRIC VOLVULUS; QUALITY; SURGERY; UTILITY AB Objective To examine the hypothesis that elective laparoscopic repair should be routinely performed on patients with asymptomatic or minimally symptomatic paraesophageal hernias. Summary Background Data The management of asymptomatic paraesophageal hernias is a controversial issue. Most surgeons believe that all paraesophageal hernias should be corrected electively on diagnosis, irrespective of symptoms, to prevent the development of complications and avoid the risk of emergency surgery. Methods A Markov Monte Carlo decision analytic model was developed to track a hypothetical cohort of patients with asymptomatic or minimally symptomatic paraesophageal hernia and reflect the possible clinical outcomes associated with two treatment strategies: elective laparoscopic paraesophageal hernia repair (ELHR) or watchful waiting (WW). The input variables for ELHR were estimated from a pooled analysis of 20 published studies, while those for WW and emergency surgery were derived from the 1997 HCUP-NIS database and surgical literature published from 1964 to 2000. Outcomes for the two strategies were expressed in quality-adjusted life-years (QALYs). Results Analysis of the HCUP-NIS database showed that published studies overestimate the mortality of emergency surgery (17% vs. 5.4%). The mortality rate of ELHR was 1.4%. The annual probability of developing acute symptoms requiring emergency surgery with the WW strategy was 1.1%. For patients 65 years of age, ELHR resulted in reduction of 0.13 QALYs (10.78 vs. 10.65) compared with WW. The model predicted that WW was the optimal treatment strategy in 83% of patients and ELHR in the remaining 17%. The model was sensitive only to alterations of the mortality rates of ELHR and emergency surgery. Conclusions If ELHR is routinely recommended, it would be more beneficial than WW in fewer than one of five patients. WW is a reasonable alternative for the initial management of patients with asymptomatic or minimally symptomatic paraesophageal hernias, and even if an emergency operation is required, the burden of the procedure is not as severe as was thought in the past. C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 55 Fruit St, Boston, MA 02114 USA. NR 56 TC 129 Z9 132 U1 0 U2 2 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 OCT PY 2002 VL 236 IS 4 BP 492 EP 501 DI 10.1097/01.SLA.0000029000.06861.17 PG 10 WC Surgery SC Surgery GA 599JB UT WOS:000178329700012 PM 12368678 ER PT J AU Mullen, JT Kasuya, H Yoon, SS Carroll, NM Pawlik, TM Chandrasekhar, S Nakamura, H Donahue, JM Tanabe, KK AF Mullen, JT Kasuya, H Yoon, SS Carroll, NM Pawlik, TM Chandrasekhar, S Nakamura, H Donahue, JM Tanabe, KK TI Regulation of herpes simplex virus 1 replication using tumor-associated promoters SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 122nd Annual Meeting of the American-Surgical-Association CY APR 24-27, 2002 CL HOT SPRINGS, VIRGINIA SP Amer Surg Assoc ID MONOCLONAL-ANTIBODY DF3; BREAST-CARCINOMA CELLS; GENE-THERAPY; LIVER METASTASES; RIBONUCLEOTIDE REDUCTASE; CYTOSINE DEAMINASE; PROTEIN-SYNTHESIS; COLON-CARCINOMA; HEPATITIS-B; ANTIGEN AB Objective To investigate use of transcriptional regulatory elements (promoters) for tumor-associated antigens to achieve HSV-1 replication preferentially in cells that overexpress the tumor-associated antigens. Summary Background Data An important advantage of replicating viruses for cancer therapy is their ability to simultaneously destroy tumor cells by replication and release progeny virion to infect and destroy adjacent cancer cells. This strategy requires regulation of the viral life cycle to obtain robust replication in neoplastic cells and minimize replication in nonneoplastic cells. Methods Promoters for the human carcinoembryonic antigen (CFA) and MUC1/DF3 tumor-associated antigens were characterized and cloned into HSV-1 mutants as heterologous promoters regulating expression of two different HSV-1 genes. Viral replication in tumor cells and cytotoxicity was quantified with in vitro assays. Antineoplastic efficacy was characterized in a flank tumor xenograft model. Results Several CEA promoters were cloned and characterized using luciferase reporter assays. The most specific promoter was used to construct and isolate two different HSV-1 mutants in which critical genes are regulated by this promoter (ICP4 and gamma(1)34.5). Similarly, the promoter for the DF3/MUC1 tumor-associated antigen was cloned into a third HSV-1 mutant such that it regulates expression of gamma(1)34.5. Regulation of ICP4 expression by the CEA promoter during HSV-1 infection overly attenuates viral replication. Regulation of gamma(1)34.5 expression by either the CEA promoter or the MUC1/DF3 promoter during HSV-1 infection modulates viral replication, with preferential replication in cells that overexpress the corresponding tumor-associated antigen. A single intratumoral inoculation of an HSV-1 mutant with the MUC1/DF3 promoter regulating gamma(1)34.5 expression results in significant antineoplastic activity in MUC1-positive pancreatic carcinoma xenografts as compared to mock inoculation. Conclusions Promoters for tumor-associated antigens may be incorporated into the HSV-1 genome to regulate HSV-1 replication. The choices of HSV-1 gene and tumor-associated promoter are important determinants of success of this strategy. Because of its preferential replication in MUC1-positive tumors, an HSV-1 mutant with the MUC1/DF3 promoter regulating gamma(1)34.5 expression will undergo further examination as a novel cancer therapy agent. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox Bldg 626, Boston, MA 02114 USA. RI Kasuya, hideki/I-7278-2014 FU NCI NIH HHS [CA71345, T32 CA071345, CA76183, R01 CA076183]; NIDDK NIH HHS [DK43352]; NIGMS NIH HHS [GM07035, T32 GM007035] NR 35 TC 43 Z9 43 U1 0 U2 1 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 OCT PY 2002 VL 236 IS 4 BP 502 EP 513 DI 10.1097/01.SLA.0000029838.54661.59 PG 12 WC Surgery SC Surgery GA 599JB UT WOS:000178329700013 PM 12368679 ER PT J AU Wallace, MB Nietert, PJ Earle, C Krasna, MJ Hawes, RH Hoffman, BJ Reed, CE AF Wallace, MB Nietert, PJ Earle, C Krasna, MJ Hawes, RH Hoffman, BJ Reed, CE TI An analysis of multiple staging management strategies for carcinoma of the esophagus: Computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy SO ANNALS OF THORACIC SURGERY LA English DT Article ID BARRETTS-ESOPHAGUS; CANCER; ADENOCARCINOMA; ENDOSONOGRAPHY; SURVEILLANCE; METASTASES; JUNCTION; EUS; CT AB Background. This study compares the health care costs and effectiveness of multiple staging options for patients with esophageal cancer. Techniques studied included computed tomographic (CT) scan, endoscopic ultrasound with fine-needle aspiration biopsy (EUS-FNA), positron emission tomography (PET), thoracoscopy/laparoscopy, and combinations of these. Methods. A decision-analysis model was constructed to compare different staging strategies. Costs were derived from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases and from other Medicare reimbursement rates. Life expectancies were obtained from the 1973-1996 SEER database and adjusted for quality of life. Cost and effectiveness measures were discounted at 0% and 3% per year. Sensitivity and specificity measures were obtained from the published literature and a parallel prospective clinical trial, and all key variables were subjected to sensitivity analyses. Results. Under baseline assumptions, CT + EUS-FNA was the most inexpensive strategy and offered more quality-adjusted life-years, on average, than all other strategies with the exception of PET + EUS-FNA. The latter was slightly more effective but also more expensive. The marginal cost-effectiveness ratio for PET + EUS-FNA was $60,544 per quality-adjusted life-year. These findings were robust and changed very little in all of the sensitivity analyses. Conclusions. The combination of PET + EUS-FNA should be the recommended staging procedure for patients with esophageal cancer, unless resources are scarce or PET is unavailable. In these instances, CT + EUS-FNA can be considered the preferred strategy. C1 Med Univ S Carolina, Div Gastroenterol & Hepatol, Ctr Digest Dis, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Hlth Care Res, Charleston, SC 29425 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Dept Surg, Baltimore, MD 21201 USA. Med Univ S Carolina, Dept Surg, Hollings Canc Ctr, Charleston, SC 29425 USA. RP Wallace, MB (reprint author), Med Univ S Carolina, Div Gastroenterol & Hepatol, Ctr Digest Dis, 96 Jonathan Lucas St,Suite 210-CSB,POB 250327, Charleston, SC 29425 USA. OI Nietert, Paul/0000-0002-3933-4986 NR 24 TC 111 Z9 113 U1 0 U2 1 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 OCT PY 2002 VL 74 IS 4 BP 1026 EP 1032 AR PII S0003-4975(02)03875-4 DI 10.1016/S0003-4975(02)03875-4 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 601NK UT WOS:000178452500013 PM 12400740 ER PT J AU Mangi, AA Wright, CD Allan, JS Wain, JC Donahue, DM Grillo, HC Mathisen, DJ AF Mangi, AA Wright, CD Allan, JS Wain, JC Donahue, DM Grillo, HC Mathisen, DJ TI Adjuvant radiation therapy for stage II thymoma SO ANNALS OF THORACIC SURGERY LA English DT Article ID POSTOPERATIVE RADIOTHERAPY; CLINICOPATHOLOGICAL FEATURES; MEDIASTINAL IRRADIATION; PROGNOSTIC FACTORS; DISEASE; SUBCLASSIFICATION; RECURRENCE; MANAGEMENT; RESECTION; SURVIVAL AB Background. Thymoma is difficult to study because of its indolent natural history. The criteria for administration of adjuvant radiation therapy remain controversial, and it is unclear whether patients with Masaoka stage H thymoma benefit from adjuvant radiation. The goal of this report was to determine whether or not this group benefits from radiation therapy in terms of disease-specific survival and tumor recurrence. Methods. Case records of the Massachusetts General Hospital were retrospectively reviewed from 1972 to 1999. One hundred fifty-five patients underwent resection for thymoma, of which, 49 had stage II disease. The world literature was reviewed using a Medline search (1966 to 2001), and a secondary review of referenced works was performed. Results. Fourteen stage II patients underwent radiation therapy. Thirty-five did not receive radiation therapy., Baseline prognostic factors between radiated and nonradiated groups were similar. All patients underwent complete resection. The addition of adjuvant radiotherapy did not significantly alter local or distant recurrence rates in stage H thymoma. Disease-specific survival at 10 years in stage II patients was 100% with radiotherapy and without radiotherapy (p = 0.87). There was one recurrence in the nonradiated group at 180 months, which was outside the usual radiation portal. Conclusions. Most stage II patients do not require adjuvant radiation therapy and can be observed after complete resection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Gen Thorac Surg Unit, Blake 1570, Boston, MA 02114 USA. NR 33 TC 69 Z9 77 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2002 VL 74 IS 4 BP 1033 EP 1037 AR PII S0003-4975(02)03828-6 DI 10.1016/S0003-4975(02)03828-6 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 601NK UT WOS:000178452500014 PM 12400741 ER PT J AU Torchiana, DF AF Torchiana, DF TI Trends in intraaortic balloon counterpulsation complications and outcomes in cardiac surgery - Commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Bull Finch 119,55 Fruit St, 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 OCT PY 2002 VL 74 IS 4 BP 1090 EP 1091 AR PII S0003-4975(02)04038-9 DI 10.1016/S0003-4975(02)04038-9 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 601NK UT WOS:000178452500029 ER PT J AU Akins, CW Hilgenberg, AD Vlahakes, GJ MacGillivray, TE Torchiana, DF Madsen, JC AF Akins, CW Hilgenberg, AD Vlahakes, GJ MacGillivray, TE Torchiana, DF Madsen, JC TI Results of bioprosthetic versus mechanical aortic valve replacement performed with concomitant coronary artery bypass grafting SO ANNALS OF THORACIC SURGERY LA English DT Article ID MYOCARDIAL REVASCULARIZATION; LATE SURVIVAL; DISEASE; TISSUE; AGE AB Background. Concomitant coronary artery disease with aortic valve disease is an established risk factor for diminished late survival. This study evaluated the results of bioprosthetic (BAVR) or mechanical aortic valve replacement (MAVR) performed with coronary artery bypass grafting (CABG). Methods. From January 1984 through July 1997, combined AVR + CABG was performed in 750 consecutive patients; 469 received BAVR and 281 received MAVR. BAVR recipients were significantly older (mean age, 75 vs 65 years), and had more nonelective operations, congestive heart failure, peripheral vascular disease, preoperative intraaortic balloons, lower cardiac indices, more severe aortic stenosis, less aortic regurgitation, and more extensive coronary artery disease. Results. Early complications included operative mortality, 32 patients (4.3% total: 3.8% BAVR and 5.0% MAVR); perioperative infarction, 10 (1.3%); and perioperative stroke 22 (2.9%). Significant multivariable predictors of early mortality were age, perioperative infarction or stroke, nonelective operation, operative year, ventricular hypertrophy, and need for intraaortic balloon. Ten-year actuarial survival was 41.7% for all patients. Predicted survival for age- and gender-matched cohorts from the general population versus observed survival were BAVR, 45% versus 36%; MAVR, 71% versus 48% (survival differences BAVR 9% vs MAVR 23%, p < 0.007). Significant multivariable predictors of late mortality included age, congestive failure, perioperative stroke, extent of coronary disease, peripheral vascular disease, and diabetes. Valve type was not significant. Ten-year actuarial freedom from valve-related complications were (BAVR vs MAVR) structural deterioration, 95% versus 100%, p = NS; thromboembolism, 86% versus 84%, p = NS; anticoagulant bleeding, 93% versus 88%, p < 0.005; reoperation, 98% versus 98%, p = NS. Conclusions. AVR + CABG has diminished late survival despite the type of prosthesis inserted. Although valve type did not predict late mortality, mechanical AVR was associated with worse survival compared with predicted and more valve-related complications due to anticoagulation requirements. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, White 503,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 25 Z9 31 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2002 VL 74 IS 4 BP 1098 EP 1106 AR PII S0003-4975(02)03840-7 DI 10.1016/S0003-4975(02)03840-7 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 601NK UT WOS:000178452500032 PM 12400752 ER PT J AU Tsukamoto, H AF Tsukamoto, H TI Redox regulation of cytokine expression in Kupffer cells SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID NF-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; NECROSIS-FACTOR-ALPHA; DNA-BINDING ACTIVITY; INDUCED LIVER-INJURY; TRANSCRIPTION FACTOR; RAT-LIVER; SIGNAL-TRANSDUCTION; ALCOHOLIC HEPATITIS; GENE-EXPRESSION AB Kupffer cells, resident macrophages in the liver, play a central role in the homeostatic response to liver injury. Ironically, this defensive mechanism, if dysregulated, also works against the liver in acute and chronic liver damage. Central to this response is activation of nuclear factor-kappaB (NF-kappaB), a redox-sensitive transcription factor that transactivates promoters of many inflammatory genes, including cytokines. Much research has been devoted to identification of upstream signaling for activation of NF-kappaB, but the precise mechanism by which oxidant stress participates in this signaling is yet to be determined. Clues to this key question may be attained through studies on the mechanisms of sustained and/or accentuated NF-kappaB activation in hepatic macrophages in chronic liver diseases. This article reviews the literature on redox regulation of cytokine gene expression by Kupffer cells. C1 Univ So Calif, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, USC Res Ctr Liver Dis, Los Angeles, CA 90033 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90033 USA. RP Univ So Calif, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, 1333 San Pablo St,MMR-402, Los Angeles, CA 90033 USA. EM htsukamo@hsc.usc.edu FU NIAAA NIH HHS [R37AA06603, P50AA11999]; NIDDK NIH HHS [P30DK48522] NR 66 TC 57 Z9 59 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD OCT PY 2002 VL 4 IS 5 BP 741 EP 748 DI 10.1089/152308602760598882 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 607NP UT WOS:000178797900006 PM 12470501 ER PT J AU Tsuang, DW Dalan, AM Eugenio, CJ Poorkaj, P Limprasert, P La Spada, AR Steinbart, E Bird, TD Leverenz, JB AF Tsuang, DW Dalan, AM Eugenio, CJ Poorkaj, P Limprasert, P La Spada, AR Steinbart, E Bird, TD Leverenz, JB TI Familial dementia with Lewy bodies - A clinical and neuropathological study of 2 families SO ARCHIVES OF NEUROLOGY LA English DT Article ID E EPSILON-4 ALLELE; APOLIPOPROTEIN-E GENE; HUMAN PARKIN GENE; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; BODY-DISEASE; HUNTINGTONS-DISEASE; PSYCHOTIC SYMPTOMS; SENILE DEMENTIA; POLYMORPHISMS AB Background: Dementia with Lewy bodies (DLB) is characterized by early dementia and associated visual hallucinations, parkinsonism, and fluctuations in cognition. Few families with DLB have been described with detailed clinical, pathological, and genetic assessments. Objective: To investigate the clinical, neuropathological, and genetic characteristics of families with 2 or more autopsy-proven cases of DLB. Design: Consecutive cases with the neuropathological diagnosis of DLB were reviewed as part of a case series. Families included in this study have 2 or more autopsy-proven cases of DLB available and a positive family history of dementia. We obtained clinical and neuropathological data on all first-degree relatives. Neuropathological evaluations included alpha-synuclein immunostaining for Lewy body detection. We conducted apolipoprotein E genotyping and sequenced the alpha-, beta-, gamma-synuclein, and parkin genes. Setting: Subjects were selected from the neuropathology core of the University of Washington's Alzheimer's Disease Research Center. Patients: The study investigated 2 families. Clinical information was obtained from 10 individuals in family 1 and 7 individuals in family 2. Neuropathological examinations were conducted in 3 individuals in family 1 and 2 individuals in family 2. Main Outcome Measures: Each subject was examined for the presence of clinical symptoms and neuropathological findings consistent with DLB. Results: While all affected individuals presented with dementia in both families, only individuals in family 1 developed visual hallucinations and delusions. Parkinsonism, if present, occurred later in the course of illness. Neuropathological examination revealed Lewy bodies in all patients, while 1 patient from each family also met the neuropathological criteria for Alzheimer disease. All affected individuals carried at least 1 APOE (apolipoprotein E) epsilon4 allele, while there were no nucleotide alterations in the synuclein or parkin genes. Conclusions: Familial DLB exists, although there is substantial clinical and neuropathological heterogeneity within and between families. Additional clinicopathologic and genetic studies are necessary to further our understanding of DLB. C1 Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. RP Tsuang, DW (reprint author), Dept Vet Affairs, NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 NR 59 TC 41 Z9 41 U1 0 U2 0 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 OCT PY 2002 VL 59 IS 10 BP 1622 EP 1630 DI 10.1001/archneur.59.10.1622 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 603LC UT WOS:000178560100014 PM 12374501 ER PT J AU Fernandez-Suntay, JP Gragoudas, ES Ferry, JA Anderson, ME Dacey, MP Dryja, TP AF Fernandez-Suntay, JP Gragoudas, ES Ferry, JA Anderson, ME Dacey, MP Dryja, TP TI High-grade uveal B-cell lymphoma as the initial feature in Richter syndrome SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 6 Z9 6 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 OCT PY 2002 VL 120 IS 10 BP 1383 EP 1385 PG 3 WC Ophthalmology SC Ophthalmology GA 603LG UT WOS:000178560500019 PM 12365922 ER PT J AU Neuzil, KM Hohlbein, C Zhu, YW AF Neuzil, KM Hohlbein, C Zhu, YW TI Illness among schoolchildren during influenza season - Effect on school absenteeism, parental absenteeism from work, and secondary illness in families SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PANDEMIC INFLUENZA; VIRUS-INFECTIONS; CHILDREN; IMPACT; MORTALITY; YOUNG; AGE; HOSPITALIZATIONS; VACCINATION; MORBIDITY AB Background: High attack rates of Influenzavirus among school-aged children tend to be expected to cause significant disruption of usual activities at school and at home. Objective: To quantify the effect of influenza season on illness episodes, school absenteeism, medication use, parental absenteeism from work, and the occurrence of secondary illness in families among a cohort of children enrolled in an elementary school during the 2000-2001 influenza season. Design: Prospective survey study. Setting: Kindergarten through eighth grade elementary school in Seattle, Wash. Patients or Other Participants: All children enrolled in the school were eligible for the study. Study participants were 313 children in 216 families. Main Outcome Measures: The primary outcome measure was missed school days. Secondary outcomes measures included total illness episodes, febrile illness episodes, medication usage, physician visits, parental workdays missed, and secondary illnesses among family members of children in the study cohort. Differences between the rates of study events among participants when influenza was circulating and the event rates during the winter season when influenza was not circulating were used to calculate influenza-attributable excess events. Results: Total illness episodes, febrile illness episodes, analgesic use, school absenteeism, parental industrial absenteeism, and secondary illness among family members were significantly higher during influenza season compared with the noninfluenza winter season. For every 100 children followed up for this influenza season, which included 37 school days, an excess 28 illness episodes and 63 missed school days occurred. Similarly, for every 100 children followed up, influenza accounted for an estimated 20 days of work missed by the parents and 22 secondary illness episodes among family members. Conclusion: Influenza season has significant adverse effects on the quality of life of school-aged children and their families. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98108 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. RP Neuzil, KM (reprint author), Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 36 TC 173 Z9 179 U1 0 U2 5 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 OCT PY 2002 VL 156 IS 10 BP 986 EP 991 PG 6 WC Pediatrics SC Pediatrics GA 602EY UT WOS:000178493900007 PM 12361443 ER PT J AU Wang, TJ Nam, BH Wilson, PWF Wolf, PA Levy, D Polak, JF D'Agostino, RB O'Donnell, CJ AF Wang, TJ Nam, BH Wilson, PWF Wolf, PA Levy, D Polak, JF D'Agostino, RB O'Donnell, CJ TI Association of C-reactive protein with carotid atherosclerosis in men and women: The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE C-reactive protein; carotid arteries; carotid stenosis; risk factors; atherosclerosis ID INTIMA-MEDIA THICKNESS; APPARENTLY HEALTHY-MEN; INTERCELLULAR-ADHESION MOLECULE-1; PREVALENT CARDIOVASCULAR-DISEASE; FUTURE MYOCARDIAL-INFARCTION; TRANSIENT ISCHEMIC ATTACK; RISK-FACTORS; PLASMA-CONCENTRATION; SUBCLINICAL DISEASE; INSULIN-RESISTANCE AB Objective-The objective of this study was to examine the relationship between C-reactive protein (CRP) and carotid atherosclerosis. Background-Levels of CRP, a nonspecific marker of inflammation, predict risk for cardiovascular events. However, the association between CRP and direct measures of atherosclerosis is not well established. Methods and Results-Subjects (n=3173, 52% women, mean age 55) in the offspring cohort of the Framingham Heart Study received a CRP measurement and then underwent carotid ultrasonography 4 years later. Carotid stenosis ( greater than or equal to 25%) was present in 24% of men and 14% of women. Age-adjusted odds ratios for carotid stenosis were 1.62 (95%CI 1.12 to 2.36) for men and 3.90 (Cl 2.44 to 6.44) for women in the fourth quartile of CRP compared with those in the lowest quartile. After further adjustment for traditional cardiovascular disease risk factors, the odds ratio remained significant for women (2.97, Cl 1.72 to 5.25) but not for men. Similarly, after multivariable adjustment, women in the fourth CRP quartile had a higher mean internal carotid intima-media thickness than those in the lowest CRP quartile (P less than or equal to 0.001). There was no association between common carotid intima-media thickness and CRP. Conclusions-There is a graded association between CRP and carotid atherosclerosis in women but not in men. The significance of this difference between sexes merits further investigation. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Div Cardiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte,Suite 2, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-25195] NR 38 TC 160 Z9 171 U1 0 U2 2 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 OCT PY 2002 VL 22 IS 10 BP 1662 EP 1667 DI 10.1161/01.ATV.0000034543.78801.69 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 605PR UT WOS:000178686700026 PM 12377746 ER PT J AU Calverley, DC Brass, E Hacker, MR Tsao-Wei, DD Espina, BM Pullarkat, VA Hodis, HN Groshen, S AF Calverley, DC Brass, E Hacker, MR Tsao-Wei, DD Espina, BM Pullarkat, VA Hodis, HN Groshen, S TI Potential role of platelet Fc gamma RIIA in collagen-mediated platelet activation associated with atherothrombosis SO ATHEROSCLEROSIS LA English DT Article DE blood platelets; diabetes mellitus; cardiovascular disease; collagen; platelet activation; receptors, Fc ID STIMULATES TYROSINE PHOSPHORYLATION; PHOSPHOLIPASE C-GAMMA-2; RECEPTOR; EXPRESSION; SYK; INTEGRIN; PROTEIN; DISEASE; ALPHA(2)BETA(1); INTERACTS AB Collagen-mediated platelet activation contributes significantly to coronary and cerebrovascular thrombus formation associated with atherosclerotic plaque destabilization. Recent clinical and laboratory observations support a potential role for the platelet Fc receptor (FcgammaRIIA) in this process. The purpose of this study was to elucidate any association between platelet Fc receptor (FcR) expression levels and both atherosclerosis risk factors (ARFs) along with collagen-dependent platelet activation. Age and gender-independent variation has been described in the expression of this receptor that is stable over time. Platelet Fc surface expression was compared between patients experiencing an acute coronary or cerebrovascular event, healthy patients with two or more ARFs, and healthy patients with fewer than two ARFs. Platelet FcR expression was significantly and stably (6-52 weeks, mean 20 weeks) increased in 101 patients with acute myocardial infarction, unstable angina, or ischemic stroke syndrome (P < 0.001) and 38 healthy patients with two or more ARFs (P = 0.027) compared with 109 healthy patients with fewer than two ARFs. Patients with diabetes mellitus from all groups had significantly increased platelet FcR expression over those without diabetes (P < 0.0001). Platelet aggregation studies suggested a correlation between number of ARFs per patient, platelet Fc expression levels, and relative sensitivity to collagen stimulation. Platelet FcR surface expression is increased in patients with an acute coronary or cerebrovascular event, non-acutely ill patients with two or more ARFs, and in patients with diabetes mellitus. Increased platelet FcR expression may therefore contribute towards risk for atherothrombotic events. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Mt States Reg Hemophilia & Thrombosis Ctr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Med Serv, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80262 USA. Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. RP Calverley, DC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, 4200 E 9th Ave,Box B171, Denver, CO 80262 USA. FU NCI NIH HHS [P30 CA 14089]; NIA NIH HHS [R01AG13860] NR 35 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2002 VL 164 IS 2 BP 261 EP 267 AR PII S0021-9150(02)00179-X DI 10.1016/S0021-9150(02)00179-X PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 594TY UT WOS:000178068100007 PM 12204796 ER PT J AU Fricchione, G AF Fricchione, G TI Catatonia: A disorder of motivation and movement SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID BASAL GANGLIA; SCHIZOPHRENIA; DISEASE AB Georg Northoff employs a comparison with Parkinson's disease in an effort to tease apart the underlying pathophysiology of psycho-genic catatonia. Northoff's extensive treatment of the subject is abetted by his own research as well as the research of others. Nevertheless, a number of points concerning basal ganglia/thalamocortical processing need to be raised, some adding support to his hypothesis and others detracting from it. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Fricchione, G (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM gfricchione@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD OCT PY 2002 VL 25 IS 5 BP 584 EP + PG 8 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 833XA UT WOS:000222373400008 ER PT J AU Patchornik, G Munson, K Goldshleger, R Shainskaya, A Sachs, G Karlish, SJD AF Patchornik, G Munson, K Goldshleger, R Shainskaya, A Sachs, G Karlish, SJD TI The ATP-Mg2+ binding site and cytoplasmic domain interactions of Na+,K+-ATPase investigated with Fe2+-catalyzed oxidative cleavage and molecular modeling SO BIOCHEMISTRY LA English DT Article ID P-TYPE ATPASE; SARCOPLASMIC-RETICULUM CA2+-ATPASE; ENERGY TRANSDUCTION MECHANISM; ALPHA-BETA PROTOMERS; (NA+ + K+)-ATPASE; NA+/K+-ATPASE; HIGH-AFFINITY; AMINO-ACID; FLUORESCEIN ISOTHIOCYANATE; CONFORMATIONAL-CHANGES AB This work utilizes Fe2+-catalyzed cleavages and molecular modeling to obtain insight into conformations of cytoplasmic domains and ATP-Mg2+ binding sites of Na+,K+-ATPasc. In E-1 conformations the ATP-Fe2+ Complex mediates specific cleavages at 712VNDS (P domain) and near 440VAGDA (N domain). In E-2(K), ATP-Fe2+ mediates cleavages near 212TGES (A domain), near 440VAGDA, and between residues 460-490 (N domain). Cleavages at high ATP-Fe2+ concentrations do not support suggestions for two ATP sites. A new reagent, fluorescein-DTPA, has been synthesized. The fluorescein-DTPA-Fe2+ Complex mediates cleavages similar to those mediated by ATP-Fe2+. The data suggest the existence of N to P domain interactions in E1Na, with bound ATP-Fe2+ or fluorescein-DPTA-Fe2+, A-N, and A-P interactions in E-2(K), and provide testable constraints for model building. Molecular models based on the Ca2+-ATPase structure are consistent with the predictions. Specifically, high-affinity ATP-Mg2+ binding in E-1 is explained with the N domain tilted ca. 80degrees toward the P domain, by comparison with well-separated N and P domains in the Ca-ATPase crystal structure. With ATP-Mg2+ docked, bound Mg2+ is close to both D710 (in 710DGVNDS) and D443 (in 440VAGDASE). D710 is known to be crucial for Mg2+ binding. The cleavage and modeling data imply that D443 could also be a candidate for Mg2+ binding. Comparison of E-1.ATP,Mg2+ and E-2 models suggests an explanation of the high or low ATP affinities, respectively. We propose a scheme of ATP-Mg2+ and Mg2+ binding and N, P, and A domain interactions in the different conformations of the catalytic cycle. C1 Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Biol Mass Spectrometry Facil, IL-76100 Rehovot, Israel. Univ Calif Los Angeles, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Karlish, SJD (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. FU NIDDK NIH HHS [DK 17294, DK 41301, DK 46971, DK 53462] NR 59 TC 21 Z9 21 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 1 PY 2002 VL 41 IS 39 BP 11740 EP 11749 DI 10.1021/bi026334d PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 598DP UT WOS:000178260400022 PM 12269816 ER PT J AU Allen, TM Kelleher, AD Zaunders, J Walker, BD AF Allen, TM Kelleher, AD Zaunders, J Walker, BD TI Structured treatment interruption and beyond SO BIOFUTUR LA French DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTE; HIV TYPE-1 INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; CELLULAR IMMUNE-RESPONSES; HIV-1-INFECTED PATIENTS; VIRAL LOAD; CLASS-I; DENDRITIC CELLS; PLASMA VIREMIA C1 Harvard Univ, Sch Med, Ctr AIDS Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Univ New S Wales, Natl Ctr VIH Epidemiol & Clin Res, Sydney, NSW, Australia. RP Allen, TM (reprint author), Harvard Univ, Sch Med, Ctr AIDS Res, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Zaunders, John/J-6553-2012 OI Zaunders, John/0000-0002-5912-5989 NR 63 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD OCT-NOV PY 2002 IS 226 BP 52 EP 58 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 630GC UT WOS:000180098300009 ER PT J AU Strangman, G Boas, DA Sutton, JP AF Strangman, G Boas, DA Sutton, JP TI Non-invasive neuroimaging using near-infrared light SO BIOLOGICAL PSYCHIATRY LA English DT Review DE NIRS; non-invasive; functional brain activity; diffuse optical tomography; optical imaging ID CEREBRAL BLOOD OXYGENATION; DIFFUSE OPTICAL TOMOGRAPHY; DENSE-SCATTERING MEDIA; HUMAN BRAIN; SPECTROSCOPY NIRS; HUMAN ADULTS; HEMOGLOBIN OXYGENATION; NONINVASIVE ASSESSMENT; TRANSCRANIAL DOPPLER; TISSUE OXYGENATION AB This article reviews diffuse optical brain imaging, a technique that employs near-infrared light to non-invasively probe the brain for changes in parameters relating to brain function. We describe the general methodology, including types of measurements and instrumentation (including the tradeoffs inherent in the various instrument components), and the basic theory required to interpret the recorded data. A brief review of diffuse optical applications is included, with an emphasis on research that has been done with psychiatric populations. Finally, we discuss some practical issues and limitations that are relevant when conducting diffuse optical experiments. We find that, while diffuse optics can provide substantial advantages to the psychiatric researcher relative to the alternative brain imaging methods, the method remains substantially underutilized in this field. (C) 2002 Society of Biological Psychiatry. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. Harvard Mit Div Hlth Sci & Technol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Athinoula M Martinos Ctr, Charlestown, MA USA. RP Strangman, G (reprint author), Neural Syst Grp, 149 13th St,Room 10018, Charlestown, MA 02129 USA. FU NINDS NIH HHS [F32-NS10567-01, R29-NS38842] NR 89 TC 385 Z9 392 U1 2 U2 53 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 OCT 1 PY 2002 VL 52 IS 7 BP 679 EP 693 AR PII S0006-3223(02)01550-0 DI 10.1016/S0006-3223(02)01550-0 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 601EM UT WOS:000178433600001 PM 12372658 ER PT J AU Fisher, JS Pastor-Soler, N Sharpe, RM Breton, S AF Fisher, JS Pastor-Soler, N Sharpe, RM Breton, S TI Modulation of the onset of postnatal development of H(+)-ATPase-rich cells by steroid hormones in rat epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article DE epididymis; estradiol; male reproductive tract; steroid hormones; testosterone ID MALE REPRODUCTIVE-TRACT; ESTROGEN-RECEPTOR-BETA; TESTOSTERONE CONCENTRATIONS; ENVIRONMENTAL ESTROGENS; NEONATAL EXPOSURE; MITOCHONDRIA-RICH; EPITHELIAL-CELLS; VAS-DEFERENS; ER-BETA; DIETHYLSTILBESTROL AB Vacuolar type H(+)-ATPase is involved in lumenal acidification of the epididymis. This protein is highly expressed in narrow and clear cells where it is located in the apical pole, and it contributes to proton secretion into the lumen. We have previously shown that in rats, epididymal cells rich in H(+)ATPase appear during postnatal development and reach maximal numbers at 3-4 wk of age. The factors that regulate the appearance of these cells have not been investigated, but androgens, estrogens, or both may be involved. This study examined whether neonatal administration of estrogens (diethylstilbestrol [DES] or ethinyl estradiol) or an antiandrogen (flutamide), or the suppression of androgen production via administration of a GnRH antagonist (GnRHa), was able to alter the appearance of cells rich in H(+)ATPase in the rat epididymis when assessed at age 25 days. Surprisingly, all of these treatments were able to significantly reduce the number of H(+)-ATPase positive cells; this was determined by immunofluorescence and confirmed by Western blotting. In contrast, neonatal coadministration of DES and testosterone maintained the expression of H(+)-ATPase in the epididymis at Day 25 despite the high level of concomitant estrogen exposure. These findings indicate that androgens, acting via the androgen receptor, are essential for the normal development of epididymal cells rich in H(+)-ATPase, and that treatments that interfere directly or indirectly with androgen production (GnRHa, DES) or action (flutamide, DES) will result in reduced expression of H(+)-ATPase. Our findings do not exclude the possibility that estrogens can directly suppress the postnatal development of cells in the epididymis that are rich in H(+)-ATPase, but if this is the case, this suppression can be prevented by testosterone administration. C1 MRC, Human Reprod Sci Unit, Edinburgh EN16 4SB, Midlothian, Scotland. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Fisher, JS (reprint author), MRC, Human Reprod Sci Unit, 49 Little France Crescent,Old Dalkeith Rd, Edinburgh EN16 4SB, Midlothian, Scotland. EM j.fisher@hrsu.mrc.ac.uk RI Sharpe, Richard/D-2725-2013 OI Sharpe, Richard/0000-0003-1686-8085 FU NICHD NIH HHS [HD40793, HD08684]; NIDDK NIH HHS [DK38452] NR 41 TC 7 Z9 7 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 2002 VL 67 IS 4 BP 1106 EP 1114 DI 10.1095/biolreprod.101.001123 PG 9 WC Reproductive Biology SC Reproductive Biology GA 598FX UT WOS:000178266200010 PM 12297525 ER PT J AU Migliorini, C Qian, YH Chen, HD Brown, EB Jain, RK Munn, LL AF Migliorini, C Qian, YH Chen, HD Brown, EB Jain, RK Munn, LL TI Red blood cells augment leukocyte rolling in a virtual blood vessel SO BIOPHYSICAL JOURNAL LA English DT Article ID PARTICULATE SUSPENSIONS; BOLTZMANN-EQUATION; SHEAR-FLOW; ERYTHROCYTES; ENDOTHELIUM; ADHESION; SURFACES; ARREST; MODEL AB Leukocyte rolling and arrest on the vascular endothelium is a central event in normal and pathological immune responses. However, rigorous estimation of the fluid and surface forces involved in leukocyte-endothelial interactions has been difficult due to the particulate, non-Newtonian nature of blood. Here we present a Lattice-Boltzmann approach to quantify forces exerted on rolling leukocytes by red blood cells in a "virtual blood vessel." We report that the normal force imparted by erythrocytes, is sufficient to increase leukocyte binding and that increases in tangential force and torque can promote rolling of previously adherent leukocytes. By simulating changes in hematocrit we show that a close "envelopment" of the leukocyte by the red blood cells is necessary to produce significant changes in the forces. This novel approach can be applied to a large number of biological and industrial problems involving the complex flow of particulate suspensions. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Exa Corp, Lexington, MA 02420 USA. RP Munn, LL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 3409 Bldg 149, Charlestown, MA 02129 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 FU NHLBI NIH HHS [R01 HL64240] NR 28 TC 98 Z9 99 U1 3 U2 18 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2002 VL 83 IS 4 BP 1834 EP 1841 PG 8 WC Biophysics SC Biophysics GA 603RA UT WOS:000178572500009 PM 12324405 ER PT J AU Sachs, GS Guille, C McMurrich, SL AF Sachs, GS Guille, C McMurrich, SL TI A clinical monitoring form for mood disorders SO BIPOLAR DISORDERS LA English DT Article DE formal rating scales; mood disorders ID SCALE; ILLNESS AB Objective: The Clinical Monitoring Form (CMF) for mood disorders was developed as a time efficient record keeping tool for routine clinical use. This report presents preliminary data evaluating the correlation between the CMF's dimensional subscales for depression and mood elevation and formal mood rating scales across a wide spectrum of mood states. Methods: To harvest data for 500 follow-up visits required collection of data from consecutive records accumulated during the conduct of seven double blind clinical trials involving a total of 58 participants. These trials utilized the CMF as a source document in conjunction with formal study outcome scales, e.g. Hamilton Rating Scale for Depression (HRSD), the Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS) and the Mania Rating Scale (MRS) from the Schedule of Affective Disorders-Current (SUM-C). Correlation coefficients were calculated to examine the relationship between the formal rating scales, Clinical Global Impression and the depression (SUM-D) and mood elevation (SUM-ME) subscales of the CMF. Results: Robust correlations were observed between SUM-D and the formal depression scales, HRSD and MADRS, r=0.79, r=0.88, respectively. Similar robust correlations were also found between the SUM-ME and the formal mood elevation scales, YMRS and the MRS, r=0.84, r=0.86, respectively. Conclusion: The CMF appears to offer a reasonable alternative to the formal rating scales typically used in research studies. C1 Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harvard Bipolar Res Program, Clin Psychopharmacol Unit, 50 Staniford St,5th Fl, Boston, MA 02114 USA. NR 10 TC 96 Z9 96 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2002 VL 4 IS 5 BP 323 EP 327 DI 10.1034/j.1399-5618.2002.01195.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 602TL UT WOS:000178520500008 PM 12479665 ER PT J AU Vardiman, JW Harris, NL Brunning, RD AF Vardiman, JW Harris, NL Brunning, RD TI The World Health Organization (WHO) classification of the myeloid neoplasms SO BLOOD LA English DT Review ID CHRONIC NEUTROPHILIC LEUKEMIA; MINIMALLY DIFFERENTIATED ERYTHROLEUKEMIA; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; FRENCH-AMERICAN-BRITISH; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; SIDEROBLASTIC ANEMIA AISA; AML-TYPE CHEMOTHERAPY AB A World Health Organization (WHO) classification of hematopoietic and lymphoid neoplasms has recently been published. This classification was developed through the collaborative efforts of the Society for Hematopathology, the European Association of Hematopathologists, and more than 100 clinical hematologists and scientists who are Internationally recognized for their expertise In hematopoietic neoplasms. For the lymphoid neoplasms, this classification provides a refinement of the entities described In the Revised European-American Lymphoma (REAL) Classification-a system that Is now used worldwide. To date, however, there has been no published explanation or rationale given for the WHO classification of the myeloid neoplasms, The purpose of this communication Is to outline briefly the WHO classification of malignant myeloid diseases, to draw attention to major differences between it and antecedent classification schemes, and to provide the rationale for those differences. (C) 2002 by The American Society of Hematology. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Vardiman, JW (reprint author), Univ Chicago Hosp, 5841 S Maryland Ave,MC 0008, Chicago, IL 60637 USA. NR 108 TC 1229 Z9 1392 U1 1 U2 50 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 OCT 1 PY 2002 VL 100 IS 7 BP 2292 EP 2302 DI 10.1182/blood-2002-04-1199 PG 11 WC Hematology SC Hematology GA 598FV UT WOS:000178266000004 PM 12239137 ER PT J AU Rizzo, JD Lichtin, AE Woolf, SH Seidenfeld, J Bennett, CL Cella, D Djulbegovic, B Goode, MJ Jakubowski, AA Lee, SJ Miller, CB Rarick, MU Regan, DH Browman, GP Gordon, MS AF Rizzo, JD Lichtin, AE Woolf, SH Seidenfeld, J Bennett, CL Cella, D Djulbegovic, B Goode, MJ Jakubowski, AA Lee, SJ Miller, CB Rarick, MU Regan, DH Browman, GP Gordon, MS TI Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology SO BLOOD LA English DT Review ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; CHEMOTHERAPY-INDUCED ANEMIA; NECROSIS-FACTOR-ALPHA; QUALITY-OF-LIFE; PLATINUM-BASED CHEMOTHERAPY; PLACEBO-CONTROLLED TRIAL; NON-HODGKINS-LYMPHOMA; DOUBLE-BLIND TRIAL; MULTIPLE-MYELOMA; CONTROLLED MULTICENTER AB Anemia resulting from cancer or its treatment is an important clinical problem increasingly treated with the recombinant hematopoietic growth factor erythropoietin. To address uncertainties regarding indications and efficacy, the American Society of Clinical Oncology and the American Society of Hematology developed an evidence-based clinical practice guideline for the use of epoetin in patients with cancer. The guideline panel found good evidence to recommend use of epoetin as a treatment option for patients with chemotherapy-associated anemia with a hemoglobin (Hgb) concentration below 10 g/dL. Use of epoetin for patients with less severe anemia (Hgb level below 12 g/dL but never below 10 g/dL) should be determined by clinical circumstances. Good evidence from clinical trials supports the use of subcutaneous epoetin thrice weekly (150 U/kg) for a minimum of 4 weeks. Less strong evidence supports an alternative weekly (40 000 U/wk) dosing regimen, based on common clinical practice. With either administration schedule, dose escalation should be considered for those not responding to the initial dose. In the absence of response, continuing epoetin beyond 6-8 weeks does not appear to be beneficial. Epoetin should betitrated once the hemoglobin concentration reaches 12 g/dL. Evidence from one randomized controlled trial supports use of epoetin for patients with anemia associated with low-risk myelodysplasia not receiving chemotherapy; however, there are no published high quality studies to support its use for anemia in other hematologic malignancies in the absence of chemotherapy. Therefore, for anemic patients with hematologic malignancies it is recommended that physicians initiate conventional therapy and observe hematologic response before considering use of epoetin. (C) 2002 by The American Society of Hematology and The American Society of Clinical Oncology. C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Virginia Commonwealth Univ, Richmond, VA USA. Blue Cross & Blue Shield Assoc Technol Evaluat Ct, Chicago, IL USA. VA Chicago Hlth Care Syst, Chicago, IL USA. Evanston Northwestern Healthcare, Evanston, IL USA. Univ S Florida, Res Inst, H Lee Moffitt Canc Ctr, Tampa, FL USA. Univ S Florida, Res Inst, Res Inst, Tampa, FL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. St Agnes Hosp, Baltimore, MD USA. NW Kaiser Permanente, Portland, OR USA. NW Canc Specialists, Portland, OR USA. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. Univ Arizona, Hlth Sci Ctr, Phoenix, AZ USA. RP Rizzo, JD (reprint author), Med Coll Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. RI Bennett, Charles/C-2050-2008; Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 68 TC 135 Z9 142 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 OCT 1 PY 2002 VL 100 IS 7 BP 2303 EP 2320 DI 10.1182/blood-2002-06-1767 PG 18 WC Hematology SC Hematology GA 598FV UT WOS:000178266000005 PM 12239138 ER PT J AU Taniguchi, T Garcia-Higuera, I Andreassen, PR Gregory, RC Grompe, M D'Andrea, AD AF Taniguchi, T Garcia-Higuera, I Andreassen, PR Gregory, RC Grompe, M D'Andrea, AD TI S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51 SO BLOOD LA English DT Article ID DNA-DAMAGE RESPONSE; ATM-DEPENDENT PHOSPHORYLATION; CELL-CYCLE; GENE; COMPLEMENTATION; REPAIR; RECOMBINATION; REPLICATION; HOMOLOGY; KINASE AB Fanconi anemia (FA) is a human autosomal recessive cancer susceptibility disorder characterized by cellular sensitivity to mitomycin C and defective cell-cycle progression. Six FA genes (corresponding to subtypes A, C, D2, E, F, and G) have been cloned, and the encoded FA proteins interact in a common pathway. DNA damage activates this pathway, leading to monoubiquitination of the downstream FANCD2 protein and targeting to nuclear foci containing BRCA1. In the current study, we demonstrate that FANCD2 also undergoes monoubliquitination during S phase of the cell cycle. Monoubiquitinated FANCD2 colocalizes with BRCA1 and RAD51 in S-phase-specific nuclear foci. Monoubiquitination of FANCD2 is required for normal cell-cycle progression following cellular exposure to mitomycin C. Our data indicate that the monoubiquitination of FANCD2 Is highly regulated, and they suggest that FANCD2/BRCA1 complexes and FANCD2/RAD51 complexes participate in an S-phase-specific cellular process, such as DNA repair by homologous recombination. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp, Boston, MA USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Garcia-Higuera, Irene/L-5004-2014 FU NCI NIH HHS [F32-CA88445-01]; NHLBI NIH HHS [P01HL54785-04, R01HL52725-04]; NIDDK NIH HHS [P01DK5654, R01DK43889-09] NR 43 TC 314 Z9 320 U1 1 U2 9 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 OCT 1 PY 2002 VL 100 IS 7 BP 2414 EP 2420 DI 10.1182/blood-2002-01-0278 PG 7 WC Hematology SC Hematology GA 598FV UT WOS:000178266000018 PM 12239151 ER PT J AU Taniguchi, T D'Andrea, AD AF Taniguchi, T D'Andrea, AD TI The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC SO BLOOD LA English DT Article ID C GENE-PRODUCT; COMPLEX; PATHWAY; FAA; CYTOPLASM; HOMOLOGY; INTERACT; BRCA1; CELLS AB Fanconi anemia is an autosomal recessive disorder characterized by aplastic anemia, cancer susceptibility, and cellular sensitivity to mitomycin C. The 6 known Fanconi anemia gene products (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG proteins) interact in a common pathway. The monoubiquitination and nuclear foci formation of FANCD2 are essential for the function of this pathway. FANCA, FANCC, FANCG, and FANCF proteins form a multisubunit nuclear complex (FA complex) required for FANCD2 monoubiquitination. Because FANCE and FANCC interact in vitro and FANCE is required for FANCD2 monoubiquitination, we reasoned that FANCE is a component of the FA complex in vivo. Here we demonstrate that retroviral transduction of Fanconi anemia subtype E (FA-E) cells with the FANCE cDNA restores the nuclear accumulation of FANCC protein, FANCA-FANCC complex formation, monoubiquitination and nuclear foci formation of FANCD2, and mitomycin C resistance. Hemagglutinin (HA)-tagged FANCE protein localizes diffusely in the nucleus. In normal cells, HA-tagged FANCE protein coimmunoprecipitates with FANCA, FANCC, and FANCG but not with FANCD2. Our data indicate that FANCE is a component of the nuclear FA complex in vivo and is required for the monoubiquitination of FANCD2 and the downstream events in the FA pathway. (C) 2002 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01HL54785, R01HL52725]; NIDDK NIH HHS [P01DK50654, R01DK43889] NR 23 TC 60 Z9 61 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 OCT 1 PY 2002 VL 100 IS 7 BP 2457 EP 2462 DI 10.1182/blood-2002-03-0860 PG 6 WC Hematology SC Hematology GA 598FV UT WOS:000178266000023 PM 12239156 ER PT J AU Park, GH McNeil, MR Doyle, PJ AF Park, GH McNeil, MR Doyle, PJ TI Effects of increased inter-word intervals following prepositions on auditory sentence comprehension in agrammatic and normal comprehenders SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 7 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 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2002 VL 83 IS 1 BP 220 EP 222 AR PII S0093-934X(02)00142-6 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 601EP UT WOS:000178433800086 ER PT J AU Antman, K Abraido-Lanza, AF Blum, D Brownfield, E Cicatelli, B Debor, MD Emmons, K Fitzgibbon, M Gapstur, SM Gradishar, W Hiatt, RA Hubbell, FA Joe, AK Klassen, AC Lee, NC Linden, HM McMullin, J Mishra, SI Neuhaus, C Olopade, FI Walas, K AF Antman, K Abraido-Lanza, AF Blum, D Brownfield, E Cicatelli, B Debor, MD Emmons, K Fitzgibbon, M Gapstur, SM Gradishar, W Hiatt, RA Hubbell, FA Joe, AK Klassen, AC Lee, NC Linden, HM McMullin, J Mishra, SI Neuhaus, C Olopade, FI Walas, K TI Reducing disparities in breast cancer survival: A Columbia University and Avon Breast Cancer Research and Care Network Symposium SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; disparities; minorities; mortality; survival; underserved ID ETHNIC-DIFFERENCES; BLACK-WOMEN; RACIAL/ETHNIC GROUPS; ESTROGEN-RECEPTOR; AFRICAN-AMERICAN; RISK PERCEPTION; WHITE WOMEN; HEALTH-CARE; FREQUENCY; EDUCATION AB On November 8th, 2001, faculty from Universities, government and non-profit community organizations met to determine how, separately and together, they could address disparities in survival of women with breast cancer in the diverse patient populations served by their institutions. Studies and initiatives directed at increasing access had to date met modest success. The day was divided into three sections, defining the issues, model programs, government initiatives and finally potential collaborations. By publishing these proceedings, interested readers will be aware of the ongoing programs and studies and can contact the investigators for more information. The Avon Foundation funded this symposium to bring together interested investigators to share programmatic experiences, data and innovative approaches to the problem. C1 Columbia Univ, New York, NY 10027 USA. Canc Care Inc, New York, NY USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Avon Prod Fdn Inc, Avon Breast Crusade, New York, NY USA. Harvard Univ, Harvard Sch Publ Hlth, Cambridge, MA 02138 USA. DFCI, Boston, MA USA. Northwestern Univ, Sch Med, Evanston, IL 60201 USA. NCI, Div Canc Control, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21224 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30333 USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Ctr Hlth Policy & Res, Irvine, CA 92717 USA. Johns Hopkins Univ, Johns Hopkins Sch Med, Baltimore, MD 21224 USA. Univ Chicago, Pritzker Sch Med, Ctr Clin Canc Genet, Chicago, IL 60637 USA. RP Antman, K (reprint author), MHB 6N 435,177 Ft Washington Ave, New York, NY 10032 USA. FU NCI NIH HHS [P30-CA13696, R03CA81619] NR 42 TC 6 Z9 7 U1 1 U2 8 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2002 VL 75 IS 3 BP 269 EP 280 DI 10.1023/A:1019947110236 PG 12 WC Oncology SC Oncology GA 588AF UT WOS:000177676700009 PM 12353816 ER PT J AU Martyn, JAJ Chang, Y Goudsouzian, NG Patel, SS AF Martyn, JAJ Chang, Y Goudsouzian, NG Patel, SS TI Pharmacodynamics of mivacurium chloride in 13-to 18-yr-old adolescents with thermal injury SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE complications, burn injury; enzymes, plasma cholinesterase; neuromuscular block, mivacurium ID BURN INJURY; NEUROMUSCULAR BLOCKADE; PEDIATRIC-PATIENTS; CHILDREN; RAT; PHARMACOKINETICS; ACETYLCHOLINE; ATRACURIUM; MUSCLES; DISTANT AB Background. Burned patients demonstrate resistance to the effects of non-depolarizing blocking drugs as a result of acetylcholine receptor changes. They also have decreased activity of plasma cholinesterase (PCHE), which metabolizes mivacurium. We hypothesized that decreased PCHE activity would decrease metabolism of mivacurium, and counteract the receptor-related resistance following burns. Methods. Thirteen burned patients and six controls, aged 13-18 yr were followed in 27 studies. The burned patients were sub-classified as having 10-30% or >30% body surface area burn, and were studied whenever possible at less than or equal to6 days, and at 1-12 weeks after the burn. Mivacurium pharmacodynamics were examined following a bolus (0.15 mg kg(-1)) dose, and during and after a continuous infusion. Results. Following a bolus, the onset time and the maximal effect were similar to controls. Recovery was prolonged in the 10-30% burn group at 1-12 weeks (P<0.008), with a similar trend in the >30% burn group at less than or equal to6 days (P<0.082) compared with controls. The infusion requirements for mivacurium were not increased in the burned groups. The PCHE activity was decreased in all burn groups and was inversely related to recovery following the bolus (r=0.73, P<0.001) and the infusion (r=0.69, P<0.001). Conclusion. In contrast to previous studies with non-depolarizers in burned patients, normal mivacurium doses can produce paralysis, at least as rapidly as in controls, but with a possibility of a prolonged recovery from block. The standard dose of mivacurium in the presence of decreased PCHE activity is in effect, a relative overdose that explains the above findings. Mivacurium is an effective drug for use in burns, irrespective of time after, or magnitude of burn injury. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Glaxo Wellcome Inc, Anaesthesia Clin Res, Res Triangle Pk, NC 27709 USA. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM 31569-20, GM 55082-6, GM 61411-4] NR 25 TC 3 Z9 3 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD OCT PY 2002 VL 89 IS 4 BP 580 EP 585 DI 10.1093/bja/aef234 PG 6 WC Anesthesiology SC Anesthesiology GA 602JX UT WOS:000178503100010 PM 12393359 ER PT J AU Mollica, RF Henderson, DC Tor, S AF Mollica, RF Henderson, DC Tor, S TI Psychiatric effects of traumatic brain injury events in Cambodian survivors of mass violence SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; COMBAT VETERANS; POW SURVIVORS; HEAD-INJURY; KOREAN CONFLICT; COGNITIVE DEFICITS; FORMER PRISONERS; MEMORY; TORTURE; WAR AB Background The prevalence of brain injury and its effects in populations exposed to war violence has not been studied in recent years. Aims To examine the association between traumatic brain injury events and psychiatric symptoms of major depression and post-traumatic stress disorder (PTSD) in Cambodian survivors of mass violence. Method The population comprised a multi-stage random sample of Cambodian refugees living in a Thai refugee camp. The main results analysed the relationship between six categories of trauma events and psychiatric symptoms of depression and PTSD during two time periods. Results Almost 15 000 trauma events were reported (n=13481, Pol Pot period; n=1249, past year). Traumatic brain injury was most common in the highly educated and in individuals with the highest levels of cumulative trauma. Of all trauma categories, traumatic brain injury revealed the strongest association with symptoms of depression, and a weaker association with PTSD. Brain injury represented 4% of the total number of traumatic events for both time periods, contributing 20% of the total symptom score for depression and 8% of that for PTSD. Conclusions Clinical identification and treatment of traumatic brain injuries in highly traumatised populations must be maintained in order to develop a new public health model for their treatment. Declaration of interest None. Funding detailed in Acknowledgements. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Program Refugee Trauma, Cambridge, MA 02138 USA. RP Henderson, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Program Refugee Trauma, 22 Putnam St, Cambridge, MA 02138 USA. NR 48 TC 18 Z9 18 U1 3 U2 8 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD OCT PY 2002 VL 181 BP 339 EP 347 DI 10.1192/bjp.181.4.339 PG 9 WC Psychiatry SC Psychiatry GA 603EE UT WOS:000178545200013 PM 12356662 ER PT J AU Tishler, RB Norris, CM Colevas, AD Lamb, CC Karp, D Busse, PM Nixon, A Frankenthaler, R Lake-Willcutt, B Costello, R Case, M Posner, MR AF Tishler, RB Norris, CM Colevas, AD Lamb, CC Karp, D Busse, PM Nixon, A Frankenthaler, R Lake-Willcutt, B Costello, R Case, M Posner, MR TI A Phase I/II trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prognosis squamous cell carcinoma of the head and neck SO CANCER 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 DE head and neck carcinoma; docetaxel; radiation; combined modality therapy ID LOCALLY ADVANCED HEAD; RANDOMIZED TRIAL; I TRIAL; ACCELERATED RADIOTHERAPY; III TRIAL; CANCER; PACLITAXEL; THERAPY; INFUSION; TAXOL AB BACKGROUND, The authors conducted a Phase I/II study in patients with a poor prognosis who had locally advanced squamous cell carcinoma of the head and neck (SCCHN) and who were treated initially with induction chemotherapy. Patients were treated with weekly docetaxel and concurrent daily fractionated radiation therapy to determine the maximum tolerated dose (MTD) of docetaxel and the efficacy of the regimen. METHODS. Twenty-two patients were enrolled, and 21 patients were treated. Eight patients had Stage III SCCHN, and 13 patients had Stage IV SCCHN without distant metastases and were treated first with 2-3 cycles of induction chemotherapy, which consisted of cisplatin plus 5-fluorouracil with or without leucovorin. Patients with a poor prognosis were identified as those who achieved a partial response to induction treatment, achieved a complete response with a positive biopsy, or were at high risk for developing recurrent disease. Patients were treated subsequently with concurrent, escalating doses of docetaxel (given weekly x 6) and once daily 200-centigray radiation fractions. RESULTS. Three patients were treated with a weekly docetaxel dose of 20 mg/m(2) without dose-limiting toxicity (DLT. Both patients who were treated at the next dose level of 30 mg/m(2) experienced DLT. A dose of 25 mg/m(2) was studied without DLT in the 16 patients who were treated, establishing this as the MTD. Sixty-seven percent of the patients are alive without disease at a median follow-up of 35 months (range, 12-59 months) after the initiation of chemoradiotherapy. CONCLUSIONS. The MTD of weekly docetaxel with concurrent daily radiation therapy in the postinduction setting was 25 mg/m(2). Disease free survival data from this study were good and indicated that this regimen was effective in the treatment of patients with SCCHN who had a poor prognosis. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. RP Tishler, RB (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, 330 Brookline Ave, Boston, MA 02215 USA. NR 43 TC 44 Z9 45 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 OCT 1 PY 2002 VL 95 IS 7 BP 1472 EP 1481 DI 10.1002/cncr.10873 PG 10 WC Oncology SC Oncology GA 595VE UT WOS:000178128600010 PM 12237916 ER PT J AU Janne, PA Freidlin, B Saxman, S Johnson, DH Livingston, RB Shepherd, FA Johnson, BE AF Janne, PA Freidlin, B Saxman, S Johnson, DH Livingston, RB Shepherd, FA Johnson, BE TI Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America - Meaningful improvements in survival SO CANCER LA English DT Article; Proceedings Paper CT 9th Meeting of the International-Association-for-the-Study-of-Lung-Cancer CY SEP 11-15, 2000 CL TOKYO, JAPAN SP Int Assoc Study Lung Canc DE lung neoplasm; small cell lung carcinoma; limited stage; randomized ID SOUTHWEST-ONCOLOGY-GROUP; PROPHYLACTIC CRANIAL IRRADIATION; PHASE-III TRIALS; LEUKEMIA GROUP-B; COMBINED MODALITY TREATMENT; ELECTIVE BRAIN IRRADIATION; CANCER-TREATMENT-GROUP; LONG-TERM SURVIVAL; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY AB BACKGROUND. To determine the changes in clinical trials and outcomes of patients with limited-stage small cell lung carcinoma (SCLC) treated on Phase III randomized trials initiated in North America between 1972 and 1992. METHODS. Phase III trials from 1972 to 1992 for patients with limited-stage SCLC were identified. Patients with limited-stage SCLC treated during a similar time interval were also evaluated in the Surveillance, Epidemiology, and End Results (SEER) database. Trends were tested in the number of trials, in the number and gender of patients entered on trial, and in survival duration over time. RESULTS. Thirty trials involving 6564 patients were eligible for analyses. Nineteen trials (61%) involving 3626 patients were initiated within the first half of thus tune period (1972-1981). The median of median survival times of all patients treated on the control arms of the Phase III trials initiated between 1972 and 1981 and between 1982 and 1992 were 12.0 months (range, 10-16 months) and 17.0 months (range, 11-20 months), respectively (P < 0.001). Of 26 studies available for survival analysis, 5 (19%) showed a statistically significant survival prolongation in the experimental arm compared with the control arm with a median prolongation of 3.4 months (range, 1-5.2 months). All five evaluated some aspect of thoracic radiation therapy. Over a similar time period, there was a 6.4-month increase in the median survival of limited-stage SCLC patients listed in the SEER database (P < 0.0001) and a more than doubling of the 5-year survival from 5.2% to 12.1% (P = 0.0001). CONCLUSIONS. Analyses of the patients with limited-stage SCLC treated on Phase III trials in North America initiated between 1972 and 1992 and those listed in the SEER database show significant improvements in median survivals. Furthermore, the 5-year survival of patients with limited-stage SCLC listed in the SEER database has more than doubled over the last 25 years. Further research will be needed to determine the relative contribution of improved therapy, supportive care, and stage migration to this prolongation in survival. C1 Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Adult Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NIH, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Clin Invest Branch, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Univ Washington, Seattle, WA 98195 USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. RI Johnson, David/A-7437-2009 NR 70 TC 85 Z9 94 U1 0 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 OCT 1 PY 2002 VL 95 IS 7 BP 1528 EP 1538 DI 10.1002/cncr.10841 PG 11 WC Oncology SC Oncology GA 595VE UT WOS:000178128600016 PM 12237922 ER PT J AU Geller, AC Sober, AJ Zhang, Z Brooks, DR Miller, DR Halpern, A Gilchrest, BA AF Geller, AC Sober, AJ Zhang, Z Brooks, DR Miller, DR Halpern, A Gilchrest, BA TI Strategies for improving melanoma education and screening for men age <= 50 years - Findings from the American Academy of Dermatology National Skin Cancer Screening Program SO CANCER LA English DT Article DE melanoma; skin cancer; screening; early detection; middle-aged and elderly men ID CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; UNITED-STATES; PEOPLE; TRENDS; YIELD; RISK AB BACKGROUND. Recently, the Institute of Medicine (2000) and the Third United States Preventive Services Task Force (2001) called for studies to help clinicians identify patients, especially elderly patients, who are at high risk for melanoma. In the current study, the authors sought to identify factors associated with a high yield in skin cancer screening and to explore strategies for improving mass screenings for melanoma. METHODS. The authors analyzed the data base of the 242,374 skin cancer screenings conducted on more than 206,000 Americans who attended the American Academy of Dermatology National Skin Cancer Screening Programs during the period 1992-1994. RESULTS. Ninety-six percent of 3476 screenees with a presumptive diagnosis of melanoma or possible melanoma were contacted, and follow-up records were obtained for 73% of screenees. Of these, 363 screenees had histologically proven melanoma. Middle-aged and older men (age greater than or equal to 50 years) comprised only 25% of screenees but comprised 44% of those with a confirmed diagnosis of melanoma. overall yield of melanoma (the number of confirmed diagnoses per the number of screenees) was 1.5 per 1000 screenings (363 diagnoses of 242,374 screenees) compared with a yield of 2.6 per 1000 screenings among men age 50 years. The yield was improved further for men age greater than or equal to 50 years who reported either a changing mole (4.6 per 1000 screenings) or skin types I and II (3.8 per 1000 screenings). The predictive value of a screening diagnosis of melanoma was more than twice as high for men age greater than or equal to 50 years with either a changing mole or skin types I and II compared with all other participants. CONCLUSIONS. The yield of mass screening for melanoma would be improved by outreach to middle-aged and older men, with particular focus on men with changing moles or with skin types I and II. Primary care physicians should be attuned to the risk factors among all of their patients but should be alerted in particular to the heightened risk of melanoma for men age greater than or equal to 50 years. Formal assessment of the impact of targeted screening on mortality warrants further study. C1 Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Dept Publ Hlth, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Dermatol, New York, NY 10021 USA. RP Geller, AC (reprint author), Boston Univ, Sch Med, Dept Dermatol, 720 Harrison Ave,DOB 801A, Boston, MA 02118 USA. NR 31 TC 56 Z9 56 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 OCT 1 PY 2002 VL 95 IS 7 BP 1554 EP 1561 DI 10.1002/cncr.10855 PG 8 WC Oncology SC Oncology GA 595VE UT WOS:000178128600019 PM 12237925 ER PT J AU Casarett, DJ Karlawish, JHT Henry, MI Hirschman, KB AF Casarett, DJ Karlawish, JHT Henry, MI Hirschman, KB TI Must patients with advanced cancer choose between a Phase I trial and hospice? SO CANCER LA English DT Article DE Phase I trials; ethics; research ethics; hospice; palliative care; informed consent ID MOTIVATION AB BACKGROUND. Phase I oncology trials offer no meaningful chance for direct medical benefit and they may prevent patients with advanced cancer from receiving palliative care in a hospice program. however, it is not known whether dual enrollment in a Phase I trial and hospice is feasible. METHODS. Five hundred thirty-four Phase I trials were identified in a national online database, of which 179 (34%) accepted patients with a life expectancy of less than 6 months. Of these, 50 were selected randomly. Their principal investigators were surveyed by fax, with follow-up telephone calls and e-mails. Ninety-two hospices were selected randomly from a national database. Surveys were conducted by telephone with intake coordinators. Principal investigators were asked whether patients enrolled in hospice could also enroll in their trials if they were eligible in all other respects. hospice intake coordinators were asked whether a patient with advanced cancer who met hospice eligibility criteria could also enroll in a Phase I trial. RESULTS. Surveys were completed by 45 of 50 principal investigators (90%) and by 89 of 92 hospices (97%). Although both groups were in favor of dual enrollment, principal investigators (41 of 45; 91%) were more likely to support dual enrollment than hospices (60 of 89; 67%; chi-square test, P = 0.004). Most hospices that did not support dual enrollment cited reasons that were based on concerns about payment or misunderstandings about the nature of Phase I trials. CONCLUSIONS. Most hospices and Phase I principal investigators believe that eligible patients should be allowed to enroll simultaneously in hospice and Phase I trials. These results suggest that the choice between hospice and a Phase I trial is a false dilemma and that greater collaboration in this area is needed. C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Social Work, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU PHS HHS [K01-00931] NR 14 TC 9 Z9 9 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 OCT 1 PY 2002 VL 95 IS 7 BP 1601 EP 1604 DI 10.1002/cncr.10820 PG 4 WC Oncology SC Oncology GA 595VE UT WOS:000178128600025 PM 12237931 ER PT J AU Inoue, A Seidel, MG Wu, WS Kamizono, S Ferrando, AA Bronson, RT Iwasaki, H Akashi, K Morimoto, A Hitzler, JK Pestina, TI Jackson, CW Tanaka, R Chong, MJ McKinnon, PJ Inukai, T Grosveld, GC Look, AT AF Inoue, A Seidel, MG Wu, WS Kamizono, S Ferrando, AA Bronson, RT Iwasaki, H Akashi, K Morimoto, A Hitzler, JK Pestina, TI Jackson, CW Tanaka, R Chong, MJ McKinnon, PJ Inukai, T Grosveld, GC Look, AT TI Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo SO CANCER CELL LA English DT Article ID C-ELEGANS; CAENORHABDITIS-ELEGANS; FACTOR SNAIL; GENE; DEATH; DROSOPHILA; EXPRESSION; THROMBOPOIETIN; MITOCHONDRIA; SUPPRESSION AB We show here that a zinc finger transcriptional repressor, Slug, which is aberrantly upregulated by the E2A-HLF oncoprotein in pro-B cell acute leukemia, functions as an antiapoptotic factor in normal hematopoietic progenitor cells. Slug(-/-) mice were much more radiosensitive than wild-type mice, dying earlier and showing accentuated decreases in peripheral blood cell counts, as well as abundant microhemorrhages and widely disseminated bacterial microabscesses throughout the body. Slug expression was detected in diverse subsets of hematopoietic progenitors, but not in more differentiated B and T lymphoid cells, and there was a significant increase in apoptotic (TUNEL-positive) bone marrow progenitor cells in irradiated Slug(-/-) mice compared to wild-type controls. These results implicate Slug in a novel survival pathway that protects hematopoietic progenitors from apoptosis after DNA damage. C1 St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Look, AT (reprint author), St Jude Childrens Res Hosp, Dept Expt Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM thomas_look@dfci.harvard.edu RI Wu, Wen-Shu/I-1258-2014 OI Wu, Wen-Shu/0000-0002-0225-2522 FU NCI NIH HHS [CA-59571]; NINDS NIH HHS [NS-37956, NS-39867] NR 54 TC 120 Z9 122 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2002 VL 2 IS 4 BP 279 EP 288 DI 10.1016/S1535-6108(02)00155-1 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 606DE UT WOS:000178717500007 PM 12398892 ER PT J AU Puchalski, TA Ryan, DP Garcia-Carbonero, R Demetri, GD Butkiewicz, L Harmon, D Seiden, MV Maki, RG Lopez-Lazaro, L Jimeno, J Guzman, C Supko, JG AF Puchalski, TA Ryan, DP Garcia-Carbonero, R Demetri, GD Butkiewicz, L Harmon, D Seiden, MV Maki, RG Lopez-Lazaro, L Jimeno, J Guzman, C Supko, JG TI Pharmacokinetics of ecteinascidin 743 administered as a 24-h continuous intravenous infusion to adult patients with soft tissue sarcomas: associations with clinical characteristics, pathophysiological variables and toxicity SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th AACR/NCI/EORTC Symposium on New Drugs in Cancer Therapy CY NOV, 2001 CL MIAMI, FLORIDA SP AACR, NCI, EORTC DE cancer; chemotherapy; clinical trials; human; phase II ID PHASE-I; ANTICANCER AGENT; RAT-LIVER; CYTOCHROME-P-450; COMPOUND; GLUCOCORTICOIDS; ACTIVATION; TURBINATA; INDUCTION AB Purpose: Ecteinascidin 743 (ET-743) is a potent cytotoxic alkaloid of marine origin that has shown promising evidence of antitumor activity during phase I clinical trials. In the study reported here, the influence of clinical characteristics and pretreatment pathophysiological variables on the pharmacokinetics of ET-743 and their associations with drug-related toxicity was examined in sarcoma patients treated in three phase 11 clinical trials. Methods: Adult patients with various histological subtypes of soft tissue sarcoma received 1.5 mg/m(2) of ET-743 by 24-h continuous i.v. infusion once every 3 weeks. Eligibility criteria were similar for each study, except for the histological subtype of the tumor or the extent of prior treatment with other anticancer agents, and all patients had normal or near-normal liver and renal function. The maximum plasma concentration (Cm,x) and area under the plasma profile from time zero to infinity (AUC) of the drug were determined during the first cycle of therapy. Patients were evaluated for toxicity every week. Results: Geometric mean +/- SD values of the pharmacokinetic parameters in 69 patients were: C-max 1.14 +/- 0.52 ng/ml, AUC 39.9 +/- 16.6 ng.h/ml, and total body clearance (CL) 36.7 +/- 16.4 1/h per m(2). The only significant correlation involving physical characteristics of the patients or pretreatment pathophysiological variables was a very weak relationship between alkaline phosphatase and AUC (r = 0.39, P < 0.01). The 15 patients with any baseline liver function test exceeding the upper limit of the normal ranges had a significantly greater (P = 0.02) incidence of severe toxicity (80% vs 44%). Although the mean AUC of ET-743 in patients with elevated serum levels of hepatic enzymes was 17% greater than that in patients with normal pretreatment liver function tests, the difference was not significant (P = 0.22). In addition, there was no distinct relationship between the grade of the most severe drug-related toxicity that occurred during the first cycle of therapy and the AUC for the entire cohort. The CL of ET-743 was found to be 27% greater in patients concurrently receiving dexamethasone as a preventative antiemetic than in those who were not, but the difference did not achieve statistical significance (P = 0.08). There were no significant associations between CL (liters per hour) and body surface area or any other variable related to body size. Conclusions: The risk of developing severe toxicity was substantially enhanced in patients with relatively moderate indications of hepatic dysfunction without a coincident effect on the CL of ET-743. Dexamethasone cotreatment appeared to decrease the incidence of severe toxicity as well as the AUC of the drug. Delivering a fixed amount of drug without adjustment for the height or weight of the patient may be more appropriate than dose normalization due to the absence of an association between CL and body surface area. Optimizing dosing strategies to further enhance the therapeutic index of ET-743 may depend upon obtaining a better understanding of the metabolic fate of the drug in humans. C1 Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Pharma Mar SA, Clin Res & Dev, Madrid, Spain. RP Supko, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 31 TC 51 Z9 52 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2002 VL 50 IS 4 BP 309 EP 319 DI 10.1007/s00280-002-0498-3 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 611TC UT WOS:000179033000009 PM 12357306 ER PT J AU Leitzmann, MF Stampfer, MJ Ma, J Chan, JM Colditz, GA Willetts, WC Giovannucci, E AF Leitzmann, MF Stampfer, MJ Ma, J Chan, JM Colditz, GA Willetts, WC Giovannucci, E TI Aspirin use in relation to risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RECEPTOR-GAMMA; LNCAP CELLS; IN-VIVO; CYCLOOXYGENASE-2; EXPRESSION; GROWTH; ASSOCIATION; PROGRESSION; INHIBITORS AB Experimental studies have shown inhibitory effects of nonsteroidal anti-inflammatory drugs on prostate cancer cell proliferation and reduction of prostate cancer metastasis, suggesting their possible preventive role for prostate cancer. We examined the association between regular aspirin use and the risk of prostate cancer among participants in the Health Professionals Follow-up Study, a prospective cohort of 47,882 United States men who were 40-75 years of age and without a history of prostate cancer in 1986. Biennial self-administered questionnaires were used to assess regular aspirin use from 1986 to 1996. We confirmed and staged incident cases of prostate cancer according to medical records and pathology reports. During 518,072 person-years of follow-up, 2,479 new cases of prostate cancer were ascertained. Of these, 608 were diagnosed as advanced (extraprostatic) prostate cancer and 258 as metastatic prostate cancer. We found no association between aspirin use and total prostate cancer. After accounting for prostate-specific antigen examinations and other potentially confounding variables, the relative risk of total prostate cancer for aspirin users compared with nonusers was 1.05 (95% confidence interval, 0.96-1.14). For metastatic prostate cancer, we observed a suggestive decrease in risk among men reporting greater frequency of aspirin use. The multivariate relative risk of metastatic prostate cancer among men using aspirin 22 or more days/month was 0.73 (95% confidence interval, 0.39-1.38) compared with nonusers. We noted no evidence of a linear dose-response relationship (P for trend = 0.40). The results from this cohort indicate that regular aspirin use is not likely to prevent the incidence of total prostate cancer, but we cannot exclude a possible benefit of frequent aspirin use on risk of developing metastatic prostate cancer. 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, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Ctr, Program Epidemiol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Leitzmann, MF (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 FU NCI NIH HHS [5T32 CA09001-26, CA55075]; NHLBI NIH HHS [HL35464] NR 24 TC 67 Z9 68 U1 0 U2 2 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 OCT PY 2002 VL 11 IS 10 BP 1108 EP 1111 PN 1 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RD UT WOS:000178634100024 PM 12376516 ER PT J AU Gariti, P Rosenthal, DI Lindell, K Hansen-Flaschen, J Shrager, J Lipkin, C Alterman, AI Kaiser, LR AF Gariti, P Rosenthal, DI Lindell, K Hansen-Flaschen, J Shrager, J Lipkin, C Alterman, AI Kaiser, LR TI Validating a dipstick method for detecting recent smoking SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CELL LUNG-CANCER; CESSATION; SURVIVORS; EXPOSURE; VALIDITY AB This report evaluates the validity of a new method for verifying self-reported smoking status in patients presenting for pulmonary medicine treatment. A prospective comparison was made between self-reports of smoking status and a new semiquantitative, enzyme-linked, immunosorbent assay-based method testing for the presence of a prime nicotine metabolite, cotinine. Results were validated by gas chromatography/mass spectrometry. Data were collected in an urban, academic, tertiary health care setting. The study included 76 consecutive new patients presenting to participating clinical practices at the Pulmonology or Thoracic Surgery Services. Before taking a smoking history, patients were informed that their urine would be tested onsite for the presence of nicotine using a new method, the NicoMeter, for determining tobacco product exposure, followed by more standard laboratory testing. The level of agreement between the biochemical measurement types was excellent, kappa = 0.777. The new biochemical measurement type used was easy to use. Self-reported smoking status corresponded closely to biochemical testing. However, there was a 5.3-9.5% misclassification of smoking status among the group studied, depending upon the measurement type used. Among 32 lung cancer patients, 15.6%, most likely misrepresented their current smoking status. The NicoMeter appears to be a valid and useful method for confirming self-reported smoking status. Lung cancer patients had a higher rate of inaccurate nonsmoking compared with patients with nonmalignant pulmonary disease. The findings have implications for investigators who accept self-reported smoking status without biochemical verification. C1 Univ Penn, Canc Ctr Grp, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15238 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Gariti, P (reprint author), Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. OI Hansen-Flaschen, John/0000-0003-1989-7244 NR 18 TC 31 Z9 32 U1 0 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 OCT PY 2002 VL 11 IS 10 BP 1123 EP 1125 PN 1 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RD UT WOS:000178634100028 PM 12376520 ER PT J AU Anton-Culver, H Finkelstein, D Griffin, C Hanson, J Isaacs, C Kasten-Sportes, C Mineau, G Nadkarni, P Potter, J Schildkraut, J Strong, L Weber, B Winn, D Ziogas, A Hiatt, R Nayfield, S AF Anton-Culver, H Finkelstein, D Griffin, C Hanson, J Isaacs, C Kasten-Sportes, C Mineau, G Nadkarni, P Potter, J Schildkraut, J Strong, L Weber, B Winn, D Ziogas, A Hiatt, R Nayfield, S TI The Cancer Genetics Network: Three years in development of a resource for research. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 MA A302 BP 1159S EP 1159S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200066 ER PT J AU Garber, JE Ng, A Mauch, P Goloubeva, O Medeiros-Nancarrow, C Byrnes, L Diller, LR AF Garber, JE Ng, A Mauch, P Goloubeva, O Medeiros-Nancarrow, C Byrnes, L Diller, LR TI A feasibility study of tamoxifen chemoprevention in Hodgkin's disease survivors. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 MA A319 BP 1163S EP 1163S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200083 ER PT J AU Patenaude, AF Orozco, S Kaelin, C Farkas, W Garber, JE Matory, Y Mayzel, K McCormick, SR Parry, BA Smith, BL AF Patenaude, AF Orozco, S Kaelin, C Farkas, W Garber, JE Matory, Y Mayzel, K McCormick, SR Parry, BA Smith, BL TI Truth and beauty: Women's emotional experience of prophylactic mastectomy. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Faulkner Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2002 VL 11 IS 10 MA A335 BP 1167S EP 1167S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200099 ER PT J AU Sorensen, G AF Sorensen, G TI A model for incorporating the social context in health behavior interventions: Applications for cancer prevention for working class, multiethnic populations. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 MA B133 BP 1176S EP 1176S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200135 ER PT J AU Mukhopadhyay, NK Weisberg, E Gilchrist, D Doerre, G Bueno, R Sugarbaker, DJ Jaklitsch, MT AF Mukhopadhyay, NK Weisberg, E Gilchrist, D Doerre, G Bueno, R Sugarbaker, DJ Jaklitsch, MT TI Inhibition of histone deacetylase is a novel target for lung cancer treatment. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 OCT PY 2002 VL 11 IS 10 MA C124 BP 1198S EP 1198S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200228 ER PT J AU Yee, KO Streit, M Hawighost, T Detmar, M Lawler, J AF Yee, KO Streit, M Hawighost, T Detmar, M Lawler, J TI The type 1 repeats of thrombospondin-1 inhibit tumor growth in mice through the TGF-beta activating sequence KRFK. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 MA C301 BP 1206S EP 1206S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200264 ER PT J AU Li, F AF Li, F TI Identification and care of people with inherited susceptibility to cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 BP 1239S EP 1240S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200404 ER PT J AU Freedman, M Pearce, C Hirschhorn, J Platko, J Daly, M Henderson, B Altshuler, D AF Freedman, M Pearce, C Hirschhorn, J Platko, J Daly, M Henderson, B Altshuler, D TI A genomic approach to evaluate the androgen receptor locus and its association to sporadic prostate cancer in a multiethnic cohort. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Massachusetts Gen Hosp, Whitehead Inst Genome Res, Boston, MA 02114 USA. USC, Keck Sch Med, Los Angeles, CA 90089 USA. Childrens Hosp, Whithead Inst Genome Res, Boston, MA 02115 USA. Whitehead Inst Genome Res, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 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 OCT PY 2002 VL 11 IS 10 BP 1242S EP 1242S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200412 ER PT J AU Polyak, K AF Polyak, K TI Molecular markers in ductal carcinoma in situ (DICIS) of the breast. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT Conference on Frontiers in Cancer Prevention Research CY OCT 14-18, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Canc Res C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 11 IS 10 BP 1261S EP 1262S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 604RE UT WOS:000178634200473 ER PT J AU Yang, XF Wu, CJ Chen, LY Alyea, EP Canning, C Kantoff, P Soiffer, RJ Dranoff, G Ritz, J AF Yang, XF Wu, CJ Chen, LY Alyea, EP Canning, C Kantoff, P Soiffer, RJ Dranoff, G Ritz, J TI CML28 is a broadly immunogenic antigen, which is overexpressed in tumor cells SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; HUMORAL IMMUNE-RESPONSE; CYTOTOXIC T-LYMPHOCYTES; VERSUS-HOST DISEASE; HUMAN PM-SCL; CANCER-PATIENTS; NUCLEOLAR ANTIGEN; PROSTATE-CANCER AB Donor lymphocyte infusion (DLI) reliably induces durable remission in 75-80% of patients with relapsed chronic myelogenous leukemia (CML) after allogeneic hematopoietic stem cell transplantation. To identify Immunological targets of the graft-versus-leukemia response (GVL) after DLI, we used CML post-DLI responder sera to screen a CML cDNA expression library. One of the antigens identified in this screen is a M-r 28,000 protein, termed CML28. CML28 is identical to hRrp46p, a component of the human exosome, a multiprotein complex involved in the 3' processing of RNA. Components of the human exosome include known autoantigens, such as PMScl-100, an autoantibody target in patients with polymyositis, scleroderma, or polymyositis-scleroderma overlap syndrome. Recombinant CML28-GST fusion protein was purified, and used in Western blot and ELISA to demonstrate the development of a high-titer CML28-specific IgG antibody response in a patient with relapsed CML who responded to DLL Northern blotting demonstrated that CML28 is highly expressed in a variety of hematopoietic and epithelial tumor cell lines, but not in normal hematopoietic tissues or other normal tissue, with the exception of testis. Purified recombinant CML28 was used to generate a CML28-specific murine monoclonal antibody. Western blotting with CML28 monoclonal antibody against whole-cell lysates derived from blood and marrow of normal donors and patients with leukemia revealed high expression of this antigen in tumor but not in normal samples. Because CML28 was highly expressed in epithelial tumor cell lines, antiCML28 responses were also examined in patients with solid tumors. By ELISA, we found specific serological responses in 10-33% of patients with lung cancer, melanoma, and prostate cancer. Our studies suggest that immunogenicity of CML28 is likely because of overexpression of this antigen in tumor cells. Moreover, given its expression and immunogenicity in a wide variety of malignancies, CML28 merits additional evaluation as a target for antigen-specific immunotherapy. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Ctr Hematol Oncol, Dana Farber Canc Inst,Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996, P01 CA066996]; NHLBI NIH HHS [K08 HL004293, KO8 HL04293]; NIAID NIH HHS [K08 AI054514, AI29530, P01 AI029530, U19 AI029530] NR 45 TC 53 Z9 63 U1 0 U2 4 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 OCT 1 PY 2002 VL 62 IS 19 BP 5517 EP 5522 PG 6 WC Oncology SC Oncology GA 600ET UT WOS:000178378200022 PM 12359762 ER PT J AU Levine, SM AF Levine, SM TI Lung transplantation and bronchiolitis obliterans syndrome - Are two lungs better than one? SO CHEST LA English DT Editorial Material ID VOLUME REDUCTION; EMPHYSEMA; SINGLE; DYSFUNCTION; REJECTION C1 Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Levine, SM (reprint author), Univ Texas, Hlth Sci Ctr, Div Pulm Dis Crit Care Med, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2002 VL 122 IS 4 BP 1112 EP 1114 DI 10.1378/chest.122.4.1112 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 605PA UT WOS:000178685200002 PM 12377826 ER PT J AU Travers, AH Rowe, BH Barker, S Jones, A Camargo, CA AF Travers, AH Rowe, BH Barker, S Jones, A Camargo, CA TI The effectiveness of IV beta-agonists in treating patients with acute asthma in the emergency department - A meta-analysis SO CHEST LA English DT Article DE asthma; beta-agonists; emergency department; IV; pulmonary function; side effects ID DOUBLE-BLIND; SALBUTAMOL; TERBUTALINE; MANAGEMENT; QUALITY; TRIALS AB Objectives: To determine the benefit of IV beta(2)-agonists for severe acute asthma treated in the emergency department (ED). Methods: Randomized controlled trials were identified using EMBASE, MEDLINE, and CINAHL; the Cochrane Airways Review Group database; hand searching; bibliographies; pharmaceutical companies; and author contact. Studies where IV beta(2)-agonists were compared to placebo and/or existing standards of care were considered. Where appropriate, trials were combined using odds ratios (ORs) or weighted mean differences with 95% confidence intervals (CIs). Results: From 746 identified references, 55 potentially relevant articles were identified and 15 articles were included. All trials were performed outside North America and were published prior to 1997. Three main treatment strategies were reviewed: strategy I (three articles), IV beta(2)-agonists with inhaled beta(2)-agonists vs inhaled beta(2)-agonists; strategy 2 (six articles), IV beta(2)-agonists alone vs inhaled beta(2)-agonists; and strategy 3 (six articles), IV beta(2)-agonists vs IV methylxanthines. Compared to all treatments, IV beta(2)-agonist use did not lead to clinical or statistical significant differences in vital signs, pulmonary functions, laboratory measures, adverse effects, or clinical success. Although statistically nonsignificant, seven methodologically strong studies demonstrated that peak expiratory flows and heart rates were unchanged following beta(2)-agonist use compared to all other treatments at 60 min (8.3 L/min [95% CI, 17.6 to 34.2] and 3.65 beats/min [95% CI, 2.9 to 10.2], respectively), with an increased risk of adverse effects (OR, 1.98; 95% CI, 0.5 to 8.2). Conclusions: Evidence is lacking to support the use of IV beta(2)-agonists in ED patients with severe acute asthma. Moreover, the clinical benefit appears questionable, while the potential clinical risks are obvious. The only recommendations for IV beta(2)-agonist use should be in those patients in whom inhaled therapy is not feasible, or in the context of a controlled clinical trial comparing IV beta(2)-agonists with standard care vs standard care alone. C1 Univ Alberta, Div Emergency Med, Edmonton, AB T6G 2B7, Canada. Univ Alberta, Dept Radiol, Edmonton, AB T6G 2B7, Canada. Capital Hlth Author, Edmonton, AB, Canada. Univ Texas, Resp Care Dept, San Antonio, TX 78285 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Travers, AH (reprint author), Univ Alberta, Div Emergency Med, 1G1-50 WMC,8440 112th St, Edmonton, AB T6G 2B7, Canada. RI Barker, Samantha/E-2698-2011 FU NHLBI NIH HHS [HL-03533] NR 24 TC 29 Z9 29 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2002 VL 122 IS 4 BP 1200 EP 1207 DI 10.1378/chest.122.4.1200 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 605PA UT WOS:000178685200018 PM 12377842 ER PT J AU Welch, TR Frenzke, M Witte, D Davis, AE AF Welch, TR Frenzke, M Witte, D Davis, AE TI C5a is important in the tubulointerstitial component of experimental immune complex glomerulonephritis SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE renal tubule; C5a receptor; complement; glomerulonephritis ID TUBULAR EPITHELIAL-CELLS; GENE-EXPRESSION; HUMAN KIDNEY; RECEPTOR; C4; C3; LOCALIZATION; PROTEINURIA AB Interstitial injury is the hallmark of glomerulonephritis which is progressing to end-stage renal disease (ESRD). In humans and experimental animals, we have shown that interstitial disease is accompanied by up-regulation of complement components in tubular epithelial cells. Glomerulonephritis was induced in mice by the intraperitoneal injection of horse spleen apoferritin (HSA) and lipopolysaccharide (LPS). In addition to wild-type C57/B6 mice, animals in which the C5a receptor had been deleted (C5aR KO) were used. Animals were killed after 3 or 6 weeks, and kidneys harvested. At three weeks, both groups had evidence of mild mesangial matrix expansion and increased cellularity; there were no crescents, sclerotic lesions, or interstitial disease. At six weeks, glomerular lesions were advanced, but identical in the two groups. Both groups had evidence of an identical pattern of C3 gene expression in the tubular epithelium by in situ hybridization. There was a marked difference, however, in the extent of interstitial injury. Wild-type animals had significantly greater numbers of infiltrating interstitial cells, greater expansion of the peritubular space, more tubular atrophy, and more apoptotic tubular cells than did C5aR KOs. The anaphylotoxic fragment of C5, C5a, is not likely to be important in the glomerular component of this model of progressive glomerulonephritis. On the other hand, the interstitial component is markedly attenuated in knockout animals. These data support a role for complement in the interstitial component of this glomerulonephritis model. They are consistent with our hypotheses of a role for complement in the progression of some forms of glomerulonephritis to ESRD. C1 Childrens Hosp Res Fdn, Div Nephrol & Hypertens, Cincinnati, OH 45229 USA. Childrens Hosp Res Fdn, Div Pathol, Cincinnati, OH 45229 USA. Univ Cincinnati, Dept Paediat, Cincinnati, OH USA. Univ Cincinnati, Dept Pathol, Cincinnati, OH USA. Ctr Blood Res, Boston, MA 02115 USA. RP Welch, TR (reprint author), SUNY Upstate Med Univ, Dept Paediat, 750 E Adams St, Syracuse, NY 13210 USA. EM welcht@upstate.edu NR 23 TC 32 Z9 36 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD OCT PY 2002 VL 130 IS 1 BP 43 EP 48 DI 10.1046/j.1365-2249.2002.01957.x PG 6 WC Immunology SC Immunology GA 595NJ UT WOS:000178115400008 PM 12296852 ER PT J AU Ringstrom, E Peters, E Hasegawa, M Posner, M Liu, M Kelsey, KT AF Ringstrom, E Peters, E Hasegawa, M Posner, M Liu, M Kelsey, KT TI Human papillomavirus type 16 and squamous cell carcinoma of the head and neck SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMERASE-CHAIN-REACTION; IN-SITU HYBRIDIZATION; 2ND PRIMARY CANCERS; ORAL-CANCER; HPV DETECTION; RISK FACTOR; INFECTION; DNA; ASSOCIATION; PREVALENCE AB Purpose: Human papillomavirus (HPV) has previously been reported to be associated with squamous cell carcinoma of the head and neck. Our objective was to investigate the presence and type of HPV infection in head and neck tumors and determine whether infection was associated with individual tumor characteristics, patients' pattern of tobacco and alcohol exposure, or with clinical outcome. Experimental Design: Using a case series design, fresh tumor samples were obtained from a series of 89 head and neck squamous cell carcinoma patients, including 64 men and 25 women. The majority of tumors were located in the oral cavity, followed by the oropharynx. A PCR-based technique with restriction fragment length polymorphism analysis was used to detect and type HPV. Results: Of the 89 patients, 18 (20%) had detectable HPV16 in their tumor samples. HPV16 was detected in 64% of tonsil tumors, 52% oropharyngeal tumors, and 5% oral cavity tumors. The mean age of subjects with HPV16-positive tumors was younger than the patients with HPV-negative tumors. Also, this group consumed less alcohol on a weekly basis and had a better clinical outcome compared with the HPV-negative group. Smoking, clinical stage, tumor grade, and tumor-node-metastasis status were not associated with HPV16 presence. Conclusions: Our study supports the previous reports that suggest HPV16 is associated with squamous cell cancers located in the oropharynx and oral cavity. The fact that HPV-positive tumors were observed in younger, lighter alcohol-consuming individuals with a better overall and disease-specific survival suggests a distinct disease process in these patients. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Head & Neck Oncol, Boston, MA 02115 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave,Bldg 1,Room 207, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014; OI /0000-0003-4928-6532 FU NCI NIH HHS [CA78609]; NIEHS NIH HHS [ES00002] NR 44 TC 189 Z9 193 U1 0 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 OCT PY 2002 VL 8 IS 10 BP 3187 EP 3192 PG 6 WC Oncology SC Oncology GA 603EB UT WOS:000178544900020 PM 12374687 ER PT J AU Virella, G Atchley, D Koskinen, S Lopes-Virella, MF AF Virella, G Atchley, D Koskinen, S Lopes-Virella, MF CA DCCT EDIC Res Grp TI Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL SO CLINICAL IMMUNOLOGY LA English DT Article DE arteriosclerosis; diabetes; autoimmunity; human oxidized LDL antibodies; immune complexes; immunological factors in atherosclerosis ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY DISEASE; MONOCYTE-DERIVED MACROPHAGES; HUMAN-ENDOTHELIAL-CELLS; MODIFIED LDL ANTIBODIES; OXIDIZED LDL; CAROTID ATHEROSCLEROSIS; METABOLIC CONTROL; HEART-DISEASE; IN-VITRO AB Immune complexes (IC) prepared with human low density lipoprotein (LDL) and rabbit LDL antibodies induce foam cell transformation of human macrophages and activate the release of proinflammatory mediators by human macrophages and THP-1 cells. Because the affinity of human oxidized LDL (oxLDL) antibodies is lower than that of rabbit antibodies, IC formed with human antibodies could have limited pathogenic potential. Immune complexes prepared with human oxidized LDL (oxLDL) and purified human oxLDL antibodies (predominantly of the IgG1 and IgG3 isotypes) were presented to THP-1 cells using two protocols previously described in studies of the properties of LDL-IC prepared with rabbit antibodies. OxLDL/human oxLDL antibody IC immobilized by adsorption to red blood cells (RBC) induced the release of significantly higher levels of TNF from THP-1 cells (872-313 pg/ml) than oxLDL adsorbed to RBC (461-75.6 pg/ml) and caused a higher degree of cholesterol ester accumulation in the same cells (5.4-0.77 in cells incubated with IC-coated RBC vs 1.99-1.16 in oxLDL-coated RBC). Insoluble IC prepared with oxLDL/human oxLDL antibody were even more effective in promoting intracellular accumulation of cholesterol in THP-1 cells (total cholesterol = 53.8-13.5 and cholesterol esters = 24.0-7.2 mg/l in THP-1 cells incubated with insoluble IC (200 jig) vs total cholesterol = 32.4-8.2 and cholesterol esters = 7.7 +/- 2.8 mug/l in THP-1 cells incubated with an identical concentration of oxLDL) and also induced the release of TNF. Thus we have demonstrated that IC prepared with human oxLDL and human oxLDL antibodies have the same atherogenic and proinflammatory properties as IC prepared with human LDL and rabbit LDL antibodies. This strongly supports the concept that modified LDL-IC present in circulation and/or tissues play an important pathogenic role in arteriosclerosis. (C) 2002 Elsevier Science (USA). C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29403 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VA Med Ctr, Strom Thrumond Res Bldg,114 Doughty St, Charleston, SC 29425 USA. FU NCRR NIH HHS [M01-RR-1070]; NHLBI NIH HHS [P01-HL55782] NR 51 TC 74 Z9 86 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD OCT PY 2002 VL 105 IS 1 BP 81 EP 92 DI 10.1006/clim.2002.5269 PG 12 WC Immunology SC Immunology GA 607RT UT WOS:000178805100010 PM 12483997 ER PT J AU Stone, DR Corcoran, C Wurcel, A McGovern, B Quirk, J Brewer, A Sutton, L D'Aquila, RT AF Stone, DR Corcoran, C Wurcel, A McGovern, B Quirk, J Brewer, A Sutton, L D'Aquila, RT TI Antiretroviral drug resistance mutations in antiretroviral-naive prisoners SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RECENT SEROCONVERTERS; HIV-1; TRANSMISSION; PREVALENCE; INFECTION AB We assessed the incidence of antiretroviral drug resistance in a cohort of 25 antiretroviral-naive, human immunodeficiency virus-positive inmates in Massachusetts. Silent mutations, unexpected mutations at resistant sites, and resistance mutations were recorded. Among these inmates, we found a prevalence of drug resistance mutations that was equivalent to the prevalence previously found in nonprison populations in the same state. C1 Lemuel Shattuck Hosp, Infect Dis Sect, Jamaica Plain, MA 02130 USA. Tufts Univ, Sch Med, Medford, MA 02155 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Correct Med Serv, Dedham, MA USA. Vanderbilt Univ, Med Ctr, Div Infect Dis, Nashville, TN USA. RP Stone, DR (reprint author), Lemuel Shattuck Hosp, Infect Dis Sect, 170 Morton St, Jamaica Plain, MA 02130 USA. NR 17 TC 11 Z9 11 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 OCT 1 PY 2002 VL 35 IS 7 BP 883 EP 886 DI 10.1086/342697 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 594DF UT WOS:000178032900015 PM 12228827 ER PT J AU Harisinghani, MG Maher, MM Hahn, PF Gervais, DA Jhaveri, K Varghese, J Mueller, PR AF Harisinghani, MG Maher, MM Hahn, PF Gervais, DA Jhaveri, K Varghese, J Mueller, PR TI Predictive value of benign percutaneous adrenal biopsies in oncology patients SO CLINICAL RADIOLOGY LA English DT Article DE adrenal gland; biopsies; interventional procedures ID CONTRAST-ENHANCED CT; CHEMICAL-SHIFT; MASSES AB PURPOSE: Percutaneous CT guided biopsy is accepted as a safe procedure for the diagnosis of indeterminate adrenal masses in oncologic patients. The purpose of this study was to evaluate the accuracy of a 'negative for tumour' adrenal biopsy in the oncologic patient population by assessing subsequent outcome including clinical course, size and imaging characteristics of the adrenal lesions on follow-up imaging studies and pathological findings at re-biopsy or following adrenal mass resection. MATERIALS AND METHODS: Retrospective analysis of 225 oncological patients (F:M, 128:87; age range 33-87 years, mean age 66 years) who had undergone CT guided biopsies of an adrenal mass over a 5-year period was performed. Those patients with a report consistent with 'negative for malignancy' were evaluated by reviewing the medical records for patient demographics, primary malignancy, histology of adrenal tumour, subsequent surgical interventions, repeat adrenal biopsy under image guidance, by open surgery or at autopsy, subsequent abdominal imaging in which the adrenal gland was imaged, and long-term outcome including hospital admissions, or death. RESULTS: Of the 225 CT-guided adrenal biopsies performed, 41 (18%) were negative for neoplasm. The primary neoplasm in these 41 patients included lung cancer (n = 32), breast (n = 5), renal cell carcinoma (n = 2), bladder (n = 1), and prostate (n = 1). The size of the adrenal lesions ranged from 2.8-5 cm. Of the 41 biopsies, which were negative for tumour; 10 were identified as adenomas and the rest showed benign adrenal cortical cells or hyperplasia on cytopathology and histopathology. Repeat biopsies were obtained in 13/41 (31 %) patients; whereas 2/41 (5%) had their adrenal gland analyzed on postmortem examination. None of these 15 repeat evaluations yielded tumour. CONCLUSION: In oncological patients, pathological analysis of tissue samples obtained by CT-guided percutaneous biopsy, suggesting benign aetiology, is reliable and predicts a benign course on long-term follow-up. A negative or benign pathology result for a CT guided percutaneous adrenal biopsy can be regarded as a true negative evaluation in oncological patients with no necessity to repeat the biopsy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 41 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD OCT PY 2002 VL 57 IS 10 BP 898 EP 901 DI 10.1053/crad.2002.1054 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 601ZF UT WOS:000178479000006 PM 12413913 ER PT J AU Bhowmick, P Eroglu, A Wright, DL Toner, M Toth, TL AF Bhowmick, P Eroglu, A Wright, DL Toner, M Toth, TL TI Osmometric behavior of mouse oocytes in the presence of different intracellular sugars SO CRYOBIOLOGY LA English DT Article DE trehalose; glucose; stachyose; osmometric behavior; osmotically inactive fraction ID WATER PERMEABILITY; ACTIVATION-ENERGY; CRYOPRESERVATION; MURINE; OVA AB In order to successfully cryopreserve oocytes using low concentrations of intracellular sugars, it is important to characterize their osmotic response in the presence of these intracellular sugars. In the present study, murine (B6D2F1) oocytes were microinjected with 0.8 M glucose, trehalose or stachyose solutions to achieve an intracellular concentration equivalent to 0.1 M, and then exposed to hypertonic solutions of increasing strength by supplementing an isotonic solution with 0.2, 0.3, 0.5, and 0.7 M of trehalose. Analysis of volumetric response of microinjected oocytes showed that the oocytes behaved as ideal osmometers in the presence of intracellular sugars and satisfied the Boyle van't Hoff relationship. Extrapolation of the osmotically inactive fraction ((V) over bar (b)) from the Boyle van't Hoff relationship yielded values of 0.188 +/- 0.028, 0.212 +/- 0.042, 0.197 +/- 0.044, and 0.211 +/- 0.042 for control, glucose, trehalose and stachyose-injected oocytes, respectively. The present data revealing osmometric behavior of mouse oocytes in the presence of different intracellular sugars are important for the optimization of cryopreservation protocols using sugars. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Toth, TL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 12 TC 6 Z9 8 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD OCT PY 2002 VL 45 IS 2 BP 183 EP 187 AR PII S0011-2240(02)00126-8 DI 10.1016/S0011-2240(02)00126-8 PG 5 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 630TB UT WOS:000180124300009 PM 12482383 ER PT J AU Arnaout, MA Goodman, SL Xiong, JP AF Arnaout, MA Goodman, SL Xiong, JP TI Coming to grips with integrin binding to ligands SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID GLYCOPROTEIN-IIB-IIIA; CELL-ADHESION MOLECULE-1; CHEMICAL CROSS-LINKING; AMINO-ACID-RESIDUES; CD11B A-DOMAIN; CRYSTAL-STRUCTURE; I-DOMAIN; ALPHA-SUBUNIT; CATION-BINDING; FIBRINOGEN-BINDING AB Integrins are alphabeta heterodimeric cell-surface receptors that are vital to the survival and function of nucleated cells. They recognize aspartic-acid- or a glutamic-acid-based sequence motifs in structurally diverse ligands. Integrin recognition of most ligands is divalent cation dependent and conformationally sensitive. In addition to this common property, there is an underlying binding specificity between integrins and ligands for which there has been no structural basis. The recently reported crystal structures of the extracellular segment of an integrin in its unliganded state and in complex with a prototypical Arg-Gly-Asp (RGD) ligand have provided an atomic basis for cation-mediated binding of aspartic-acid-based ligands rho integrins. They also serve as a basis for modelling other integrins in complex with larger physiologic ligands. These models provide new insights into the molecular basis for ligand binding specificity in integrins and its regulation by activation-cl riven tertiary and quaternary changes. C1 Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, Charlestown, MA 02129 USA. Merck KGaA, Oncol, Dept Biomed Res, D-64271 Darmstadt, Germany. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Struct Biol Program, Leukocyte Biol & Inflammat Program, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. NR 112 TC 145 Z9 153 U1 3 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2002 VL 14 IS 5 BP 641 EP 651 DI 10.1016/S095506740200371X PG 11 WC Cell Biology SC Cell Biology GA 590TJ UT WOS:000177837900018 PM 12231361 ER PT J AU Daley, GQ AF Daley, GQ TI Prospects for stem cell therapeutics: myths and medicines SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID BONE-MARROW TRANSPLANTATION; IN-VITRO; ES CELLS; HEMATOPOIETIC PROGENITORS; DIFFERENTIATED STATE; PARKINSONS-DISEASE; PANCREATIC-ISLETS; MUSCLE; PRECURSORS; BLOOD AB With common scientific themes and experimental strategies, stem cell biology is evolving into a recognizable discipline. Its clinical arm, regenerative medicine, is also gaining momentum-invigorated by the potential of stem cells to provide treatments for a host of medical conditions that are poorly served by drug therapy. But are the expectations for stem cell therapies realistic or overstated? In the past year, neurons, insulin-producing cells, and hematopoietic stem cells have been generated from embryonic stem cells or cultivated from somatic tissues of the adult. These cells have yielded modest and preliminary hints of functional reconstitution in animal models. Although encouraging, significant hurdles remain before the promise of stem cells will be realized in the clinic. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA76418]; NHLBI NIH HHS [HL71265]; NIDDK NIH HHS [DK59279] NR 63 TC 23 Z9 26 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2002 VL 12 IS 5 BP 607 EP 613 DI 10.1016/S0959-437X(02)00346-5 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 591UG UT WOS:000177898200015 PM 12200167 ER PT J AU Gupta, SN Shaw, JC AF Gupta, SN Shaw, JC TI Anterolateral leg alopecia revisited SO CUTIS LA English DT Article AB Alopecia of the leg-an extremely common yet ill-defined condition-is described in few contemporary dermatology textbooks. In this article, we describe 3 patients with anterolateral alopecia of the legs and further characterize this condition through a review of the literature. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Univ Toronto, Div Dermatol, Toronto, ON, Canada. RP Gupta, SN (reprint author), Wellman Labs, 55 Fruit St BAR 413, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU QUADRANT HEALTHCOM INC PI CHATHAM PA 26 MAIN ST, STE A, CHATHAM, NJ 07928-2402 USA SN 0011-4162 J9 CUTIS JI Cutis PD OCT PY 2002 VL 70 IS 4 BP 215 EP 216 PG 2 WC Dermatology SC Dermatology GA 605RK UT WOS:000178690700004 PM 12403312 ER PT J AU Bevona, C Sober, AJ AF Bevona, C Sober, AJ TI Melanoma incidence trends SO DERMATOLOGIC CLINICS LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; LONG-TERM INCREASE; UNITED-STATES; NEW-ZEALAND; JAPANESE PATIENTS; ANATOMIC SITE; EPIDEMIOLOGY; MORTALITY; CANCER; ISSUES AB This article describes melanoma as an important health concern because of its rapid and continuous growth in many parts of the world. In the United States, a persistent increase in incidence is seen, which has started to slow in recent years. In some countries, differing trends are seen in younger people, with incidence and mortality rates leveling off or decreasing in this population. This article describes that despite this leveling off, melanoma incidence is likely to continue to rise in the near future, because rates are still increasing in older people who comprise most of those afflicted with melanoma. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sober, AJ (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA. NR 61 TC 63 Z9 65 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 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2002 VL 20 IS 4 BP 589 EP + AR PII S0733-8635(02)00037-2 DI 10.1016/S0733-8635(02)00037-2 PG 8 WC Dermatology SC Dermatology GA 598ED UT WOS:000178261700003 PM 12380045 ER PT J AU Tevosian, SG Albrecht, KH Crispino, JD Fujiwara, Y Eicher, EM Orkin, SH AF Tevosian, SG Albrecht, KH Crispino, JD Fujiwara, Y Eicher, EM Orkin, SH TI Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2 SO DEVELOPMENT LA English DT Article DE testis; GATA4; FOG2; Sry; Sertoli cell; sex reversal; mouse ID TESTIS-DETERMINING GENE; STEROIDOGENIC FACTOR-I; ZINC-FINGER PROTEINS; HEART TUBE FORMATION; SIDE-CHAIN-CLEAVAGE; SERTOLI CELLS; TESTICULAR-DIFFERENTIATION; VENTRAL MORPHOGENESIS; CAMPOMELIC DYSPLASIA; LATERAL MESODERM AB In mammals, Sry expression in the bipotential, undifferentiated gonad directs the support cell precursors to differentiate as Sertoli cells, thus initiating the testis differentiation pathway. In the absence of Sry, or if Sry is expressed at insufficient levels, the, support cell precursors differentiate as granulosa cells, thus initiating the ovarian pathway. The molecular mechanisms upstream and downstream of Sry are not well understood. We demonstrate that the transcription factor GATA4 and its co-factor FOG2 are required for gonadal differentiation. Mouse fetuses homozygous for a null allele of Fog2 or homozygous for a targeted mutation in Gata4 (Gata4(ki)) that abrogates the interaction of GATA4 with FOG co-factors exhibit abnormalities in gonadogenesis. We found that Sry transcript levels were significantly reduced in XY Fog2(-/-) gonads at E11.5, which is the time when Sry expression normally reaches its peak. In addition, three genes crucial for normal Sertoli cell function (Sox9, Mis and Dhh) and three Leydig cell steroid biosynthetic enzymes (p450scc, 3betaHSD and p450c17) were not expressed in XY Fog2(-/-) and Gata(ki/ki) gonads, whereas Wnt4, a gene required for normal ovarian development, was expressed ectopically. By contrast, Wt1 and Sf1, which are expressed prior to Sry and necessary for gonad development in both sexes, were expressed normally in both types of mutant XY gonads. These results indicate that GATA4 and FOG2 and their physical interaction are required for normal gonadal development. C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol & Oncol, 300 Longwood Ave, Boston, MA 02115 USA. OI Crispino, John/0000-0002-8182-8306 FU NCI NIH HHS [CA 34196]; NIGMS NIH HHS [GM 20919] NR 69 TC 207 Z9 216 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 2002 VL 129 IS 19 BP 4627 EP 4634 PG 8 WC Developmental Biology SC Developmental Biology GA 604UU UT WOS:000178640100022 PM 12223418 ER PT J AU Garrity, DM Childs, S Fishman, MC AF Garrity, DM Childs, S Fishman, MC TI The heartstrings mutation in zebrafish causes heart/fin Tbx5 deficiency syndrome SO DEVELOPMENT LA English DT Article DE Holt-Oram syndrome; zebrafish; T-box; Tbx5; heart; pectoral fin; limb induction ID HOLT-ORAM-SYNDROME; T-BOX GENES; ULNAR-MAMMARY SYNDROME; TRANSCRIPTION FACTOR; DANIO-RERIO; ANTEROPOSTERIOR POLARITY; DIFFERENTIAL EXPRESSION; EMBRYONIC-DEVELOPMENT; CHAMBER FORMATION; MUTANT EMBRYOS AB Holt-Oram syndrome is one of the autosomal dominant human 'heart-hand' disorders, with a combination of upper limb malformations and cardiac defects. Holt-Oram syndrome is caused by mutations in the TBX5 gene, a member of a large family of T-box transcription factors that play important roles in cell-type specification and morphogenesis. In a screen for mutations affecting zebrafish cardiac function, we isolated the recessive lethal mutant heartstrings, which lacks pectoral fins and exhibits severe cardiac dysfunction, beginning with a slow heart rate and progressing to a stretched, non-functional heart. We mapped and cloned the heartstrings mutation and find it to encode the zebrafish ortholog of the TBX5 gene. The heartstrings mutation causes premature termination at amino acid 316. Homozygous mutant embryos never develop pectoral fin buds and do not express several markers of early fin differentiation. The total absence of any fin bud differentiation distinguishes heartstrings from most other mutations that affect zebrafish fin development, suggesting that Tbx5 functions very early in the pectoral fin induction pathway. Moderate reduction of Tbx5 by morpholino causes fin malformations, revealing an additional early requirement for Tbx5 in coordinating the axes of fin outgrowth. The heart of heartstrings mutant embryos appears to form and function normally through the early heart tube stage, manifesting only a slight bradycardia compared with wild-type siblings. However, the heart fails to loop and then progressively deteriorates, a process affecting the ventricle as well as the atrium. Relative to mammals, fish require lower levels of Tbx5 to produce malformed appendages and display whole-heart rather than atrial-predominant cardiac defects. However, the syndromic deficiencies of tbx5 mutation are remarkably well retained between fish and mammals. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL 49579, HL 63206]; NIDDK NIH HHS [DK 55383] NR 91 TC 162 Z9 171 U1 3 U2 18 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 2002 VL 129 IS 19 BP 4635 EP 4645 PG 11 WC Developmental Biology SC Developmental Biology GA 604UU UT WOS:000178640100023 PM 12223419 ER PT J AU Willi, SM Kennedy, A Wallace, P Ganaway, E Rogers, NL Garvey, WT AF Willi, SM Kennedy, A Wallace, P Ganaway, E Rogers, NL Garvey, WT TI Troglitazone antagonizes metabolic effects of glucocorticoids in humans - Effects on glucose tolerance, insulin sensitivity, suppression of free fatty acids, and leptin SO DIABETES LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; RAT SKELETAL-MUSCLE; OB GENE-EXPRESSION; PRIMARY CULTURED ADIPOCYTES; II DIABETES-MELLITUS; OBESE ZUCKER RATS; ADIPOSE-TISSUE; ENERGY-EXPENDITURE; 3T3-L1 ADIPOCYTES; HEALTHY-SUBJECTS AB Glucocorticoids induce insulin resistance in humans, whereas thiazolidinediones enhance insulin sensitivity. Although the effects of glucocorticoids and thiazolidinediones have been assessed in isolation, interaction between these drugs, which both act as ligands for nuclear receptors, has been less Well studied. Therefore, we examined the metabolic effects of dexamethasone and troglitazone, alone and in combination, for the first time in humans. A total of 10 healthy individuals with normal glucose tolerance (age 40 +/- 11 years, BMI 31 +/- 6.1 kg/m(2)) were sequentially studied at baseline, after 4 days of dexamethasone (4 mg/day), after 4-6 weeks on troglitazone alone (400 mg/day), and again after 4 days of dexamethasone added to troglitazone. Key metabolic variables included glucose tolerance assessed by blood glucose and insulin responses to an oral glucose tolerance test (OGTT), insulin sensitivity evaluated via hyperinsulinemic-euglycemic clamp, free fatty acids (FFAs) and FFA suppressibility by insulin during the clamp study, and fasting serum leptin. Dexamethasone drastically impaired glucose tolerance, with fasting and 2-h OGTT insulin values increasing by 2.3-fold (P < 0.001) and 4.4-fold (P < 0.001) over baseline values, respectively. The glucocorticoid also induced a profound state of insulin resistance, with a 34% reduction in maximal glucose disposal rates (GDRs; P < 0.001). Troglitazone alone increased GDRs by 20% over baseline (P = 0.007) and completely prevented the deleterious effects of dexamethasone on glucose tolerance and insulin sensitivity, as illustrated by a return of OGTT glucose and insulin values and maximal GDR to near-baseline levels. Insulin-mediated FFA suppressibility (FFA decline at 30 min during clamp/FFA at time 0) was also markedly reduced by dexamethasone (P 0.002). Troglitazone had no effect per se, but it was able to normalize FFA suppressibility in subjects co-administered dexamethasone. Futhermore, the magnitudes of response of FFA suppressibility and GDR to dexamethasone were proportionate. The same was true for the reversal of dexamethasone-induced insulin resistance by troglitazone, but not in response to troglitazone alone. Leptin levels were increased 2.2-fold above baseline by dexamethasone. Again, troglitazone had no effect per se but blocked the dexamethasone-induced increase in leptin. Subjects experienced a 1.7-kg weight gain while taking troglitazone but no other untoward effects. We conclude that in healthy humans, thiazolidinediones antagonize the action of dexamethasone with respect to multiple metabolic effects. Specifically, troglitazone reverses both glucocorticoid-induced insulin resistance and impairment of glucose tolerance, prevents dexamethasone from impairing the antilipolytic action of insulin, and blocks the increase in leptin levels induced by dexamethasone. Even though changes in FFA suppressibility were correlated with dexamethasone-induced insulin resistance and its reversal by troglitazone, a cause-and-effect relationship cannot be established. However, the data suggest that glucocorticoids and thiazolidinediones exert fundamentally antagonistic effects on human metabolism in both adipose and muscle tissues. By preventing or reversing insulin resistance, troglitazone may prove to be a valuable therapeutic agent in the difficult clinical task of controlling diabetes in patients receiving glucocorticoids. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Willi, SM (reprint author), Med Univ S Carolina, Dept Pediat, 171 Ashley Ave, Charleston, SC 29425 USA. FU NCRR NIH HHS [M01 RR-01070-20S3]; NIDDK NIH HHS [DK-38764] NR 63 TC 52 Z9 60 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2002 VL 51 IS 10 BP 2895 EP 2902 DI 10.2337/diabetes.51.10.2895 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 599LT UT WOS:000178336600003 PM 12351424 ER PT J AU Mei, Q Mundinger, TO Lernmark, A Taborsky, GJ AF Mei, Q Mundinger, TO Lernmark, A Taborsky, GJ TI Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats SO DIABETES LA English DT Article ID AUTONOMIC NEUROPATHY; GROWTH-FACTOR; BB RAT; NERVOUS-SYSTEM; BETA-CELLS; ALPHA; GLUCAGON; PANCREAS; INSULIN; NOREPINEPHRINE AB To discover whether islet sympathetic nerves are damaged during the autoimmune destruction of islet B-cells, we immunostained sections of pancreas from Bio-Breeder (BB) diabetic rats, using antibodies against vesicular monoamine transporter 2 (VMAT2), a marker of sympathetic nerve terminals. We found a marked decrease in the VMAT2-positive fiber area in the islets of BB rats that had been diabetic for only 1-2 weeks compared with their nondiabetic controls. In contrast, there was no significant decrease in the VMAT2-positive fiber area in the exocrine pancreas in these early diabetic BB rats. Furthermore, streptozotocin-diabetic rats showed no decrease in VMAT2-positive fiber area in their islets compared with controls. The classical diabetic autonomic neuropathy (DAN) that eventually occurs in the heart was not present in BB diabetic rats at this early stage as evidenced by normal cardiac VMAT2 immunostaining and normal cardiac norepinephrine content. Also, in contrast to DAN, this islet neuropathy did not worsen with duration of diabetes. These data provide evidence of a heretofore unrecognized early sympathetic islet neuropathy (eSIN). Because eSIN occurs selectively in the islet, is rapid in onset, and is associated with autoimmune but not chemically induced diabetes, it is distinct from DAN in location, time course, and mechanism. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Mei, Q (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab 151, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-12047, DK-50154, DK-12829] NR 32 TC 60 Z9 61 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2002 VL 51 IS 10 BP 2997 EP 3002 DI 10.2337/diabetes.51.10.2997 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 599LT UT WOS:000178336600018 PM 12351439 ER PT J AU Nelson, KM Reiber, G Boyko, EJ AF Nelson, KM Reiber, G Boyko, EJ TI Diet and exercise among adults with type Z diabetes SO DIABETES CARE LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the American-Diabetes-Association CY JUN 14-18, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Diabet Assoc ID FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; MEXICAN-AMERICAN WOMEN; 3RD NATIONAL-HEALTH; PHYSICAL-ACTIVITY; SELF-MANAGEMENT; MELLITUS; PREVENTION; RECOMMENDATIONS; COMPLICATIONS AB OBJECTIVE - To describe diet and exercise practices from a nationally representative sample of U.S. adults with type 2 diabetes. METHODS- We analyzed data from 1,480 adults older than 17 years with a self-reported diagnosis of type 2 diabetes in the Third National Health and Nutrition Examination Survey (NHANES III). Fruit and vegetable consumption was obtained from a food frequency questionnaire; the percentages of total calories from fat and saturated fat were obtained from a 24-h food recall. Physical activity was based on self report during the month before the survey. RESULTS- Of individuals with-type 2 diabetes, 31% reported no regular physical activity and another 38% reported less than recommended levels of physical activity. Sixty-two percent of respondents ate fewer than five servings of fruits and vegetables per day. Almost two thirds of the respondents consumed >30% of their daily calories from fat and >10% of total calories from saturated fat: Mexican Americans and individuals over the age of 65 years ate a higher number of fruits and vegetables and a lower percentage of total calories from fat. Lower income and increasing age were associated with physical inactivity. Thirty-six percent of the sample were overweight an another 46% were obese. CONCLUSIONS- The majority of individuals with type 2 diabetes were overweight, did pot engage in recommended levels of physical activity, and did not follow dietary guidelines for fat and fruit and vegetable consumption. Additional measures are needed to encourage regular physical activity and improve dietary habits in this population. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Serv, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 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 45 TC 191 Z9 202 U1 4 U2 12 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 OCT PY 2002 VL 25 IS 10 BP 1722 EP 1728 DI 10.2337/diacare.25.10.1722 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UF UT WOS:000185504500009 PM 12351468 ER PT J AU Boyko, EJ Fihn, SD Scholes, D Chen, CL Normand, EH Yarbro, P AF Boyko, EJ Fihn, SD Scholes, D Chen, CL Normand, EH Yarbro, P TI Diabetes and the risk of acute urinary tract infection among postmenopausal women SO DIABETES CARE LA English DT Article ID ASYMPTOMATIC BACTERIURIA; MELLITUS; PREVALENCE; DIAGNOSIS; NIDDM AB OBJECTIVE - To examine whether the presence of diabetes alters the risk of acute urinary tract infection (UTI) in postmenopausal women. RESEARCH DESIGN AND METHODS - A case-control study of the Group Health Cooperative of Puget Sound (GHC), a staff-model nonprofit health maintenance organization in Washington State, was conducted. Subjects were women aged 55-75 years who had been members of GHC for at least 1 year and who had had an acute symptomatic UTI within the preceding month. Laboratory files were used to identify women with a urine culture that grew greater than or equal to 10(5) colonies of a urinary pathogen. Medical records were reviewed to confirm the presence of acute, clinically symptomatic UTI. Control subjects were randomly selected from the GHC enrollment file, screened to remove women with recent UTI, and frequency matched to cases by age within 2 years. An interviewer ascertained self-reported clinician-diagnosed diabetes. Diagnosis of diabetes was confirmed by the GHC diabetes registry. A subsample of women underwent measurement of postvoid residual bladder volume (n = 748) and culture of vaginal flora (n = 454). RESULTS- Of the 901 case and 913 control subjects; diabetes was reported in 13.1 and 6.8%, respectively. The health plan diabetes registry confirmed the diagnosis in 92% of women who self-reported the condition. The age-adjusted odds ratio (OR) for UTI in relation to self-reported clinician-diagnosed diabetes was 2.2 (95% CI 1.6=3.0). Adjustment for frequency of sexual intercourse and history of UTI had little effect on this estimate. Compared with nondiabetic women, higher UTI odds were seen in subjects who used oral hypoglycemic agents (OR 2.9 [95% CI 1.7-5.1]) and insulin (2.6 [1.5-4.6]) but not,in subjects with untreated diabetes or diabetes treated by lifestyle changes.(1.3 [0.7-2.3]). No significant difference was seen in the OR for UTI in diabetic women with disease of shorter duration (<10 years, OR 1.9) or longer duration (>=10 years, OR 2.6) or in relation to HbA(1c) level. Similar microbiologic pathogens were seen in diabetic and nondiabetic women. No significant differences were seen by diabetes status in mean postvoid residual bladder volume or vaginal flora. CONCLUSIONS- Diabetes under pharmacologic treatment is associated with increased risk of clinically apparent UTI in postmenopausal women. C1 Seattle ERIC, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound, NW Hlth Serv Res & Dev Program, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA USA. RP Boyko, EJ (reprint author), Seattle ERIC, VA Puget Sound 152E,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01-DK-43134] NR 27 TC 75 Z9 78 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 OCT PY 2002 VL 25 IS 10 BP 1778 EP 1783 DI 10.2337/diacare.25.10.1778 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UF UT WOS:000185504500018 PM 12351477 ER PT J AU Meigs, JB Nathan, DM D'Agostino, RB Wilson, PWF AF Meigs, JB Nathan, DM D'Agostino, RB Wilson, PWF TI Fasting and postchallenge glycemia and cardiovascular disease risk - The framingham offspring study SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; AMERICAN-DIABETES-ASSOCIATION; IMPAIRED GLUCOSE-TOLERANCE; DIAGNOSTIC-CRITERIA; MICROVASCULAR COMPLICATIONS; BLOOD-GLUCOSE; OLDER ADULTS; HYPERGLYCEMIA; MELLITUS; MEN AB Objective - To test the hypothesis that fasting hyperglycemia (FHG) and 2-h postchallenge glycemia (2hPG) independently increase the risk for cardiovascular disease (CVD). Research Design and Methods - During 1991-1995, we examined 3,370 subjects from the Framingham Offspring Study who were free from clinical CVD (coronary heart disease, stroke, or intermittent claudication) or medication-treated diabetes, and we followed them for 4 years for incident CVD events. We used proportional-hazards regression to assess the risk associated with FHG (fasting plasma glucose greater than or equal to7.0 mmol/l) and 2hPG, independent of the risk predicted by standard CVD risk factors. Results - Mean subject age was 54 years, 54% were women, and previously undiagnosed diabetes was present in 3.2% by FHG and 4.9% (164) by FHG or a 2hPG greater than or equal to 11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPGgreater than or equal to11.1 without FHG, but these 55 subjects represented only 1.7% of the 3,261 subjects without FHG. During 12,242 person-years of follow-up, there were 118 CVD events. In separate sex- and CVD risk-adjusted models, relative risk (RR) for CVD with fasting plasma glucose greater than or equal to7.0 mmol/l was 2.8 (95% CI 1.6-5.0); RR for CVD per 2.1 mmol/l increase in 2hPG was 1.2 (1.1-1.3). When modeled together, the RR for FHG decreased to 1.5 (0.7-3.6), whereas the RR for 2hPG remained significant (1.1, 1.02-1.3). The c-statistic for a FHG, it was 0.746, an wit model including CVD risk factors alone was 0.744; with addition of FHG and 2hPG, it was 0.752. Conclusions - Postchallenge hyperglycemia is an independent risk factor for CVD, but the marginal predictive value of 2hPG beyond knowledge of standard CVD risk factors is small. 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 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Consulting Unit, Boston, MA 02215 USA. Boston Univ, Sch Med, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083] NR 37 TC 310 Z9 330 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 OCT PY 2002 VL 25 IS 10 BP 1845 EP 1850 DI 10.2337/diacare.25.10.1845 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UF UT WOS:000185504500030 PM 12351489 ER PT J AU Taborsky, GJ Ahren, B Mundinger, TO Mei, Q Havel, PJ AF Taborsky, GJ Ahren, B Mundinger, TO Mei, Q Havel, PJ TI Autonomic mechanism and defects in the glucagon response to insulin-induced hypoglycaemia SO DIABETES NUTRITION & METABOLISM LA English DT Article; Proceedings Paper CT Symposium on Hypoglycaemia 2001 - From Research to Practice CY MAY 26-29, 2001 CL ASSISI, ITALY DE sympathetic; type 1 diabetes; parasympathetic ID PANCREATIC-POLYPEPTIDE; INDUCED HYPOGLYCEMIA; SYMPATHETIC-NERVES; SECRETION; STIMULATION; CELL; ACTIVATION; RELEASE; RATS C1 Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Lund Univ, Dept Med, Lund, Sweden. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. RP Taborsky, GJ (reprint author), VA Puget Sound Hlth Care Syst, MS 151,Bldg 1,Room 501,1660 Columbian Way S, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-12829, DK-50154, DK-12047] NR 27 TC 18 Z9 18 U1 0 U2 1 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0394-3402 J9 DIABETES NUTR METAB JI Diabetes Nutr. Metab. PD OCT PY 2002 VL 15 IS 5 BP 318 EP 322 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 645QZ UT WOS:000180991000023 PM 12625478 ER PT J AU Habener, JF AF Habener, JF TI The role of pancreatic duodenum homeobox protein-1 in the development of diabetes mellitus SO DRUG NEWS & PERSPECTIVES LA English DT Article ID INSULIN PROMOTER FACTOR-1; FACTOR-I GENE; GLUCAGON-LIKE PEPTIDE-1; BETA-CELL MASS; TRANSCRIPTIONAL ACTIVATION; MISSENSE MUTATIONS; IPF-1 GENE; STEM-CELLS; EXPRESSION; YOUNG AB Pancreatic duodenum homeobox protein-1 (Pdx-1, also known as Idx-1, Ipf-1, Stf-1) is a homeodomain protein of 283 amino acids whose expression is required for pancreas development to occur. This protein is now recognized to be a critically important transcription factor involved in the regulation of the expression of multiple genes essential for the proper functioning of the beta cells in the endocrine pancreas (islets of Langerhans) that produce insulin, a lack of which results in the development of diabetes mellitus. Finding a way to increase Pdx-1 expression and the neogenesis of beta cells, perhaps through the stimulating effects of glucagon-like peptide-1, may be useful for the treatment of this crippling disease. (C) 2002 Prous Science. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. NR 56 TC 8 Z9 8 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD OCT PY 2002 VL 15 IS 8 BP 491 EP 497 DI 10.1358/dnp.2002.15.8.740224 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 619JY UT WOS:000179473900003 ER PT J AU Leviton, A Holmes, LB Allred, EN Vargas, J AF Leviton, A Holmes, LB Allred, EN Vargas, J TI Methodologic issues in epidemiologic studies of congenital microcephaly SO EARLY HUMAN DEVELOPMENT LA English DT Article DE microcephaly; newborn; epidemiology; growth restriction ID INTRAUTERINE GROWTH-RETARDATION; BIRTH-WEIGHT; HEAD CIRCUMFERENCE; GESTATIONAL-AGE; FETAL GROWTH; INFANTS; MAPS; PREGNANCY; STANDARDS; LOCUS AB In this methodological paper, we explore a number of issues that pose problems for those who seek the antecedents of congenital microcephaly. We pay particular attention to three concerns: Who is a case? How should cases be classified? To whom should cases be compared? (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Neuroepidemiol Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Harvard, MA USA. Brigham & Womens Hosp, Harvard, MA USA. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. RP Leviton, A (reprint author), Harvard Univ, Sch Med, Dept Neurol, Box 122,300 Longwood Ave, Boston, MA 02115 USA. FU NINDS NIH HHS [NS26093] NR 47 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 2002 VL 69 IS 1-2 BP 91 EP 105 AR PII S0378-3782(02)00065-8 DI 10.1016/S0378-3782(02)00065-8 PG 15 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 610YH UT WOS:000178989300010 PM 12324187 ER PT J AU Schlozman, SC AF Schlozman, SC TI Fighting school violence SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD OCT PY 2002 VL 60 IS 2 BP 89 EP 90 PG 2 WC Education & Educational Research SC Education & Educational Research GA 601MM UT WOS:000178450300024 ER PT J AU Devine, SA Kirkley, SM Palumbo, CL White, RF AF Devine, SA Kirkley, SM Palumbo, CL White, RF TI MRI and neuropsychological correlates of carbon monoxide exposure: A case report SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE carbon monoxide; neuropsychology; toxicant-induced encephalopathy; neuroimaging; MRI; neurobehavioral methods ID HYPERBARIC-OXYGEN; FOLLOW-UP; INTOXICATION; BRAIN; ENCEPHALOPATHY; SEQUELAE; NEED AB A 45-year-old woman experienced long-term, chronic exposure to carbon monoxide in the restaurant kitchen where she was employed as a cook. After returning to the restaurant after 5 days off work, she noticed that her symptoms returned immediately; she then aired out the room and called the gas company. Approximately 6 hr after a leak was detected, the patient went to the hospital, where her carboxyhemoglobin was found to be within normal limits and results of a neurologic examination were described as normal. Based on her symptoms, the patient believed she had been exposed to CO for at least I year before the leak was discovered. Initially, she experienced flu-like symptoms, which eventually resolved. At the time of her first neuropsychological. evaluation (17 months after the exposure was identified), her persisting complaints included difficulties in reading, writing, speaking and word retrieval. The test results were consistent with secondary frontal lobe dysfunction associated with subcortical disorders such as those seen after CO exposure. Results of a subsequent neuropsychological examination (29 months postexposure) showed slight improvement in performance, but her performance was still consistent with mild frontal/subcortical dysfunction. Although the initial screening of a brain magnetic resonance image (MRI) performed 15 months after the exposure was interpreted as being within normal limits, two subsequent blind reviews of the same scans identified multiple bilateral lesions in the basal ganglia, which were consistent with chronic CO exposure. We present this case as an example of the utility of MRI and neuropsychological examinations in detecting central nervous system dysfunction secondary to CO exposure. C1 VA Boston Healthcare Syst, Boston Environm Hazards Ctr, Boston, MA 02130 USA. VA Boston Healthcare Syst, Psychol Serv, Boston, MA 02130 USA. Boston Univ, Neurol Associates, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Sch Med, Boston, MA 02215 USA. Boston Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Environm Hlth, Sch Arts & Sci, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Sch Arts & Sci, Boston, MA 02215 USA. RP White, RF (reprint author), VA Boston Healthcare Syst, Boston Environm Hazards Ctr, 150 S Huntington Ave,116B-4, Boston, MA 02130 USA. NR 33 TC 18 Z9 22 U1 0 U2 1 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 OCT PY 2002 VL 110 IS 10 BP 1051 EP 1055 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 600VE UT WOS:000178411800039 PM 12361932 ER PT J AU Gemmel, A Tavares, M Alperin, S Soncini, J Daniel, D Dunn, J Crawford, S Braveman, N Clarkson, TW McKinlay, S Bellinger, DC AF Gemmel, A Tavares, M Alperin, S Soncini, J Daniel, D Dunn, J Crawford, S Braveman, N Clarkson, TW McKinlay, S Bellinger, DC TI Blood lead level and dental caries in school-age children SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood lead; dental caries; epidemiology; tooth; toxicology ID NON-EXPOSED POPULATION; SOUTHERN BAVARIA FRG; HUMAN BONES; NHANES-III; TOOTH; SALIVA; ASSOCIATION; CHILDHOOD; DISEASE; HEALTH AB The association between blood lead level and dental caries was evaluated in cross-sectional analyses of baseline data for 543 children 6-10 years old screened for enrollment in the Children's Amalgam Trial, a study designed to assess potential health effects of mercury in silver fillings. Approximately half of the children were recruited from an urban setting (Boston/Cambridge, MA, USA) and approximately half from a rural setting (Farmington, ME, USA). Mean blood lead level was significantly greater among the urban subgroup, as was the mean number of carious tooth surfaces. Blood lead level was positively associated with number of caries among urban children, even with adjustment for demographic and maternal factors and child dental practices. This association was stronger in primary than in permanent dentition and stronger for occlusal, lingual, and buccal tooth surfaces than for mesial or distal surfaces. In general, blood lead was not associated with caries in the rural subgroup. The difference between the strength of the associations in the urban and rural settings might reflect the presence of residual confounding in the former setting, the presence of greater variability in the latter setting in terms of important caries risk factors (e.g., fluoride exposure), or greater exposure misclassification in the rural setting. These findings add to the evidence supporting a weak association between children's lead exposure and caries prevalence. A biologic mechanism for lead cariogenicity has not been identified, however. Our data are also consistent with residual confounding by factors associated with both elevated lead exposure and dental caries. C1 Childrens Hosp Boston, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Forsyth Inst, Boston, MA USA. Univ Maine, Farmington, ME USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bellinger, DC (reprint author), Childrens Hosp Boston, Farley Basement Box 127,300 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [U01 DE11886] NR 42 TC 22 Z9 22 U1 2 U2 3 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 OCT PY 2002 VL 110 IS 10 BP A625 EP A630 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 600VE UT WOS:000178411800044 PM 12361944 ER PT J AU Eisenberg, JNS Wade, TJ Hubbard, A Abrams, DI Leiser, RJ Charles, S Vu, M Saha, S Wright, CC Levy, DA Jensen, P Colford, JM AF Eisenberg, JNS Wade, TJ Hubbard, A Abrams, DI Leiser, RJ Charles, S Vu, M Saha, S Wright, CC Levy, DA Jensen, P Colford, JM TI Associations between water-treatment methods and diarrhoea in HIV-positive individuals SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID DRINKING-WATER; CRYPTOSPORIDIUM INFECTION; RISK; CONSUMPTION; OUTBREAK AB This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we employed logistic regression and marginal structural modelling of the data. The relative risk of diarrhoea for 'always' vs. 'never' drinking boiled water was 0.68 (95% CI 0.45-1.04) and for 'always' vs. 'never' drinking bottled water was 1.22 (95 % CI 0.82-1.82). Drinking filtered water was unrelated to diarrhoea [1.03 (95 % CI 0.78, 1.35) for 'always' vs. 'never' drinking filtered water]. Adjustment for confounding did not have any notable effect on the point estimates (0.61, 1.35 and 0.98 for boiled, bottled, and filtered water respectively, as defined above). The risk of diarrhoea was lower among those consuming boiled water but this finding was not statistically significant. Because of these findings, the importance of diarrhoea in immunocompromised individuals, and the limitations of cross-sectional data further prospective investigations of water consumption and diarrhoea among HIV-positive individuals are needed. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Univ Calif San Francisco, Community Consortium, San Francisco, CA 94143 USA. San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USA. RP Eisenberg, JNS (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall,MC 7360, Berkeley, CA 94720 USA. FU ODCDC CDC HHS [UR2/CCU916252-02] NR 17 TC 4 Z9 4 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 2002 VL 129 IS 2 BP 315 EP 323 DI 10.1017/S0950268802007422 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 608YW UT WOS:000178876800010 PM 12405100 ER PT J AU Dahme, T Wood, J Livingston, DM Gaubatz, S AF Dahme, T Wood, J Livingston, DM Gaubatz, S TI Two different E2F6 proteins generated by alternative splicing and internal translation initiation SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE E2F; transcription factor; cell cycle; alternative splicing; internal ribosomal entry ID RIBOSOME ENTRY; TRANSCRIPTION; MEMBER; FAMILY; GENE; REPRESSOR; SITES; RNA AB E2F transcription factors play an important role in the regulation of cell cycle progression. E2F6, the most recently identified member of the E2F family, is a retinoblastoma-protein-independent transcriptional repressor that is required for developmental patterning of the axial skeleton. It has recently been shown that the E2f6 locus produces two different mRNAs, E2F6 and E2F6b. The E2F6b mRNA contains an additional exon that is inserted by alternative splicing. This exon contains an in-frame stop-codon and an in-frame translation initiation codon. However, whether a protein is translated from the E2F6b mRNA has not yet been addressed. We now show that internal translation initiation gives rise to E2F6b, an amino-terminal truncated E2F6 protein. We also show that E2F6 and E2F6b mRNAs are ubiquitously expressed in primary mouse tissues. During the cell cycle, the highest expression of both forms is found at the G1 to S transition. The 5' untranslated regions of E2F6 and E2F6b are unusually long, and they contain several upstream AUG codons followed by short reading frames. Our results suggest that translation of E2F6b is initiated by internal ribosome entry. We propose that regulated translation initiation can produce distinct E2F6 isoforms under different physiological conditions. C1 Univ Marburg, Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gaubatz, S (reprint author), Univ Marburg, Inst Mol Biol & Tumor Res, D-35037 Marburg, Germany. NR 21 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT PY 2002 VL 269 IS 20 BP 5030 EP 5036 DI 10.1046/j.1432-1033.2002.03210.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 604GJ UT WOS:000178608400014 PM 12383262 ER PT J AU Monticelli, S Rao, A AF Monticelli, S Rao, A TI NFAT1 and NFAT2 are positive regulators of IL-4 gene transcription SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; transcription factor; gene regulation ID T-CELL DIFFERENTIATION; ATP-DEFICIENT MICE; NF-ATC; ACTIVATION; EXPRESSION; BINDING; FAMILY; DEPHOSPHORYLATION; RESPONSES; SIGNALS AB The nuclear factor of activated T cells (NFAT) plays a key role in gene transcription in both immune and non-immune cell types. Genetic ablation of individual NFAT proteins produces complex phenotypes in mice; in particular, NFAT1(-/-) and NFAT2(-/-) T cells show overproduction and underproduction of IL-4, respectively. We have taken a positive approach to the question of whether these two NFAT family members differentially regulate IL-4 gene transcription. Using constitutively-active NFAT proteins with alanine substitutions instead of phosphorylated serine residues in the regulatory domain, we find that NFAT1(-/-) and NFAT2 are both positive regulators of IL-4 gene transcription, intrinsically very similar in their ability to induce and sustain transcription of the IL-4 gene. Thus the disparate phenotypes of NFAT1(-/-) and NFAT2(-/-) T cells do not reflect differences in DNA-binding or transcriptional activity at the IL-4 gene, but most likely arise from differential regulation of the two proteins or other indirect effects. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Alpert Bldg Rm 152,200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 42471]; NHLBI NIH HHS [HL 67664] NR 32 TC 73 Z9 73 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2002 VL 32 IS 10 BP 2971 EP 2978 DI 10.1002/1521-4141(2002010)32:10<2971::AID-IMMU2971>3.0.CO;2-G PG 8 WC Immunology SC Immunology GA 606RH UT WOS:000178746600030 PM 12355451 ER PT J AU Hu, J Fink, D Mata, M AF Hu, J Fink, D Mata, M TI Microarray analysis suggests the involvement of proteasomes, lysosomes, and matrix metalloproteinases in the response of motor neurons to root avulsion SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; degeneration; rat; regeneration ID SPINAL-CORD INJURY; SCIATIC-NERVE TRANSECTION; TRAUMATIC BRAIN INJURY; PROGRAMMED CELL-DEATH; CYCLIN D1; INDEPENDENT APOPTOSIS; MESSENGER-RNA; EXPRESSION; INDUCTION; RECEPTOR AB We used microarray analysis of RNA expression from punch samples from ventral horn of spinal cord to identify alterations in gene expression in motor neurons 3 days after proximal spinal root avulsion, a traumatic injury that results in the death of 80% of the motor neurons. This analysis identified the anticipated increases in expression of genes coding for proteins involved in the apoptosis cascades and abortive cell cycle re-entry, as well as decreases in expression of genes coding for proteins related to neuronal functional activity, including groups of genes related to energy metabolism, transporter proteins, ion channels, and receptors. It was also found that cathepsins, metalloproteinases, and proteasome-related protein products were highly upregulated in motor neurons following axotomy. Each of these products represent pathways that have been implicated in other models of neuronal damage, but which have not previously been described as a response to axotomy. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15213 USA. GRECC, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Mata, M (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-520 BST,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 45 TC 23 Z9 25 U1 0 U2 0 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 OCT PY 2002 VL 16 IS 8 BP 1409 EP 1416 DI 10.1046/j.1460-9568.2002.02218.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 609UL UT WOS:000178922900001 PM 12405953 ER PT J AU Ryu, O Hu, JCC Yamakoshi, Y Villemain, JL Cao, XH Zhang, CH Bartlett, JD Simmer, JP AF Ryu, O Hu, JCC Yamakoshi, Y Villemain, JL Cao, XH Zhang, CH Bartlett, JD Simmer, JP TI Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE kallikrein-4; enamel matrix serine protease 1; enamel; prostase; PRSS17 ID GENE FAMILY; ENAMEL MATURATION; SERINE-PROTEASE; DENTAL ENAMEL; PROSTATE; KLK4; PURIFICATION; PROTEINASES; CLONING; MOUSE AB Kallikrein-4 (KLK4) is a serine proteinase believed to be important in the normal development of dental enamel. We isolated native KLK4 from developing pig enamel and expressed four recombinant forms. Pig KLK4 was expressed in bacteria with and without the propeptide, and in two eukaryotic systems. Recombinant pig KLK4 was secreted as a zymogen by '293' cells and purified. The proKLK4 was activated in vitro by thermolysin and recombinant pig enamelysin, but not by native KLK4. These results were confirmed using a fluorescent peptide analog of the KLK4 propeptide-enzyme junction. Native KLK4 appears as a doublet at 37 kDa and 34 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Removal of N-linked oligosaccharides by digestion with deglycosidase-F reduced the doublet to a single band at approximately 28 kDa, demonstrating that the active enzyme is glycosylated, and that the 37 kDa and 34 kDa forms differ only in their number of glycosylations. Deglycosylation was also associated with a loss of proteolytic activity. We digested recombinant pig amelogenin with native KLK4 and characterized the cleavage products by N-terminal sequencing and mass spectrometry. Eleven cleavage sites in the amelogenin protein were identified, demonstrating that KLK4 degrades amelogenin and is likely to participate in the degradation of enamel proteins in vivo. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78229 USA. Tsurumi Univ, Sch Dent Med, Dept Biochem, Yokohama, Kanagawa, Japan. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Simmer, JP (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [R01 DE014084, DE13237, R01-DE12769] NR 36 TC 66 Z9 67 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0909-8836 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD OCT PY 2002 VL 110 IS 5 BP 358 EP 365 DI 10.1034/j.1600-0722.2002.21349.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 600FL UT WOS:000178379900005 PM 12664466 ER PT J AU Biederman, J Wilens, TE AF Biederman, J Wilens, TE TI Effects of a controlled-release formulation of methylphenidate on vital signs in school-aged youths with attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S414 EP S414 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000706 ER PT J AU Biederman, J Mick, E AF Biederman, J Mick, E TI Longitudinal course of pediatric-onset bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S221 EP S221 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000254 ER PT J AU Brown, WJ Biederman, J Spencer, T Heiligenstein, J Wernicke, J Allen, AJ Faries, D Michelson, D AF Brown, WJ Biederman, J Spencer, T Heiligenstein, J Wernicke, J Allen, AJ Faries, D Michelson, D TI Efficacy and safety of atomoxetine in the treatment of attention deficit/hyperactivity disorder in children and adolescents SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S411 EP S411 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000699 ER PT J AU Cohen, L Davis, S O'Brien, PMS Brown, E Miner, C Jacobson, J AF Cohen, L Davis, S O'Brien, PMS Brown, E Miner, C Jacobson, J TI Predictors of response to luteal phase fluoxetine treatment of PMDD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. N Staffordshire Hosp, Stoke On Trent, Staffs, England. Jean Hailes Fdn, Clayton, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S176 EP S176 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000135 ER PT J AU Dickson, RA Violato, C Smekal, T Glazer, WM Remington, GJ Stip, E Walker, DJ Jones, B AF Dickson, RA Violato, C Smekal, T Glazer, WM Remington, GJ Stip, E Walker, DJ Jones, B TI Serial measurement of sexual function using the DGSFi in an olanzapine switch trial SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Eli Lilly Canada Inc, Toronto, ON, Canada. Univ Calgary, Dept Appl Psychol, Calgary, AB, Canada. Cassovia Software, Calgary, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Ctr Rech Fernand Seguin, Dept Psychiat, Montreal, PQ, Canada. Lilly Res Labs, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S313 EP S314 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000468 ER PT J AU Fava, M Falk, W Schatzberg, A Kremer, C Murphy, G Rodrigues, H AF Fava, M Falk, W Schatzberg, A Kremer, C Murphy, G Rodrigues, H TI Mirtazapine versus paroxetine in elderly patients with anxious depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Organon Pharmaceut Inc, CNS, W Orange, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S425 EP S426 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000732 ER PT J AU Mick, E Biederman, J Faraone, S AF Mick, E Biederman, J Faraone, S TI A meta analsis of the core features of pediatric bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S226 EP S227 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000266 ER PT J AU Parikh, R Chakraborthy, N Sonawalla, S Mehra, G Dracas, S Fava, M AF Parikh, R Chakraborthy, N Sonawalla, S Mehra, G Dracas, S Fava, M TI Depression in college students in Bombay: A study of 2273 individuals SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Jaslok Hosp & Res Ctr, Bombay, Maharashtra, India. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S247 EP S247 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000314 ER PT J AU Pollack, MH Bose, A Zheng, H AF Pollack, MH Bose, A Zheng, H TI Efficacy and tolerability of escitalopram in the treatment of anxiety disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Forest Labs Inc, New York, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S344 EP S344 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000542 ER PT J AU Sachs, G Mullen, JA Devine, NA Sweitzer, DE AF Sachs, G Mullen, JA Devine, NA Sweitzer, DE TI Quetiapine vs placebo as adjunct to mood stabilizer for the treatment of acute mania SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. AstraZeneca, Wilmington, DE 19850 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S235 EP S236 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000287 ER PT J AU Sonawalla, S Neault, N Hughes, M Petersen, T Dording, C Yeung, A Fava, M AF Sonawalla, S Neault, N Hughes, M Petersen, T Dording, C Yeung, A Fava, M TI Depressive disorders among minority and nonminority college students SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S247 EP S247 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000315 ER PT J AU Spencer, T AF Spencer, T TI Attention-deficit/hyperactivity disorder treatment with a once-daily formulation of methylphenidate: Effect on growth and tics SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract ID DEFICIT HYPERACTIVITY DISORDER; CHILDREN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S413 EP S414 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000705 ER PT J AU Tohen, M Vieta, E Kettter, T Centorino, F Calabrese, J Sachs, G Bowden, CL Risser, RC Baker, RW Evans, AR Dube, S Tollefson, GD Breier, A AF Tohen, M Vieta, E Kettter, T Centorino, F Calabrese, J Sachs, G Bowden, CL Risser, RC Baker, RW Evans, AR Dube, S Tollefson, GD Breier, A TI Olanzapine in the treatment of bipolar depression SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Barcelona, Hosp Clin, Dept Psychiat, Barcelona, Spain. Stanford Univ, Stanford, CA 94305 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. Cleveland State Univ, Mood Disorders Program, Cleveland, OH 44115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RI Vieta, Eduard/I-6330-2013 OI Vieta, Eduard/0000-0002-0548-0053 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S238 EP S239 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000294 ER PT J AU Yildiz, A Sachs, GS AF Yildiz, A Sachs, GS TI Tolerability of single versus split daily dosing of antidepressants: A meta-analysis SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Program, Boston, MA USA. Dept Psychiat, Izmir, Turkey. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2002 VL 12 SU 3 BP S195 EP S196 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 609LL UT WOS:000178905000186 ER PT J AU Hergan, K Schaefer, PW Sorensen, AG Gonzalez, RG Huisman, TAGM AF Hergan, K Schaefer, PW Sorensen, AG Gonzalez, RG Huisman, TAGM TI Diffusion-weighted MRI in diffuse axonal injury of the brain SO EUROPEAN RADIOLOGY LA English DT Article DE diffusion-weighted imaging; diffuse axonal injury; brain injury ID HEAD-INJURY; IMAGING FINDINGS; EDEMA; TRAUMA; RATS AB The goal of this study was to identify and describe the different types and patterns of tissue injury which are encountered by diffusion-weighted imaging (DWI) in diffuse axonal injury (DAI) of the brain. The DWI data sets of 98 patients who suffered from a closed-head injury were retrospectively evaluated. Medical records were reviewed to rule out pre-existing neurological diseases. Lesions were studied for their DWI signal characteristics and lesion size or extension. Traumatic lesions were classified into three categories depending on their signal characteristica on DWI and apparent diffusion coefficient (ADC) maps: type 1, DWI- and ADC-hyperintense most likely representing lesions with vasogenic edema; type 2, DWI-hyperintense, ADC-hypointense indicating cytotoxic edema; type 3, central hemorrhagic lesion surrounded by an area of increased diffusion. According to the size and extent of lesions, injury was classified into three groups: group A, focal injury; group B, regional/confluent injury; and group C, extensive/diffuse injury. Our study showed that diffusion-weighted imaging differentiates between lesions with decreased and increased diffusion in patients with DAI. Different degrees of tissue injury extent were noticed. Future prospective studies should study if this additional information can be used as a predictor of injury reversibility, final outcome and prognosis. C1 Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. LKH Feldkirch, Dept Radiol, Feldkirch, Austria. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Sect, Bldg 149,13th St,Mailcode 149-2301, Boston, MA 02129 USA. NR 20 TC 60 Z9 69 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD OCT PY 2002 VL 12 IS 10 BP 2536 EP + DI 10.1007/s00030-002-1333-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 606EG UT WOS:000178720500018 PM 12271396 ER PT J AU Welt, C Sidis, Y Keutmann, H Schneyer, A AF Welt, C Sidis, Y Keutmann, H Schneyer, A TI Activins, inhibins, and follistatins: From endocrinology to signaling. A paradigm for the new millennium SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Review DE activin; inhibin; follistatin; follistatin-related protein; FSRP/FLRG; transforming growth factor beta; SMADs; activin receptors; signaling; endocrinology; paracrine actions; autocrine actions ID FOLLICLE-STIMULATING-HORMONE; GROWTH-FACTOR-BETA; GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RIBONUCLEIC-ACID; HUMAN MENSTRUAL-CYCLE; POLYCYSTIC-OVARIAN-SYNDROME; GRANULOSA-CELL TUMORS; RAT ESTROUS-CYCLE; MALE RHESUS-MONKEY; BONE-MORPHOGENETIC PROTEIN AB It has been 70 years since the name inhibin was used to describe a gonadal factor that negatively regulated pituitary hormone secretion, The majority of this period was required to achieve purification and definitive characterization of inhibin, an event closely followed by identification and characterization of activin and follistatin (FS). In contrast, the last 15-20 years saw a virtual explosion of information regarding the biochemistry, physiology, and biosynthesis of these proteins, as well as identification of activin receptors, and a unique mechanism for FS action-the nearly irreversible binding and neutralization of activin. Many of these discoveries have been previously summarized; therefore, this review will cover the period from the mid 1990s to present, with particular emphasis on emerging themes and recent advances. As the field has matured, recent efforts have focused more on human studies, so the endocrinology of inhibin, activin, and FS in the human is summarized first. Another area receiving significant recent attention is local actions of activin and its regulation by both FS and inhibin. Because activin and FS are produced in many tissues, we chose to focus on a few particular examples with the most extensive experimental support, the pituitary and the developing follicle, although nonreproductive actions of activin and FS are also discussed. At the cellular level, it now seems that activin acts largely as an autocrine and/or paracrine growth factor, similar to other members of the transforming growh factor beta superfamily. As we discuss in the next section, its actions are regulated extracellularly by both inhibin and FS. In the final section, intracellular mediators and modulators of activin signaling are reviewed in detail. Many of these are shared with other transforming growh factor P superfamily members as well as unrelated molecules, and in a number of cases, their physiological relevance to activin signal propagation remains to be elucidated. Nevertheless, taken together, recent findings suggest that it may be more appropriate to consider a new paradigm for inhibin, activin, and FS in which activin signaling is regulated extracellularly by both inhibin and FS whereas a number of intracellular proteins act to modulate cellular responses to these activin signals. It is therefore the balance between activin and all of its modulators, rather than the actions of any one component, that determines the final biological outcome. As technology and model systems become more sophisticated in the next few years, it should become possible to test this concept directly to more clearly define the role of activin, inhibin, and FS in reproductive physiology. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA. EM Schneyer.alan@mgh.harvard.edu OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01RR01066]; NICHD NIH HHS [R01HD39777, U54HD29164]; NIDDK NIH HHS [R01DK53828, R01DK55838] NR 379 TC 206 Z9 222 U1 0 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1535-3702 EI 1535-3699 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2002 VL 227 IS 9 BP 724 EP 752 PG 29 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 595TB UT WOS:000178123900005 PM 12324653 ER PT J AU Battle, TE Yen, A AF Battle, TE Yen, A TI Ectopic expression of CXCR5/BLR1 accelerates retinoic acid- and vitamin D-3-induced monocytic differentiation of U937 cells SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; KINASE PATHWAY; HL-60 CELLS; RECEPTOR; LINE; ACTIVATION; CHEMOKINE; LYMPHOMA; HYPOPHOSPHORYLATION; MATURATION AB The product of the blr1 gene is a CXC chemokine receptor (CXCR5) that regulates B lymphocyte migration and has been implicated in myelomonocytic differentiation. The U937 human leukemia cell line was used to study the role of blr1 in retinoic acid-regulated monocytio leukemia cell growth and differentiation. blr1 mRNA expression was induced within 12 hr by retinoic acid in U937 cells. To determine whether the early induction of blr1 might regulate inducible monocytic cell differentiation, U937 cells were stably transfected with blr1 (U937/blr1 cells). Ectopic expression of blr1 caused no significant cell cycle or differentiation changes, but caused the U937/blr1 cells to differentiate faster when treated with either retinoic acid or 1alpha,25-dihydroxyvitamin D-3. Treated with retinoic acids U937/blr1 cells showed a greater increase In the percentage of CD11b expressing cells than vector control cells. Retinoic acid also induced a higher percentage of functionally differentiated blr1 transfectants as assessed by nitroblue tetrazolium reduction. U937/blr1 cells underwent moderate growth inhibition on treatment with retinoic acid. Similar results occurred with 1alpha,25-dihydroxyvitamin D-3. Because blr1 was induced early during cell differentiation and because its overexpression accelerated monocytic differentiation, it may be important for signals controlling cell differentiation. C1 Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. RP Battle, TE (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Mayer 549,44 Binney St, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES07052] NR 28 TC 3 Z9 3 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2002 VL 227 IS 9 BP 753 EP 762 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 595TB UT WOS:000178123900006 PM 12324654 ER PT J AU Kuperberg, G Kerwin, R Murray, R AF Kuperberg, G Kerwin, R Murray, R TI Developments in the pharmacological treatment of schizophrenia SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE 5-HT2A receptor; amisulpride; antipsychotic; aripiprazole; atypical; clozapine; D 1 receptor; D3 receptor; D4 receptor; dopamine; glutamate receptor; iloperidone; olanzapine; pharmacotherapy; quetiapine; risperidone; schizophrenia; ziprasidone ID TREATMENT-RESISTANT SCHIZOPHRENIA; FIRST-EPISODE SCHIZOPHRENIA; NEGATIVE SYMPTOMS; EMISSION TOMOGRAPHY; BIOCHEMICAL PROFILE; ANTIPSYCHOTIC-DRUGS; ACUTE EXACERBATION; CONTROLLED TRIAL; RECEPTOR GENE; HIGH-AFFINITY AB Schizophrenia is, at once, a biological disease, a neuropsychological disorder and a dysfunction of social interactions. This presents clinicians with a series of problems with regards to therapy. In the first section of this article, some of the clinical challenges that face those attempting to develop new drugs, are summarised. Several potential pharmacological therapeutic targets that have been, and are continuing to be used, in the development of new antipsychotic drugs, are then considered. This is followed by an outline of the pharmacological and clinical profiles of some of the newer generation antipsychotics, as well as investigational drugs in the pipeline for schizophrenia. Finally, the implications of the introduction of these new drugs for the management of schizophrenia, are discussed. C1 Inst Psychiat, Dept Psychol Med, London, England. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Inst Psychiat, Sect Clin Neuropharmacol, London, England. RP Kuperberg, G (reprint author), Inst Psychiat, Dept Psychol Med, London, England. OI murray, robin/0000-0003-0829-0519 NR 83 TC 4 Z9 4 U1 5 U2 6 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2002 VL 11 IS 10 BP 1335 EP 1341 DI 10.1517/13543784.11.10.1335 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 606RE UT WOS:000178746300001 PM 12387698 ER PT J AU Morishita, T Tsutsui, M Shimokawa, H Horiuchi, M Tanimoto, A Suda, O Tasaki, H Huang, PL Sasaguri, Y Yanagihara, N Nakashima, Y AF Morishita, T Tsutsui, M Shimokawa, H Horiuchi, M Tanimoto, A Suda, O Tasaki, H Huang, PL Sasaguri, Y Yanagihara, N Nakashima, Y TI Vasculoprotective roles of neuronal nitric oxide synthase SO FASEB JOURNAL LA English DT Article DE arteriosclerosis; neointimal formation; vascular remodeling ID SMOOTH-MUSCLE CELLS; SELECTIVE-INHIBITION; MOLECULAR MECHANISMS; GENETIC DEFICIENCY; LESION FORMATION; VASCULAR LESION; ANGIOTENSIN-II; KNOCKOUT MICE; ATHEROSCLEROSIS; INJURY AB Nitric oxide (NO) has multiple important actions that contribute to the maintenance of vascular homeostasis. NO is synthesized by three different isoforms of NO synthase (NOS), all of which have been reported to be expressed in human atherosclerotic vascular lesions. Although the regulatory roles of endothelial NOS (eNOS) and inducible NOS (iNOS) on the development of atherosclerosis have been described, little is known about the role of neuronal NOS (nNOS). Here, we show that nNOS also exerts important vasculoprotective effects in vivo. In a carotid artery ligation model, nNOS gene-deficient (nNOS-KO) mice exhibited accelerated neointimal formation and constrictive vascular remodeling caused by blood flow disruption. In a rat balloon injury model, the selective inhibition of nNOS activity potently enhanced vasoconstrictor responses to a variety of calcium-mobilizing stimuli, suppressed tissue cGMP concentrations, a marker of vascular NO production, and exacerbated neointimal formation. In both models, nNOS was absent before injury and was up-regulated only after the injury, and was predominantly expressed in the neointima and medial smooth muscle cells. These results provide the first direct evidence that nNOS plays important roles in suppressing arteriosclerotic vascular lesion formation in vivo. C1 Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 2, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. Univ Occupat & Environm Hlth, Sch Med, Dept Pharmacol, Kitakyushu, Fukuoka 8078555, Japan. Univ Occupat & Environm Hlth, Sch Med, Dept Pathol & Cell Biol, Kitakyushu, Fukuoka 8078555, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Fukuoka 812, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Tsutsui, M (reprint author), Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 2, Yahatanishi Ku, 1-1 Iseigaoka, Kitakyushu, Fukuoka 8078555, Japan. EM mt2498@med.uoeh-u.ac.jp NR 36 TC 61 Z9 64 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2002 VL 16 IS 12 BP 1994 EP + DI 10.1096/fj.02-0155fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 614BN UT WOS:000179167600014 PM 12397095 ER PT J AU Baldus, S Eiserich, JP Brennan, ML Jackson, RM Alexander, CB Freeman, BA AF Baldus, S Eiserich, JP Brennan, ML Jackson, RM Alexander, CB Freeman, BA TI Spatial mapping of pulmonary and vascular nitrotyrosine reveals the pivotal role of myeloperoxidase as a catalyst for tyrosine nitration in inflammatory diseases SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE myeloperoxidase; peroxynitrite; nitric oxide; nitrotyrosine; free radical; inflammation ID NITRIC-OXIDE PRODUCTION; ALVEOLAR MACROPHAGES; HYDROGEN-PEROXIDE; HYPERTENSIVE RATS; REACTIVE OXYGEN; PEROXYNITRITE; PROTEINS; ATHEROSCLEROSIS; BRONCHIOLITIS; DEGRANULATION AB Nitrotyrosine (NO(2)Tyr) formation is a hallmark of acute and chronic inflammation and has been detected in a wide variety of human pathologies. However, the mechanisms responsible for this posttranslational protein modification remain elusive. While NO(2)Tyr has been considered a marker of peroxynitrite (ONOO-) formation previously, there is growing evidence that heme-protein peroxidase activity, in particular neutrophil-derived myeloperoxidase (MPO), significantly contributes to NO(2)Tyr formation in vivo via the oxidation of nitrite (NO2-) to nitrogen dioxide ((NO2)-N-.). Coronary arteries from a patient with coronary artery disease, liver and lung tissues from a sickle cell disease patient, and an open lung biopsy from a lung transplant patient undergoing rejection were analyzed immunohistochemically to map relative tissue distributions of MPO and NO(2)Tyr. MPO immunodistribution was concentrated along the subendothelium in coronary tissue and hepatic veins as well as in the alveolar epithelial compartment of lung tissue from patients with sickle cell disease or acute rejection. MPO immunoreactivity strongly colocalized with NO(2)Tyr formation, which was similarly distributed in the subendothelial and epithelial regions of these tissues. The extracellular matrix protein fibronectin (FN), previously identified as a primary site of MPO association in vascular inflammatory reactions, proved to be a major target protein for tyrosine nitration, with a strong colocalization of MPO, NO(2)Tyr, and tissue FN occurring. Finally, lung tissue from MPO-/- mice, having tissue inflammatory responses Stimulated by intraperitoneal zymosan administration, revealed less subendothelial NO(2)Tyr immunoreactivity than tissue from wild-type mice, confirming the significant role that MPO plays in catalyzing tissue nitration reactions. These observations reveal that (i) sequestration of neutrophil-derived MPO in vascular endothelial and alveolar epithelial compartments is an important aspect of MPO distribution and action in vivo, (ii) MPO-catalyzed NO(2)Tyr formation occurs in diverse vascular and pulmonary inflammatory pathologies, and (iii) extracellular matrix FN is an important target of tyrosine nitration in these inflammatory processes. (C) 2002 Elsevier Science Inc. C1 Univ Alabama, Dept Anesthesiol, Birmingham, AL 35233 USA. Univ Alabama, Dept Pulm Allergy & Crit Care Med, Birmingham, AL 35233 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35233 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35233 USA. Birmingham VAMC, Birmingham, AL USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35233 USA. Cleveland Clin Fdn, Dept Cell Biol, Cleveland, OH 44195 USA. Univ Hamburg, Hosp Eppendorf, Dept Cardiol, D-20246 Hamburg, Germany. RP Freeman, BA (reprint author), Univ Alabama, Dept Anesthesiol, 946 Tinsley Harrison Tower,619 19th St S, Birmingham, AL 35233 USA. RI Freeman, Bruce/H-9342-2012 NR 43 TC 116 Z9 119 U1 0 U2 2 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 OCT 1 PY 2002 VL 33 IS 7 BP 1010 EP 1019 DI 10.1016/S0891-5849(02)00993-0 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 598NN UT WOS:000178282700012 PM 12361810 ER PT J AU Schneider, A Suman, A Rossi, L Barmada, MM Beglinger, C Parvin, S Sattar, S Ali, L Khan, AKA Gyr, N Whitcomb, DC AF Schneider, A Suman, A Rossi, L Barmada, MM Beglinger, C Parvin, S Sattar, S Ali, L Khan, AKA Gyr, N Whitcomb, DC TI SPINK1/PSTI mutations are associated with tropical pancreatitis and type II diabetes mellitus in Bangladesh SO GASTROENTEROLOGY LA English DT Article ID SECRETORY TRYPSIN-INHIBITOR; GENOME SCAN; GENE; HEREDITARY AB Background & Aims: Tropical pancreatitis, including tropical calcific pancreatitis and fibrocalculous pancreatic diabetes, is endemic in parts of Asia and Africa. In a preliminary study, we found serine protease inhibitor, Kazal type 1 (SPINK1) mutations in 6 of 8 patients with fibrocalculous pancreatic diabetes in Bangladesh. A more extensive investigation of patients with pancreatic diseases in Bangladesh, including non-insulin-dependent diabetes mellitus, was undertaken. Methods: Patients with fibrocalculous pancreatic diabetes (n = 22), tropical calcific pancreatitis (n = 15), and non-insulin-dependent diabetes mellitus (n = 43) and controls (n = 76) from Bangladesh were studied. DNA was extracted, and the SPINK1 gene was sequenced in all patients and 50 controls. Exon 3 was sequenced in an additional 26 controls. Results: SPINK1 N34S mutations appeared in 1 of 76 controls (13%), 12 of 22 patients with fibrocalculous pancreatic diabetes (55%; odds ratio, 83; P < 0.00001), 3 of :15 with tropical calcific pancreatitis (20%; odds ratio, 11.2; P = 0.04), and 6 of 43 with non-insulin-dependent diabetes mellitus (14%; odds ratio, 11.9; P = 0.009). P55S was present in 2 of 76 controls (3%) and in I of 22 patients with fibrocalculous pancreatic diabetes (5%; P = not significant). A novel Y54H (160T>C) mutation was identified in 1 of 15 tropical calcific pancreatitis patients. Conclusions: In Bangladesh, the SPINK1 N34S mutation increases the risk of several forms of pancreatic disease, including fibrocalculous pancreatic diabetes, tropical calcific pancreatitis, and non-insulin-dependent diabetes mellitus. C1 Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15261 USA. Kantonsspital, Dept Gastroenterol, Luzern, Switzerland. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Basel Hosp, Dept Med, CH-4031 Basel, Switzerland. Bangladesh Inst Res & Rehabil Diabet Endocrine &, Dhaka, Bangladesh. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Suman, A (reprint author), Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Room 571,Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. RI Beglinger, Christoph/D-2247-2010; OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 33 TC 91 Z9 92 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2002 VL 123 IS 4 BP 1026 EP 1030 DI 10.1053/gast.2002.36059 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WY UT WOS:000178415800014 PM 12360464 ER PT J AU McHutchison, JG Manns, M Patel, K Poynard, T Lindsay, KL Trepo, C Dienstag, J Lee, WM Mak, C Garaud, JJ Albrecht, JK AF McHutchison, JG Manns, M Patel, K Poynard, T Lindsay, KL Trepo, C Dienstag, J Lee, WM Mak, C Garaud, JJ Albrecht, JK CA Int Hepatitis Interventional Ther TI Adherence to combination therapy enhances sustained response in genotyp-1-infected patients with chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; INITIAL TREATMENT; RANDOMIZED TRIAL; ALPHA THERAPY; HCV RNA; INFECTION; VIRUS AB Background & Aims: Patient adherence to prescribed antiviral therapy in human immunodeficiency virus infection enhances response. We evaluated the impact of adherence to combination therapy with interferon or peginterferon plus ribavirin in chronic hepatitis C patients. Methods: We assessed the effect of dose reduction on sustained virologic response (SVR) from prior trials with interferon alpha-2b plus ribavirin (n = 1010) or peginterferon alpha-2b 1.5 mug/kg/week plus ribavirin (n = 511). The actual treatment administered was verified from drug dispensing/return records and patient diaries. Two groups were defined: (1) patients who received greater than or equal to80% of both their total interferon and ribavirin doses for greater than or equal to80% of the expected duration of therapy and (2) patients who received reduced doses (<80% of one or both drugs for greater than or equal to80% of the expected duration of therapy). A statistical model provided comparative estimates of the response rates in compliant patients. Results: Most patients were at least 80% compliant with interferon alpha-2b/ribavirin or peginterferon alpha-2b/ribavirin therapy and had SVR rates of 52% and 63%, respectively, for the 2 regimens. This was most apparent for HCV-1-infected patients. The impacts of adherence on efficacy from subgroup analysis and the statistical modeling approach were similar. Conclusions: HCV-1-infected patients who can be maintained on >80% of their interferon or peginterferon alpha-2b and ribavirin dosage for the duration of treatment in the setting of a clinical trial exhibit enhanced sustained response rates. Our results suggest that adherence will enhance the likelihood of achieving an initial virologic response. Adherence beyond 12-24 weeks will be advantageous only for those patients who have achieved such an early virologic response. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. Hannover Med Sch, Div Gastroenterol & Hepatol, D-3000 Hannover, Germany. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Univ So Calif, Div Gastroenterol & Hepatol, Los Angeles, CA USA. Hop Hotel Dieu, Serv Hepato Gastroenterol, Lyon, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75235 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP McHutchison, JG (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. OI Poynard, Thierry/0000-0002-2050-640X FU NCRR NIH HHS [M01-RR00043, M01-RR00833, M01-RR01066] NR 22 TC 712 Z9 741 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2002 VL 123 IS 4 BP 1061 EP 1069 DI 10.1053/gast.2002.35950 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WY UT WOS:000178415800018 PM 12360468 ER PT J AU Brand, S Wang, TD Schomacker, KT Poneros, JM Lauwers, GY Compton, CC Pedrosa, MC Nishioka, NS AF Brand, S Wang, TD Schomacker, KT Poneros, JM Lauwers, GY Compton, CC Pedrosa, MC Nishioka, NS TI Detection of high-grade dysplasia in Barrett's esophagus by spectroscopy measurement of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Gastroenterological-Association CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Gastroenterol Assoc ID LASER-INDUCED FLUORESCENCE; PHOTODYNAMIC THERAPY; AMINOLEVULINIC ACID; COLONIC DYSPLASIA; ADENOCARCINOMA; PHOTOSENSITIZATION; LESIONS; CANCER; DIAGNOSIS; ENDOSCOPY AB Background. Preliminary studies with qualitative detection methods suggest that 5-aminolevulinic acid-induced protoporphyrin IX fluorescence might improve the detection of dysplastic Barrett's epithelium. This study used quantitative methods to determine whether aminolevulinic acid-induced protoporphyrin IX fluorescence can differentiate between Barrett's mucosa with and without dysplasia. Methods: Patients were given 10 mg/kg of aminolevulinic acid orally 3 hours before endoscopy. Quantitative fluorescence spectra were acquired by using a nitrogen-pumped dye laser (lambda 400 nm) spectrograph system. The protoporphyrin IX fluorescence intensity at 635 nm was compared with the histopathologic diagnosis for mucosal biopsy specimens taken immediately after the fluorescence measurements. Results: Ninety-seven spectra were obtained from 20 patients. The mean ( standard error) standardized protoporphyrin IX fluorescence intensity was significantly greater (p < 0.05) for high-grade dysplastic Barrett's epithelium (0.29 +/- 0.07, n = 13) than for nondysplastic Barrett's epithelium (0.11 +/- 0.02, n = 43). By using protoporphyrin IX fluorescence alone, high-grade dysplasia was distinguished from nondysplastic tissue types with 77% sensitivity and 71% specificity. Decreased autofluorescence was particularly found in nodular high-grade dysplasia. By using the fluorescence intensity ratio of 635 nm/480 nm, nodular high-grade dysplasia could be differentiated from nondysplastic tissue with 100% sensitivity and 100% specificity. Conclusion: Protoporphyrin IX fluorescence may be useful for identifying areas of high-grade dysplasia in Barrett's esophagus and for targeting of biopsies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Boston Univ, Sch Med, Gastroenterol Sect, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP Nishioka, NS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Gastrointestinal Unit, BAR-703,50 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [P01 CA084203]; NIDDK NIH HHS [T32 DK07191] NR 42 TC 44 Z9 45 U1 0 U2 3 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 OCT PY 2002 VL 56 IS 4 BP 479 EP 487 DI 10.1067/mge.2002.128172 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WL UT WOS:000178414700003 PM 12297761 ER PT J AU Brugge, W AF Brugge, W TI Diagnosis of pancreatic cystadenomas: A report of the National Cooperative Pancreatic Cyst Study SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 13th International Symposium on Endoscopic Ultrasonography CY OCT 04-06, 2002 CL NEW YORK, NEW YORK C1 Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2002 VL 56 IS 4 SU S MA 73 BP S119 EP S119 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WP UT WOS:000178415000094 ER PT J AU Faigel, DO Hunt, GC Gopal, D AF Faigel, DO Hunt, GC Gopal, D TI Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and follow-up of esophageal cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 13th International Symposium on Endoscopic Ultrasonography CY OCT 04-06, 2002 CL NEW YORK, NEW YORK C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 56 IS 4 SU S MA 36 BP S109 EP S109 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WP UT WOS:000178415000057 ER PT J AU Jacobson, BC Bounds, BC Brugge, WR AF Jacobson, BC Bounds, BC Brugge, WR TI Diagnosis of infected pancreatic fluid collection by endoscopic ultrasound-guided fine-needle aspiration SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 13th International Symposium on Endoscopic Ultrasonography CY OCT 04-06, 2002 CL NEW YORK, NEW YORK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2002 VL 56 IS 4 SU S MA 58 BP S115 EP S115 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WP UT WOS:000178415000079 ER PT J AU Poneros, J Brugge, W AF Poneros, J Brugge, W TI Safety and efficacy of endoscopic ultrasound (EUS)-guided portal vein catheterization in a porcine model SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract CT 13th International Symposium on Endoscopic Ultrasonography CY OCT 04-06, 2002 CL NEW YORK, NEW YORK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2002 VL 56 IS 4 SU S MA 22 BP S105 EP S105 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 600WP UT WOS:000178415000043 ER PT J AU Harley, JB AF Harley, JB TI The genetic etiology of systemic lupus erythematosus: a short dispatch from the combat zone SO GENES AND IMMUNITY LA English DT Editorial Material DE SLE; lupus; genetics; review; linkage ID SUSCEPTIBILITY LOCUS; AUTOIMMUNITY; LINKAGE C1 Univ Oklahoma, Oklahoma Med Res Fdn, Med Ctr, US Dept Vet Affairs,Dept Med, Oklahoma City, OK 73104 USA. RP Harley, JB (reprint author), Univ Oklahoma, Oklahoma Med Res Fdn, Med Ctr, US Dept Vet Affairs,Dept Med, 825 NE 13th St, Oklahoma City, OK 73104 USA. NR 31 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S1 EP S4 DI 10.1038/sj.gene.6363908 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300001 PM 12215895 ER PT J AU Kelly, JA Moser, KL Harley, JB AF Kelly, JA Moser, KL Harley, JB TI The genetics of systemic lupus erythematosus: putting the pieces together SO GENES AND IMMUNITY LA English DT Article; Proceedings Paper CT Lupus Genetics Conference CY SEP 07-09, 2001 CL OKLAHOMA CITY, OKLAHOMA SP Oklahoma Med Res Fdn, Amgen Corp DE genetics; systemic lupus erythematosus; genome scan; linkage ID MAJOR HISTOCOMPATIBILITY COMPLEX; MANNOSE-BINDING-PROTEIN; FC-RECEPTOR-III; GAMMA-RIIA POLYMORPHISM; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER CELLS; SIB-PAIR FAMILIES; LYMPHOPROLIFERATIVE DISEASE; SUSCEPTIBILITY LOCUS; AUTOIMMUNE-DISEASE AB With A,, estimates of 10 to 20 and other evidence of familial aggregation, as well as a monozygotic twin concordance rate >20, systemic lupus erythematosus (SLE) would appear to be a very promising phenotype using modem genetic approaches. Indeed, genetic associations are already known at numerous candidate loci including various HLA alleles, complement component genes, Fcgamma receptors, and others, and murine genetic studies of lupus models have provided additional candidate genes and potential syntenic linkages to evaluate in man. The completed genetic linkage studies performed on various collections of pedigrees multiplex for SLE have identified 60 susceptibility loci with varying degrees of evidence for linkage in man. Seven of these meet or exceed the threshold for significant linkage (LOD greater than or equal to 3.3 or P less than or equal to 0.00005) at 1q22-23, 1q41, 2q37, 4p16, 6p21-11, 16q13 and 17p13. In addition, these linkages usually dominate in one ethnicity or another, suggesting that the responsible polymorphisms, once identified, will also vary by ethnicity. Evidence that these linkages can be reproduced range from outright independent confirmation (1q41, 4p16 and 6p21) to additional suggestive evidence in the genomic region of the purported linkage (1q22-23 and 2q37). The results now available suggest that human lupus genetics are robust and that gene identification should be possible using existing genetic approaches and technologies. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NCRR NIH HHS [RR03655]; NHGRI NIH HHS [HG01577]; NIAID NIH HHS [AI31585, AI24717]; NIAMS NIH HHS [AR42460, AR45231] NR 145 TC 70 Z9 73 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S71 EP S85 DI 10.1038/sj.gene.6363885 PG 15 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300013 PM 12215907 ER PT J AU Namjou, B Nath, SK Kilpatrick, J Kelly, JA Reid, J Reichlin, M James, JA Harley, JB AF Namjou, B Nath, SK Kilpatrick, J Kelly, JA Reid, J Reichlin, M James, JA Harley, JB TI Genome scan stratified by the presence of anti-double-stranded DNA (dsDNA) autoantibody in pedigrees multiplex for systemic lupus erythematosus (SLE) establishes linkages at 19p13.2 (SLED1)and 18q21.1 (SLED2) SO GENES AND IMMUNITY LA English DT Article; Proceedings Paper CT Lupus Genetics Conference CY SEP 07-09, 2001 CL OKLAHOMA CITY, OKLAHOMA SP Oklahoma Med Res Fdn, Amgen Corp DE SLE; linkage analysis; anti-double stranded DNA; Crithidia luciliae ID DEOXYRIBONUCLEASE-II; ANTIBODIES; NEPHRITIS; IMMUNOFLUORESCENCE; CALRETICULIN; ASSOCIATION; DIAGNOSIS; FAMILIES; HOMOLOGS; DISEASE AB Anti-double-stranded DNA (anti-dsDNA) is arguably one of the most specific autoantibodies in systemic lupus erythematosus (SLE). This antibody is associated with more severe SLE and with glomerulonephritis. From 196 pedigrees multiplex for SLE, we selected those that had any SLE affected positive for anti-dsDNA by the Crithidia luciliae kinetoplast imunofluorescence assay. This stratification strategy tested the hypothesis that anti-dsDNA would identify a more genetically homogeneous group of pedigrees, in which previously undetected linkage effects could be established. A genome screen data for linkage to SLE was available at 307 microsatellite markers for this selected group of 71 pedigrees: 37 European-American, 29 African-American, and five others. The most significant results were obtained at 19p13.2 (LODEmax = 4.93), named SLED1, in the 37 European-American pedigrees using a dominant model with mixed penetrances (92% for females and 49% for males) at 100% homogeneity (theta = 0). A second linkage effect, SLED2, was established in the 29 African-American pedigrees at 18q21.1 (LODmax = 3.40) using a recessive model with 100% penetrance (theta = 0.1). Parametric and non-parametric multipoint analyses were performed, which provided further evidence and support of susceptibility genes residing in these regions. In conclusion, two powerful linkages have been detected with SLE based on the presence of anti-dsDNA. These findings show SLE to be a richly complicated disease phenotype that is now ripe for important new discovery through a genetic approach. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Norman, OK 73019 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NCRR NIH HHS [RR15577]; NIAID NIH HHS [AI24717, AI31584]; NIAMS NIH HHS [AR45231, AR42460, AR12253] NR 43 TC 22 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S35 EP S41 DI 10.1038/sj.gene.6363905 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300006 PM 12215900 ER PT J AU Olson, JM Song, Y Dudek, DM Moser, KL Kelly, JA Bruner, GR Downing, KJ Berry, CK James, JA Harley, JB AF Olson, JM Song, Y Dudek, DM Moser, KL Kelly, JA Bruner, GR Downing, KJ Berry, CK James, JA Harley, JB TI A genome screen of systemic lupus erythematosus using affected-relative-pair linkage analysis with covariates demonstrates genetic heterogeneity SO GENES AND IMMUNITY LA English DT Article; Proceedings Paper CT Lupus Genetics Conference CY SEP 07-09, 2001 CL OKLAHOMA CITY, OKLAHOMA SP Oklahoma Med Res Fdn, Amgen Corp DE systemic lupus erythematosus; genetic linkage analysis; affected relative pairs ID SUSCEPTIBILITY LOCUS; REVISED CRITERIA; FAMILIES; SCAN; CLASSIFICATION; MANIFESTATIONS; PSORIASIS AB Systemic lupus erythematosus (SLE) appears to be the consequence of complex genetics and of only partly understood environmental contributions. Previous work by ourselves and by others has established genetic effects on 1q, 2q, 4p, 6p, and 16p using SLE as the phenotype. However, individual SLE affecteds are extraordinarily different from one another by clinical and laboratory measures. This variation may have a genetic basis; if so, it is advantageous to incorporate measures of between-family clinical variability as covariates in a genetic linkage analysis of affected relative pairs (ARPs) to allow for locus heterogeneity. This approach was applied to genome scan marker data from 160 pedigrees multiplex for SLE and containing 202 ARPs. Because the number of potential covariates was large, we used both ad hoc methods and formal principal components analysis to construct four composite covariates using the SLE classification criteria plus age of onset, ethnicity, and sex. Linkage analysis without covariates has detected evidence for linkage at 1q22-24, 2q37, 4p16, 12p12-11, and 17p13. Linkage analysis with these covariates uncovered linkage at 13p11, 17q11-25, and 20q12 and greatly improved evidence for linkage at 1q22-24, 2q37, 12p12-11, and 17p13. Follow-up analysis identified the original variables contributing to locus heterogeneity in each of these locations. In conclusion, allowing for locus heterogeneity through the incorporation of covariates in linkage analysis is a useful way to dissect the genetic contributions to SLE and uncover new genetic effects. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Rammelkamp Ctr Educ & Res, Cleveland, OH 44109 USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Inst Human Genet, Minneapolis, MN 55455 USA. Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Olson, JM (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Rammelkamp Ctr Educ & Res, 2500 MetroHlth Dr,R258,MetroHlth Campus, Cleveland, OH 44109 USA. FU NCRR NIH HHS [RR15577, RR03655]; NHGRI NIH HHS [HG01577]; NIAID NIH HHS [AI31584, AI24717]; NIAMS NIH HHS [AR42460, AR45231, AR52221] NR 30 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S5 EP S12 DI 10.1038/sj.gene.6363860 PG 8 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300002 PM 12215896 ER PT J AU Quintero-Del-Rio, AI Kelly, JA Kilpatrick, J James, JA Harley, JB AF Quintero-Del-Rio, AI Kelly, JA Kilpatrick, J James, JA Harley, JB TI The genetics of systemic lupus erythematosus stratified by renal disease: linkage at 10q22.3 (SLEN1), 2q34-35 (SLEN2), and 11p 15.6 (SLEN3) SO GENES AND IMMUNITY LA English DT Article; Proceedings Paper CT Lupus Genetics Conference CY SEP 07-09, 2001 CL OKLAHOMA CITY, OKLAHOMA SP Oklahoma Med Res Fdn, Amgen Corp DE proteinuria; cellular casts; lupus; ethnicity; linkage ID LYMPHOPROLIFERATIVE SYNDROME; AFRICAN-AMERICANS; GENOME SCAN; NEPHRITIS; AUTOANTIBODIES; EXPRESSION; FAMILIES AB Renal disease occurs in 40-75% of systemic lupus erythematosus (SLE) patients and significantly contributes to morbidity and mortality. We used two pedigree stratification strategies to explore the impact of the ACR renal criterion for SLE classification upon genetic linkage with SLE In both we used SLE as the phenotype. First, we evaluated genome scan data from >300 microsatellite markers in the 75 pedigrees that had at least one SLE affected with the SLE renal criterion. A maximum-likehood parametric model approach produced a maximum screening LOD score of 3.16 at 10q22.3 in the European-American (EA) pedigrees. The African-American (AA) pedigrees obtained a maximum screening LOD score of 2.58 at 11p15.6. A multipoint sib-pair regression analysis produced P = 0.0000008 in EA at 10q22.3 (SLEN1) and P = 0.000001 in AA at 2q34-35 (SLEN2). A second stratification strategy explored the renal criterion in 35 pedigrees with two or more SLE patients with renal disease and produced a LOD score of 3.34 at 11p 15.6 in AA (SLEN3). Sib-pair analysis in these 35 pedigrees revealed P = 0.00003 at 4q13.1 in EA, P = 0.00003 at 11p13 and 0.00007 at 3q23 in AA. Thus, multiple genetic linkages are related to the renal criterion in SLE. Of the significant genetic linkages with SLE described herein, those at 10q22.3 in the EA pedigrees (SLEN1) and at 2q34-35 in the AA pedigrees (SLEN2) have not been previously described. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Quintero-Del-Rio, AI (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI42460, AI31584]; NIAMS NIH HHS [AR24717, AR45231, AR52221, AR-1-2253] NR 30 TC 50 Z9 52 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S57 EP S62 DI 10.1038/sj.gene.6363901 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300010 PM 12215904 ER PT J AU Sawalha, AH Namjou, B Nath, SK Kilpatrick, J Germundson, A Kelly, JA Hutchings, D James, J Harley, J AF Sawalha, AH Namjou, B Nath, SK Kilpatrick, J Germundson, A Kelly, JA Hutchings, D James, J Harley, J TI Genetic linkage of systemic lupus erythematosus with chromosome 11q14 (SLEH1) in African-American families stratified by a nucleolar antinuclear antibody pattern SO GENES AND IMMUNITY LA English DT Article; Proceedings Paper CT Lupus Genetics Conference CY SEP 07-09, 2001 CL OKLAHOMA CITY, OKLAHOMA SP Oklahoma Med Res Fdn, Amgen Corp DE SLE; genetics; antinucleolar pattern; linkage analysis ID SIB-PAIR FAMILIES; SUSCEPTIBILITY GENES; GENOME SCAN; MODELS AB Systemic lupus erythematosus (SLE) is an autoimmune disease with complex genetics. We evaluated pedigrees multiplex for SLE that had an affected with antinucleolar antibodies to increase the homogeneity for genetic linkage analysis. We found a significant linkage effect on chromosome 11q14 at marker D11S2002 in African-American Pedigrees. This effect produced a maximum LOD score of 5.62 using a dominant inheritance model with 95% penetrance in males and 99% penetrance in females. The results were supported by multipoint linkage analysis. Fine mapping of the region with two additional markers within 6 cM of D11S2002 further provided evidence of linkage in this region. Linkage at D11S2002, named SLEW, was previously found in some of these same African-American pedigrees multiplex for SLE, but who were stratified by hemolytic anemia (Kelly et al, submitted).(1) In conclusion, an important SLE susceptibility gene, SLEH1 at 11q14, is identified in African-Americans when stratifying pedigrees by antinucleolar autoantibodies. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Norman, OK 73019 USA. Oklahoma Med Res Fdn, Genet Epidemiol Unit, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, J (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NCRR NIH HHS [RR03655]; NHGRI NIH HHS [HG01577]; NIAID NIH HHS [AI31584, AI45231, AI24717]; NIAMS NIH HHS [AR42460, AR12253] NR 23 TC 15 Z9 15 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2002 VL 3 SU 1 BP S31 EP S34 DI 10.1038/sj.gene.6363904 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 601BB UT WOS:000178425300005 PM 12215899 ER PT J AU Burton, L Leff, B Clark, B Guido, S Greenough, W Burton, J Steinwachs, D Burl, J Naughton, B Mader, S Donius, M Saltzman, S Delano, C AF Burton, L Leff, B Clark, B Guido, S Greenough, W Burton, J Steinwachs, D Burl, J Naughton, B Mader, S Donius, M Saltzman, S Delano, C TI Comparison of caregiver stress between caregivers of patients treated in hospital or a home hospital SO GERONTOLOGIST LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. Johns Hopkins Sch Med, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Buffalo Gen Hosp, Buffalo, NY 14203 USA. Fallon Healthcare, Worcester, MA USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 13 EP 14 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400053 ER PT J AU Rankin, S Carroll, D Hamilton, G Winder, P Hiltunen, E Rait, M Butzlaff, A AF Rankin, S Carroll, D Hamilton, G Winder, P Hiltunen, E Rait, M Butzlaff, A TI Relationship provision for unpartnered elders: An intervention to enhance cardiac recovery SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Lancaster, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2002 VL 42 SI 1 BP 16 EP 16 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400064 ER PT J AU Tucker, K Spiro, A McDonald, IR AF Tucker, K Spiro, A McDonald, IR TI Homocysteine, B vitamins and cognitive function among men in the normative aging study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Tufts Univ, USDA, HNRCA, Boston, MA 02111 USA. VA Boston Healthcare Syst, Boston, MA USA. RI Tucker, Katherine/A-4545-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2002 VL 42 SI 1 BP 30 EP 30 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400114 ER PT J AU Whitmer, R Haan, M Jagust, W AF Whitmer, R Haan, M Jagust, W TI Does hormone replacement therapy modify the effect of homocysteine on cognitive decline? SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Ctr, GRECC, Sepulveda, CA 91343 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 33 EP 33 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400121 ER PT J AU Valcour, V Goodkin, K Shiramizu, B Shikuma, C Asthana, D Shapshak, P Concha, M Wilkie, F Khamis, I Lee, D Ardila, A Lecusay, R Suarez, P Rigg, D Zheng, W O'Mellan, S Neundorfer, M Camp, C Lee, M Malone, M Carr, J Skrajner, M Justice, A McGinnis, K Wagner, J Conigliaro, J Rabeneck, L Stoff, D Linsk, N AF Valcour, V Goodkin, K Shiramizu, B Shikuma, C Asthana, D Shapshak, P Concha, M Wilkie, F Khamis, I Lee, D Ardila, A Lecusay, R Suarez, P Rigg, D Zheng, W O'Mellan, S Neundorfer, M Camp, C Lee, M Malone, M Carr, J Skrajner, M Justice, A McGinnis, K Wagner, J Conigliaro, J Rabeneck, L Stoff, D Linsk, N TI Aging, HIV-1 infection and neurocognitive function: Clinical correlates SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Hawaii, Sch Med, Honolulu, HI 96816 USA. Univ Miami, Sch Med, Miami, FL 33136 USA. Myers Res Inst, Beachwood, OH USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ctr Mental Hlth Res, Bethesda, MD USA. Univ Illinois, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 OCT PY 2002 VL 42 SI 1 BP 81 EP 82 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400279 ER PT J AU Baumgarten, M Margolis, D Lowe, R Localio, R Kagan, S Kavesh, W Kinosian, B Abbuhl, S Holmes, J AF Baumgarten, M Margolis, D Lowe, R Localio, R Kagan, S Kavesh, W Kinosian, B Abbuhl, S Holmes, J TI Extrinsic risk factors for pressure ulcers in elderly hospital patients SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Maryland, Baltimore, MD 21201 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Dept Emergency Med, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 153 EP 154 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400541 ER PT J AU Teri, L Hedrick, S Tornatore, J Logsdon, R McCurry, S Kane, R AF Teri, L Hedrick, S Tornatore, J Logsdon, R McCurry, S Kane, R TI Dementia patients in assisted living facilities: Innovations on clinical care and research SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, NW Res Grp Aging, Seattle, WA 98115 USA. Screen Inc, Seattle, WA USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 OCT PY 2002 VL 42 SI 1 BP 159 EP 160 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400561 ER PT J AU Murray, E Rubenstein, L Perry, H Murray, S Fink, H AF Murray, E Rubenstein, L Perry, H Murray, S Fink, H TI VA GRECC symposium: Osteoporosis and falls prevention: New developments SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Ctr, GRECC 11E, Sepulveda, CA 91343 USA. Vet Adm Med Ctr, St Louis, MO USA. Minneapolis GRECC, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 187 EP 188 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400669 ER PT J AU Aiken, J Joseph, J Van Remmen, H Cadenas, E AF Aiken, J Joseph, J Van Remmen, H Cadenas, E TI Oxidative stress and aging SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53706 USA. Tufts Univ, USDA,HNRCA, Boston, MA USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. Univ Wisconsin, Madison, WI USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 204 EP 204 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400724 ER PT J AU Rodriguez, K Young, A Granieri, E AF Rodriguez, K Young, A Granieri, E TI Patient and provider understanding of the VA advance directive: A matched pair, mixed methods analysis SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 225 EP 225 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400794 ER PT J AU Kyomen, H Hennen, J Gottlieb, G Wei, J Renshaw, P AF Kyomen, H Hennen, J Gottlieb, G Wei, J Renshaw, P TI Cerebral blood volume measures associated with depressive symptoms in elderly patients with memory complaints SO GERONTOLOGIST LA English DT Meeting Abstract C1 McLean Hosp, Belmont, MA 02178 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 257 EP 257 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400912 ER PT J AU McDermott, S Tennstedt, S Portenoy, R Billings, J Doherty, M AF McDermott, S Tennstedt, S Portenoy, R Billings, J Doherty, M TI The relative contribution of symptom burden vs. disease severity to function in patients with end-stage disease SO GERONTOLOGIST LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 262 EP 263 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400935 ER PT J AU Tennstedt, S Portenoy, R Billings, J McDermott, S Doherty, M AF Tennstedt, S Portenoy, R Billings, J McDermott, S Doherty, M TI Symptom burden and quality of life at the end of life SO GERONTOLOGIST LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 269 EP 270 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400964 ER PT J AU Curto, T Portenoy, R McDermott, S Tennstedt, S Billings, J Doherty, M AF Curto, T Portenoy, R McDermott, S Tennstedt, S Billings, J Doherty, M TI Relative distress of symptoms in endstage CHF and COPD SO GERONTOLOGIST LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 270 EP 270 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541400966 ER PT J AU Braun, U Beyth, R AF Braun, U Beyth, R TI Racial disparities in tube feeding practices for patients with dementia SO GERONTOLOGIST LA English DT Meeting Abstract C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 300 EP 300 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541401071 ER PT J AU Talerico, K Miller, L Harvath, T Ganzini, L Ersek, M Norton, S Quinn, J Baggs, J Catwright, J Tilden, V AF Talerico, K Miller, L Harvath, T Ganzini, L Ersek, M Norton, S Quinn, J Baggs, J Catwright, J Tilden, V TI Issues and challenges in end-of-life care SO GERONTOLOGIST LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Swedish Med Ctr, Seattle, WA USA. Univ Rochester, Sch Nursing, Rochester, NY 14627 USA. Oregon Hlth Sci Univ, Son Ashland, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 329 EP 329 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541401160 ER PT J AU Rubenstein, L Cole, G Schellenberg, G Kraemer, B Poorkaj, P Turner, R Griffin, S Frautschy, S Morley, J Asthana, S AF Rubenstein, L Cole, G Schellenberg, G Kraemer, B Poorkaj, P Turner, R Griffin, S Frautschy, S Morley, J Asthana, S TI VA GRECC symposium: From molecular biology and animal models to future treatments for Alzheimer's disease SO GERONTOLOGIST LA English DT Meeting Abstract C1 Vet Affairs Greater Los Angeles GRECC, Sepulveda, CA 91343 USA. VA Greater Los Angeles Healthcare Ctr, GRECC, Sepulveda, CA 91343 USA. Seattle VA Med Ctr, Seattle, WA USA. Vet Affairs Med Ctr, GRECC, Seattle, WA USA. Ann Arbor VA Med Ctr, Ann Arbor, MI USA. Little Rock VA Med Ctr, Little Rock, AR USA. VAGLA, GRECC, North Hills, CA USA. VAGLA, Dept Med, North Hills, CA USA. VAMC, GRECC, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 402 EP 402 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541401423 ER PT J AU Harvath, T Caley, J Wanlass, W Ralls, W Schulling, J AF Harvath, T Caley, J Wanlass, W Ralls, W Schulling, J TI The nursing home resident with a history of pedophilia: Issues and challenges SO GERONTOLOGIST LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 OCT PY 2002 VL 42 SI 1 BP 411 EP 411 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 620PH UT WOS:000179541401448 ER PT J AU M'Rini, C Askari, S Cheng, GY Hynes, RO Wagner, DD Lowe, JB von Andrian, UH AF M'Rini, C Askari, S Cheng, GY Hynes, RO Wagner, DD Lowe, JB von Andrian, UH TI In vivo analysis of endothelial L-selectin ligands SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2002 VL 12 IS 10 MA 13 BP 645 EP 645 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200021 ER PT J AU Moody, AM North, S Reinhold, B Van Dyken, S Rogers, ME Dell, A Morris, HR Marth, JD Reinherz, EL AF Moody, AM North, S Reinhold, B Van Dyken, S Rogers, ME Dell, A Morris, HR Marth, JD Reinherz, EL TI Sialic acid capping of CD8 beta core IO-glycans controls thymocyte-MHCI interaction SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 Dana Farber Canc Inst, Immunobiol Lab, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AY, England. MSCAN, Res & Training Ctr, Ascot SL5 7PZ, Berks, England. MSCAN Inc, W Chester, PA 19380 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2002 VL 12 IS 10 MA 17 BP 646 EP 647 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200025 ER PT J AU Longas, MO Garg, HG Trinkle-Pereira, JM Hales, CA AF Longas, MO Garg, HG Trinkle-Pereira, JM Hales, CA TI Heparin antiproliferative activity on bovine pulmonary artery smooth muscle cells requires both N-acetylation and N-sulfonation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 Purdue Univ Calumet, Dept Chem & Phys, Hammond, IN 46323 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2002 VL 12 IS 10 MA 69 BP 665 EP 665 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200074 ER PT J AU Wu, ZLL Zhang, LJ Yabe, T Kuberan, B Beeler, DL Love, A Rosenberg, RD AF Wu, ZLL Zhang, LJ Yabe, T Kuberan, B Beeler, DL Love, A Rosenberg, RD TI The involvement of heparan sulfate in FGF1/FGFR1 signaling complex SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 7th Annual Conference of the Society-for-Glycobiology CY NOV 09-12, 2002 CL BOSTON, MASSACHUSETTS SP Soc Glycobiol C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA 02215 USA. Tokyo Metropolitan Inst Neurosci, Dept Mol Dev Biol, Tokyo 1838526, Japan. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2002 VL 12 IS 10 MA 129 BP 685 EP 685 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 601LT UT WOS:000178448200134 ER PT J AU Lea, JS Shin, CH Sheets, EE Coleman, RL Gehrig, PA Duska, LR Miller, DS Schorge, JO AF Lea, JS Shin, CH Sheets, EE Coleman, RL Gehrig, PA Duska, LR Miller, DS Schorge, JO TI Endocervical curettage at conization to predict residual cervical adenocarcinoma in situ SO GYNECOLOGIC ONCOLOGY LA English DT Article DE cervical adenocarcinoma; endocervical curettage; uterine preservation ID CONE BIOPSY MARGINS; IN-SITU; INVASIVE ADENOCARCINOMA; UTERINE CERVIX; MANAGEMENT; EXCISION; INSITU AB Objective. To determine if performing an endocervical curettage (ECC) at the time of conization is a useful diagnostic tool for predicting residual cervical adenocarcinoma in situ (AIS) among women who might wish to preserve their fertility. Methods. All patients diagnosed with AIS from 1995 to 2000 at four institutions were identified. Data were retrospectively extracted from clinical records. Women included in the statistical analysis were (1) younger than 40 years, (2) had an ECC performed at the time of the initial cone biopsy, (3) had a clearly demarcated surgical margin pathologically, and (4) underwent a second surgical procedure. Results. Twenty-nine (24%) of 123 AIS patients met criteria for inclusion. The median age was 33 years (range, 17 to 39) and 13 (46%) were nulliparous. Initial surgery was a cold-knife conization (n = 17) or loop electrosurgical excision procedure (n = 12). Twelve (41%) ECCs and 15 (52%) cone margins were histologically positive. Sixteen patients underwent a repeat conization; 13 underwent hysterectomy. Thirteen (45%) patients had residual AIS at the time of their second surgical procedure. ECC had a superior positive predictive value (100% vs 47%; P < 0.01) and negative predictive value (94% vs 57%; P = 0.01) compared to cone margin in predicting residual AIS. None of the women undergoing fertility-sparing surgery developed recurrent AIS or adenocarcinoma. Conclusion. ECC performed at the time of conization may be a useful tool for predicting residual AIS in women considering fertility preservation. (C) 2002 Elsevier Science (USA). C1 Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 5323 Harry Hines Blvd,J7-124, Dallas, TX 75390 USA. RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 16 TC 30 Z9 31 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2002 VL 87 IS 1 BP 129 EP 132 DI 10.1006/gyno.2002.6791 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 605QN UT WOS:000178688700019 PM 12468353 ER PT J AU Peterson, KE Sorensen, G Pearson, M Hebert, JR Gottlieb, BR McCormick, MC AF Peterson, KE Sorensen, G Pearson, M Hebert, JR Gottlieb, BR McCormick, MC TI Design of an intervention addressing multiple levels of influence on dietary and activity patterns of low-income, postpartum women SO HEALTH EDUCATION RESEARCH LA English DT Article ID PHYSICAL-ACTIVITY; WEIGHT-LOSS; HEALTH PROMOTION; SOCIAL NETWORKS; OBESE CHILDREN; UNITED-STATES; LIFE-STYLE; PROGRAM; PREVENTION; EDUCATION AB Low-income, multi-ethnic women are at elevated risk for obesity and chronic diseases, yet influences at different levels may act as barriers to changing risk behaviors. Following the birth of a child, childrearing and social isolation can exacerbate these influences. The social ecological framework integrates behavior-change strategies at different levels, providing a strong theoretical base for developing interventions in this high-risk population. The primary purpose of this randomized controlled trial is to test the efficacy of an educational model delivered by community-based paraprofessionals in improving diet, activity and weight loss among new mothers over a 12-month postpartum period and a 6-month maintenance period. This model fosters institutional change to support behavior changes influenced at intrapersonal and interpersonal levels, through collaboration with federal programs for low-income families: the Special Supplemental Food Program for Women, Infants and Children (WIC), and the Expanded Food and Nutrition Education Program (EFNEP). Participants are randomized to the Usual Care, e.g. WIC nutrition and breastfeeding education, or Enhanced EFNEP intervention arm, consisting of Usual WIC Care plus a sustained, multi-component intervention including home visits, group classes and monthly telephone counseling. If shown to be efficacious, this program will be readily sustainable through existing federal agencies. C1 Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Dept Nutr, Amherst, MA 01003 USA. Univ S Carolina, Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Peterson, KE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, 665 Huntington Ave, Boston, MA 02115 USA. OI McCormmick, Marie/0000-0002-3938-1707 FU NICHD NIH HHS [R01 HD37368]; NIH HHS [OD-98-002] NR 60 TC 49 Z9 50 U1 3 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD OCT PY 2002 VL 17 IS 5 BP 531 EP 540 DI 10.1093/her/17.5.531 PG 10 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 603KC UT WOS:000178557500006 PM 12408198 ER PT J AU Demetri, GD AF Demetri, GD TI Targeting the molecular pathophysiology of gastrointestinal stromal tumors with imatinib - Mechanisms, successes, and challenges to rational drug development SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TYROSINE KINASE INHIBITOR; BCR-ABL; DIFFERENTIAL-DIAGNOSIS; C-KIT; EFFICACY; GROWTH; SAFETY; STI571; MUTATIONS; ST1571 AB The improved understanding of the molecular pathophysiology of gastrointestinal stromal tumors (GIST), a disease that was previously untreatable with any available systemic therapy, has led to the development of imatinib, a well-tolerated agent that can inhibit the dysregulated KIT signaling pathways in GIST. Imatinib represents the first (and currently the only) effective systemic therapy for patients with unresectable GIST. Imatinib therapy can induce objective responses and stabilization of disease and can provide clinical benefit in the majority of GIST patients treated with the drug. Other strategies are just beginning to be explored, such as the use of imatinib earlier the in course of GIST (eg, as adjuvant therapy after definitive surgical resection of early-stage disease). Integration of signal transduction inhibitors into the armamentarium of cancer therapeutics will undoubtedly continue based on this important paradigm of GIST. C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St SW, Boston, MA 02115 USA. NR 28 TC 39 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2002 VL 16 IS 5 BP 1115 EP + AR PII S0889-8588(02)00052-7 DI 10.1016/S0889-8588(02)00052-7 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 656HU UT WOS:000181603200006 PM 12512386 ER PT J AU Sosef, M Baust, J Toner, M AF Sosef, M Baust, J Toner, M TI Successful cryopreservation of isolated primary rat hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 25 BP 173A EP 173A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700026 ER PT J AU Ochoa, ER Dwyer, PJ Misdraji, J Dorer, DJ Campo-Ruiz, V Lauwers, GY Gonzalez, S AF Ochoa, ER Dwyer, PJ Misdraji, J Dorer, DJ Campo-Ruiz, V Lauwers, GY Gonzalez, S TI Intraoperative assessment of human liver using confocal reflectance microscopy. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 31 BP 174A EP 174A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700031 ER PT J AU Kanwal, F Kilbourne, A Hays, RD Gralnek, IM AF Kanwal, F Kilbourne, A Hays, RD Gralnek, IM TI Does model for end-stage liver disease (MELD) predict health related quality of life (HRQOL) in patients with advanced, chronic liver disease?. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Calif Los Angeles, Sch Med,VA Greater Los Angeles Hlth Care Syst, CURE Digest Dis Res, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA USA. RI Hays, Ronald/D-5629-2013 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 87 BP 188A EP 188A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700087 ER PT J AU Hiasa, Y Blackard, J Kamegaya, Y Schmidt, EV Chung, RT AF Hiasa, Y Blackard, J Kamegaya, Y Schmidt, EV Chung, RT TI Sustained HCV replication ina cell-based HCV replication system using replication-defective adenoviral vectors. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 151 BP 204A EP 204A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700151 ER PT J AU Delgado, A Purkis, D Somsouk, M Terella, A Jordan, SH Rodriguez, G Pascual, M Baid, S Ko, D Hertl, M Cosimi, AB Chung, RT AF Delgado, A Purkis, D Somsouk, M Terella, A Jordan, SH Rodriguez, G Pascual, M Baid, S Ko, D Hertl, M Cosimi, AB Chung, RT TI HCV independently associated with increased insulin resistance following liver transplantation. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 216 BP 220A EP 220A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700217 ER PT J AU Kamegaya, Y Hiasa, Y Fowler, NL Zukerberg, LR Schmidt, EV Chung, RT AF Kamegaya, Y Hiasa, Y Fowler, NL Zukerberg, LR Schmidt, EV Chung, RT TI HCV acts as an accelerant of hepatocellular carcinoma in a chemical model of hepatocarcinogenesis. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 399 BP 263A EP 263A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700382 ER PT J AU Merriman, N Brensinger, C Reddy, KR Chang, KM AF Merriman, N Brensinger, C Reddy, KR Chang, KM TI Increased morbidity and mortality with HCV/HIV coinfection relative to HCV or HIV monoinfection among US veterans. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 409 BP 265A EP 265A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700391 ER PT J AU Ikeda, F Sugimoto, K Standanlick, J Valiga, M Dhopesh, V Weinrieb, R Chang, KM AF Ikeda, F Sugimoto, K Standanlick, J Valiga, M Dhopesh, V Weinrieb, R Chang, KM TI Influence of alcohol and HIV coinfection on HCV-specific CD4 T cell response. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philidelphia VA Med Ctr, Philadelphia, PA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 431 BP 271A EP 271A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700417 ER PT J AU Sugimoto, K Ikeda, F Stadanlick, J Valiga, M Chang, KM AF Sugimoto, K Ikeda, F Stadanlick, J Valiga, M Chang, KM TI CD4 and CD8 T cell response to the entire HCV core and NS3-NS5 antigens in HCV persistence and clearance. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 443 BP 274A EP 274A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700426 ER PT J AU Kim, AY Lauer, GM Ouchi, K Day, CL Basgoz, NO Chung, RT Walker, BD AF Kim, AY Lauer, GM Ouchi, K Day, CL Basgoz, NO Chung, RT Walker, BD TI Multiple CD8+ responses against hepatitis C virus in chronically-infected HIV positive individuals. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oxford, Oxford, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 457 BP 277A EP 277A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700439 ER PT J AU McHutchison, JG Patel, K Manns, MP Poynard, T Dienstag, JL Albrecht, JK AF McHutchison, JG Patel, K Manns, MP Poynard, T Dienstag, JL Albrecht, JK TI Lower levels of adherence to therapy influence sustained response rates in chronic hepatitis C patients receiving peginterferon alfa 2b plus ribavirin. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Hannover Med Sch, La Jolla, CA USA. Hepato Gastro Grp Hosp, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Schering Plough Res Inst, Kenilworth, NJ 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 497 BP 287A EP 287A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700479 ER PT J AU Schiano, TD Branch, AD Chung, RT Kim-Schluger, L Schwartz, ME Bodenheimer, HC AF Schiano, TD Branch, AD Chung, RT Kim-Schluger, L Schwartz, ME Bodenheimer, HC TI HCV RNA levels after liver transplantation: Cadaveric versus live donor. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Mt Sinai Sch Med, Div Liver Dis, Recanati Miller Transportat Inst, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 572 BP 306A EP 306A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700556 ER PT J AU Xu, YQ Leo, MA Lieber, CS AF Xu, YQ Leo, MA Lieber, CS TI Lycopene attenuates arachidonic acid-induced toxicity in Hepg2 cells transfected with CYPE21. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Bronx Vet Adm Med Ctr, Sect Liver dis & Nutr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 658 BP 327A EP 327A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700641 ER PT J AU Cao, Q Mak, KM Lieber, CS AF Cao, Q Mak, KM Lieber, CS TI Lipopolysaccharide signaling cascades mediate TNF-alpha overproduction in raw 264.7 macrophages transfected with cytochrome P4502E1 (CYP2E1). SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Bronx, NY 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 666 BP 329A EP 329A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700649 ER PT J AU Arora, S Lau, D Gish, R Rossi, S Lin, CC Lau, JY Fang, JW AF Arora, S Lau, D Gish, R Rossi, S Lin, CC Lau, JY Fang, JW TI Phase I clinical studies of viramidine - A liver-targeting prodrug of ribavirin. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ New Mexico, Albuquerque, NM 87131 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Calif Pacific Med Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Ribapharm Inc, Costa Mesa, CA USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 773 BP 356A EP 356A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700755 ER PT J AU Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S Fye, CL Lowe, N Feinman, L Leo, MA Fimmel, CJ Lissoos, TW Anand, BS Morgan, TR Bloor, JH Simon, F Mendenhall, CL Linscheer, WG Iber, FL Schiff, ER Jeffers, L Gebhard, RL Bond, J Foust, RT Knapple, W Willner, I Tamburro, C Cecil, B Bay, M Marsano, L McClain, CJ Trotter, JF Muir, A Sninsky, CA Mishra, G Lumeng, L Born, LJ AF Lieber, CS Weiss, DG Groszmann, R Paronetto, F Schenker, S Fye, CL Lowe, N Feinman, L Leo, MA Fimmel, CJ Lissoos, TW Anand, BS Morgan, TR Bloor, JH Simon, F Mendenhall, CL Linscheer, WG Iber, FL Schiff, ER Jeffers, L Gebhard, RL Bond, J Foust, RT Knapple, W Willner, I Tamburro, C Cecil, B Bay, M Marsano, L McClain, CJ Trotter, JF Muir, A Sninsky, CA Mishra, G Lumeng, L Born, LJ TI Effect of moderation of ethanol consumption combined with PPC administration on liver injury in alcoholics: Prospective, randomized, placebo-controlled, multicenter va trial (CSP 391). SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Perry Point VA Med Ctr, Perry Point, MD USA. W Haven VA Med Ctr, West Haven, CT USA. San Antonio VA Med Ctr, San Antonio, TX USA. Albuquerque VA Med Ctr, Albuquerque, NM USA. St Louis VA Med Ctr, St Louis, MO USA. Houston VA Med Ctr, Houston, TX USA. Long Beach VA Med Ctr, Long Beach, CA USA. Denver VA Med Ctr, Denver, CO USA. Cincinatii VA Med Ctr, Cincinnati, OH USA. Syracuse VA Med Ctr, Syracuse, NY USA. Hines VA Med Ctr, Hines, IL USA. Miami VA Med Ctr, Miami, FL USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. Charleston VA Med Ctr, Charleston, SC USA. Louisville VA Med Ctr, Louisville, KY USA. San Antonio VA Med Ctr, San Antonio, TX USA. Lexington VA Med Ctr, Lexington, KY USA. Durham VA Med Ctr, Durham, NC USA. Gainesville VA Med Ctr, Gainesville, FL USA. Indianapolis VA Med Ctr, Indianapolis, IN USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 874 BP 381A EP 381A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700856 ER PT J AU Piasecki, B Reddy, R Lewis, JD Brensinger, CM Stieritz, DD Chang, KM AF Piasecki, B Reddy, R Lewis, JD Brensinger, CM Stieritz, DD Chang, KM TI Heavy alcohol consumption and spontaneous clearance of hepatitis C virus infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 887 BP 385A EP 385A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301700869 ER PT J AU Lu, XM Carter, EA Lu, M Fischman, AJ Tompkins, RG AF Lu, XM Carter, EA Lu, M Fischman, AJ Tompkins, RG TI Analysis of stable isotope labeled phenylalanine distribution in mice albumin using liquid chromatographyelectrospray ionization mass spectrometry. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Shriners Hosp Children, 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1108 BP 440A EP 440A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701091 ER PT J AU Karsan, HA Morton, SC Suttorp, MJ Shekelle, PG Edelstein, M Gralnek, IM AF Karsan, HA Morton, SC Suttorp, MJ Shekelle, PG Edelstein, M Gralnek, IM TI Combination endoscopic band ligation and sclerotherapy compared with band ligation alone for the secondary prophylaxis of esophageal variceal hemorrhage: A meta-analysis. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. RAND Corp, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, CURS,Digest Dis Res Ctr, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1399 BP 513A EP 513A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701381 ER PT J AU Kamal, SM Abdel Monsief, WA El Sherif, HT Koziel, MJ He, Q Hussien, OH Madwar, MA AF Kamal, SM Abdel Monsief, WA El Sherif, HT Koziel, MJ He, Q Hussien, OH Madwar, MA TI Prospective study of nitric oxide and cytokines in cirrohsis: Relations to systemic and splanchnic hemodynamics. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Harvard Inst Med, BIDMC, Boston, MA USA. Ain Sahms Univ, Cairo, Egypt. 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1445 BP 524A EP 524A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701426 ER PT J AU Nieto, JM Saab, S AF Nieto, JM Saab, S TI Medical versus surgical and radiological treatment of refractory ascites: A meta-analysis of randomized controlled trials. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Dumont UCLA, Liver Transplant Program, Los Angeles, CA 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1465 BP 529A EP 529A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701446 ER PT J AU Lauer, GM Lucas, M Chung, RT Ouchi, K Day, CL Kim, AY Klenerman, P Walker, BD AF Lauer, GM Lucas, M Chung, RT Ouchi, K Day, CL Kim, AY Klenerman, P Walker, BD TI Comprehensive longitudinal analysis of cellular immune responses and viral evolution in a person with acute HCV infection requiring antiviral treatment. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis ID HEPATITIS-C VIRUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. Univ Oxford, Oxford, England. NR 2 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1521 BP 543A EP 543A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701502 ER PT J AU Meyer-Olson, D Shoukry, NH Hartman, K Brady, KW Walker, CM Kalams, SA AF Meyer-Olson, D Shoukry, NH Hartman, K Brady, KW Walker, CM Kalams, SA TI Characterization of the antigen specific T cell receptor repertoire in HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Charlestown, MA USA. Childrens Res Inst, Columbus, OH USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1525 BP 544A EP 544A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701506 ER PT J AU El-Serag, HB Rabeneck, L AF El-Serag, HB Rabeneck, L TI HCV coinfection increases the risk of clinically relevant liver disease in HIV-infected patients. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1581 BP 558A EP 558A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701562 ER PT J AU Hu, KQ Cheung, R Rossi, S Bini, EJ Jeffers, L Wright, T AF Hu, KQ Cheung, R Rossi, S Bini, EJ Jeffers, L Wright, T TI Risk factors for hepatitis C virus (HCV) infection in US veterans: A large VA multicenter study. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Loma Linda VAMC, Loma Linda, CA USA. Palo Valto VAMC, Palo Alto, CA USA. San Francisco VAMC, San Francisco, CA USA. New York Harbor VAMC, New York, NY USA. Miami VAMC, Miami, FL 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1595 BP 562A EP 562A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701577 ER PT J AU Anand, BS Mendenhall, CL Bini, EJ Wright, T Rossi, SJ Jeffers, L AF Anand, BS Mendenhall, CL Bini, EJ Wright, T Rossi, SJ Jeffers, L CA VA HVC 001 Study Grp TI Alcohol consumption decreases overtime in US veterans with HCV infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 VA Med Ctr, Houston, TX USA. VA Med Ctr, Cincinnati, OH USA. VA Med Ctr, New York, NY USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Miami, FL 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1610 BP 565A EP 565A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701592 ER PT J AU Ruimy, SS Jazrawi, S Zucker, BL Sasaki, AW AF Ruimy, SS Jazrawi, S Zucker, BL Sasaki, AW TI Hepatitis C and veterans: An evaluation of patient education at the Portland, Oregon VA medical center SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Portland VA Med Ctr, Portland, OR 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1616 BP 567A EP 567A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701599 ER PT J AU Kim, AY Purkis, DR Abraczinskas, DR Loomis, SC Franzini, J Twitchell, K Dienstag, JL Robbins, GK Chung, RT AF Kim, AY Purkis, DR Abraczinskas, DR Loomis, SC Franzini, J Twitchell, K Dienstag, JL Robbins, GK Chung, RT TI A pilot study of post-exposure prophylaxis with PEG-IFN after occupational exposure to HCV. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Robbins, Gregory/F-7988-2011 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1647 BP 575A EP 575A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701629 ER PT J AU Rodriquez-Torres, M Gonzalez-Garcia, J Mendes-Correa, M Katlama, C Nelson, M Cooper, D Staszewski, S Carosi, G Smaill, F Brau, N AF Rodriquez-Torres, M Gonzalez-Garcia, J Mendes-Correa, M Katlama, C Nelson, M Cooper, D Staszewski, S Carosi, G Smaill, F Brau, N TI Prevalence of occult hepatitis B in a large multinational trial of the treatment of HCV with peginterferon alfa 2a (40KD) (Pegasis (R)) in patients coinfected with HIV. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Fundac Gastroenterol Diego, Santurce, PR USA. Hop La Paz, Madrid, Spain. Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Chelsea & Westminster Hosp, London, England. St Vincents Hosp, Sydney, NSW 2010, Australia. Klin III Infectionsambulanz, Frankfurt, Germany. Clin Infect & Trop Dis, Brescia, Italy. Chedoke McMaster Hosp, Hamilton, ON, Canada. Bronx Vet Adm Med Ctr, Bronx, NY USA. RI mendes correa, maria cassia /A-6779-2013 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1659 BP 578A EP 578A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701641 ER PT J AU Schiffman, ML Goncales, FL Bronowicki, JP Fried, MW Wright, T Hadziyannis, SJ Brouwer, J Zeuzem, S Hoffmann, J AF Schiffman, ML Goncales, FL Bronowicki, JP Fried, MW Wright, T Hadziyannis, SJ Brouwer, J Zeuzem, S Hoffmann, J TI Hepatitis C virus genotype 2 and 3 infection: A curable disease?. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. UNICAMP, Hosp Clin, Sao Paulo, Brazil. CHU Nancy, Nancy, France. Univ N Carolina, Chapel Hill, NC USA. San Francisco VA Med Ctr, San Francisco, CA USA. Henry Dunant Hosp, Athens, Greece. Univ Rotterdam, Rotterdam, Netherlands. Univ Saarlandes Kliniken, Frankfurt, Germany. Hoffmann La Roche Inc, Nutley, NJ 07110 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1677 BP 582A EP 582A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701658 ER PT J AU Anand, BS Yoffe, B Tavakoli-Tabasi, S AF Anand, BS Yoffe, B Tavakoli-Tabasi, S TI Effect of previous hepatitis B infection on hepatitis C virus infection. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 VA Med Ctr, Digest Dis Sect, Houston, TX USA. VA Med Ctr, Infect Dis Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1703 BP 589A EP 589A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701685 ER PT J AU Kulig, CC Martin, BK Bialkowski, DB Clapp, LK Goldberg, JL Mangum, LE Everson, GT Beresford, TP AF Kulig, CC Martin, BK Bialkowski, DB Clapp, LK Goldberg, JL Mangum, LE Everson, GT Beresford, TP TI Absence of liver injury in hepatitis C positive alcoholics prescribed disulfiram (Antabuse (R)) for up to one year, a pilot toxicity study. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1737 BP 597A EP 597A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701718 ER PT J AU Sulkowski, MS Rossi, SJ Arora, S Lamb, MW Modi, M AF Sulkowski, MS Rossi, SJ Arora, S Lamb, MW Modi, M TI Peginterferon alfa-2a (40KD) monotherapy induces early antiviral response in CHC patients on methadone maintenance therapy. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Johns Hopkins Univ, Baltimore, MD USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ New Mexico Albuquerque Hlth, Albuquerque, NM USA. Hoffmann La Roche Inc, Nutley, NJ 07110 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1765 BP 604A EP 604A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701746 ER PT J AU Loftis, JM Thornton, AJ Schultz, RL Hill, JA Howell, CD Hauser, P AF Loftis, JM Thornton, AJ Schultz, RL Hill, JA Howell, CD Hauser, P TI Interferon-induced depression and end-of-treatment response rates in patients with hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. Univ Maryland, Baltimore VA Med Ctr, Coll Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1773 BP 606A EP 606A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701754 ER PT J AU Somsouk, M Abraczinskas, SR Purkis, DR Terella, A Ko, DS Hertl, M Cosimi, AB Chung, RT AF Somsouk, M Abraczinskas, SR Purkis, DR Terella, A Ko, DS Hertl, M Cosimi, AB Chung, RT TI A pilot study of prophylactic suppressive PEG-IFN-alpha-2b plus ribavirin to prevent recurrent post-OLT HCV. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 1967 BP 655A EP 655A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301701949 ER PT J AU Nguyen, MH Wright, TL Garcia, RT Mahood, G Bacchetti, P Keeffe, EB AF Nguyen, MH Wright, TL Garcia, RT Mahood, G Bacchetti, P Keeffe, EB TI Effects of ethnicity on risk for hepatocelluiar carcinoma (HCC) in US patients with hepatitis C cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract CT 53rd Annual Meeting of the Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 01-05, 2002 CL BOSTON, MASSACHUSETTS SP Amer Assoc Study Liver Dis C1 Stanford Univ, Palo Alto, CA 94304 USA. Univ Calif San Francisco, San Francisco Vet Adm Med Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA 94143 USA. Stanford Univ, Palo Alto, CA 94304 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2002 VL 36 IS 4 SU S MA 2099 BP 688A EP 688A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 598XK UT WOS:000178301702081 ER PT J AU Folias, A Matkovic, M Bruun, D Reid, S Hejna, J Grompe, M D'Andrea, A Moses, R AF Folias, A Matkovic, M Bruun, D Reid, S Hejna, J Grompe, M D'Andrea, A Moses, R TI BRCA1 interacts directly with the Fanconi anemia protein FANCA SO HUMAN MOLECULAR GENETICS LA English DT Article ID POSITIONAL CLONING; NUCLEAR-COMPLEX; GENE; PATHWAY; FAA; COMPLEMENTATION; FANCG/XRCC9; CANCER; REPAIR; CDNA AB Fanconi anemia (FA) is a rare autosomal recessive disease characterized by skeletal defects, anemia, chromosomal instability and increased risk of leukemia. At the cellular level FA is characterized by increased sensitivity to agents forming interstrand crosslinks (ICL) in DNA. Six FA genes have been cloned and interactions among individual FANC proteins have been found. The FANCD2 protein co-localizes in nuclear foci with the BRCA1 protein following DNA damage and during S-phase, requiring the FANCA, C, E and G proteins to do so. This finding may reflect a direct role for the BRCA1 protein in double strand break (DSB) repair and interaction with the FANC proteins. Therefore interactions between BRCA1 and the FANC proteins were investigated. Among the known FANC proteins, we find evidence for direct interaction only between the FANCA protein and BRCA1. The evidence rests on three different tests: yeast two-hybrid analysis, coimmunoprecipitation from in vitro synthesis, and coimmunoprecipitation from cell extracts. The amino terminal portion of FANCA and the central part (aa 740-1083) of BRCA1 contain the sites of interaction. The interaction does not depend on DNA damage, thus FANCA and BRCA1 are constitutively interacting. The demonstrated interaction directly connects BRCA1 to the FA pathway of DNA repair. C1 Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Moses, R (reprint author), Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. FU NHLBI NIH HHS [P01 HL48546, P01HL54785, R01HL52725]; NIDDK NIH HHS [R01DK43889] NR 30 TC 71 Z9 73 U1 0 U2 4 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 OCT 1 PY 2002 VL 11 IS 21 BP 2591 EP 2597 DI 10.1093/hmg/11.21.2591 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 602QM UT WOS:000178516000006 PM 12354784 ER PT J AU Campo-Ruiz, V Ochoa, ER Lauwers, GY Gonzalez, S AF Campo-Ruiz, V Ochoa, ER Lauwers, GY Gonzalez, S TI Evaluation of hepatic histology by near-infrared confocal microscopy: A pilot study SO HUMAN PATHOLOGY LA English DT Article DE liver biopsy; laser confocal microscopy ID SCANNING LASER MICROSCOPY; IN-VIVO; LIVER AB Liver biopsy is a necessary procedure in establishing the tissue diagnosis of many liver conditions and often guides therapeutic strategies. Current histopathologic techniques are either time-consuming or tissue-destroying; hence the potential need for a fast and nondestructive imaging technique of unfixed human liver. This pilot study evaluates the use of near-infrared reflectance confocal microscopy (CM) in the study of human liver histopathology. Without cutting or staining the tissue, CM provides images of bulk parenchyma showing cellular and subcellular detail and depicting morphologic features of hepatic parenchyma in both diseased and nondiseased states. This article presents a series of 12 human liver biopsy samples, providing an overview on the potential of this technique in assessing common findings from light microscopy. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gonzalez, S (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 16 Z9 16 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2002 VL 33 IS 10 BP 975 EP 982 DI 10.1053/hupa.2002.127445 PG 8 WC Pathology SC Pathology GA 609KR UT WOS:000178903200004 PM 12395369 ER PT J AU Ogino, S Franks, TJ Yong, M Koss, MN AF Ogino, S Franks, TJ Yong, M Koss, MN TI Extensive squamous metaplasia with cytologic atypia in diffuse alveolar damage mimicking squamous cell carcinoma: A report of 2 cases SO HUMAN PATHOLOGY LA English DT Editorial Material DE squamous metaplasia; squamous cell carcinoma; atypia; diffuse alveolar damage; acute lung injury ID RESPIRATORY CYTOLOGY; BIOPSY; LUNG AB Squamous metaplasia in the setting of diffuse alveolar damage, a form of acute lung injury, in rare cases can be very extensive with cytologic atypia, mimicking squamous cell carcinoma. We describe 2 such cases that posed diagnostic difficulty in the evaluation of biopsy specimens. These cases demonstrate that histologic findings must be correlated with clinical and radiologic information to avoid a misdiagnosis of malignancy. Copyright 2002, Elsevier Science (USA). All rights reserved. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. RP Franks, TJ (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 16th St NW,Bldg 54,Room M003B, Washington, DC 20306 USA. NR 14 TC 6 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2002 VL 33 IS 10 BP 1052 EP 1054 DI 10.1053/hupa.2002.128246 PG 3 WC Pathology SC Pathology GA 609KR UT WOS:000178903200016 PM 12395381 ER PT J AU Bhandoola, A Tai, XG Eckhaus, M Auchincloss, H Mason, K Rubin, SA Carbone, KM Grossman, Z Rosenberg, AS Singer, A AF Bhandoola, A Tai, XG Eckhaus, M Auchincloss, H Mason, K Rubin, SA Carbone, KM Grossman, Z Rosenberg, AS Singer, A TI Peripheral expression of self-MHC-II influences the reactivity and self-tolerance of mature CD4(+) T cells: Evidence from a lymphopenic T cell model SO IMMUNITY LA English DT Article ID POSITIVE SELECTION; HOMEOSTATIC PROLIFERATION; ACTIVATION THRESHOLD; PEPTIDE LIGANDS; SURVIVAL; THYMUS; COMPLEX; MOLECULES; ANTIGENS; MOUSE AB While intrathymic MHC expression influences the specificity of developing thymocytes, we considered that peripheral MHC expression might influence the reactivity of postthymic T cells. We now report for CD4(+) T cells that peripheral MHC-II expression does influence their reactivity and self-tolerance. Upon transfer into MHC-II-deficient lymphopenic hosts, mature CD4(+) T cells were found to acquire an activated memory phenotype and to become: (1) autoreactive against syngeneic MHC-II+ skin grafts, (2) hyperreactive against third-party MHC-II+ skin grafts, and (3) functionally dysregulated, resulting in a lymphoproliferative disorder characterized by intraepithelial infiltrations. Peripheral MHC-II expression appeared to influence CD4+ T cell reactivity by two complementary mechanisms: maintenance of CD4(+)CD25(+) regulatory T cells ("suppression") and direct dampening of CD4(+) T cell reactivity ("tuning"). C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Tel Aviv Univ, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIAID, Immunol Lab, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bldg 10, Bethesda, MD 20892 USA. RI Grossman, Zvi/A-9643-2008 NR 40 TC 68 Z9 68 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2002 VL 17 IS 4 BP 425 EP 436 DI 10.1016/S1074-7613(02)00417-X PG 12 WC Immunology SC Immunology GA 605FQ UT WOS:000178667100004 PM 12387737 ER PT J AU Dranoff, G AF Dranoff, G TI GM-CSF-based cancer vaccines SO IMMUNOLOGICAL REVIEWS LA English DT Review ID COLONY-STIMULATING FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; RENAL-CELL CARCINOMA; POTENT ANTITUMOR IMMUNITY; MHC CLASS-I; DENDRITIC CELLS; T-CELLS; GENE-THERAPY; PROGNOSTIC FACTOR; MELANOMA-CELLS AB The crafting of genetic and biochemical techniques to identify cancer antigens yielded the unexpected discovery that immune recognition of tumors regularly accompanies cancer development. The failure of the host to suppress tumor formation or attenuate disease progression may thus reflect the limited immunogenicity of nascent tumors. One critical determinant of host immunity is the mixture of cytokines produced in the tumor microenvironment. We have compared a large number of secreted and surface molecules for their relative abilities to augment tumor immunity following gene transfer into cancer cells. In multiple murine models, granulocyte-macrophage colony stimulating factor (GM-CSF) proved to be the most potent immunostimulatory product. Vaccination with irradiated tumor cells engineered to secrete GMCSF involves enhanced tumor antigen presentation by recruited dendritic cells (DCs) and macrophages; the coordinated functions of CD4(+) and CD8(+) T cells, CD1d-restricted NKT cells and antibodies mediate protective immunity. The evaluation of this vaccination strategy in patients with advanced melanoma revealed the consistent induction of cellular and humoral antitumor responses capable of effectuating substantial necrosis of distant metastases. The formulation of simplified methods for manufacturing autologous, GM-CSF-secreting tumor cells has enabled more extensive clinical testing in diverse patient settings. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74886, CA39542] NR 73 TC 175 Z9 189 U1 0 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 OCT PY 2002 VL 188 BP 147 EP 154 DI 10.1034/j.1600-065X.2002.18813.x PG 8 WC Immunology SC Immunology GA 614UZ UT WOS:000179211000013 PM 12445288 ER PT J AU Cavanagh, LL Von Andrian, UH AF Cavanagh, LL Von Andrian, UH TI Travellers in many guises: The origins and destinations of dendritic cells SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Review DE adhesion molecules; chemokines; dendritic cells; immunoregulation; migration ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; EPIDERMAL LANGERHANS CELL; HIGH ENDOTHELIAL VENULES; PLASMACYTOID T-CELLS; INTERCELLULAR-ADHESION MOLECULE-1; COMMON PRECURSOR POPULATION; INTERFERON-PRODUCING CELLS; LYMPHOID-TISSUE CHEMOKINE; PRIMARY IMMUNE-RESPONSE AB The migratory behaviour of dendritic cells (DC) is tightly linked to their differentiation state. Precursor DC constitutively repopulate normal tissues from the bloodstream, and are recruited in elevated numbers to sites of inflammation. Whilst maturing in response to antigenic stimulation, DC acquire the capability to enter lymph nodes via afferent lymphatic vessels, thus facilitating their presentation of antigen to naive T cells. Peripheral blood monocytes constitute a second DC precursor population, which during an inflammatory response are recruited to the affected site where some differentiate into functional DC. The availability of separate DC precursor populations is thought to be significant for the character, amplification and perpetuation of the resultant immune response. In addition, the balance between steady-state trafficking of incompletely activated DC bearing self-antigens from the periphery, and the migration of fully mature DC from inflammatory sites into lymph nodes might have profound effects upon tolerance induction and activation of T cells, respectively. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cavanagh, LL (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM loisc@cbr.med.harvard.edu; uva@cbr.med.harvard.edu RI von Andrian, Ulrich/A-5775-2008 NR 184 TC 113 Z9 119 U1 2 U2 6 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 2002 VL 80 IS 5 BP 448 EP 462 DI 10.1046/j.1440-1711.2002.01119.x PG 15 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 592YM UT WOS:000177964500006 PM 12225381 ER PT J AU Sifri, CD Mylonakis, E Singh, KV Qin, X Garsin, DA Murray, BE Ausubel, FM Calderwood, SB AF Sifri, CD Mylonakis, E Singh, KV Qin, X Garsin, DA Murray, BE Ausubel, FM Calderwood, SB TI Virulence effect of Enterococcus faecalis protease genes and the quorum-sensing locus fsr in Caenorhabditis elegans and mice SO INFECTION AND IMMUNITY LA English DT Article ID VANCOMYCIN-RESISTANT ENTEROCOCCI; SERINE-PROTEASE; MODEL; GELATINASE; GENERATION; MUTANTS; PATHOGENESIS; PERITONITIS; MECHANISMS; REGULATOR AB The expression of two Enterococcus faecalis extracellular virulence-related proteins, gelatinase (GelE) and serine protease (SprE), has been shown to be positively regulated by the fsr quorum-sensing system. We recently developed a novel system for studying E. faecalis pathogenicity that involves killing of the nematode worm Caenorhabditis elegans and showed that an E. faecalis fsrB mutant (strain TX5266) exhibited attenuated killing. We explore here the role of the fsr/gelE-sprE locus in pathogenicity by comparing results obtained in the nematode system with a mouse peritonitis model of E. faecalis infection. Insertion mutants of fsrA (TX5240) and fsrC (TX5242), like fsrB (TX5266), were attenuated in their ability to kill C. elegans. A deletion mutant of gelE (TX5264) and an insertion mutant of sprE (TX5243) were also attenuated in C. elegans killing, although to a lesser extent than the fsr mutants. Complementation of fsrB (TX5266) with a 6-kb fragment containing the entire fsr locus restored virulence in both the nematode and the mouse peritonitis models. The fsr mutants were not impaired in their ability to colonize the nematode intestine. These data show that extracellular proteases and the quorum-sensing fsr system are important for E. faecalis virulence in two highly divergent hosts: nematodes and mice. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Univ Texas, Div Infect Dis, Houston, TX USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI47923, R01 AI047923, R37 AI047923] NR 33 TC 116 Z9 119 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2002 VL 70 IS 10 BP 5647 EP 5650 DI 10.1128/IAI.70.10.5647-5650.2002 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 595TU UT WOS:000178125500037 PM 12228293 ER PT J AU Drinka, PJ Krause, P Nest, L Gravenstein, S Goodman, B Shult, P AF Drinka, PJ Krause, P Nest, L Gravenstein, S Goodman, B Shult, P TI Delays in the application of outbreak control prophylaxis for influenza A in a nursing home SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID OSELTAMIVIR; PREVENTION AB OBJECTIVE: To identify delayed prophylaxis from a preexisting database and strategies to improve performance. SETTING: A skilled nursing facility with 14 floors (4 buildings). The "outbreak unit" was a 50- to 60-bed floor. METHODS: We performed surveillance during six seasons using one protocol. Prophylaxis was started when influenza was cultured in the building and 10% of residents on the floor had a new respiratory illness within 7 days. We defined delayed prophylaxis as four or more residents on a floor with positive cultures whose specimens had been collected within 5 days before the application of prophylaxis. RESULTS: We identified 14 examples of delayed prophylaxis. In three, delayed prophylaxis was related to the 3.9-day delay between culture collection and culture report There was a high degree of commonality among building attack rates within a season. During six seasons, the first case in the last building occurred 27 to 64 days after the first case in the facility The two seasons with the greatest activity (68 and 154 cases, respectively) began with explosive, multi-floor outbreaks in a single building. The match between the circulating strain and the vaccine was good, except in 1997-1998 when there were seven examples of delayed prophylaxis. CONCLUSIONS: Influenza may involve buildings sequentially with a commonality of building attack rates. Explosive, multi-floor outbreaks early in the season could lead to a lower threshold for prophylaxis within a larger area when initial cases are encountered later in the season. This strategy could have prevented five examples of delayed prophylaxis. Rapid testing of multiple specimens while waiting for culture confirmation could have prevented three examples of delayed prophylaxis. C1 Wisconsin Vet Home, King, WI 54946 USA. Univ Wisconsin, Madison, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. State Lab Hyg, Communicable Dis Div, Madison, WI USA. RP Drinka, PJ (reprint author), Wisconsin Vet Home, N2665 Cty Rd QQ, King, WI 54946 USA. FU NIA NIH HHS [AG 09632] NR 14 TC 11 Z9 11 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2002 VL 23 IS 10 BP 600 EP 603 DI 10.1086/501978 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 604FE UT WOS:000178605200011 PM 12400890 ER PT J AU Sasaki, H Ide, N Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y AF Sasaki, H Ide, N Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y TI Gene expression analysis of human thymoma correlates with tumor stage SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE microarray; thymoma; JUN; AL050002; FLJ00237 ID THYMIC EPITHELIAL TUMORS; TRANSCRIPTIONAL PROGRAM; CANCER; HYBRIDIZATION; METASTASES; THYMOCYTE; DISEASES; JUN AB Thymoma is one of the most common solid tumors in the mediastinum. The recent development of high-density oligonucleotide arrays provides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in actual neoplastic tissues. We used oligonucleotide arrays to monitor in vivo gene expression levels in early- (stage I or II) and late- (stage IVa) stage thymoma tissues in 36 patients. These in vivo gene expression profiles were verified by real-time quantitative RT-PCR using LightCycler. Using both methods, 2 candidate genes were identified that were more highly expressed in advanced-stage thymomas. One was a well-known gene, c-JUN, and another was an unknown gene, AL050002. AL050002 expression, but not c-JUN expression, was also correlated with the WHO classification (type B3 vs. type B1, B2 or AB). The combined use of oligonucleotide microarray and real-time RT-PCR analyses provides a powerful new approach to elucidate the in vivo molecular events correlated with tumor stage of thymoma. (C) Wiley-Liss, Inc. C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Kawasumi 1, Nagoya, Aichi 4678601, Japan. NR 26 TC 24 Z9 27 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2002 VL 101 IS 4 BP 342 EP 347 DI 10.1002/ijc.10624 PG 6 WC Oncology SC Oncology GA 590EN UT WOS:000177805500006 PM 12209958 ER PT J AU Gunderson, LL Sargent, DJ Tepper, JE O'Connell, MJ Allmer, C Smalley, SR Martenson, JA Haller, DG Mayer, RJ Rich, TA Ajani, JA MacDonald, JS Goldberg, RM AF Gunderson, LL Sargent, DJ Tepper, JE O'Connell, MJ Allmer, C Smalley, SR Martenson, JA Haller, DG Mayer, RJ Rich, TA Ajani, JA MacDonald, JS Goldberg, RM TI Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: A pooled analysis 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 rectal cancer; adjuvant chemoradiation; staging ID POSTOPERATIVE RADIATION-THERAPY; POTENTIALLY CURATIVE SURGERY; RECURRENCE FOLLOWING SURGERY; WHOLE-ABDOMINAL RADIATION; III COLON-CARCINOMA; COLORECTAL-CANCER; CONTROLLED TRIAL; PATTERNS; FLUOROURACIL; ADENOCARCINOMA AB Purpose: To determine the rates of survival and disease control by TNM and MAC stage in three randomized North American rectal adjuvant studies. Materials and Methods: Data were merged from 2551 eligible patients on NCCTG 79-47-51 (n = 200), NCCTG 86-47-51 (n = 656), and INT 114 (n = 1695). All patients received postoperative radiation, and 96% were randomized to receive concomitant and maintenance chemotherapy. Five-year follow-up was available in 94% of patients and 7-yr follow-up in 84%. Kaplan-Meier curves were used to estimate the distribution of overall survival (OS) and disease-free survival (DFS), and p values were derived using the log-rank test. Time to local and distant relapse was estimated using cumulative incidence methodology. Analyses were adjusted for treatment effect using Cox proportional hazards models. Results: OS and DFS were dependent on both TN stage and NT stage (N substage within T stage and T substage within N stage). Even among N2 patients (4 or more LN+), T stage influenced 5-yr OS (T1-2, 69%; T3, 48%; T4, 38%). Three risk groups of patients were defined: (1) intermediate: T3N0, T1-2N1; (2) moderately high: T4N0, T1-2N2, T3N1; and (3) high: T3N2, T4N1, T4N2. For Group 1, 5-yr OS was 74% and 81%, and 5-yr DFS was 66% and 74%. For Group 2, 5-yr OS ranged from 61% to 69%, and for Group 3, OS ranged from 33% to 48%. Cumulative incidence rates of local relapse and distant metastases revealed similar differences by TN and NT stage, as seen in the survival analyses. Conclusion: Patients with a single high-risk factor of either extension beyond the rectal wall (T3N0) or nodal involvement (T1-2N1) have improved OS, DFS, and disease control when compared to those with both high risk factors. Different treatment strategies may be indicated for intermediate- (T3N0, T1-2N1) vs. moderately high or high-risk patients in view of differential survival and rates of relapse. For future trial design, it may be preferable to perform separate studies, or a planned statistical analysis, for the "intermediate-risk" vs. the "moderately high" or "high-risk" subsets of patients. (C) 2002 Elsevier Science Inc. C1 Mayo Clin Scottsdale, Ctr Canc, Dept Radiat Oncol, Scottsdale, AZ 85259 USA. Mayo Clin, Canc Ctr Stat, Rochester, MN USA. Mayo Clin, Dept Oncol, Rochester, MN USA. Univ N Carolina, Dept Radiat Oncol, Chapel Hill, NC USA. Kansas City Community Clin Oncol Program, Dept Radiat Oncol, Kansas City, MO USA. Univ Penn, Dept Med Oncol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Virginia, Dept Radiat Oncol, Charlottesville, VA USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. St Vincents Comprehens Canc Ctr, Dept Med Oncol, New York, NY USA. RP Gunderson, LL (reprint author), Mayo Clin Scottsdale, Ctr Canc, Dept Radiat Oncol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. RI Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 NR 50 TC 77 Z9 79 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 OCT 1 PY 2002 VL 54 IS 2 BP 386 EP 396 DI 10.1016/S0360-3016(02)02945-0 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 596ZE UT WOS:000178196200013 PM 12243812 ER PT J AU Yock, TI Zietman, AL Shipley, WU Thakral, HK Coen, JJ AF Yock, TI Zietman, AL Shipley, WU Thakral, HK Coen, JJ TI Long-term durability of PSA failure-free survival after radiotherapy for localized prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiotherapy; prostate-specific antigen; hazard rates; durability ID EXTERNAL-BEAM RADIOTHERAPY; RADIATION-THERAPY; RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; DOSE-ESCALATION; RTOG 85-31; ANTIGEN; ADENOCARCINOMA; PROGRESSION; CARCINOMA AB Purpose: To determine the durability of prostate-specific antigen (PSA) progression-free survival beyond 5 years in patients biochemically free of relapse 5 years after external beam radiotherapy (EBRT). Methods and Materials: This study identified 328 men treated with EBRT to the prostate who were biochemically (American Society for Therapeutic Radiology and Oncology definition) disease free 5 years after treatment. The median follow-up was 7.4 years. The patients were divided into four groups according to their PSA values 5 years after treatment: PSA less than or equal to50.5, 0.5 to less than or equal to1.0, 1.0 to less than or equal to2.0, and 2.0-4.0 ng/mL. PSA progression-free rates were calculated in each subgroup at 10 years after treatment. Yearly hazard rates of biochemical progression were also calculated for the 5-10 years after treatment. Results: The PSA progression-free survival rate was 87%, 79%, and 67%, respectively, 8, 10, and 13 years after treatment in patients biochemically free of disease 5 years after treatment. The progression-free rates at 10 years after treatment according to the PSA level at 5 years was 92% for PSA less than or equal to0.5 ng/mL; 71% for PSA 0.5 to :5 1.0 ng/mL; 78% for PSA 1.0 to less than or equal to2.0 ng/mL; and 56% for PSA 2.0 to less than or equal to4.0. The lower the PSA level at 5 years, the more durable the probability of maintained biochemical disease-free survival (p <0.0001). The yearly hazard rates of biochemical progression ranged from 3.1% to 6.6% in the 5-10 years after RT. Conclusion: When PSA levels remain low (<2 ng/mL) 5 years after EBRT, the great majority of patients will be biochemically disease free at 10 years. The hazard rates of biochemical progression in the 6-10 years after treatment are low and are comparable to those published for prostatectomy series. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM azietman@partners.org NR 25 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2002 VL 54 IS 2 BP 420 EP 426 DI 10.1016/S0360-3016(02)02957-7 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 596ZE UT WOS:000178196200018 PM 12243817 ER PT J AU D'Amico, AV Chen, MH Oh-Ung, J Renshaw, AA Cote, K Loffredo, M Richie, JP AF D'Amico, AV Chen, MH Oh-Ung, J Renshaw, AA Cote, K Loffredo, M Richie, JP TI Changing prostate-specific antigen outcome after surgery or radiotherapy for localized prostate cancer during the prostate-specific antigen era SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY, 2002 CL ORLANDO, FLORIDA SP Amer Soc Clin Oncol DE prostatic neoplasms; prostate-specific antigen; radical prostatectomy; radiotherapy; presentation; outcome ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; CLINICAL UTILITY; FREE SURVIVAL; BIOPSIES AB Purpose: To evaluate the change in prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) or external beam radiotherapy (EBRT), controlling for follow-up during the PSA era. Methods and Materials: The study cohort consisted of 1440 patients with clinically localized prostate cancer managed with RP (n = 1059) or EBRT (n = 381) between 1989 and 2000. A single genitourinary pathologist reviewed all pathology specimens. For patients with a 2-year minimal follow-up, the 2-year actual PSA outcome stratified by risk group (low vs. high) was calculated for three periods (January 1, 1989 to December 31, 1992; January 1, 1993 to December 31, 1996; and January 1, 1997 to December 31, 2000) and compared for each treatment modality. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition for all patients, and comparisons were made using a chi-square metric. Results: During the study period, the proportion of patients treated with RP and EBRT with low-risk disease increased significantly (p < 0.0001) from 60% to 89% and from 26% to 76%, respectively. In addition, the 2-year actual PSA outcome also improved from 60% to 82% (RP: p < 0.0001) and from 67% to 91% (RT: p = 0.0008). The 2-year actual PSA outcome was not significantly different in the low-risk patients but improved during the three periods in the high-risk patients treated with RP (from 20% to 39% to 75%, p = 0.0004) or EBRT (from 50% to 59% to 83%, p = 0.01). This improvement in PSA outcome could be explained by a shift toward a more favorable PSA level (RP: p = 0.0002; RT: p = 0.006) and clinical T stage (RP: p = 0.0008, RT: p < 0.0001) distribution for patients with biopsy Gleason score &GE;7 disease. Conclusion: Improved PSA outcome during the PSA era after RP or EBRT has resulted from a shift in presentation toward low-risk disease and earlier detection of high-grade disease. © 2002 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 20 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2002 VL 54 IS 2 BP 436 EP 441 DI 10.1016/S0360-3016(02)02940-1 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 596ZE UT WOS:000178196200020 PM 12243819 ER PT J AU Chawla, AK Kachnic, LA Taghian, AG Niemierko, A Zapton, DT Powell, SN AF Chawla, AK Kachnic, LA Taghian, AG Niemierko, A Zapton, DT Powell, SN TI Radiotherapy and breast reconstruction: Complications and cosmesis with tram versus tissue expander/implant 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 breast cancer; breast reconstruction; radiotherapy ID PREVIOUSLY IRRADIATED PATIENTS; RADIATION-THERAPY; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; CANCER; IMMEDIATE; EXPANDERS; CHEMOTHERAPY; MASTECTOMY; EXPANSION AB Purpose: Radiotherapy (RT) has an important role in breast cancer treatment after modified radical mastectomy. Many of these patients also undergo breast reconstruction. We reviewed our institutions' experience to determine the outcome of patients treated with breast reconstruction and RT. Methods and Materials: Between 1981 and 1999, 48 breast cancer patients underwent modified radical mastectomy, breast reconstruction, and ipsilateral breast RT during their treatment course. Reconstruction either preceded or followed RT. Autologous reconstruction with a transverse rectus abdominus myocutaneous (TRAM) flap was performed in 30 patients, and 18 underwent expander and implant (E/I) reconstruction. The primary endpoint was the quality of the reconstructed, irradiated breast, as measured by analyzing the actuarial incidence of complications. The cosmetic outcome was also assessed by multidisciplinary review of the follow-up visits. Results: The median follow-up from reconstruction was 32 months. The actuarial 2-year complication rate was 53% for patients receiving E/I vs. 12% for those receiving TRAM reconstruction (p <0.01). No other patient or treatment-related factors had a significant impact on complications. The cosmetic outcome was also significantly better in the TRAM subgroup than in the E/I subgroup. Conclusion: The tolerance and cosmetic outcome of breast reconstruction for breast cancer patients in irradiated sites depends significantly on the type of reconstruction used. (C) 2002 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Kachnic, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 302, Boston, MA 02114 USA. NR 23 TC 82 Z9 86 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2002 VL 54 IS 2 BP 520 EP 526 AR PII S0360-3016(02)02951-6 DI 10.1016/S0360-3016(02)02951-6 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 596ZE UT WOS:000178196200032 PM 12243831 ER PT J AU Roth, C Tello, R Sutherland, K Ptak, T AF Roth, C Tello, R Sutherland, K Ptak, T TI Prediction rule for etiology of vague abdominal pain in the emergency room - Utility for imaging triage SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT ARRS 2001 Meeting CY 2001 CL SEATTLE, WASHINGTON SP ARRS ID SUSPECTED ACUTE APPENDICITIS; HELICAL CT; DIAGNOSIS; DIVERTICULITIS; SCORE AB RATIONALE AND OBJECTIVES. To determine the predictive value of clinical parameters in patients with nonspecific abdominal pain undergoing computed tomography (CT) evaluation of the abdomen and pelvis in the emergency room (ER). MATERIALS AND METHODS. A cross-sectional study of a total of 164 sequential abdominal CT exams of the abdomen and pelvis during a 4 month period for nonspecific abdominal pain in the ER setting identified 100 abnormal scans in 164 patients (61 men, 103 women) of average age 46 years (range 4-97). Patient demographic characteristics (age, sex, temperature, white blood cell (WBC) count, and presence of peritoneal signs) were recorded at the time of CT examination. Results of the CT studies were correlated with the clinical data and discharge diagnosis to assess their positive predictive value using ordinal logistic regression. RESULTS. There were 17 cases of appendicitis, 9 cases of diverticulitis, 3 neoplasms, 3 abdominal abscesses, 2 pancreatitis, 2 duodenitis, 5 with fluid collections, 1 buttocks abscess, and I epiploic appendagitis were diagnosed with CT, 57 patients had unrelated findings on CT (common but not usually associated with vague pain). A diagnosis of appendicitis correlated with; elevated WBC count (>11.5) (P = 0.002), male sex (P = 0.001), and younger age (<25 years old) (P = 0.002). A positive CT correlated with an elevated WBC >11.5 (OR, 7.7; 95% CI, 3.3-18). The presence of peritoneal signs and fever did not correlate with a positive CT finding and diverticulitis had no predictive variables. Alternative diagnoses were correlated with female sex (P = 0.014). The combination of; age, sex, and WBC count allowed for a prediction rule with Area under the receiver operator curve of 0.92 to be generated. CONCLUSION. An elevated white blood cell (WBC) count is strong evidence of the presence of an inflammatory process. Alternative diagnostic considerations should be entertained in the context of a normal WBC count without strong clinical suspicion, particularly in women. The use of these factors alone allowed the construction of a prediction rule that can be used for CT protocol optimization. C1 Boston Univ, Sch Med, Boston Med Ctr, Dept Radiol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Tello, R (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Radiol, 88 E Newton St,Atrium 2, Boston, MA 02118 USA. NR 19 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD OCT PY 2002 VL 37 IS 10 BP 552 EP 556 DI 10.1097/00004424-200210000-00003 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 598LB UT WOS:000178276400003 PM 12352163 ER PT J AU Gatzke-Kopp, LM Raine, A Loeber, R Stouthamer-Loeber, M Steinhauer, SR AF Gatzke-Kopp, LM Raine, A Loeber, R Stouthamer-Loeber, M Steinhauer, SR TI Serious delinquent behavior, sensation seeking, and electrodermal arousal SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE recidivists; skin conductance; antisocial; stimulation-seeking; arousal ID STIMULATION-SEEKING; ORIENTING RESPONSE; AUTONOMIC MEASURES; HIGH-RISK; ADOLESCENTS; PERSONALITY; AGE; IQ; PSYCHOPATHY; IMPULSIVITY AB Low tonic skin conductance level (SCL) has been related, inconsistently, to both delinquency and sensation-seeking. This study tests the hypothesis that there is an interaction such that high sensation seeking delinquents, in particular, have low SCLs. Participants consisted of 335 boys from the Pittsburgh Youth Study classified as serious delinquents or controls based upon 10 years of prospectively collected self-report delinquency data. Participants' skin conductance was evaluated at age 16 along with several personality and neuropsychological measures. Both delinquency and sensation seeking were characterized by low SCL. However, there was no evidence to suggest that the presence of both of these factors together lead to especially low skin conductance levels. This finding is not explained by differences between the groups on measures of negative emotionality, IQ, socioeconomic status, or impulsivity. C1 Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Life Hist Studies Program, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Gatzke-Kopp, LM (reprint author), Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. EM gatzke@usc.edu NR 55 TC 51 Z9 54 U1 1 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD OCT PY 2002 VL 30 IS 5 BP 477 EP 486 AR UNSP 0091-0627/02/1000-0477/0 DI 10.1023/A:1019816930615 PG 10 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 585UB UT WOS:000177542000004 PM 12403151 ER PT J AU Kellogg, DL Liu, Y McAllister, K Friel, C Pergola, PE AF Kellogg, DL Liu, Y McAllister, K Friel, C Pergola, PE TI Bradykinin does not mediate cutaneous active vasodilation during heat stress in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE microdialysis; laser-Doppler flowmetry ID SKIN BLOOD-FLOW; NITRIC-OXIDE; RESPONSES; EXERCISE AB To test the hypothesis that bradykinin effects cutaneous active vasodilation during hyperthermia, we examined whether the increase in skin blood flow (SkBF) during heat stress was affected by blockade of bradykinin B-2 receptors with the receptor antagonist HOE-140. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for local delivery of drugs in eight healthy subjects. HOE-140 was dissolved in Ringer solution (40 muM) and perfused at one site, whereas the second site was perfused with Ringer alone. SkBF was monitored by laser-Doppler flowmetry (LDF) at both sites. Mean arterial pressure (MAP) was monitored from a finger, and cutaneous vascular conductance (CVC) was calculated (CVC = LDF/MAP). Water-perfused suits were used to control body temperature and evoke hyperthermia. After hyperthermia, both microdialysis sites were perfused with 28 mM nitroprusside to effect maximal vasodilation. During hyperthermia, CVC increased at HOE-140 (69 +/- 2% maximal CVC, P < 0.01) and untreated sites (65 +/- 2% maximal CVC, P < 0.01). These responses did not differ between sites (P > 0.05). Because the bradykinin B-2-receptor antagonist HOE-140 did not alter SkBF responses to heat stress, we conclude that bradykinin does not mediate cutaneous active vasodilation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-65599] NR 32 TC 13 Z9 14 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2002 VL 93 IS 4 BP 1215 EP 1221 DI 10.1152/japplphysiol.01142.2001 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 594DZ UT WOS:000178034600006 PM 12235017 ER PT J AU Ring, D Quintero, J Jupiter, JB AF Ring, D Quintero, J Jupiter, JB TI Open reduction and internal fixation of fractures of the radial head SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT; ELBOW; DISLOCATION AB Background: The purpose of this retrospective study was to analyze the functional results following open reduction and internal fixation of fractures of the radial head and to determine which fracture patterns are most amenable to this treatment. Methods: Fifty-six patients in whom an intra-articular fracture of the radial head had been treated with open reduction and internal fixation were evaluated at an average of forty-eight months after injury. Thirty patients had a Mason Type-2 (partial articular) fracture, and twenty-six had a Mason Type-3 (complete articular) fracture. Twenty-seven of the fifty-six fractures were associated with a fracture-dis location of the forearm or elbow or an injury of the medial collateral ligament. Fifteen of the thirty Type-2 fractures were comminuted. Fourteen of the twenty-six Type-3 fractures consisted of more than three fragments, and twelve consisted of two or three fragments. The result at the final evaluation was judged to be unsatisfactory when there was early failure of fixation or nonunion requiring a second operation to excise the radial head, <100degrees of forearm rotation, or a fair or poor rating according to the system of Broberg and Morrey. Results: The result was unsatisfactory for four of the fifteen patients with a comminuted Mason Type-2 fracture of the radial head; all four fractures had been associated with a fracture-dislocation of the forearm or elbow, and all four patients recovered <100degrees of forearm rotation. Thirteen of the fourteen patients with a Mason Type-3 comminuted fracture with more than three articular fragments had an unsatisfactory result. In contrast, all fifteen patients with an isolated, noncomminuted Type-2 fracture had a satisfactory result. Of the twelve patients with a Type-3 fracture that split the radial head into two or three simple fragments, none had early failure, one had nonunion, and all had an arc of forearm rotation of greater than or equal to100degrees. Conclusions: Although current implants and techniques for internal fixation of small articular fractures have made it possible to repair most fractures of the radial head, our data suggest that open reduction and internal fixation is best reserved for minimally comminuted fractures with three or fewer articular fragments. Associated fracture-dislocation of the elbow or forearm may also compromise the long-term result of radial head repair, especially with regard to restoration of forearm rotation. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Hosp Univ Clin San Rafael, Dept Ortoped & Traumatol, Bogota, Colombia. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 15 Parkman St,WACC525, Boston, MA 02114 USA. NR 38 TC 146 Z9 168 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 OCT PY 2002 VL 84A IS 10 BP 1811 EP 1815 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 602BR UT WOS:000178485600011 PM 12377912 ER PT J AU Klein, RF Turner, RJ Skinner, LD Vartanian, KA Serang, M Carlos, AS Shea, M Belknap, JK Orwoll, ES AF Klein, RF Turner, RJ Skinner, LD Vartanian, KA Serang, M Carlos, AS Shea, M Belknap, JK Orwoll, ES TI Mapping quantitative trait loci that influence femoral cross-sectional area in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE femoral cross-sectional area; osteoporosis; heredity; quantitative trait; quantitative trait locus analysis ID BONE-MINERAL DENSITY; X-RAY ABSORPTIOMETRY; STRESS-FRACTURE; GENOME SCREEN; HIP FRACTURE; OSTEOPOROTIC FRACTURES; GENETIC-DETERMINANTS; INBRED STRAINS; MOUSE STRAINS; MASS AB Size and shape are critical determinants of the mechanical properties of skeletal elements and can be anticipated to be highly heritable. Moreover, the genes responsible may be independent of those that regulate bone mineral density (BMD). To begin to identify the heritable determinants of skeletal geometry, we have examined femoral cross-sectional area (FCSA) in male and female mice from two inbred strains of mice with divergent FCSA (C57BL/6 [B6] and DBA/2 [D2]), a large genetically heterogeneous population (n = 964) of B6D2F(2) mice and 18 BXD recombinant inbred (RI) strains derived from their F-2 cross. Femora were harvested from 16-week-old mice and FCSA (bone and marrow space enclosed within the periosteum) was measured at the midshaft by digital image analysis. In all mouse populations examined, FCSA was positively correlated with body weight and weight-corrected FCSA (WC-FCSA) values were normally distributed in the BXD-RI and F-2 populations, suggesting polygenic control of this trait. Genome-wide quantitative trait locus (QTL) analysis of the B6D2F(2) population revealed regions on four different chromosomes that were very strongly linked to WC-FCSA (chromosomes 6, 8, 10, and X) in both genders. Evidence of gender-specific genetic influences on femoral geometry was also identified at three other chromosomal sites (chromosomes 2, 7, and 12). Supporting evidence for the WC-FCSA QTLs on chromosomes 2, 7, 8, 10, and 12 also was present in the RI strains. Interestingly, none of these WC-FCSA QTLs were identified in our previous QTL analysis of whole body BMD in the same B6D2F(2) population. Thus, the genetic determinants of bone size appear to be largely, if not entirely, distinct from those that regulate BMD attainment. The identification of the genes responsible for geometric differences in bone development should reveal fundamentally important processes in the control of skeletal integrity. C1 Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Orthoped, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Klein, RF (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Unit CR113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 FU NIAAA NIH HHS [AA 10760]; NIAMS NIH HHS [AR 44659, R01 AR044659, R01 AR044659-07] NR 51 TC 76 Z9 77 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 OCT PY 2002 VL 17 IS 10 BP 1752 EP 1760 DI 10.1359/jbmr.2002.17.10.1752 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 595GU UT WOS:000178100900003 PM 12369778 ER PT J AU Maulik, G Madhiwala, P Brooks, S Ma, PC Kijima, T Tibaldi, EV Schaefer, E Parmar, K Salgia, R AF Maulik, G Madhiwala, P Brooks, S Ma, PC Kijima, T Tibaldi, EV Schaefer, E Parmar, K Salgia, R TI Activated c-Met signals through PI3K with dramatic effects on cytoskeletal functions in small cell lung cancer SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE signal transduction in lung cancer; PI3-K; cell motility; c-Met/HGF; geldanamycin ID FACTOR SCATTER FACTOR; INTERNAL TANDEM DUPLICATION; ACUTE MYELOID-LEUKEMIA; ACTIN STRESS FIBERS; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CDC42 GTPASES; FLT3 GENE; GROWTH; RECEPTOR AB Small cell lung cancer (SCLC) is an aggressive illness with early metastases. There are several receptor tyrosine kinases (RTKs) overexpressed in SCLC, including c-Met. c-Met contains an external semaphorin-like domain, a cytoplasmic juxtamembrane domain, tyrosine kinase domain and multiple tyrosines that bind to adapter molecules. We have previously reported that c-Met is abundantly expressed in the NCI-H69 SCLC cell line and now have determined the downstream effects of stimulating c-Met via its ligand hepatocyte growth factor (HGF). Utilizing unique phospho-specific antibodies generated against various tyrosines of c-Met, we show that Y1003 (binding site for c-Cbl and a negative regulatory site), Y1313 (binding site for PI3K), Y1230/Y1234/Y1235 (autophosphorylation site), Y1349 (binding site for Grb2), Y1365 (important in cell morphogenesis) are phosphorylated in response to HGF (40 ng/ml, 7.5 min) in H69 cells. Since multiple biological and biochemical effects are transduced through the PI3K pathway, we determine the role of PI3K in the c-Met/HGF stimulation pathway. We initially determined that by inhibiting PI3K with LY294002 (50 M over 72 hours), there was at least a 55% decrease in viability of H69 cells. Since H69 SCLC cells form clusters in cell culture, we determined the effects of HGF and LY294002 on cell motility of the clusters by time-lapse video microscopy. In response to HGF, SCLC moved much faster and formed more clusters, and this was inhibited by LY294002. Finally, we determined the downstream signal transduction of HGF stimulation of c-Met with and without inhibition of c-Met (with geldanamycin, an anisamycin antibiotic that inhibits c-Met in SCLC) or PI3K (with LY294002). We show that association of c-Met with PI3K and GAB2 is diminished by inhibiting c-Met. In summary, activation of the c-Met pathway targets the PI3K pathway in SCLC and this may be an important therapeutic target. C1 Dana Farber Canc Inst, Div Adult Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Div Hematol & Oncol, Boston, MA 02111 USA. Dana Farber Canc Inst, Dept Immunobiol, Boston, MA 02115 USA. Biosource Int, Hopkinton, MA USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, Div Adult Oncol, Dept Adult Oncol, Dana 1234B,44 Binney St, Boston, MA 02115 USA. FU PHS HHS [75348-04] NR 42 TC 54 Z9 56 U1 0 U2 4 PU CAROL DAVILA UNIV PRESS PI BUCHARESST PA 8 EROILOR SANITARI BLVD, BUCHARESST 76241, ROMANIA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD OCT-DEC PY 2002 VL 6 IS 4 BP 539 EP 553 DI 10.1111/j.1582-4934.2002.tb00453.x PG 15 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 650EA UT WOS:000181248600006 PM 12611639 ER PT J AU Hardy, DJ Hinkin, CH AF Hardy, DJ Hinkin, CH TI Reaction time performance in adults with HIV/AIDS SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED INDIVIDUALS; AIDS DEMENTIA COMPLEX; WORKING-MEMORY; ANTIRETROVIRAL THERAPY; NEUROPSYCHOLOGICAL PERFORMANCE; DECISION-MAKING; STROOP TASK; HUMAN-BRAIN; ABNORMALITIES AB Infection with the Human Immunodeficiency Virus-Type 1 (HIV-1) has been shown to lead to cognitive decline in a substantial proportion of infected adults. The characteristic neuropsychological symptomatology includes memory dysfunction, higher order attentional disturbance, executive dysfunction and, most relevant to this manuscript, cognitive slowing. This paper reviews the extant literature on reaction time (RT) performance in HIV-infected adults with an emphasis on mental chronometry. In addition to discussing studies of simple and choice RT, we also examine the utility of RT paradigms in the assessment of selective attention, covert orienting, sustained attention, divided attention, working memory, and implicit memory. Studies documenting the utility of RT tasks to track treatment response are also introduced. In aggregate, research to date that has employed RT tasks in the evaluation of HIV-infected patients has found that HIV infection leads to a mild degree of cognitive slowing that tends to worsen with increasing disease severity. It needs to be noted, however, that a significant percentage of studies failed to find HIV infection to lead to RT slowing. Results of Brinley plot analyses, a technique that shares commonalities with meta-analysis, reveal that HIV-infected patients diagnosed with AIDS are on an average 22% slower than uninfected controls. This paper also reviews data that has shown that HIV associated cognitive slowing, as indexed by single and dual choice RT, is amenable to pharmacologic intervention using the psychostimulant methylphenidate. Given the demonstrated sensitivity of RT tasks to the neuropsychological effects of HIV infection, it is recommended that RT tasks be included whenever possible in the routine clinical evaluation of HIV-infected patients. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Psychol Serv, Los Angeles, CA USA. RP Hardy, DJ (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Room C-8747, Los Angeles, CA 90024 USA. FU NIA NIH HHS [R03 AG18549]; NIDA NIH HHS [R01 DA13799]; NIMH NIH HHS [R01 MH58552, R01 MH058552] NR 78 TC 32 Z9 33 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 2002 VL 24 IS 7 BP 912 EP 929 DI 10.1076/jcen.24.7.912.8391 PG 18 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 642GY UT WOS:000180796900005 PM 12647768 ER PT J AU Hirschhorn, JN Altshuler, D AF Hirschhorn, JN Altshuler, D TI Editorial: Once and again - Issues surrounding replication in genetic association studies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID MELANOCORTIN-4 RECEPTOR GENE; FRAMESHIFT MUTATION; OBESITY; IDENTIFICATION; VARIANTS; DISEASES; MC4R C1 Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. MIT, Whitehead Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Hirschhorn, JN (reprint author), Childrens Hosp, Div Genet & Endocrinol, Enders 561,300 Longwood Ave, Boston, MA 02115 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 14 TC 121 Z9 122 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2002 VL 87 IS 10 BP 4438 EP 4441 DI 10.1210/jc.2002-021329 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 604YZ UT WOS:000178649800004 PM 12364414 ER PT J AU Cook, DM Biller, BMK Vance, ML Hoffman, AR Phillips, LS Ford, KM Benziger, DP Illeperuma, A Blethen, SL Attie, KM Dao, LN Reimann, JD Fielder, PJ AF Cook, DM Biller, BMK Vance, ML Hoffman, AR Phillips, LS Ford, KM Benziger, DP Illeperuma, A Blethen, SL Attie, KM Dao, LN Reimann, JD Fielder, PJ TI The pharmacokinetic and pharmacodynamic characteristics of a long-acting growth hormone (GH) preparation (Nutropin Depot) in GH-deficient adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACID-LABILE SUBUNIT; QUALITY-OF-LIFE; REPLACEMENT THERAPY; BODY-COMPOSITION; INSULIN SENSITIVITY; DOSE TITRATION; PROTEIN; METABOLISM; EFFICACY; COMPLEX AB A pharmacokinetic-pharmacodynamic study of a long-acting GH [Nutropin Depot; somatropin (rDNA origin) for injectable suspension] was performed in 25 patients with adult GH deficiency. Single doses of 0.25 mg/kg and 0.5 mg/kg, based on ideal body weight, were administered se. After either dose, serum GH concentrations rose rapidly in both sexes. In men, the lower dose maintained serum IGF-I levels within 1 SD Of the mean for age and sex for 14-17 d; the higher dose raised IGF-I levels 2 SD above the mean. In most women, all of whom were receiving oral estrogen, the lower dose did not normalize IGF-I levels; the higher dose maintained IGF-I near the mean for approximately 14 d. Increases in IGF binding protein-3 and acid-labile subunit levels were observed in both sexes; however, a sex-related difference was not obvious. Fasting glucose and insulin concentrations were transiently elevated in men receiving the higher dose. Patients tolerated the injections well. We concluded that a single injection of Nutropin Depot at these doses in patients with adult GH deficiency increased serum IGF-I to within normal limits for 14-17 d. Estrogen-treated women required approximately twice the dose needed in men to produce comparable IGF-I concentrations. C1 Oregon Hlth Sci Univ, Dept Med, Div Endocrinol, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Virginia, Charlottesville, VA 22901 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Emory Univ, Atlanta, GA 30322 USA. Alkermes Inc, Cambridge, MA 02139 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Cook, DM (reprint author), Oregon Hlth Sci Univ, Dept Med, Div Endocrinol, 3181 SW Sam Jackson Pk Rd,M-S L-607, Portland, OR 97201 USA. EM cookd@ohsu.edu FU AHRQ HHS [HS-07922] NR 22 TC 45 Z9 47 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2002 VL 87 IS 10 BP 4508 EP 4514 DI 10.1210/jc.2002-020480 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 604YZ UT WOS:000178649800018 PM 12364427 ER EF