FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Taylor, AE AF Taylor, AE TI The gonadotropic axis in hyperandrogenic adolescents SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 2nd International Symposium on the Developmental Aspects of Androgen Excess Disorders CY JUN 20-21, 2000 CL TORONTO, CANADA DE polycystic ovary syndrome; gonadotropin secretion; puberty; luteinizing hormone; LH/FSH ratio; androgen; hyperandrogenism ID POLYCYSTIC-OVARY-SYNDROME; LUTEINIZING-HORMONE; GIRLS; WOMEN AB Polycystic ovary syndrome (PCOS) is a common reproductive disorder that is first clinically diagnosable approximately 3 years after menarche. Women with PCOS have exaggerated gonadotropin secretion, with an elevated LH/FSH ratio, as well as an increased frequency and amplitude of LH pulsations. Since the elevated pulse frequency is a marker of unusually rapid hypothalamic GnRH secretion, these results imply a defect at the level of the hypothalamus. Such an abnormality could theoretically be a primary defect that could cause PCOS, and if so, would be expected to be detectable at the onset of puberty. How these abnormalities of hypothalamic and pituitary function relate to other, seemingly disparate, organ defects has not yet been delineated. We studied 99 PCOS patients and 42 normal controls with 8 to 12 hours of q10 min frequent blood sampling. Women with PCOS had significantly elevated mean LH levels, LH pulse amplitude, LH pulse frequency, and LH/FSH ratios compared to normal women. However, these abnormalities were not randomly distributed. All gonadotropin secretion parameters tended to be normal in PCOS patients when measured during the luteal phase or first 7 days after an ovulatory menses. There was a strong inverse relationship of mean LH, LW FSH ratio, and LH pulse amplitude, but not frequency, with BMI. We hypothesize that this effect of body size occurs at the pituitary level. Several investigators have performed similar investigations in adolescent girls with regular and irregular menstrual cycles. Taken together, this evidence suggests that the gonadotropin defects appear as a very early finding in the development of PCOS, but the presence of abnormalities in both gonadotropin secretion and androgen secretion does not allow one to conclude that the gonadotropin defects are causal. We conclude that gonadotropin defects, particularly excess of serum LH, is a predominant finding in hyperandrogenic women, whether they are young peripubertal adolescents, or older perimenopausal women. Whether there is a primary neuroendocrine abnormality driving excess gonadotropin secretion that causes the hyperandrogenic condition, or whether the excess gonadotropin secretion reflects abnormal feedback of another factor, still remains unknown. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, BHX-5,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [R03-HD-35251, U54-HD-29164, R29-HD-33509] NR 8 TC 2 Z9 2 U1 0 U2 1 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD DEC PY 2000 VL 13 SU 5 BP 1281 EP 1284 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 380QD UT WOS:000165712800009 PM 11117670 ER PT J AU Kahn, CR Bruning, JC Michael, MD Kulkarni, RN AF Kahn, CR Bruning, JC Michael, MD Kulkarni, RN TI Knockout mice challenge our concepts of glucose homeostasis and the pathogenesis of diabetes mellitus SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 29th International Symposium on Growth Hormone and Growth Factors in Endocrinology and Metabolism CY APR 07-08, 2000 CL MARRAKECH, MOROCCO DE diabetes mellitus; glucose homeostasis; insulin action; insulin receptors; insulin receptor substrates; insulin resistance; phosphatidylinositol 3-kinase ID INSULIN-RECEPTOR SUBSTRATE-1; TYROSINE PHOSPHORYLATION; HOMOLOGOUS RECOMBINATION; JUXTAMEMBRANE REGION; TARGETED DISRUPTION; KINASE-ACTIVITY; BETA-CELLS; GENE; PROTEINS; GROWTH AB The failure of insulin to stimulate muscle glucose uptake and suppress hepatic glucose production represents two of the fundamental pathophysiologic lesions in type 2 diabetes mellitus (DM), Defining insulin action at the molecular level, therefore, provides the critical background against which to elucidate the mechanisms of insulin resistance that underlie type 2 DM, obesity and many other disorders. Over the past two decades substantial progress has been made in identifying many of the molecular mechanisms involved in insulin signaling, Much of this progress has been due to the use of homologous recombinant gene targeting, The present review examines the various insights that have been provided by studies of knockout mice strains, Taken together, the results present the possibility of a unifying hypothesis for type 2 DM, in which insulin resistance in the beta -cell synergizes with insulin resistance in the periphery to produce the two classic defects of this disease: relative hypoinsulinemia and peripheral insulin resistance. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 53 TC 27 Z9 29 U1 4 U2 5 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD DEC PY 2000 VL 13 SU 6 BP 1377 EP 1384 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 395QN UT WOS:000166592400011 PM 11202213 ER PT J AU St Croix, CM Morgan, BJ Wetter, TJ Dempsey, JA AF St Croix, CM Morgan, BJ Wetter, TJ Dempsey, JA TI Fatiguing inspiratory muscle work causes reflex sympathetic activation in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LEG BLOOD-FLOW; NERVE ACTIVITY; RESPIRATORY MODULATION; SKELETAL-MUSCLE; GROUP-III; EXERCISE; RESPONSES; AFFERENTS; PRESSURE; STIMULATION AB 1. We tested the hypothesis that reflexes arising from working respiratory muscle can elicit increases in sympathetic vasoconstrictor outflow to limb skeletal muscle, in seven healthy human subjects at rest. 2. We measured muscle sympathetic nerve activity (MSNA) with intraneural electrodes in the peroneal nerve while the subject inspired (primarily with the diaphragm) against resistance, with mouth pressure (P-M) equal to 60% of maximal, a prolonged duty cycle (T-I/T-Tot) of 0.70, breathing frequency (f(b)) of 15 breaths min(-1) and tidal volume (V-T) equivalent to twice eupnoea. This protocol was known to reduce diaphragm blood flow and cause fatigue. 3. MSNA was unchanged during the first 1-2 min but then increased over time, to 77 +/- 51% (S.D.) greater than control at exhaustion (mean time, 7 +/- 3 min). Mean arterial blood pressure (+12 mmHg) and heart rate (+ 27 heats min(-1)) also increased. 4. When the V-T, f(b) and T-I/T-Tot of these trials were mimicked with no added resistance, neither MSNA nor arterial blood pressure increased. 5. MSNA and arterial blood pressure also did not change in response to two types of increased central respiratory motor output that did not produce fatigue: (a) high inspiratory flow rate and f(b) without added resistance; or (b) high inspiratory effort against resistance with P-M of 95% maximal, T-I/T-Tot of 0.35 and f(b) of 12 breaths min(-1). The heart rate increased by 5-16 beats min(-1) during these trials. 6. Thus, in the absence of any effect of increased central respiratory motor output per se on limb MSNA, we attributed the time-dependent increase in MSNA during high resistance, prolonged duty cycle breathing to a reflex arising from a diaphragm that was accumulating metabolic end products in the face of high force output plus compromised blood flow. C1 Univ Wisconsin, Dept Prevent Med, John Rankin Lab Pulm Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, John Rankin Lab Pulm Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. RP St Croix, CM (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol, 13th Floor,Biomed Sci Tower,200 Lothrop St, Pittsburgh, PA 15261 USA. FU PHS HHS [R29-57401, R01-15469] NR 36 TC 112 Z9 114 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 2000 VL 529 IS 2 BP 493 EP 504 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 386YE UT WOS:000166092600019 PM 11101657 ER PT J AU Shera, CA Talmadge, CL Tubis, A AF Shera, CA Talmadge, CL Tubis, A TI Interrelations among distortion-product phase-gradient delays: Their connection to sealing symmetry and its breaking SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID EVOKED OTOACOUSTIC EMISSIONS; MOSSBAUER TECHNIQUE; BASILAR-MEMBRANE; FILTER RESPONSE; FINE-STRUCTURE; HUMAN ADULTS; GUINEA-PIG; COCHLEA; LATENCY; MECHANICS AB Distortion-product-otoacoustic-emission (DPOAE) phase-versus-frequency functions and corresponding phase-gradient delays have, received considerable attention because of their potential for providing information about mechanisms of emission generation, cochlear wave latencies, and characteristics of cochlear tuning. The three measurement paradigms in common use (fixed-f(1), fixed-f(2), and fixed-f(2)/f(1)) yield significantly different delays, suggesting that they depend on qualitatively different aspects of cochlear mechanics. In this paper, theory and experiment are combined to demonstrate that simple phenomenological arguments, which make no detailed mechanistic assumptions concerning the underlying cochlear mechanics, predict relationships among the delays that are in good quantitative agreement with experimental data obtained in guinea pigs. To understand deviations between the simple theory and experiment, a general equation is found that relates the three delays for any deterministic model of DPOAE generation. Both model-independent and exact, the general relation provides a powerful consistency check on the measurements and a useful tool for organizing and understanding the structure in DPOAE phase data (e.g., for interpreting the relative magnitudes and intensity-dependencies of the three delays). Analysis of the general relation demonstrates that the success of the simple, phenomenological approach can be understood as a consequence of the mechanisms of emission generation and the approximate local scaling symmetry of cochlear mechanics. The general relation is used to quantify deviations from scaling manifest in the measured phase-gradient delays; the results indicate that deviations from scaling are typically small and that both linear and nonlinear mechanisms contribute significantly to these deviations. Intensity-dependent mechanisms contributing to deviations from scaling include cochlear-reflection and wave-interference effects associated with the mixing of distortion- and reflection-source emissions las in DPOAE fine structure). Finally, the ratio of the fixed-f(1) and fixed-f(2) phase-gradient delays is shown to follow from the choice of experimental paradigm and, in the scaling limit, contains no information about cochlear physiology whatsoever. These results cast considerable doubt on the theoretical basis of recent attempts to use relative DPOAE phase-gradient delays to estimate the bandwidths of peripheral auditory filters. (C) 2000 Acoustical Society of America. [S0001-4966(00)03012-5]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. Purdue Univ, Dept Phys, W Lafayette, IN 47907 USA. Univ Calif San Diego, Inst Nonlinear Sci, La Jolla, CA 92093 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R29 DC03094, R01 DC03687, R01 DC003687] NR 65 TC 45 Z9 45 U1 1 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2000 VL 108 IS 6 BP 2933 EP 2948 DI 10.1121/1.1323234 PG 16 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 381TV UT WOS:000165780300025 PM 11144585 ER PT J AU Kearns, ME Jellinek, MS AF Kearns, ME Jellinek, MS TI Commentary: Guides to quality: Evidence and values SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Child Psychiat Clin, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Clin, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2000 VL 39 IS 12 BP 1502 EP 1503 DI 10.1097/00004583-200012000-00010 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 378GA UT WOS:000165575600010 PM 11128326 ER PT J AU Bostic, JQ Pataki, C AF Bostic, JQ Pataki, C TI All the world's a stage SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Harvard Med Sch, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, WAC 725, Boston, MA 02114 USA. NR 35 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2000 VL 39 IS 12 BP 1565 EP 1567 DI 10.1097/00004583-200012000-00021 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 378GA UT WOS:000165575600019 PM 11128335 ER PT J AU Beresin, EV AF Beresin, EV TI Doing child and adolescent psychotherapy. The ways and whys. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Boston, MA 02115 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2000 VL 39 IS 12 BP 1574 EP 1575 DI 10.1097/00004583-200012000-00024 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 378GA UT WOS:000165575600022 ER PT J AU Ratcliffe, M AF Ratcliffe, M TI Batista's operation: What have we learned? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID PARTIAL LEFT VENTRICULECTOMY; STAGE HEART-DISEASE; DILATED CARDIOMYOPATHY; CONDUCTANCE CATHETER; PARALLEL CONDUCTANCE; VOLUME MEASUREMENT; LEFT-VENTRICLE; PERFORMANCE C1 San Francisco Vet Adm Med Ctr, San Francisco, CA 94121 USA. RP Ratcliffe, M (reprint author), San Francisco Vet Adm Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. NR 33 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2000 VL 36 IS 7 BP 2115 EP 2118 DI 10.1016/S0735-1097(00)01035-4 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 378TM UT WOS:000165600400015 PM 11127449 ER PT J AU Tawakol, A Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H AF Tawakol, A Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Picard, MH Gewirtz, H TI Evidence of reduced resting blood flow in viable myocardial regions with chronic asynergy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR DYSFUNCTION; ISCHEMIC-HEART-DISEASE; COLLATERAL-DEPENDENT MYOCARDIUM; WALL-MOTION ABNORMALITIES; LOW-DOSE DOBUTAMINE; HIBERNATING MYOCARDIUM; CONTRACTILE RESPONSE; VIABILITY; HUMANS AB OBJECTIVES We tested the hypothesis in patients (n = 24) with ischemic heart disease that chronic contractile dysfunction occurs in myocardial regions with true reduction in rest blood flow. BACKGROUND Whether viable myocardial regions with chronic contractile dysfunction have true reduction in rest myocardial blood flow is controversial. METHODS Positron emission tomography (PET) N-13-ammonia was used to measure myocardial blood flow in combination with F-18-fluorodeoxyglucose ((18)FDG) to assess myocardial viability. Viability also was assessed by dobutamine echo and recovery of function after coronary artery bypass grafting (CABG). Segments (n = 252) were selected based on PET measured reduced resting blood flow and rest asynergy on echo. RESULTS Regional myocardial viability was present in 20 of 23 patients by PET, 13 of 23 by dobutamine echo and 10 of 11 by postrevascularization criteria. Rest blood how in normal regions was 1.14 +/- 0.52 ml/min/g and by definition exceeded (p < 0.005) that in both viable (0.48 +/- 0.15; n = 8 patients) and nonviable (0.45 +/- 0.14; n = 8 patients) regions (post-CABG criteria), which did not differ. Correction of rest myocardial blood flow in viable asynergic segments, only, for fibrosis and incomplete tracer recovery raised the level to 0.67 +/- 0.21 (p < 0.005 vs. normal). Finally, evidence of both stunning (rest asynergy with normal flow) and hibernation was present in 15 of 23 (65%) patients. CONCLUSIONS Reduced rest blood flow in viable myocardial regions with chronic asynergy is common and cannot be accounted for by partial volume effect. Thus, hypotheses concerning physiologic mechanisms underlying chronic contractile dysfunction should consider the role played by chronic reduction of basal myocardial blood flow. (C) 2000 by the American College of Cardiology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA 02114 USA. RP Gewirtz, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Vincent Burnham 3, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 37 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 2000 VL 36 IS 7 BP 2146 EP 2153 DI 10.1016/S0735-1097(00)00999-2 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 378TM UT WOS:000165600400020 PM 11127454 ER PT J AU Siebens, H Aronow, H Edwards, D Ghasemi, Z AF Siebens, H Aronow, H Edwards, D Ghasemi, Z TI A randomized controlled trial of exercise to improve outcomes of acute hospitalization in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE deconditioning; exercise; rehabilitation; hospitalization; physical therapy ID GERIATRIC CONSULTATION TEAM; CONTROLLED CLINICAL-TRIAL; LIFE-STYLE ACTIVITY; BED REST; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; WOMEN; CARE; DISABILITY; MORTALITY AB OBJECTIVE: Older adults hospitalized for nondisabling diagnoses can lose functional ability. Lack of exercise or physical activity during the acute illness and recovery may be contributory. This study evaluated whether increased exercise in hospital and afterward would shorten length of stay and improve physical function at 1 month. DESIGN: A randomized controlled trial. SETTING: A 700-bed community-based hospital with academic and teaching programs. PARTICIPANTS: Three hundred patients (mean age 78.2 years +/- 5.6) with nondisabling medical and surgical diagnoses who were admitted to an acute care hospital between December 1990 and April 1992. All patients had an expected length of stay 5 or more days, were ambulatory before admission, and were not expected to die within 12 months. INTERVENTION: A hospital-based general exercise program was administered to intervention patients along with encouragement to continue the program, self-administered, at home. MEASUREMENTS: The primary outcome was hospital length of stay. Secondary outcomes at 1 month postdischarge included measures of physical function and other general health indicators. RESULTS: There was no significant difference in length of stay between treatment and control groups controlling for baseline characteristics and diagnoses. The intervention was associated with better function in instrumental activities of daily living (beta = .433 (95% CI, 0.044-0.842)) at 1 month but no change in perceived general health status and other measures of physical function. CONCLUSIONS: An exercise program started during hospitalization and continued for 1 month did not shorten length of stay but did improve functional outcome at 1 month. C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Casa Colina Ctr Rehabil, Pomona, CA USA. Saddleback Coll, Mission Viejo, CA USA. RP Siebens, H (reprint author), Massachusetts Gen Hosp, Med & Rehabil Serv, VBK 820,55 Fruit St, Boston, MA 02114 USA. NR 46 TC 52 Z9 55 U1 0 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1545 EP 1552 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200001 PM 11129741 ER PT J AU Hartman, CA Manos, TM Winter, C Hartman, DM Li, BQ Smith, JC AF Hartman, CA Manos, TM Winter, C Hartman, DM Li, BQ Smith, JC TI Effects of T'ai Chi training on function and quality of life indicators in older adults with osteoarthritis SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE osteoarthritis; T'ai Chi; physical activity; quality of life; rehabilitation ID RHEUMATOID-ARTHRITIS; SELF-EFFICACY; HEALTH-STATUS; EXERCISE; DISABILITY; KNEE; PEOPLE AB OBJECTIVE: To determine the effects of T'ai Chi training on arthritis self-efficacy, quality of life indicators, and lower extremity functional mobility in older adults with osteoarthritis. DESIGN: A prospective, randomized, controlled clinical trial. Intervention length was 12 weeks, with outcomes measured before and after intervention using blinded testers. Group (T'ai Chi vs Control) x time (2 x 2) mixed factorial ANOVA. SETTING: Allied Health Sciences Center at Springfield College, Springfield, MA PARTICIPANTS: A total of 33 community-dwelling participants (mean age 68) diagnosed with lower extremity osteoarthritis and having no prior T'ai Chi training longer than 2 weeks. INTERVENTION: T'ai Chi training included two 1-hour T'ai Chi classes per week for 12 weeks. MEASUREMENTS: Arthritis self-efficacy (Arthritis Self-Efficacy Scale), quality of life indicators (Arthritis Impact Measurement Scale), functional outcomes (one-leg standing balance, 50-foot walking speed, time to rise from a chair). RESULTS: T'ai Chi participants experienced significant (P < .05) improvements in self-efficacy for arthritis symptoms, total arthritis self-efficacy, level of tension, and satisfaction with general health status. CONCLUSIONS: A moderate T'ai Chi intervention can enhance arthritis self-efficacy, quality of life, and functional mobility among older adults with osteoarthritis. T'ai Chi training is a safe and effective complementary therapy in the medical management of lower extremity osteoarthritis. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Springfield Coll, Springfield, MA USA. Lahey Clin, Burlington, MA USA. Sch Tai Chi, Springfield, MA USA. RP Hartman, CA (reprint author), 1475 Massacusetts Ave,459, Lexington, MA 02420 USA. NR 39 TC 108 Z9 115 U1 3 U2 12 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1553 EP 1559 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200002 PM 11129742 ER PT J AU Counsell, SR Holder, CM Liebenauer, LL Palmer, RM Fortinsky, RH Kresevic, DM Quinn, LM Allen, KR Covinsky, KE Landefeld, CS AF Counsell, SR Holder, CM Liebenauer, LL Palmer, RM Fortinsky, RH Kresevic, DM Quinn, LM Allen, KR Covinsky, KE Landefeld, CS TI Effects of a multicomponent intervention on functional outcomes and process of care in hospitalized older patients: A randomized controlled trial of Acute Care for Elders (ACE) in a community hospital SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-General-Internal-Medicine CY APR 23-25, 1998 CL CHICAGO, ILLINOIS SP Soc Gen Internal Med DE aged; hospital outcomes; functional decline; institutionalization; quality of care ID COMPREHENSIVE GERIATRIC ASSESSMENT; MEDICAL UNIT; DEPRESSION; ILLNESS; CONSULTATION; PROGRAM; DECLINE AB BACKGROUND: Older persons frequently experience a decline in function following an acute medical illness and hospitalization. OBJECTIVE: To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: A total of 1531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997. INTERVENTION: ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness. MEASUREMENTS: The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction. RESULTS: Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P =.027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; r = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P <.05). CONCLUSIONS: ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes. C1 Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Summa Hlth Syst, ACE Clin Res Off, Akron, OH USA. Univ Pittsburgh, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Univ Connecticut, Ctr Aging, Farmington, CT USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Northeastern Ohio Univ, Coll Med, Rootstown, OH USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Counsell, SR (reprint author), Indiana Univ, Sch Med, 1001 West 10th St,WOP M200, Indianapolis, IN 46202 USA. FU NIA NIH HHS [AG10418] NR 40 TC 167 Z9 170 U1 4 U2 14 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1572 EP 1581 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200005 PM 11129745 ER PT J AU Stout, JE Brennen, C Muder, RR AF Stout, JE Brennen, C Muder, RR TI Legionnaires' disease in a newly constructed long-term care facility SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 7th Annual Meeting of the Society-for-Healthcare-Epidemiology-of-America CY APR 27-29, 1997 CL ST LOUIS, MISSOURI SP Soc Healthcare Epidemiol Amer DE Legionella; long-term care; pneumonia ID WATER DISTRIBUTION-SYSTEMS; NURSING-HOME; LEGIONELLA-PNEUMOPHILA; ACQUIRED PNEUMONIA; CONTAMINATION AB OBJECTIVES: To determine whether a newly-constructed long-term care facility would become colonized with Legionella and whether Legionnaires' disease would occur in residents of this new facility, DESIGN: Prospective environmental surveillance of the hospital's water distribution system for the presence of Legionella pneumophila during construction. Utilization of diagnostic tests for Legionnaires' disease in cases of nosocomial pneumonia. SETTING: The Pittsburgh Vh Health Care System, Aspin-wall Division, a two-building 400-bed complex. PARTICIPANTS: Sis patients who acquired Legionnaires' disease while in the facility. INTERVENTION: Installation of copper-silver ionization systems. MEASUREMENTS: Isolation of L. pneumophila from potable water and the occurrence of Legionnaires' disease. RESULTS: L. pneumophila serogroup I was recovered from the water distribution system within 1 month of operation; 74% (61/82) of distal sites were positive during construction. In the first 2 years of occupancy, six cases of legionellosis were diagnosed. Both clinical isolates of L. pneumophilia were identical to environmental isolates by pulsed field gel electrophoresis (PFGE). Copper-silver ionization systems were installed to control Legionella in the water system. CONCLUSIONS: We conclude that long-term care residents are at risk for acquiring nosocomial Legionnaires' disease in the presence of a colonized water system, even in a newly constructed building. C1 VA Pittsburgh Hlth Care Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. VA Pittsburgh Hlth Care Syst, Special Pathogens Lab, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), VA Pittsburgh Hlth Care Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 22 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2000 VL 48 IS 12 BP 1589 EP 1592 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 409EH UT WOS:000167371200007 PM 11129747 ER PT J AU Shimizu, A Yamada, K Meehan, SM Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Meehan, SM Sachs, DH Colvin, RB TI Acceptance reaction: Intragraft events associated with tolerance to renal allografts in miniature swine SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; LIVER-TRANSPLANTATION; SPLIT TOLERANCE; T-LYMPHOCYTES; NUCLEAR-DNA; REJECTION; APOPTOSIS; KIDNEY; INDUCTION; BIOPSIES AB Inbred miniature swine that are treated for 12 d with a high dose of cyclosporin A develop tolerance to MHC class II matched, class I-mismatched renal allografts. The aim of this study was to clarify the intrarenal allograft events associated with the development of tolerance in this protocol. Morphologic and immunologic studies were performed in serial biopsies from accepting grafts after 12 d of cyclosporin A treatment (n = 4) and were compared with those from untreated control rejecting grafts (n = 4). In accepting grafts with stable function, a transient interstitial infiltrate developed. The cellular infiltrate had many similarities to that in rejecting grafts; both had T cells and macrophages, similar proportions of T-cell subsets, and a similar frequency of in situ nick end labeling (TUNEL) + apoptotic infiltrating cells. However, the cellular infiltrate in the acceptance reaction was distinguished by less T-cell activation (interleukin-2 receptor+), less proliferation (proliferating cell nuclear antigen+) of infiltrating cells, and less graft cell apoptosis in arteries, tubules, glomeruli, and peritubular capillaries. Thereafter, the infiltrate in the accepting grafts progressively resolved with decreased cell proliferation, activation, and apoptotic graft parenchymal cell injury, but the high frequency of apoptosis persisted in graft-infiltrating cells. In parallel to the intragraft events, donor-specific unresponsiveness developed as assessed by cell-mediated cytotoxicity by blood mononuclear cells in vitro. In conclusion, the acceptance reaction in transplanted grafts is characterized by progressive resolution of T-cell proliferation and activation and of cell-mediated graft injury, as well as prolonged T-cell apoptosis. These intragraft events suggest that both T-cell anergy and T-cell deletion occur in the graft during the development of tolerance. Some of the described immunopathologic findings (activation, proliferation, apoptosis) may be useful in distinguishing acceptance from rejection, as well as in predicting later graft acceptance in tolerance induction protocols. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr,Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr,Dept Transplantat, Boston, MA 02114 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. RP Colvin, RB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biol Res Ctr,Dept Pathol, 55 Fruit St WRN 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01-HL 18646, 2PO1-HL 01846-21A1]; NIAID NIH HHS [2RO1-AI 31046B08] NR 42 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2000 VL 11 IS 12 BP 2371 EP 2380 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 378QT UT WOS:000165595600022 PM 11095661 ER PT J AU Stock, UA Sakamoto, T Hatsuoka, S Martin, DP Nagashima, M Moran, AM Moses, MA Khalil, PN Schoen, FJ Vacanti, JP Mayer, JE AF Stock, UA Sakamoto, T Hatsuoka, S Martin, DP Nagashima, M Moran, AM Moses, MA Khalil, PN Schoen, FJ Vacanti, JP Mayer, JE TI Patch augmentation of the pulmonary artery with bioabsorbable polymers and autologous cell seeding SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ENDOTHELIAL-CELLS; LONG-TERM; TISSUE; APOPTOSIS AB Objective: In recent years bioabsorbable synthetic or biologic materials have been used to augment the pulmonary artery or the right ventricular outflow tract. However, each of these polymers has one or more shortcomings. None of these patch materials has been seeded with cells. Thus, we have tested a fast-absorbing biopolymer, poly-4-hydroxybutyric acid, with autologous cell seeding for patch augmentation of the pulmonary artery in a juvenile sheep model. Methods: Vascular cells were isolated from ovine peripheral veins. (n = 6). Bioabsorbable porous poly-4-hydroxybutyric acid patches (porosity > 95%) were seeded on 3 consecutive days with a mixed vascular cell suspension (21.3 +/- 1.3 x 10(6) cells), Forty-five (+/- 2) days after the vessel harvest, 1 unseeded and 6 autologously seeded control patches were implanted into the proximal pulmonary artery. The animals received no postoperative anticoagulation. Follow-up was performed with echocardiography after 1 week and before explantation after 1, 7, and 24 weeks (2 animals each) for the seeded control patches and after 20 weeks for the nonseeded control patch. Results: All animals survived the procedure, Postoperative echocardiography of the seeded patches demonstrated a smooth surface without dilatation or stenosis. Macroscopic appearance showed a smooth internal surface with increasing tissue formation. Histology at 169 days demonstrated a near-complete resorption of the polymer and formation of organized and functional tissue. Biochemical assays revealed increasing cellular and extracellular matrix contents. The control patch showed a slight bulging, indicating a beginning dilatation. Conclusion: This experiment showed that poly-4-hydroxybutyric acid is a feasible patch material in the pulmonary circulation. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiovasc Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tepha Inc, Cambridge, MA USA. RP Mayer, JE (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiovasc Surg, 300 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-97-005] NR 22 TC 53 Z9 58 U1 0 U2 10 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2000 VL 120 IS 6 BP 1158 EP 1167 DI 10.1067/mtc.2000.109539 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 381EF UT WOS:000165748800022 PM 11088041 ER PT J AU Frank, DA Meuse, J Hirsch, D Ibrahim, JG van den Abbeele, AD AF Frank, DA Meuse, J Hirsch, D Ibrahim, JG van den Abbeele, AD TI The treatment and outcome of cancer patients with thromboses on central venous catheters SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE central venous catheter; thrombosis; cancer; radionuclide venography ID UPPER EXTREMITY DVT; VEIN-THROMBOSIS; HICKMAN; COMPLICATIONS; INFUSION; TRANSPLANTATION; CHEMOTHERAPY; MARROW AB Thromboses are a common complication of central venous catheters in cancer patients. This study was performed to analyze retrospectively the treatment and outcome of all patients with venous thromboses related to central venous catheters at a major cancer center. From 1992 through 1995, 319 oncology patients with central venous catheters underwent radionuclide venography (RNV) at the Dana-Farber Cancer Institute for suspected catheter or venous thrombosis. The treatment and outcome of patients found to have venous thromboses were evaluated. Of the 319 patients, 112 were found to have evidence of venous thrombosis. The median age and platelet counts were not significantly different between the patients with and without thromboses. The most common indication for obtaining RNV was difficulty in aspirating or infusing material through the catheter. Patients who had pain or edema, or both, of the neck or upper extremity were more likely to have a venous thrombosis. Regardless of therapeutic intervention, including anticoagulation with heparin or coumadin, or both; line removal or replacement; or a combination thereof, no patients had a major adverse outcome such as pulmonary embolism, compromise of limb, or death. Only 4 patients did not have resolution of their presenting symptoms, all of whom were treated with line replacement. The overall survival of patients with and without thromboses was not significantly different. Either anticoagulation or removal of the central venous catheter (or both) appears to be adequate treatment for catheter-related thrombosis. A prospective trial to evaluate these approaches may be worthwhile so that the use of unnecessary procedures may be avoided in this patient population. 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, Cambridge, MA 02138 USA. Pentucket Med Associates, Newburyport, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Nucl Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 25 TC 28 Z9 30 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD DEC PY 2000 VL 10 IS 3 BP 271 EP 275 DI 10.1023/A:1026503526188 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 386DR UT WOS:000166045300010 PM 11122548 ER PT J AU Freeman, VL Meydani, M Yong, S Pyle, J Flanigan, RC Waters, WB Wojcik, EM AF Freeman, VL Meydani, M Yong, S Pyle, J Flanigan, RC Waters, WB Wojcik, EM TI Prostatic levels of fatty acids and the histopathology of localized prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; fatty acids; prostatectomy; neoplasm invasiveness ID BREAST-CANCER; DIETARY-FAT; PLASMA; RISK AB Purpose: The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer. Materials and Methods: Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test. Results: The percent of total prostatic poly-unsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha -Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega -3 and omega -3-to-omega -6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined. Conclusions: These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Prevent Med, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Epidemiol, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Surg Pathol, Maywood, IL 60153 USA. Tufts Univ, Human Nutr Res Ctr Aging, Vasc Biol Lab, Jean Mayer USDA, Boston, MA 02111 USA. RP Freeman, VL (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv & Policy Res, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 25 TC 31 Z9 34 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2000 VL 164 IS 6 BP 2168 EP 2172 DI 10.1016/S0022-5347(05)66991-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 372KJ UT WOS:000165232600092 PM 11061949 ER PT J AU Bannert, N Schenten, D Craig, S Sodroski, J AF Bannert, N Schenten, D Craig, S Sodroski, J TI The level of CD4 expression limits infection of primary rhesus monkey macrophages by a T-tropic simian immunodeficiency virus and macrophagetropic human immunodeficiency viruses SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTORS; ENVELOPE GLYCOPROTEINS; HIV-1 ENTRY; FUNCTIONAL CORECEPTOR; ALVEOLAR MACROPHAGES; VIRAL DETERMINANTS; ENDOTHELIAL-CELLS; ORPHAN RECEPTORS; TYPE-1 INFECTION; SOLUBLE CD4 AB The entry of primate immunodeficiency viruses into cells is dependent on the interaction of the viral envelope glycoproteins with receptors, CD4, and specific members of the chemokine receptor family. Although in many cases the tropism of these viruses is explained by the qualitative pattern of coreceptor expression, several instances have been observed where the expression of a coreceptor on the cell surface is not sufficient to allow infection by a virus that successfully utilizes the coreceptor in a different context. For example, both the T-tropic simian immunodeficiency virus (SM SIVmac239 and the macrophagetropic (M-tropic) SIVmac316 can utilize CD4 and CCR5 as coreceptors, and both viruses can infect primary T lymphocytes, yet only SIVmac316 can efficiently infect CCR5-expressing primary macrophages from rhesus monkeys. Likewise, M-tropic strains of human immunodeficiency virus type 1 (HIV-1) do not infect primary rhesus monkey macrophages efficiently. Here we show that the basis of this restriction is the low level of CD4 on the surface of these cells. Overexpression of human or rhesus monkey CD4 in primary rhesus monkey macrophages allowed infection by both T-tropic and M-tropic SIV and by primary M-tropic HIV-1. By contrast, CCR5 overexpression did not specifically compensate for the inefficient infection of primary monkey macrophages by T-tropic SIV or M-tropic HIV-1. Apparently, the limited ability of these viruses to utilize a low density of CD4 for target cell entry accounts for the restriction of these viruses in primary rhesus monkey macrophages. C1 Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI28691, AI41851, P30 AI028691, R01 AI041851, R37 AI024755] NR 79 TC 93 Z9 93 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 10984 EP 10993 DI 10.1128/JVI.74.23.10984-10993.2000 PG 10 WC Virology SC Virology GA 461LM UT WOS:000170365800014 PM 11069993 ER PT J AU Ohagen, A Gabuzda, D AF Ohagen, A Gabuzda, D TI Role of Vif in stability of the human immunodeficiency virus type 1 core SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE REACTION; INFECTIOUS-ANEMIA VIRUS; VIRAL-DNA SYNTHESIS; CYCLOPHILIN-A; VIRION INCORPORATION; HIV-1 VIRIONS; SOR GENE; NONPERMISSIVE CELLS; PRIMARY LYMPHOCYTES; RESTRICTIVE CELLS AB The Vif protein of human immunodeficiency virus type 1 (HIV-1) is important for virion infectivity. Previous studies have shown that vif-defective virions exhibit structural abnormalities in the virus core and are defective in the ability to complete proviral DNA synthesis in acutely infected cells. We developed novel assays to assess the relative stability of the core in HIV-1 virions. Using these assays, we examined the role of Vif in the stability of the HIV-1 core. The integrity of the core was examined following virion permeabilization or removal of the lipid envelope and treatment with various triggers, including S100 cytosol, deoxynucleoside triphosphates, detergents, NaCl, and buffers of different pH to mimic aspects of the uncoating and disassembly process which occurs after virus entry but preceding or during reverse transcription. vif mutant cores were more sensitive to disruption by all triggers tested than wild-type cores, as determined by endogenous reverse transcriptase (RT) assays, biochemical analyses, and electron microscopy. RT and the p7 nucleocapsid protein were released more readily from vif mutant virions than from wild-type virions, suggesting that the internal nucleocapsid is less stably packaged in the absence of Vif. Purified cores could be isolated from wild-type but not vif mutant virions by sedimentation through detergent-treated gradients. These results demonstrate that Vif increases the stability of virion cores. This may permit efficient viral DNA synthesis by preventing premature degradation or disassembly of viral nucleoprotein complexes during early events after virus entry. C1 Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, JF816,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI36186] NR 70 TC 59 Z9 61 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 11055 EP 11066 DI 10.1128/JVI.74.23.11055-11066.2000 PG 12 WC Virology SC Virology GA 461LM UT WOS:000170365800021 PM 11070000 ER PT J AU Wang, XZ Zeng, W Murakawa, M Freeman, MW Seed, B AF Wang, XZ Zeng, W Murakawa, M Freeman, MW Seed, B TI Episomal segregation of the adenovirus enhancer sequence by conditional genome rearrangement abrogates late viral gene expression SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTIONAL CONTROL REGION; HEPATIC CONTROL REGION; CRE-MEDIATED EXCISION; EPSTEIN-BARR VIRUS; RECOMBINANT ADENOVIRUSES; MAMMALIAN-CELLS; IN-VITRO; EFFICIENT GENERATION; STABLE REPLICATION; CODING SEQUENCES AB We have constructed a recombinant adenovirus gene delivery system that is capable of undergoing growth phase-dependent site-specific recombination. When propagated in 293 producer cells, the vector retains its linear double-stranded form and can be propagated to high titer and purified by conventional procedures. Upon introduction into target cells, the viral chromosome undergoes cyclization to generate an autonomously replicating circular episome and a detached linear fragment. The viral enhancer and reporter gene segregate with the circular episome, which contains no adenovirus open reading frames. The effect of rearrangement of adenovirus gene expression was assessed by quantitative reverse transcription-PCR measurement of the abundance of transcripts encoding the tripartite leader sequence (TPL) of the major late promoter. Whereas nonrearranging viruses produced approximately 10(4) TPL transcripts per 10(6) infecting genomes in the HepG2 liver cell line, no transcripts were detectable in the same cells infected with comparable levels of circularizing vector. Because no helper virus is required to propagate these vectors, the problems of recombination with and contamination by helper virus are eliminated. We also present an efficient and reliable method for generating recombinant adenoviruses. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nessel Gene Therapy Ctr, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 9, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL45098, HL53694, R01 HL045098]; NIAID NIH HHS [F32 AI10059, F32 AI010059] NR 51 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 23 BP 11296 EP 11303 DI 10.1128/JVI.74.23.11296-11303.2000 PG 8 WC Virology SC Virology GA 461LM UT WOS:000170365800050 PM 11070029 ER PT J AU Mo, CJ Schneeberger, EE Arvin, AM AF Mo, CJ Schneeberger, EE Arvin, AM TI Glycoprotein e of varicella-zoster virus enhances cell-cell contact in polarized epithelial cells SO JOURNAL OF VIROLOGY LA English DT Article ID TRANS-GOLGI NETWORK; HERPES-SIMPLEX VIRUS; HUMAN CYTOMEGALOVIRUS GLYCOPROTEIN; ADHESION MOLECULE UVOMORULIN; CANINE KIDNEY-CELLS; TIGHT JUNCTION; E-CADHERIN; PSEUDORABIES VIRUS; CYTOPLASMIC TAIL; FC RECEPTOR AB Varicella-zoster virus (VZV) infection involves the cell-cell spread of virions, but how viral proteins interact with the host cell membranes that comprise intercellular junctions is not known. Madin-Darby canine kidney (MDCK) cells were constructed to express the glycoproteins gE, gl, or gE/gI constitutively and were used to examine the effects of these VZV glycoproteins in polarized epithelial cells. At low cell density, VZV gE induced partial tight junction (TJ) formation under low-calcium conditions, whether expressed alone or with gl. Although most VZV gE was intracellular, gE was also shown to colocalize with the TJ protein ZO-1 with or without concomitant expression of gI. Freeze fracture electron microscopy revealed normal TJ strand morphology in gE-expressing MDCK cells. Functionally, the expression of gE was associated with a marked acceleration in the establishment of maximum transepithelial electrical resistance (TER) in MDCK-gE cells; MDCK-gl and MDCK-gE/gI cells exhibited a similar pattern of early TER compared to MDCK cells, although peak resistances were lower than those of gE alone. VZV gE expression altered F-actin organization and lipid distribution, but coexpression of gI modulated these effects. Two regions of the gE ectodomain, amino acids (aa) 278 to 355 and aa 467 to 498, although lacking Ca2+ binding motifs, exhibit similarities with corresponding regions of the cell adhesion molecules, E-cadherin and desmocollin. These observations suggest that VZV gE and gE/gI may contribute to viral pathogenesis by facilitating epithelial cell-cell contacts. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mo, CJ (reprint author), Stanford Univ, Sch Med, Dept Pediat, 300 Pasteur Dr, Stanford, CA 94305 USA. FU NIAID NIH HHS [R01 AI020459, AI20459] NR 59 TC 29 Z9 31 U1 1 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 DEC PY 2000 VL 74 IS 23 BP 11377 EP 11387 DI 10.1128/JVI.74.23.11377-11387.2000 PG 11 WC Virology SC Virology GA 461LM UT WOS:000170365800059 PM 11070038 ER PT J AU Ye, YJ Si, ZH Moore, JP Sodroski, J AF Ye, YJ Si, ZH Moore, JP Sodroski, J TI Association of structural changes in the V2 and V3 loops of the gp120 envelope glycoprotein with acquisition of neutralization resistance in a simian-human immunodeficiency virus passaged in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID GP41 TRANSMEMBRANE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; PERSISTENT INFECTION; RECEPTOR-BINDING; VARIABLE LOOP; IN-VIVO; TYPE-1; HIV-1; MACAQUES; SENSITIVITY AB The in vivo passage of a neutralization-sensitive, laboratory-adapted simian-human immunodeficiency virus (SHIV-HXBc2) generated a pathogenic, neutralization-resistant virus, SHIV-HXBc2P 3.2. SHIV-HXBc2P 3.2 differs from SHIV-HXBc2 only in 13 amino acid residues of the viral envelope glycoproteins. Here we used antibody competition analysis to examine the structural changes that occurred in the SHIV-HXBc2P 3.2 gp120 exterior envelope glycoprotein. The relationships among the antibody epitopes on the conserved gp120 core of SHIV-HXBc2 and SHIV-HXBc2P 3.2 were similar. The third variable (V3) loop was more closely associated with the fourth conserved (C4) region and CD4-induced epitopes on the gp120 core in the HXBc2P 3.2 gp120 glycoprotein compared with the HXBc2 gp120 glycoprotein. Rearrangements of the second variable (V2) loop with respect to the CD4 binding site and associated epitopes were evident in comparisons of the two gp120 glycoproteins. Thus, the in vivo evolution of a neutralization-resistant virus involves conformational adjustments of the V2 and V3 variable loops with respect to the conserved receptor-binding regions of the gp120 core. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31783, AI36082, AI39420, R01 AI031783, R01 AI039420, R37 AI036082] NR 38 TC 53 Z9 54 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 DEC PY 2000 VL 74 IS 24 BP 11955 EP 11962 DI 10.1128/JVI.74.24.11955-11962.2000 PG 8 WC Virology SC Virology GA 461LN UT WOS:000170365900059 PM 11090196 ER PT J AU Cayabyab, M Hinuma, S Farzan, M Choe, H Fukusumi, S Kitada, C Nishizawa, N Hosoya, M Nishimura, O Messele, T Pollakis, G Goudsmit, J Fujino, M Sodroski, J AF Cayabyab, M Hinuma, S Farzan, M Choe, H Fukusumi, S Kitada, C Nishizawa, N Hosoya, M Nishimura, O Messele, T Pollakis, G Goudsmit, J Fujino, M Sodroski, J TI Apelin, the natural ligand of the orphan seven-transmembrane receptor APJ, inhibits human immunodeficiency virus type 1 entry SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTORS; HIV-1 ENTRY; 7-TRANSMEMBRANE RECEPTOR; FUSION COFACTOR; CO-RECEPTORS; CCR5; CORECEPTOR; INFECTION; BRAIN; AIDS AB In addition to the CCR5 and CXCR4 chemokine receptors, a subset of primary human immunodeficiency virus type I (HIV-1) isolates can also use the seven-transmembrane-domain receptor APJ as a coreceptor. A previously identified ligand of APJ, apelin, specifically inhibited the entry of primary T-tropic and dualtropic HIV-1 isolates from different clades into cells expressing CD4 and APJ. Analysis of apelin analogues demonstrated that potent and specific antiviral activity was retained by a 13-residue, arginine-rich peptide. Antiviral potency was influenced by the integrity of methionine 75, which contributes to APJ-binding affinity, and by the retention of apelin residues 63 to 65. These studies demonstrate the ability of a small peptide ligand to block the function of APJ as an HIV-1 coreceptor, identify apelin sequences important for the inhibition, and provide new reagents for the investigation of the significance of APJ to HIV-1 infection and pathogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Beth Israel Hosp, Dept Med & Pediat, Boston, MA 02115 USA. Takeda Chem Ind Ltd, Pharmaceut Discovery Res Div, Tsukuba, Ibaraki 3004293, Japan. Ethiopian Hlth & Nutr Res Inst, Addis Ababa, Ethiopia. Univ Amsterdam, Acad Med Ctr, Fac Med, Dept Human Retrovirol, NL-1105 AZ Amsterdam, Netherlands. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI041851, AI24755, AI41851, R37 AI024755] NR 43 TC 58 Z9 60 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2000 VL 74 IS 24 BP 11972 EP 11976 DI 10.1128/JVI.74.24.11972-11976.2000 PG 5 WC Virology SC Virology GA 461LN UT WOS:000170365900062 PM 11090199 ER PT J AU Saliba, D Orlando, M Wenger, NS Hays, RD Rubenstein, LZ AF Saliba, D Orlando, M Wenger, NS Hays, RD Rubenstein, LZ TI Identifying a short functional disability screen for older persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID INSTRUMENTAL ACTIVITIES; HIERARCHICAL STRUCTURE; HEALTH-STATUS; SELF-REPORT; ADL; POPULATIONS; DIFFICULTY; MORTALITY; ADULTS; SCALE AB Background. Disability in instrumental activities of daily living (IADLs) or activities of daily living (ADLs) is an indicator of health risk. The inclusion of these items in population screens may be limited by variation in item performance across gender and rife groups. Further, identification of shortened lists may encourage inclusion of these items in screens. Methods. We applied item response theory (IRT) methods to assess the responses of 9865 community-dwelling elders in the 1993 Medicare Current Beneficiary Survey to 11 IADL/ADL items. Items were classified as "receive help/ not receive help" for the overall population and stratified by age and gender. We assessed the same IADL/ADL items using responses classified as "difficulty/no difficulty." After eliminating items that performed poorly, we performed all subsets analyses to identify abbreviated sets of items that would select the highest proportion of persons with IADL/ ADL disability. Results. Responses classified in receive help format showed consistency by gender and age group. Changing the responsive classification to difficulty/no difficulty influenced the reported order and relationship of IADL/ADL items. Receipt of help for any one of five items-shopping, doing light housework? walking, bathing, or managing finances-identified 93% of individuals receiving help with any IADL/ADL. A slightly different set of five items-walking, shopping, transferring, doing light housework, or bathing-identified 91% of persons reporting difficulty with any IADL or ADL. Conclusions. The relationship of IADL and ADL items to the underlying construct of disability was similar for men and women. The relationship was also similar for oldest-old and younger-old individuals. This study also identified abbreviated lists of disability items that can be used to efficiently screen community-dwelling elders for the presence of IADL/ADL disability. C1 RAND Corp, Santa Monica, CA USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Multicampus Program Geriatr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RP Saliba, D (reprint author), RAND Corp, 1700 Main St, Santa Monica, CA USA. RI Hays, Ronald/D-5629-2013 FU NIA NIH HHS [AG10415] NR 33 TC 56 Z9 57 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2000 VL 55 IS 12 BP M750 EP M756 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 390MH UT WOS:000166299600014 PM 11129398 ER PT J AU Shimizu, A Yamada, K Sachs, DH Colvin, RB AF Shimizu, A Yamada, K Sachs, DH Colvin, RB TI Intragraft events preceding chronic renal allograft rejection in a modified tolerance protocol SO KIDNEY INTERNATIONAL LA English DT Article DE apoptosis; anti-MHC class I antibody; transplantation; cytotoxic T cell; kidney rejection prediction; parenchymal cells; major histocompatibility complex; xenograft model ID TRANSPLANTED MOUSE HEARTS; MAJOR HISTOCOMPATIBILITY COMPLEX; CELL-MEDIATED CYTOTOXICITY; MINIATURE SWINE; CLASS-I; CORONARY ATHEROSCLEROSIS; T-CELL; KIDNEY ALLOGRAFTS; STABLE INDUCTION; NUCLEAR-DNA AB Background Inbred miniature st-vine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half developed chronic rejection (progression group) and the other half recovered (recovery group). This provides an excellent experimental model to identify the mechanisms of chronic rejection as well as the early changes that may predict chronic rejection. Methods. We assessed the cellular infiltration, immune activation, humoral immunity, and cell- and antibody-mediated graft injury in the progression and the recovery groups. In addition, we also examined circulating donor reactive cytotoxic T lymphocyte (CTL) and antidonor antibody in both groups. Results. From days 8 to 18 after transplantation, the two groups were indistinguishable. Both showed acute rejection with endarteritis (type II); had IgG and IgM deposition in glomeruli and small vessels; had an infiltrate with similar numbers of T cells, proliferating (PCNA+) and activated (interleukin-2 receptor +) cells; and had a similar degree of parenchymal cell apoptosis [in situ DNA nick-end labeling (TUNEL)+]. However, by days 30 to 60, the two groups could be distinguished by several intragraft features. The recovery group became tolerant and had diminished T-cell infiltration, activation and proliferation, and no detectable antibody deposition. The number of TUNEL+-injured parenchymal cells decreased. In contrast, the progression group showed persistent cell infiltration with activation and proliferation. Significantly prominent TUNEL+ apoptotic parenchymal cells in tubules, glomeruli, peritubular capillaries and arteries were seen from day 30 to day 100. Circulating donor reactive CTL and antidonor class I IgG were detected in the progression group at higher levels than in the recovery group from days 30 to 60. Conclusion. In tolerance-induction protocols, unstable tolerance induction is associated with the persistent immunologic activation that mediates immunologic destruction of graft parenchymal cells and chronic rejection. Certain of the described immunopathologic findings (activation, proliferation, apoptosis, and antibody deposition) may be useful in distinguishing the type of rejection, that is, whether the allograft will progress to chronic rejection or recovery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Boston, MA 02114 USA. Nippon Med Sch, Dept Pathol, Tokyo 113, Japan. RP Colvin, RB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Pathol, Warren 225, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01HL18646]; NIAID NIH HHS [R01AI31046]; PHS HHS [P01H218646] NR 50 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2000 VL 58 IS 6 BP 2546 EP 2558 DI 10.1046/j.1523-1755.2000.00440.x PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 379WA UT WOS:000165665100031 PM 11115090 ER PT J AU Arnaout, MA Madias, NE Harrington, JT Perrone, RD King, AJ Levey, AS AF Arnaout, MA Madias, NE Harrington, JT Perrone, RD King, AJ Levey, AS TI The vasculopathy of autosomal dominant polycystic kidney disease: Insights from animal models SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE PKD1 and PKD2 genes; polycystin; intracranial aneurysms; cystogenesis ID LEFT-VENTRICULAR MASS; OF-FUNCTION MODEL; CARDIOVASCULAR-ABNORMALITIES; INTRACRANIAL ANEURYSMS; GENE-PRODUCT; PKD1 GENE; TUBEROUS SCLEROSIS; SEQUENCE-ANALYSIS; MOUSE HOMOLOG; CYSTIC TISSUE C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [P01DK54711] NR 100 TC 11 Z9 13 U1 2 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2000 VL 58 IS 6 BP 2599 EP 2610 DI 10.1046/j.1523-1755.2000.00446.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 379WA UT WOS:000165665100043 PM 11115102 ER PT J AU Urba, SG Wolf, GT Bradford, CR Thornton, AF Eisbruch, A Terrell, JE Carpenter, V Miller, T Tang, G Strawderman, M AF Urba, SG Wolf, GT Bradford, CR Thornton, AF Eisbruch, A Terrell, JE Carpenter, V Miller, T Tang, G Strawderman, M TI Neoadjuvant therapy for organ preservation in head and neck cancer SO LARYNGOSCOPE LA English DT Article DE head and neck neoplasms; organ preservation; chemotherapy; radiation therapy ID ADVANCED RESECTABLE HEAD; INDUCTION CHEMOTHERAPY; ONCOLOGY-GROUP; CIS-PLATINUM; 5-FLUOROURACIL; RADIATION; CARCINOMA; TRIAL AB Objectives/Hypothesis: We designed two sequential trials of induction chemotherapy followed by definitive radiation in patients with potentially resectable head and neck cancer to determine whether organ preservation is feasible without apparent compromise of survival. Study Design: Both trials were Phase II studies. Methods: Two clinical trials were conducted sequentially at the University of Michigan, Fifty-two patients enrolled in the first study and were treated with a planned three cycles of carboplatin and 5-fluorouracil, Patients who achieved at least 50% reduction in the size of the primary tumor received definitive radiation therapy, to a dose of 6600 to 1380 cGy. Patients with minimal response or progression had immediate salvage surgery. Thirty-seven patients enrolled in the second trial, in which the chemotherapy consisted of carboplatin, 5-fluororuracil, and leukovorin, Responders were treated with accelerated radiation therapy to a total dose of 7120 cGy delivered in 41 fractions over 5.5 weeks. Results: Toxicity and response were similar in both trials; therefore, the results are reported first separately and then combined for all 89 patients. Tumor sites included: oropharynx, 55 patients; hypopharynx, 34 patients. Eighty-three percent of patients tolerated all three cycles of chemotherapy and toxicity was mild. Response to chemotherapy was: 48% complete response at the primary tumor site, and 34% partial response at the primary tumor site. initial organ preservation at individual tumor sites was: oropharynx, 58% hypopharynx, 59%. Median survival was 28 months, and Survival at 3 and 5 years was 40% and 24%, respectively, Conclusions: These two regimens were well tolerated, and survival did not appear to be compromised by organ preservation treatment compared with historical controls, This approach warrants further investigation, particularly in those patients for whom surgery could be functionally debilitating. C1 Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Dept Otolaryngol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Dept Radiat Therapy, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Comprehens Canc, Dept Biostat, Ann Arbor, MI 48109 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Urba, SG (reprint author), Univ Michigan, Med Ctr, Canc Ctr 1366, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [P30 CA-46592] NR 14 TC 30 Z9 31 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 DEC PY 2000 VL 110 IS 12 BP 2074 EP 2080 DI 10.1097/00005537-200012000-00019 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 382ZE UT WOS:000165856600019 PM 11129024 ER PT J AU Silverman, LB Declerck, L Gelber, RD Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Lipton, JM Cohen, HJ Sallan, SE AF Silverman, LB Declerck, L Gelber, RD Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Lipton, JM Cohen, HJ Sallan, SE TI Results of Dana-Farber Cancer Institute Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995) SO LEUKEMIA LA English DT Article DE acute lymphoblastic leukemia; childhood; asparaginase; doxorubicin ID PEDIATRIC-ONCOLOGY-GROUP; ACUTE LYMPHOCYTIC-LEUKEMIA; BERLIN-FRANKFURT-MUNSTER; ACUTE MYELOID-LEUKEMIA; INTRATHECAL METHOTREXATE; COMBINATION CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; INTENSIVE ASPARAGINASE; CRANIAL RADIATION; EARLY RESPONSE AB The Dana-Farber Cancer Institute (DFCI) ALL consortium has been conducting clinical trials in childhood acute lymphoblastic leukemia (ALL) since 1981. The treatment backbone has included intensive, multi-agent remission induction, early intensification with weekly, high-dose asparaginase, cranial radiation for the majority of patients, frequent vincristine/corticosteroid pulses during post-remission therapy, and for high-risk patients, doxorubicin during intensification. Between 1981 and 1995, 1255 children with newly diagnosed ALL were evaluated on four consecutive protocols: 81-01 (1981-1985), 85-01 (1985-1987), 87-01 (1987-1991) and 91-01 (1991-1995). The 5-year event-free survival (EFS) rates (+/- standard error) for all patients by protocol were as follows: 74 +/- 3% (81-01), 78 +/- 3% (85-01), 77 +/- 2% (87-01) and 83 +/- 2% (91-01). The B-year EFS rates ranged from 78 to 85% for patients with B-progenitor phenotype retrospectively classified as NCI standard-risk, 63-82% for NCI high-risk B-progenitor patients, and 70-79% for patients with T cell phenotype. Results of randomized studies revealed that neither high-dose methotrexate during induction (protocol 87-01) nor high-dose g-mercaptopurine during intensification (protocol 91-01) were associated with improvement in EFS compared with standard doses. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Dept Hematol Oncol, Rochester, NY 14627 USA. McMaster Univ, Dept Pediat, Hamilton, ON, Canada. San Jorge Childrens Hosp, San Juan, PR 00912 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Maine Childrens Canc Program, Portland, ME 04102 USA. Hosp Ste Justine, Montreal, PQ, Canada. CHU Laval, Laval, PQ, Canada. Oschner Med Inst, Dept Pediat, New Orleans, LA USA. Schneider Childrens Hosp, New Hyde Park, NY USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 06516, CA 68484] NR 46 TC 117 Z9 124 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2000 VL 14 IS 12 BP 2247 EP 2256 DI 10.1038/sj.leu.2401980 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 388WX UT WOS:000166207000030 PM 11187916 ER PT J AU Akashi, K Mizuno, S AF Akashi, K Mizuno, S TI Epstein-Barr virus-infected natural killer cell leukemia SO LEUKEMIA & LYMPHOMA LA English DT Review DE EBV; NK cells; NK cell leukemia; hemophagocytic lymphohistiocytosis ID GRANULAR LYMPHOCYTE LEUKEMIA; SEVERE COMBINED IMMUNODEFICIENCY; RESCUES T-LYMPHOPOIESIS; RECEPTOR-GAMMA CHAIN; INTERFERON-GAMMA; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; LYMPHOPROLIFERATIVE DISEASE; BONE-MARROW; PROLIFERATIVE DISORDERS; MEMBRANE-PROTEIN AB Natural killer cell leukemia (NK leukemia) is an aggressive form of lymphoproliferative disease of granular lymphocytes, and frequently complicates fulminant hemophagocytic lymphohistiocytosis. NK leukemia cells usually possess a single episomal form of Epstein-Barr virus (EBV), and therefore originate from a single EBV-infected NK cell. The NK leukemia cells lack endogenous Bcl-2 expression and are sensitive to apoptotic cell death. However, they constitutively produce interferon-gamma and maintain their survival in an autocrine fashion. The interferon-gamma released from NK leukemia cells may trigger the occurrence of hemophagocytic lymphohistiocytosis through activating macrophages/histiocytes. In the primary infection of EBV, T cells infected with the episomal form of EBV sometimes produce a high amount of interferon-gamma that may lead to the occurrence of hemophagocytic lymphohistiocytosis. Thus, it is important to determine the role of EBV in the increased production of interferon-gamma that occurs in EBV-infected T and NK cells to clarify the developmental mechanism of NK leukemia and its paraneoplastic hemophagocytic lymphohistiocytosis. C1 Stanford Univ, Sch Med, Dept Pathol, Beckman Ctr, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Dev Biol, Beckman Ctr, Stanford, CA 94305 USA. Kyushu Univ, Fac Med, Dept Internal Med 1, Higashi Ku, Fukuoka 8128582, Japan. RP Akashi, K (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. NR 45 TC 21 Z9 23 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 2000 VL 40 IS 1-2 BP 57 EP + DI 10.3109/10428190009054881 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 395NC UT WOS:000166585600005 PM 11426629 ER PT J AU Kim, SW Ibrahim, JG AF Kim, SW Ibrahim, JG TI On Bayesian inference for proportional hazards models using noninformative priors SO LIFETIME DATA ANALYSIS LA English DT Article DE extreme-value model; improper prior; Weibull model; uniform prior ID GENERALIZED LINEAR-MODELS AB In this article, we investigate the properties of the posterior distribution under the uniform improper prior for two commonly used proportional hazards models; the Weibull regression model and the extreme value regression model. We allow the observations to be right censored. We obtain sufficient conditions for the existence of the posterior moment generating function of the regression coefficients. A dataset involving a lung cancer clinical trial and a simulation are presented to illustrate our results. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kim, SW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 18 TC 8 Z9 9 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD DEC PY 2000 VL 6 IS 4 BP 331 EP 341 DI 10.1023/A:1026505331236 PG 11 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 382EK UT WOS:000165809900003 PM 11190603 ER PT J AU Lipinski, B Lipinska, I AF Lipinski, B Lipinska, I TI Effect of magnesium on fibrin formation from lower molecular weight (LMW) fibrinogen SO MAGNESIUM RESEARCH LA English DT Article DE hemostasis; magnesium; LMW fibrinogen; thrombin clotting time; electrophoresis AB Fibrinogen circulating in human blood is comprised of high molecular weight (HMW) and lower molecular weight [LMW] fractions. As previously documented by means of SDS-polyacrylamide gel electrophoresis (PAGE), LMW fraction was significantly increased in patients with cardiovascular disease and with diabetes mellitus [DM). We have recently observed that the values of fibrinogen measured by thrombin clotting time (the method of Clauss) were consistently lower in EDTA plasma than those obtained with citrated plasma. However, supplementation of EDTA plasma with magnesium (Mg) ions gave comparable results. In this study we documented by SDS-PAGE that fibrin formed with thrombin alone in EDTA plasma originated from HMW fibrinogen, whereas that formed after addition of Mg was derived from LMW fibrinogen. Thus, measurement of thrombin clotting time in EDTA plasma with and without Mg may serve asa quick method for the determination of HMW and LMW fibrinogens in human blood. Preliminary result obtained with this new method revealed that LMW fibrinogen tvas significantly increased in DM patients. We have therefore concluded that measurement of this fraction of fibrinogen may prove to be of clinical diagnostic significance. C1 Joslin Diabet Ctr, Dept Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. RP Lipinski, B (reprint author), Joslin Diabet Ctr, Dept Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. NR 12 TC 7 Z9 7 U1 1 U2 1 PU JOHN LIBBEY & CO LTD PI LONDON PA 13 SMITHS YARD, SUMMERLEY ST, LONDON SW18 4HR, ENGLAND SN 0953-1424 J9 MAGNESIUM RES JI Magnes. Res. PD DEC PY 2000 VL 13 IS 4 BP 233 EP 237 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 389MB UT WOS:000166240800002 PM 11153893 ER PT J AU Donovan, J Temel, J Zuckerman, A Gribben, J Fang, JJ Pierson, G Ross, A Diller, L Grupp, SA AF Donovan, J Temel, J Zuckerman, A Gribben, J Fang, JJ Pierson, G Ross, A Diller, L Grupp, SA TI CD34 selection as a stem cell purging strategy for neuroblastoma: Preclinical and clinical studies SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on Advances in Neuroblastoma Research CY MAY 15-18, 2000 CL PHILADELPHIA, PENNSYLVANIA DE pediatric; CD34 selection; stem cell transplant; neuroblastoma ID AUTOLOGOUS BONE-MARROW; TERM FOLLOW-UP; PERIPHERAL-BLOOD; TRANSPLANTATION; CHEMOTHERAPY; EXPRESSION AB Background. The suitability of CD34 selection for purging peripheral blood progenitor cells (PBPC) collected from patients with neuroblastoma (NB) has been called into question, largely because of reports of detection of low levels of CD34 on the surface of some NE cell lines and tumors. Procedure. We used three approaches to address the issue of purging of NE from stem cell specimens and possible labeling of NE: 1) Flow cytometric detection of CD34 on NE cell lines. We assessed CD34 expression using a panel of anti-CD34 monoclonal antibodies (MoAbs) including 9C5, 12.8, and QBend10 and showed no increase in labeling over secondary-only control. 2) Spiking experiments with the Isolex 50 system. NE cell lines were used to contaminate aliquots of PBPC collections, after which the products were purified using the Isolex 50. Purging of NE was assessed by quantitative multiplex RT-PCR (TaqMan system) using a tumor-specific transcript, CAGE. We demonstrated >2 logs of tu- mor cell depletion from these specimens. 3) Analysis of clinical specimens. PBPC pre- and post-CD34 selection were analyzed from patients treated on the CHP-594 transplant trial. Results. In nine specimens selected using the Ceprate LC CD34 selection system where tumor was detectable by immunocytochemistry preselection, we observed >2.4 to >4.6 logs of NE purging after selection. We then analyzed 23 aliquots of PBPC infused into patients post-CD34 selection and compared them to the product preselection; 20/23 specimens showed depletion of NE, although some level of GAGE message was observed in most post-CD34 selection specimens. Conclusion. These data show that purging of NE from PBPC specimens using CD34 selection is feasible, yielding infused products that are negative at the level of ICC but often positive at the level of RT-PCR. (C) 2000 Wiley-Liss, Inc. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Nexell Therapeut Inc, Div Diagnost, Irvine, CA USA. RP Grupp, SA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, 3516 Civic Ctr Blvd,Abramson 902, Philadelphia, PA 19104 USA. NR 19 TC 23 Z9 26 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD DEC PY 2000 VL 35 IS 6 BP 677 EP 682 DI 10.1002/1096-911X(20001201)35:6<677::AID-MPO42>3.0.CO;2-H PG 6 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 379PM UT WOS:000165651700042 PM 11107145 ER PT J AU Grupp, SA Stern, JW Bunin, N Nancarrow, C Adams, R Gorlin, JB Griffin, G Diller, L AF Grupp, SA Stern, JW Bunin, N Nancarrow, C Adams, R Gorlin, JB Griffin, G Diller, L TI Rapid-sequence tandem transplant for children with high-risk neuroblastoma SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT Conference on Advances in Neuroblastoma Research CY MAY 15-18, 2000 CL PHILADELPHIA, PENNSYLVANIA DE pediatric; tandem transplant; CD34 selection; stem cell transplant; neuroblastoma ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; STEM-CELL RESCUE; PEDIATRIC-PATIENTS; BREAST-CANCER; ENGRAFTMENT; THERAPY; BLOOD AB Background. The majority of patients with high risk neuroblastoma (NB) still relapse. Procedure. We designed a Phase Il trial for children with advanced NE utilizing a program of induction chemotherapy followed by tandem high-dose chemoradiotherapy with stem cell rescue (HDC/SCR) in rapid sequence. Fifty-five patients were evaluable, ages 1-14 years, and 97 cycles of HDC/SCR have been completed to date. Pheresis was possible far every patient, despite their young age, with an average of 7.2 x 10(6) CD34+ cells/kg available to support each HDC/SCR cycle. Results. Engraftment was rapid, with median time to neutrophil engraftment of 11 days. Five patients who completed the first HDC course did not complete the second and there were four toxic deaths. With a median follow-up of 24 months from diagnosis, 38 of 55 patients (3-year EFS 59%) remain event-free. A subset of the patients received stem cells purged by CD34 selection. The engraftment and EFS of these patients are similar to the overall group. Conclusion. This work demonstrates that a tandem transplant regimen for high-risk NE is a feasible treatment strategy in children and may improve disease-free survival. (C) 2000 Wiley-Liss, Inc. C1 Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, Philadelphia, PA 19104 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Primary Childrens Hosp, Salt Lake City, UT USA. Univ Minnesota, Minneapolis, MN USA. Mem Blood Ctr Minnesota, Minneapolis, MN USA. AI Dupont Hosp, Dept Pediat, Wilmington, DE USA. RP Grupp, SA (reprint author), Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat,Div Oncol, 324 S 34th St,Abramson 902, Philadelphia, PA 19104 USA. NR 20 TC 20 Z9 21 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD DEC PY 2000 VL 35 IS 6 BP 696 EP 700 DI 10.1002/1096-911X(20001201)35:6<696::AID-MPO46>3.0.CO;2-0 PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 379PM UT WOS:000165651700046 PM 11107149 ER PT J AU Desai, S Lim, SD Jimenez, RE Chun, T Keane, TE McKenney, JK Zavala-Pompa, A Cohen, C Young, RH Amin, MB AF Desai, S Lim, SD Jimenez, RE Chun, T Keane, TE McKenney, JK Zavala-Pompa, A Cohen, C Young, RH Amin, MB TI Relationship of cytokeratin 20 and CD44 protein expression with WHO/ISUP grade in pTa and pT1 papillary urothelial neoplasia SO MODERN PATHOLOGY LA English DT Article DE urinary bladder; papillary neoplasia; transitional cell carcinoma; WHO/ISUP classification; pathologic stage; CK20; CD44; prognosis ID TRANSITIONAL-CELL-CARCINOMA; GROWTH-FACTOR RECEPTOR; HUMAN URINARY-BLADDER; BREAST-CANCER CELLS; ADHESION MOLECULE; BIOLOGIC IMPLICATIONS; GENE-EXPRESSION; FOLLOW-UP; RECURRENCE; MARKER AB The aim of this study was to assess the relationship of immunoreactivity of cytokeratin 20 (CK20) and CD44 across the spectrum of urothelial neoplasia using the WHO/ISUP consensus classification A total of 120 papillary urothelial pTa and pTl tumors (8 papillomas, 8 neoplasms of low malignant potential, and 42 low-grade and 62 high-grade carcinomas) were immunostained by using CK20 and CD44 antibodies. The relationships of tumor grade, pathologic stage, recurrences, and progression In stage with CK20 and CD44 immunoreactivity were assessed, WHO/ISUP grade correlated with tumor stage (P < 0.005), recurrence (P = 0.02), and progression in stage (P = 0.031). Normal urothelium showed CK20 immunoreactivity restricted to a few umbrella cells. Expression of CD44 in normal urothelium was restricted to the basal cell layer. Loss of CD44 immunoreactivity and increasing CK20 positivity were significantly associated with increasing tumor grade and stage (P < 0.005). An inverse relationship was observed in the staining patterns of CK20 and CD44 within individual cases, as wed as In the aggregate data, with 79.2% of tumors with CD44 loss showing CK20 positivity (P < 0.001). In conclusion, CK20 and CD44 immunoreactivity are significantly related to the WHO/ISUP grade and to each other, and our data suggest their potential combined utility in predicting biologic behavior In patients with papillary urothelial pTa and pTl neoplasms. C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Urol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Amin, MB (reprint author), Emory Univ Hosp, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 49 TC 78 Z9 84 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2000 VL 13 IS 12 BP 1315 EP 1323 DI 10.1038/modpathol.3880241 PG 9 WC Pathology SC Pathology GA 387RJ UT WOS:000166135400008 PM 11144928 ER PT J AU Lamb, J Ladha, MH McMahon, C Sutherland, RL Ewen, ME AF Lamb, J Ladha, MH McMahon, C Sutherland, RL Ewen, ME TI Regulation of the functional interaction between cyclin D1 and the estrogen receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOUSE MAMMARY-GLAND; HUMAN BREAST-CANCER; RECONSTITUTED BASEMENT-MEMBRANE; DEPENDENT PROTEIN-KINASE; AMP BINDING-PROTEINS; CELL-CYCLE; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVITY; ADENYLATE-CYCLASE; TRANSGENIC MICE AB We report that the functional interaction between cyclin D1 and the estrogen receptor (ER) is regulated by a signal transduction pathway involving the second messenger, cyclic AMP (cAMP). The cell-permeable cAMP analogue 8-bromo-cAMP caused a concentration-dependent enhancement of cyclin DI-ER complex formation, as judged both by coimmunoprecipitation and mammalian two-hybrid analysis. This effect was paralleled by increases in ligand-independent ER-mediated transcription from an estrogen response element containing reporter construct. These effects of 8-bromo-cAMP were antagonized by a specific protein kinase A (PKA) inhibitor, indicating that the signaling pathway involved was PKA dependent. Further, we show that culture of MCF-7 cells on a cellular substratum of murine preadipocytes also enhanced the functional interaction between cyclin D1 and ER in a PKA-dependent manner. These findings demonstrate a collaboration between cAMP signaling and cyclin D1 in the ligand-independent activation of ER-mediated transcription in mammary epithelial cells and show that the functional associations of cyclin D1 are regulated as a function of cellular context. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia. RP Ewen, ME (reprint author), Dana Farber Canc Inst, D728,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA080111, P01 CA80111] NR 82 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 DEC PY 2000 VL 20 IS 23 BP 8667 EP 8675 DI 10.1128/MCB.20.23.8667-8675.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000004 PM 11073968 ER PT J AU Miyake, S Sellers, WR Safran, M Li, XT Zhao, WQ Grossman, SR Gan, JM DeCaprio, JA Adams, PD Kaelin, WG AF Miyake, S Sellers, WR Safran, M Li, XT Zhao, WQ Grossman, SR Gan, JM DeCaprio, JA Adams, PD Kaelin, WG TI Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTIONAL COACTIVATORS P300; UBIQUITIN-PROTEASOME PATHWAY; ADENOVIRAL ONCOPROTEIN E1A; RUBINSTEIN-TAYBI SYNDROME; SKELETAL-MUSCLE CELLS; TUMOR-SUPPRESSOR P53; HISTONE ACETYLTRANSFERASE; GLUCOCORTICOID RECEPTOR; GROWTH SUPPRESSION AB Control of proliferation and differentiation by the retinoblastoma tumor suppressor protein (pRB) and related family members depends upon their interactions with key cellular substrates. Efforts to identify such cellular targets led to the isolation of a novel protein, EID-1 (for E1A-like inhibitor of differentiation 1). Here, we show that EID-1 is a potent inhibitor of differentiation and link this activity to its ability to inhibit p300 land the highly related molecule, CREB-binding protein, or CBP) histone acetylation activity. EID-1 is rapidly degraded by the proteasome as cells exit the cell cycle. Ubiquitination of EID-1 requires an intact C-terminal region that is also necessary for stable binding to p300 and pRB, two proteins that bind to the ubiquitin ligase MDM2. A pRB variant that can bind to EID1, but not MDM2, stabilizes EID-1 in cells. Thus, EID-1 may act at a nodal point that couples cell cycle exit to the transcriptional activation of genes required for differentiation. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Fox Chase Canc Ctr, Dept Mol Oncol, Philadelphia, PA 19111 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 77 TC 80 Z9 83 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 DEC PY 2000 VL 20 IS 23 BP 8889 EP 8902 DI 10.1128/MCB.20.23.8889-8902.2000 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000025 PM 11073989 ER PT J AU Nakamura, N Ramaswamy, S Vazquez, F Signoretti, S Loda, M Sellers, WR AF Nakamura, N Ramaswamy, S Vazquez, F Signoretti, S Loda, M Sellers, WR TI Forkhead transcription factors are critical effectors of cell death and cell cycle arrest downstream of PTEN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PTEN; PROTEIN-KINASE-B; SERINE-THREONINE KINASE; AGE-1 PI3 KINASE; CAENORHABDITIS-ELEGANS; SIGNALING PATHWAY; ALVEOLAR RHABDOMYOSARCOMA; PHOSPHATASE-ACTIVITY; PROSTATE-CANCER; NEGATIVE REGULATION AB PTEN acts as a tumor suppressor, at least in part, by antagonizing phosphoinositide 3-kinase (PI3K)/Akt signaling. Here we show that Forkhead transcription factors FKHRL1 and FKHR, substrates of the Akt kinase, are aberrantly localized to the cytoplasm and cannot activate transcription in PTEN-deficient cells. Restoration of PTEN function restores FKHR to the nucleus and restores transcriptional activation. Expression of a constitutively active form of FKHR that cannot be phosphorylated by Akt produces the same effect as reconstitution of PTEN on PTEN-deficient tumor cells. Specifically, activated FKHR induces apoptosis in cells that undergo PTEN-mediated cell death and induces G(1) arrest in cells that undergo PTEN-mediated cell cycle arrest. Furthermore, both PTEN and constitutively active FKHR induce p27(KIP1) protein but not p21. These data suggest that Forkhead transcription factors are critical effecters of PTEN-mediated tumor suppression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Adult Oncol, 44 Binney St,D720C, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA085912, R01CA85912] NR 75 TC 408 Z9 418 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2000 VL 20 IS 23 BP 8969 EP 8982 DI 10.1128/MCB.20.23.8969-8982.2000 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000032 PM 11073996 ER PT J AU Kenney, AM Rowitch, DH AF Kenney, AM Rowitch, DH TI Sonic hedgehog promotes G(1) cyclin expression and sustained cell cycle progression in mammalian neuronal precursors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; CEREBELLAR GRANULE CELLS; EPIDERMAL GROWTH-FACTOR; KINESIN-RELATED PROTEIN; SIGNALING PATHWAY; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; HUMAN HOMOLOG; REGULATES PROLIFERATION; TRANSCRIPTION FACTOR AB Sonic hedgehog (Shh) signal transduction via the G-protein-coupled receptor, Smoothened, is required for proliferation of cerebellar granule neuron precursors (CGNPs) during development. Activating mutations in the Hedgehog pathway are also implicated in basal cell carcinoma and medulloblastoma, a tumor of the cerebellum in humans. However, Shh signaling interactions with cell cycle regulatory components in neural precursors are poorly understood, in part because appropriate immortalized cell lines are not available. We have utilized primary cultures from neonatal mouse cerebella in order to determine (i) whether Shh initiates or maintains cell cycle progression in CGNPs, (ii) if G(1) regulation by Shh resembles that of classical mitogens, and (iii) whether individual D-type cyclins are essential components of Shh proliferative signaling in CGNPs. Our results indicate that Shh can drive continued cycling in immature, proliferating CGNPs. Shh treatment resulted in sustained activity of the G(1) cyclin-Rb axis by regulating levels of cyclinD1, cyclinD2, and cyclinE mRNA transcripts and proteins. Analysis of CGNPs from cyclinD1(-/-) or cyclinD2(-/-) mice demonstrates that the Shh proliferative pathway does not require unique functions of cyclinD1 or cyclinD2 and that D-type cyclins overlap functionally in this regard. In contrast to many known mitogenic pathways, we show that Shh proliferative signaling is mitogen-activated protein kinase independent. Furthermore, protein synthesis is required for early effects on cyclin gene expression. Together, our results suggest that Shh proliferative signaling promotes synthesis of regulatory factor intermediates that upregulate or maintain cyclin gene expression and activity of the G(1) cyclin-Rb axis in proliferating granule neuron precursors. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 640D,44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD01182] NR 95 TC 342 Z9 353 U1 0 U2 8 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 DEC PY 2000 VL 20 IS 23 BP 9055 EP 9067 DI 10.1128/MCB.20.23.9055-9067.2000 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UD UT WOS:000168366000039 PM 11074003 ER PT J AU McBride, AE Weiss, VH Soriano, MA Filman, DJ Hogle, JM Silver, PA AF McBride, AE Weiss, VH Soriano, MA Filman, DJ Hogle, JM Silver, PA TI Molecular dissection of the role of the major arginine methyltransferase in nuclear transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 2 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 DEC PY 2000 VL 11 SU S MA 92 BP 18A EP 18A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900093 ER PT J AU Hanada, T Asaba, N Lin, LH Tibaldi, EV Reinherd, EL Chishti, AH AF Hanada, T Asaba, N Lin, LH Tibaldi, EV Reinherd, EL Chishti, AH TI GAKIN: A novel kinesin-like protein associates with the guanylate kinase domain of hDLG and PSD-95 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Tufts Univ, St Elizabeths Med Ctr, Boston, MA 02135 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, 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 DEC PY 2000 VL 11 SU S MA 410 BP 78A EP 79A PG 2 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900410 ER PT J AU Boucher, Y Jain, RK Burton, K AF Boucher, Y Jain, RK Burton, K TI Traction forces and rates of migration in several cancer cell lines SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 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 DEC PY 2000 VL 11 SU S MA 439 BP 84A EP 84A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900440 ER PT J AU Parng, C Piepenhagen, PA Casanova, J Pillai, S AF Parng, C Piepenhagen, PA Casanova, J Pillai, S TI TOB3, a novel AAA-ATPase, is involved in protein transport. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Univ Virginia, Charlottesville, VA 22903 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 DEC PY 2000 VL 11 SU S MA 694 BP 134A EP 134A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900696 ER PT J AU Gillespie, PG Holt, JR Shokat, KM Mercer, JA AF Gillespie, PG Holt, JR Shokat, KM Mercer, JA TI Design of myosin mutants to provide specific inhibition SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA. McLaughlin Res Inst, Great Falls, MT 59405 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 DEC PY 2000 VL 11 SU S MA 852 BP 164A EP 164A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525900856 ER PT J AU Raitt, DC Posas, F Saito, H AF Raitt, DC Posas, F Saito, H TI The role of SHO1, STE20 and CDC42 in activation of the yeast HOG1 MAP kinase in response to osmotic stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 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 DEC PY 2000 VL 11 SU S MA 1279 BP 246A EP 246A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901283 ER PT J AU Wu, SL Mikhailov, AV Hara, K Yonezawa, K Avruch, J AF Wu, SL Mikhailov, AV Hara, K Yonezawa, K Avruch, J TI Identification and characterization of a new mTOR interacting protein, ubiquilin 1. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kobe Univ, Biosignal Res Ctr, Kobe, Hyogo 657, Japan. 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 DEC PY 2000 VL 11 SU S MA 1290 BP 248A EP 248A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901294 ER PT J AU Partovian, C Murakami, M Li, J Horowitz, A Simons, M AF Partovian, C Murakami, M Li, J Horowitz, A Simons, M TI Basic fibroblast growth factor and vascular endothelial growth factor induce nitric oxide release via distinctly different signaling pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Angiogenesis Res Ctr, BIDMC, Boston, MA 02215 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 DEC PY 2000 VL 11 SU S MA 1295 BP 249A EP 249A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901299 ER PT J AU Aballay, A Ausubel, FM AF Aballay, A Ausubel, FM TI Salmonella typhimurium infection induces program cell death in Caenorhabditis elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 DEC PY 2000 VL 11 SU S MA 1324 BP 254A EP 254A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901328 ER PT J AU Deans, MR Li, TS Goodenough, DA Paul, DL AF Deans, MR Li, TS Goodenough, DA Paul, DL TI Connexin36 gene expression and retinal function in Connexin36 knockout mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, 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 DEC PY 2000 VL 11 SU S MA 1438 BP 276A EP 276A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901442 ER PT J AU Sheng, MH Lee, SH Lin, JW Naisbitt, S Passafaro, M Sala, C AF Sheng, MH Lee, SH Lin, JW Naisbitt, S Passafaro, M Sala, C TI Molecular dynamics of the postsynaptic specialization SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RI Sala, Carlo/A-2493-2009 OI Sala, Carlo/0000-0003-0662-9523 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 DEC PY 2000 VL 11 SU S MA 1476 BP 283A EP 283A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901480 ER PT J AU Toomre, DK Keller, P Diaz, E White, J Simons, K AF Toomre, DK Keller, P Diaz, E White, J Simons, K TI Dynamics of post-Golgi sorting in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. Massachusetts Gen Hosp, Ctr Canc, 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 DEC PY 2000 VL 11 SU S MA 1656 BP 319A EP 319A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901660 ER PT J AU Kang, JX Zan, Y AF Kang, JX Zan, Y TI Mechanisms of apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 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 DEC PY 2000 VL 11 SU S MA 1798 BP 347A EP 347A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525901802 ER PT J AU Liao, YF Gotwals, PJ Koteliansky, VE Sheppard, D Van de Water, L AF Liao, YF Gotwals, PJ Koteliansky, VE Sheppard, D Van de Water, L TI The EIIIA (ED-A) segment of fibronectin is a novel ligand for integrins alpha 4 beta 1 and alpha 9 beta 1 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 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 DEC PY 2000 VL 11 SU S MA 2044 BP 394A EP 394A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902048 ER PT J AU Thomas, SM Hagel, M Tamimi, R George, B Turner, C AF Thomas, SM Hagel, M Tamimi, R George, B Turner, C TI Cytoskeletal adaptor proteins in development SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Med & Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. SUNY Syracuse, Syracuse, NY 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 DEC PY 2000 VL 11 SU S MA 2230 BP 429A EP 429A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902234 ER PT J AU Dai, Y Kysela, B Manolis, K Harville, T Jeggo, PA Oettinger, MA AF Dai, Y Kysela, B Manolis, K Harville, T Jeggo, PA Oettinger, MA TI Defective V(D)J recombination and double strand break repair in a patient with severe combined immunodeficiency SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Sussex, Brighton BN1 9RH, E Sussex, England. 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 DEC PY 2000 VL 11 SU S MA 2280 BP 439A EP 439A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902284 ER PT J AU Wiederhold, T James, MF Hull, N Smith, N Gusella, JF Ramesh, V AF Wiederhold, T James, MF Hull, N Smith, N Gusella, JF Ramesh, V TI Isolation and characterization of a novel interactor for merlin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 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 DEC PY 2000 VL 11 SU S MA 2386 BP 459A EP 459A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902390 ER PT J AU Yu, WH Woessner, JF Stamenkovic, I AF Yu, WH Woessner, JF Stamenkovic, I TI A glycosaminoglycan-modified CD44v3-containing isoform mediates surface localization of MMP-7 and facilitates processing of proHB-EGF. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Univ Miami, Sch Med, Coral Gables, FL 33124 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 DEC PY 2000 VL 11 SU S MA 2476 BP 478A EP 478A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902480 ER PT J AU Fathallah, DM Bebbiche, N Zerria, K Barbouche, RM Arnaout, AM Dellagi, KM AF Fathallah, DM Bebbiche, N Zerria, K Barbouche, RM Arnaout, AM Dellagi, KM TI The rat ICAM-1 (CD54) soluble recombinant domains 1 and 3 interact with cell surface LFA-1 and recombinant CD11b A-domain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Inst Pasteur, Tunis 1002, Tunisia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 DEC PY 2000 VL 11 SU S MA 2515 BP 486A EP 486A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902519 ER PT J AU Criss, AK Ahlgren, DM Jou, TS McCormick, BA Casanova, JE AF Criss, AK Ahlgren, DM Jou, TS McCormick, BA Casanova, JE TI The GTPase Rac1 selectively regulates Salmonella invasion at the apical plasma membrane of polarized epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Charlottesville, VA 22908 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. 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 DEC PY 2000 VL 11 SU S MA 2536 BP 490A EP 490A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902540 ER PT J AU Blackstone, CD Roberts, RG Seeburg, DP Sheng, MH AF Blackstone, CD Roberts, RG Seeburg, DP Sheng, MH TI Targeting of the dynamin-like GTPase DVLP by the mitochondrial deafness-dystonia protein DDP/TIM8a SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Guys Hosp, London SE1 9RT, England. RI Roberts, Roland/C-3596-2009 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 DEC PY 2000 VL 11 SU S MA 2749 BP 531A EP 531A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902753 ER PT J AU Seeburg, DP Roberts, RG Star, K Blackstone, CD Sheng, MH AF Seeburg, DP Roberts, RG Star, K Blackstone, CD Sheng, MH TI Interaction of the signal transducing adaptor molecule STAM1 with the mitochondrial deafness-dystonia protein DDP/TIM8a SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. Guys Hosp, London SE1 9RT, England. Harvard Univ, Sch Med, Boston, MA 02114 USA. RI Roberts, Roland/C-3596-2009 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 DEC PY 2000 VL 11 SU S MA 2748 BP 531A EP 531A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902752 ER PT J AU Schuyler, SC Liu, JY Morphew, M Pellman, DS AF Schuyler, SC Liu, JY Morphew, M Pellman, DS TI Ase1p is a dynamic mitotic crossbridge essential for the slow phase of anaphase B SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Boulder Lab 3D Fine Struct, Boulder, CO 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 DEC PY 2000 VL 11 SU S MA 2932 BP 567A EP 567A PG 1 WC Cell Biology SC Cell Biology GA 377QY UT WOS:000165525902936 ER PT J AU Zuber, C Spiro, MJ Guhl, B Spiro, RG Roth, J AF Zuber, C Spiro, MJ Guhl, B Spiro, RG Roth, J TI Golgi apparatus immunolocalization of endomannosidase suggests post-endoplasmic reticulum glucose trimming: Implications for quality control SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; GLC-GLYCOPROTEIN GLUCOSYLTRANSFERASE; ULTRATHIN FROZEN-SECTIONS; RAT-LIVER GOLGI; SECRETORY PATHWAY; INTERMEDIATE COMPARTMENT; PROCESSING ENZYME; SACCHAROMYCES-CEREVISIAE; LIVING CELLS AB Trimming of N-linked oligosaccharides by endoplasmic reticulum (ER) glucosidase II is implicated in quality control of protein folding. An alternate glucosidase II-independent deglucosylation pathway exists, in which endo-ar-mannosidase cleaves internally the glucose-substituted mannose residue of oligosaccharides. By immunogold labeling, we detected most endomannosidase in cis/medial Golgi cisternae (83.8% of immunogold labeling) and less in the intermediate compartment (15.1%), but none in the trans-Golgi apparatus and ER, including its transitional elements. This dual localization became more pronounced under 15 degreesC conditions indicative of two endomannosidase locations. Under experimental conditions when the intermediate compartment marker p58 was retained in peripheral sites, endomannosidase was redistributed to the Golgi apparatus. Double immunogold labeling established a mutually exclusive distribution of endomannosidase and glucosidase II, whereas calreticulin was observed in endomannosidase-reactive sites (17.3% in intermediate compartment, 5.7% in Golgi apparatus) in addition to the ER (77%). Our results demonstrate that glucose trimming of N-linked oligosaccharides is not Limited to the ER and that protein deglucosylation by endomannosidase in the Golgi apparatus and intermediate compartment additionally ensures that processing to mature oligosaccharides can continue. Thus, endomannosidase localization suggests that a quality control of N-glycosylation exists in the Golgi apparatus. C1 Univ Zurich, Div Cell & Mol Pathol, Dept Pathol, CH-8091 Zurich, Switzerland. Harvard Med Sch, Dept Biol Chem, Boston, MA 02215 USA. Harvard Med Sch, Dept Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Roth, J (reprint author), Univ Zurich, Div Cell & Mol Pathol, Dept Pathol, CH-8091 Zurich, Switzerland. FU NIDDK NIH HHS [DK17477] NR 77 TC 67 Z9 67 U1 0 U2 3 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 DEC PY 2000 VL 11 IS 12 BP 4227 EP 4240 PG 14 WC Cell Biology SC Cell Biology GA 384PX UT WOS:000165955000014 PM 11102520 ER PT J AU Lindsten, T Ross, AJ King, A Zong, WX Rathmell, JC Shiels, HA Ulrich, E Waymire, KG Mahar, P Frauwirth, K Chen, YF Wei, M Eng, VM Adelman, DM Simon, MC Ma, A Golden, JA Evan, G Korsmeyer, SJ MacGregor, GR Thompson, CB AF Lindsten, T Ross, AJ King, A Zong, WX Rathmell, JC Shiels, HA Ulrich, E Waymire, KG Mahar, P Frauwirth, K Chen, YF Wei, M Eng, VM Adelman, DM Simon, MC Ma, A Golden, JA Evan, G Korsmeyer, SJ MacGregor, GR Thompson, CB TI The combined functions of proapoptotic Bcl-2 family members Bak and Bax are essential for normal development of multiple tissues SO MOLECULAR CELL LA English DT Article ID PROGRAMMED CELL-DEATH; CYTOCHROME-C; DEFICIENT MICE; THYMOCYTE APOPTOSIS; BRAIN-DEVELOPMENT; PROTEIN FAMILY; HOMOLOG BAK; IN-VIVO; MITOCHONDRIA; RELEASE AB Proapoptotic Bcl-2 family members have been proposed to play a central role in regulating apoptosis. However, mice lacking bax display limited phenotypic abnormalities. As presented here, bak(-/-) mice were found to be developmentally normal and reproductively fit and failed to develop any age-related disorders. However, when Bak-deficient mice were mated to Bax-deficient mice to create mice lacking both genes, the majority of bax(-/-)bak(-/-) animals died perinatally with fewer than 10% surviving into adulthood. bax(-/-)bak(-/-) mice displayed multiple developmental defects, including persistence of interdigital webs, an imperforate vaginal canal, and accumulation of excess cells within both the central nervous and hematopoietic systems. Thus, Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis. C1 Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Grad Program Biochem Cell & Dev Biol, Atlanta, GA 30322 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Calif San Francisco, Ctr Canc, Inst Canc Res, San Francisco, CA 94143 USA. Emory Univ, Sch Med, Ctr Mol Med, Atlanta, GA USA. Univ Penn, Univ Lab Anim Resources, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. RP Thompson, CB (reprint author), Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. FU NICHD NIH HHS [R01 HD036437-02, R01 HD036437-03, R01 HD036437-04] NR 47 TC 890 Z9 914 U1 3 U2 39 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 2000 VL 6 IS 6 BP 1389 EP 1399 DI 10.1016/S1097-2765(00)00136-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 389LN UT WOS:000166239500011 PM 11163212 ER PT J AU Zhou, YL Sun, HP Danila, DC Johnson, SR Sigai, DP Zhang, X Klibanski, A AF Zhou, YL Sun, HP Danila, DC Johnson, SR Sigai, DP Zhang, X Klibanski, A TI Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; DEPENDENT TRANSCRIPTION; PITUITARY-ADENOMAS; CELL-GROWTH; EXPRESSION; KINASE; DIFFERENTIATION; COMPLEX; PROTEIN AB Activin, a member of the transforming growth factor beta (TGF beta) superfamily of cytokines, inhibits cell proliferation in a variety of cell types. The functions of activin are mediated by type I and type II serine/threonine kinase receptors. The main type I receptor mediating activin signaling in human cells is ActRIB, also called Alk4. We have previously reported that several truncated AIk4 receptor isoforms are exclusively expressed in human pituitary tumors, and that the majority of such tumors did not exhibit activin-induced growth arrest in culture. We therefore studied the function of these truncated receptor isoforms. Transient expression of these truncated receptors inhibited activin-activated transcription from an activin-responsive reporter construct, 3TPLux. When each of these truncated Alk4 receptors was stably transfected into K562 cells, activin-induced expression of an endogenous gene, junB, was blocked, indicating that inhibition of gene expression also occurred at the chromosomal level. Furthermore, activin administration failed to cause growth inhibition and an increase of the G(1) population in these cells. Coimmunoprecipitation experiments showed that the truncated Alk4 receptors formed complexes with type II activin receptors, but were not phosphorylated. These data indicate that the truncated activin type I receptors, predominantly expressed in human pituitary adenomas, function as dominant negative receptors to interfere with wild-type receptor function and block the antiproliferative effect of activin. This may contribute to uncontrolled pituitary cell growth and the development of human pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01-DK-40947] NR 30 TC 38 Z9 38 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 DEC PY 2000 VL 14 IS 12 BP 2066 EP 2075 DI 10.1210/me.14.12.2066 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 378DK UT WOS:000165569600015 PM 11117535 ER PT J AU Li, YZ Li, CJ Yu, DH Pardee, AB AF Li, YZ Li, CJ Yu, DH Pardee, AB TI Potent induction of apoptosis by beta-lapachone in human multiple myeloma cell lines and patient cells SO MOLECULAR MEDICINE LA English DT Article ID TOPOISOMERASE-I; SURVIVAL; INHIBITION; EXPRESSION; TOXICITY; BCL-2 AB Background: Human multiple myeloma (MM) remains an incurable hematological malignancy. We have reported that beta -lapachone, a pure compound derived from a plant, can induce cell death in a variety of human carcinoma cells, including ovary, colon, lung, prostate, pancreas, and breast, suggesting a wide spectrum of anticancer activity. Materials and Methods: We first studied anti-survival effects of beta -lapachone in human MM cells by colony formation assay. To determine whether the differential inhibition of colony formation occurs through antiproliferative activity, we performed MTT assays. The cytotoxicity of beta -lapachone on human peripheral blood mononuclear cells was also measured by MTT assay. To determine whether the cell death induced by beta -lapachone occurs through necrosis or apoptosis, we used the propidium iodide staining procedure to determine the sub-G1 fraction, Annexin-V staining for externalization of phosphatidylserine, and fragmentation of cellular genomic DNA subjected to gel electrophoresis. To investigate the mechanism of anti-MM activity, we examined Bcl-2 expression, cytochrome C release, and poly(ADP ribose) polymerase cleavage by Western blot assay. Results: We found that beta -lapachone (less than 4 muM) inhibits cell survival and proliferation by triggering cell death with characteristics of apoptosis in ARH-77, HS Sultan, and MM.1S cell lines, in freshly derived patient MM cells (MM.As), MM cell lines resistant to dexamethasone (MM.1R), doxorubicin (DOX.40), mitoxantrone (MR.20), and mephalan (LR5). Importantly, after treatment with beta -lapachone, we observed no apoptosis in peripheral blood mononuclear cells in either quiescent or proliferative states, freshly isolated from healthy donors. In beta -lapachone treated ARH-77, cytochrome C was released from mitochondria to cytosol, and poly (ADP ribose) polymerase was cleaved, signature events of apoptosis. Finally, the apoptosis induced by beta -lapachone in MM cells was not blocked by either interleukin-6 or Bcl-2, which confer multidrug resistance in MM. Conclusions: Our results suggest potential therapeutic application of beta -lapachone against MM, particularly to overcome drug resistance in relapsed patients. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Li, YZ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA61253] NR 24 TC 43 Z9 45 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 2000 VL 6 IS 12 BP 1008 EP 1015 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 392MT UT WOS:000166415800002 PM 11474117 ER PT J AU Hillman, LJ Burns, SP Kraft, GH AF Hillman, LJ Burns, SP Kraft, GH TI Neurological worsening due to infection from renal stones in a multiple sclerosis patient SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; complications; neurogenic bladder; quadriplegic; infection ID URINARY-TRACT DYSFUNCTION; VESICOURETHRAL DYSFUNCTION; URODYNAMIC FINDINGS; BLADDER; ABNORMALITIES AB Symptomatic bladder dysfunction occurs in the majority of patients with multiple sclerosis (MS). Although guidelines have been established for diagnosis and management of bladder dysfunction in these patients, they are sometimes overlooked in the primary core setting, leading to severe, life threatening complications. A 64-year-old mole with a 31-year history of spastic quadriparetic MS and neurogenic bladder dysfunction managed with on indwelling catheter, presented to the hospital with worsening neurological function. He had developed increased weakness and cognitive impairment several weeks after being treated for a urinary trace infection (UTI). He hod become unable to perform any activities of daily living or drive his power wheelchair. After on extensive work-up, he was found to have a large (14 x 18 x 30 cm) retroperitoneal abscess and multiple renal stones, including a large obstructing calculus in the collecting system near the ureteropelvic junction, end he underwent nephrectomy end abscess drainage. Of note, he had been found to have multiple renal stones end hydronephrosis on renal ultrasound 3 years earlier, but he had received no treatment Following drainage of the abscess, his upper extremity neurological function returned to baseline, his cognitive status improved and he regained the ability to perform activities of daily living. Patients with paralysis from MS, much like those with traumatic spinel cord injuries, are at grave risk of mortality and morbidity from undiagnosed and under-treated urinary complications. This case demonstrates that evaluation end appropriate treatment for complications of neurogenic bladder should be part of routine care for patients with MS. Current recommendations for evaluation and management of bladder dysfunction in patients with MS will be reviewed. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Hillman, LJ (reprint author), Iowa Orthoped Ctr, 411 Laurel St,Ste 3300, Des Moines, IA 50314 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD DEC PY 2000 VL 6 IS 6 BP 403 EP 406 DI 10.1191/135245800701566395 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 393GK UT WOS:000166460700008 PM 11212137 ER PT J AU Wu, LZ Aster, JC Blacklow, SC Lake, R Artavanis-Tsakonas, S Griffin, JD AF Wu, LZ Aster, JC Blacklow, SC Lake, R Artavanis-Tsakonas, S Griffin, JD TI MAML1, a human homologue of Drosophila Mastermind, is a transcriptional co-activator for NOTCH receptors SO NATURE GENETICS LA English DT Article ID NEUROGENIC LOCUS MASTERMIND; CREB BINDING-PROTEIN; SIGNAL-TRANSDUCTION; PATHWAY; LOCALIZATION; MELANOGASTER; REGULATOR; COMPLEX; DOMAIN; DELTEX AB Notch receptors are involved in cell-fate determination in organisms as diverse as flies, frogs and humans'. In Drosophila melanogaster, loss-of-function mutations of Notch produce a 'neurogenic' phenotype in which cells destined to become epidermis switch fate and differentiate to neural cells. Upon ligand activation, the intracellular domain of Notch (ICN) translocates to the nucleus', and interacts directly with the DNA-binding protein Suppressor of hairless (Su(H)) in flies, or recombination signal binding protein J kappa (RBP-J kappa) in mammals(3), to activate gene transcription(4). But the precise mechanisms of Notch-induced gene expression are not completely understood. The gene mastermind has been identified in multiple genetic screens for modifiers of Notch mutations in Drosophila(5-8). Here we clone MAML1, a human homologue of the Drosophila gene Mastermind, and show that it encodes a protein of 130 kD localizing to nuclear bodies. MAML1 binds to the ankyrin repeat domain of all four mammalian NOTCH receptors, forms a DNA-binding complex with ICN and RBP-J kappa and amplifies NOTCH-induced transcription of HES1. These studies provide a molecular mechanism to explain the genetic links between mastermind and Notch in Drosophila and indicate that MAML1 functions as a transcriptional co-activator for NOTCH signalling. 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, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA82308, CA09362]; NHLBI NIH HHS [HL61001] NR 28 TC 354 Z9 370 U1 2 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2000 VL 26 IS 4 BP 484 EP 489 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 379YX UT WOS:000165671700026 PM 11101851 ER PT J AU Holler, N Zaru, R Micheau, O Thome, M Attinger, A Valitutti, S Bodmer, JL Schneider, P Seed, B Tschopp, J AF Holler, N Zaru, R Micheau, O Thome, M Attinger, A Valitutti, S Bodmer, JL Schneider, P Seed, B Tschopp, J TI Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule SO NATURE IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; T-CELLS; APOPTOSIS; ACTIVATION; PROTEIN; DOMAIN; LYMPHOCYTES; INHIBITION; INITIATION AB Cell death is achieved by two fundamentally different mechanisms: apoptosis and necrosis,Apoptosis is dependent on caspase activation, whereas the caspase-independent necrotic signaling pathway remains largely uncharacterized. We show here that Pas kills activated primary T cells efficiently in the absence of active caspases, which results in necrotic morphological changes and late mitochondrial damage but no cytochrome c release,This Pas ligand-induced caspase-independent death is absent in T cells that are deficient in either Fas-associated death domain (FADD) or receptor-interacting protein (RIP), RIP is also required for necrotic death induced by tumor necrosis factor (INF) and TNF-related apoptosis-inducing ligand (TRAIL), In contrast to its role in nuclear factor kappaB activation, RIP requires its own kinase activity for death signaling. Thus, pas, TRAIL and TNF receptors can initiate cell death by two alternative pathways, one relying on caspase-8 and the other dependent on the kinase RIP. C1 Univ Lausanne, Inst Biochem, BIL Biomed Res Ctr, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Tschopp, J (reprint author), Univ Lausanne, Inst Biochem, BIL Biomed Res Ctr, Chemin des Boveresses, CH-1066 Epalinges, Switzerland. RI Thome, Margot/F-8167-2011; Micheau, Olivier/C-3574-2011; Valitutti, Salvatore/M-2999-2014 OI Thome, Margot/0000-0002-5656-2139; Micheau, Olivier/0000-0001-8499-7984; NR 37 TC 780 Z9 815 U1 3 U2 32 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2000 VL 1 IS 6 BP 489 EP 495 DI 10.1038/82732 PG 7 WC Immunology SC Immunology GA 380VR UT WOS:000165724600012 PM 11101870 ER PT J AU Kung, AL Wang, S Klco, JM Kaelin, WG Livingston, DM AF Kung, AL Wang, S Klco, JM Kaelin, WG Livingston, DM TI Suppression of tumor growth through disruption of hypoxia-inducible transcription SO NATURE MEDICINE LA English DT Article ID BINDING-PROTEIN; FACTOR 1-ALPHA; SOLID TUMORS; TRANSACTIVATION; ANGIOGENESIS; HIF-1-ALPHA; ACTIVATION; P300/CBP; CELLS; STABILIZATION AB Chronic hypoxia, a hallmark of many tumors, is associated with angiogenesis and tumor progression. Strategies to treat tumors have been developed in which tumor cells are targeted with drugs or gene-therapy vectors specifically activated under hypoxic conditions. Here we report a different approach, in which the normal transcriptional response to hypoxia is selectively disrupted. Our data indicate that specific blockade of the interaction of hypoxia-inducible factor with the CH1 domain of its p300 and CREB binding protein transcriptional coactivators leads to attenuation of hypoxia-inducible gene expression and diminution of tumor growth. Thus, disrupting the normal co-activational response to hypoxia may be a new and useful therapeutic strategy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. OI Kung, Andrew/0000-0002-9091-488X; Klco, Jeffery/0000-0003-2961-6960 NR 44 TC 395 Z9 412 U1 2 U2 14 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 DEC PY 2000 VL 6 IS 12 BP 1335 EP 1340 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 380LV UT WOS:000165704100036 PM 11100117 ER PT J AU Liu, Y Jones, M Hingtgen, CM Bu, GJ Laribee, N Tanzi, RE Moir, RD Nath, A He, JJ AF Liu, Y Jones, M Hingtgen, CM Bu, GJ Laribee, N Tanzi, RE Moir, RD Nath, A He, JJ TI Uptake of HIV-1 Tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BETA-AMYLOID PRECURSOR; LONG TERMINAL REPEAT; ALZHEIMER-DISEASE; INFECTION; EXPRESSION; APOPTOSIS; CELLS; ASTROCYTES; ACTIVATION AB Neurological disorders develop in most people infected with human immunodeficiency virus type 1 (HIV-1). However, the underlying mechanisms remain largely unknown. Here we report that binding of HIV-1 transactivator (Tat) protein to low-density lipoprotein receptor-related protein (LRP) promoted efficient uptake of Tat into neurons. LRP-mediated uptake of Tat was followed by translocation to the neuronal nucleus. Furthermore, the binding of Tat to LRP resulted in substantial inhibition of neuronal binding, uptake and degradation of physiological ligands for LRP, including alpha (2)-macroglobulin, apolipoprotein E4, amyloid precursor protein and amyloid beta -protein. In a model of macaques infected with a chimeric strain of simian-human immunodeficiency virus, increased staining of amyloid precursor protein was associated with Tat expression in the brains of simian-human immunodeficiency virus-infected macaques with encephalitis. These results indicate that HIV-1 Tat may mediate HIV-1-induced neuropathology through a pathway involving disruption of the metabolic balance of LRP ligands and direct activation of neuronal genes. C1 Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Neurol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Immunol, Lexington, KY 40536 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Walther Canc Inst, Indianapolis, IN 46206 USA. RP He, JJ (reprint author), Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. OI Laribee, R. Nicholas/0000-0003-4519-4470 FU NINDS NIH HHS [NS39253] NR 46 TC 246 Z9 251 U1 2 U2 9 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 DEC PY 2000 VL 6 IS 12 BP 1380 EP 1387 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 380LV UT WOS:000165704100043 PM 11100124 ER PT J AU Lin, JW Ju, W Foster, K Lee, SH Ahmadian, G Wyszynski, M Wang, YT Sheng, M AF Lin, JW Ju, W Foster, K Lee, SH Ahmadian, G Wyszynski, M Wang, YT Sheng, M TI Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptors internalization SO NATURE NEUROSCIENCE LA English DT Article ID LONG-TERM DEPRESSION; DOMAIN-CONTAINING PROTEIN; GLUTAMATE RECEPTORS; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS; INTERACTING PROTEIN; SURFACE EXPRESSION; MEMBRANE-FUSION; GLUR1 SUBUNIT; C-TERMINUS AB Internalization of postsynaptic AMPA receptors depresses excitatory transmission, but the underlying dynamics and mechanisms of this process are unclear. Using immunofluorescence and surface biotinylation, we characterized and quantified basal and regulated AMPA receptor endocytosis in cultured hippocampal neurons, in response to synaptic activity, AMPA and insulin. AMPA-induced AMPA receptor internalization is mediated in part by secondary activation of voltage-dependent calcium channels, and in part by ligand binding independent of receptor activation. Although both require dynamin, insulin- and AMPA-induced AMPA receptor internalization are differentially dependent on protein phosphatases and sequence determinants within the cytoplasmic tails of GluR1 and GluR2 subunits. AMPA receptors internalized in response to AMPA stimulation enter a recycling endosome system, whereas those internalized in response to insulin diverge into a distinct compartment. Thus, the molecular mechanisms and intracellular sorting of AMPA receptors are diverse, and depend on the internalizing stimulus. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Hosp Sick Children, Programme Brain & Behav, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1X8, Canada. RP Lin, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. RI Wang, Yu Tian/A-4729-2008; Wang, Yu Tian/J-8255-2015 OI Wang, Yu Tian/0000-0001-8592-0698 FU NINDS NIH HHS [NS35050] NR 50 TC 355 Z9 370 U1 0 U2 11 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2000 VL 3 IS 12 BP 1282 EP 1290 DI 10.1038/81814 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 405UA UT WOS:000167177900014 PM 11100149 ER PT J AU Weiss, VH McBride, AE Soriano, MA Filman, DJ Silver, PA Hogle, JM AF Weiss, VH McBride, AE Soriano, MA Filman, DJ Silver, PA Hogle, JM TI The structure and oligomerization of the yeast arginine methyltransferase, Hmt1 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID N-METHYLTRANSFERASE; RECOGNITION MOTIF; PROTEIN; RECEPTOR; IDENTIFICATION; METHYLATION; GRAPHICS; BINDING; DOMAIN; PRMT1 AB Protein methylation at arginines is ubiquitous in eukaryotes and affects signal transduction. gene expression and protein sorting. Hmt1/Rmt1, the major arginine methyltransferase in yeast, catalyzes methylation of arginine residues in several mRNA-binding proteins and facilitates their export from the nucleus. We now report the crystal structure of Hmt1 at 2.9 Angstrom resolution. Hmt1 forms a hexamer with approximate 32 symmetry. The surface of the oligomer is dominated by large acidic cavities at the dimer interfaces. Mutation of dimer contact sites eliminates activity of Hmt1 both in vivo and in vitro. Mutating residues in the acidic cavity significantly reduces binding and methylation of the substrate Np13. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. RP Hogle, JM (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI020566] NR 26 TC 122 Z9 126 U1 1 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD DEC PY 2000 VL 7 IS 12 BP 1165 EP 1171 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 379YU UT WOS:000165671400022 PM 11101900 ER PT J AU Yano, N Endoh, M Fadden, KJ Yamashita, H Sakai, H Kurokawa, K Abboud, HE Rifai, A AF Yano, N Endoh, M Fadden, KJ Yamashita, H Sakai, H Kurokawa, K Abboud, HE Rifai, A TI Genomic repertoire of human mesangial cells: comprehensive analysis of gene expression by cDNA array hybridization SO NEPHROLOGY LA English DT Article DE cultured mesangial cell; gene expression; genomics; high-density DNA array; mouse orthologue ID PROLIFERATIVE GLOMERULONEPHRITIS; GLOMERULAR CELLS; IN-VITRO; FIBRONECTIN; MICROARRAY; PROTEIN; ALPHA-1(I); DEPOSITS; PATTERNS; HSP47 AB Knowing when and where a gene is expressed in a cell often provides a strong clue as to its physiological role. It is estimated the human genome contains 80 000-100 000 genes. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed experimental strategy to expand the scope of biological investigation from a single gene to studying all genes at once in a systematic way. Capitalizing on the recently developed methodology of cDNA array hybridization, we monitored the simultaneous expression of thousands of genes in primary human mesangial cells. Complex alpha-P-33-labelled cDNA probes were prepared from cultured mesangial cells. The probe was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Bioinformatics from public genomic databases was utilized to assign a chromosomal location of each expressed transcript. Approximately 7460 different gene transcripts were detected in mesangial cells. Close to 13% (957 genes) were full-length mRNA human transcripts (HTs), the remainder 6503 being expressed sequence tags (ESTs). Using special imaging computer software, the transcriptional level of the 957 HTs was compared with the expression of the ribosomal protein S28 (housekeeping gene). The HTs were also classified by function of the gene product and listed with information on their chromosomal loci. To allow comparison between clinical and experimental studies of gene expression, the detected human gene transcripts were cross-referenced to orthologous mouse genes. Thus, the presented data constitute a quantitative preliminary blueprint of the transcriptional map of the human mesangial cell. The information may serve as a resource for speeding up the discovery of genes underlying human glomerular diseases. The complete listing of the full-length expressed genes is available upon request via E-mail: (Abdalla_Rifai@Brown.edu). C1 Brown Univ, Rhode Isl Hosp, Dept Pathol, Providence, RI 02903 USA. Brown Univ, Sch Med, Providence, RI 02903 USA. Tokai Univ, Sch Med, Dept Internal Med, Div Nephrol & Metab, Kanagawa 2591100, Japan. Univ Texas, Hlth Sci Ctr, Dept Med, Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX 78284 USA. RP Rifai, A (reprint author), Brown Univ, Rhode Isl Hosp, Dept Pathol, 593 Eddy St, Providence, RI 02903 USA. NR 32 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD DEC PY 2000 VL 5 IS 4 BP 215 EP 223 DI 10.1046/j.1440-1797.2000.00008.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 400LW UT WOS:000166873900002 ER PT J AU Tortosa, A Ino, Y Odell, N Swilley, S Sasaki, H Louis, DN Henson, JW AF Tortosa, A Ino, Y Odell, N Swilley, S Sasaki, H Louis, DN Henson, JW TI Molecular genetics of radiographically defined de novo glioblastoma multiforme SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE CDKN2A; p16; de novo glioblastoma; EGFR; genetics; glioblastoma multiforme; p53; PTEN ID BRAIN-TUMOR SPECIMENS; P53 MUTATIONS; SECONDARY GLIOBLASTOMAS; P16 EXPRESSION; RB ALTERATIONS; EGF RECEPTOR; GLIOMAS; AMPLIFICATION; HISTOPATHOLOGY; OVEREXPRESSION AB Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM. C1 Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA. RI Tortosa, Avelina/O-7788-2016 OI Tortosa, Avelina/0000-0002-9080-2976 FU NCI NIH HHS [CA 57683] NR 27 TC 12 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD DEC PY 2000 VL 26 IS 6 BP 544 EP 552 DI 10.1046/j.0305-1846.2000.00290.x PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 384XL UT WOS:000165972500008 PM 11123721 ER PT J AU Dougherty, CM Spertus, JA Dewhurst, TA Nichol, WP AF Dougherty, CM Spertus, JA Dewhurst, TA Nichol, WP TI Outpatient nursing case management for cardiovascular disease SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID INTENSIVE CASE-MANAGEMENT; CORONARY-ARTERY DISEASE; HEALTH SURVEY; OUTCOMES; PRACTITIONER; VALIDITY; IMPACT; SYSTEM; CARE AB Case management has been an effective treatment model for maintaining costs while preserving quality of care for vulnerable populations who are frequent care users. Nursing case management has been effective in improving health outcomes in chronically ill populations. Specifically, nurse practitioner care has been as effective, and in some areas, more effective in managing chronic health problems of patients than care provided by physicians. Cardiovascular disease is a chronic condition, often accompanied by longterm symptoms and disability, that is prevalent in the United States population. Outpatient nursing case management for chronic health problems associated with cardiovascular disease is posited as a model for a heavily used system that maintains quality of care in this group. C1 Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Polyclin, Seattle, WA USA. Mid Amer Heart Inst, Kansas City, MO USA. RP Dougherty, CM (reprint author), Univ Washington, Sch Nursing, Box 357266, Seattle, WA 98195 USA. NR 36 TC 6 Z9 6 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 2000 VL 35 IS 4 BP 993 EP + PG 12 WC Nursing SC Nursing GA 382WA UT WOS:000165849300014 PM 11072284 ER PT J AU Ryan, DP AF Ryan, DP TI Rectal cancer: Integrating oxaliplatin into chemoradiation studies SO ONCOLOGY-NEW YORK LA English DT Article ID PREOPERATIVE INFUSIONAL CHEMORADIATION; PELVIC RADIATION-THERAPY; ADJUVANT THERAPY; DOSE LEUCOVORIN; CHEMOTHERAPY; FLUOROURACIL; CARCINOMA; ADENOCARCINOMA; IRRADIATION; SURGERY AB The current standard of care for patients,with stage T3 rectal cancer is adjuvant combined-modality treatment,with radiation and fluorouracil (5-FU)-based chemotherapy. Although data from randomized phase III trials comparing preoperative and postoperative combined-modality therapy are lacking, preoperative therapy is an option in T3 disease and cart be considered the standard of care for T4 disease, Given its effects in reducing systemic disease in stage IV rectal cancer and its potential for radio sensitization of target tumors, oxaliplatin (Eloxatin), a new cytotoxic agent from the diaminocyclohexane platinum family is being evaluated in preoperative combined-modality regimens in a Cancer and Leukemia Group B (CALGB) phase I/II study (protocol 89901) irt T4 disease and an Eastern Cooperative Group (ECOG)phase I study (E-1297) irt locally advanced T3 or T4 disease. C1 Massachusetts Gen Hosp, Ctr Canc, Gastrointestinal Canc Ctr, Dana Farber Partners Canc Care, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Gastrointestinal Canc Ctr, Dana Farber Partners Canc Care, 100 Blossom St COX640, Boston, MA 02114 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2000 VL 14 IS 12 SU 11 BP 38 EP 41 PG 4 WC Oncology SC Oncology GA 390DE UT WOS:000166279700007 PM 11204662 ER PT J AU Melki, SA Talamo, JH Demetriades, AM Jabbur, NS Essepian, JP O'Brien, TP Azar, DT AF Melki, SA Talamo, JH Demetriades, AM Jabbur, NS Essepian, JP O'Brien, TP Azar, DT TI Late traumatic dislocation of laser in situ keratomileusis corneal flags SO OPHTHALMOLOGY 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 LAMELLAR REFRACTIVE SURGERY; PHOTOREFRACTIVE KERATECTOMY; INSITU KERATOMILEUSIS; COMPLICATIONS; MANAGEMENT; LASIK; MYOPIA; CAP; EYE AB Purpose: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. Design: Retrospective, observational case series. Participants: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days-2 months) after the procedure. Intervention: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stroma[ bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. Main Outcome Measures: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. Results: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. Conclusions: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes. (C) 2000 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Cornea Consultants Boston, Boston, MA USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 24 TC 65 Z9 66 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2000 VL 107 IS 12 BP 2136 EP 2139 DI 10.1016/S0161-6420(00)00405-X PG 4 WC Ophthalmology SC Ophthalmology GA 378LY UT WOS:000165586900028 PM 11097584 ER PT J AU Weiss, EI Shaniztki, B Dotan, M Ganeshkumar, N Kolenbrander, PE Metzger, Z AF Weiss, EI Shaniztki, B Dotan, M Ganeshkumar, N Kolenbrander, PE Metzger, Z TI Attachment of Fusobacterium nucleatum PK1594 to mammalian cells and its coaggregation with periodontopathogenic bacteria are mediated by the same galactose-binding adhesin SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE coaggregation; attachment; oral bacteria; Fusobacterium nucleatum ID CAPNOCYTOPHAGA-OCHRACEA ATCC-33596; ORAL BACTERIA; POLYMORPHONUCLEAR LEUKOCYTES; PORPHYROMONAS-GINGIVALIS; ACTINOMYCES-NAESLUNDII; BACTEROIDES-GINGIVALIS; MONOCLONAL-ANTIBODIES; LECTIN; STRAINS; IDENTIFICATION AB It has been shown that Fusobacterium nucleatum PK1594 coaggregates with Prophyromonas gingivalis PK1924 through a galactose binding adhesin. In the present study, attachment of F. nucleatum PK1594 to a variety of mammalian cells was characterized. F. nucleatum PK1594 attached to all eukaryotic cells tested, including human buccal epithelial cells, gingival and periodontal ligament fibroblasts, HeLa cells and murine lymphocytes, macrophages, and polymorphonuclear leukocytes, These attachments were (i) inhibited by galactose, lactose and N-acetylgalactosamine and (ii) inhibited by monoclonal antibody specific for the galactose-binding adhesin of F. nucleatum PK1594. In addition, a coaggregation-defective mutant of F. nucleatum PK1594 (PK2172), which does not exhibit galactose binding activity, did not attach to the mammalian cells. Coaggregation of F. nucleatum PK1594 with P. gingivalis PK 1924 and Actinobacillus actinomycetemcomitans JP2, but not with other bacteria, showed a similar pattern with sugars, monoclonal antibody, and the adhesin-deficient mutant. The results suggest that the attachment of F. nucleatum PK1594 to mammalian cells and its coaggregation with periodontal pathogens are mediated by the same galactose-binding adhesin. C1 Tel Aviv Univ, Maurice & Gabriella Goldshleger Sch Dent Med, Dept Oral Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Weiss, EI (reprint author), Tel Aviv Univ, Maurice & Gabriella Goldshleger Sch Dent Med, Dept Oral Biol, Sackler Fac Med, IL-69978 Tel Aviv, Israel. FU NIDCR NIH HHS [DE-10969] NR 47 TC 41 Z9 46 U1 1 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD DEC PY 2000 VL 15 IS 6 BP 371 EP 377 DI 10.1034/j.1399-302x.2000.150606.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 371ND UT WOS:000165184300006 PM 11154434 ER PT J AU Mankarious, L Ansley, J AF Mankarious, L Ansley, J TI Apoptosis in the developing human cricoid cartilage: A pilot study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Combined Otolaryngological Spring Meeting CY APR 26-28, 1999 CL PALM DESERT, CALIFORNIA ID HUMAN LARYNX; TRANSFERASE; SECTIONS; CELLS AB Apoptosis is widely recognized as a major phenomenon in normal development. Deficiencies in this process may lead to developmental abnormalities such as congenital subglottic stenosis. We studied apoptosis using in situ end labeling of the 3'-OH ends of fragmented DNA in 5 progressively older, normal, human cricoid cartilage specimens, Results show that apoptosis is a very active process in fetal and neonatal tissue. The process gradually slows with advancing age, In the 4- and 13-year-old specimens, minimal to no apoptosis was seen. We conclude that apoptosis plays a critical role in the intraluminal and extraluminal expansion of the cricoid cartilage. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Mankarious, L (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 20 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2000 VL 123 IS 6 BP 677 EP 681 DI 10.1067/mhn.2000.111287 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 381PQ UT WOS:000165772400002 PM 11112956 ER PT J AU Busaba, NY AF Busaba, NY TI Primary melanoma of the sphenoid sinus SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Eastern Section Meeting of the Triologic-Society CY JAN 28-30, 2000 CL PITTSBURGH, PENNSYLVANIA SP Triol Soc ID HEAD; NECK C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Boston Vet Affairs Healthcare Syst, Div Otolaryngol, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 6 Z9 6 U1 0 U2 2 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 DEC PY 2000 VL 123 IS 6 BP 748 EP 749 DI 10.1067/mhn.2000.110724 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 381PQ UT WOS:000165772400018 PM 11112972 ER PT J AU Mele, D Alboni, P Fuca, G Scarfo, S Paparella, N Levine, RA AF Mele, D Alboni, P Fuca, G Scarfo, S Paparella, N Levine, RA TI Atrioventricular nodal versus atrioventricular supraventricular reentrant tachycardias: Characterization by an integrated Doppler electrophysiological hemodynamic study SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE Doppler; electrophysiology; supraventricular tachycardias; arrhythmias ID RIGHT ATRIAL PRESSURE AB During reentrant supraventricular tachycardias involving the atrioventricular node (AVN-SVT) or an AV bypass tract (AV-SVT), atrial pressure increases. While in AVN-SVT this increase relates to atrial contraction during ventricular systole, the? mechanism remains unclear in AV-SVT. This study sought to clarify this mechanism. During 11 AVN-SVTs and 9 AV-SVTs, anterograde flow through the AV valves and retrograde flow in the pulmonary and hepatic veins were studied by pulsed-wave (PW) Doppler measuring the time interval between the ECG-R wave and (1) the end of venous retrograde flows, and (2) the beginning of valvular anterograde flows. The positive or negative difference between these two time intervals guided recognizing the atrial con traction against open or closed AV valves. Intracavitary pressures and cardiac index were also measured. During AVN-SVTs, venous retrograde flows always ended before the anterograde valvular flows, indicating atrial contraction against closed AV valves. During AV-SVTs, pulmonary retrograde flow ended before the beginning of mitral anterograde flow in five cases, began before but ended during the anterograde flow in three cases, and overlapped to the anterograde flow in one case. A corresponding behavior wets observed at the right side of the heart. In both SVTs, atrial pressures increased and end-diastolic ventricular pressure and cardiac index decreased similarly. During AVN-SVT, the atrial contraction always occurs against closed AV valves, and during AV-SVT it generally occurs against totally or partially closed AV valves. explaining similar atrial pressure and cardiac index changes in both SVTs. C1 Osped Civile SS Annunziata, Div Cardiol, I-44042 Cento, Italy. Massachusetts Gen Hosp, Noninvas Cardiac Lab, Boston, MA 02114 USA. RP Mele, D (reprint author), Osped Civile SS Annunziata, Div Cardiol, Via Vicini 2, I-44042 Cento, Italy. NR 14 TC 6 Z9 6 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2000 VL 23 IS 12 BP 2078 EP 2085 DI 10.1111/j.1540-8159.2000.tb00780.x PG 8 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 394TQ UT WOS:000166539700012 PM 11202251 ER PT J AU Gelder, RN Galvin, JM Albert, CM Keane, D Ruskin, JN AF Gelder, RN Galvin, JM Albert, CM Keane, D Ruskin, JN TI Lead noise with an active-fixation defibrillation lead SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE implantable defibrillator; artifact; sensing; ventricular arrhythmia ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; INTRACARDIAC ELECTROGRAMS; RISK AB Inappropriate detection and therapy is the most common adverse effect of implantable cardioverter defibrillator therapy. One mechanism is lead artifact, which usually presents late and is due to stress and fatigue of the lead components, Our experience with a defibrillator lead (Endotak Endurance EZ leads, Models 0154/0155/0156) and its method of active fixation is described. Of 20 implants with this lead, four patients were found to have noise that resulted in inappropriate detections in three. No patient received therapy as a consequence of these detections. The artifact appeared soon after implant and resolved in three of four cases by 4 weeks, None of the 16 remaining patients developed noise after this time. This is a unique lead problem that resolves with time, but it may result in inappropriate therapies and difficult management decisions in high risk patients with ventricular arrhythmias. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Gelder, RN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Fruit St, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD DEC PY 2000 VL 23 IS 12 BP 2113 EP 2116 DI 10.1111/j.1540-8159.2000.tb00785.x PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 394TQ UT WOS:000166539700017 PM 11202256 ER PT J AU Sanchez, LA Holdsworth, M Bartel, SB AF Sanchez, LA Holdsworth, M Bartel, SB TI Stratified administration of serotonin 5-HT3 receptor antagonists (setrons) for chemotherapy-induced emesis - Economic implications SO PHARMACOECONOMICS LA English DT Review ID CISPLATIN-INDUCED EMESIS; MODERATELY EMETOGENIC CHEMOTHERAPY; ONDANSETRON PLUS DEXAMETHASONE; HIGH-DOSE CISPLATIN; QUALITY-OF-LIFE; DOUBLE-BLIND; INTRAVENOUS ONDANSETRON; ANTIEMETIC EFFICACY; ORAL GRANISETRON; CANCER-CHEMOTHERAPY AB The serotonin 5-HT3 receptor antagonists or 'setrons' have become the standard of care for the prevention of chemotherapy-induced emesis (CIE) and are first-line therapy for acute CIE in healthcare organisations worldwide. However, their superior efficacy versus standard antiemetics comes at a significant cost. Currently, 3 agents are available in the US: ondansetron, granisetron and dolasetron. The most important treatment-related factor contributing to CIE is the emetogenicity of chemotherapy. The ability to customise, or stratify, the setron dose to match the emetogenic challenge of the chemotherapy administered has potential benefits, both clinically and economically. In adults, there is an appreciable amount of clinical literature addressing stratified administration: however, the amount of 'hard' economic data is rather limited. Intuitively, if clinical outcomes are equivalent, then stratified administration should be associated with economic benefits, as it generally promotes the use of doses lower than those recommended by the manufacturer. The literature strongly substantiates this for ondansetron, but is not as favourable for granisetron or dolasetron. As the rationale and justification for dose stratification is contained in the clinical literature, the authors have reviewed the pertinent literature supporting the clinical and economic benefits of dose stratification in both adult and paediatric patients. The authors also provide a discussion of various additional strategies that can be employed to ensure the appropriate and cost-effective use of setrons in real-world practice settings. These strategies include the use of lower doses than recommended by manufacturers, use for acute versus delayed phase emesis, enhancing the antiemetic efficacy by the addition of a corticosteroid, use of oral versus injectable formulations (when appropriate) and the implementation and use of local, national and international drug use guidelines. C1 PE Applicat Inc, Boston, MA 02108 USA. Univ New Mexico, Dept Pharm Practice, Albuquerque, NM 87131 USA. Dana Farber Canc Inst, Dept Pharm, Boston, MA 02115 USA. RP Sanchez, LA (reprint author), PE Applicat Inc, 51 Mt Vernon St 1, Boston, MA 02108 USA. NR 112 TC 13 Z9 13 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD DEC PY 2000 VL 18 IS 6 BP 533 EP 556 DI 10.2165/00019053-200018060-00002 PG 24 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA 387AF UT WOS:000166097400002 PM 11227393 ER PT J AU Choo, PW Rand, CS Inui, TS Lee, MLT Ma, CC Platt, R AF Choo, PW Rand, CS Inui, TS Lee, MLT Ma, CC Platt, R TI A pharmacodynamic assessment of the impact of antihypertensive non-adherence on blood pressure control SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE hypertension; adherence; compliance; pharmacodynamics; statistical interaction ID HYPERTENSIVE PATIENTS; PERSPECTIVE AB Objectives - To evaluate if antihypertensive regimens that conform to present FDA guidelines by maintaining greater than or equal to 50% of their peak effect at the end of the dosing interval protect patients during sporadic lapses in adherence. Methods - 169 patients on monotherapy for high blood pressure underwent electronic adherence monitoring for 3 months. Blood pressures were measured during non-study office visits and were retrieved from automated medical records. Questionnaires were used to obtain other covariate information. The ratio of the dosing interval to the half-life of drug activity (I') was used to capture conformity with FDA guidelines. Data analysis focused on the interaction between I' and the impact on blood pressure of delayed dosing. Results - The average (+/- standard deviation) blood pressure during the study was 139.0(+/-12.0)/85.0(+/-6.9) mm Hg. Lisinopril followed by sustained-release verapamil, atenolol, and hydrochlorothiazide were the most frequently prescribed agents. The majority of regimens (99%) conformed to FDA dosing guidelines. Of the patients 23% missed a dose before their blood pressure check. Non-adherence, however, did not have a direct impact on blood pressure, and no interaction with I' of was detected. Conclusions - Among patients with relatively mild hypertension on single-drug therapy, regimens that conform to current FDA dosing guidelines may prevent losses of blood pressure control during episodic lapses of adherence. These findings should be replicated in other patient populations with standardized blood pressure measurement to confirm their validity. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Johns Hopkins Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Choo, PW (reprint author), 181 Longwood Ave,Room 433, Boston, MA 02115 USA. FU AHRQ HHS [HS07821]; NHLBI NIH HHS [HL64273-02] NR 13 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2000 VL 9 IS 7 BP 557 EP 563 DI 10.1002/pds.539 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 423ML UT WOS:000168180000002 PM 11338913 ER PT J AU Waldrep, TW Summers, KK Chiliade, PA AF Waldrep, TW Summers, KK Chiliade, PA TI Coinfection with HIV and HCV: More questions than answers? SO PHARMACOTHERAPY LA English DT Review ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; LIVER FIBROSIS PROGRESSION; DYNAMICS IN-VIVO; INTERFERON-ALPHA; INFECTED PATIENTS; NATURAL-HISTORY; UNITED-STATES; INFANT TRANSMISSION; COMBINATION THERAPY AB Chronic infection with the hepatitis C virus (HCV) is a major public health threat in the United States and worldwide. By sharing some routes of transmission, persons infected with the human immunodeficiency virus (HIV) are at risk for coinfection with HCV; As a result, hepatic cirrhosis, endstage liver disease, and hepatocellular carcinoma due to chronic infection with HCV are important causes of both morbidity and mortality in coinfected patients. The advent of highly active antiretroviral therapy improved the management of patients with HIV, leading to decreased morbidity and better survival. As patients infected with HIV live longer, their risk of long-term sequelae from chronic HCV increases. Coinfection with HIV may be associated with rapid progression of chronic HCV In contrast, the effect of HCV on the natural history of HIV is less clear. Data regarding treatment of HCV in HIV-coinfected patients are limited. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp, Immunosuppress Clin, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. RP Waldrep, TW (reprint author), Parkland Hlth & Hosp Syst, 5201 Harry Hines Blvd, Dallas, TX 75235 USA. NR 80 TC 9 Z9 9 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2000 VL 20 IS 12 BP 1499 EP 1507 DI 10.1592/phco.20.19.1499.34859 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 380CL UT WOS:000165680700011 PM 11130222 ER PT J AU Tao, Y Yuan, FH Leister, RT Ausubel, FM Katagiri, F AF Tao, Y Yuan, FH Leister, RT Ausubel, FM Katagiri, F TI Mutational analysis of the Arabidopsis nucleotide binding site-leucine-rich repeat resistance gene RPS2 SO PLANT CELL LA English DT Article ID PLANT-DISEASE RESISTANCE; ESCHERICHIA-COLI; AVIRULENCE GENE; CELL-DEATH; BACTERIAL; PROTEIN; TOMATO; THALIANA; SPECIFICITY; SECRETION AB Disease resistance proteins containing a nucleotide binding site (NBS) and a leucine-rich repeat (LRR) region compose the largest class of disease resistance proteins. These so-called NBS-LRR proteins confer resistance against a wide variety of phytopathogens. To help elucidate the mechanism by which NBS-LRR proteins recognize and transmit pathogen-derived signals, we analyzed mutant versions of the Arabidopsis NBS-LRR protein RPS2. The RPS2 gene confers resistance against Pseudomonas syringae strains carrying the avirulence gene avrRpt2. The activity of RPS2 derivatives in response to AvrRpt2 was measured by using a functional transient expression assay or by expressing the mutant proteins in transgenic plants. Directed mutagenesis revealed that the NBS and an N-terminal leucine zipper (LZ) motif were critical for RPS2 function. Mutations near the N terminus, including an LZ mutation, resulted in proteins that exhibited a dominant negative effect on wild-type RPS2. Scanning the RPS2 molecule with a small in-frame internal deletion demonstrated that RPS2 does not have a large dispensable region. Overexpression of RPS2 in the transient assay in the absence of avrRpt2! also led to an apparent resistant response, presumably a consequence of a low basal activity of RPS2. The NBS and LZ were essential for this overdose effect, whereas the entire LRR was dispensable. RPSP interaction with a 75-kD protein (p75) required an N-terminal portion of RPSP that is smaller than the region required for the overdose effect. These findings illuminate the pathogen recognition mechanisms common among NBS-LRR proteins. C1 Univ Maryland Baltimore Cty, Dept Sci Biol, Baltimore, MD 21250 USA. Scripps Res Inst, Grad Program Macromol & Cellular Struct & Chem, La Jolla, CA 92037 USA. Novartis Agr Discovery Inst Inc, San Diego, CA 92121 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Katagiri, F (reprint author), Univ Maryland Baltimore Cty, Dept Sci Biol, Baltimore, MD 21250 USA. RI Yuan, Fenghua/F-8736-2011; Tao, Yi/B-7718-2012 FU NIGMS NIH HHS [R37 GM048707, GM48707, R01 GM048707] NR 43 TC 127 Z9 141 U1 1 U2 8 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD DEC PY 2000 VL 12 IS 12 BP 2541 EP 2554 DI 10.1105/tpc.12.12.2541 PG 14 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 395BE UT WOS:000166558200018 PM 11148296 ER PT J AU Ausubel, FM AF Ausubel, FM TI Arabidopsis genome. A milestone in plant biology SO PLANT PHYSIOLOGY LA English DT Editorial Material ID THALIANA C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NR 17 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2000 VL 124 IS 4 BP 1451 EP 1454 DI 10.1104/pp.124.4.1451 PG 4 WC Plant Sciences SC Plant Sciences GA 385BV UT WOS:000165982500002 PM 11115856 ER PT J AU Drenkard, E Richter, BG Rozen, S Stutius, LM Angell, NA Mindrinos, M Cho, RJ Oefner, PJ Davis, RW Ausubel, FM AF Drenkard, E Richter, BG Rozen, S Stutius, LM Angell, NA Mindrinos, M Cho, RJ Oefner, PJ Davis, RW Ausubel, FM TI A simple procedure for the analysis of single nucleotide polymorphisms facilitates map-based cloning in Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA-POLYMERASE; MARKERS; PCR; THALIANA; DISCRIMINATION; MUTATION; FIDELITY; ASSAY AB We developed a modified allele-specific PCR procedure for assaying single nucleotide polymorphisms (SNPs) and used the procedure (called SNAP for single-nucleotide amplified polymorphisms) to generate 62 Arabidopsis mapping markers. SNAP primers contain a single base pair mismatch within three nucleotides from the 3' end of one allele (the specific allele) and in addition have a 3' mismatch with the nonspecific allele. A computer program called SNAPER was used to facilitate the design of primers that generate at least a 1,000-fold difference in the quantity of the amplification products from the specific and nonspecific SNP alleles. Because SNAP markers can be readily assayed by electrophoresis on standard agarose gels and because a public database of over 25,000 SNPs is available between the Arabidopsis Columbia and Landsberg erectra ecotypes, the SNAP method greatly facilitates the map-based cloning of Arabidopsis genes defined by a mutant phenotype. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Harvard Coll, Cambridge, MA 02138 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Oefner, Peter/K-1116-2016 OI Oefner, Peter/0000-0002-1499-3977 NR 25 TC 144 Z9 159 U1 4 U2 14 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2000 VL 124 IS 4 BP 1483 EP 1492 DI 10.1104/pp.124.4.1483 PG 10 WC Plant Sciences SC Plant Sciences GA 385BV UT WOS:000165982500011 PM 11115864 ER PT J AU Plotnikova, JM Rahme, LG Ausubel, FM AF Plotnikova, JM Rahme, LG Ausubel, FM TI Pathogenesis of the human opportunistic pathogen Pseudomonas aeruginosa PA14 in Arabidopsis SO PLANT PHYSIOLOGY LA English DT Article ID ENHANCED DISEASE SUSCEPTIBILITY; CAENORHABDITIS-ELEGANS; VIRULENCE FACTORS; MODEL; INDUCTION; SYRINGAE; MUTANTS; GENE AB The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 is a multihost pathogen that can infect Arabidopsis. We found that PA14 pathogenesis in Arabidopsis involves the following steps: attachment to the leaf surface, congregation of bacteria at and invasion through stomata or wounds, colonization of intercellular spaces, and concomitant disruption of plant cell wall and membrane structures, basipetal movement along the vascular parenchyma, and maceration and rotting of the petiole and central bud. Distinctive features of P. aeruginosa pathogenesis are that the surface of mesophyll. cell walls adopt an unusual convoluted or undulated appearance, that PA14 cells orient themselves perpendicularly to the outer surface of mesophyll cell walls, and that PA14 cells make circular perforations, approximately equal to the diameter of P. aeruginosa, in mesophyll cell walls. Taken together, our data show that P, aeruginosa strain PA14 is a facultative pathogen of Arabidopsis that is capable of causing local and systemic infection, which can result in the death of the infected plant. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. FU NIGMS NIH HHS [R37 GM048707, R01 GM048707] NR 25 TC 65 Z9 72 U1 1 U2 6 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 2000 VL 124 IS 4 BP 1766 EP 1774 DI 10.1104/pp.124.4.1766 PG 9 WC Plant Sciences SC Plant Sciences GA 385BV UT WOS:000165982500039 PM 11115892 ER PT J AU Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA AF Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA TI Atypical antipsychotic medications: Pharmacological profiles and psychological implications SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Review ID TREATMENT-REFRACTORY SCHIZOPHRENIA; TREATMENT-RESISTANT SCHIZOPHRENIA; DOUBLE-BLIND; NEGATIVE SYMPTOMS; CLOZAPINE TREATMENT; TARDIVE-DYSKINESIA; DOPAMINE-RECEPTORS; CLINICAL EFFICACY; PERSONAL THERAPY; 3-YEAR TRIALS AB Advances in psychopharmacology and the development of new antipsychotic medications may represent increased opportunities for psychologists to provide expanded psychosocial services to patients with schizophrenia The new agents, referred to as the atypical antipsychotics, are as efficacious as the older conventional antipsychotics but demonstrate a mole favorable side effect profile. Preliminary data suggest improvements in cognitive deficits and negative symptoms typically associated with schizophrenia, which may enhance long-term outcome. Psychologists may be increasingly called on to provide psychosocial services to this population, thereby requiring that they have a sound working knowledge of the pharmacological and psychological properties of these agents. C1 Univ Miami, Neurol Ctr S Florida, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Miami, Citrus Hlth Network, Coral Gables, FL 33124 USA. RP Rivas-Vazquez, RA (reprint author), 8940 N Kendall Dr,Suite 802-E, Miami, FL 33176 USA. NR 126 TC 2 Z9 2 U1 7 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2000 VL 31 IS 6 BP 628 EP 640 DI 10.1037//0735-7028.31.6.628 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 383LE UT WOS:000165883400007 ER PT J AU Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA AF Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA TI Sexual dysfunction associated with antidepressant treatment SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; PREMATURE EJACULATION; MAJOR DEPRESSION; FLUOXETINE USE; DOUBLE-BLIND; PAROXETINE; SERTRALINE; BUPROPION; PRIAPISM; NEFAZODONE AB Psychologists rendering psychotherapeutic services to patients receiving pharmacological treatment with the newer antidepressants are becoming more familiar with their distinct therapeutic and side effect profiles. Increased attention has recently been directed at the sexual dysfunction associated with the use of these antidepressants. Among the newer agents, risk for the emergence of sexual side effects is greater with the selective serotonin reuptake inhibitors than with the atypical antidepressants. Psychologists who are aware of treatment-related sexual dysfunction may be more effective in collaborating with prescribing professionals to develop strategies that allow patients to minimize or better tolerate these side effects. C1 Univ Miami, Sch Med, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rivas-Vazquez, RA (reprint author), 8940 N Kendall Dr,Suite 802-E, Miami, FL 33176 USA. NR 95 TC 3 Z9 4 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 2000 VL 31 IS 6 BP 641 EP 651 DI 10.1037//0735-7028.31.6.641 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 383LE UT WOS:000165883400008 ER PT J AU Kent, JM Sullivan, GM Rauch, SL AF Kent, JM Sullivan, GM Rauch, SL TI The neurobiology of fear: Relevance to panic disorder and posttraumatic stress SO PSYCHIATRIC ANNALS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CHILDHOOD SEXUAL ABUSE; VIETNAM COMBAT VETERANS; CEREBRAL BLOOD-FLOW; CONDITIONED FEAR; BENZODIAZEPINE RECEPTOR; HIPPOCAMPAL VOLUME; PREFRONTAL CORTEX; DIFFERENTIAL CONTRIBUTION; NORADRENERGIC FUNCTION C1 Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Kent, JM (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA. NR 71 TC 5 Z9 6 U1 3 U2 4 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 2000 VL 30 IS 12 BP 733 EP 742 PG 10 WC Psychiatry SC Psychiatry GA 382QB UT WOS:000165832800003 ER PT J AU Smoller, JW Finn, C White, C AF Smoller, JW Finn, C White, C TI The genetics of anxiety disorders: An overview SO PSYCHIATRIC ANNALS LA English DT Article ID SEROTONIN TRANSPORTER GENE; OBSESSIVE-COMPULSIVE DISORDER; REGULATORY REGION POLYMORPHISM; POSTTRAUMATIC-STRESS-DISORDER; POPULATION-BASED TWIN; GENERALIZED SOCIAL PHOBIA; DIRECT-INTERVIEW FAMILY; PANIC DISORDER; MAJOR DEPRESSION; NO ASSOCIATION C1 Massachusetts Gen Hosp, Dept Psychiat, Outpatient Div, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. RP Smoller, JW (reprint author), 15 Parkman St,WAC-812, Boston, MA 02114 USA. NR 93 TC 7 Z9 8 U1 4 U2 8 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 2000 VL 30 IS 12 BP 745 EP 753 PG 9 WC Psychiatry SC Psychiatry GA 382QB UT WOS:000165832800004 ER PT J AU Nierenberg, AA AF Nierenberg, AA TI Depression: Recent developments and innovative treatments - Preface SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkham St,WAC 812, Boston, MA 02114 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP IX EP X DI 10.1016/S0193-953X(05)70191-X PG 2 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300001 ER PT J AU Nierenberg, AA Alpert, JE AF Nierenberg, AA Alpert, JE TI Depressive breakthrough SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MAJOR DEPRESSION; RECURRENT DEPRESSION; REFRACTORY DEPRESSION; FOLLOW-UP; MAINTENANCE THERAPIES; FLUOXETINE TREATMENT; DOUBLE-BLIND; 20 MG; LITHIUM; RELAPSE AB Patients with major depression tend to have multiple episodes. Episodes that redevelop within 6 months of acute response are called relapses, whereas those that occur after 6 months are called recurrences.(17) Theoretically, relapses are considered a return of the original episode, whereas recurrences represent a new episode; but these are hypotheses without any substantiating data. Without long-term antidepressant treatment, depressive relapses or recurrences occur in 50% to 80% of patients.(11,17,23,26,38) Double-blind, discontinuation studies reveal that antidepressants decrease the risk for relapse and recurrence and have repeatedly been shown antidepressants to be more efficacious than placebo substitution.(11,16,30,42,48) Nonetheless, observational studies have shown that, within 1 to 5 years after an acute response, 20% to 80% of patients develop another depressive episode even while taking longterm antidepressants for prophylaxis.(27,30,36,40) A succinct term for relapse or recurrence during long-term antidepressant treatment is depressive breakthrough. Several case series and only a few controlled studies have described the return of major depression during: long-term antidepressant therapy, but fewer studies have examined the management of patients who have depressive breakthrough. With increasing emphasis on long-term treatment of chronic relapsing and recurring depressive disorders, and the dramatic increase in the number of patients who use selective serotonin reuptake inhibitor (SSRI) antidepressant therapy within the past 5 years, the treatment of depressive breakthrough must be improved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 49 TC 21 Z9 23 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP 731 EP + DI 10.1016/S0193-953X(05)70194-5 PG 13 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300004 PM 11147244 ER PT J AU Dording, CM AF Dording, CM TI Antidepressant augmentation and combinations SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; TREATMENT-REFRACTORY DEPRESSION; PLACEBO-CONTROLLED TRIAL; TREATMENT-RESISTANT-DEPRESSION; LITHIUM AUGMENTATION; MAJOR DEPRESSION; DOUBLE-BLIND; TRIIODOTHYRONINE AUGMENTATION; TRICYCLIC ANTIDEPRESSANTS; BUSPIRONE AUGMENTATION AB Although effective, the selective serotonin (5-HT) reuptake inhibitors (SSRIs) and the newer generation of antidepressants are far from perfect; 10% to 30% of depressed patients fail to respond to those therapies, and 12% to 25% respond but fail to remit fully with adequate therapy.(47,55a) After depressed patients fail to respond to adequate antidepressant trials, several treatment strategies can be used, including augmenting the failed antidepressant, combining antidepressants, or switching to another antidepressant.(19,55a) Many agents may augment antidepressants, and combinations of antidepressants also are useful, but data to support these strategies are limited; no available data support one over the other. This article critically reviews augmentation strategies, including lithium, thyroid hormone, stimulants, dopamine agonists and modafinil, buspirone, pindolol, anticonvulsants, atypical antipsychotics, and combinations of antidepressants.(21) C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Dording, CM (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 63 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP 743 EP + DI 10.1016/S0193-953X(05)70195-7 PG 14 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300005 PM 11147245 ER PT J AU George, MS Sackeim, HA Marangell, LB Husain, MM Nahas, Z Lisanby, SH Ballenger, JC Rush, AJ AF George, MS Sackeim, HA Marangell, LB Husain, MM Nahas, Z Lisanby, SH Ballenger, JC Rush, AJ TI Vagus nerve stimulation - A potential therapy for resistant depression? SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; PARTIAL SEIZURES; ELECTROCONVULSIVE-THERAPY; BLOOD-FLOW; ELECTRICAL-STIMULATION; REFRACTORY EPILEPSY; ELECTRODE PLACEMENT; TREATMENT RESPONSE; SLEEP-DEPRIVATION; VAGAL-STIMULATION AB For more than a century, neuroscientists have tried to develop noninvasive methods to stimulate the brain, thereby avoiding brain surgery and open craniotomy. As early as 1938, some investigators conjectured that vagus nerve stimulation (VNS) would alter higher brain activity. Within the past 20 years, VNS in the neck has become routine, and a specific type of VNS has been approved by the US Food and Drug Administration for treatment-resistant partial onset seizure disorder, with 9000 patients receiving implants worldwide. This year, a pilot study(51) using VNS in subjects with treatment-resistant depression showed encouraging results. This article summarizes the theory and practice of VNS and addresses many of the issues that must considered in the development of VNS as a potential antidepressant therapy and neuroscience probe. VNS seems to be a promising new somatic intervention that also may improve the understanding of brain function. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. New York State Psychiat Inst, Dept Biol Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Radiol, New York, NY USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. OI Rush, Augustus/0000-0003-2004-2382 NR 73 TC 50 Z9 50 U1 4 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP 757 EP + DI 10.1016/S0193-953X(05)70196-9 PG 28 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300006 PM 11147246 ER PT J AU Mischoulon, D Fava, M AF Mischoulon, D Fava, M TI Docosahexanoic acid and omega-3 fatty acids in depression SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID RED-BLOOD-CELL; INFANT CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; MAJOR DEPRESSION; DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; CEREBROSPINAL-FLUID; MULTIPLE-SCLEROSIS; CHOLESTERYL ESTERS; MEMBRANE FLUIDITY AB lished studies have compared natural antidepressants to the selective serotonin (5-HT) reuptake inhibitors, which are the first-line agents for treating depression; however, several such studies are under way in the United States. Clearly, more research is necessary to clarify the gaps in knowledge about natural psychotropics.(38,39) This article reviews the state of knowledge regarding docosahexanoic acid (DHA) and other omega -3 fatty acids (FAs) and their potential role in the treatment of depression and other mood disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 60 TC 43 Z9 44 U1 2 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP 785 EP + DI 10.1016/S0193-953X(05)70197-0 PG 11 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300007 PM 11147247 ER PT J AU Deckersbach, T Gershuny, BS Otto, MW AF Deckersbach, T Gershuny, BS Otto, MW TI Cognitive-behavioral therapy for depression - Applications and outcome SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID FOLLOW-UP; ENDOGENOUS-DEPRESSION; UNIPOLAR DEPRESSION; ATYPICAL DEPRESSION; RESIDUAL SYMPTOMS; MAJOR DEPRESSION; MARITAL-THERAPY; PHARMACOTHERAPY; RELAPSE; PREDICTORS AB Patients with major depression have a choice between several empirically supported therapies, including pharmacotherapy, cognitive-behavior therapy (CBT), and interpersonal therapy (IPT). This article reviews the application and outcome of CBT for major depression. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 64 TC 17 Z9 19 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 2000 VL 23 IS 4 BP 795 EP + DI 10.1016/S0193-953X(05)70198-2 PG 16 WC Psychiatry SC Psychiatry GA 385BG UT WOS:000165981300008 PM 11147248 ER PT J AU Kerrigan, AJ Kaough, JE Wilson, BL Wilson, JV Boeringa, JA Monga, TN AF Kerrigan, AJ Kaough, JE Wilson, BL Wilson, JV Boeringa, JA Monga, TN TI Vocational rehabilitation outcomes of veterans with substance use disorders in a partial hospitalization program SO PSYCHIATRIC SERVICES LA English DT Article AB The authors examined factors that influenced the employment rates of 529 veterans with severe alcohol and other substance use disorders who were being treated at an addictions partial hospitalization program. The employment rate was significantly higher for veterans who completed the hospitalization program, participated in a Veterans Industries work-for-pay program, and received drug-free supportive housing. C1 VA Med Ctr, Psychol Serv 116B, Hlth Care Homeless Vet Dept, Houston, TX 77030 USA. Baylor Coll Med, Fac Dept Phys Med & Rehabil, Houston, TX 77030 USA. RP Kerrigan, AJ (reprint author), VA Med Ctr, Psychol Serv 116B, Hlth Care Homeless Vet Dept, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 10 TC 9 Z9 9 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD DEC PY 2000 VL 51 IS 12 BP 1570 EP 1572 DI 10.1176/appi.ps.51.12.1570 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 380CT UT WOS:000165681400018 PM 11097656 ER PT J AU Gazelle, GS Goldberg, SN Solbiati, L Livraghi, T AF Gazelle, GS Goldberg, SN Solbiati, L Livraghi, T TI Tumor ablation with radio-frequency energy SO RADIOLOGY LA English DT Article DE interventional procedures, technology; interventional procedures, utilization; radiofrequency (RF) ablation; State of the Art ID RADIOFREQUENCY TISSUE ABLATION; COLORECTAL LIVER METASTASES; PERIOPERATIVE BLOOD-TRANSFUSION; INTERSTITIAL THERMAL ABLATION; HEPATIC RESECTION; NATURAL-HISTORY; COAGULATION NECROSIS; CARCINOMA METASTASES; HEPATOCELLULAR-CARCINOMA; PATIENT SELECTION AB Tumor ablation by using radio-frequency energy has begun to receive increased attention as an effective minimally invasive approach for the treatment of patients with a variety of primary and secondary malignant neoplasms. To date, these techniques have been used to treat tumors located in the brain, musculoskeletal system, thyroid and parathyroid glands, pancreas, kidney, lung, and breast; however, liver tumor ablation has received the greatest attention and has been the subject of a large number of published reports. In this article, the authors review the technical developments and early laboratory results obtained with radio-frequency ablation techniques, describe some of the early clinical applications of these techniques, and conclude with a discussion of challenges and opportunities for the future. C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Gr, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Minimally Invas Therapies Lab, Boston, MA 02215 USA. Gen Hosp, Dept Radiol, Busto Arsizo, Italy. Osped Civile, Dept Radiol, Milan, Italy. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Gr, Zero Emerson Pl,Ste 2H, Boston, MA 02114 USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 91 TC 440 Z9 489 U1 7 U2 31 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2000 VL 217 IS 3 BP 633 EP 646 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377CX UT WOS:000165495300004 PM 11110923 ER PT J AU Gervais, DA McGovern, FJ Wood, BJ Goldberg, SN McDougal, WS Mueller, PR AF Gervais, DA McGovern, FJ Wood, BJ Goldberg, SN McDougal, WS Mueller, PR TI Radio-frequency ablation of renal cell carcinoma: Early clinical experience SO RADIOLOGY LA English DT Article DE kidney, interventional procedures; kidney neoplasms, CT; kidney neoplasms, MR; radiofrequency (RF) ablation ID RADIOFREQUENCY TISSUE ABLATION; COAGULATION NECROSIS; CANCER; ELECTRODE; NEPHRECTOMY; METASTASES; NEOPLASMS; GROWTH; VOLUME AB PURPOSE: To report the authors' early experience with radio-frequency (RF) ablation of renal cell carcinoma. MATERIALS AND METHODS: Twenty-four percutaneous RF ablation treatments for nine tumors were performed in eight patients with renal cell carcinoma. Indications included coexistent morbidity, previous surgery, or solitary kidney in patients with a life expectancy shorter than 10 years. Smaller (less than or equal to 3-cm) peripheral lesions (n = 3) were treated with single electrodes. All but one of the larger (> 3 cm) and/or central lesions (n = 6) were treated with cluster or multiple electrodes. Patients returned for a second treatment when follow-up imaging depicted tumor enhancement. Follow-up imaging was performed at 1 and 3 months and then at B-month intervals, with a mean follow-up of 10.3 months. Seven patients were alive at least 6 months after their initial treatment. RESULTS: All five exophytic tumors were free of enhancement. One of three central tumors was free of enhancement. One tumor had both central and exophytic components and was free of enhancement. Three tumors were 3 cm or smaller and free of enhancement. Of the six tumors larger than 3 cm, four were free of enhancement. CONCLUSION: Percutaneous RF ablation is a promising treatment for select patients with renal cell carcinoma. The ultimate role of this modality will continue to evolve and warrants further study. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Fruit St, Boston, MA 02114 USA. NR 26 TC 212 Z9 221 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2000 VL 217 IS 3 BP 665 EP 672 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377CX UT WOS:000165495300007 PM 11110926 ER PT J AU Pena, CS Boland, GWL Hahn, PF Lee, MJ Mueller, PR AF Pena, CS Boland, GWL Hahn, PF Lee, MJ Mueller, PR TI Characterization of indeterminate (lipid-poor) adrenal masses: Use of washout characteristics at contrast-enhanced CT SO RADIOLOGY LA English DT Article DE adrenal gland, CT; adrenal gland, neoplasms; computed tomography (CF), contrast enhancement; fat ID ADENOMAS; NONADENOMAS; DIFFERENTIATION; MR AB PURPOSE: To determine whether computed tomographic (CT) scans and attenuation measurements on contrast material-enhanced and nonenhanced CT scans could be used to characterize adrenal masses, in particular, to characterize these lesions by using adrenal washout characteristics at contrast-enhanced CT. MATERIALS AND METHODS: Eighty-six patients (49 men, 37 women; age range, 29-86 years; mean age, 72 years) with 101 adrenal lesions depicted at contrast-enhanced CT underwent delayed (mean, 9 minutes) enhanced scanning. Seventy-eight patients also underwent nonenhanced CT. Mean diameter of the benign lesions was 2.1 cm (range, 1.0-4.2 cm); mean diameter of the malignant lesions was 2.3 cm (range, 1.0-4.1 cm). Region-of-interest. measurements were obtained at nonenhanced, dynamic enhanced, and delayed enhanced CT and were used to calculate a relative percentage washout as follows: 1 - (Hounsfield unit measurement on delayed image divided by Hounsfield unit measurement on dynamic image) x 100%. RESULTS: Ninety-nine of 101 lesions were correctly characterized as benign or malignant with a relative percentage washout threshold of 50% on delayed scans; benign lesions demonstrated more than 50% washout; and malignant lesions, less than 50% washout. Two benign lesions demonstrating less than 50% washout were characterized as benign by using conventional CT. CONCLUSION: Calculation of relative percentage washout on dynamic and delayed enhanced CT scans may lead to a highly specific test for adrenal lesion characterization, reduce the need for, and possibly obviate, follow-up imaging or biopsy. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 188 Z9 205 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2000 VL 217 IS 3 BP 798 EP 802 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377CX UT WOS:000165495300025 PM 11110946 ER PT J AU Goldberg, SN Kruskal, JB Oliver, BS Clouse, ME Gazelle, GS AF Goldberg, SN Kruskal, JB Oliver, BS Clouse, ME Gazelle, GS TI Percutaneous tumor ablation: Increased coagulation by combining radio-frequency ablation and ethanol instillation in a rat breast tumor model SO RADIOLOGY LA English DT Article DE alcohol ablation; animals; interventional procedures, experimental studies; neoplasms, therapy; radiofrequency (RF) ablation ID RADIOFREQUENCY TISSUE ABLATION; SMALL HEPATOCELLULAR-CARCINOMA; MICROWAVE COAGULATION; INJECTION THERAPY; THERMAL ABLATION; NEEDLE ELECTRODE; BLOOD-FLOW; IN-VIVO; EXPERIENCE; NECROSIS AB PURPOSE: To determine if percutaneously applied radio frequency (RF) combined with percutaneous ethanol instillation (PEI) can increase the extent of ablation in rat breast tumors. MATERIALS AND METHODS: R3230 mammary adenocarcinoma was implanted bilaterally in the mammary fat pads of 18 female rats. The tumor nodules measured 1.2-1.5 cm. Eight tumors each were treated with (a) conventional, monopolar RF (96 mA +/- 28; 70 degreesC for 5 minutes); (b) PEI (250 muL of ethanol infused over 1 minute); (c) combined therapy of PEI immediately followed by RF ablation; or (d) combined therapy of RF ablation immediately followed by PEI. Four tumors were not treated and served as controls. Histopathologic examination included staining for mitochondrial enzyme activity. Resultant coagulation necrosis was compared between treatment groups. RESULTS: Coagulation necrosis was observed only within treated tumors. Tumors treated with RF alone had 6.7 mm +/- 0.6 of coagulation surrounding the electrode, and those treated with PEI alone had 6.4 mm +/- 0.6 of coagulation around the instillation needle (not significant). Significantly increased coagulation of 10.1 mm +/- 0.9 (P < .001) was observed with the combined therapy of PEI followed by RF. RF followed by PEI did not increase coagulation (6.4 mm +/- 0.8 around the needle; not significant). CONCLUSION: PEI followed by RF ablation therapy increases the extent of induced coagulation necrosis in rat breast tumors, as compared with either therapy alone. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 44 TC 64 Z9 69 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2000 VL 217 IS 3 BP 827 EP 831 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377CX UT WOS:000165495300029 PM 11110950 ER PT J AU Brodsky, AS Silver, PA AF Brodsky, AS Silver, PA TI Pre-mRNA processing factors are required for nuclear export SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE 3 ' processing; ASH1 3 ' UTR; mRNA export; polyadenylation ID MESSENGER-RNA EXPORT; IN-SITU HYBRIDIZATION; PORE COMPLEX PROTEINS; SACCHAROMYCES-CEREVISIAE; POLY(A)(+) RNA; NUCLEOCYTOPLASMIC TRANSPORT; 3'-END FORMATION; BINDING DOMAIN; BUDDING YEAST; HEAT-SHOCK AB RNA export from the nucleus is thought to be linked to proper processing and packaging into ribonucleoprotein protein complexes. A system to observe mRNA nuclear export in living yeast cells was developed by fusing the U1A RNA-binding protein to the green fluorescent protein to follow specific mRNAs with U1A hairpins engineered into them. RNAs encoding Rp125, Pgkl, and Ssa4 were examined for the effects of 3' UTRs, introns, RNA processing factors, nucleoporins, and transport factors on their export. All accumulated in the nucleus in mutants affecting components of the nuclear export machinery and certain nucleoporins. However, under conditions of stress, PGK1 and RPL25 transcripts accumulate in the nucleus whereas SSA4 RNA is exported. Moreover, when export is blocked, only RNAs containing the ASH13'UTR accumulated in the nucleolus. Mutations in the splicing machinery selectively blocked export of only intron-containing RNAs. Mutations in RNA14 RNA15, and PAP1, which encode factors important for 3' processing, also blocked export of all RNAs, including SSA4 thereby linking export to the process of polyadenlyation. Taken together, these data graphically display the connections between mRNA processing and nuclear export. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 130 Z9 134 U1 1 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD DEC PY 2000 VL 6 IS 12 BP 1737 EP 1749 DI 10.1017/S1355838200001059 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 384BF UT WOS:000165918600009 PM 11142374 ER PT J AU Zha, JP Weiler, S Oh, KJ Wei, MC Korsmeyer, SJ AF Zha, JP Weiler, S Oh, KJ Wei, MC Korsmeyer, SJ TI Posttranslational N-myristoylation of BID as a molecular switch for targeting mitochondria and apoptosis SO SCIENCE LA English DT Article ID CYTOCHROME-C RELEASE; PROTEIN; DEATH; MEMBRANES; SURVIVAL; PATHWAY; BCL-2; DNA AB Many apoptotic molecules relocate subcellularly in cells undergoing apoptosis. The pro-apoptotic protein BID underwent posttranslational (rather than classic cotranslational) N-myristoylation when cleavage by caspase 8 caused exposure of a glycine residue. N-myristoylation enabled the targeting of a complex of p7 and myristoylated p15 fragments of BID to artificial membranes bearing the Lipid composition of mitochondria, as well as to intact mitochondria. This post-proteolytic N-myristoylation serves as an activating switch, enhancing BID-induced release of cytochrome c and cell death. C1 Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA50239-13, K01 CA82231, T32 CA72320-01A1] NR 24 TC 396 Z9 407 U1 1 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 1 PY 2000 VL 290 IS 5497 BP 1761 EP 1765 DI 10.1126/science.290.5497.1761 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 379FY UT WOS:000165632400042 PM 11099414 ER PT J AU Stamenkovic, I AF Stamenkovic, I TI Matrix metalloproteinases in tumor invasion and metastasis SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE metalloproteinases; matrix; metastasis; tumor ID B16-F10 MELANOMA-CELLS; EPIDERMAL-GROWTH-FACTOR; RECOMBINANT TISSUE INHIBITOR; PROSTATE-CANCER CELLS; RAT EMBRYO CELLS; EXTRACELLULAR-MATRIX; COLLAGENASE-3 MMP-13; PLASMINOGEN-ACTIVATOR; GELATINASE-A; INTERSTITIAL COLLAGENASE AB Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include Intent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Unit, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Stamenkovic, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Pathol Unit, 149 13th St,Charlestown Navy Yard, Boston, MA 02129 USA. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM48614] NR 171 TC 459 Z9 487 U1 2 U2 28 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD DEC PY 2000 VL 10 IS 6 BP 415 EP 433 DI 10.1006/scbi.2000.0333 PG 19 WC Oncology SC Oncology GA 405AB UT WOS:000167134100004 PM 11170864 ER PT J AU Dierickx, CC AF Dierickx, CC TI Hair removal by lasers and intense pulsed light sources SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID MODE RUBY-LASER; PHOTODYNAMIC THERAPY; SELECTIVE PHOTOTHERMOLYSIS; ENDOGENOUS PROTOPORPHYRIN; FOLLICLES; OPTICS; DAMAGE; SKIN; IX AB Unwanted pigmented hair is a common problem for many patients. Traditional methods of hair removal have included shaving, bleaching, plucking, waxing, use of chemical depilatories, and electrolysis. These techniques have been limited by their pain. inconvenience, and poor long-term efficacy. only electrolysis has offered the potential for permanent hair removal. However, the technique is tedious, highly operator-dependent, and impractical for the treatment of large numbers of hairs. Recently, a number of lasers and other light sources have been developed specifically to target hair follicles. These include ruby, alexandrite, diode, and Nd:YAG losers and an intense pulsed light source. These devices offer the potential for rapid treatment of large areas and long-lasting hair removal. This article explains the mechanisms of using light to remove hair, examines the attributes of specific laser systems, and explains the importance of patient selection and treatment protocol for the various systems in order to provide a safe and effective treatment. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Dierickx, CC (reprint author), Praktijk Dermatol & Lasertherapie, Beukenlaan 52, B-2850 Boom, Belgium. RI huang, hongqi/N-1473-2014 NR 42 TC 19 Z9 19 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 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD DEC PY 2000 VL 19 IS 4 BP 267 EP 275 PG 9 WC Dermatology; Surgery SC Dermatology; Surgery GA 388EJ UT WOS:000166164200007 PM 11149607 ER PT J AU Treon, SP Anderson, KC AF Treon, SP Anderson, KC TI The use of rituximab in the treatment of malignant and nonmalignant plasma cell disorders SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual Oncology Consensus Conference on Recent Advances and New Therapeutic Directions for Hematologic Malignacies CY JAN 12-16, 2000 CL NW UNIV MED SCH, KAILUA-KONA, HAWAII HO NW UNIV MED SCH ID TRANSCRIPTION FACTOR PU.1; MULTIPLE-MYELOMA; B-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; EXPRESSION; ANTIBODY; DIFFERENTIATION; IMMUNOTHERAPY; LYMPHOCYTES C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, M555,44 Binney St, Boston, MA 02115 USA. NR 49 TC 80 Z9 83 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2000 VL 27 IS 6 SU 12 BP 79 EP 85 PG 7 WC Oncology SC Oncology GA 401ZD UT WOS:000166958700012 PM 11226004 ER PT J AU Berkowitz, RS Tuncer, ZS Bernstein, MR Goldstein, DP AF Berkowitz, RS Tuncer, ZS Bernstein, MR Goldstein, DP TI Management of gestational trophoblastic diseases: Subsequent pregnancy experience SO SEMINARS IN ONCOLOGY LA English DT Review ID PARTIAL MOLAR PREGNANCY; IN-VITRO FERTILIZATION; HYDATIDIFORM MOLE; PROPHYLACTIC CHEMOTHERAPY; REPRODUCTIVE EXPERIENCE; FOLLOW-UP; TUMORS; RECURRENT; RISK; ENTITIES C1 Harvard Univ, Sch Med,Brigham & Womens Hosp,Div Gynecol Oncol, New England Trophoblast Dis Ctr, Gillette Ctr Womens Canc,Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med,Brigham & Womens Hosp,Div Gynecol Oncol, New England Trophoblast Dis Ctr, Gillette Ctr Womens Canc,Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 58 TC 17 Z9 18 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2000 VL 27 IS 6 BP 678 EP 685 PG 8 WC Oncology SC Oncology GA 381TD UT WOS:000165778800009 PM 11130475 ER PT J AU Partridge, AH Garber, JE AF Partridge, AH Garber, JE TI Long-term outcomes of children exposed to antineoplastic agents in utero SO SEMINARS IN ONCOLOGY LA English DT Review ID ACUTE MYELOGENOUS LEUKEMIA; LOW-BIRTH-WEIGHT; EPITHELIAL OVARIAN-CARCINOMA; NON-HODGKINS-LYMPHOMA; BREAST-CANCER; IN-UTERO; COMBINATION CHEMOTHERAPY; CONGENITAL-ANOMALIES; FOLLOW-UP; NEOADJUVANT CHEMOTHERAPY C1 Dana Farber Canc Inst, Adult Oncol Dept, Boston, MA 02115 USA. RP Garber, JE (reprint author), Dana Farber Canc Inst, Adult Oncol Dept, 44 Binney St, Boston, MA 02115 USA. NR 109 TC 19 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 2000 VL 27 IS 6 BP 712 EP 726 DI 10.1053/sonc.2000.18549 PG 15 WC Oncology SC Oncology GA 381TD UT WOS:000165778800013 PM 11130479 ER PT J AU Aksoy, FG Lev, MH AF Aksoy, FG Lev, MH TI Dynamic contrast-enhanced brain perfusion imaging: Technique and clinical applications SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; MEAN TRANSIT-TIME; MAGNETIC-RESONANCE; MR PERFUSION; ISCHEMIC PENUMBRA; HYPERACUTE STROKE; VOLUME; SUSCEPTIBILITY; CT C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Ankara Training & Teaching Hosp, Dept Radiol, Ankara, Turkey. RP Aksoy, FG (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, Gray B285,55 Fruit St, Boston, MA 02116 USA. NR 73 TC 55 Z9 64 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 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD DEC PY 2000 VL 21 IS 6 BP 462 EP 477 DI 10.1016/S0887-2171(00)90038-6 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 383PR UT WOS:000165891800006 PM 11138635 ER PT J AU Woodcock, SA Kyriakides, C Wang, Y Austen, WG Moore, FD Valeri, R Hartwell, D Hechtman, HB AF Woodcock, SA Kyriakides, C Wang, Y Austen, WG Moore, FD Valeri, R Hartwell, D Hechtman, HB TI Soluble P-selectin moderates complement dependent injury SO SHOCK LA English DT Article DE ischemia reperfusion complement soluble P-selectin platelets short consensus repeats ID GRANULE MEMBRANE-PROTEIN; EPIDERMAL GROWTH-FACTOR; INTESTINAL ISCHEMIA-REPERFUSION; WEIBEL-PALADE BODIES; PLASMA-MEMBRANE; GLYCOPROTEIN LIGAND-1; PLATELET ACTIVATION; ENDOTHELIAL-CELLS; IN-VIVO; ADHESION AB P-selectin is an adhesion molecule expressed on activated endothelial and platelet membranes containing 9 short consensus repeats (SCRs) similar to the composition of complement regulatory proteins. In our murine model of intestinal ischemia and reperfusion where local injury is mediated by the classical complement pathway we hypothesized the SCRs would moderate the complement response. Confirmatory data were sought following hindlimb ischemia and reperfusion where injury is both complement- and neutrophil-mediated. Mice deficient in P-selectin (P-/-) were found to have similar intestinal and hindlimb permeability compared to normal wild types mice (P+/+). When reconstituted with P+/+ platelets, but not P-/- platelets, P-/- mice subjected to intestinal ischemia had a significant 29% decrease in permeability (P<0.05) and after hindlimb ischemia the decrease was 33% (P<0.05). Reperfusion after intestinal ischemia led to a 76% fall in CH50 in P-/- compared to sham animals (P<0.05) indicating complement activation and consumption, but only a 36% fall in animals reconstituted with P+/+ platelets (P<0.05). Full-length, soluble P-selectin (sPsel) derived from processed platelets, but not the truncated version of sPsel has been shown to adhere to a heat labile fraction of serum and sensitized red blood cells thereby reducing Clq adherence to the sensitized red cell. From these data we conclude that sPsel moderates complement activation by competing with Clq binding to antibody, thereby limiting activation of the classical pathway that mediates murine reperfusion injury. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Boston Univ, Naval Blood Res Lab, Boston, MA 02215 USA. RP Hechtman, HB (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM-35141, GM-07560, GM-52585] NR 33 TC 10 Z9 10 U1 0 U2 1 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9,, AUGUSTA, GA 30901 USA SN 1073-2322 J9 SHOCK JI Shock PD DEC PY 2000 VL 14 IS 6 BP 610 EP 615 DI 10.1097/00024382-200014060-00007 PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 390NC UT WOS:000166301600007 PM 11131910 ER PT J AU Redline, S Tishler, PV AF Redline, S Tishler, PV TI The genetics of sleep apnea SO SLEEP MEDICINE REVIEWS LA English DT Review DE genetic epidemiology; heritability; sleep apnea ID CENTRAL HYPOVENTILATION SYNDROME; RECEPTOR TYROSINE KINASE; HYPERCAPNIC VENTILATORY RESPONSES; OBSTRUCTIVE PULMONARY-DISEASE; HYPOPNEA SYNDROME; RET PROTOONCOGENE; KNOCKOUT MICE; BREATHING DISTURBANCES; HIRSCHSPRUNGS-DISEASE; FAMILIAL AGGREGATION AB Obstructive sleep apnea hypopnea syndrome (OSAHS) is a complex chronic condition that is undoubtedly influenced by multiple factors. Accumulating data suggest that there are strong genetic underpinnings for this condition. It has been estimated that approximately 40% of the variance in the apnea hypopnea index (AHI) may be explained by familial factors. It is likely that genetic factors associated with craniofacial structure, body fat distribution and neural control of the upper airway muscles interact to produce the OSAHS phenotype. Although the role of specific genes that influence the development of OSAHS have not yet been identified, current research in rodents suggest that several genetic systems may be important. In this chapter, we shall first define the OSAHS phenotype, and then review the evidence that suggests an underlying genetic basis of OSAHS, the risk factors for OSAHS that may be inherited, and potential candidate genes. (C) 2000 Harcourt Publishers Ltd. C1 Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Redline, S (reprint author), Rainbow Babies & Childrens Hosp, 11100 Euclid Ave, Cleveland, OH 44106 USA. NR 115 TC 68 Z9 71 U1 2 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD DEC PY 2000 VL 4 IS 6 BP 583 EP 602 DI 10.1053/smrv.2000.0120 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 403LE UT WOS:000167042700007 ER PT J AU White, WM Tearney, GJ Pilch, BZ Fabian, RL Anderson, RR Gaz, RD AF White, WM Tearney, GJ Pilch, BZ Fabian, RL Anderson, RR Gaz, RD TI A novel, noninvasive imaging technique for intraoperative assessment of parathyroid glands: Confocal reflectance microscopy SO SURGERY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-Association-of-Endocrine-Surgeons CY MAY 22-25, 2000 CL LONDON, ENGLAND SP Amer Assoc Endocrine Surgeons ID SCANNING LASER OPHTHALMOSCOPE; IN-VIVO; PRIMARY HYPERPARATHYROIDISM; SURGICAL-MANAGEMENT; STROMAL FAT; HUMAN SKIN; HYPERPLASIA; DISEASE; HORMONE AB Background. Successful surgical management of primary hyperparathyroidism requires the ability to identify and distinguish normal from abnormal parathyroid tissue. Microscopic pathologic confirmation often helps with the diagnoses and decisions regarding the extent of parathyroid resection. Confocal reflectance microscopy (CRM) is an optical method of noninvasively imaging tissue without fixation, sectioning, and staining as in standard histopathology. The goal of this study was to determine if CRM imaging could be used to distinguish normal from diseased parathyroid tissue intraoperatively. Methods. In this study, 44 parathyroid glands from 21 patients undergoing operations for primary hyperparathyroidism were imaged immediately after excision. CRM images were compared with conventional hematoxylin-and-eosin stained sections obtained from the same gland. The percentage area occupied by fat cells was calculated in images of both normal and diseased glands. Results, Characteristic microscopic features of parathyroid glands were distinguishable by CRM and correlated well with, histopathology. The stromal fat content of normal and diseased glands could easily be determined. The percentage area occupied by fat cells differed significantly (P < .00001) in normal glands (average, 23.0% +/- 10.9%) and adenomatous glands (average, 0.4% +/- 0.7%). Conclusions. CRM imaging rapidly revealed microscopic features that reliably differentiated normal and diseased parathyroid glands. The success of this preliminary ex vivo study promotes interest in further development of an in situ probe for in vivo clinical diagnostic use. C1 Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Gaz, RD (reprint author), Massachusetts Gen Hosp, Ctr Ambulatory Care, Room 716,15 Parkman St, Boston, MA 02114 USA. NR 25 TC 22 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 2000 VL 128 IS 6 BP 1088 EP 1100 DI 10.1067/msy.2000.111190 PG 13 WC Surgery SC Surgery GA 381RC UT WOS:000165776000056 PM 11114647 ER PT J AU Carlin, JB Ryan, LM Harvey, EA Holmes, LB AF Carlin, JB Ryan, LM Harvey, EA Holmes, LB TI Anticonvulsant teratogenesis 4: Inter-rater agreement in assessing minor physical features related to anticonvulsant therapy SO TERATOLOGY LA English DT Article ID OBSERVER AGREEMENT; PREDICTIVE VALUE; KAPPA; MALFORMATIONS; ANOMALIES; NEWBORN AB Background: We report on inter-rater agreement in the assessment of newborn infants with respect to a range of minor physical features in a cohort study of the fetal effects of maternal anticonvulsant use during pregnancy. Methods: Infants from three groups (exposed to anticonvulsants, seizure history but no medication exposure, and unexposed controls) were examined by both a pediatrician/teratologist, who was blinded with respect to the mother's exposure status, and an unblinded research assistant. Agreement on assessments for selected anomalies associated with anticonvulsant therapy was measured by kappa-statistics, as well as by more sensitive log-linear modeling techniques, which allow examination of possible covariate effects on the strength of agreement. Although the physician and research assistant agreed on a high proportion of cases (80-90%), kappa values were modest (0.2-0.5), partly because of the low prevalence of the anomalies considered. To explore how agreement varies within subgroups, we used recently developed methods for studying agreement based on log-linear models. Results: Log-linear modeling indicated that there was substantial variation in pattern of agreement between different individual research assistants but that other factors (e.g., exposure category, sex, and birthweight) did not appear to be related to agreement. Our results suggest that research assistants with more experience showed the highest degree of agreement with the physicians. Conclusions: Our results have implications for both clinical practice and epidemiologic research and underline the importance of thorough training of staff in the definitions to be used and also the need for multiple independent assessments of these subtle anomalies. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Royal Childrens Hosp, Res Inst, Clin Epidemiol & Biostat Unit, Parkville, Vic 3052, Australia. Univ Melbourne, Royal Melbourne Hosp, Dept Paediat, Parkville, Vic 3052, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Ryan, LM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Carlin, John/B-3492-2012 OI Ryan, Louise/0000-0001-5957-2490; Carlin, John/0000-0002-2694-9463 FU NCI NIH HHS [CA48061]; NINDS NIH HHS [NS24125] NR 23 TC 12 Z9 12 U1 1 U2 1 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 DEC PY 2000 VL 62 IS 6 BP 406 EP 412 DI 10.1002/1096-9926(200012)62:6<406::AID-TERA7>3.0.CO;2-E PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 380DH UT WOS:000165683000007 PM 11091362 ER PT J AU Adams, MR Fisher, DM Dumont, LJ Dzik, WH Heaton, WA AF Adams, MR Fisher, DM Dumont, LJ Dzik, WH Heaton, WA TI Detecting failed WBC-reduction processes: computer simulations of intermittent and continuous process failure SO TRANSFUSION LA English DT Article AB BACKGROUND: By regulation, ongoing process control of WBC-reduced processes is performed on 1 percent of WBC-reduced components, typically four to five samples per month. However, prospective study of the power of this small sample has been difficult. Using computer-generated "residual WBC" distributions, sample size sensitivity to continuous or intermittent WBC-reduction failure was examined. STUDY DESIGN AND METHODS: Populations of log-normally distributed values (mean +/- SD, 4.5 +/- 0.5; n = 10(5)) were generated. Continuous failure (log-normality maintained) was simulated by incrementally increasing the population mean or its SD. Intermittent failure (bimodal distributions with discrete subpopulations of WBCs > the FDA cutoff) was simulated by admiring increasing percentages of secondary outlier populations. Sample sizes of 4 to 60 were examined (500 repetitions each) for their power to detect drift or failure by standard control criteria. RESULTS: Normally distributed low variance failure was easily detected by comparison of the mean of four samples to an upper control limit (95% confidence of detecting 2% failure). However, 40 samples were required to detect > 5 percent intermittent (bimodal) failure or high variance failure with 90-percent confidence, and only if individual WBC values were compared to cutoff. CONCLUSION: Sampling error limits the detection of high variance or bimodal distributions. While the mean of a small sample is highly sensitive to shifts in a low-variance normal distribution, the detection of a high-variance bimodal population requires a large number of individual values compared to cutoff. Therefore, the number of samples required for confident failure detection depends on both the nature of the underlying distribution and the interpretive criteria. Further research is necessary to determine the true distributions of WBC-reduction process failure, as well as clinically relevant quality limits. C1 Univ Calif San Francisco, Dept Med Nephrol, San Francisco, CA 94143 USA. Blood Ctr Pacific, San Francisco, CA USA. COBE BCT Inc, Lakewood, CO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Adams, MR (reprint author), Univ Calif San Francisco, Dept Med Nephrol, HSE 672,513 Parnassus Ave, San Francisco, CA 94143 USA. RI Dumont, Larry/B-3994-2011; Selogie, Eileen/L-3628-2016 OI Dumont, Larry/0000-0002-1715-0748; NR 8 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2000 VL 40 IS 12 BP 1427 EP 1433 DI 10.1046/j.1537-2995.2000.40121427.x PG 7 WC Hematology SC Hematology GA 389DW UT WOS:000166224200003 PM 11134560 ER PT J AU Labow, BI Souba, WW AF Labow, BI Souba, WW TI Glutamine SO WORLD JOURNAL OF SURGERY LA English DT Review ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; SYNTHETASE GENE-EXPRESSION; AMINO-ACID-METABOLISM; SKELETAL-MUSCLE CELLS; PROTEIN-SYNTHESIS; ENDOTHELIAL-CELLS; SMALL-INTESTINE; DOUBLE-BLIND; INTRACELLULAR GLUTAMINE AB Relatively little was known about glutamine metabolism until the 1930s, when Sir Hans Krebs first demonstrated glutamine hydrolysis apd biosynthesis in the kidney. Subsequent studies by Rose in 1938 demonstrated that glutamine is a nonessential (dispensable) amino acid, as it can be readily synthesized de novo in virtually all tissues in the body. Because the body has the capacity to synthesize considerable quantities of glutamine, it has been assumed that glutamine is not required in the diet. However, this amino acid becomes quite depleted during the course of a catabolic insult such as injury or infection, indicating that the ability of glutamine production to meet demands during a variety of surgical illnesses is impaired. In states of health, the assumption that glutamine is not required in the diet is probably valid, although it is difficult to test the hypothesis, as glutamine is present in virtually all dietary proteins. Most naturally occurring food proteins contain 4% to 8% of their amino acid residues as glutamine; therefore less than 10 g of dietary glutamine is likely to be consumed daily by the average person. In contrast to this usual dietary availability, studies in stressed patients indicate that considerably larger amounts of glutamine (20-40 g/day) may be necessary to maintain glutamine homeostasis. Thus from a nutritional standpoint, glutamine may be thought of as a drug as well as a nutrient. This paper reviews the physiology and biochemistry of glutamine with an emphasis on its metabolism in surgical illnesses and its role as a conditionally essential amino acid. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA 02115 USA. RP Souba, WW (reprint author), Penn State Coll Med, Dept Surg, H051,500 Univ Dr, Hershey, PA 17003 USA. NR 125 TC 102 Z9 112 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD DEC PY 2000 VL 24 IS 12 BP 1503 EP 1513 PG 11 WC Surgery SC Surgery GA 386XE UT WOS:000166089500009 PM 11193715 ER PT J AU Terada, S Sato, M Sevy, A Vacanti, JP AF Terada, S Sato, M Sevy, A Vacanti, JP TI Tissue engineering in the twenty-first century SO YONSEI MEDICAL JOURNAL LA English DT Article DE cell; culture; biology; polymer; biodegradation; liver; intestine; heart; finger; bone; cartilage; capillary ID BIODEGRADABLE POLYMER SCAFFOLDS; NATIVE SMALL-BOWEL; HEPATOCYTE TRANSPLANTATION; HEPATOTROPHIC STIMULATION; INTESTINE; ANASTOMOSIS; MODEL AB In the 20(th) century, free tissue transfers have been successfully introduced using microvascular anastomosis techniques. Transplants not only include whole organs such as the kidney, liver and lung, but also bone, muscle and skin. However, there are a limited number of organs available for transplantation. This leads to the patient not only suffering from the malfunctioning tissue or organ, but also from the psychological trauma of an indefinite waiting period. The rapidly evolving field of tissue engineering is beginning to have an impact on free tissue transfers including organ. Small biopsy specimens can be grown into a large number of cells. These cultured cells can then be seeded onto biodegradable polymers, which serve several purposes. Firstly, the polymers function as a cell delivery system that enables the transplantation of a large numbers of cells into an organism. Secondly, they create a three-dimensional space for cell growth and serve as a template, thereby providing a structure for the extracellular matrix. These approaches have been demonstrated as practical strategies for the reconstruction of many tissues such as the liver, intestines, heart valve leaflets, bone and cartilage. C1 Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med,Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Harvard Univ, Dept Surg, Massachusetts Gen Hosp, Sch Med,Ctr Innovat Minimally Invas Therapy, Warren 11,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 24 Z9 37 U1 0 U2 1 PU YONSEI UNIV COLLEGE MEDICINE PI SEOUL PA C/O KYUN0-IL IM, M.D., PH.D, SHINCHON DONG 134, SEODAEMOON KU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 J9 YONSEI MED J JI Yonsei Med. J. PD DEC PY 2000 VL 41 IS 6 BP 685 EP 691 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 396LK UT WOS:000166637700002 PM 11204820 ER PT J AU Lindholm, CK Frantz, JD Shoelson, SE Welsh, M AF Lindholm, CK Frantz, JD Shoelson, SE Welsh, M TI Shf, a Shb-like adapter protein, is involved in PDGF-alpha-receptor regulation of apoptosis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Shf; Shb; PDGF-receptor; PDGF; apoptosis; cell signaling ID TYROSINE KINASE; HOMOLOGY-2 AB Recent work has implicated the importance of adapter proteins in signal transduction. To identify homologues of the previously identified adapter protein Shb, database searches were performed. A Shb-like protein was found which we have named Shf. Shf contains an SH2 domain and four putative tyrosine phosphorylation sites and is mainly expressed in skeletal muscle, brain, liver, prostate, testis, ovary, small intestine, and colon. The SH2 domain of Shf bound to the PDGF-alpha -receptor at tyrosine-720, but not to the PDGF-beta -receptor in PAE cells. Pervanadate induced tyrosine phosphorylation of Shf in NIH3T3 fibroblasts overexpressing this protein, whereas PDGF-AA alone had no detectable effect. NIH3T3 cells overexpressing Shf displayed significantly lower rates of apoptosis than control cells in the presence of PDGF-AA Our findings suggest a role for the novel adapter Shf in PDGF-receptor signaling and regulation of apoptosis. (C) 2000 Academic Press. C1 Univ Uppsala, Dept Med Cell Biol, S-75123 Uppsala, Sweden. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Welsh, M (reprint author), Univ Uppsala, Dept Med Cell Biol, Box 571, S-75123 Uppsala, Sweden. OI Welsh, Michael/0000-0002-5467-9755 NR 13 TC 23 Z9 26 U1 0 U2 2 PU ACADEMIC PRESS INC 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 NOV 30 PY 2000 VL 278 IS 3 BP 537 EP 543 DI 10.1006/bbrc.2000.3847 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 380KW UT WOS:000165701900007 PM 11095946 ER PT J AU Aballay, A Yorgey, P Ausubel, FM AF Aballay, A Yorgey, P Ausubel, FM TI Salmonella typhimurium proliferates and establishes a persistent infection in the intestine of Caenorhabditis elegans SO CURRENT BIOLOGY LA English DT Article ID VIRULENCE; PATHOGENESIS; MODEL AB Genetic analysis of host-pathogen interactions has been hampered by the lack of genetically tractable models of such interactions. We showed previously that the human opportunistic pathogen Pseudomonas aeruginosa kills Caenorhabditis elegans, that P. aeruginosa and C. elegans genes can be identified that affect this killing, and that most of these P. aeruginosa genes are also important for mammalian pathogenesis. Here, we show that Salmonella typhimurium as well as other Salmonella enterica serovars including S. enteritidis and S. dublin can also kill C. elegans. When C. elegans is placed on a lawn of S. typhimurium, the bacteria accumulate in the lumen of the worm intestine and the nematodes die over the course of several days. This killing requires contact with live bacterial cells. The worms die with similar kinetics when placed on a lawn of S. typhimurium for a relatively short time (3-5 hours) before transfer to a lawn of E. coli. After the transfer to E. coli, a high titer of S. typhimurium persists in the C. elegans intestinal lumen for the rest of the worms' life. Furthermore, feeding for 5 hours on a 1:1000 mixture of S. typhimurium and E. coli followed by transfer to 100% E. coli, also led to death after several days. This killing correlated with an increase in the titer of S. typhimurium in the C. elegans lumen, which reached 10,000 bacteria per worm. These data indicate that, in contrast to P. aeruginosa, a small inoculum of S. typhimurium can proliferate in the C. elegans intestine and establish a persistent infection. S. typhimurium mutated in the PhoP/PhoQ signal transduction system caused significantly less killing of C. elegans. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM ausubel@frodo.mgh.harvard.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 13 TC 202 Z9 206 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD NOV 30 PY 2000 VL 10 IS 23 BP 1539 EP 1542 DI 10.1016/S0960-9822(00)00830-7 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 382JK UT WOS:000165819000026 PM 11114525 ER PT J AU Ready, JE Keel, SB Bramson, RT Hornicek, FJ Mark, EJ Mankin, KP AF Ready, JE Keel, SB Bramson, RT Hornicek, FJ Mark, EJ Mankin, KP TI An 11-day-old boy with an osteolytic tibial lesion - Fibrous dysplasia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BONE C1 Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ready, JE (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 30 PY 2000 VL 343 IS 22 BP 1634 EP 1638 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 377JT UT WOS:000165511000009 ER PT J AU Bernardo, MVP Ibrahim, JG AF Bernardo, MVP Ibrahim, JG TI Group sequential designs for cure rate models with early stopping in favour of the null hypothesis SO STATISTICS IN MEDICINE LA English DT Article ID MIXTURE-MODELS; CLINICAL-TRIALS; REGRESSION; POWER; TESTS; RANK AB Ewell and Ibrahim derived the large sample distribution of the logrank statistic under general local alternatives. Their asymptotic results enable us to extend several group sequential designs which allow for early stopping in favour of the null hypothesis to the setting in which the cure rate model is appropriate. In particular, we derive stopping rules for the cure rate model using conditional power, predictive power and repeated confidence intervals methods. We illustrate the methods proposed using a hypothetical phase III clinical trial which is typical for melanoma studies. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Bernardo, MVP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 3 Z9 3 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 2000 VL 19 IS 22 BP 3023 EP 3035 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 373LC UT WOS:000165290100001 ER PT J AU El-Serag, HB Mason, AC AF El-Serag, HB Mason, AC TI Risk factors for the rising rates of primary liver cancer in the United States SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CHRONIC HEPATITIS-C; HEPATOCELLULAR-CARCINOMA; INTERFERON THERAPY AB Background: A recent increase in the incidence of hepatocellular carcinoma was reported in the United States. The cause of this witnessed rise remains unknown. Methods: We examined the temporal changes in both age-specific and age-standardized hospitalization rates of primary liver cancer associated with hepatitis C, hepatitis B, and alcoholic cirrhosis in the Department of Veterans Affairs Medical Center's Patient Treatment File. Results: A total of 1605 patients were diagnosed with primary liver cancer between 1993 and 1998. The over all age-adjusted proportional hospitalization rate for primary liver cancer increased from 36.4 per 100 000 (95% confidence interval [CI], 34.0-38.9) between 1993 and 1995 to 47.5 per 100 000 (95% CI, 44.6-50.1) between 1996 and 1998. There was a 3-fold increase in the age-adjusted rates for primary liver cancer associated with hepatitis C virus, from 2.3 per 100 000 (95%, CI, 1.8-3.0) between 1993 and 1995 to 7.0 per 100 000 (95% CI, 5.9-8.1) between 1996 and 1998. Concomitant with this rise, the age-specific rates for primary liver cancer associated with hepatitis C also shifted toward younger patients. During the same periods, the age-adjusted rates for primary liver cancer associated with either hepatitis B virus (2.2 vs 3.1 per 100 000) or alcoholic cirrhosis (8.4 vs 9.1 per 100 000) remained stable. The rates for primary liver cancer without risk factors also remained without a statistically significant change, from 17.5 (95% CI, 15.8-19.1) between 1993 and 1995 to 19.0 per 100 000 (95% CI, 17.3-20.7) between 1996 and 1998. Conclusions: Hepatitis C virus infection accounts for most of the increase in the number of cases of primary liver cancer among US veterans. The rates of primary liver cancer associated with alcoholic cirrhosis and hepatitis B virus infection have remained stable. C1 Houston Veterans Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Veterans Affairs Med Ctr, Hlth Serv Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ New Mexico, Dept Gastroenterol, Albuquerque, NM 87131 USA. RP El-Serag, HB (reprint author), Houston VA Med CTr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 16 TC 264 Z9 273 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 NOV 27 PY 2000 VL 160 IS 21 BP 3227 EP 3230 DI 10.1001/archinte.160.21.3227 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 376KL UT WOS:000165456700007 PM 11088082 ER PT J AU Neuberger, J Ubel, PA AF Neuberger, J Ubel, PA TI Finding a place for public preferences in liver allocation decisions SO TRANSPLANTATION LA English DT Article ID HEALTH-CARE; PRIORITY; TRANSPLANTATION AB Over the last decade there have been major advances in all aspects of liver transplantation with the consequence that the number of patients who could benefit from the procedure is increasing. As a result, the number of patients listed for liver transplantation is growing while the donor pool is remaining constant or even falling. The effect of this donor shortage is seen clearly both in Europe and in North America. For example, in North America data from UNOS shows that between 1988 and 1997 the number of cadaveric donor liver transplants rose from 1713 to 4100. The number of patients waiting for transplant rose over the same time from 616 to 9647. This shortage of organs has tragic consequences. Although the proportion of patients dying on the waiting list is falling, the number of patients dying on the liver transplant waiting list increased from 196 to 1129 over this same period of time. C1 Queen Elizabeth Hosp, Liver Unit, Birmingham B15 2TH, W Midlands, England. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Neuberger, J (reprint author), Queen Elizabeth Hosp, Liver Unit, Birmingham B15 2TH, W Midlands, England. NR 13 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2000 VL 70 IS 10 BP 1411 EP 1413 DI 10.1097/00007890-200011270-00001 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 376XK UT WOS:000165481900001 PM 11118080 ER PT J AU Pekary, AE Meyerhoff, JL Sattin, A AF Pekary, AE Meyerhoff, JL Sattin, A TI Electroconvulsive seizures modulate levels of thyrotropin releasing hormone and related peptides in rat hypothalamus, cingulate and lateral cerebellum SO BRAIN RESEARCH LA English DT Article DE depression; limbic system; high-pressure liquid chromatography; radioimmunoassay ID INHIBITING FACTOR; HIPPOCAMPAL-NEURONS; KINDLED SEIZURES; GENE-EXPRESSION; PREPRO-TRH; BRAIN; INCREASES; CORTEX; PREPRO-TRH-(160-169); MECHANISMS AB We have studied the neuroanatomic extent of electroconvulsive (ECS)-responsive prepro-TRH and TRH-related gene expression and its possible interaction with forced swimming. Young adult male Wistar rats were treated in a 2X2 Latin square protocol of swimming, no swimming, three daily ECS or sham ECS. Sixteen different brain regions were dissected and immunoreactivity measured for TRH (pGlu-His-Pro-NH2); TRH-Gly, a TRH precursor; Ps4, a prepro-TRH-derived TRH-enhancing decapeptide, and EEP (pGlu-Glu-Pro-NH2). ECS, in addition to elevating TRH-immunoreactivity (TRH-IR), TRH-Gly-IR, Ps4-IR and EEP-IR levels in the limbic regions, as we have previously reported, also significantly increased Ps4-IR levels in hypothalamus, posterior cingulate and lateral cerebellum, and increased TRH-Gly-IR levels in hypothalamus. Interestingly, the combination of ECS and swimming significantly reduced the levels of TRH-Gly-IR in the anterior cingulate compared to the sham ECS-no swim group. The combined use of high-pressure liquid chromatography and the EEP radioimmunoassay (RIA) revealed that pGlu-Tyr-Pro-NH2 and/or pGlu-Phe-Pro-NH2 occur in amygdala, anterior cingulate, frontal cortex, entorhinal cortex, lateral cerebellum and striatum and make a substantial contribution to the EEP-IR and TRH-IR. We conclude that ECS can alter the expression and secretion of TRH-related peptides in the hypothalamus, cingulate and lateral cerebellum. Such effects have not previously been reported in these limbic and extra-limbic regions which are increasingly implicated in the autonomic, behavioral and volitional changes which accompany severe depression and its treatment. (C) 2000 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. Walter Reed Army Inst Res, Div Neurosci, Dept Neuroendocrinol & Neurochem, Washington, DC 20307 USA. RP Pekary, AE (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. NR 47 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 24 PY 2000 VL 884 IS 1-2 BP 174 EP 183 DI 10.1016/S0006-8993(00)02930-9 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 381EK UT WOS:000165749200019 PM 11082499 ER PT J AU Wu, G MacKenzie, R Durda, PJ Tsang, P AF Wu, G MacKenzie, R Durda, PJ Tsang, P TI The binding of a glycoprotein 120 V3 loop peptide to HIV-1 neutralizing antibodies - Structural implications SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PANCREATIC TRYPSIN-INHIBITOR; NUCLEAR-MAGNETIC-RESONANCE; 2-DIMENSIONAL NMR-SPECTROSCOPY; SURFACE-PLASMON RESONANCE; C-13 RELAXATION-TIMES; SOLUTION CONFORMATIONS; SYNTHETIC PEPTIDES; ENVELOPE PROTEIN; MONOCLONAL-ANTIBODIES AB The structural and antigenic properties of a peptide ("CRK") derived from the V3 loop of HIV-1 gp120 protein were studied using NMR and SPR techniques. The sequence of CRK corresponds to the central portion of the V3 loop containing the highly conserved ''GPGR'' residue sequence. Although the biological significance of this conserved sequence is unknown, the adoption of conserved secondary structure (type II beta -turn) in this region has been proposed. The tendency of CRK (while free or conjugated to protein), to adopt such structure and the influence of such structure upon CRK antigenicity were investigated by NMR and SPR, respectively. Regardless of conjugation, CRK is conformationally averaged in solution but a weak tendency of the CRK "GPGR'' residues to adopt a beta -turn conformation was observed after conjugation. The influence of GPGR structure upon CRK antigenicity was investigated by measuring the affinities of two cognate antibodies: "5023A" and "5025A," for CRK, protein-conjugated CRK and gp120 protein. Each antibody bound to all the antigens with nearly the same affinity. From these data, it appears that: (a) antibody binding most likely involves an induced fit of the peptide and (b) the gp120 V3 loop is probably conformationally heterogeneous. Since 5023A and 5025A are HIV-1 neutralizing antibodies, neutralization in these cases appears to be independent of adopted GPGR beta -turn structure. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Tsang, P (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. FU NIGMS NIH HHS [GM-47013] NR 68 TC 23 Z9 24 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 2000 VL 275 IS 47 BP 36645 EP 36652 DI 10.1074/jbc.M005369200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700028 PM 10967109 ER PT J AU Xu, W Longo, FJ Wintermantel, MR Jiang, XY Clark, RA DeLisle, S AF Xu, W Longo, FJ Wintermantel, MR Jiang, XY Clark, RA DeLisle, S TI Calreticulin modulates capacitative Ca2+ influx by controlling the extent of inositol 1,4,5-trisphosphate-induced Ca2+ store depletion SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS-LAEVIS OOCYTES; INTRACELLULAR CALCIUM; GENE-EXPRESSION; BINDING PROTEIN; RECEPTOR; TRISPHOSPHATE; ACTIVATION; OVEREXPRESSION; MESSENGER; CURRENTS AB Calreticulin (CRT) is a highly conserved Ca2+-binding protein that resides in the lumen of the endoplasmic reticulum (ER). We overexpressed CRT in Xenopus oocytes to determine how it could modulate inositol 1,4-5-trisphosphate (InsP(3))-induced Ca2+ influx. Under conditions where it did not affect the spatially complex elevations in free cytosolic Ca2+ concentration ([Ca2+](i)) due to InsP(3)-induced Ca2+ release, overexpressed CRT decreased by 46% the Ca2+-gated Cl- current due to Ca2+ influx. Deletion mutants revealed that CRT requires its high capacity Ca2+-binding domain to reduce the elevations of [Ca2+](i), due to Ca2+ influx. This functional domain was also required for CRT to attenuate the InsP(3)-induced decline in the free Ca2+ concentration within the ER lumen ([Ca2+](ER)), as monitored with a "chameleon" indicator. Our data suggest that by buffering [Ca2+](ER) near resting levels, CRT may prevent InsP(3) from depleting the intracellular stores sufficiently to activate Ca2+ influx. C1 Univ Maryland, Sch Med, Vet Affairs Med Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Iowa, Coll Med, Dept Anat, Iowa City, IA 52242 USA. S Texas Vet Hlth Care Syst, Dept Med, San Antonio, TX 78230 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78230 USA. RP DeLisle, S (reprint author), Univ Maryland, Dept Med, Vet Affairs Med Ctr 3B185, 10 N Greene St, Baltimore, MD 21201 USA. NR 55 TC 39 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 2000 VL 275 IS 47 BP 36676 EP 36682 DI 10.1074/jbc.M002041200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700033 PM 10973951 ER PT J AU Ha, TU Segev, DL Barbie, D Masiakos, PT Tran, TT Dombkowski, D Glander, M Clarke, TR Lorenzo, HK Donahue, PK Maheswaran, S AF Ha, TU Segev, DL Barbie, D Masiakos, PT Tran, TT Dombkowski, D Glander, M Clarke, TR Lorenzo, HK Donahue, PK Maheswaran, S TI Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR E2F-1; U343 ASTROCYTOMA-CELLS; D-DEPENDENT KINASES; RETINOBLASTOMA PROTEIN; CYCLE ARREST; II RECEPTOR; P16 GENE; RECOMBINANT ADENOVIRUS; SEXUAL DEVELOPMENT; TGF-BETA AB Mullerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Mullerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers, MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor pie through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein, Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that pig is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, WRN 1024,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA17393, T32-CA-71345]; NICHD NIH HHS [HD32112] NR 63 TC 65 Z9 67 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 24 PY 2000 VL 275 IS 47 BP 37101 EP 37109 DI 10.1074/jbc.M005701200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 378GY UT WOS:000165577700090 PM 10958795 ER PT J AU Buxbaum, JD Lilliehook, C Chan, JY Go, RCP Bassett, SS Tanzi, RE Wasco, W Blacker, D AF Buxbaum, JD Lilliehook, C Chan, JY Go, RCP Bassett, SS Tanzi, RE Wasco, W Blacker, D TI Genomic structure, expression pattern, and chromosomal localization of the human calsenilin gene: no association between an exonic polymorphism and Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; calsenilin gene; presenilin-1 and-2 ID PRESENILINS; PROTEIN; ONSET; PROTEOLYSIS AB Calsenilin is a recently-identified member of the neuronal calcium sensor family. Like other members of this family, it is found in the brain and binds calcium. Calsenilin was discovered by virtue of its interaction with both presenilin-1 and -2, proteins that are involved in the etiology of Alzheimer's disease. Because calsenilin may play a role in Alzheimer's disease and other disease with alterations in calcium homeostasis, we characterized the human gene. The gene, which we localized to chromosome 2, extends over a region of at least 74 kb and includes nine exons. Interestingly, the ninth exon of calsenilin contains a highly polymorphic CA repeat, adjacent to the stop codon. In a study of Alzheimer patients and their unaffected siblings, there was no evidence of association of AD with any calsenilin allele. This CA repeat will be useful for linkage and linkage disequilibrium studies to determine whether calsenilin variants contribute to risk in other diseases. (C) 2000 Published by Elsevier Science Ireland Ltd. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA 02129 USA. RP Buxbaum, JD (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, 1 Gustave L Levy Pl,Box 1230, New York, NY 10029 USA. OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG05138, AG15801]; NIMH NIH HHS [MH60009] NR 15 TC 3 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 24 PY 2000 VL 294 IS 3 BP 135 EP 138 DI 10.1016/S0304-3940(00)01553-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 375KC UT WOS:000165397300001 PM 11072133 ER PT J AU Scully, R Livingston, DM AF Scully, R Livingston, DM TI In search of the tumour-suppressor functions of BRCA1 and BRCA2 SO NATURE LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; DNA-DAMAGE; MEIOTIC CELLS; GENE BRCA1; STRAND; REPAIR; BREAST; ATM; PHOSPHORYLATION; PRODUCT AB Hereditary breast and ovarian cancer syndromes can be caused by loss-of-function germline mutations in one of two tumour-suppressor genes, BRCA1 and BRCA2 (ref. 1). Each gene product interacts with recombination/DNA repair proteins in pathways that participate in preserving intact chromosome structure. However, it is unclear to what extent such functions specifically suppress breast and ovarian cancer. Here we analyse what is known of BRCA gene function and highlight some unanswered questions in the field. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [K01 CA079576, K01 CA079576-01] NR 42 TC 442 Z9 466 U1 2 U2 50 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 23 PY 2000 VL 408 IS 6811 BP 429 EP 432 DI 10.1038/35044000 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 375YD UT WOS:000165429800037 PM 11100717 ER PT J AU Ranganathan, R Cannon, SC Horvitz, HR AF Ranganathan, R Cannon, SC Horvitz, HR TI MOD-1 is a serotonin-gated chloride channel that modulates locomotory behaviour in C. elegans SO NATURE LA English DT Article ID XENOPUS-LAEVIS OOCYTES; NICOTINIC ACETYLCHOLINE-RECEPTOR; CAENORHABDITIS-ELEGANS; MEDICINAL LEECH; ION CURRENTS; NEURONS; EXPRESSION; MUTATIONS; GENETICS; SUBUNIT AB The neurotransmitter and neuromodulator serotonin (5-HT) functions by binding either to metabotropic G-protein-coupled receptors (for example, 5-HT1, 5-HT2, 5-HT4 to 5-HT7), which mediate 'slow' modulatory responses through numerous second messenger pathways(1), or to the ionotropic 5-HT3 receptor, a non-selective cation channel that mediates 'fast' membrane depolarizations(2). Here we report that the gene mod-1 (for modulation of locomotion defective) from the nematode Caenorhabditis elegans encodes a new type of ionotropic 5-HT receptor, a 5-HT-gated chloride channel. The predicted MOD-1 protein is similar to members of the nicotinic acetylcholine receptor family of ligand-gated ion channels, in particular to GABA (gamma -aminobutyric acid)- and glycine-gated chloride channels. The MOD-1 channel has distinctive ion selectivity and pharmacological properties. The reversal potential of the MOD-1 channel is dependent on the concentration of chloride ions but not of cations. The MOD-1 channel is not blocked by calcium ions or 5-HT3a-specific antagonists but is inhibited by the metabotropic 5-HT receptor antagonists mianserin and methiothepin. mod-1 mutant animals are defective in a 5-HT-mediated experience-dependent behaviour(3) and are resistant to exogenous 5-HT, confirming that MOD-1 functions as a 5-HT receptor in vivo. C1 MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP MIT, Howard Hughes Med Inst, Dept Biol, Room 68-425,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM horvitz@mit.edu NR 30 TC 126 Z9 136 U1 3 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 23 PY 2000 VL 408 IS 6811 BP 470 EP 475 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 375YD UT WOS:000165429800048 PM 11100728 ER PT J AU Epstein, AM Ayanian, JZ Keogh, JH Noonan, SJ Armistead, N Cleary, PD Weissman, JS David-Kasdan, JA Carlson, D Fuller, J Marsh, D Conti, RM AF Epstein, AM Ayanian, JZ Keogh, JH Noonan, SJ Armistead, N Cleary, PD Weissman, JS David-Kasdan, JA Carlson, D Fuller, J Marsh, D Conti, RM TI Racial disparities in access to renal transplantation - Clinically appropriate or due to underuse or overuse? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY ANGIOGRAPHY; REVASCULARIZATION PROCEDURES; SURGICAL-PROCEDURES; MEDICAL PROCEDURES; DISEASE; RACE; QUALITY; LIFE; CANDIDATES; RECIPIENTS AB Background: Despite abundant evidence of racial disparities in the use of surgical procedures, it is uncertain whether these disparities reflect racial differences in clinical appropriateness or overuse or underuse of care. Methods: We performed a literature review and used an expert panel to develop criteria for determining the appropriateness of renal transplantation for patients with end-stage renal disease. Using data from five states and the District of Columbia on patients who had started to undergo dialysis in 1996 or 1997, we selected a random sample of 1518 patients (age range, 18 to 54 years), stratified according to race and sex. We classified the appropriateness of patients as candidates for transplantation and analyzed data on rates of referral to a transplantation center for evaluation, placement on a waiting list, and receipt of a transplant according to race. Results: Black patients were less likely than white patients to be rated as appropriate candidates for transplantation according to appropriateness criteria based on expert opinion (71 blacks [9.0 percent] vs. 152 whites [20.9 percent]) and were more likely to have had incomplete evaluations (368 [46.5 percent] vs. 282 [38.8 percent], P<0.001 for the overall chi-square). Among patients considered to be appropriate candidates for transplantation, blacks were less likely than whites to be referred for evaluation, according to the chart review (90.1 percent vs. 98.0 percent, P=0.008), to be placed on a waiting list (71.0 percent vs. 86.7 percent, P=0.007), or to undergo transplantation (16.9 percent vs. 52.0 percent, P<0.001). Among patients classified as inappropriate candidates, whites were more likely than blacks to be referred for evaluation (57.8 percent vs. 38.4 percent), to be placed on a waiting list (30.9 percent vs. 17.4 percent), and to undergo transplantation (10.3 percent vs. 2.2 percent, P<0.001 for all three comparisons). Conclusions: Racial disparities in rates of renal transplantation stem from differences in clinical characteristics that affect appropriateness as well as from underuse of transplantation among blacks and overuse among whites. Reducing racial disparities will require efforts to distinguish their specific causes and the development of interventions tailored to address them. (N Engl J Med 2000;343:1537-44.) (C) 2000, Massachusetts Medical Society. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. CliGnosis, Boston, MA USA. Midatlantic Renal Coalit, Midlothian, VA USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Renal Network Upper Midwest, St Paul, MN USA. Network 8, Jackson, MS USA. So Calif Renal Dis Council, Hollywood, CA USA. RP Epstein, AM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. FU NIMH NIH HHS [F31 MH070201] NR 40 TC 373 Z9 374 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 23 PY 2000 VL 343 IS 21 BP 1537 EP U8 DI 10.1056/NEJM200011233432106 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 375PR UT WOS:000165410900006 PM 11087884 ER PT J AU Haber, D AF Haber, D TI Roads leading to breast cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ATM C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Haber, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 22 Z9 24 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 23 PY 2000 VL 343 IS 21 BP 1566 EP 1568 DI 10.1056/NEJM200011233432111 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 375PR UT WOS:000165410900011 PM 11087889 ER PT J AU Siegert, JL Rushton, JJ Sellers, WR Kaelin, WG Robbins, PD AF Siegert, JL Rushton, JJ Sellers, WR Kaelin, WG Robbins, PD TI Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAF(II)250 kinase activity SO ONCOGENE LA English DT Article DE cyclin D1; Rb; TAF(II)250; kinase ID RNA-POLYMERASE-II; SUSCEPTIBILITY GENE-PRODUCT; CELL-CYCLE; HISTONE DEACETYLASE; SP1-MEDIATED TRANSCRIPTION; REPRESSES TRANSCRIPTION; DIFFERENTIAL REGULATION; ESTROGEN-RECEPTOR; INITIATION-FACTOR; RB INTERACTS AB The retinoblastoma tumor suppressor protein has been shown to bind directly and inhibit a transcriptionally-important amino-terminal kinase domain of TATA-binding protein-associated factor TAF(II)250. Cyclin D1 also is able to associate! with the amino terminus of TAF(II)250 in a region, cry similar to or overlapping the Rb-binding site. In this study, we ha,le examined whether cyclin D1 affects the functional interaction between Rb and TAF(II)250. We observed that when cyclin D1 is coincubated with Rb and TAF(II)250, the ability of Rb to inhibit TAF(II)250 kinase activity is effectively blocked, However, cyclin D1 by itself has no apparent effect on TAF(II)250 kinase activity. We further found that the Rb-related protein p107 can inhibit TAF(II)250 kinase activity, and this inhibition is likewise alleviated by cyclin D1, Cyclin D1 prevents the kinase-inhibitory effect of an Rb mutant unable to bind to D-type cyclins, indicating that it is acting through its association with TAF(II)250 and not with Rb, However, we found no evidence of TAF(II)250-binding competition between Rb and cyclin D1 in vitro. The adenovirus ELA protein, which also binds to both Rb and TAF(II)250, exhibited a suppressive effect on Rb-mediated kinase inhibition similar to that seen with cyclin D1, Our results suggest a novel means by which cyclin D1 may be able to independently regulate the activity of Rb. C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Robbins, PD (reprint author), Univ New Mexico, Dept Mol Genet & Microbiol, Canc Res Ctr 125, Sch Med, Albuquerque, NM 87131 USA. FU PHS HHS [55227] NR 51 TC 16 Z9 16 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 23 PY 2000 VL 19 IS 50 BP 5703 EP 5711 DI 10.1038/sj.onc.1203966 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 376VP UT WOS:000165477700001 PM 11126356 ER PT J AU Huang, LL Sowa, Y Sakai, T Pardee, AB AF Huang, LL Sowa, Y Sakai, T Pardee, AB TI Activation of the p21(WAF1/CIP1) promoter independent of p53 by the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) through the Sp1 sites SO ONCOGENE LA English DT Article DE SAHA; p31 promoter; Sp1/Sp3 ID TRANSFORMED-CELL DIFFERENTIATION; WAF1/CIP1 GENE PROMOTER; TRANSCRIPTIONAL REPRESSION; N-COR; BINDING; COMPLEX; BETA; INDUCTION; INDUCERS; HOMOLOG AB Suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with high potency in inducing differentiation of cultured murine erythroleukemia cells. We have recently demonstrated that SAHA induces cell cycle arrest and apoptosis in human breast cancer cells, accompanied by up-regulation of the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1) via a p53-independent mechanism. In this study, we used p21 gene expression as a model system to elucidate the molecular mechanism(s) underlying SAHA-mediated gene activation. Treatment of human breast cancer cell line MICF7 cells with SAHA induced p21 mRNA as a consequence of an immediate-early gene activation. Moreover, SAHA activated the p21 promoter primarily through two Spl sites located at -82 and -69 relative to the transcription start site. Furthermore, Spl and Sp3 proteins were the major factors binding to the Spl site of the p21 promoter. However, SAHA did not alter their DNA binding activities, suggesting that SAHA mediates p21 promoter activity by a mechanism other than altering the DNA binding activities of Spl and Sp3, Further studies using the GAL4 luciferase assay system demonstrated that both GAL4-Sp1 and GAL4-Sp3 fusion proteins supported SAHA-mediated gene activation from a promoter driven by five GAL4 DNA binding sites, and that GAL4-Sp3 fusion protein,vas suppressive in the absence of SAHA treatment. Collectively, our results suggest that SAHA activates the p21 promoter through the Spl sites, and that both Spl and Sp3 proteins can mediate SAHA-induced gene activation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Kyoto Prefectural Univ Med, Dept Prevent Med, Kamigyo Ku, Kyoto 6028566, Japan. RP Pardee, AB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [R01CA61253] NR 41 TC 170 Z9 173 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 23 PY 2000 VL 19 IS 50 BP 5712 EP 5719 DI 10.1038/sj.onc.1203963 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 376VP UT WOS:000165477700002 PM 11126357 ER PT J AU Hilditch-Maguire, P Trettel, F Passani, LA Auerbach, A Persichetti, F MacDonald, ME AF Hilditch-Maguire, P Trettel, F Passani, LA Auerbach, A Persichetti, F MacDonald, ME TI Huntingtin: an iron-regulated protein essential for normal nuclear and perinuclear organelles SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE GENE-PRODUCT; EMBRYONIC LETHALITY; MUTANT HUNTINGTIN; CELL-LINES; WILD-TYPE; IN-VIVO; LOCALIZATION; HOMOLOG; BRAIN; IDENTIFICATION AB Huntington's; disease (HD), with its selective neuronal cell loss, is caused by an elongated glutamine tract in the huntingtin protein, To discover the pathways that are candidates for the protein's normal and/or abnormal function, we surveyed 19 classes of organelle in Hdh(ex4/5)/Hdh(ex4/5) knock-out compared with wild-type embryonic stem cells to identify any that might be affected by huntingtin deficiency, Although the majority did not differ, dramatic changes in six classes revealed that huntingtin's function is essential for the normal nuclear (nucleoli, transcription factor-speckles) and perinuclear membrane (mitochondria, endoplasmic reticulum, Golgi and recycling endosomes) organelles and for proper regulation of the iron pathway. Moreover, upmodulation by deferoxamine mesylate implicates huntingtin as an iron-response protein, However, excess huntingtin produced abnormal organelles that resemble the deficiency phenotype, suggesting the importance of huntingtin level to the protein's normal pathway, Thus, organelles that require huntingtin to function suggest roles for the protein in RNA biogenesis, trafficking and iron homeostasis to be explored in HD pathogenesis. C1 Massachusetts Gen Hosp, Mol Neurogenet Lab, Charlestown, MA 02129 USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, Dept Cell Biol, New York, NY 10016 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. OI trettel, flavia/0000-0002-7983-2955 FU NINDS NIH HHS [NS32765, NS16367]; Telethon [E.0087] NR 40 TC 138 Z9 140 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 NOV 22 PY 2000 VL 9 IS 19 BP 2789 EP 2797 DI 10.1093/hmg/9.19.2789 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 379BD UT WOS:000165620300002 PM 11092755 ER PT J AU Trettel, F Rigamonti, D Hilditch-Maguire, P Wheeler, VC Sharp, AH Persichetti, F Cattaneo, E MacDonald, ME AF Trettel, F Rigamonti, D Hilditch-Maguire, P Wheeler, VC Sharp, AH Persichetti, F Cattaneo, E MacDonald, ME TI Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells SO HUMAN MOLECULAR GENETICS LA English DT Article ID DISEASE GENE-PRODUCT; HUNTINGTONS-DISEASE; MUTANT HUNTINGTIN; IN-VIVO; PROTEINS; LOCALIZATION; EXPRESSION; PATHOLOGY; NUCLEAR; FAMILY AB Lengthening a glutamine tract in huntingtin confers a dominant attribute that initiates degeneration of striatal neurons in Huntington's disease (HD). To identify pathways that ave candidates for the mutant protein's abnormal function, we compared striatal cell lines established from wild-type and Hdh(Q111) knock-in embryos. Alternate versions of full-length huntingtin, distinguished by epitope accessibility, were localized to different sets of nuclear and perinuclear organelles involved in RNA biogenesis and membrane trafficking, However, mutant STHdh(Q111) cells also exhibited additional forms of the full-length mutant protein and displayed dominant phenotypes that did not mirror phenotypes caused by either huntingtin deficiency or excess. These phenotypes; indicate a disruption of striatal cell homeostasis by the mutant protein, via a mechanism that is separate front its normal activity. They also support specific stress pathways, including elevated p53, endoplasmic reticulum stress response and hypoxia, as potential players in HD. C1 Massachusetts Gen Hosp, Mol Neurogenet Lab, Charlestown, MA 02129 USA. Univ Milan, Inst Pharmacol Sci, I-20133 Milan, Italy. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. OI trettel, flavia/0000-0002-7983-2955; CATTANEO, ELENA/0000-0002-0755-4917 FU NINDS NIH HHS [NS32765, NS16367]; Telethon [E.0840] NR 45 TC 327 Z9 330 U1 0 U2 8 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 NOV 22 PY 2000 VL 9 IS 19 BP 2799 EP 2809 DI 10.1093/hmg/9.19.2799 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 379BD UT WOS:000165620300003 PM 11092756 ER PT J AU Catlin, DH Leder, BZ Ahrens, B Starcevic, B Hatton, CK Green, GA Finkelstein, JS AF Catlin, DH Leder, BZ Ahrens, B Starcevic, B Hatton, CK Green, GA Finkelstein, JS TI Trace contamination of over-the-counter androstenedione and positive urine test results for a nandrolone metabolite SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; 19-NORANDROSTERONE; EXCRETION AB Context Several anabolic steroids are sold over-the-counter (OTC) in the United States, and their production is not regulated by the US Food and Drug Administration. Reports have suggested that use of these supplements can cause positive urine test results for metabolites of the prohibited steroid nandrolone. Objectives To assess the content and purity of OTC androstenedione and to determine if androstenedione and 19-norandrostenedione administration causes positive urine test results for 19-norandrosterone, a nandrolone metabolite. Design Randomized controlled trial of androstenedione, open-label trial of 19-norandrostenedione, and mass spectrometry of androstenedione preparations, conducted between October 1998 and April 2000. Setting Outpatient facility of a university hospital. Participants A total of 41 healthy men aged 20 to 44 years. Intervention Participants were randomly assigned to receive oral androstenedione, 100 mg/d (n = 13) or 300 mg/d (n = 11) for 7 days, or no androstenedione (n = 13); in addition, 4 patients received 10 mug of 19-norandrostenedione. Main Outcome Measures Content of OTC androstenedione preparations; level of 19-norandrosterone in urine samples, determined by mass spectrometry, compared among the 3 randomized groups at day 1 and day 7, and among the participants who received 19-norandrostenedione from October 1998 to April 2000, Results All urine samples from participants treated with androstenedione contained 19-norandrosterone, while no samples from the no-androstenedione group did, Urinary concentrations were averaged for day 1 vs day 7 measurements; mean (SD) 19-norandrosterone concentrations in the 100-mg/d and 300-mg/d groups were 3.8 (2.5) ng/mL and 10,2 (6.9) ng/mL, respectively (P = .006),The 19-norandrosterone content exceeded the cut-off for reporting positive cases (>2.0 ng/mL) in 20 of 24. The androstenedione preparation used was pure at a sensitivity of 0.1%, but at 0.001% 19-norandrostenedione was found. For the 4 participants to whom 10 mug of 19-norandrostenedione was administered, 19-norandrosterone was found in all urine samples. Of 7 brands of androstenedione analyzed at the 1% level, 1 contained no androstenedione, 1 contained 10 mg of testosterone, and 4 more contained 90% or less of the amount stated on the label, Conclusion Our study suggests that trace contamination of androstenedione with 19-norandrostenedione is sufficient to cause urine test results positive for 19-norandrosterone, the standard marker for nandrolone use. Oral steroid doses as small as 10 mug are absorbed and excreted in urine. Some brands of androstenedione are grossly mislabeled. Careful analysis of androstenedione preparations is recommended in all studies of its biological effects. C1 Univ Calif Los Angeles, Olymp Analyt Lab, Dept Mol & Med Pharmacol, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90025 USA. Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA 90025 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Catlin, DH (reprint author), Univ Calif Los Angeles, Olymp Analyt Lab, Dept Mol & Med Pharmacol, 2122 Granville Ave, Los Angeles, CA 90025 USA. FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [DK02759] NR 17 TC 82 Z9 84 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 22 PY 2000 VL 284 IS 20 BP 2618 EP 2621 DI 10.1001/jama.284.20.2618 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 373NU UT WOS:000165296200036 PM 11086369 ER PT J AU Grinspoon, S Thomas, E Pitts, S Gross, E Mickley, D Miller, K Herzog, D Klibanski, A AF Grinspoon, S Thomas, E Pitts, S Gross, E Mickley, D Miller, K Herzog, D Klibanski, A TI Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OSTEOPOROSIS; DENSITY AB Background: Anorexia nervosa is highly prevalent among young women. Objective: To determine prevalence and predictive factors for regional bone loss. Design: Prospective cohort analysis. Setting: University hospital. Patients: 130 women with anorexia nervosa. Measurements: Dual-energy x-ray absorptiometry. Results: The prevalence of osteopenia (-1.0 SD greater than or equal to T-score > -2.5 SD) and osteoporosis (T-score less than or equal to -2.5 SD) was 50% and 13% for the anterior-posterior spine, 57% and 24% for the lateral spine, and 47% and 16% for the total hip, respectively. Bone mineral density (BMD) was reduced by at least 1.0 SD at one or more skeletal sites in 92% of patients and by at least 2.5 SD in 38% of patients. Weight was the most consistent predictor of BMD at all skeletal sites. Twenty-three percent of patients were current estrogen users, and 58% were previous estrogen users. Bone mineral density did not differ by history of estrogen use at any site. Conclusions: Bone mineral density is reduced at several skeletal sites in most women with anorexia nervosa. Weight, but not estrogen use, is a significant predictor of BMD in this population at all skeletal sites. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wilkins Ctr, Greenwich, CT USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR001066, MO1-RR01066]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-06, R01 DK052625, R01-DK52625, T32 DK007028]; NIMH NIH HHS [R01 MH038333, R01-MH38333] NR 18 TC 189 Z9 195 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 21 PY 2000 VL 133 IS 10 BP 790 EP 794 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 374AA UT WOS:000165321200004 PM 11085841 ER PT J AU Strack, B Calistri, A Accola, MA Palu, G Gottlinger, HG AF Strack, B Calistri, A Accola, MA Palu, G Gottlinger, HG TI A role for ubiquitin ligase recruitment in retrovirus release SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ROUS-SARCOMA VIRUS; VESICULAR STOMATITIS-VIRUS; MURINE LEUKEMIA-VIRUS; LATE ASSEMBLY DOMAIN; PROLINE-RICH MOTIF; BLUETONGUE VIRUS; IMMUNODEFICIENCY-VIRUS; GAG PROTEIN; NONSTRUCTURAL PROTEIN; INFECTED-CELLS AB Retroviral Gag polyproteins have specific regions, commonly referred to as late assembly (L) domains, which are required for the efficient separation of assembled virions from the host cell. The L domain of HIV-1 is in the C-terminal p6(gag) domain and contains an essential P(T/S)AP core motif that is widely conserved among lentiviruses, In contrast, the L domains of oncoretroviruses such as Rous sarcoma virus (RSV) have a more N-terminal location and a PPxY core motif. In the present study, we used chimeric Gag constructs to probe for L domain activity, and observed that the unrelated L domains of RSV and HIV-1 both induced the appearance of Gag-ubiquitin conjugates in virus-like particles (VLP). Furthermore, a single-amino acid substitution that abolished the activity of the RSV L domain in VLP release also abrogated its ability to induce Gag ubiquitination, Particularly robust Gag ubiquitination and enhancement of VLP release were observed in the presence of the candidate L domain of Ebola virus, which contains overlapping P(T/S)AP and PPxY motifs, The release defect of a minimal Gag construct could also be corrected through the attachment of a peptide that serves as a physiological docking site for the ubiquitin ligase Nedd4. Furthermore, VLP formation by a full-length Gag polyprotein was sensitive to lactacystin, which depletes the levels of free ubiquitin through inhibition of the proteasome, Our findings suggest that the engagement of the ubiquitin conjugation machinery by L domains plays a crucial role in the release of a diverse group of enveloped viruses. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35121 Padua, Italy. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB824,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA09141, T32 CA009141]; NIAID NIH HHS [R01 AI029873, P30 AI028691, AI28691, R37 AI029873, AI29873] NR 40 TC 231 Z9 235 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 21 PY 2000 VL 97 IS 24 BP 13063 EP 13068 DI 10.1073/pnas.97.24.13063 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 376UZ UT WOS:000165476300032 PM 11087860 ER PT J AU Babich, JW Coco, WG Barrow, S Fischman, AJ Femia, FJ Zubieta, J AF Babich, JW Coco, WG Barrow, S Fischman, AJ Femia, FJ Zubieta, J TI Tc-99m-labeled chemotactic peptides: influence of coligand on distribution of molecular species and infection imaging properties. Synthesis and structural characterization of model complexes with the {Re(eta(2)-HNNC5H4N)(eta(1)-NNC5H4N)} core SO INORGANICA CHIMICA ACTA LA English DT Article DE Tc-99m-labeled hydrazino nicotinamide; rhenium complexes; Tc-99m-coligand complexes; reverse-phase HPLC; Tc-99m-labeled chemotactic peptides ID IIB/IIIA-RECEPTOR ANTAGONIST; POLYCLONAL IMMUNOGLOBULIN-G; SCHIFF-BASE LIGANDS; FOCAL SITES; BACTERIAL-INFECTION; IN-VITRO; TC-99M; TECHNETIUM; ANALOGS; RATS AB Tc-99m-labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptides are useful infection imaging agents. However, the reagent that is used for radiolabeling ('coligand') can have profound effects on biodistribution. In this study, the distribution of molecular species formed with a variety of coligands was correlated with infection localization and biodistribution in E. coli infected rabbits. Five Tc-99m-coligand complexes (mannitol, glucamine, glucarate, tricine and glucoheptonate) were used to label f-MLFK-HYNIC and radiolabeled species were characterized by reverse phase HPLC. One mCi of each Tc-99m-coligand-peptide complex was injected into rabbits 24 h after infection and imaging was performed 3-4 and 16-17 h later. After acquiring the final images, the animals were euthanized and biodistribution was measured. With all five coligands, Tc-99m-labeled peptide was obtained in > 90% radiochemical purity. Multiple radiolabeled species were obtained with each reagent; however, mannitol yielded the most homogeneous product. Model studies on the robust {Re(eta (2)-HNNC5H4N)(eta (1)-NNC5H4)} core demonstrate that ligands such as mannitol, tricine, tris(hydroxymethyl)propane, glucarate-a, glucarate-b, and glucoheptonate yield intractable mixtures of products as a consequence of the ambidentate nature of these ligands and their facile displacement by other donor groups, including solvent molecules. In contrast, dihydroxylic ligands with an additional imine functionality and a meridional geometric preference yield monophasic materials upon reaction with [ReCl3(eta (1)-NNC5H4NH)(eta (2)-HNNC5H4N)]. Both [Re{eta (C5H3N)-C-3-2,6-(CH2O)(2)} (eta (1)-NNC5H4N)(eta (2)-HNNC5H4N)] (1) and [Re{eta (3)-OC6H4C(H)=NC6H4O}(eta (1)-NNC5H4N)(eta (2)-HNNC5H4N)] (2) exhibit distorted octahedral geometries with a meridional disposition of the bidentate pyridinediazene and pyridinediazenido(1 -) ligands and the three remaining meridional positions occupied by the two oxygen and the nitrogen donors of the tridentate coligand. Image analysis demonstrated that Tc-99m-mannitol-f-MLFK-HYNIC produced the highest target to background ratios (T/B). The T/B values were: 3.91 +/- 0.99, 6.15 +/- 1.07, 2.8 +/- 1.07, 2.57 +/- 1.07, 3.41 +/- 1.07 and 1.8 +/- 1.07 at 3-4 h and 11.9 +/- 0.99, 3.94 +/- 1.07, 3.79 +/- 1.07, 4.81 +/- 1.17, 7.0 +/- 1.31 and 5.32 +/- 1.07 at 16-17 h for mannitol, tricine, glucamine, glucarate-a, glucarate-b, and glucoheptonate, respectively. At both imaging times, Tc-99m-mannitol-f-MLFK-HYNIC had the lowest relative levels of accumulation in bowel. Biodistribution measurements demonstrated that the mannitol preparation had the highest level of accumulation (%ID g(-1)) in infected tissue; mannitol > glucoheptonate = glucarate-b > glucarate-a > glucamine > tricine; P < 0.01. The infected to normal muscle ratio for Tc-99m-mannitol-f-MLFK-HYNIC was 50:1. These results support our previous findings in rats that coligands can markedly effect the biodistribution and infection localization of Tc-99m-labeled HYNIC chemotactic peptides. For infection imaging, the mannitol preparation had the most favorable combination of accumulation in infected tissue, T/B ratio and biodistribution in uninfected organs. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Biostream Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. RP Babich, JW (reprint author), Biostream Inc, 160 2nd St, Cambridge, MA 02142 USA. EM jbabich@biostream.net; jazubiet@syr.edu NR 51 TC 28 Z9 29 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 NOV 20 PY 2000 VL 309 IS 1-2 BP 123 EP 136 DI 10.1016/S0020-1693(00)00255-3 PG 14 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 380NQ UT WOS:000165708300016 ER PT J AU Kumar, A Bilker, W Lavretsky, H Gottlieb, G AF Kumar, A Bilker, W Lavretsky, H Gottlieb, G TI Volumetric asymmetries in late-onset mood disorders: an attenuation of frontal asymmetry with depression severity SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE asymmetry; late-onset depression; geriatric depression; neuroanatomy; MRI ID CEREBRAL ASYMMETRY; PLANUM TEMPORALE; MAJOR DEPRESSION; BRAIN; SCHIZOPHRENIA; LOBES; MRI AB The purpose of the study was to examine global and regional volumetric asymmetries in patients with late-onset mood disorders and non-depressed control subjects. Our sample comprised 34 patients with late-onset major depression, 18 patients diagnosed with late-onset minor depression and 30 control subjects. All subjects were scanned using a 1.5 Tesla GE Scanner, and quantitative estimates of global and focal brain volumes were obtained. Control subjects and patients displayed significant right-left Volumetric differences across several regions, with right-sided regions being larger than the left. In the frontal lobes, the asymmetry differed significantly in the three groups (P = 0.02). It was most pronounced in the control group and decreased significantly in the minor and major depression groups. There was a significant trend (P = 0.005) in the magnitude of frontal asymmetry across groups, with the frontal asymmetry decreasing with increasing severity of depression. Hemispheric and temporal asymmetries were comparable in all three groups. These data suggest that an attenuation of the 'normal' volumetric asymmetry in the frontal regions may provide a structural basis to late-onset mood disorders (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mental Hlth Serv, Boston, MA 02114 USA. RP Kumar, A (reprint author), Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, 760 Westwood Plaza,Rm 37-384, Los Angeles, CA 90024 USA. RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 FU NIA NIH HHS [1P50AG 16570]; NIMH NIH HHS [MH 55115, MH 61567] NR 29 TC 27 Z9 27 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 20 PY 2000 VL 100 IS 1 BP 41 EP 47 DI 10.1016/S0925-4927(00)00067-6 PG 7 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 379UE UT WOS:000165660200005 PM 11090724 ER PT J AU Oesterle, SN Sanborn, TA Ali, N Resar, J Ramee, SR Heuser, R Dean, L Knopf, W Schofield, P Schaer, GL Reeder, G Masden, R Yeung, AC Burkhoff, D AF Oesterle, SN Sanborn, TA Ali, N Resar, J Ramee, SR Heuser, R Dean, L Knopf, W Schofield, P Schaer, GL Reeder, G Masden, R Yeung, AC Burkhoff, D TI Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trial SO LANCET LA English DT Article ID CORONARY-ARTERY DISEASE; MYOCARDIAL REVASCULARIZATION; REFRACTORY ANGINA; MEDICAL THERAPY; BLOOD-FLOW; ANGIOGENESIS; PECTORIS; CHANNELS AB Background Percutaneous transmyocardial laser revascularisation (PTMR) is a proposed catheter-based therapy for refractory angina pectoris when bypass surgery or angioplasty is not possible. We undertook a randomised trial to assess the safety and efficacy of this technique. Methods 221 patients with reversible ischaemia of Canadian Cardiovascular Society angina class 111 (61%) or IV (39%) and incomplete response to other therapies were recruited from 13 centres. Patients were randomly assigned PTMR with a holmium:YAG laser plus continued medical treatment (n=110) or continued medical treatment only (n=111). The primary endpoint was the exercise tolerance at 12 months. Analyses were by intention to treat. Findings 11 patients died and 19 withdrew; 92 PTMR-group and 99 medical-treatment-group patients completed the study. Exercise tolerance at 12 months had increased by a median of 89.0 s (IQR -15 to 183) with PTMR compared with 12.5 s (-67 to 125) with medical treatment only (p=0.008). On masked assessment, angina class was II or lower in 34.1% of PTMR patients compared with 13.0% of those medically treated. All indices of the Seattle angina questionnaire improved more with PTMR than with medical care only. By 12 months there had been eight deaths in the PTMR group and three in the medical treatment group, with similar survival in the two groups. Interpretation PTMR was associated with increased exercise tolerance time, low morbidity, lower angina scores assessed by masked reviewers, and improved quality of life. Although there is controversy about the mechanism of action, and the contribution of the placebo effect cannot be quantified, this unmasked study suggests that this palliative procedure provides some clinical benefits in the defined population of patients. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. New York Presbyterian Hosp, New York, NY USA. Baylor Univ VA Hosp, Houston, TX USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Oschner Clin, New Orleans, LA USA. Columbia Hosp, Phoenix, AZ USA. Univ Alabama, Birmingham, AL USA. St Josephs Hosp, Atlanta, GA USA. Papworth Hosp, Cambridge CB3 8RE, England. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Mayo Clin, Rochester, MN USA. Jewish Hosp, Louisville, KY USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Columbia Univ, New York, NY USA. RP Oesterle, SN (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. RI Burkhoff, Daniel/D-7674-2011 NR 20 TC 108 Z9 114 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 18 PY 2000 VL 356 IS 9243 BP 1705 EP 1710 DI 10.1016/S0140-6736(00)03203-7 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 376MX UT WOS:000165462300008 PM 11095257 ER PT J AU Spiro, RG AF Spiro, RG TI Glucose residues as key determinants in the biosynthesis and quality control of glycoproteins with N-linked oligosaccharides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ALPHA-D-MANNOSIDASE; MOUSE LYMPHOMA-CELLS; RAT-LIVER GOLGI; ENDOPLASMIC-RETICULUM; PROCESSING ENZYME; ENDOMANNOSIDASE PATHWAY; MOLECULAR CHAPERONE; II-DEFICIENT; GLYCOSYLATION; CALNEXIN AB Although glucose residues do not occur as constituents of mature N-linked oligosaccharides in eukaryotic cells, it has been appreciated for some time that they are integral components of the polymannose oligosaccharides of newly synthesized glycoproteins and their lipid-linked precursors (1). Indeed it has been shown that they play an essential role in the cotranslational. transfer of a preassembled triglucosylated oligosaccharide (Glc(3)Man(9)GlcNAc(2)) from a dolichyl pyrophosphoryl carrier to asparagine in Asn-X-Ser(Thr) sequences on the polypeptide chain (2, 3). Moreover, it has recently become apparent that the most internal of the three glucose residues, after being brought to a terminal position through the action of ER1-situated glucosidases, interacts with lectin-like chaperones to mediate proper folding and/or oligomerization during protein quality control (4, 5). From these observations it has become evident that the presence of transient glucose residues on the polymannose oligosaccharides provides ideal recognition signals for crucial biological events, which have implications for a number of disease states as well as for viral replication. A rather complicated enzymatic machinery occurs in eukaryotic cells to achieve glucose attachment (6) and removal (7, 8), and this has been studied effectively with the help of mutants and inhibitors. It is the purpose of this article to provide a succinct overview of this distinctive area of glycobiology. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 58 TC 69 Z9 69 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 2000 VL 275 IS 46 BP 35657 EP 35660 DI 10.1074/jbc.R000022200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000001 PM 11007802 ER PT J AU Medley, QG Serra-Pages, C Iannotti, E Seipel, K Tang, M O'Brien, SP Streuli, M AF Medley, QG Serra-Pages, C Iannotti, E Seipel, K Tang, M O'Brien, SP Streuli, M TI The Trio guanine nucleotide exchange factor is a RhoA target - Binding of RhoA to the Trio immunoglobulin-like domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; LIGHT-CHAIN KINASE; CELL-SHAPE CHANGES; FAMILY G-PROTEINS; ACTIN CYTOSKELETON; SIGNALING PATHWAYS; C-ELEGANS; GTPASES; VAV; ACTIVATION AB Trio isa complex protein containing two guanine nucleotide exchange factor domains each with associated pleckstrin homology domains, a serine/threonine kinase domain, two SH3 domains, an immunoglobulin-like domain, and spectrin-like repeats. Trio was originally identified as a LAR tyrosine phosphatase-binding protein and is involved in actin remodeling, cell migration, and cell growth. Herein we provide evidence that Trio not only activates RhoA but is also a RhoA target. The RhoA-binding site was mapped to the Trio immunoglobulin-like domain. RhoA isoprenylation is necessary for the RhoA-Trio interaction, because mutation of the RhoA carboxyl-terminal cysteine residue blocked binding, The:existence of an intramolecular functional link between RhoA activation and RhoA binding is suggested by the finding that Trio exchange activity enhanced RhoA binding to Trio. Furthermore, immunofluorescence studies of HeLa cells showed that although ectopically:expressed Trio was evenly distributed within the cell, co-expression of Trio with RhoA resulted in relocalization of Trio into punctate structures. Relocalization was not observed with Trio constructs lacking the immunoglobulin-like domain, indicating that RhoA acts to regulate,Trio localization via binding to the immunoglobulin-like domain. We propose that Trio-mediated RhoA: activation and subsequent RhoA-mediated relocalization of Trio functions to modulate and coordinate Trio signaling. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Streuli, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55547, CA75091] NR 53 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 2000 VL 275 IS 46 BP 36116 EP 36123 DI 10.1074/jbc.M003775200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000068 PM 10948190 ER PT J AU Lyu, RM Germano, PM Choi, JK Le, SV Pisegna, JR AF Lyu, RM Germano, PM Choi, JK Le, SV Pisegna, JR TI Identification of an essential amino acid motif within the C terminus of the pituitary adenylate cyclase-activating polypeptide type I receptor that is critical for signal transduction but not for receptor internalization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTOR; CARBOXYL-TERMINUS; FUNCTIONAL EXPRESSION; CYTOPLASMIC DOMAINS; PEPTIDE RECEPTOR; SPLICE VARIANTS; A RECEPTOR; CELLS AB The pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 (PAC1) receptor is a G protein-coupled receptor and class II receptor member. The receptor domains critical for signaling are unknown. To explore the role of the C terminus, truncations of 63 residues(Tr-406), 53 residues (Tr-416), 49 residues (Tr-420), 44 residues (Tr-424), and 37 residues (Tr-433) were constructed and expressed in NIH/3T3 cells, and immunofluorescence, radioligand binding, adenylyl cyclase (AC) and phospholipase C (PLC) assays were performed. I-125-PACAP-27 binding (K-d = 0.6-1.5 nM) for the Tr-406 and Tr-433 were similar to wild type Hop and Null splice variants (K-d = similar to1.1 nM), Although internalization of ligand for both the Tr-406 and Tr-433 mutants was reduced to 50-60% at 60 min compared with 76-87% for WT, loss of G-protein coupling did not account for differences in internalization. Despite similar binding properties Tr-406 and Tr-416 mutants showed no AC or PLC response. Addition of 14 amino acids distal to HopTr(406) resulted in normal AC and PLC responses. Site-directed mutagenesis indicated that Arg(416) and Ser(417) are essential for G protein activation. The proximal C terminus mediates signal transduction, and the distal is involved with internalization. Two residues within the C terminus, Arg(416) and Ser(417) conserved among class II receptors are the likely sites for G protein coupling. C1 VA Greater Los Angeles Healthcare Syst 111C, Gastroenterol & Hepatol Sect, CURE, Vet Affairs UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst 111C, Gastroenterol & Hepatol Sect, CURE, Vet Affairs UCLA Digest Dis Res Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 52274-01] NR 42 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 17 PY 2000 VL 275 IS 46 BP 36134 EP 36142 DI 10.1074/jbc.M004612200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375CM UT WOS:000165382000070 PM 10908567 ER PT J AU Takagi, Y Nozaki, K Sugino, T Hattori, I Hashimoto, N AF Takagi, Y Nozaki, K Sugino, T Hattori, I Hashimoto, N TI Phosphorylation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice SO NEUROSCIENCE LETTERS LA English DT Article DE c-Jun NH2-terminal kinase; p38 mitogen-activated protein kinase; transient forebrain ischemia; mouse; immediate early genes; apoptosis ID CEREBRAL-ISCHEMIA; TRANSGENIC MICE; JNK ACTIVATION; CELL-DEATH; APOPTOSIS; SUSCEPTIBILITY; OVEREXPRESSION; PROLIFERATION; HIPPOCAMPUS; DAMAGE AB We investigated the activation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) during transient forebrain ischemia to clarify the roles of these stress kinases du ring brain ischemia. Mice were subjected bilateral common carotid artery (BCCA) occlusion for 20 min followed by reperfusion. Immunohistochemical analysis and Western blot analysis for active JNK and active p38 MAPK were performed at 0, 5, 10, 30 and 150 min after reperfusion. After 5 min of reperfusion, active JNK and p38 MAPK immunoreactivities were enhanced in neurons in the cerebral cortex and hippocampus; this activation peaked at 30 min of reperfusion. Stress kinases activation dominantly occurred in the similar regions, in which neurons with fragmented DNA were detected at 72 h after reperfusion. Western blot analysis indicated that JNK 1,JNK 2 and p38 MAPK were activated at 10 and 30 min after reperfusion. These findings indicate that JNK and p38 MAPK pathways may play important roles in neuronal death during brain ischemia. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto 6068507, Japan. RP Takagi, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol & Neurosurg Stroke & Neurovasc Regula, 149th 13th St, Charlestown, MA 02129 USA. NR 19 TC 46 Z9 53 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 17 PY 2000 VL 294 IS 2 BP 117 EP 120 DI 10.1016/S0304-3940(00)01552-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 372ZD UT WOS:000165263200013 PM 11058801 ER PT J AU Hirano, N Kojima, S von Bergwelt-Baildon, MS Maecker, B Butler, MO Schultze, JL Guinan, EC Nadler, LM AF Hirano, N Kojima, S von Bergwelt-Baildon, MS Maecker, B Butler, MO Schultze, JL Guinan, EC Nadler, LM TI Distinct autoantigens in American and Japanese immune-mediated aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Nagoya Univ, Nagoya, Aichi, Japan. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 8 BP 6A EP 6A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100009 ER PT J AU Gazda, H Zhong, R Lipton, JM Niemeyer, CM Viskochil, DH Pospisilova, D Nathan, DG Beggs, AH Sieff, CA AF Gazda, H Zhong, R Lipton, JM Niemeyer, CM Viskochil, DH Pospisilova, D Nathan, DG Beggs, AH Sieff, CA TI Novel RPS19 missense and splice site mutations found in Diamond-Blackfan anemia patients. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Div Pediat Hematol & Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Genet, Boston, MA 02115 USA. Albert Einstein Coll Med, Schneider Childrens Hosp, New York, NY USA. Univ Freiburg, Childrens Hosp, Freiburg, Germany. Utah Sch Med, Div Med Genet, Salt Lake City, UT USA. Palacky Univ Hosp, Dept Pediat, CR-77147 Olomouc, Czech Republic. 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 NOV 16 PY 2000 VL 96 IS 11 MA 14 BP 7A EP 7A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100015 ER PT J AU Nisbet-Brown, E Stegmaier, K Walker, L Waye, JS Chui, DHK AF Nisbet-Brown, E Stegmaier, K Walker, L Waye, JS Chui, DHK TI Sickle cell disease in a four year old child with apparent HbS trait. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Hematol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. McMaster Univ, Fac Hlth Sci, Prov DNA Diagnost Lab, Hamilton, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3740 BP 20B EP 20B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200080 ER PT J AU Whelan, P Reilly, N Scadden, DT AF Whelan, P Reilly, N Scadden, DT TI KSHV-associated primary effusion lymphomas display a characteristic chemokine receptor expression pattern and respond chemotactically to components present in the effusion. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 76 BP 21A EP 21A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100077 ER PT J AU Snapper, SB Nguyen, D Rosen, FS Mulligan, RC Alt, FW von Andrian, UH Klein, C AF Snapper, SB Nguyen, D Rosen, FS Mulligan, RC Alt, FW von Andrian, UH Klein, C TI WASP-deficiency causes impaired migration of T-cells, dendritic cells, and neutrophils. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Blood Res, Boston, MA 02115 USA. Fdn Oswaldo Cruz, Rio De Janeiro, Brazil. Childrens Hosp, Boston, MA 02115 USA. Hannover Med Sch, D-3000 Hannover, Germany. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 87 BP 23A EP 23A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100088 ER PT J AU Poznansky, MC Olszak, IT Foxall, R Evans, RR Adams, GB Wyatt, R Brander, C Sodroski, J Walker, BD Scadden, DT AF Poznansky, MC Olszak, IT Foxall, R Evans, RR Adams, GB Wyatt, R Brander, C Sodroski, J Walker, BD Scadden, DT TI Active movement of immune effector cells away from HIV-1 gp120. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. OI Foxall, Russell/0000-0001-9821-0708 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 NOV 16 PY 2000 VL 96 IS 11 MA 92 BP 24A EP 25A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100093 ER PT J AU Krackhardt, AM Harig, S Witzens, M Barrett, P Broderick, R Gribben, JG AF Krackhardt, AM Harig, S Witzens, M Barrett, P Broderick, R Gribben, JG TI T cell responses in CLL: Superiority of TH2 responses might contribute to reduced cytotoxic autologous antitumor responses. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 109 BP 28A EP 28A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100110 ER PT J AU Butler, MO Hirano, N Nadler, LM AF Butler, MO Hirano, N Nadler, LM TI CD80 expressing ovarian cancer stimulation of cytokine secretion by allo PBMC at the single cell level. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 118 BP 30A EP 31A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100119 ER PT J AU Seibel, J Khetawat, R Wilson, B Racke, F AF Seibel, J Khetawat, R Wilson, B Racke, F TI Expression of CD1d in various histiocytic and dendritic processes. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. 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 NOV 16 PY 2000 VL 96 IS 11 MA 3800 BP 33B EP 33B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200140 ER PT J AU Van Laer, A Dallalio, G McKenzie, SW Means, RT AF Van Laer, A Dallalio, G McKenzie, SW Means, RT TI Thioredoxin and protein nitrotyrosine in bone marrow supernatant from patients with human immunodeficiency virus infection. SO BLOOD LA English DT Meeting Abstract C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RI Means, Robert/A-4454-2008 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 NOV 16 PY 2000 VL 96 IS 11 MA 3824 BP 38B EP 38B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200164 ER PT J AU Grabowski, EF Lee, PK Grabowski, PE AF Grabowski, EF Lee, PK Grabowski, PE TI Compared to unfractionated heparin, dalteparin induces a lower rate of secretion of tissue factor pathway inhibitor (TFPI) from cellular pools within vascular endothelium, thereby better preserving the anticoagulant activity of endothelium. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 227 BP 55A EP 55A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100228 ER PT J AU Chapman, J Purmal, A Dzik, W AF Chapman, J Purmal, A Dzik, W TI Preclinical safety assessment of red cells virally inactivated by INACTINE (TM): Lack of neoantigenicity. SO BLOOD LA English DT Meeting Abstract C1 VITEX, Watertown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 257 BP 61A EP 61A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100258 ER PT J AU Purmal, A Dzik, W Valeri, CR AF Purmal, A Dzik, W Valeri, CR TI Treatment of baboon red cells with the INACTINE (TM) pathogen inactivation technology does not affect their in vivo survival or antigenicity. SO BLOOD LA English DT Meeting Abstract C1 VITEX, Watertown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Naval Blood Res Lab, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 255 BP 61A EP 61A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100256 ER PT J AU Bahary, N Ransom, DG Barut, B Daniluk, DA Ferrando, AA Saganic, WJ Fenton, L Zhou, Y Amemiya, CT Zon, LI AF Bahary, N Ransom, DG Barut, B Daniluk, DA Ferrando, AA Saganic, WJ Fenton, L Zhou, Y Amemiya, CT Zon, LI TI Characterization, genetic and physical mapping of the zebrafish mutant cloche. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 297 BP 70A EP 70A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100298 ER PT J AU Hui, X Uchida, T White, MF Yang, YC AF Hui, X Uchida, T White, MF Yang, YC TI Specificity of IL-2 receptor gamma chain superfamily cytokines is in part mediated by insulin receptor substrates (IRS). SO BLOOD LA English DT Meeting Abstract C1 Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Canc, Cleveland, OH USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 325 BP 76A EP 76A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100326 ER PT J AU Tang, RP DeCaprio, JA Ajchenbaum-Cymbalista, F AF Tang, RP DeCaprio, JA Ajchenbaum-Cymbalista, F TI Histone deacetylase inhibitors induce cell cycle specific gene expression and apoptosis in B-cell chronic lymphocytic leukemia (B-CLL). SO BLOOD LA English DT Meeting Abstract C1 INSERM, E9912 EA1529, Hotel Dieu, Paris, France. 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 NOV 16 PY 2000 VL 96 IS 11 MA 347 BP 81A EP 81A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100348 ER PT J AU Sarkar, S Svoboda, M Freedman, AS AF Sarkar, S Svoboda, M Freedman, AS TI Activation of Akt following beta 1 integrin ligation modulates survival of B cell acute lymphoblastic leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 349 BP 82A EP 82A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100350 ER PT J AU Liu, TX Zhou, Y Kanki, JP Zon, LI Look, AT AF Liu, TX Zhou, Y Kanki, JP Zon, LI Look, AT TI Syntenic region shared by zebrafish and patients with 5q-syndrome. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med 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 NOV 16 PY 2000 VL 96 IS 11 MA 380 BP 89A EP 89A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100381 ER PT J AU Treon, SP Mitsiades, CS Mitsiades, NS Young, G Doss, DS Schlossman, RL Anderson, KC AF Treon, SP Mitsiades, CS Mitsiades, NS Young, G Doss, DS Schlossman, RL Anderson, KC TI Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in B-cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2000 VL 96 IS 11 MA 426 BP 99A EP 99A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100427 ER PT J AU Olipitz, W Hopfinger, G Hoefler, G Girschikofsky, M Bodner, C Hiden, K Aguiar, R Linkesch, W Sill, H AF Olipitz, W Hopfinger, G Hoefler, G Girschikofsky, M Bodner, C Hiden, K Aguiar, R Linkesch, W Sill, H TI Microsatellite instability but lack of alternations of genes targeted by defective DNA-mismatch repair in therapy-related MDS and leukemia. SO BLOOD LA English DT Meeting Abstract C1 Karl Franzens Univ Graz, Div Hematol, Graz, Austria. Hanusch Hosp, Vienna, Austria. Karl Franzens Univ Graz, Inst Pathol, Graz, Austria. Dana Farber Canc Inst, Boston, MA 02115 USA. Elisabethinen Hosp, Linz, Austria. RI Hoefler, Gerald/B-7006-2008; Hopfinger, Georg/E-7602-2016 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 NOV 16 PY 2000 VL 96 IS 11 MA 447 BP 104A EP 104A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100448 ER PT J AU Veiga, JP Sallan, SE Nadler, LM Cardoso, AA AF Veiga, JP Sallan, SE Nadler, LM Cardoso, AA TI Human acute lymphoblastic leukemia promotes angiogenesis in vivo: Pre-clinical models to develop targeted intervention. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 484 BP 113A EP 113A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100485 ER PT J AU Bennett, CM Fleming, MD Kanki, JP Rhodes, J Delahaye-Brown, A Langenau, DM Liu, TX Paw, BH Zon, LI Look, AT AF Bennett, CM Fleming, MD Kanki, JP Rhodes, J Delahaye-Brown, A Langenau, DM Liu, TX Paw, BH Zon, LI Look, AT TI Genetic analysis of myelopoiesis the zebrafish. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 4177 BP 114B EP 114B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200517 ER PT J AU Veiga, JP Nunes, R Konopleva, M Sallan, SE Sporn, MB Nadler, LM Andreeff, M Cardoso, AA AF Veiga, JP Nunes, R Konopleva, M Sallan, SE Sporn, MB Nadler, LM Andreeff, M Cardoso, AA TI The synthetic triterpenoid CDDO-Me is an effective inhibitor of the leukemia-associated de novo angiogenesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dartmouth Coll, Hanover, NH 03755 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 515 BP 120A EP 120A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100516 ER PT J AU Gong, JL Kodo, S Kato, Y Tanaka, Y Shen, DS Wu, ZK Yang, XP Galinsky, I Janosova, A DeAngelo, D Avigan, D Kufe, D Stone, R AF Gong, JL Kodo, S Kato, Y Tanaka, Y Shen, DS Wu, ZK Yang, XP Galinsky, I Janosova, A DeAngelo, D Avigan, D Kufe, D Stone, R TI Human leukemic myeloblast-autologous dendritic cell fusions stimulate potent anti-tumor T-cell autoreactivity: A pre-clinical model for vaccine therapy in patients with acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, 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 HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 520 BP 121A EP 121A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100521 ER PT J AU Preffer, FI Dombkowski, D Sykes, M Yang, Y AF Preffer, FI Dombkowski, D Sykes, M Yang, Y TI Side population cells with hematopoietic differentiating capacity circulate in normal adult human blood. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 4229 BP 125B EP 125B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200569 ER PT J AU Wang, ZY Miura, N Bonelli, A Mole, P Scadden, DT AF Wang, ZY Miura, N Bonelli, A Mole, P Scadden, DT TI The receptor tyrosine kinase, EphB4 (HTK), promotes megakaryocytic and erythroid differentiation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 4247 BP 129B EP 129B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200587 ER PT J AU Yang, XF Wu, CJ McLaughlin, S Chillemi, A Wang, KS Dranoff, G Ritz, J AF Yang, XF Wu, CJ McLaughlin, S Chillemi, A Wang, KS Dranoff, G Ritz, J TI CML66, a novel tumor antigen, is the target of a humoral immune response associated with remission of chronic myelocytic leukemia after donor lymphocytic infusion. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 612 BP 143A EP 143A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100613 ER PT J AU Wu, CJ Yang, XF McLaughlin, SF Canning, C Alyea, EP Soiffer, RJ Dranoff, G Ritz, J AF Wu, CJ Yang, XF McLaughlin, SF Canning, C Alyea, EP Soiffer, RJ Dranoff, G Ritz, J TI Recombination signal binding protein-J kappa (RBP-Jk) is a B cell defined antigen associated with chronic myelocytic leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 617 BP 144A EP 144A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100618 ER PT J AU Yagi, M Roth, GJ AF Yagi, M Roth, GJ TI Altered regulation of mitosis polyploidizing megakaryocytes. SO BLOOD LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Div Hematol, Seattle, WA 98195 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 NOV 16 PY 2000 VL 96 IS 11 MA 4339 BP 148B EP 148B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200679 ER PT J AU Fonseca, R Harrington, D Oken, MM Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Greipp, PR Blood, EA Dewald, GW AF Fonseca, R Harrington, D Oken, MM Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Greipp, PR Blood, EA Dewald, GW TI Deletions of 13q14 in myeloma plasma cells usually represent large deletions of the q arm or monosomy. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 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 NOV 16 PY 2000 VL 96 IS 11 MA 648 BP 151A EP 151A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100649 ER PT J AU Fonseca, R Harrington, D Oken, MM Hoyer, JD Dewald, GW Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE van Ness, B Blood, EA Greipp, PR AF Fonseca, R Harrington, D Oken, MM Hoyer, JD Dewald, GW Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE van Ness, B Blood, EA Greipp, PR TI Myeloma (MM) and the t(11;14)(q13;q32); Increasing evidence for a biologically distinct subset of patients. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 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 NOV 16 PY 2000 VL 96 IS 11 MA 646 BP 151A EP 151A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100647 ER PT J AU Greipp, PR Jacobsen, JL Crowley, JJ Henderson, KJ Anderson, KC Kyle, RA Barlogie, B AF Greipp, PR Jacobsen, JL Crowley, JJ Henderson, KJ Anderson, KC Kyle, RA Barlogie, B TI Beta 2 microglobulin (beta 2M) and plasma cell labeling index (PCLI) constitute a strong prognostic index in the SWOG intergroup transplant trial S9321: Observations on gender and age. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 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 NOV 16 PY 2000 VL 96 IS 11 MA 653 BP 152A EP 152A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100654 ER PT J AU Harris, KW Burns, SC Arcasoy, MO AF Harris, KW Burns, SC Arcasoy, MO TI Purification and characterization of yeast-expressed erythropoietin (R103A), an erythropoietin antagonist. SO BLOOD LA English DT Meeting Abstract C1 So Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 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 NOV 16 PY 2000 VL 96 IS 11 MA 4366 BP 154B EP 154B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200706 ER PT J AU Ladetto, M Omede, P Sametti, S Donovan, JW Astolfi, M Giaccone, L Giaretta, F Volpato, F Bringhen, S Palumbo, A Bruno, B Pileri, A Gribben, JG Boccadoro, M AF Ladetto, M Omede, P Sametti, S Donovan, JW Astolfi, M Giaccone, L Giaretta, F Volpato, F Bringhen, S Palumbo, A Bruno, B Pileri, A Gribben, JG Boccadoro, M TI Real time quantitative PCR shows that peripheral blood stem cell (PBPC) harvests are significantly less contaminated than bone marrow (BM) in multiple myeloma patients (MM). SO BLOOD LA English DT Meeting Abstract C1 Univ Turin, Cattedra Ematol, Turin, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 660 BP 154A EP 154A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100661 ER PT J AU Battle, TE Wierda, WG Rassenti, LZ Kipps, TJ Frank, DA AF Battle, TE Wierda, WG Rassenti, LZ Kipps, TJ Frank, DA TI CD154 (CD40-ligand) gene therapy for chronic lymphocytic leukemia leads to in vivo activation of the STAT1 signaling pathway. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 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 NOV 16 PY 2000 VL 96 IS 11 MA 675 BP 157A EP 157A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100676 ER PT J AU Tai, YT Podar, K Hideshima, T Wang, FF Davies, FE Young, G Chauhan, D Lin, B Treon, SP Mitsiades, CS Lentzsch, S Gupta, D Hayashi, T Mitsiades, N Raje, N Koike, M Taccioli, GE Anderson, KC AF Tai, YT Podar, K Hideshima, T Wang, FF Davies, FE Young, G Chauhan, D Lin, B Treon, SP Mitsiades, CS Lentzsch, S Gupta, D Hayashi, T Mitsiades, N Raje, N Koike, M Taccioli, GE Anderson, KC TI Ku86v translocates into cell membrane and associates with Ku70 in human multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Inst Radiol Sci, Genome Res Grp, Chiba 260, Japan. Boston Univ, Sch Med, Boston, MA 02118 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 NOV 16 PY 2000 VL 96 IS 11 MA 679 BP 158A EP 158A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100680 ER PT J AU Grdisa, M Tang, RP Delmer, A Levy, V Gribben, JG Ajchenbaum-Cymbalista, F AF Grdisa, M Tang, RP Delmer, A Levy, V Gribben, JG Ajchenbaum-Cymbalista, F TI Ligation of CD40 on B-cell chronic lymphocytic leukemia (B-CLL) cells promotes increased survival but does not impair fludarabine induced apoptosis. SO BLOOD LA English DT Meeting Abstract C1 INSERM, Hotel Dieu, E9912, EA1529, Paris, France. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 684 BP 159A EP 159A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100685 ER PT J AU Treon, SP Belch, AR Grossbard, ML Schlossman, RL Ellman, L Harmon, D Doss, DS Preffer, FI Kelliher, AS Pilarski, LM Anderson, KC AF Treon, SP Belch, AR Grossbard, ML Schlossman, RL Ellman, L Harmon, D Doss, DS Preffer, FI Kelliher, AS Pilarski, LM Anderson, KC TI Phase II study of single agent rituximab in previously treated multiple myeloma patients: Patients with CD20+BM plasma cells may derive benefit from rituximab. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Cross Canc Inst, Dept Med Oncol, Edmonton, AB, Canada. Univ Alberta, Dept Med, Edmonton, AB, Canada. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 704 BP 164A EP 164A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100705 ER PT J AU Krackhardt, AM Witzens, M Donovan, JW Chessia, M Harig, S Gribben, JG AF Krackhardt, AM Witzens, M Donovan, JW Chessia, M Harig, S Gribben, JG TI Identification of tumor associated genes in CLL by subtractive hybridization. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 4420 BP 165B EP 165B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200760 ER PT J AU Vonderheide, RH Gross, DA Alves, P Tourdot, S Scardino, A Graff-Dubois, S Faure, O Opolon, P Chouaib, S Lemmonier, FA Cardoso, AA Schultze, JL Nadler, LM Kosmatopoulos, K AF Vonderheide, RH Gross, DA Alves, P Tourdot, S Scardino, A Graff-Dubois, S Faure, O Opolon, P Chouaib, S Lemmonier, FA Cardoso, AA Schultze, JL Nadler, LM Kosmatopoulos, K TI Targeting dominant and cryptic peptide epitopes from the telomerase catalytic subunit reveals anti-tumor responses and autoimmune phenomena. SO BLOOD LA English DT Meeting Abstract C1 Inst Gustave Roussy, INSERM 487, F-94805 Villejuif, France. Inst Pasteur, Unite Immunite Cellularie Antivirale, Dept SIDA Retrovirus, Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011; Chouaib, Salem/F-7939-2016 OI Schultze, Joachim/0000-0003-2812-9853; NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 709 BP 165A EP 165A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100710 ER PT J AU Witzens, M Krackhardt, AM Harig, S Donovan, JW Gribben, JG AF Witzens, M Krackhardt, AM Harig, S Donovan, JW Gribben, JG TI Overexpression of ribosomal proteins in chronic lymphocytic leukemia identified by subtractive hybridization. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 4437 BP 168B EP 168B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256200777 ER PT J AU Mapara, MY Kim, YM Sachs, DH Sykes, M AF Mapara, MY Kim, YM Sachs, DH Sykes, M TI Administration of donor lymphocyte infusions (DLI) leads to superior graft-versus-leukemia-reactions in mixed hematopoietic chimeras than in full donor chimeras. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. RI mapara, markus/A-2134-2013 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 NOV 16 PY 2000 VL 96 IS 11 MA 759 BP 176A EP 176A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100760 ER PT J AU Mapara, MY Kim, YM Sykes, M AF Mapara, MY Kim, YM Sykes, M TI Donor lymphocyte infusions (DLI) can induce alloresponses in graft-versus-host (GVH) and host-versus-graft (HVG) direction. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. RI mapara, markus/A-2134-2013 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 NOV 16 PY 2000 VL 96 IS 11 MA 758 BP 176A EP 176A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100759 ER PT J AU Anderson, KS Wucherpfennig, KA Haining, WN Schultze, JL Maecker, B Xia, Z Butler, MO Vonderheide, RH Nadler, LM AF Anderson, KS Wucherpfennig, KA Haining, WN Schultze, JL Maecker, B Xia, Z Butler, MO Vonderheide, RH Nadler, LM TI Potential of antigen-specific adoptive immunotherapy using peptide/MHC tetramers and microbeads for high-yield purification of cytotoxic T lymphocytes from peripheral blood. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 761 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100762 ER PT J AU Kim, YM Mapara, MY Sykes, M AF Kim, YM Mapara, MY Sykes, M TI Graft-versus-leukemia effect of donor lymphocyte infusion (DLI) without GvHD in mixed chimeras prepared with non-myeloablative conditioning: Can recipient leukocyte infu-sion (RLI) also induce GvL effects? SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Boston, MA USA. RI mapara, markus/A-2134-2013 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 NOV 16 PY 2000 VL 96 IS 11 MA 760 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100761 ER PT J AU Ash, S Donovan, JW Temel, J Zuckerman, A Grupp, SD Diller, L Gribben, JG AF Ash, S Donovan, JW Temel, J Zuckerman, A Grupp, SD Diller, L Gribben, JG TI Detection of minimal residual disease and assessment of stem cell purging by TaqMan real time PCR quantitation of GAGE expression in patients with neuroblastoma. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 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 NOV 16 PY 2000 VL 96 IS 11 MA 801 BP 187A EP 187A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100802 ER PT J AU Porter, D Luger, S Duffy, K Orloff, G Tsai, D Stadtmauer, E Laport, G Schuster, S McDaid, K Kathakali, A Leonard, D Antin, J AF Porter, D Luger, S Duffy, K Orloff, G Tsai, D Stadtmauer, E Laport, G Schuster, S McDaid, K Kathakali, A Leonard, D Antin, J TI Allogeneic cell therapy (ACT) after relapse from autologous stem cell transplantation (autoSCT). SO BLOOD LA English DT Meeting Abstract C1 Univ Penn, Stem Cell Transplant Program, Philadelphia, PA 19104 USA. Inova Fairfax Hosp, Bone Marrow Transplant Program, Annandale, VA USA. Dana Farber Canc Inst, Bone Marrow Transplant Program, 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 NOV 16 PY 2000 VL 96 IS 11 MA 836 BP 195A EP 195A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100837 ER PT J AU Soiffer, RJ Alyea, EP Canning, CM Weller, E Webb, I Schlossman, RL Anderson, KC Ritz, J AF Soiffer, RJ Alyea, EP Canning, CM Weller, E Webb, I Schlossman, RL Anderson, KC Ritz, J TI Effects of donor lymphocyte infusions (DLI) on prevention of disease relapse after 0T-cell depleted (TCD) allogeneic bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 838 BP 196A EP 196A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100839 ER PT J AU Kraus, A Spitzer, T Lee, S Toh, HC Shaffer, J McAfee, S Sackstein, R Colby, C Preffer, F Saidman, S Dombkowski, D Weymouth, D Sykes, M AF Kraus, A Spitzer, T Lee, S Toh, HC Shaffer, J McAfee, S Sackstein, R Colby, C Preffer, F Saidman, S Dombkowski, D Weymouth, D Sykes, M TI Early CD8 T-cell recovery and sensitized cytotoxic T cell response correlate with marrow graft rejection following bone marrow transplantation (BMT) with a nonmyeloablative regimen. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 866 BP 202A EP 203A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256100867 ER PT J AU Roberts, TF Ryan, H Schenkein, D Sprague, K Mitus, J Parsons, SK Wheeler, C Antin, JH Miller, KB AF Roberts, TF Ryan, H Schenkein, D Sprague, K Mitus, J Parsons, SK Wheeler, C Antin, JH Miller, KB TI Long-term outcome of de novo AML treated with allogeneic versus autologous bone marrow transplant. SO BLOOD LA English DT Meeting Abstract C1 Tufts Univ, New England Med Ctr, Medford, MA 02155 USA. 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 NOV 16 PY 2000 VL 96 IS 11 MA 873 BP 204A EP 204A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100874 ER PT J AU Cutler, C Giri, S Jeyapalan, S Paniagua, D Viswanathan, A Antin, J AF Cutler, C Giri, S Jeyapalan, S Paniagua, D Viswanathan, A Antin, J TI Incidence of acute and chronic GVHD after allogeneic peripheral blood stem cell and bone marrow transplantation: A meta-analysis. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 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 NOV 16 PY 2000 VL 96 IS 11 MA 876 BP 205A EP 205A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100877 ER PT J AU Shipp, M Tamayo, P Angelo, M Ray, T Reich, M Neuberg, D Last, K Aster, J Mesirov, J Lister, A Golub, TR AF Shipp, M Tamayo, P Angelo, M Ray, T Reich, M Neuberg, D Last, K Aster, J Mesirov, J Lister, A Golub, TR TI Diffuse large B cell lymphoma outcome prediction by gene expression profiling. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. St Bartholomews Hosp, Imperial Canc Res Fund, Med Oncol Unit, London, England. NR 0 TC 6 Z9 6 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 NOV 16 PY 2000 VL 96 IS 11 MA 948 BP 222A EP 222A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100949 ER PT J AU Janicek, MJ Janicek, MR Friedberg, JW Demetri, GD AF Janicek, MJ Janicek, MR Friedberg, JW Demetri, GD TI Dynamic infrared imaging (DIRI) of newly diagnosed lymphoma. Correlation with gallium-67 imaging (GA) and F-18FDG positron emission tomography (PET). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 4698 BP 224B EP 225B PN 2 PG 2 WC Hematology SC Hematology GA 372WC UT WOS:000165256201038 ER PT J AU Haining, WN Moreau, L Taniguchi, T De Oca, RM Garcia-Higuera, I Guinan, EC Grompe, M D'Andrea, AD AF Haining, WN Moreau, L Taniguchi, T De Oca, RM Garcia-Higuera, I Guinan, EC Grompe, M D'Andrea, AD TI Rapid assessment of Fanconi pathway function: A new diagnostic approach to Fanconi Anemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97201 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 NOV 16 PY 2000 VL 96 IS 11 MA 977 BP 229A EP 229A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256100978 ER PT J AU Wang, KS Ritz, J AF Wang, KS Ritz, J TI Identification of IL-12 induced genes in human T cells and NK cells by gene expression profiling. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 1012 BP 236A EP 236A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101013 ER PT J AU Aguiar, RCT Kreinbrink, KD Shipp, MA AF Aguiar, RCT Kreinbrink, KD Shipp, MA TI The B-lymphoid protein tyrosine phosphatase PTPROt modulates B-cell activation following BCR engagement. SO BLOOD LA English DT Meeting Abstract 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 SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1014 BP 237A EP 237A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101015 ER PT J AU Grader-Beck, T van Puijenbroek, AAFL Nadler, LM Boussiotis, VA AF Grader-Beck, T van Puijenbroek, AAFL Nadler, LM Boussiotis, VA TI Increase of endogenous cyclic AMP recapitulates functional and biochemical properties of T cell anergy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 1024 BP 239A EP 239A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101025 ER PT J AU Tse, WT Beyer, W Pendleton, JD D'Andrea, A Guinan, EC AF Tse, WT Beyer, W Pendleton, JD D'Andrea, A Guinan, EC TI Bone marrow-derived mesenchymal stem cells suppress T cell activation without inducing allogeneic anergy. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 9 Z9 10 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 NOV 16 PY 2000 VL 96 IS 11 MA 1034 BP 241A EP 241A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101035 ER PT J AU Resendiz, JC Feng, SJ Christodoulides, N Arboleda, D Berndt, MC Kroll, MH AF Resendiz, JC Feng, SJ Christodoulides, N Arboleda, D Berndt, MC Kroll, MH TI Phosphoinositide 3-kinase (PI3-K) is activated and associates with glycoprotein (GP) IB alpha in platelets exposed to pathological shear stress. SO BLOOD LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Rice Univ, Houston, TX 77251 USA. Baker Med Res Inst, Hazel & Pip Appel Vasc Biol Lab, Prahran, Vic, Australia. RI Berndt, Michael/D-5580-2012 NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 1045 BP 243A EP 243A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101046 ER PT J AU Carcao, MD Zerem, A Christensen, H Freedman, MH Rand, M Blanchett, V Kuter, D Butchart, S Dror, Y AF Carcao, MD Zerem, A Christensen, H Freedman, MH Rand, M Blanchett, V Kuter, D Butchart, S Dror, Y TI Familial thrombocytopenia: Characterization of the disease and the basis for the hematological abnormalities. SO BLOOD LA English DT Meeting Abstract C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Massachusetts Gen Hosp, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 1099 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101100 ER PT J AU Peyvandi, F Carew, JA Perry, DJ Hunault, M Khanduri, U Perkins, S Mannucci, PM Bauer, KA AF Peyvandi, F Carew, JA Perry, DJ Hunault, M Khanduri, U Perkins, S Mannucci, PM Bauer, KA TI A homozygous 15 bp insertion in the human factor VII gene results in modification of a calcium binding site and reduced secretion/function. SO BLOOD LA English DT Meeting Abstract C1 Univ Milan, A Bianchi Bonomi Hemophilia & Thrombosis Ctr, I-20122 Milan, Italy. Boston VA Healthcare Syst, Dept Med, Boston, MA USA. Univ London Royal Free Hosp, Sch Med, London, England. Sultan Qaboos Univ, Dept Hematol, Oman, Oman. RI Mannucci, Pier/C-3102-2014 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 NOV 16 PY 2000 VL 96 IS 11 MA 1121 BP 261A EP 261A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101122 ER PT J AU Stone, R DeAngelo, D Galinsky, I Yang, XP Daftary, F Xu, GG Liou, S AF Stone, R DeAngelo, D Galinsky, I Yang, XP Daftary, F Xu, GG Liou, S TI A phase IIb trial of all-trans retinoic acid (ATRA) combined with bryostatin 1 (BRYO) in patients (pts) with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 4879 BP 265B EP 265B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201219 ER PT J AU Grabowski, EF Khan, Y Shih, S Ingelfinger, JR AF Grabowski, EF Khan, Y Shih, S Ingelfinger, JR TI Shigatoxin augments the expression of functional tissue factor by activated human glomerular endothelial cells, indicating a potentially important role for the tissue factor pathway in the hemolytic uremic syndrome. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 1166 BP 271A EP 271A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101167 ER PT J AU Miyamoto, T Akashi, K Weissman, IL AF Miyamoto, T Akashi, K Weissman, IL TI Simultaneous priming of multilineage genes in common myeloid progenitor. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Med Ctr, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 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 NOV 16 PY 2000 VL 96 IS 11 MA 1214 BP 282A EP 283A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101215 ER PT J AU Kelley, CM Georgopoulos, K AF Kelley, CM Georgopoulos, K TI The role of the transcriptional co-repressor, Sin3B, in development, hematopoiesis and cell proliferation. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RI Kelley, Clair/O-2688-2015 NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 1235 BP 287A EP 287A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101236 ER PT J AU Avigan, D Wu, Z Joyce, R Elias, A Richardson, P McDermott, D Levine, J Kennedy, L Tetreault, J Giallombardo, N Hurley, D Gong, J Kufe, D AF Avigan, D Wu, Z Joyce, R Elias, A Richardson, P McDermott, D Levine, J Kennedy, L Tetreault, J Giallombardo, N Hurley, D Gong, J Kufe, D TI The impact of GM-CSF on immune recovery following high dose chemotherapy with stem cell rescue for patients with advanced breast cancer. SO BLOOD LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. 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 NOV 16 PY 2000 VL 96 IS 11 MA 5026 BP 297B EP 297B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201366 ER PT J AU Sasaki, K North, T Speck, H Golub, TR AF Sasaki, K North, T Speck, H Golub, TR TI Transcriptional targets of core binding factor fusion proteins. SO BLOOD LA English DT Meeting Abstract C1 Dartmouth Med Sch, Dept Biochem, Hanover, NH USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead MIT Ctr Genome Res, Cambridge, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 1299 BP 301A EP 301A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101300 ER PT J AU Le Guern, AC Giovino, MA Sonntag, KC Sykes, M White-Scharf, ME Down, J AF Le Guern, AC Giovino, MA Sonntag, KC Sykes, M White-Scharf, ME Down, J TI Porcine c-kit high hematopoietic cells display more primitive progenitor cell characteristics than their primate counterparts. SO BLOOD LA English DT Meeting Abstract C1 BioTransplant Inc, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 5050 BP 302B EP 302B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201390 ER PT J AU Levy, O Sisson, RB Fryer, HE Ganz, T White, M Carroll, SF Guinan, EC AF Levy, O Sisson, RB Fryer, HE Ganz, T White, M Carroll, SF Guinan, EC TI Innate immunity in patients undergoing bone marrow transplantation: Studies of bactericidal/permeability-increasing protein (BPI) & defensins in graft-derived neutrophils. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Gen Clin Res Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. XOMA US LLC, Preclin Res, Berkeley, CA USA. Childrens Hosp, 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 NOV 16 PY 2000 VL 96 IS 11 MA 5052 BP 303B EP 303B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201392 ER PT J AU Hideshima, T Chauhan, D Shima, Y Noopur, R Davies, FE Tai, YT Treon, SP Lin, BK Schlossman, RL Richardson, PG Gupta, D Muller, GW Stirling, DI Anderson, KC AF Hideshima, T Chauhan, D Shima, Y Noopur, R Davies, FE Tai, YT Treon, SP Lin, BK Schlossman, RL Richardson, PG Gupta, D Muller, GW Stirling, DI Anderson, KC TI Thalidomide (Thal) and its analogs overcome drug resistance of human multiple myeloma (MM) cells to conventional therapy. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 5 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 NOV 16 PY 2000 VL 96 IS 11 MA 1313 BP 304A EP 304A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101314 ER PT J AU Gupta, D Li, YZ Li, CJ Lin, BK Hideshima, T Podar, K Davies, FE Raje, N Lentzsch, S Tai, YT Mitsiades, C Mitsiades, N Hayashi, T Chauhan, D Treon, SP Richardson, PG Pardee, AB Anderson, KC AF Gupta, D Li, YZ Li, CJ Lin, BK Hideshima, T Podar, K Davies, FE Raje, N Lentzsch, S Tai, YT Mitsiades, C Mitsiades, N Hayashi, T Chauhan, D Treon, SP Richardson, PG Pardee, AB Anderson, KC TI beta-Lapachone demonstrates activity against drug resistant multiple myeloma (MM) cell lines and patient cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1325 BP 307A EP 307A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101326 ER PT J AU Mapara, MY Kim, YM Sykes, M AF Mapara, MY Kim, YM Sykes, M TI Induction of graft-versus-leukemia (GVL) effects by donor lymphocyte infusions (DLI) after non-myeloablative conditioning: Evidence for loss of GVL reactivity over time. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI mapara, markus/A-2134-2013 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 NOV 16 PY 2000 VL 96 IS 11 MA 5090 BP 311B EP 311B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201430 ER PT J AU Donovan, JW Zuckerman, A Waters, S Silverman, L Sallan, S Gribben, JG AF Donovan, JW Zuckerman, A Waters, S Silverman, L Sallan, S Gribben, JG TI Analysis of residual disease levels in pediatric acute lymphoblastic leukemia by TaqMan quantitative PCR. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1355 BP 314A EP 314A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101356 ER PT J AU Cripe, LD Neuberg, D Tallman, MS Litzow, MR O'Brien, TE Bedrosian, C Paietta, E Bennett, J Rowe, J AF Cripe, LD Neuberg, D Tallman, MS Litzow, MR O'Brien, TE Bedrosian, C Paietta, E Bennett, J Rowe, J TI A phase II trial of subcutaneous recombinant human interleukin 11 (rhIL-11) with subcutaneous recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) in patients with acute myeloid leukemia (AML) receiving high-dose cytarabine during induction: ECOG 3997. SO BLOOD LA English DT Meeting Abstract C1 Indiana Univ, Med Ctr, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Genet Inst, Boston, MA USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Univ Rochester, Rochester, NY USA. Rambam Med Ctr, Haifa, Israel. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1393 BP 323A EP 323A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101394 ER PT J AU Appleman, LJ Nadler, LM Boussiotis, VA AF Appleman, LJ Nadler, LM Boussiotis, VA TI Split functional and signaling properties of splenic T cells in patients with marginal zone lymphoma. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1413 BP 327A EP 327A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101414 ER PT J AU von Bergwelt-Baildon, MS Vonderheide, RH Maecker, B Anderson, KS Hirano, N Wucherpfennig, KW Nadler, LM Schultze, JL AF von Bergwelt-Baildon, MS Vonderheide, RH Maecker, B Anderson, KS Hirano, N Wucherpfennig, KW Nadler, LM Schultze, JL TI B cells generated in the CD40-system prime naive T cells: Implications for cellular vaccines in B cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 1466 BP 339A EP 339A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101467 ER PT J AU Okuda, K Weisberg, E Gilliland, DG Griffin, JD AF Okuda, K Weisberg, E Gilliland, DG Griffin, JD TI The ARG tyrosine kinase is inhibited by STI571. SO BLOOD LA English DT Meeting Abstract 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 SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1487 BP 344A EP 344A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101488 ER PT J AU Sattler, H Verma, S Pride, YB Salgia, R Griffin, JD AF Sattler, H Verma, S Pride, YB Salgia, R Griffin, JD TI BCR/ABL, TEL/ABL, TEL/JAK2 and oxidative stress reduce expression of the proto-oncogene CBL-B, a regulator of lymphocyte activation. SO BLOOD LA English DT Meeting Abstract 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 SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1498 BP 347A EP 347A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101499 ER PT J AU Zhang, J Zhang, XW Gillessen, S Dranoff, G Ren, R AF Zhang, J Zhang, XW Gillessen, S Dranoff, G Ren, R TI Bcr-abl induces CML-like myeloproliferative disorder with expansion of bystander myeloid cells independent of IL-3 and GM-CSF in mice. SO BLOOD LA English DT Meeting Abstract C1 Brandeis Univ, Waltham, MA 02254 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 HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1505 BP 348A EP 349A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101506 ER PT J AU Teoh, G Raje, N Hideshima, T Tai, YT Sun, L Khoo, S Zhao, Y Chauhan, D Davies, F Shima, Y Anderson, KC AF Teoh, G Raje, N Hideshima, T Tai, YT Sun, L Khoo, S Zhao, Y Chauhan, D Davies, F Shima, Y Anderson, KC TI Development of long-term human multiple myeloma cells using Dexter-type cultures containing autologous serum. SO BLOOD LA English DT Meeting Abstract C1 Singapore Gen Hosp, Singapore 0316, Singapore. 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 HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1558 BP 361A EP 361A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101559 ER PT J AU Hideshima, T Chauhan, D Richardson, PG Palombella, VJ Elliot, PJ Adams, J Anderson, KC AF Hideshima, T Chauhan, D Richardson, PG Palombella, VJ Elliot, PJ Adams, J Anderson, KC TI Role of TNF alpha in the pathophysiology of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1573 BP 364A EP 364A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101574 ER PT J AU Widhopf, GF Marathe, CM Rassenti, LZ Byrd, JC Flinn, IW Gribben, JG Kipps, TJ AF Widhopf, GF Marathe, CM Rassenti, LZ Byrd, JC Flinn, IW Gribben, JG Kipps, TJ TI Lack of correlation between immunoglobulin somatic mutation and expression of CD38 in chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 NIH, NCI, CLL Res Consortium, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Div Hematol Oncol, La Jolla, CA 92093 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1586 BP 367A EP 367A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101587 ER PT J AU Tzachanis, D Nadler, LM Boussiotis, VA AF Tzachanis, D Nadler, LM Boussiotis, VA TI Blockade of B7/CD28 pathway results in the generation of alternatively activated macrophages. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1615 BP 374A EP 374A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101616 ER PT J AU Nikolic, B Cooke, DT Zhao, G Sykes, M AF Nikolic, B Cooke, DT Zhao, G Sykes, M TI Role of gamma/delta T cells and NK cells in resisting the engraftment of xenogeneic rat bone marrow cells in mice. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 1618 BP 375A EP 375A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101619 ER PT J AU Boussiotis, VA Taylor, P Greenwald, R Berezovskaya, A Nadler, LM Sharpe, AH Blazar, BR AF Boussiotis, VA Taylor, P Greenwald, R Berezovskaya, A Nadler, LM Sharpe, AH Blazar, BR TI Increased T cell alloresponses in mice lacking B7-1 and B7-2 molecules. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Dept Pediat, Ctr Canc, Minneapolis, MN 55455 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, 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 NOV 16 PY 2000 VL 96 IS 11 MA 1625 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101626 ER PT J AU Vieira, APZ Kasahara, N Cardoso, A Pullarkat, V Levine, AM Stripecke, R AF Vieira, APZ Kasahara, N Cardoso, A Pullarkat, V Levine, AM Stripecke, R TI Third generation lentiviral vectors to "boost" an immune response against acute myeloid leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 Univ So Calif, Inst Med Genet, Los Angeles, CA USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Univ So Calif, Div Hematol, Los Angeles, CA USA. Dana Farber Canc Inst, Dept Adult Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 5423 BP 385B EP 385B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201763 ER PT J AU Bhoopalam, N Hynes, D Marriott, E AF Bhoopalam, N Hynes, D Marriott, E TI Evaluating clinical trials productivity in a hematology/oncology division. SO BLOOD LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Hematol Oncol Sect, Maywood, IL USA. Midwest Ctr Hlth Serv & Policy Res, Maywood, IL USA. Loyola Univ, Med Ctr, Maywood, IL 60153 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 NOV 16 PY 2000 VL 96 IS 11 MA 5438 BP 388B EP 388B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201778 ER PT J AU Tse, WT Beyer, W Pendleton, JD Richardson, P Guinan, EC AF Tse, WT Beyer, W Pendleton, JD Richardson, P Guinan, EC TI Genetic polymorphisms in glutathione S-transferase and plasminogen activator inhibitor and risk of veno-occlusive disease (VOD). SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1681 BP 390A EP 390A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101682 ER PT J AU Shklovsky, N Zingerman, B Goldberg, S Krol, M AF Shklovsky, N Zingerman, B Goldberg, S Krol, M TI Normalization of a picture representation of the clinical information. Harmony of curves. SO BLOOD LA English DT Meeting Abstract C1 Natl Ctr Hematol, Moscow, Russia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, New York, NY 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 NOV 16 PY 2000 VL 96 IS 11 MA 5450 BP 391B EP 391B PN 2 PG 1 WC Hematology SC Hematology GA 372WC UT WOS:000165256201790 ER PT J AU Cahn, JY Cordonnier, JM Lee, S Milpied, N Blaise, D Leblond, V Klein, J Horowitz, MM Socie, G AF Cahn, JY Cordonnier, JM Lee, S Milpied, N Blaise, D Leblond, V Klein, J Horowitz, MM Socie, G TI Societe Francaise de Greffe de Moelle (SFGM) and Dana Farber Cancer Institute (DFCI) prospective multicenter evaluation of two acute graft versus host disease grading systems: A preliminary analysis on 607 patients. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, SFGM, Boston, MA 02115 USA. IBMTR, SFGM, Milwaukee, WI USA. RI Cahn, Jean-Yves/M-6493-2014 NR 2 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 1713 BP 397A EP 397A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101714 ER PT J AU Dey, BR McAfee, S Sackstein, R Colby, C Saidman, S Weymouth, D Poliquin, C Vanderklish, J Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, S Sackstein, R Colby, C Saidman, S Weymouth, D Poliquin, C Vanderklish, J Sachs, DH Sykes, M Spitzer, TR TI Successful second allogeneic marrow transplantation following non-myeloablative conditioning for patients with relapsed/refractory lymphoma after failure of autologous transplant. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 1775 BP 412A EP 412A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101776 ER PT J AU Soiffer, RJ Weller, E Lee, SJ Alyea, EP Schlossman, RL Gribben, JG Ritz, J Antin, JH AF Soiffer, RJ Weller, E Lee, SJ Alyea, EP Schlossman, RL Gribben, JG Ritz, J Antin, JH TI Comparative outcomes of cyclosporine/methotrexate and CD6+T cell depletion (TCD) as graft-vs-host disease (GVHD) prophylaxis for allogeneic bone marrow transplantation (BMT) from unrelated donors (URD). SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1784 BP 415A EP 415A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101785 ER PT J AU Tse, WT Tang, J Jin, O Korsgren, C John, KM Gwynn, B Peters, LL Lux, SE AF Tse, WT Tang, J Jin, O Korsgren, C John, KM Gwynn, B Peters, LL Lux, SE TI A new spectrin, beta IV, has a major N-terminally truncated isoform that associates with PML nuclear bodies and the nuclear matrix. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Jackson Lab, Bar Harbor, ME 04609 USA. OI TANG, JIH-LUH/0000-0003-4021-3281 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 NOV 16 PY 2000 VL 96 IS 11 MA 1896 BP 440A EP 441A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101897 ER PT J AU Martinez, R Golub, TR AF Martinez, R Golub, TR TI Transcriptional repression of Idl by the leukemogenic Ets protein TEL. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. MIT, Ctr Genome Res, Cambridge, MA 02139 USA. NR 0 TC 7 Z9 7 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 NOV 16 PY 2000 VL 96 IS 11 MA 1950 BP 453A EP 453A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101951 ER PT J AU Pharr, PN Kawada, H Ito, T Spyropoulos, D Watson, DK Ogawa, M AF Pharr, PN Kawada, H Ito, T Spyropoulos, D Watson, DK Ogawa, M TI Amegakarypoiesis and dyserythropoiesis in Flil-null mice. SO BLOOD LA English DT Meeting Abstract C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Mol & Struct Biol, Charleston, SC 29425 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 NOV 16 PY 2000 VL 96 IS 11 MA 1956 BP 454A EP 454A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101957 ER PT J AU Tomasson, MH Williams, IR Li, SG Kutok, J Gillessen, S Dranoff, G Van Etten, RA Gilliland, DG AF Tomasson, MH Williams, IR Li, SG Kutok, J Gillessen, S Dranoff, G Van Etten, RA Gilliland, DG TI Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require GM-CSF or IL-3. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. 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 NOV 16 PY 2000 VL 96 IS 11 MA 1977 BP 459A EP 459A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101978 ER PT J AU Mitsiades, NS Mitsiades, CS Anderson, KC Treon, SP AF Mitsiades, NS Mitsiades, CS Anderson, KC Treon, SP TI Doxorubicin and NF-kB inhibitors sensitize multiple myeloma cells to trail induced apoptosis. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1983 BP 460A EP 461A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256101984 ER PT J AU Hideshima, T Richardson, PG Chauhan, D Palombella, VJ Elliott, PJ Adams, J Anderson, KC AF Hideshima, T Richardson, PG Chauhan, D Palombella, VJ Elliott, PJ Adams, J Anderson, KC TI The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2000 VL 96 IS 11 MA 1985 BP 461A EP 461A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101986 ER PT J AU Barata, JT Cardoso, AA Keenan, T Sallan, S Nadler, LM Boussiotis, VA AF Barata, JT Cardoso, AA Keenan, T Sallan, S Nadler, LM Boussiotis, VA TI Downregulation of p27(kip1) by IL-7 is mandatory for induction of bcl-2. Promotion of viability and cell cycle progression in T cell acute lymphoblastic leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1989 BP 462A EP 462A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101990 ER PT J AU Cardoso, AA Maia, S Nadler, LM AF Cardoso, AA Maia, S Nadler, LM TI Mechanisms facilitating failure of immune surveillance in acute lymphoblastic leukemia: Detection of regulatory supressive T-cells in the bone marrow. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Maia, Sara/B-2513-2013 OI Maia, Sara/0000-0001-8638-0566 NR 0 TC 1 Z9 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 1998 BP 464A EP 464A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256101999 ER PT J AU Roumiantsev, S Brasher, BB Van Etten, RA AF Roumiantsev, S Brasher, BB Van Etten, RA TI A point mutation in the ABL catalytic domain induces resistance to the tyrosine kinase inhibitor STI 571. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2023 BP 470A EP 470A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102024 ER PT J AU Chauhan, D Hideshima, T Rosen, S Reed, J Anderson, KC AF Chauhan, D Hideshima, T Rosen, S Reed, J Anderson, KC TI Role of caspase-9 and inhibitors of apoptosis proteins (IAP's) during dexamethasone (DEX)-induced apoptosis in multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Robert H Laurie Canc Ctr, Chicago, IL USA. Burnham Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 2031 BP 472A EP 472A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102032 ER PT J AU Hsu, JH Shi, YJ Chin, J Krajewski, S Reed, J Lichtenstein, AK AF Hsu, JH Shi, YJ Chin, J Krajewski, S Reed, J Lichtenstein, AK TI Central role for the AKT kinase in multiple myeloma cell expansion. SO BLOOD LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Burnham Inst, Dept Oncogene Apoptosis Res, La Jolla, CA 92037 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 NOV 16 PY 2000 VL 96 IS 11 MA 2032 BP 472A EP 472A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102033 ER PT J AU Ned, RM Swat, WA Levy, JE Andrews, NC AF Ned, RM Swat, WA Levy, JE Andrews, NC TI Transferrin receptor I (Trfr) is essential for lymphopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Ned, Renee/D-3746-2009 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 NOV 16 PY 2000 VL 96 IS 11 MA 2096 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102097 ER PT J AU Poznansky, MC Olszak, IT Evans, RH Wang, ZY Foxall, RB Olson, D Weibrecht, K Scadden, DT AF Poznansky, MC Olszak, IT Evans, RH Wang, ZY Foxall, RB Olson, D Weibrecht, K Scadden, DT TI T-cell emigration from the thymus is the result of chemofugetaxis in response to stromal chemokinetic agents including SDF-1. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2100 BP 488A EP 488A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102101 ER PT J AU Zhang, P Phelan, ML Zhang, XB Nelson, EA Kingston, RE Tenen, DG AF Zhang, P Phelan, ML Zhang, XB Nelson, EA Kingston, RE Tenen, DG TI C/EBP alpha physically interacts with and recruits the chromatin remodeling complex (SWI-SNF) to myeloid promoters. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2137 BP 496A EP 496A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102138 ER PT J AU Aguiar, RCT Kreinbrink, KD Shipp, MA AF Aguiar, RCT Kreinbrink, KD Shipp, MA TI Cloning and characterization of BAL2, a novel member of a risk-related gene family in diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 2175 BP 505A EP 505A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102176 ER PT J AU Gu, LQ Aguiar, RCT Freeman, GJ Shipp, MA AF Gu, LQ Aguiar, RCT Freeman, GJ Shipp, MA TI Molecular and functional analyses of a novel risk-related gene, BBAP, in diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract 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 SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2174 BP 505A EP 505A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102175 ER PT J AU Krackhardt, AM Witzens, M Donovan, JW Chessia, M Harig, S Gribben, JG AF Krackhardt, AM Witzens, M Donovan, JW Chessia, M Harig, S Gribben, JG TI JM1, isolation and characterization of a novel CLL antigen recognized by autologous and syngeneic IgG antibodies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2208 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102209 ER PT J AU Witzens, M Krackhardt, AM Harig, S Zauls, AJ Donovan, JW Gribben, JG AF Witzens, M Krackhardt, AM Harig, S Zauls, AJ Donovan, JW Gribben, JG TI Chronic lymphocytic leukemia antigens elicit specific immune responses in the autologous host. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 2209 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102210 ER PT J AU Colby, C McAfee, S Sackstein, R Dey, B Saidman, S Sachs, DH Sykes, M Spitzer, TR AF Colby, C McAfee, S Sackstein, R Dey, B Saidman, S Sachs, DH Sykes, M Spitzer, TR TI Engraftment syndrome following nonmyeloablative conditioning therapy and HLA-matched bone marrow transplantation (BMT) for hematologic malignancy (HM). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 11 Z9 11 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 NOV 16 PY 2000 VL 96 IS 11 MA 2238 BP 520A EP 520A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102238 ER PT J AU Kratz, A Alexander, SI McAfee, SL Grossberg, H Sackstein, R Colby, C Hope, I Preffer, FL Saidman, SL Weymouth, D Dombkowski, D Sachs, DH Spitzer, TR Sykes, M AF Kratz, A Alexander, SI McAfee, SL Grossberg, H Sackstein, R Colby, C Hope, I Preffer, FL Saidman, SL Weymouth, D Dombkowski, D Sachs, DH Spitzer, TR Sykes, M TI Early predominance of host or donor T-cells correlates with graft failure and GVHD, respectively, in recipients of extensively HLA-mismatched bone marrow transplants following non-myeloablative conditioning. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. BioTransplant Inc, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2244 BP 522A EP 522A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102244 ER PT J AU Lee, SJ Fairclough, D Antin, JH Weeks, JC AF Lee, SJ Fairclough, D Antin, JH Weeks, JC TI Accuracy of patient and physician estimates for survival and recovery following stem cell transplantation (SCT). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. AMC Canc Res Ctr, Denver, CO 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 NOV 16 PY 2000 VL 96 IS 11 MA 2252 BP 524A EP 524A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102252 ER PT J AU Tao, C Rodrigues, N Dombkowski, D Stier, S Scadden, D AF Tao, C Rodrigues, N Dombkowski, D Stier, S Scadden, D TI Enhanced hematopoietic repopulation without increased stem cell number in the absence of the CDK inhibitor, p27 SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr & MGH Canc Ctr, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2304 BP 536A EP 536A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102304 ER PT J AU Fonseca, R Harrington, D Oken, MM Dewald, GW Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Blood, EA Greipp, PR AF Fonseca, R Harrington, D Oken, MM Dewald, GW Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Blood, EA Greipp, PR TI Prognostic significance of 13q deletions and the t(11;14)(q13;q32) in myeloma (MM); An interphase FISH study of 351 patients entered into the Eastern Cooperative Oncology Group E9487 clinical trial. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. NR 0 TC 8 Z9 8 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 NOV 16 PY 2000 VL 96 IS 11 MA 2352 BP 547A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102352 ER PT J AU Taniguchi, T Ganesan, S Meyn, S Timmers, C Grompe, M D'Andrea, AD AF Taniguchi, T Ganesan, S Meyn, S Timmers, C Grompe, M D'Andrea, AD TI DNA damage-induced association of the Fanconi Anemia protein, FANCD2, with BRCA1 nuclear foci. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Sick Children, Dept Genet, Toronto, ON M5G 1X8, Canada. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2402 BP 559A EP 559A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102402 ER PT J AU Siddique, MA Taniguchi, T Hays, TG D'Andrea, AD AF Siddique, MA Taniguchi, T Hays, TG D'Andrea, AD TI The Fanconi Anemia protein, FANCF, is a component of the functional FA protein complex. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 2403 BP 560A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102403 ER PT J AU Schwer, HD Tiwari, S Lecine, P Shivdasani, RA AF Schwer, HD Tiwari, S Lecine, P Shivdasani, RA TI Essential role of the megakaryocyte-specific beta-tubulin isoform beta 1 in formation and function of blood platelets. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Lecine, Patrick/H-9338-2016 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 NOV 16 PY 2000 VL 96 IS 11 MA 2417 BP 563A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102417 ER PT J AU Gillessen, S Mach, N Small, C Mihm, M Dranoff, G AF Gillessen, S Mach, N Small, C Mihm, M Dranoff, G TI Mice deficient in GM-CSF and IL-3 show defects in hematopoiesis and immunity. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Geneva, Div Oncol, Geneva, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 2440 BP 568A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102440 ER PT J AU Husson, H Carideo, EG Neuberg, D Schultze, JL O'Connell, P Freedman, AS AF Husson, H Carideo, EG Neuberg, D Schultze, JL O'Connell, P Freedman, AS TI Comparison of the gene expression profile of follicular lymphomas and normal germinal center B cells using cDNA arrays. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 2465 BP 574A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102465 ER PT J AU Chauhan, D Auclair, D Hideshima, T Rosen, S Chen, LB Anderson, KC AF Chauhan, D Auclair, D Hideshima, T Rosen, S Chen, LB Anderson, KC TI Identification of genes regulated by dexamethasone (Dex) in multiple myeloma (MM) cells using oligonucleotide arrays. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Robert H Laurie Canc Ctr, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2484 BP 578A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102484 ER PT J AU Lentzsch, S Podar, K Davies, FE Hideshima, T Tai, YT Chauhan, D Lin, BK Treon, SP Gupta, D Mitsiades, C Mitsiades, N Hayashi, T Muller, GW Stirling, DI Anderson, KC AF Lentzsch, S Podar, K Davies, FE Hideshima, T Tai, YT Chauhan, D Lin, BK Treon, SP Gupta, D Mitsiades, C Mitsiades, N Hayashi, T Muller, GW Stirling, DI Anderson, KC TI Immunomodulatory derivatives (IMiDs) of thalidomide (Thal) inhibit the proliferation of multiple myeloma (MM) cell lines and block VEGF-induced activation of the MAPK-pathway. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. NR 0 TC 2 Z9 2 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 2486 BP 579A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102486 ER PT J AU Payvandi, F Wu, L Gupta, D Hideshima, T Haley, M Muller, G Chen, R Anderson, KC Stirling, S AF Payvandi, F Wu, L Gupta, D Hideshima, T Haley, M Muller, G Chen, R Anderson, KC Stirling, S TI Effects of a thalidomide analog on binding activity of transcription factors and cell cycle progression of multiple myeloma cell lines. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 2487 BP 579A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102487 ER PT J AU Adams, GB Chabner, KT Foxall, RB Rodriques, NP Poznansky, MC Scadden, DT AF Adams, GB Chabner, KT Foxall, RB Rodriques, NP Poznansky, MC Scadden, DT TI Lymphocyte augmentation of hematopoietic stem cell engraftment is due to cooperative effects of CD8+T cells on CD34+cell migration. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr & MGH Canc Ctr, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2490 BP 580A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102490 ER PT J AU Ladetto, M Sametti, S Donovan, JW Ferrero, D Astolfi, M Mitterer, M Ricca, I Drandi, D Corradini, P Coser, P Pileri, A Gribben, JG Tarella, C AF Ladetto, M Sametti, S Donovan, JW Ferrero, D Astolfi, M Mitterer, M Ricca, I Drandi, D Corradini, P Coser, P Pileri, A Gribben, JG Tarella, C TI An extensively valitaded real-time quantitative PCR approach shows a correlation between tumour burden (tb) and successful ex vivo purging in follicular lymphoma (FL) patients. SO BLOOD LA English DT Meeting Abstract C1 Univ Turin, Div Univ Ematol, Turin, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Osped Gen Reg, Div Ematol & Trapianto Midollo Osseo, Bolzano, Italy. Osped Gen Reg, Div Ematol & Trapianto Midollo Osseo, Bozen, Italy. RI drandi, daniela/Q-6504-2016 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 NOV 16 PY 2000 VL 96 IS 11 MA 2503 BP 583A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102503 ER PT J AU Richardson, PG Murakami, C Warren, DL Jin, Z Neuberg, D Elias, AD Antin, J Soiffer, R Bearman, SI Vredenburgh, J Vogelsang, G Hoppensteadt, D Fareed, J Iacobelli, M McDonald, GB Guinan, EC AF Richardson, PG Murakami, C Warren, DL Jin, Z Neuberg, D Elias, AD Antin, J Soiffer, R Bearman, SI Vredenburgh, J Vogelsang, G Hoppensteadt, D Fareed, J Iacobelli, M McDonald, GB Guinan, EC TI Multi-institutional emergency use of defibrotide (DF) in 75 pts post SCT with severe VOD and multi-system organ failure (MOF): Response without significant toxicity in a high risk population. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Onc Ctr, Baltimore, MD USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Crinos SpA, Como, Italy. NR 0 TC 2 Z9 2 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 NOV 16 PY 2000 VL 96 IS 11 MA 2510 BP 585A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102510 ER PT J AU Klein, C Nguyen, D Liu, CH Rosen, FS Alt, FW Mulligan, RC Snapper, SB AF Klein, C Nguyen, D Liu, CH Rosen, FS Alt, FW Mulligan, RC Snapper, SB TI Restoration of wasp-deficient T-cell signaling defects in mice upon transplantation of retrovirally transduced hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 Hannover Med Sch, D-3000 Hannover, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, 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 NOV 16 PY 2000 VL 96 IS 11 MA 2535 BP 591A EP 591A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102535 ER PT J AU Park, HY Shelley, CS Arnaout, MA AF Park, HY Shelley, CS Arnaout, MA TI The zinc finger transcription factor, ZBP-89 is a repressor of the human beta-2 integrin CD11b gene. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Leukocyte Biol & Inflammat Program, Charlestown, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2624 BP 611A EP + PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256102624 ER PT J AU Li, JZ Coburn, JP Bertino, AM Qi, XQ Xia, YP Kuter, DJ AF Li, JZ Coburn, JP Bertino, AM Qi, XQ Xia, YP Kuter, DJ TI Stress-induced caspase activation is associated with shortened platelet life span in rats. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 2827 BP 657A EP 657A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102827 ER PT J AU Hoffmeister, KM Falet, H Salib, L Denis, CV Wagner, DD Stossel, TP Hartwig, JH AF Hoffmeister, KM Falet, H Salib, L Denis, CV Wagner, DD Stossel, TP Hartwig, JH TI Chilled apoptotic and senescent platelets clear by distinct mechanisms. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, 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 NOV 16 PY 2000 VL 96 IS 11 MA 2828 BP 658A EP 658A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102828 ER PT J AU Lee, BC Cheng, T Saito, Y Olszak, I Dombkowski, D Hancock, J Miura, N Lee, SB Haber, DA Luster, AD Scadden, DT AF Lee, BC Cheng, T Saito, Y Olszak, I Dombkowski, D Hancock, J Miura, N Lee, SB Haber, DA Luster, AD Scadden, DT TI SC-GPR1 is a chemoattractant receptor mediating differentiation and homing of hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AIDS Res Ctr, Ctr Canc, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 2847 BP 662A EP 662A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102847 ER PT J AU Stier, S Cheng, T Miura, N Dombkowski, D Sarmento, LM Scadden, DT AF Stier, S Cheng, T Miura, N Dombkowski, D Sarmento, LM Scadden, DT TI Ex vivo expansion of primitive hematopoietic cells by reduction of p21(cip1/waf1) expression level. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Bonn, Med Poliklin, D-5300 Bonn, Germany. 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 NOV 16 PY 2000 VL 96 IS 11 MA 2869 BP 667A EP 667A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102869 ER PT J AU Tiwari, S Italiano, J Schwer, H Novak, E Hartwig, J Seabra, M Swank, R Shivdasani, RA AF Tiwari, S Italiano, J Schwer, H Novak, E Hartwig, J Seabra, M Swank, R Shivdasani, RA TI A role for the Rab sub-family of Ras GTPases in formation and release of blood platelets. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ London Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 2914 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102914 ER PT J AU Wang, FF Wu, EX Shipp, MA AF Wang, FF Wu, EX Shipp, MA TI Interleukin 6 is released by stromal cells following direct contact with diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract 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 SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2971 BP 690A EP 690A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102971 ER PT J AU Ferrando, AA Loh, M Neuberg, DS Raimondi, SC Behm, FG Downing, JR Golub, TR Gilliland, DG Look, AT AF Ferrando, AA Loh, M Neuberg, DS Raimondi, SC Behm, FG Downing, JR Golub, TR Gilliland, DG Look, AT TI Quantitative analysis of oncogenic transcription factors in T-cell acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 2997 BP 696A EP 696A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102997 ER PT J AU Klein, U Cattoretti, G Husson, H Inghirami, G Freedman, A Califano, A Dalla-Favera, R AF Klein, U Cattoretti, G Husson, H Inghirami, G Freedman, A Califano, A Dalla-Favera, R TI Gene expression profiles of normal peripheral human B-cell subpopulations and B-cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Columbia Univ, Inst Canc Genet, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. IBM Corp, Thomas J Watson Res Ctr, Funct & Struct Genom Grp, Yorktown Heights, NY 10598 USA. RI Califano, Andrea/F-7239-2012 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 NOV 16 PY 2000 VL 96 IS 11 MA 2996 BP 696A EP 696A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102996 ER PT J AU Rettig, MB Lichtenstein, AK An, JB AF Rettig, MB Lichtenstein, AK An, JB TI HHV8 latent nuclear antigen upregulates cellular IL-6 expression through the AP1 response element. SO BLOOD LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 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 NOV 16 PY 2000 VL 96 IS 11 MA 2998 BP 696A EP 696A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256102998 ER PT J AU Chuang, R McGill, G Ding, HF Fisher, DE AF Chuang, R McGill, G Ding, HF Fisher, DE TI A cell-free system for the analysis of p53-dependent apoptosis and inhibitors. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3024 BP 701A EP 701A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103024 ER PT J AU Artandi, SE Chang, S Alson, S Lee, SL Gottlieb, G Chin, L DePinho, RA AF Artandi, SE Chang, S Alson, S Lee, SL Gottlieb, G Chin, L DePinho, RA TI Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CPI Ameripath Lab, Beachwood, OH USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3041 BP 705A EP 705A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103041 ER PT J AU Donovan, JW Zuckerman, A Stephans, K Gribben, JC AF Donovan, JW Zuckerman, A Stephans, K Gribben, JC TI Quantitative analysis of residual disease levels by TaqMan PCR following bone marrow transplantation in chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3085 BP 714A EP 714A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103085 ER PT J AU Friedberg, JW Neuberg, D Gribben, JG Canning, C Daley, JF Kuhlman, C Koval, M Donovan, J Soiffer, RJ Freedman, AS AF Friedberg, JW Neuberg, D Gribben, JG Canning, C Daley, JF Kuhlman, C Koval, M Donovan, J Soiffer, RJ Freedman, AS TI Phase II study of combination immunotherapy with interleukin-2 (IL-2) and rituximab in patients with relapsed or refractory follicular non-Hodgkin's lymphoma (NHL). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3159 BP 730A EP 731A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256103158 ER PT J AU Li, SG Couvillon, A Brasher, BB Cantley, LC Van Etten, RA AF Li, SG Couvillon, A Brasher, BB Cantley, LC Van Etten, RA TI Tyrosine phosphorylation of the GRB2 adapter protein by Bcr/Abl and EGF receptor: A novel regulatory mechanism for tyrosine kinase signaling. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Signal Transduction, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 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 NOV 16 PY 2000 VL 96 IS 11 MA 3194 BP 739A EP 739A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103193 ER PT J AU Roumiantsev, S de Aos, IA Varticovski, L Ilaria, RL Van Etten, RA AF Roumiantsev, S de Aos, IA Varticovski, L Ilaria, RL Van Etten, RA TI Src homology 2 domain mutations decrease the intrinsic tyrosine kinase activity of Bcr/Abl and attenuate induction of CML-like myeloproliferative disease in mice, but do not cause qualitative defects in known signaling pathways. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Tufts Univ, St Elizabeths Hosp, Dept Biomed Res, Boston, MA USA. Univ Texas, SW Med Ctr, Hamon Ctr Oncol Res, Dallas, TX 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 NOV 16 PY 2000 VL 96 IS 11 MA 3193 BP 739A EP 739A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103192 ER PT J AU Tang, RP Delmer, P Levy, V Porcher, R DeCaprio, JA Ajchenbaum-Cymbalista, F AF Tang, RP Delmer, P Levy, V Porcher, R DeCaprio, JA Ajchenbaum-Cymbalista, F TI Histone deacetylase inhibitors and fludarabine have additive effects on in vitro apoptosis of B chronic lymphocytic leukemia (B-CLL) cells. SO BLOOD LA English DT Meeting Abstract C1 INSERM, E9912 E1529, Hotel Dieu, Paris, France. Hop St Louis, DBIM, Paris, France. 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 NOV 16 PY 2000 VL 96 IS 11 MA 3245 BP 750A EP 751A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256103244 ER PT J AU Raje, N Brander, C Davies, FE Chauhan, D Treon, SP Hideshima, T Tai, YT Lin, BK Gupta, D Lentzsch, S Podar, K Scadden, D Anderson, KC AF Raje, N Brander, C Davies, FE Chauhan, D Treon, SP Hideshima, T Tai, YT Lin, BK Gupta, D Lentzsch, S Podar, K Scadden, D Anderson, KC TI Absence of biologically significant gene products and cellular immune responses to Kaposi's sarcoma-associated herpesvirus (KSHV) in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Aids Res Ctr, Boston, MA 02114 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 NOV 16 PY 2000 VL 96 IS 11 MA 3251 BP 752A EP 752A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103250 ER PT J AU Mitsiades, CS Treon, SP Mitsiades, NS Anderson, KC AF Mitsiades, CS Treon, SP Mitsiades, NS Anderson, KC TI TRAIL induces apoptosis of chemotherapy sensitive and resistant myeloma cell lines and inhibits growth of human plasmacytomas xenografted in NU/XID/BG mice. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 3269 BP 756A EP 756A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103268 ER PT J AU Kim, YM Mapara, MY Sykes, M AF Kim, YM Mapara, MY Sykes, M TI Immunogenetic requirements for lymphohematopoietic graft-versus-host-reactions in murine mixed chimeras. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. RI mapara, markus/A-2134-2013 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 NOV 16 PY 2000 VL 96 IS 11 MA 3327 BP 769A EP 769A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103326 ER PT J AU Mapara, MY Kim, YM Nikolic, B Bronson, R Luster, AD Sykes, M AF Mapara, MY Kim, YM Nikolic, B Bronson, R Luster, AD Sykes, M TI Expression of chemokines in GvHD target organs following lethal irradiation and syngeneic or allogeneic bone marrow transplantation: Possible role of MCP-1 and eotaxin as initiating chemokines in liver and skin GvHD. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Harvard Ctr Canc Biol, Boston, MA USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 3334 BP 771A EP 771A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103333 ER PT J AU Shaughnessy, P Ririe, D Ornstein, D Callander, N Anderson, JE Pollack, M Freytes, C Cruz, J Rodriguez, T Bachier, C LeMaistre, CF AF Shaughnessy, P Ririe, D Ornstein, D Callander, N Anderson, JE Pollack, M Freytes, C Cruz, J Rodriguez, T Bachier, C LeMaistre, CF TI Phase II study of a moderate intensity preparative regimen and allogeneic peripheral blood stem cell transplantation (PBSCT) for hematologic diseases: The Texas Transplant Consortium experience. SO BLOOD LA English DT Meeting Abstract C1 Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. Texas Tech Univ, Lubbock, TX 79409 USA. Scott & White Mem Hosp & Clin, Temple, TX 76508 USA. Texas Transplant Inst, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3389 BP 784A EP 784A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103388 ER PT J AU Antin, JH Lee, SJ Harkness, S Alyea, E Soiffer, RJ Rimm, IJ Ferrara, J AF Antin, JH Lee, SJ Harkness, S Alyea, E Soiffer, RJ Rimm, IJ Ferrara, J TI Preliminary results of a phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 (rhIL-11) for mucositis and GVHD prevention in allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3399 BP 786A EP 786A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103398 ER PT J AU Bellucci, R Chillemi, A Wu, CJ Alyea, EP Canning, C Schlossman, R Soiffer, RJ Anderson, KA Ritz, J AF Bellucci, R Chillemi, A Wu, CJ Alyea, EP Canning, C Schlossman, R Soiffer, RJ Anderson, KA Ritz, J TI Reconstitution of immune deficiency after prophylactic CD4+donor lymphocyte infusion in patients with multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 3404 BP 787A EP 787A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103403 ER PT J AU Rhodes, J Bennett, CM Kanki, JP Liu, TX Paw, BH Zon, LI Look, AT AF Rhodes, J Bennett, CM Kanki, JP Liu, TX Paw, BH Zon, LI Look, AT TI Molecular analysis of zebrafish myelopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med 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 NOV 16 PY 2000 VL 96 IS 11 MA 3483 BP 806A EP 806A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103482 ER PT J AU Vonderheide, RH Schultze, JL Anderson, KS Maecker, B Butler, MO von Bergwelt-Baildon, MS Wucherpfennig, KW Hahn, WC Nadler, LM AF Vonderheide, RH Schultze, JL Anderson, KS Maecker, B Butler, MO von Bergwelt-Baildon, MS Wucherpfennig, KW Hahn, WC Nadler, LM TI Telomerase-specific CTL from tumor-bearing patients are spared functional inactivation due to immunological ignorance. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 3488 BP 807A EP 807A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103487 ER PT J AU Meyer, T Reitter, J Pykett, MJ Evans, R Poznansky, M Ritz, J Scadden, DT Rosenzweig, M AF Meyer, T Reitter, J Pykett, MJ Evans, R Poznansky, M Ritz, J Scadden, DT Rosenzweig, M TI T cell generation in a thymic organoid. SO BLOOD LA English DT Meeting Abstract C1 Cytomatrix, Woburn, MA USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. 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 NOV 16 PY 2000 VL 96 IS 11 MA 3490 BP 808A EP 808A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103489 ER PT J AU Boussiotis, VA Greenwald, RJ Berezovskaya, A Abbas, AK Sharpe, AH AF Boussiotis, VA Greenwald, RJ Berezovskaya, A Abbas, AK Sharpe, AH TI CTLA4 has an obligatory role for the induction of tolerance of naive T cells in vivo. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Univ Calif San Francisco, Dept Immunol, San Francisco, CA 94143 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 NOV 16 PY 2000 VL 96 IS 11 MA 3501 BP 810A EP 810A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103500 ER PT J AU Freeman, GJ Long, AJ Iwai, Y Latchman, Y Bourque, K Brown, JA Boussiotis, VA Dorfman, DM Chernova, T Nishimura, H Fitz, L Malenkovich, N Okazaki, T Byrne, M Horton, H Fouser, L Carter, L Sharpe, AH Carreno, B Collins, M Wood, CR Honjo, T AF Freeman, GJ Long, AJ Iwai, Y Latchman, Y Bourque, K Brown, JA Boussiotis, VA Dorfman, DM Chernova, T Nishimura, H Fitz, L Malenkovich, N Okazaki, T Byrne, M Horton, H Fouser, L Carter, L Sharpe, AH Carreno, B Collins, M Wood, CR Honjo, T TI Engagement of the PD-1 immunoinhibitory receptor by a novel B7-family member leads to negative regulation of lymphocyte activation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Genet Inst Inc, Cambridge, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Kyoto Univ, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 7 U2 16 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 NOV 16 PY 2000 VL 96 IS 11 MA 3502 BP 810A EP 811A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256103501 ER PT J AU Kiani, A Garcia-Cozar, FJ Ehninger, G Rao, A AF Kiani, A Garcia-Cozar, FJ Ehninger, G Rao, A TI Regulation of IFN-gamma gene expression by NFAT1. SO BLOOD LA English DT Meeting Abstract C1 Universitaetsklinikum Carl Gustav Carus, Med Klin & Poliklin 1, Dresden, Germany. Univ Cadiz, Fac Sci, Dept Biochem & Mol Biol, Cadiz, Spain. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Garcia-Cozar, Francisco/A-6212-2013 OI Garcia-Cozar, Francisco/0000-0003-3720-259X NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 3499 BP 810A EP 810A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103498 ER PT J AU Tzachanis, D Hirano, N Freeman, GJ Nadler, LM Boussiotis, VA AF Tzachanis, D Hirano, N Freeman, GJ Nadler, LM Boussiotis, VA TI Tob, a novel Tob/BTG1 family member that associates with the CCR4 transcriptional regulatory couples is selectively expressed in anergic T cells and inhibits IL-2 transcription. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3500 BP 810A EP 810A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103499 ER PT J AU Andre, P Denis, CV Saffaripour, S Wagner, DD AF Andre, P Denis, CV Saffaripour, S Wagner, DD TI Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice. SO BLOOD LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, 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 NOV 16 PY 2000 VL 96 IS 11 MA 3511 BP 812A EP 813A PN 1 PG 2 WC Hematology SC Hematology GA 372WB UT WOS:000165256103510 ER PT J AU Ni, HY Ramakrishnan, V Papalia, JM Phillips, DR Wagner, DD AF Ni, HY Ramakrishnan, V Papalia, JM Phillips, DR Wagner, DD TI Increased thrombogenesis and embolus formation in mice lacking glycoprotein SO BLOOD LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. COR Therapeut Inc, S San Francisco, CA USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3508 BP 812A EP 812A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103507 ER PT J AU Ruggeri, ZM Subramanian, M Dent, JA Wagner, DD Saldivar, E AF Ruggeri, ZM Subramanian, M Dent, JA Wagner, DD Saldivar, E TI P-selectin and the three-dimensional structure of platelet thrombi. SO BLOOD LA English DT Meeting Abstract C1 Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA. Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2000 VL 96 IS 11 MA 3509 BP 812A EP 812A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103508 ER PT J AU Andre, P Hartwell, D Hrachovinova, I Saffaripour, S Wagner, DD AF Andre, P Hartwell, D Hrachovinova, I Saffaripour, S Wagner, DD TI Pro-coagulant state resulting from high levels of soluble P-selectin in blood. SO BLOOD LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 3532 BP 817A EP 817A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103531 ER PT J AU Manz, MG Traver, D Miyamoto, T Merad, M Engleman, EG Weissman, IL Akashi, K AF Manz, MG Traver, D Miyamoto, T Merad, M Engleman, EG Weissman, IL Akashi, K TI Dendritic cell development from lymphoid and myeloid committed hematopoietic progenitors. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Dana Faber Canc Inst, Boston, MA 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 NOV 16 PY 2000 VL 96 IS 11 MA 3547 BP 821A EP 821A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103546 ER PT J AU Staunton, JE Slonim, DK Coller, HA Tamayo, P Angelo, MJ Scherf, U Weinstein, JN Mesirov, JP Lander, ES Golub, TR AF Staunton, JE Slonim, DK Coller, HA Tamayo, P Angelo, MJ Scherf, U Weinstein, JN Mesirov, JP Lander, ES Golub, TR TI Gene expression predicts chemosensitivity of cancer cell lines. SO BLOOD LA English DT Meeting Abstract C1 MIT, Ctr Genome Res, Cambridge, MA 02139 USA. NCI, Bethesda, MD 20892 USA. MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2000 VL 96 IS 11 MA 3559 BP 823A EP 823A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103558 ER PT J AU Olson, DP Taylor, BJ Reaman, G Sather, H Ivy, SP AF Olson, DP Taylor, BJ Reaman, G Sather, H Ivy, SP TI The expression and function of Pgp, MRP1 and LRP in pediatric acute lymphoblastic leukemia (ALL): A retrospective study of 297 newly diagnosed patients by the Children's Oncology Group. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH Ctr Canc, Boston, MA USA. Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. Grp Operat, Childrens Oncol Grp, Arcadia, CA 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 NOV 16 PY 2000 VL 96 IS 11 MA 3566 BP 825A EP 825A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103565 ER PT J AU Soignet, SL Frankel, S Tallman, M Douer, D Scheinberg, DA Dahlberg, S Kantarjian, H Stone, R Sievers, E Kalaycio, M Coutre, S Warrell, RP AF Soignet, SL Frankel, S Tallman, M Douer, D Scheinberg, DA Dahlberg, S Kantarjian, H Stone, R Sievers, E Kalaycio, M Coutre, S Warrell, RP TI Arsenic trioxide (ATO) in relapsed acute promyelocytic leukemia (APL): The combine results and follow-up from the US pilot and multicenter trials. SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cell Therapeut Inc, Seattle, WA USA. Georgetown Univ, Washington, DC 20057 USA. Northwestern Univ, Chicago, IL USA. Norris Cotton Canc Ctr, Los Angeles, CA USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 9 Z9 9 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 NOV 16 PY 2000 VL 96 IS 11 MA 3575 BP 827A EP 827A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103574 ER PT J AU Harig, S Witzens, M Trojan, A Krackhardt, AM Broderick, R Barrett, P Donovan, JW Gribben, JG AF Harig, S Witzens, M Trojan, A Krackhardt, AM Broderick, R Barrett, P Donovan, JW Gribben, JG TI Induction of cytotoxic T-cell responses against immunoglobulin derived peptides modified at HLA-A2 binding residues. SO BLOOD LA English DT Meeting Abstract C1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3588 BP 830A EP 830A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103587 ER PT J AU Maecker, B Sherr, DH Vonderheide, RH von Bergwelt-Baildon, MS Anderson, KS Wucherpfennig, KW Nadler, LM Schultze, JL AF Maecker, B Sherr, DH Vonderheide, RH von Bergwelt-Baildon, MS Anderson, KS Wucherpfennig, KW Nadler, LM Schultze, JL TI Defining the carcinogen activator cytochrome P4501B1 as a universal tumor antigen for lymphoma and leukemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 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 NOV 16 PY 2000 VL 96 IS 11 MA 3589 BP 831A EP 831A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103588 ER PT J AU Podar, K Tai, YT Sattler, M Treon, SP Mitsiades, C Davies, FE Lentzsch, S Lin, BK Gupta, D Hideshima, T Shima, Y Raje, N Chauhan, D Mitsiades, N Hayashi, T Anderson, KC AF Podar, K Tai, YT Sattler, M Treon, SP Mitsiades, C Davies, FE Lentzsch, S Lin, BK Gupta, D Hideshima, T Shima, Y Raje, N Chauhan, D Mitsiades, N Hayashi, T Anderson, KC TI The role of vascular endothelial growth factor (VEGF) in the pathophysiology of multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3613 BP 836A EP 836A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103612 ER PT J AU Davies, FE Raje, N Hideshima, T Lentzsch, S Young, G Tai, YT Lin, BK Podar, K Chauhan, D Treon, SP Gupta, D Mitsiades, C Mitsiades, N Hayashi, T Richardson, PG Schlossman, RL Muller, GW Stirling, DI Anderson, KC AF Davies, FE Raje, N Hideshima, T Lentzsch, S Young, G Tai, YT Lin, BK Podar, K Chauhan, D Treon, SP Gupta, D Mitsiades, C Mitsiades, N Hayashi, T Richardson, PG Schlossman, RL Muller, GW Stirling, DI Anderson, KC TI Thalidomide (Thal) and immunomodulatory derivatives (IMiDS) augment natural killer (NK) cell cytotoxicty in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene Corp, Warren, NJ USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2000 VL 96 IS 11 MA 3617 BP 837A EP 837A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103616 ER PT J AU Raje, N Hideshima, T Davies, FE Avigan, D Gong, JL Chauhan, D Treon, SP Young, G Tai, YT Brander, C Schlossman, RL Richardson, PG Kufe, DW Anderson, KC AF Raje, N Hideshima, T Davies, FE Avigan, D Gong, JL Chauhan, D Treon, SP Young, G Tai, YT Brander, C Schlossman, RL Richardson, PG Kufe, DW Anderson, KC TI Tumor cell/dendritic cell fusions as a vaccination strategy for multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 1 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 NOV 16 PY 2000 VL 96 IS 11 MA 3618 BP 837A EP 837A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103617 ER PT J AU Spitzer, TR McAfee, S Sackstein, R Dey, B Colby, C Grossberg, H Hope, J Saidman, S Preffer, F Alexander, S Sachs, DH Sykes, M AF Spitzer, TR McAfee, S Sackstein, R Dey, B Colby, C Grossberg, H Hope, J Saidman, S Preffer, F Alexander, S Sachs, DH Sykes, M TI Haploidentical donor bone marrow transplantation (BMT) for advanced hematologic malignancy (HM) following non-myeloablative preparative therapy: Role of in vivo T-cell depletion with anti-thymocyte globulin or anti-CD2 monoclonal antibody therapy (MEDI-507). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BioTransplant Inc, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2000 VL 96 IS 11 MA 3633 BP 841A EP 841A PN 1 PG 1 WC Hematology SC Hematology GA 372WB UT WOS:000165256103632 ER PT J AU Meigs, JB AF Meigs, JB TI Invited commentary: Insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material DE factor analysis, statistical; hemostasis; inflammation; insulin resistance; metabolism; risk factors ID CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; ADULTS; MEN; POPULATION; PREDICTS; SMOKING; SYSTEM AB Factor analysis has emerged as a useful method for understanding patterns underlying the co-occurrence of metabolic risk factors for both type 2 diabetes and atherosclerosis-often referred to as "insulin resistance syndrome." In factor analysis of data on 322 healthy elderly people from the Cardiovascular Health Study, Sakkinen et at. (Am J Epidemiol 2000;152:897-907) confirmed findings from a dozen prior studies that as many as four distinct physiologic domains comprise the syndrome, with a unifying role for markers of insulin resistance. With the addition of markers of hemostasis and inflammation, they also found that impaired fibrinolysis and endothelial dysfunction are central features of the syndrome, while inflammation is only weakly linked to insulin resistance through associations with obesity. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, S50-9, Boston, MA 02114 USA. NR 31 TC 234 Z9 247 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2000 VL 152 IS 10 BP 908 EP 911 DI 10.1093/aje/152.10.908 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 372WV UT WOS:000165257800002 PM 11092432 ER PT J AU George, MS Nahas, Z Molloy, M Speer, AM Oliver, NC Li, XB Arana, GW Risch, SC Ballenger, JC AF George, MS Nahas, Z Molloy, M Speer, AM Oliver, NC Li, XB Arana, GW Risch, SC Ballenger, JC TI A controlled trial of daily left prefrontal cortex TMS for treating depression SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-for-Biological-Psychiatry CY MAY 13-16, 1999 CL WASHINGTON, D.C. SP Soc Biol Psychiat DE transcranial magnetic stimulation; depression; prefrontal cortex; treatments; mood; emotion; clinical trials ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; RESISTANT MAJOR DEPRESSION; RTMS IMPROVES MOOD; AFFECTIVE-DISORDERS; SLEEP-DEPRIVATION; BLOOD-FLOW; BRAIN AB Background: Transcranial magnetic stimulation (TMS) is a new technology for noninvasively stimulating the brain, Several studies have suggested that daily stimulation of the left prefrontal cortex with TMS for 2 weeks has probable antidepressant effects. We conducted a parallel-design, double-masked, sham-controlled study to address whether 2 weeks of daily TMS over the left prefrontal cortex has antidepressant activity greater than sham. Methods: Thirty medication-free adult outpatients with nonpsychotic, major depressive (n = 21) or bipolar (n = 9) (depressed phase) disorder who were in a current major depression (Hamilton Rating Scale for Depression [HRSD] 21-item score of >18) were treated each weekday for 2 weeks. Subjects were randomly assigned to receive either daily active (20 subjects) or sham (10 subjects) stimulation. Additionally, the 20 active subjects I were equally divided between slower (5 Hz) andfaster (20 Hz) frequency treatment. Antidepressant response was defined as greater than a 50% improvement in the baseline HRSD, Results: Active TMS resulted in significantly more responders (9/20) than did sham (0/10) (chi (2) = 6.42, p < .01), The number of responders did not differ significantly between the two active cells (3/10 faster and 6/10 slower). Expressed as a percent change from baseline, active TMS subjects had significantly greater improvement on the Beck Depression Inventory as well as the Hamilton Anxiety Rating Scale than did those who received sham. Conclusions: Daily left prefrontal TMS for 2 weeks significantly reduced depression symptoms greater than did sham, The two forms of active TMS treatment did not differ significantly, (C) 2000 Society of Biological Psychiatry. C1 Med Univ S Carolina, Funct Neuroimaging Div, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Dept Psychiat, Charleston, SC USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Shangdong Med Univ, Dept Psychiat, Jinan, Peoples R China. RP George, MS (reprint author), Med Univ S Carolina, Funct Neuroimaging Div, Dept Psychiat, Brain Stimulat Lab, 171 Ashley Ave, Charleston, SC 29425 USA. NR 53 TC 232 Z9 242 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2000 VL 48 IS 10 BP 962 EP 970 DI 10.1016/S0006-3223(00)01048-9 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 374PP UT WOS:000165353800002 PM 11082469 ER PT J AU Cohen, LS Heller, VL Bailey, JW Grush, L Ablon, JS Bouffard, SM AF Cohen, LS Heller, VL Bailey, JW Grush, L Ablon, JS Bouffard, SM TI Birth outcomes following prenatal exposure to fluoxetine SO BIOLOGICAL PSYCHIATRY LA English DT Article DE pregnancy; depression; fluoxetine; perinatal outcome ID PREGNANCY; DEPRESSION AB Background: Although pregnancy has frequently been described as a time of emotional well-being, some women experience significant antenatal depression that may require treatment with antidepressants. The purpose of this investigation was to examine the relative effects of early and late trimester exposure to fluoxetine and perinatal outcome. Methods: Obstetric and neonatal records were reviewed for 64 mother-infant pairs where there was documented rise of fluoxetine at some point during pregnancy. Differences in several measures of obstetrical outcome and neonatal well-being were examined in early trimesterand late trimester-exposed infants, Results: No differences in birth weight and acute neonatal outcome were evident across the two groups, though there rr ns a higher frequency of special care nursery admissions for infants with exposure to fluoxetine late in pregnancy. Special care nursery admissions could not be attributed to any specific factor Conclusions: Given the growing numbers of women who are treated with antidepressants, including fluoxetine, during pregnancy, and the strong association between depression during pregnancy and risk for postpartum depression, patients may be best advised to continue treatment with antidepressants through labor and delivery Versus making any change in intensity of treatment during the acute peripartum period, (C) 2000 Society of Biological Psychiatry. C1 Harvard Univ, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Franciscan Childrens Hosp, Brighton, MA USA. RP Cohen, LS (reprint author), Harvard Univ, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Massachusetts Gen Hosp,Sch Med, WAC 815,15 Parkman St, Boston, MA 02114 USA. NR 9 TC 99 Z9 100 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2000 VL 48 IS 10 BP 996 EP 1000 DI 10.1016/S0006-3223(00)00877-5 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 374PP UT WOS:000165353800007 PM 11082474 ER PT J AU Andre, P Denis, CV Ware, J Saffaripour, S Hynes, RO Ruggeri, ZM Wagner, DD AF Andre, P Denis, CV Ware, J Saffaripour, S Hynes, RO Ruggeri, ZM Wagner, DD TI Platelets adhere to and translocate on von Willebrand factor presented by endothelium in simulated veins SO BLOOD LA English DT Article ID VONWILLEBRAND-FACTOR MULTIMERS; GLYCOPROTEIN IB-ALPHA; WEIBEL-PALADE BODIES; P-SELECTIN; VESSEL WALL; IN-VIVO; ACTIVATED PLATELETS; BINDING DOMAIN; CELL-ADHESION; RELEASE AB With the use of intravital microscopy, a new type of platelet-endothelial interaction in mouse mesenteric venules at low shear (80-100 seconds(-1)) is described. Stimulation of these vessels with calcium ionophore A23187, a known secretagogue of Welbel-Palade bodies, induced immediate platelet adhesion (within 15 seconds) and translocation without the formation of aggregates. This stop-and-go process reached a maximum in approximately 1 minute, when approximately 25 000 platelets adhered/mm(2.)s, and then adhesion progressively decreased. This adhesion process was dependent on von Willebrand factor (vWF) and independent of P-selectin. Immunohistologic analysis showed that the venules were not denuded with A23187 treat ment, suggesting that platelets adhered to VWF secreted on the luminal face of the endothelial cells. Histamine treatment induced a similar adhesion phenomenon. Platelet adhesion was not abolished in beta3-deficient mice or when the platelets were treated with inhibitory antibodies to PECAM-1 or PSGL-1, indicating that these molecules are not required for platelet-endothelium interaction at low shear, The adhesion was mediated by platelet glycoprotein lb alpha (GPlb alpha) because the adhesion of murine platelets expressing exclusively the human GPlb alpha could be prevented by a pretreatment with mocarhagin, a snake venom protease that cleaves human GPlb alpha. The results indicate that VWF released from Weibel-Palade bodies can dramatically increase the concentration of platelets along the vessel wall through an interaction with GPlb alpha. It is proposed that this process may rapidly recruit platelets to sites of injury or inflammation in veins. (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Scripps Res Inst, Roon Res Ctr Arteriosclerosis & Thrombosis, La Jolla, CA USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [P01 HL066105, P01HL56949, R01 HL050545, R01 HL050545-11, R37HL41002] NR 47 TC 180 Z9 184 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2000 VL 96 IS 10 BP 3322 EP 3328 PG 7 WC Hematology SC Hematology GA 372HA UT WOS:000165227200004 PM 11071623 ER PT J AU Reed, GL Fitzgerald, ML Polgar, J AF Reed, GL Fitzgerald, ML Polgar, J TI Molecular mechanisms of platelet exocytosis: insights into the "secrete" life of thrombocytes SO BLOOD LA English DT Review ID CHEDIAK-HIGASHI-SYNDROME; STORAGE POOL DEFICIENCY; HERMANSKY-PUDLAK-SYNDROME; PROTEIN-KINASE-C; PERMEABILIZED HUMAN-PLATELETS; ALPHA-GRANULE MEMBRANE; GLYCOPROTEIN-IIB-IIIA; HUMAN BLOOD-PLATELETS; ADRENAL CHROMAFFIN CELLS; GUINEA-PIG MEGAKARYOCYTE AB The critical role played by platelets in hemostasis, thrombosis, vascular remodeling, and healing is related to their function as exocytotic cells that secrete important effector molecules al:the site of vascular injury. Recent insights into molecular mechanisms of secretion indicate that platelet granule secretion is homologous to exocytosis in neurons and other cells but involves a platelet-selective machinery that is uniquely coupled to cell activation. This review summarizes these recent insights in the context of the burgeoning literature on mechanisms of exocytosis in neurons and other cells-illustrating the fundamental homologies and the unique characteristics of platelet secretion. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 11-127,677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-64057] NR 176 TC 97 Z9 99 U1 0 U2 7 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 NOV 15 PY 2000 VL 96 IS 10 BP 3334 EP 3342 PG 9 WC Hematology SC Hematology GA 372HA UT WOS:000165227200006 PM 11071625 ER PT J AU Duarte, RF Frank, DA AF Duarte, RF Frank, DA TI SCF and C-CSF lead to the synergistic induction of proliferation and gene expression through complementary signaling pathways SO BLOOD LA English DT Article ID STEM-CELL FACTOR; COLONY-STIMULATING FACTOR; ACTIVATED PROTEIN-KINASE; BLOOD PROGENITOR CELLS; PERIPHERAL-BLOOD; SERINE PHOSPHORYLATION; GROWTH-FACTOR; FACTOR-RECEPTOR; STAT PROTEINS; KIT LIGAND AB Stem cell factor (SCF) is a potent costimulatory molecule for many cytokines, Its synergy with granulocyte colony-stimulating factor (G-CSF) results in important biologic and clinical effects, although the mechanism by which this occurs remains poorly understood. To investigate this interaction, this study used a retroviral vector to transduce the G-CSF receptor into MO7e cells, which are known to express the SCF receptor. The transduced G-CSF receptor is functionally active, and the resultant MO7e-G cells recapitulate the proliferative synergy between SCF and G-CSF. When treated with both cytokines, a marked shortening of the G(0)/G(1) phase of the cell cycle occurs, associated with a suppression of the cyclin-dependent kinase inhibitor p27(kip-1), I, addition, SCF and G-CSF induce the synergistic activation of c-fas, a proto-oncogene involved in propagation of mitogenic signals in hematopoietic cells. G-CSF, but not SCF, induces the tyrosine phosphorylation of STAT1 and STATE, transcription factors that can mediate the induction of c-fos, However, SCF induces phosphorylation of STAT3 on serine727 (ser727), which is necessary for maximal STAT transcriptional activity, and the combination of SCF and G-CSF leads to complete STAT3 phosphorylation on ser727. The pathways by which SCF and G-CSF lead to serine phosphorylation of STAT3 are distinct and are partially dependent on phosphatidylinositol-3 kinase and ERKs, pathways that are also necessary for the synergistic effects of SCF and G-CSF on proliferation and c-fos induction. Thus, MO7e-G cells provide a powerful system in which the molecular basis of the synergy between SCF and G-CSF can be dissected. (C) 2000 by The American Society of Hematology. 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, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA79547] NR 81 TC 42 Z9 47 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 NOV 15 PY 2000 VL 96 IS 10 BP 3422 EP 3430 PG 9 WC Hematology SC Hematology GA 372HA UT WOS:000165227200018 PM 11071637 ER PT J AU Tsuzuki, Y Fukumura, D Oosthuyse, B Koike, C Carmeliet, P Jain, RK AF Tsuzuki, Y Fukumura, D Oosthuyse, B Koike, C Carmeliet, P Jain, RK TI Vascular endothelial growth factor (VEGF) modulation by targeting hypoxia-inducible factor-1 alpha -> hypoxia response element -> VEGF cascade differentially regulates vascular response and growth rate in tumors SO CANCER RESEARCH LA English DT Article ID PERMEABILITY FACTOR; ANGIOGENESIS; ADHESION; EXPRESSION; XENOGRAFTS; MICE; PROLIFERATION; HIF-1-ALPHA; LETHALITY; VESSELS AB Although tumors can activate vascular endothelial growth factor (VEGF) promoter in host stromal cells, the relative contribution to VEGF production of host versus tumor cells and the resulting vascular response have not been quantitated to date, To this end, we implanted VEGF(-/-) and wild-type (WT) embryonic stem (ES) cells in transparent dorsal skin windows in severe combined immunodeficient mice. VEGF(-/-) ES cell-derived tumors produced similar to 50% of VEGF compared with the WT tumors, suggesting significant contribution of host stromal cells. To discern the hypoxia-induced hypoxia inducible factor (HIF)-1 alpha --> hypoxia response element (HRE) --> VEGF signaling cascade, we also examined tumors derived from HIF-1 alpha (-/-) and HRE-/- ES cells, As expected, the VEGF protein level in HIF-1 alpha (-/-) ES tumors was intermediate between VEGF-'- and WT ES cell tumors. Surprisingly, HRE-/- ES tumors produced the same level of VEGF as the VEGF(-/-) ES tumors, suggesting a critical rot of HRE in tumor cell VEGF production, Angiogenesis in these tumors war proportional to their VEGF levels (VEGF(-/-) approximate to HRE-/- HIF-1 alpha (-/-) < WT). In contrast, vascular permeability, leukocyte-endothelial adhesion, and tumor growth were reduced in VEGF(-/-) and HRE-/- tumors but were comparable in HIF-1(-/-) and WT tumors, This discrepancy suggests that different intracellular signaling pathways may be involved in each of these functions of VEGF, More importantly, these data suggest that host cells are active players in tumor angiogenesis and growth and need to be taken into account in the design of any therapeutic strategy. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,COX-7, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NCI NIH HHS [R35-CA56591] NR 28 TC 177 Z9 197 U1 3 U2 9 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 NOV 15 PY 2000 VL 60 IS 22 BP 6248 EP 6252 PG 5 WC Oncology SC Oncology GA 375ZD UT WOS:000165432600007 PM 11103778 ER PT J AU Dai, H Hogan, C Gopalakrishnan, B Torres-Vazquez, J Nguyen, M Park, SB Raftery, LA Warrior, R Arora, K AF Dai, H Hogan, C Gopalakrishnan, B Torres-Vazquez, J Nguyen, M Park, SB Raftery, LA Warrior, R Arora, K TI The zinc finger protein schnurri nets as a smad partner in mediating the transcriptional response to decapentaplegic SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; BMP; Ultrabithorax ID FACTOR-BETA FAMILY; MAJOR HISTOCOMPATIBILITY COMPLEX; DROSOPHILA ENDODERM INDUCTION; DPP MORPHOGEN GRADIENT; DNA-BINDING; SIGNALING PATHWAY; I RECEPTORS; FUNCTIONAL INTERACTION; GERM LAYERS; GENE AB In Drosophila, a BMP-related ligand Decapentaplegic (Dpp) is essential for cell fate specification during embryogenesis and in imaginal disc development. Dpp signaling culminates in the phosphorylation and nuclear translocation of Mothers against dpp (Mad), a receptor-specific Smad that can bind DNA and regulate the transcription of Dpp-responsive genes. Genetic analysis has implicated Schnurri (Shn), a zinc finger protein that shares homology with mammalian transcription factors, in the Dpp signal transduction pathway. However, a direct role for Shn in regulating the transcriptional response to Dpp has not been demonstrated. In this study we show that Shn acts as a DNA -binding Mad cofactor in the nuclear response to Dpp. Shn can bind DNA in a sequence-specific manner and recognizes sites within a well-characterized Dpp-responsive promoter element, the B enhancer of the Ultrabithorax (Ubx) gene. The Shn-binding sites are relevant for in vivo expression, since mutations in these sites affect the ability of the enhancer to respond to Dpp. Furthermore we find that Shn and Mad can interact directly through discrete domains. To examine the relative contribution of the two proteins in the regulation of endogenous Dpp target genes we developed a cell culture assay and show that Shn and Mad act synergistically to induce transcription. Our results suggest that cooperative interactions between these two transcription factors could play an important role in the regulation of Dpp target genes. This is the first evidence that Dpp/BMP signaling in flies requires the direct interaction of Mad with a partner transcription factor, (C) 2000 Academic Press. C1 Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. Univ So Calif, Dept Biol Sci, Program Mol Biol, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Arora, K (reprint author), Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NHLBI NIH HHS [R01 HL092263]; NIGMS NIH HHS [GM48659, GM55422] NR 83 TC 51 Z9 53 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2000 VL 227 IS 2 BP 373 EP 387 DI 10.1006/dbio.2000.9901 PG 15 WC Developmental Biology SC Developmental Biology GA 374UP UT WOS:000165363000010 PM 11071761 ER PT J AU Kennedy, BK Barbie, DA Classon, M Dyson, N Harlow, E AF Kennedy, BK Barbie, DA Classon, M Dyson, N Harlow, E TI Nuclear organization of DNA replication in primary mammalian cells SO GENES & DEVELOPMENT LA English DT Article DE DNA replication; nuclear structure; lamin; perinucleolar foci; retinoblastoma protein ID S-PHASE; AUXILIARY PROTEIN; POLYMERASE-DELTA; CYCLIN PCNA; MATRIX; SITES; INVITRO; FIBROBLASTS; 5-BROMODEOXYURIDINE; VISUALIZATION AB Using methods that conserve nuclear architecture, we have reanalyzed the spatial organization of the initiation of mammalian DNA synthesis. Contrary to the commonly held view that replication begins at hundreds of dispersed nuclear sites, primary fibroblasts initiate synthesis in a limited number of foci that contain replication proteins, surround the nucleolus, and overlap with previously identified internal lamin A/C structures. These foci are established in early G(1)-phase and also contain members of the retinoblastoma protein family. Later, in S-phase, DNA replication sites distribute to regions located throughout the nucleus. As this progression occurs, association with the lamin structure and pRB family members is lost. A similar temporal progression is found in all the primary cells we have examined but not in most established cell lines, indicating that the immortalization process modifies spatial control of DNA replication. These findings indicate that in normal mammalian cells, the onset of DNA synthesis is coordinately regulated at a small number of previously unrecognized perinucleolar sites that are selected in early G(1)-phase. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Kennedy, BK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 52 TC 198 Z9 203 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2000 VL 14 IS 22 BP 2855 EP 2868 DI 10.1101/gad.842600 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 378BA UT WOS:000165560400007 PM 11090133 ER PT J AU Bergeron, B AF Bergeron, B TI Your defensive line against hackers SO HOSPITAL PRACTICE LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD NOV 15 PY 2000 VL 35 IS 11 BP E40 EP E40 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 373FJ UT WOS:000165277400011 ER PT J AU Wolfe, J Klar, N Grier, HE Duncan, J Salem-Schatz, S Emanuel, EJ Weeks, JC AF Wolfe, J Klar, N Grier, HE Duncan, J Salem-Schatz, S Emanuel, EJ Weeks, JC TI Understanding of prognosis among parents of children who died of cancer - Impact on treatment goals and integration of palliative care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PEDIATRIC ONCOLOGY; PERSPECTIVES; PREFERENCES; GUIDELINES; PATIENT AB Context Parents' understanding of prognosis or decision making about palliative care for children who die of cancer is largely unknown. However, a more accurate under standing of prognosis could alter treatment goals and expectations and lead to more effective care. Objectives To evaluate parental understanding of prognosis in children who die of cancer and to assess the association of this factor with treatment goals and the palliative care received by children. Design, Setting, and Participants Survey, conducted between September 1997 and August 1998, of 103 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital, Boston, Mass, and who died of cancer between 1990 and 1997 (72 % of those eligible and those located) and 42 pediatric oncologists. Main Outcome Measure Timing of parental understanding that the child had no realistic chance for cure compared with the timing of physician understanding of this prognosis, as documented in the medical record. Results Parents first recognized that the child had no realistic chance for cure a mean (SD) of 106 (150) days before the child's death, while physician recognition occurred earlier at 206 (330) days before death. Among children who died of progressive disease, the group characterized by earlier recognition of this prognosis by both parents and physicians had earlier discussions of hospice care (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01 -1.06; P=.01), better parental ratings of the quality of home care (OR, 3.31; 95% CI, 1.15-9.54; P=.03), earlier institution of a do-not-resuscitate order (OR, 1.03; 95% CI, 1.00-1.06; P=.02), less use of cancer-directed therapy during the last month of life (OR, 2.80; 95% CI, 1.05-7.50; P=.04), and higher likelihood that the goal of cancer-directed therapy identified by both physician and parent was to lessen suffering (OR, 5.17; 95% CI, 1.86-14.4; P=.002 for physician and OR, 6.56; 95% CI, 1.54-27.86; P=.01 for parents). Conclusion Considerable delay exists in parental recognition that children have no realistic chance for cure, but earlier recognition of this prognosis by both physicians and parents is associated with a stronger emphasis on treatment directed at lessening suffering and greater integration of palliative care. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Div Prevent Oncol Canc Care Ontario, Toronto, ON, Canada. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wolfe, J (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [5 T32 HS00063] NR 31 TC 218 Z9 218 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 15 PY 2000 VL 284 IS 19 BP 2469 EP 2475 DI 10.1001/jama.284.19.2469 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 371MY UT WOS:000165183800020 PM 11074776 ER PT J AU Coates, AS Hurny, C Peterson, HF Bernhard, J Castiglione-Gertsch, M Gelber, RD Goldhirsch, A AF Coates, AS Hurny, C Peterson, HF Bernhard, J Castiglione-Gertsch, M Gelber, RD Goldhirsch, A CA Int Breast Canc Study Grp TI Quality-of-life scores predict outcome in metastatic but not early breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LUNG-CANCER; RECEIVING END; POSTMENOPAUSAL PATIENTS; PSYCHOLOGICAL RESPONSE; PSYCHOSOCIAL TREATMENT; ADJUVANT THERAPY; PROGNOSTIC VALUE; SURVIVAL; CHEMOTHERAPY; POPULATION AB Purpose: We compared the prognostic valve of quality-of-life (QL) scores in the adjuvant setting and after relapse in two randomized trials of the International Breast Cancer Study Group. Patients and Methods: More than 2,000 premenopausal and postmenopausal patients with node-positive breast cancer who were participating in randomized trials that compared adjuvant therapies completed QL assessments for physical well-being, mood, appetite, and coping at study entry and at months 3 and 18 if they remained relapse-free and, in case of relapse, at 1 month and at 6 months after relapse. Cox regression models were used to test the relationship between QL scores and disease-free survival (DFS), in the adjuvant setting, or overall survival, in the case of postrelapse QL measurement. All models were stratified by language/country group and included other factors related to QL and/or outcome. Results: DFS was not significantly predicted by QL scores at baseline or month 18, or by changes in QL score between baseline and months 3 or 18. In contrast, after relapse, QL scores were predictive for subsequent overall survival. One month after relapse, better mood (P =.04) in premenopausal patients and better appetite (P =.005) in postmenopausal patients were associated with longer survival. Six months after relapse, better physical well-being (P =.03) and appetite (P =.03) in premenopausal patients and better physical well-being (P <.0001), mood (P =.002), appetite (P =,0001), and coping (P =.0001) in postmenopausal patients predicted longer survival. Conclusion: Any prognostic significance of QL scores in the adjuvant setting is minimal or obscured by chemotherapy effects, but there is strong prognostic significance of QL scores after disease relapse. The contrast suggests that patient perception of the severity of underlying illness may determine reported QL scores. a 2000 by American Society of Clinical Oncology. C1 Australian Canc Soc, Sydney, NSW 2001, Australia. Univ Sydney, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW, Australia. Burgerspital, St Gallen, Switzerland. Coordinating Ctr, Int Breast Canc Study Grp, Bern, Switzerland. Dana Farber Canc Inst, Ctr Stat, Int Breast Canc Study Grp, Boston, MA 02115 USA. European Inst Oncol, Milan, Italy. RP Coates, AS (reprint author), Australian Canc Soc, GPO Box 4708, Sydney, NSW 2001, Australia. FU NCI NIH HHS [CA-75362] NR 37 TC 90 Z9 92 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2000 VL 18 IS 22 BP 3768 EP 3774 PG 7 WC Oncology SC Oncology GA 374NY UT WOS:000165352300004 PM 11078489 ER PT J AU Manola, J Atkins, M Ibrahim, J Kirkwood, J AF Manola, J Atkins, M Ibrahim, J Kirkwood, J TI Prognostic factors in metastatic melanoma: A pooled analysis of Eastern Cooperative Oncology Group trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; SURVIVAL; THERAPY AB Purpose: To identify factors that are prognostic for survival in patients with metastatic melanoma treated in eight Eastern Cooperative Oncology Group (ECOG) trials conducted over the past 25 years. Methods: We identified common, significant patient characteristics collected at baseline on 1,362 eligible patients for inclusion in a pooled analysis. Proportional hazards models were used to examine simultaneously the effects of multiple covariates on survival. Results: Median survival wets 6.4 months (95% confidence interval, 6,1 to 6.9 months.) Factors conferring the greatest increased risk of death included number of metastatic sites (relative risk [RR] = 1,12), ECOG performance status of 1 or more (RR = 1.49), or metastatic disease in the gastrointestinal (GI) tract (RR = 1.49), liver (RR = 1,44), pleura (RR = 1.35)1 or lung (RR = 1.19). Prior immunotherapy (RR = 0.84) and female sex (RR = 0.87) were associated with prolonged survival. Although only 12% of patients responded to protocol treatment, landmark analysis showed this to be a significant prognostic factor (RR = 0,57), A model based on three recent studies in which baseline values for alka- line phosphatase, lactate dehydrogenase (LDH), and platelets were available identified an increased number of sites of metastasis (RR = 1.30), abnormal LDH (RR = 1.89), abnormal alkaline phosphatase (RR = 1,76), abnormal platelets (RR = 1.63), and GI metastases ( = 1,66) as prognostic for poorer survival. Response to treatment, when examined by landmark analysis of studies with laboratory parameters, wets associated with decreased risk of death (RR = 0,47). Conclusion: This study demonstrates the importance and utility of laboratory parameters as prognostic factors for survival and confirmed the deleterious effects of multiple metastatic sites, Prior immunotherapy and female sex were associated with improved prognosis. Prognostic factors identified in this analysis are consistent with the findings of prior published studies and argue for the adoption of laboratory findings in the staging systems that are used for entry and stratification of clinical trials in the future. (C) 2000 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. RP Manola, J (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-23318] NR 23 TC 167 Z9 173 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 15 PY 2000 VL 18 IS 22 BP 3782 EP 3793 PG 12 WC Oncology SC Oncology GA 374NY UT WOS:000165352300006 PM 11078491 ER PT J AU Ohdan, H Swenson, KG Gray, HSK Yang, YG Xu, YX Thall, AD Sykes, M AF Ohdan, H Swenson, KG Gray, HSK Yang, YG Xu, YX Thall, AD Sykes, M TI Mac-1-negative B-1b phenotype of natural antibody-producing cells, including those responding to Gal alpha 1,3Gal epitopes in alpha 1,3-galactosyltransferase-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELLS; POSITIVE SELECTION; PERITONEAL-CAVITY; PROTEIN CONJUGATE; MIXED CHIMERISM; MARGINAL ZONE; GAL ANTIBODY; MOUSE; LINEAGES; XENOTRANSPLANTATION AB Human natural Abs against Gal alpha1-3Gal beta1-4GlcNAc (Gal) epitopes are a major barrier to xenotransplantation, Studies in this report, which use combined multiparameter flow cytometric sorting and enzyme-linked immunospot assay, demonstrate that anti-Gal IgM-producing cells are found exclusively in a small B cell subpopulation (i.e., CD21(-/low) IgM(high) B220(low) CD5(-) Mac-1(-)493(-) cells) in the spleens of alpha1,3-galactosyltransferase-deficient mice. All IgM-producing cells were detected in a similar splenic subpopulation of alpha1,3-galactosyltransferase-deficient and wild-type mice. A higher frequency of B cells with anti-Gal surface IgM receptors was observed in the peritoneal cavity than in the spleen, but these did not actively secrete Abs, and showed phenotypic properties of B-lb cells (CD21(-/low) IgM(high) CD5(-) CD43(+) Mac-1(+)). However, these became Mac-1(-) and developed anti-Gal Ab-producing activity after in vitro culture with LPS, The splenic B cells with anti-Gal receptors consisted of both Mac-1(+) B-1b cells and Mac-1(-) B-1b-like cells. The latter comprised most anti-Gal IgM-producing cells, Our studies indicate that anti-Gal natural IgM Abs are produced by a Bib-like, Mac-1(-) splenic B cell population and not by plasma cells or B-la cells, They are consistent with a model whereby B-lb cells lose Mac-1 expression upon Ag exposure and that these, rather than plasma cells, become the major IgM Ab-producing cell population. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Transplantat Biol Res Ctr,Surg Serv, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. BioTransplant Inc, Charlestown, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Transplantat Biol Res Ctr,Surg Serv, Bone Marrow Transplantat Sect, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [P0I HL 18646, R0I HL 49915] NR 51 TC 79 Z9 80 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 15 PY 2000 VL 165 IS 10 BP 5518 EP 5529 PG 12 WC Immunology SC Immunology GA 372VK UT WOS:000165254600019 PM 11067905 ER PT J AU Mystkowski, P Seeley, RJ Hahn, TM Baskin, DG Havel, PJ Matsumoto, AM Wilkinson, CW Peacock-Kinzig, K Blake, KA Schwartz, MW AF Mystkowski, P Seeley, RJ Hahn, TM Baskin, DG Havel, PJ Matsumoto, AM Wilkinson, CW Peacock-Kinzig, K Blake, KA Schwartz, MW TI Hypothalamic melanin-concentrating hormone and estrogen-induced weight loss SO JOURNAL OF NEUROSCIENCE LA English DT Article DE MCH; estrogen; body weight; energy balance; lateral hypothalamus; anorexia; pair-feeding ID NEUROPEPTIDE-Y; ENERGY-BALANCE; FOOD-INTAKE; RAT HYPOTHALAMUS; BODY-WEIGHT; LEPTIN; ANOREXIA; TUMOR; AREA; ESTRADIOL AB Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen. C1 Univ Washington, Harborview Med Ctr, Dept Med, Div Endocrinol Metab, Seattle, WA 98104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98104 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati, OH 45267 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Div Endocrinol Metab, 325 9th Ave,Box 359757, Seattle, WA 98104 USA. RI Schwartz, Michael/H-9950-2012 FU NHLBI NIH HHS [HL07028]; NIDDK NIH HHS [DK-12829]; NINDS NIH HHS [NS-32273] NR 32 TC 53 Z9 53 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 15 PY 2000 VL 20 IS 22 BP 8637 EP 8642 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 370PM UT WOS:000165131500051 PM 11069973 ER PT J AU Kerr, AJ Buck, T Chia, K Chow, CM Fox, E Levine, RA Picard, MH AF Kerr, AJ Buck, T Chia, K Chow, CM Fox, E Levine, RA Picard, MH TI Transmitral Doppler: A new transthoracic contrast method for patent foramen ovale detection and quantification SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID YOUNG STROKE PATIENTS; TO-LEFT SHUNT; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; ISCHEMIC STROKE; SONOGRAPHY; EMBOLISM; EVENTS; RISK; SIZE AB `This study compared a new transthoracic echocardiographic (TTE) method for detection of right to left bubble passage, transmitral Doppler (TMD), against two-dimensional (2D) TTE contrast study and the gold standard, of transesophageal echocardiography (TEE), and assessed its utility in quantitative assessment of patent foramen ovales (PFO). BACKGROUND Current TTE methods are relatively insensitive in PFO detection and do not allow quantitative assessment of right to left shunt. METHODS In 44 patients (59 years, range 34 to 76 years) saline contrast and color Doppler studies were performed in three conditions-TTE TMD, TTE 2D and TEE. Bubble transit on the TMD was measured semiquantitatively by a visual bubble score and objectively by integrating the acoustic power within the mitral velocity envelope. RESULTS By TEE it was determined that 17 patients (39%) had PFOs; 16 had right to left contrast passage, and only 1 had left to right flow by color Doppler. Against TEE contrast study, the sensitivity of TMD and 2D contrast studies were 100% and 75%, respectively, with specificity of 96% and 100%. Greater than 10 bubbles on a single beat of the resting contrast TMD identified patients with a maximum resting TEE PFO opening diameter >2 mm with 78% sensitivity and 100% specificity. There was a strong correlation (r(2) = 0.72, p < 0.01) between the TMD acoustic power and PFO opening diameter. CONCLUSIONS Transmitral Doppler is a sensitive and specific method for TTE PFO detection that allows quantification of right to left bubble passage and may obviate the need for TEE in many patients after stroke. (C) 2000 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, VBK508,55 Fruit St, Boston, MA 02114 USA. RI Chia, Karin /F-5035-2011; OI Picard, Michael/0000-0002-9264-3243 NR 22 TC 37 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 2000 VL 36 IS 6 BP 1959 EP 1966 DI 10.1016/S0735-1097(00)00951-7 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 375FL UT WOS:000165388800033 PM 11092671 ER PT J AU Buhler, L Basker, M Alwayn, IPJ Goepfert, C Kitamura, H Kawai, T Gojo, S Kozlowski, T Ierino, FL Awwad, M Sachs, DH Sackstein, R Robson, SC Cooper, DKC AF Buhler, L Basker, M Alwayn, IPJ Goepfert, C Kitamura, H Kawai, T Gojo, S Kozlowski, T Ierino, FL Awwad, M Sachs, DH Sackstein, R Robson, SC Cooper, DKC TI Coagulation and thrombotic disorders associated with pig organ and hematopoietic cell transplantation in nonhuman primates SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; BABOON CARDIAC TRANSPLANTS; ENDOTHELIAL-CELLS; XENOGRAFT REJECTION; HUMAN XENOTRANSPLANTATION; COMPLEMENT DEPLETION; HYPERACUTE REJECTION; HUMAN PROTHROMBIN; IN-VITRO; PORCINE AB Background. Efforts to achieve tolerance to transplanted pig organs in nonhuman primates by the induction of a state of mixed hematopoietic chimerism have been associated with disorders of coagulation and thrombosis. Activation of recipient vascular endothelium and platelets by porcine hematopoietic cells and/or activation of donor organ vascular endothelium and/or molecular differences between the species may play roles, Irradiation or drug therapy could possibly potentiate endothelial cell activation and/or injury, Methods. We have investigated parameters of coagulation and platelet activation in nonhuman primates after (1) a regimen aimed at inducing mixed hematopoietic chimerism and tolerance (TIR that included total body irradiation, T cell depletion, and splenectomy; (2) pig bone marrow or pig peripheral blood mobilized progenitor cell transplantation (PCTx); and/or (3) pig organ transplantation (POTx), Five experimental groups were studied. Baboons were the recipient subjects in all groups except Group 1. Gp 1 Cynomolgus monkeys (n = 6) underwent TIR + allotransplantation of hematopoietic cells and a kidney or heart or TIR + concordant xenotransplantation (using baboons as donors) of cells and a kidney; Gp 2 Baboons (n = 4) underwent TIR with or without (+) autologous hematopoietic cell infusion; Gp 3 (n = 12) PCTx +/- TIR; Gp 4 (n = 5) POTx +/- TIR; Gp 5 (n = 4) TIR + PCTx + POTx. Platelet counts, with plasma prothrombin time, partial thromboplastin time, fibrinogen levels, fibrin split products and/or D-dimer were measured. Results. In the absence of a discordant (porcine) cellular or organ transplant (Groups 1 and 2), TIR resulted in transient thrombocytopenia only, in keeping with bone marrow depression from irradiation. PCTx alone (Group 3) was associated with the rapid development of a thrombotic thrombocytopenic (TTP)-like microangiopathic state, that persisted longer when PCTx was combined with TIR. POTx (+/-TIR) (Group 4) was associated with a gradual fall lover several days) in platelet counts and fibrinogen with disseminated intravascular coagulation (DIC); after graft excision, the DIC generally resolved. When TIR, PCTx and POTx were combined (Group 5), an initial TTP-like state was superseded by a consumptive picture of DIC within the first week, necessitating graft removal, Conclusions. Both PCTx and POTx lead to profound alterations in hemostasis and coagulation parameters that must be overcome if discordant xenotransplantation of hematopoietic cells and organs is to be fully successful. Disordered thromboregulation could exacerbate vascular damage and potentiate activation of coagulation pathways after exposure to xenogeneic cells or a vascularized xenograft. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. BioTransplant Inc, Charlestown, MA USA. RP Cooper, DKC (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 39 TC 109 Z9 109 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2000 VL 70 IS 9 BP 1323 EP 1331 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 376XH UT WOS:000165481700010 PM 11087147 ER PT J AU Friedman, JRL Klein, C Leung, J Woodward, H Ozelius, LJ Breakefield, XO Charness, ME AF Friedman, JRL Klein, C Leung, J Woodward, H Ozelius, LJ Breakefield, XO Charness, ME TI The GAG deletion of the DYT1 gene is infrequent in musicians with focal dystonia SO NEUROLOGY LA English DT Article ID MUTATION; ONSET C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Genet & Neurosci Program, Boston, MA 02115 USA. VA Boston Healthcare Syst, Neurol Serv, W Roxburg, MA 02132 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Charness, ME (reprint author), VA Boston Healthcare Syst, Neurol Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NINDS NIH HHS [NS38142, NS37409] NR 7 TC 16 Z9 16 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 14 PY 2000 VL 55 IS 9 BP 1417 EP 1418 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 373GY UT WOS:000165282000041 PM 11087801 ER PT J AU Lin, AE Birch, PH Korf, BR Tenconi, B Niimura, M Poyhonen, M Uhas, KA Sigorini, M Virdis, R Romano, C Bonioli, E Wolkenstein, P Pivnick, EK Lawrence, M Friedman, JM AF Lin, AE Birch, PH Korf, BR Tenconi, B Niimura, M Poyhonen, M Uhas, KA Sigorini, M Virdis, R Romano, C Bonioli, E Wolkenstein, P Pivnick, EK Lawrence, M Friedman, JM CA NNFF Int Database Participants TI Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT Meeting of the American-Society-of-Human-Genetics CY OCT, 1997 CL DENVER, CO SP Amer Soc Human Genet DE cardiovascular malformation; congenital heart defect; database; hypertrophic cardiomyopathy; neurofibromatosis type 1; NF1; NF1-Noonan syndrome; peripheral arterial stenosis; pulmonic stenosis; Watson syndrome ID NF1 GENE DELETIONS; NOONAN-SYNDROME; TYPE-1 NEUROFIBROMATOSIS; MOLECULAR-GENETICS; WATSON SYNDROME; PHENOTYPE; CARDIOMYOPATHIES; HEART; MANIFESTATIONS; CHILDREN AB Although it is well recognized that a peripheral vasculopathy may occur in patients with neurofibromatosis 1 (NF1), it is unclear whether cardiovascular abnormalities are more common. We reviewed the frequency of cardiovascular abnormalities, in particular, cardiovascular malformations (CVMs), among 2322 patients with definite NF1 in the National Neurofibromatosis Foundation International Database from 1991-98. Cardiovascular malformations were reported in 54/2322 (2.3%) of the NF1 patients, only 4 of whom had Watson syndrome or NF1-Noonan syndrome. There was a predominance of Class II "flow" defects [Clark, 1995: Moss and Adams' Heart Disease in Infants, Children, and Adolescents Including the Fetus and Young Adult. p 60-70] (43/54, 80%) among the NF1 patients with CVMs. Pulmonic stenosis, that was present in 25 NF1 patients, and aortic coarctation, that occurred in 5, constitute much larger proportions of all CVMs than expected. Of interest was the paucity of Class I conotruncal defects (2 patients with tetralogy of Fallot), and the absence of atrioventricular canal, anomalous pulmonary venous return, complex single ventricle and laterality defects. Besides the 54 patients with CVMs, there were 27 patients with other cardiac abnormalities (16 with murmur, 5 with mitral valve prolapse, 1 with intracardiac tumor, and 5 with electrocardiogram abnormalities), No patient in this study had hypertrophic cardiomyopathy. There were 16 patients who had a peripheral vascular abnormality without an intracardiac CVM, plus an additional 4 patients among those with a CVM who also had a peripheral vascular abnormality. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediatr Serv, Boston, MA 02114 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Harvard Univ, Childrens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. Univ Padua, Dipartimento Pediat, Serv Genet Clin & Epidemiol, I-35128 Padua, Italy. Jikei Univ, Sch Med, Dept Dermatol, Tokyo, Japan. Family Fed Finland, Dept Med Genet, Helsinki, Finland. Scottish Rite Childrens Med Ctr, Atlanta, GA USA. Univ Parma, Ist Clin Pediat, Ctr Genet, I-43100 Parma, Italy. Ist Oasi, Troina, Italy. Univ Genoa, Ist Gaslini, Ctr Genet, Genoa, Italy. Univ Paris 12, Hop Henri Mondor, Dept Dermatol, F-94010 Creteil, France. Univ Tennessee, Dept Pediat, Div Clin Genet, Memphis, TN USA. Le Bonheur Childrens Hosp, Memphis, TN USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediatr Serv, 55 Fruit St, Boston, MA 02114 USA. EM lin.angela@mgh.harvard.edu RI Romano, Corrado/B-9695-2008 OI Romano, Corrado/0000-0003-1049-0683 NR 79 TC 89 Z9 94 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 EI 1096-8628 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 13 PY 2000 VL 95 IS 2 BP 108 EP 117 DI 10.1002/1096-8628(20001113)95:2<108::AID-AJMG4>3.0.CO;2-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 366VX UT WOS:000090027900004 PM 11078559 ER PT J AU Leech, CA Holz, GG Chepurny, O Habener, JF AF Leech, CA Holz, GG Chepurny, O Habener, JF TI Expression of cAMP-regulated guanine nucleotide exchange factors in pancreatic beta-cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cAMP-GEF; GLP-1; MAPK; IDX; PDX; Rap1A; beta-cell ID GLUCAGON-LIKE PEPTIDE-1; ACTIVATED PROTEIN-KINASE; INSULIN-SECRETION; CALCIUM MOBILIZATION; BINDING PROTEINS; RECEPTOR; GLUCOSE; PATHWAY; STORES; ISLETS AB The insulinotropic hormone glucagon-like peptide-1 (GLP-1) binds to a Gs-coupled receptor on pancreatic beta -cells and potentiates glucose-induced insulin secretion, insulin gene transcription, and beta -cell growth. These stimulatory effects have been attributed to the elevation of intracellular cAMP levels, though it is now apparent that some stimulatory effects of GLP-1 occur independently of the cAMP-mediated activation of protein kinase A (PKA). The nature of this alternative, PKA-independent signaling pathway remains unknown. Here we present evidence for the expression of type 1 and type 2 cAMP-regulated guanine nucleotide exchange factors (cAMP-GEFs) in beta -cells. GEFs are activated by their binding of cAMP. Because cAMP-GEFs activate Ras/MAPK proliferation signaling pathways, they may play an important role in PKA-independent, GLP-1-mediated, signaling pathways in the regulation of beta -cell growth and differentiation. (C) 2000 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 55 Fruit St,WEL320, Boston, MA 02114 USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [R01 DK045817-08, R01 DK045817] NR 32 TC 47 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC 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 NOV 11 PY 2000 VL 278 IS 1 BP 44 EP 47 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375QP UT WOS:000165413000008 PM 11071853 ER PT J AU Chen, B Zhou, GF Kim, MY Chishti, Y Hussey, RE Ely, B Skehel, JJ Reinherz, EL Harrison, SC Wiley, DC AF Chen, B Zhou, GF Kim, MY Chishti, Y Hussey, RE Ely, B Skehel, JJ Reinherz, EL Harrison, SC Wiley, DC TI Expression, purification, and characterization of gp160e, the soluble trimeric ectodomain of the simian immunodeficiency virus envelope glycoprotein, gp160 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; INFLUENZA-VIRUS; MEMBRANE-FUSION; HIV-1 GP41; OLIGOMERIC STRUCTURE; CD4 BINDING; SIV GP41; RECEPTOR; TYPE-1; GP120 AB The envelope glycoprotein, gp160, of simian immunodeficiency virus (SIV) shares similar to 25% sequence identity with gp160 from the human immunodeficiency virus, type I,, indicating a close structural similarity. As a result of binding to cell surface CD4 and co-receptor (e.g. CCR5 and CXCR4), both SIV and human immunodeficiency virus gp160 mediate viral entry by membrane fusion. We report here the characterization of gp160e, the soluble ectodomain of SIV gp160. The ectodomain has been expressed in both insect cells and Chinese hamster ovary (CHO)-Lec3.2.8.1 cells, deficient in enzymes necessary for synthesizing complex oligosaccharides. Both the primary and a secondary proteolytic cleavage sites between the gp120 and gp41 subunits of gp160 were mutated to prevent cleavage and shedding of gp120. The purified, soluble glycoprotein is shown to be trimeric by chemical cross-linking, gel filtration chromatography, and analytical ultracentrifugation. It forms soluble, tight complexes with soluble CD4 and a number of Fab fragments from neutralizing monoclonal antibodies. Soluble complexes were also produced of enzymatically deglycosylated gp160e and of gp160e variants with deletions in the variable segments. C1 Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Natl Inst Med Res, London NW7 1AA, England. RP Wiley, DC (reprint author), Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, 320 Longwood Ave,Enders 673, Boston, MA 02215 USA. FU NIAID NIH HHS [AI43649] NR 56 TC 28 Z9 28 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 10 PY 2000 VL 275 IS 45 BP 34946 EP 34953 DI 10.1074/jbc.M004905200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375VW UT WOS:000165422800018 PM 10944528 ER PT J AU Laser, M Willey, CD Jiang, WJ Cooper, G Menick, DR Zile, MR Kuppuswamy, D AF Laser, M Willey, CD Jiang, WJ Cooper, G Menick, DR Zile, MR Kuppuswamy, D TI Integrin activation and focal complex formation in cardiac hypertrophy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; CELL-CYCLE PROGRESSION; ADHESION KINASE FAK; SRC FAMILY KINASES; MYOCYTES IN-VITRO; PROTEIN-KINASE; C-SRC; FIBRONECTIN RECEPTOR; TYROSINE PHOSPHORYLATION; CONTRACTILE DYSFUNCTION AB Cardiac hypertrophy is characterized by both remodeling of the extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. Here we show increased expression and cytoskeletal association of the ECM: proteins fibronectin and vitronectin in pressure-overloaded feline myocardium. These changes are accompanied by cytoskeletal binding and phosphorylation of focal adhesion kinase (FAK) at Tyr-397 and Tyr-925, c-Src at Tyr-416, recruitment of the adapter proteins p130(Cas), Shc, and Nck, and activation of the extracellular-regulated: kinases ERK1/2. A synthetic peptide containing the Arg-Gly-Asp (RGD) motif of fibronectin and vitronectin was used to stimulate adult feline cardiomyocytes cultured on laminin or within a type-1 collagen matrix. Whereas cardiocytes under both conditions showed RGD-stimulated ERK1/2 activation, only collagen-embedded cells exhibited cytoskeletal assembly of FAK, c-Src, Nck, and Shc. In ROD-stimulated collagen-embedded cells, FAK was phosphorylated only at Tyr-397 and; c-Src association occurred without Tyr-416 phosphorylation and p130(Cas) association. Therefore, c-Src activation is not required for its cytoskeletal binding:but may be important for additional phosphorylation of:FAK. Overall, our study suggests that multiple signaling pathways originate in pressure-overloaded heart following integrin engagement with ECM proteins, including focal complex formation and ERK1/2 activation, and many of these pathways can be activated in cardiomyocytes via RGD-stimulated integrin activation. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Cell Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Physiol, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Cell Biol, 114 Doughty St, Charleston, SC 29425 USA. OI Willey, Christopher/0000-0001-9953-0279 FU NHLBI NIH HHS [HL-48788] NR 59 TC 93 Z9 97 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 10 PY 2000 VL 275 IS 45 BP 35624 EP 35630 DI 10.1074/jbc.M006124200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375VW UT WOS:000165422800105 PM 10958798 ER PT J AU Brasher, BB Van Etten, RA AF Brasher, BB Van Etten, RA TI c-Ab1 has high intrinsic tyrosine kinase activity that is stimulated by mutation of the Src homology 3 domain and by autophosphorylation at two distinct regulatory tyrosines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ABL TRANSFORMING ACTIVITY; C-ABL; PROTEIN-BINDING; IN-VIVO; INTERMOLECULAR AUTOPHOSPHORYLATION; CRYSTAL-STRUCTURE; GENE-PRODUCT; CELL-CYCLE; V-ABL; ACTIVATION AB Using the specific Abl tyrosine kinase inhibitor STI 571, we purified unphosphorylated murine type IV c-Abl and measured the kinetic parameters of c-Abl tyrosine kinase activity in a solution with a peptide-based assay. Unphosphorylated c-Abl exhibited substantial peptide kinase activity with K-m of 204 muM and V-max of 33 pmol min(-1). Contrary to previous observations using immune complex kinase assays, we found that a transforming c-Abl mutant with a Src homology 3 domain point mutation (P131L) had significantly (about 6-fold) higher intrinsic kinase activity than wild-type c-Abl (K-m = 91 muM, V-max = 112 pmol min(-1)). Autophosphorylation stimulated the activity of wild-type c-Abl about 18-fold and c-Abl P131L about 3.6-fold, resulting in highly active kinases with similar catalytic rates, The autophosphorylation rate was dependent on Abl protein concentration consistent with an intermolecular reaction, A tyrosine to phenylalanine mutation (Y412F) at the c-Abl residue homologous to the c-Src catalytic domain autophosphorylation site impaired the activation of wildtype c-Abl by 90% but reduced activation of c-Abl P131L by only 45%. Mutation of a tyrosine (Tyr-245) in the linker region between the Src homology 2 and catalytic domains that is conserved among the Abl family inhibited the autophosphorylation-induced activation of wild-type c-Abl by 50%, whereas the c-Abl Y245F/Y412F double mutant was minimally activated by autophosphorylation, These results support a model where c-Abl is inhibited in part through an intramolecular Src homology 3-linker interaction and stimulated to full catalytic activity by sequential phosphorylation at Tyr-412 and Tyr-245. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA72465] NR 46 TC 178 Z9 179 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 10 PY 2000 VL 275 IS 45 BP 35631 EP 35637 DI 10.1074/jbc.M005401200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 375VW UT WOS:000165422800106 PM 10964922 ER PT J AU DePinho, RA AF DePinho, RA TI The age of cancer SO NATURE LA English DT Review ID COMPARATIVE GENOMIC HYBRIDIZATION; TELOMERASE ACTIVITY; HUMAN FIBROBLASTS; MOUSE TELOMERASE; COLORECTAL-CANCER; REPLICATIVE SENESCENCE; GENETIC ALTERATIONS; IMMORTAL CELLS; LIVER-DISEASES; ONCOGENIC RAS AB A striking link exists between advanced age and increased incidence of cancer. Here I review how several of the age-related molecular and physiological changes might act in concert to promote cancer, and in particular epithelial carcinogenesis. Experimental data indicate that the aged, cancer-prone phenotype might represent the combined pathogenetic effects of mutation load, epigenetic regulation, telomere dysfunction and altered stromal milieu. Further verification of the role of these effects should in turn lead to the design of effective therapeutics for the treatment and prevention of cancer in the aged. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 95 TC 547 Z9 574 U1 7 U2 34 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 9 PY 2000 VL 408 IS 6809 BP 248 EP 254 DI 10.1038/35041694 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 371LL UT WOS:000165180400055 PM 11089982 ER PT J AU Methippara, MM Alam, MN Szymusiak, R McGinty, D AF Methippara, MM Alam, MN Szymusiak, R McGinty, D TI Effects of lateral preoptic area application of orexin-A on sleep-wakefulness SO NEUROREPORT LA English DT Article DE lateral preoptic area; narcolepsy; orexin-A; rat; sleep; temperature; wakefulness ID NEURONS; NARCOLEPSY; RAT; PEPTIDES; SYSTEMS; AROUSAL AB Deficiency of orexin, a newly discovered hypothalamic peptide, is thought to lead to abnormal sleepiness and cataplexy in both human narcolepsy and animal models of the disease. As the POA contains extensive orexin terminals and is established as a sleep/arousal regulatory site, we evaluated a hypothesis that this site is a target for the arousal-inducing effects of orexin. Orexin-A was microinjected into lateral preoptic area (IPOA) and the effects on sleep-wakefulness and brain temperature were studied. Compared to saline vehicle control, orexin-A induced an increase in wakefulness for 70 min and suppressed all sleep stages, especially SWS2 and REM for 80 and 90 min, respectively. Brain temperature was not differentially affected by orexin-A compared to saline control. The orexin-induced arousal and REM suppression are consistent with the orexin-deficiency model of narcolepsy. Our results suggest that the IPOA orexin terminal field or adjacent structures may be a locus of arousal regulation by this peptide and a substrate of sleep-wake regulatory deficits in:narcolepsy. NeuroReport 11:3423-3426 (C) 2000 Lippincott Williams & Wilkins. C1 Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90033 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90033 USA. RP McGinty, D (reprint author), Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90033 USA. FU NHLBI NIH HHS [HL 60296]; NIMH NIH HHS [MH 47480] NR 24 TC 84 Z9 85 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 9 PY 2000 VL 11 IS 16 BP 3423 EP 3426 DI 10.1097/00001756-200011090-00004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 373RA UT WOS:000165301600004 PM 11095491 ER PT J AU Albert, CM Mittleman, MA Chae, CU Lee, IM Hennekens, CH Manson, JE AF Albert, CM Mittleman, MA Chae, CU Lee, IM Hennekens, CH Manson, JE TI Triggering of sudden death from cardiac causes by vigorous exertion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; TIME PHYSICAL-ACTIVITY; LEISURE-TIME; CASE-CROSSOVER; EXERCISE; RISK; MORTALITY; MEN; FITNESS AB Background Retrospective and cross-sectional data suggest that vigorous exertion can trigger cardiac arrest or sudden death and that habitual exercise may diminish this risk. However, the role of physical activity in precipitating or preventing sudden death from cardiac causes has not been assessed prospectively in a large number of subjects. Methods We used a prospective, nested case crossover design within the Physicians Health Study to compare the risk of sudden death during and up to 30 minutes after an episode of vigorous exertion with that during periods of lighter exertion or none. We then evaluated whether habitual vigorous exercise modified the risk of sudden death that was associated with vigorous exertion. In addition, the relation of vigorous exercise to the overall risk of sudden death and nonsudden death from coronary heart disease was assessed. Results During 12 years of follow-up, 122 sudden deaths were confirmed among the 21,481 male physicians who were initially free of self-reported cardiovascular disease and who provided information on their habitual level of exercise at base line. The relative risk of sudden death during and up to 30 minutes after vigorous exertion was 16.9 (95 percent confidence interval, 10.5 to 27.0; P < 0.001). However, the absolute risk of sudden death during any particular episode of vigorous exertion was extremely low (1 sudden death per 1.51 million episodes of exertion). Habitual vigorous exercise attenuated the relative risk of sudden death that was associated with an episode of vigorous exertion (P value for trend = 0.006). The base-line level of exercise was not associated with the overall risk of subsequent sudden death. Conclusions These prospective data from a study of U.S. male physicians suggest that habitual vigorous exercise diminishes the risk of sudden death during vigorous exertion. (N Engl J Med 2000; 343:1355-61.) (C) 2000, Massachusetts Medical Society. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth Med, Miami, FL USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NCI NIH HHS [CA-40360]; NHLBI NIH HHS [1-K08-HL-03783, HL-34595] NR 39 TC 431 Z9 440 U1 2 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 9 PY 2000 VL 343 IS 19 BP 1355 EP 1361 DI 10.1056/NEJM200011093431902 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 370ZH UT WOS:000165152800002 PM 11070099 ER PT J AU Asch, SM Sloss, EEM Hogan, C Brook, RH Kravitz, RL AF Asch, SM Sloss, EEM Hogan, C Brook, RH Kravitz, RL TI Measuring underuse of necessary care among elderly Medicare beneficiaries using inpatient and outpatient claims SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-CARE; ADMINISTRATIVE DATA; MEASURING QUALITY; EPIDEMIOLOGY; INFORMATION; INSURANCE; SYSTEM; RATES AB Context Continuing changes in the health care delivery system make it essential to monitor underuse of needed care, even for relatively well-insured populations. Traditional approaches to measuring underuse have relied on patient surveys and chart reviews, which are expensive, or simple single-condition claims-based indicators, which are not clinically convincing. Objective To develop a comprehensive, low-cost system for measuring underuse of necessary care among elderly patients using inpatient and outpatient Medicare claims. Design A 7-member, multispecialty expert physician panel was assembled and used a modified Delphi method to develop clinically detailed underuse indicators likely to be associated with avoidable poor outcomes for 15 common acute and chronic medical and surgical conditions. An automated system was developed to calculate the indicators using administrative data. Setting and Subjects A total of 345253 randomly selected elderly US Medicare beneficiaries in 1994-1996, Main Outcome Measures Proportion of beneficiaries receiving care, stratified by indicators of necessary care (n=40, including 3 for preventive care), and avoidable outcomes (n=6). Results For 16 of 40 necessary care indicators (including preventive care indicators), beneficiaries received the indicated care less than two thirds of the time. Of all indicators, African Americans scored significantly worse than whites on 16 and better on 2; residents of poverty areas scored significantly lower than nonresidents on 17 and higher on 1; residents of federally defined Health Professional Shortage Areas scored significantly lower than nonresidents on 16 and higher on none (P<.05 for all). Conclusions This claims-based method detected substantial underuse problems likely to result in negative outcomes in elderly populations. Significantly more underuse problems were detected in populations known to receive less-than-average medical care, The method can serve as a reliable, valid tool for monitoring trends in underuse of needed care for older patients and for comparing care across health care plans and geographic areas based on claims data. C1 RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Direct Res, Vienna, VA USA. Univ Calif Davis, Ctr Hlth Serv Res Primary Care, Davis, CA 95616 USA. RP Asch, SM (reprint author), 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. OI Kravitz, Richard/0000-0001-5575-529X NR 45 TC 119 Z9 120 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 8 PY 2000 VL 284 IS 18 BP 2325 EP 2333 DI 10.1001/jama.284.18.2325 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 369NU UT WOS:000165074500026 PM 11066182 ER PT J AU Berkwits, M AF Berkwits, M TI CAPTURE! SHOCK! EXCITE! Clinical trial acronyms and the "branding" of clinical research SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID AVID TRIAL; ANTIARRHYTHMICS; ACTIVATION C1 Univ Penn Hlth Syst, Div Gen Internal Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Berkwits, M (reprint author), Univ Penn Hlth Syst, Div Gen Internal Med, Philadelphia Vet Affairs Med Ctr, 1229 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 25 TC 15 Z9 15 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 7 PY 2000 VL 133 IS 9 BP 755 EP 759 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 369PC UT WOS:000165075300029 PM 11074930 ER PT J AU Sodian, R Hoerstrup, SP Sperling, JS Daebritz, S Martin, DP Moran, AM Kim, BS Schoen, FJ Vacanti, JP Mayer, JE AF Sodian, R Hoerstrup, SP Sperling, JS Daebritz, S Martin, DP Moran, AM Kim, BS Schoen, FJ Vacanti, JP Mayer, JE TI Early in vivo experience with tissue-engineered trileaflet heart valves SO CIRCULATION LA English DT Article DE tissue engineering; valves; polymers ID IN-VITRO; PROSTHESES; LEAFLETS AB Background-Tissue engineering is a new approach in which techniques are being developed to transplant autologous cells onto biodegradable scaffolds to ultimately form new functional autologous tissue. Workers at our laboratory have focused on tissue engineering of heart valves. The present study was designed to evaluate the implantation of a whole trileaflet tissue-engineered heart valve in the pulmonary position in a lamb model. Methods and Results-We constructed a biodegradable and biocompatible trileaflet heart valve scaffold that was fabricated from a porous polyhydroxyalkanoate (pore size 180 to 240 mum; Tepha Inc). Vascular cells were harvested from ovine carotid arteries, expanded in vitro, and seeded onto our heart valve scaffold. With the use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and 2-cm segments of pulmonary artery were replaced by autologous cell-seeded heart valve constructs (n=4). One animal received an acellular valved conduit. No animal received any anticoagulation therapy. Animals were killed at 1, 5, 13, and 17 weeks. Explanted valves were examined histologically with scanning electron microscopy, biochemically, and biomechanically. All animals survived the procedure. The valves showed minimal regurgitation, and valve gradients were <20 mm Hg on echocardiography. The maximum gradient was 10 mm Hg with direct pressures. Macroscopically, the tissue-engineered constructs were covered with tissue, and there was no thrombus formation on any of the specimens, Scanning electron microscopy showed smooth flow surfaces during the follow-up period. Histological examination demonstrated laminated fibrous tissue with predominant glycosaminoglycans as extracellular matrix. 4-Hydroxyproline assays demonstrated an increase in collagen content as a percentage of native pulmonary artery (1 week 45.8%, 17 weeks 116%). DNA assays showed a comparable number of cells in all explanted samples. There was no tissue formation in the acellular control. Conclusions-Tissue-engineered heart valve scaffolds fabricated from polyhydroxyalkanoates can be used for implantation in the pulmonary position with an appropriate function for 120 days in lambs. C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiac Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA USA. Metabolix Inc, Cambridge, MA USA. RP Mayer, JE (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Cardiac Surg, 300 Longwood Ave, Boston, MA 02115 USA. RI Kim, Byung-Soo/O-2352-2013 NR 23 TC 171 Z9 183 U1 4 U2 32 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 7 PY 2000 VL 102 IS 19 SU S BP 22 EP 29 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 371KC UT WOS:000165177300005 ER PT J AU Steinhoff, G Stock, U Karim, N Mertsching, H Timke, A Meliss, RR Pethig, K Haverich, A Bader, A AF Steinhoff, G Stock, U Karim, N Mertsching, H Timke, A Meliss, RR Pethig, K Haverich, A Bader, A TI Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits - In vivo restoration of valve tissue SO CIRCULATION LA English DT Article DE tissue; valves; surgery; heart diseases ID ENDOTHELIAL-CELLS; IN-VITRO; FIBRINOGEN; EXPRESSION AB Background-Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. Methods non Results-Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days. resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed pal-tial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha -actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. Conclusions-The in vitro tissue-engineering approach using acellular matrix conduits lends to the in vivo reconstitution of viable heart valve tissue. C1 Hannover Med Sch, Leibniz Res Labs Biotechnol & Artifical Organs, D-3000 Hannover, Germany. Hannover Med Sch, Dept Thorac & Cardiovasc Surg, D-3000 Hannover, Germany. Hannover Med Sch, Dept Pathol, D-3000 Hannover, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Steinhoff, G (reprint author), Univ Rostock, Fak Med, Klin Herzchirurg, Schillingallee 35, D-18105 Rostock, Germany. EM GustavSteinhoff@aol.com NR 20 TC 209 Z9 229 U1 5 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 7 PY 2000 VL 102 IS 19 SU S BP 50 EP 55 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 371KC UT WOS:000165177300010 ER PT J AU Philbin, EF McCullough, PA DiSalvo, TG Dec, GW Jenkins, PL Weaver, WD AF Philbin, EF McCullough, PA DiSalvo, TG Dec, GW Jenkins, PL Weaver, WD TI Socioeconomic status is an important determinant of the use of invasive procedures after acute myocardial infarction in New York State SO CIRCULATION LA English DT Article DE myocardial infarction; socioeconomic status; race; sex; women; catheterization; angioplasty; grafting ID CARDIAC PROCEDURES; CORONARY ANGIOGRAPHY; REVASCULARIZATION PROCEDURES; RESOURCE UTILIZATION; UNITED-STATES; HEALTH-CARE; MORTALITY; CATHETERIZATION; RECOMMENDATIONS; ASSOCIATION AB Background-Patient and hospital characteristics influence the use of invasive cardiac procedures. Whether socioeconomic status (SES) has an influence that is independent of these other determinants is unclear. The purpose of the present study wits to examine the influence of household income as a measure of SES on the use of invasive cardiac procedures among a large group of patients with acute myocardial infarction. Methods and Results-We analyzed administrative discharge data from 231 nonfederal acute care hospitals in New York State that involved 78 698 black or white inpatients with International Classification of Diseases, Ninth Revision, Clinical Modification code 410.XX in the principal diagnosis position between January 1 and December 31, 1995. Household income was derived from postal ZIP codes and census data. The use of cardiac catheterization, PTCA, CABG, and any revascularization procedure was examined across groups stratified by income. Patients who resided in lower-income neighborhoods were more often female or black, had a higher prevalence of coexistent illness, had a higher use of Medicaid insurance, and were less often admitted to urban hospitals ol hospitals that provide on-site CABG and PTCA. Crude and adjusted odds ratios for catheterization, PTCA, CABG, and any revascularization procedure were related to income in a graded fashion. After adjustment, patients in the highest quintile of income were 22% more likely to undergo catheterization, 74% more likely to undergo PTCA, 48% more likely to undergo CABG, and 76% moro likely to undergo any revascularization procedure than were patients in the lowest quintile. The difference in cardiac catheterization did not fully account for income-based differences in revascularization, because income remained a significant determinant of revascularization after accounting for whether a catheterization was performed. Even among patients treated in hospitals that provide on-site CABC and PTCA, income was a significant determinant of procedures, Conclusions-Lower-income patients hospitalized for acute myocardial infarction are more often female or black, have more coexisting illnesses, and are less often admitted to urban hospitals or hospitals that provide CABG and PTCA. Even after adjustment for these and other factors, lower income is a negative predictor of procedure use. C1 Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Basett Healthcare, Bassett Res Inst, Cooperstown, NY USA. RP Philbin, EF (reprint author), Albany Med Coll, Div Cardiol, George E Pataki Chair Cardiol, Mail Code 44,47 New Scotland Ave, Albany, NY 12208 USA. NR 24 TC 70 Z9 70 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 7 PY 2000 VL 102 IS 19 SU S BP 107 EP 115 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 371KC UT WOS:000165177300020 ER PT J AU Aboody, KS Brown, A Rainov, NG Bower, KA Liu, SX Yang, W Small, JE Herrlinger, U Ourednik, V Black, PM Breakefield, XO Snyder, EY AF Aboody, KS Brown, A Rainov, NG Bower, KA Liu, SX Yang, W Small, JE Herrlinger, U Ourednik, V Black, PM Breakefield, XO Snyder, EY TI Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene therapy; transplantation; migration; brain tumors; vascular ID CYTOSINE DEAMINASE GENE; NERVOUS-SYSTEM; MOUSE-BRAIN; 5-FLUOROCYTOSINE; REPLACEMENT; RETROVIRUS; NEURONS; THERAPY; TUMORS; LINES AB One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them "elusive" to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs "surround" the invading tumor border while "chasing down" infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly. NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule-cytosine deaminase-such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Layton Biosci, Sunnyvale, CA 94086 USA. RP Snyder, EY (reprint author), Childrens Hosp, Dept Neurol, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA69246, CA86768, P01 CA069246]; NICHD NIH HHS [HD07466, T32 HD007466] NR 23 TC 718 Z9 779 U1 3 U2 25 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 NOV 7 PY 2000 VL 97 IS 23 BP 12846 EP 12851 DI 10.1073/pnas.97.23.12846 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 372GK UT WOS:000165225800089 PM 11070094 ER PT J AU Feschenko, MS Stevenson, E Sweadner, KJ AF Feschenko, MS Stevenson, E Sweadner, KJ TI Interaction of protein kinase C and cAMP-dependent pathways in the phosphorylation of the Na,K-ATPase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; ALPHA-SUBUNIT; INTACT-CELLS; CATALYTIC SUBUNIT; EPITHELIAL-CELLS; STRUCTURAL BASIS; PLASMA-MEMBRANE; XENOPUS OOCYTES; CHOROID-PLEXUS; NA+,K+-ATPASE AB To test the hypothesis that there is cross-talk between the protein kinase C (PKC) and protein kinase A (PKA) pathways in the regulation of the Na,K-ATPase, we measured its phosphorylation in mammalian cell cultures. Phosphorylation of the PKC site, Ser-18, appeared to be due to the activation of the a isoform of the kinase. In NRK-52E and L6 cells, this phosphorylation was reduced by prior activation of a cAMP-dependent signaling pathway with forskolin. In principle this would be consistent with direct interaction between the two phosphorylation sites, but further investigation suggested a more indirect mechanism. First, phosphorylation of Ser-938, the PKA site, could not be detected despite the presence of active PKA. Second, there was a major reduction in the phosphorylation of unrelated phosphoproteins as a consequence of elevation of cAMP, suggesting generalized reduction of kinase activity or activation of phosphatase activity. In NRK-52E and L6, phosphorylation of the Na,K-ATPase at Ser-18 paralleled this global change. In C6 cells, in contrast, there was no cAMP effect on Na,K-ATPase phosphorylation at Ser-18 and no global cAMP effect on other phosphoproteins. The cross-talk is evidently mediated by events occurring at the cellular level. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01NS27653] NR 58 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 3 PY 2000 VL 275 IS 44 BP 34693 EP 34700 DI 10.1074/jbc.M005869200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 369YL UT WOS:000165095300093 PM 10940309 ER PT J AU Pasquinelli, AE Reinhart, BJ Slack, F Martindale, MQ Kuroda, MI Maller, B Hayward, DC Ball, EE Degnan, B Muller, P Spring, J Srinivasan, A Fishman, M Finnerty, J Corbo, J Levine, M Leahy, P Davidson, E Ruvkun, G AF Pasquinelli, AE Reinhart, BJ Slack, F Martindale, MQ Kuroda, MI Maller, B Hayward, DC Ball, EE Degnan, B Muller, P Spring, J Srinivasan, A Fishman, M Finnerty, J Corbo, J Levine, M Leahy, P Davidson, E Ruvkun, G TI Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA SO NATURE LA English DT Article ID DOUBLE-STRANDED-RNA; C-ELEGANS; CAENORHABDITIS-ELEGANS; GENETIC INTERFERENCE; LIN-14 AB Two small RNAs regulate the timing of Caenorhabditis elegans development(1,2). Transition from the first to the second larval stage fates requires the 22-nucleotide lin-4 RNA(1,3,4), and transition from late larval to adult cell fates requires the 21-nucleotide let-7 RNA 2. The lin-4 and let-7 RNA genes are not homologous to each other, but are each complementary to sequences in the 3' untranslated regions of a set of protein-coding target genes that are normally negatively regulated by the RNAs1,2,5,6. Here we have detected let-7 RNAs of similar to 21 nucleotides in samples from a wide range of animal species, including vertebrate, ascidian, hemichordate, mollusc, annelid and arthropod, but not in RNAs from several cnidarian and poriferan species, Saccharomyces cerevisiae, Escherichia coli or Arabidopsis. We did not detect lin-4 RNA in these species. We found that let-7 temporal regulation is also conserved: let-7 RNA expression is first detected at late larval stages in C. elegans and Drosophila, at 48 hours after fertilization in zebrafish, and in adult stages of annelids and molluscs. The let-7 regulatory RNA may control late temporal transitions during development across animal phylogeny. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Univ Hawaii, Pacific Biomed Res Ctr, Kewalo Marine Lab, Honolulu, HI 96813 USA. Baylor Univ, Howard Hughes Med Inst, Houston, TX 77030 USA. Australian Natl Univ, Res Sch Biol Sci, Canberra, ACT 2601, Australia. Univ Queensland, Dept Zool & Entomol, Brisbane, Qld 4072, Australia. Univ Basel, Inst Zool, CH-4051 Basel, Switzerland. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Boston Univ, Dept Biol, Boston, MA 02215 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. CALTECH, Div Biol 156 29, Pasadena, CA 91125 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RI Ball, Eldon/C-9261-2009; OI Ball, Eldon/0000-0002-6052-1495; Corbo, Joseph/0000-0002-9323-7140; Slack, Frank/0000-0001-8263-0409 FU NIAMS NIH HHS [P30 AR046032]; NIGMS NIH HHS [R01 GM045744] NR 14 TC 1242 Z9 1367 U1 5 U2 101 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 2 PY 2000 VL 408 IS 6808 BP 86 EP 89 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 369DH UT WOS:000165050400056 PM 11081512 ER PT J AU Sachs, G Shin, JM Munson, K Vagin, O Lambrecht, N Scott, DR Weeks, DL Melchers, K AF Sachs, G Shin, JM Munson, K Vagin, O Lambrecht, N Scott, DR Weeks, DL Melchers, K TI Review article: the control of gastric acid and Helicobacter pylori eradication SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SARCOPLASMIC-RETICULUM; DUODENAL-ULCER; REVERSIBLE INHIBITORS; PEPTIC-ULCERATION; CATALYTIC CYCLE; ALPHA-SUBUNIT; BETA-SUBUNIT; H+-ATPASE; SECRETION; PUMP AB This review focuses on the gastric acid pump as a therapeutic target for the control of acid secretion in peptic ulcer and gastro-oesophageal reflux disease. The mechanism of the proton pump inhibitors is discussed as well as their clinical use. The biology of Helicobacter pylori as a gastric denizen is then discussed, with special regard to its mechanisms of acid resistance. Here the properties of the products of the urease gene clusters, ureA, B and ureI, E, F, G and H are explored in order to explain the unique location of this pathogen. The dominant requirement for acid resistance is the presence of a proton gated urea transporter, UreI, which increases access of gastric juice urea to the intrabacterial urease 300-fold. This enables rapid and continuous buffering of the bacterial periplasm to approximate to pH 6.0, allowing acid resistance and growth at acidic pH in the presence of 1 mM urea. A hypothesis for the basis of combination therapy for eradication is also presented. C1 Univ Calif Los Angeles, Digest Res Ctr, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, Digest Res Ctr, Dept Med, Los Angeles, CA USA. BYK Gulden, Constance, Germany. RP Sachs, G (reprint author), VA Greater Los Angeles Heath Care Syst, Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK17294, DK40615, DK41301] NR 58 TC 38 Z9 41 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD NOV PY 2000 VL 14 IS 11 BP 1383 EP 1401 DI 10.1046/j.1365-2036.2000.00837.x PG 19 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 373EB UT WOS:000165274500001 PM 11069309 ER PT J AU Taylor, E AF Taylor, E TI Mind-body medicine and alternative therapies at Harvard: Is this the reintroduction of psychology into general medical practice? SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Article ID UNITED-STATES C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Taylor, E (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD NOV PY 2000 VL 6 IS 6 BP 32 EP + PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 371AD UT WOS:000165154700009 PM 11076444 ER PT J AU Horrigan, B Lukoff, D AF Horrigan, B Lukoff, D TI David Lukoff, PhD - The importance of spirituality in mental health SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 Saybrook Grad Sch & Res Ctr, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Horrigan, B (reprint author), InnoVision Commun, 101 Columbia, Aliso Viejo, CA 92656 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD NOV PY 2000 VL 6 IS 6 BP 80 EP 87 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 371AD UT WOS:000165154700016 ER PT J AU Walsh, CR Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ AF Walsh, CR Lloyd-Jones, DM Camargo, CA Giugliano, RP O'Donnell, CJ TI Clinical trials of unfractionated heparin and low-molecular-weight heparin in addition to aspirin for the treatment of unstable angina pectoris: Do the results apply to all patients? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; MANAGEMENT; ISCHEMIA; DEATH AB We sought to determine how the results of available randomized controlled trials of intravenous unfractionated heparin (UH) and low-molecular weight heparin (LMWH) apply to unselected patients with unstable angina pectoris (UAP). Although UH is widely used in addition to aspirin for treatment of UAP, the evidence is weak for a net benefit over aspirin alone. LMWH preparations may confer a net benefit over UH for the treatment of UAP in clinical trials. It is not clear, however, how trial results are generalized to unselected patients with UAP, Using criteria from the Agency for Health Care Policy and Research Unstable Angina Clinical Practice Guideline, we identified 277 consecutive patients with primary UAP, Exclusion criteria were applied from 6 trials of UH in addition to aspirin and 5 trials of LMWH in addition to aspirin for the treatment of UAP. Clinical outcomes were compared among ineligible and eligible patients for trial enrollment. Patients meeting exclusion criteria were older and had more extensive coexisting medical illness than eligible patients for trial enrollment. Thirty-eight percent to 42% of our study population met greater than or equal to1 exclusion criteria for each of the 6 trials of UH, and 14% to 46% met greater than or equal to1 exclusion criteria for each of the 5 LMWH trials. The I-year all-cause death rate was higher in UH ineligible patients compared with UH eligible patients (16% vs 4%, p = 0.003) and in LMWH ineligible patients compared with LMWH eligible patients (16% vs 7%, p = 0.005). Thus, clinical trials of UH and LMWH may have limited generalizability to unselected patients with UAP, many of whom have characteristics that would exclude them from trial enrollment and put them at risk for adverse outcomes. (C)2000 by Excerpta Medica, Inc. C1 NHLBI Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. RP O'Donnell, CJ (reprint author), NHLBI Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-07575, HL-03533] NR 21 TC 5 Z9 5 U1 3 U2 3 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 NOV 1 PY 2000 VL 86 IS 9 BP 908 EP 912 DI 10.1016/S0002-9149(00)01120-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 369YU UT WOS:000165096000003 PM 11053697 ER PT J AU Ceballos, KM Nielsen, GP Selig, MK O'Connell, JX AF Ceballos, KM Nielsen, GP Selig, MK O'Connell, JX TI Is anti-h-caldesmon useful for distinguishing smooth muscle and myofibroblastic tumors? An immunohistochemical study SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE h-caldesmon; immunohistochemistry; myofibroblast; smooth muscle ID MALIGNANT FIBROUS HISTIOCYTOMA; EXPRESSION; DIFFERENTIATION; CELLS; CALPONIN; SARCOMA; PROTEIN AB Misinterpretation of positive staining of antibodies to desmin, smooth muscle actin, and muscle actin as representing smooth muscle differentiation in the context of a spindle cell tumor is not uncommon. Anti-h-caldesmon is a promising novel immunohistochemical reagent for more specific smooth muscle differentiation. We studied 72 tumors (II leiomyosarcomas, 26 malignant fibrous histiocytomas [MFHs], 11 fibromatoses, 11 cellular cutaneous fibrous histiocytomas [CCFHs], 5 malignant peripheral nerve sheath tumors, 4 synovial sarcomas, and 4 cases of nodular fasciitis), the reactive myofibroblastic response in 5 cases of acute cholecystitis, and the desmoplastic response surrounding 5 invasive breast carcinomas. Tissues were examined for expression of h-caldesmon, desmin, smooth muscle actin, and muscle actin. Diffuse staining for h-caldesmon was present only within the leiomyosarcomas. Focal staining for h-caldesmon involving less than 1% of lesional cells was present in 3 of 26 MFHs and 1 of 1 CCFHs. There was overlap in staining for the other "myoid" markers in all of the lesions that contained myofibroblasts. Anti-h-caldesmon seems to be a reliable marker of smooth muscle differentiation, and its inclusion in a panel of myoid immunohistochemical reagents should allow distinction of smooth muscle and myofibroblastic tumors. C1 Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP O'Connell, JX (reprint author), Vancouver Gen Hosp, Dept Pathol, 855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. NR 13 TC 77 Z9 82 U1 0 U2 1 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 2000 VL 114 IS 5 BP 746 EP 753 PG 8 WC Pathology SC Pathology GA 367JL UT WOS:000090057900011 PM 11068549 ER PT J AU Kociszewski, C Thomas, SH Harrison, T Wedel, SK AF Kociszewski, C Thomas, SH Harrison, T Wedel, SK TI Etomidate versus succinylcholine for intubation in an air medical setting SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Association-of-Emergency-Medical-Services (EMS) CY JAN, 2000 CL DANA POINT, CALIFORNIA SP Natl Assoc Emergency Med Serv DE etomidate; succinylcholine; air medical transport; prehospital transport; airway management; intubation ID RAPID-SEQUENCE INDUCTION; TRAUMA PATIENTS; EMERGENCY-MEDICINE; ROCURONIUM; TRANSPORT; SEDATION AB The objective was to compare rates of successful endotracheal intubation (ETI) and requirement for multiple ETI attempts in patients receiving etomidate (ETOM) versus succinylcholine (SUX), This retrospective study analyzed adults in whom oral ETI was attempted by a helicopter EMS (HEMS) service between July 1997 to July 1999, Data were from records of the HEMS service, which uses a RN/EMTP crew; analysis was with chi-square and logistic regression (P = .05), ETI was successful in 269 (97.8%) of 275 patients, with multiple attempts occurring in 54 (20.1%) of 269, Success rates for SUX (209 of 213, 98.1%) and ETOM (60 of 62, 96.8%) were similar (P =,62), However, of 60 ETOM patients successfully intubated, 7 (11.7%) required rescue succinylcholine. When these patients are tallied as ETOM failures and SUX successes, resultant success rates for ETOM (86.9%) and SUX (98.2%) are different (P = .001), ETOM patients were more likely (P = .004) than SUX patients to require multiple attempts (33.3% versus 16.3%), ETI success rates were high in patients receiving SUX or ETOM as primary adjuncts for airway control, but initial success was more likely with SUX, and ETOM patients were more likely to require multiple attempts. Copyright (C) 2000 by W.B, Saunders Company. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Boston Medflight Crit Care Transport Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 115, Boston, MA 02114 USA. NR 31 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2000 VL 18 IS 7 BP 757 EP 763 DI 10.1053/ajem.2000.18033 PG 7 WC Emergency Medicine SC Emergency Medicine GA 372EK UT WOS:000165221200003 PM 11103724 ER PT J AU Call, SA Heudebert, G Saag, M Wilcox, CM AF Call, SA Heudebert, G Saag, M Wilcox, CM TI The changing etiology of chronic diarrhea in HIV-infected patients with CD4 cell counts less than 200 cells/mm(3) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-College-of-Gastroenterology CY OCT 12-14, 1998 CL BOSTON, MASSACHUSETTS SP Amer Coll Gastroenterol ID HUMAN-IMMUNODEFICIENCY-VIRUS; DIFFICILE-ASSOCIATED DIARRHEA; QUALITY-OF-LIFE; PNEUMOCYSTIS-CARINII PNEUMONIA; CLOSTRIDIUM-DIFFICILE; ANTIRETROVIRAL THERAPY; DECLINING MORBIDITY; RISK-FACTORS; AIDS; DISCONTINUATION AB PURPOSE: The purpose of this study was to evaluate the incidence and causes of chronic diarrhea in patients with AIDS over a period of time that included the pre-HAART (highly:active antiretroviral therapy) era and the introduction of HAART. METHODS: The study cohort was comprised of patients receiving primary care at a university-associated outpatient HIV clinic from January 1, 1995 to December 31, 1997. Patients were identified retrospectively through a clinical database and were included in the study if their diarrhea had persisted for longer than two weeks and their CD4 cell count at time of symptoms was <200 cells/mm(3). Further data were obtained by chart review. RESULTS: Over the 36-month period, the occurrence of chronic diarrhea did not change significantly, ranging from 8 to 10.5% per year in patients with CD4 cell counts <200 cells/mm(3). The percentage of patients diagnosed with opportunistic infectious etiologies decreased over the three-year period from 53% (1995) to 13% (1997). The percentage of patients diagnosed with noninfectious causes increased from 32% to 70% over this same time period. CONCLUSIONS: Over the three years of the study, the incidence of chronic diarrhea in AIDS patients in our clinic did not change. The etiologies of diarrhea did change significantly, with an increased incidence of noninfectious causes and a:decreased incidence of opportunistic infectious causes. This shift in etiologies coincides with the introduction and increased use of HAART in our clinic population (1996). (C) 2000 by Am. Cell. of Gastroenterology). C1 Univ Alabama, Div Infect Dis, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Gastroenterol & Hepatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Div Gen Internal Med, Birmingham, AL USA. RP Wilcox, CM (reprint author), UAB, GI Div, Birmingham, AL 35294 USA. NR 28 TC 39 Z9 41 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2000 VL 95 IS 11 BP 3142 EP 3146 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 371NZ UT WOS:000165186200022 PM 11095332 ER PT J AU Klein, C Schilling, K Saunders-Pullman, RJ Garrels, J Breakefield, XO Brin, MF deLeon, D Doheny, D Fahn, S Fink, JS Forsgren, L Friedman, J Frucht, S Harris, J Holmgren, G Kis, B Kurlan, R Kyllerman, M Lang, AE Leung, J Raymond, D Robishaw, JD Sanner, G Schwinger, E Tabamo, RE Tagliati, M Vieregge, P Wahlstrom, J Wendt, KJ Kramer, PL Bressman, SB Ozelius, LJ AF Klein, C Schilling, K Saunders-Pullman, RJ Garrels, J Breakefield, XO Brin, MF deLeon, D Doheny, D Fahn, S Fink, JS Forsgren, L Friedman, J Frucht, S Harris, J Holmgren, G Kis, B Kurlan, R Kyllerman, M Lang, AE Leung, J Raymond, D Robishaw, JD Sanner, G Schwinger, E Tabamo, RE Tagliati, M Vieregge, P Wahlstrom, J Wendt, KJ Kramer, PL Bressman, SB Ozelius, LJ TI A major locus for myoclonus-dystonia maps to chromosome 7q in eight families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DOMINANT INHERITANCE AB Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported in another. We performed genetic studies, using eight additional families with M-D, to assess these two loci. No evidence for linkage was found for 11q markers. However, all eight of these families showed linkage to chromosome 7 markers, with a combined multipoint LOD score of 11.71. Recombination events in the families define the disease gene within a 14-cM interval flanked by D7S2212 and D7S821. These data provide evidence for a major locus for M-D on chromosome 7q21. C1 Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Dept Human Genet, D-23538 Lubeck, Germany. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Mt Sinai Sch Med, Dept Neurol, New York, NY 10003 USA. Columbia Univ, Dept Neurol, New York, NY 10027 USA. Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Umea Univ, Dept Neurol, S-90187 Umea, Sweden. Umea Univ, Dept Clin Genet, S-90187 Umea, Sweden. Univ Rochester, Sch Med, Dept Neurol, Rochester, NY 14627 USA. Univ Gothenburg, Dept Pediat, Gothenburg, Sweden. Univ Gothenburg, Dept Clin Genet, Gothenburg, Sweden. Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Penn State Coll Med, Henry Hood Res Program, Danville, PA USA. Cent Hosp Karlstad, Child Habilitat Ctr, Karlstad, Sweden. RP Ozelius, LJ (reprint author), Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Kis, Bernhard/A-8731-2008; OI Kis, Bernhard/0000-0003-3244-9737; Tagliati, Michele/0000-0002-6722-8208 FU NINDS NIH HHS [NS26656, NS28384, R01 NS026656, R01 NS028384] NR 14 TC 43 Z9 45 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2000 VL 67 IS 5 BP 1314 EP 1319 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 369WW UT WOS:000165091600028 PM 11022010 ER PT J AU Thurston, SW Ryan, L Christiani, DC Snow, R Carlson, J You, LY Cui, SC Ma, GH Wang, LH Huang, YM AF Thurston, SW Ryan, L Christiani, DC Snow, R Carlson, J You, LY Cui, SC Ma, GH Wang, LH Huang, YM TI Petrochemical exposure and menstrual disturbances SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE benzene; ergonomic; occupational; menstrual disorders ID PRIMATE OVARIAN CYCLE; ESTROGEN METABOLISM; ORGANIC-SOLVENTS; CHINESE-WOMEN; BREAST-CANCER; RISK; WORKERS; ASSOCIATION; AGE; FOLLICULOGENESIS AB Background Art exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. Methods The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 clays or less than 21 days, is the major outcome of interest. Results After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also all important predictor Conclusions This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Heidelberg, Sch Med, Dept Trop Hyg & Publ Hlth, Heidelberg, Germany. Yanshan Antiepidem Stn, Beijing, Peoples R China. Beijing Med Univ, Ctr Ecogenet & Reprod Hlth, Beijing 100083, Peoples R China. Beijing Med Univ, Sch Publ Hlth, Dept Environm Hlth, Beijing 100083, Peoples R China. RP Thurston, SW (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM sthursto@hsph.harvard.edu RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [HD32505]; NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [OH03027] NR 44 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2000 VL 38 IS 5 BP 555 EP 564 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 361CD UT WOS:000089703400008 PM 11025497 ER PT J AU Manson, JE Ajani, UA Liu, SM Nathan, DM Hennekens, CH AF Manson, JE Ajani, UA Liu, SM Nathan, DM Hennekens, CH TI A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; MIDDLE-AGED MEN; GLUCOSE-TOLERANCE; BODY-FAT; INSULIN; NICOTINE; WOMEN AB PURPOSE: To determine the association between cigarette smoking and the incidence of type 2 diabetes mellitus. SUBJECTS AND METHODS: We studied 21,068 US male physicians aged 40 to 84 years in the Physicians' Health Study who were initially free of diagnosed diabetes mellitus, cardiovascular disease, and cancer. Information about cigarette smoking and other risk indicators was obtained at baseline. The primary outcome was reported diagnosis of type 2 diabetes mellitus. RESULTS: During 255,830 person-years of follow-up, 770 new cases of type 2 diabetes mellitus were identified. Smokers had a dose-dependent increased risk of developing type 2 diabetes mellitus: compared with never smokers, the age-adjusted relative risk was 2.1 (95% confidence interval [CI]: 1.7 to 2.6) for current smokers of greater than or equal to 20 cigarettes per day, 1.4 (95% CT: 1.0 to 2.0) for current smokers of <20 cigarettes per day, and 1.2 (95% CI: 1.0 to 1.4) for past smokers. After multivariate adjustment for body mass index, physical activity, and other risk factors, the relative risks were 1.7 (95% CI: 1.3 to 2.3) for current smokers of 20 cigarettes per day, 1.5 (95% CI: 1.0 to 2.2) for current smokers of <20 cigarettes per day, and 1.1 (95% CI: 1.0 to 1.4) for past smokers. Total pack-years of cigarette smoking was also associated with the risk of type 2 diabetes mellitus (P for trend <0.001). CONCLUSIONS: These prospective data support the hypothesis that cigarette smoking is an independent and modifiable determinant of type 2 diabetes mellitus. Am J Med. 2000;109: 538-542. (C) 2000 by Excerpta Medica, Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Diabet, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Univ Miami, Sch Med, Dept Epidemiol, Miami, FL USA. Univ Miami, Sch Med, Dept Publ Hlth, Miami, FL USA. RP Manson, JE (reprint author), 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA40360]; NIDDK NIH HHS [DK36798] NR 27 TC 118 Z9 125 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2000 VL 109 IS 7 BP 538 EP 542 DI 10.1016/S0002-9343(00)00568-4 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 370HP UT WOS:000165117700003 PM 11063954 ER PT J AU Mylonakis, E Paliou, M Lally, M Flanigan, TP Rich, JD AF Mylonakis, E Paliou, M Lally, M Flanigan, TP Rich, JD TI Laboratory testing for infection with the human immunodeficiency virus: Established and novel approaches SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID POLYMERASE CHAIN-REACTION; GROUP-O INFECTIONS; HIV-INFECTION; BLOOD-DONORS; WESTERN-BLOT; SEROLOGIC TESTS; POOLED SERA; PERFORMANCE-CHARACTERISTICS; SCREENING ASSAYS; FIELD-EVALUATION AB The enzyme-linked immunosorbent assay (ELISA) and the Western blot are the primary tests for the diagnosis and confirmation of human immunodeficiency virus (HIV) infection. The ELISA, an inexpensive screening test for antibodies to HIV-1, is both sensitive and specific. The HIV-1 Western blot is a reliable confirmatory test following a repeatedly reactive ELISA. False-positive HIV-1 results with this sequence of tests are extremely rare but can occur, and test results that are inconsistent with clinical or other laboratory information should be questioned, repeated, or supplemented. The US Food and Drug Administration has also approved rapid and more accessible testing methods. Oral mucosal transudate and urine testing are noninvasive testing methods; rapid and home sample collection kits offer easier access to testing. Am J Med. 2000;109: 568-576. (C) 2000 by Excerpta Medica, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Brown Univ, Sch Med, Miriam Hosp, Dept Med,Div Infect Dis, Providence, RI 02912 USA. RP Mylonakis, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. RI Lally, Michelle/I-4865-2016 OI Lally, Michelle/0000-0003-0716-4668 FU NIAID NIH HHS [AI-42853]; NIDA NIH HHS [DA00268] NR 80 TC 63 Z9 73 U1 3 U2 12 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 NOV PY 2000 VL 109 IS 7 BP 568 EP 576 DI 10.1016/S0002-9343(00)00583-0 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 370HP UT WOS:000165117700008 PM 11063959 ER PT J AU Zelop, CM Shipp, TD Repke, JT Cohen, A Lieberman, E AF Zelop, CM Shipp, TD Repke, JT Cohen, A Lieberman, E TI Effect of previous vaginal delivery on the risk of uterine rupture during a subsequent trial of labor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 31-FEB 05, 2000 CL MIAMI BEACH, FLORIDA SP Soc Maternal Fetal Med DE trial of label; uterine rupture; previous vaginal delivery ID WOMEN AB OBJECTIVE: We examined the effect of prior vaginal delivery on the risk of uterine rupture in pregnant women undergoing a trial of labor after prior cesarean delivery. STUDY DESIGN: The medical records of all pregnant women with a history of cesarean delivery who attempted a trial of labor during a 12-year period at a single center were reviewed. For the current analysis, the study population was limited to term pregnancies. The effect of previous vaginal delivery on the risk of uterine rupture during a subsequent trial of labor was evaluated. Separate analyses were performed for women with a single previous cesarean delivery and for those with >1 prior cesarean delivery. For each of these subgroups, the rate of uterine rupture among women who had >1 prior vaginal delivery was compared with the rate among women with no prior vaginal delivery. Logistic regression analysis was used to examine the associations with control for confounding factors. RESULTS: Of 3783 women with 1 prior scar, 1021 (27.0%) also had >1 prior vaginal delivery. During a subsequent trial of labor, the rate of uterine rupture was 1.1% among pregnant women without prior vaginal delivery and 0.2% among pregnant women with prior vaginal delivery (P = .01). Logistic regression analysis controlling for duration of labor, induction, birth weight, maternal age, year of birth, epidural analgesia, and oxytocin augmentation indicated that, among women with a single scar, those with a prior vaginal delivery had a risk of uterine rupture that was one fifth that of women without a previous vaginal delivery (odds ratio, 0.2; 95% confidence interval, 0.04-0.8). In the group of 143 pregnant women with >1 previous cesarean delivery, women with a prior vaginal delivery had a somewhat lower risk of uterine rupture (3.9% vs 2.5%; adjusted odds ratio, 0.6; 95% confidence interval, 0.01-6.7). This difference was not statistically significant. CONCLUSION.. Among women with 1 prior cesarean delivery undergoing a subsequent trial of labor, those with a prior vaginal delivery were at substantially lower risk of uterine rupture than women without a previous vaginal delivery. C1 Lenox Hill Hosp, Dept Obstet & Gynecol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Univ Nebraska, Med Ctr, Dept Obstet & Gynecol, Omaha, NE USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Zelop, CM (reprint author), Lenox Hill Hosp, Dept Obstet & Gynecol, 100 E 77th St, New York, NY 10021 USA. NR 5 TC 52 Z9 53 U1 0 U2 1 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 NOV PY 2000 VL 183 IS 5 BP 1184 EP 1186 DI 10.1067/mob.2000.109048 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 377KD UT WOS:000165512000025 PM 11084564 ER PT J AU Dryja, TP AF Dryja, TP TI Molecular genetics of Oguchi disease, fundus albipunctatus, and other forms of stationary night blindness: LVII Edward Jackson Memorial Lecture SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HETEROZYGOUS MISSENSE MUTATION; RHODOPSIN KINASE GENE; RETINITIS-PIGMENTOSA; ARRESTIN GENE; NOUGARET FORM; VITAMIN-A; ROD; CONE; DARK; ABETALIPOPROTEINEMIA AB PURPOSE: To compare the clinical findings of the various forms of stationary night blindness caused by mutations in identified genes encoding proteins of photoreceptors or the retinal pigment epithelium. METHODS: Review of the visual acuities, visual fields, fundi, dark-adaptation curves, and electroretinograms from patients with stationary night blindness caused by mutations in the genes RHO, GNAT1, PDE6B, RHOK, SAG, RDH5, and CACNA1F, respectively encoding rhodopsin, the alpha subunit of rod transducin, the beta subunit of rod cGMP-phosphodiesterase, rhodopsin kinase, arrestin, Il-cis retinol dehydrogenase, and a retinal L-type calcium channel. RESULTS: In the evaluated forms of stationary night blindness, the time course of dark adaptation and the characteristics of the electroretinogram indicate that rod photoreceptors are present and that they function, although abnormally, In night blindness resulting from defects in rhodopsin, the alpha subunit of rod transducin, or the beta subunit of rod cGMP phosphodiesterase, rod photoreceptors respond only to light intensities far brighter than normal, and the sensitivity of rods to light is similar to that of normal individuals who are not dark adapted. In fundus albipunctatus and in Oguchi disease, the rod photoreceptors can achieve normal sensitivity to dim light but only after 2 or more hours of dark adaptation, compared with approximately 0.5 hours for normal individuals. In each of these forms of stationary night blindness, the poor rod sensitivity and the time course of dark adaptation correlate with the known or presumed physiologic abnormalities caused by the identified gene defects. Patients with some forms of stationary night blindness, such as fundus albipunctatus and Oguchi disease, may develop degeneration of the retina leading to severe loss of vision in later life. CONCLUSIONS: The identification of the mutant genes causing forms of stationary night blindness refines the classification of these diseases and enhances our understanding of the underlying physiologic defects, Ophthalmologists must be aware that although these diseases are traditionally categorized as "stationary," some of them lead to reduced visual acuity or constricted visual fields, especially in older patients, Efforts to develop therapies for these diseases should concentrate on these more severe forms. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683] NR 74 TC 88 Z9 92 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2000 VL 130 IS 5 BP 547 EP 563 DI 10.1016/S0002-9394(00)00737-6 PG 17 WC Ophthalmology SC Ophthalmology GA 375DY UT WOS:000165385300001 PM 11078833 ER PT J AU Friedman, E AF Friedman, E TI The role of the atherosclerotic process in the pathogenesis of age-related macular degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID BRUCHS MEMBRANE; STARGARDT-DISEASE; ALPHA-TOCOPHEROL; BETA-CAROTENE; MACULOPATHY; DRUSEN; ANGIOGRAPHY; GENE; ABCR C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP Friedman, E (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 59 TC 130 Z9 139 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2000 VL 130 IS 5 BP 658 EP 663 DI 10.1016/S0002-9394(00)00643-7 PG 6 WC Ophthalmology SC Ophthalmology GA 375DY UT WOS:000165385300014 PM 11078846 ER PT J AU Salman, SD AF Salman, SD TI Acute nasopharyngitis in adults: An independent clinical entity? SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID PURULENT NASOPHARYNGITIS; BACTERIOLOGY AB Acute adult nasopharyngitis may exist as an independent clinical entity without preceding or following symptoms and signs of the usual and common upper respiratory tract infections. Three representative cases with color photographs are presented to support this conclusion. Routine endoscopic nasopharyngoscopy allows a better understanding of this uncommon nasopharyngeal and other disorders. Copyright (C) 2000 by W.B. Saunders Company. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Salman, SD (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 8 TC 1 Z9 2 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2000 VL 21 IS 6 BP 409 EP 411 DI 10.1053/ajot.2000.18880 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 383JV UT WOS:000165880100010 PM 11115528 ER PT J AU Marino, M McCluskey, RT AF Marino, M McCluskey, RT TI Role of thyroglobulin endocytic pathways in the control of thyroid hormone release SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Review DE receptor; endocytosis ID HEPARAN-SULFATE PROTEOGLYCANS; ACETYLGLUCOSAMINE-SPECIFIC RECEPTOR; LIVER ASIALOGLYCOPROTEIN RECEPTOR; SODIUM/IODIDE SYMPORTER GENE; LOW-DENSITY; ENDOPLASMIC-RETICULUM; FOLLICLE CELLS; HEYMANN NEPHRITIS; LDL RECEPTOR; LIPOPROTEIN-LIPASE AB Thyroglobulin (Tg), the thyroid hormone precursor, is synthesized by thyrocytes and secreted into the colloid. Hormone release requires uptake of Tg by thyrocytes and degradation in lysosomes. This process must be precisely regulated. Tg uptake occurs mainly by micropinocytosis, which can result from both fluid-phase pinocytosis and receptor-mediated endocytosis. Because Tg is highly concentrated in the colloid, fluid-phase pinocytosis or low-affinity receptors should provide sufficient Tg uptake for hormone release; high-affinity receptors may serve to target Tg away from lysosomes, through recycling into the colloid or by transcytosis into the bloodstream. Several apical receptors have been suggested to play roles in Tg uptake and intracellular trafficking. A thyroid asialoglycoprotein receptor may internalize and recycle immature forms of Tg back to the colloid, a function also attributed to an as yet unidentified N-acetylglucosamine receptor. Megalin mediates Tg uptake by thyrocytes, especially under intense thyroid-stimulating hormone stimulation, resulting in transcytosis of Tg from the colloid to the bloodstream, a function that prevents excessive hormone release. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA 02129 USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. FU NIDDK NIH HHS [DK46301] NR 106 TC 33 Z9 35 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2000 VL 279 IS 5 BP C1295 EP C1306 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 362QT UT WOS:000089790300001 PM 11029276 ER PT J AU Yasuhara, S Perez, ME Kanakubo, E Yasuhara, Y Shin, YS Kaneki, M Fujita, T Martyn, JAJ AF Yasuhara, S Perez, ME Kanakubo, E Yasuhara, Y Shin, YS Kaneki, M Fujita, T Martyn, JAJ TI Skeletal muscle apoptosis after burns is associated with activation of proapoptotic signals SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE muscle wasting; mitochondria; caspase; thermal injury ID UBIQUITIN-PROTEASOME PATHWAY; GROWTH-FACTOR-I; THERMAL-INJURY; CYTOCHROME-C; GUINEA-PIGS; INSULIN; MITOCHONDRIA; MECHANISMS; SEPSIS; BCL-2 AB Critical illness is associated with muscle wasting and muscle weakness. Using burn injury as a model of local and systemic inflammatory response, we tested the hypothesis that thermal injury causes apoptosis in muscle. After a 40% body surface area burn to rats, abdominal muscles beneath the burn and limb muscles distant from the burn were examined for apoptosis at varying times after burn. Ladder assay, ELISA, and histological methods showed evidence of apoptosis in the abdominal muscles within 4-12 h with peak changes occurring at 3-7 days. Maximal apoptosis was also evident at distant limb muscles at 3-7 days. Investigation of proapoptotic pathways indicated mitochondrial membrane potential to be altered by Ih after burn. Starting at 15 min after burn, cytochrome c was released from the mitochondria into the cytosol, followed by increased activity of caspase-3, starting at 6 h after burn. These studies suggest that mitochondria and caspase-mediated apoptotic pathways may be an additional mechanism of muscle weight loss in burns and may be potential therapeutic targets for prevention of muscle wasting. C1 Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Tokyo, Dept Internal Med, Tokyo 1120015, Japan. RP Martyn, JAJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM-55801-4, R01 GM-31569-17, R01 GM-61411-01] NR 51 TC 65 Z9 69 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2000 VL 279 IS 5 BP E1114 EP E1121 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 367FZ UT WOS:000090052200020 PM 11052967 ER PT J AU Garg, HG Thompson, BT Hales, CA AF Garg, HG Thompson, BT Hales, CA TI Structural determinants of antiproliferative activity of heparin on pulmonary artery smooth muscle cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA Rumanian DT Review DE heparitinase I; heparitinase II; glycosaminoglycan; heparan sulfate; core protein; Delta-disaccharide; anticoagulation activity; biosynthesis ID FIBROBLAST GROWTH-FACTOR; MYC MESSENGER-RNA; ENDOTHELIAL-CELLS; ANTICOAGULANT ACTIVITY; SULFATE PROTEOGLYCANS; BASEMENT-MEMBRANES; ANTITHROMBIN-III; IN-VITRO; C-FOS; PROLIFERATION AB In addition to its anticoagulant properties, heparin (HP), a complex polysaccharide covalently linked to a protein core, inhibits proliferation of several cell types including pulmonary artery smooth muscle cells (PASMCs). Commercial lots of HP exhibit varying degrees of antiproliferative activity on PASMCs that may due to structural differences in the lots. Fractionation of a potent antiproliferative HP preparation into high and low molecular weight components does not alter the antiproliferative effect on PASMCs, suggesting that the size of HP is not the major determinant of this biological activity. The protein core of HP obtained by cleaving the carbohydrate-protein linkage has no growth inhibition on PASMCs, demonstrating that the antiproliferative activity resides in the glycosaminoglycan component. Basic sugar residues of glucosamine can be replaced with another basic sugar, i.e., galactosamine, without affecting growth inhibition of PASMCs. N-sulfonate groups on these sugar residues of HP are not essential for growth inhibition. However, O-sulfonate groups on both sugar residues are essential for the antiproliferative activity on PASMCs. In whole HP, in contrast to an earlier finding based on a synthetic pentasaccharide of HP, 3-O-sulfonation is not critical for the antiproliferative activity against PASMCs. The amounts and distribution of sulfonate groups on both sugar residues of the glycosaminoglycan chain are the major determinant of antiproliferative activity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm Crit Care Unit, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL039150, HL-39501] NR 79 TC 25 Z9 25 U1 1 U2 3 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 NOV PY 2000 VL 279 IS 5 BP L779 EP L789 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 367HT UT WOS:000090056200001 PM 11053011 ER PT J AU Hirschfeld, RMA Williams, JBW Spitzer, RL Calabrese, JR Flynn, L Keck, PE Lewis, L McElroy, SL Post, RM Rapport, DJ Russell, JM Sachs, GS Zajecka, J AF Hirschfeld, RMA Williams, JBW Spitzer, RL Calabrese, JR Flynn, L Keck, PE Lewis, L McElroy, SL Post, RM Rapport, DJ Russell, JM Sachs, GS Zajecka, J TI Development and validation of a screening instrument for bipolar spectrum disorder: The mood disorder questionnaire SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Bipolar spectrum disorders, which include bipolar I, bipolar II, and bipolar disorder not otherwise specified, frequently go unrecognized, undiagnosed, and untreated. This report describes the validation of a new brief self-report screening instrument for bipolar spectrum disorders called the Mood Disorder Questionnaire. Method: A total of 198 patients attending five outpatient clinics that primarily treat patients with mood disorders completed the Mood Disorder Questionnaire. A research professional, blind to the Mood Disorder Questionnaire results, conducted a telephone research diagnostic interview by means of the bipolar module of the Structured Clinical Interview for DSM-IV. Results: A Mood Disorder Questionnaire screening score of 7 or more items yielded good sensitivity (0.73) and very good specificity (0.90). Conclusions: The Mood Disorder Questionnaire is a useful screening instrument for bipolar spectrum disorder in a psychiatric outpatient population. C1 Univ Texas, Dept Psychiat & Behav Sci, Med Branch, Galveston, TX 77555 USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst, New York, NY 10032 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Natl Assoc Mentally Ill, Washington, DC USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH USA. Natl Depress & Man Depress Assoc, Chicago, IL USA. NIMH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Hirschfeld, RMA (reprint author), Univ Texas, Dept Psychiat & Behav Sci, Med Branch, 1-302 Rebecca Sealy,301 Univ Blvd, Galveston, TX 77555 USA. NR 8 TC 664 Z9 679 U1 2 U2 36 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 NOV PY 2000 VL 157 IS 11 BP 1873 EP 1875 DI 10.1176/appi.ajp.157.11.1873 PG 3 WC Psychiatry SC Psychiatry GA 369YJ UT WOS:000165095100028 PM 11058490 ER PT J AU Pillar, F Malhotra, A Fogel, R Beauregard, J Schnall, R White, DP AF Pillar, F Malhotra, A Fogel, R Beauregard, J Schnall, R White, DP TI Airway mechanics and ventilation in response to resistive loading during sleep - Influence of gender SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID NORMAL MEN; MUSCLE-ACTIVITY; INDUCED INCREASES; FLOW LIMITATION; RESISTANCE; WOMEN; APNEA; PRESSURE; OBESITY; SIZE AB The male predominance in obstructive sleep apnea (OSA) is currently poorly understood although differences in pharyngeal airway anatomy and physiology have been proposed. As the response to inspiratory resistive loading (IRL) provides important information on both airway collapsibility (mechanics) and ventilatory control, we compared this respiratory response in eight normal women and eight age and body mass index (BMI)-matched men, during stable nonrapid eye movement (NREM) sleep. Upper airway mechanics, ventilation, plus activation of two dilator muscles (genioglossus [GG] and tensor palatini [TP]) were monitored during basal breathing (BL), followed by four sequentially applied loads (5, 10, 15, 25 cm H2O/L/s) for three breaths each. Men developed more severe hypopnea in response to identical applied external loads than did women. At a resistance of 25 cm H2O/L/s, VT decreased by 26 +/- 1% in women compared with 44 +/- 1% in men (differences between sexes p < 0.05). Pharyngeal resistance (Rpha) in response to IRL increased significantly more in men than women (37.3 +/- 11.2 cm H2O/L/s in men at maximal load, compared with an increase of 6.6 +/- 3.9 cm H2O/L/s in women, p < 0.05). Men and women had near identical minute ventilation responses to total load (applied extrinsic plus measured intrinsic), implying no differences in central drive or load response. There were no significant increases in CC or TP activation in response to IRL in either sex. We conclude that normal men are more vulnerable to load-induced hypoventilation than women, due to increased upper airway collapse, which could not be explained by differences in dilator muscle activation. This implies a fundamental difference in the upper airway anatomy and/or tissue characteristics between the two sexes. C1 Brigham & Womens Hosp, Dept Med, Div Endocrinol, Sleep Disorders Sect, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Sleep Disorders Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP White, DP (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrinol, Sleep Disorders Sect, RF 485,221 Longwood Ave, Boston, MA 02115 USA. NR 28 TC 37 Z9 37 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV PY 2000 VL 162 IS 5 BP 1627 EP 1632 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 371WU UT WOS:000165202900007 ER PT J AU Mandel, J Mark, EJ Hales, CA AF Mandel, J Mark, EJ Hales, CA TI Pulmonary veno-occlusive disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; VENOOCCLUSIVE DISEASE; CT FINDINGS; LUNG TRANSPLANTATION; VASODILATOR AGENTS; HEMOLYTIC-ANEMIA; HYPERTENSION; PROSTACYCLIN; CHEMOTHERAPY; SURVIVAL C1 Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mandel, J (reprint author), Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, 330 Brookline Ave, Boston, MA 02215 USA. NR 94 TC 138 Z9 142 U1 0 U2 4 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 NOV PY 2000 VL 162 IS 5 BP 1964 EP 1973 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 371WU UT WOS:000165202900061 PM 11069841 ER PT J AU Alberico, RA Loud, P Pollina, J Greco, W Patel, M Klufas, R AF Alberico, RA Loud, P Pollina, J Greco, W Patel, M Klufas, R TI Thick-section reformatting of thinly collimated helical CT for reduction of skull base-related artifacts SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY, 1997 CL BOSTON, MASSACHUSETTS SP Amer Roentgen Ray Soc ID COMPUTED-TOMOGRAPHY; GANTRY ANGULATION; POSTERIOR-FOSSA AB OBJECTIVE. Our purpose was to evaluate thick-section reformatted helical CT of the brain base as a technique for reducing skull base-related artifacts and to compare it with conventional CT. MATERIALS AND METHODS. Twenty-three patients with suspected intracranial abnormalities related to the brain base, as determined either by clinical examination or at the time of imaging, were evaluated with contrast-enhanced conventional CT of the brain (5-mm collimation, 140 kVp, 170 mA, 2-sec rotation time) and reformatted helical CT (l-mm collimation, 1.5 pitch, 120 kVp, 220 mA). Helical sections were reformatted to a thickness of 5 mm by a volume-averaging algorithm using a computer workstation. Three observers retrospectively and blindly reviewed the images and qualitatively scored artifacts at the foramen magnum, middle cranial fossa, anterior cranial fossa, interpetrous region, and internal occipital protuberance. Image graininess and observer confidence were also scored. Paired statistical analyses using score differences in each patient were possible. RESULTS. Reformatted helical CT reduced skull base-related artifacts across all five anatomic regions (p < 0.05). The foramen magnum showed the greatest reduction in artifacts and the anterior cranial fossa the least. Image graininess was increased on reformatted CT compared with conventional CT (p < 0.05), but observer confidence remained higher for reformatted CT (p < 0.05). Total additional scan time was 3.15 +/- 0.38 min with 5.3 +/- 1.2 min required for reformatting. CONCLUSION. Reformatted CT significantly decreases skull base-related artifacts in the brain, improving observer confidence in evaluation of the brain base and adding an average of only 8.45 +/- 1.6 min of scanning and processing time to each examination. C1 Roswell Pk Canc Inst, Dept Radiol Neuroradiol Head & Neck Imaging, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Ultrasound, Buffalo, NY 14263 USA. SUNY Buffalo, Millard Fillmore Hosp, Dept Neurosurg, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. Boston Deaconess Beth Israel Med Ctr, Dept Diagnost Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Diagnost Radiol, Boston, MA 02115 USA. RP Alberico, RA (reprint author), Roswell Pk Canc Inst, Dept Radiol Neuroradiol Head & Neck Imaging, Elm St,Carlton St, Buffalo, NY 14263 USA. NR 10 TC 18 Z9 19 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2000 VL 175 IS 5 BP 1361 EP 1366 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366MZ UT WOS:000090010300033 PM 11044042 ER PT J AU Gervais, DA Hahn, PF O'Neill, MJ Mueller, PR AF Gervais, DA Hahn, PF O'Neill, MJ Mueller, PR TI Original report - CT-guided transgluteal drainage of deep pelvic abscesses in children: Selective use as an alternative to transrectal drainage SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GREATER SCIATIC FORAMEN; GUIDANCE AB OBJECTIVE. The transgluteal approach to abscess drainage through the greater sciatic foramen has been described in adults, but this route has not been as extensively studied in children. We performed CT-guided transgluteal percutaneous abscess drainage in seven children and assessed the results of drainage and catheter tolerance. CONCLUSION. Transgluteal catheters are well tolerated by children, and the transgluteal route is an effective approach to selected pelvic abscesses in children. C1 Massachusetts Gen Hosp, Dept Radiol, Abdominal Radiol Div, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Abdominal Radiol Div, 32 Fruit St,White 270, Boston, MA 02114 USA. NR 8 TC 21 Z9 23 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2000 VL 175 IS 5 BP 1393 EP 1396 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366MZ UT WOS:000090010300039 PM 11044050 ER PT J AU Boland, GWL Murphy, B Arellano, R Niklason, L Mueller, PR AF Boland, GWL Murphy, B Arellano, R Niklason, L Mueller, PR TI Dose reduction in gastrointestinal and genitourinary fluoroscopy: Use of grid-controlled pulsed fluoroscopy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PERSONNEL AB OBJECTIVE, We evaluated the diagnostic accuracy of a grid-controlled fluoroscopy unit compared with a conventional continuous fluoroscopy unit for a variety of abdominal and pelvic fluoroscopic examinations. SUBJECTS AND METHODS. Seventy patients (29 men and 41 women; age range, 24-78 years) were enrolled in one of seven abdominal and pelvic fluoroscopic examinations, including upper gastrointestinal series (n = 20), barium enema (n = 10), voiding cystourethrogram (n = 10), percutaneous abdominal catheter tube injection (n = 10), hysterosalpingogram (n = 10), and percutaneous needle insertion and catheter placement (nephrostomy, percutaneous biliary drainage) (n = 10). Each patient underwent at least 10 sec of continuous fluoroscopy that was randomly and blindly compared with 10-sec periods of pulsed fluoroscopy at 15, 7.5, and 3.75 frames per second. A radiologist outside the examination room, unaware of the frame rate per second, evaluated the procedure in real time on a television monitor. The radiologist assessed image quality and diagnostic acceptability using a scoring system. Statistical analysis was performed using the paired Student's t test. RESULTS. For all procedures at all frame rates, we found no statistically significant superiority of one frame rate over another. For most procedures, the slower frame rates were considered equivalent to continuous fluoroscopy when the images were assessed for image quality and diagnostic confidence. CONCLUSION. Our findings suggest that most abdominal and pelvic fluoroscopic procedures can be performed at substantially lower frame rates than those used for continuous fluoroscopy; adopting this procedure may lead to substantial dose savings for the patient and the fluoroscopy operator. C1 Massachusetts Gen Hosp, Div Adbominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Div Adbominal Imaging & Intervent Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 25 Z9 26 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2000 VL 175 IS 5 BP 1453 EP 1457 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 366MZ UT WOS:000090010300051 PM 11044062 ER PT J AU Lee, KR Scully, RE AF Lee, KR Scully, RE TI Mucinous tumors of the ovary - A clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with 'pseudomyxoma peritonei' SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; carcinoma; mucinous tumors; borderline tumors; epithelial tumors; microinvasion; pseudomyxoma peritonei; pseudomyxoma ovarii; prognosis; tumor stage; appendix ID MALIGNANT POTENTIAL TUMORS; K-RAS PROTOONCOGENE; TERM FOLLOW-UP; EPITHELIAL TUMORS; PROGNOSTIC FACTORS; CLINICAL BEHAVIOR; APPENDIX; ORIGIN; MICROINVASION; EMPHASIS AB Mucinous ovarian neoplasms other than cystadenomas and adenofibromas have been classified as either borderline tumors or carcinomas for many years. Borderline tumors have been subdivided more recently into endocervical-like (mullerian) and intestinal forms. Such a distinction is rarely made in the mucinous carcinoma category. We did not encounter a pure endocervical-like carcinoma in the present series. Criteria for distinguishing an intestinal-type mucinous borderline tumor from a mucinous carcinoma have been controversial. In this study of 164 mucinous borderline tumors of intestinal type and 32 mucinous carcinomas, the former were further subdivided into 74 cases with epithelial atypia only and 90 with focal intraepithelial carcinoma. Of the 67 stage I tumors in the borderline (with atypia) category, all 49 with follow-up data were clinically benign; in the seven cases that had been designated stage III, the intraoperative appearance was that of "pseudomyxoma peritonei," which was fatal in four cases. Most of these tumors, however, were probably metastatic to the ovary rather than truly primary borderline tumors, although failure to examine the appendix in six cases compromised their interpretation. All 90 mucinous borderline tumors that had foci of intraepithelial carcinoma were recorded as stage I, but two of the 69 patients with follow-up data (3%) had fatal recurrences. Both of these tumors were incompletely staged, however, and one had ruptured intraoperatively. Thirty-two invasive carcinomas were subdivided into 12 expansile and 20 infiltrative subtypes; within the latter category seven tumors were only microinvasive. All 12 carcinomas with only expansile invasion were stage I; none of the 10 with follow-up data recurred. All seven microinvasive infiltrative carcinomas were stage I; none of the five with follow-up data recurred. One of five patients with stage I infiltrative carcinomas that were more than microinvasive and were adequately followed had a fatal recurrence, but staging had been incomplete in that case. Seven of the remaining eight infiltrative carcinomas were higher than stage I; five of the six (83%) with follow-up data persisted or recurred and were fatal. Considering all stages, increasing tumor grade in the carcinoma category correlated with an unfavorable outcome. However, grade did not influence prognosis in stage I carcinomas. Among 13 stage I cases in all categories with either preoperative or intraoperative tumor rupture and followup data, one recurred, a tumor in the borderline with intraepithelial carcinoma category. "Pseudomyxoma peritonei" is an ill-defined term and should not be used as a pathologic diagnosis. The presence of mucin in the abdominal cavity requires careful histologic evaluation to characterize it for prognostic purposes. Adequate and sometimes extensive sampling of mucinous ovarian tumors, the appendix and the peritoneum in cases of "pseudomyxoma peritonei" is necessary to achieve an accurate diagnosis and prognosis. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Lee, KR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 65 TC 135 Z9 153 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2000 VL 24 IS 11 BP 1447 EP 1464 DI 10.1097/00000478-200011000-00001 PG 18 WC Pathology; Surgery SC Pathology; Surgery GA 370RR UT WOS:000165136500001 PM 11075847 ER PT J AU Ibebunjo, C Martyn, JAJ AF Ibebunjo, C Martyn, JAJ TI Thermal injury induces greater resistance to d-tubocurarine in local rather than in distant muscles in the rat SO ANESTHESIA AND ANALGESIA LA English DT Article ID ACETYLCHOLINE-RECEPTORS; BURN INJURY; GASTROCNEMIUS-MUSCLE; PEDIATRIC-PATIENTS; SKELETAL-MUSCLE; ATRACURIUM; PHARMACODYNAMICS; METOCURINE; PARALYSIS AB We tested the hypothesis that resistance to d-tubocurarine (dTC) is more intense in muscles closer to, than distant from, burn, and is related to the expression of immature and total acetylcholine receptors (AChRs). Anesthetized rats received approximately 4% surface area burn over the tibialis muscle of one leg with the contralateral leg serving as control, or approximately 45% of the flank burn, with sham-burned pair fed controls. At 1, 4, 7, or 14 days later, the 50% effective dose of dTC, membrane AChRs, and messenger ribonucleic acid (mRNA) that encode the AChR gamma -subunit (AChR gamma -mRNA) were quantified in the tibialis. After the local leg burn, AChRs increased at Days 4, 7, and 14, and AChR gamma -mRNA at Days 4 and 7 after burn. The increased AChR gamma -mRNA correlated with total AChRs (r = 0.82), suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of dTC after the local leg burn increased 1.2- to 1.5-fold at all periods and correlated significantly with AChRs (r = 0.54) and AChR gamma -mRNA (r = 0.57). After the flank burn, resistance was seen at Day 14 in association with muscle atrophy; AChRs and AChR gamma -mRNA were unaltered. The resistance to dTC after a local burn occurs sooner, is more marked, and is probably related to both increases and isoform changes in AChRs. The resistance at distant muscles appears unrelated to AChR changes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. RP Martyn, JAJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM 31569-18, R01 GM 61411-01, R01 GM 55082-04] NR 27 TC 16 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2000 VL 91 IS 5 BP 1243 EP 1249 DI 10.1097/00000539-200011000-00036 PG 7 WC Anesthesiology SC Anesthesiology GA 369ET UT WOS:000165053600036 PM 11049916 ER PT J AU Brenner, BE Chavda, KK Camargo, CA AF Brenner, BE Chavda, KK Camargo, CA TI Randomized trial of inhaled flunisolide versus placebo among asthmatic patients discharged from the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID STEROIDS BECLOMETHASONE DIPROPIONATE; ORAL PREDNISOLONE; DOSING FREQUENCY; CLINICAL-TRIAL; BUDESONIDE; CORTICOSTEROIDS; AEROSOL; RELAPSE; GLUCOCORTICOIDS; MULTICENTER AB Study objective: Inhaled corticosteroids (ICs) improve airflow and decrease symptoms in patients with chronic asthma. We examined whether high-dose inhaled flunisolide would have similar benefits after an emergency department visit for acute asthma. Methods: Over a 16-month period at one inner-city ED, we documented 551 eligible patients (acute asthma; age 18 to 50 years; no ICs in past week; no oral corticosteroids in past month; and peak expiratory flow rate [PEFR] <70% of predicted value after first -agonist treatment); 104 patients agreed to participate. At ED discharge, all patients were given prednisone 40 mg/d for 5 days and inhaled beta -agonists as needed and were randomly assigned to receive high-dose inhaled flunisolide 2 mg/d (n=51) or placebo (n=53). Patients were telephoned daily and asked to return for PEER measurement at 3, 7, 12, 21, and 24 days. Results: Despite precautions, 28% (16 receiving flunisolide and 13 receiving placebo) of patients were completely lost to follow-up, 2 patients had only one follow-up (day 3), 2 patients receiving flunisolide withdrew because of medication-related bronchospasm, and 4 patients in each group experienced relapse. Among the 63 remaining patients, we found no difference between flunisolide and placebo at day 24 follow-up in percent predicted PEFR (87% versus 83% on day 24, P=.36; difference 4%, 95% confidence interval [CI] -5% to 13%). Nocturnal wheezing and nocturnal albuterol inhaler use was higher among patients receiving flunisolide than those receiving placebo on day 24 (48% versus 18% for nocturnal wheezing, P=.01; mean difference 30%, 95% CI 11% to 49%; 3.8 versus 1.4 nocturnal albuterol puffs, P=.03; mean difference 2.4 puffs, (95% CI 0.2 to 4). levels of dyspnea, cough, and overall wellbeing were similar between the flunisolide and placebo groups. Conclusion: Addition of high-dose inhaled flunisolide to standard therapy does not benefit inner-city patients with acute asthma in the first 24 days alter ED discharge. Airway inflammation during acute asthma may require higher doses or more potent anti-inflammatory agents. C1 Cornell Univ, Weill Col Med, Brooklyn Hosp Ctr, Dept Emergency Med,Div Res, Brooklyn, NY 11201 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 Brenner, BE (reprint author), Cornell Univ, Weill Col Med, Brooklyn Hosp Ctr, Dept Emergency Med,Div Res, 121 DeKalb Ave, Brooklyn, NY 11201 USA. FU NHLBI NIH HHS [HL-03533] NR 48 TC 15 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2000 VL 36 IS 5 BP 417 EP 426 DI 10.1067/mem.2000.110842 PG 10 WC Emergency Medicine SC Emergency Medicine GA 379AU UT WOS:000165619400001 PM 11054193 ER PT J AU Brendel, DH Bodkin, JA Yang, JM AF Brendel, DH Bodkin, JA Yang, JM TI Massive sertraline overdose SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID SEROTONIN SYNDROME C1 Massachusetts Gen Hosp, Dept Lab Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. RP Yang, JM (reprint author), Massachusetts Gen Hosp, Dept Lab Med, Gray Bldg,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 13 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2000 VL 36 IS 5 BP 524 EP 526 DI 10.1016/S0196-0644(00)66384-9 PG 3 WC Emergency Medicine SC Emergency Medicine GA 379AU UT WOS:000165619400016 PM 11054208 ER PT J AU Warshaw, AL AF Warshaw, AL TI Pancreatic necrosis - To debride or not to debride - That is the question SO ANNALS OF SURGERY LA English DT Editorial Material ID ACUTE NECROTIZING PANCREATITIS; INFECTION C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 25 Z9 31 U1 0 U2 0 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 NOV PY 2000 VL 232 IS 5 BP 627 EP 629 DI 10.1097/00000658-200011000-00002 PG 3 WC Surgery SC Surgery GA 367QZ UT WOS:000090074100002 PM 11066132 ER PT J AU Feller, AJ Duan, ZF Penson, R Toh, HC Seiden, MV AF Feller, AJ Duan, ZF Penson, R Toh, HC Seiden, MV TI TRAG-3, a novel cancer/testis antigen, is overexpressed in the majority of melanoma cell lines and malignant melanoma SO ANTICANCER RESEARCH LA English DT Article DE melanoma; TRAG-3; cancer testis antigen ID CYTOLYTIC T-LYMPHOCYTES; GENE; PROSTATE; PAGE-1 AB Background: We have identified a novel cancer/testis antigen, TRAG-3 (Taxol Resistance Associated Gene-3) that was initially discovered in search for new genes involved in drug resistance by differential display. Early study of TRAG-3 revealed minimal to absent expression in various normal tissues and over-expression in many carcinoma cell lines including several melanoma lines. Materials and Methods: Northern and RT-PCR technologies were used to evaluate TRAG-3 expression in numerous cell lines and tumor tissue. Results: Analysis of a wider panel of normal tissues, 32 melanoma cell fines and 4 malignant melanomas demonstrates TRAG-3 expression in 25 of the 32 melanoma cell lines (78%) and four of four of the malignant melanoma armors (100%). Of the additional eight normal tissues screened, expression was present in normal testis but absent in all other tissues. RT-PCR evaluation of TRAG-3 reveals two transcripts in many carcinoma cell lines with sequencing of these products demonstrating the 799 bp TRAG-3 transcript and a second alternatively spliced transcript, TRAG-3(long). TRAG-3 maps to band Xq28 within a IMAGE gene complex, however sequence analysis demonstrates that TRAG-3 is not homologous to other known cancer/testis antigens. Conclusion. TRAG-3 appears to be a novel cancer/testis antigen. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 16 TC 27 Z9 31 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2000 VL 20 IS 6B BP 4147 EP 4151 PG 5 WC Oncology SC Oncology GA 396QP UT WOS:000166648300003 PM 11205240 ER PT J AU Jorgensen, JH Weigel, LM Swenson, JM Whitney, CG Ferraro, MJ Tenover, FC AF Jorgensen, JH Weigel, LM Swenson, JM Whitney, CG Ferraro, MJ Tenover, FC TI Activities of clinafloxacin, gatifloxacin, gemifloxacin, and trovafloxacin against recent clinical isolates of levofloxacin-resistant Streptococcus pneumoniae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FLUOROQUINOLONE RESISTANCE; TOPOISOMERASE-IV; UNITED-STATES; DNA GYRASE; ANTIMICROBIAL RESISTANCE; IN-VITRO; PARC; EMERGENCE; MUTATIONS; GENE AB The activities of two investigational fluoroquinolones and three fluoroquinolones that are currently marketed were determined for 182 clinical isolates of Streptococcus pneumoniae. The collection included 57 pneumococcal isolates resistant to levofloxacin (MIC greater than or equal to 8 mug/ml) recovered from patients in North America and Europe. All isolates were tested with clinafloxacin, gatifloxacin, gemifloxacin, levofloxacin, and trovafloxacin by the National Committee for Clinical Laboratory Standards broth microdilution and disk diffusion susceptibility test methods. Gemifloxacin demonstrated the greatest activity on a per gram basis, followed by clinafloxacin, trovafloxacin, gatifloxacin, and levofloxacin, Scatterplots of the MICs and disk diffusion zone sizes revealed a well-defined separation of levofloxacin-resistant and -susceptible strains when the isolates were tested against clinafloxacin and gatifloxacin, DNA sequence analyses of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE from 21 of the levofloxacin-resistant strains identified eight different patterns of amino acid changes. Mutations among the four loci had the least effect on the MICs of gemifloxacin and clinafloxacin, while the MICs of gatifloxacin and trovafloxacin increased by up to six doubling dilutions. These data indicate that the newer fluoroquinolones have greater activities than levofloxacin against pneumococci with mutations in the DNA gyrase or topoisomerase IV genes, Depending upon pharmacokinetics and safety, the greater potency of these agents could provide improved clinical efficacy against levofloxacin-resistant pneumococcal strains. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Ctr Dis Control & Prevent, Hosp Infect Program, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 29 TC 45 Z9 45 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2000 VL 44 IS 11 BP 2962 EP 2968 DI 10.1128/AAC.44.11.2962-2968.2000 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 366WL UT WOS:000090029200006 PM 11036007 ER PT J AU Harper, CMG Dangler, CA Xu, SL Feng, Y Shen, ZL Sheppard, B Stamper, A Dewhirst, FE Paster, BJ Fox, JG AF Harper, CMG Dangler, CA Xu, SL Feng, Y Shen, ZL Sheppard, B Stamper, A Dewhirst, FE Paster, BJ Fox, JG TI Isolation and characterization of a Helicobacter sp from the gastric mucosa of dolphins, Lagenorhynchus acutus and Delphinus delphis SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SP-NOV; PYLORI; FECES; TRANSMISSION; CETACEANS; PHYLOGENY; INFECTION; DISEASES; MUSTELAE; FERRETS AB Gastric ulcerations in dolphins have been reported for decades. Some of these lesions were associated with parasitic infections. However, cases of nonparasitic gastric ulcers with no clearly defined etiology also have been reported in wild and captive dolphins. Considerable speculation exists as to whether dolphins have Helicobacter-associated gastritis and peptic ulcer disease. The stomachs of seven stranded Atlantic white-sided dolphins, Lagenorhynchus acutus, and 1 common dolphin, Delphinus delphis, were assessed for the presence of Helicobacter species. Novel Helicobacter species were identified by culture in the gastric mucosa of two of the eight dolphins studied and by PCR in seven of the eight dolphins. The gram-negative organisms were urease, catalase, and oxidase positive. Spiral to fusiform bacteria were detected in gastric mucosa by Warthin Starry staining. Histopathology revealed mild to moderate diffuse lymphoplasmacytic gastritis within the superficial mucosa of the main stomach. The pyloric stomach was less inflamed, and bacteria did not extend deep into the glands. The lesions parallel those observed in Helicobacter pylori-infected humans. Bacteria from two dolphins classified by 16S rRNA analysis clustered with gastric helicobacters and represent a novel Helicobacter sp. most closely related to H. pylori. These findings suggest that a novel Helicobacter sp. may play a role in the etiopathogenesis of gastritis and gastric ulcers in dolphins. To our knowledge this represents the first isolation and characterization of a novel Helicobacter sp. from a marine mammal and emphasizes the wide host distribution and pathogenic potential of this increasingly important genus. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. New England Aquarium, Boston, MA 02110 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Rm 825C, Cambridge, MA 02139 USA. FU NCRR NIH HHS [T32RR07036, T32 RR007036]; NIAID NIH HHS [R01 AI037750, R01AI37750] NR 37 TC 29 Z9 31 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2000 VL 66 IS 11 BP 4751 EP 4757 DI 10.1128/AEM.66.11.4751-4757.2000 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 369FM UT WOS:000165055300021 PM 11055919 ER PT J AU Finckh, U von der Kammer, H Velden, J Michel, T Andresen, B Deng, A Zhang, J Muller-Thomsen, T Zuchowski, K Menzer, G Mann, U Papassotiropoulos, A Heun, R Zurdel, J Holst, F Benussi, L Stoppe, G Reiss, J Miserez, AR Staehelin, HB Rebeck, GW Hyman, BT Binetti, G Hock, C Growdon, JH Nitsch, RM AF Finckh, U von der Kammer, H Velden, J Michel, T Andresen, B Deng, A Zhang, J Muller-Thomsen, T Zuchowski, K Menzer, G Mann, U Papassotiropoulos, A Heun, R Zurdel, J Holst, F Benussi, L Stoppe, G Reiss, J Miserez, AR Staehelin, HB Rebeck, GW Hyman, BT Binetti, G Hock, C Growdon, JH Nitsch, RM TI Genetic association of a cystatin C gene polymorphism with late-onset Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E; GAMMA-TRACE; AMYLOID ANGIOPATHY; CATHEPSIN-S; RAT; EXPRESSION; BRAIN; ALPHA-2-MACROGLOBULIN; INHIBITOR; PROTEASE AB Objective: To determine whether the cystatin C gene (CST3) is genetically associated with late-onset Alzheimer disease (AD). Design: A case-control study with 2 independent study populations of patients with AD and age-matched, cognitively normal control subjects. Setting: The Alzheimer's Disease Research Unit at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, for the initial study (n=260). For the independent multicenter study (n=647), an international consortium that included the Massachusetts Alzheimer's Disease Research Center at the Massachusetts General Hospital, Boston; the Scientific Institute for Research and Patient Care, Brescia, Italy; and Alzheimer's research units at the Universities of Baseland Zurich, Switzerland, and Bonn, Goettingen, and Hamburg, Germany. Participants: Five hundred seventeen patients with AD and 390 control subjects. Measures: Molecular testing of the KspI polymorphisms in the 5' flanking region and exon 1 of CST3 and the apolipoprotein E (APOE) genotype. Mini-Mental State Examination scores for both patients with AD and control subjects. Results: Homozygosity for haplotype B of CST3 was significantly associated with late-onset AD in both study populations, with an odds ratio of 3.8 (95% confidence interval, 1.56-9.25) in the combined data set; heterozygosity was not associated with an increased risk. The odds ratios for CST3 B/B increased from 2.6 in those younger than 75 years to 8.8 for those aged 75 years and older. The association of CST3 B/B with AD was independent of APOE epsilon4; both genotypes independently reduced disease-free survival. Conclusions: CST3 is a susceptibility gene for late-onset AD, especially in patients aged 75 years and older. To our knowledge, CST3 B is the first autosomal recessive risk allele in late-onset AD. C1 Univ Zurich, Div Psychiat Res, CH-8008 Zurich, Switzerland. Univ Hamburg, Hosp Eppendorf, Dept Human Genet, D-20246 Hamburg, Germany. Univ Hamburg, Hosp Eppendorf, Dept Psychiat, D-20246 Hamburg, Germany. Univ Hamburg, Ctr Mol Neurobiol, D-2000 Hamburg, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Univ Goettingen, Dept Psychiat, Goettingen, Germany. Univ Goettingen, Dept Human Genet, Goettingen, Germany. Univ Basel, Basel, Switzerland. Sci Inst Res & Patient Care, Brescia, Italy. RP Nitsch, RM (reprint author), Univ Zurich, Div Psychiat Res, August Forel Str 1, CH-8008 Zurich, Switzerland. RI BENUSSI, LUISA/K-4409-2016; Binetti, Giuliano/K-4519-2016 OI BENUSSI, LUISA/0000-0003-2836-8141; Binetti, Giuliano/0000-0003-2759-5844 FU NIA NIH HHS [P50AG05134]; Telethon [E.1084] NR 46 TC 94 Z9 94 U1 0 U2 7 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 NOV PY 2000 VL 57 IS 11 BP 1579 EP 1583 DI 10.1001/archneur.57.11.1579 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 370NM UT WOS:000165129200003 PM 11074789 ER PT J AU Cunningham, MJ Chiu, EJ Landgraf, JM Gliklich, RE AF Cunningham, MJ Chiu, EJ Landgraf, JM Gliklich, RE TI The health impact of chronic recurrent rhinosinusitis in children SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY APR 24-29, 1999 CL PALM DESERT, CALIFORNIA SP Amer Soc Pediatr Otolaryngol ID ENDOSCOPIC SINUS SURGERY; FUNCTIONAL STATUS AB Objectives: To report and quantify the health-related quality of life of children who require surgical intervention for chronic recurrent rhinosinusitis and to assess the perspective of the child vs that of the parent. Design: Prospective, observational. Patients and Intervention: Twenty-one of a consecutive sample; of 35 children undergoing endoscopic sinus surgery for infectious indications completed, along with their parents, the Child Health Questionnaire. The Child Health Questionnaire measures in parallel both child and parent perceptions of health by means of separate parent proxy report (Child Health Questionnaire-Parent Form 50) and child self-report (Child Health Questionnaire-Child Form 87) questionnaires concerning physical and psychosocial functioning. Main Outcome Measures: Tabulated scores from both the Child Health Questionnaire-Parent Form 50 and Child Health Questionnaire-Child Form 87 were compared with published data from age-matched normative populations and several pediatric chronic disease groups. Results: Significant decrements in the general health of children with chronic recurrent rhinosinusitis compared with a normative sample were observed for both child- and parent-reported data, particularly in the physical domains. Children with rhinosinusitis were perceived by their parents to have significantly more bodily pain (P<.001)and to be more limited in their physical activities (P<.05) than children with asthma, juvenile rheumatoid arthritis, and other chronic disorders. Parent-child perceptions did vary, with parents reporting more pain and general behavioral effects relative to their children's reports in these areas. Conclusion: The health impact of chronic recurrent rhinosinusitis as reported by the subjective evaluations of pediatric patients and their parents is severe. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Hlth Act, Boston, MA USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 49 Z9 50 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2000 VL 126 IS 11 BP 1363 EP 1368 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 373HQ UT WOS:000165283600009 PM 11074834 ER PT J AU Santos, F Mankarious, LA Eavey, RD AF Santos, F Mankarious, LA Eavey, RD TI Methicillin-resistant Staphylococcus aureus - Pediatric otitis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID INFECTION AB Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a potentially lethal organism in pediatric patients. MRSA is an uncommon otologic pathogen that requires special diagnostic and therapeutic intervention. Methods: Three pediatric patients with community-acquired MRSA otologic infections were identified during 1999. Setting: Tertiary care ear institution. Results: All patients required intravenous antibiotic therapy to achieve resolution of the infections. Conclusions: MRSA in children can be community acquired and can cause otitis externa, otitis media with otorrhea, or acute mastoiditis; intravenous therapy that includes vancomycin is necessary for resolution. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Eavey, RD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. OI Santos, Felipe/0000-0002-3523-665X NR 17 TC 24 Z9 25 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2000 VL 126 IS 11 BP 1383 EP 1385 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 373HQ UT WOS:000165283600013 PM 11074838 ER PT J AU Yueh, B AF Yueh, B TI Digital hearing aids SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article C1 Univ Washington, Dept Otolaryngol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Surg Serv, Seattle, WA 98195 USA. RP Yueh, B (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2000 VL 126 IS 11 BP 1394 EP 1397 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 373HQ UT WOS:000165283600017 PM 11074842 ER PT J AU Yogo, K Shimokawa, H Funakoshi, H Kandabashi, T Miyata, K Okamoto, S Egashira, K Huang, P Akaike, T Takeshita, A AF Yogo, K Shimokawa, H Funakoshi, H Kandabashi, T Miyata, K Okamoto, S Egashira, K Huang, P Akaike, T Takeshita, A TI Different vasculoprotective roles of NO synthase isoforms in vascular lesion formation in mice SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article; Proceedings Paper CT 72nd Annual Scientific Session of the American-Heart-Association CY NOV 07-10, 1999 CL ATLANTA, GEORGIA SP Amer Heart Assoc DE nitric oxide; nitric oxide synthase; arteriosclerosis; neointimal formation; vascular remodeling ID NITRIC-OXIDE SYNTHASE; DEFICIENT MICE; IN-VIVO; GENE; RATS; LACKING; INJURY AB NO is known to have several important vasculoprotective actions. Although NO is synthesized by 3 different NO synthase (NOS) isoforms, the vasculoprotective action of individual NOS isoforms remains to be clarified. Permanent ligation of the left common carotid artery was performed in control, endothelial NOS (eNOS) knockout (eNOS-KO), and inducible NOS (iNOS) knockout (iNOS-KO) mice. Four weeks after the procedure, neointimal formation and reduction of cross-sectional vascular area (constrictive remodeling) were noted in the left carotid artery. In the eNOS-KO mice, the extent of neointimal formation was significantly larger than in the control or iNOS-KO mice, whereas the extent of vascular remodeling was the highest in the iNOS-KO mice compared with other 2 strains. Antiplatelet therapy with aspirin or antihypertensive treatment with bunazosin failed to inhibit the accelerated neointimal formation in the eNOS-KO mice. These results indicate that eNOS and iNOS have different vasculoprotective actions against the vascular lesion formation caused by blood flow disruption in vivo: NO derived from eNOS inhibits neointimal formation, whereas NO derived from iNOS suppresses the development of constrictive remodeling. C1 Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, Fukuoka 8128582, Japan. Kumamoto Univ, Sch Med, Dept Microbiol, Kumamoto 860, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Cardiovasc, Boston, MA USA. RP Shimokawa, H (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. NR 13 TC 57 Z9 57 U1 0 U2 0 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 NOV PY 2000 VL 20 IS 11 BP E96 EP E100 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 373UA UT WOS:000165306600014 PM 11073861 ER PT J AU Choi, HK Slot, MC Pan, GL Weissbach, CA Niles, JL Merkel, PA AF Choi, HK Slot, MC Pan, GL Weissbach, CA Niles, JL Merkel, PA TI Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; ANTIMYELOPEROXIDASE ANTIBODIES; WEGENERS-GRANULOMATOSIS; SYSTEMIC-SCLEROSIS; CONTROLLED TRIAL; DOUBLE-BLIND; VASCULITIS; ANCA; GLOMERULONEPHRITIS; AUTOANTIBODIES AB Objective, Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis, This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. Methods, The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine, ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3), Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing, Results. No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA, There were no findings suggestive of vasculitis in any of these patients. Conclusion. From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine, However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs. C1 Boston Univ, Sch Med, Arthrit Ctr, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Groningen Hosp, Groningen, Netherlands. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Arthrit Ctr, K5,715 Albany St, Boston, MA 02118 USA. NR 23 TC 34 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2000 VL 43 IS 11 BP 2488 EP 2492 DI 10.1002/1529-0131(200011)43:11<2488::AID-ANR16>3.0.CO;2-X PG 5 WC Rheumatology SC Rheumatology GA 371WD UT WOS:000165201500016 PM 11083272 ER PT J AU Szymusiak, R Alam, N McGinty, D AF Szymusiak, R Alam, N McGinty, D TI Discharge patterns of neurons in cholinergic regions of the basal forebrain during waking and sleep SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE basal forebrain; hypothalamus sleep; arousal; acetylcholine; adenosine; GABA ID LONG-TERM ENHANCEMENT; EYE-MOVEMENT SLEEP; NUCLEUS BASALIS; DIAGONAL BAND; CORTICAL ACETYLCHOLINE; SOMATOSENSORY CORTEX; CEREBRAL-CORTEX; AUDITORY-CORTEX; SUBSTANTIA INNOMINATA; SENSORY STIMULATION AB A subset of neurons recorded in the magnocellular basal forebrain (mBF) of cats and rats exhibit elevated discharge rates during waking and REM sleep, and diminished discharge during sleep with cortical EEG synchrony (nonREM sleep). This pattern is observed in mBF neurons in cats with identified ascending projections, and in neurons located in cholinergic regions of the rat mBF. However, the cholinergic versus noncholinergic nature of recorded cells could not be determined with the extracellular recording method employed. During waking, discharge of mBF neurons is strongly movement-related. Peak discharge rates occur during a variety of head and limb movements. Discharge rates during waking immobility are reduced by >50% compared to rates during waking movement. The absence of movement accounts for more of the variance in discharge across the sleep-wake cycle than does the presence of cortical EEG synchronization. Several factors participate in the regulation of mBF neuronal activity across arousal states. Tonic inhibition mediated by adenosine appears to be present during both waking and sleep. In some mBF neurons, increased GABAergic inhibition contributes to nonREM sleep-related reductions in discharge rate. Fluctuations in mBF cell activity during waking behaviors may reflect changing excitatory input from neurons in the pontine and midbrain tegmentum. (C) 2000 Elsevier Science B.V. All rights reserved. C1 VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Szymusiak, R (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM rszym@ucal.edu NR 79 TC 65 Z9 67 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD NOV PY 2000 VL 115 IS 2 BP 171 EP 182 DI 10.1016/S0166-4328(00)00257-6 PG 12 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 357GF UT WOS:000089489600005 PM 11000419 ER PT J AU Yauch, RL Hemler, ME AF Yauch, RL Hemler, ME TI Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase SO BIOCHEMICAL JOURNAL LA English DT Article DE CD9; CD53; CD63; CD81; CD82; CD151; tetraspanins ID PHOSPHATIDYLINOSITOL 4-KINASE; CELL MOTILITY; PLASMA-MEMBRANE; INTEGRIN ALPHA-3-BETA-1; ENDOTHELIAL-CELLS; ALPHA-GRANULE; T-CELLS; CD63; CD9; ASSOCIATION AB In earlier work we established that phosphoinositide 4-kinase (PI 4-kinase) may associate with transmembrane 4 superfamily (TM4SF, tetraspanin) proteins, but critical specificity issues were not addressed. Here we demonstrate that at least five different TM4SF proteins (CD9, CD63, CD81, CD151 and A15/ TALLA1) can associate with a similar or identical 55 kDa type II PI 4-kinase. These associations were specific, since we found no evidence for other phosphoinositide kinases (e.g. phosphoinositide 3-kinase and phosphoinositide-4-phosphate 5-kinase) associating with TM4SF proteins, and many other TM4SF proteins (including CD82 and CD53) did not associate with PT 4-kinase. CD63-PI 4-kinase complexes were almost entirely intracellular, and thus are distinct from other TM4SF-PI 4-kinase complexes (e.g. involving CD9), which are largely located in the plasma membrane. These results suggest that a specific subset of TM4SF proteins may recruit PI 4-kinase to specific membrane locations, and thereby influence phosphoinositide-dependent signalling. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM38903] NR 65 TC 121 Z9 126 U1 3 U2 7 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2000 VL 351 BP 629 EP 637 DI 10.1042/0264-6021:3510629 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372GY UT WOS:000165227000011 PM 11042117 ER PT J AU Hogemann, D Josephson, L Weissleder, R Basilion, JP AF Hogemann, D Josephson, L Weissleder, R Basilion, JP TI Improvement of MRI probes to allow efficient detection of gene expression SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IN-VIVO; TRANSFERRIN; CELLS; IMMUNOTOXINS; CONJUGATE; PEPTIDE AB Recently, it has been demonstrated that magnetic resonance imaging (MRI) utilizing monocrystalline iron oxide nanoparticles (MIONs) targeted to an engineered transferrin receptor enables imaging of gene expression. However, the relatively high doses of iron oxides used indicated the need for improved MR imaging probes to monitor changes in gene expression in vivo. Using alternative conjugation chemistries to link targeting ligands and iron oxide nanoparticles, we present the development and characterization as well as improved receptor binding and MRI detection of a novel imaging probe. Iron oxide nanoparticles with a cross-linked dextran coat were conjugated to transferrin (Tf) through the linker molecule N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) to yield Tf-S-S-CLIO. The characteristics of this conjugate were evaluated in comparison to Tf-MION and Tf-CLIO generated by oxidative activation of the dextran-coat with subsequent reduction of Schiffs base. SPDP conjugation allowed approximately a 4-fold increase in the number of Tf molecules attached per iron oxide nanoparticle and resulted in a more than 10-fold improvement of binding and uptake by cells. This translated into an imaging probe that was 16 times better for imaging gene expression in a cellular MRI assay. This novel probe for MRI may substantially increase the sensitivity for the detection of endogenous or genetically induced transferrin receptor expression in small numbers of cells and may significantly reduce the imaging dose from over 100 mg/kg to doses of iron oxides that are currently used in clinical imaging. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Basilion, JP (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. FU NCI NIH HHS [R01CA85240] NR 21 TC 181 Z9 189 U1 2 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 2000 VL 11 IS 6 BP 941 EP 946 DI 10.1021/bc000079x PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 378UB UT WOS:000165601900027 PM 11087345 ER PT J AU Morrison, AR Sanford, LD Ross, RJ AF Morrison, AR Sanford, LD Ross, RJ TI The amygdala: A critical modulator of sensory influence on sleep SO BIOLOGICAL SIGNALS AND RECEPTORS LA English DT Article DE sleep; amygdala; rapid-eye-movement sleep; ponto-geniculo-occipital waves; fear conditioning; serotonin ID EYE-MOVEMENT SLEEP; FREELY BEHAVING RATS; ELICITED PGO WAVES; PARADOXICAL SLEEP; ELECTRICAL-STIMULATION; BASAL FOREBRAIN; LOCUS-COERULEUS; CENTRAL NUCLEUS; UNIT-ACTIVITY; BRAIN-STEM AB The influence of external stimuli and the memories of both unpleasant and pleasant conditions clearly can have a considerable impact on the quality of sleep. The amygdala, a structure that plays an important role in coding the emotional significance of stimuli and is heavily interconnected with brainstem nuclei known to be involved in sleep control, has received little attention from sleep researchers. We report on a series of studies, focusing on its central nucleus (Ace), Presence of serotonin (5-HT) in Ace caused a rapid change of state when injected in rapid-eye-movement sleep (REM) compared with non-REM (NREM) injections. A 5-HT antagonist released ponto-geniculo-occipital waves (PGO) into NREM. Stimuli conditioned by pairing with aversive stimuli in a fear-conditioning paradigm significantly increased sound-elicited PGO and reduced REM, Copyright (C) 2000 S. Karger AG, Basel. C1 Univ Penn, Sch Med, Dept Biol Anim, Lab Study Brain Sheep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Morrison, AR (reprint author), Univ Penn, Sch Med, Dept Biol Anim, Lab Study Brain Sheep, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH42903]; NINDS NIH HHS [NS35281] NR 55 TC 24 Z9 25 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-4933 J9 BIOL SIGNAL RECEPT JI Biol. Signal Recept. PD NOV-DEC PY 2000 VL 9 IS 6 BP 283 EP 296 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 365GQ UT WOS:000089943300002 PM 11025335 ER PT J AU Perez, GI Maravei, DV Trbovich, AM Cidlowski, JA Tilly, JL Hughes, FM AF Perez, GI Maravei, DV Trbovich, AM Cidlowski, JA Tilly, JL Hughes, FM TI Identification of potassium-dependent and -independent components of the apoptotic machinery in mouse ovarian germ cells and granulosa cells SO BIOLOGY OF REPRODUCTION LA English DT Article DE apoptosis; follicle; granulosa cells; ovum ID DIEPOXIDE-INDUCED OVOTOXICITY; BCL-2 GENE FAMILY; DNA FRAGMENTATION; ENDONUCLEASE ACTIVITY; FOLLICULAR ATRESIA; RAT GRANULOSA; INTACT-CELLS; IN-VITRO; DEATH; EXPRESSION AB Recent studies with thymocytes have suggested a critical role for intracellular potassium in the regulation of apoptosis. In this study, we examined the pathways of K+ regulation during ovarian cell death. In initial studies, fluorographic analysis demonstrated a significant loss of K+ during apoptosis stimulated by doxorubicin in oocytes and trophic hormone deprivation in granulosa cells. In oocytes, suppression of potassium efflux by potassium-enriched medium prevented condensation, budding, and fragmentation, although it did not block DNA degradation, suggesting the existence of potassium-independent nucleases in oocytes. Culture of granulosa cells in potassium-enriched medium inhibited internucleosomal DNA cleavage, although high-molecular weight DNA cleavage was apparent, suggesting that the nuclease or nucleases responsible for generating 50-kilobase (kb) fragments in these cells is potassium independent. To address this directly, isolated granulosa cell nuclei were stimulated to autodigest their DNA, and internucleosomal, but not large-fragment, cleavage was completely blocked by 150 mM potassium. We next examined whether the proapoptotic caspases are targets for potassium regulation. In cell-free assays, processing of pro-interleukin-1 beta and proteolysis of cellular actin by recombinant caspase-1 and caspase-3, respectively, were suppressed by the presence of 150 mM potassium. Other monovalent ions (NaCl, LiCl) exerted a similar effect in these cell-free assays. Thus, in oocytes and granulosa cells, potassium efflux appears to occur early in the cell death program and may regulate a number of apoptotic events including caspase activity and internucleosomal DNA cleavage. However, there also exist novel potassium-independent pathways in both ovarian germ cells and somatic cells that signal certain apoptotic events, such as large-fragment DNA cleavage. C1 Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NIEHS, Lab Integrat Biol, NIH, Res Triangle Pk, NC 27709 USA. RP Hughes, FM (reprint author), Univ N Carolina, Dept Biol, 9201 Univ City Blvd, Charlotte, NC 28223 USA. FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226]; NIEHS NIH HHS [R01-ES08430] NR 50 TC 43 Z9 48 U1 0 U2 1 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 NOV PY 2000 VL 63 IS 5 BP 1358 EP 1369 DI 10.1095/biolreprod63.5.1358 PG 12 WC Reproductive Biology SC Reproductive Biology GA 369VT UT WOS:000165089000017 PM 11058539 ER PT J AU Biswas, DK Cruz, AP Pardee, AB AF Biswas, DK Cruz, AP Pardee, AB TI Detection of the level of estrogen receptor and functional variants in human breast cancers by novel assays SO BIOTECHNIQUES LA English DT Article ID HORMONE; ACTIVATION; BINDING; TARGET; CELLS AB The level of estrogen receptor (ER) is a key determinant for the management of ER-positive [ER(+)] breast cancer patients. Growth of many human breast cancers is regulated by estrogen (E2) and progesterone (Pr). Generally; the ER in ER(+) breast cancer is targeted for therapy with antihormones. However 40% of ER(+) patients do not respond to antihormone therapy. Thus, the identification of antihormone resistant ER(+) breast cancers is essential therapeutic predictions. Although H-3-E2 binding and immunodetection can identify ER, these procedures do not assess the functional state of the receptor molecule. In this study we describe a novel and rapid assay for the detection of ER and its functional state on the basis of the downstream interaction with its response element based on the preferential binding of DNA-protein complex (ERE-ER) to a nitrocellulose membrane (NBMA). This method permits measurement of both the total and the functional fraction of ER. The ER status was examined in breast cancer cell lines and iii breast cancer biopsy specimens by (i) H-3-E2 binding assay, (ii) immunodetection assays and (iii) by its interaction with P-32-ERE The sensitive NMBA assay was validated with well-characterized ER(+) breast cancer cell lines and also identified functional variants of ER among breast tumor biopsy specimens. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biswas, DK (reprint author), Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA61253-07] NR 22 TC 3 Z9 3 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2000 VL 29 IS 5 BP 1056 EP + PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373EF UT WOS:000165274900019 PM 11084868 ER PT J AU Corman, JM Penson, DF Hur, K Khuri, SF Daley, J Henderson, W Krieger, JN AF Corman, JM Penson, DF Hur, K Khuri, SF Daley, J Henderson, W Krieger, JN TI Comparison of complications after radical and partial nephrectomy: Results from the National Veterans Administration Surgical Quality Improvement Program SO BJU INTERNATIONAL LA English DT Article DE renal cell carcinoma; radical nephrectomy; partial nephrectomy; morbidity; mortality ID RENAL-CELL CARCINOMA; NEPHRON-SPARING SURGERY; CONSERVATIVE SURGERY; RISK ADJUSTMENT; EXPERIENCE; TUMORS; CARE; MANAGEMENT AB Objective To determine whether radical nephrectomy causes less morbidity, less mortality and is associated with a shorter hospital stay than is partial nephrectomy. Patients and methods A total of 1885 nephrectomies (1373 radical and 512 partial) conducted between 1991 and 1998 in the Department of Veterans Affairs (VA) National Surgical Quality Improvement Program were evaluated. Using multivariate analyses, outcomes were risk-adjusted based on 45 preoperative variables to compare mortality and morbidity rates. Results The unadjusted 30-day mortality was 2.0% for radical and 1.6% for partial nephrectomy (P = 0.58). Risk-adjusting the two groups did not result in a statistically significant difference in mortality. The 30-day overall morbidity rate was 15% for radical and 16.2% for partial nephrectomy (P = 0.52); risk-adjusted morbidity rates were not statistically different. There were no statistically significant differences in the rates of postoperative progressive renal failure, acute renal failure, urinary tract infection, prolonged ileus, transfusion requirement, deep wound infection, or extended length of stay. Conclusions Partial nephrectomy carried out in the VA program has low morbidity and mortality rates, comparable with the complication rates after radical nephrectomy. C1 VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. W Roxbury Harvard Med Sch, Brockton W Roxbury VA Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp Partners Healthcare Syst, Inst Hlth Policy, Boston, MA USA. RP Corman, JM (reprint author), Virginia Mason Med Ctr, C7-URO,1100 9th Ave,POB 900, Seattle, WA 98111 USA. NR 49 TC 70 Z9 73 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2000 VL 86 IS 7 BP 782 EP 789 DI 10.1046/j.1464-410x.2000.00919.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 375HX UT WOS:000165394400004 PM 11069401 ER PT J AU Hideshima, T Chauhan, D Shima, Y Raje, N Davies, FE Tai, YT Treon, SP Lin, B Schlossman, RL Richardson, P Muller, G Stirling, DI Anderson, KC AF Hideshima, T Chauhan, D Shima, Y Raje, N Davies, FE Tai, YT Treon, SP Lin, B Schlossman, RL Richardson, P Muller, G Stirling, DI Anderson, KC TI Thalidomide and its analogs overcome drug resistance of human multiple myeloma cells to conventional therapy SO BLOOD LA English DT Article ID PROTEIN-KINASE CASCADE; MARROW STROMAL CELLS; INTERLEUKIN-6 SECRETION; GROWTH ARREST; APOPTOSIS; ACTIVATION; ADHESION; DEXAMETHASONE; ANGIOGENESIS; PROGRESSION AB Although thalidomide (Thal) was initially used to treat multiple myeloma (MM) because of its known antiangiogenic effects, the mechanism of its anti-MM activity is unclear. These studies demonstrate clinical activity of Thal against NIM that is refractory to conventional therapy and delineate mechanisms of anti-tumor activity of Thal and its potent analogs (immunomodulatory drugs [IMiDs]). Importantly, these agents act directly, by inducing apoptosis or G1 growth arrest, in MM cell lines and in patient MM cells that are resistant to melphalan, doxorubicin, and dexamethasone (Dex), Moreover, Thal and the IMiDs enhance the anti-MM activity of Dex and, conversely, are inhibited by interleukin 6. As for Dex, apoptotic signaling triggered by Thal and the IMiDs is associated with activation of related adhesion focal tyrosine kinase, These studies establish the framework for the development and testing of Thal and the IMiDs in a new treatment paradigm to target both the tumor cell and the micro-environment, overcome classical drug resistance, and achieve improved outcome in this presently incurable disease. (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Celgene Corp, Warren, NJ USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0178378] NR 31 TC 635 Z9 682 U1 1 U2 38 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 NOV 1 PY 2000 VL 96 IS 9 BP 2943 EP 2950 PG 8 WC Hematology SC Hematology GA 367RA UT WOS:000090074200004 PM 11049970 ER PT J AU Bracy, JL Iacomini, J AF Bracy, JL Iacomini, J TI Induction of B-cell tolerance by retroviral gene therapy SO BLOOD LA English DT Article ID ALPHA-GALACTOSYL EPITOPES; HUMAN NATURAL ANTIBODIES; ANTI-GAL ANTIBODY; XENOTRANSPLANTATION; EXPRESSION; CHIMERISM; REJECTION; PORCINE; MOUSE; MICE AB The primary immunologic barrier to overcome before clinical xenotransplantation can be successful is rejection mediated by preformed natural antibodies in the host, directed toward a single carbohydrate epitope Gal alpha1-3Gal beta1-4GlcNAc-R (alpha Gal) present on porcine tissue, encoded for by the enzyme glucosyltransferase UDP galactose:beta -D-galactosyl-l,CN-acetyl-D-glucosaminide alpha>(*) over bar * (1-3)galactosyltransferase (EC 2.4.1.151) or simply alpha GT. Although we have shown previously that a gene therapy approach could be used to prevent production of natural antibodies specific for alpha Gal, the ability to induce and maintain tolerance after rigorous antigen challenge would be required if similar approaches are to be used clinically. Here, we demonstrate in alpha GT knockout mice (GT(0) mice), which, like humans, contain in their serum antibodies that bind alpha Gal, that the efficient transduction and expression of a retrovirally transduced alpha GT gene in bone marrow-derived cells induces stable long-term tolerance to the alpha Gal epitope. GT(0) mice reconstituted with alpha GT-transduced bone marrow cells were unable to produce antibodies that bind alpha Gal after extensive immunization with pig cells. Furthermore, using ELISPOT assays, we were unable to detect the presence of B cells that produce alpha Gal reactive antibodies after immunization, suggesting that such B cells were eliminated from the immunologic repertoire after gene therapy. Interestingly, after tolerance to alpha Gal is induced by gene therapy, the antiporcine non-alpha Gal humoral response changes from a predominantly IgM to an IgG response. This suggests that once the natural antibody barrier Is eliminated by the induction of tolerance, the antipig response changes to a typical T-cell-dependent response involving isotype switching. Thus, gene therapy approaches may be used to overcome immunologic responses leading to xenograft rejection, and similar gene therapy approaches could be used to overcome autoimmunity. (C) 2000 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [T32AI07529, AI44268, AI43619] NR 36 TC 44 Z9 46 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 NOV 1 PY 2000 VL 96 IS 9 BP 3008 EP 3015 PG 8 WC Hematology SC Hematology GA 367RA UT WOS:000090074200012 PM 11049978 ER PT J AU Shanker, P Russo, M Harnisch, B Patterson, M Skolnik, P Lieberman, J AF Shanker, P Russo, M Harnisch, B Patterson, M Skolnik, P Lieberman, J TI Impaired function of circulating HIV-specific CD8(+) T cells in chronic human immunodeficiency virus infection SO BLOOD LA English DT Article ID CD38 ANTIGEN EXPRESSION; EPSTEIN-BARR VIRUS; DISEASE PROGRESSION; LYMPHOCYTE RESPONSES; IMMUNE-RESPONSE; REVERSE-TRANSCRIPTASE; EFFECTOR FUNCTION; VIRAL-INFECTION; PLASMA VIREMIA; FLOW-CYTOMETRY AB The functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-gamma after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-gamma -producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-gamma -producing cells could be detected only after IL-2 was added. IFN-gamma -producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex-peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2-expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-gamma was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2. (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. RP Shanker, 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 [R29AI38819, R01AI45406, R21AI45306] NR 61 TC 199 Z9 203 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 NOV 1 PY 2000 VL 96 IS 9 BP 3094 EP 3101 PG 8 WC Hematology SC Hematology GA 367RA UT WOS:000090074200023 PM 11049989 ER PT J AU Treon, SP Maimonis, P Bua, D Young, G Raje, N Mollick, J Chauhan, D Tai, YT Hideshima, T Shima, Y Hilgers, J von Mensdorff-Pouilly, S Belch, AR Pilarski, LM Anderson, KC AF Treon, SP Maimonis, P Bua, D Young, G Raje, N Mollick, J Chauhan, D Tai, YT Hideshima, T Shima, Y Hilgers, J von Mensdorff-Pouilly, S Belch, AR Pilarski, LM Anderson, KC TI Elevated soluble MUC1 levels and decreased anti-MUC1 antibody levels in patients with multiple myeloma SO BLOOD LA English DT Article ID BREAST-CANCER PATIENTS; MARROW PLASMA-CELLS; MONOCLONAL-ANTIBODIES; EPITHELIAL MUCIN; CORE PROTEIN; BONE-MARROW; B-CELLS; ANTIGEN LEVELS; MESSENGER-RNA; DF3 ANTIGEN AB Soluble MUC1 (sMUC1) levels are elevated in many MUC1(+) cancers. We and others have shown that MUC1 is expressed on multiple myeloma (MM) plasma cells and B cells. In this study, we measured sMUC1 levels in bone marrow (BM) plasma from 71 MM patients and 21 healthy donors (HDs), and in peripheral blood (PB) plasma from 42 MM patients and 13 HDs using an immunoassay that detects the CA27.29 epitope of MUC1. sMUC1 levels were found to be significantly greater (mean 31.76 U/mL, range 5.69 to 142.48 U/mL) in MM patient BM plasma versus HD BM plasma (mean 9.68 U/mL, range 0.65 to 39.83 U/mL) (P < .001). Importantly, BM plasma sMUC1 levels were related to tumor burden because sMUC1 levels were significantly higher for NIM patients with active disease (34.62 U/mL, range 5.69 to 142.48 U/mL) versus MM patients with minimal residual disease (16.16 U/mL, range 5.7 to 56.68 U/mL) (P = .0026), sMUC1 levels were also elevated in the PB plasma of MM patients (32.79 U/mL, range 4.15 to 148.84 U/ml) versus HDs (18.47 U/ml, range 8.84 to 42.49) (P = .0052). Lastly, circulating immunglobulin M (IgM) and IgG antibodies to MUC1 were measured in 114 MM patients and 31 HDs, because natural antibodies to MUC1 have been detected in patients with other MUC1-bearing malignancies. These studies demonstrated lower levels of circulating IgM (P < .001) and IgG (P = .078) antibodies to MUC1 in MM patients compared with HDs. Our data therefore show that in MM patients, sMUC1 levels are elevated and correlate with disease burden, whereas anti-MUC1 antibody levels are decreased. (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Bayer Diagnost, Walpole, MA USA. Vrije Univ Amsterdam, Acad Hosp, Amsterdam, Netherlands. Cross Canc Inst, Dept Med Oncol, Edmonton, AB T6G 1Z2, Canada. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 51 TC 52 Z9 53 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 NOV 1 PY 2000 VL 96 IS 9 BP 3147 EP 3153 PG 7 WC Hematology SC Hematology GA 367RA UT WOS:000090074200030 PM 11049996 ER PT J AU Garcia-Higuera, I Kuang, Y Denham, J D'Andrea, AD AF Garcia-Higuera, I Kuang, Y Denham, J D'Andrea, AD TI The Fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex SO BLOOD LA English DT Article ID C-GENE; CELLS; FAA; INTERACT; FORM; COMPLEMENTATION; INSTABILITY; FANCG/XRCC9; INTERFERON; THERAPY AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FAA cell line, with a reciprocal increase in the half-life of FANCG, Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm, The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA. (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Garcia-Higuera, Irene/L-5004-2014 FU NHLBI NIH HHS [P01HL54785-04, R01HL52725-04] NR 42 TC 88 Z9 88 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 NOV 1 PY 2000 VL 96 IS 9 BP 3224 EP 3230 PG 7 WC Hematology SC Hematology GA 367RA UT WOS:000090074200041 PM 11050007 ER PT J AU Fields, KK Crump, M Bence-Bruckler, I Bernstein, S Williams, S Frankel, S Miller, A Demetri, G Nabholtz, JM Cruickshank, S Lill, M AF Fields, KK Crump, M Bence-Bruckler, I Bernstein, S Williams, S Frankel, S Miller, A Demetri, G Nabholtz, JM Cruickshank, S Lill, M TI Use of PEG-rHuMGDF in platelet engraftment after autologous stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE PEG-rHuMGDF; platelet; engraftment; transplantation; clinical trial ID HUMAN MEGAKARYOCYTE GROWTH; BLOOD PROGENITOR-CELL; C-MPL LIGAND; ADVANCED CANCER; CHEMOTHERAPY; THROMBOPOIETIN; IDENTIFICATION; PURIFICATION; STIMULATION; COLLECTIONS AB This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT), Patients were randomized to receive either placebo (n = 11) Or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) mug/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to greater than or equal to 20 x 10(9)/l by day 21, The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages, The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33617 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Ottawa Gen Hosp, Ottawa, ON K1H 8L6, Canada. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Tulane Univ, Med Ctr, New Orleans, LA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cross Canc Ctr, Edmonton, AB, Canada. Amgen Inc, Thousand Oaks, CA 91320 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Fields, KK (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, 12902 Magnolia Dr, Tampa, FL 33617 USA. NR 21 TC 6 Z9 6 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2000 VL 26 IS 10 BP 1083 EP 1088 DI 10.1038/sj.bmt.1702662 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 375ZA UT WOS:000165432300009 PM 11108307 ER PT J AU Akasheh, MS Freytes, CO Vesole, DH AF Akasheh, MS Freytes, CO Vesole, DH TI Melphalan-associated pulmonary toxicity following high-dose therapy with autologous hematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE melphalan-associated pulmonary toxicity; cyclophosphamide-associated pulmonary toxicity; diffuse interstitial pneumonitis; high-dose therapy; autologous hematopoietic stem cell transplant ID CYCLOPHOSPHAMIDE AB Melphalan can rarely cause interstitial pneumonitis and fibrosis, Although it has been reported previously in patients after conventional doses, we report four cases developing diffuse interstitial pneumonitis (DIP) after high-dose melphalan-based therapy. In a 3-year period, four of 57 (7%) consecutive patients undergoing high-dose melphalan (200 mg/m(2); MEL 200) were identified with DIP. Two patients who were heavily pre-treated with alkylators developed progressive respiratory failure despite high-dose steroids and eventually died. The other two patients previously treated with vincristine, adriamycin, and dexamethasone (VAD) improved dramatically on high-dose steroids with complete resolution of their pneumonitis. Melphalan should be added to the growing list of alkylators causing pulmonary toxicity. C1 Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA. Univ Texas, Ctr Hlth, Adult Bone Marrow Transplantat Program, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Vesole, DH (reprint author), Med Coll Wisconsin, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. NR 10 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2000 VL 26 IS 10 BP 1107 EP 1109 DI 10.1038/sj.bmt.1702664 PG 3 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 375ZA UT WOS:000165432300013 PM 11108311 ER PT J AU Weber, GF Ashkar, S AF Weber, GF Ashkar, S TI Molecular mechanisms of tumor dissemination in primary and metastatic brain cancers SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT 9th International Symposium on New Frontiers of Neurochemistry and Biophysics in the Acute and Chronic Neurological Diseases CY AUG 16-19, 1999 CL MARTIN, SLOVAKIA DE invasion; homing receptors; cytokines; proteinases; stress response ID ENDOTHELIAL-CELL MIGRATION; EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; OSTEOPONTIN GENE; GLIOMA INVASION; IN-VITRO; CD44; ANGIOGENESIS; INTEGRIN AB Cancer is characterized by dysregulated growth control, overcoming of replicative senescence, and metastasis formation. Tumor dissemination distinguishes malignant from benign neoplasms and is mediated by homing receptors, their ligands, and proteinases. The homing receptor CD44 is frequently expressed on primary brain tumors and brain metastases, Its engagement by osteopontin physiologically induces macrophage chemotaxis, a mechanism that may be utilized by metastatic brain tumors in the process of dissemination, In host defense, osteopontin and its receptors, CD44 and integrin alpha (V)beta (3), play key roles in mediating delayed type hypersensitivity responses by activating macrophages to induce Th1 cytokines while inhibiting Th2 cytokines, Other metastasis associated gene products similarly contribute to host defenses. Hence, cancer spread is regulated by a set of developmentally nonessential genes which physiologically mediate stress responses, inflammation, wound healing, and neovascularization. Function of the relevant gene products is extensively modified post-transcriptionally and their dysregulation in cancer occurs on the levels of expression and splicing. Consistent patterns of organ preference by malignancies of particular tissue origin suggest a necessary connection between loss of growth control and senescence genes and expression of genes mediating the dissemination of tumor cells. (C) 2000 Elsevier Science Inc. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Childrens Hosp,Lab Skeletal Disorders & Rehab, Boston, MA USA. RP Weber, GF (reprint author), New England Med Ctr, 750 Washington St,NEMC 824, Boston, MA 02111 USA. FU NCI NIH HHS [CA76176] NR 27 TC 21 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 1 PY 2000 VL 53 IS 4 BP 421 EP 424 DI 10.1016/S0361-9230(00)00379-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 386GG UT WOS:000166052100008 PM 11136998 ER PT J AU Ames, A AF Ames, A TI CNS energy metabolism as related to function SO BRAIN RESEARCH REVIEWS LA English DT Review DE CNS; energy metabolism; aerobic glycolysis; creatine kinase; adenylate kinase; carbonic anhydrase; calcium ID MAGNETIC-RESONANCE SPECTROSCOPY; VASCULAR SMOOTH-MUSCLE; RAT-BRAIN SYNAPTOSOMES; ACTIVATED POTASSIUM CHANNELS; CEREBRAL GLUCOSE-UTILIZATION; INTACT SKELETAL-MUSCLE; HUMAN VISUAL-CORTEX; PROTEIN-SYNTHESIS; CULTURED ASTROCYTES; NEURONAL-ACTIVITY AB Large amounts of energy are required to maintain the signaling activities of CNS cells. Because of the fine-grained heterogeneity of brain and the rapid changes in energy demand, it has been difficult to monitor rates of energy generation and consumption at the cellular level and even more difficult at the subcellular level. Mechanisms to facilitate energy transfer within cells include the juxtaposition of sites of generation with sites of consumption and the transfer of similar toP by the creatine kinase/creatine phosphate and the adenylate kinase systems. There is evidence that glycolysis is separated from oxidative metabolism at some sites with lactate becoming an important substrate. Carbonic anhydrase may play a role in buffering activity-induced increases in lactic acid. Relatively little energy is used for 'vegetative' processes. The great majority is used for signaling processes, particularly Na+ transport. The brain has very small energy reserves, and the margin of safety between the energy that can be generated and the energy required for maximum activity is also small. It seems probable that the supply of energy may impose a limit on the activity of a neuron under normal conditions. A number of mechanisms have evolved to reduce activity when energy levels are diminished. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Ames, A (reprint author), 84 Jenckes Rd, Brattleboro, VT 05301 USA. NR 258 TC 354 Z9 362 U1 2 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD NOV PY 2000 VL 34 IS 1-2 BP 42 EP 68 DI 10.1016/S0165-0173(00)00038-2 PG 27 WC Neurosciences SC Neurosciences & Neurology GA 380TM UT WOS:000165719600003 PM 11086186 ER PT J AU Heng, MCY Song, MK Harker, J Heng, MK AF Heng, MCY Song, MK Harker, J Heng, MK TI Drug-induced suppression of phosphorylase kinase activity correlates with resolution of psoriasis as assessed by clinical, histological and immunohistochemical parameters SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE calcipotriol; cell migration; cell proliferation; curcumin; phosphorylase kinase; psoriasis ID DEPENDENT PROTEIN-KINASE; CALMODULIN LEVELS; CELL-CYCLE; CATALYTIC DOMAIN; PLAQUE-FORMATION; DNA-SYNTHESIS; FACTOR-ALPHA; T-CELLS; EXPRESSION; EPIDERMIS AB Background Phosphorylase kinase (PhK), also known as adenosine triphosphate (ATP)-phosphorylase b phosphotransferase, integrates multiple calcium/calmodulin-dependent signalling pathways, including those involved in cell migration and cell proliferation, while coupling these pathways to glycogenolysis and ATP-dependent phosphorylation, thus ensuring continuing energy supply for these activities. Objectives Our laboratory recently reported correlation of elevated PhK activity with psoriatic activity. This study further evaluates the significance of drug-induced suppression of PhK activity on psoriatic activity. Patients and methods PhK activity was assayed in four groups, each with 10 patients: (i) active untreated psoriasis; (ii) resolving psoriasis treated by calcipotriol (Dovonex(R), Bristol Myers Squibb, Princeton, NJ, U.S.A.), a vitamin D-3 analogue and an indirect inhibitor of PhK; (iii) curcumin (diferuloylmethane), a selective PhK inhibitor; and (iv) 10 normal non-psoriatic subjects. Results PhK activity in units mg(-1) protein was highest in active untreated psoriasis (1204 +/- 804.3; mean +/- SD), lower in the calcipotriol-treated group (550.7 +/- 192.9), lower in curcumin-treated group (207.2 +/- 97.6), and lowest in normal skin (105.4 +/- 44.6). One-way analysis of variance performed on log-transformed PhK activity measure showed significant differences among the four groups, F-3,F-36 = 48.79, P < 0.0001. Decreased PhK activity in curcumin-and calcipotriol-treated psoriasis was associated with corresponding decreases in keratinocyte transferrin receptor (TRR) expression, severity of parakeratosis and density of epidermal CD8+ T cells. Conclusions Our results demonstrate that drug-induced suppression of PhK activity is associated with resolution of psoriatic activity as assessed by clinical, histological and immunohistochemical criteria, and support the hypothesis that effective antipsoriatic activity may be achieved through modulation of PhK activity. C1 Univ Calif Los Angeles, San Fernando Valley Program, VA Greater Los Angeles Healthcare Syst Sepulveda, Dept Med,Div Dermatol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, San Fernando Valley Program, VA Greater Los Angeles Healthcare Syst Sepulveda, Dept Med,Div Cardiol, Sepulveda, CA 91343 USA. RP Heng, MCY (reprint author), Univ Calif Los Angeles, San Fernando Valley Program, VA Greater Los Angeles Healthcare Syst Sepulveda, Dept Med,Div Dermatol, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 63 TC 67 Z9 73 U1 0 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2000 VL 143 IS 5 BP 937 EP 949 DI 10.1046/j.1365-2133.2000.03767.x PG 13 WC Dermatology SC Dermatology GA 375KF UT WOS:000165397700006 PM 11069500 ER PT J AU van Os, R Robinson, SN Drukteinis, D Sheridan, TM Mauch, PM AF van Os, R Robinson, SN Drukteinis, D Sheridan, TM Mauch, PM TI Respiratory burst of neutrophils is not required for stem cell mobilization in mice SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE mobilization; stem cells; IL-8; G-CSF; respiratory burst ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; IN-VIVO; COMPETITIVE REPOPULATION; SIGNAL-TRANSDUCTION; RAPID MOBILIZATION; PHOSPHOLIPASE-D; RHESUS-MONKEYS; BONE-MARROW; INTERLEUKIN-8 AB It has been suggested that mature neutrophils may play an essential role in the cascade of events leading to egress of stem cells from the bone marrow to the peripheral blood. To investigate further the role of mature neutrophils and of reactive oxygen intermediates (ROIs), known to be involved in the signal transduction of neutrophils, we used mice deficient in respiratory burst, and thus the production of ROIs, to study the involvement of this activation pathway in stem cell mobilization. B6 mice with chronic granulomatous disease (CGD) received either cyclophosphamide (200 mg/kg) on day 1 and granulocyte colony-stimulating factor (G-CSF) (250 mug/kg/d) on days 3-6 or a single dose of interleukin 8 (IL-8; 30 mug/mouse) as a mobilization regimen. On day 7, the number of stem and progenitor cells in blood and bone marrow was compared with control B6 animals (with intact respiratory burst). White blood cell counts, bone marrow cellularity and the frequency of granulocyte-macrophage colony-forming cells (GM-CFC), and cobblestone area-forming cells (CAFC) on days 7 (CAFC-7) and 28 (CAFC-28) were determined. After cyclophosphamide and G-CSF (CY + G), both mouse strains showed considerable mobilization of CAFC-7 and CFU-GM to the blood. Normal mice showed up to a 1905-fold increase in progenitors per ml blood, whereas CGD mice showed up to a 264-fold increase in blood progenitors. IL-8 also induced mobilization in both mouse strains. In addition to progenitors, primitive stem cells measured as CAFC-28 and as CAFC at day 35 were also mobilized by both mobilization protocols in normal as well as in CGD mice. In conclusion, respiratory burst and the subsequent signal transduction pathway do not appear to be required for mobilization of stem cells. Accordingly, neutrophils either are not involved in stem cell mobilization or other signalling pathways within neutrophils must exist that lead to the release of factors which activate stem cell egress from the bone marrow. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP van Os, R (reprint author), Leiden Univ, Med Ctr, Dept Haematol, Bldg 1,C2-R,POB 9600, NL-2300 RC Leiden, Netherlands. RI van Os, Ronald/I-1516-2013 FU NCI NIH HHS [CA 10941-28]; NHLBI NIH HHS [P50 HL54785-01] NR 27 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2000 VL 111 IS 2 BP 695 EP 699 DI 10.1046/j.1365-2141.2000.02374.x PG 5 WC Hematology SC Hematology GA 382MR UT WOS:000165827300049 PM 11122123 ER PT J AU Sheridan, RL Schulz, JT Weber, JM Ryan, CM Pasternack, MS Tompkins, RG AF Sheridan, RL Schulz, JT Weber, JM Ryan, CM Pasternack, MS Tompkins, RG TI Cutaneous herpetic infections complicating burns SO BURNS LA English DT Article DE burns; viral infection; herpes simplex ID SIMPLEX VIRUS; EPIDEMIOLOGY; VARICELLA AB Many people harbor herpes simplex virus, often with a known history of "cold sores". During the relatively immunosuppressed state associated with a serious burn, recrudescence of such infections can occur. We report four adults and two children who developed severe herpetic ulceration, over the face and neck in five patients and in a partial thickness wound in one patient. Herpetic infection was diagnosed by culture and direct immunofluorescence testing and treatment was immediately instituted with systemic and topical Acylovir(R) (Zovirar, Glare Wellcome). Ulceration healed under treatment and did not leave visible scarring in any of the patients. Although these infections are rapidly progressive, they respond to prompt treatment with antiviral chemotherapy. Rapidly progressive vesicles and ulceration appearing on the face or in the wounds of burn patients should prompt immediate evaluation for herpetic infection. (C) 2000 Elsevier Science Ltd and ISBI. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. NR 16 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-4179 J9 BURNS JI Burns PD NOV PY 2000 VL 26 IS 7 BP 621 EP 624 DI 10.1016/S0305-4179(00)00025-5 PG 4 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA 354CV UT WOS:000089313000004 PM 10925184 ER PT J AU Shepard, TF Platz, EA Kantoff, PW Nelson, WG Isaacs, WB Freije, D Febbo, PG Stampfer, MJ Giovannucci, E AF Shepard, TF Platz, EA Kantoff, PW Nelson, WG Isaacs, WB Freije, D Febbo, PG Stampfer, MJ Giovannucci, E TI No association between the I105V polymorphism of the glutathione S-transferase P1 gene (GSTP1) and prostate cancer risk: A prospective study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Brady Urol Inst, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21287 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Adult Oncol, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Channing Lab, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA-34944]; NHLBI NIH HHS [HL-34595, HL-26490] NR 6 TC 30 Z9 30 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 NOV PY 2000 VL 9 IS 11 BP 1267 EP 1268 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 373YW UT WOS:000165318500019 PM 11097238 ER PT J AU Houser, SL Aretz, HT Quist, WC Chang, YC Schreiber, AD AF Houser, SL Aretz, HT Quist, WC Chang, YC Schreiber, AD TI Serum lipids and arterial plaque load are altered independently with high-dose progesterone in hypercholesterolemic male rabbits SO CARDIOVASCULAR PATHOLOGY LA English DT Article ID CHOLESTEROL-FED RABBITS; MUSCLE CELL-PROLIFERATION; LOW-DENSITY-LIPOPROTEIN; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; CORONARY-ARTERIES; SMOOTH-MUSCLE; EXPERIMENTAL ATHEROSCLEROSIS; AORTIC ACCUMULATION; CAROTID-ARTERY AB Antiatherogenic effects of sex steroids in premenopausal women are not well defined. Therefore, we employed an established rabbit model for atherosclerosis to study the effects of exogenous estrogen and a progesterone analogue (P) on serum lipids and aortic plaque load. Serum cholesterol (C) and triglyceride (T) levers and atherosclerotic plaque loads were compared in 5 groups of male New Zealand White rabbits fed a 12-week, C-rich diet: 1 control group (CG) and 4 groups treated with estriol (E), haloperidol (H), low-dose 17-hydroxyprogesterone (LDP), or high-dose 17-hydroxyprogesterone (HDP). Serum P was measured in the LDP and HDP groups. Serial histologic sections (15 each of 27 ascending aortas) were studied by light microscopy and computerized morphometric analysis. Plaque load is defined as the ratio of intimal area to medial area (I/M). Exogenous E (p < 0.001), H (P = 0.02), LDP and HDP (P < 0.001, each) were found to be significantly associated with less aortic plaque load than controls. In a multivariate analysis, after controlling for the differences in serum C and T levels, HDP Co = 0.014) was found to be associated with less aortic plaque load than controls, and this association approached statistical significance in the E (p = 0.052) and H (p = 0.069) groups. These data suggest that the mechanism(s) involved with the antiatherogenic effect of HDP in this animal model is, or are, independent of an alteration in serum lipids. (C) 2000 by Elsevier Science Inc. C1 Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr, Boston, MA USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Houser, SL (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Warren-2,Fruit St, Boston, MA 02114 USA. NR 49 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD NOV-DEC PY 2000 VL 9 IS 6 BP 317 EP 322 DI 10.1016/S1054-8807(00)00051-X PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 385ZB UT WOS:000166034100002 PM 11146301 ER PT J AU Abernethy, WB Choo, JK Oesterle, SN Jang, IK AF Abernethy, WB Choo, JK Oesterle, SN Jang, IK TI Balloon deflection technique: A method to facilitate entry of a balloon catheter into a deployed stent SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE angioplasty; percutaneous coronary intervention ID INTRACORONARY AB The entry of an angioplasty balloon into a coronary stent is occasionally difficult due to poorly expanded stent struts or calcified tissue blocking balloon passage. We describe a simple technique using a second guidewire and balloon to facilitate entry into the stent, Cathet. Cardiovasc. Intervent. 51:312-313, 2000. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV PY 2000 VL 51 IS 3 BP 312 EP 313 DI 10.1002/1522-726X(200011)51:3<312::AID-CCD15>3.0.CO;2-3 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 370UP UT WOS:000165141100015 PM 11066114 ER PT J AU Bangs, P Franc, N White, K AF Bangs, P Franc, N White, K TI Molecular mechanisms of cell death and phagocytosis in Drosophila SO CELL DEATH AND DIFFERENTIATION LA English DT Review DE apoptosis; Drosophila; macrophage ID REAPER-INDUCED APOPTOSIS; CAENORHABDITIS-ELEGANS; C-ELEGANS; SCAVENGER RECEPTOR; MAMMALIAN-CELLS; GENETIC-CONTROL; INHIBITOR; CASPASE; PROTEINS; GRIM AB The genetic tools available in Drosophila have facilitated our understanding of how apoptosis is regulated and executed in the context of the developing organism. All embryonic apoptosis is initiated by the activity of three genes, rpr, grim and hid. Each of these genes is independently regulated, allowing developmental apoptosis to be finely controlled. These initiators in turn activate the core apoptotic machinery, including the caspases, Drosophila counterparts to other conserved components of the apoptotic machinery have been recently identified, and we discuss how these may be integrated into the process of normal developmentally regulated cell death. We also outline the role that phagocytosis plays in the final stages of apoptosis and consider the molecular mechanisms guiding the elimination of apoptotic corpses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. EM kristin.white@CBRG2.MGH.Harvard.edu RI Franc, Nathalie/C-2208-2009; White, Kristin/D-7936-2013 NR 99 TC 32 Z9 33 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2000 VL 7 IS 11 BP 1027 EP 1034 DI 10.1038/sj.cdd.4400754 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 374NW UT WOS:000165352100003 PM 11139274 ER PT J AU Ruffolo, SC Breckenridge, DG Nguyen, M Goping, IS Gross, A Korsmeyer, SJ Li, H Yuan, J Shore, GC AF Ruffolo, SC Breckenridge, DG Nguyen, M Goping, IS Gross, A Korsmeyer, SJ Li, H Yuan, J Shore, GC TI BID-dependent and BID-independent pathways for BAX insertion into mitochondria SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; BAX; BID; mitochondria; Fas; TNF; E1A ID CYTOCHROME-C RELEASE; SIGNALING COMPLEX DISC; BCL-2 FAMILY MEMBER; INDUCED CELL-DEATH; ENDOPLASMIC-RETICULUM; BH3 DOMAIN; X-L; APOPTOSIS; PROTEIN; TRANSLOCATION AB In the absence of an apoptotic signal, BAX adopts a conformation that constrains the protein from integrating into mitochondrial membranes. Here, we show that caspases, including caspase-8, can initiate BAX insertion into mitochondria in vivo and in vitro. The cleavage product of caspase-8, tBID, induced insertion of BAX into mitochondria in vivo, and reconstitution in vitro showed that tBID, either directly or indirectly, relieved inhibition of the BAX transmembrane signal-anchor by the NH2-terminal domain, resulting in integration of BAX into mitochondrial membrane. In contrast to these findings, however, Bid-null mouse embryo fibroblasts supported Bax insertion into mitochondria in response to death signaling by either TNF alpha or E1A, despite the fact that cytochrome c release from the organelle was inhibited. We conclude, therefore, that a parallel Bid-independent pathway exists in these cells for mitochondrial insertion of Bax and that, in the absence of Bid, cytochrome c release can be uncoupled from Bax membrane insertion. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Shore, GC (reprint author), McGill Univ, Dept Biochem, McIntyre Med Sch Bldg, Montreal, PQ H3G 1Y6, Canada. NR 46 TC 95 Z9 97 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2000 VL 7 IS 11 BP 1101 EP 1108 DI 10.1038/sj.cdd.4400739 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 374NW UT WOS:000165352100013 PM 11139284 ER PT J AU Liu, XB Masago, R Kong, L Zhang, BX Masago, S Vela-Roch, N Katz, MS Yeh, CK Zhang, GH Talal, N Dang, H AF Liu, XB Masago, R Kong, L Zhang, BX Masago, S Vela-Roch, N Katz, MS Yeh, CK Zhang, GH Talal, N Dang, H TI G-protein signaling abnormalities mediated by CD95 in salivary epithelial cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Sjogren's syndrome; signal transduction; CD95; Bcl-2 ID SYSTEMIC LUPUS-ERYTHEMATOSUS; GROWTH-FACTOR RECEPTOR; T-LYMPHOCYTES; FAS ANTIGEN; ACIDIC SPHINGOMYELINASE; SURFACE ANTIGEN; ACINAR-CELLS; APOPTOSIS; DEATH; ACTIVATION AB Salivary epithelial cells from patients with primary Sjogren's syndrome (SS) undergo Fas-mediated apoptosis. Bcl-2 and Bcl-xL are apoptosis suppressing oncogenes, Very little is known about the role of these oncogene molecules in salivary epithelial cells. To investigate the possible prevention of salivary glandular destruction in SS by Bcl-2 and Bcl-xL, stable transfectants expressing these molecules were made from HSY cells, a human salivary epithelial cell line. HSY cells were transfected with an expression vector for human Bcl-2 or Bcl-xL. Stable transfectants were selected and apoptosis was induced by anti-fas antibody. Apoptosis was quantified by propidium iodide staining followed by flow cytometry, Caspase activity was detected by immunohistochemical analysis and enzyme cleavage of DEVD-AMC, a fluorescent substrate. Response to carbachol, a muscarinic receptor agonist, and EGF was measured by Ca2+ mobilization and influx. Fas-mediated apoptosis was significantly inhibited in Bcl-2 and Bcl-xL transfectants compared to wild-type and control transfectants (empty vector). Surprisingly, caspase activity was not inhibited in Bcl-2 and Bcl-xL transfectants. Activation of the Fas pathway in the Bcl-2 and Bcl-xL transfectants by antibody also inhibited carbachol and EGF responsiveness (i.e., Ca2+ mobilization and/or influx) by 50-60%, This Fas-mediated inhibition of cell activation was partially or completely restored by specific peptide interference of caspase enzyme activity. The prevention of Fas-mediated apoptosis by the overexpression of Bcl-2 and Bcl-xL in salivary gland epithelial cells results in injured cells expressing caspase activity and unable to respond normally to receptor agonists, Such damaged cells may exist in SS patients and could explain the severe dryness out of proportion to the actual number of apoptotic cells seen on salivary gland biopsy. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Educ & Clin Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Res Serv, San Antonio, TX 78284 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. RP Dang, H (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Immunol, 7703 Floyd Curl Dr,Mail Code 7874, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE10863, DE12188, DE90270, DE12203] NR 53 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD NOV PY 2000 VL 7 IS 11 BP 1119 EP 1126 DI 10.1038/sj.cdd.4400745 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 374NW UT WOS:000165352100015 PM 11139286 ER PT J AU He, HY Chen, CM Xie, Y Asea, A Calderwood, SK AF He, HY Chen, CM Xie, Y Asea, A Calderwood, SK TI HSP70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene SO CELL STRESS & CHAPERONES LA English DT Article ID MOLECULAR CHAPERONES; PROTEIN; STRESS; BINDING; CELLS; EUKARYOTES; EXPRESSION AB Heat shock protein 70 (HSP70) is a molecular chaperone involved in protein folding and resistance to the deleterious effects of stress. Here we show that HSP70 suppresses transcription of c-fos, an early response gene that is a key component of the ubiquitous AP-1 transcription factor complex. HSP70 repressed Ras-induced c-fos transcription only in the presence of functional heat shock factor1 (HSF1). This suggests that HSP70 functions as a corepressor with HSF1 to inhibit c-fos gene transcription. Therefore, besides its known function in the stress response, HSP70 also has the property of a corepressor and combines with HSF1 to antagonize Fos expression and may thus impact multiple aspects of cell regulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 15 Z9 17 U1 0 U2 1 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 406 EP 411 DI 10.1379/1466-1268(2000)005<0406:HAHSFC>2.0.CO;2 PG 6 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900003 PM 11189444 ER PT J AU Hecker, KH Asea, A Kobayashi, K Green, S Tang, D Calderwood, SK AF Hecker, KH Asea, A Kobayashi, K Green, S Tang, D Calderwood, SK TI Mutation detection in the human HSP70B ' gene by denaturing high-performance liquid chromatography SO CELL STRESS & CHAPERONES LA English DT Article ID DNA; POLYMORPHISMS AB Variances, particularly single nucleotide polymorphisms (SNP), in the genomic sequence of individuals are the primary key to understanding gene function as it relates to differences in the susceptibility to disease, environmental influences, and therapy. In this report, the HSP70B' gene is the target sequence for mutation detection in biopsy samples from human prostate cancer patients undergoing combined hyperthermia and radiation therapy at the Dana-Farber Cancer Institute, using temperature-modulated heteroduplex analysis (TMHA). The underlying principles of TMHA for mutation detection using DHPLC technology are discussed. The procedures involved in amplicon design for mutation analysis by DHPLC are detailed. The melting behavior of the complete coding sequence of the target gene is characterized using WAVEMAKER(TM) software. Four overlapping amplicons, which span the complete coding region of the HSP70B' gene, amenable to mutation detection by DHPLC were identified based on the software-predicted melting profile of the target sequence. TMHA was performed on PCR products of individual amplicons of the HSP70B' gene on the WAVE(R) Nucleic Acid Fragment Analysis System. The criteria for mutation calling by comparing wild-type and mutant chromatographic patterns are discussed. C1 Transgenom Inc, San Jose, CA 95131 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hecker, KH (reprint author), Transgenom Inc, San Jose, CA 95131 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 NR 13 TC 6 Z9 6 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 415 EP 424 DI 10.1379/1466-1268(2000)005<0415:MDITHH>2.0.CO;2 PG 10 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900005 PM 11189446 ER PT J AU Asea, A Kabingu, E Stevenson, MA Calderwood, SK AF Asea, A Kabingu, E Stevenson, MA Calderwood, SK TI HSP70 peptide-bearing and peptide-negative preparations act as chaperokines SO CELL STRESS & CHAPERONES LA English DT Article ID HEAT-SHOCK PROTEINS; STRESS-INDUCED PROTEINS; KILLER NK CELLS; NF-KAPPA-B; T-CELLS; IMMUNITY; BINDING; CANCER; HSP90; GRP94 AB We recently elucidated a novel function for the 70-kDa heat shock protein (HSP70) as a chaperone and a cytokine, a chaperokine in human monocytes. Here we show that peptide-bearing and peptide-negative HSP70 preparations isolated from EMT6 mammary adenocarcinoma cells (EMT6-HSP70) act as chaperokines when admired with murine splenocytes. EMT6-HSP70 bound with high affinity to the surface of splenocytes recovered from naive BALB/c mice. The [Ca2+]i inhibitor BAPTA dose dependently inhibited HSP70- but not LPS-induced NF-kappaB activity and subsequent augmentation of proinflammatory cytokine TNF-alpha, IL-1 beta, and IL-6 production. Taken together, these results suggest that presence of peptide in the HSP70 preparation is not required for spontaneous activation of cells of the innate immune system. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [CA31303, CA47407, CA50642, R01 CA047407, R01 CA077465] NR 36 TC 96 Z9 104 U1 0 U2 1 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 425 EP 431 DI 10.1379/1466-1268(2000)005<0425:HPBAPN>2.0.CO;2 PG 7 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900006 PM 11189447 ER PT J AU Wang, XZ Asea, A Xie, Y Kabingu, E Stevenson, MA Calderwood, SK AF Wang, XZ Asea, A Xie, Y Kabingu, E Stevenson, MA Calderwood, SK TI RSK2 represses HSF1 activation during heat shock SO CELL STRESS & CHAPERONES LA English DT Article ID COFFIN-LOWRY SYNDROME; TRANSCRIPTIONAL ACTIVATION; PROTEIN-KINASE; FACTOR-1; GENE; PHOSPHORYLATION; STRESS; CELLS; BINDING; LOCALIZATION AB Heat shock transcription factor 1(HSF1) activation is a multistep process. The conversion of a latent cytoplasmic form to a nuclear, DNA binding state appears to be activated by nonsteroidal anti-inflammatory drugs. in previous studies, we showed that HSF 1 is phosphorylated by the protein kinase RSK2 in vitro and that this effect is inhibited by nonsteroidal anti-inflammatory drugs at the concentration that leads to the activation of HSF1 in vivo (Stevenson et at 1999). In the present study, using cells from a patient with Coffin-Lowry syndrome (deficient in RSK2), we demonstrate that RSK2 slightly represses activation of HSF1 in vivo at 37 degreesC. in Coffin-Lowry syndrome cells, HSF1-HSE DNA binding activity after treatment with sodium salicylate was slightly higher than that in untreated cells, indicating that although RSK2 is involved in HSF1 regulation, it is not the unique protein kinase that suppresses HSF1-HSE binding activity at 37 degreesC. However, heat shock treatment resulted in significantly higher HSF1-HSE binding activity in Coffin-Lowly syndrome cells as compared with normal controls, suggesting that RSK2 represses HSF1-HSE binding activity during heat shock. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [CA47407, CA31303, CA50642, R01 CA047407, R01 CA077465] NR 30 TC 18 Z9 18 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 432 EP 437 DI 10.1379/1466-1268(2000)005<0432:RRHADH>2.0.CO;2 PG 6 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900007 PM 11189448 ER PT J AU He, HY Chen, CM Xie, Y Asea, A Calderwood, SK AF He, HY Chen, CM Xie, Y Asea, A Calderwood, SK TI Hsp70 and heat shock factor 1 cooperate to repress Ras-induced transcriptional activation of the c-fos gene SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 485 EP 485 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900017 ER PT J AU Hecker, KH Asea, A Kobayashi, K Green, S Tang, D Calderwood, SK AF Hecker, KH Asea, A Kobayashi, K Green, S Tang, D Calderwood, SK TI Mutation detection in the Hsp70B ' gene by denaturing high performance liquid chromatography SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Transgenom Inc, San Jose, CA 95131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 485 EP 486 PG 2 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900018 ER PT J AU Wang, XZ Asea, A Calderwood, SK AF Wang, XZ Asea, A Calderwood, SK TI The role of MAPKAPK2 and RSK2 in regulating Hsf1 activation SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 486 EP 486 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900020 ER PT J AU Wang, XZ Asea, A Xie, Y Kabingu, E Stevenson, MA Calderwood, SK AF Wang, XZ Asea, A Xie, Y Kabingu, E Stevenson, MA Calderwood, SK TI RSK2 represses Hsf1 activation during heat shock SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 486 EP 486 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900019 ER PT J AU Xie, Y Chen, CM Zhong, R Stevenson, MA Calderwood, SK AF Xie, Y Chen, CM Zhong, R Stevenson, MA Calderwood, SK TI Identification of Hsf1 domains involved in transcription repression SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Mol & Cellular Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 486 EP 486 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900021 ER PT J AU Tang, D Xie, Y Zhao, MJ Calderwood, SK AF Tang, D Xie, Y Zhao, MJ Calderwood, SK TI Repression of Hsp70B promoter by NFIL6, Ku, and MAPK involves three complementary mechanisms SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 487 EP 487 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900022 ER PT J AU Wang, YQ Calderwood, SK AF Wang, YQ Calderwood, SK TI Expression of dominant negative Hsf1 antagonizes the development of aneuploidy in prostate carcinoma cells SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 487 EP 487 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900023 ER PT J AU Xie, Y Chen, CM Calderwood, SK AF Xie, Y Chen, CM Calderwood, SK TI Transcriptional repression of the c-fms gene by Hsf1 SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 487 EP 488 PG 2 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900025 ER PT J AU Asea, A Kraeft, SK Kurt-Jones, EA Stevenson, MA Chen, LB Finberg, RW Koo, GC Calderwood, SK AF Asea, A Kraeft, SK Kurt-Jones, EA Stevenson, MA Chen, LB Finberg, RW Koo, GC Calderwood, SK TI Hsp70 stimulates cytokine production via a CD14-dependent pathway: a "chaperokine" SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 491 EP 491 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900036 ER PT J AU Asea, A Kabingu, E Stevenson, MA Calderwood, SK AF Asea, A Kabingu, E Stevenson, MA Calderwood, SK TI Hsp70 peptide-bearing and peptide-negative preparations function as chaperokines SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 492 EP 492 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900042 ER PT J AU Tanabe, K AF Tanabe, K TI Ablation of liver tumors by radiofrequency heating SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 499 EP 499 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900060 ER PT J AU Tang, D Calderwood, SK AF Tang, D Calderwood, SK TI Gene expression in human prostate carcinoma treated with heat shock and radiation SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 499 EP 499 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900062 ER PT J AU Asea, A Ara, G Teicher, BA Stevenson, MA Calderwood, SK AF Asea, A Ara, G Teicher, BA Stevenson, MA Calderwood, SK TI Effects of the flavnoid drug quercetin on the response of human prostate tumors to hyperthermia in vivo SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 500 EP 500 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900065 ER PT J AU He, HY Soncin, F Chen, CM March, J Li, YL Brown, SA Kingston, RE Calderwood, SK AF He, HY Soncin, F Chen, CM March, J Li, YL Brown, SA Kingston, RE Calderwood, SK TI Shock factor 2 is activated by differential expression and alternative splicing and transactivates the Hsp70 promoter during stress by association with heat shock factor I SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Div Radiat Oncol, Boston, MA 02115 USA. RI SONCIN, Fabrice/A-1475-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 500 EP 501 PG 2 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900066 ER PT J AU Lechpammer, S Asea, A Kropa, R Sherman, MY Calderwood, SK AF Lechpammer, S Asea, A Kropa, R Sherman, MY Calderwood, SK TI Chemical library screening for Hsp72 inhibitors - a search for new anti-cancer therapy SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Boston Biomed Res Inst, Watertown, MA 02472 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 500 EP 500 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900063 ER PT J AU Stevenson, MA Zhau, MJ Calderwood, SK AF Stevenson, MA Zhau, MJ Calderwood, SK TI Inhibition of heat shock protein expression in protein kinase R knockout cells at the posttranscriptional level SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Harvard Univ, Med Ctr, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Med Ctr, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 500 EP 500 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900064 ER PT J AU Asea, A Ara, G Teicher, BA Calderwood, SK AF Asea, A Ara, G Teicher, BA Calderwood, SK TI Cyclooxygenase inhibitors are potent sensitizers of DU-145 prostate tumors to hyperthermia in vivo SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD NOV PY 2000 VL 5 IS 5 BP 501 EP 501 PG 1 WC Cell Biology SC Cell Biology GA 388DV UT WOS:000166162900067 ER PT J AU Grinn, DR Chandy, D Almenoff, PL Schilero, G Lesser, M AF Grinn, DR Chandy, D Almenoff, PL Schilero, G Lesser, M TI Airway hyperreactivity in subjects with tetraplegia is associated with reduced baseline airway caliber SO CHEST LA English DT Article DE airway hyperresponsiveness; bronchoprovocation; pulmonary function; spinal cord injury ID SPINAL-CORD INJURY; HEALTHY NONSMOKING ADULTS; LOWER RESPIRATORY-TRACT; PULMONARY-FUNCTION; BRONCHIAL RESPONSIVENESS; IPRATROPIUM BROMIDE; GENERAL-POPULATION; SMOOTH-MUSCLE; LUNG-VOLUMES; METHACHOLINE AB Objectives: We administered aerosolized histamine to 32 subjects with tetraplegia to determine whether there were differences in spirometric and/or lung volume parameters between responders and nonresponders. Results: Baseline pulmonary function parameters revealed mild to moderate restrictive dysfunction. We found that 25 subjects (78%) were hyperreactive to histamine (mean provocative concentration of a substance causing a 20% fall in FEV1 [PC20], 1.77 mg/mL). Responders (PC20, < 8 mg/mL) had significantly lower values for forced expiratory flow between 25% and 79% of the outflow curve (FEF25-75), FEF25-75 percent predicted, and FEF25-75/FVC ratio. Among all 32 subjects, the natural logarithmic transformation performed on PC20 values (lnPC(20)) correlated with FEF25-75 percent predicted, FEV1 percent predicted, and FEF25-75/FVC ratio but not with FVC percent predicted. Responders with PC20 values < 2 mg/mL (n = 13) had significantly reduced values for FVC, FVC percent predicted, FEV1, and FEV1 percent predicted compared to those with PC20 values between 2 mg/mL and 8 mg/mL. In addition, among responders, there was a significant correlation between lnPC(20) and FVC percent predicted. A. significant relationship was found between maximal inspiratory pressure (PImax) and both FEV1 percent predicted and FEF25-75 percent predicted, but not between lnPC(20) and either PImax or maximal expiratory pressure (PEmax). Conclusions: These findings demonstrate that subjects with tetraplegia who exhibit airway hyperreactivity (AHR) have reduced baseline airway caliber and that lower values for lnPC(20) are associated with parallel reductions in surrogate spirometric indexes of airway size (FEV1 percent predicted and FEF25-75 percent predicted) and airway size relative to lung size (FEF25-75/FVC ratio). The absence of an association between lnPC(20) and FVC percent predicted for the entire group or between lnPC(20) and either PImax or PEmax indicates that reduced lung volumes secondary to respiratory muscle weakness cannot explain the mechanism(s) underlying AHR. Among responders, however, a possible role for reduction in lung volume, as it pertains to increasing AHR, cannot be excluded. Proposed mechanisms for reduced baseline airway caliber relative to lung size in subjects with tetraplegia include unopposed parasympathetic activity secondary to the loss of sympathetic innervation to the lungs and/or the inability to stretch airway smooth muscle with deep inhalation. C1 Bronx Vet Affairs Med Ctr, Pulm Crit Care Med Sect, Bronx, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Lesser, M (reprint author), Vet Affairs Med Ctr, Pulm Sect, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 44 TC 0 Z9 0 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 NOV PY 2000 VL 118 IS 5 BP 1397 EP 1404 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 373JV UT WOS:000165286600028 ER PT J AU Ma, HJ Sjak-Shie, NN Vescio, RA Kaminsky, M Mikail, A Pold, M Parker, K Beksac, M Belson, D Moss, TJ Wu, CH Zhou, J Zhang, L Chen, G Said, JW Berenson, JR AF Ma, HJ Sjak-Shie, NN Vescio, RA Kaminsky, M Mikail, A Pold, M Parker, K Beksac, M Belson, D Moss, TJ Wu, CH Zhou, J Zhang, L Chen, G Said, JW Berenson, JR TI Human herpesvirus 8 open reading frame 26 and open reading frame 65 sequences from multiple myeloma patients: A shared pattern not found in Kaposi's sarcoma or primary effusion lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID VIRAL CAPSID ANTIGEN; DNA-SEQUENCES; STRAIN VARIABILITY; DENDRITIC CELLS; HUMAN-HERPESVIRUS-8; INFECTION; HHV-8; ANTIBODIES; IDENTIFICATION; LESIONS AB Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus, has been implicated in the pathogenesis of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman's disease, and recently multiple myeloma (MM), DNA sequence analyses of HHV-8 suggest that multiple HHV-8 strains exist. We extracted DNA from 24 patients with MM and 3 patients with monoclonal gammopathy of undetermined significance and compared HHV-8 open reading frames (ORFs) 26 and 65 sequences with those derived from patients with KS, PEL, and two HHV-8-positive PEL cell lines KS-1 and BC-1, ORF26 sequence data suggest that MR I patients are consistently carriers of HHV-8 strain subtype C3, All MM patients also consistently revealed either a single bp deletion or substitution at position 112197 in ORF65, This unique alteration is not present in patients with KS or PEL or in PEL cell lines. It occurs in the portion of ORF65 that is known to be responsible for a serological response to HHV-8. C1 Cedars Sinai Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90048 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Div Hematol & Oncol, Los Angeles, CA USA. Univ Calif Los Angeles, Div Pathol, Sch Med, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90048 USA. Ibni Sina Hosp, Dept Hematol, Ankara, Turkey. BIS Labs, Reseda, CA USA. RP Berenson, JR (reprint author), Cedars Sinai Med Ctr, Myeloma Program, Beverly Modular 1,Room 120,8700 Beverly Blvd, Los Angeles, CA 90048 USA. RI Beksac, Meral/D-6411-2013 NR 37 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 IS 11 BP 4226 EP 4233 PG 8 WC Oncology SC Oncology GA 374LX UT WOS:000165347600009 PM 11106236 ER PT J AU Elliott, PJ Aghajanian, C Cusack, J Orlowski, R Logothetis, C Papandreou, C Pien, C Smith, M Spriggs, D Adams, J AF Elliott, PJ Aghajanian, C Cusack, J Orlowski, R Logothetis, C Papandreou, C Pien, C Smith, M Spriggs, D Adams, J TI Clinical development of PS-341: From mice to man. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Millennium Pharmaceut Inc, Cambridge, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ N Carolina, Chapel Hill, NC USA. MD Anderson Canc Ctr, Houston, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 169 BP 4500S EP 4500S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000129 ER PT J AU Zang, Y Kang, JX AF Zang, Y Kang, JX TI Mechanisms of apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 174 BP 4501S EP 4501S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000134 ER PT J AU Garcia-Carbonero, R Demetri, G Ryan, D Seiden, M Harmon, D Butkiewicz, L Merriam, P Guzman, C Lopez-Lazaro, L Jimeno, J Supko, JG AF Garcia-Carbonero, R Demetri, G Ryan, D Seiden, M Harmon, D Butkiewicz, L Merriam, P Guzman, C Lopez-Lazaro, L Jimeno, J Supko, JG TI Population pharmacokinetics of ecteinascidin 743 in patients with advanced soft tissue sarcoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Partners Canc Care, Boston, MA USA. PharmaMar SA, Madrid, Spain. RI IBIS, NUEVAS TERAPIA/P-3415-2015 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 211 BP 4508S EP 4508S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000170 ER PT J AU Hamilton, M Sparreboom, A Loos, W Verweij, J Demetri, G Gelmon, K Eisenhauer, E Warren, S Ptaszynski, M AF Hamilton, M Sparreboom, A Loos, W Verweij, J Demetri, G Gelmon, K Eisenhauer, E Warren, S Ptaszynski, M TI Pharmacokinetics of NX 211 (liposomal lurtotecan) in phase I patients with solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Gilead Sci Inc, Boulder, CO USA. Rotterdam Canc Inst, Rotterdam, Netherlands. Dana Farber Partners Canc Care, Boston, MA USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NCI, Canada Clin Trials Grp, Kingston, ON, Canada. RI Sparreboom, Alex/B-3247-2008 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 238 BP 4513S EP 4514S PG 2 WC Oncology SC Oncology GA 375NW UT WOS:000165409000197 ER PT J AU Eder, JP Clark, JW Supko, JG Shulman, LN Garcia-Carbonero, R Roper, K Proper, J Keogan, M Schnipper, L Connors, S Butterfield, C Fogler, W Xu, G Gubish, E Folkman, J Kufe, DW AF Eder, JP Clark, JW Supko, JG Shulman, LN Garcia-Carbonero, R Roper, K Proper, J Keogan, M Schnipper, L Connors, S Butterfield, C Fogler, W Xu, G Gubish, E Folkman, J Kufe, DW TI Recombinant human endostatin demonstrates safety, linear pharmacokinetics and biological effects on tumor growth factors: Results of a phase I clinical study. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Harvard Canc Ctr, Boston, MA 02115 USA. EntreMed, Rockville, MD 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 258 BP 4518S EP 4518S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000217 ER PT J AU Von Holf, DD Cox, JV Eder, JP Tempero, MA Eckhardt, SG Rowinsky, EK Smith, SL Smith, CL Stuart, KE Proper, J Campbell, ER MacDonald, JR AF Von Holf, DD Cox, JV Eder, JP Tempero, MA Eckhardt, SG Rowinsky, EK Smith, SL Smith, CL Stuart, KE Proper, J Campbell, ER MacDonald, JR TI Activity of Irofulven (MGI 114)in patients with advanced pancreatic cancer refractory to gemcitabine. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Arizona Canc Ctr, Tucson, AZ USA. Texas Canc Ctr, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Inst Drug Dev, San Antonio, TX USA. MGI PHARMA Inc, Bloomington, MN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 365 BP 4539S EP 4539S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000323 ER PT J AU Hamilton, A Eder, JP Pavlick, A Clark, JW Chachoua, A Ryan, DP Farrell, K Wasserstrom, H Liebes, L Wright, J Elliott, P Adams, J Muggia, F AF Hamilton, A Eder, JP Pavlick, A Clark, JW Chachoua, A Ryan, DP Farrell, K Wasserstrom, H Liebes, L Wright, J Elliott, P Adams, J Muggia, F TI Proteasome inhibition by PS-341: A phase I study. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NYU, Sch Med, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, CTEP, Bethesda, MD 20892 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2000 VL 6 SU S MA 417 BP 4549S EP 4549S PG 1 WC Oncology SC Oncology GA 375NW UT WOS:000165409000375 ER PT J AU Wang, TJ Liang, MH Sangha, O Phillips, CB Lew, RA Wright, EA Berardi, V Fossel, AH Shadick, NA AF Wang, TJ Liang, MH Sangha, O Phillips, CB Lew, RA Wright, EA Berardi, V Fossel, AH Shadick, NA TI Coexposure to Borrelia burgdorferi and Babesia microti does not worsen the long-term outcome of Lyme disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NANTUCKET-ISLAND; MANIFESTATIONS; SERODIAGNOSIS; INFECTIONS; ANTIBODY; CHILDREN; FEVER AB Previous studies suggest that concurrent Lyme disease and babesiosis produce a more sever illness than either disease alone. The majority of babesiosis infections, however, are subclinical, Our objective was to characterize on the basis of a total-population survey of Nantucket Island, Massachusetts, whether coexposure to Lyme disease and babesiosis causes more severe illness or poorer long-term outcomes than Lyme disease alone. In this retrospective cohort study, residents indicating a history of Lyme disease were compared with randomly selected population controls on a standardized medical history, blinded physical examination, and serological studies for Borrelia burgdorferi and Babesia microti. Serological evidence of exposure to babesiosis was not associated with increased severity of acute Lyme disease. The groups did not differ with regard to the prevalence of constitutional, musculoskeletal, or neurological symptoms a mean of 6 years after acute Lyme disease. Prior Lyme disease and serological exposure to B. microti are not associated with poorer long-term outcomes or more persistent symptoms Lyme disease alone. C1 Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Imugen, Norwood, MA USA. RP Shadick, NA (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, PBB-B2,75 Francis St, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR02033, AR36308] NR 28 TC 26 Z9 28 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 2000 VL 31 IS 5 BP 1149 EP 1154 DI 10.1086/317465 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 380LY UT WOS:000165704400009 PM 11073744 ER PT J AU Rietschel, P Corcoran, C Stanley, T Basgoz, N Klibanski, A Grinspoon, S AF Rietschel, P Corcoran, C Stanley, T Basgoz, N Klibanski, A Grinspoon, S TI Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LOW TESTOSTERONE; AIDS; DISORDERS; ILLNESS; SYSTEM; TRIAL; BODY AB Previous studies have indicated that there is a significant prevalence (50%) of hypogonadism among men with acquired immunodeficiency syndrome (AIDS)-associated wasting, and for these patients testosterone administration has been shown to increase lean body mass and improve quality of Life. However, the prevalence of hypogonadism is not known among men with weight loss related to human immunodeficiency virus (HIV) infection who are receiving highly active antiretroviral therapy (HAART). From 1997 through 1999, we investigated total and free testosterone levels in 90 men who were <90% of ideal body weight or had weight loss of >10% from preillness weight; 71% of these subjects were receiving HAART. Twenty-one percent of the subjects receiving HAART had low free testosterone levels, No correlation was seen between weight, CD4 cell count, medication status, and other clinical factors. These data suggest that hypogonadism remains relatively common in men with AIDS wasting, despite treatment with HAART. HIV-infected men with wasting syndrome should be screened for hypogonadism and receive physiological androgen replacement therapy if they are hypogonadal. C1 Massachusetts Gen Hosp, Neuroendoctrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendoctrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIDDK NIH HHS [F32-DK09218, R01-DK49302] NR 26 TC 77 Z9 80 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 2000 VL 31 IS 5 BP 1240 EP 1244 DI 10.1086/317457 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 380LY UT WOS:000165704400023 PM 11073758 ER PT J AU Lee, FS Chu, FK Tackley, M Wu, AD Atri, A Wessels, MR AF Lee, FS Chu, FK Tackley, M Wu, AD Atri, A Wessels, MR TI Human granulocytic ehrlichiosis presenting as facial diplegia in a 42-year-old woman SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NERVE PALSY; AGENT; IDENTIFICATION; CHAFFEENSIS; MORULAE AB Neurologic manifestations of human ehrlichiosis are unusual and have been described almost exclusively in human monocytic ehrlichiosis associated with Ehrlichia chaffeensis. We report here a case of a previously healthy 42-year-old woman who developed bilateral facial nerve palsies in association with infection by the agent of human granulocytic ehrlichiosis (aoHGE). The diagnosis was made by specific polymerase chain reaction amplification of aoHGE sequences from samples of the patient's blood and cerebrospinal fluid (CSF), as well as propagation of aoHGE in culture of HL60 cells inoculated with the patient's CSF To our knowledge, this is the first report directly demonstrating the presence of aoHGE in CSF, and it underscores the importance of considering HGE in patients presenting with a nonspecific febrile illness and unexplained neurologic manifestations. HGE should also be considered in the differential diagnosis of bilateral facial palsy-a rare occurrence. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. New York State Dept Hlth, David Axelrod Inst, Albany, NY USA. Lahey Hitchcock Clin, Dept Neurol, Burlington, MA USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Wessels, MR (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. NR 19 TC 13 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 2000 VL 31 IS 5 BP 1288 EP 1291 DI 10.1086/317466 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 380LY UT WOS:000165704400032 PM 11073767 ER PT J AU Hoeffel, DP Rubash, HE AF Hoeffel, DP Rubash, HE TI Revision total knee arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID REPLACEMENT; RECONSTRUCTION; AUGMENTATION AB Revision total knee arthroplasty often requires solutions for the multiple complexities that exist on the femoral side, including the treatment of bone loss, component position, ligamentous laxity, and component stability, Surgical decisions regarding the proper use of bone grafts, component augmentation, proper axial and rotational alignment, and femoral stems must be addressed systematically to achieve consistently successful outcomes. A review of currently used femoral revision techniques and their rationale and a classification system of femoral deficiencies designed to guide the surgical decision making process are presented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Rubash, HE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gray 606, Boston, MA 02114 USA. NR 55 TC 23 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2000 IS 380 BP 116 EP 132 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 367PV UT WOS:000090071400017 PM 11064981 ER PT J AU Feinstein, AR Heinemann, LAJ Dalessio, D Fox, JM Goldstein, J Haag, G Ladewig, D O'Brien, CP AF Feinstein, AR Heinemann, LAJ Dalessio, D Fox, JM Goldstein, J Haag, G Ladewig, D O'Brien, CP CA Ad Hoc Review Comm TI Do caffeine-containing analgesics promote dependence? A review and evaluation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID DOUBLE-BLIND; PHYSICAL-DEPENDENCE; PSYCHOMOTOR PERFORMANCE; INDIVIDUAL-DIFFERENCES; CEREBRAL METABOLISM; NUCLEUS-ACCUMBENS; COFFEE-DRINKERS; HEADACHE PAIN; WITHDRAWAL; MOOD AB Objective: Debates about the suspected association between kidney disease and use of analgesics have led to concern about whether caffeine could stimulate an undesirable overuse of phenacetin-free combined analgesics. A committee was asked to critically review the pertinent literature and to suggest guides for clinical practice and for consideration of international regulatory authorities. Participants: A group of international scientists, jointly selected by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry. Evidence: All invited experts evaluated relevant literature and reports and added further information and comments. Conclusions Caffeine has a synergistic effectiveness with analgesics. Although caffeine has a dependence potential, the potential is low. Experimental data regarding dependence potential for caffeine alone may not correspond to the conditions in patients with pain. Withdrawal is not likely to cause stimulation or sustainment of analgesic intake. For drug-induced headache, no single or combined analgesic was consistently identified as causative, and no evidence exists for a special role of caffeine. Strong dependence behavior was observed only in patients using phenacetin-containing preparations, coformulated with antipyretics/analgesics and caffeine. This finding may have led to the impression that caffeine stimulates overuse of analgesics, Summary: Although more experimental and long-term data would be desirable to show possible mechanisms of dependence and to offer unequivocal proof of safety, the committee concluded that the available evidence does not support the claim that analgesics coformulated with caffeine, in the absence of phenacetin, stimulate or sustain overuse. C1 Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. ZEG, Ctr Epidemiol & Hlth Res, Berlin, Germany. Scripps Clin & Res Fdn, Div Neurol, La Jolla, CA 92037 USA. Univ Saar, Fac Theoret Med, Frankfurt, Germany. Merz & Co GmbH & Co, Frankfurt, Germany. San Francisco Clin Res Ctr, SF Headache Clin, San Francisco, CA USA. Elztal Klin, Basel, Switzerland. Elzach Oberprechtal, Basel, Switzerland. Univ Basel, Psychiat Klin, Basel, Switzerland. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Feinstein, AR (reprint author), Yale Univ, Sch Med, Dept Med, 333 Cedar St,Room I,456 SHM, New Haven, CT 06510 USA. NR 122 TC 24 Z9 26 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2000 VL 68 IS 5 BP 457 EP 467 DI 10.1067/mcp.2000.110974 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 377TY UT WOS:000165543400001 PM 11103748 ER PT J AU Buckley, TC Blanchard, EB Neill, WT AF Buckley, TC Blanchard, EB Neill, WT TI Information processing and PTSD: A review of the empirical literature SO CLINICAL PSYCHOLOGY REVIEW LA English DT Review DE information-processing; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; MOTOR-VEHICLE ACCIDENTS; GENERALIZED SOCIAL PHOBIA; VIETNAM COMBAT VETERANS; SHORT-TERM-MEMORY; AUTOBIOGRAPHICAL MEMORY; RAPE VICTIMS; THREAT CUES; PHYSIOLOGICAL-RESPONSES; EMOTIONAL INFORMATION AB This article reviews a series of studies that have utilized information-processing paradigms with posttraumatic stress disorder (PTSD) populations. The review suggests that pretrauma measures of intelligence (IQ) are predictive of the development of PTSD symptoms following trauma. There is also evidence of impaired performance on standardized texts of memory (independent of IQ) in PTSD populations. PTSD populations are found to exhibit deficits in memory function that may be due to hippocampus damage secondary to excessive neuroendocrine responses to conditioned stimuli. In addition, individuals with PTSD evince an attentional bias towards trauma-related stimuli at postrecognition stages of information processing. The review also includes that there is insufficient evidence to either support, or reject, the theoretical proposition that PTSD patients are sensitive to global valence effects at the earliest stages of information processing relative to traumatized non-PTSD populations. Finally, there is some evidence to suggest that the process associated with autobiographical memory in PTSD populations are similar to those seen in depression. The implications of these findings for the behavioral and cognitive treatment of PTSD are discussed. Directions for future research with such paradigms are also discussed in light of contemporary information processing theories of PTSD. (C) 2000 Elsevier Science Ltd. C1 Natl Ctr PTSD, VA Boston Healthcare Syst, Behav Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. SUNY Albany, Albany, NY 12222 USA. RP Buckley, TC (reprint author), Natl Ctr PTSD, VA Boston Healthcare Syst, Behav Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. NR 99 TC 205 Z9 210 U1 9 U2 43 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD NOV PY 2000 VL 20 IS 8 BP 1041 EP 1065 DI 10.1016/S0272-7358(99)00030-6 PG 25 WC Psychology, Clinical SC Psychology GA 372JD UT WOS:000165229800005 PM 11098399 ER PT J AU Walker, WA AF Walker, WA TI Immunology SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, 149 13th St,Room 3401, Charlestown, MA 02129 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 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2000 VL 16 IS 6 BP 527 EP 530 DI 10.1097/00001574-200011000-00011 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365UY UT WOS:000089969900011 ER PT J AU Fischman, AJ Bonab, AA Rubin, RH AF Fischman, AJ Bonab, AA Rubin, RH TI Regional pharmacokinetics of orally administered PET tracers SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; HEALTHY-HUMAN SUBJECTS; RECEPTOR OCCUPANCY; SCHIZOPHRENIC-PATIENTS; F-18 FLEROXACIN; RACLOPRIDE; CLOZAPINE; BINDING; D-2 AB Positron emission tomography (PET) is currently the most useful imaging technique for noninvasive measurement of drug pharmacokinetics regionally in a variety of tissues. Over the past decade, PET measurements have provided many critical insights about the tissue distribution of several classes of drugs; neuro leptics, antimicrobials, antineoplastics, etc. PET measurements can be performed after any route of drug administration, intravenous, inhalation or oral, however, intravenously administered drugs have been the most extensively evaluated. Studies of orally administered drugs are clearly of great interest; however, formulation issues have precluded widespread applications in these areas. In this report, we discuss the unique problems associated with studying orally administered drugs and review the results of recent studies performed in our laboratory. C1 Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, MIT, Ctr Expt Pharmacol & Therapeut, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2000 VL 6 IS 16 BP 1625 EP 1629 DI 10.2174/1381612003398771 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 363MB UT WOS:000089838500005 PM 10974157 ER PT J AU Brouns, MR Matheson, SF Hu, KQ Delalle, I Caviness, VS Silver, J Bronson, RT Settleman, J AF Brouns, MR Matheson, SF Hu, KQ Delalle, I Caviness, VS Silver, J Bronson, RT Settleman, J TI The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development SO DEVELOPMENT LA English DT Article DE Rho GTPase; morphogenesis; signal transduction; actin; PKC; cell adhesion; mouse ID PROTEIN-KINASE-C; CELL-ADHESION; TYROSINE PHOSPHORYLATION; EMBRYONIC-DEVELOPMENT; EXTRACELLULAR-MATRIX; ACTIN CYTOSKELETON; TUBE DEFECTS; N-CADHERIN; IN-VITRO; GTPASE AB Rho GTPases direct actin rearrangements in response to a variety of extracellular signals. P190 RhoGAP (GTPase activating protein) is a potent Rho regulator that mediates integrin-dependent adhesion signaling in cultured cells. We have determined that p190 RhoGAP is specifically expressed at high levels throughout the developing nervous system. Mice lacking functional p190 RhoGAP exhibit several defects in neural development that are reminiscent of those described in mice lacking certain mediators of neural cell adhesion. The defects reflect aberrant tissue morphogenesis and include abnormalities in forebrain hemisphere fusion, ventricle shape, optic cup formation, neural tube closure, and layering of the cerebral cortex. In cells of the neural tube floor plate of p190 RhoGAP mutant mice, polymerized actin accumulates excessively, suggesting a role for p190 RhoGAP in the regulation of Rho-mediated actin assembly within the neuroepithelium. Significantly, several of the observed tissue fusion defects seen in the mutant mice are also found in mice lacking MARCKS, the major substrate of protein kinase C (PKC), and we have found that p190 RhoGAP is also a PKC substrate in vivo. Upon either direct activation of PKC or in response to integrin engagement, p190 RhoGAP is rapidly translocated to regions of membrane ruffling, where it colocalizes with polymerized actin, Together, these results suggest that upon activation of neural adhesion molecules, the action of PKC and p190 RhoGAP leads to a modulation of Rho GTPase activity to direct several actin-dependent morphogenetic processes required for normal neural development. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Dept Pathol, Boston, MA 02111 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. OI Matheson, Stephen/0000-0003-0561-8152 NR 54 TC 159 Z9 159 U1 0 U2 5 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 NOV PY 2000 VL 127 IS 22 BP 4891 EP 4903 PG 13 WC Developmental Biology SC Developmental Biology GA 381GN UT WOS:000165754100014 PM 11044403 ER PT J AU Kagoshima, H Sommer, R Reinhart, BJ Cassata, G Ruvkun, G Burglin, TR AF Kagoshima, H Sommer, R Reinhart, BJ Cassata, G Ruvkun, G Burglin, TR TI Graded expression of ceh-14 reporters in the hypodermis is induced by a gonadal signal SO DEVELOPMENT GENES AND EVOLUTION LA English DT Article DE LIM homeobox gene; ceh-14; gradient expression; gonadal signal ID CAENORHABDITIS-ELEGANS; C-ELEGANS; VULVAR DEVELOPMENT; MIGRATION; MUTATIONS; ENCODES; GENES AB Caenorhabditis elegans, is the orthologue of the vertebrate Lhx3/Lhx4 genes. ceh-14 reporter constructs are expressed in several different cell types: head and tail neurons, spermatheca and hypodermis. An intriguing aspect of the hypodermal expression pattern is that it takes the form of a gradient which is strongest in the central body region in L4 to young adult hermaphrodites. Promoter deletion analyses revealed that important regulatory elements for hypodermal expression are located within the transcribed region of ceh-14. Since a large part of the hypodermis is a syncytium, we hypothesized that this expression is triggered in a non-cell-autonomous fashion, a possible source being the underlying gonad. In males, which have a different gonadal organisation, the ceh-14 reporter constructs are expressed in a gradient that is strongest in the tail. By laser ablation of the gonadal precursor cells we found that ceh-14 reporter construct expression is eliminated in the hermaphrodite hypodermis, suggesting that the gonad plays a role in the generation of the gradient. Several signaling pathways are known in the gonad and the vulva, thus we crossed the mutations lin-3, egl-17 and lin-12 with the ceh-14 reporter lines. However, the expression of the reporter constructs is not affected in these mutant backgrounds. This suggests that another, presently unknown, signal triggers the graded hypodermal expression. C1 Univ Basel, Biozentrum, Abt Zellbiol, CH-4056 Basel, Switzerland. Max Planck Inst Entwicklungsbiol, Abt Evolut Biol 4, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Burglin, TR (reprint author), Univ Basel, Biozentrum, Abt Zellbiol, Klingelbergstr 70, CH-4056 Basel, Switzerland. NR 24 TC 4 Z9 8 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-944X J9 DEV GENES EVOL JI Dev. Genes Evol. PD NOV PY 2000 VL 210 IS 11 BP 564 EP 569 DI 10.1007/s004270000099 PG 6 WC Cell Biology; Evolutionary Biology; Developmental Biology SC Cell Biology; Evolutionary Biology; Developmental Biology GA 375TB UT WOS:000165416400005 PM 11180807 ER PT J AU Clocquet, AR Egan, JM Stoffers, DA Muller, DC Wideman, L Chin, GA Clarke, WL Hanks, JB Habener, JF Elahi, D AF Clocquet, AR Egan, JM Stoffers, DA Muller, DC Wideman, L Chin, GA Clarke, WL Hanks, JB Habener, JF Elahi, D TI Impaired insulin secretion and increased insulin sensitivity in familial maturity-onset diabetes of the young 4 (Insulin promoter factor 1 gene) SO DIABETES LA English DT Article ID NUCLEAR FACTOR-1-ALPHA GENE; PANCREATIC BETA-CELLS; GLUCOKINASE GENE; GLUCOSE; MUTATIONS; TRANSCRIPTION; MELLITUS; DEFECT; MODY3; ACTIVATION AB Diabetes resulting from heterozygosity for an inactivating mutation of the homeodomain transcription factor insulin promoter factor 1 (IPF-1) is due to a genetic defect of beta -cell function referred to as maturity-onset diabetes of the young 4, IPF-1 is required for the development of the pancreas and mediates glucose-responsive stimulation of insulin gene transcription. To quantitate islet cell responses in a family harboring a Pro63fsdelC mutation in IPF-1, we performed a five-step (1-h intervals) hyperglycemic clamp on seven heterozygous members (NM) and eight normal genotype members (NN), During the last 30 min of the fifth glucose step, glucagon-like peptide 1 (GLP-1) was also infused (1.5 pmol . kg(-1) . min(-1)). Fasting plasma glucose levels were greater in the NM group than in the NN group (9.2 vs. 5.9 mmol/l, respectively; P < 0.05). Fasting insulin levels were similar in both groups (72 vs. 105 pmol/l for NN vs. NM, respectively). First-phase insulin and C-peptide responses were absent in individuals in the NM group, who had markedly attenuated insulin responses to glucose alone compared with the NN group, At a glucose level of 16.8 mmol/l above fasting level, GLP-1 augmented insulin secretion equivalently (fold increase) in both groups, but the insulin and C-peptide responses to GLP-1 were sevenfold less in the NM subjects than in the NN subjects. In both groups, glucagon levels fell during each glycemic plateau, and a further reduction occurred during the GLP-1 infusion, Sigmoidal dose-response curves of glucose clearance versus insulin levels during the hyperglycemic clamp in the two small groups showed both a left shift and a lower maximal response in the NM group compared with the NN group, which is consistent with an increased insulin sensitivity in the NM subjects, A sharp decline occurred in the dose-response curve for suppression of nonesterified fatty acids versus insulin levels in the NM group. We conclude that the Pro63fsdelC IPF-1 mutation is associated with a severe impairment of -cell sensitivity to glucose and an apparent increase in peripheral tissue sensitivity to insulin and is a genetically determined cause of beta -cell dysfunction. C1 Massachusetts Gen Hosp, Geriatr Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA USA. Univ Virginia, Hlth Sci Ctr, Dept Pediat, Charlottesville, VA USA. Univ Virginia, Hlth Sci Ctr, Dept Surg, Charlottesville, VA 22908 USA. RP Elahi, D (reprint author), Massachusetts Gen Hosp, Geriatr Res Lab, GRB SB 0015,55 Fruit St, Boston, MA 02114 USA. RI Stoffers, Doris/H-6157-2012 FU NIA NIH HHS [AG-00599]; NIDDK NIH HHS [DK-30834, DK-30457] NR 37 TC 44 Z9 49 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2000 VL 49 IS 11 BP 1856 EP 1864 DI 10.2337/diabetes.49.11.1856 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 370LC UT WOS:000165123700013 PM 11078452 ER PT J AU Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Melancon, LE Morris, LH Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tucker, E Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Tobian, JA Matulik, MJ Clarke, B Collins, DA Czech, KB DeSandre, C Ehrmann, DA Geiger, G Harding-Clay, B Hilbrich, RM McNabb, WL Polonsky, KS Semenske, AR Stepp, KA Watson, PG Mendoza, JT Smith, KA Goldstein, BJ Lark, C Liberoni, R Murphy, L Pepe, C Spandorfer, JM Goldberg, RB Rowe, P Calles, J Casanova, P Donahue, RP Florez, HJ Giannella, A McLymont, V Mendez, J O'Hara, P Ojito, J Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Rozek, MM Hamman, RF Nash, PV Calonge, BN Hill, JO Hoyer, SR Jortberg, BT Miller-Stone, M Regensteiner, JG Seagle, H Steinke, SC Testaverde, L Van-Dorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaghan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Fujimoto, WY Knopp, RH Lipkin, EW Marr, M McCann, BS Nguyen, TT Palmer, JP Schwartz, RS Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Crisler, A Cunningham, G Franklin, AW Frieson, SL Green, DL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Ricks, H Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Behrends, C Cook, ML Fitzgibbon, M Heard, D McPherson, D Molitch, ME Moore, M Pitts, T Roston, S Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Bissett, L Cagliero, E Crowell, S Delahanty, L Fritz, S Levina, E Michel, T Norman, D O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Turgeon, H Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel-Mills, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio-Hurley, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Marrero, DG Kukman-Kelly, MS Dotson, YF Fineberg, SE Guare, JC Hadden, A Ignaut, JM Jackson, MA Kirkman, MS Porter, BD Prince, MJ Wheeler, ML Ratner, RE Youssef, G Boner, A Bronsord, M Brown, E Cheatham, WW Cola, S Comfort, A Boggs, G Evans, C Levetan, C Kellum, T Nair, AK Passaro, MD Rubin, R Shapiro, S Saad, MF Budgett, M Jinagouda, SD Aziz, A Bernaba, B Bodkin, SL Ciobanu, V Cosenza, C Hagar, JE Khan, A Kumar, D Khawaja, Q Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AS Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Butler, L Canady, JL Chai, L Guillen, M Gutierrez, M Hornbeck, D Johannes, C Katz, P King, C McCalman, R Montoya, DA Rassam, A Senter, W Shamoon, H Brown, JO Adames, J Blanco, E Cox, L Duffy, H Engel, S Friedler, A Harroun, T Howard-Century, CJ Kloiber, S Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Gilligan, R Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, TJ Otto, A Smith, M Stapinski, V Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Cooeyate, NJ Hoskin, MA Percy, CA Acton, KJ Andre, VL Antone, S Baptisto, NM Barber, R Bennett, PH Benson, MB Bird, EC Broussard, BA Chavez, M Dacawyma, TS Duncan, R Ghahate, JM Glass, M Gohdes, D Grant, G Hanson, RL Horse, E Hughte, G Ingraham, LE Jackson, MC Jay, PA Kaskalla, RS Kessler, D Kobus, KM Morgan, T Nashboo, Y Poirier, S Reidy, M Ridpath, S Roumain, J Rowse, DH Roy, RJ Sangster, S Sewemaenewa, J Wilson, C Yazzie, M Fowler, S Bain, R Bamdad, J Brenneman, T Callaghan, J Edelstein, SL Grimes, KL Jones, S Jones, TL Lachin, JM Mucik, P Orlosky, R Stimpson, CE Suiter, C Temprosa, E Van Aerden, C Eastman, R Garfield, S Andres, R Engelgau, MM Narayan, KMV Williamson, DF Herman, WH Marcovina, SM Aldrich, A Chandler, WL Rautaharju, PM Alexander, T Pemberton, NT Prineas, R Rautaharju, FSR Zhang, Z Mayer-Davis, EJ Martin, M O'Leary, DH Funk, LRC O'Leary, KA Polak, JF Stamm, ER Scherzinger, AL Wing, RR Gillis, BP Kriska, AM Huffmyer, C Venditti, EM Kaplan, RM David, KM Sieber, WJ AF Bray, GA Culbert, IW Champagne, CM Dawson, L Eberhardt, B Greenway, FL Guillory, FG Hebert, AA Jeffirs, ML Kennedy, BM Lovejoy, JC Melancon, LE Morris, LH Reed, L Perault, J Ryan, DH Sanford, DA Smith, KG Smith, LL St Amant, JA Tucker, E Tulley, RT Vicknair, PC Williamson, D Zachwieja, JJ Tobian, JA Matulik, MJ Clarke, B Collins, DA Czech, KB DeSandre, C Ehrmann, DA Geiger, G Harding-Clay, B Hilbrich, RM McNabb, WL Polonsky, KS Semenske, AR Stepp, KA Watson, PG Mendoza, JT Smith, KA Goldstein, BJ Lark, C Liberoni, R Murphy, L Pepe, C Spandorfer, JM Goldberg, RB Rowe, P Calles, J Casanova, P Donahue, RP Florez, HJ Giannella, A McLymont, V Mendez, J O'Hara, P Ojito, J Prineas, R Haffner, SM Montez, MG Miettinen, H Mobley, CM Mykkanen, LA Rozek, MM Hamman, RF Nash, PV Calonge, BN Hill, JO Hoyer, SR Jortberg, BT Miller-Stone, M Regensteiner, JG Seagle, H Steinke, SC Testaverde, L Van-Dorsten, B Horton, ES Lawton, KE Arky, RA Bryant, M Burke, JP Caballero, E Callaghan, KM Ganda, OP Franklin, T Jackson, SD Jacobsen, AM Kula, LM Kocal, M Malloy, MA Nicosia, M Oldmixon, CF Pan, J Quitingon, M Rubtchinsky, S Seely, EW Schweizer, D Simonson, D Smith, F Solomon, CG Warram, J Kahn, SE Montgomery, BK Fujimoto, WY Knopp, RH Lipkin, EW Marr, M McCann, BS Nguyen, TT Palmer, JP Schwartz, RS Kitabchi, AE Murphy, ME Applegate, WB Bryer-Ash, M Crisler, A Cunningham, G Franklin, AW Frieson, SL Green, DL Imseis, R Kennedy, CL Lambeth, HC Lichtermann, LC Oktaei, H O'Toole, ML Ricks, H Rutledge, LMK Sherman, AR Smith, CM Soberman, JE Williams-Cleaves, BJ Metzger, BE Johnson, MK Behrends, C Cook, ML Fitzgibbon, M Heard, D McPherson, D Molitch, ME Moore, M Pitts, T Roston, S Schinleber, PA Nathan, DM McKitrick, C Abbott, K Anderson, E Bissett, L Cagliero, E Crowell, S Delahanty, L Fritz, S Levina, E Michel, T Norman, D O'Keefe, J Poulos, A Ronan, L Rosal, M Salerno, M Shagensky, C Steiner, B Turgeon, H Young, A Olefsky, JM Carrion-Petersen, ML Barrett-Connor, E Beltran, M Caenepeel-Mills, K Edelman, SV Ford, RO Garcia, J Henry, RR Hill, M Horne, J Leos, D Mudaliar, S Pollard, A Torio-Hurley, J Pi-Sunyer, FX Lee, JE Allison, DB Aronoff, NJ Barreras, IM Crandall, JP Orlando, SJ Parkes, K Rooney, ES Van Wye, GEH Viscovich, KA Marrero, DG Kukman-Kelly, MS Dotson, YF Fineberg, SE Guare, JC Hadden, A Ignaut, JM Jackson, MA Kirkman, MS Porter, BD Prince, MJ Wheeler, ML Ratner, RE Youssef, G Boner, A Bronsord, M Brown, E Cheatham, WW Cola, S Comfort, A Boggs, G Evans, C Levetan, C Kellum, T Nair, AK Passaro, MD Rubin, R Shapiro, S Saad, MF Budgett, M Jinagouda, SD Aziz, A Bernaba, B Bodkin, SL Ciobanu, V Cosenza, C Hagar, JE Khan, A Kumar, D Khawaja, Q Lui, G Marston, AR Mehta, V Sharma, AR Szamos, K Vargas, A Vargas, B Zambrana, N Dagogo-Jack, S Santiago, AS Brendle, JS Fisher, EB Gherardini, DC Heins, JM Marsala, JM Raspberry, CC Santiago, JV Saudek, CD Bradley, VL Brancati, FL Cappelli, S Charleston, JB Rubin, RR Stewart, KJ Sullivan, E Schade, DS Adams, KS Atler, LF Bowling, DA Boyle, PJ Burge, MR Butler, L Canady, JL Chai, L Guillen, M Gutierrez, M Hornbeck, D Johannes, C Katz, P King, C McCalman, R Montoya, DA Rassam, A Senter, W Shamoon, H Brown, JO Adames, J Blanco, E Cox, L Duffy, H Engel, S Friedler, A Harroun, T Howard-Century, CJ Kloiber, S Longchamp, N Pompi, D Walker, EA Wylie-Rosett, J Zonszein, J Wing, RR Kramer, MK Barr, S Clifford, L Culyba, R Frazier, M Gilligan, R Harris, L Harrier, S Henderson, W Jeffries, S Koenning, G Maholic, K Mullen, M Noel, A Orchard, TJ Otto, A Smith, M Stapinski, V Viteri, J Wilson, T Williams, KV Zgibor, J Arakaki, RF Latimer, RW Baker-Ladao, NK Beddow, RM Dias, LM Dupont, DA Fukuhara, LL Mau, MK Odom, SK Perry, RU Tokunaga, JS Knowler, WC Cooeyate, NJ Hoskin, MA Percy, CA Acton, KJ Andre, VL Antone, S Baptisto, NM Barber, R Bennett, PH Benson, MB Bird, EC Broussard, BA Chavez, M Dacawyma, TS Duncan, R Ghahate, JM Glass, M Gohdes, D Grant, G Hanson, RL Horse, E Hughte, G Ingraham, LE Jackson, MC Jay, PA Kaskalla, RS Kessler, D Kobus, KM Morgan, T Nashboo, Y Poirier, S Reidy, M Ridpath, S Roumain, J Rowse, DH Roy, RJ Sangster, S Sewemaenewa, J Wilson, C Yazzie, M Fowler, S Bain, R Bamdad, J Brenneman, T Callaghan, J Edelstein, SL Grimes, KL Jones, S Jones, TL Lachin, JM Mucik, P Orlosky, R Stimpson, CE Suiter, C Temprosa, E Van Aerden, C Eastman, R Garfield, S Andres, R Engelgau, MM Narayan, KMV Williamson, DF Herman, WH Marcovina, SM Aldrich, A Chandler, WL Rautaharju, PM Alexander, T Pemberton, NT Prineas, R Rautaharju, FSR Zhang, Z Mayer-Davis, EJ Martin, M O'Leary, DH Funk, LRC O'Leary, KA Polak, JF Stamm, ER Scherzinger, AL Wing, RR Gillis, BP Kriska, AM Huffmyer, C Venditti, EM Kaplan, RM David, KM Sieber, WJ CA Diabet Prevention Program Res Grp TI The Diabetes Prevention Program - Baseline characteristics of the randomized cohort SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; 10-YEAR FOLLOW-UP; FAT DISTRIBUTION; PIMA-INDIANS; MELLITUS; INSULIN; MEN; NIDDM; DIET; CLASSIFICATION AB OBJECTIVE - The Diabetes Prevention Program (DPP) is a 27-center randomized clinical trial designed to evaluate the safety and efficacy of interventions that may delay or prevent development of diabetes in people at increased risk for type 2 diabetes. RESEARCH DESIGN AND METHODS - Eligibility requirements were age greater than or equal to 25 years, BMI greater than or equal to 24 kg/m(2) (greater than or equal to 22 kg/m(2) for Asian-Americans), and impaired glucose tolerance plus a fasting plasma glucose of 5.3-6.9 mmol/l (or less than or equal to6.9 mmol for American Indians). Randomization of participants into the DPP over 2.7 years ended in June 1999. Baseline data for the three treatment groups-intensive lifestyle modification, standard care plus metformin, and standard care plus placebo-are presented for the 3,234 participants who have been randomized. RESULTS - Of all participants, 55% were Caucasian, 20% were African-American, 16% were Hispanic, 5% were American Indian, and 4% were Asian-American. Their average age at entry was 51 +/- 10.7 years (mean +/- SD), and 67.7% were women. Moreover, 16% were <40 years of age, and 20% were 60 years of age. Of the women, 48% were postmenopausal. Men and women had similar frequencies of history of hypercholesterolemia (37 and 33%, respectively) or hypertension (29 and 26%, respectively). On the basis of fasting lipid determinations, 54% of men and 40% of women fit National Cholesterol Education Program criteria for abnormal lipid profiles. More men than women were current or former cigarette smokers or had a history of coronary heart disease. Furthermore, 66% of men and 71% of women had a first-degree relative with diabetes. Overall, BMI averaged 34.0 +/- 6.7 kg/m(2) at baseline with 57% of the men and 73% of women having a BMI greater than or equal to 30 kg/m(2). Average fasting plasma glucose (6.0 +/- 0.5 mmol/l) and HbA(1c) (5.9 +/- 0.5%) in men were comparable with values in women (5.9 +/- 0.4 mmol/l and 5.9 +/- 0.5%, respectively). CONCLUSIONS - The DPP has successfully randomized a large cohort of participants with a wide distribution of age, obesity, and ethnic and racial backgrounds who are at high risk for developing type 2 diabetes. The study will examine the effects of interventions on the development of diabetes. C1 George Washington Univ, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Chicago, Chicago, IL 60637 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Univ Miami, Coral Gables, FL 33124 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Univ Colorado, Boulder, CO 80309 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Tennessee, Knoxville, TN 37996 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Indiana Univ, Bloomington, IN 47405 USA. Medstar Res Inst, New York, NY USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Hawaii, Honolulu, HI 96822 USA. George Washington Univ, Ctr Biostat, Data Coordinating Ctr, Washington, DC 20052 USA. NIDDKD, Program Off, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Wake Forest Univ, Sch Med, Epicare Ctr, Winston Salem, NC 27109 USA. Univ S Carolina, Nutr Coding Ctr, Columbia, SC 29208 USA. New England Med Ctr, Cent Carotid Ultrasound Unit, Boston, MA 02111 USA. Univ Colorado, Hlth Sci Ctr, CT Scan Reading Unit, Boulder, CO 80309 USA. Univ Calif San Diego, Qual Well Being Reading Unit, San Diego, CA 92103 USA. RP Bray, GA (reprint author), George Washington Univ, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 48 TC 125 Z9 127 U1 0 U2 11 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2000 VL 23 IS 11 BP 1619 EP 1629 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368FD UT WOS:000090106300004 ER PT J AU Horton, ES Clinkingbeard, C Gatlin, M Foley, J Mallows, S Shen, S AF Horton, ES Clinkingbeard, C Gatlin, M Foley, J Mallows, S Shen, S TI Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes SO DIABETES CARE LA English DT Article ID ORAL HYPOGLYCEMIC AGENTS; INSULIN-RESISTANCE; DOUBLE-BLIND; EFFICACY; MELLITUS; TRIAL; NIDDM AB OBJECTIVE - To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA(1c), fasting plasma glucose (FPG), and mealtime glucose excursions. RESEARCH DESIGN AND METHODS - In this randomized double-blind study, patients with an HbA(1c) level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mp nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA(1c) and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded. RESULTS - At study end point, HbA(1c) was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P less than or equal to 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P less than or equal to 0.0001). Combination therapy was additive (HbA(1c) -1.4% and FPG -2.4 mmol/l; P less than or equal to 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUCl(0-130min) - 2.1, - 1.1, and -0.6 mmol . h(-1) . l(-1); P less than or equal to 0.0001). An even greater effect was observed with combination therapy (AUC(0-130min) -2.5 mmol . h(-1) . l(-1); P less than or equal to 0.0001 vs. metformin and placebo). All regimens were well tolerated. CONCLUSIONS - Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas rnetformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA(1c), FPG, and postprandial hyperglycemia. C1 Idaho Endocrine Specialists, Boise, ID USA. Novartis Pharmaceut, Cardiovasc Metab & Endocrine Dept, Div Clin Res, E Hanover, NJ USA. Novartis Pharmaceut, Div Biostat, E Hanover, NJ USA. RP Horton, ES (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 24 TC 148 Z9 157 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2000 VL 23 IS 11 BP 1660 EP 1665 DI 10.2337/diacare.23.11.1660 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368FD UT WOS:000090106300010 PM 11092289 ER PT J AU Feng, DL Bursell, SE Clermont, AC Lipinska, I Aiello, LP Laffel, L King, GL Tofler, GH AF Feng, DL Bursell, SE Clermont, AC Lipinska, I Aiello, LP Laffel, L King, GL Tofler, GH TI von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes SO DIABETES CARE LA English DT Article ID BLOOD-FLOW; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; VONWILLEBRAND-FACTOR; MELLITUS; PLASMA; DAMAGE; ABNORMALITIES; HEMODYNAMICS AB OBJECTIVE - Although retinopathy is a common microvascular complication of type 1 diabetes, the mechanism for this complication is still unknown. Changes in retinal, circulation have been noted before the development of overt retinal pathology, Because von Willebrand factor (VWF) is a marker for endothelial dysfunction and mediates platelet adhesion, we determined if there was an association between VWF and retinal. circulation in the early stages of diabetic retinopathy. RESEARCH DESIGN AMID METHODS - Twenty subjects (aged 32.4 +/- 7.8 years) with type 1 diabetes and minimal or no retinopathy were studied. The mean duration of diabetes was 4.7 +/- 2.6 years. Data were collected at baseline and after 4 months of 1,800 IU vitamin E therapy or placebo. Retinal circulation was evaluated by video fluorescein angiography. Plasma vWF antigen levers were measured by enzyme-linked immunosorbent assay and fibrinogen by the Clauss method. RESULTS - Retinal blood flow was negatively correlated with vWF levels (r = -0.44 P = 0.008), whereas retinal circulation time was positively correlated with vWF levels (r = 0.33, P = 0.048). Fibrinogen levels were not significantly associated with either retinal index. How ever, fibrinogen levels were positively associated with HbA(1c) levels (r = 0.34, P = 0.01), indicating an association between poor glycemic control and higher fibrinogen levels. CONCLUSIONS - Increased vWF was associated with a prolonged retinal circulation time and reduced retinal blood flow in early-stage retinopathy of type 1 diabetes. Reduced blood flow associated with increased vWF levels may promote stasis in the retinal circulation and lead to local hypoxemia. These changes might contribute to the microvascular complications of diabetes. Whether the VWF levels predict retinal complications deserves further investigation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Royal N Shore Hosp, Sydney, NSW, Australia. RP Feng, DL (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Inst Prevent Cardiovasc Dis, 1 Autumn St,5th Floor, Boston, MA 02215 USA. NR 32 TC 20 Z9 20 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2000 VL 23 IS 11 BP 1694 EP 1698 DI 10.2337/diacare.23.11.1694 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 368FD UT WOS:000090106300015 PM 11092294 ER PT J AU Lark, RL Chenoweth, C Saint, S Zemencuk, JK Lipsky, BA Plorde, JJ AF Lark, RL Chenoweth, C Saint, S Zemencuk, JK Lipsky, BA Plorde, JJ TI Four year prospective evaluation of nosocomial bacteremia: epidemiology, microbiology, and patient outcome SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID BLOOD-STREAM INFECTIONS; CENTRAL VENOUS CATHETERS; ATTRIBUTABLE MORTALITY; CLINICAL-SIGNIFICANCE; COMPREHENSIVE ANALYSIS; UNITED-STATES; EXCESS LENGTH; 500 EPISODES; CULTURES; CANDIDEMIA AB A prospective study of all patients with clinically significant nosocomial bacteremia at one institution from 1994 to 1997 was performed to: (1) describe the epidemiology and microbiology of nosocomial bacteremias; (2) determine the crude mortality associated with such infections; and (3) identify independent predictors of mortality. Four hundred four episodes of bacteremia occurred in 322 patients; the crude in-hospital mortality was 31%. Coagulase-negative staphylococci, Staphylococcus aureus, and enterococci were the leading pathogens, and intravascular catheters were the mast frequently identified source. The highest mortality occurred in patients with candidemia (67%). Independent predictors of mortality included evidence of shock at the time of infection, acquisition of bacteremia in an intensive care unit, a ''Do Not Attempt Resuscitation" order, and the presence of certain comorbid conditions (e.g., malignancy, HIV infection). Because many of these infections may be preventable, education of health care providers and strict adherence to established infection control practices are critical. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Michigan, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Infect Control & Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA. Ann Arbor VA Hlth Serv, Res & Dev & Field Program, Ctr Practice Management & Outcomes Res, Ann Arbor, MI 48109 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98104 USA. Univ Washington, Dept Med, Div Infect Dis, Seattle, WA 98195 USA. RP Chenoweth, C (reprint author), Univ Michigan Hlth Syst, Div Infect Dis, 1500 E Med Ctr Dr,3116 TC, Ann Arbor, MI 48109 USA. RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Lipsky, Benjamin A./0000-0001-9886-5114 NR 26 TC 52 Z9 57 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD NOV PY 2000 VL 38 IS 3 BP 131 EP 140 DI 10.1016/S0732-8893(00)00192-9 PG 10 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 383VD UT WOS:000165903000001 PM 11109010 ER PT J AU Goldberg, RT Goldstein, R AF Goldberg, RT Goldstein, R TI A comparison of chronic pain patients and controls on traumatic events in childhood SO DISABILITY AND REHABILITATION LA English DT Article ID CHRONIC PELVIC PAIN; SEXUAL ABUSE; PSYCHIATRIC DIAGNOSES; WOMEN; FIBROMYALGIA; HISTORY; STRESS AB Purpose : The purpose was to examine the incidence of traumatic events in childhood, such as sexual and physical abuse, in a chronic pain group and a control group of hospital employees without chronic pain. Method: Ninety two patients with chronic pain, age range 20-62, were consecutively recruited from the outpatient clinics of a rehabilitation hospital and a general hospital. Ninety eight hospital employees, age range 20-62, were consecutively recruited from the employee health office of a rehabilitation hospital. All participants responded to nine questions related to sexual, physical and verbal abuse in childhood and completed the Childhood Traumatic Events Scale. A logistic regression with age, gender, sexual, physical, and verbal abuse, death of a family member, childhood illness, major upheaval before age 17, as independent variables were used to predict membership in the pain group contrasted with the control group. Results : Child abuse was reported in the childhood history by 54.4% of the chronic pain group, compared with 21.4% of the control group. A logistic regression showed that after adjusting for gender and age, sexual and verbal abuse were statistically significant predictors of being a member of the pain group. Odds ratios were sexual abuse: 2.67, p<0.05, CI 1.00-7.14. Verbal abuse: 4.39, p<0.001, CI 1.93-9.97. A logistic regression was modelled to predict child abuse when gender was taken into account. The results of the logistic regression showed that pain was a significant predictor for sexual abuse after adjusting for gender and age : odds ratio 4.37, p<0.001, CI 1.80-10.60. Gender was not a statistically significant predictor for sexual abuse, after adjusting for pain and age : odds ratio 2.92, p<0.072, CI 0.91-9.42. Conclusions : A history of physical, sexual and verbal abuse is more likely to occur in a chronic pain group than in a control group of hospital employees. Although child abuse is reported to be as high as 25% in the general American population, the statistics for chronic pain patients are twice as high as in the general population. The mechanisms for abuse include age, gender, and early family environment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp,Dept Pediat, Boston, MA 02114 USA. Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. RP Goldberg, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp,Dept Pediat, Boston, MA 02114 USA. NR 22 TC 18 Z9 18 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PD NOV PY 2000 VL 22 IS 17 BP 756 EP 763 DI 10.1080/09638280050200250 PG 8 WC Rehabilitation SC Rehabilitation GA 378QN UT WOS:000165595200002 PM 11194616 ER PT J AU Gariti, P Alterman, AI Mulvaney, FD Epperson, L AF Gariti, P Alterman, AI Mulvaney, FD Epperson, L TI The relationship between psychopathology and smoking cessation treatment response SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE smokers; psychiatric diagnosis; patch treatment; mental disorder; DSM-IV ID NICOTINE PATCH; MAJOR DEPRESSION; CIGARETTE-SMOKING; DRUG PROBLEMS; SMOKERS; ALCOHOL; RELIABILITY; DISORDER; HISTORY; TOBACCO AB The study evaluated the relationship of psychopathology to treatment response of 208 smokers prescribed transdermal nicotine (8 weeks). Participants were relatively high functioning (DSM-IV axis V score) outpatients in a university-based clinic. The primary study objective was to determine whether patients with a history of either a DSM-IV axis I or II diagnosis would have poorer during treatment response (patch adherence, smoking) and lower rates of smoking cessation at post-patch follow-up (study weeks 9, 26, 52) than those without a diagnosis. While there was some indication that patients with a history of psychopathology wore the patch less Frequently, psychopathology was not associated with during- and post-treatment smoking. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gariti, P (reprint author), Univ Penn, Sch Med, Treatment Res Ctr, Dept Psychiat, 3900 Chesternut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA10070] NR 38 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2000 VL 60 IS 3 BP 267 EP 273 DI 10.1016/S0376-8716(00)00114-9 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 368AV UT WOS:000090096100006 PM 11053761 ER PT J AU Kitch, BT Levy, BD Fanta, CH AF Kitch, BT Levy, BD Fanta, CH TI Late onset asthma - Epidemiology, diagnosis and treatment SO DRUGS & AGING LA English DT Review ID GENERAL-POPULATION SAMPLE; OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED TRIAL; AIR-FLOW OBSTRUCTION; LONG-TERM TREATMENT; INHALED CORTICOSTEROIDS; OCCUPATIONAL ASTHMA; ELDERLY SUBJECTS; THERAPY; SMOKING AB Asthma is common among older persons, affecting approximately 4 to 8% of those above the age of 65 years. Despite its prevalence, late onset asthma may be misdiagnosed and inadequately treated, with important negative consequences for the patient's health. The histopathology of late onset disease appears to be similar to that of asthma in general, with persistent airway inflammation a characteristic feature. It is less clear, however, that allergic exposure and sensitisation play the same role in the development of disease in adults as they do in children. Atopy is less common among those with late onset asthma, and the prevalence of elevated immunoglobulin E levels is lower among those aged over 55 years of age than younger patients. Occupational asthma is an aetiological consideration unique to adult onset disease, with important implications for treatment. The differential diagnosis for cough, wheeze, and dyspnoea in the elderly is broad, and includes chronic obstructive bronchitis, bronchiectasis, congestive heart failure, lung cancer with endobronchial lesion and vocal cord dysfunction. Keys to accurate diagnosis include a good history and physical examination, the demonstration of reversible airways obstruction on pulmonary function tests and a favorable response to treatment. Inhaled corticosteroid therapy is recommended for patients with persistent disease, and careful instruction in the use of metered-dose inhalers is particularly important for the elderly. C1 Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Partners Asthma Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Asthma Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP Fanta, CH (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 78 TC 21 Z9 21 U1 2 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD NOV PY 2000 VL 17 IS 5 BP 385 EP 397 DI 10.2165/00002512-200017050-00005 PG 13 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 379CY UT WOS:000165624400005 PM 11190418 ER PT J AU Schlozman, SC Schlozman, VR AF Schlozman, SC Schlozman, VR TI Chaos in the classroom: Looking at ADHD SO EDUCATIONAL LEADERSHIP LA English DT Article ID DEFICIT-HYPERACTIVITY DISORDER C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WACC-725, Boston, MA 02114 USA. NR 10 TC 1 Z9 2 U1 1 U2 1 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD NOV PY 2000 VL 58 IS 3 BP 28 EP 33 PG 6 WC Education & Educational Research SC Education & Educational Research GA 371FN UT WOS:000165168100005 ER PT J AU Pannell, D Osborne, CS Yao, SY Sukonnik, T Pasceri, P Karaiskakis, A Okano, M Li, E Lipshitz, HD Ellis, J AF Pannell, D Osborne, CS Yao, SY Sukonnik, T Pasceri, P Karaiskakis, A Okano, M Li, E Lipshitz, HD Ellis, J TI Retrovirus vector silencing is de novo methylase independent and marked by a repressive histone code SO EMBO JOURNAL LA English DT Article DE chromatin; gene silencing; methylase; stem cells ID BETA-GLOBIN GENE; LOCUS-CONTROL REGION; I-HYPERSENSITIVE SITES; TRANSGENIC MICE; CHROMATIN STRUCTURE; DENOVO METHYLATION; DROSOPHILA-MELANOGASTER; CPG METHYLATION; STEM-CELLS; DNA AB Retrovirus vectors are de novo methylated and transcriptionally silent in mammalian stem cells. Here, we identify epigenetic modifications that mark retrovirus-silenced transgenes, We show that murine stem cell virus (MSCV) and human immunodeficiency virus type 1 (HIV-1) vectors dominantly silence a linked locus control region (LCR) beta -globin reporter gene in transgenic mice. MSCV silencing blocks LCR hypersensitive site formation, and silent transgene chromatin is marked differentially by a histone code composed of abundant linker histone H1, deacetylated H3 and acetylated H3, Retrovirus-transduced embryonic stem (ES) cells are silenced predominanely 3 days post-infection, with a small subset expressing enhanced green fluorescent protein to low levels, and silencing is not relieved in de novo methylase-null [dnmt3a-/-;dnmt3b-/-] ES cells. MSCV and HIV-1 sequences also repress reporter transgene expression in Drosophila, demonstrating establishment of silencing in the absence of de novo and maintenance methylases. These findings provide mechanistic insight into a conserved gene silencing mechanism that is de novo methylase independent and that epigenetically marks retrovirus chromatin with a repressive histone code. C1 Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Program Canc & Biol Res, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Ellis, J (reprint author), Hosp Sick Children, Program Dev Biol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. RI Ellis, James/F-4789-2011 NR 48 TC 117 Z9 118 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2000 VL 19 IS 21 BP 5884 EP 5894 DI 10.1093/emboj/19.21.5884 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 372LK UT WOS:000165235000029 PM 11060039 ER PT J AU Daniel, PB Rohrbach, L Habener, JF AF Daniel, PB Rohrbach, L Habener, JF TI Novel cyclic adenosine 3 ',5 '-monophosphate (cAMP) response element modulator theta isoforms expressed by two newly identified cAMP-responsive promoters active in the testis SO ENDOCRINOLOGY LA English DT Article ID EARLY REPRESSOR; CREM GENE; TRANSCRIPTIONAL RESPONSE; BINDING PROTEIN; SPERMATOGENESIS; ICER; AMP; INDUCIBILITY; ANTAGONISTS; DEFICIENCY AB cAMP signaling contributes to the control of the developmental progression of germ cells during the spermatogenic cycle. Genes regulated by cAMP include those encoding transcription factors such as the cAMP-responsive element modulator (CREM). The disruption of CREM gene expression in crem null mice results in arrest of spermatogenesis and infertility. The transcriptional control of the CREM gene is attributed to two promoters, P1 and P2. The P1 promoter constitutively activates the synthesis of messenger RNAs encoding activator (tau) and repressor (alpha) forms of CREM, whereas the cAMP-responsive P2 promoter activates the formation of messenger RNAs encoding the inducible cAMP early repressor. Here we report the identification of two additional promoters in the CREM gene, P3 and P4, that in the rat testis encode two novel transcriptional activator CREM isoforms, termed CREM theta1 and CREM theta2, respectively. Notably, the P3 and P4 promoters are activated by cAMP-dependent protein kinase, thereby providing cAMP-regulated transcription of CREM activators in addition to the established cAMP-regulated inducible cAMP early repressor. Analysis ex vivo of CREM gene ex expression in temporally staged segments of the seminiferous tubule during the spermatogenic cycle shows that the activities of the P1, P3, and P4 promoters are independently regulated. Our identification of the cAMP-activated P3 and P4 promoters that direct expression of the novel theta1 and theta2 activator isoforms of CREM brings further insight into the complex expression of the CREM gene during germ cell development and may have implications in understanding the control of fertility. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM jhabener@partners.org NR 28 TC 38 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2000 VL 141 IS 11 BP 3923 EP 3930 DI 10.1210/en.141.11.3923 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365VC UT WOS:000089970300002 PM 11089521 ER PT J AU Macrae, CA AF Macrae, CA TI Genetics and dilated cardiomyopathy: limitations of candidate gene strategies SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; MISSENSE MUTATIONS; CARDIAC ACTIN; DISEASE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Macrae, CA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL075431, K08 HL068711] NR 14 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2000 VL 21 IS 22 BP 1817 EP 1819 DI 10.1053/euhj.2000.2374 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373QG UT WOS:000165299700005 PM 11052851 ER PT J AU Demuth, I Wlodarski, M Tipping, AJ Morgan, NV de Winter, JP Thiel, M Grasl, S Schindler, D D'Andrea, AD Altay, C Kayserili, H Zatterale, A Kunze, J Ebell, W Mathew, CG Joenje, H Sperling, K Digweed, M AF Demuth, I Wlodarski, M Tipping, AJ Morgan, NV de Winter, JP Thiel, M Grasl, S Schindler, D D'Andrea, AD Altay, C Kayserili, H Zatterale, A Kunze, J Ebell, W Mathew, CG Joenje, H Sperling, K Digweed, M TI Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE Fanconi anaemia; FANCG/XRCC9; mutation screening; founder mutation ID GROUP-A GENE; COMPLEMENTATION; PROTEIN; FIBROBLASTS; ANOMALIES; DEFICIENT; CLONING; XRCC9 AB FANCG was the third Faconi anaemia gene identified and proved to be identical to the previously cloned XRCC9 gene. We present the pathogenic mutations and sequence variants we have so far identified in a panel of FA-C patients. Mutation screening was performed by PCR, single strand conformational polymorphism analysis and protein truncation tests. Altogether 18 mutations have been determined in 20 families - 97% of all expected mutant alleles. All mutation types have been found, with the exception of large deletions, the large majority is predicted to lead to shortened proteins. One stop codon mutation, E105X, has been found in several German patients and this founder mutation accounts for 44% of the mutant FANCG alleles in German FA-G patients. Comparison of clinical phenotypes shows that patients homozygous for this mutation have an earlier onset of the haematological disorder than most other FA-C patients. The mouse Fancg sequence was established in order to evaluate missense mutations. A putative missense mutation, L71P, in a possible leucine zipper motif may affect FANCG binding of FANCA and seems to be associated with a milder clinical phenotype. C1 Humboldt Univ, Charite, Inst Human Genet, D-13353 Berlin, Germany. Guys Kings & St Thomas Sch Med, Div Med & Mol Genet, London, England. Free Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, Amsterdam, Netherlands. Univ Wurzburg, Inst Human Genet, D-97070 Wurzburg, Germany. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Hacettepe Univ, Dept Pediat, Hematol Unit, Ankara, Turkey. Inst Child Hlth, Istanbul, Turkey. Osped Elena dAosta, Serv Citogenet, Naples, Italy. Humboldt Univ, Charite, Childrens Hosp, Berlin, Germany. RP Digweed, M (reprint author), Humboldt Univ, Charite, Inst Human Genet, Campus Virchow Klinikum,Augustenburger Pl 1, D-13353 Berlin, Germany. RI Morgan, Neil/A-5475-2009; Mathew, Christopher/G-3434-2015 OI Morgan, Neil/0000-0001-6433-5692; Mathew, Christopher/0000-0003-4178-1838 NR 25 TC 34 Z9 36 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2000 VL 8 IS 11 BP 861 EP 868 DI 10.1038/sj.ejhg.5200552 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 379AR UT WOS:000165619200007 PM 11093276 ER PT J AU Ito, T Tajima, F Ogawa, M AF Ito, T Tajima, F Ogawa, M TI Developmental changes of CD34 expression by murine hematopoietic stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE stem cells; CD31; development; hematopoiesis ID CORD-BLOOD TRANSPLANTATION; MARROW-CELLS AB Objective. It has been reported that fetal murine hematopoietic stem cells are CD34(+), whereas adult stem cells are CD34(-). We sought to delineate the developmental changes of CD34 expression by hematopoietic stem cells and carried out systematic analysis of long-term engrafting cells in the bone marrow and/or blood of perinatal, juvenile, and adult mice. Materials and Methods. To obtain information on the total population of stem cells, we prepared CD34(+) and CD34(-) populations of mononuclear cells without prior enrichment and assayed their long-term reconstituting abilities by transplantation into lethally irradiated Ly-5 congenic mice. Results, All stem cells from perinatal to 5-week-old mice were CD34(+). In 7-week-old mice, CD3(4)- stem cells began to emerge, and the majority of the stem cells mere CD34(-) in the 10- and IO-week-old mice, Approximately 20% of adult stem cells expressed CD34. Conclusions. Developmental changes of CD34 expression from the positive to the negative state takes place between 7 and 10 weeks of age for the majority of murine stem cells. Approximately 20% of adult stem cells remain CD34(+). These observations provide insight into the current controversy regarding CD34 expression by adult hematopoietic stem cells and suggest that the majority of stem cells in human umbilical cord blood and bone marrow of young children are CD34(+). (C) 2000 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 14 TC 73 Z9 76 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2000 VL 28 IS 11 BP 1269 EP 1273 DI 10.1016/S0301-472X(00)00535-X PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 374RQ UT WOS:000165358500009 PM 11063875 ER PT J AU Llevadot, J Giugliano, RP AF Llevadot, J Giugliano, RP TI Pharmacology and clinical trial results of lanoteplase in acute myocardial infarction SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Article DE acute myocardial infarction; clinical trials results; fibrinolytic therapy; lanoteplase ID PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; RABBITS AB New bolus fibrinolytic agents derived from the recombinant human tissue plasminogen activator (t-PA) have emerged as a new means of dissolution of the occlusive thrombosis associated with acute myocardial infarction. Lanoteplase is a fibrinolytic drug derived from t-PA by deleting its fibronectin finger-like and epidermal growth factor domains and mutating Asn-117 to Gln-117. Lanoteplase has a reduced plasma clearance and a prolonged half-life such that it can be administered as a single bolus. In the InTIME I trial, patency (TIMI grade 2 or 3 flow) with the 120 KU/kg dose was higher compared with front-loaded t-PA. The InTIME II trial demonstrated that lanoteplase was as effective as alteplase with regard to mortality. However, the rate of intracranial haemorrhage was significantly higher in lanoteplase-treated patients and further development of this compound has been halted. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Giugliano, RP (reprint author), TIMI Study Off, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA. NR 25 TC 3 Z9 4 U1 0 U2 1 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 NOV PY 2000 VL 9 IS 11 BP 2689 EP 2694 DI 10.1517/13543784.9.11.2689 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 370YR UT WOS:000165151300015 PM 11060830 ER PT J AU McHutchison, JG Poynard, T Pianko, S Gordon, SC Reid, AE Dienstag, J Morgan, T Yao, RJ Albrecht, J AF McHutchison, JG Poynard, T Pianko, S Gordon, SC Reid, AE Dienstag, J Morgan, T Yao, RJ Albrecht, J CA Int Hepatitis Interventional Thera TI The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID QUALITY-OF-LIFE; RACIAL-DIFFERENCES; COST-EFFECTIVENESS; VIRUS; DISEASE; INFECTION; BENEFITS; ALFA AB Background & Aims: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. Methods: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 dr 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. Results: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. Conclusions: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy. C1 Scripps Clin & Res Fdn, Div Gastroenterol Hepatol 203N, La Jolla, CA 92037 USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. William Beaumont Hosp, Royal Oak, MI 48072 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. VA Med Ctr, Long Beach, CA USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. RP McHutchison, JG (reprint author), Scripps Clin & Res Fdn, Div Gastroenterol Hepatol 203N, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Poynard, Thierry/0000-0002-2050-640X FU NCRR NIH HHS [M01-1RR01066, M01-RR00833] NR 26 TC 136 Z9 137 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2000 VL 119 IS 5 BP 1317 EP 1323 DI 10.1053/gast.2000.19289 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367KU UT WOS:000090060900020 PM 11054390 ER PT J AU Hinton, D Ba, P Peou, S Um, K AF Hinton, D Ba, P Peou, S Um, K TI Panic disorder among cambodian refugees attending a psychiatric clinic - Prevalence and subtypes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SOUTHEAST-ASIAN REFUGEES; ANXIETY SENSITIVITY; TRAUMA; ATTACKS; SYMPTOMS; HYPERVENTILATION; EXPERIENCES; SUFFOCATION; TORTURE AB This study surveys Khmer refugees attending two Psychiatric clinics to determine both the prevalence of panic disorder as well as panic attack subtypes in those suffering panic disorder. A culturally valid adaptation of the SCID-panic module, the Cambodian Panic Disorder Survey (CPDS), was administered to 89 consecutive Cambodian refugees attending these psychiatric clinics. Utilizing culturally sensitive panic probes, the CPDS provides information regarding both the presence of panic disorder and panic-attack subtypes during the month prior to interview. Of 89 patients surveyed at two psychiatric clinics, 53 (60%) currently suffered panic disorder. Among the 53 patients suffering panic disorder, the most common panic attack subtypes during the previous month were the following: "sore neck" [51% of the 53 panic disorder patients (PDPs)], orthostatic dizziness (49% of PDPs), gastrointestinal distress (26% of PDPs), effort induced (21% of PDPs), olfactory induced (21% of PDPs), and "while-sitting dizziness" (16% of PDPs). (C) 2000 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. N Suffolk Mental Hlth Ctr, SE Asian Clin, Revere, MA USA. Arbour Counseling, Lowell, MA USA. RP Hinton, D (reprint author), Revere Counseling Ctr, 265 Beach St, Revere, MA 02151 USA. FU NIMH NIH HHS [K23 MH066253, K23 MH066253-05, R01 MH094312] NR 69 TC 49 Z9 50 U1 8 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2000 VL 22 IS 6 BP 437 EP 444 DI 10.1016/S0163-8343(00)00102-X PG 8 WC Psychiatry SC Psychiatry GA 373FK UT WOS:000165277500006 PM 11072060 ER PT J AU Bentley, A MacLennan, B Calvo, J Dearolf, CR AF Bentley, A MacLennan, B Calvo, J Dearolf, CR TI Targeted recovery of mutations in drosophila SO GENETICS LA English DT Article ID HAMSTER OVARY CELLS; ETHYL METHANESULFONATE; LETHAL INTERACTION; ALKYLATING-AGENTS; DNA-REPAIR; SPECIFICITY; SITE; O-6-METHYLGUANINE; MUTAGENESIS; SPECTRUM AB Reverse genetic techniques will be necessary to take full advantage of the genomic sequence data for Drosophila and other experimental organisms. To develop a method for the targeted recovery of mutations, we combined an EMS chemical mutagenesis regimen with mutation detection by denaturing high performance liquid chromatography (DHPLC). We recovered mutant strains at the high rate of similar to4.8 mutations/kb for every 1000 mutagenized chromosomes from a screen for new mutations in the Drosophila and gene. Furthermore, we observed that the EMS mutational spectrum in Drosophila germ cells shows a strong preference for 5'-PuG-3' sites, and for G/C within a stretch of three or more G/C base pairs. Our method should prove useful for targeted mutagenesis screens in Drosophila and other genetically tractable organisms and for more precise studies of mutagenesis and DNA repair mechanisms. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 84 Z9 92 U1 2 U2 5 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2000 VL 156 IS 3 BP 1169 EP 1173 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 370VK UT WOS:000165143200020 PM 11063692 ER PT J AU Spiro, NJ Spiro, RG AF Spiro, NJ Spiro, RG TI Sulfation of the N-linked oligosaccharides of influenza virus hemagglutinin: temporal relationships and localization of sulfotransferases SO GLYCOBIOLOGY LA English DT Article DE sulfated N-linked oligosaccharides; influenza virus hemagglutinin; sulfotransferases; subcellular localization; glycoprotein processing sequence ID TRANS-GOLGI NETWORK; COMPLEX CARBOHYDRATE UNITS; D-GALACTOSYL RESIDUES; BREFELDIN-A; MDCK CELLS; STRUCTURAL ELUCIDATION; KIDNEY-CELLS; RAT-LIVER; GLYCOPROTEINS; PROTEINS AB The occurrence of sulfate substituents on several positions of glycoprotein N-linked oligosaccharides prompted us to determine the subcellular localization and temporal relationships of the addition of these anionic groups employing as a model system the hemagglutinin (HA) produced by influenza virus-infected Madin-Darby canine kidney (MDCK) cells. It became apparent from a study of the HA glycoprotein in subcellular fractions resolved by Nycodenz gradient centrifugation following pulse-chase radiolabeling that sulfation of the complex N-linked oligosaccharides occurs only after they have been processed to an endo-beta -N-acetylglucosaminidase-resistant state and have reached the medial/trans Golgi and the trans Golgi network (TGN), with the former carrying out most of the sulfation activity. Hydrazine/nitrous acid/NaBH4 treatment of the HA from the subcellular fractions indicated that C-3 of the galactose as well as C-6 of the N-acetylglucosamine residues of the N-acetyllactosamine chains became sulfated in these post ER fractions, as did the C-6 of the outer N-acetylglucosamine of the di-N-acetylchitobiose core. Consistent with the specificities of the stepwise assembly of the N-acetyllactosamine branches, we observed that the 3'-phosphoadenosine 5'-phosphosulfate (PAPS):GlcNAc-6-O-sulfotransferase migrated in the gradient to a medial/trans Golgi position while in contrast the PAPS:Gal-3-O-sulfotransferase was found in both Golgi and TGN locations. In accordance with the concept that beta -galactosylation must precede the sulfation catalyzed by the latter enzyme, we observed the presence of UDP-Gal:GlcNAc galactosyltransferase in both these sites in the MDCK cells. The presence of the Gal-3-O-sulfotransferase in the TGN is particularly important in the influenza virus-infected cells, as it makes possible the addition of terminal anionic groups after removal of the sialic acid residues by the viral neuraminidase. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Elliot P Joslin Res Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02215 USA. RP Spiro, RG (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Elliot P Joslin Res Lab, 1 Joslin Pl, Boston, MA 02215 USA. NR 41 TC 6 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2000 VL 10 IS 11 BP 1235 EP 1242 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 374VA UT WOS:000165364000013 ER PT J AU Higgins, MC AF Higgins, MC TI What should CJ do? SO HARVARD BUSINESS REVIEW LA English DT Editorial Material C1 Harvard Univ, Sch Business, Boston, MA 02163 USA. GE, Ind Syst, Plainville, CT 06062 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Boston Psychoanalyt Soc & Inst Inc, Boston, MA USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. RP Higgins, MC (reprint author), Harvard Univ, Sch Business, Boston, MA 02163 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARVARD BUSINESS SCHOOL PUBLISHING CORPORATION PI BOSTON PA 60 HARVARD WAY, BOSTON, MA 02163 USA SN 0017-8012 J9 HARVARD BUS REV JI Harv. Bus. Rev. PD NOV-DEC PY 2000 VL 78 IS 6 BP 43 EP + PG 5 WC Business; Management SC Business & Economics GA 368KL UT WOS:000090116100010 ER PT J AU Ganzini, L Cohen, LM AF Ganzini, L Cohen, LM TI Resolution and ambivalence - Commentary SO HASTINGS CENTER REPORT LA English DT Editorial Material C1 Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. Bay State Med Ctr, Psychiat Consultat Serv, Springfield, MA USA. RP Ganzini, L (reprint author), Portland Vet Affairs Med Ctr, Portland, OR 97207 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 2000 VL 30 IS 6 BP 25 EP 25 PG 1 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 386FW UT WOS:000166051000011 ER PT J AU Nicholson, S Pauly, MV Burns, LR Baumritter, A Asch, DA AF Nicholson, S Pauly, MV Burns, LR Baumritter, A Asch, DA TI Measuring community benefits provided by for-profit and nonprofit hospitals SO HEALTH AFFAIRS LA English DT Article AB Nonprofit hospitals are expected to provide benefits to their community in return for being exempt from most taxes. In this paper we develop a new method of identifying activities that should qualify as community benefits and of determining a benchmark for the amount of community benefits a nonprofit hospital should be expected to provide. We then compare estimates of nonprofits' current level of community benefits with our benchmark and show that actual provision appears to fall short. Either nonprofit hospitals as a group ought to provide more community benefits. or they are performing activities that cannot be measured. In either case, better measurement and accounting of community benefits would improve public policy. C1 Univ Penn, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Nicholson, S (reprint author), Univ Penn, Wharton Sch, Hlth Care Syst Dept, Philadelphia, PA 19104 USA. NR 10 TC 32 Z9 32 U1 1 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2000 VL 19 IS 6 BP 168 EP 177 DI 10.1377/hlthaff.19.6.168 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 373PH UT WOS:000165297500019 PM 11192400 ER PT J AU Mathurin, P Deng, QG Keshavarzian, A Choudhary, S Holmes, EW Tsukamoto, H AF Mathurin, P Deng, QG Keshavarzian, A Choudhary, S Holmes, EW Tsukamoto, H TI Exacerbation of alcoholic liver injury by enteral endotoxin in rats SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; LIPOPOLYSACCHARIDE-BINDING-PROTEIN; CYTOKINE GENE-EXPRESSION; KUPFFER CELLS; INTESTINAL PERMEABILITY; DISEASE; ETHANOL; CIRRHOSIS; HEPATITIS AB Increased gut permeability (leaky gut) and endotoxin-mediated Kupffer cell activation are proposed as the mechanisms of alcoholic liver injury. Although ethanol feeding is shown to sensitize the liver for injury induced by parental administration of lipopolysaccharide (LPS), how enteral LPS loading affects alcoholic liver injury is yet to be tested. The present study provides direct evidence for enhanced entrance to portal circulation of LPS enterally administered to the intragastric ethanol infusion model. Portal and systemic blood endotoxin levels increased to 43.0 +/- 4.1 and 6.2 +/- 4.3 pg/mL at 2 hours following enteral LPS administration (5 mg/kg) in alcohol-fed animals, while no such increases were observed in pair-fed controls. However, endotoxin levels in systemic blood of alcohol-fed rats were reduced to 0 to 1.5 pg/mL 16 hours after LPS administration. Weekly enteral administration of LPS to the model for 9 weeks exacerbated an increase in plasma alanine transaminase (ALT) levels (227 +/- 75 vs. 140 +/- 70; P <.01), mononuclear infiltration (25 +/- 22 vs. 6.4 +/- 4.4/10 mm(2); P=.02), sinusoidal congestion, and spotty necrosis, and induced diffuse coagulative necrosis and centrilobular fibrosis in some animals. Reverse-transcription polymerase chain reaction (RT-PCR) analysis confirmed the LPS effect at the tissue level by demonstrating accentuated induction of tumor necrosis factor (TNF-alpha) and Cox-2 mRNA, In conclusion, enteral LPS administration potentiates alcoholic liver necrosis, inflammation, and fibrosis despite efficient endotoxin clearance by the liver and mild systemic endotoxemia that occurs episodically following enteral LPS challenge. C1 Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Greater Los Angeles VA Hlth Care Syst, Sepulveda, CA USA. Rush Presbyterian St Lukes Med Ctr, Div Digest Dis, Chicago, IL 60612 USA. Loyola Univ, Stritch Sch Med, Dept Pathol, Chicago, IL 60611 USA. RP Tsukamoto, H (reprint author), Univ So Calif, Keck Sch Med, Dept Med, 1333 San Pablo St,MMR-414, Los Angeles, CA 90033 USA. FU NIAAA NIH HHS [R37-AA06603, P50-AA11999] NR 45 TC 165 Z9 178 U1 3 U2 7 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 NOV PY 2000 VL 32 IS 5 BP 1008 EP 1017 DI 10.1053/jhep.2000.19621 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 367KV UT WOS:000090061000017 PM 11050051 ER PT J AU Haataja, R Ramet, M Marttila, R Hallman, M AF Haataja, R Ramet, M Marttila, R Hallman, M TI Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome SO HUMAN MOLECULAR GENETICS LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; HUMAN SP-A; PULMONARY SURFACTANT; STRUCTURAL REQUIREMENTS; RACIAL-DIFFERENCES; CODING SEQUENCE; DISEASE; LUNG; POLYMORPHISMS; APOPROTEIN AB Prematurity is the most important risk factor predisposing to neonatal respiratory distress syndrome (RDS), Genetic factors are likely to contribute to the risk of this complex disease. The present study was designed to investigate whether the surfactant protein B (SP-B) gene or interaction between the SP-A and SP-B genes has a role in the genetic susceptibility to RDS, The genotype analyses were performed on 684 prematurely born neonates, of whom 184 developed RDS, Of the two SP-B polymorphisms genotyped, the Ile131Thr variation affects a putative N-terminal N-linked glycosylation site of proSP-B and the length variation of intron 4 has previously been suggested to associate with RDS, Neither of the two SP-B polymorphisms associated directly with RDS or with prematurity. Instead, our data show that the previously identified association between SP-A alleles and RDS was dependent on the SP-B Ile131Thr genotype, On the basis of chi (2) and logistic regression analyses, the SP-A allele, haplotype and genotype distributions differed significantly between the RDS infants and controls only when the SP-B genotype was Thr/Thr, Among the infants born before 32 weeks of gestation and having the SP-B genotype Thr/Thr, the SP-AI allele 6A(2) was over-represented in RDS group compared with controls (P = 0.001, OR = 4.7, CI 1.8-12.2), In the same comparison, the SP-AI allele 6A(3) was under-represented in RDS (P = 0.001, OR = 0.2, CI 0.1-0.6). We propose that the SP-B Ile131Thr polymorphism is a determinant for certain SP-A alleles as factors causing genetic susceptibility to RDS (6A(2), 1A(0)) or protection against it (6A(3), 1A(2)). C1 Univ Oulu, Dept Paediat, FIN-90014 Oulu, Finland. Univ Oulu, Bioctr Oulu, FIN-90014 Oulu, Finland. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. RP Hallman, M (reprint author), Univ Oulu, Dept Paediat, POB 5000, FIN-90014 Oulu, Finland. NR 58 TC 71 Z9 79 U1 1 U2 1 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 NOV 1 PY 2000 VL 9 IS 18 BP 2751 EP 2760 DI 10.1093/hmg/9.18.2751 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 373FM UT WOS:000165277700018 PM 11063734 ER PT J AU Deeds, J Cronin, F Duncan, LM AF Deeds, J Cronin, F Duncan, LM TI Patterns of melastatin mRNA expression in melanocytic tumors SO HUMAN PATHOLOGY LA English DT Article DE melanoma; pigmented nevus; oncogene; histology; metastasis; human; mRNA ID INTERCELLULAR-ADHESION MOLECULE-1; CUTANEOUS MALIGNANT-MELANOMA; STEREOLOGIC ESTIMATION; NUCLEAR VOLUME; PROGRESSION; METASTASIS; PROGNOSIS; INTEGRIN; LESIONS; LOCALIZATION AB The melanocyte-specific gene Melastatin (MLSN1) shows an inverse correlation of mRNA expression with metastatic potential in human and murine cell lines in vitro. Melastatin mRNA expression in primary cutaneous melanoma also has been found to correlate with disease-free survival. The histologic patterns of Melastatin mRNA expression in nevi, primary melanoma, and melanoma metastases have not been described previously. Using in situ hybridization with S-35-labeled probes, we examined Melastatin mRNA expression in 64 cases of normal skin, benign melanocytic nevi, primary cutaneous melanomas, and melanoma metastases. Ubiquitous melanocytic expression of Melastatin mRNA was observed in all benign melanocytic proliferations (14 of 14), although some nevi showed a gradient of reduced Melastatin expression with increased dermal depth (3 of 14). Uniform expression of Melastatin mRNA was observed in 49% of primary cutaneous melanomas (18 of 37 cases, including 1 case of in situ melanoma). Melastatin mRNA loss by a portion of the melanoma was identified in 53% of the invasive melanoma samples (19 of 36) and 100% of the melanoma metastases (11 of 11). Primary melanomas without mRNA loss ranged in thickness from 0.17 to 2.75 mm (median, 0.5 mm; mean, 0.73 mm), whereas tumors that showed Melastatin mRNA down-regulation ranged in thickness from 0.28 to 5.75 mm (median, 1.7 mm; mean, 2.13 mm). A focal aggregate or nodule of melanoma cells without detectable signal was the most commonly observed pattern of Melastatin loss (13 of 19 cases), whereas complete loss of Melastatin mRNA expression by ah of the dermal melanoma cells was observed in only 1 of the 19 cases. Two invasive melanomas displayed a scattered, nonfocal pattern of Melastatin mRNA loss. OF the 11 melanoma metastases examined, 64% displayed focal Melastatin mRNA loss, and 36% had complete loss of Melastatin mRNA expression. We observed several patterns of Melastatin mRNA expression in primary melanoma that may be distinguished from expression in benign melanocytic nevi. Melastatin mRNA expression appears to correlate with melanocytic tumor progression, melanoma tumor thickness, and the potential for melanoma metastasis. HUM PATHOL 31:1346-1356, Copyright (C) 2000 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Millennium Predict Med, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Warren 827,55 Fruit St, Boston, MA 02114 USA. RI Duncan, Lyn/E-9878-2013 NR 34 TC 64 Z9 66 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2000 VL 31 IS 11 BP 1346 EP 1356 DI 10.1016/S0046-8177(00)80003-9 PG 11 WC Pathology SC Pathology GA 376JJ UT WOS:000165454200003 PM 11112208 ER PT J AU Ehsan, A Fan, HX Eagan, PA Siddiqui, HA Gulley, ML AF Ehsan, A Fan, HX Eagan, PA Siddiqui, HA Gulley, ML TI Accumulation of p53 in infectious mononucleosis tissues SO HUMAN PATHOLOGY LA English DT Article DE Epstein-Barr virus; infectious mononucleosis; EBER1; p53; BZLF1; LMP1 ID EPSTEIN-BARR-VIRUS; BURKITTS-LYMPHOMA CELL; NON-HODGKINS-LYMPHOMAS; TUMOR-SUPPRESSOR GENE; REED-STERNBERG CELLS; PROTEIN EXPRESSION; CARRIER STATE; B-CELLS; REPLICATION; DISEASE AB Epstein-Barr virus (EBV) infects lymphocytes, where it persists indefinitely for the life of the host; whether the virus interacts with p53 to maintain itself in these cells is unknown. Lymphoid biopsy samples from 10 patients with infectious mononucleosis (IM) were examined for expression of p53 by immunohistochemistry. Accumulation of p53 was detected in all 10 cases, primarily in large lymphocytes of the expanded paracortex. The presence of EBV was con firmed in all 10 cases by EBER1 (EBV-encoded RNA) in situ hybridization, whereas 11 non-IM control samples lacked significant EBER1 and did not express p53 in paracortical lymphocytes. Interestingly, EBV infection alone does not cause accumulation of intracellular p53, because many more cells expressed EBER1 than p53 in the IM tissues. To determine whether p53 was confined to the subset of infected cells in which viral replication was occurring, BZLF1 immunostains were performed. Viral BZLF1 was detected in 8 of 10 IM tissues; however, the paucity and small size of the BZLF1-expressing lymphocytes suggests that they are not the same cells overexpressing p53. To further examine the relationship between p53 and EBV gene expression, the tissues were studied for latent membrane protein 1 (LMP1) expression by immunohistochemistry. Viral LMP1 was observed in the large paracortical lymphocytes of all 10 cases of IM, indicating co-localization of p53 and LMP1 in these cells. Our findings confirm that p53 overexpression is not specific for nodal malignancy and that p53 accumulation is characteristic of IM. Because p53 was not coexpressed in the same cells as BZLF1, it appears that BZLF1 is not directly responsible for p53 accumulation. Nevertheless, co-localization of p53 and LMP1 in activated-appearing lymphocytes suggests that EBV infection is responsible for p53 accumulation. HUM PATHOL 31:1397-1403. Copyright (C) 2000 by W.B. Saunders Company. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Ehsan, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, MSC 7750,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 38 TC 9 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2000 VL 31 IS 11 BP 1397 EP 1403 DI 10.1053/hupa.2000.19447 PG 7 WC Pathology SC Pathology GA 376JJ UT WOS:000165454200010 PM 11112215 ER PT J AU Lee, S Russo, DCW Pu, J Ho, M Redman, CM AF Lee, S Russo, DCW Pu, J Ho, M Redman, CM TI The mouse Kell blood group gene (Kel): cDNA sequence, genomic organization, expression, and enzymatic function SO IMMUNOGENETICS LA English DT Article DE mouse kell blood group system; Kel gene; endothelin ID ENDOTHELIN-B RECEPTOR; GROUP PROTEIN; MICE DEFICIENT; KX PROTEIN; MEMBRANE; ANEMIA; CELLS; PHENOTYPES; ANTIBODIES; ANTIGENS AB The human Kell blood group system is important in transfusion medicine, since Kell is a polymorphic protein and some of its antigens can cause severe reactions if mismatched blood is transfused, while maternal alloimmunization may lead to fetal and neonatal anemia. In humans, Kell is an M-r 93,000 type II membrane glycoprotein with endothelin-3-converting enzyme activity that is linked by a single disulfide bond to another protein, XK, that spans the membrane ten times. An absence of XK leads to clinical symptoms termed the McLeod syndrome. We determined the cDNA sequence of the mouse Kell homologue, the organization of the gene, expression of the protein and its enzymatic function on red cells. Comparison of human and mouse Kell cDNA showed 80% nucleotide and 74% amino acid sequence identity. Notable differences are that the mouse Kell protein has eight probable N-linked carbohydrate side chains, compared to five for human Kell, and that the mouse homologue has one more extracellular cysteine than human Kell protein. The mouse Kell gene (Kel), like its human counterpart, is similarly organized into 19 exons. Kel was located to proximal Chromosome 6. Northern blot analysis showed high expression in spleen and weaker levels in testis and heart. Western blot analysis of red cell membrane proteins demonstrated that mouse Kell glycoprotein has an apparent M-r of 110,000 and, on removal of N-linked sugars, 80,000. As in human red cells, Kell is disulfide-linked to XK and mouse red cells have endothelin-3-converting enzyme activity. C1 New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cecil B Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. RP Redman, CM (reprint author), New York Blood Ctr, Lindsley F Kimball Res Inst, 310 E 67 St, New York, NY 10021 USA. OI Pu, Jeffrey/0000-0001-7498-3159 FU NHLBI NIH HHS [HL54459] NR 31 TC 10 Z9 12 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD NOV PY 2000 VL 52 IS 1-2 BP 53 EP 62 DI 10.1007/s002510000251 PG 10 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 380EM UT WOS:000165686300008 PM 11132157 ER PT J AU Gong, J Apostolopoulos, V Chen, D Chen, H Koido, S Gendler, SJ McKenzie, IF Kufe, D AF Gong, J Apostolopoulos, V Chen, D Chen, H Koido, S Gendler, SJ McKenzie, IF Kufe, D TI Selection and characterization of MUC1-specific CD8(+) T cells from MUC1 transgenic mice immunized with dendritic-carcinoma fusion cells SO IMMUNOLOGY LA English DT Article ID POLYMORPHIC EPITHELIAL MUCIN; CLASS-I MOLECULES; CD40 LIGAND; MONOCLONAL-ANTIBODIES; EXOGENOUS ANTIGENS; EPISIALIN MUC1; LYMPHOCYTES-T; TUMOR-CELLS; BREAST; PROTEIN AB Mice transgenic for the human MUC1 carcinoma-associated antigen (MUC1.Tg) are tolerant to immunization with MUC1 antigen. Recent studies, however, have demonstrated that immunization of MUC1.Tg mice with fusions of MUC1-positive tumour and dendritic cells (FC/MUC1) reverses MUC1 unresponsiveness and results in rejection of established MUC1-positive pulmonary metastases. Here we demonstrate that lymph node cells from MUC1.Tg mice immunized with the FC/MUC1 fusion cells proliferate in response to MUC1 antigen by a mechanism dependent on the function of CD4, major histocompatibility complex (MHC) class II, B7-1, B7-2, CD28, CD40 and CD40 ligand. The findings demonstrate that stimulation of lymph node cells with MUC1 results in selection of MUC1-specific CD8(+) T cells. We show that the CD8(+) T cells exhibit MUC1-specific cytotoxic T lymphocyte (CTL) activity by recognition of MUC1 peptides presented in the context of MHC class I molecules K-b and D-b. The MUC1-specific CD8(+) T cells also exhibit antitumour activity against MUC1-positive metastases, but with no apparent reactivity against normal tissues. These results indicate that immunization of MUC1.Tg mice with FC/MUC1 reverses immunological unresponsiveness to MUC1 by presentation of MUC1 peptides in the presence of costimulatory signals and generates MHC-restricted MUC1-specific CD8(+) T cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Austin Res Inst, Heidelberg, Vic, Australia. Scripps Res Inst, La Jolla, CA USA. Mayo Clin, Scottsdale, AZ USA. RP Gong, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA078378, CA78378, CA87058, R01 CA087057] NR 50 TC 43 Z9 46 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 2000 VL 101 IS 3 BP 316 EP 324 DI 10.1046/j.1365-2567.2000.00101.x PG 9 WC Immunology SC Immunology GA 379VG UT WOS:000165663100004 PM 11106934 ER PT J AU Parada, JP Shapiro, DS AF Parada, JP Shapiro, DS TI Salmonella abscess of the ovary SO INFECTIONS IN MEDICINE LA English DT Article DE ovarian cyst; Salmonella; abscess; zoonosis AB A 21-year-old vegetarian with a household exposure to a pet turtle and a history of an ovarian cyst presented with an ovarian abscess caused by Salmonella hartford. This case highlights the facts that Salmonella species are associated with reptilian zoonotic transmission and have a predilection for localization in a site of preexisting abnormality. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Parada, JP (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD NOV PY 2000 VL 17 IS 11 BP 761 EP 762 PG 2 WC Infectious Diseases SC Infectious Diseases GA 373GJ UT WOS:000165280200015 ER PT J AU Reid, AE AF Reid, AE TI Same disease, different impact SO INFLAMMATORY BOWEL DISEASES LA English DT Article C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Reid, AE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2000 VL 6 IS 4 BP 330 EP 331 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 384VE UT WOS:000165966100011 PM 11149566 ER PT J AU Hadigan, CM Anderson, EJ Miller, KK Hubbard, JL Herzog, DB Klibanski, A Grinspoon, SK AF Hadigan, CM Anderson, EJ Miller, KK Hubbard, JL Herzog, DB Klibanski, A Grinspoon, SK TI Assessment of macronutrient and micronutrient intake in women with anorexia nervosa SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE diet history; anorexia nervosa; observed food intake ID TOTAL-ENERGY EXPENDITURE; DOUBLY LABELED WATER; DIETARY MEASUREMENTS; NUTRITIONAL-STATUS; FOOD; VALIDITY; OSTEOPOROSIS; DISORDER; CALCIUM; HISTORY AB Objective: The purpose of this study is to evaluate the accuracy of diet history compared to observed food intake in the nutritional assessment of women with anorexia nervosa (AN) and healthy age-matched controls. Method: One-month diet history was compared to 1-day observed food intake in 30 women with AN and 28 control subjects. Results: Reported intake by diet history was similar to observed intake for macronutrient composition and fat intake for patients with AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal vs. 1,289 +/- 750 kcal, p < .05), but was in agreement with predicted energy expenditure by the Harris-Benedict equation (1,594 +/- 78 kcal, p = .97) in patients with AN. Micronutrient intake by diet history was highly correlated with observed intake in patients with AN. More than one half of the patients with AN failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium, folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history. In contrast to patients with AN, diet history did not correlate with observed intake of energy, macronutrients, or most micronutrients among the controls. Discussion: Diet history is an accurate tool to assess fat intake and macronutrient composition in patients with AN and demonstrates significant micronutrient deficiencies in tl,is population. The agreement between total energy intake and predicted energy expenditure supports the overall utility of the diet history in the nutritional assessment of patients with AN. (C) 2000 by John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Harvard Univ, Boston Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Clin Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01-DK52625, T32-DK07703] NR 27 TC 75 Z9 79 U1 1 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2000 VL 28 IS 3 BP 284 EP 292 DI 10.1002/1098-108X(200011)28:3<284::AID-EAT5>3.0.CO;2-G PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 347NP UT WOS:000088936300005 PM 10942914 ER PT J AU Spiegelman, BM Puigserver, P Wu, Z AF Spiegelman, BM Puigserver, P Wu, Z TI Regulation of adipogenesis and energy balance by PPAR gamma and PGC-1 SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Symposium on Recent Advances in Adipose Tissue Biology and Their Implications for Obesity CY NOV 19-20, 1999 CL QUEBEC CITY, CANADA SP Hoffmann La Roche Canada DE PPAR gamma; adipogenesis; fat cells; energy balance ID ACTIVATED RECEPTOR-GAMMA; C/EBP-ALPHA; EXPRESSION; LIGAND; FAMILY; DIFFERENTIATION; TROGLITAZONE; FIBROBLASTS; COACTIVATOR; PATHWAY AB There has been a great deal of recent progress in our understanding of the transcriptional control of adipogenesis. Current data suggest that fat cell differentiation involves an interplay between the C/EBP family of transcription factors and PPAR gamma, The thermogenic program of brown fat cells may also include a contribution from a new coactivator, PGC-1. Recent data suggests that this cosactivator is responsible for activation of thermogenesis and oxidative metabolism in both brown fat and muscle. The PGC-1 dependent program includes both mitochondrial biogenesis and tissue-specific expression of uncoupling proteins. C1 Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Div Cellular & Mol Biol, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 58 Z9 59 U1 2 U2 7 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 2000 VL 24 SU 4 BP S8 EP S10 PG 3 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 374CX UT WOS:000165327800004 PM 11126248 ER PT J AU Russo, SP Fiorellini, JP Weber, HP Niederman, R AF Russo, SP Fiorellini, JP Weber, HP Niederman, R TI Benchmarking the dental implant evidence on MEDLINE SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE bibliometrics; diagnosis; etiology; implants; prognosis; therapeutics ID RANDOMIZED CONTROLLED TRIALS; SEARCHES; MEDICINE; HEALTH; PAPER; CARE; READ AB The purpose of this study was to estimate the quantity of dental implant literature available on MEDLINE for evidence-based clinical decision-making and to identify its location. A search strategy based on Medical Subject Headings for dental implants was developed to examine MEDLINE using the Ovid Web Gateway search engine. Sensitive and specific methodologic search filters identified 4 categories of information: etiology, diagnosis, therapy, and prognosis. The results were then subdivided by year to identify trends and sorted to identify the sources of publications. The searches identified 4,655 articles published in English between 1989 and 1999 on human dental implants on MEDLINE, The mean number of articles (+/- SD) per year ranged from 15 +/- 11 for specific searches to 107 +/- 50 for sensitive searches. The number of articles increased by 14% to 43% each year for the sensitive search. When subdivided by clinical category, the mean numbers of articles per year for sensitive and specific searches were, respectively: diagnosis 12 +/- 7.5 and 1.5 +/- 1.6, etiology 58 +/- 33 and 1.9 +/- 2.5, therapy 23 +/- 15 and 0.3 +/- 0.5 and prognosis 67 +/- 33 and 12 +/- 8.3. Four dental journals account for approximately half of these publications. These results provide 6 key central findings: (1) there appears to be a substantial literature of clinically relevant information on implants upon which to base clinical decisions; (2) the implant literature is significantly biased toward articles addressing prognosis; (3) to stay current, one would need to read between 1 and 2 articles per week 52 weeks per year, and this number increases significantly each year; (4) approximately 50% of the articles were published in 4 journals, whereas the remainder reside in approximately 97 other journals, making it difficult to stay current; (5) these trends reaffirm the need for lifelong learning; (6) these trends also suggest the need for computer-based clinical knowledge systems. C1 Harvard Univ, Sch Dent Med, Off Evidence Based Dent, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Periodont, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Restorat Dent, Boston, MA 02115 USA. Forsyth Inst, Off Evidence Based Dent, Boston, MA USA. RP Niederman, R (reprint author), Harvard Univ, Sch Dent Med, Off Evidence Based Dent, 188 Longwood Ave, Boston, MA 02115 USA. NR 16 TC 5 Z9 5 U1 0 U2 2 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD NOV-DEC PY 2000 VL 15 IS 6 BP 792 EP 800 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 385RH UT WOS:000166017100004 PM 11151577 ER PT J AU Dewhirst, FE Fox, JG On, SLW AF Dewhirst, FE Fox, JG On, SLW TI Recommended minimal standards for describing new species of the genus Helicobacter SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Helicobacter; minimal standards ID PYLORI SUBSP MUSTELAE; SP-NOV; CAMPYLOBACTER-PYLORI; GASTRIC HELICOBACTER; ALLIED TAXA; IDENTIFICATION; BACTERIUM; MUCOSA; MICE; CANDIDATUS AB The International Committee of Systematic Bacteriology Subcommittee on the taxonomy of Campylobacter and related bacteria has agreed in principle on minimum requirements for the description of new species of the genus Helicobacter. These requirements include the recommendation that the description of a putative new species or subspecies be based on examination of at least five strains in order to provide a measure of phenotypic and genotypic variation. Recommendations for required phenotypic and molecular data are presented. The requirements are consistent with the polyphasic approach to bacterial systematics. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Danish Vet Lab, DK-1790 Copenhagen, Denmark. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. NR 70 TC 53 Z9 54 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD NOV PY 2000 VL 50 BP 2231 EP 2237 PN 6 PG 7 WC Microbiology SC Microbiology GA 388BC UT WOS:000166156700034 PM 11156001 ER PT J AU Mori, F King, GL Clermont, AC Bursell, DK Bursell, SE AF Mori, F King, GL Clermont, AC Bursell, DK Bursell, SE TI Endothelin-3 regulation of retinal hemodynamics in nondiabetic and diabetic rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE RELEASE; BLOOD-FLOW CHANGES; PHOSPHOINOSITIDE BREAKDOWN; VASOCONSTRICTOR PEPTIDE; MESENTERIC-ARTERIES; ET(B) RECEPTOR; CELLS; CIRCULATION; EXPRESSION AB PURPOSE. To investigate the mechanisms of action of endothelin (ET)-3 on the regulation of retinal hemodynamics in diabetic and nondiabetic rats. METHODS. Retinal blood flow changes were measured using video fluorescein angiography. Measurements were made before and after intravitreal injections of different ET-3 concentrations in nondiabetic rats and rats with streptozotocin (STZ)-induced diabetes. The effect of ET-3 on retinal blood flow was also investigated in nondiabetic rats after pretreatment with N-G-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase ((NOS) inhibitor; BQ-788, an ET receptor B (ETB) antagonist; and BQ-123, an ET receptor A (ETA) antagonist. Control animals were injected intravitreally with vehicle alone. RESULTS. In nondiabetic rats, ET-3 induced a dose-dependent rapid increase in retinal blood now 2 minutes after intravitreal injection (maximal at 10(-8) M, P < 0.01) followed 15 and 30 minutes after ET-3 injection by dose-dependent decreases in retinal blood flow (maximal effect at 10(-6) M, P < 0.05). The ET-3-stimulated retinal blood how increase was inhibited by 10(-4) M BQ-788 (P < 0.01) and 10(-3) M L-NMMA. (P < 0.05). The ET-3-stimulated decrease in retinal blood flow at later times (15 minutes) was inhibited (P < 0.03) by 10(-4) M BQ-123. In diabetic rats, baseline retinal blood flows were decreased compared with nondiabetic rats (P < 0.01), showed dose-dependent increases 2 minutes after ET-3 injection (P < 0.03), and at later times remained significantly increased (P < 0.05) in contrast to flows in nondiabetic rats. CONCLUSIONS. The ET-3-induced initial rapid retinal blood flow increase in nondiabetic rats is mediated by the ET-3/ETB and NOS action. The subsequent retinal blood flow decrease is mediated by ET-3/ETA action. Diabetic rats showed comparable ET-3-induced retinal blood flow increases indicating normal ET-3/ETB action. However, at later times, retinal blood flow remained increased, suggesting an abnormal ET-3/ETA action. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Bursell, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY09178] NR 49 TC 6 Z9 7 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2000 VL 41 IS 12 BP 3955 EP 3962 PG 8 WC Ophthalmology SC Ophthalmology GA 369LH UT WOS:000165066400040 PM 11053299 ER PT J AU Renno, RZ Delori, FC Holzer, RA Gragoudas, ES Miller, JW AF Renno, RZ Delori, FC Holzer, RA Gragoudas, ES Miller, JW TI Photodynamic therapy using Lu-Tex induces apoptosis in vitro, and its effect is potentiated by angiostatin in retinal capillary endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; LUTETIUM TEXAPHYRIN PCI-0123; MACULAR DEGENERATION; PROTOONCOGENE BCL-2; IONIZING-RADIATION; DNA FRAGMENTATION; CELLULAR UPTAKE; LYMPHOMA-CELLS; BENZOPORPHYRIN; VERTEPORFIN AB PURPOSE. To examine the effect of combining angiostatin with photodynamic therapy (PDT) using Lutetium Texaphyrin (Lu-Tex; Alcon, Fort Worth, TX) as a photosensitizer in bovine retinal capillary endothelial (BRCE) and retinal pigment epithelial (RPE) cells and to determine the mode of PDT-induced cell death in these cell lines. METHODS. Cultured BRCE and RPE cells were incubated with angiostatin (500 ng/ml) for 18 hours and subjected to Lu-Tex/PDT, using treatment parameters previously optimized (3 mug/ml Lu-Tex for 30 minutes followed by timed irradiation at 732 nm). Cellular survival was assessed after a 1-week cellular proliferation. Data were analyzed using Student's t-test. Caspase 3 activity was monitored in cells after PDT using a fluorogenic substrate, (Asp-Glu-Val-Asp)-AFC (7-amino-4-trifluoromethyl coumarin) [DEVD-AFC], of caspase 3. After PDT, expression of Bcl-2, Bcl-X-L, Bax, and Bak was also examined in cell lysates by Western blot analysis. RESULTS. A synergistic cytotoxic effect of angiostatin and Lu-Tex/PDT was observed in BRCE cells at all fluences used (5, 10, and 20 J/cm(2); P less than or equal to 0.05). These findings applied only if angiostatin was delivered before PDT. No such interactive killing effect was observed in RPE cells. Caspase 3 activity was elevated within 10 minutes of PDT in BRCE and RPE cells and was fluence dependent. Differential modulation of Bcl-2 family members was observed after PDT in BRCE and RPE cells. CONCLUSIONS. The combination of angiostatin and Lu-Tex/PDT potentiates the cytotoxic effect of Lu-Tex/PDT on BRCE but not on RPE cells. This may provide a strategy to increase the selectivity of PDT in damaging capillary endothelial cells with less damage to RPE cells. Lu-Tex/PDT induces rapid caspase-dependent apoptosis in BRCE and RPE cells. Furthermore, Lu-Tex/PDT induces apoptosis through selective modulation of members of the Bcl-2 family and differs between BRCE and RPE cells. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Lab, Boston, MA 02114 USA. Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Laser Lab, 243 Charles St, Boston, MA 02114 USA. NR 49 TC 17 Z9 20 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2000 VL 41 IS 12 BP 3963 EP 3971 PG 9 WC Ophthalmology SC Ophthalmology GA 369LH UT WOS:000165066400041 PM 11053300 ER PT J AU Bohning, DE Shastri, A McGavin, L McConnell, KA Nahas, Z Lorberbaum, JP Roberts, DR George, MS AF Bohning, DE Shastri, A McGavin, L McConnell, KA Nahas, Z Lorberbaum, JP Roberts, DR George, MS TI Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement SO INVESTIGATIVE RADIOLOGY LA English DT Article DE transcranial magnetic stimulation, functional MR imaging, human; motor cortex, volitional movement, blood flow, imaging ID HUMAN CEREBRAL-CORTEX; ACTIVATION; CONNECTIVITY; EXCITATION; FMRI; TOOL; TMS; PET AB RATIONALE AND OBJECTIVES. The relatively high temporal and spatial resolution of functional MR imaging was used to compare the blood oxygenation level dependent (BOLD) response associated with movement induced by transcranial magnetic stimulation (TMS) with that for a similar movement executed volitionally (VOL). METHODS. Seven healthy adults were studied in a 1.5-T MR scanner. One hertz TMS at 110% of motor threshold was applied over the motor cortex for the thumb in 21-pulse trains in alternation,vith VOL every 63 seconds and interleaved with functional MR imaging. RESULTS. BOLD increases in motor cortex associated with TMS and VOL movement were similar (2%-3%). Mean separation of their centers of activity was 3.7 +/- 1.9 mm (mean displacement: left/right = 0.3 +/- 4.1 mm; superior/inferior = 0.7 +/- 1.9 mm), There was no indication of supraphysiological brain activity, CONCLUSIONS. Motor cortex BOLD response associated with thumb movement induced by 1-Hz TMS at 110% motor threshold is similar in both location and level to that caused by a similar movement executed volitionally. C1 Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Funct Neuroimaging Res Div, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, 171 Ashley Ave, Charleston, SC 29425 USA. NR 19 TC 55 Z9 56 U1 0 U2 5 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 NOV PY 2000 VL 35 IS 11 BP 676 EP 683 DI 10.1097/00004424-200011000-00005 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 374CF UT WOS:000165326300005 PM 11110304 ER PT J AU Steinman, MA AF Steinman, MA TI Gifts to physicians in the consumer marketing era SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID PHARMACEUTICAL SALES REPRESENTATIVES; ATTITUDES; RESIDENTS; BEHAVIOR; INDUSTRY; FACULTY C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Steinman, MA (reprint author), San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. NR 15 TC 8 Z9 9 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 1 PY 2000 VL 284 IS 17 BP 2243 EP 2243 DI 10.1001/jama.284.17.2243 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 367GD UT WOS:000090052600038 PM 11056602 ER PT J AU King, DW King, LA Erickson, DJ Huang, MT Sharkansky, EJ Wolfe, J AF King, DW King, LA Erickson, DJ Huang, MT Sharkansky, EJ Wolfe, J TI Posttraumatic stress disorder and retrospectively reported stressor exposure: A longitudinal prediction model SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; RECIPROCAL RELATIONSHIPS; MISSISSIPPI SCALE; TRAUMATIC EVENTS; CAUSAL-ANALYSIS; SOCIAL SUPPORT; FIT INDEXES; LIFE EVENTS; GULF-WAR AB There has been recent concern about the degree to which posttraumatic stress disorder (PTSD) symptomatology influences reports of prior exposure to highly stressful life events. In this longitudinal study of 2.942 male and female Gulf War veterans, the authors documented change in stressor reporting across 2 occasions and the association between change and PTSD symptom severity. A regression-based cross-lagged analysis was used to examine the relationship between PTSD symptom severity and later reported stressor exposure. Shifts in reporting over time were modestly associated with PTSD symptom severity. The cross-lagged analysis revealed a marginal association between Time 1 PTSD symptom severity and Time 2 reported stressor exposure for men and suggested that later reports of stressor exposure are primarily accounted for by earlier reports and less so by earlier PTSD symptomatology. C1 Vet Affairs VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP King, DW (reprint author), Vet Affairs VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. NR 60 TC 82 Z9 83 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2000 VL 109 IS 4 BP 624 EP 633 DI 10.1037//0021-843X.109.4.633 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 390QA UT WOS:000166306800007 PM 11195986 ER PT J AU Kwon, DH Pena, JA Osato, MS Fox, JG Graham, DY Versalovic, J AF Kwon, DH Pena, JA Osato, MS Fox, JG Graham, DY Versalovic, J TI Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID GENE; NITROREDUCTASE; CLARITHROMYCIN AB In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likely to activate metronidazole (Mtz) by reduction and formation of cytotoxic intermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysis of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nine Mtz-resistant H. pylori isolates contained insertion or deletion mutations ('indel' mutations). One isolate contained a substitution mutation at codon position 148 that resulted in the introduction of a premature stop codon. Creation of stop codons within the rdxA coding sequence by either frameshift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides. C1 Massachusetts Gen Hosp, Microbiol Labs, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Northeastern Univ, Dept Med, Sci Lab, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Versalovic, J (reprint author), Massachusetts Gen Hosp, Microbiol Labs, Div Lab Med, Dept Pathol, Gray B526,Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI37750] NR 10 TC 19 Z9 20 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD NOV PY 2000 VL 46 IS 5 BP 793 EP 796 DI 10.1093/jac/46.5.793 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 377JJ UT WOS:000165510200019 PM 11062200 ER PT J AU Folch, A Jo, BH Hurtado, O Beebe, DJ Toner, M AF Folch, A Jo, BH Hurtado, O Beebe, DJ Toner, M TI Microfabricated elastomeric stencils for micropatterning cell cultures SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE cellular micropatterns; microfabricated stencil; microfluidic; PDMS; biocompatible materials ID SURFACES; HEPATOCYTES; COCULTURES; NETWORKS; BIOMOLECULES; ATTACHMENT; SUBSTRATUM; ADHESION; GROWTH; SHAPE AB Here we present an inexpensive method to fabricate microscopic cellular cultures, which does not require any surface modification of the substrate prior to cell seeding. The method utilizes a reusable elastomeric stencil (i.e., a membrane containing thru holes) which seals spontaneously against the surface. The stencil is applied to the cell-culture substrate before seeding. During seeding, the stencil prevents the substrate from being exposed to the cell suspension except on the hole areas. After cells are allowed to attach and the stencil is peeled off, cellular islands with a shape similar to the holes remain on the cell-culture substrate. This solvent-free method can be combined with a wide range of substrates (including biocompatible polymers, homogeneous or nonplanar surfaces, microelectronic chips, and gels), biomolecules, and virtually any adherent cell type. (C) 2000 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Elect & Comp Engn, Urbana, IL 61801 USA. Univ Wisconsin, Dept Biomed Engn, Madison, WI USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, 55 Fruit St,Bigelow 1401, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13322] NR 31 TC 250 Z9 258 U1 2 U2 46 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD NOV PY 2000 VL 52 IS 2 BP 346 EP 353 DI 10.1002/1097-4636(200011)52:2<346::AID-JBM14>3.0.CO;2-H PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 345JM UT WOS:000088812900014 PM 10951374 ER PT J AU Tsou, R Cole, JK Nathens, AB Isik, FF Heimbach, DM Engrav, LH Gibran, NS AF Tsou, R Cole, JK Nathens, AB Isik, FF Heimbach, DM Engrav, LH Gibran, NS TI Analysis of hypertrophic and normal scar gene expression with cDNA microarrays SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Burn-Association CY MAR 14-17, 2000 CL LAS VEGAS, NEVADA SP Amer Burn Assoc ID GROWTH-FACTOR-I; MESSENGER-RNAS; TISSUE; LOCALIZATION; IDENTIFICATION; COLLAGENASE; DISCOVERY; ARRAYS; TIMP AB Hypertrophic scar is one form of abnormal wound healing. Previous studies have suggested that hypertrophic scar formation results from altered gene expression of extracellular matrix molecules. A broadscale evaluation of gene expression in hypertrophic scars has not been reported. To better understand abnormalities in hypertrophic scar gene expression, we compared messenger RNA expression in hypertrophic scars, normal scars, and uninjured skin with the use of complementary (c)DNA microarrays. Total RNA was extracted from freshly excised human hypertrophic scars, normal scars, or uninjured skin and reverse transcribed into cDNA with the incorporation of [P-33] deoxycytidine triphosphate. The resulting radioactive cDNA probes were hybridized onto cDNA microarrays of 4000 genes. Hybridization signals were normalized and analyzed. In the comparison of tissue samples, mean intensities were calculated for each gene within each group (hypertrophic scars, normal scars, and uninjured skin). Ratios of the mean intensities of hypertrophic scars to normal scars, hypertrophic scars to uninjured skin, and normal scars to uninjured skin were generated. A ratio that was greater than 1 indicated upregulation of any particular gene and a ratio that was less than 1 indicated downregulation of any particular gene. Our data indicated that 142 genes were overexpressed and 50 genes were underexpressed in normal scars compared with uninjured skin, 107 genes were overexpressed and 71 were underexpressed in hypertrophic scars compared with uninjured skin, and 44 genes were overexpressed and 124 were underexpressed in hypertrophic scars compared with normal scars. Our analysis of collagen, growth factor, and metalloproteinase gene expression confirmed that our molecular data were consistent with published biochemical and clinical observations of normal scars and hypertrophic scars. cDNA microarray analysis provides a powerful tool for the investigation of differential gene expression in hypertrophic scar samples and either uninjured skin or normal scars. Our data validate the use of this technology for future studies on gene expression during repair processes of normal and abnormal wounds. C1 Univ Washington, Harborview Med Ctr, Burn Ctr, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, Harborview Med Ctr, Dept Surg, Seattle, WA USA. RP Gibran, NS (reprint author), Univ Washington, Harborview Med Ctr, Burn Ctr, 325 9Th Ave,Box 359796, Seattle, WA 98104 USA. NR 26 TC 39 Z9 46 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 2000 VL 21 IS 6 BP 541 EP 550 DI 10.1067/mbc.2000.110808 PG 10 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 390EE UT WOS:000166282100012 PM 11194809 ER PT J AU Soyka, LA Fairfield, WP Klibanski, A AF Soyka, LA Fairfield, WP Klibanski, A TI Hormonal determinants and disorders of peak bone mass in children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; JUVENILE RHEUMATOID-ARTHRITIS; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; RECEPTOR GENE POLYMORPHISMS; DEPENDENT DIABETES-MELLITUS; LONG-TERM TREATMENT; MINERAL DENSITY; GROWTH-HORMONE; CYSTIC-FIBROSIS C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA 01655 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01-DK-52625, T32-DK-07028-25] NR 133 TC 100 Z9 109 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2000 VL 85 IS 11 BP 3951 EP 3963 DI 10.1210/jc.85.11.3951 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 402ML UT WOS:000166992000001 PM 11095413 ER EF