FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Katragadda, S Xie, AL Puleo, D Skatrud, JB Morgan, BJ AF Katragadda, S Xie, AL Puleo, D Skatrud, JB Morgan, BJ TI Neural mechanism of the pressor response to obstructive and nonobstructive apnea SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sympathetic nervous system; arterial pressure; obstructive sleep apnea ID SYMPATHETIC-NERVE ACTIVITY; LEFT-VENTRICULAR HEMODYNAMICS; BLOOD-PRESSURE; NEUROCIRCULATORY CONSEQUENCES; VOLUNTARY APNEA; STROKE VOLUME; SLEEP STATE; HYPOXEMIA; RESPIRATION; HUMANS AB Obstructive and nonobstructive apneas elicit substantial increases in muscle sympathetic nerve activity and arterial pressure. The time course of change in these variables suggests a causal relationship; however, mechanical influences, such as release of negative intrathoracic pressure and reinflation of the lungs, are potential contributors to the arterial pressure rise. To test the hypothesis that apnea-induced presser responses are neurally mediated, we measured arterial pressure (photoelectric plethysmography), muscle sympathetic nerve activity (peroneal microneurography), arterial O-2 saturation (pulse oximeter), and end-tidal CO2 tension (gas analyzer) during sustained Mueller maneuvers, intermittent Mueller maneuvers, and simple breath holds in six healthy humans before, during, and after ganglionic blockade with trimethaphan (3-4 mg/min, titrated to produce complete disappearance of sympathetic bursts from the neurogram). Ganglionic blockade abolished the presser responses to sustained and intermittent Mueller maneuvers (-4 +/- 1 vs. +15 +/- 3 and 0 +/- 2 vs. +/- 15 +/- 5 mmHg) and breath holds (0 +/- 3 vs. +11 +/- 3, all P < 0.05). We conclude that the acute presser response to obstructive and nonobstructive voluntary apnea is sympathetically mediated. C1 UNIV WISCONSIN,DEPT SURG,MADISON,WI 53706. UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53706. NR 23 TC 52 Z9 52 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 1997 VL 83 IS 6 BP 2048 EP 2054 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YK807 UT WOS:A1997YK80700035 PM 9390980 ER PT J AU Riedel, H Wang, J Hansen, H Yousaf, N AF Riedel, H Wang, J Hansen, H Yousaf, N TI PSM, an insulin-dependent, pro-rich, PH, SH2 domain containing partner of the insulin receptor SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE cDNA cloning; insulin receptor; SH2 domain association; splice variants; yeast two-hybrid system ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION; SIGNAL-TRANSDUCTION PATHWAYS; TYROSINE KINASE; PROTEIN-KINASE; GLUT4 TRANSLOCATION; TARGETED DISRUPTION; 2-HYBRID SYSTEM; BINDING-SITES; ECTO-ATPASE; GRB-IR AB Insulin stimulation results in a considerable spectrum of cellular responses, only part of which have been firmly correlated with the activation of established insulin receptor (IR) targets such as IRS-1, IRS-2, and Shc. Many responses may be transduced by alternative direct IR targets, some of which may still be unknown, may act in parallel to but independently of IRS-1, IRS-2, and Shc, and may be members of the growing family of SH2 domain-containing signaling adaptors, An SH2 domain-coding region of a protein termed PSM was cloned based on its interaction with an activated IR cytoplasmic fragment in a yeast two-hybrid screen, When used as a hybridization probe this region led to the isolation of a protein-coding cDNA which is expressed with a wide tissue distribution and exists in several variant forms, A pleckstrin homology domain and three Pro-rich regions including a putative SH3 domain binding site were identified in addition to the SH2 domain in the deduced 756 amino acid sequence, They imply a role of PSM in tyrosine kinase and phosphatase-mediated signaling pathways, A similar sequence termed SH2-B had been reported in an earlier study, which may represent the rat homolog of PSM, A role of PSM specifically in insulin action is suggested by the interaction of its SH2 domain with an activated but not with an inactive catalytic fragment of the IR in the yeast two-hybrid system in vivo, by the insulin-dependent association of a glutathione S-transferase (GST) PSM SH2 domain fusion protein with purified IR in vitro, and by the insulin-dependent association of GST PSM SH2 with the IR in cell extracts, In contrast, PSM was not found to associate with the established IR substrate IRS-1 under any conditions and appears to act independently of IRS-1, All of our findings are compatible with a putative role of PSM in insulin action. C1 WAYNE STATE UNIV,KARMANOS CANC INST,DETROIT,MI 48202. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,MOL BIOL SECT,BOSTON,MA 02215. RP Riedel, H (reprint author), WAYNE STATE UNIV,DEPT BIOL SCI,2171 BSB,5047 GULLEN MALL,DETROIT,MI 48202, USA. FU NIDDK NIH HHS [DK36836] NR 73 TC 56 Z9 62 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD DEC PY 1997 VL 122 IS 6 BP 1105 EP 1113 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YL149 UT WOS:A1997YL14900005 PM 9498552 ER PT J AU Reppert, SM AF Reppert, SM TI Melatonin receptors: Molecular biology of a new family of G protein-coupled receptors SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE melatonin; receptors; G protein; cyclic AMP; signal transduction; circadian rhythms ID CIRCADIAN RESPONSES; BINDING-SITES; CLONING; EXPRESSION; SUBTYPES; PITUITARY; HAMSTERS; RETINA; BRAIN; GENE AB A family of high-affinity, G protein-coupled receptors for the pineal hormone melatonin has been cloned from vertebrates. These recombinant receptors exhibit similar affinity and pharmacological characteristics to each other and to endogenous receptors, as defined with the melatonin agonist 2-[I-125]iodomelatonin (I-125-Mel). Two mammalian melatonin receptor subtypes have been identified by molecular cloning studies. The mammalian Mel(1a) melatonin receptor is expressed in most sites containing I-125-Mel binding. This includes the hypothalamic suprachiasmatic nucleus and hypophyseal pars tuberalis, presumed sites of the circadian and some of the reproductive actions of melatonin, respectively. The mammalian Mel(1b) melatonin receptor is expressed in retina and brain and may mediate the reported effects of melatonin on retinal physiology in some mammals. A third receptor subtype, the Mel(1c) melatonin receptor, has been cloned from zebra fish, Xenopus, and chickens but not from mammals. Molecular cloning of a melatonin receptor family now makes possible gene targeting to precisely determine the physiological role(s) of each receptor subtype. RP Reppert, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,LAB DEV CHRONOBIOL,BOSTON,MA 02114, USA. NR 17 TC 172 Z9 175 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 1997 VL 12 IS 6 BP 528 EP 531 DI 10.1177/074873049701200606 PG 4 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA YJ449 UT WOS:A1997YJ44900006 PM 9406026 ER PT J AU Weaver, DR AF Weaver, DR TI Reproductive safety of melatonin: A ''wonder drug'' to wonder about SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE melatonin; reproduction; toxicity; contraception; prenatal exposure; puberty ID SERUM MELATONIN; BREAST-CANCER; HYPOTHALAMUS; EXPRESSION; RESPONSES; RECEPTORS; PITUITARY; HAMSTERS; PREVENT; AREA AB By some accounts, melatonin is the wonder drug of the 1990s. This previously obscure hormone came to the public's full attention as the result of a series of popular books claiming therapeutic benefits of melatonin ingestion. Some of these claims deserve serious consideration and investigation, whereas others appear unfounded. Without waiting for the outcome of the ongoing scientific debate, however, melatonin set astounding sales records. The hormone is now ingested on a daily basis by many thousands of people. There is little information on the potential adverse effects of melatonin ingestion in humans. Melatonin, its analogs, and its metabolites are not mutagenic, and melatonin possesses remarkably low acute toxicity in animals and humans. It is more difficult to exclude toxic effects of long-term melatonin treatment. The fact that melatonin is normally secreted each night does not ensure that exogenous melatonin, taken at other times and/or in supraphysiological doses, will not have adverse effects. Despite the well-recognized role of melatonin in the regulation of reproduction in photoperiodic species, it seems unlikely that chronic ingestion of moderate melatonin doses will have a profound impact on reproductive function in humans. Evidence that melatonin modulates steroid hormone action in some steroid-responsive tissues suggests that these tissues should be carefully examined when attempting to assess whether melatonin has chronic toxicity in humans. In the absence of sufficient information regarding the longterm safety of exogenous melatonin, the conservative course of action is to restrict melatonin use to those therapeutic applications in which a significant benefit is expected. The decision to ingest melatonin should be preceded by careful consideration of the expected benefits as well as the potential costs of treatment, with recognition of the fact that there has been exaggeration of the benefits and Little attention paid to the potential costs in most discussions of this issue to date. RP Weaver, DR (reprint author), MASSACHUSETTS GEN HOSP,LAB DEV CHRONOBIOL,GRJ 1226,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD14427]; NIDDK NIH HHS [DK42125] NR 28 TC 28 Z9 29 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD DEC PY 1997 VL 12 IS 6 BP 682 EP 689 DI 10.1177/074873049701200625 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA YJ449 UT WOS:A1997YJ44900025 PM 9406045 ER PT J AU Shea, K Fernandez, DL Jupiter, JB Martin, C AF Shea, K Fernandez, DL Jupiter, JB Martin, C TI Corrective osteotomy for malunited, volarly displaced fractures of the distal end of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Twenty-five patients who had had an opening-wedge osteotomy for the treatment of a malunited, volarly diplaced fracture of the distal end of the radius were studied retrospectively. The indications for the operation were pain and functional limitations rather than the degree of anatomical deformity. Fifteen patients were men and ten were women; their average age was forty-six years (range, twenty-one to eighty-four years). Preoperative radiographs revealed an average ulnar inclination of 14 degrees, an average ulnar variance of five millimeters, and an average volar inclination of 24 degrees. Extension of the wrist averaged 25 degrees; flexion of the wrist, 53 degrees; supination of the forearm, 41 degrees; and pronation of the forearm, 64 degrees. The average grip strength was a force of seventeen kilograms compared with a force of forty kilograms compared with a force of forty kilograms in the contralateral hand. At an average of sixty-one months (range, eighteen to 114 months) after the osteotomy, supination of the forearm had improved to an average of 69 degrees and pronation had improved to an average of 75 degrees (p < 0.05 for both), Extension of the wrist had improved to an average of 55 degrees, and grip strength had improved to a force of thirty kilograms (p < 0.05 for both), Volar inclination averaged 5 degrees; ulnar variance, zero millimeters; and ulnar inclination, 22 degrees, A reoperation was performed in eleven patients, Seven patients had removal of the hardware only two had a procedure involving the distal radioulnar Joint, one had a procedure because the site of the osteotomy had not healed, and one had a median-nerve release. The functional result was rated as very good in ten patients, good in eight, fair in three, and poor in four. C1 Univ Utah, Dept Orthopaed Surg, Salt Lake City, UT 84132 USA. Orthopaed Chirurg FMH, CH-3012 Bern, Switzerland. Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. Kantonsspital, Aarau, Switzerland. RP Shea, K (reprint author), Univ Utah, Dept Orthopaed Surg, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 35 TC 47 Z9 51 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1997 VL 79A IS 12 BP 1816 EP 1826 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA YL909 UT WOS:000071006800007 PM 9409795 ER PT J AU Stuart, SE Harris, WH AF Stuart, SE Harris, WH TI Total hip arthroplasty performed with insertion of the femoral component with cement and the acetabular component without cement - Ten to thirteen-year results SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT AB Fifty-two consecutive primary total hip arthroplasties were performed in forty-seven unselected patients by one surgeon. The prosthesis included a hemispherical porous-coated acetabular component, inserted without cement and with the use of screws through three peripheral flanges, and a femoral component, inserted with a so-called second-generation cementing technique. No patient was lost to radiographic follow-up? and the clinical result was known for all patients. The average age at the time of the index operation was fifty-seven years (range, twenty-nine to seventy-nine years). Four patients (four hips) who died mere last examined less than ten gears postoperatively (the minimum follow-up period for this study) and one hip was revised, leaving forty-seven non-revised hips in forty-two surviving patients who were followed for at least ten years. The duration of clinical follow-up of these forty-two patients averaged 12.3 years (range, 10.8 to 13.3 years), and the duration of radiographic follow-up averaged 12.1 rears (range, 10.0 to 13.0 years). One (2 per cent) of the original fifty-two hips was revised for late recurrent dislocation, without loosening, 9.7 years after the index arthroplasty. The rate of dislocation was relatively high (13 per cent; seven hips), and we believed it to be related to the shallow-chamfer acetabular design combined with the small femoral head. At the time of the latest follow-up, no femoral component was loose. One (2 per cent) of the fifty-two acetabular components was loose according to radiographic criteria, but the hip functioned well (Harris hip score, 94 points) 12.4 years after the index arthroplasty. Pelvic osteolysis developed in one hip (2 per cent); femoral osteolysis, in eight (15 per cent); and distal femoral osteolysis, in three (6 per cent). The average Harris hip score for the forty-seven non-revised hips increased from 48 points (range, 26 to 63 points) preoperatively to 89 points (range, 67 to 100 points) at the time of the most recent follow-up. Forty (85 per cent) of the forty-seven hips had a good or excellent result, whereas five (11 per cent) had a fair result (score, 74 to 79 points) and two (4 per cent) had a poor result (score, 67 and 69 points). The hybrid primary total hip arthroplasty resulted in very good clinical function at ten to thirteen years, although the rate of dislocation was high. C1 Tennessee Orthopaed Associates, Nashville, TN 37203 USA. Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hip & Implant Unit, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Stuart, SE (reprint author), Tennessee Orthopaed Associates, 301 21st Ave N, Nashville, TN 37203 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD DEC PY 1997 VL 79A IS 12 BP 1827 EP 1833 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA YL909 UT WOS:000071006800008 ER PT J AU Sayegh, RA Tao, XJ Leykin, L Isaacson, KB AF Sayegh, RA Tao, XJ Leykin, L Isaacson, KB TI Endometrial alpha-2 macroglobulin; localization by in situ hybridization and effect on mouse embryo development in vitro SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-RELATED PROTEIN; MENSTRUAL-CYCLE; PROGESTERONE-RECEPTORS; ALPHA(2)-MACROGLOBULIN; EXPRESSION; UTERINE; RAT; INHIBITORS; BINDING; MECHANISM AB alpha-2 macroglobulin (A2M) is a 718,000-kDa broad spectrum plasma protease inhibitor whose production by the human endometrium was recently reported. The multifunctional A2M receptor, also known as low-density lipoprotein receptor-related protein, was also recently immunolocalized to the endometrial stroma. The objective of this study was to further characterize the endometrial site of expression of A2M, and to study its effects on mouse embryo development in vitro, to gain some insight into the functional significance of its endometrial production. Formalin-fixed, paraffin-embedded human endometrium from hysterectomy and endometrial biopsy specimen was used for in situ hybridization analysis, with S-35-labeled riboprobes representing subcloned A2M complementary DNA (cDNA) fragments. Duplicate sections of human endometrium were hybridized with sense and antisense probe and coated with photographic emulsion. Resultant autoradiograms were analyzed qualitatively by light-and darkfield microscopy and quantitatively by a computerized analysis of the signal intensity. Immunohistochemistry and immunoblotting for endometrial tissues were performed using an affinity-purified polyclonal antibody to human A2M. The effect of A2M on mouse embryo development was studied by exposure of one cell mouse embryo in culture to physiological concentrations of biologically active and inactive A2M. Expression signals for A2M were more numerous and intense in the secretory endometrium, compared with proliferative endometrium. Endothelial cells lining the endometrial blood vessels seemed to be the main source of A2M expression. The A2M expression signals in secretory endothelium were 2- to 3-fold stronger than the proliferative endothelium, suggesting transcriptional activation of A2M expression in the secretory endothelium. Glandular expression was observed in secretory endometrium from two patients with endometriosis. Ectopic endometrial tissues also produced A2M. A2M at concentrations of 400-500 mu mol/L significantly inhibited blastocyst development of mouse embryos in vitro. A2M is expressed predominantly by the endometrial endothelial cells and may be involved in endometrial physiology. Physiological concentrations of A2M. inhibit mouse embryo development in vitro, suggesting that endometrial production of A2M may play a role in regulating preimplantation embryo development. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Div Reprod Endocrinol & Infertil, Vincent Mem Ob & Gyn Serv,Wang Ambulat Care Ctr, Boston, MA 02114 USA. RP Isaacson, KB (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Div Reprod Endocrinol & Infertil, Vincent Mem Ob & Gyn Serv,Wang Ambulat Care Ctr, Boston, MA 02114 USA. NR 29 TC 9 Z9 9 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1997 VL 82 IS 12 BP 4189 EP 4195 DI 10.1210/jc.82.12.4189 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YL869 UT WOS:000071002000054 PM 9398738 ER PT J AU Field, AE Herzog, DB Keller, MB West, J Nussbaum, K Colditz, GA AF Field, AE Herzog, DB Keller, MB West, J Nussbaum, K Colditz, GA TI Distinguishing recovery from remission in a cohort of bulimic women: How should asymptomatic periods be described? SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE eating disorders; bulimia nervosa; psychiatric epidemiology; female; outcome; recovery; remission ID MAJOR DEPRESSIVE DISORDER; FOLLOW-UP; NERVOSA; RELAPSE; RECURRENCE; HISTORY AB Background: Empirical definitions of remission and recovery from eating disorders are needed to understand outcome data and compare results across studies. Method: 106 treatment-seeking women with bulimia nervosa, who had abstained from binging and purging for at least 4 weeks, were followed prospectively. Relapse was defined as at least 4 consecutive weeks of either binging and purging weekly or hinging two or more times per week, regardless of purging. Recovery was differentiated from remission based on the probability of relapse. The minimum number of weeks after which the risk of relapse leveled off was used as the cut-off to distinguish between the two outcomes. Kaplan-Meier methods were used to estimate the weekly probability of relapse. Results: When defining remission as at least 4 weeks of being asymptomatic, a quarter of the women relapsed within 11 weeks. By 37 weeks, only 49% of the women remained asymptomatic (95% CI, 41-61). The probability of relapse was substantial for approximately a year after a woman ceased to binge and purge. Conclusion: Bulimia nervosa is an episodic disorder. As a conservative approach, periods of being asymptomatic that last less than 1 year should be labeled as remissions, not recoveries. (C) 1997 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Field, AE (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK 42600]; NIMH NIH HHS [R01-MH38333] NR 25 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 1997 VL 50 IS 12 BP 1339 EP 1345 DI 10.1016/S0895-4356(97)00220-5 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA YM557 UT WOS:000071076700004 PM 9449937 ER PT J AU Schultze, JL Michalak, S Seamon, MJ Dranoff, G Jung, K Daley, J Delgado, JC Gribben, JG Nadler, LM AF Schultze, JL Michalak, S Seamon, MJ Dranoff, G Jung, K Daley, J Delgado, JC Gribben, JG Nadler, LM TI CD40-activated human B cells: An alternative source of highly efficient antigen presenting cells to generate autologous antigen-specific T cells for adoptive immunotherapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE B lymphocytes; dendritic cells; antigens, CD40; immunotherapy, adoptive; T cell proliferation ID EPSTEIN-BARR-VIRUS; COLONY-STIMULATING FACTOR; ALLOGENEIC BONE-MARROW; CHRONIC MYELOID-LEUKEMIA; NECROSIS-FACTOR-ALPHA; C-KIT-LIGAND; DENDRITIC CELLS; PROTEIN ANTIGENS; HUMAN BLOOD; IN-VITRO AB Multiple clinical trials have shown the efficacy of adoptively transferred allogeneic antigen-specific T cells for the treatment of viral infections and relapsed hematologic malignancies. In contrast, the therapeutic potential of autologous antigen-specific T cells has yet to be established since it has been technically difficult to generate sufficient numbers of these T cells, ex vivo. A major obstacle to the success of this objective derives from our inability to simply and rapidly isolate and/or expand large numbers of highly efficient antigen presenting cells (APCs) for repetitive stimulations of antigen-specific T cells in vitro. We show that autologous CD40-activated B cells represent a readily available source of highly efficient APC that appear to have several important advantages over other APCs for ex vivo T cell expansion including: (a) methodological simplicity necessary to generate continuously large numbers of APCs from just 50 cm(3) of peripheral blood without loss of APC function; (b) capacity to induce high peak T cell proliferation and interferon-gamma production without IL-10 production; (c) ease in cryopreservation; and (d) markedly reduced cost. We, therefore, contend that CD40-activated B cells are an alternative source of highly efficient APCs with which to generate antigen-specific T cells ex vivo for autologous adoptive immunotherapy. 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. Dana Farber Canc Inst, Div Immunogenet, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D742, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA66996] NR 57 TC 250 Z9 256 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1997 VL 100 IS 11 BP 2757 EP 2765 DI 10.1172/JCI119822 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YL912 UT WOS:000071007300016 PM 9389740 ER PT J AU Siegrist-Kaiser, CA Pauli, V Juge-Aubry, CE Boss, O Pernin, A Chin, WW Cusin, I Rohner-Jeanrenaud, F Burger, AG Zapf, J Meier, CA AF Siegrist-Kaiser, CA Pauli, V Juge-Aubry, CE Boss, O Pernin, A Chin, WW Cusin, I Rohner-Jeanrenaud, F Burger, AG Zapf, J Meier, CA TI Direct effects of leptin on brown and white adipose tissue SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE leptin; adipocytes; lipolysis; Jak/STAT ID OBESE GENE; UNCOUPLING PROTEIN; DIABETIC MICE; MESSENGER-RNA; OB/OB MICE; DB/DB MICE; RAT FATTY; OB-R; RECEPTOR; EXPRESSION AB Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin receptor (OB-Rb), which is present in the hypothalamus and in certain peripheral organs, including adipose tissue. In this study, we examined whether leptin has direct effects on the function of brown and white adipose tissue (BAT and WAT, respectively) at the metabolic and molecular levels, The chronic peripheral intravenous administration of leptin in vivo for 4 d resulted in a 1.6-fold increase in the in vivo glucose utilization index of EAT, whereas no significant change was found after intracerebroventricular administration compared with pair-fed control rats, compatible with a direct effect of leptin on BAT, The effect of leptin on WAT fat pads from lean Zucker Fal fa rats was assessed ex vivo, where a 9- and 16-fold increase in the rate of lipolysis tvas observed after 2 h of exposure to 0.1 and 10 nM leptin, respectively, In contrast, no increase in Lipolysis was observed in the fat pads from obese fa/fa rats, which harbor an inactivating mutation in the OB-Rb. At the level of gene expression, leptin treatment for 24 h increased malic enzyme acid lipoprotein lipase RNA 1.8 +/- 0.17 and 1.9 +/- 0.14-fold, respectively, while aP2 mRNA levels were unaltered in primary cultures of brown adipocytes from lean Fa/fa rats. Importantly, however, no significant effect of leptin was observed on these genes in brown adipocytes from obese fa/fa animals, The presence of OB-Rb receptors in adipose tissue was substantiated by the detection of its transcripts by RT-PCR, and leptin treatment in vivo and in vitro activated the specific STATs implicated in the signaling pathway of the OB-Rb. Taken together, our data strongly suggest that leptin has direct effects on BAT and WAT, resulting in the activation of the Jak/STAT pathway and the increased expression of certain target genes, which may partially account for the observed increase in glucose utilization and lipolysis in leptin-treated adipose tissue. C1 Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Univ Hosp Geneva, Div Endocrinol & Diabetol, Unite Thyroide, Geneva, Switzerland. Univ Geneva, Med Ctr, CH-1211 Geneva 4, Switzerland. Univ Geneva, Fac Med, Lab Rech Metab, CH-1211 Geneva 14, Switzerland. Univ Zurich Hosp, Div Endocrinol & Diabet, CH-8091 Zurich, Switzerland. Univ Hosp Geneva, Dept Med, Med Clin 2, CH-1211 Geneva 14, Switzerland. Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. RP Meier, CA (reprint author), Brigham & Womens Hosp, Dept Med, Div Genet, Thorn 10,20 Shattuck St, Boston, MA 02115 USA. NR 45 TC 260 Z9 266 U1 2 U2 14 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1997 VL 100 IS 11 BP 2858 EP 2864 DI 10.1172/JCI119834 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YL912 UT WOS:000071007300028 PM 9389752 ER PT J AU Hynes, RO Wagner, DD AF Hynes, RO Wagner, DD TI Genetic manipulation of vascular adhesion molecules in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article C1 MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Hynes, RO (reprint author), MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC 1 PY 1997 VL 100 IS 11 SU S BP S11 EP S13 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YN850 UT WOS:000071214400004 PM 9413394 ER PT J AU Hofgartner, WT Swanzy, SR Bacina, RM Condon, J Gupta, M Matlock, PE Bergeron, DL Plorde, JJ Fritsche, TR AF Hofgartner, WT Swanzy, SR Bacina, RM Condon, J Gupta, M Matlock, PE Bergeron, DL Plorde, JJ Fritsche, TR TI Detection of immunoglobulin G (IgG) and IgM antibodies to Toxoplasma gondii: Evaluation of four commercial immunoassay systems SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ENZYME-IMMUNOASSAY; PERFORMANCE; DIAGNOSIS; ASSAY AB A comparative evaluation of the following commercial immunoassays for the determination of antibodies to Toxoplasma gondii was performed: Behring Diagnostics OPUS Toxo G and Toro M, Abbott Diagnostics IMX Toxo-IgG 2.0 and Toxo-IgM, Sanofi Diagnostics Pasteur Platelia Toxo IgG and Toxo IgM, and bioMerieux Vitek VIDAS Toxo IgG and IgM. Of 676 specimens that were tested for Toxoplasma-specific immunoglobulin G (IgG) antibodies, 26% were reactive by all methods while 8% displayed some discrepancy. Of 718 specimens that were tested for Toxoplasma-specific IgM antibodies, 3% were reactive by all methods while 10% displayed some discrepancy. Analysis of discrepant specimens revealed performance shortcomings with all IgM-specific assays. The impact of such shortcomings is magnified in a population with a low prevalence of toxoplasmosis. C1 UNIV WASHINGTON,MED CTR,DEPT LAB MED,SEATTLE,WA 98195. VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. NR 13 TC 45 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1997 VL 35 IS 12 BP 3313 EP 3315 PG 3 WC Microbiology SC Microbiology GA YG967 UT WOS:A1997YG96700059 PM 9399544 ER PT J AU Mason, W Louis, DN Cairncross, JG AF Mason, W Louis, DN Cairncross, JG TI Chemosensitive gliomas in adults: Which ones and why? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID MALIGNANT GLIOMA; HUMAN ASTROCYTOMAS; P53 PROTEIN; CHEMOTHERAPY; OLIGODENDROGLIOMA; TUMORS; GENE; GLIOBLASTOMAS; RADIOTHERAPY; PROCARBAZINE C1 UNIV TORONTO,TORONTO,ON,CANADA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV WESTERN ONTARIO,LONDON,ON,CANADA. LONDON REG CANC CTR,LONDON,ON N6A 4L6,CANADA. RP Mason, W (reprint author), PRINCESS MARGARET HOSP,TORONTO,ON M4X 1K9,CANADA. NR 34 TC 32 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1997 VL 15 IS 12 BP 3423 EP 3426 PG 4 WC Oncology SC Oncology GA YJ712 UT WOS:A1997YJ71200001 PM 9396392 ER PT J AU Marder, SR Davis, JM Chouinard, G AF Marder, SR Davis, JM Chouinard, G TI The effects of risperidone on the five dimensions of schizophrenia derived by factor analysis: Combined results of the North American trials SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID NEGATIVE SYNDROME SCALE; 5 FACTOR MODEL; SYMPTOMS; COMPONENT; PANSS AB Background: In two double-blind trials conducted in North America, 513 patients with chronic schizophrenia received risperidone, haloperidol, or placebo. In the present study, combined data from the two trials were analyzed. Method: Patients were randomly assigned to receive placebo,fixed doses of risperidone (2, 6, 10, and 16 mg/day), or 20 mg/day of haloperidol for 8 weeks. Factor analysis of scores on the Positive and Negative Syndrome Scale (PANSS) produced five dimensions (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, and anxiety/depression), similar to the five dimensions of previous factor-analytic studies of PANSS data. Results: Mean changes (symptom reductions) in PANSS factor scores from baseline to treatment Weeks 6 and 8 were significantly greater in patients receiving 6-16 mg/day of risperidone than in patients receiving placebo or haloperidol. The advantages of risperidone were greatest for negative symptoms, uncontrolled hostility/excitement, and anxiety/depression. Even at the lowest dose, 2 mg/day, risperidone was significantly (p less than or equal to .05) superior to haloperidol in reducing negative symptoms. The differences in outcomes between risperidone and haloperidol on PANSS scores were not related to extrapyramidal symptoms. Conclusion: Risperidone produced significantly (p less than or equal to .05) greater improvements than haloperidol on all five dimensions. The large between-group differences on negative symptoms, hostility/excitement, and anxiety/depression suggest that risperidone and other serotonin/dopamine antagonists have qualitatively different effects from those of conventional antipsychotic agents. C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, Brentwood Div, Los Angeles, CA 90037 USA. Univ Illinois, Inst Psychiat, Chicago, IL USA. Hop Louis H Lafontaine, Quebec City, PQ, Canada. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Serv 116A, Brentwood Div, 11301 Wilshire Blvd, Los Angeles, CA 90037 USA. NR 33 TC 450 Z9 459 U1 2 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD DEC PY 1997 VL 58 IS 12 BP 538 EP 546 DI 10.4088/JCP.v58n1205 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA YQ930 UT WOS:000071438900005 PM 9448657 ER PT J AU Frueh, BC Henning, KR Pellegrin, KL Chobot, K AF Frueh, BC Henning, KR Pellegrin, KL Chobot, K TI Relationship between scores on anger measures and PTSD symptomatology, employment, and compensation-seeking status in combat veterans SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; HOSTILITY; DEPRESSION; VALIDITY AB The interrelationship between the theoretically related constructs of anger and posttraumatic stress disorder (PTSD) symptoms was examined in a group of 42 combat veterans with PTSD using a multimeasure assessment strategy. Scores on several anger measures were found to be guile high in this sample and were significantly correlated with PTSD symptomatology. Furthermore, anger measures were found to be related to employment status independent of PTSD severity, but were not related to disability compensation-seeking status. Clinicians are advised to be aware of the potential implications for physical health and interpersonal functioning. and to incorporate anger management strategies into treatment plans for this population. (C) 1997 John Wiley & Sons, Inc. C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. RP Frueh, BC (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,MENTAL HLTH SERV 116,109 BEE ST,CHARLESTON,SC 29401, USA. NR 30 TC 33 Z9 34 U1 0 U2 1 PU CLINICAL PSYCHOLOGY PUBL CO PI BRANDON PA 4 CONANT SQUARE, BRANDON, VT 05733 SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD DEC PY 1997 VL 53 IS 8 BP 871 EP 878 PG 8 WC Psychology, Clinical SC Psychology GA YH741 UT WOS:A1997YH74100013 PM 9403390 ER PT J AU Litz, BT King, LA King, DW Orsillo, SM Friedman, MJ AF Litz, BT King, LA King, DW Orsillo, SM Friedman, MJ TI Warriors as peacekeepers: Features of the Somalia experience and PTSD SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; VALIDITY; MODELS; TESTS; FIT AB There has been scant empirical study of the psychological consequences of contemporary peacekeeping missions. This study examined relationships among 4 variables characterizing this type of operation (traditional combat events, negative aspects of peacekeeping, pressure to uphold restraint, and positive aspects of peacekeeping) and symptoms of posttraumatic stress disorder (PTSD). Participants were 3,310 male and female soldiers who served in the 1992-1994 Somalia mission. Structural equation modeling procedures were applied to data from subsamples of non-African Americans and African Americans. For both groups, traditional combat and negative aspects of peacekeeping were associated with PTSD, frustration with restraint, and positive aspects of peacekeeping; however, restraint was not related to PTSD. Discrepancies between the groups involved relationships among the restraint, positive aspects, and PTSD variables. Recommendations are offered to foster inquiry into this new research. C1 BOSTON UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02118. BOSTON DEPT VET AFFAIRS MED CTR,NATL CTR POST TRAUMAT STRESS DISORDER,WOMENS HLTH SCI DIV,BOSTON,MA 02130. OKLAHOMA STATE UNIV,DEPT PSYCHOL,STILLWATER,OK 74078. WHITE RIVER JUNCT DEPT VET AFFAIRS MED CTR,NATL CTR POST TRAUMAT STRESS DISORDER,EXECUT DIV,WHITE RIVER JCT,VT. DARTMOUTH COLL,SCH MED,DEPT PHARMACOL & PSYCHIAT,HANOVER,NH 03755. RP Litz, BT (reprint author), BOSTON DEPT VET AFFAIRS MED CTR,NATL CTR POST TRAUMAT STRESS DISORDER,BEHAV SCI DIV,BOSTON,MA 02130, USA. NR 58 TC 56 Z9 56 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 1997 VL 65 IS 6 BP 1001 EP 1010 DI 10.1037/0022-006X.65.6.1001 PG 10 WC Psychology, Clinical SC Psychology GA YJ463 UT WOS:A1997YJ46300010 PM 9420361 ER PT J AU Tang, T Rosenkranz, A Assmann, KJM Goodman, MJ GutierrezRamos, JC Carroll, MC Cotran, RS Mayadas, TN AF Tang, T Rosenkranz, A Assmann, KJM Goodman, MJ GutierrezRamos, JC Carroll, MC Cotran, RS Mayadas, TN TI A role for Mac-1 (CDIIb/CD18) in immune complex-stimulated neutrophil function in vivo: Mac-1 deficiency abrogates sustained Fc gamma receptor-dependent neutrophil adhesion and complement-dependent proteinuria in acute glomerulonephritis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MEDIATED GLOMERULONEPHRITIS; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODIES; HETEROLOGOUS PHASE; CD11B/CD18; PHAGOCYTOSIS; MOLECULES; NEPHRITIS; CR3; ALPHA(M)BETA(2) AB Mac-1 (alpha(m) beta(2)), a leukocyte adhesion receptor, has been shown in vitro to functionally interact with Fc gamma receptors to facilitate immune complex (IC)-stimulated polymorphonuclear neutrophil (PMN) functions. To investigate the relevance of Mac-1-Fc gamma R interactions in IC-mediated injury in vivo, we induced a model of Fc-dependent anti-glomerular basement membrane (GEM) nephritis in wild-type and Mac-1-deficient mice by the intravenous injection of anti-GBM antibody. The initial glomerular PMN accumulation was equivalent in Mac-1 null and wild-type mice, but thereafter increased in wild-type and decreased in mutant mice. The absence of Mac-1 interactions with obvious ligands, intercellular adhesion molecule 1 (ICAM-1), and C3 complement, is not responsible for the decrease in neutrophil accumulation in Mac-1-deficient mice since glomerular PMN accumulation in mice deficient in these ligands was comparable to those in wild-type mice. In vitro studies showed that spreading of Mac-1-null PMNs to IC-coated dishes was equivalent to that of wild-type PMNs at 5-12 min but was markedly reduced thereafter, and was associated with an inability of mutant neutrophils to redistribute filamentous actin. This suggests that in vivo, Mac-1 is not required for the initiation of Fc-mediated PMN recruitment but that Mac-1-Fc gamma R interactions are required for filamentous actin reorganization leading to sustained PMN adhesion, and this represents the first demonstration of the relevance of Mac-1-Fc gamma R interactions in vivo. PMN-dependent proteinuria, maximal in wild-type mice at 8 h, was absent in Mac-1 mutant mice at all time points. Complement C3-deficient mice also had significantly decreased proteinuria compared to wild-type mice. Since Mac-1 on PMNs is the principal ligand for ic3b, an absence of Mac-1 interaction with C3 probably contributed to the abrogation of proteinuria in Mac-1-null mice. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV NIJMEGEN HOSP,NL-6500 HB NIJMEGEN,NETHERLANDS. FU NHLBI NIH HHS [P01 HL-36028, P01 HL036028]; NIDDK NIH HHS [DK-51643, R01 DK051643]; NINDS NIH HHS [NS-33296] NR 30 TC 142 Z9 143 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 1 PY 1997 VL 186 IS 11 BP 1853 EP 1863 DI 10.1084/jem.186.11.1853 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YK681 UT WOS:A1997YK68100007 PM 9382884 ER PT J AU Cantiello, HF AF Cantiello, HF TI Role of actin filament organization in cell volume and ion channel regulation SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Membrane Transport in Honor of Arnost Kleinzeller CY AUG 01-03, 1996 CL MT DESERT ISL BIOL LAB, SALSBURY COVE, ME HO MT DESERT ISL BIOL LAB ID EPITHELIAL NA+ CHANNELS; BINDING-PROTEIN; F-ACTIN; PHASE-TRANSITIONS; PLASMA-MEMBRANES; SODIUM-CHANNEL; CYTOCHALASIN-D; KIDNEY-CELLS; CYTOSKELETON; IDENTIFICATION AB The actin cytoskeleton is an intracellular structure, which is involved in the onset and control of cell shape and function. In order for this relevant network to control its own and thus cell volume, specific interactions between the actin cytoskeleton and ion channel regulation controlling intracellular salt and water homeostasis may be invoked. The hypotonic shock-induced, cell volume regulatory decrease (RVD) of most eukaryotic cells is a particularly useful example, as it is initiated and regulated by concerted processes involving both adaptive changes in actin filament organization and bulk fluid extrusion triggered by saline movement and the consequent decrease in cell water. The onset of RVD is linked to the selective activation of osmotically-sensitive ion channels and other relevant ion transport mechanisms involved in the net ionic movement from the cytosol. Such regulatory processes, entailing effector changes in actin filament organization which target the plasma membrane, are largely unknown. In this report, recent studies are summarized implicating dynamic changes in gel properties of the actin cytoskeleton as the effector mechanism in the regulation of ion channel activity, and thus cell volume, in human melanoma cells. Based on the characterization of the hypotonic cell volume regulatory response of human melanoma cells devoid of a functional actin-binding protein (ABP-280, a filamin homolog) and their genetically rescued counterpart transfected with a functional ABP, a hypothesis is raised which is consistent with a regulatory ''sensory'' mechanism based on the ability of actin networks to respond to changes in the intracellular water-salt homeostasis, which in turn effects signals controlling membrane function, including ion channel activity. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP Cantiello, HF (reprint author), MASSACHUSETTS GEN HOSP EAST,RENAL UNIT,149 13TH ST,CHARLESTOWN,MA 02129, USA. FU NIDDK NIH HHS [R01-DK48040] NR 64 TC 84 Z9 90 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD DEC 1 PY 1997 VL 279 IS 5 BP 425 EP 435 DI 10.1002/(SICI)1097-010X(19971201)279:5<425::AID-JEZ4>3.0.CO;2-Q PG 11 WC Zoology SC Zoology GA YH746 UT WOS:A1997YH74600004 PM 9392863 ER PT J AU Silva, P Solomon, RJ Epstein, FH AF Silva, P Solomon, RJ Epstein, FH TI Transport mechanisms that mediate the secretion of chloride by the rectal gland of Squalus acanthias SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT Symposium on Cellular and Molecular Membrane Transport in Honor of Arnost Kleinzeller CY AUG 01-03, 1996 CL MT DESERT ISL BIOL LAB, SALSBURY COVE, ME HO MT DESERT ISL BIOL LAB ID K-CL COTRANSPORT; PROTEIN-KINASE-A; MOLECULAR-CLONING; LUMINAL MEMBRANE; XENOPUS OOCYTES; CONDUCTANCE; SODIUM; PHOSPHORYLATION; NA,K-ATPASE; STIMULATION AB The rectal gland of Squalus acanthias secretes chloride by a mechanism that has been termed ''secondary active transport'' because it depends on the activity of Na-K-ATPase. As currently described, chloride enters the cell across the basolateral cell membrane via the 2 chloride: sodium: potassium cotransporter. The energy for this electroneutral uphill movement of chloride and potassium is provided by the gradient for sodium directed into the cell. Present in the basolateral cell membrane is Na-K-ATPase that maintains the gradient for sodium. A potassium conductance, present as well in the basolateral cell membrane, recirculates the potassium. Chloride exits the cell across the luminal membrane via CFTR, the chloride conductance. This mechanism is widely distributed throughout vertebrates. This report reviews the experimental observations that led to the current definition of the mechanism of chloride transport in the rectal gland. (C) 1997 Wiley-Liss, Inc. C1 MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. BETH ISRAEL MED CTR,DIV NEPHROL,BOSTON,MA 02215. RP Silva, P (reprint author), JOSLIN DIABET CTR,DIV NEPHROL,BOSTON,MA 02215, USA. NR 42 TC 23 Z9 23 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD DEC 1 PY 1997 VL 279 IS 5 BP 504 EP 508 PG 5 WC Zoology SC Zoology GA YH746 UT WOS:A1997YH74600014 PM 9392873 ER PT J AU Yu, CL Jove, R Burakoff, SJ AF Yu, CL Jove, R Burakoff, SJ TI Constitutive activation of the Janus kinase STAT pathway in T lymphoma overexpressing the Lck protein tyrosine kinase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; DNA-BINDING ACTIVITY; SIGNAL-TRANSDUCTION; HTLV-I; LEUKEMIA; GENE; PHOSPHORYLATION; INTERLEUKIN-2; INVOLVEMENT; EXPRESSION AB The Lck protein, a Src family tyrosine kinase, plays a critical role in T cell maturation and activation. Dysregulation of Lck expression or Lck kinase activity has been implicated in T cell leukemias from mice to humans, although the mechanism underlying Lck-mediated oncogenesis is still largely unclear. We report here that both DNA binding activities and tyrosine phosphorylation of STAT3 and STAT5, but not STAT1, are constitutively enhanced in the mouse T cell lymphoma LSTRA, which is a well-characterized cell line that overexpresses Lck protein and exhibits high levels of Lck kinase activity, Furthermore, Janus kinase 1 (Jak1) and Jak2 protein tyrosine kinases are constantly activated in these cells, as determined by their autophosphorylation in an in vitro kinase assay and increased levels of tyrosine phosphorylation on immunoblots. Therefore, like Src-transformed cells, Lck-overexpressing LSTRA cells also exhibit constitutive activation of distinct Jak and STAT proteins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Tampa, FL 33612 USA. RP Burakoff, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 FU NCI NIH HHS [CA70758, CA55652] NR 34 TC 86 Z9 89 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1997 VL 159 IS 11 BP 5206 EP 5210 PG 5 WC Immunology SC Immunology GA YW263 UT WOS:000071914800006 PM 9548458 ER PT J AU Tanabe, S Lu, ZJ Luo, Y Quackenbush, EJ Berman, MA Collins-Racie, LA Mi, S Reilly, C Lo, D Jacobs, KA Dorf, ME AF Tanabe, S Lu, ZJ Luo, Y Quackenbush, EJ Berman, MA Collins-Racie, LA Mi, S Reilly, C Lo, D Jacobs, KA Dorf, ME TI Identification of a new mouse beta-chemokine, thymus-derived chemotactic agent 4, with activity on T lymphocytes and mesangial cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BIOLOGIC ACTIVITIES; DENDRITIC CELLS; MESSENGER-RNA; TCA3 BINDS; EXPRESSION; MURINE; CLONING; PROLIFERATION; GENERATION AB Thymus-derived chemotactic agent 4 (TCA4), a new member of the beta-chemokine family, was cloned from a mouse thymic cDNA library, High levels of TCA4 mRNA are expressed in thymus; lower levels of message are found in spleen, heart, and kidney, Anti-TCA4 antibodies were used to localize sites of TCA4 expression within lymphoid tissues, In the thymus, UEA-1(+) medullary epithelial cells, some endothelial cells, and additional undefined stromal elements were stained with anti-TCA4, TCA4 was also expressed as a meshlike network in splenic white pulp and in the medullary region of the lymph nodes, In addition, some lymph node and splenic blood vessels stained with anti-TCA4 antibodies, Rel B NF kappa B-deficient mice lack a transcription factor required for the generation of dendritic cells and the development of an organized thymic medulla, Rel B-deficient animals express very low levels of TCA4 in the thymus and little or no TCA4 in the periphery, At subnanomolar concentrations, TCA4 is a chemoattractant of mature T cells; the potential role of this novel chemokine in facilitating normal lymphocyte traffic is discussed, TCA4 is also a chemoattractant of cultured mesangial cells, Neutralizing anti-TCA4 mAb was used to demonstrate the specificity of TCA4-mediated cell migration, Finally, competitive binding studies with a SV40-transformed mouse mesangial cell line demonstrated that other murine beta-chemokines (monocyte chemotactic protein-1, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and thymus-derived chemotactic agent 3) do not compete for TCA4 binding. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Childrens Hosp, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, Div Clin Genet, Boston, MA 02115 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Dorf, ME (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. EM dorf@warren.med.harvard.edu FU NCI NIH HHS [CA56057, CA67416]; NIAID NIH HHS [AI38375] NR 44 TC 100 Z9 103 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1997 VL 159 IS 11 BP 5671 EP 5679 PG 9 WC Immunology SC Immunology GA YW263 UT WOS:000071914800060 PM 9548511 ER PT J AU Bates, DW Sands, K Miller, E Lanken, PN Hibberd, PL Graman, PS Schwartz, JS Kahn, K Snydman, DR Parsonnet, J Moore, R Black, E Johnson, BL Jha, A Platt, R AF Bates, DW Sands, K Miller, E Lanken, PN Hibberd, PL Graman, PS Schwartz, JS Kahn, K Snydman, DR Parsonnet, J Moore, R Black, E Johnson, BL Jha, A Platt, R TI Predicting bacteremia in patients with sepsis syndrome SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE BACTEREMIA; ANTIENDOTOXIN MONOCLONAL-ANTIBODIES; CLINICAL-PREDICTION; SEPTIC SHOCK; RISK-FACTORS; HOSPITALIZED-PATIENTS; PROJECTED IMPACT; MORTALITY; THERAPY; CANDIDEMIA AB The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome, Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low-and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia, Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low-to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated. C1 BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02114. TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL & MED,DIV INFECT DIS,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,BOSTON,MA. HOSP UNIV PENN,DIV PULM & CRIT CARE,PHILADELPHIA,PA 19104. HOSP UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV ROCHESTER,SCH MED,DEPT MED,DIV GEN INTERNAL MED,ROCHESTER,NY. UNIV CALIF LOS ANGELES,MED CTR,DIV INFECT DIS,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,MED CTR,DIV GEN INTERNAL MED,LOS ANGELES,CA 90024. DARTMOUTH HITCHCOCK MED CTR,INFECT DIS SECT,LEBANON,NH 03766. JOHNS HOPKINS UNIV HOSP,DIV INFECT DIS,BALTIMORE,MD 21287. RP Bates, DW (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 43 TC 105 Z9 111 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1997 VL 176 IS 6 BP 1538 EP 1551 PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YH160 UT WOS:A1997YH16000018 PM 9395366 ER PT J AU Alexenko, AP Leaman, DW Li, JZ Roberts, RM AF Alexenko, AP Leaman, DW Li, JZ Roberts, RM TI The antiproliferative and antiviral activities of IFN-tau variants in human cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN INTERFERON-ALPHA; PREGNANCY RECOGNITION HORMONE; OVINE TROPHOBLAST PROTEIN-1; SITE-DIRECTED MUTAGENESIS; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; GENE-EXPRESSION; ACTIVATION; PATHWAYS; RESIDUES AB The IFN-gamma are type I IFN expressed by the early trophoblast of cattle and sheep but have activity on human cells and have been predicted to have potential therapeutic value, We have compared a series of mutant bovine and ovine IFN-I with regard to their ability to inhibit the proliferation of Daudi cells and to evoke an antiviral (AV) response in WISH cells, Whereas Daudi cell growth was inhibited by Bo-IFN-tau 1 in the 1 nM range, WISH cells were much less responsive, requiring exposure to 150 nM for protection against vesicular stomatitis virus, Replacement of lysines at positions 34, 107, 121, and 132 in Bo-IFN-tau, which are in regions predicted to interact with the type I receptor, led to modest but significant alterations in antiproliferative (AP) and AV activities, Replacement of the lysine residues at 160 and 164 had marked effects on biopotency, with K160 being particularly important, The different IFN-tau were able to activate the transcription factors ISGF3 and AAF (GAF) in Daudi cells at concentrations that correlated reasonably web with their AP potencies, Stat activation occurred in WISH cells in response to similar to 2 nM Bo-IFN-tau 1, but ISGF3 formation could not be demonstrated even at the 100-fold higher IFN-tau concentrations that gave viral protection, Pretreatment of WISH cells with Hu-IFN-gamma allowed ISGF3 formation to be observed in response to subsequent treatment with Bo-IFN-tau 1 or type I human IFN but did not increase the AV responsiveness of the cells, No evidence was found that IFN-tau elicit uniquely different responses on human cells than type I Hu-IFN, except they are much less potent, The data emphasize the importance of a region near the carboxyl terminus for the functional activity of type I IFN, and that although ISFG3 formation may be necessary, its mere presence is not sufficient to provide an antiviral response. C1 Univ Missouri, Anim Sci Res Ctr 158, Dept Anim Sci, Columbia, MO 65211 USA. Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Cleveland Clin Fdn, Dept Mol Biol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roberts, RM (reprint author), Univ Missouri, Anim Sci Res Ctr 158, Dept Anim Sci, Columbia, MO 65211 USA. FU NIAID NIH HHS [F3 AIO8956]; NICHD NIH HHS [R37 HD21896] NR 42 TC 28 Z9 29 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 1997 VL 17 IS 12 BP 769 EP 779 DI 10.1089/jir.1997.17.769 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA YP857 UT WOS:000071322800007 PM 9452365 ER PT J AU Ubel, PA Merz, JF Shea, J Asch, DA AF Ubel, PA Merz, JF Shea, J Asch, DA TI How preliminary data affect people's stated willingness to enter a hypothetical randomized controlled trial SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE randomized control trial; decision making; ethics; survey; equipoise; informed consent ID CONSENT AB Purpose: To explore how preliminary trial data affect the general public's stated willingness to enter a randomized clinical trial, Methods: We asked 165 prospective jurors to imagine that their physicians wanted them to enroll in a clinical trial, We then presented them with scenarios portraying preliminary trial results-for example, 9 out of 10 patients get better with drug A and 5 out of 10 get better with drug B-and asked after each scenario, whether they would choose to be part of the trial. We designed the scenarios to test how stated willingness to enter the trial would be influenced by: 1) the difference in effectiveness of the 2 treatments based on the patients enrolled thus far; and 2) by the chance that the difference in effectiveness was random tie, the P value), The subjects' willingness to enter the trial at various decision points was analyzed using logistic regression. Results: Fewer subjects were willing to enter the trial as preliminary data indicated either an increasing difference in the effectiveness of the two treatments or an increasing statistical significance of that difference, For example 75% of subjects were willing to enter the research trial before any preliminary data were presented, but this number fell to 49% when subjects were presented with preliminary data showing that 9 out of 10 patients improved with one treatment and 5 out of 10 with the other, Multivariable logistic regression revealed that higher P values (odds ratio = 4.29; P < 0.001; 95% CI: 2.22-8.28) and smaller differences in effectiveness (odds ratio = 0.02; P < 0.001; 95% CI: 0.00-0.07) implicit in preliminary data presented to subjects made subjects less likely to agree to enter clinical trials. After adjustment for other relevant variables, male gender was associated with increased willingness to enter the trial. Conclusion: A subjects' willingness to enter the hypothetical trial was influenced by preliminary data, Fewer subjects were willing to enter the trial as the differences in benefit between 2 treatment groups increased, However, the majority of subjects were willing to enter the hypothetical trial even when preliminary evidence strongly favored one treatment over another, Given the importance of informed consent in entering patients in clinical trials, these results should be confirmed in actual trial settings. C1 Univ Penn, Ctr Bioeth, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Univ Penn, Ctr Bioeth, Div Gen Internal Med, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. NR 9 TC 18 Z9 18 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD DEC PY 1997 VL 45 IS 9 BP 561 EP 566 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA YQ215 UT WOS:000071362200007 PM 9444883 ER PT J AU Collins, MM Fowler, FJ Roberts, RG Oesterling, JE Annas, GJ Barry, MJ AF Collins, MM Fowler, FJ Roberts, RG Oesterling, JE Annas, GJ Barry, MJ TI Medical malpractice implications of PSA testing for early detection of prostate cancer SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article; Proceedings Paper CT Joint Eastern Regional Meeting of the American-Federation-for-Medical-Research/Society-of-General-Internal-Med icine CY OCT 05-06, 1996 CL BOSTON, MASSACHUSETTS SP Amer Federat Med Res, Soc Gen Internal Med ID DEFENSIVE MEDICINE; INFORMED CONSENT; UNITED-STATES; ANTIGEN; MEN; HYPERPLASIA; LITIGATION; DIAGNOSIS; TRENDS; REFORM AB Prostate cancer screening is controversial. We conducted a national survey of primary care physicians and urologists to examine their use of prostate-specific antigen testing and their views on medical liability issues involved. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Wisconsin, Sch Med, Madison, WI 53706 USA. Midwest Prostate Inst, Saginaw, MI USA. St Marys Med Ctr, Saginaw, MI USA. Boston Univ, Sch Publ Hlth, Hlth Law Dept, Boston, MA 02215 USA. RP Collins, MM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. FU AHRQ HHS [HS 08397]; BHP HRSA HHS [5T 32PE11001-08] NR 64 TC 8 Z9 8 U1 1 U2 1 PU AMER SOC LAW MEDICINE ETHICS PI BOSTON PA 765 COMMONWEALTH AVE, 16TH FL, BOSTON, MA 02215 USA SN 0277-8459 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 1997 VL 25 IS 4 BP 234 EP + DI 10.1111/j.1748-720X.1997.tb01405.x PG 10 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA ZD314 UT WOS:000072672800001 PM 11066505 ER PT J AU Brown, GE Reiff, J Allen, RC Silver, GM Fink, MP AF Brown, GE Reiff, J Allen, RC Silver, GM Fink, MP TI Maintenance and down-regulation of primed neutrophil chemiluminescence activity in human whole blood SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE tumor necrosis factor alpha; interleukin-8; platelet-activating factor; leukotriene B-4; N-formyl-methionyl-leucylalanine; phorbol myristate acetate ID RESPIRATORY-DISTRESS SYNDROME; SUPEROXIDE PRODUCTION; CHEMOTACTIC FACTORS; TRAUMA PATIENTS; BURST ENZYME; ACTIVATION; EXPRESSION; PROTEIN; LIPOPOLYSACCHARIDE; ABNORMALITIES AB Priming of polymorphonuclear neutrophils (PMN) in whole blood (by tumor necrosis factor alpha and interleukin-8 for enhancement of luminol-dependent chemiluminescence induced by human complement-opsonized zymosan) Tvas stable for 120 min. In contrast, priming of isolated PMN in plasma-free suspension for responses to opsonized zymosan, formyl-methionyl-leucyl-phenylalanine, and phorbol myristate acetate was markedly less stable, Decay of priming was not due to irreversible inactivation of the terminal CL production machinery because PMN could be reprimed by platelet-activating factor or leukotriene B-4. The tumor necrosis factor-alpha-primed state of isolated PMN was stabilized by host plasma in a concentration-dependent fashion. We conclude that PMN printing results in a dynamic state that is reversible, Our findings suggest the existence of blood-borne components that may act to stabilize or modify PMN priming. C1 BETH ISRAEL DEACONESS MED CTR E,DEPT BIOL CHEM & MOL PHARMACOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. EXOXEMIS INC,LITTLE ROCK,AR. RP Brown, GE (reprint author), BETH ISRAEL DEACONESS MED CTR E,DEPT SURG,330 BROOKLINE AVE,BOSTON,MA 02215, USA. RI Allen, Robert/B-6529-2008 FU NIGMS NIH HHS [2R01GM37631] NR 34 TC 22 Z9 22 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1997 VL 62 IS 6 BP 837 EP 844 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YJ991 UT WOS:A1997YJ99100017 PM 9400825 ER PT J AU Wu, MJ Chen-Liu, LW Xiao, QN Phillips, ML Elovson, J Linton, MF Young, SG Schumaker, VN AF Wu, MJ Chen-Liu, LW Xiao, QN Phillips, ML Elovson, J Linton, MF Young, SG Schumaker, VN TI Secretion from cell culture of HDL and VLDL bearing apoB-33 with a large internal deletion SO JOURNAL OF LIPID RESEARCH LA English DT Article DE very low density lipoproteins; low density lipoproteins; lipoprotein biosynthesis; apolipoprotein B; microsomal triglyceride transfer proteins ID LOW-DENSITY LIPOPROTEINS; APOLIPOPROTEIN-B-GENE; TRIGLYCERIDE-RICH LIPOPROTEINS; RAT-LIVER; FAMILIAL HYPOBETALIPOPROTEINEMIA; PLASMA-LIPOPROTEINS; 2-STEP MODEL; EXPRESSION; MUTATION; CONFORMATION AB Rat hepatoma McA-RH7777 cells synthesize and secrete two populations of apoB-containing lipoproteins: a larger, VLDL-sized population floating in the S-f 40-150 range and a smaller, LDL and HDL-sized population. Three permanently transfected cell lines of McA-RH7777 cells secreted (in addition to the endogenous lipoproteins) lipoproteins containing 1) a carboxyl-terminally truncated human apoB-53 (2377 amino acids in length); 2) a carboxyl-terminally truncated human apoB-31 (1420 amino acids in length); or 3) an internally deleted human apoB protein, apoB-18/95, containing a total of 1490 amino acid residues, equivalent in length to an apoB-33. The apoB-18/95 protein contained amino acid residues 1-782 joined to 708 residues near the C-terminus of apoB (residues 3636-4343). All three of the apoB peptides, apoB-53, apoB-31, and apoB-18/95, were present on smaller LDL-HCL-class lipoproteins, with buoyant densities in the HDL density range. The sizes of the HDL class lipoproteins agreed with prior observations that lipoprotein core circumference is directly proportional to apoB size. As HDL containing apoB-18/95 conformed to this rule, contiguous apoB amino acid sequence is not required for the rule to be obeyed. In addition, apoB-18/95, but not apoB-31, was also present on the VLDL-sized lipoproteins even in the absence of serum or oleate supplementation. As the latter two constructs encode equally sized apoB peptides, their particular amino acid sequences rather than just overall length must determine whether they can assemble into a VLDL particle. C1 Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif San Francisco, Dept Med, Inst Cardiovasc Res, Gladstone Fdn Labs Cardiovasc Dis, San Francisco, CA 94141 USA. RP Schumaker, VN (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL-06172, HL-28481, HL-41633] NR 34 TC 4 Z9 4 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD DEC PY 1997 VL 38 IS 12 BP 2473 EP 2482 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YP442 UT WOS:000071277200009 PM 9458271 ER PT J AU Chauhan, NB Lee, JM Siegel, GJ AF Chauhan, NB Lee, JM Siegel, GJ TI Na,K-ATPase mRNA levels and plaque load in Alzheimer's disease SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE in situ hybridization; mRNA; Northern blot; image analysis; beta-amyloid; superior frontal cortex; pyramidal neurons; cerebellum; Purkinje cell ID AMYLOID PRECURSOR PROTEIN; MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; HUMAN-BRAIN; DIFFERENTIAL DISTRIBUTION; DIFFUSE PLAQUES; GENE-EXPRESSION; DOWNS-SYNDROME; ALPHA-ISOFORM; AGED HUMAN AB The expression of Na,K-ATPase alpha 1- and alpha 3-mRNAs was analyzed by in situ hybridization in the superior frontal cortex and cerebellum of brains from five Alzheimer's disease (AD), five nondemented age-matched, and three young control subjects. Brains with well-preserved RNA, tested by Northern hybridization of immobilized RNA with [P-32]-labeled human beta-actin riboprobe, were chosen for analysis. In situ hybridization was performed on formalin-fixed, 5 mu m-thick Paraplast sections with [S-35]-labeled riboprobes prepared by in vitro transcription of the respective linearized clones: a 537-bp EcoRI-PstI fragment of alpha 1-cDNA and a 342-bp PstI-EcoRI fragment of alpha 3-cDNA. In cortex, grains related to mRNA were measured by density per unit area in five cortical columns separated by 1.0-1.2 cm in each of two adjacent sections. Each cortical column of 180-mu m width was divided into four depths orthogonal to the pial surface between the pia and the white matter. Amyloid plaques were counted in the same regions of adjacent sections. In addition, alpha 3-mRNA grain clusters over individual pyramidal neurons within depth 4 were analyzed. We found the following significant changes (p < 0.05): 1. Increases in total alpha 1-mRNA by 13-19% in AD compared to young and by 7-12% in AD compared to age-matched controls,. 2. Decrease in total alpha 3-mRNA by 31-38% in AD compared to young and age-matched controls. 3. Decrease in alpha 3-mRNA content over individual pyramidal perikarya by 14% in normal aged brains without plaques compared to young controls, and by 44% in AD relative to young controls and by 35% compared to age-matched controls. No significant difference (p < 0.2) was found with respect to alpha 1- or alpha 3-mRNA in cerebellar cortex or individual Purkinje cells among any of the groups. In addition, there was a trend toward an inverse correlation between the levels of alpha 3-mRNA and of diffuse plaques, but not of neuritic plaques, in AD cases. In conclusion: 1. The increases in alpha 1-mRNA in AD may be related to an increased reactive gliosis. 2. The declines in alpha 3-mRNA per individual neuron found in normal aging occur prior to the formation of diffuse plaques and are greatly accelerated in AD. 3. The declines in alpha 3-mRNA per neuron found in normal aging may predispose to or potentiate AD pathogenesis. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Mol & Cellular Neurosci Lab, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Pharmacol & Expt Therapeut, Maywood, IL 60153 USA. RP Siegel, GJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Neurol Serv, Mol & Cellular Neurosci Lab, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 57 TC 35 Z9 35 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD DEC PY 1997 VL 9 IS 3 BP 151 EP 166 DI 10.1007/BF02800498 PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YU389 UT WOS:000071712200002 PM 9481617 ER PT J AU Black, PM Westphal, M AF Black, PM Westphal, M TI Preface - Growth factors, glial cells and neuro-oncology. Perspectives for treatment? SO JOURNAL OF NEURO-ONCOLOGY LA English DT Editorial Material ID EXPRESSION; ONCOGENES; LINE C1 Harvard Univ, Brigham & Womens Hosp, Childrens Hosp,Dana Farber Canc Inst,Med Sch, Joint Ctr Radiat Therapy,Dept Surg,Neurosurg Labs, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Childrens Hosp,Dana Farber Canc Inst,Med Sch, Joint Ctr Radiat Therapy,Dept Surg,Brain Tumor Ct, Boston, MA 02115 USA. Univ Hosp Eppendorf, Dept Neurol Surg, Lab Brain Tumor Biol, Hamburg, Germany. RP Black, PM (reprint author), Harvard Univ, Brigham & Womens Hosp, Childrens Hosp,Dana Farber Canc Inst,Med Sch, Joint Ctr Radiat Therapy,Dept Surg,Neurosurg Labs, Boston, MA 02115 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 1997 VL 35 IS 3 BP 189 EP 190 DI 10.1023/A:1005994528511 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA YM289 UT WOS:000071048700001 PM 9440019 ER PT J AU Kirsch, M Wilson, JC Black, P AF Kirsch, M Wilson, JC Black, P TI Platelet-derived growth factor in human brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review ID GLIOMA CELL-LINES; HUMAN ASTROCYTOMA-CELLS; HUMAN MENINGIOMA CELLS; PDGF-RECEPTOR GENES; PROTEIN-KINASE-C; CALCIUM-CHANNEL ANTAGONISTS; DOMINANT-NEGATIVE MUTANTS; DIFFERENT DIMERIC FORMS; CENTRAL-NERVOUS-SYSTEM; FACTOR ALPHA-RECEPTOR AB This paper initially reviews ligand and receptor systems for the PDGF family and the signalling systems they use as well as their role in neural developments. It then describes the putative role of this family in astrocytoma, meningioma, and pituitary adenoma pathogenesis. Potential therapies with receptor antagonists or dominant negative mutants are discussed in the final sections. C1 Harvard Univ, Childrens Hosp,Dept Surg,Neurosurg Labs, Brigham & Womens Hosp,Sch Med,Dept Neurosurg, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp,Dept Surg,Brain Tumor Ctr, Brigham & Womens Hosp,Sch Med, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Tech Univ Dresden, Carl Gustav Carus Univ Klinikum, Klin & Poliklin Neurochirurg, Dresden, Germany. RP Black, P (reprint author), Harvard Univ, Childrens Hosp,Dept Surg,Neurosurg Labs, Brigham & Womens Hosp,Sch Med,Dept Neurosurg, Dana Farber Canc Inst,Joint Ctr Radiat Therapy, 300 Longwood Ave, Boston, MA 02115 USA. RI Kirsch, Matthias/F-2824-2014 NR 102 TC 17 Z9 17 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD DEC PY 1997 VL 35 IS 3 BP 289 EP 301 DI 10.1023/A:1005872718547 PG 13 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA YM289 UT WOS:000071048700008 PM 9440026 ER PT J AU Kujawa, SG Liberman, MC AF Kujawa, SG Liberman, MC TI Conditioning-related protection from acoustic injury: Effects of chronic deefferentation and sham surgery SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CROSSED OLIVOCOCHLEAR BUNDLE; MIDDLE-EAR MUSCLES; COCHLEAR DE-EFFERENTATION; SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE RESPONSE; INDUCED HEARING-LOSS; OUTER HAIR-CELLS; GUINEA-PIG; THRESHOLD SHIFT; NOISE EXPOSURE AB The inner ear can be made less vulnerable to acoustic injury by a "conditioning" treatment involving exposure to a moderate-level acoustic stimulus before the acoustic overexposure. The present study was designed to explore the role of the olivocochlear (OC) system in this "protection" Guinea pigs were divided into a number of groups: some (trauma-only) were exposed to a traumatic noise for 4 h at 109 dB SPL; others (condition/trauma) were conditioned by daily exposure to the same noise at 85 dB SPL before the traumatic exposure. In OC-intact animals, the condition/trauma group showed significantly less permanent threshold shift (PTS) than the trauma-only group as measured via compound action potentials and distortion-product otoacoustic-emissions (DPOAEs). Other animals with identical noise-exposure regimens underwent deefferentation surgery before the start of conditioning: the OC bundle (OCB) was cut in the brain stem, either at the midline (cutting the crossed OCB to both ears) or at the sulcus limitans (cutting all OC fibers to 1 side). Lesion success was quantified by measuring OC fascicles to the outer hair cell region in each ear. The results from the surgical groups showed that total loss of the OCB significantly increased the noise-induced PTS, whereas loss of the COCB only did not; that the conditioning exposure in deefferented animals increased, rather than decreased, the PTS from the traumatic exposure; and that animals undergoing sham surgery (brain stem cuts that failed to transect the OCB) appeared protected whether or not they received the conditioning noise exposure. The latter result suggests that conditioning-related protection may arise from a generalized stress response, which can be elicited by noise exposure, brain surgery, or a variety of other means. The former results make an OC role in the conditioning process, per se, difficult to assess, given the large effects of OC activity on general acoustic vulnerability. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC-000188, F32 DC-00180] NR 51 TC 77 Z9 80 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 3095 EP 3106 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900027 PM 9405529 ER PT J AU Sober, SJ Stark, JM Yamasaki, DS Lytton, WW AF Sober, SJ Stark, JM Yamasaki, DS Lytton, WW TI Receptive field changes after strokelike cortical ablation: A role for activation dynamics SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MAP REORGANIZATION; CORTEX; PARVALBUMIN; NEURONS; IMMUNOREACTIVITY; RECOVERY; MONKEYS; MODEL; GABA AB The reorganization of neural activity that takes place after stroke is of paramount importance in producing functional recovery. Experimental stroke models have suggested that this reorganization may have two phases, but physiology alone cannot fully resolve what causes each phase. Computer modeling suggests that these phases might involve an initial change in dynamics occurring immediately, followed by synaptic plasticity. We combined physiological recording from macaque middle temporal cortex (area MT) with a neural network computer model to examine this first phase of altered cortical function after a small, experimentally induced cortical lesion. Major receptive field (RF) changes seen in the first few days postlesion included both expansion and contraction of receptive fields. Although only expansion could be reproduced in an initial model, addition of inhibitory interneuron loss in a ring around the primary ablation, suggested by immunohistochemical examination, permitted contraction to be replicated as well. We therefore predict that this immunochemical observation reflects an immediate extension of the lesion rather than a late response. Additionally our model successfully predicted a correlation between increased firing rate and RF size. Our model suggests that activation dynamics alone, without anatomic remodeling, can cause the large receptive field changes that allow the rapid behavioral recovery seen after middle temporal lesions. C1 Univ Wisconsin, Dept Neurol, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. Univ Wisconsin, Dept Anat, William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. RP Lytton, WW (reprint author), Univ Wisconsin, Dept Neurol, William S Middleton Mem Vet Hosp, 1300 Univ Ave,MSC 1720, Madison, WI 53706 USA. NR 21 TC 24 Z9 24 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1997 VL 78 IS 6 BP 3438 EP 3443 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YP840 UT WOS:000071320900055 PM 9405557 ER PT J AU George, MS Ketter, TA Parekh, PI Rosinsky, N Ring, HA Pazzaglia, PJ Marangell, LB Callahan, AM Post, RM AF George, MS Ketter, TA Parekh, PI Rosinsky, N Ring, HA Pazzaglia, PJ Marangell, LB Callahan, AM Post, RM TI Blunted left cingulate activation in mood disorder subjects during a response interference task (the stroop) SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID SLEEP-DEPRIVATION; EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; BLOOD-FLOW; DEPRESSION; PERFORMANCE; CORTEX; SPECT AB Functional neuroimaging studies have found abnormal anterior cingulate activity in depressed subjects, and other studies have shown that the cingulate gyrus becomes active in healthy subjects during interference tasks. The authors hypothesized that subjects with mood disorder might show blunted cingulate activation during the standard Stroop interference task or during a modified version involving sadness-laden wards. In contrast to 11 age- and sex-matched healthy control subjects who activated the left cingulate during the standard Stroop, 11 mood-disordered subjects activated the right anterior cingulate gyrus only slightly and instead showed increased activity in the left dorso-lateral prefrontal and visual cortex. This study supports theories of blunted limbic and paralimbic activation and abnormal cingulate activity in depression and adds to the growing knowledge of the functional neuroanatomy of depression. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT NEUROL,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS HOSP,DEPT PSYCHIAT,CHARLESTON,SC. NEUROL INST,RAYMOND WAY NEUROPSYCHIAT RES GRP,LONDON,ENGLAND. NIMH,BIOL PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. RP George, MS (reprint author), MED UNIV S CAROLINA,DEPT RADIOL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. RI Ring, Howard/G-6684-2011 NR 62 TC 188 Z9 193 U1 0 U2 10 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1997 VL 9 IS 1 BP 55 EP 63 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA WD688 UT WOS:A1997WD68800007 PM 9017529 ER PT J AU Kawamata, T Peterson, JW Bun, T Zervas, NT AF Kawamata, T Peterson, JW Bun, T Zervas, NT TI Augmentation of both hemolysate-induced contraction and activation of protein kinase C by submaximum activation in canine cerebral arteries in vitro SO JOURNAL OF NEUROSURGERY LA English DT Article DE cerebral vasospasm; protein kinase C; phorbol ester; hemolysate; calphostin C; membrane potential; dog ID SMOOTH-MUSCLE CONTRACTION; SUBARACHNOID HEMORRHAGE; BASILAR ARTERY; DIACYLGLYCEROL CONTENT; CHRONIC VASOSPASM; ISOTYPE-ALPHA; IN-VITRO; PATHOGENESIS; MECHANISM; CALCIUM AB Although phorbol esters synthetic activators uf protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8-12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro is (50-85% of maximum) in normal canine cerebral arteries. increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar Lo those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6-8% of total FKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm. C1 MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL 22573] NR 38 TC 10 Z9 13 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 1997 VL 87 IS 6 BP 908 EP 915 DI 10.3171/jns.1997.87.6.0908 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YH193 UT WOS:A1997YH19300016 PM 9384403 ER PT J AU Dodson, TB Kaban, LB AF Dodson, TB Kaban, LB TI Recommendations for management of trigeminal nerve defects based on a critical appraisal of the literature SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RECONSTRUCTION; CONDUIT; GRAFTS; REPAIR AB Purpose: Management of trigeminal nerve injuries continues to challenge oral and maxillofacial surgeons. The purpose of this review article is to apply the principles of evidence-based medicine (E-BM) to determine the optimal operative technique for managing defects involving the inferior alveolar (IAN) or lingual nerves when direct tie, primary) repair is not feasible. Methods: To address the research purpose, the four steps of the E-BM critical appraisal process were applied: I) identify the clinical problem, 2) efficiently search the literature, 3) select relevant articles and apply rules of evidence, and 4) apply the findings to patient care. Parameters for the literature search included using Medline to identify English language articles, publication dates from 1986 through 1996, and studies involving human subjects. Results: The studies reviewed showed that the clinical literature on operative management of trigeminal nerve injuries is sparse, preoperative and postoperative neurosensory examinations are poorly documented, and the data are derived completely from reports using case series methods. Given these limitations, the available literature suggests that 1) tension-free, primary (direct) suture repair of an injured nerve, if possible, provides optimal results; 2) if direct repair is not possible, autogenous nerve grafts should be used for acute injuries, for example, immediate nerve repair after tumor resection or at the time of acute repair after traumatic injury; and 3) if direct repair is not possible, autogenous nerve grafts or hollow conduits (entubulization) to bridge the defect are equally successful for delayed reconstruction of gaps of 3 cm or smaller. Conclusions: Based on the weakness of the current literature, recommendations for future research include I) better standardization and documentation of sensory deficits resulting from nerve injuries and their recovery, 2) using multicenter studies to accumulate large samples of patients rapidly, 3) using case series or prospective cohort study designs to assess the value of operative management of nerve injuries, and 4) progressing to randomized clinical trials to ascertain the optimal operative management of nerve injuries. C1 HARVARD UNIV,SCH DENT MED,MASSACHUSETTS GEN HOSP,DEPT ORAL MAXILLOFACIAL SURG,BOSTON,MA 02115. RP Dodson, TB (reprint author), EMORY CLIN,SCH MED,DEPT SURG,DIV ORAL MAXILLOFACIAL SURG,1365B CLIFTON RD NE,SUITE 2300,ATLANTA,GA 30322, USA. NR 30 TC 38 Z9 38 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1997 VL 55 IS 12 BP 1380 EP 1386 DI 10.1016/S0278-2391(97)90632-7 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YH768 UT WOS:A1997YH76800004 PM 9393396 ER PT J AU Tannous, M Labbe, N Redmond, RW Mutus, B AF Tannous, M Labbe, N Redmond, RW Mutus, B TI A photo-activated, protein-based, NO/H2O2 generating system with tumoricidal activity composed of the nitric oxide derivative of apo-metallothionein (thionein-NO) and glucose oxidase SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE metallothionein; nitric oxide; glucose oxidase; peroxynitrite; hydrogen peroxide ID PHOTOCHEMICAL RELEASE; S-NITROSOGLUTATHIONE; HYDROGEN-PEROXIDE; PEROXYNITRITE; GLUTATHIONE; NITRATION; NITROSO; CELLS AB The S-nitroso derivative of apo-metallothionein (thionein) was prepared by transnitrosation with S-nitrosoglutathione. The thionein-NO thus formed has an absorption maximum at 334 nm. Light-induced NO release from thionein-NO was demonstrated by flash photolysis. This system produces peroxynitrite at neutral pH as evidenced by nitrotyrosine formation. The cytotoxic potential of this protein-based, light-activated NO/H2O2 generating system was demonstrated by exposing human colon adenocarcinoma cells (SW 948) in culture to thionein-NO and glucose oxidase in the presence and absence of light. The cell density of the samples, 72 h subsequent to receiving 1 h of light exposure, decreased by similar to 98%, relative to controls. In comparison, cell density of the samples that were incubated in the presence of catalase and did not receive light treatment, decreased by only similar to 22% after 72 h. (C) 1997 Elsevier Science S.A. C1 Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Mutus, B (reprint author), Univ Windsor, Dept Chem & Biochem, Windsor, ON N9B 3P4, Canada. EM mutusb@uwindsor.ca NR 27 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD DEC PY 1997 VL 41 IS 3 BP 249 EP 254 DI 10.1016/S1011-1344(97)00115-2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YQ061 UT WOS:000071343600008 PM 9447722 ER PT J AU Pang, XD Guinan, JJ AF Pang, XD Guinan, JJ TI Growth rate of simultaneous mashing in cat auditory-nerve fibers: Relationship to the growth of basilar-membrane motion and the origin of two-tone suppression SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID 2-TONE RATE SUPPRESSION; INPUT-OUTPUT FUNCTIONS; GUINEA-PIG COCHLEAE; INNER HAIR CELL; TUNING CURVES; ELECTRICAL-STIMULATION; HOOK REGION; NOISE; RESPONSES; MECHANICS AB Although many aspects of the mechanisms by which low-frequency sounds exert their powerful masking on responses to high-frequency sounds are well documented and understood, there are few data on the growth of masking for signal frequencies near, but not necessarily at, auditory-nerve-fiber characteristic frequency (CF). Masking of responses to 6- or 8-kHz tones by a continuous 300-Hz band of noise centered at 500 Hz was measured in single auditory-nerve fibers with various CFs, The growth rare of maskings averaged approximately 2 dB/dB, was typically largest for tones about 10% above fiber CF, and decreased al higher and lower frequencies. This pattern of masking versus frequency relative to CF resembles the pattern of compression of the growth of basilar membrane motion versus frequency at a fixed cochlear place. This correspondence supports the hypothesis that the high growth rate of masking by low-frequency sounds is due to the same mechanisms which produce the compression in the growth of basilar membrane motion. (C) 1997 Acoustical Society of America. [S0001-4966(97)03112-3]. C1 MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. MIT,ELECT RES LAB,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Pang, XD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01 DC000119] NR 58 TC 22 Z9 23 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 1997 VL 102 IS 6 BP 3564 EP 3575 DI 10.1121/1.420147 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA YL015 UT WOS:A1997YL01500036 PM 9407650 ER PT J AU Pang, XD Guinan, JJ AF Pang, XD Guinan, JJ TI Effects of stapedius-muscle contractions on the maskingg of auditory-nerve responses SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ELECTRICAL-STIMULATION; NOISE; FIBERS; TONES; GROWTH; SPEECH; LEVEL; CATS AB There has been little exploration of the mechanisms by which stapedius muscle contractions reduce the masking of responses to high-frequency sounds by law-frequency sounds. To fill this gap in knowledge, controlled stapedius contractions were elicited with direct shocks in anesthetized cats, and measurements were made of the effects of these contractions on the masking of single auditory-nerve fibers and on the attenuation of middle-ear transmission. The results show that the stapedius-induced reductions of masking can be much larger than the attenuations of low-frequency sound. With a 300-Hz band of masking noise centered at 500 Hz, and signal tones at 6 or 8 Mit, unmasking effects over 40 dB were observed for sounds 100 dB SPL or less. The data suggest that much larger unmasking might occur. The observed unmasking can be explained completely by a linear stapedius-induced attenuation of sound transmission through the middle ear and a nonlinear growth rate of masking for auditory-nerve fibers. Na central effects are required, it is argued that the reduction of the upward spread of masking is probably one of the most important functions of the stapedius muscle. (C) 1997 Acoustical Society of America. [S0001-4966(97)03212-8]. C1 MIT, DEPT ELECT ENGN & COMP SCI, CAMBRIDGE, MA 02139 USA. MIT, ELECT RES LAB, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02115 USA. RP Pang, XD (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOLARYNGOL, EATON PEABODY LAB AUDITORY PHYSIOL, BOSTON, MA 02114 USA. FU NIDCD NIH HHS [P01 DC00119] NR 45 TC 16 Z9 16 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 1997 VL 102 IS 6 BP 3576 EP 3586 DI 10.1121/1.420399 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA YL015 UT WOS:A1997YL01500037 PM 9407651 ER PT J AU Biederman, J Faraone, SV Weber, W Russell, RL Rater, M Park, KS AF Biederman, J Faraone, SV Weber, W Russell, RL Rater, M Park, KS TI Correspondence between DSM-III-R and DSM-IV attention-deficit/hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; DSM-III-R; DSM-IV; correspondence ID DEFICIT HYPERACTIVITY DISORDER; DIAGNOSTIC-CRITERIA; CHILDREN; SAMPLE AB Objective: To evaluate the correspondence between DSM-III-R and DSM-IV of attention-deficit/hyperactivity disorder (ADHD) in clinically referred children. Results of the field trials led to the hypothesis that there would be a strong correspondence between DSM-III-R and DSM-IV subtypes. Method: The sample consisted of all children and adolescents consecutively referred to a pediatric psychopharmacology clinic (N = 405). Children were comprehensively evaluated with structured diagnostic interviews assessing both DSM-III-R and DSM-IV ADHD. DSM-III-R symptoms were used to approximate DSM-IV subtypes. Kappa statistics and conditional probabilities were used to examine the correspondence between DSM-III-R and DSM-IV ADHD. Results: Ninety-three percent of children who received a DSM-III-R diagnosis of ADHD also received a DSM-IV ADHD diagnosis. The kappa coefficient assessing the agreement between DSM-III-R and DSM-IV ADHD was .73 (z = 14.6, p <.0001). The kappa coefficient assessing the agreement between the DSM-III-R-approximated subtypes and the actual DSM-IV subtypes was .71 (z = 15, p <.0001). Conclusion: these results confirm previous findings and indicate that the change from DSM-III-R to DSM-IV results in minimal changes in case identification and provides support for diagnostic continuity between the two classification systems. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MCLEAN HOSP,BELMONT,MA 02178. HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,CAMBRIDGE,MA 02138. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BROCKTON,MA. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 6 TC 54 Z9 54 U1 0 U2 8 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 1997 VL 36 IS 12 BP 1682 EP 1687 DI 10.1097/00004583-199712000-00016 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YJ171 UT WOS:A1997YJ17100018 PM 9401329 ER PT J AU Phillips, SB Kollias, N Gillies, R Muccini, JA Drake, LA AF Phillips, SB Kollias, N Gillies, R Muccini, JA Drake, LA TI Polarized light photography enhances visualization of inflammatory lesions of acne vulgaris SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: Polarized light photography has been used to selectively differentiate surface from subsurface features of photoaged skin, Objective: Our purpose was to compare acne assessments obtained from clinical evaluations with assessments from photographs obtained with Rash photography and with perpendicular polarized light photography. Methods: Assessments of acne with the Cunliffe scale were made of 32 subjects. Retrospective evaluations of standard and perpendicular polarized light photographs were made in a blinded fashion by a panel of evaluators, Results: Visualization of inflammatory acne lesions was enhanced with perpendicular polarized Light photography, with clear delineation of erythematous borders. Acne assessments with the use of a Cunliffe scale were significantly higher (p = 0.001) from perpendicular polarized light photographs than for clinical evaluations. Conclusion: Polarized light photography enhances visualization of inflammatory acne lesions in a manner nor possible with conventional flash photographs, permitting accurate evaluation of the extent of disease and the effectiveness of therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Wellman Labs Photomed, Dept Dermatol,Dermatol Clin Invest Unit, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Wellman Labs Photomed, Dept Dermatol,Dermatol Clin Invest Unit, M-S BHX 630, Boston, MA 02114 USA. NR 11 TC 23 Z9 23 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD DEC PY 1997 VL 37 IS 6 BP 948 EP 952 DI 10.1016/S0190-9622(97)70070-7 PG 5 WC Dermatology SC Dermatology GA YM517 UT WOS:000071072700006 PM 9418762 ER PT J AU Colvin, RB Cohen, AH Saiontz, C Bonsib, S Buick, M Burke, B Carter, S Cavallo, T Haas, M Lindblad, A Manivel, JC Nast, CC Salomon, D Weaver, C Weiss, M AF Colvin, RB Cohen, AH Saiontz, C Bonsib, S Buick, M Burke, B Carter, S Cavallo, T Haas, M Lindblad, A Manivel, JC Nast, CC Salomon, D Weaver, C Weiss, M TI Evaluation of pathologic criteria for acute renal allograft rejection: Reproducibility, sensitivity, and clinical correlation SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BANFF CLASSIFICATION; KIDNEY-TRANSPLANTATION; MONONUCLEAR-CELLS; PREDICTIVE VALUE; BIOPSIES; DIAGNOSIS; SCHEMA; CYCLOSPORINE; MANAGEMENT; MORPHOLOGY AB This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in greater than or equal to 5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type In: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist's diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of greater than or equal to 1 tubule with tubulitis and greater than or equal to 5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P < 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P > 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. EMMES CORP,POTOMAC,MD. UNIV IOWA,IOWA CITY,IA. WASHINGTON HOSP CTR,WASHINGTON,DC 20010. UNIV MINNESOTA,MINNEAPOLIS,MN. UNIV CINCINNATI,CINCINNATI,OH. UNIV CHICAGO,CHICAGO,IL 60637. SCRIPPS CLIN,LA JOLLA,CA 92037. UNIV ALABAMA,BIRMINGHAM,AL. RP Colvin, RB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WRN 225 MGH,32 FRUIT ST,BOSTON,MA 02114, USA. RI Salomon, Daniel/E-9380-2012; OI Weaver, Casey/0000-0002-2180-1793 FU NIAID NIH HHS [U01-AI-31440, U01-AI-31457, U01-AI-31492] NR 36 TC 173 Z9 183 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1997 VL 8 IS 12 BP 1930 EP 1941 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA YH761 UT WOS:A1997YH76100015 PM 9402096 ER PT J AU Donahue, DM Grillo, HC Wain, JC Wright, CD Mathisen, DJ AF Donahue, DM Grillo, HC Wain, JC Wright, CD Mathisen, DJ TI Reoperative tracheal resection and reconstruction for unsuccessful repair of postintubation stenosis SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-08, 1997 CL WASHINGTON, D.C. SP Amer Assoc Thorac Surg ID LARYNGEAL; AIRWAY AB Objective: Our objective was to analyze characteristics and results of redo tracheal resection and reconstruction. Methods: Seventy-five patients were operated on between 1966 and 1997 after unsuccessful initial repairs for postintubation tracheal stenosis. Results: Sixteen of these patients came from a group of 32 patients with unsuccessful repair among the 450 primary resections and reconstructions performed at our institution. Fifty-nine patients were referred to us after unsuccessful initial repair elsewhere. Initial management was a T-tube or tracheotomy in 39 patients. The length of repeat resection ranged from 1.0 cm to 5.5 cm (mean 3.5 cm). A laryngeal release was used in 19 patients (25%) to reduce anastomotic tension. Complications occurred in 29 patients (39%) and Here most frequent in the group requiring laryngeal release (12/19, 63.2%). Overall outcome was good in 59 patients (78.6%) and satisfactory in 10 (13.3%). The repair was unsuccessful in four patients (5.3%), and two patients died (2.6%). Conclusions: Despite difficulties encountered in reoperative surgery after failed tracheal reconstruction for postintubation stenosis, successful outcome may be achieved in a large number of cases. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. Harvard Med Sch, Dept Surg, Boston, MA USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Thorac Surg Unit, Blake 1570, Boston, MA 02114 USA. NR 13 TC 46 Z9 48 U1 2 U2 4 PU MOSBY-YEAR BOOK 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 1997 VL 114 IS 6 BP 934 EP 938 DI 10.1016/S0022-5223(97)70007-2 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA YN810 UT WOS:000071210100010 PM 9434688 ER PT J AU de Oliveira, NC Boeve, TJ Torchiana, DF Kantor, HL Titus, JS Schmidt, CJ Lu, CZ Kim, J Daggett, WM Geffin, GA AF de Oliveira, NC Boeve, TJ Torchiana, DF Kantor, HL Titus, JS Schmidt, CJ Lu, CZ Kim, J Daggett, WM Geffin, GA TI Ischemic intervals during warm blood cardioplegia in the canine heart evaluated by phosphorus 31 magnetic resonance spectroscopy SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MYOCARDIAL PRESERVATION; VENTRICULAR PRESSURE; SURGERY; METABOLISM; PROTECTION; ANTEGRADE; RECOVERY; TIME AB Objective: Warm blood cardioplegia requires interruption by ischemic intervals to aid visualization. We evaluated the safety of repeated interruption of warm blood cardioplegia by normothermic ischemic periods of varying durations. Methods: In three groups of isolated cross-perfused canine hearts, left ventricular function was measured before and for 2 hours of recovery after arrest, which comprised four IS-minute periods of cardioplegia alternating with three ischemic intervals of 15, 20, or 30 minutes (I-15, I-20, and I-30). Metabolism vas continuously measured by phosphorus 31-magnetic resonance spectroscopy: Results: Adenosine triphosphate levels fell progressively as ischemia was prolonged; after recovery, adenosine triphosphate was 99% +/- 6%, 90% +/- 1% (p = 0.0004 vs control), and 68% +/- 3% (p = 0.0002) of control levels in I-15, I-20, and I-30, respectively. Intracellular acidosis with ischemia was most marked in I-30. After recovery, left ventricular maximal systolic elastance at constant heart rate and coronary perfusion pressure was maintained in It, but fell to 85% +/- 3% in I-20, (p = 0.003) and to 65% +/- 6% (p = 0.003) of control values in I-30, while relaxation (tau) was prolonged only in I-30 (p = 0.007). Conclusions: Hearts recover fully after three IS-minute periods of ischemia during warm blood cardioplegia, but deterioration, significant with 20-minute periods, is profound when the ischemic periods are lengthened to 30 minutes. This suggests that in the clinical setting warm cardioplegia can be safely interrupted for short intervals, hut longer interruptions require caution. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Daggett, WM (reprint author), Massachusetts Gen Hosp, Dept Surg, BUL-119,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL12777] NR 29 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 1997 VL 114 IS 6 BP 1070 EP 1079 DI 10.1016/S0022-5223(97)70021-7 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA YN810 UT WOS:000071210100034 PM 9434702 ER PT J AU Kashyap, VS Cambria, RP Davison, JK L'Italien, GJ AF Kashyap, VS Cambria, RP Davison, JK L'Italien, GJ TI Renal failure after thoracoabdominal aortic surgery SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Eastern-Vascular-Society CY MAY 02-04, 1997 CL ATLANTIC CITY, NEW JERSEY SP E Vasc Soc ID ANEURYSM REPAIR; RISK; EXPERIENCE; REPLACEMENT; OPERATIONS AB Purpose: Renal failure remains a common and morbid complication after complex aortic surgery. This study was performed to identify perioperative factors that contribute to postoperative renal failure. Methods: The perioperative outcomes of 183 patients who underwent thoracoabdominal aortic surgery with supraceliac clamping were reviewed. During the interval from Tan. 1987 to Nov. 1996, thoracoabdominal aneurysm repair was performed in 154 patients (type I, 49 patients [27%]; type II, 21 patients [11.5%]; type III, 55 patients [30%]; type TV, 29 patients [16%]), suprarenal abdominal aortic aneurysm repair in 17 patients (9%), and visceral/renal revascularization procedures in 12 patients (6.5%). Intraoperative management included thoracoabdominal aortic exposure and clamp-and-sew technique with renal artery cold perfusion whenever the renal arteries were accessible (79% of cases). Results: Relevant clinical features included preoperative hypertension (85%), diabetes mellitus (8%), single functioning kidney (10%), recent intravenous contrast injection (34%), renal insufficiency (creatinine level greater than 1.5 mg/dl; 24%), and emergent operation (19%). Acute renal failure, defined as both a doubling of serum creatinine level and an absolute value greater than 3.0 mg/dl, occurred in 21 patients (11.5%), of whom five required hemodialysis (2.7%). Variables associated with this complication included a preoperative creatinine level greater than 1.5 mg/dl (p = 0.004) and a total cross-clamp time greater than 100 minutes (p = 0.035). The operative mortality risk (within 30 days; 8%) was significantly increased with renal failure (odds ratio, 9.2; 95% confidence interval, 2.6 to 33; p < 0.005). Conclusions: Renal failure, although uncommon in contemporary practice, greatly increases the risk of early death after thoracoabdominal aortic surgery. The overall incidence of renal failure and dialysis requirement in the present series compare favorably with those reported using other operative techniques, specifically partial left heart bypass and distal aortic perfusion. These data suggest that patients who have preoperative renal insufficiency are prone to postoperative renal failure. Furthermore, regional hypothermic perfusion and minimal clamp times are important elements in the prevention of renal failure after thoracoabdominal aortic surgery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. NR 22 TC 76 Z9 81 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 1997 VL 26 IS 6 BP 949 EP 955 DI 10.1016/S0741-5214(97)70006-5 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA YP428 UT WOS:000071275800010 PM 9423709 ER PT J AU Bouyac, M Courcoul, M Bertola, G Baudat, Y Gabuzda, D Blanc, D Chazal, N Boulanger, P Sire, J Vigne, R Spire, B AF Bouyac, M Courcoul, M Bertola, G Baudat, Y Gabuzda, D Blanc, D Chazal, N Boulanger, P Sire, J Vigne, R Spire, B TI Human immunodeficiency virus type 1 Vif protein binds to the Pr55(Gag) precursor SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL LIFE-CYCLE; NUCLEOCAPSID PROTEIN; VIRION INCORPORATION; BIOLOGICAL-ACTIVITY; DELETION MUTANTS; MOLECULAR CLONE; INFECTED-CELLS; RNA-POLYMERASE; GAG PRECURSOR; T-LYMPHOCYTES AB The Vif protein of human immunodeficiency virus type 1 is required for productive replication in peripheral blood lymphocytes. Previous reports suggest that vif-deleted viruses are limited in replication because of a defect in the late steps of the virus life cycle. One of the remaining questions is to determine whether the functional role of Vif involves a specific interaction with virus core proteins. In this study, we demonstrate a direct interaction between Vif and the pr55(Gag) precursor in vitro as well as in infected cells. No interaction is observed between Vif and the mature capsid protein. The pr55(Gag)-Vif interaction is detected (i) in the glutathione S-transferase system, with in vitro-translated proteins demonstrating a critical role of the NC p7 domain of the Gag precursor; (ii) with proteins expressed in infected cells; and (iii) by coimmunoprecipitation experiments. Deletion of the C-terminal 22 amino acids of Vif abolishes its interaction with the Pr55(Gag) precursor. Furthermore, point mutations in the C-terminal domain of Vif which have been previously shown to abolish virus infectivity and binding to cell membranes dramatically decrease the Gag-Vif interaction. These results suggest that the interaction between Vif and the Pr55(Gag) precursor is a critical determinant of Vif function. C1 INSERM,U372,F-13276 MARSEILLE 09,FRANCE. FAC MED MONTPELLIER,INST BIOL,CNRS URA 1487,VIRAL & MOL PATHOGENESIS LAB,MONTPELLIER,FRANCE. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RI Spire, Bruno/F-5546-2013 OI Spire, Bruno/0000-0002-3546-8020 FU NIAID NIH HHS [AI 36186] NR 49 TC 89 Z9 93 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9358 EP 9365 PG 8 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600045 PM 9371595 ER PT J AU Sheng, Q Denis, D Ratnofsky, M Roberts, TM DeCaprio, JA Schaffhausen, B AF Sheng, Q Denis, D Ratnofsky, M Roberts, TM DeCaprio, JA Schaffhausen, B TI The DnaJ domain of polyomavirus large T antigen is required to regulate Rb family tumor suppressor function SO JOURNAL OF VIROLOGY LA English DT Article ID ESCHERICHIA-COLI DNAJ; HEAT-SHOCK PROTEINS; RETINOBLASTOMA GENE-PRODUCT; N-TERMINAL REGION; MOLECULAR CHAPERONES; SECONDARY STRUCTURE; ATPASE ACTIVITY; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS; AMINO-TERMINUS AB Tumor suppressors of the retinoblastoma susceptibility gene family regulate cell growth and differentiation, Polyomavirus large T antigens (large T) bind Rb family members and block their function, Mutations of large T sequences conserved with the DnaJ family affect large T binding to a cellular DnaK, heat shock protein 70, The same mutations abolish large T activation of E2F-containing promoters and Rb binding-dependent large T activation of cell cycle progression, Cotransfection of a cellular DnaJ domain blocks wild-type large T action, showing that the connection between the chaperone system and tumor suppressors is direct, Although they are inactive in assays dependent on Rb family binding, mutants in the J region retain the ability to associate with pRb, p107, and p130. This suggests that binding of Rb family members by large T is not sufficient for their inactivation and that a functional J domain is required as well, This work connects the DnaJ and DnaK molecular chaperones to regulation of tumor suppressors by polyomavirus large T. C1 TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA32222, CA34722, CA50661] NR 66 TC 69 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9410 EP 9416 PG 7 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600051 PM 9371601 ER PT J AU Wyatt, R Desjardin, E Olshevsky, U Nixon, C Binley, J Olshevsky, V Sodroski, J AF Wyatt, R Desjardin, E Olshevsky, U Nixon, C Binley, J Olshevsky, V Sodroski, J TI Analysis of the interaction of the human immunodeficiency virus type 1 gp120 envelope glycoprotein with the gp41 transmembrane glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID CHANGES; SOLUBLE CD4; T-CELL; SURFACE GLYCOPROTEIN; OLIGOMERIC STRUCTURE; SYNCYTIUM FORMATION; HTLV-III; NEUTRALIZING ANTIBODIES; MACROPHAGE TROPISM AB The human immunodeficiency virus type 1 (HIV-1) gp120 exterior envelope glycoprotein interacts with the viral receptor (CD4) and with the gp41 transmembrane envelope glycoprotein. To study the interaction of the gp120 and gp41 envelope glycoproteins, we compared the abilities of anti-gp120 monoclonal antibodies to bind soluble gp120 and a soluble glycoprotein, sgp140, that contains gp120 and gp41 exterior domains. The occlusion or alteration of a subset of gp120 epitopes on the latter molecule allowed the definition of a gp41 ''footprint'' on the gp120 antibody competition map. The occlusion of these epitopes on the sgp140 glycoprotein was decreased by the binding of soluble CD4. The gp120 epitopes implicated in the interaction with the gp41 ectodomain were disrupted by deletions of the first (C1) and fifth (C5) conserved gp120 regions. These deletions did not affect the integrity of the discontinuous binding sites for CD4 and neutralizing monoclonal antibodies. Thus, the gp41 interface on the HIV-1 gp120 glycoprotein, which elicits nonneutralizing antibodies, can be removed while retaining immunologically desirable gp120 structures. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. ROCKEFELLER UNIV,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. FU NIAID NIH HHS [AI 28691, AI 31783, AI 39420, R01 AI100790] NR 91 TC 83 Z9 85 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9722 EP 9731 PG 10 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600088 PM 9371638 ER PT J AU Cao, J Sullivan, N Desjardin, E Parolin, C Robinson, J Wyatt, R Sodroski, J AF Cao, J Sullivan, N Desjardin, E Parolin, C Robinson, J Wyatt, R Sodroski, J TI Replication and neutralization of human immunodeficiency virus type 1 lacking the V1 and V2 variable loops of the gp120 envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; AMINO-ACID CHANGES; RECEPTOR-BINDING; HTLV-III; MACROPHAGE TROPISM; EPITOPE EXPOSURE; CELL TROPISM; CD4 RECEPTOR; HIV-1 ENTRY; T4 MOLECULE AB A human immunodeficiency virus type 1 (HIV-1) mutant lacking the V1 and V2 variable loops in the gp120 exterior envelope glycoprotein replicated in Jurkat lymphocytes with only modest delays compared with the wild-type virus. Revertants that replicated with wild-type efficiency rapidly emerged and contained only a few amino acid changes in the envelope glycoproteins compared with the parent virus. Both the parent and revertant viruses exhibited increased sensitivity to neutralization by antibodies directed against the V3 loop or a CD4-induced epitope on gp120 but not by soluble CD4 or an antibody against the CD4 binding site. This result demonstrates the role of the gp120 V1 and V2 loops in protecting HIV-1 from some subsets of neutralizing antibodies. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV PADUA,INST MICROBIOL,I-35121 PADUA,ITALY. TULANE UNIV,MED CTR,DEPT PEDIAT,NEW ORLEANS,LA 70112. FU NIAID NIH HHS [AI 24755, AI 28691, AI 31783] NR 66 TC 191 Z9 194 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1997 VL 71 IS 12 BP 9808 EP 9812 PG 5 WC Virology SC Virology GA YF896 UT WOS:A1997YF89600101 PM 9371651 ER PT J AU Agodoa, L Eknoyan, G Ingelfinger, J Keane, W Mauer, M Mitch, W Striker, G Wilcox, C AF Agodoa, L Eknoyan, G Ingelfinger, J Keane, W Mauer, M Mitch, W Striker, G Wilcox, C TI Assessment of structure and function in progressive renal disease SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Progression of Renal Disease - Clinical Patterns, Therapeutic Options and What We Have Learned from Clinical Trials CY MAY 31-JUN 03, 1997 CL COOLUM, AUSTRALIA SP Takeda Chem Ind Ltd, Tokyo, Novartis Pharma AG, Basel, PMSI Japan Ltd, ICMS Australasia PTY Ltd DE progression of renal disease; end-stage renal disease; measurement of renal function; imaging ID GLOMERULAR-FILTRATION RATE; INJURY AB The incidence and prevalence rates of end-stage renal disease (ESRD) in the United States continue to increase. In 1995, the incidence rate was 262 per million population, with a point prevalence rate of 975 per million population. The exact number of individuals with abnormal renal function but not yet at end stage is difficult to assess. Crude estimates suggest that approximately 0.4% of the U.S. population has serum creatinine values greater than 2.0 mg/dl. In some sub-populations, such as African Americans, the estimate is+ as high as 1.0%. The rate of progression, likewise, is difficult to assess. In general. renal manifestations of certain systemic diseases such as diabetes mellitus and systemic lupus erythematosus, and those with significant proteinuria (usually greater that 3.0 g/24 hr) seem to have a more rapid progressive course to end stage. If intervention is expected to be successful in halting or slowing down progression, accurate assessment of the early manifestations of renal disease, structure, and function need to be established. Currently accepted methods of assessment of renal disease include measurement of renal function such as serum creatinine and glomerular filtration rate, measurement of proteinuria, assessment of tubular function, glomerular sieving and permselectivity, radiologic imaging techniques, and evaluation of histo-morphometry. Interventions that have been shown to slow progression include control of hypertension, and treatment modalities that reduce proteinuria, such as, the use of angiotensin converting enzyme inhibitors. Further clinical and basic science studies are needed to accurately define the important predictors of progression, and interventions that are effective in slowing or halting progression. C1 BAYLOR COLL MED, DEPT MED, HOUSTON, TX 77030 USA. MASSACHUSETTS GEN HOSP, DEPT PEDIAT NEPHROL, BOSTON, MA 02114 USA. HENNEPIN CTY MED CTR, DEPT MED, MINNEAPOLIS, MN 55415 USA. UNIV MINNESOTA, SCH MED, DEPT PEDIAT, MINNEAPOLIS, MN 55455 USA. EMORY UNIV, SCH MED, DIV RENAL, ATLANTA, GA 30322 USA. GEORGETOWN UNIV, MED CTR, DIV NEPHROL, WASHINGTON, DC 20007 USA. RP Agodoa, L (reprint author), NIDDK, END STAGE RENAL DIS PROGRAM, DIV KIDNEY UROL & HEMATOL DIS,NIH,BLDG 45, ROOM 6AS13B, BETHESDA, MD 20392 USA. NR 29 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1997 SU 63 BP S144 EP S150 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA YJ605 UT WOS:A1997YJ60500036 ER PT J AU Rauch, SD Herrmann, BS Davis, LA Nadol, JB AF Rauch, SD Herrmann, BS Davis, LA Nadol, JB TI Nucleus 22 cochlear implantation results in postmeningitic deafness SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MA SP Amer Laryngol Rhinol & Otol Soc, E Sect ID MENINGOGENIC LABYRINTHITIS; OBLITERATED COCHLEAS; OSSIFICANS; BONE AB Cochlear implant surgery was performed on 13 patients with postmeningitic deafness (seven adults, six children). Two adults and two children (30.8%) had severe labyrinthitis ossificans requiring radical ''drill-out.'' Five of 13 (38.5%) had some bone growth requiring partial drill-out, and four of 13 (30.8%) had normal insertion with no drill-out. Hearing results for patients with no bone growth were similar to nonmeningitic patients; three of four (75%) had open-set speech recognition. Performance of patients with total drill-out was poor; ''auditory only'' performance was limited to detection and pattern perception of speech, and no patients had open-set speech recognition. Results for patients with partial drill-out were similar to results in patients with no bone growth. Labyrinthitis ossificans not only presents surgical challenges to cochlear implantation but may also adversely affect hearing outcome. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT AUDIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Rauch, SD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 20 TC 38 Z9 42 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 1997 VL 107 IS 12 BP 1606 EP 1609 DI 10.1097/00005537-199712000-00005 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA YJ769 UT WOS:A1997YJ76900005 PM 9396672 ER PT J AU Astier, A Manie, SN Law, SF Canty, T Haghayghi, N Druker, BJ Salgia, R Golemis, EA Freedman, AS AF Astier, A Manie, SN Law, SF Canty, T Haghayghi, N Druker, BJ Salgia, R Golemis, EA Freedman, AS TI Association of the Cas-like molecule HEF1 with CrkL following integrin and antigen receptor signaling in human B-cells: Potential relevance to neoplastic lymphohematopoietic cells SO LEUKEMIA & LYMPHOMA LA English DT Article DE Cas-like molecule; HEF1; CrkL; integrins; B-cell; CrkL; B-cell antigen receptor; HEF1; Cas; integrins; antigen receptor signaling human B-cells ID PROTEIN-TYROSINE PHOSPHORYLATION; CHRONIC MYELOGENOUS LEUKEMIA; FOCAL ADHESION KINASE; BONE-MARROW STROMA; C-CRK; EXTRACELLULAR-MATRIX; BETA-1 INTEGRINS; SH3 DOMAINS; FACTOR C3G; SRC AB CrkL, a cellular homologue of the v-crk oncogene, belongs to the family of adaptor proteins, containing SH2 and SH3 domains, but no catalytic domain. Stimulation of normal B-cells and B-cell lines through beta 1 integrin or - cell antigen receptor (BCR) promoted the association of CrkL with a set of 105-130 kD tyrosine phosphorylated substrates. The principal substrate is a recently identified molecule known as p105(HEF1) (HEF1), which is highly homologous to p130(Cas) (Cas), the major tyrosine-phosphorylated protein detected in fibroblasts after transformation by v-crk. Immunodepletion studies indicated that all the tyrosine phosphorylated HEF1 or Cas was complexed with CrkL. Furthermore, the guanine nucleotide exchange factor C3G, which is thought to be involved in the regulation of the ras pathway and constituvely binds to the C-terminal SH3 domain of CrkL, could be detected in HEF1 immunoprecipitates. Therefore, CrkL is involved in the formation of a HEF1-CrkL-C3G ternary complex in B-cells, suggesting that it is likely to play an important role, allowing the propagation of the stimulation initiated by both BCR and beta 1 integrin ligation. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RI Astier, Anne/A-1641-2008 OI Astier, Anne/0000-0002-0144-3431 FU NCI NIH HHS [CA-09035, CA55207, CA66996] NR 48 TC 34 Z9 35 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD DEC PY 1997 VL 28 IS 1-2 BP 65 EP 72 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA YU068 UT WOS:000071677900008 PM 9498705 ER PT J AU Walter, CA Grabowski, DT Street, KA Conrad, CC Richardson, A AF Walter, CA Grabowski, DT Street, KA Conrad, CC Richardson, A TI Analysis and modulation of DNA repair in aging SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 1st International NILS Workshop on Longevity Sciences - The Role of Molecular Genetics in Longevity Sciences CY NOV 29, 1996 CL OBU, JAPAN SP Natl Inst Longev Sci DE DNA repair; transgenic mice; quantitative extended-length PCR; mitochondrial DNA damage; aging ID METALLOTHIONEIN-II GENES; BASAL-CELL CARCINOMA; MITOCHONDRIAL-DNA; HUMAN-LYMPHOCYTES; OXIDATIVE DAMAGE; WERNER SYNDROME; DIETARY RESTRICTION; CHROMOSOMAL-ABERRATIONS; IONIZING-RADIATION; ALKYLATING-AGENTS AB Nearly 40 years ago it was proposed that accumulation of mutations or increased levels of DNA damage might contribute to aging processes. Despite several correlative studies in this area, the answer as to whether genomic integrity contributes to aging has remained illusive. More recently it has been hypothesized that decreased mitochondrial DNA integrity plays a role in aging. To begin to test these hypotheses more directly we are developing transgenic mouse and cell culture model systems. For example, transgenic mice overexpressing the DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) have been made and have a reduced spontaneous frequency of hepatocellular carcinoma. A lifespan study using the MGMT transgenic mice is in progress in an effort to determine whether cancer impacts on the median or maximal lifespan of a species. Second, a quantitative PCR technique is being used to measure mitochondrial DNA damage in mitotic and post-mitotic cells to determine if the level of damage and/or repair is different based on mitotic status. Finally, mice deficient in metallothionein-I and -II are being used in an effort to determine if the subcellular distribution of metals impact on oxidative damage with increased age. (C) 1997 Elsevier Science Ireland Ltd. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP Walter, CA (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NCI NIH HHS [CA61335]; NIA NIH HHS [AG 13560]; NIEHS NIH HHS [ES05798] NR 84 TC 31 Z9 33 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD DEC PY 1997 VL 98 IS 3 BP 203 EP 222 DI 10.1016/S0047-6374(97)00108-5 PG 20 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA YB781 UT WOS:A1997YB78100003 PM 9352490 ER PT J AU Gazit, Y Baish, JW Safabakhsh, N Leunig, M Baxter, LT Jain, RK AF Gazit, Y Baish, JW Safabakhsh, N Leunig, M Baxter, LT Jain, RK TI Fractal characteristics of tumor vascular architecture during tumor growth and regression SO MICROCIRCULATION-LONDON LA English DT Article DE tumor vasculature; fractals; angiogenesis network analysis; percolation ID RETINAL-VESSELS; MICROVASCULAR ARCHITECTURE; DIABETIC-RETINOPATHY; SOLID TUMORS; BLOOD-FLOW; ANGIOGENESIS; DELIVERY; GEOMETRY; PRESSURE; TISSUE AB Objective: Tumor vascular networks are different from normal vascular networks: but the mechanisms underlying these differences are not known. Understanding these mechanisms may be the key to improving the efficacy of treatment of solid tumors. Methods: We studied the fractal characteristics of two-dimensional normal and tumor vascular networks grown in a murine dol sal chamber preparation and imaged with an intravital microscopy station. Results: During tumor growth and regression, the vasculature in the tumor has scaling characteristics that reflect the changing state of the tissue. Growing turners show vascular networks that progressively deviate from their normal pattern, in which they seem to follow diffusion-limited. aggregation tu a pathological condition in which they display scaling similar to percolation clusters near the percolation threshold. The percolation-like scaling indicates that the key determinants of tumor vascular architecture are local substrate properties rather than gradients of a diffusing substance, such as an angiogenic growth factor. During tumor regression, the fractal characteristics of the vasculature return to an intermediate between those of growing tumors and those of healthy tissues. Previous studies have shown that percolation-like scaling generally inhibits transport. Conclusions: In the present contest, the percolation-like nature of tumor vasculature implies that tumor vascular networks possess inherent architectural obstacles to the delivery of diffusible substances such as oxygen and drugs. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL, EDWIN L STEELE LAB, BOSTON, MA 02114 USA. MIT, HARVARD MIT DIV HLTH SCI & TECHNOL, CAMBRIDGE, MA 02139 USA. BUCKNELL UNIV, DEPT MECH ENGN, LEWISBURG, PA 17837 USA. RI Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [R15-CA-74366, R35-CA-56591] NR 33 TC 102 Z9 112 U1 3 U2 14 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 1073-9688 J9 MICROCIRCULATION-LON JI Microcirculation-London PD DEC PY 1997 VL 4 IS 4 BP 395 EP 402 DI 10.3109/10739689709146803 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA YL455 UT WOS:A1997YL45500001 PM 9431507 ER PT J AU Rieger, A Rainov, NG Sanchin, L Burkert, W AF Rieger, A Rainov, NG Sanchin, L Burkert, W TI Dorsal spondylodesis of unstable thoracolumbar fractures by a far-lateral approach to the disc SO MINIMALLY INVASIVE NEUROSURGERY LA English DT Article DE far-lateral approach; internal fixation; spinal fracture; thoracolumbar spine; transpedicular screws ID LUMBAR SPINE AB This paper describes a modified and less traumatic approach to the thoracolumbar spine and compares it with standard techniques for instrumented spinal fusion. Ten patients with unstable fractures of the thoracolumbar spine were included in the open prospective investigation, and were treated by a surgical technique consisting of a dorsolateral approach to the injured segment, filling the disk space and the fractured vertebra with autologous bone, and transpedicular fixation with an AO internal fixator. All patients were followed for 6 to 12 months after surgery by clinical tests and spinal X-rays. Excellent short-term and long-term results were obtained. A stable bony fusion was achieved in all cases, and a minimal mean decrease of 2 degrees in the kyphosis angle was found at late follow-up. No major complications related to the procedure were encountered, and no worsening of neurological deficits occurred after surgery. In conclusion, the far-lateral approach to the thoracolumbar spine yields results which are equivalent or better than those of standard techniques. Major advantages of our procedure, as evaluated in this rather small group of patients, are selective immobilization of the injured segment without involvement of functionally intact spinal levels, no manipulations within the spinal canal boundaries, and relatively limited exposure of the spine. C1 Massachusetts Gen Hosp, Neurol Serv, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Univ Halle Wittenberg, Fac Med, Dept Neurosurg, Halle, Germany. RP Rainov, NG (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, 13th St,Bldg 149,6th Fl, Charlestown, MA 02129 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0946-7211 J9 MINIM INVAS NEUROSUR JI Minim. Invasive Neurosurg. PD DEC PY 1997 VL 40 IS 4 BP 130 EP 133 DI 10.1055/s-2008-1053433 PG 4 WC Clinical Neurology; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA YX193 UT WOS:000072015700004 PM 9477401 ER PT J AU Young, RH Rosenberg, AE Clement, PB AF Young, RH Rosenberg, AE Clement, PB TI Mucin deposits within inguinal hernia sacs: A presenting finding of low-grade mucinous cystic tumors of the appendix. A report of two cases and a review of the literature SO MODERN PATHOLOGY LA English DT Review DE appendix; extravasated mucin; Hernia sac; low-grade mucinous cystic tumor ID PSEUDOMYXOMA PERITONEI; AGGRESSIVE ANGIOMYXOMA; ORIGIN AB Two male patients, both 41 years of age, presented clinically with a typical inguinal hernia. The herniorrhaphy specimens were found on routine pathologic examination to contain abundant mucin that was focally organizing and was devoid of associated epithelial cells, Both cases were seen in consultation because of uncertainty as to the nature of the process. The possibility that the mucin might represent spread from an appendiceal mucinous cystic tumor led to the investigation of the appendix and in both cases such a tumor was discovered, The widespread involvement of the peritoneum that is characteristic of pseudomyxoma peritonei was absent in each case. These cases represent one of the marry "surprise" findings that may be encountered in hernia sac specimens and one of the many problematic pathologic manifestations that may be associated with low-grade mucinous neoplasms of the appendix. Although this phenomenon is described in the literature, experience with our two cases indicates that it may still pose a significant diagnostic challenge. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1997 VL 10 IS 12 BP 1228 EP 1232 PG 5 WC Pathology SC Pathology GA YM640 UT WOS:000071085000008 PM 9436968 ER PT J AU Bergman, S Graeme-Cook, F Pitman, MB AF Bergman, S Graeme-Cook, F Pitman, MB TI The usefulness of the reticulin stain in the differential diagnosis of liver nodules on fine-needle aspiration biopsy cell block preparations SO MODERN PATHOLOGY LA English DT Article DE cell block; cytology; fine-needle aspiration biopsy; hepatocellular carcinoma; liver; reticulin stain ID HEPATOCELLULAR-CARCINOMA; REGENERATIVE HYPERPLASIA; CIRRHOTIC LIVERS; FEATURES; CRITERIA; DISEASE; LESIONS; AUTOPSY; BENIGN AB We reviewed fine-needle aspiration biopsy (FNAB) cell blocks of hepatocellular carcinoma (I-ICC) (n = 16) and benign hepatic processes (n = 16) to evaluate the significance of reticulin staining (Gomori stain) in combination with standard cytomorphologic and architectural criteria. We analyzed the staining pattern using semiquantitative grading: normal, variable, decreased, or virtually absent. Also, we graded the cell thickness of the hepatic trabeculae as greater than or less than three cells. Fourteen of 16 biopsy specimens of benign processes demonstrated a normal reticulin framework, with staining outlining hepatic trabeculae less than three cell layers in thickness. Staining was markedly decreased in one case of steatosis and virtually absent in one case of cirrhosis. In contrast, all of the 16 HCCs demonstrated either a virtually absent (7 of 16), decreased (6 of 16), or variable (3 of 16) reticulin staining pattern, with thickened trabeculae greater than three cell layers. We conclude that the reticulin stain is a useful adjunct in the differential diagnosis of liver nodules on FNAB cell block preparations and that it is particularly useful in distinguishing HCC ii om benign hepatic processes. Virtually absent or decreased reticulin staining and staining outlining trabeculae greater-than three cells in thickness support the diagnosis of HCG. Normal reticulin staining outlining well-defined hepatic trabeculae less than three cell layers in thickness supports the diagnosis of a benign hepatic process. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 14 Fruit St, Boston, MA 02114 USA. NR 31 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1997 VL 10 IS 12 BP 1258 EP 1264 PG 7 WC Pathology SC Pathology GA YM640 UT WOS:000071085000013 PM 9436973 ER PT J AU Seol, W Chung, M Moore, DD AF Seol, W Chung, M Moore, DD TI Novel receptor interaction and repression domains in the orphan receptor SHP SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR HORMONE RECEPTORS; LIGAND-BINDING DOMAIN; REV-ERBA-ALPHA; THYROID-HORMONE; TRANSCRIPTIONAL REPRESSION; ESTROGEN-RECEPTOR; CO-REPRESSOR; PROTEIN; GENE; SUPERFAMILY AB SHP (short heterodimer partner) is a novel orphan receptor that lacks a conventional DNA binding domain and interacts with other members of the nuclear hormone receptor superfamily. We have characterized the SHP sequences required for interaction with other superfamily members, and have defined an SHP repressor domain, In the mammalian two-hybrid system, a fusion of full-length SHP to the GAL4 DNA binding domain shows 9-cis-retinoic acid-dependent interaction with a VP16-retinoid X receptor alpha (RXR alpha) fusion. By deletion analysis, sequences required for this RXR interaction map to the central portion of SHP (amino acids 92 to 148). The same region is required for interaction with RXR in vitro and in the yeast two-hybrid system, and results front the yeast system suggest that the same SHP sequences are required for interaction with other members of the nuclear hormone receptor superfamily such as thyroid hormone receptor and retinoic acid receptor. In mammalian cells, a GAL4-SHP fusion protein shows about 10-fold-decreased transcriptional activation relative to GAL4 alone, and fusion of SHP to the C terminus of a GAL4-VP16 fusion to generate a triple chimera also results in a strong decrease in transactivation activity. Sequences required for this repressor function were mapped to the C terminus of SHP. This region is distinct from that required for corepressor interaction by other members of the nuclear hormone receptor superfamily, and SHP did not interact with N-CoR in either the yeast or mammalian two-hybrid system. Together, these results identify novel receptor interaction and repressor domains in SHP and suggest two distinct mechanisms for inhibition of receptor signaling pathways by SHP. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. FU NIDDK NIH HHS [R01 DK46546, R01 DK43382] NR 44 TC 113 Z9 114 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 7126 EP 7131 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100037 PM 9372944 ER PT J AU Hussain, MA Lee, J Miller, CP Habener, JF AF Hussain, MA Lee, J Miller, CP Habener, JF TI POU domain transcription factor brain 4 confers pancreatic alpha-cell-specific expression of the proglucagon gene through interaction with a novel proximal promoter G1 element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OCTAMER-BINDING-PROTEINS; GLUCAGON GENE; BETA-CELLS; ENDOCRINE-CELLS; HOMEOBOX FACTOR; INSULIN GENE; ISLET CELLS; COACTIVATOR; RAT; SOMATOSTATIN AB The proglucagon gene is expressed in a highly restricted tissue-specific manner in the alpha cells of the pancreatic islet, the hypothalamus, and the small and large intestines. proglucagon is processed to glucagon and glucagon-like peptides GLP-1 and -2. Glucagon is expressed in alpha cells and regulates glucose homeostasis. GLP-1 is implicated in the control of insulin secretion, food intake, and satiety signaling, and GLP-2 is implicated in regulating small-bowel growth. Cell-specific expression of the proglucagon gene is mediated by proteins that interact with the proximal G1 promoter element which contains several AT-rich domains with binding sites for homeodomain transcription factors. In an attempt to identify major homeodomain proteins involved in pancreatic alpha-cell-specific proglucagon expression, we found that the POU domain transcription factor brain 4 is abundantly expressed in proglucagon-producing islet cell lines and rat pancreatic islets. In the latter, brain 4 and glucagon immunoreactivity colocalize in the outer mantle of islets. Electrophoretic mobility shift assays with specific antisera identify brain 4 as a major constituent of nuclear proteins of glucagon-producing cells that bind to the G1 element of the proglucagon gene proximal promoter. Transcriptional transactivation experiments reveal that brain 4 is a major regulator of proglucagon gene expression by its interaction with the G1 element. The finding that a neuronal transcription factor is involved in glucagon gene transcription may explain the presence of proglucagon in certain areas of the brain as well as in pancreatic alpha cells. Further, this finding supports the idea that the neuronal properties of endodermis-derived endocrine pancreatic cells may find their basis in regulation of gene expression by neuronal transcription factors. C1 MASSACHUSETTS GEN HOSP,MOL ENDOCRINOL LAB,HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R01DK30834] NR 52 TC 70 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1997 VL 17 IS 12 BP 7186 EP 7194 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG441 UT WOS:A1997YG44100044 PM 9372951 ER PT J AU Pujades, C Alon, R Yauch, RL Masumoto, A Burkly, LC Chen, C Springer, TA Lobb, RR Hemler, ME AF Pujades, C Alon, R Yauch, RL Masumoto, A Burkly, LC Chen, C Springer, TA Lobb, RR Hemler, ME TI Defining extracellular integrin alpha-chain sites that affect cell adhesion and adhesion strengthening without altering soluble ligand binding SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID I-DOMAIN; MONOCLONAL-ANTIBODY; VITRONECTIN RECEPTOR; SIGNAL-TRANSDUCTION; PLATELET INTEGRIN; RECOGNITION SITE; COUNTER-RECEPTOR; SPLICED DOMAIN; LATE ANTIGEN-4; CROSS-LINKING AB It was previously shown that mutations of integrin alpha 4 chain sites, within putative EF-hand-type divalent cation-binding domains, each caused a marked reduction in alpha 4 beta 1-dependent cell adhesion. Some reports have suggested that alpha-chain ''EF-hand'' sites may interact directly with ligands. However, we show here that mutations of three different alpha 4 ''EF-hand'' sites each had no effect on binding of soluble monovalent or bivalent vascular cell adhesion molecule 1 whether measured indirectly or directly. Furthermore, these mutations had minimal effect on alpha 4 beta 1-dependent cell tethering to vascular cell adhesion molecule 1 under shear. However, EF-hand mutants did show severe impairments in cellular resistance to detachment under shear flow. Thus, mutation of integrin alpha 4 ''EF-hand-like'' sites may impair 1) static cell adhesion and 2) adhesion strengthening under shear flow by a mechanism that does not involve alterations of initial ligand binding. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. WEIZMANN INST SCI,DEPT IMMUNOL,IL-76100 REHOVOT,ISRAEL. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. BIOGEN INC,CAMBRIDGE,MA 02142. RI Pujades, Cristina/F-7908-2014 OI Pujades, Cristina/0000-0001-6423-7451 FU NCI NIH HHS [CA317978]; NHLBI NIH HHS [HL48675, P01 HL048675]; NIGMS NIH HHS [GM-38903, R01 GM038903] NR 76 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1997 VL 8 IS 12 BP 2647 EP 2657 PG 11 WC Cell Biology SC Cell Biology GA YK930 UT WOS:A1997YK93000022 PM 9398682 ER PT J AU Mothe, I Delahaye, L Filloux, C Pons, S White, MF VanObberghen, E AF Mothe, I Delahaye, L Filloux, C Pons, S White, MF VanObberghen, E TI Interaction of wild type and dominant-negative p55(PIK) regulatory subunit of phosphatidylinositol 3-kinase with insulin-like growth factor-1 signaling proteins SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FACTOR-I RECEPTOR; YEAST 2-HYBRID SYSTEM; HIGH-EFFICIENCY TRANSFORMATION; SERINE KINASE-ACTIVITY; SH2 DOMAINS; PI 3-KINASE; PHOSPHOINOSITIDE 3-KINASE; 3T3-L1 ADIPOCYTES; TYROSINE KINASE; SUBSTRATE-1 AB In a first series of experiments done in the yeast two-hybrid system, we investigated the nature of protein-protein interaction between the regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase), p55(PIK) and several of its potential signaling partners. The region between the Src homology 2 (SH2) domains of p55(PIK) bound to the NH2 terminus region of p110 alpha, as previously shown for p85 alpha. Moreover, we found that the insulin-like growth factor-1 receptor (IGF-IR) bound to p55(PIK); the interaction occurred at the receptor tyrosine 1316 and involved both p55(PIK) SH2 domains. Interaction between p55(PIK) and IGF-IR was seen not only in the yeast two-hybrid system, but also using in vitro binding and coimmunoprecipitation of lysates from IGF-1 stimulated 293 cells overexpressing p55(PIK). Further, IGF-I stimulation of these cells led to tyrosine phosphorylation of p55(PIK). In 293 cells association of p55(PIK) with insulin receptor substrate-1 and with IGF-IR was dependent on PI 3-kinase, since it was increased by wortmannin, an inhibitor of PI 3-kinase. Further, by deleting amino acids 203-217 of p55(PIK) inter-SH2 domain, we engineered a p55(PIK) mutant unable to bind to the p110 alpha catalytic subunit of PI 3-kinase. This mutant had a dominant-negative action on insulin-stimulated glucose transport, since insulin's effect on Glut 4 myc translocation was inhibited in adipocytes expressing mutant p55(PIK). Importantly, this dominant-negative mutant was more efficient than wild type p55(PIK) in associating to IGF-IR and insulin receptor substrate-1 in 293 cells. Taken together, results show that p55(PIK) interacts with key elements in the IGF-I signaling pathway, and that these interactions are negatively modulated by PI 3-kinase itself, providing circuitry for regulatory feedback control. C1 HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02215 USA. RP Mothe, I (reprint author), FAC MED, INSERM U145, AVE VALLOMBROSE, F-06107 NICE 2, FRANCE. RI Pons , Sebastian/K-7794-2014; OI Pons , Sebastian/0000-0003-1027-0621; MOTHE-SATNEY, ISABELLE/0000-0002-2693-8385 FU NIDDK NIH HHS [DK-38712, DK-43808] NR 44 TC 10 Z9 11 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1997 VL 11 IS 13 BP 1911 EP 1923 DI 10.1210/me.11.13.1911 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YK065 UT WOS:A1997YK06500004 PM 9415396 ER PT J AU Fraefel, C Jacoby, DR Lage, C Hilderbrand, H Chou, JY Alt, FW Breakefield, XO Majzoub, JA AF Fraefel, C Jacoby, DR Lage, C Hilderbrand, H Chou, JY Alt, FW Breakefield, XO Majzoub, JA TI Gene transfer into hepatocytes mediated by helper virus-free HSV/AAV hybrid vectors SO MOLECULAR MEDICINE LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; ADENOASSOCIATED VIRUS; IN-VIVO; TRANSGENIC MICE; FACTOR-IX; EXPRESSION; THERAPY; LIVER; TYPE-1; CELLS AB Background: Vectors based on herpes simplex virus type 1 (HSV-1) can efficiently transduce hepatocytes in the mouse Liver, and vector genomes can persist for at least 2 months. However, 24 hr after gene transfer, the number of cells that express the transgene decreases rapidly and no transduced cells are detectable after 7 days. Ln this study, we examined the capability of a helper virus-free HSV/AAV hybrid amplicon vector to extend transgene expression in hepatocytes in vivo. Materials and Methods: HSV-1 amplicon or HSV/ AAV hybrid amplicon vectors that express reporter genes from different transcriptional regulatory sequences were packaged into HSV-1 virions using a helper virus-free packaging system. To determine relative transduction efficiencies, vector stocks were titered on four different cell lines, including hamster kidney (BHK21) and human lung (Hs913T) fibroblasts, and mouse (G6Pase-/-) and human (NPLC) hepatocytes. After in vivo injection of vector stocks into mouse liver, tissue sections were examined for reporter gene expression and cellular inflammatory response. Blood samples were collected to measure serum transaminase levels as a biochemical index of liver toxicity. Results: Expression of a reporter gene from liver-specific promoter sequences was consistently more effective in hepatic cells compared with fibroblasts, whereas the opposite was true when using an HSV-1 immediate-early promoter. Expression in hepatocytes in vivo was markedly longer from HSV/AAV hybrid vector compared with traditional HSV-1 amplicon vector: the number of transduced cells (similar to 2% of all hepatocytes) remained stable over 7 days after injection of HSV/AAV hybrid vector, whereas no transduced cells were detected 7 days after gene transfer with standard HSV-1 amplicon vector. The rapid decline in reporter gene expression from standard amplicons was not solely caused by a B or T lymphocyte-mediated immune response, as it also occurred in RAG2-/- mice. Hepatocyte toxicity and cellular inflammatory effects associated with HSV/ AAV hybrid vector-mediated gene transfer were minimal, and readministration of vector stock proved equally effective in naive mice and in animals that received a first vector dose 4 weeks earlier. Conclusions: HSV/AAV hybrid amplicon vectors support gene expression in vivo for considerably longer than do traditional HSV-1 amplicon vectors. Moreover, expression from these vectors does not provoke an overt inflammatory or immune response, allowing efficacious expression following repeated in vivo dosing. These characteristics suggest that such vectors may hold future promise for hepatic gene replacement therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Fraefel, C (reprint author), Univ Zurich, Inst Virol, Winterthurerstr 266A, CH-8057 Zurich, Switzerland. FU NCI NIH HHS [CA69246]; NIDCD NIH HHS [DC002281]; NINDS NIH HHS [NS24279] NR 45 TC 71 Z9 73 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 1997 VL 3 IS 12 BP 813 EP 825 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YN075 UT WOS:000071130600003 PM 9440115 ER PT J AU Gurdal, H Seasholtz, TM Wang, HY Brown, RD Johnson, MD Friedman, E AF Gurdal, H Seasholtz, TM Wang, HY Brown, RD Johnson, MD Friedman, E TI Role of G(alpha q) or G(alpha o) proteins in alpha(1)-adrenoceptor subtype mediated responses in Fischer 344 rat aorta SO MOLECULAR PHARMACOLOGY LA English DT Article ID CARDIOVASCULAR-SYSTEM; PULMONARY-ARTERY; PERTUSSIS TOXIN; XENOPUS-OOCYTES; SMOOTH-MUSCLE; RECEPTOR; EXPRESSION; BINDING; IDENTIFICATION; CONTRACTIONS AB Previous studies showed that alpha-adrenoceptor (AR) stimulation with norepinephrine is more potent at eliciting contraction in aortas from 1-month-old Fischer 344 rats than from older rats and that this response is mediated by alpha(1b)- and alpha(1d)-AR subtypes in 1-month-old rats. We examined the G proteins responsible for alpha(1)-AR-mediated contractile response and inositol phosphate accumulation in the aortas of 1-month-old Fischer 344 rats. Pertussis toxin (PTX) treatment (2.5 mu g/ml for 4 hr) of aortic rings partially inhibited phenylephrine (PHE)-stimulated contraction and inositol phosphate accumulation, suggesting the involvement of PTX-sensitive and -insensitive G proteins. Specific antisera directed against G(alpha q) and G(alpha o) but not G(alpha s) and G(alpha i) precipitated specific alpha(1)-AR binding sites labeled with 2-[beta-(4-hydroxy-3-[I-125]iodophenyl)ethylaminomethyl]tetralone. The number of 2-[beta-(4-hydroxy-3-[I-125] iodophenyl)ethylaminomethyl]tetralone binding sites precipitated by G(alpha) proteins was increased by activating membrane alpha(1)-ARs with PHE. Moreover, PHE stimulated the palmitoylation of G(alpha q) and G(alpha o), and this response was blocked by the alpha(1)-AR antagonist prazosin. Characterization of the alpha(1)-AR subtypes that couple to G proteins indicates that although aortic alpha(1a)- alpha(1b)- and alpha(1d)-ARs were associated with G(alpha q), alpha(1b)-AR was also linked to G(alpha o). These results suggest that alpha(1)-ARs mediate the contractile response in rat aorta by coupling to both G(q) protein and the PTX-sensitive G(o) protein. C1 Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Div Mol Pharmacol, Philadelphia, PA 19129 USA. Ankara Univ, Sch Med, Dept Pharmacol, TR-06100 Ankara, Turkey. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res & Dev Serv, Hines, IL 60141 USA. RP Friedman, E (reprint author), Allegheny Univ Hlth Sci, MCP Hahnemann Sch Med, Div Mol Pharmacol, 3200 Henry Ave, Philadelphia, PA 19129 USA. RI Gurdal, Hakan/A-3570-2016 OI Gurdal, Hakan/0000-0003-4751-2372 FU NIA NIH HHS [AG14510, AG07700, AG13282] NR 26 TC 35 Z9 35 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1997 VL 52 IS 6 BP 1064 EP 1070 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YM055 UT WOS:000071023400017 PM 9415716 ER PT J AU Smith, AB AF Smith, AB TI A "cumulative" method of quantifying tonal consonance in musical key contexts SO MUSIC PERCEPTION LA English DT Article ID HIERARCHIES; PERCEPTION; PITCH AB Huron (1994) recently calculated the tonal (sensory) consonance for interval categories for all scales that can be drawn from the 12 equally tempered pitch classes. Among scales with seven tones, the combinations that allow the highest tonal consonance were found in the diatonic major, natural minor, and several other scales. In this paper, an extension of Huron's approach that begins with a single tone and successively adds tones that bring the most tonal consonance to the existing set is tested. Based on (1) the order in which tones are added and (2) the mean tonal consonance of the intervals after each addition, values are assigned to each tone that are significantly correlated (p < .001) with ratings of stability that tones display in major and minor key contexts reported by Krumhansl and Kessler (1982). These findings suggest that tonal consonance is not only facilitated in major and minor scales, as Huron found, but that tonal consonance may also account for the tonal hierarchy for tones in both major and minor key contexts. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Smith, AB (reprint author), Old Mill Pond Sch, Palmer, MA 01069 USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU UNIV CALIF PRESS PI BERKELEY PA JOURNALS DEPT 2120 BERKELEY WAY, BERKELEY, CA 94720 USA SN 0730-7829 J9 MUSIC PERCEPT JI Music Percept. PD WIN PY 1997 VL 15 IS 2 BP 175 EP 188 PG 14 WC Music; Psychology, Experimental SC Music; Psychology GA YP349 UT WOS:000071268000005 ER PT J AU White, JK Auerbach, W Duyao, MP Vonsattel, JP Gusella, JF Joyner, AL MacDonald, ME AF White, JK Auerbach, W Duyao, MP Vonsattel, JP Gusella, JF Joyner, AL MacDonald, ME TI Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion SO NATURE GENETICS LA English DT Article ID ABNORMAL BRAIN-DEVELOPMENT; GENE HOMOLOG HDH; TRANSGENIC MICE; TRINUCLEOTIDE REPEAT; EMBRYONIC LETHALITY; PROTEIN; MOUSE; POLYGLUTAMINE; PHENOTYPE; LOCALIZATION AB Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder caused by a CAG repeat expansion that lengthens a glutamine segment in the novel huntingtin protein. To elucidate the molecular basis of HD, we extended the polyglutamine tract of the mouse homologue, Hdh, by targetted introduction of an expanded human HD CAG repeat, creating mutant Hdh(neoQ50) and Hdh(Q50) alleles that express reduced and wildtype levels of altered huntingtin, respectively. Mice homozygous for reduced levels displayed characteristic aberrant brain development and perinatal lethality, indicating a critical function for Hdh in neurogenesis. However, mice with normal levels of mutant huntingtin did not display these abnormalities, indicating that the expanded CAG repeat does not eliminate or detectably impair huntingtin's neurogenic function. Thus, the HD defect in man does not mimic complete or partial Hdh inactivation and appears to cause neurodegenerative disease by a gain-of-function mechanism. C1 MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,CHARLESTOWN,MA 02129. NYU,MED CTR,DEPT CELL BIOL,NEW YORK,NY 10016. NYU,MED CTR,SKIRBALL INST BIOMOL MED,DEV GENET PROGRAM,NEW YORK,NY 10016. MASSACHUSETTS GEN HOSP,MOL NEUROPATHOL LAB,CHARLESTOWN,MA 02129. FU NINDS NIH HHS [NS16367, NS32765] NR 47 TC 314 Z9 323 U1 0 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 404 EP 410 DI 10.1038/ng1297-404 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400020 PM 9398841 ER PT J AU Kupfer, GM Naf, D Suliman, A Pulsipher, M DAndrea, AD AF Kupfer, GM Naf, D Suliman, A Pulsipher, M DAndrea, AD TI The Fanconi anaemia proteins, FAA and FAG, interact to form a nuclear complex SO NATURE GENETICS LA English DT Article ID GROUP-C; ANEMIA; COMPLEMENTATION; GENE; POLYPEPTIDE; CLONING; FACC; PHOSPHORYLATION; EXPRESSION; CYTOPLASM AB Fanconi anaemia (FA) is an autosomal-recessive disorder characterized by genomic instability, developmental defects, DNA crosslinking agent hypersensitivity and cancer susceptibility(1-3). Somatic-cell hybrid studies have revealed five FA complementation groups (A-E; refs 4-6) displaying similar phenotypes, suggesting that FA genes are functionally related(7). The two cloned FA genes, FAA and FAG, encode proteins that are unrelated to each other or to other proteins in GenBank(8-10). In the current study, we demonstrate that FAA and FAC bind each other and form a complex. Protein binding correlates with the functional activity of FAA and FAG, as patient-derived mutant FAC (L554P) fails to bind FAA. Although unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex is found in similar abundance in both cytoplasm and nucleus. Our results confirm the interrelatedness of the FA genes in a pathway, suggesting the cooperation of FAA and FAC in a nuclear function. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Kupfer, GM (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA39542]; NHLBI NIH HHS [R01-HL5725, K08-HL03420] NR 23 TC 153 Z9 153 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1997 VL 17 IS 4 BP 487 EP 490 DI 10.1038/ng1297-487 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA YJ924 UT WOS:A1997YJ92400036 PM 9398857 ER PT J AU Goodell, MA Rosenzweig, M Kim, H Marks, DF DeMaria, M Paradis, G Grupp, SA Sieff, CA Mulligan, RC Johnson, RP AF Goodell, MA Rosenzweig, M Kim, H Marks, DF DeMaria, M Paradis, G Grupp, SA Sieff, CA Mulligan, RC Johnson, RP TI Dye efflux studies suggest that hematopoietic stem cells expressing low or undetectable levels of CD34 antigen exist in multiple species SO NATURE MEDICINE LA English DT Article ID LONG-TERM-CULTURE; UMBILICAL-CORD BLOOD; HUMAN FETAL LIVER; BONE-MARROW; PROGENITOR CELLS; GENE-THERAPY; IN-VITRO; DIFFERENTIATION; PURIFICATION; ENGRAFTMENT AB We previously described a method for isolating murine hematopoietic stem cells capable of reconstituting lethally irradiated recipients, which depends solely on dual-wavelength flow cytometric analysis of murine bone marrow cells stained with the fluorescent DNA-binding dye Hoechst 33342. This method, which appears to rely on the differential ability of stem cells to efflux the Hoechst dye, defines an extremely small and homogeneous population of cells (termed SP cells). We show here that dual-wavelength analysis of Hoechst dye-stained human, rhesus and miniature swine bone marrow cells reveals a small, distinct population of cells that efflux the dye in a manner identical to murine SP cells. Like the murine SP cells, both human and rhesus SP cells are primarily CD34-negative and lineage marker-negative. In vitro culture studies demonstrated that rhesus SP cells are highly enriched for long-term culture-initiating cells (LTC-ICs), an indicator of primitive hematopoietic cells, and have the capacity for differentiation into T cells. Although rhesus SP cells do not initially possess any hematopoietic colony-forming capability, they acquire the ability to form colonies after long-term culture on bone marrow stroma, coincident with their conversion to a CD34-positive phenotype. These studies suggest the existence of a hitherto unrecognized population of hematopoietic stem cells that lack the CD34 surface marker classically associated with primitive hematopoietic cells. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. MIT, Flow Cytometry Lab, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Mulligan, RC (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. OI Goodell, Margaret/0000-0003-1111-2932 FU NCRR NIH HHS [RR-00055]; NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI-36550] NR 32 TC 804 Z9 834 U1 0 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 1997 VL 3 IS 12 BP 1337 EP 1345 DI 10.1038/nm1297-1337 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA YZ389 UT WOS:000072249500029 PM 9396603 ER PT J AU Barnes, JL AF Barnes, JL TI Platelets in glomerular disease SO NEPHRON LA English DT Review DE migration; proliferation; extracellular matrix; glomerular permeability ID SYSTEMIC LUPUS-ERYTHEMATOSUS; HUMAN MESANGIAL CELLS; HABU SNAKE-VENOM; IMMUNE-COMPLEX NEPHRITIS; GROWTH-FACTOR-BETA; PLASMINOGEN-ACTIVATOR INHIBITOR-1; EXTRACELLULAR-MATRIX COMPONENTS; PLASMA SEROTONIN CONCENTRATIONS; NEPHROTOXIC SERUM NEPHRITIS; TUMOR-NECROSIS-FACTOR AB Platelets are viewed as inflammatory cells and play an important role in hemostasis and wound repair. During activation, platelets secrete a wide variety of products that have multiple effects on target cell behavior during tissue remodeling. Among these secretory products are chemotactins, growth factors and fibrogenic substances. This review examines evidence for a role of platelets in glomerular disease and discusses mechanisms of how platelet secretory products may alter permselectivity of the glomerular basement membrane, resulting in enhanced immune complex localization. Also, platelet secretory products may stimulate glomerular remodeling after injury through mechanisms involving cell migration, proliferation and extracellular matrix synthesis, ultimately distorting the normal glomerular architecture and function. C1 AUDIE L MURPHY MEM VET ADM MED CTR,MED RES SERV,SAN ANTONIO,TX 78284. RP Barnes, JL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 185 TC 21 Z9 21 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD DEC PY 1997 VL 77 IS 4 BP 378 EP 393 PG 16 WC Urology & Nephrology SC Urology & Nephrology GA YK445 UT WOS:A1997YK44500002 PM 9434058 ER PT J AU Lai, EC Felice, KJ Festoff, BW Gawel, MJ Gelinas, DF Kratz, R Murphy, MF Natter, HM Norris, FH Rudnicki, SA AF Lai, EC Felice, KJ Festoff, BW Gawel, MJ Gelinas, DF Kratz, R Murphy, MF Natter, HM Norris, FH Rudnicki, SA CA N Amer ALS IGF I Study Grp TI Effect of recombinant human insulin-like growth factor-I on progression of ALS - A placebo-controlled study SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SICKNESS IMPACT PROFILE; NATURAL-HISTORY; SPINAL-CORD; DISORDERS; SYSTEM AB The objective of this study was to investigate the safety and efficacy of recombinant human insulinlike growth factor-I (rhIGF-I) in the treatment of sporadic ALS. A double-blind, placebo-controlled, randomized study of 266 patients was conducted at eight centers in North America. Placebo or rhIGF-I (0.05 mg/kg/day or 0.10 mg/kg/day) was administered for 9 months. The primary outcome measure was disease symptom progression, assessed by the rate of change (per patient slope) in the Appel ALS rating scale total score. The Sickness Impact Profile (STP), a patient-perceived, health-related quality of life assessment, was a secondary outcome variable. Progression of functional impairment in patients receiving high-dose (0.10 mg/kg/day) rhIGF-I was 26% slower than in patients receiving placebo (p = 0.01). The high-dose treatment group was less likely to terminate the study due to protocol-defined markers of disease symptom progression, and members in this group exhibited a slower decline in quality of life, as assessed by the SIP. Patients receiving 0.05 mg/kg/day of rhIGF-I exhibited trends similar to those associated with high-dose treatment, suggesting a dose-dependent response. The incidence of clinically significant adverse experiences was comparable among the three treatment groups. Recombinant human insulin-like growth factor-I slowed the progression of functional impairment and the decline in health-related quality of life in patients with ALS with no medically important adverse effects. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Univ Connecticut, Sch Med, Dept Neurol, Farmington, CT USA. Univ Kansas, Sch Med, VA Med Ctr, Kansas City, MO USA. Calif Pacific Med Ctr, Forbes Norris ALS & Neuromuscular Res Ctr, San Francisco, CA USA. Georgetown Univ, Dept Neurol, Washington, DC USA. Cephalon Inc, W Chester, PA USA. Allegheny Univ Hlth Sci, Hahnemann Hosp, Philadelphia, PA 19102 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. Univ Toronto Clin, Sunnybrook Hlth Sci Ctr, N York, ON, Canada. RP Lai, EC (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. NR 33 TC 267 Z9 272 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD DEC PY 1997 VL 49 IS 6 BP 1621 EP 1630 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA YL495 UT WOS:000070961600024 PM 9409357 ER PT J AU Wen, PY Alyea, EP Simon, D Herbst, RS Soiffer, RJ Antin, JH AF Wen, PY Alyea, EP Simon, D Herbst, RS Soiffer, RJ Antin, JH TI Guillain-Barre syndrome following allogeneic bone marrow transplantation SO NEUROLOGY LA English DT Article ID DEMYELINATING POLYNEUROPATHY AB We describe four patients who developed Guillain-Barre syndrome (GBS) following allogeneic bone marrow transplantation (BMT). All four patients had a febrile illness before developing GBS. Two patients had mild graft-versus-host disease but did not require immunosuppression. These patients add to the increasing number of BMT patients whose courses have been complicated by GBS and raise the possibility that BMT patients, especially those undergoing allogeneic BMT, may have a higher risk of developing GBS. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 48 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1997 VL 49 IS 6 BP 1711 EP 1714 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA YL495 UT WOS:000070961600042 PM 9409375 ER PT J AU Shearman, LP Zylka, MJ Weaver, DR Kolakowski, LF Reppert, SM AF Shearman, LP Zylka, MJ Weaver, DR Kolakowski, LF Reppert, SM TI Two period homologs: Circadian expression and photic regulation in the suprachiasmatic nuclei SO NEURON LA English DT Article ID SILKMOTH ANTHERAEA-PERNYI; MULTIPLE SEQUENCE ALIGNMENTS; CLOCK GENE; TIMELESS; RHYTHMS; PROTEIN; LIGHT; MECHANISMS; BEHAVIOR; NEURONS AB We have characterized a mammalian homolog of the Drosophila period gene and designated it Per?. The PERS protein shows >40% amino acid identity to the protein of another mammalian per homolog (designated Per1) that was recently cloned and characterized. Both PER1 and PER2 proteins share several regions of homology with the Drosophila PER protein, including the protein dimerization PAS domain. Phylogenetic analysis supports the existence of a family of mammalian per genes. In the mouse, Per1 and Per2 RNA levels exhibit circadian rhythms in the SCN and eyes, sites of circadian clocks. Both Per1 and Per2 RNAs in the SCN are increased by light exposure during subjective night but not during subjective day. The results advance our knowledge of candidate clock elements in mammals. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol Pediat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol Pediat Serv, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547] NR 34 TC 518 Z9 529 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC PY 1997 VL 19 IS 6 BP 1261 EP 1269 DI 10.1016/S0896-6273(00)80417-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA YP053 UT WOS:000071236500013 PM 9427249 ER PT J AU AboodyGuterman, KS Pechan, PA Rainov, NG SenaEsteves, M Jacobs, A Snyder, EY Wild, P Schraner, E Tobler, K Breakefield, XO Fraefel, C AF AboodyGuterman, KS Pechan, PA Rainov, NG SenaEsteves, M Jacobs, A Snyder, EY Wild, P Schraner, E Tobler, K Breakefield, XO Fraefel, C TI Green fluorescent protein as a reporter for retrovirus and helper virus-free HSV-1 amplicon vector-mediated gene transfer into neural cells in culture and in vivo SO NEUROREPORT LA English DT Article DE CNS; gene transfer; green fluorescent protein; gliomas; helper virus free HSV-1 amplicon vector; neural progenitor cells; retrovirus vector ID EXPRESSION; TYPE-1; LINES; MODEL AB GREEN fluorescent protein (GFP) is an effective marker for retrovirus and herpes virus vector-mediated gene transfer into various central nervous system-derived cells, both proliferative and non-proliferative, in culture and in vivo. Retrovirus vectors were used to stably transduce several rat and human glioma lines, and a multipotent mouse neural progenitor line in culture. Implantation of selected pools of transduced glioma cells into rodent brain allowed clear visualization of the tumor and the invading tumor edge. Helper virus-free HSV-1 amplicon vectors successfully transferred gfp into non-dividing primary neural cells in culture and in the rat brain. This study describes the versatility of GFP for: (i) labelling of glioma cells in experimental brain tumor models and neural progenitor cells by retrovirus vectors, and (ii) efficient, non-toxic delivery of genes to Post mitotic cells of the nervous system using helper-virus free HSV-1 amplicon vectors. C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROL SERV,MOL NEUROGENET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PROGRAM NEUROSCI,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA. UNIV ZURICH,INST ANAT,ZURICH,SWITZERLAND. UNIV ZURICH,INST VIROL,ZURICH,SWITZERLAND. UNIV HALLE WITTENBERG,DEPT NEUROSURG,D-06097 HALLE,GERMANY. NORTHWESTERN UNIV,BMBCB,EVANSTON,IL 60208. FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS34247, NS33852] NR 25 TC 33 Z9 33 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 1 PY 1997 VL 8 IS 17 BP 3801 EP 3808 DI 10.1097/00001756-199712010-00029 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YJ817 UT WOS:A1997YJ81700033 PM 9427374 ER PT J AU Rutecki, PA Yang, Y AF Rutecki, PA Yang, Y TI Metabotropic glutamate receptor activation modulates epileptiform activity in the hippocampus SO NEUROSCIENCE LA English DT Article DE bicuculline; 4-aminopyridine; carbachol; isoproterenol; afterhyperpolarization; ACPD ID RAT HIPPOCAMPUS; SYNAPTIC INHIBITION; PYRAMIDAL NEURONS; HIGH POTASSIUM; GUINEA-PIG; TRANS-ACPD; SLICE; CA1; AGONISTS; INVITRO AB Synchronous neuronal activity that resembles interictal epileptiform discharges occurs in hippocampal slices if there is an imbalance of inhibitory and excitatory synaptic activity. Antagonists of the GABA(A) receptor and agonists of the ionotropic glutamate receptors are convulsants that produce epileptiform discharges in hippocampal slices. We evaluated the effects of activation of the metabotropic class of glutamate receptors on epileptiform activity produced by convulsants. The metabotropic glutamate agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD, 30-100 mu M) accelerated the rate of interictal epileptiform discharges produced by either bicuculline methiodide or 4-aminopyridine and had minimal effects on discharges produced by high [K+](o). The increase in rate was associated with a significant decrease in the amplitude and duration of the afterhyperpolarization that follows the paroxysmal depolarizing shift, the intracellular correlate of the interictal epileptiform discharge. A modest increase in input resistance (similar to 10%) accompanied the rate increase. beta-adrenergic or muscarinic agonists, neurotransmitters that also decrease the afterhyperpolarization, acted synergistically with ACPD (100 mu M) to increase the control rate of bicuculline-induced interictal discharges by more than eight-fold. Antagonists of beta-adrenergic or muscarinic receptors reduced, but did not block, the acceleration of bicuculline-induced discharge rate produced by 30 mu M ACPD. The results show that metabotropic glutamate receptors enhance the rate of interictal epileptiform discharges produced by bicuculline or 4-aminopyridine. ACPD had no effect on interictal epileptiform activity induced by high [K+](o), a finding that may indicate that in high [K+](o) conditions the metabotropic receptor is activated or that the effects of high [K+](o) already reduced the effect of depolarizing currents that are enhanced by ACPD. The acceleration in interictal discharge rate was associated with a reduction in the afterhyperpolarization that follows the paroxysmal depolarizing shift and this action appears to be important in determining the synchronization of neurons and the rate of interictal epileptiform discharges. Furthermore, interaction between mGluR activation and either muscarinic or beta-adrenergic activation may be important for seizure generation. (C) 1997 IBRO. Published by Elsevier Science Ltd. C1 UNIV WISCONSIN,SCH MED,DEPT NEUROSURG,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,NEUROSCI TRAINING PROGRAM,WILLIAM S MIDDLETON MEM VET ADM HOSP,MADISON,WI 53705. RP Rutecki, PA (reprint author), UNIV WISCONSIN,SCH MED,DEPT NEUROL,WILLIAM S MIDDLETON MEM VET ADM HOSP,2500 OVERLOOK TR,MADISON,WI 53705, USA. FU NINDS NIH HHS [NS28580] NR 47 TC 20 Z9 20 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD DEC PY 1997 VL 81 IS 4 BP 927 EP 935 DI 10.1016/S0306-4522(97)00264-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA XY724 UT WOS:A1997XY72400003 PM 9330356 ER PT J AU Krings, T Buchbinder, BR Butler, WE Chiappa, KH Jiang, HJ Rosen, BR Cosgrove, GR AF Krings, T Buchbinder, BR Butler, WE Chiappa, KH Jiang, HJ Rosen, BR Cosgrove, GR TI Stereotactic transcranial magnetic stimulation: Correlation with direct electrical cortical stimulation SO NEUROSURGERY LA English DT Article DE cortical mapping; frameless stereotaxy; presurgical planning; transcranial magnetic stimulation ID HUMAN MOTOR CORTEX AB OBJECTIVE: To evaluate stereotactic transcranial magnetic stimulation (TMS) as a tool for presurgical functional mapping of human motor cortex. METHODS: Transcranial magnetic stimulation using a frameless stereotactic system was performed in two patients with tumors near the central sulcus. TMS motor function maps were plotted on the patients' three-dimensional volumetric magnetic resonance imaging data and compared with direct electrical cortical stimulation at surgery with the patient under local anesthesia. RESULTS: Stereotactic TMS was well tolerated by both patients and was consistent with known somatotopic representation of human motor cortex. The results demonstrated a good correlation between the TMS and electrical cortical stimulation maps, with all TMS responses eliciting more than 75% of the maximum motor evoked potential falling within 1 cm of the electrical cortical stimulation site. CONCLUSIONS: Our findings indicate that stereotactic TMS is feasible and can provide accurate noninvasive localization of cortical motor function. It may prove to be a useful method for presurgical planning. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG, DIV NEURORADIOL,CLIN NEUROPHYSIOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL, MGH NMR CTR, BOSTON, MA 02114 USA. NR 20 TC 85 Z9 85 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 1997 VL 41 IS 6 BP 1319 EP 1325 DI 10.1097/00006123-199712000-00016 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YH863 UT WOS:A1997YH86300047 PM 9402583 ER PT J AU Sampson, JH Ashley, DM Archer, GE Fuchs, HE Dranoff, G Hale, LP Bigner, DD AF Sampson, JH Ashley, DM Archer, GE Fuchs, HE Dranoff, G Hale, LP Bigner, DD TI Characterization of spontaneous murine astrocytoma and abrogation of its tumorigenicity by cytokine secretion SO NEUROSURGERY LA English DT Article DE animal models; astrocytomas; central nervous system neoplasms; cytokines; gliomas; VM/Dk mice ID TRANSFORMING GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; FACTOR-BETA; BRAIN-TUMORS; MONOCLONAL-ANTIBODIES; GLIOBLASTOMA CELLS; MALIGNANT GLIOMAS; INTERFERON-GAMMA; GENE-THERAPY; EXPRESSION AB OBJECTIVE: The promise of immunotherapies developed against brain tumors in animal models has not been realized in human clinical trials. Thio may be because of the routine use of rodent tumors artificially induced by chemicals or viruses that do not accurately portray the intrinsic qualities of spontaneously arising human tumors and that often fail to incorporate the role of immunosuppressants, such as transforming growth factor-beta, that are secreted by human gliomas. From an astrocytoma that arose spontaneously in inbred VM/Dk mice, we have characterized a highly tumorigenic spontaneous murine astrocytoma cell line (SMA-560) that retains features of glial differentiation and naturally produces high levels of biologically active transforming growth factor-beta. We have used this model to determine whether cytokine production by tumor cells will inhibit intracerebral astrocytoma growth. METHODS: Packaging cell lines producing replication-incompetent retroviral vectors were used to transfect the SMA-560 cell line in vitro with the genes encoding the murine cytokines interleukin (IL)-2, IL-3, IL-4, IL-6, tumor necrosis factor-cv, gamma-interferon, or granulocyte-macrophage colony-stimulating factor or the costimulatory molecule B7.1 (CD80). RESULTS: Mice challenged intracerebrally with 5000 untransfected SMA-560 cells all succumbed to tumor within 30 days, with a median survival of 25 days. In contrast, mice challenged with SMA-560 cells producing IL-2, IL-4, or tumor necrosis factor-alpha each had a more than 400% increase in median survival (P < 0.0001). In these groups, 78.3% (18 of 23 mice), 66.7% (10 of 15 mice), and 60% (6 of 10 mice) of the mice, respectively, remained alive without evidence of tumor for longer than 100 days after the initial tumor challenge. All other cytokines tested and the expression of B7.1 failed to result in an increase in median survival. CONCLUSION: Using a spontaneous astrocytoma model in an inbred mouse strain, we have shown that cytokine production by glial tumors can abrogate their tumorigenicity in vivo despite production of transforming growth factor-beta. These results predict that approaches directed at cytokine production within intracerebral astrocytomas may be efficacious in human trials and that the ''immunological privilege'' of the brain may not be absolute under such conditions. C1 DUKE UNIV,DEPT PEDIAT NEUROONCOL,DURHAM,NC 27710. DUKE UNIV,DEPT SURG NEUROSURG,DURHAM,NC 27710. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. RP Sampson, JH (reprint author), DUKE UNIV,MED CTR,DEPT PATHOL,BOX 3156,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA 56115, CA 11898]; NINDS NIH HHS [NS 20023] NR 55 TC 63 Z9 63 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD DEC PY 1997 VL 41 IS 6 BP 1365 EP 1372 DI 10.1097/00006123-199712000-00024 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA YH863 UT WOS:A1997YH86300072 PM 9402588 ER PT J AU Kasahara, N Smith, TJ Sibayan, SA Montenegro, MH Simmons, RB Simmons, RJ AF Kasahara, N Smith, TJ Sibayan, SA Montenegro, MH Simmons, RB Simmons, RJ TI Midterm reversible failure in trabeculectomies with adjunctive mitomycin-C SO OPHTHALMIC SURGERY AND LASERS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 30-NOV 03, 1994 CL SAN FRANCISCO, CA SP Amer Acad Ophthalmol ID LASER SUTURE LYSIS; SCLERAL FLAP TRABECULECTOMY; BLEB LEAK; HYPOTONY; PROLIFERATION; FIBROBLASTS; GLAUCOMA; FEATURES AB BACKGROUND AND OBJECTIVES: Trabeculectomies usually fail early (< 21 days) or late (> 6 months) when no antifibrotic agent is used. Failure is uncommon during the midterm period, between 3 weeks and 6 months. The purpose of this study is to verify the incidence of failure of trabeculectomies with mitomycin-C (MMC) during the midterm period and to evaluate the safety and efficacy of laser suture lysis (LSL) for reversing it. PATIENTS AND METHODS: The authors reviewed the records of 130 consecutive patients who underwent trabeculectomy with adjunctive MMC. RESULTS: Fourteen patients (15 eyes) had increased intraocular pressure (IOP), between 21 and 185 days (median 41 days). LSL was effective in decreasing the IOP to acceptable levels in 10 (66.6%) of the 15 eyes. No complications related to LSL were noticed. CONCLUSION: The reversibility of midterm failure seems to be a unique feature of trabeculectomies with MMC. C1 NEW ENGLAND GLAUCOMA RES FDN,BOSTON,MA. SCHEPENS EYE RES INST,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Kasahara, Niro/N-8865-2014 OI Kasahara, Niro/0000-0003-4101-0304 NR 24 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD DEC PY 1997 VL 28 IS 12 BP 986 EP 991 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA YL045 UT WOS:A1997YL04500002 PM 9427985 ER PT J AU Zhang, J Kashket, S AF Zhang, J Kashket, S TI Cytotoxic effects of short-chain carboxylic acids on human gingival epithelial cells SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE carboxylic acid; cytotoxicity; epithelial cell; gingival ID FATTY-ACIDS; ANAEROBIC-BACTERIA; SODIUM-BUTYRATE; BY-PRODUCT; PROLIFERATION; PROPIONATE; DIFFERENTIATION; NEUTROPHILS; BACTEROIDES; INHIBITION AB Previous studies showed that foods that are retained on the dentition can accumulate high levels of short-chain carboxylic acids (acetic, formic, lactic and propionic). Since gingival epithelium is the first periodontal tissue to be challenged by oral factors, a study was undertaken to determine whether short-chain carboxylic acids can affect epithelial cells in vitro. Immortalized human oral epithelial cells were grown in supplemented keratinocyte growth medium at 37 degrees C, and the effects of short-chain carboxylic acids were determined with tetrazolium-based and trypan blue exclusion assays. Low concentrations of short-chain carboxylic acids inhibited the growth of human oral epithelial cells, while higher concentrations led to cell death. The effects of short-chain carboxylic acids on the cells were dose-dependent and varied among the individual acids (propionate >formate >lactate >acetate). Growth inhibition was partly reversible and growth resumed after removal of the acids. However, the time needed for recovery of the cells increased with short-chain carboxylic acids concentration, consistent with progressively greater damage to the cells at higher short-chain carboxylic acids concentrations. The observed effects of short-chain carboxylic acids on gingival cells in vitro supported our hypothesis that short-chain carboxylic acids can damage the integrity of gingival epithelium in situ. C1 FORSYTH DENT CTR,NUTR SECT,BOSTON,MA 02115. FORSYTH DENT CTR,CTR RES ORAL BIOL EFFECTS FOODS,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-05253] NR 27 TC 3 Z9 3 U1 0 U2 0 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 1997 VL 12 IS 6 BP 345 EP 349 DI 10.1111/j.1399-302X.1997.tb00736.x PG 5 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA YH865 UT WOS:A1997YH86500004 PM 9573808 ER PT J AU Kieff, DA Boey, H Schaefer, PW Goodman, M Joseph, MP AF Kieff, DA Boey, H Schaefer, PW Goodman, M Joseph, MP TI Isolated neurosarcoidosis presenting as anosmia and visual changes SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID SARCOIDOSIS; MANIFESTATIONS C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept ENT Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. RP Kieff, DA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 5 Z9 5 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 1997 VL 117 IS 6 BP S183 EP S186 DI 10.1016/S0194-5998(97)70097-4 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA YM622 UT WOS:000071083200064 PM 9419143 ER PT J AU Bostic, JQ Wilens, T Spencer, T Biederman, J AF Bostic, JQ Wilens, T Spencer, T Biederman, J TI Juvenile mood disorders and office psychopharmacology SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID MAJOR DEPRESSIVE DISORDER; PLASMA-LEVEL DESIGN; FOLLOW-UP; DOUBLE-BLIND; ADOLESCENT DEPRESSION; PREPUBERTAL CHILDREN; BIPOLAR DISORDER; CONTROLLED TRIAL; LITHIUM; PLACEBO AB Mood disorders occur in children and adolescents, although these disorders may appear differently in younger patients. Research suggests that these disorders may respond to pharmacologic agents, enhancing treatment options for outpatient pediatric practice. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP Bostic, JQ (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL CLIN,15 PARKMAN ST,WAC 725,BOSTON,MA 02114, USA. NR 81 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 SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD DEC PY 1997 VL 44 IS 6 BP 1487 EP & DI 10.1016/S0031-3955(05)70570-8 PG 18 WC Pediatrics SC Pediatrics GA YK335 UT WOS:A1997YK33500009 PM 9400583 ER PT J AU Englund, JA Glezen, WP Thompson, C Anwaruddin, R Turner, CE Siber, GR AF Englund, JA Glezen, WP Thompson, C Anwaruddin, R Turner, CE Siber, GR TI Haemophilus influenzae type b-specific antibody in infants after maternal immunization SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Haemophilus influenzae; maternal immunization; antibody in infants ID HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; STREPTOCOCCUS-PNEUMONIAE; VARIABLE REGION; CHILDREN BORN; VACCINE; TETANUS; PROTECTION; RESPONSES; PREGNANCY AB Objective, To study the kinetics of Haemophilus influenzae type b (Hib)-specific antibody in infants born to mothers immunized with an Hib polysaccharide or one of two Hib conjugate vaccines. Study design, Serum antibody to the polyribosylribitol (PRP) moiety of Hib was measured by radioimmunoassay and enzyme-linked immunosorbent assay at birth and at 2 and 6 months of age in infants born to women immunized with Hib polysaccharide or conjugate vaccine (PRP-D and HbOC). A subset of infants greater than or equal to 6 months of age was immunized with Hib conjugate vaccine after licensure of this vaccine for infants, A comparison group of 18 infants born to unimmunized women received the same Hib conjugate vaccine on a similar schedule. Results. Total PRP antibody concentrations were 1.50, 14.4 and 20.4 mu g/ml in 2-month-old infants born to mothers immunized with polysaccharide, PRP-D and HbOC vaccines, respectively, and 2.54, 1.35 and 2.46 mu g/ml in 6-month old infants, Infants born to mothers immunized with polysaccharide vaccine had significantly less PRP antibody at 2 months of age but similar antibody concentrations at 6 months of age, Persistence or increases in total PRP antibody during 6 months were noted in 21 of 47 (44.6%) study infants. A subset of study and comparison infants was immunized with a mean of 2.6 doses of Hib vaccines between 6 months and 2 years of age, and all infants had total PRP antibody concentrations greater than or equal to 0.15 mu g/ml. Conclusion. Conjugate Hib vaccines administered during the last trimester of pregnancy resulted in significantly higher PRP antibody titers in infants at birth and 2 months of age than did polysaccharide vaccine. A subset of infants born to immunized mothers was subsequently immunized with Hib conjugate vaccine and had antibody concentrations similar to those in infants born to nonimmunized women. C1 BAYLOR COLL MED,DEPT IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. RP Englund, JA (reprint author), BAYLOR COLL MED,DEPT MICROBIOL,HOUSTON,TX 77030, USA. FU NIAID NIH HHS [AI-18125, AI-15126, N01 AI-25135] NR 39 TC 24 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD DEC PY 1997 VL 16 IS 12 BP 1122 EP 1130 DI 10.1097/00006454-199712000-00005 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA YL245 UT WOS:A1997YL24500004 PM 9427456 ER PT J AU Pontius, AA AF Pontius, AA TI Spatial representation in face drawing and block design by nine groups from hunter-gatherers to literates SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID SIMILARITY; JUDGMENTS AB A rank-order correlation was performed for nine cultural groups ranging from preliterate hunter-gatherers to literate medium-city dwellers. Two spatial tests of intrapattern spatial relations were used, the Draw-A-Person-With-Face-In-Front test and the Kohs Block Design, a test of constructive praxia. In contrast to traditional ''Western'' evaluations, credit was given for the preservation of the essential intrapattern shapes even when exact spatial relations among these shapes was incorrect. Such ''errors'' were labelled ''neolithic face'' patterns and ''nonrandom errors,'' respectively. Analysis suggested that the neglected intrapattern (in contrast to interobject) spatial relational skills emerge with literacy but is not yet actualized in preliterates whose survival requires quick fight or flight response upon prompt, albeit gross, assessment of salient shapes of prey or predators (human or animals). The positive Spearman rank-order correlation of absent or low literacy skills with the percent of ''neolithic face'' drawings was .95 and with the ''nonrandom'' block designs .67. Suggestions were developed for assessing certain unusual ''ecological'' present situations or certain brain dysfunctions. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT APS,BOSTON,MA 02114. RP Pontius, AA (reprint author), HARVARD UNIV,SCH MED,55 FRUIT ST,BOSTON,MA 02114, USA. NR 26 TC 4 Z9 4 U1 0 U2 1 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD DEC PY 1997 VL 85 IS 3 BP 947 EP 959 PN 1 PG 13 WC Psychology, Experimental SC Psychology GA YJ160 UT WOS:A1997YJ16000030 PM 9399304 ER PT J AU Matthias, P Tashkin, DP MarquesMagallanes, JA Wilkins, JN Simmons, MS AF Matthias, P Tashkin, DP MarquesMagallanes, JA Wilkins, JN Simmons, MS TI Effects of varying marijuana potency on deposition of tar and Delta(9)-THC in the lung during smoking SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE marijuana; Delta(9)-tetrahydrocannabinol (THC); smoking topography; tar yield; tar deposition; lung; carboxyhemoglobin boost; ''high'' ID CIGARETTE; CO AB To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired lever of intoxication (''high'') reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and Delta(9)-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (Delta HR) and ''high'' during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb, boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger Ma preparation. (C) 1997 Elsevier Science Inc. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DIV PULM & CRIT CARE MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,CLIN PSYCHOPHARMACOL UNIT,LOS ANGELES,CA 90073. FU NIDA NIH HHS [R01 DA03018] NR 16 TC 25 Z9 25 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1997 VL 58 IS 4 BP 1145 EP 1150 DI 10.1016/S0091-3057(97)00328-6 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA YH611 UT WOS:A1997YH61100044 PM 9408226 ER PT J AU Moor, ACE Lagerberg, JWN Tijssen, K Foley, S Truscott, TG Kochevar, IE Brand, A Dubbelman, TMAR VanSteveninck, J AF Moor, ACE Lagerberg, JWN Tijssen, K Foley, S Truscott, TG Kochevar, IE Brand, A Dubbelman, TMAR VanSteveninck, J TI In vitro fluence rate effects in photodynamic reactions with AlPcS4 as sensitizer SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ALUMINUM PHTHALOCYANINE DERIVATIVES; MOLECULAR-OXYGEN; THERAPY; BLOOD; PHOTOSENSITIZATION; CELLS; INACTIVATION; DEACTIVATION; MECHANISMS; INVITRO AB It has been shown previously that the efficiency of photodynamic therapy (PDT) both in vivo and in vitro is dependent on fluence rate, In this study, different in vitro experiments showed that tetrasulfonated aluminum phthalocyanine (AlPcS4) is more efficient in photosensitization if the light is delivered at low fluence rate, Erythrocyte damage, virus inactivation and photooxidation of reduced glutathione (GSH) and histidine were all enhanced if light was delivered at 100 W/m(2) as compared to 500 W/m(2). Bleaching did not occur under these conditions, Oxygen depletion, shown to be important in fluence rate effects observed in vivo, does not seem to be involved, On theoretical grounds saturation of the triplet state is not likely under these conditions, A possible explanation for the observed fluence rate effects might be found in different reaction pathways, that are favored under high or low fluence rate illuminations, These reactions might involve uni-or bimolecular reactions of intermediate products, resulting in less efficiency at higher fluence rate, It proves to be important, under all circumstances, to monitor fluence rate, because a change in fluence rate, even with similar total fluences, might influence photobiological results in an unexpected way. C1 Leiden Univ, Dept Mol Cell Biol, Leiden, Netherlands. Leiden Univ Hosp, Dept Immunohaematol, NL-2333 AA Leiden, Netherlands. Leiden Univ Hosp, Blood Bank, NL-2333 AA Leiden, Netherlands. Univ Keele, Dept Chem, Keele ST5 5BG, Staffs, England. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moor, ACE (reprint author), Sylvius Lab, POB 9503, NL-2300 RA Leiden, Netherlands. NR 33 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD DEC PY 1997 VL 66 IS 6 BP 860 EP 865 DI 10.1111/j.1751-1097.1997.tb03238.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YN097 UT WOS:000071132800023 PM 9421972 ER PT J AU Niemierko, A AF Niemierko, A TI Present and future of the clinical use of radiobiological models in radiation therapy treatment planning SO PHYSICA MEDICA LA English DT Article; Proceedings Paper CT V International Conference on Application of Physics in Medicine and Biology (Trieste Medical Physics 96) / IX Congresso AIFB / EFOMP Medical Physics 96 / EUTECH 96 CY SEP 02-06, 1996 CL TRIESTE, ITALY SP Int Ctr Theoret Phys, Ist Nazl Fis Nucl, Univ Studi Trieste, Assoc Italiana Fis Biomed, European Federat Org Med Phys, CNR, Regione Autonoma Friuli Venezia Giulia, Comune Trieste, Provincia Trieste DE modeling; TCP; NTCP ID TUMOR-CONTROL PROBABILITY; NORMAL TISSUE RESPONSES; COMPLICATION PROBABILITY; VOLUME; RADIOTHERAPY; OPTIMIZATION; IRRADIATION; TOLERANCE; ARCHITECTURE AB Recent technological advances in radiation therapy make possible prescribing and delivering very conformal dose distributions which can be individually tailored to a complex patient geometry. To take full advantage of these new developments new treatment planning tools are necessary. In particular, there is a need for new tools for biologically and clinically relevant quantitative evaluation and assessment of three-dimensional dose distributions. This paper presents biological models of tumor and normal tissue response to radiation that have shown strong potential to be effective in modern treatment planning. The models an based on rather general radiobiological principles and are consistent with existing clinical and experimental data. Possible future developments and applications of biological models in radiation therapy are also discussed. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU GIARDINI EDITORI S A LUGANO PI LUGANO PA PIAZZA MONTE CENERI 13,, CH6901 LUGANO, SWITZERLAND SN 1120-1797 J9 PHYS MEDICA JI Phys. Medica PD DEC PY 1997 VL 13 SU 1 BP 34 EP 38 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZT180 UT WOS:000074057200009 ER PT J AU Zhang, H Goodman, HM Jansson, S AF Zhang, H Goodman, HM Jansson, S TI Antisense inhibition of the photosystem I antenna protein Lhca4 in Arabidopsis thaliana SO PLANT PHYSIOLOGY LA English DT Article ID A/B-BINDING-PROTEINS; CAB GENE; CHLOROPHYLL-A; HIGHER-PLANTS; LIGHT; EXPRESSION; TOBACCO; COMPLEXES; PHOTOSYNTHESIS; IDENTIFICATION AB The function of Lhca4, a gene encoding the photosystem I type IV chlorophyll a/b-binding protein complex in Arabidopsis, was investigated using antisense technology. Lhca4 protein was reduced in a number of mutant lines and abolished in one. The inhibition of protein was not correlated with the inhibition of mRNA. No depletion of Lhca1 was observed, but the low-temperature fluorescence emission spectrum was drastically altered in the mutants. The emission maximum was blue-shifted by 6 nm, showing that chlorophyll molecules bound to Lhca4 are responsible for most of the long-wavelength fluorescence emission. Some mutants also showed an unexplainable delay in flowering time and an increase in seed weight. C1 Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Umea Univ, Dept Plant Physiol, S-90187 Umea, Sweden. RP Zhang, H (reprint author), Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. RI Jansson, Stefan/A-1119-2009 OI Jansson, Stefan/0000-0002-7906-6891 NR 37 TC 47 Z9 49 U1 0 U2 4 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 1997 VL 115 IS 4 BP 1525 EP 1531 DI 10.1104/pp.115.4.1525 PG 7 WC Plant Sciences SC Plant Sciences GA YM207 UT WOS:000071040500025 PM 9414561 ER PT J AU RivasVazquez, RA Blais, MA AF RivasVazquez, RA Blais, MA TI Selective serotonin reuptake inhibitors and atypical antidepressants: A review and update for psychologists SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COGNITIVE THERAPY; PERSONALITY-DISORDER; FLUOXETINE TREATMENT; LONG-TERM; IN-VIVO; DEPRESSION; PHARMACOTHERAPY AB Psychologists are increasingly being required to care for patients who are concurrently undergoing pharmacological treatment, particularly when patients suffer from mood disorders, such as major depression. In addition, nonpsychiatric physicians are prescribing antidepressant medications with greater frequency, thereby increasing the likelihood that the physician with which the psychologist must collaborate will have a limited understanding of psychiatric illnesses, As independent mental health professionals, psychologists have a right and a responsibility to be actively engaged in all aspects of their patients' treatment, including pharmacotherapy. A prerequisite for providing this level of professional care is a solid grounding in the principles and actions of pharmacological agents. C1 MASSACHUSETTS GEN HOSP,INPATIENT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. NR 75 TC 6 Z9 6 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD DEC PY 1997 VL 28 IS 6 BP 526 EP 536 DI 10.1037//0735-7028.28.6.526 PG 11 WC Psychology, Multidisciplinary SC Psychology GA YH473 UT WOS:A1997YH47300005 ER PT J AU Miguel, EC Rauch, SL Leckman, JF AF Miguel, EC Rauch, SL Leckman, JF TI Neuropsychiatry of the basal ganglia - Preface SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 USP, Fac Med, Hosp Clin, Inst Psiquiatria, BR-OS430010 Sao Paulo, Brazil. Massachusetts Gen Hosp East, Dept Psychiat, Neuroimaging Res Grp, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. RP Miguel, EC (reprint author), USP, Fac Med, Hosp Clin, Inst Psiquiatria, Rua Ovidio Pires Campos, BR-OS430010 Sao Paulo, Brazil. RI Miguel, Euripedes/B-2871-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1997 VL 20 IS 4 BP XV EP XVI DI 10.1016/S0193-953X(05)70339-7 PG 2 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800001 ER PT J AU Rauch, SL Savage, CR AF Rauch, SL Savage, CR TI Neuroimaging and neuropsychology of the striatum - Bridging basic science and clinical practice SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE IMAGES; POSITRON EMISSION TOMOGRAPHY; MULTIPLE SYSTEM ATROPHY; F-18 DOPA-PET; GANGLIA-THALAMOCORTICAL CIRCUITS; RICHARDSON-OLSZEWSKI SYNDROME; GLUCOSE METABOLIC-RATE; PARKINSONS-DISEASE AB Neuroimaging and neuropsychology are complementary disciplines that provide powerful means for assessing the structure and function of corticostriatal systems. Findings from four model basal ganglia disorders-OCD, TS, HD, and PD-are reviewed. This survey is intended as a vehicle for illustrating the breadth of current clinical and research applications, as well as the potential for future advances. The perspectives brought by neuroimaging and neuropsychology serve as a natural bridge from the basic neuroscience to the clinical practice articles in this issue. C1 Massachusetts Gen Hosp East, Dept Psychiat, Neuroimaging Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp East, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rauch, SL (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, Neuroimaging Res Grp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU PHS HHS [01230, 1215] NR 193 TC 73 Z9 76 U1 15 U2 15 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 1997 VL 20 IS 4 BP 741 EP + DI 10.1016/S0193-953X(05)70343-9 PG 29 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800005 PM 9443348 ER PT J AU Miguel, EC Rauch, SL Jenike, MA AF Miguel, EC Rauch, SL Jenike, MA TI Obsessive-compulsive disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID GLUCOSE METABOLIC RATES; LA-TOURETTES SYNDROME; POSITRON EMISSION TOMOGRAPHY; CHRONIC TIC DISORDER; TERM FOLLOW-UP; SYMPTOM PROVOCATION; CAUDATE-NUCLEUS; BASAL GANGLIA; CLOMIPRAMINE TREATMENT; PERSONALITY-DISORDERS AB Obsessive-compulsive disorder (OCD), the fourth most common psychiatric disorder, is a chronic and heterogeneous condition characterized by sudden, recurrent upsetting cognitions that intrude into consciousness (obsessions), and rule-governed acts that the person feels driven to perform (compulsions). C1 USP, Fac Med, Hosp Clin, Inst Psiquiatria,Dept Psychiat, BR-05403010 Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Miguel, EC (reprint author), USP, Fac Med, Hosp Clin, Inst Psiquiatria,Dept Psychiat, Rua Ovidio Pires Campos S-N, BR-05403010 Sao Paulo, Brazil. RI Miguel, Euripedes/B-2871-2008 FU NIMH NIH HHS [MH01215] NR 153 TC 32 Z9 33 U1 13 U2 16 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 1997 VL 20 IS 4 BP 863 EP + DI 10.1016/S0193-953X(05)70349-X PG 22 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800011 PM 9443354 ER PT J AU Savage, CR AF Savage, CR TI Neuropsychology of subcortical dementias SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID PROGRESSIVE SUPRANUCLEAR PALSY; EARLY PARKINSONS-DISEASE; POSITRON EMISSION TOMOGRAPHY; MULTIPLE SYSTEM ATROPHY; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; EXPLICIT MEMORY; VISUOSPATIAL MEMORY; COGNITIVE DEFICITS; PREFRONTAL CORTEX AB Subcortical dementias are a heterogeneous group of disorders that share primary pathology in subcortical structures and a characteristic pattern of neuropsychological impairment. This article describes the neurobiological and cognitive features of three prototypical subcortical dementias, Parkinson's disease, Huntington's disease, and progressive supranuclear palsy, concentrating of traits shared by disorders. Clinical features are also discussed, especially those which differentiate subcortical dementias from cortical dementias, such as Alzheimer's disease. The cortical-subcortical nomenclature has been criticized over the years, but it continues to provide an effective means of classifying dementia profiles in clinically and theoretically useful ways. C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, 149-9102,Bldg 149,13th St, Charlestown, MA 02129 USA. FU PHS HHS [1230] NR 127 TC 40 Z9 41 U1 2 U2 5 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 1997 VL 20 IS 4 BP 911 EP + DI 10.1016/S0193-953X(05)70352-X PG 22 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800014 PM 9443357 ER PT J AU Marino, R Cosgrove, GR AF Marino, R Cosgrove, GR TI Neurosurgical treatment of neuropsychiatric illness SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER AB Neurosurgical treatment of neuropsychiatric illness has evolved considerably since its inception in 1935. The most common psychiatric indications for the procedure, including obsessive-compulsive disorder and major depression, are conceptualized as disorders involving the basal ganglia and Limbic system. In this article, the various operations and their contemporary applications are discussed. Neurosurgical treatment represents a viable option in appropriate candidates suffering from severe and otherwise treatment-refractory neuropsychiatric diseases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Univ Sao Paulo, Sch Med, Dept Neurol & Neurosurg, Sao Paulo, Brazil. RP Cosgrove, GR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, 15 Parkman St, Boston, MA 02114 USA. NR 35 TC 20 Z9 20 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1997 VL 20 IS 4 BP 933 EP + DI 10.1016/S0193-953X(05)70353-1 PG 12 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800015 PM 9443358 ER PT J AU Garcia-Cairasco, N Miguel, EC Rauch, SL Leckman, JF AF Garcia-Cairasco, N Miguel, EC Rauch, SL Leckman, JF TI Current controversies and future directions in basal ganglia research - Integrating basic neuroscience and clinical investigation SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID PRIMATE SUBTHALAMIC NUCLEUS; OBSESSIVE-COMPULSIVE DISORDER; TEMPORAL-LOBE ONSET; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NEURONAL-ACTIVITY; AUDIOGENIC-SEIZURES; WISTAR RATS; MPTP MODEL; IRON AB This article discusses current controversies and future directions in basal ganglia research, detailing behavioral aspects, anatomic models, neurochemistry, pharmacology, and diagnostic methods as well as surgical techniques. A neuroethologic perspective is highlighted. Furthermore, the relevant literature pertaining to contemporary molecular approaches such as brain microinjections of embryonic or genetically modified cells, for therapeutic purposes and the use of transgenic and knockout animals. C1 Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Physiol, Neurophysiol & Expt Neuroethol Lab, BR-14049900 Ribeirao Preto, Brazil. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Hosp Clin, Inst Psychiat, Sao Paulo, Brazil. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT USA. Yale Univ, Sch Med, Childrens Clin Res Ctr, New Haven, CT USA. RP Garcia-Cairasco, N (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Physiol, Neurophysiol & Expt Neuroethol Lab, BR-14049900 Ribeirao Preto, Brazil. RI Miguel, Euripedes/B-2871-2008 FU NIMH NIH HHS [MH01215, MH49351, MH44843] NR 110 TC 2 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1997 VL 20 IS 4 BP 945 EP + DI 10.1016/S0193-953X(05)70354-3 PG 20 WC Psychiatry SC Psychiatry GA YN520 UT WOS:000071176800016 PM 9443359 ER PT J AU Weiden, P Glazer, W AF Weiden, P Glazer, W TI Assessment and treatment selection for ''revolving door'' inpatients with schizophrenia SO PSYCHIATRIC QUARTERLY LA English DT Article; Proceedings Paper CT 9th Annual New-York-State-Office-of-Mental-Health-Research-Conference CY DEC, 1996 CL ALBANY, NY SP NY State Off Mental Hlth Res ID THERAPY AB Goals: The goals of this study are 1) to determine causes and patterns of relapse for a cohort of ''revolving door'' schizophrenia inpatients, and 2) to assess the feasibility of starting a new psychopharmacologic intervention before discharge, either depot therapy or an atypical antipsychotic. Methods: Consecutive admissions to an acute inpatient unit in New York City were screened for ''revolving door'' criteria. Patients had to have a primary diagnosis of schizophrenia or schizoaffective disorder and have either I) two hospitalizations in the last year, or 2) three hospitalizations in the last three years. Patients were then assessed for probable causes of relapse for the index and prior two hospitalizations. Treatment selection, based on this information, was trichotomized to: 1) oral conventional antipsychotic, 2) depot conventional antipsychotic (either haloperidol or fluphenazine decanoate), or 3) atypical antipsychotic (either risperidone or clozapine). Results: Sixty-three out of 131 screened admissions met the above revolving door criteria. They were indeed ''revolving'', having an average of 1.3 hospitalizations per year over the last 3 years and were only out of the hospital for five months (median) before index admission. The treatment selection process was hampered by lack of information about events leading to relapse, and by the lack of outpatient participation in the medication selection process. Of the 50 patients with complete histories about precipitants for the index episode, the most common reason for rehospitalization was judged to be medication noncompliance (n = 25; 50%), followed by medication nonresponse (n = 13; 26%). Not surprisingly, medication recommendations were closely linked to the assessed reason for relapse (depot therapy [n = 27; 49%] with medication non-compliance; atypical antipsychotic [n = 20; 37%] with medication nonresponse [X-2 = 26.9, p<.001]). These two recommendations were implemented before discharge for about one-half of the cases. Patient refusal was a relatively greater problem for depot recommendation while constraints in the outpatient environment were more problematic for patients recommended for atypical antipsychotics. Conclusions: Medication noncompliance and medication nonresponse, in that order, were judged to be the most common causes of relapse for ''revolving door'' inpatients. Both depot therapy and atypical antipsychotics were commonly recommended and ultimately accepted by about 2/3rds of patients. Choice between depot and atypical was driven by the assessed cause of relapse. In summary, it seems possible to identify ''revolving door'' inpatients, and to target specific medication interventions within the time frame of an acute inpatient admission. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Weiden, P (reprint author), ST LUKES ROOSEVELT HOSP,NEUROBIOL DISORDER SERV,411 W 114TH ST,NEW YORK,NY 10025, USA. NR 18 TC 77 Z9 79 U1 0 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0033-2720 J9 PSYCHIAT QUART JI Psychiatr. Q. PD WIN PY 1997 VL 68 IS 4 BP 377 EP 392 DI 10.1023/A:1025499131905 PG 16 WC Psychiatry SC Psychiatry GA YC029 UT WOS:A1997YC02900006 PM 9355136 ER PT J AU Toomey, R Wallace, CJ Corrigan, PW Schuldberg, D Green, MF AF Toomey, R Wallace, CJ Corrigan, PW Schuldberg, D Green, MF TI Social processing correlates of nonverbal social perception in schizophrenia SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID AFFECTIVE-DISORDERS; RECOGNITION; EMOTION; JUDGMENT; ISSUES; SKILLS AB THIS study examines the relationship of nonverbal social perception to other areas of social functioning in schizophrenia, One model of interpersonal problem-solving skills presents a sequence of receiving, processing, and sending skills, Social perception skills best fit the first stage in this model: receiving skills, As expected, schizophrenic subjects (N = 29) were less skillful than normal subjects (N = 15) on measures of social problem solving, understanding of social sequences, and social judgment, In addition, performance on these tasks was significantly related to nonverbal social perception, but only for the schizophrenic group. Thus, deficits in nonverbal social perception are related to other measures of social functioning in schizophrenia. Implications of these findings for understanding and treating social deficits in schizophrenia are discussed. C1 HMS Brockton VAMC, Dept Psychiat 116A, Belmont, MA 02401 USA. Harvard Univ, Massachusetts Mental Hlth Ctr, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Chicago, Ctr Psychiat Rehabil, Chicago, IL 60637 USA. Univ Montana, Missoula, MT 59812 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Toomey, R (reprint author), HMS Brockton VAMC, Dept Psychiat 116A, 940 Belmont St, Belmont, MA 02401 USA. NR 31 TC 29 Z9 31 U1 0 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 1997 VL 60 IS 4 BP 292 EP 300 PG 9 WC Psychiatry SC Psychiatry GA YT249 UT WOS:000071580800003 PM 9460098 ER PT J AU Manevich, Y Held, KD Biaglow, JE AF Manevich, Y Held, KD Biaglow, JE TI Coumarin-3-carboxylic acid as a detector for hydroxyl radicals generated chemically and by gamma radiation SO RADIATION RESEARCH LA English DT Article ID SUPEROXIDE; COUMARIN; PROTEINS; PEROXIDE; DAMAGE; PROBE; DNA AB Coumarin-3-carboxylic acid (3-CCA) was used as a detector for hydroxyl radicals ((OH)-O-.) in aqueous solution. The (OH)-O-. was generated by gamma irradiation or chemically by the Cu2+-mediated oxidation of ascorbic acid (ASC). The excitation and emission spectra of 3-CCA, hydroxylated either chemically or by gamma irradiation, were nearly identical to those of an authentic 7-hydroxycoumarin-3-carboxylic acid (7-OHCCA). The pH-titration curves for the fluorescence at 450 nm (excitation at 395 nm) of 3-CCA, hydroxylated either chemically or by gamma radiation, were also identical to those of authentic 7-OHCCA (pK = 7.4). Time-resolved measurements of the fluorescence decays of radiation- or chemically hydroxylated 3-CCA, as well as those of 7-OHCCA, indicate a monoexponential fit. The fluorescence lifetime for the product of 3-CCA hydroxylation was identical to that of 7-OHCCA (similar to 4 ns). These data, together with analysis of end products by high-performance liquid chromatography, show that the major fluorescent product formed by radiation-induced or chemical hydroxylation of 3-CCA is 7-OHCCA. Fluorescence detection of 3-CCA hydroxylation allows real-time measurement of the kinetics of (OH)-O-. generation. The kinetics of 3-CCA hydroxylation by gamma radiation is linear, although the kinetics of 3-CCA hydroxylation by the Cu2+-ASC reaction shows a sigmoid shape. The initial (slow) step of 3-CCA hydroxylation is sensitive to Cu2+, but the steeper (fast) step is sensitive to ASC. Analysis of the kinetics of 3-CCA hydroxylation shows a diffusion-controlled reaction with a rate constant 5.0 +/- 1.0 X 10(9) M-1 s(-1). The scavenging of (OH)-O-. by 3-CCA was similar to 14% for chemical generation with Cu2+-ASC and similar to 50% for gamma-radiation-produced . OH. The yield of 7-OHCCA under the same radiation conditions was similar to 4.4% and increased linearly with radiation dose. The 3-CCA method of detection of (OH)-O-. is quantitative, sensitive, specific and therefore accurate. It has an excellent potential for use in biological systems. (C) 1997 by Radiation Research Society. C1 UNIV PENN, SCH MED, DEPT RADIAT ONCOL, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT BIOCHEM & BIOPHYS, PHILADELPHIA, PA 19104 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. FU NCI NIH HHS [CA44982, CA63997] NR 37 TC 89 Z9 92 U1 10 U2 57 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1997 VL 148 IS 6 BP 580 EP 591 DI 10.2307/3579734 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA YK074 UT WOS:A1997YK07400007 PM 9399704 ER PT J AU Hulka, CA Edmister, WB Smith, BL Tan, LJ Sgroi, DC Campbell, T Kopans, DB Weisskoff, RM AF Hulka, CA Edmister, WB Smith, BL Tan, LJ Sgroi, DC Campbell, T Kopans, DB Weisskoff, RM TI Dynamic echo-planar imaging of the breast: Experience in diagnosing breast carcinoma and correlation with tumor angiogenesis SO RADIOLOGY LA English DT Article DE breast neoplasms, diagnosis; breast neoplasms, MR; gadolinium; magnetic resonance (MR), contrast enhancement; neoplasms, blood supply ID RADIOLOGIC-PATHOLOGICAL CORRELATION; GD-DTPA; GADOLINIUM-DTPA; CONTRAST; LESIONS; ENHANCEMENT; TISSUE AB PURPOSE: To correlate quantitative echo-planar magnetic resonance (MR) imaging measures of gadopentetate dimeglumine tumor uptake with histologic diagnoses and microvessel density (MVD) and to compare dynamic echo-planar imaging of breast lesions with conventional dynamic MR imaging techniques. MATERIALS AND METHODS: The study group comprised 63 patients (aged 13-70 years) with 71 breast lesions who underwent conventional and echo-planar MR imaging. The T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with the echo-planar imaging data and were correlated with histologic findings and MVD estimates. Extraction-now product data normalized to pectoral muscle gadopentetate dimeglumine concentration in invasive cancers was also correlated with MVD. RESULTS: On average, cancer T1 values were shorter than benign values, but there was substantial overlap between the two groups. Cancers had higher extraction-flow products than benign lesions (P < .001). Sensitivity, specificity, positive predictive value, and negative predictive value were 83%, 79%, 67%, and 90%, respectively. Receiver operating characteristic analysis showed improved performance with extraction-flow products than with percentages of signal intensity change. Among the invasive cancers, there was no significant correlation between extraction-flow product and MVD. CONCLUSION: The T1 value remains important in more precise quantitative estimation of gadopentetate dimeglumine uptake in breast tumors, which helps improve the specificity of dynamic imaging. Tumor MVD affects the contrast medium enhancement of breast lesions, but other factors contribute. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP Hulka, CA (reprint author), BETH ISRAEL DEACONESS MED CTR,DEPT RADIOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [R01CA 66072] NR 30 TC 126 Z9 134 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1997 VL 205 IS 3 BP 837 EP 842 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YG850 UT WOS:A1997YG85000035 PM 9393545 ER PT J AU Stone, ME AF Stone, ME TI Gay & lesbian biography. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD WIN PY 1997 VL 37 IS 2 BP 220 EP 220 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA ZT090 UT WOS:000074047400028 ER PT J AU Vaisanen, ML Matto, J Salminen, K Jousimies-Somer, H AF Vaisanen, ML Matto, J Salminen, K Jousimies-Somer, H TI In vitro activity of trovafloxacin against anaerobic bacteria SO REVIEWS IN MEDICAL MICROBIOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium of the Society-for-Anaerobic-Microbiology CY JUL 09-11, 1997 CL CHURCHILL COLL CAMBRIDGE, CAMBRIDGE, ENGLAND SP Soc Anaerob Microbiol HO CHURCHILL COLL CAMBRIDGE DE antimicrobial activity; trovafloxacin; azithromycin; cefoxitin; metronidazole; anaerobe C1 Natl Publ Hlth Inst, Helsinki, Finland. Univ Helsinki, Inst Dent, FIN-00014 Helsinki, Finland. Pfizer Finland, Espoo, Finland. RP Vaisanen, ML (reprint author), W Los Angeles Vet Affairs Med Ctr, Wadsworth Anaerob Bacteriol Lab, 11301 Wilshire Blvd,Mail Code 113J,Bldg 500,Room, Los Angeles, CA 90073 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0954-139X J9 REV MED MICROBIOL JI Rev. Med. Microbiol. PD DEC PY 1997 VL 8 SU 1 BP S81 EP S83 PG 3 WC Microbiology SC Microbiology GA YU761 UT WOS:000071751600045 ER PT J AU De Sanctis, JT Mueller, PR AF De Sanctis, JT Mueller, PR TI Thoracic interventions: The role of ultrasound guidance for diagnostic and therapeutic procedures SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE ultrasound (US) guidance; lung; biopsy; mediastinum; biopsy; empyema; intrapleural fibrinolysis; sclerotherapy ID MALIGNANT PLEURAL EFFUSIONS; GUIDED ASPIRATION BIOPSY; COMPLICATED PARAPNEUMONIC EFFUSIONS; PERIPHERAL PULMONARY MASSES; REAL-TIME SONOGRAPHY; INTRAPLEURAL STREPTOKINASE; MEDIASTINAL MASSES; NEEDLE-BIOPSY; INTRACAVITARY BLEOMYCIN; CORYNEBACTERIUM-PARVUM AB In recent years, ultrasound has assumed a major role in imaging-guided percutaneous thoracic interventions. Ultrasound guidance for thoracic interventions began as an application of techniques in the thorax that had been developed originally for abdominal biopsies and drainages. Advances in ultrasound technology and the development of techniques and catheters specifically designed for use in the thorax have contributed to the increasing use of ultrasound guidance for thoracic interventions. Once used most often when other guided or unguided interventions had failed or were not feasible, ultrasound has become the preferred method of guidance for many thoracic procedures. This review will update the current application of ultrasound guidance for diagnostic and therapeutic percutaneous thoracic interventions, including biopsies of the lung, mediastinum, and pleura as well as diagnostic aspiration and therapeutic drainage of pleural collections. Pleurodesis for malignant effusions and fibrinolytic therapy for empyema and hemothorax also will be considered. Technique, success rate, and complications will be discussed. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP De Sanctis, JT (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 220, Boston, MA 02114 USA. NR 110 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD DEC PY 1997 VL 14 IS 4 BP 429 EP 448 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RR UT WOS:000078938500009 ER PT J AU Loeffler, JS Smith, AR Suit, HD AF Loeffler, JS Smith, AR Suit, HD TI The potential role of proton beams in radiation oncology SO SEMINARS IN ONCOLOGY LA English DT Review ID RADIOTHERAPY; IRRADIATION; THERAPY C1 Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 12 TC 39 Z9 40 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1997 VL 24 IS 6 BP 686 EP 695 PG 10 WC Oncology SC Oncology GA YP504 UT WOS:000071284300012 PM 9422264 ER PT J AU Corn, BW Curran, WJ Shrieve, DC Loeffler, JS AF Corn, BW Curran, WJ Shrieve, DC Loeffler, JS TI Stereotactic radiosurgery and radiotherapy: New developments and new directions SO SEMINARS IN ONCOLOGY LA English DT Review ID RADIATION-THERAPY; BRAIN METASTASIS; PHASE-I; SINGLE; EXPERIENCE; EFFICACY; GLIOMAS; SURGERY; SYSTEM C1 Thomas Jefferson Univ Hosp, Jefferson Med Coll, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Harvard Univ, Joint Ctr Radiat Therapy, Dept Radiat Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Corn, BW (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Radiat Oncol, Bodine Ctr Canc Treatment, 111 S 11th St, Philadelphia, PA 19107 USA. NR 34 TC 15 Z9 15 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 1997 VL 24 IS 6 BP 707 EP 714 PG 8 WC Oncology SC Oncology GA YP504 UT WOS:000071284300014 PM 9422266 ER PT J AU Gunderson, LL Willett, CG Harrison, LB Petersen, IA Haddock, MG AF Gunderson, LL Willett, CG Harrison, LB Petersen, IA Haddock, MG TI Intraoperative irradiation: Current and future status SO SEMINARS IN ONCOLOGY LA English DT Review ID EXTERNAL-BEAM IRRADIATION; RECURRENT COLORECTAL-CANCER; LARGE ANIMAL-MODEL; RADIATION-THERAPY; RECTOSIGMOID CARCINOMA; PANCREATIC-CARCINOMA; SURGICAL RESECTION; CERVICAL-CANCER; BLADDER-TUMORS; BILE-DUCT C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Oncol, Rochester, MN 55905 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Med, Boston, MA USA. Beth Israel Hlth Care Syst, Dept Radiat Oncol, New York, NY USA. RP Gunderson, LL (reprint author), Mayo Clin & Mayo Fdn, Desk R,200 1st St SW, Rochester, MN 55905 USA. NR 71 TC 18 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1997 VL 24 IS 6 BP 715 EP 731 PG 17 WC Oncology SC Oncology GA YP504 UT WOS:000071284300015 PM 9422267 ER PT J AU Levine, SM Marianacci, EB Kattapuram, SV AF Levine, SM Marianacci, EB Kattapuram, SV TI Tuberculosis of contralateral costo-transverse joints SO SKELETAL RADIOLOGY LA English DT Article DE tuberculosis; costotransverse; multifocal AB We present a case of multifocal tuberculosis of contralateral costo-transverse joints. Even in countries where tuberculosis is common, extrapulmonary multifocal infection is uncommon. Furthermore, a bilateral, symmetric distribution is distinctly unusual. The index of suspicion for tuberculosis should increase when the patient is from a country where tuberculosis is endemic or when a history of AIDS is present. C1 Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. Massachusetts Gen Hosp, Dept Bone & Joint Imaging, Boston, MA 02114 USA. Suburban Radiol Associates, Lexington, MA USA. RP Levine, SM (reprint author), Rhode Isl Hosp, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 1997 VL 26 IS 12 BP 741 EP 743 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA YM681 UT WOS:000071089100011 PM 9453111 ER PT J AU Asch, DA Shea, JA Jedrziewski, MK Bosk, CL AF Asch, DA Shea, JA Jedrziewski, MK Bosk, CL TI The limits of suffering: Critical care nurses' views of hospital care at the end of life SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE euthanasia; life-support; critical care nursing ID PHYSICIAN-ASSISTED SUICIDE; SUSTAINING TREATMENTS; VOLUNTARY EUTHANASIA; WASHINGTON-STATE; DECISION-MAKING; ATTITUDES; WITHDRAW; SUPPORT; ONCOLOGISTS; REQUESTS AB This study explores critical care nurses' beliefs, motivations, and experiences regarding end of life care. We performed a content analysis of the text comments provided by 468 U.S. critical care nurses in response to an anonymous mail survey about euthanasia. These comments reveal that these U.S. critical care nurses' feelings about issues surrounding the end of life are extremely complex. Eight themes emerged from 37 coded concepts, and the median number of themes volunteered per nurse was three. Among the most prevalent themes were patient concerns (53%), family concerns (33%), clinical circumstances (42%), the nurses' personal concerns (38%), and external or structural issues (68%). A profound sense of compassion and often conflicting forces were noted within and across themes. The nurses' comments offer a unique perspective on the care of critically ill patients and reveal much about that care that should be improved. In particular, (1) some nurses are frustrated about their limited role in the management of patients at the end of life, given their special understanding of these patients' experiences and wishes; (2) considerable confusion remains about the most appropriate way to care for these patients; and (3) the environment of some critical care settings may be unable to foster the compassion that many patients need. (C) 1997 Elsevier Science Ltd. C1 Univ Penn, Sch Med, Div Gen Internal Med, Ralston Penn Ctr 317, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, Ralston Penn Ctr 317, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 41 TC 51 Z9 52 U1 4 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 1997 VL 45 IS 11 BP 1661 EP 1668 DI 10.1016/S0277-9536(97)00125-1 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA YM110 UT WOS:000071029500007 PM 9428086 ER PT J AU Margolis, ML Montoya, FJ Palma, WR AF Margolis, ML Montoya, FJ Palma, WR TI Pulmonary function tests: Comparison of 95th percentile-based and conventional criteria of normality SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID VALUES AB Background. Although 95th percentile-based normal limits are recommended instead of conventional criteria of normality to guide pulmonary function test (PFT) readings, we have found no objective assessment of how the choice of normal limits mig]lt influence PFT interpretation. Methods. We did a retrospective comparison of PFT leadings referenced to conventional criteria of normality versus independent repeat assessments influenced by 95th percentile-based normal limits in 166 veterans. We also conducted a nationwide telephone survey of VA Hospital PFT laboratories. Results. Discordant readings occurred in only 7.2% of 616 individual PFTs; however, these discrepancies could potentially influence at least one component of the PFT report of 26.5% of our subjects. The 95th percentile-based normal limits were used by only 40% of VA PFT laboratories, without relationship to geography or hospital size. Conclusions. Discrepancies between 95th percentile-based and conventional normal limits can potentially influence PFT readings, and 95th percentile-based criteria are not used in the majority of VA PFT laboratories. C1 MED COLL PENN & HAHNEMANN UNIV,DEPT MED,PHILADELPHIA,PA. ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA. RP Margolis, ML (reprint author), PHILADELPHIA VET AFFAIRS MED CTR,PULM SECT,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD DEC PY 1997 VL 90 IS 12 BP 1187 EP 1191 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YL069 UT WOS:A1997YL06900005 PM 9404903 ER PT J AU Ferrucci, L Guralnik, JM Pahor, M Harris, T Corti, MC Hyman, BT Wallace, RB Havlik, RJ AF Ferrucci, L Guralnik, JM Pahor, M Harris, T Corti, MC Hyman, BT Wallace, RB Havlik, RJ TI Apolipoprotein E epsilon 2 allele and risk of stroke in the older population SO STROKE LA English DT Article DE aging; apolipoproteins; risk factors; stroke ID CORONARY HEART-DISEASE; ONSET ALZHEIMERS-DISEASE; E POLYMORPHISM; EUROPEAN POPULATIONS; LIPOPROTEIN-LIPASE; VASCULAR DEMENTIA; ARTERY DISEASE; E GENE; MEN; CHOLESTEROL AB Background and Purpose There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an epsilon 4 allele and lower in those carrying an epsilon 2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. Methods At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged greater than or equal to 71 years and free of stroke were genotyped for apo E Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. Results One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group, Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged greater than or equal to 80 years had even higher risks of stroke but without any difference according to presence/absence of epsilon 2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages greater than or equal to 80 years (94 events). Conclusions The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range. C1 I FRATICINI NATL RES INST,DEPT GERIATR,INRCA,FLORENCE,ITALY. UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP Ferrucci, L (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,NIH,7201 WISCONSIN AVE,GATEWAY BLDG,SUITE 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0 TO 2105] NR 53 TC 44 Z9 45 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1997 VL 28 IS 12 BP 2410 EP 2416 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YL157 UT WOS:A1997YL15700013 PM 9412623 ER PT J AU Cramer, SC Nelles, G Benson, RR Kaplan, JD Parker, RA Kwong, KK Kennedy, DN Finklestein, SP Rosen, BR AF Cramer, SC Nelles, G Benson, RR Kaplan, JD Parker, RA Kwong, KK Kennedy, DN Finklestein, SP Rosen, BR TI A functional MRI study of subjects recovered from hemiparetic stroke SO STROKE LA English DT Article DE stroke outcome; magnetic resonance imaging; motor activity ID CORTICAL MOTOR AREAS; MAGNETIC-RESONANCE; HUMAN BRAIN; FINGER MOVEMENTS; HAND MOVEMENTS; CORTEX; REORGANIZATION; INFARCTION; ACTIVATION; HANDEDNESS AB Background and Purpose Stroke recovery mechanisms remain incompletely understood, particularly for subjects with cortical stroke, in whom limited data are available. We used functional magnetic resonance imaging to compare brain activations in normal controls and subjects who recovered from hemiparetic stroke. Methods Functional magnetic resonance imaging was performed in ten stroke subjects with good recovery, five with deep, and five with cortical infarcts. Brain activation was achieved by index finger-tappine. Statistical parametric activation maps were obtained using a t lest and a threshold of P<.001. In five bilateral motor regions, the volume of activated brain for each stroke subject was compared with the distribution of activation volumes among nine controls. Results Control subjects activated several motor regions. During recovered hand finger-tapping, stroke subjects activated the same regions as controls, often in a larger brain volume. In the unaffected hemisphere, sensorimotor cortex activation was increased in six of nine stroke subjects compared with controls. Cerebellar hemisphere contralateral and premotor cortex ipsilateral to this region, as a ell as supplementary motor areas, also had increased activation In the stroke hemisphere, activation exceeding controls was uncommon, except that three of five cortical strokes showed peri-infarct activation foci. During unaffected hand finger-tapping, increased activation by stroke subjects compared with controls was uncommon; however, decreased activation was seen in unaffected sensorimotor cortex, suggesting that this region's responsiveness increased to the ipsilateral hand and decreased to contralateral hand movements. Use of a different threshold for defining activation (P<.01) did not change the overall findings (K=.75). Conclusions Recovered finger-tapping by stroke subjects activated the same motor regions as controls but to a larger extent, particularly in the unaffected hemisphere. Increased reliance on these motor areas may represent an important component of motor recovery. Functional magnetic resonance imaging studies of subjects who recovered from stroke provide evidence for several processes that may be related to restoration of neurologic function. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEURORECOVERY PROGRAM,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,NMR CTR,BOSTON,MA. HARVARD UNIV,BETH ISRAEL DEACONESS MED CTR,SCH MED,BIOMETR CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MORPHOMETR ANAL,CHARLESTOWN,MA. HARVARD UNIV,SPAULDING REHABIL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP Cramer, SC (reprint author), VET ADM MED CTR,DEPT NEUROL 127,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. RI Kennedy, David/H-3627-2012 NR 71 TC 613 Z9 648 U1 3 U2 15 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1997 VL 28 IS 12 BP 2518 EP 2527 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YL157 UT WOS:A1997YL15700033 PM 9412643 ER PT J AU Coger, R Toner, M Moghe, P Ezzell, RM Yarmush, ML AF Coger, R Toner, M Moghe, P Ezzell, RM Yarmush, ML TI Hepatocyte aggregation and reorganization of EHS matrix gel SO TISSUE ENGINEERING LA English DT Article ID RAT-LIVER CELLS; EXTRACELLULAR-MATRIX; SANDWICH CONFIGURATION; EPITHELIAL-CELLS; IN-VITRO; INVITRO; DIFFERENTIATION; SUBSTRATA; CULTURE; MICROFILAMENTS AB The nature of the extracellular matrix profoundly influences the morphology and function of epithelial cells, such as hepatocytes, in tissue culture. For Engelbroth-Holm-Swarm (EHS) sarcoma-derived gels (e.g., Matrigel), rat hepatocytes exhibit limited spreading, and within 1-2 days they form spheroidal aggregates that progressively enlarge in culture. Using time-lapse video microscopy and object-tracking analysis, we found that hepatocyte aggregation correlates directly with EHS matrix reorganization. Reorganization refers to the displacement of regions of the EHS matrix substrate through the activity of the cells. Our results indicate that both aggregates and isolated hepatocytes were able to create "zones of influence" within which they effectively reorganized their EHS matrix environment. Matrix reorganization and hepatocyte movement were significantly reduced either by altering the deformability of the matrix (via chemical cross-linking) with gluteraldehyde or by disrupting the actin cytoskeleton with cytochalasin D. C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 32 TC 18 Z9 19 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD WIN PY 1997 VL 3 IS 4 BP 375 EP 390 DI 10.1089/ten.1997.3.375 PG 16 WC Cell & Tissue Engineering SC Cell Biology GA YR133 UT WOS:000071463400006 ER PT J AU Yamaguchi, K Matulka, RA Shneider, AM Toselli, P Trombino, AF Yang, S Hafer, LJ Mann, KK Tao, XJ Tilly, JL Near, RI Sherr, DH AF Yamaguchi, K Matulka, RA Shneider, AM Toselli, P Trombino, AF Yang, S Hafer, LJ Mann, KK Tao, XJ Tilly, JL Near, RI Sherr, DH TI Induction of PreB cell apoptosis by 7,12-dimethylbenz[a]anthracene in long-term primary murine bone marrow cultures SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; HUMORAL IMMUNE-RESPONSE; AH-RECEPTOR; ALPHA-NAPHTHOFLAVONE; DBA/2 MICE; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; INDUCED SUPPRESSION; MOUSE SPLENOCYTES; ENZYME-INDUCTION; IMMUNOSUPPRESSION AB Numerous studies demonstrate that polycyclic aromatic hydrocarbons (PAH) suppress immunity by modifying the function of both B and T cells. Relatively few studies have assessed the effects of these common environmental chemicals on immature lymphocytes. In the present study, long-term primary bone marrow cultures were employed to investigate the effects of a prototypic PAH and aryl hydrocarbon receptor (AhR) agonist, 7, 12-dimethylbenz[a]anthracene (DMBA), on immature B lymphocytes. In this system, immature preB cells are maintained in a supportive microenvironment provided by bone marrow stromal cells. Results presented here demonstrate that (1) exposure of primary bone marrow cultures to DMBA results in preB cell death ty apoptosis; (2) notably low doses of DMBA (greater than or equal to 10(-8) M) induce preB cell apoptosis; (3) in long-term cultures, bone marrow stromal cells, but not preB cells, express AhR mRNA and protein as determined by in situ hybridization, RT-PCR, and immunoblotting; (4) freshly isolated unfractionated bone marrow cells, but not purified bone marrow B cells, express AhR protein as assessed by immunohistochemistry; (5) alpha-naphthoflavone, a competitive AhR inhibitor and cytochrome P450 antagonist, completely blocks DMBA-induced preB cell apoptosis in primary bone marrow cultures; and (6) DMBA or benzo[a]pyrene injection in vivo results in bone marrow cell apoptosis consistent with the death of hematopoietic cells clustered around stromal elements. The results implicate programmed cell death as a mechanism underlying DMBA-mediated immunosuppression and suggest that preB cell death is influenced by local interactions with AhR(+) bone marrow stromal cells. (C) 1997 Academic Press. C1 Boston Univ, Sch Med, Dept Environm Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02118 USA. RP Yamaguchi, K (reprint author), Boston Univ, Sch Med, Dept Environm Med, Boston, MA 02118 USA. FU NIEHS NIH HHS [R01-ES06086] NR 56 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC PY 1997 VL 147 IS 2 BP 190 EP 203 DI 10.1006/taap.1997.8263 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA YR553 UT WOS:000071506800004 PM 9439715 ER PT J AU Niklason, LE Langer, RS AF Niklason, LE Langer, RS TI Advances in tissue engineering of blood vessels and other tissues SO TRANSPLANT IMMUNOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on the Etiology and Pathobiology of Transplant Vascular Sclerosis CY MAR 05-09, 1997 CL BERMUDA ID BIODEGRADABLE POLYMER SCAFFOLDS; CARDIAC ALLOGRAFT VASCULOPATHY; SEEDED VASCULAR GRAFTS; SMOOTH-MUSCLE CELLS; MODEL; TRANSPLANTATION; PATHOGENESIS; FABRICATION; COPOLYMERS; ADHESION AB Tissue engineering is a new and rapidly expanding field, in which techniques are being developed for culturing a variety of tissues both in vitro and in vivo using polymer 'scaffolds' to support tissue growth. Polymer scaffolds used in tissue engineering are generally biodegradable, often involving compounds which are already approved for human implantation. In some cases, these polymers may be chemically modified to exhibit selective cell adhesion properties, which enhance cell attachment and subsequent tissue growth. Many cell types have been successfully cultured on these scaffolds, including smooth muscle cells, endothelial cells, hepatocytes and chondrocytes. Tissue engineering holds the potential for the in vitro development of autologous or allogeneic transplantable vascular conduits. Each year in the USA, there are approximately 1.4 million procedures performed which require arterial prostheses. Most of these procedures are in small calibre (<6 mm) vessels, for which synthetic graft materials are not generally suitable. While autologous venous or arterial vessels are gener ally used, not all patients possess adequate conduit for revascularization. Tubular scaffolds have been specially designed for culturing small calibre arteries in vitro. Bovine aortic vascular cells were seeded and cultured on these polymer scaffolds, and grown under conditions of pulsatile pressure and intra-luminal flow. To minimize contamination during the weeks of tissue culture required to produce an arterial prosthesis, a sterile incubator system was developed. Preliminary studies have achieved good cell densities of both smooth muscle cells and endothelial cells on biodegradable polymer scaffolds. C1 Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Niklason, LE (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03492-02] NR 30 TC 124 Z9 127 U1 0 U2 16 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON, ENGLAND NW1 3BH SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD DEC PY 1997 VL 5 IS 4 BP 303 EP 306 PG 4 WC Immunology; Transplantation SC Immunology; Transplantation GA YQ775 UT WOS:000071422000013 PM 9504152 ER PT J AU Sucher, NJ Lipton, SA Dreyer, EB AF Sucher, NJ Lipton, SA Dreyer, EB TI Molecular basis of glutamate toxicity in retinal ganglion cells SO VISION RESEARCH LA English DT Article DE N-methyl-D-aspartate; retinal ganglion cells; neurons; excitotoxicity; glutamate; cell death ID METHYL-D-ASPARTATE; RECEPTOR-MEDIATED NEUROTOXICITY; CALCIUM-CHANNEL ANTAGONISTS; REDOX MODULATORY SITE; AMINO-ACID RECEPTORS; NITRIC-OXIDE; EXPERIMENTAL GLAUCOMA; COAT PROTEIN; OPTIC-NERVE; MAMMALIAN RETINA AB Loss of retinal ganglion cells (RGCs) is a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due to central artery occlusion, anterior ischemic optic neuropathy and may be significant in optic neuritis, optic nerve trauma, and AIDS. Recent research indicates that neurotoxicity is caused by excessive stimulation of receptors for excitatory amino acids (EAAs). In particular, the amino acid glutamate has been shown to act as a neurotoxin which exerts its toxic effect an RGCs predominantly through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, NMDA-receptor-mediated toxicity in RGCs is dependent on the influx of extracellular Ca2+. The increase in [Ca2+](i) acts as a second messenger that sets in motion the cascade leading to eventual cell death. Glutamate stimulates its own release in a positive feedback loop by its interaction with the non-NMDA receptor subtypes, Ca2+-induced Ca2+ release and further influx Df Ca2+ through voltage gated Ca2+ channels after glutamate-induced depolarization contribute to glutamate toxicity. In vitro and in vivo studies suggest that the use of selective NMDA receptor antagonists or Ca2+ channel blockers should be useful in preventing or at least abating normal loss in the retina. Of particular importance for future clinical use of NMDA receptor antagonists in the treatment of acute vascular insults is the finding that some drugs can prevent glutamate-induced (C) 1997 Published by Elsevier Science Ltd. C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Beth Israel Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. RP Lipton, SA (reprint author), Childrens Hosp, Dept Neurol, Enders Bldg,Room 361,300 Longwood Ave, Boston, MA 02115 USA. OI Sucher, Nikolaus/0000-0001-6233-1612 FU NEI NIH HHS [R01 EY05477, R01 EY09024, R01 EY10009] NR 77 TC 243 Z9 260 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD DEC PY 1997 VL 37 IS 24 BP 3483 EP 3493 DI 10.1016/S0042-6989(97)00047-3 PG 11 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA YM180 UT WOS:000071037800006 PM 9425525 ER PT J AU Smith, CB AF Smith, CB TI The future of Veterans Affairs medical centers SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID CARE AB In the past four years, the Department of Veterans Affairs (VA) has experienced unprecedented changes in the ways it provides medical care, trains medical residents, and supports its clinical research program, For the most part, these changes have improved the quality and efficiency of care provided to veterans, and they have improved the chances that the VA will survive in an increasingly competitive medical market place. While the changes in priorities for training medical residents and funding clinical research have been designed to be more consistent with the overall mission of the VA, these changes have been stressful for many of the VA/medical school affiliations. Our challenge is to understand and manage these changes so that the many benefits that have derived from more than fifty years of VA/medical school affiliations can be retained. C1 UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA 98195. RP Smith, CB (reprint author), VA PUGET SOUND HLTH CARE SYST,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD DEC PY 1997 VL 167 IS 6 BP 420 EP 425 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YL334 UT WOS:A1997YL33400007 PM 9426482 ER PT J AU Albert, MS AF Albert, MS TI The ageing brain: normal and abnormal memory SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article ID MONKEY CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; RHESUS-MONKEY; AGED MONKEYS; RECOGNITION MEMORY; MACACA-MULATTA; NEURONAL LOSS; HIPPOCAMPUS; DEMENTIA AB With advancing-age, the majority of individuals experience declines in their ability to learn and remember. An examination of brain structure and function in healthy older persons across the age range indicates that there are substantial changes in the brain that appear to be related to alterations in memory. The nature of the cognitive and neurobiological alterations associated with age-related change is substantially different from that seen in the early stages of a dementing illness, such as Alzheimer's disease. These differences have implications for potential intervention strategies. RP Albert, MS (reprint author), MASSACHUSETTS GEN HOSP,BLDG 149,13TH ST,,CHARLESTOWN,MA 02129, USA. FU NIA NIH HHS [P01-AG04953] NR 67 TC 53 Z9 55 U1 1 U2 3 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD NOV 29 PY 1997 VL 352 IS 1362 BP 1703 EP 1709 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA YK200 UT WOS:A1997YK20000007 PM 9415922 ER PT J AU Haber, DA AF Haber, DA TI Splicing into senescence: The curious case of p(16) and p19(ARF) SO CELL LA English DT Review ID CYCLIN-DEPENDENT KINASES; FAMILIAL MELANOMA; CELL; MUTATIONS; P16; TRANSCRIPT; INHIBITORS; CANCER; LOCUS; CDK4 C1 HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. RP Haber, DA (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129, USA. NR 20 TC 125 Z9 126 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 28 PY 1997 VL 91 IS 5 BP 555 EP 558 DI 10.1016/S0092-8674(00)80441-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YH960 UT WOS:A1997YH96000001 PM 9393847 ER PT J AU Chauhan, D Pandey, P Ogata, A Teoh, G Krett, N Halgren, R Rosen, S Kufe, D Kharbanda, S Anderson, K AF Chauhan, D Pandey, P Ogata, A Teoh, G Krett, N Halgren, R Rosen, S Kufe, D Kharbanda, S Anderson, K TI Cytochrome c-dependent and -independent induction of apoptosis in multiple myeloma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN; DEATH; CED-3; ICE; ACTIVATION; INHIBITION; PROTEASES; CLEAVAGE; KINASE; P35 AB Cytochrome c is a mitochondrial protein that induces apoptosis when accumulated in the cytosol in response to diverse stress inducers. This protein has also been shown to cause apoptosis when added to cell free extracts. In this report, we studied the role of cytochrome c (cyto-c) in dexamethasone (Dex), anti-Fas monoclonal antibody (mAb), and ionizing radiation-induced apoptosis in multiple myeloma cells, The results demonstrate that ionizing radiation-induced apoptosis is associated with an increase in cytosolic cyto-c levels, whereas apoptosis induced by Dex or anti Fas mAb has no detectable effect on cyto-e release. By contrast, caspase-3 was activated in response to all of these agents. Thus, our findings suggest that Dex or anti-Fas mAb-induced apoptosis is not accompanied by cyto-c release and that there are at least two different pathways leading to activation of caspases and induction of apoptosis in multiple myeloma cells that can be distinguished by accumulation of cytosolic cyto-c. C1 NORTHWESTERN UNIV,SCH MED,ROBERT H LURIE CANC CTR,CHICAGO,IL 60611. RP Chauhan, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 50947] NR 24 TC 162 Z9 164 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 29995 EP 29997 DI 10.1074/jbc.272.48.29995 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300004 PM 9374472 ER PT J AU Habecker, BA Symes, AJ Stahl, N Francis, NJ Economides, A Fink, JS Yancopoulos, G Landis, SC AF Habecker, BA Symes, AJ Stahl, N Francis, NJ Economides, A Fink, JS Yancopoulos, G Landis, SC TI A sweat gland-derived differentiation activity acts through known cytokine signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; CILIARY NEUROTROPHIC FACTOR; CULTURED SYMPATHETIC NEURONS; NEUROTRANSMITTER PLASTICITY INVIVO; NEUROPEPTIDE MESSENGER-RNAS; TRIPARTITE CNTF RECEPTOR; NEUROBLASTOMA CELL-LINE; ONCOSTATIN-M; CHOLINERGIC DIFFERENTIATION; NEUROPOIETIC CYTOKINES AB The sympathetic innervation of sweat glands undergoes a target-induced noradrenergic to cholinergic/peptidergic switch during development. Similar changes are induced in cultured sympathetic neurons by sweat gland cells or by one of the following cytokines: leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), or cardiotrophin-1 (CT-1), None of these is the sweat gland-derived differentiation activity. LIF, CNTF, and CT-1 act through the known receptors LIF receptor beta (LIFR beta) and gp130 and well defined signaling pathways including receptor phosphorylation and STAT3 activation. Therefore, to determine whether the gland-derived differentiation activity was a member of the LIF/CNTF cytokine family, we tested whether it acted via these same receptors and signal cascades. Blockade of LIFR beta inhibited the sweat gland differentiation activity in neuron/gland co-cultures, and extracts of gland containing footpads stimulated tyrosine phosphorylation of LIFR beta and gp130, An inhibitor (CGX) of molecules that bind the CNTFR alpha, which is required for CNTF signaling, did not affect the gland derived differentiation activity. Soluble footpad extracts induced the same changes In NBFL neuroblastoma cells as LIF and CNTF, including increased vasoactive intestinal peptide mRNA, STAT3 dimerization, and DNA binding, and stimulation of transcription from the vasoactive intestinal peptide cytokine-responsive element. Thus, the sweat gland-derived differentiation activity uses the same signaling pathway as the neuropoietic cytokines, and is likely to be a family member. C1 CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,MOL NEUROBIOL LAB,BOSTON,MA 02114. REGENERON PHARMACEUT INC,TARRYTOWN,NY 10591. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. RP Habecker, BA (reprint author), NINCDS,NEURAL DEV SECT,NIH,BLDG 36-5A05,36 CONVENT DR,BETHESDA,MD 20892, USA. RI Symes, Aviva/S-7471-2016; OI Symes, Aviva/0000-0003-2557-9939; Habecker, Beth/0000-0002-4658-8730 FU NINDS NIH HHS [NS023678, NS27514] NR 89 TC 52 Z9 55 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 28 PY 1997 VL 272 IS 48 BP 30421 EP 30428 DI 10.1074/jbc.272.48.30421 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YH613 UT WOS:A1997YH61300065 PM 9374533 ER PT J AU Boehm, T Folkman, J Browder, T OReilly, MS AF Boehm, T Folkman, J Browder, T OReilly, MS TI Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance SO NATURE LA English DT Article ID ANGIOGENESIS AB Acquired drug resistance is a major problem in the treatment of cancer. Of the more than 500,000 annual deaths from cancer in the United States', many follow the development of resistance to chemotherapy. The emergence of resistance depends in part on the genetic instability, heterogeneity and high mutational rate of tumour cells'. In contrast, endothelial cells are genetically stable, homogenous and have a low mutational rate. Therefore, anti-angiogenic therapy directed against a tumour's endothelial cells should, in principle, induce little or no drug resistance, Endostatin(3), a potent angiogenesis inhibitor, was administered to mice bearing Lewis lung carcinoma, T241 fibrosarcoma or B16F10 melanoma. Treatment was stopped when tumours had regressed. Tumours were then allowed to re-grow and endostatin therapy was resumed. After 6, 4 or 2 treatment cycles, respectively, no tumours recurred after discontinuation of therapy, These experiments show that drug resistance does not develop in three tumour types treated with a potent angiogenesis inhibitor, An unexpected finding is that repeated cycles of antiangiogenic therapy are followed by prolonged tumour dormancy without further therapy. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC CTR,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP Boehm, T (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,HUNNEWELL 103,300 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 13 TC 1331 Z9 1496 U1 4 U2 38 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 27 PY 1997 VL 390 IS 6658 BP 404 EP 407 DI 10.1038/37126 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YH549 UT WOS:A1997YH54900064 PM 9389480 ER PT J AU MacDermott, RP Shepard, JAO GraemeCook, FM Bloch, KJ AF MacDermott, RP Shepard, JAO GraemeCook, FM Bloch, KJ TI A 59-year-old man with anorexia, weight loss, and a mediastinal mass - Whipple's disease involving the small intestine and mesenteric and mediastinal lymph nodes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GASTROINTESTINAL SARCOIDOSIS; GRANULOMAS; BACILLUS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD MED SCH,BOSTON,MA. RP MacDermott, RP (reprint author), LAHEY HITCHCOCK CLIN,GASTROENTEROL SECT,BURLINGTON,MA 01805, USA. NR 19 TC 4 Z9 4 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 1997 VL 337 IS 22 BP 1612 EP 1619 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA YH521 UT WOS:A1997YH52100008 ER PT J AU Greene, MF AF Greene, MF TI Screening for gestational diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP Greene, MF (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 10 TC 21 Z9 23 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 1997 VL 337 IS 22 BP 1625 EP 1626 DI 10.1056/NEJM199711273372211 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YH521 UT WOS:A1997YH52100011 PM 9371862 ER PT J AU Emery, DW Sablinski, T Shimada, H Germana, S Gianello, P Foley, A Shulman, S Arn, S Fishman, J Lorf, T Nickeleit, V Colvin, RB Sachs, DH LeGuern, C AF Emery, DW Sablinski, T Shimada, H Germana, S Gianello, P Foley, A Shulman, S Arn, S Fishman, J Lorf, T Nickeleit, V Colvin, RB Sachs, DH LeGuern, C TI Expression of an allogeneic MHC DRB transgene, through retroviral transduction of bone marrow, induces specific reduction of alloreactivity SO TRANSPLANTATION LA English DT Article ID CLASS-II GENES; HEMATOPOIETIC STEM-CELLS; MAJOR HISTOCOMPATIBILITY COMPLEX; MINIATURE SWINE; RENAL-ALLOGRAFTS; PROGENITOR CELLS; GM-CSF; TRANSPLANTATION; TOLERANCE; VECTOR AB Background.: Transfer of MHC class II genes, through allogeneic bone marrow (BM) transplantation, induced long-lasting acceptance of renal allografts in miniature swine. To adapt this approach to the clinic, we have now examined whether somatic transfer of allogeneic class II DR genes, into otherwise autologous bone marrow cells (BMC), can provide the matching required for inducing immune tolerance. Methods. Autologous BMC were transduced ex vivo with recombinant retroviruses for allogeneic DRB followed by BM transplantation, The recipients were then challenged with kidney allografts solely matched to the DRB transgene. Results. Five miniature swine received autologous BMC conditioned with growth factors and transduced with recombinant retrovirus vectors containing allogeneic (n=4) or syngeneic (n=1) class II DRB genes and a drug-resistance marker. Expression of retrovirus-derived products in BM-derived cells was demonstrated by the detection of drug-resistant colony-forming progenitors and the presence of DRB retrovirus transcripts in peripheral cells. Analysis of selective mixed lymphocyte reaction responses to DR or DQ antigens indicated decreased reactivity toward the transduced DR gene product. Among all of the animals receiving fully mismatched kidney allografts, but with DRB matched to the transduced DRB, the one with the highest gene transduction rate showed stable allograft function and essentially normal renal histology for 2.5 years. A control animal, which received a syngeneic DRB gene, rejected its kidney allograft in 120 days after an earlier rejection crisis. Conclusions. These studies demonstrate that allogeneic MHC gene transfer into BM provides a new strategy for inducing tolerance across MHC barriers. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU NHLBI NIH HHS [HL46532]; NIAID NIH HHS [AI31046, AI33053] NR 52 TC 35 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 1997 VL 64 IS 10 BP 1414 EP 1423 DI 10.1097/00007890-199711270-00007 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YH592 UT WOS:A1997YH59200007 PM 9392304 ER PT J AU Halm, EA Causino, N Blumenthal, D AF Halm, EA Causino, N Blumenthal, D TI Is gatekeeping better than traditional care? A survey of physicians' attitudes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLINICAL-PRACTICE; HEALTH-CARE; EXPERIENCE; LESSONS AB Context.-Nearly all managed care plans rely on a physician ''gatekeeper'' to control use of specialty, hospital, and other expensive services. Gatekeeping is intended to reduce costs while maintaining or improving quality of care by increasing coordination and prevention and reducing duplicative or inappropriate care. Whether gatekeeping achieves these goals remains largely unproven. Objective.-To assess physicians' attitudes about the effects of gatekeeping compared with traditional care on administrative work, quality of patient care, appropriateness of resource use, and cost. Design.-Cross-sectional survey of primary care physicians Setting.-Outpatient facilities in metropolitan Boston, Mass. Participants.-All physicians who served as both primary care gatekeepers and traditional Blue Cross/Blue Shield providers for the employees of Massachusetts General Hospital, Boston. Of the 330 physicians surveyed, 202 (61%) responded. Outcomes Measures.-Physician ratings of the effects of gatekeeping on 21 aspects of care, including administrative work, physician-patient interactions, decision making, appropriateness of resource use, cost, and quality of care. Results.-Physicians reported that gatekeeping (compared with traditional care) had a positive effect on control of costs, frequency, and appropriateness of preventive services and knowledge of a patient's overall care (P<.001), They also felt that gatekeeping increased paperwork and telephone calls and negatively affected the overall quality of care, access to specialists, ability to order expensive tests and procedures, freedom in clinical decisions, time spent with patients, physician-patient relationships, and appropriate use of hospitalizations and laboratory tests (P<.001). Overall, 32% of physicians rated gatekeeping as better than traditional care, 40% the same, 21% gatekeeping as worse, and 7% were of mixed opinion, Positive ratings of gatekeeping were associated with fewer years in clinical practice, generalist training, and experience with gatekeeping and health maintenance organization plans. Conclusions.-Physicians identified both positive and negative effects of gatekeeping. Overall, 72% of physicians thought gatekeeping was better than or comparable to traditional care arrangements. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU BHP HRSA HHS [PE11001-08] NR 23 TC 94 Z9 95 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 26 PY 1997 VL 278 IS 20 BP 1677 EP 1681 DI 10.1001/jama.278.20.1677 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YG859 UT WOS:A1997YG85900029 PM 9388087 ER PT J AU Kraeft, SK Chen, DS Li, HP Chen, LB Lai, MMC AF Kraeft, SK Chen, DS Li, HP Chen, LB Lai, MMC TI Mouse hepatitis virus infection induces an early, transient calcium influx in mouse astrocytoma cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-for-Cell-Biology CY DEC 07-11, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Cell Biol DE mouse hepatitis virus; mouse astrocytoma cells; intracellular calcium; fluo-3; confocal laser scanning microscopy; immunofluorescence ID CARCINOEMBRYONIC ANTIGEN FAMILY; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; MURINE CORONAVIRUSES; EPITHELIAL-CELLS; RECEPTOR; LYMPHOCYTE; VARIANTS; NEURONS; MEMBER AB Mouse hepatitis virus (MHV), a murine coronavirus, utilizes murine carcinoembryonic antigens as receptors, The events that follow virus-receptor binding and eventually lead to virus entry are poorly understood. We studied the possible effects of MHV infection on intracellular calcium in a mouse astrocytoma cell line. Using the calcium-sensitive dye fluo-3 and confocal laser scanning microscopy, we found that MHV strain JHM induced an immediate (within 20 s) and transient (lasting no longer than 2 min) calcium increase in about 5% of the infected cells. The calcium increase was blocked by antibodies against the viral spike protein, suggesting that it was specifically triggered by the interaction of the viral spikes with cells. It was also inhibited by L-type calcium channel blockers and was not detected in calcium-free medium, suggesting that the calcium increase was caused by calcium influx from the extracellular medium. Studies of the kinetics of viral replication by immunofluorescence staining of the viral nucleocapsid protein revealed that at 3 h postinfection there was roughly the same percentage of cells (5%) that produced the viral protein as the percentage of cells that had responded with a calcium signal. This finding and the virus dilution studies together suggest that calcium responders may represent cells that had been infected with multiple viruses and undergone rapid viral replication. Furthermore, calcium channel blockers, including verapamil and cadmium chloride, and the calcium chelator EGTA inhibited virus infection. Therefore, the transient intracellular calcium increase reported here may be an early signaling event associated with virus infection. (C) 1997 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Univ So Calif, Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90033 USA. RP Chen, LB (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cellular & Mol Biol, 44 Binney St, Boston, MA 02115 USA. RI Lai, Michael Ming-Chao/I-7001-2012; Li, Hsin-Pai/C-7305-2014 FU NINDS NIH HHS [NS 18146] NR 25 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 25 PY 1997 VL 237 IS 1 BP 55 EP 62 DI 10.1006/excr.1997.3768 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YN237 UT WOS:000071146800008 PM 9417866 ER PT J AU Damon, SE Haugk, KL Swisshelm, K Quinn, LS AF Damon, SE Haugk, KL Swisshelm, K Quinn, LS TI Developmental regulation of mac25/insulin-like growth factor-binding protein-7 expression in skeletal myogenesis SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; FOLLISTATIN-LIKE GENE; MYOBLAST DIFFERENTIATION; RETINOIC ACID; MUSCLE; MAC25; BETA; PROLIFERATION; CANCER AB Mac25 is a newly discovered member of the insulin-like growth factor-binding protein (IGFBP) family, recently assigned the name IGFBP-7. Mac25/IGFBP-7 is hypothesized to have growth-suppressing activity, since mac25/IGFBP-7 mRNA is down-regulated in several tumor cell lines and is highly expressed in senescent mammary epithelial cells. In this study, mac25/IGFBP-7 mRNA expression was characterized in the C2 skeletal myogenic cell line, which undergoes a transition from actively dividing, undifferentiated myoblasts to nondividing, differentiated myotubes, Mac25/IGFBP-7 mRNA levels were 2.5-fold higher in dividing C2 myoblasts than in nondividing myotubes. The inverse correlation between mac25/IGFBP-7 expression and myogenic differentiation was further examined by treating myogenic cultures with transforming growth factor-beta (TGF-beta) or insulin-like growth factor-I (IGF-I). TGF-beta inhibited myogenic differentiation by 98% and stimulated mac25/IGFBP-7 mRNA expression 2-fold. IGF-I stimulated differentiation by 50% and inhibited mac25/IGFBP-7 expression 2- to 3-fold. These findings indicate that, in contrast to other cell systems examined so far, expression of this new member of the IGFBP family is not always correlated with a nonproliferative state. (C) 1997 Academic Press. C1 Amer Lake Div, VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Quinn, LS (reprint author), Amer Lake Div, VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. NR 24 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 25 PY 1997 VL 237 IS 1 BP 192 EP 195 DI 10.1006/excr.1997.3787 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA YN237 UT WOS:000071146800024 PM 9417882 ER PT J AU Zhu, JW Kahn, R AF Zhu, JW Kahn, R TI Analysis of a peptide hormone-receptor interaction in the yeast two-hybrid system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-I; PROTEIN-PROTEIN INTERACTIONS; NECROSIS-FACTOR RECEPTOR; INSULIN-RECEPTOR; 2-HYBRID SYSTEM; LIGAND-BINDING; DOMAIN; MUTAGENESIS; SUBUNIT; GENES AB Interaction between a peptide hormone and extracellular domains of its receptor is a crucial step for initiation of hormone action, We have developed a modification of the yeast two-hybrid system to study this interaction and have used it to characterize the interaction of insulin-like growth factor 1 (IGF-1) with its receptor by using GAL4 transcriptional regulation with a beta-galactosidase assay as readout, In this system, IGF-1 and proIGF-1 bound to the cysteine-rich domain, extracellular domain, or entire IGF-1 proreceptor, This interaction was specific, Thus, proinsulin showed no significant interaction with the IGF-1 receptor, while a chimeric proinsulin containing the C-peptide of IGF-1 had an intermediate interaction, consistent with its affinity for the IGF-1 receptor, Over 2000 IGF-1 mutants were generated by PCR and screened for interaction with the color assay, About 40% showed a strong interaction, 20% showed an intermediate interaction, and 40% give little or no signal, Of 50 mutants that were sequenced, several (Leu-5 --> His, Glu-9 --> Val, Arg-37 --> Gly, and Met-59 --> Leu) appeared to enhance receptor association, others resulted in weaker receptor interaction (Tyr-31 --> Phe and Ile-43 --> Phe), and two gave no detectable signal (Leu-14 --> Arg and Glu-46 --> Ala), Using PCR-based mutagenesis with proinsulin, we also identified a gain of function mutant (proinsulin Leu-17 --> Pro) that allowed for a strong IGF-1-receptor interaction, These data demonstrate that the specificity of the interaction between a hormone and its 0receptor can be characterized with high efficiency in the two-hybrid system and that novel hormone analogues may be found by this method. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [P30 DK036836, DK31036, P30 DK36836, R01 DK031036, R37 DK031036] NR 36 TC 16 Z9 17 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13063 EP 13068 DI 10.1073/pnas.94.24.13063 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600067 PM 9371800 ER PT J AU Rahme, LG Tan, MW Le, L Wong, SM Tompkins, RG Calderwood, SB Ausubel, FM AF Rahme, LG Tan, MW Le, L Wong, SM Tompkins, RG Calderwood, SB Ausubel, FM TI Use of model plant hosts to identify Pseudomonas aeruginosa virulence factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gacA; pyocyanin; virulence model ID HEMOLYTIC PHOSPHOLIPASE-C; SYRINGAE PV PHASEOLICOLA; SHIGELLA-FLEXNERI; ESCHERICHIA-COLI; EPITHELIAL-CELLS; VIBRIO-CHOLERAE; GENES; IDENTIFICATION; SELECTION; PATHOGENICITY AB We used plants as an in vivo pathogenesis model for the identification of virulence factors of the human opportunistic pathogen Pseudomonas aeruginosa. Nine of nine TnphoA mutant derivatives of P. aeruginosa strain UCBPP-PA14 that were identified in a plant leaf assay for less pathogenic mutants also exhibited significantly reduced pathogenicity in a burned mouse pathogenicity model, suggesting that P. aeruginosa utilizes common strategies to infect both hosts. Seven of these nine mutants contain TnphoA insertions in previously unknown genes. These results demonstrate that an alternative nonvertebrate host of a human bacterial pathogen can be used in an in vivo high throughput screen to identify novel bacterial virulence factors involved in mammalian pathogenesis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GENET,DEPT MOL BIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV INFECT DIS,BOSTON,MA 02114. HARVARD UNIV,DEPT ORGANISM & EVOLUTIONARY BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02114. NR 49 TC 201 Z9 210 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13245 EP 13250 DI 10.1073/pnas.94.24.13245 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600098 PM 9371831 ER PT J AU Li, J Kasper, DL Ausubel, FM Rosner, B Michel, JL AF Li, J Kasper, DL Ausubel, FM Rosner, B Michel, JL TI Inactivation of the alpha C protein antigen gene, bca, by a novel shuttle/suicide vector results in attenuation of virulence and immunity in group B Streptococcus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Streptococcus agalactiae; surface antigens; bacterial pathogenesis; bacterial vaccines ID MOUSE-PROTECTIVE ANTIBODIES; TOXOID CONJUGATE VACCINE; GRAM-POSITIVE BACTERIA; MATERNAL IMMUNIZATION; SURFACE PROTEIN; IBC PROTEINS; IDENTIFICATION; INFECTION; SPECIFICITY; SEROTYPES AB The alpha C protein of group B Streptococcus (GBS) is a major surface-associated antigen. Although its role in the biology and virulence of GBS has not been defined, it is opsonic and capable of eliciting protective immunity. The alpha C protein is widely distributed among clinical isolates and is a potential protein carrier and antigen in conjugate vaccines to prevent GBS infections. The structural gene for the alpha C protein, bca, has been cloned and sequenced. The protein encoded by bca is related to a class of surface-associated proteins of Gram-positive cocci involved in virulence and immunity. To investigate the potential roles of the alpha C protein, bca null mutants were generated in which the bca gene was replaced with a kanamycin resistance cassette via homologous recombination using a novel shuttle/suicide vector. Studies of lethality in neonatal mice showed that the virulence of the bca null mutants was attenuated 5- to 7-fold when compared with the isogenic wild-type strain A909. Significant differences in mortality occurred in the first 24 h, suggesting that the role of the alpha antigen is important in the initial stages of the infection. In contrast to A909, bca mutants were no longer killed by polymorphonuclear leukocytes in the presence of alpha-specific antibodies in an in vitro opsonophagocytic assay. In contrast to previous studies, alpha antigen expression does not appear to play a role in resistance to opsonophagocytosis in the absence of alpha-specific antibodies. In addition, antibodies to the alpha C protein did not passively protect neonatal mice from lethal challenge with bca mutants, suggesting that these epitopes are uniquely present within the alpha antigen as expressed from the bca gene. Therefore, the alpha C protein is important in the pathogenesis of GBS infection and is a target for protective immunity in the development of GBS vaccines. C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02115. FU NIAID NIH HHS [R39-AI23339, R01-AI33963, R29-AI28500, T32 AI007410] NR 47 TC 46 Z9 48 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 1997 VL 94 IS 24 BP 13251 EP 13256 DI 10.1073/pnas.94.24.13251 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YJ456 UT WOS:A1997YJ45600099 PM 9371832 ER PT J AU Black, HR Cohen, JD Kaplan, NM Ferdinand, KC Chobanian, AV Dustan, HP Gifford, RW Moser, M Sheps, SG Agodoa, L August, PA Bakris, GL Burt, V Busse, W Carter, BL Chesley, FD Cleeman, J Cohn, JN Cregler, LL Crespo, C Cushman, WC Cutler, J Darrow, MD DeQuattro, VL Devereux, RB Dworkin, LD Elliott, WJ Epstein, M Falkner, B Ferrario, CM Flack, JM Frishman, W Frohlich, ED Green, LA Grimm, RH Hagberg, JM Hall, WD Handler, J Havas, S Hill, MN Horan, MJ Hsueh, WA Hyman, BN Izzo, JL Jamerson, K Kiley, JP Kochar, MS Kolasa, KM Krakoff, LR Levy, D Lindheimer, MD Luepker, RV Malone, MEL Massie, B Materson, BJ Merchant, J Messerli, FH Miller, NH Moore, MA MustoneAlexander, L Oparil, S Perry, HM Pickering, TG Pratt, JH Ram, CVS Randall, OS Reed, JW Roberts, RW Roccella, EJ Rogus, SD Saunders, E Schron, E Schwartz, G Sibai, BM Snyder, D Sowers, JR Stamler, J Temple, R Textor, S Thom, T Vidt, DG Weber, M Weinberger, MH Weinshilboum, R Whelton, PK Whisnant, JP Wiebers, DO Winston, MC Wright, JT Lenfant, C Casser, L Colman, PJ Edwards, T Feeley, DM Gajewski, J Levine, D Manger, W Marshall, EC Nickey, WA Robert, RW Secrest, BG Singer, EH Whisnant, JP Wilson, GJ Young, JM Bachman, JW Campese, VM Carr, AA Hand, M Holden, DC Jamieson, MJ Julius, S Mensah, GA Prisant, M Sullivan, JM Wilson, DJ Morosco, G Anderson, DE Waugh, D AF Black, HR Cohen, JD Kaplan, NM Ferdinand, KC Chobanian, AV Dustan, HP Gifford, RW Moser, M Sheps, SG Agodoa, L August, PA Bakris, GL Burt, V Busse, W Carter, BL Chesley, FD Cleeman, J Cohn, JN Cregler, LL Crespo, C Cushman, WC Cutler, J Darrow, MD DeQuattro, VL Devereux, RB Dworkin, LD Elliott, WJ Epstein, M Falkner, B Ferrario, CM Flack, JM Frishman, W Frohlich, ED Green, LA Grimm, RH Hagberg, JM Hall, WD Handler, J Havas, S Hill, MN Horan, MJ Hsueh, WA Hyman, BN Izzo, JL Jamerson, K Kiley, JP Kochar, MS Kolasa, KM Krakoff, LR Levy, D Lindheimer, MD Luepker, RV Malone, MEL Massie, B Materson, BJ Merchant, J Messerli, FH Miller, NH Moore, MA MustoneAlexander, L Oparil, S Perry, HM Pickering, TG Pratt, JH Ram, CVS Randall, OS Reed, JW Roberts, RW Roccella, EJ Rogus, SD Saunders, E Schron, E Schwartz, G Sibai, BM Snyder, D Sowers, JR Stamler, J Temple, R Textor, S Thom, T Vidt, DG Weber, M Weinberger, MH Weinshilboum, R Whelton, PK Whisnant, JP Wiebers, DO Winston, MC Wright, JT Lenfant, C Casser, L Colman, PJ Edwards, T Feeley, DM Gajewski, J Levine, D Manger, W Marshall, EC Nickey, WA Robert, RW Secrest, BG Singer, EH Whisnant, JP Wilson, GJ Young, JM Bachman, JW Campese, VM Carr, AA Hand, M Holden, DC Jamieson, MJ Julius, S Mensah, GA Prisant, M Sullivan, JM Wilson, DJ Morosco, G Anderson, DE Waugh, D TI The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CORONARY HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; ISOLATED SYSTOLIC HYPERTENSION; CONVERTING ENZYME-INHIBITION; RANDOMIZED CONTROLLED TRIALS; ACUTE MYOCARDIAL-INFARCTION; STAGE RENAL-DISEASE; FOLLOW-UP PROGRAM; ANTIHYPERTENSIVE THERAPY; CARDIOVASCULAR-DISEASE C1 NHLBI, INFORMAT CTR, NATL HIGH BLOOD PRESSURE EDUC PROGRAM, BETHESDA, MD 20894 USA. MAYO CLIN & MAYO FDN, MAYO MED SCH, ROCHESTER, MN 55905 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, CHICAGO, IL 60612 USA. ST LOUIS UNIV, HLTH SCI CTR, ST LOUIS, MO 63103 USA. UNIV TEXAS, SW MED SCH, DALLAS, TX 75230 USA. HEARTBEATS LIFE CTR, NEW ORLEANS, LA USA. BOSTON UNIV, BOSTON, MA 02215 USA. UNIV VERMONT, COLL MED, BURLINGTON, VT 05405 USA. CLEVELAND CLIN FDN, CLEVELAND, OH 44195 USA. YALE UNIV, SCH MED, NEW HAVEN, CT 06520 USA. NIDDK, BETHESDA, MD USA. NEW YORK HOSP, NEW YORK, NY 10021 USA. NATL CTR HLTH STAT, HYATTSVILLE, MD 20782 USA. UNIV WISCONSIN, MADISON, WI 53706 USA. UNIV COLORADO, DENVER, CO 80202 USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. UNIV MINNESOTA, SCH MED, MINNEAPOLIS, MN 55455 USA. CUNY, SCH MED, NEW YORK, NY 10031 USA. UNIV TENNESSEE, COLL MED, MEMPHIS, TN USA. E CAROLINA UNIV, SCH MED, GREENVILLE, NC 27858 USA. UNIV SO CALIF, MED CTR, LOS ANGELES, CA 90089 USA. CORNELL UNIV, MED CTR, NEW YORK, NY 10021 USA. RHODE ISL HOSP, PROVIDENCE, RI USA. UNIV MIAMI, SCH MED, MIAMI, FL USA. ALLEGHENY UNIV HLTH SCI, PHILADELPHIA, PA 19102 USA. WAKE FOREST UNIV, BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. MONTEFIORE MED CTR, ALBERT EINSTEIN COLL MED, BRONX, NY 10467 USA. ALTON OCHSNER MED FDN & OCHSNER CLIN, NEW ORLEANS, LA 70121 USA. UNIV MICHIGAN, ANN ARBOR, MI 48109 USA. UNIV MARYLAND, COLLEGE PK, MD 20742 USA. EMORY UNIV, ATLANTA, GA 30322 USA. KAISER PERMANENTE, ANAHEIM, CA USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. JOHNS HOPKINS UNIV, BALTIMORE, MD 21218 USA. BAYLOR COLL MED, HOUSTON, TX 77030 USA. SUNY BUFFALO, BUFFALO, NY 14260 USA. MED COLL WISCONSIN, MILWAUKEE, WI 53226 USA. E CAROLINA UNIV, SCH MED, GREENVILLE, NC 27858 USA. ENGLEWOOD HOSP, ENGLEWOOD, CO USA. NHLBI, FRAMINGHAM HEART STUDY, BETHESDA, MD 20894 USA. UNIV CHICAGO HOSP, CHICAGO, IL 60637 USA. JEFFERSON COMMUNITY COLL, LOUISVILLE, KY USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. HLTH CARE FINANCING ADM, WASHINGTON, DC USA. STANFORD CARDIAC REHABIL PROGRAM, PALO ALTO, CA USA. GEORGE WASHINGTON UNIV, SCH MED & HLTH SCI, WASHINGTON, DC 20052 USA. UNIV ALABAMA, BIRMINGHAM, AL USA. VET AFFAIRS MED CTR, WASHINGTON, DC 20422 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO 63130 USA. INDIANA UNIV, SCH MED, INDIANAPOLIS, IN USA. UNIV TEXAS, SW MED CTR, DALLAS, TX USA. HOWARD UNIV HOSP, WASHINGTON, DC USA. MOREHOUSE SCH MED, ATLANTA, GA 30310 USA. VENCOR, LOUISVILLE, KY USA. US HLTH RESOURCES & SERV ADM, ROCKVILLE, MD 20857 USA. WAYNE STATE UNIV, DETROIT, MI 48202 USA. NORTHWESTERN UNIV, SCH MED, CHICAGO, IL USA. US FDA, ROCKVILLE, MD 20857 USA. BROOKDALE HOSP, BROOKLYN, NY USA. TULANE UNIV, SCH PUBL HLTH & TROP MED, NEW ORLEANS, LA 70118 USA. AMER HEART ASSOC, DALLAS, TX USA. CASE WESTERN RESERVE UNIV, CLEVELAND, OH 44106 USA. CTR DIS CONTROL & PREVENT, NATL CTR HLTH STAT, ATLANTA, GA 30333 USA. AMER OPTOMETR ASSOC, ST LOUIS, MO USA. US DEPT HHS, AGCY HLTH CARE POLICY & RES, ROCKVILLE, MD 20852 USA. AMER COLL PHYSICIANS, PHILADELPHIA, PA USA. AMER PODIATR MED ASSOC, BETHESDA, MD USA. NATL KIDNEY FDN, NEW YORK, NY USA. AMER RED CROSS, WASHINGTON, DC 20006 USA. NHLBI, AD HOC COMM MINOR POPULAT, BETHESDA, MD 20894 USA. AMER COLL CARDIOL, BETHESDA, MD USA. AMER MED ASSOC, CHICAGO, IL 60610 USA. AMER ACAD FAMILY PHYS, KANSAS CITY, MO USA. AMER PUBL HLTH ASSOC, WASHINGTON, DC 20005 USA. AMER ACAD OPHTHALMOL, SAN FRANCISCO, CA USA. AMER NURSES ASSOC, WASHINGTON, DC 20024 USA. AMER ACAD PHYS ASSISTANTS, ALEXANDRIA, VA 22314 USA. AMER OSTEOPATH ASSOC, CHICAGO, IL 60611 USA. US DEPT VET AFFAIRS, WASHINGTON, DC USA. AMER PHARMACEUT ASSOC, WASHINGTON, DC USA. AMER DENT ASSOC, CHICAGO, IL 60611 USA. AMER COLL CHEST PHYS, NORTHBROOK, IL 60062 USA. AMER DIABET ASSOC, ALEXANDRIA, VA USA. AMER ACAD NEUROL, MINNEAPOLIS, MN USA. AMER DIETET ASSOC, CHICAGO, IL USA. AMER COLL OCCUPAT & ENVIRONM MED, ARLINGTON HTS, IL 60005 USA. AUGUSTA PREVENT CARDIOL, CIRCULATORY DIS CTR, AUGUSTA, GA USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX USA. MED COLL GEORGIA, AUGUSTA, GA 30912 USA. ROW SCI INC, ROCKVILLE, MD USA. NR 252 TC 4448 Z9 4569 U1 4 U2 67 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 24 PY 1997 VL 157 IS 21 BP 2413 EP 2446 PG 34 WC Medicine, General & Internal SC General & Internal Medicine GA YH222 UT WOS:A1997YH22200004 ER PT J AU Stafford, RS Saglam, D Blumenthal, D AF Stafford, RS Saglam, D Blumenthal, D TI National patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 69th Annual Scientific Session of the American-Heart-Association CY NOV 09-16, 1996 CL NEW ORLEANS, LA SP Amer Heart Assoc, Hoechst Marion Roussel Inc, Kansas City ID LEFT-VENTRICULAR DYSFUNCTION; MORTALITY; PROGRESSION; MANAGEMENT; MORBIDITY; ENALAPRIL; TRIAL AB Background: While the use of angiotensin-converting enzyme (ACE) inhibitors for patients with congestive heart failure (CHF) is supported by the results of clinical trials and expert guidelines, national physician practices are unknown. Methods: We analyzed 1529 physician office visits by patients with CHF available from the 1989 through 1994 National Ambulatory Medical Care Surveys. We examined changes over time in the use of ACE inhibitors and use of other medications for CHF. Potential clinical and nonclinical predictors of use of ACE inhibitors were evaluated using multiple logistic regression. Results: The prevalence of CHF increased from 0.9% of all office visits in 1989 to 1.1% in 1994. Use of ACE inhibitors increased from 24% in visits by patients with CHF in 1989 to 31% in 1994 (P=.02), From 1989 through 1994, use of ACE inhibitors was more likely in visits to cardiologists (46% vs 22% for all other physicians), in the Midwest (31% vs 24% in all other regions), in whites (27% vs 21% in nonwhites), in privately insured patients (31% vs 24% in all others), and in men (29% vs 23% in women). Multiple logistic regression analysis showed independent effects of specialty, region, and sex. Other medications commonly used for patients with CHF included diuretics (62% of visits for 1989-1994), digoxin (38%), and calcium channel antagonists (15%). Use of diuretics showed no significant trend between 1989 and 1994, whereas use of digoxin decreased significantly. Conclusion: The low rates of use of ACE inhibitors in patients with CHF and the wide variations in their use suggest a need to move beyond clinical trials and focus attention on modifying physician practices. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Stafford, RS (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,HLTH POLICY RES & DEV UNIT,50 STANIFORD ST,BOSTON,MA 02114, USA. FU AHRQ HHS [HS07892]; NHLBI NIH HHS [HL03548] NR 33 TC 130 Z9 133 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 24 PY 1997 VL 157 IS 21 BP 2460 EP 2464 DI 10.1001/archinte.157.21.2460 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YH222 UT WOS:A1997YH22200007 PM 9385297 ER PT J AU Kowluru, A Metz, SA AF Kowluru, A Metz, SA TI Ceramide-activated protein phosphatase-2A activity in insulin-secreting cells SO FEBS LETTERS LA English DT Article DE pancreatic beta cell; protein phosphatase 2A; okadaic acid; ceramide; carboxyl methylation; apoptosis ID CAMP; 2A AB Okadaic acid (OKA)-sensitive phosphatase (PP2A) activity may modulate nutrient-induced insulin secretion front pancreatic beta cells [Kowluru et al., Endocrinology 137 (1996) 2315-2323]. Ceramides, a new class of lipid second messengers may regulate PP2A [Dobrowsky and Hannun, J. Biol, Chem, (1992) 267, 5048-5051], and might play a role in cytokine-mediated apoptosis in beta cells [Sjoholm, FEBS Lett. 367 (1995) 283-286]. Therefore, we investigated the regulation of PP2A-like activity by ceramides in isolated beta (HIT-T15 or INS-1) cells, Cell-permeable (C2, C6 or C18) ceramides stimulated OKA-sensitive (but not -insensitive) phosphatase activity in a concentration-dependent manner (0-12.5 mu M), with maximal stimulation (+50-100%) at < 12.5 mu M. C2-dihydroceramide (a biologically inactive analog of C2 ceramide) failed to augment PP2A-like activity, Stimulatory effects of ceramides do not appear to be mediated via activation of the carboxyl methylation of the catalytic subunit of protein phosphatase 2A, since no effects of ceramides (up to 25 mu M) mere demonstrable on this parameter, These data identify a ceramide-activated protein phosphatase as a possible locus at which ceramides might exert their effects on beta cells leading to altered insulin secretion, and decreased cell viability followed by apoptotic cell demise. (C) 1997 Federation of European Biochemical Societies. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,RES SERV,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,MADISON,WI. UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53717. UNIV WISCONSIN,SCH MED,ENDOCRINOL SECT,MADISON,WI 53717. FU NIDDK NIH HHS [DK 37312] NR 19 TC 39 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 24 PY 1997 VL 418 IS 1-2 BP 179 EP 182 DI 10.1016/S0014-5793(97)01379-3 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA YJ818 UT WOS:A1997YJ81800041 PM 9414122 ER PT J AU Faraone, SV Biederman, J AF Faraone, SV Biederman, J TI Familial transmission of attention deficit hyperactivity disorder and mood disorders. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HARVARD INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. NR 0 TC 1 Z9 2 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 569 EP 569 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400052 ER PT J AU Xian, H True, W Eisen, SA Scherrer, JF Madden, P Goldberg, J Lyons, M Tsuang, M AF Xian, H True, W Eisen, SA Scherrer, JF Madden, P Goldberg, J Lyons, M Tsuang, M TI Evidence for a common genetic contribution to nicotine dependence and alcohol dependence. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,DIV GEN MED SCI,ST LOUIS,MO 63110. VAMC,MED SERV,ST LOUIS,MO 63106. VAMC,RES SERV,ST LOUIS,MO 63106. ST LOUIS UNIV,SCH PUBL HLTH,ST LOUIS,MO 63106. UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63106. US DEPT VET AFFAIRS,HSRD,COOPERAT STUDIES HLTH SERV,HINES,IL 60141. UNIV ILLINOIS,SCH PUBL HLTH,PROGRAM EPIDEMIOL,CHICAGO,IL 60680. BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02401. RI Lyons, Michael/B-6119-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 578 EP 578 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400083 ER PT J AU Collins, JS Perry, RT Watson, B Blacker, D Meyers, DA Albert, MS Tanzi, R Bassett, SS Rodes, L Go, RCP AF Collins, JS Perry, RT Watson, B Blacker, D Meyers, DA Albert, MS Tanzi, R Bassett, SS Rodes, L Go, RCP TI Evidence for linkage with markers on chromosome 1P in families with late-onset Alzheimer's disease: The NIMH Genetics Initiative AD Study Group. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 UNIV ALABAMA,TUSCALOOSA,AL 35487. JOHNS HOPKINS UNIV,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 21 PY 1997 VL 74 IS 6 BP 654 EP 654 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA YB414 UT WOS:A1997YB41400337 ER PT J AU Cryns, VL Byun, Y Rana, A Mellor, H Lustig, KD Ghanem, L Parker, PJ Kirschner, MW Yuan, JY AF Cryns, VL Byun, Y Rana, A Mellor, H Lustig, KD Ghanem, L Parker, PJ Kirschner, MW Yuan, JY TI Specific proteolysis of the kinase protein kinase C-related kinase 2 by caspase-3 during apoptosis - Identification by a novel, small pool expression cloning strategy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLY(ADP-RIBOSE) POLYMERASE; ACTIVATION; CLEAVAGE; CELLS; ICE; PKN AB The caspase family of proteases plays a critical role in the execution of apoptosis, However, efforts to decipher the molecular mechanisms by which caspases induce cell death have been greatly hindered by the lack of systematic and broadly applicable strategies to identify their substrates. Here we describe a novel expression cloning strategy to rapidly isolate cDNAs encoding caspase substrates that are cleaved during apoptosis, Small cDNA pools (approximately 100 clones each) are transcribed/translated in vitro in the presence of [S-35]methionine; these labeled protein pools are then incubated with cytosolic extracts from control and apoptotic cells, cDNA pools encoding proteins that are specifically cleaved by the apoptotic extract and whose cleavage is prevented by the caspase inhibitor acetyl-Tyr-Val-Ala-Asp chloromethylketone are subdivided and retested until a single cDNA is isolated, Using this approach, we isolated a partial cDNA encoding protein kinase C-related kinase 2 (PRK2), a serine-threonine kinase, and demonstrate that full-length human PRK2 is proteolyzed by caspase-3 at Asp(117) and Asp(700) in vitro, In addition, PRK2 is cleaved rapidly during Fas-and staurosporine-induced apoptosis in vitro by caspase-3 or a closely related caspase, Both of the major apoptotic cleavage sites of PRK2 in vivo lie within its regulatory domain, suggesting that its activity may be deregulated by proteolysis. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIABET UNIT,CHARLESTOWN,MA 02129. IMPERIAL CANC RES FUND,PROT PHOSPHORYLAT LAB,LONDON WC2A 3PX,ENGLAND. RI Parker, Peter/D-5192-2013; Ghanem, Louis/R-3733-2016 OI Ghanem, Louis/0000-0002-7723-5241 FU NCI NIH HHS [K08-CA01752-04]; NIA NIH HHS [AG12859-01]; NIGMS NIH HHS [GM26875] NR 26 TC 75 Z9 80 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 21 PY 1997 VL 272 IS 47 BP 29449 EP 29453 DI 10.1074/jbc.272.47.29449 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YG647 UT WOS:A1997YG64700013 PM 9368003 ER PT J AU Bitsch, A Trostdorf, F Bruck, W Schmidt, H Fischer, FR Nau, R AF Bitsch, A Trostdorf, F Bruck, W Schmidt, H Fischer, FR Nau, R TI Central nervous system TNF alpha-mRNA expression during rabbit experimental pneumococcal meningitis SO NEUROSCIENCE LETTERS LA English DT Article DE tumor necrosis factor alpha; meningitis; Streptococcus pneumoniae; monocytes ID TUMOR-NECROSIS-FACTOR; CEREBROSPINAL-FLUID; BACTERIAL-MENINGITIS; NITRIC-OXIDE; INTERLEUKIN-1-BETA; INFLAMMATION; CYTOKINE; PROBES; DAMAGE; BRAIN AB In pneumococcal meningitis inflammatory mediators such as tumor necrosis factor alpha (TNF alpha) are produced in large quantities and play a major role in pathogenesis. It is not known exactly which cells produce these mediators during infection. We investigated the localisation of TNF alpha-mRNA in the central nervous system (CNS) by in situ hybridisation during experimental Streptococcus pneumoniae meningitis. TNF-positive cells were detected only in inflammatory infiltrates within the meninges. Cells within the brain parenchyma and the choroid plexus were completely negative. After monocyte depletion, no TNF alpha-mRNA positive cells were detected in the CNS. These findings suggest that TNF alpha in pneumococcal meningitis is produced in the CNS mainly by blood-derived, infiltrating monocytes. (C) 1997 Elsevier Science Ireland Ltd. C1 Univ Gottingen, Dept Neurol, D-37075 Gottingen, Germany. Univ Gottingen, Dept Neuropathol, D-37075 Gottingen, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bitsch, A (reprint author), Univ Gottingen, Dept Neurol, Robert Koch Str 40, D-37075 Gottingen, Germany. NR 20 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 21 PY 1997 VL 237 IS 2-3 BP 105 EP 108 DI 10.1016/S0304-3940(97)00830-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YL936 UT WOS:000071010000013 PM 9453226 ER PT J AU Rosenberg, ES Billingsley, JM Caliendo, AM Boswell, SL Sax, PE Kalams, SA Walker, BD AF Rosenberg, ES Billingsley, JM Caliendo, AM Boswell, SL Sax, PE Kalams, SA Walker, BD TI Vigorous HIV-1-specific CD4(+) T cell responses associated with control of viremia SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; IN-VITRO; IMMUNE-RESPONSE; DEFICIENT MICE; LYMPHOCYTES; RECOGNITION; ANTIGEN; CYTOMEGALOVIRUS; IMMUNIZATION AB Virus-specific CD4(+) T helper lymphocytes are critical to the maintenance of effective immunity in a number of chronic viral infections, but are characteristically undetectable in chronic human immunodeficiency virus-type 1 (HIV-1) infection. In individuals who control viremia in the absence of antiviral therapy, polyclonal, persistent, and vigorous HIV-1-specific CD4(+) T cell proliferative responses were present, resulting in the elaboration of interferon-gamma and antiviral beta chemokines. In persons with chronic infection, HIV-1-specific proliferative responses to p24 were inversely related to viral load. Strong HIV-1-specific proliferative responses were also detected following treatment of acutely infected persons with potent antiviral therapy. The HIV-1-specific helper cells are likely to be important in immunotherapeutic interventions and vaccine development. C1 MASSACHUSETTS GEN HOSP,PARTNERS AIDS RES CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FENWAY COMMUNITY HLTH CTR,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. FU NIAID NIH HHS [F32-AI09738, R01-AI28568]; PHS HHS [R01-A136550] NR 42 TC 1515 Z9 1537 U1 7 U2 46 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1447 EP 1450 DI 10.1126/science.278.5342.1447 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800040 PM 9367954 ER PT J AU Martin, KA Wyatt, R Farzan, M Choe, H Marcon, L Desjardins, E Robinson, J Sodroski, J Gerard, C Gerard, NP AF Martin, KA Wyatt, R Farzan, M Choe, H Marcon, L Desjardins, E Robinson, J Sodroski, J Gerard, C Gerard, NP TI CD4-independent binding of SIV gp120 to rhesus CCR5 SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; OLIGOMERIC STRUCTURE; HTLV-III; AIDS PATIENTS; T-CELLS; RECEPTOR; HIV-1; CD4; IDENTIFICATION AB CCR5 and CD4 are coreceptors for immunodeficiency virus entry into target cells, The gp120 envelope glycoprotein from human immunodeficiency virus strain HIV-1(YU2) bound human CCR5 (CCR5(hu)) or rhesus macaque CCR5 (CCR5(rh)) only in the presence of CD4. The gp120 from simian immunodeficiency virus strain SIVmac239 bound CCR5(rh) without CD4, but CCR5(hu) remained CD4-dependent. The CD4-independent binding of SIVmac239 gp120 depended on a single amino acid, Asp(13), in the CCR5(rh) amino-terminus. Thus, CCR5-binding moieties on the immunodeficiency virus envelope glycoprotein can be generated by interaction with CD4 or by direct interaction with the CCR5 amino-terminus. These results may have implications for the evolution of receptor use among lentiviruses as well as utility in the development of effective intervention. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,PERLMUTTER LAB,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV PADUA,SCH MED,INST MICROBIOL,I-35121 PADUA,ITALY. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. TULANE UNIV,MED CTR,DEPT PEDIAT,NEW ORLEANS,LA 70112. BETH ISRAEL DEACONESS HOSP,DEPT MED,CHILDRENS HOSP,PERLMUTTER LAB,BOSTON,MA 02115. BETH ISRAEL DEACONESS HOSP,DEPT PEDIAT,CHILDRENS HOSP,PERLMUTTER LAB,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36162, HL51366]; NIAID NIH HHS [AI41581] NR 35 TC 104 Z9 104 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD NOV 21 PY 1997 VL 278 IS 5342 BP 1470 EP 1473 DI 10.1126/science.278.5342.1470 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YG858 UT WOS:A1997YG85800047 PM 9367961 ER PT J AU Barsoum, J Brown, R McKee, M Boyce, FM AF Barsoum, J Brown, R McKee, M Boyce, FM TI Efficient transduction of mammalian cells by a recombinant baculovirus having the vesicular stomatitis virus G glycoprotein SO HUMAN GENE THERAPY LA English DT Article ID PSEUDOTYPED RETROVIRAL VECTORS; MEDIATED GENE-TRANSFER; MURINE LEUKEMIA-VIRUS; HIGH-TITER; G-PROTEIN; HEPATOCYTES; EXPRESSION; THERAPY AB Baculovirus vectors recently have been shown to be capable of efficient transduction of human hepatoma cells and primary hepatocytes in culture, This paper describes the generation of a novel recombinant baculovirus (VGZ3) in which the vesicular stomatitis virus glycoprotein G (VSV G) is present in the viral envelope, The gene encoding VSV G was inserted into the baculovirus genome under the control of the polyhedrin promoter such that it was expressed at very high levels in infected insect cells but not in mammalian cells, Expression of the lacZ reporter gene was driven by a promoter that is functional in mammalian cells (the Rous sarcoma virus long terminal repeat), We show by Western analysis that VSV G protein was present in purified baculovirus preparations, A VSV G monoclonal antibody blocked transduction of mammalian cells by VGZ3. This virus was morphologically distinct from baculovirus lacking VSV G, with virions adopting an oval rather than rod-shaped morphology, VGZ3 transduced human hepatoma cells in vitro at an efficiency roughly 10-fold greater than baculovirus lacking VSV G (the virus Z4), VGZ3 was also capable of transducing cell lines that could not be transduced efficiently by 24, We provide evidence that VSV G protein may enhance transduction by increasing the efficiency of escape of baculovirus from intracellular vesicles rather than by increasing cell binding or uptake of the virus, The possible use of this and related baculoviruses in gene therapy is discussed. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,CHARLESTOWN,MA 02129. RP Barsoum, J (reprint author), BIOGEN INC,12 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. NR 22 TC 136 Z9 154 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1997 VL 8 IS 17 BP 2011 EP 2018 DI 10.1089/hum.1997.8.17-2011 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YJ340 UT WOS:A1997YJ34000003 PM 9414250 ER PT J AU Ono, Y Ikeda, K Wei, MX Harsh, GR Tamiya, T Chiocca, EA AF Ono, Y Ikeda, K Wei, MX Harsh, GR Tamiya, T Chiocca, EA TI Regression of experimental brain tumors with 6-thioxanthine and Escherichia coli gpt gene therapy SO HUMAN GENE THERAPY LA English DT Article ID THYMIDINE KINASE GENES; VECTOR PRODUCER CELLS; MAMMALIAN-CELLS; CYTOSINE DEAMINASE; IN-VIVO; BACTERIAL GENE; GLIOMA-CELLS; RAT-BRAIN; RETROVIRUS; EXPRESSION AB The identification of transgenes with antitumor activity is critical to the development of gene therapy of cancer. Retrovirus-mediated transfer of the Escherichia coli gpt gene into rat C6 glioma cells without subsequent selection still inhibited the proliferation of this mixed polyclonal population upon addition of the prodrug, 6-thioxanthine, with an ID50 of 4.1 mu M, whereas parental C6 cells were not affected at a concentration of 500 mu M. In a time-course assay, effects of the prodrug on the mixed polyclonal cell proliferation required at least 10 days of exposure, In mixed co-cultures, a bystander effect was not present over the first 4 days of prodrug exposure, but required trypsinization of the co-cultures and replating at lower densities, This ''modified'' bystander assay thus revealed a 50% decrease in C6 cell proliferation, even when the initial ratio of gpt-expressing to parental C6 cells was as low as 1:19, In a nude mouse model of subcutaneous tumors, co-grafts of C6 glioma and gpt-retrovirus producer cells displayed retarded growth upon exposure to 6-thioxanthine (6-TX), In a nude mouse model of intracerebral tumors, grafting of the gpt-retrovirus producer cells leads to an 80% reduction in intracerebral tumor volumes after 6-TX treatment, This reduction results in a 28% increase in the mean time of survival of animals that harbor intracerebral tumors (p < 0.0005), These antitumor effects indicate that the gpt/6-TX enzyme/prodrug pair is a promising alternative to the thymidine kinase gene and ganciclovir combination in the gene therapy of cancer. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOL NEUROONCOL LAB,NEUROSURG SERV,BOSTON,MA 02114. FU ONDIEH CDC HHS [ND24279]; PHS HHS [P01 6924602] NR 37 TC 18 Z9 20 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1997 VL 8 IS 17 BP 2043 EP 2055 DI 10.1089/hum.1997.8.17-2043 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA YJ340 UT WOS:A1997YJ34000006 PM 9414253 ER PT J AU Sands, BE Compton, CC Scully, RE Mark, EJ McNeely, WF Ebeling, SH Phillips, LD Ryan, JM Brugge, WR AF Sands, BE Compton, CC Scully, RE Mark, EJ McNeely, WF Ebeling, SH Phillips, LD Ryan, JM Brugge, WR TI A 58-year-old man with recurrent ulcerative colitis, bloody diarrhea, and abdominal distention - Fulminant colitis and toxic megacolon complicating subtotal ulcerative colitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INFLAMMATORY BOWEL-DISEASE; CROHNS COLITIS; DILATATION; MANAGEMENT; THERAPY C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Sands, BE (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 1997 VL 337 IS 21 BP 1532 EP 1540 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA YG249 UT WOS:A1997YG24900008 ER PT J AU Blumenthal, D Campbell, EG Weissman, JS AF Blumenthal, D Campbell, EG Weissman, JS TI The social missions of academic health centers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INDUSTRY; CARE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 14 TC 49 Z9 50 U1 4 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 20 PY 1997 VL 337 IS 21 BP 1550 EP 1553 DI 10.1056/NEJM199711203372113 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YG249 UT WOS:A1997YG24900013 PM 9366591 ER PT J AU Blumenthal, D AF Blumenthal, D TI The future of quality measurement and management in a transforming health care system SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PHYSICIANS C1 PARTNERS HEALTHCARE SYST,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. RP Blumenthal, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,9TH FLOOR,50 STANIFORD ST,BOSTON,MA 02114, USA. NR 11 TC 40 Z9 40 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 19 PY 1997 VL 278 IS 19 BP 1622 EP 1625 DI 10.1001/jama.278.19.1622 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YF407 UT WOS:A1997YF40700048 PM 9370511 ER PT J AU Skopicki, HA Abraham, SA Picard, MH Alpert, NM Fischman, AJ Gewirtz, H AF Skopicki, HA Abraham, SA Picard, MH Alpert, NM Fischman, AJ Gewirtz, H TI Effects of dobutamine at maximally tolerated dose on myocardial blood flow in humans with ischemic heart disease SO CIRCULATION LA English DT Article DE dobutamine; blood flow; ischemia ID CORONARY-ARTERY DISEASE; VENTRICULAR PERFORMANCE; PHYSIOLOGIC BASIS; CONSCIOUS DOGS; WALL-MOTION; STENOSIS; STRESS; DIPYRIDAMOLE; TOMOGRAPHY; ADENOSINE AB Background This study tests the hypothesis in humans with ischemic heart disease that myocardial blood flow response to dobutamine is linearly correlated with blood flow response to adenosine. Methods and Results PET with [N-13]ammonia was used to measure myocardial blood flow at rest and during adenosine and dobutamine at the maximally tolerated dose. Myocardial segments were defined physiologically on the basis of blood flow response to adenosine: normal, greater than or equal to 2 mL.min(-1).g(-1); abnormal, < 2 mL.min(-1).g(-1); and ''steal,'' decline versus baseline greater than or equal to 0.15 mL.min(-1).g(-1). The patient population consisted of 11 men and 2 women. Dobutamine increased heart rate (79 +/- 22 to 115 +/- 28 bpm) and rate-pressure product (9748 +/- 2862 to 15157 +/- 3433 mm Hg/min) significantly (both P < .01). Myocardial blood flow at rest in abnormal segments (0.50 +/- 0.23 mL.min(-1).g(-1)) was reduced (P < .001) versus normal (0.90 +/- 0.45) and steal (0.92 +/- 0.60). Nevertheless, in abnormal segments, blood flow increased versus rest (P < .001) with dobutamine (0.83 +/- 0.43) and adenosine (0.90 +/- 0.49). In steal segments, myocardial blood flow declined versus baseline (P < .001) with dobutamine (0.68 +/- 0.46) and adenosine (0.50 +/- 0.45). In normal segments, myocardial blood flow increased (P < .001) with dobutamine (2.16 +/- 0.99) and adenosine (3.10 +/- 0.90). Over the range of flows, the correlation between adenosine and dobutamine was good (r = .78, P < .0001). Although flow with dobutamine in normal segments correlated with rate-pressure product (r = .81, P < .05), the slope of the line was 2.7 +/- 0.8 (P < .02), and normalized blood flow (3.3 +/- 2.5 x rest) exceeded normalized rate-pressure product (1.9 +/- 0.8 x rest; P < .05). Conclusions In humans with ischemic heart disease, myocardial blood flow responses to dobutamine and adenosine are linearly correlated over a wide range. The hyperemic response to dobutamine is in excess of that predicted by rate-pressure product and reflects the unmeasured inotropic, oxygen-wasting, and beta(2)-agonist effects of the drug. Dobutamine induces coronary steal with a frequency approaching that of adenosine. 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. OI Picard, Michael/0000-0002-9264-3243 NR 21 TC 37 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 1997 VL 96 IS 10 BP 3346 EP 3352 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YH188 UT WOS:A1997YH18800019 PM 9396426 ER PT J AU Jenkins, TM Esposito, D Engelman, A Craigie, R AF Jenkins, TM Esposito, D Engelman, A Craigie, R TI Critical contacts between HIV-1 integrase and viral DNA identified by structure-based analysis and photo-crosslinking SO EMBO JOURNAL LA English DT Article DE HIV-1; integrase; photo-crosslinking; protein-DNA interaction ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID-RESIDUES; CARBOXYL-TERMINAL DOMAINS; TYPE-1 INTEGRASE; CATALYTIC DOMAIN; BINDING DOMAIN; IN-VITRO; SUBSTRATE-SPECIFICITY; RETROVIRAL INTEGRASES; ESCHERICHIA-COLI AB Analysis of the crystal structure of HIV-I integrase reveals a cluster of lysine residues near the active site. Using site-directed mutagenesis and photo-crosslinking we find that Lys156 and Lys159 are critical for the functional interaction of integrase with viral DNA. Mutation of Lys156 or Lys159 to glutamate led to a loss of both 3' processing and strand transfer activities irt vitro while maintaining the ability to interact with nonspecific DNA and support disintegration, However, mutation of both residues to glutamate produced a synergistic effect eliminating nearly all nonspecific DNA interaction and disintegration activity, In addition, virus containing either of these changes was replication-defective at the step of integration, Photo-crosslinking, using 5-iododeoxyuracil-substituted oligonucleotides, suggests that Lys159 interacts at the N7 position of the conserved deoxyadenosine adjacent to the scissile phosphodiester bond of viral DNA. Sequence conservation throughout retroviral integrases and certain bacterial transposases (e.g. Tn10/IS10) supports the premise that within those families of polynucleotidyl transferases, these residues are strategic for DNA interaction. C1 NCI,MOL BIOL LAB,NIH,BETHESDA,MD 20892. DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NCRR NIH HHS [RR-01081]; NIAID NIH HHS [AI39394] NR 70 TC 199 Z9 203 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 17 PY 1997 VL 16 IS 22 BP 6849 EP 6859 DI 10.1093/emboj/16.22.6849 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YJ207 UT WOS:A1997YJ20700023 PM 9362498 ER PT J AU Jin, SF Weaver, DT AF Jin, SF Weaver, DT TI Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions SO EMBO JOURNAL LA English DT Article DE double-strand break repair; DNA-dependent protein kinase; heterodimerization; ionizing radiation; Ku ID DEPENDENT PROTEIN-KINASE; X-RAY RESISTANCE; V(D)J RECOMBINATION; SACCHAROMYCES-CEREVISIAE; END-BINDING; CATALYTIC SUBUNIT; AUTOANTIGEN; CELLS; ANTIGEN; COMPLEMENTATION AB Heterodimers of the 70 and 80 kDa Ku autoantigens (Ku70 and Ku80) activate the DNA-dependent protein kinase (DNA-PK). Mutations in any of the three subunits of this protein kinase (Ku70, Ku80 and DNA-PKcs) lead to sensitivity to ionizing radiation (IR) and to DNA double-strand breaks, and V(D)J recombination product formation defects. Here we show that the IR repair, DNA end binding and DNA-PK defects in Ku70-/- embryonic stem cells can be counteracted by introducing epitope-tagged wild-type Ku70 cDNA, Truncations and chimeras of Ku70 were used to identify the regions necessary for DNA end binding and TR repair, Site-specific mutational analysis revealed a core region of Ku70 responsible for DNA end binding and heterodimerization, The propensity for Ku70 to associate with Ku80 and to bind DNA correlates with the ability to activate DNA-PK, although two mutants showed that the roles of Ku70 in DNA-PK activation and IR repair are separate. Mutation of DNA-PK autophosphorylation sites and other structural motifs in Ku70 showed that these sites are not necessary for IR repair in vivo. These studies reveal Ku70 features required for double-strand break repair. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. NR 42 TC 111 Z9 113 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 17 PY 1997 VL 16 IS 22 BP 6874 EP 6885 DI 10.1093/emboj/16.22.6874 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YJ207 UT WOS:A1997YJ20700025 PM 9362500 ER PT J AU Mizoguchi, A Mizoguchi, E Smith, RN Preffer, FI Bhan, AK AF Mizoguchi, A Mizoguchi, E Smith, RN Preffer, FI Bhan, AK TI Suppressive role of B cells in chronic colitis of T cell receptor alpha mutant mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; ULCERATIVE-COLITIS; LAMINA PROPRIA; AUTOANTIBODY; CD4(+); TCR; AUTOIMMUNITY; DEFICIENT; GENE; MOUSE AB The role of antibodies (Abs) in the development of chronic colitis in T cell receptor (TCR-alpha(-/-) mice was explored by creating double mutant mice (TCR-alpha(-/-) X immunoglobulin (Ig)mu(-/-)), which lack B cells. TCR-alpha(-/-) X Ig mu(-/-) mice spontaneously developed colitis at an earlier age, and the colitis was more severe than in TCR-alpha(-/-) mice. Colitis was induced in recombination-activating gene-1 (RAG-1(-/-)) mice by the transfer of mesenteric lymph node (MLN) cells from TCR-alpha(-/-) X Ig mu(-/-) mice. When purified B cells from TCR-alpha(-/-) mice were mixed with MLN cells before cell transfer, colitis did not develop in RAG-1(-/-) mice. Administration of the purified Ig from TCR-alpha(-/-) mice and a mixture of monoclonal autoAbs reactive with colonic epithelial cells led to attenuation of colitis in TCR-alpha(-/-) X Ig mu (-/-) mice. Apoptotic cells were increased in the colon, MLN, and spleen of TCR-alpha(-/-) X Ig mu(-/-) mice as compared to Ig mu(-/-) mice and TCR-alpha(-/-) mice. Administration of the purified Ig from TCR-alpha(-/-) mice into TCR-alpha(-/-) X Ig mu(-/-) mice led to decrease in the number of apoptotic cells. These findings suggest that although B cells are not required for the initiation of colitis, B cells and Igs (autoAbs) can suppress colitis, presumably by affecting the clearance of apoptotic cells. C1 MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT COX5,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R01 DK047677, DK43551, DK47677] NR 44 TC 206 Z9 227 U1 2 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 17 PY 1997 VL 186 IS 10 BP 1749 EP 1756 DI 10.1084/jem.186.10.1749 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YH435 UT WOS:A1997YH43500013 PM 9362534 ER PT J AU Kowluru, A Li, GD Rabaglia, ME Segu, VB Hofmann, F Aktories, K Metz, SA AF Kowluru, A Li, GD Rabaglia, ME Segu, VB Hofmann, F Aktories, K Metz, SA TI Evidence for differential roles of the Rho subfamily of GTP-binding proteins in glucose- and calcium-induced insulin secretion from pancreatic beta cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 16th International-Diabetes-Federation Congress CY JUL 20-25, 1997 CL HELSINKI, FINLAND SP Int Diabet Federat DE Cdc42; Rho; Rap; Rac; C3 exoenzyme; insulin secretion; pancreatic beta cell; clostridial toxins ID DIFFICILE TOXIN-B; CLOSTRIDIUM-DIFFICILE; RAT ISLETS; PURIFICATION; INHIBITION; GLUCOSYLATION; MODULATION; CDC42 AB We utilized clostridial toxins (with known specificities for inhibition of GTPases) to ascertain the contribution of candidate GTPases in physiologic insulin secretion from beta cells. Exposure of normal rat islets or isolated beta (HIT-T15) cells to Clostridium difficile toxins A and B catalyzed the glucosylation (and thereby the inactivation) of Rac, Cdc42, and Rho endogenous to beta cells; concomitantly, either toxin reduced glucose-or potassium-induced insulin secretion from rat islets and HIT cells. Treatment of beta cells with Clostridium sordellii lethal toxin (LT; which modified only Ras, Rap, and Rac) also reduced glucose-or potassium-induced secretion. However, clostridial toxin C3-exoenzyme (which ADP-ribosylates and inactivates only Rho) was without any effect on either glucose-or potassium-induced insulin secretion. These data suggest that Cdc42, Rac, Ras, and/or Rap (but not Rho) may be needed for glucose-or potassium-mediated secretion. The effects of these toxins appear to be specific on stimulus-secretion coupling, since no difference in metabolic viability (assessed colorimetrically by quantitating the conversion of the tetrazolium salt into a formazan in a reduction reaction driven by nutrient metabolism) was demonstrable between control and toxin (A or LT)-treated beta cells. Toxin (A or LT) treatment also did not alter glucose-or potassium-mediated rises in cytosolic free calcium concentrations ([Ca2+](i)), suggesting that these GTPases are involved in steps distal to elevations in [Ca2+](i). Recent findings indicate that: the carboxyl methylation of Cdc42 is stimulated by only glucose, whereas that of Rap (Kowluru et al., J Clin Invest 98: 540-555, 1996) and Rac (present study) are regulated by glucose or potassium. Together, these findings provide direct evidence, for the first time, that the Rho subfamily of GTPases plays a key regulatory role(s) in insulin secretion, and they suggest that Cdc42 may be required for early steps in glucose stimulation of insulin release, whereas Rap and/or Rac may be required for a later step(s) in the stimulus-secretion coupling cascade (i.e. Ca2+-induced exocytosis of insulin). (C) 1997 Elsevier Science Inc. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, MADISON, WI 53705 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, RES SERV, MADISON, WI 53705 USA. NATL UNIV SINGAPORE, NATL MED INST, SINGAPORE 119260, SINGAPORE. UNIV FREIBURG, INST PHARMAKOL & TOXIKOL, D-79104 FREIBURG, GERMANY. RP Kowluru, A (reprint author), UNIV WISCONSIN, CTR CLIN SCI,SCH MED,ENDOCRINOL SECT,H4-568, 600 HIGHLAND AVE, MADISON, WI 53792 USA. FU NIDDK NIH HHS [DK 37312] NR 31 TC 73 Z9 74 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 15 PY 1997 VL 54 IS 10 BP 1097 EP 1108 DI 10.1016/S0006-2952(97)00314-6 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YD492 UT WOS:A1997YD49200005 PM 9464452 ER PT J AU Boussiotis, VA Berezovskaya, A Nadler, LM AF Boussiotis, VA Berezovskaya, A Nadler, LM TI Absence of activation of SHP-1 phosphotryosine phosphatase results in increased fyn tyrosine kinase activity in human T cell anergy. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 78 EP 78 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400078 ER PT J AU Berger, G Wagner, DD AF Berger, G Wagner, DD TI P-selectin and platelet clearance. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 154 EP 154 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400154 ER PT J AU Li, JZ Xia, YP Romo, J Kuter, DJ AF Li, JZ Xia, YP Romo, J Kuter, DJ TI C-mpl-mediated thrombopoietin internalization in human platelets. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 234 EP 234 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400234 ER PT J AU Liu, L Ilaria, R Kingsley, PD Iwama, A VanEtten, RA Palis, J Zhang, DE AF Liu, L Ilaria, R Kingsley, PD Iwama, A VanEtten, RA Palis, J Zhang, DE TI A novel member of the ubiquitin protease gene family is highly expressed in hematopoietic organs of AML1-ETO knock-in mice. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA 02115. UNIV ROCHESTER,MED CTR,DEPT PEDIAT,ROCHESTER,NY 14627. UNIV ROCHESTER,MED CTR,CTR CANC,ROCHESTER,NY 14627. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 257 EP 257 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400257 ER PT J AU Finberg, RW Cross, A Reinhardt, J Donowitz, G Wong, M AF Finberg, RW Cross, A Reinhardt, J Donowitz, G Wong, M TI Reduced toxicity of AmBisome in neutropenic patients: Results of a double-blind comparative trial against traditional amphotericin B. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 312 EP 312 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400312 ER PT J AU Zhang, Q Wang, ZY Sun, X Ratajczak, MZ Wasik, MA AF Zhang, Q Wang, ZY Sun, X Ratajczak, MZ Wasik, MA TI Constitutive phosphorylation of receptor for IGF-I (IGF-IR) in malignant T-cell lymphoma cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. JOSLIN DIABET CTR,BOSTON,MA 02215. RI Ratajczak, Mariusz Zdzislaw/N-1599-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 322 EP 322 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400322 ER PT J AU Krajewska, M Krajewska, S Young, M Weller, E Neiman, R Mederios, J Glick, J Venkatraj, U Gordon, L Cassileth, P Reed, JC AF Krajewska, M Krajewska, S Young, M Weller, E Neiman, R Mederios, J Glick, J Venkatraj, U Gordon, L Cassileth, P Reed, JC TI Expression of apoptosis-regulatory proteins Bcl-2, Bax and caspase-3 in non-Hodgkin's lymphomas: An ECOG study (E6491). SO BLOOD LA English DT Meeting Abstract C1 BURNHAM INST,LA JOLLA,CA 92037. DANA FARBER CANC INST,BOSTON,MA 02115. INDIANA UNIV,INDIANAPOLIS,IN 46204. CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. ALBERT EINSTEIN COLL MED,BRONX,NY 10467. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MIAMI,SCH MED,MIAMI,FL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 328 EP 328 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400328 ER PT J AU Alsina, M Gao, SJ Montalvo, EA Leach, CT Roodman, GD Jenson, HB AF Alsina, M Gao, SJ Montalvo, EA Leach, CT Roodman, GD Jenson, HB TI Increased prevalence of antibodies to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RI Gao, Shou-Jiang/B-8641-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 379 EP 379 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400379 ER PT J AU Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Nadler, L Pilarski, LM Belch, AR Anderson, KC AF Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Nadler, L Pilarski, LM Belch, AR Anderson, KC TI Myeloma cell lines and myeloma patient B-cell clonotypic cells selectively express core protein Muc-1 on their cell surface. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA. UNIV ALBERTA,CROSS CANC INST,EDMONTON,AB,CANADA. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 382 EP 382 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400382 ER PT J AU Teoh, G Urashima, M Chauhan, D Ogata, A Treon, SP Raje, N Anderson, KC AF Teoh, G Urashima, M Chauhan, D Ogata, A Treon, SP Raje, N Anderson, KC TI DNA-dependent protein kinase Ku holoenzyme on the cell surface membrane mediates signal transduction for the growth and survival of multiple myeloma cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 388 EP 388 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400388 ER PT J AU Teoh, G Urashima, M Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Ogata, A Treon, SP Raje, N Anderson, KC AF Teoh, G Urashima, M Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Ogata, A Treon, SP Raje, N Anderson, KC TI Cell surface membrane expression of the 86 kD subunit of the Ku autoantigen after CD40 ligand activation of multiple myeloma tells mediates tumor cell adhesion SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 389 EP 389 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400389 ER PT J AU Lee, SJ Anasetti, C Kuntz, KM Patten, J Antin, JH Weeks, JC AF Lee, SJ Anasetti, C Kuntz, KM Patten, J Antin, JH Weeks, JC TI The cost-effectiveness of unrelated donor bone marrow transplantation (URD BMT) for chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 472 EP 472 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400472 ER PT J AU Guinan, EC Nadler, LM Boussiotis, VA Brennan, LL Webb, IJ Gribben, JG AF Guinan, EC Nadler, LM Boussiotis, VA Brennan, LL Webb, IJ Gribben, JG TI Induction of alloantigen specific anergy via ex vivo blockade of the B7-CD28 pathway: Results of a pilot clinical trial demonstrate engraftment and absence of severe GVHD after haploidentical BMT. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 486 EP 486 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400486 ER PT J AU Gardner, JP Gaynor, K SilvaArrieta, S Scadden, DT AF Gardner, JP Gaynor, K SilvaArrieta, S Scadden, DT TI Effect of anti-HIV drugs on human T-lymphopoiesis in vitro. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,AIDS RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 579 EP 579 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400579 ER PT J AU Boussiotis, VA Lee, BJ Freeman, GJ Nadler, LM AF Boussiotis, VA Lee, BJ Freeman, GJ Nadler, LM TI Ligation of CD28 alone in the presence of IL-12 primes for Fas mediated apoptosis thereby eliminating bystander T cells. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,SCH MED,DEPT ADULT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 604 EP 604 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400604 ER PT J AU Ilaria, RL VanEtten, RA AF Ilaria, RL VanEtten, RA TI Analysis of murine STAT5A reveals multiple possible mechanisms for a dominant negative effect on cytokine signaling. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 730 EP 730 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400730 ER PT J AU Kaneki, M Pandey, P Liou, JR Stone, RM Kharbanda, S Kufe, DW AF Kaneki, M Pandey, P Liou, JR Stone, RM Kharbanda, S Kufe, DW TI Role for protein kinase C beta II (PKC beta II) as an upstream regulator of JNK in phorbol ester induced differentiation of human myeloid leukemia cells SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 737 EP 737 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400737 ER PT J AU Harris, K Arcasoy, M Forget, B Schultz, S AF Harris, K Arcasoy, M Forget, B Schultz, S TI The erythropoietin receptor distal cytoplasmic domain induces granulocytic differentiation in 32D cells. SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,S TEXAS VET HLTH CARE SYST,DIV HEMATOL,SAN ANTONIO,TX. YALE UNIV,DIV HEMATOL,NEW HAVEN,CT. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 748 EP 748 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400748 ER PT J AU Yakushijin, Y Aguiar, R Steckel, J Kharbanda, S Freeman, G Shipp, MA AF Yakushijin, Y Aguiar, R Steckel, J Kharbanda, S Freeman, G Shipp, MA TI Molecular characterization of a novel gene, bal, which regulates the proliferation of aggressive B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 782 EP 782 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400782 ER PT J AU Schwaller, J Frantsve, J Udomsakdi, C Carroll, M Ross, T Peeters, P Marynen, P vanEtten, R Ilaria, R Gilliland, DG AF Schwaller, J Frantsve, J Udomsakdi, C Carroll, M Ross, T Peeters, P Marynen, P vanEtten, R Ilaria, R Gilliland, DG TI Transforming properties of TEL/JAK2 fusion proteins in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, CTR BLOOD RES, BOSTON, MA 02115 USA. UNIV CATHOLIQUE LOUVAIN, CTR HUMAN GENET, B-3000 LOUVAIN LA NEUVE, BELGIUM. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 788 EP 788 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400788 ER PT J AU Palmer, AM Mahajan, S Frank, D Gilliland, DG Carroll, M AF Palmer, AM Mahajan, S Frank, D Gilliland, DG Carroll, M TI The TEL-PDGF beta R transforming protein activates STAT1. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. DEPT HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 789 EP 789 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400789 ER PT J AU Farah, RA Billett, AL Pollock, BH Buchanan, GR Schneider, NR AF Farah, RA Billett, AL Pollock, BH Buchanan, GR Schneider, NR TI Significance of cytogenetic findings in childhood acute lymphoblastic leukemia (ALL) at first marrow relapse. A pediatric oncology group (FOG) study. SO BLOOD LA English DT Meeting Abstract C1 UNIV TEXAS,SW MED CTR,DALLAS,TX. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV S FLORIDA,GAINESVILLE,FL. POG,CHICAGO,IL. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 818 EP 818 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400818 ER PT J AU Vallera, DA Seo, SY Jin, N Griffin, JD Blazar, BR AF Vallera, DA Seo, SY Jin, N Griffin, JD Blazar, BR TI Ex vivo purging of myeloid leukemia cells from murine BM with a fusion immunotoxin recognizing the interleukin-3 receptor. SO BLOOD LA English DT Meeting Abstract C1 UNIV MINNESOTA,CTR CANC,MINNEAPOLIS,MN. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 828 EP 828 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400828 ER PT J AU DunussiJoannopoulos, K Croop, JM AF DunussiJoannopoulos, K Croop, JM TI CTL cross-activation by ex vivo generated dendritic cells (DC) induces antileukemia immune responses in vivo in murine AML. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 830 EP 830 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400830 ER PT J AU Ross, TS Bernard, OA Berger, R Gilliland, DG AF Ross, TS Bernard, OA Berger, R Gilliland, DG TI Fusion of Huntington interacting protein 1 (HIP1) gene on 7q11.2 to the platelet-derived growth factor B (PDGFBR) gene on 5q33 in CMML SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV ONCOL,BOSTON,MA 02115. U301 INSERM,PARIS,FRANCE. INST MOL GENET,PARIS,FRANCE. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 898 EP 898 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400898 ER PT J AU Hill, GR Cooke, KR Crawford, JM Brinson, Y Bungard, D Delmonte, J Ferrara, JLM AF Hill, GR Cooke, KR Crawford, JM Brinson, Y Bungard, D Delmonte, J Ferrara, JLM TI IL-11 reduces the severity of graft-versus-host disease following allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 900 EP 900 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400900 ER PT J AU Hill, GR Cooke, KR Crawford, JM Brinson, Y Pan, L Bungard, D Delmonte, J Ferrara, JLM AF Hill, GR Cooke, KR Crawford, JM Brinson, Y Pan, L Bungard, D Delmonte, J Ferrara, JLM TI Cyclophosphamide and total body irradiation conditioning induces IL-1 mediated graft-versus-host disease mortality SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 901 EP 901 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400901 ER PT J AU Dey, B Yang, YG Preffer, F Dombkowski, D Swenson, K Sykes, M AF Dey, B Yang, YG Preffer, F Dombkowski, D Swenson, K Sykes, M TI Activation-induced cell death in donor TCR transgenic T cells with known host antigen specificity. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 908 EP 908 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400908 ER PT J AU Grass, J Delmonte, J Wages, D Lin, L Ferrara, J Corash, L AF Grass, J Delmonte, J Wages, D Lin, L Ferrara, J Corash, L TI Prevention of transfusion-associated graft vs host disease (TA-GVHD) in immunocompromised mice by photochemical treatment (PCT) of donor T cells SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. CERUS CORP,CONCORD,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 912 EP 912 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400912 ER PT J AU Schiller, G Stewart, AK Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Taranfolo, S Stiff, P Pineiro, L Dalton, W Ho, A Vescio, R Benyunes, M Jacobs, C DiPersio, J Anderson, K Berenson, J AF Schiller, G Stewart, AK Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Taranfolo, S Stiff, P Pineiro, L Dalton, W Ho, A Vescio, R Benyunes, M Jacobs, C DiPersio, J Anderson, K Berenson, J TI A phase III study evaluating CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation for patients with advanced multiple myeloma: Engraftment results. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. UNIV S FLORIDA,TAMPA,FL 33620. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV TEXAS,AUSTIN,TX. UNIV PENN,PHILADELPHIA,PA 19104. KAISER PERMANENTE,OAKLAND,CA. UNIV NEBRASKA,LINCOLN,NE 68583. LOYOLA UNIV,CHICAGO,IL. BAYLOR UNIV,WACO,TX 76798. UNIV ARIZONA,TUCSON,AZ 85721. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. WASHINGTON UNIV,ST LOUIS,MO 63130. DANA FARBER CANC INST,BOSTON,MA. CELLPRO INC,BOTHELL,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 960 EP 960 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400960 ER PT J AU Richardson, P Hoppensteadt, D Elias, K Frei, E Iacobelli, M Guinan, E Fareed, J AF Richardson, P Hoppensteadt, D Elias, K Frei, E Iacobelli, M Guinan, E Fareed, J TI Elevation of tissue factor pathway inhibitor [TFPI], thrombomodulin [TM] and plasminogen activator inhibitor-1 [PAI-1] levels in stem cell transplant [SCT]-associated veno-occlusive disease [VOD] and changes seen with the use of defibrotide [DF] SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. LOYOLA UNIV,MED CTR,HEMOSTASIS & THROMBOSIS RES LABS,CHICAGO,IL 60611. CRINOS ITALY SPA,COMO,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 965 EP 965 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400965 ER PT J AU Vredenburgh, J Glaspy, J Bolwell, B Demetri, GD Kin, B JelacaMaxwell, K Shpall, EJ AF Vredenburgh, J Glaspy, J Bolwell, B Demetri, GD Kin, B JelacaMaxwell, K Shpall, EJ TI The incidence of thrombotic and embolic events in controlled clinical trials of breast cancer (CA) patients (pts) undergoing high dose chemotherapy (HDC) with the stamp I regimen and autologous peripheral blood progenitor cell (PBPC) transplantation. SO BLOOD LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC 27706. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. DANA FARBER CC,BOSTON,MA. AMGEN INC,THOUSAND OAKS,CA. UNIV COLORADO,HSC,BOULDER,CO 80309. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 972 EP 972 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400972 ER PT J AU Schlossman, RL Webb, I Alyea, EP Soiffer, RJ Fisher, D Vance, E Gribben, J Freedman, A Nadler, L Ritz, J Anderson, KC AF Schlossman, RL Webb, I Alyea, EP Soiffer, RJ Fisher, D Vance, E Gribben, J Freedman, A Nadler, L Ritz, J Anderson, KC TI Similar disease-free survival (DFS) after allografting and autografting for multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 994 EP 994 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42400994 ER PT J AU Sehn, LH Antin, JH Weller, E Alyea, EP Canning, C Ritz, J Soiffer, RJ AF Sehn, LH Antin, JH Weller, E Alyea, EP Canning, C Ritz, J Soiffer, RJ TI Outcome following T-cell depleted (TCD) versus non-T-cell depleted (non-TCD) allogeneic bone marrow transplantation (allo BMT) for chronic myelogenous leukemia (CML): Impact of donor lymphocyte infusions (DLI). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1006 EP 1006 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401006 ER PT J AU Soiffer, RJ Mauch, P Neuberg, D Alyea, E Fisher, D Schlossman, R Gribben, J Vance, E Freedman, A Anderson, K Kuhlman, C Marcus, K Nadler, L Ritz, J AF Soiffer, RJ Mauch, P Neuberg, D Alyea, E Fisher, D Schlossman, R Gribben, J Vance, E Freedman, A Anderson, K Kuhlman, C Marcus, K Nadler, L Ritz, J TI Dose escalation of total body irradiation (TBI) in recipients of CD6 depleted allogeneic bone marrow: Toxicity and anti-tumor effects. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV ADULT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1011 EP 1011 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401011 ER PT J AU Bauer, TR Schwartz, BR Liles, WC Ochs, HD Hickstein, DD AF Bauer, TR Schwartz, BR Liles, WC Ochs, HD Hickstein, DD TI Retroviral-mediated gene transfer of human CD18 into CD34(+) cells from a patient with leukocyte adherence deficiency: Implications for human gene therapy. SO BLOOD LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1045 EP 1045 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401045 ER PT J AU Pulsipher, M Kupfer, GM Naf, D Suliman, A Jakobs, P Grompe, M Mulligan, R Sieff, C DAndrea, AD AF Pulsipher, M Kupfer, GM Naf, D Suliman, A Jakobs, P Grompe, M Mulligan, R Sieff, C DAndrea, AD TI Functionally active retroviral vectors for subtyping analysis and gene therapy in Fanconi anemia. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DIV PEDIAT ONCOL,DANA FARBER CANC INST,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DEPT MOL & MED GENET,PORTLAND,DORSET,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1049 EP 1049 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401049 ER PT J AU Kwiatkowski, BA Hickstein, DD AF Kwiatkowski, BA Hickstein, DD TI ETS family member Tel binds to Fli-1 and inhibits its transcription activity. SO BLOOD LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SCH MED,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1075 EP 1075 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401075 ER PT J AU Ghia, P Boussiotis, VA Cardoso, AA Freedman, AS Nadler, LM AF Ghia, P Boussiotis, VA Cardoso, AA Freedman, AS Nadler, LM TI Lymphoma cells display defective regulation of death effector proteins potentially contributing to their resistance to treatment. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1082 EP 1082 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401082 ER PT J AU VanEtten, RA Smith, K AF VanEtten, RA Smith, K TI Activation of c-ABL kinase activity and transformation by a chemical inducer of dimerization. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1086 EP 1086 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401086 ER PT J AU Salgia, R Quackenbush, E Ewaniuk, D Lin, J Sattler, M GuitterezRamos, JC Griffin, JD AF Salgia, R Quackenbush, E Ewaniuk, D Lin, J Sattler, M GuitterezRamos, JC Griffin, JD TI BCR/ABL transformed hematopoietic cells have reduced chemotaxis to the chemokine SDF-1. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1088 EP 1088 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401088 ER PT J AU Okuda, K VanEtten, R DAndrea, A Griffin, JD AF Okuda, K VanEtten, R DAndrea, A Griffin, JD TI The C-terminus of C-ABL is required for proliferation and viability signalling in a C-ABL/EPO receptor fusion protein. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC CTR,BOSTON,MA. CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1100 EP 1100 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401100 ER PT J AU Sattler, M Shrikhande, G Verma, S Chen, TY Salgia, R Griffin, JD AF Sattler, M Shrikhande, G Verma, S Chen, TY Salgia, R Griffin, JD TI The cellular redox status in hematopoietic cells regulates BCR/ABL tyrosine kinase activity. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1101 EP 1101 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401101 ER PT J AU Richardson, PG Elias, AD Krishnan, A Wheeler, C Nath, R Hoppensteadt, D Waller, EK Antin, JH Soiffer, RJ Vredenburgh, J Bearman, SI Iacobelli, M Fareed, J Guinan, EC AF Richardson, PG Elias, AD Krishnan, A Wheeler, C Nath, R Hoppensteadt, D Waller, EK Antin, JH Soiffer, RJ Vredenburgh, J Bearman, SI Iacobelli, M Fareed, J Guinan, EC TI Treatment of sever veno-occlusive disease (VOD) with defibrotide (DF): Compassionate use results in efficacy without significant toxicity in a high risk population. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. DUKE UNIV,MED CTR,DURHAM,NC. UNIV COLORADO,CTR HLTH,DENVER,CO. EMORY UNIV,MED CTR,ATLANTA,GA 30322. WESTERN PENN CANC INST,PITTSBURGH,PA. LOYOLA UNIV,MED CTR,CHICAGO,IL 60611. CRINOS ITALY SPA,COMO,ITALY. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1107 EP 1107 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401107 ER PT J AU DeFranceschi, L Bachir, D Galacteros, F Tchernia, GJ Cynober, T Williams, J Neuberg, D Beuzard, Y Brugnara, C AF DeFranceschi, L Bachir, D Galacteros, F Tchernia, GJ Cynober, T Williams, J Neuberg, D Beuzard, Y Brugnara, C TI Dietary magnesium supplementation reduces pain crises in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract C1 UNIV VERONA,DEPT MED,I-37100 VERONA,ITALY. HOP ST LOUIS,EXPT LAB GENE THERAPY,PARIS,FRANCE. CTR HOSP,LE KREMLIN BICETR,FRANCE. HOP HENRI MONDOR,CTR DREPANOCYTOSE,F-94010 CRETEIL,FRANCE. HOP HENRI MONDOR,INSERM,U91,F-94010 CRETEIL,FRANCE. HARVARD UNIV,SCH MED,DEPT PATHOL,CHILDRENS HOSP,DIV BIOSTAT,DANA FARBER CANC INST,BOSTON,MA 02115. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1159 EP 1159 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401158 ER PT J AU Robertson, MJ Cameron, C Atkins, MB Gordon, MS Lotze, MT Sherman, ML Ritz, J AF Robertson, MJ Cameron, C Atkins, MB Gordon, MS Lotze, MT Sherman, ML Ritz, J TI Immunologic effects of interleukin-12 administered by bolus intravenous injection to patients with advanced cancer. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. GENET INST INC,CAMBRIDGE,MA 02140. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1227 EP 1227 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401226 ER PT J AU Frenette, PS Moyna, C Hartwell, DW Lowe, JB Hynes, RO Wagner, DD AF Frenette, PS Moyna, C Hartwell, DW Lowe, JB Hynes, RO Wagner, DD TI Selectin-mediated platelet-endothelial interactions in inflamed mesenteric venules. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA. UNIV MICHIGAN,ANN ARBOR,MI 48109. RI Frenette, Paul/J-8272-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1257 EP 1257 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401256 ER PT J AU Martins, RG Colowick, AB Stark, P Kuter, DJ Ewenstein, B AF Martins, RG Colowick, AB Stark, P Kuter, DJ Ewenstein, B TI Warfarin therapy in cancer patients with venous thromboembolic disease (VTD). SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DIV HEMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV ONCOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT BIOSTAT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1313 EP 1313 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401312 ER PT J AU Deveaux, S CohenKaminsky, S Shivdasani, RA Orkin, SH Romeo, PH Mignotte, V AF Deveaux, S CohenKaminsky, S Shivdasani, RA Orkin, SH Romeo, PH Mignotte, V TI p45 NF-E2 regulates expression of thromboxane synthase in megakaryocytes. SO BLOOD LA English DT Meeting Abstract C1 HOP HENRI MONDOR,INSERM,U91,F-94010 CRETEIL,FRANCE. DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1339 EP 1339 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401338 ER PT J AU Lecine, P Shivdasani, R AF Lecine, P Shivdasani, R TI Subunit composition and DNA-binding specificity of transcription factor NF-E2 in primary murine megakaryocytes. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RI Lecine, Patrick/H-9338-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1340 EP 1340 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401339 ER PT J AU Gokemeijer, J Deligiannidis, K Ernst, T AF Gokemeijer, J Deligiannidis, K Ernst, T TI The adapter protein, 3BP2, expressed in hematopoietic cells, is functionally regulated by serine and tyrosine phosphorylation and transforms fibroblasts. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1386 EP 1386 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401385 ER PT J AU Krijanovski, OI Sieff, CA AF Krijanovski, OI Sieff, CA TI A peptide containing Y704 of the G-CSFR associates with 93 kD and 120 kD proteins in G-CSFR-Ba/F3 cells that are inducible (CD11b) in response to G-CSF. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1392 EP 1392 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401391 ER PT J AU Billett, AL Pollock, BH Abshire, TC Buchanan, GR AF Billett, AL Pollock, BH Abshire, TC Buchanan, GR TI Outcome of children with B-lineage acute lymphoblastic leukemia (ALL) in first bone marrow relapse. SO BLOOD LA English DT Meeting Abstract C1 EMORY UNIV,ATLANTA,GA 30322. UNIV FLORIDA,GAINESVILLE,FL. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TEXAS,SW MED CTR,DALLAS,TX. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1481 EP 1481 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401479 ER PT J AU Asselin, BL NDive, S Welle, S Sallan, SE AF Asselin, BL NDive, S Welle, S Sallan, SE TI Significant differences in asparagine depletion following L-asparaginase therapy with E-coli vs. Erwinia - Derived preparations. SO BLOOD LA English DT Meeting Abstract C1 UNIV ROCHESTER,MED CTR,CHILDRENS HOSP STRONG,ROCHESTER,NY 14642. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1489 EP 1489 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401487 ER PT J AU Greipp, PR Leong, T Kay, NE VanNess, BG Oken, MM Kyle, RA AF Greipp, PR Leong, T Kay, NE VanNess, BG Oken, MM Kyle, RA TI From ECOG myeloma trial E9486: A prognostic index based on tumor burden, proliferation and host immune status. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,EASTERN COOPERAT ONCOL GRP,MYELOMA LAB,STUDIES GRP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1561 EP 1561 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401557 ER PT J AU Kroning, R Nagami, G Weiss, D Solomon, A Lichtenstein, A AF Kroning, R Nagami, G Weiss, D Solomon, A Lichtenstein, A TI In vitro cytotoxicity to renal tubular epithelial cells is induced by nephrotoxic Bence Jones proteins and enhanced by interleukin-6. SO BLOOD LA English DT Meeting Abstract C1 UNIV TENNESSEE,MED CTR,KNOXVILLE,TN. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1568 EP 1568 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401564 ER PT J AU Chauhan, D Pandey, P Ogata, A Teoh, G Krett, N Halgren, R Rosen, S Kufe, D Kharbanda, S Anderson, KC AF Chauhan, D Pandey, P Ogata, A Teoh, G Krett, N Halgren, R Rosen, S Kufe, D Kharbanda, S Anderson, KC TI Cytochrome-c dependent and independent induction of apoptosis in multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,ROBERT H LURIE CANC CTR,CHICAGO,IL. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1570 EP 1570 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401566 ER PT J AU Friedman, T Sachs, DH Iacomini, J AF Friedman, T Sachs, DH Iacomini, J TI The human cellular immune response to porcine tissue in an immunodeficient mouse model. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1622 EP 1622 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401618 ER PT J AU Lee, SJ Weller, E Alyea, EP Ritz, J Soiffer, RJ AF Lee, SJ Weller, E Alyea, EP Ritz, J Soiffer, RJ TI Granulocyte colony stimulating factor (GCSF) after T-cell depicted (TCD) allogeneic transplantation (alloBMT). Efficacy and costs. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1659 EP 1659 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401655 ER PT J AU Nikolic, B Grusby, MJ Sykes, M AF Nikolic, B Grusby, MJ Sykes, M TI Th1 and Th2 responses cause distinct clinical GVHD syndromes after fully MHC-mismatched STAT 4 and STAT 6 KO bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BMT SECT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1756 EP 1756 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401752 ER PT J AU Cooke, KR Hill, G Crawford, JM Bungard, D Brinson, Y Delmonte, J Ferrara, JLM AF Cooke, KR Hill, G Crawford, JM Bungard, D Brinson, Y Delmonte, J Ferrara, JLM TI Donor hyporesponsiveness to LPS reduces graft-versus-host disease by attenuating early TNF alpha mediated intestinal toxicity. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1757 EP 1757 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401753 ER PT J AU Birnbaum, R OMarcaigh, A Wardak, Z Zhang, Y Dranoff, G Jacks, T Clapp, DW Shannon, KM AF Birnbaum, R OMarcaigh, A Wardak, Z Zhang, Y Dranoff, G Jacks, T Clapp, DW Shannon, KM TI Interaction between NF1 and GMCSF in leukemogenesis and hematopoietic engraftment. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. INDIANA UNIV,HERMAN B WELLS RES INST,INDIANAPOLIS,IN 46204. DANA FARBER CANC CTR,BOSTON,MA. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1828 EP 1828 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401824 ER PT J AU Yakushijin, Y Steckel, J Kharbanda, S Hasserjian, R Neuberg, D Jiang, WM Anderson, I Shipp, MA AF Yakushijin, Y Steckel, J Kharbanda, S Hasserjian, R Neuberg, D Jiang, WM Anderson, I Shipp, MA TI CD44ex10 promotes the metastasis of aggressive B-cell lymphomas and modulates adhesion to an additional cell surface ligand. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1835 EP 1835 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401831 ER PT J AU Schultze, JL Dorfman, DM Michalak, S Gribben, JG Nadler, LM AF Schultze, JL Dorfman, DM Michalak, S Gribben, JG Nadler, LM TI Low level expression of B7-1 and B7-2 by germinal center lymphomas is sufficient to prevent tolerance but not to induce anti-tumor immunity. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1837 EP 1837 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401833 ER PT J AU Tallman, MS Schiffer, CA Appelbaum, FR Feusner, JH Ogden, A Shepherd, L Andersen, JW Rowe, JM Wiernik, PH AF Tallman, MS Schiffer, CA Appelbaum, FR Feusner, JH Ogden, A Shepherd, L Andersen, JW Rowe, JM Wiernik, PH TI Incidence and clinical course of patients with acute promyelocytic leukemia who develop the retinoic acid syndrome. SO BLOOD LA English DT Meeting Abstract C1 GREENEBAUM CANC CTR,BALTIMORE,MD. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. CHILDRENS HOSP OAKLAND,OAKLAND,CA. TEXAS CHILDRENS CANC CTR,HOUSTON,TX. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,ROCHESTER,NY 14627. ALBERT EINSTEIN CANC CTR,BRONX,NY. NATL CANC INST,CLIN TRIALS GRP,KINGSTON,ON,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1848 EP 1848 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401844 ER PT J AU Spitzer, TR MCafee, SL Saidman, S Weymouth, D Preffer, F Olson, D Colby, C Sachs, DH Sykes, M AF Spitzer, TR MCafee, SL Saidman, S Weymouth, D Preffer, F Olson, D Colby, C Sachs, DH Sykes, M TI Clinical remission of refractory non-Hodgkin's lymphoma induced by allogeneic bone marrow transplantation (BMT) with mixed chimerism non-myeloablated recipients. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BONE MARROW TRANSPLANT PROGRAM,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1856 EP 1856 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401852 ER PT J AU Vance, EA George, S Guinan, EC Wheeler, C Antin, JH Ambrosino, DM Molrine, DC AF Vance, EA George, S Guinan, EC Wheeler, C Antin, JH Ambrosino, DM Molrine, DC TI A comparison of different immunization schedules with HIB-conjugate and tetanus toxoid vaccines following BMT. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BETH ISRAEL DEACONESS MED CTR,DIV INFECT DIS,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1869 EP 1869 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401865 ER PT J AU Vescio, R Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J AF Vescio, R Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J TI Myeloma cell tumor reduction in PBPC autografts following CD34 selection: The results of a phase III trial using the CEPRATE device. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, LOS ANGELES, CA 90024 USA. UNIV TORONTO, TORONTO, ON, CANADA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. UNIV NEBRASKA, LINCOLN, NE 68583 USA. LOYOLA UNIV, NEW ORLEANS, LA 70118 USA. BAYLOR UNIV, WACO, TX 76798 USA. ARIZONA CANC CTR, TUCSON, AZ USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. CELLPRO INC, SEATTLE, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1872 EP 1872 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401868 ER PT J AU Cecile, D Nassia, M Rayburn, H Hynes, RO Wagner, DD AF Cecile, D Nassia, M Rayburn, H Hynes, RO Wagner, DD TI Generation and characterization of von Willebrand factor-deficient mice. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1906 EP 1906 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401902 ER PT J AU Boussiotis, VA Freeman, GJ Berezovskaya, K Barber, DL Nadler, LM AF Boussiotis, VA Freeman, GJ Berezovskaya, K Barber, DL Nadler, LM TI Activated Rap1 and its downstream targets block IL-2 gene transcription and induce T cell anergy. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1912 EP 1912 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401908 ER PT J AU Pless, M Palmer, D Callus, B Rebel, V MatheyPrevot, B AF Pless, M Palmer, D Callus, B Rebel, V MatheyPrevot, B TI The cytoplasmic alpha-chain of the interleukin-5 receptor determines selectivity in the signaling receptor. SO BLOOD LA English DT Meeting Abstract C1 KANTONSSPITAL,DEPT ONCOL,CH-4031 BASEL,SWITZERLAND. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1922 EP 1922 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401918 ER PT J AU Kupfer, GM Naf, D Suliman, A Pulsipher, M DAndrea, AD AF Kupfer, GM Naf, D Suliman, A Pulsipher, M DAndrea, AD TI The Fanconi anemia proteins, FAA and FAC, bind and form a nuclear complex. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV PEDIAT ONCOL,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1924 EP 1924 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401920 ER PT J AU Yamashita, T Kupfer, G Joenje, H Asano, S DAndrea, AD AF Yamashita, T Kupfer, G Joenje, H Asano, S DAndrea, AD TI Phosphorylation of the Fanconi anemia protein, FAA, is required for signaling by the FA pathway. SO BLOOD LA English DT Meeting Abstract C1 UNIV TOKYO,INST MED SCI,TOKYO,JAPAN. FREE UNIV AMSTERDAM,DEPT HUMAN GENET,AMSTERDAM,NETHERLANDS. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV PEDIAT ONCOL,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1925 EP 1925 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401921 ER PT J AU Paw, BH Pratt, SJ Brownlie, A Trede, NS Oates, AC Guo, W Liao, EC Ransom, DG Postlethwait, J Zon, LI AF Paw, BH Pratt, SJ Brownlie, A Trede, NS Oates, AC Guo, W Liao, EC Ransom, DG Postlethwait, J Zon, LI TI The zebrafish blood mutant retsina: A genetic model for studying erythroid differentiation and dyserythropoiesis. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1957 EP 1957 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401953 ER PT J AU Shohet, SB Thevenin, BJM Sherman, IW Ballas, SK Diacovo, T vonAndrian, UH AF Shohet, SB Thevenin, BJM Sherman, IW Ballas, SK Diacovo, T vonAndrian, UH TI Modulation of increased sickle cell-endothelial adhesion in vivo. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV CALIF RIVERSIDE,RIVERSIDE,CA 92521. HARVARD UNIV,SCH MED,CTR BLOOD RES,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 1962 EP 1962 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42401958 ER PT J AU Beresford, PJ Jaju, M Yoon, MJ Lieberman, J AF Beresford, PJ Jaju, M Yoon, MJ Lieberman, J TI A role for the small heat shock protein HSP27 in cytotoxic T lymphocyte mediated cell death. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2020 EP 2020 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402016 ER PT J AU Voss, SD Ritz, J Robertson, MJ AF Voss, SD Ritz, J Robertson, MJ TI Participation of the CD94/NKG2 receptor complex in costimulation of human natural killer cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,SCH MED,BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2023 EP 2023 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402019 ER PT J AU Gardner, JP Rosenzweig, M Marks, DF Harper, D Gaynor, K Fallon, RJ Wall, DA Johnson, RP Scadden, DT AF Gardner, JP Rosenzweig, M Marks, DF Harper, D Gaynor, K Fallon, RJ Wall, DA Johnson, RP Scadden, DT TI T lymphopoietic capacity of cord blood-derived CD34(+) progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,NEW ENGLAND PRIMATE RES CTR,BOSTON,MA. ST LOUIS UNIV HOSP,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2118 EP 2118 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402114 ER PT J AU Uemura, N Salgia, R Ewaniuk, D Sattler, M Griffin, JD AF Uemura, N Salgia, R Ewaniuk, D Sattler, M Griffin, JD TI Overexpression of the adapter protein CRKL in hematopoietic cells alters cell morphology, motility and adhesion to extracellular matrix proteins. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2154 EP 2154 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402150 ER PT J AU Schmaltz, C Hardenbergh, PH Fisher, DE AF Schmaltz, C Hardenbergh, PH Fisher, DE TI Proliferation/survival decisions and p53 expression during tumor cell hypoxia. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2178 EP 2178 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402174 ER PT J AU Aguiar, RCT Yakushijin, Y Freeman, G Li, J Tantravahi, R Shipp, MA AF Aguiar, RCT Yakushijin, Y Freeman, G Li, J Tantravahi, R Shipp, MA TI Molecular characterization of a tissue-specific protein tyrosine phosphatase (PTP) and putative tumor suppressor which is down-regulated in high risk diffuse large B-cell lymphomas (DLB-CLs). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2185 EP 2185 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402181 ER PT J AU Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Makino, T Nakahara, K Takeuchi, S Arima, T Takahashi, H AF Suzuki, S Hanada, S Ishitsuka, K Uozumi, K Utsunomiya, A Makino, T Nakahara, K Takeuchi, S Arima, T Takahashi, H TI Chimeric SF-25 monoclonal antibody mediated apoptosis of adult T-cell leukemia cells by human blood lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. KAGOSHIMA UNIV,FAC MED,DEPT INTERNAL MED 2,KAGOSHIMA 890,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2288 EP 2288 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402284 ER PT J AU Ernst, TJ Vance, E Alyea, E Soiffer, R Quartulli, M Ritz, J AF Ernst, TJ Vance, E Alyea, E Soiffer, R Quartulli, M Ritz, J TI Homoharringtonine and low-dose Ara-C is a highly effective combination for the treatment of CML in chronic phase. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2305 EP 2305 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402301 ER PT J AU Alsina, M Choi, SJ Devlin, RD Cruz, JC Roodman, GD AF Alsina, M Choi, SJ Devlin, RD Cruz, JC Roodman, GD TI Assessment of the role of IL-1 beta in the pathogenesis of myeloma bone disease. SO BLOOD LA English DT Meeting Abstract C1 VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2346 EP 2346 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402342 ER PT J AU Cooke, KR Kobzik, L Hill, G Martin, TR Brewer, J Bungard, D Ferrara, JLM AF Cooke, KR Kobzik, L Hill, G Martin, TR Brewer, J Bungard, D Ferrara, JLM TI TNF alpha blockade reduces lung injury and abrogates pulmonary toxicity and mortality of LPS challenge after experimental bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DIV PEDIAT PULMONOL,DANA FARBER CANC INST,DIV PEDIAT PULMONOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2375 EP 2375 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402371 ER PT J AU Cooke, KR Krenger, W Martin, TR Kobzik, L Crawford, JM Simmons, R Brewer, J Ferrara, JLM AF Cooke, KR Krenger, W Martin, TR Kobzik, L Crawford, JM Simmons, R Brewer, J Ferrara, JLM TI Lung injury after experimental T cell depleted allogeneic BRIT is mediated by alloreactive donor T cells in the absence of GVHD. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DIV PEDIAT PULMONOL,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06510. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2376 EP 2376 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402372 ER PT J AU Adler, H Beland, JL Kozlow, W DelPan, NC Kobzik, L Rimm, IJ AF Adler, H Beland, JL Kozlow, W DelPan, NC Kobzik, L Rimm, IJ TI A role for transforming growth factor-beta (TGF-beta) in the increased pneumonitis in murine allogeneic bone marrow transplant recipients with GVHD after pulmonary herpes simplex virus-type 1 (HSV-1) infection. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2377 EP 2377 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402373 ER PT J AU Vance, EA Ritz, J Soiffer, R AF Vance, EA Ritz, J Soiffer, R TI CMV infection and disease following T-cell depleted allogeneic BMT: The influence of serologic status. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2422 EP 2422 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402418 ER PT J AU Alyea, EP Canning, C Soiffer, RJ Ritz, J AF Alyea, EP Canning, C Soiffer, RJ Ritz, J TI Prolonged time to cytogenetic and molecular response in patients with relapsed chronic myelogenous leukemia (CML) after donor lymphocyte infusion (DLI). SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2442 EP 2442 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402438 ER PT J AU Porter, DL Collins, R Drobyski, W Connors, JM VanHoef, M Antin, J AF Porter, DL Collins, R Drobyski, W Connors, JM VanHoef, M Antin, J TI Long term follow-up of 55 patients who achieved complete remission (CR) after donor leukocyte infusions (DLI) for relapse after allogeneic bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. BAYLOR UNIV,MED CTR,DALLAS,TX. MED COLL WISCONSIN,MILWAUKEE,WI 53226. INT BONE MARROW TRANSPLANT REGISTRY,MILWAUKEE,WI. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2444 EP 2444 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402440 ER PT J AU Porter, DL Connors, JM Doyle, B McGarigle, C Saidman, S VanDeerlin, V Leonard, D Antin, JH AF Porter, DL Connors, JM Doyle, B McGarigle, C Saidman, S VanDeerlin, V Leonard, D Antin, JH TI Donor leukocyte infusions (DLI) as primary allogeneic adoptive immunotherapy for patients with malignancies. SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,DIV HEMATOL ONCOL,PHILADELPHIA,PA 19104. UNIV PENN,CANC CTR MOL CORE FACIL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2445 EP 2445 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402441 ER PT J AU Orsini, E Alyea, EP Schlossman, R Soiffer, RJ Anderson, KC Ritz, J AF Orsini, E Alyea, EP Schlossman, R Soiffer, RJ Anderson, KC Ritz, J TI Expansion of pre-existing clonal populations following donor lymphocyte infusion for relapsed multiple myeloma after allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2446 EP 2446 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402442 ER PT J AU Williams, CD Dranoff, G Mulligan, R Griffin, JD AF Williams, CD Dranoff, G Mulligan, R Griffin, JD TI Hematopoietic cytokines enhance adenovirus-mediated gene transfer into primary human acute myeloblastic leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2461 EP 2461 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402457 ER PT J AU Adler, HT Nallaseth, FS Walter, G Tkachuk, DC AF Adler, HT Nallaseth, FS Walter, G Tkachuk, DC TI Evidence that HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein set and protein phosphatase 2A. SO BLOOD LA English DT Meeting Abstract C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE DIV,SEATTLE,WA. UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2478 EP 2478 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402474 ER PT J AU Dalton, VMK Gelber, RD Donnelly, MJ Tarbell, NJ Sallan, SE AF Dalton, VMK Gelber, RD Donnelly, MJ Tarbell, NJ Sallan, SE TI Second malignant neoplasms (SMN) in children treated for acute lymphoblastic leukemia (ALL). SO BLOOD LA English DT Meeting Abstract C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2491 EP 2491 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402487 ER PT J AU Boussiotis, VA Berezovskaya, A Guinan, EC Gribben, JG Barber, DL Nadler, LM AF Boussiotis, VA Berezovskaya, A Guinan, EC Gribben, JG Barber, DL Nadler, LM TI In the presence of a T cell receptor (TCR) signal, rapamycin but not cyclosporin-A, inhibits CD28 and IL-2 mediated pathways resulting in the induction of anergy. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2505 EP 2505 PN 1 PG 2 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402501 ER PT J AU Vescio, R Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J AF Vescio, R Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J TI Increase in circulating tumor cell burden during mobilization chemotherapy predicts for relapse after autologous transplantation in multiple myeloma patients. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. UNIV TORONTO, TORONTO, ON M5S 1A1, CANADA. UNIV S FLORIDA, TAMPA, FL 33620 USA. UCSF, SAN FRANCISCO, CA USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. UNIV NEBRASKA, LINCOLN, NE 68583 USA. LOYOLA UNIV, NEW ORLEANS, LA 70118 USA. BAYLOR UNIV, WACO, TX 76798 USA. ARIZONA CANC CTR, TUCSON, AZ 90034 USA. UCSD, SAN DIEGO, CA USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2515 EP 2515 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402511 ER PT J AU Vescio, R Wu, C Rettig, M Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J AF Vescio, R Wu, C Rettig, M Stewart, A Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Kogut, N Tarantolo, S Stiff, P Pinero, L Dalton, W Ho, A Schiller, G Benyunes, M Jacobs, C Dipersio, J Anderson, K Berenson, J TI The detection of KSHV is increased by mobilization chemotherapy and reduced in autografts by CD34-selection. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, LOS ANGELES, CA USA. UNIV TORONTO, TORONTO, ON M5S 1A1, CANADA. UNIV S FLORIDA, TAMPA, FL 33620 USA. UCSF, SAN FRANCISCO, CA USA. UNIV TEXAS SAN ANTONIO, SAN ANTONIO, TX 78285 USA. UNIV PENN, PHILADELPHIA, PA 19104 USA. UNIV NEBRASKA, LINCOLN, NE 68583 USA. LOYOLA UNIV, NEW ORLEANS, LA 70118 USA. BAYLOR UNIV, WACO, TX 76798 USA. ARIZONA CANC CTR, TUCSON, AZ 90034 USA. UCSD, SAN DIEGO, CA USA. UNIV WASHINGTON, SEATTLE, WA 98195 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 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2516 EP 2516 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402512 ER PT J AU Hartwell, DW Mayadas, TN Frenette, SP Rayburn, H Hynes, OR Denisa, D Wagner, D AF Hartwell, DW Mayadas, TN Frenette, SP Rayburn, H Hynes, OR Denisa, D Wagner, D TI Characterization of mice expressing p-selectin with a deleted cytoplasmic domain. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,CAMBRIDGE,MA 02138. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2523 EP 2523 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402519 ER PT J AU Diacovo, TG Catalina, MD Siegelman, MH vonAndrian, UH AF Diacovo, TG Catalina, MD Siegelman, MH vonAndrian, UH TI Circulating-activated platelets reconstitute lymphocyte homing and immunity in L-selectin deficient mice. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV TEXAS,DEPT PATHOL,DALLAS,TX 75230. TUFTS UNIV,SCH MED,NEMC,DEPT PEDIAT,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2524 EP 2524 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402520 ER PT J AU Mari, B Anderson, I Moses, M Wiederschain, D Mari, S Shipp, MA AF Mari, B Anderson, I Moses, M Wiederschain, D Mari, S Shipp, MA TI bFGF is released by fibroblasts in tumor/stroma cocultures: Implications for the ''angiogenic switch'' in primary epithelial malignancies. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,DANA FARBER CANC INST,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV SURG RES,BOSTON,MA. RI Mari, Bernard/F-8960-2013; Mari, Bernard/D-7445-2015 OI Mari, Bernard/0000-0002-0422-9182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2527 EP 2527 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402523 ER PT J AU Tsang, AP Fujiwara, Y Hom, DB Orkin, SH AF Tsang, AP Fujiwara, Y Hom, DB Orkin, SH TI The GATA-1 cofactor FOG (friend of GATA-1) is essential for normal erythroid differentiation and megakaryocyte development. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2559 EP 2559 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402555 ER PT J AU Shen, H Cheng, T Yang, O Tomasson, M Golan, DE Preffer, FI Luster, AD Scadden, DT AF Shen, H Cheng, T Yang, O Tomasson, M Golan, DE Preffer, FI Luster, AD Scadden, DT TI Expression of HIV-1 receptors is insufficient for infection of hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,AIDS RES CTR,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2567 EP 2567 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402563 ER PT J AU Kuter, D McCullough, J Romo, J DiPersio, J Peterson, R Armstrong, S Menchaca, D Tomita, D Goodnough, LT AF Kuter, D McCullough, J Romo, J DiPersio, J Peterson, R Armstrong, S Menchaca, D Tomita, D Goodnough, LT TI Treatment of platelet (PLT) donors with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increases circulating PLT counts (CTS) and PLT apheresis yields and increases platelet increments in recipients of PLT transfusions. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. WASHINGTON UNIV,MED CTR,ST LOUIS,MO 63130. AMGEN INC,THOUSAND OAKS,CA 91320. NR 0 TC 2 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2579 EP 2579 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402575 ER PT J AU Glaspy, J Vredenburgh, J Demetri, GD Chap, L Gilbert, C Overmoyer, B Warren, DL Berg, R Scarlata, D Menchaca, D Bolwell, B AF Glaspy, J Vredenburgh, J Demetri, GD Chap, L Gilbert, C Overmoyer, B Warren, DL Berg, R Scarlata, D Menchaca, D Bolwell, B TI Effects of PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) before high dose chemotherapy (HDC) with peripheral blood progenitor cell (PBPC) support. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. DUKE UNIV,MED CTR,DURHAM,NC 27706. DANA FARBER CANC CTR,BOSTON,MA. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. AMGEN INC,THOUSAND OAKS,CA. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2582 EP 2582 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402578 ER PT J AU Cardoso, AA Afonso, HM Ghia, P Veiga, JP Sallan, SE Nadler, LM AF Cardoso, AA Afonso, HM Ghia, P Veiga, JP Sallan, SE Nadler, LM TI Ex-vivo generated autologous anti-leukemia specific T cells: Evidence for transendothelial migration and function in the presence of bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2602 EP 2602 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402598 ER PT J AU Berenson, J Rettig, M Heppner, K Vescio, R Ma, H Schiller, G Belson, D Savage, A Nishikubo, C Shintaku, I Koeffler, H Asou, H Pinkus, G Schrage, M Green, E Said, J AF Berenson, J Rettig, M Heppner, K Vescio, R Ma, H Schiller, G Belson, D Savage, A Nishikubo, C Shintaku, I Koeffler, H Asou, H Pinkus, G Schrage, M Green, E Said, J TI Bone marrow biopsies from bone multiple myeloma patients contain Kaposi's sarcoma-associated herpesvirus. SO BLOOD LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2612 EP 2612 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402608 ER PT J AU Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Nadler, L Anderson, KC AF Treon, SP Mollick, JA Urashima, M Teoh, G Chauhan, D Ogata, A Nadler, L Anderson, KC TI Muc-1 expression in multiple myeloma cells is upregulated by dexamethasone. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2615 EP 2615 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402611 ER PT J AU Alyea, EP Chillemi, A Canning, C Soiffer, RJ Ritz, J AF Alyea, EP Chillemi, A Canning, C Soiffer, RJ Ritz, J TI Allogeneic graft-versus-leukemia is directed against host hematopoietic antigens and is not leukemia specific as determined by cytogenetic and molecular analysis in patients with CML following donor lymphocyte infusion. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2620 EP 2620 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402616 ER PT J AU Porter, D Collins, R Mick, R Kernan, N Giralt, S Flowers, M Casper, J Drobyski, W Leahey, A Parker, P Bates, B King, R Antin, J AF Porter, D Collins, R Mick, R Kernan, N Giralt, S Flowers, M Casper, J Drobyski, W Leahey, A Parker, P Bates, B King, R Antin, J TI Unrelated donor leukocyte infusions (U-DLI) to treat relapse or EBV-lymphoproliferative disease (EBV-LPD) after unrelated donor bone marrow transplantation (BMT). SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. BAYLOR UNIV,WACO,TX 76798. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. MED COLL WISCONSIN,MILWAUKEE,WI 53226. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2622 EP 2622 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402618 ER PT J AU MachPascual, S Legare, RD Lu, D Kroon, M Neuberg, D Stone, RM Freedman, AS Nadler, LM Gribben, JG Gilliland, DG AF MachPascual, S Legare, RD Lu, D Kroon, M Neuberg, D Stone, RM Freedman, AS Nadler, LM Gribben, JG Gilliland, DG TI Predictive value of clonality analysis in patients with non-Hodgkin's lymphoma (NHL) undergoing autologous bone marrow transplant (ABMT): A single institution study. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2626 EP 2626 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402622 ER PT J AU Shpall, EJ Wheeler, CA Turner, SA Yanovich, S Brown, RA Pecora, AL Shea, TC Mangan, KF Williams, SF LeMaistre, CF Long, GD MurphyFilkins, R Parker, W Glaspy, JA AF Shpall, EJ Wheeler, CA Turner, SA Yanovich, S Brown, RA Pecora, AL Shea, TC Mangan, KF Williams, SF LeMaistre, CF Long, GD MurphyFilkins, R Parker, W Glaspy, JA TI A randomized phase 3 study of PBPC mobilization by stem cell factor (SCF, STEMGEN(R)) and Filgrastim in patients with high-risk breast cancer. SO BLOOD LA English DT Meeting Abstract C1 UNIV COLORADO,BOULDER,CO 80309. DANA FARBER CANC INST,BOSTON,MA 02115. AMGEN INC,THOUSAND OAKS,CA 91320. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. HACKENSACK U,HACKENSACK,NJ. LINEBURGER CANC CTR,CHAPEL HILL,NC. TEMPLE UNIV,PHILADELPHIA,PA 19122. STANFORD MED CTR,STANFORD,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NR 0 TC 2 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2627 EP 2627 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402623 ER PT J AU Rebel, VI Tanaka, M Lee, JS Nathan, DG Mulligan, RC Sieff, CA AF Rebel, VI Tanaka, M Lee, JS Nathan, DG Mulligan, RC Sieff, CA TI Efficient gene transfer into human NOD/SCID repopulating cells using high titer VSV-G pseudotyped retrovirus. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2668 EP 2668 PN 1 PG 1 WC Hematology SC Hematology GA YG424 UT WOS:A1997YG42402664 ER PT J AU Grabowski, EF Ebb, DH McMahon, LC AF Grabowski, EF Ebb, DH McMahon, LC TI Enhanced hemoglobin F production in an eight-year-old with sickle cell disease receiving weekly IV methotrexate and daily oral 6-mercaptopurine for acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 BOSTON MED CTR,DEPT PEDIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2805 EP 2805 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500115 ER PT J AU NisbetBrown, E Waye, JS Olivieri, NF AF NisbetBrown, E Waye, JS Olivieri, NF TI Unusually severe presentation of sickle cell disease in patients with triplicated and quadruplicated alpha gene loci SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. MCMASTER UNIV,MED CTR,HAMILTON,ON,CANADA. HOSP SICK CHILDREN,TORONTO,ON M5G 1X8,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2821 EP 2821 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500131 ER PT J AU Bunting, R Selig, M AF Bunting, R Selig, M TI Nuclear trash: DNA dumping in patients with low serum cobalamin. SO BLOOD LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. SPAULDING REHABIL HOSP,DEPT HEMATOL,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2869 EP 2869 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500179 ER PT J AU Trimble, LA Lieberman, J AF Trimble, LA Lieberman, J TI Circulating CD8 T lymphocytes in HIV-infected individuals have impaired function and downmodulate CD3 zeta, signaling chain of the T cell receptor complex. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 2952 EP 2952 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500262 ER PT J AU Grabowski, EF Boor, SE Carter, C Gori, J Kim, M AF Grabowski, EF Boor, SE Carter, C Gori, J Kim, M TI Shear stress downregulates the expression of tissue factor by activated endothelial cells. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3041 EP 3041 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500351 ER PT J AU Herbert, V AF Herbert, V TI Two steps to eliminate the chronic US blood donor shortage. 1. Add serum transferrin saturation to the routine blood screen on first doctor visit. 2. Give high iron blood to those who need blood. SO BLOOD LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3306 EP 3306 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500616 ER PT J AU Bastian, LS Kwiatkowski, B Danner, S Roth, G AF Bastian, LS Kwiatkowski, B Danner, S Roth, G TI Regulation of the megakaryocytic glycoprotein IX promoter by GATA-1 and Fli-1. SO BLOOD LA English DT Meeting Abstract C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3404 EP 3404 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500714 ER PT J AU Yang, C Xia, YP Kuter, DJ AF Yang, C Xia, YP Kuter, DJ TI The HepG2 cell as a model system for studying thrombopoietin production and regulation. SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HEMATOL ONCOL UNIT,BOSTON,MA. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3427 EP 3427 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500737 ER PT J AU Liou, JR Liu, TC Kaneki, M Zaleskas, JM Stone, RM AF Liou, JR Liu, TC Kaneki, M Zaleskas, JM Stone, RM TI Cytosolic down-regulation of mitogen-activated protein kinases during bryostatin 1-induced monocytic differentiation in human myeloid leukemia HL-60 cells pretreated with all-trans retinoic acid SO BLOOD LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3450 EP 3450 PN 2 PG 2 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500760 ER PT J AU Connors, JM Kronauge, J Castronovo, F Mannting, F Jones, A Sieff, C Antin, JH AF Connors, JM Kronauge, J Castronovo, F Mannting, F Jones, A Sieff, C Antin, JH TI Pharmacokinetics and biodistribution of In-111-DTPA-G-CSF non-human primates. SO BLOOD LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DANA FARBER PARTNERS CANC CARE,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3548 EP 3548 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500858 ER PT J AU Chen, TY Verma, S Shrikhande, G Ittel, L Salgia, R Griffin, JD Sattler, M AF Chen, TY Verma, S Shrikhande, G Ittel, L Salgia, R Griffin, JD Sattler, M TI BCR/ABL induces differential signaling through the related proteins CBL and CBL-B. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3590 EP 3590 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42500900 ER PT J AU Paietta, E Neuberg, D Bennett, JM Rowe, JM Cassileth, PA Wiernik, PH AF Paietta, E Neuberg, D Bennett, JM Rowe, JM Cassileth, PA Wiernik, PH TI Novel definition of undifferentiated (UNDIF) acute myeloid leukemia (AML) by low expression of the CD65s carbohydrate molecule: Analysis of 996 patients from the ECOG database. SO BLOOD LA English DT Meeting Abstract C1 MONTEFIORE & ALBERT EINSTEIN CANC CTR,BRONX,NY. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,ROCHESTER,NY. EASTERN COOPERAT ONCOL GRP,BROOKLINE,MA. UNIV MIAMI,MIAMI,FL 33152. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 3723 EP 3723 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501033 ER PT J AU Aiba, Y Ogawa, M AF Aiba, Y Ogawa, M TI Development of natural killer cells, B lymphocytes, macrophages, and mast cells from single hematopoietic progenitors in culture of murine fetal liver cells SO BLOOD LA English DT Article ID LYMPHOHEMATOPOIETIC PROGENITORS; MONOCLONAL-ANTIBODY; BONE-MARROW; STEM-CELLS; NK CELLS; LYMPHOID DIFFERENTIATION; NEGATIVE REGULATION; T-CELLS; C-KIT; MOUSE AB We have recently established a clonal culture system that supports the growth of immature natural killer (NK) cells from murine fetal thymocytes. We now describe a culture system for mixed NK cell colony formation from single lymphohematopoietic progenitors, When Sca-1(+)c-kit(+) fetal liver cells were cultured in methylcellulose media with interleukin (IL)-2, IL-7, IL-11, and steel factor (SF), we found mixed colonies consisting of diffuse small round cells characteristic of immature NK cells and other types of cells. The single cell origin of the mixed colonies was established by micromanipulation, Individual mixed colonies derived from single cells were characterized by flow cytometric analysis and May-Grunwald Giemsa staining. All mixed colonies contained Thy-1(+)B220(-) cells, which can differentiate to mature NK cells in fetal thymus organ culture. Most of the colonies contained B220(+) B-lineage cells and macrophages, and some contained mast cells. IL-1 alpha and IL-3, which have previously been shown to inhibit the T- and B-cell potentials of blast colonies, suppressed the formation of mixed NK cell colonies, The clonal culture assay presented here may be useful in analysis of the developmental pathway and commitment of NK cells from multipotential progenitors. (C) 1997 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC. FU NIDDK NIH HHS [DK/HL48714, DK32294] NR 37 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 3923 EP 3930 PG 8 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900012 PM 9354659 ER PT J AU Urashima, M DeCaprio, JA Chauhan, D Teoh, G Ogata, A Treon, SP Hoshi, Y Anderson, KC AF Urashima, M DeCaprio, JA Chauhan, D Teoh, G Ogata, A Treon, SP Hoshi, Y Anderson, KC TI p16(INK4A) promotes differentiation and inhibits apoptosis of JKB acute lymphoblastic leukemia cells SO BLOOD LA English DT Article ID DEPENDENT KINASE INHIBITORS; HOMOZYGOUS DELETIONS; FAMILIAL MELANOMA; TUMOR-SUPPRESSOR; MULTIPLE-MYELOMA; P16 GENE; LUNG-CANCER; INACTIVATION; MUTATIONS; PROTEIN AB Homozygous p16(INK4A) (p16) gene deletion is frequent in primary tumor cells from acute lymphoblastic leukemia (ALL), suggesting that loss of p16 may be an important precursor to transformation in ALL. We have previously described JKB, a human ALL cell line, that contains homozygous deletion of the p16 gene. Because ectopic expression of p16 suppresses cell growth, we created a temperature sensitive p16 mutant to develop a system for inducible p16 function in human ALL. JKB cells were transfected either with a p16 gene mutated at position 119 (E119G) to confer temperature sensitivity (JKB p16MT) or with control vector. The percentage of cells in G1 phase was similar in JKB control cells or in JKB p16MT cells cultured at restrictive conditions (40 degrees C). However, with lowering of temperature from 40 degrees C to permissive conditions (31 degrees C), the percentage of JKB p16MT cells in G1 phase and binding of p16 to CDK4 and CDK6 increased, with associated decreases in CDK4 and CDK6 kinase activities, and dephosphorylation of retinoblastoma protein (pRB). Culture of JKB p16MT cells at 31 degrees C for greater than or equal to 13 days irreversibly inhibited growth. Moreover, JKB p16MT cells cultured under these permissive conditions showed a less transformed morphology and more differentiated phenotype than did these cells cultured under restrictive temperatures. Finally, dexamethasone (Dex) induced apoptosis of JKB p16MT cells cultured at 40 degrees C, but did not trigger death of these cells cultured at 31 degrees C. These results suggest that deletion of p16 gene in JKB human ALL cells is associated with dysregulated growth of less differentiated tumor cells, which nonetheless remain susceptible to apoptosis triggered by Dex. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA. HARVARD UNIV,SCH MED,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA 50947] NR 46 TC 30 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4106 EP 4115 PG 10 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900034 PM 9354681 ER PT J AU Eichbaum, Q Heney, D Raveh, D Chung, M Davidson, M Epstein, J Ezekowitz, RAB AF Eichbaum, Q Heney, D Raveh, D Chung, M Davidson, M Epstein, J Ezekowitz, RAB TI Murine macrophage mannose receptor promoter is regulated by the transcription factors PU.1 and SP1 SO BLOOD LA English DT Article ID CCAAT DISPLACEMENT PROTEIN; RNA POLYMERASE-II; INTERFERON-GAMMA; DOWN-REGULATION; ALVEOLAR MACROPHAGES; GENE-EXPRESSION; FACTOR GATA-1; ETS ONCOGENE; DNA-SEQUENCE; INITIATOR AB The mannose receptor (MR) is a transmembrane protein that functions primarily as a phagocytic receptor for a wide range of microorganisms. Its expression appears to be restricted to tissue macrophages and Langerhans cells. To gain an understanding of the regulation of the gene, we have isolated the 5' flanking sequence of the murine MR gene and have analyzed a 536-bp sequence upstream of the ATG start site for transcriptional activity. This sequence lacks a TATA box but contains an initiator (Inr) consensus element overlapping the single transcriptional start site, Transcription factor binding sites contained within this sequence include PU.1, Spl, ETS, GATA, and MYB motifs. Serial 100-bp deletions of this promoter fragment fused to a luciferase reporter gene showed various patterns of activity when transfected into different cell types. In myeloid cells, sequence elements upstream of bp-300 appeared to have a silencing effect on promoter activity. Of the four potential PU.1 binding sites contained within the fragment, one site (at -164) bound the PU.1 factor most strongly, whereas the adjacent PU.1 site (at -177 bp) bound PU.1 to a lesser degree. Mutations of these sites decreased transcriptional activity but did not abolish it. However, promoter activity was abrogated when both the -164 bp PU.1 site and the adjacent -177 bp PU.1 site were mutated. In addition, mutation of the Spl site also significantly reduced promoter activity. Cotransfection studies' in Drosophila Schneider cells indicated that PU.1 and Spl may function synergistically in transactivating the murine MR. This study indicates that MR gene expression is regulated in part by the interaction between the ubiquitously expressed factor Spl and the lymphoid/myeloid factor PU.1 and provides a basis for studying the regulation of this gene. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,DEPT PEDIAT,SERV PEDIAT,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. CHILDRENS HOSP,DIV INFECT DIS & HEMATOL ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL43510, R01HL48929] NR 49 TC 51 Z9 52 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4135 EP 4143 PG 9 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900037 PM 9354684 ER PT J AU Andersen, NS Donovan, JW Borus, JS Poor, CM Neuberg, D Aster, JC Nadler, LM Freedman, AS Gribben, JG AF Andersen, NS Donovan, JW Borus, JS Poor, CM Neuberg, D Aster, JC Nadler, LM Freedman, AS Gribben, JG TI Failure of immunologic purging in mantle cell lymphoma assessed by polymerase chain reaction detection of minimal residual disease SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; T(11-14) CHROMOSOME-TRANSLOCATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMAS; HIGH-DOSE THERAPY; FOLLICULAR LYMPHOMA; BCL-2 TRANSLOCATION; SOMATIC MUTATIONS; GENES; RELAPSE AB To assess the clinical significance of minimal residual disease (MRD) detection by polymerase chain reaction (PCR) we analyzed samples from 26 patients with mantle cell lymphoma (MCL) who had undergone bone marrow transplantation (BMT) at the Dana-Farber Cancer Institute. The BCL-1/lgH translocation and clonally rearranged lg heavy chain genes (lgH) provided molecular markers for detection and follow-up of MRD by polymerase chain reaction (PCR) amplification in 19 of the 26 (73%) MCL patients studied. lgH gene sequencing analysis showed somatic mutations in MCL that are characteristic of an antigen driven process suggesting that, in MCL, the final malignant transformation occurs in a mature B cell. Of the 19 patients with a PCR amplifiable marker, 17 underwent autologous, 1 an allogeneic, and 1 a syngeneic bone marrow transplantation (BMT). All patients had PCR-detectable MRD in the bone marrow (BM) at the time of BMT, irrespective of any history of histological BM involvement. In contrast to other B-cell malignancies, we found that immunological purging with complement-mediated lysis eradicated PCR-detectable MCL in only two patients. Moreover reinfusion of MRD was associated with a poor outcome. More than half of the patients undergoing autologous BMT had relapsed by the time of restaging at 2 years after autologous BMT. In four MCL patients in whom no residual lymphoma was reinfused, including the allogeneic and the syngeneic BMT, only one patient relapsed. Persistence of MRD detection after BMT was also associated with a high probability of relapse, although one patient did not have PCR-detectable MRD in peripheral blood or BM before relapse at nodal sites. We conclude that PCR amplification of disease-specific markers is a feasible and sensitive method to assess MRD and its clinical significance in patients with MCL. Moreover, PCR amplification provides a tool to evaluate modifications of purging and stem cell collection procedures that may be required for the management of this otherwise incurable disease. (C) 1997 by The American Society of Hematology. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA66996] NR 45 TC 123 Z9 124 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4212 EP 4221 PG 10 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900047 PM 9354694 ER PT J AU Sato, T Ohashi, Y Tachibana, K Soiffer, RJ Ritz, J Morimoto, C AF Sato, T Ohashi, Y Tachibana, K Soiffer, RJ Ritz, J Morimoto, C TI Altered tyrosine phosphorylation via the very late antigen (VLA)/beta 1 integrin stimulation is associated with impaired T-cell signaling through VLA-4 after allogeneic bone marrow transplantation SO BLOOD LA English DT Article ID FOCAL ADHESION KINASE; PP125(FAK); PROTEIN; FIBRONECTIN; ACTIVATION; PAXILLIN; IDENTIFICATION; RECONSTITUTION; INTERLEUKIN-2; INFECTION AB Our previous study showed that the cross-linking of very late antigen (VLA)/beta 1 with anti-CD29 monoclonal antibody (MoAb), or interactions with extracellular matrix (ECM) proteins through VLA/beta 1, failed to induce T-cell costimulation via the CD3/T cell receptor (TCR) pathway for over 1 year after allogeneic bone marrow transplantation (allo-BMT), although normal CD29 and CD3 expression was observed after 3 months following allo-BMT. Molecular analysis revealed altered tyrosine phosphorylation of cellular proteins by the solid-phase cross-linking of VLA/beta 1 molecules in T cells from patients after allo-BMT. In T cells from early allo-BMT patients (<4 months), various sizes of highly tyrosine phosphorylated proteins were observed as high background even without the stimulation through VLA/beta 1 integrin. The high tyrosine phosphorylation pattern gradually disappeared and it was finally returned to normal tyrosine phosphorylation patterns by 2 years after BMT. Interestingly, poor expression of focal adhesion kinase (pp125(FAK)), a VLA/beta 1-mediated signaling molecule, was observed within 1 year after BMT. These results suggest that these molecular defects appear to be implicated in the impaired VLA/beta 1-mediated signaling in T cells from patients after allo-BMT, and it could explain, in part, the persistent immunoincompetent state after allo-BMT at least 1 year. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DEPT MED,BOSTON,MA 02115. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 32 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 BP 4222 EP 4229 PG 8 WC Hematology SC Hematology GA YF299 UT WOS:A1997YF29900048 PM 9354695 ER PT J AU Avigan, D Gong, J Chen, D Milano, J Chen, L Anderson, K Kufe, D AF Avigan, D Gong, J Chen, D Milano, J Chen, L Anderson, K Kufe, D TI Functionally active dendritic cells (DC) are generated from GM-CSF and G-CSF or G-CSF alone mobilized peripheral blood progenitor cells (PBPC) from patients with advanced breast cancer undergoing autologous transplantation. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BETH ISRAEL DEACONESS MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4276 EP 4276 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501585 ER PT J AU Eppich, H Gaynor, K Gardner, JP Preffer, FI Dombkowski, D SilvaArrieta, S Mangano, JA Pugh, ER Scadden, DT AF Eppich, H Gaynor, K Gardner, JP Preffer, FI Dombkowski, D SilvaArrieta, S Mangano, JA Pugh, ER Scadden, DT TI Pulsed electric fields function to size-select hematopoietic cells and deplete tumor cell contaminants. SO BLOOD LA English DT Meeting Abstract C1 SCI RES LAB INC,SOMERVILLE,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,AIDS RES CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4326 EP 4326 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501635 ER PT J AU Chauncey, TR Thompson, AR Stewart, L Gooley, T McDonald, GB AF Chauncey, TR Thompson, AR Stewart, L Gooley, T McDonald, GB TI No association between activated protein C (APC) resistance and hepatic venoocclusive disease (VOD) following stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. PUGET SOUND BLOOD CTR,VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98104. UNIV WASHINGTON,SCH MED,SEATTLE,WA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4353 EP 4353 PN 2 PG 2 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501662 ER PT J AU Cirenza, E Duma, C McAfee, S Scavone, ME Spitzer, T AF Cirenza, E Duma, C McAfee, S Scavone, ME Spitzer, T TI Do the numbers of mononuclear cells/KG, CFU-GM/KG, OR CD34+ cells/KG correlate with long term (1 year) engraftment? SO BLOOD LA English DT Meeting Abstract C1 ALBANY MED CTR,ALBANY,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4354 EP 4354 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501663 ER PT J AU Demetri, GD Stefanowicz, L Geiger, EA Xu, G Richardson, P Elias, AD AF Demetri, GD Stefanowicz, L Geiger, EA Xu, G Richardson, P Elias, AD TI Dose intensification of liposome-encapsulated daunorubicin (Daunoxome(R)) with Filgrastim support in patients (PTS) with solid tumors. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4357 EP 4357 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501666 ER PT J AU Ramaswamy, S Schlossman, RL Doss, D Vance, EA AF Ramaswamy, S Schlossman, RL Doss, D Vance, EA TI EBV associated lymphoproliferative disorder following autologous BMT with CD34+ stem cell support. SO BLOOD LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4431 EP 4431 PN 2 PG 2 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501740 ER PT J AU Porter, D Schenkein, D Rauch, A Longtine, J Miller, K Antin, J AF Porter, D Schenkein, D Rauch, A Longtine, J Miller, K Antin, J TI Unusual pattern of relapse after donor leukocyte infusions (DLI) for relapsed CML: Lack of graft-v-leukemia (GVL) effect for isolated chloromas. SO BLOOD LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. ALBANY MED CTR,ALBANY,NY. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4473 EP 4473 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501782 ER PT J AU Wheeler, C Khurshid, A Ibrahim, J Elias, A Mauch, P Antin, J AF Wheeler, C Khurshid, A Ibrahim, J Elias, A Mauch, P Antin, J TI Low incidence of post-transplant myelodysplasia acute leukemia (MDS/AML) in NHL patients autotransplanted after after cyclophosphamide, carmustine and etoposide (CBV). SO BLOOD LA English DT Meeting Abstract C1 BETH ISRAEL MED CTR,DIV HEMATOL ONCOL,BOSTON,MA. BRIGHAM & WOMENS HOSP,JOINT CTR RADIAT THERAPY,DEPT BIOSTAT,DANA FARBER CANC INST,BOSTON,MA 02115. 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 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4480 EP 4480 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501789 ER PT J AU Weinreb, S Yunis, EJ Cohn, G Zwirello, LB Stec, T Mitner, L Riswan, N Higby, D MakariJusdon, G Andrzejewski, C AF Weinreb, S Yunis, EJ Cohn, G Zwirello, LB Stec, T Mitner, L Riswan, N Higby, D MakariJusdon, G Andrzejewski, C TI Transplantation of multiple units of HLA mismatched human cord blood in the treatment of adult CML in accelerated phase: Results of initial studies. SO BLOOD LA English DT Meeting Abstract C1 BAYSTATE MED CTR,SPRINGFIELD,MA. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1997 VL 90 IS 10 SU 1 BP 4541 EP 4541 PN 2 PG 1 WC Hematology SC Hematology GA YG425 UT WOS:A1997YG42501850 ER PT J AU Greenberg, DB Kornblith, AB Herndon, JE Zuckerman, E Schiffer, CA Weiss, RB Mayer, RJ Wolchok, SM Holland, JC AF Greenberg, DB Kornblith, AB Herndon, JE Zuckerman, E Schiffer, CA Weiss, RB Mayer, RJ Wolchok, SM Holland, JC TI Quality of life for adult leukemia survivors treated on clinical trials of cancer and leukemia group B during the period 1971-1988 - Predictors for later psychologic distress SO CANCER LA English DT Article ID BONE-MARROW TRANSPLANTATION; ANTICIPATORY NAUSEA; CHEMOTHERAPY; ADJUSTMENT; ADAPTATION; ANXIETY; STRESS AB BACKGROUND. To identify predictors of psychosocial adjustment for survivors of adult acute leukemia, the adaptation of 206 survivors (77% with acute myelogenous leukemia, and 23% with acute lymphocytic leukemia) treated on any of 13 Cancer and Leukemia Group B trials during the period 1971-1988 was examined. METHODS. Survivors (median age, 41 years) who were at least 1 year from completion of all treatment (median, 5 years) were interviewed by telephone about psychologic symptoms; social, sexual, and vocational function; and beliefs about control over health. Standardized psychologic instruments were used to evaluate survivors' responses. RESULTS, Most survivors adapted well; however, 14% were 1.5 standard deviations above normal on the Global Severity Index of the Brief Symptom Inventory. Predictors of greater psychologic distress included less education, younger age, anticipatory distress during chemotherapy treatment, and the combination of more medical problems after treatment with poorer family function. Anticipatory nausea and distress during chemotherapy predicted persistent visceral distress later, which occurred with reminders of treatment. Anticipatory vomiting predicted a greater tendency toward cancer-related intrusive thoughts and avoidance of reminders. CONCLUSIONS. Patients experiencing anticipatory distress during treatment who are younger and less educated should be monitored for depressive syndromes later. (C) 1997 American Cancer Society. C1 MEM SLOAN KETTERING CANC CTR,DEPT PSYCHIAT & BEHAV SCI,NEW YORK,NY 10021. STAT OFF,CANC & LEUKEMIA GRP B,DURHAM,NC. UNIV MARYLAND,CTR CANC,DEPT MED,BALTIMORE,MD 21201. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,100 BLOSSOM ST,COX BLDG,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA12449, CA31946, CA33601] NR 31 TC 81 Z9 82 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1997 VL 80 IS 10 BP 1936 EP 1944 DI 10.1002/(SICI)1097-0142(19971115)80:10<1936::AID-CNCR10>3.0.CO;2-Z PG 9 WC Oncology SC Oncology GA YE286 UT WOS:A1997YE28600010 PM 9366296 ER PT J AU Stafford, RS Cyr, PL AF Stafford, RS Cyr, PL TI The impact of cancer on the physical function of the elderly and their utilization of health care SO CANCER LA English DT Article DE cancer; elderly; functional status; health resource utilization; patient satisfaction AB BACKGROUND. Controversy about whether cancer has an independent impact on patient quality of life led the authors to evaluate the effects of cancer on a range of quality-of-life and health care utilization measures within an elderly population. METHODS. The authors analyzed a nationally representative sample of 9745 elderly community-based Medicare beneficiaries sampled in the 1991 Medicare Current Beneficiary Survey. Of these, 1647 reported being diagnosed by a physician as having a malignancy that was not of the skin. Multiple logistic regression was used to identify the independent predictors of functional limitation, poor health status, health care utilization, and patient satisfaction with medical care. RESULTS. Cancer was reported by 17% of the elderly. Individuals with cancer reported poorer health, more limitations of the activities of daily living (ADLs) and the instrumental activities of daily living (IADLs), and greater health care utilization than individuals without cancer. For individuals with cancer, difficulty walking (38%) and getting out of a chair (21%) were the most commonly reported ADL limitations, whereas difficulty completing heavy housework (34%) and shopping (17%) were the most common IADL limitations. Carcinomas of the lung, prostate, and colon independently predicted poorer health status. Lung carcinoma was independently associated with more ADL limitations. Lung, bladder, and prostate carcinomas predicted increased health care utilization. Overall, cancer patients were at least as satisfied with their medical care as those without cancer. CONCLUSIONS. Cancer increased the use of health care resources and modestly reduced physical function. By identifying specific connections between cancer and physical function, these findings have implications for improving cancer care. [See editorial on pages 1883-6, this issue.] (C) 1997 American Cancer Society. C1 MASSACHUSETTS GEN HOSP,DIV GEN MED,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 28 TC 68 Z9 69 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1997 VL 80 IS 10 BP 1973 EP 1980 DI 10.1002/(SICI)1097-0142(19971115)80:10<1973::AID-CNCR15>3.0.CO;2-V PG 8 WC Oncology SC Oncology GA YE286 UT WOS:A1997YE28600015 PM 9366301 ER PT J AU Marsh, DJ Roth, S Lunetta, KL Hemminki, A Dahia, PLM Sistonen, P Zheng, ZM Caron, S vanOrsouw, NJ Bodmer, WF Cottrell, SE Dunlop, MG Eccles, D Hodgson, SV Jarvinen, H Kellokumpu, I Markie, D Neale, K Phillips, R Rozen, P Syngal, S Vijg, J Tomlinson, IPM Aaltonen, LA Eng, C AF Marsh, DJ Roth, S Lunetta, KL Hemminki, A Dahia, PLM Sistonen, P Zheng, ZM Caron, S vanOrsouw, NJ Bodmer, WF Cottrell, SE Dunlop, MG Eccles, D Hodgson, SV Jarvinen, H Kellokumpu, I Markie, D Neale, K Phillips, R Rozen, P Syngal, S Vijg, J Tomlinson, IPM Aaltonen, LA Eng, C TI Exclusion of PTEN and 10q22-24 as the susceptibility locus for juvenile polyposis syndrome SO CANCER RESEARCH LA English DT Article ID MULTILOCUS LINKAGE ANALYSIS; GENE AB Juvenile polyposis syndrome (JPS; MIM 174900) is an autosomal dominant condition with incomplete penetrance characterized by hamartomatous polyps of the gastrointestinal tract and a risk of gastrointestinal cancer. Gastrointestinal hamartomatous polyps are also present in Cowden syndrome (CS; MIM 158350) and Bannayan-Zonana syndrome (BZS; also called Ruvalcaba-Myhre-Smith syndrome; MIM 153480). The susceptibility locus for both CS and BZS has recently been identified as the novel tumor suppressor gene PTEN, encoding a dual specificity phosphatase, located at 10q23.3. A putative JPS locus, JP1, which most likely functions as a tumor suppressor, had previously been mapped to 10q22-24 in both familial and sporadic juvenile polyps. Given the shared clinical features of gastrointestinal hamartomatous polyps among the three syndromes and the coincident mapping of JP1 to the region of PTEN, we sought to determine whether JPS was allelic to CS and BZS by mutation analysis of PTEN and linkage approaches. Microsatellite markers spanning the CS/BZS locus (D10S219, D10S551, D10S579, and D10S541) were used to compute multipoint lod scores in eight informative families with JPS. lod scores of < -2.0 were generated for the entire region, thus excluding PTEN and any genes within the flanking 20-cM interval as candidate loci for familial JPS under our statistical models. In addition, analysis of PTEN using a combination of denaturing gradient gel electrophoresis and direct sequencing was unable to identify a germline mutation in 14 families sith JPS and 11 sporadic cases. Therefore, at least a proportion of JPS cases are not caused by germline PTEN alteration or by an alternative locus at 10q22-24. C1 DANA FARBER CANC INST,HUMAN CANC GENET UNIT,BOSTON,MA 02115. DANA FARBER CANC INST,PROGRAM POPULAT SCI,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT SCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. UNIV HELSINKI,HAARTMAN INST,DEPT MED GENET,FIN-00014 HELSINKI,FINLAND. FINNISH RED CROSS & BLOOD TRANSFUS SERV,FIN-00014 HELSINKI,FINLAND. UNIV HELSINKI,CENT HOSP,DEPT SURG 2,FIN-00014 HELSINKI,FINLAND. JOHN RADCLIFFE HOSP,IMPERIAL CANC RES FUND,CANC & IMMUNOGENET LAB,INST MOL MED,OXFORD OX3 9DU,ENGLAND. IMPERIAL CANC RES FUND,CANC GENET LAB,LONDON WC2A 3PX,ENGLAND. UNIV EDINBURGH,ROYAL INFIRM,DEPT SURG,EDINBURGH EH8 9YL,MIDLOTHIAN,SCOTLAND. PRINCESS ANNE HOSP,WESSEX REG GENET SERV,SOUTHAMPTON SO16 5YA,HANTS,ENGLAND. UNITED MED & DENT SCH GUYS & ST THOMAS HOSP,DEPT MED GENET,LONDON SE1 9RT,ENGLAND. ST MARKS HOSP,POLYPOSIS REGISTRY,HARROW HA1 3UJ,MIDDX,ENGLAND. BRIGHAM & WOMENS HOSP,DIV GASTROENTEROL,BOSTON,MA 02115. BETH ISRAEL MED CTR,DEPT MED,DIV GASTROENTEROL,MOL GENET SECT,BOSTON,MA 02115. TEL AVIV MED CTR & SCH MED,DEPT GASTROENTEROL,IL-64239 TEL AVIV,ISRAEL. ROYAL MARSDEN HOSP,INST CANC RES,SUTTON SM2 5PT,SURREY,ENGLAND. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. RP Marsh, DJ (reprint author), DANA FARBER CANC INST,DEPT ADULT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Dunlop, Malcolm/F-1973-2011; Marsh, Deborah/I-1491-2014; Aaltonen, Lauri/A-5375-2010; OI Dunlop, Malcolm/0000-0002-3033-5851; Marsh, Deborah/0000-0001-5899-4931; Aaltonen, Lauri/0000-0001-6839-4286; Eng, Charis/0000-0002-3693-5145; Bodmer, Walter/0000-0001-6244-9792 NR 28 TC 71 Z9 71 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1997 VL 57 IS 22 BP 5017 EP 5021 PG 5 WC Oncology SC Oncology GA YF745 UT WOS:A1997YF74500009 PM 9371495 ER PT J AU Hollsberg, P Scholz, C Anderson, DE Greenfield, EA Kuchroo, VK Freeman, GJ Hafler, DA AF Hollsberg, P Scholz, C Anderson, DE Greenfield, EA Kuchroo, VK Freeman, GJ Hafler, DA TI Expression of a hypoglycosylated form of CD86 (B7-2) on human T cells with altered binding properties to CD28 and CTLA-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MESSENGER-RNA; COSTIMULATORY SIGNALS; IN-VITRO; ACTIVATION; CLONES; PROLIFERATION; MOUSE; ACCUMULATION; INDUCTION; RECEPTORS AB CD80 (B7-1) and CD86 (B7-2) on APC provide a major costimulatory signal through interactions with CD28 on T cells. Absent from resting human T cells, CD86 is up-regulated early upon T cell activation, whereas CD80 expression appears later. Whereas T cell expression of CD80 has been implicated in costimulation, the functional significance of CD86 expression on T cells is unclear. We now demonstrate that CD86 expressed on human CD4(+) T cell clones does not provide a costimulatory signal for other CD4(+) T cell clones, Binding studies using CD28-Ig and CTLA-4-Ig fusion proteins demonstrate that CD86 expressed on T cells has significantly reduced binding affinity for CTLA-4 and no detectable binding to CD28. Biochemical analysis demonstrates that post-translational modifications of CD86 in human T cells are different from those of CD86-transfected Chinese hamster ovary cells or EBV-transformed B cells, in that T cells express a hypoglycosylated form of CD86 on the surface membrane. Thus, our results suggest that while CD86 is expressed on a number of different cell types, its costimulatory function and affinity for its ligands may be regulated by cell type-specific post-translational modifications. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Hollsberg, P (reprint author), Harvard Inst Med, Ctr Neurol Dis, Room 784,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [CA 40216]; NIAID NIH HHS [P01 AI 39671]; NINDS NIH HHS [NS 24247] NR 40 TC 49 Z9 49 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 1997 VL 159 IS 10 BP 4799 EP 4805 PG 7 WC Immunology SC Immunology GA YW262 UT WOS:000071914700019 PM 9366404 ER PT J AU Geissler, M Gesien, A Wands, JR AF Geissler, M Gesien, A Wands, JR TI Inhibitory effects of chronic ethanol consumption on cellular immune responses to hepatitis C virus core protein are reversed by genetic immunizations augmented with cytokine-expressing plasmids SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSE; ALCOHOLIC LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; ANTIGEN PRESENTATION; DNA VACCINATION; RISK-FACTORS; B VIRUS; INFECTION; CELLS; ANTIBODIES AB Chronic hepatitis C viral (HCV) infection is a major clinical problem in alcoholics with liver disease and may result from ethanol effects on the host immune response. To experimentally assess such effects, the DNA-based immunization approach was used to produce humoral and cellular immune responses against the HCV core protein in mice. Mice were fed an ethanol or isocaloric pair-fed control liquid diet followed by immunizations with HCV core DNA-expressing constructs. Chronic ethanol feeding was found to inhibit Th cell and CTL activities and substantially reduced cytokine secretion as well. In addition, a switch from Th1 to Th0 subtype was observed in proliferating CD4(+) T cells derived from chronic ethanol-fed mice, These immunosuppressive effects were directly due to ethanol since crossover experiments to an isocaloric control diet restored the defects in cellular immunity. Furthermore, we determined if coadministration of an IL-2 or GM-CSF DNA expression plasmid with a plasmid expressing the HCV core protein (pHCV2-2) would reverse the inhibitory effects of chronic ethanol feeding on cellular immune responses, Coimmunization of chronic ethanol-fed mice with either IL-2 or GM-CSF expression plasmids restored cellular immunity and induced CD4(+) inflammatory T cell and CD8(+) CTL responses comparable with control mice immunized with pHCV2-2 alone. These studies provide evidence of how chronic ethanol feeding may effect cellular immune responses to a viral structural protein in the context of genetic immunization. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wands, JR (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. EM wands@helix.mgh.harvard.edu FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 55 TC 74 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 1997 VL 159 IS 10 BP 5107 EP 5113 PG 7 WC Immunology SC Immunology GA YW262 UT WOS:000071914700055 PM 9366440 ER PT J AU Holt, JR Corey, DP Eatock, RA AF Holt, JR Corey, DP Eatock, RA TI Mechanoelectrical transduction and adaptation in hair cells of the mouse utricle, a low-frequency vestibular organ SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hair cell; utricle; mechanoelectrical transduction; adaptation; inner ear; vestibular ID INNERVATING OTOLITH ORGANS; RESPONSE DYNAMICS; DELAYED RECTIFIER; SQUIRREL-MONKEY; SENSITIVITY; CALCIUM; EAR; CONDUCTANCE; PHYSIOLOGY; CHANNELS AB Hair cells of inner ear organs sensitive to frequencies above 10 Hz adapt to maintained hair bundle deflections at rates that reduce their responses to lower frequencies. Mammalian vestibular organs detect head movements at frequencies well below 10 Hz. We asked whether hair cells of the mouse utricle adapt, and if so, whether the adaptation was similar to that in higher frequency organs such as the frog saccule. Whole-cell transduction currents were recorded from hair cells in the epithelium of the mouse utricle. Hair bundles were deflected by a fluid jet or a stiff probe. The transduction currents evoked by step deflections adapted over 10-100 msec. The mean operating range was 1.5 mu m (deflection of the tip of the bundle), approximately threefold larger than in frog saccule. Taller and more compact bundles of the mouse utricle account for this difference. As in frog saccular hair cells, adaptation shifted the current-deflection (I(X)) relation along the deflection axis. These adaptive shifts had time constants of 10-20 msec and reached 60-80% of stimulus amplitude. The adaptive shift and voltage-dependent bundle movement are consistent with the motor model of adaptation. When the fluid jet was used, adaptation also broadened the I(X) relation and reduced the maximum current. Adaptation attenuated the transduction currents evoked by sinusoidal bundle deflections below 5 Hz, within the frequency range of the utricle, but because it was incomplete, substantial responses remained. Moreover, the adaptive shift mechanism preserves sensitivity even in the presence of large stimuli that would otherwise saturate transduction. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HOWARD HUGHES MED INST,BOSTON,MA 02114. BAYLOR COLL MED,BOBBY R ALFORD DEPT OTORHINOLARYNGOL & COMMUNICAT,HOUSTON,TX 77030. RI Eatock, Ruth/F-6404-2013; OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC00304, DC02290] NR 38 TC 68 Z9 70 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1997 VL 17 IS 22 BP 8739 EP 8748 PG 10 WC Neurosciences SC Neurosciences & Neurology GA YE666 UT WOS:A1997YE66600010 PM 9348343 ER PT J AU Choo, JK Seebach, JD Nickeleit, V Shimizu, A Lei, H Sachs, DH Madsen, JC AF Choo, JK Seebach, JD Nickeleit, V Shimizu, A Lei, H Sachs, DH Madsen, JC TI Species differences in the expression of major histocompatibility complex class II antigens on coronary artery endothelium - Implications for cell-mediated xenoreactivity SO TRANSPLANTATION LA English DT Article ID HUMAN T-CELLS; VASCULAR ENDOTHELIUM; MINIATURE SWINE; MHC ANTIGENS; MONOCLONAL-ANTIBODIES; LYMPHOCYTE SUBSETS; ALLOGRAFT SURVIVAL; PRESENTING CELLS; HLA; TRANSPLANTATION AB Background. There is controversy in the Literature as to whether swine coronary endothelium expresses major histocompatibility complex (MHC) class LI antigens constitutively. Methods., Because this issue has implications for cell-mediated human anti-swine xenogeneic responses, we stained tissue sections from human, pig, rat, and mouse hearts with the anti-class II monoclonal antibody ISCR3, which has a similar specificity and titer when binding to human, porcine, and rodent class II molecules. Results. Immunoperoxidase staining of human and porcine hearts with ISCR3 resulted in a dense reaction on the coronary endothelium of epicardial arteries, intramuscular arterioles, and capillaries. In contrast, the coronary endothelium of rat and mouse hearts did not stain with ISCR3. When freshly harvested porcine aortic endothelial cells were placed in culture, class II MHC antigen expression was lost within three to four passages. Conclusions. Thus, using a single antibody with cross-species reactivities, we demonstrate that swine coronary endothelium, unlike rodent coronary arteries, expresses similar basal amounts of class LI MHC antigens to human coronary vessels, The constitutive expression of class II NMC antigens on swine coronary artery endothelium may contribute to host T cell-mediated xenogeneic responses in clinical pig-to-human cardiac xenotransplantation and thus become a target for therapeutic intervention. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC SURG UNIT,BOSTON,MA 02114. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NHLBI NIH HHS [R01-HL54211] NR 48 TC 59 Z9 60 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1997 VL 64 IS 9 BP 1315 EP 1322 DI 10.1097/00007890-199711150-00014 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YG537 UT WOS:A1997YG53700014 PM 9371674 ER PT J AU Yang, YG Dey, B Sergio, JJ Sykes, M AF Yang, YG Dey, B Sergio, JJ Sykes, M TI Interleukin-12 prevents severe acute graft-versus-host disease (GVHD) and GVHD-associated immune dysfunction in a fully major histocompatibility complex haplotype-mismatched murine bone marrow transplantation model SO TRANSPLANTATION LA English DT Article ID TOXIC LYMPHOCYTES-T; REPERTOIRE SELECTION; CELLS; MICE; AUTOANTIBODIES; SUPERANTIGENS; DEFICIENCY; EXPRESSION; DEPLETION; PHENOTYPE AB Background, We have recently reported that interleukin (IL)-12 prevents acute graft-versus-host disease (GVHD)-induced mortality in a full major histocompatibility complex-plus multiple minor antigen-mismatched A/J-->B10 bone marrow transplantation (BMT) model, Because most patients have access to a haploidentical, one haplotype-mismatched donor, we have now investigated the protective effect of IL-12 against GVHD and GVHD-associated immune dysfunction in a haploidentical CBD2F1 (H2(kxd)) --> B6D2F1 (H2(bxd)) strain combination, Methods. GVHD was induced by injecting CBD2F1 marrow and spleen cells into lethally irradiated B6D2F1 mice, Results, In untreated control mice, GVHD resulted in 87% mortality by day 8 after BRIT, with no survivors beyond day 17. Treatment with a single injection of IL-12 on the day of BMT led to 87% long-term survival, with no significant weight loss, diarrhea or GVHD skin changes, The majority of T cells recovering: in these mice showed the CD62L(+), CD4(low), CD45RB(high) naive phenotype, These T cells showed specific tolerance to both host and donor histocompatibility antigens, but normal anti-third party (H2(s)) alloresponses in vitro., B-cell proliferative responses to lipopolysaccharide were also normal in IL-12-protected mice, Moreover, normal negative selection of thymocytes bearing T cell receptors with V beta that recognize endogenous superantigens was observed among CD4(+)CD8(-) thymocytes, indicating a lack of GVHD-associated thymic selection abnormalities in IL-18-protected allogeneic BMT recipients, Conclusions, IL-12 provides permanent protection against an otherwise severe, rapidly lethal GVHD, with no clinical manifestations of chronic GVHD, immunosuppression or autoimmune features, in a full major histocompatibilty complex haplotype-mismatched murine BMT model. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU PHS HHS [R0164912] NR 48 TC 20 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1997 VL 64 IS 9 BP 1343 EP 1352 DI 10.1097/00007890-199711150-00018 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YG537 UT WOS:A1997YG53700018 PM 9371678 ER PT J AU Pascual, M Thadhani, R Laposata, M Williams, WW Farrell, ML Johnson, SM TolkoffRubin, N Cosimi, AB AF Pascual, M Thadhani, R Laposata, M Williams, WW Farrell, ML Johnson, SM TolkoffRubin, N Cosimi, AB TI Anticardiolipin antibodies and hepatic artery thrombosis after liver transplantation SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Transplant-Surgeons CY MAY 14-16, 1997 CL CHICAGO, IL SP Amer Soc Transplant Surgeons ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIPHOSPHOLIPID ANTIBODIES; CIRRHOSIS; ANTICOAGULANT; PREVALENCE; REJECTION; DISORDERS; EVENT AB Background. Hepatic artery thrombosis (HAT) remains a devastating complication after liver transplantation, Various factors have been implicated in the pathogenesis of HAT, such as clotting abnormalities, increased hematocrit, and technical complications, but the role of anticardiolipin antibodies has not been evaluated, We investigated the possible association between HAT and anticardiolipin antibodies in adult patients who underwent liver transplantation. Methods. Seven patients with HAT after orthotopic liver transplantation 28 liver recipients without HAT, and 35 normal blood donors were evaluated, Determination of IgM and IgG anticardiolipin antibodies was performed by enzyme-linked immunosorbent assay using pretransplant serum from all allograft recipients. Clinical information was obtained from chart review. Fisher's exact test and Wilcoxon rank sum test were used for statistical analysis, and all P-values were two-tailed. Results. Overall, 22 of 35 (63%) liver recipients had a positive anticardiolipin antibody test (either IgG or IgM titer >4 SD from the normal controls). The test was positive in 7 liver recipients (100%) with HAT compared with 15 out of 28 patients (54%) without HAT (P=0.031). As compared with liver recipients without HAT, patients with HAT also tended to have a higher mean anticardiolipin titer of IgG and IgM and a lower pretransplant platelet count; however, these differences were not significant. Conclusions, Our findings indicate that anticardiolipin antibodies are frequently elevated in patients with liver failure and may contribute to the pathogenesis of HAT after liver transplantation, Other potential consequences of anticardiolipin antibodies in end-stage liver disease remain to be determined. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT CLIN PATHOL,BOSTON,MA 02114. RP Pascual, M (reprint author), MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOX MZ-70,55 FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 18 Z9 20 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1997 VL 64 IS 9 BP 1361 EP 1364 DI 10.1097/00007890-199711150-00021 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YG537 UT WOS:A1997YG53700021 PM 9371681 ER PT J AU Edelmann, W Yang, K Umar, A Heyer, J Lau, K Fan, KH Liedtke, W Cohen, PE Kane, MF Lipford, JR Yu, NJ Crouse, GF Pollard, JW Kunkel, T Lipkin, M Kolodner, R Kucherlapati, R AF Edelmann, W Yang, K Umar, A Heyer, J Lau, K Fan, KH Liedtke, W Cohen, PE Kane, MF Lipford, JR Yu, NJ Crouse, GF Pollard, JW Kunkel, T Lipkin, M Kolodner, R Kucherlapati, R TI Mutation in the mismatch repair gene Msh6 causes cancer susceptibility SO CELL LA English DT Article ID NONPOLYPOSIS COLON-CANCER; COLORECTAL TUMORIGENESIS; HETERODUPLEX REPAIR; TUMOR-CELLS; DNA; MICE; HETERODIMER; HOMOLOG; MOUSE; DEFICIENCY AB Mice carrying a null mutation in the mismatch repair gene Msh6 were generated by gene targeting. Cells that were homozygous for the mutation did not produce any detectable MSH6 protein, and extracts prepared from these cells were defective for repair of single nucleotide mismatches. Repair of 1, 2, and 4 nucleotide insertion/deletion mismatches was unaffected. Mice that were homozygous for the mutation had a reduced life span. The mice developed a spectrum of tumors, the most predominant of which were gastrointestinal tumors and B-as well as T-cell lymphomas. The tumors did not show any microsatellite instability. We conclude that MSH6 mutations, like those in some other members bf the family of mismatch repair genes, lead to cancer susceptibility, and germline mutations in this gene may be associated with a cancer predisposition syndrome that does not show microsatellite instability. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOL GENET,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT DEV & MOL BIOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,STRANG CANC RES LAB,BRONX,NY 10461. NIEHS,NIH,RES TRIANGLE PK,NC 27709. DANA FARBER CANC INST,BOSTON,MA 02115. LUDWIG INST CANC RES,LA JOLLA,CA 92093. EMORY UNIV,ATLANTA,GA 30322. RP Edelmann, W (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT CELL BIOL,1300 MORRIS PK AVE,BRONX,NY 10461, USA. RI Liedtke, Wolfgang/G-4633-2011 FU NCI NIH HHS [CA 67944, CA 44704, CA 54050] NR 51 TC 274 Z9 280 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 14 PY 1997 VL 91 IS 4 BP 467 EP 477 DI 10.1016/S0092-8674(00)80433-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YG492 UT WOS:A1997YG49200008 PM 9390556 ER PT J AU Bergwitz, C Jusseaume, SA Luck, MD Juppner, H Gardella, TJ AF Bergwitz, C Jusseaume, SA Luck, MD Juppner, H Gardella, TJ TI Residues in the membrane-spanning and extracellular loop regions of the parathyroid hormone (PTH)-2 receptor determine signaling selectivity for PTH and PTH-related peptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID (PTH)/PTH-RELATED PEPTIDE; CHIMERIC RECEPTORS; ADENYLATE-CYCLASE; BINDING-AFFINITY; COMMON RECEPTOR; INDIAN HEDGEHOG; PROTEIN; EXPRESSION; ACTIVATION; SECRETIN AB The parathyroid hormone (PTH)-2 receptor displays strong ligand selectivity in that it responds fully to PTH but not at all to PTH-related peptide (PTHrP), In contrast, the PTH-1 receptor (PTH/PTHrP receptor) responds fully to both ligands, Previously it was shown that two divergent residues in PTH and PTHrP account for PTH-2 receptor selectivity; position 23 (Trp in PTH and Phe in PTHrP) determines binding selectivity and position 5 (Ile in PTH and His in PTHrP) determines signaling selectivity, To identify sites in the PTH-2 receptor involved in discriminating between His(5) and Ile(5), we constructed PTH-S receptor/PTH-1 receptor chimeras, expressed them in COS-7 cells, and tested for cAMP responsiveness to [Trp(23)] PTHrP-(1-36), and to the nondiscriminating peptide [Ile(5),Trp(23)]PTHrP-(1-36) (the Phe(23) --> Trp modification enabled high affinity binding of each ligand to the PTH-2 receptor), The chimeras revealed that the membrane-spanning/loop region of the receptor determined His(5)/Ile(5) signaling selectivity, Subsequent analysis of smaller cassette substitutions and then individual point mutations led to the identification of two single residues that function as major determinants of residue 5 signaling selectivity, These residues, Ile(244) at the extracellular end of transmembrane helix 3, and Tyr(318) at the COOH-terminal portion of extracellular loop 2, are replaced by Leu and Ile in the PTH-1 receptor, respectively, The results thus indicate a functional interaction between two residues in the core region of the PTH-2 receptor and residue 5 of the ligand. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-11794] NR 32 TC 67 Z9 67 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 28861 EP 28868 DI 10.1074/jbc.272.46.28861 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400012 PM 9360953 ER PT J AU Tachibana, K Urano, T Fujita, H Ohashi, Y Kamiguchi, K Iwata, S Hirai, H Morimoto, C AF Tachibana, K Urano, T Fujita, H Ohashi, Y Kamiguchi, K Iwata, S Hirai, H Morimoto, C TI Tyrosine phosphorylation of Crk-associated substrates by focal adhesion kinase - A putative mechanism for the integrin-mediated tyrosine phosphorylation of Crk-associated substrates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SRC FAMILY KINASES; CELL-ADHESION; EXTRACELLULAR-MATRIX; V-SRC; SIGNAL TRANSDUCTION; T-CELLS; PROTEIN; PP125(FAK); P130(CAS); BINDING AB Integrin-ligand binding induces the tyrosine phosphorylation of various proteins including focal adhesion kinase (pp125(FAK)) and Crk-associated substrate (Gas). FAK is activated and autophosphorylated by the ligation of integrins, although the substrate of FAK has not been revealed. We show here that p130(Cas) and Cas-L are FAX substrates. FAK directly phosphorylates Cas proteins primarily at the YDYVHL sequence that is conserved among all Cas proteins. Furthermore, the phosphorylated YDYVHL sequence is a binding site for Src family protein-tyrosine kinases, and the recruited Src family kinase phosphorylates the other tyrosine residues within Gas. The Cas-L YDYVHL sequence is phosphorylated upon integrin-ligand binding, and this integrin-mediated tyrosine phosphorylation is inhibited by the cotransfection of the FAX COOH-terminal domain that does not contain a kinase domain, These findings strongly suggest that FAK initiates integrin-mediated tyrosine phosphorylation of Cas proteins; then, Src family tyrosine kinases, which are recruited to phosphorylated Cas and FAK, further phosphorylate Cas proteins. C1 TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. UNIV TOKYO,FAC MED,DEPT INTERNAL MED 3,BUNKYO KU,TOKYO 113,JAPAN. UNIV TOKYO,INST MED SCI,DEPT CLIN IMMUNOL,MINATO KU,TOKYO 108,JAPAN. UNIV TOKYO,INST MED SCI,AIDS RES CTR,MINATO KU,TOKYO 108,JAPAN. RP Tachibana, K (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CANC IMMUNOL & AIDS,44 BINNEY ST,BOSTON,MA 02115, USA. RI Iwata, Satoshi/A-8819-2011; OI Urano, Takeshi/0000-0003-3383-3554 FU NIAID NIH HHS [AI-29530]; NIAMS NIH HHS [AR-33713] NR 50 TC 135 Z9 138 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29083 EP 29090 DI 10.1074/jbc.272.46.29083 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400042 PM 9360983 ER PT J AU Berditchevski, F Chang, S Bodorova, J Hemler, ME AF Berditchevski, F Chang, S Bodorova, J Hemler, ME TI Generation of monoclonal antibodies to integrin-associated proteins - Evidence that alpha(3)beta(1) complexes with EMMPRIN/basigin/OX47/M6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLOOD-BRAIN-BARRIER; CELL-ADHESION; IMMUNOGLOBULIN SUPERFAMILY; T-CELLS; HISTOCOMPATIBILITY ANTIGENS; UROKINASE RECEPTOR; BETA-1 INTEGRINS; CD9 ANTIGEN; SURFACE; DOMAIN AB The alpha(3) beta(1) integrin forms complexes with other cell-surface proteins, including transmembrane-4 superfamily (TM4SF) proteins (e.g. CD9, CD53, CD63, CD81, and CD82). To identify additional cell-surface proteins associated with alpha(3) beta(1) integrin, a monoclonal antibody selection protocol was developed, Mice were immunized with integrin alpha(3) beta(1)-containing complexes isolated from HT1080 fibrosarcoma cells, and then 712 hybridoma clones were produced, and 95 secreted antibodies that recognized the HT1080 cell surface, Among these, 12 antibodies directly recognizing integrin alpha(3) or beta(1) subunits were eliminated, Of the remaining 83, 16 co-immunoprecipitated proteins that resembled integrins under non-stringent detergent conditions. These 16 included 15 monoclonal antibodies recognizing EMMPRIN/basigin/OX-47/M6, a 45-55-kDa transmembrane protein with two immunoglobulin domains. The EMMPRIN protein associated with alpha(3) beta(1) and alpha(6) beta(1), but not alpha(2) beta(1) or alpha(5) beta(1), as shown by reciprocal immunoprecipitation experiments, Also, association with alpha(3) beta(1) was confirmed by cell-surface cross-linking and immunofluorescence co-localization experiments, Importantly, EMMPRIN-alpha(3) beta(1) complexes appear not to contain TM4SF proteins, suggesting that they are distinct from TM4SF protein-alpha(3) beta(1) complexes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA42368] NR 59 TC 212 Z9 227 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29174 EP 29180 DI 10.1074/jbc.272.46.29174 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400054 PM 9360995 ER PT J AU Tachibana, I Bodorova, J Berditchevski, F Zutter, MM Hemler, ME AF Tachibana, I Bodorova, J Berditchevski, F Zutter, MM Hemler, ME TI NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-VIRUS TYPE-1; MHC CLASS-II; MONOCLONAL-ANTIBODIES; T-CELLS; TYROSINE PHOSPHORYLATION; MEMBRANE GLYCOPROTEIN; SYNCYTIUM FORMATION; SEQUENCE-ANALYSIS; B-LYMPHOCYTES; C33 ANTIGEN AB Transmembrane-4 superfamily (TM4SF) proteins form complexes with integrins and other cell-surface proteins. To further characterize the major proteins present in a typical TM4SF protein complex, we raised monoclonal antibodies against proteins co-immunoprecipitated with CD81 from MDA-MB-435 breast cancer cells. Only two types of cell-surface proteins were recognized by our 35 selected antibodies. These included an integrin (alpha(6) beta(1)) and three different TM4SF proteins (CD9, CD63, and NAG-2). The protein NAG-P (novel anti gen-a) is a previously unknown 30-kDa cell-surface protein. Using an expression cloning protocol, cDNA encoding NAG-2 was isolated. When aligned with other TM4SF proteins, the deduced amino acid sequence of NAG-2 showed most identity (34%) to CD53. Flow cytometry, Northern blotting, and immunohistochemistry showed that NAG-2 is widely present in multiple tissues and cell types but is absent from brain, lymphoid cells, and platelets, Within various tissues, strongest staining was seen on fibroblasts, endothelial cells, follicular dendritic cells, and mesothelial cells. In nonstringent detergent, NAG-2 protein was co-immunoprecipitated with other TM4SF members (CD9 and CD81) and integrins (alpha(3) beta(1) and alpha(6) beta(1)). Also, two-color immunofluorescence showed that NAG-S was co-localized with CD81 on the surface of spread HT1080 cells. These results confirm the presence of NAG-S in specific TM4SF.TM4SF and TM4SF-integrin complexes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. FU NCI NIH HHS [CA70275]; NIGMS NIH HHS [GM38903] NR 51 TC 75 Z9 77 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29181 EP 29189 DI 10.1074/jbc.272.46.29181 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400055 PM 9360996 ER PT J AU Spiro, MJ Bhoyroo, VD Spiro, RG AF Spiro, MJ Bhoyroo, VD Spiro, RG TI Molecular cloning and expression of rat liver endo-alpha-mannosidase, an N-linked oligosaccharide processing enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN PHENYLALANINE-HYDROXYLASE; GLUCOSIDASE-II-DEFICIENT; NITRIC-OXIDE SYNTHASE; ESCHERICHIA-COLI; POLYACRYLAMIDE GELS; GOLGI; ENDOMANNOSIDASE; PROTEIN; PATHWAY; INHIBITORS AB A clone containing the open reading frame of endo-alpha-D-mannosidase, an enzyme involved in early N-linked oligosaccharide processing, has been isolated from a rat Liver lambda gt11 cDNA library. This was accomplished by a strategy that involved purification of the endomannosidase from rat liver Golgi by Ligand affinity chromatography (Hiraizumi, S., Spohr, U., and Spiro, R. G, (1991) J, Biol, Chem. 269, 4697-4700) and preparative electrophoresis, followed by sequence determinations of tryptic peptides. Using degenerate primers based on these sequences, the polymerase chain reaction with rat liver cDNA as a template yielded a 470-base pair product suitable for library screening as web as Northern blot hybridization. EcoRI digestion of the purified lambda DNA released a 5.4-kilobase fragment that was amplified in Bluescript II SK(-) vector. Sequence analysis indicated that the deduced open reading frame of the endomannosidase extended from nucleotides 89 to 1441, encoding a protein of 451 amino acids and corresponding to a molecular mass of 52 kDa. Data base searches revealed no homology with any other known protein. When a vector coding for this protein fused to an NH2-terminal peptide containing a polyhistidine region was introduced into Escherichia coli, high levels of the enzyme were expressed upon induction with isopropyl-beta-D-thiogalactoside. Purification of the endomannosidase to electrophoretic homogeneity from E. coli lysates was accomplished by Ni2+-chelate and Glc alpha 1-->3Man-O-(CH2)(8)CONH-Affi-Gel Ligand chromatographies. Polyclonal antibodies raised against this protein reacted with Golgi endomannosidase. By both immunoblotting and silver staining, the purified E. coli-expressed enzyme was approximately 8 kDa smaller than anticipated from the open reading frame; timed induction studies indicated that this was due to scission of the enzyme's COOH-terminal end by host cell proteases. All rat tissues examined demonstrated mRNA levels (4,9-kilobase message) for the endomannosidase that correlated well with their enzyme activity. C1 JOSLIN DIABET CTR, ELLIOT P JOSLIN RES LAB, 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. FU NIDDK NIH HHS [DK 17477] NR 31 TC 26 Z9 28 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 1997 VL 272 IS 46 BP 29356 EP 29363 DI 10.1074/jbc.272.46.29356 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF684 UT WOS:A1997YF68400076 PM 9361017 ER PT J AU Newton, TF Khalsa-Denison, ME Gawin, FH AF Newton, TF Khalsa-Denison, ME Gawin, FH TI The face of craving? Facial muscle EMG and reported craving in abstinent and non-abstinent cocaine users SO PSYCHIATRY RESEARCH LA English DT Article DE cocaine; craving; EMG; facial expression ID AFFECTIVE IMAGERY AB We studied 12 subjects, half of whom were current cocaine users and half of whom were abstinent former users, using facial EMG before and after subjects completed questionnaires describing cocaine use, craving and mood. Changes in zygomatic EMG tone before and after cocaine questionnaire completion correlated with reported craving in current users. This preliminary study suggests that facial EMG correlates with cocaine craving in current users. (C) 1997 Elsevier Science Ireland Ltd. C1 W Los Angeles Vet Affairs Med Ctr, Dept Psychiat W116AC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Drug Abuse Res Ctr, Los Angeles, CA USA. Mood & Addict Neurosci Fdn, W Hollywood, CA 90046 USA. RP Newton, TF (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Psychiat W116AC, Wilshire & Sawtelle Blvd, Los Angeles, CA 90073 USA. OI newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [DA08082, DA07200, DA07699] NR 7 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 14 PY 1997 VL 73 IS 1-2 BP 115 EP 118 DI 10.1016/S0165-1781(97)00115-7 PG 4 WC Psychiatry SC Psychiatry GA YQ291 UT WOS:000071370600012 PM 9463845 ER PT J AU Shuster, E AF Shuster, E TI Fifty years later: The significance of the Nuremberg Code SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-RIGHTS RP Shuster, E (reprint author), VET AFFAIRS MED CTR,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 21 TC 123 Z9 127 U1 1 U2 16 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 13 PY 1997 VL 337 IS 20 BP 1436 EP 1440 DI 10.1056/NEJM199711133372006 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA YF253 UT WOS:A1997YF25300006 PM 9358142 ER PT J AU Collins, MM Ransohoff, DF Barry, MJ AF Collins, MM Ransohoff, DF Barry, MJ TI Early detection of prostate cancer - Serendipity strikes again SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 19th Annual National Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, DC SP Soc Gen Internal Med ID DIGITAL RECTAL EXAMINATION; FECAL OCCULT BLOOD; COLORECTAL-CANCER; ANTIGEN; ADENOCARCINOMA; DIAGNOSIS; STAGE-T1C; BIOPSIES; VOLUME; TRIAL AB An underappreciated characteristic of prostate cancer screening is that it may detect some prostate cancers solely by serendipity or chance, Serendipity, previously described in the detection of colonic neoplasms, could affect prostate cancer detection when a screening test result is abnormal for reasons other than the presence of prostate cancer, but prostate cancer is coincidentally detected during the subsequent evaluation of the abnormal screening result. We reviewed published articles about prostate cancer screening, searching for evidence of serendipity. We defined serendipity in digital rectal examination (DRE) screening as the discovery of a prostate cancer by the random biopsy of an area of the prostate gland other than the palpable suspicious area that prompted the biopsy. We defined serendipity in prostate-specific antigen (PSA) screening as the discovery of a prostate cancer by the random biopsy of a nonpalpable (stage T1c) prostate cancer less than 1.0 cm(3) in volume, since tumors less than 1.0 cm(3) are generally too small to cause elevated PSA levels. We found that serendipity may be responsible for the detection of more than one quarter of apparently DRE-detected prostate cancers and up to one quarter of apparently PSA-detected cancers. Additionally, serendipity played a larger role in the detection of smaller tumors that are common but of uncertain clinical significance. We conclude that serendipity-detected prostate cancers contribute to an overestimation of the true information value of DRE and PSA screening. Whether serendipity is advantageous in prostate cancer screening depends on the as yet uncertain outcomes for men with smaller prostate cancers. However, given our estimates of the potential magnitude of the impact of serendipity, the currently popular DRE- and PSA-based screening strategy may not be optimal. If smaller prostate cancers are important, then we are not finding enough; if they are unimportant, then we are finding too many that we may feel compelled to treat aggressively. C1 MASSACHUSETTS GEN HOSP,MED SERV,DIV GEN MED,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC. UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC. FU AHRQ HHS [HS 08397]; BHP HRSA HHS [5T32PE11001-08] NR 34 TC 37 Z9 37 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 12 PY 1997 VL 278 IS 18 BP 1516 EP 1519 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YE445 UT WOS:A1997YE44500036 PM 9363972 ER PT J AU Cody, V Galitsky, N Luft, JR Pangborn, W Rosowsky, A Blakley, RL AF Cody, V Galitsky, N Luft, JR Pangborn, W Rosowsky, A Blakley, RL TI Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523 SO BIOCHEMISTRY LA English DT Article ID METHOTREXATE-RESISTANT VARIANTS; SIDE-CHAIN; BIOLOGICAL-ACTIVITY; FOLYLPOLYGLUTAMATE SYNTHETASE; AMINOPTERIN ANALOGS; FOLATE ANTAGONISTS; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI; ACID; 5-DEAZAFOLATE AB Structural data for two independent crystal forms (monoclinic, C2, and orthorhombic, P2(1)2(1)2(1)) of the ternary complex of the potent antitumor agent PT523 [N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine], reduced nicotinamide adenine dinucleotide phosphate (NADPH), and recombinant human dihydrofolate reductase (hDHFR) reveals multiple binding orientations for the hemiphthaloyl group of the inhibitor. Analysis of these data shows that PT523 binds with its pteridine ring in the same orientation observed for methotrexate (MTX) analogues, However, in each structure, the hemiphthaloyl ring occupies three alternate conformations. In the C2 lattice, the phthaloyl moiety binds in two extended conformations, A and C, with each conformer having a 180 degrees flip of the o-carboxylate group, and a third, lower occupancy conformer B, with the phthaloyl group folded within contact of the active-site pocket. In the orthorhombic lattice, PT523 also has three conformers for the phthaloyl group; however, these differ from those observed in the monoclinic lattice. Two major conformers, A and C, are displaced on either side of the extended position observed in the C2 lattice, one near the folded B conformer of the C2 lattice and the other extended, These conformers form tighter intermolecular contacts than those in the C2 lattice. Conformer B is folded back away from the active site in a unique position. There are also significant differences in the conformation of the adenine-ribose moiety of NADPH in both complexes that differ from that observed for other inhibitor-NADPH-hDHFR ternary complexes. These data suggest that the added intermolecular contacts made by the hemiphthaloyl group of PT523 contribute to its tighter binding to hDHFR than MTX, which does not extend as far from the active site and cannot make these contacts. These crystallographic observations of multiple conformations for the neral agreement with solution NMR data for the binding of PT523 to hDHFR [Johnson et al, (1997) Biochemistry 36, 4399-4411], which show that the hemiphthaloyl group may adopt more than one conformation. However, the crystallographic data reveal more discretely occupied positions than can be interpreted from the solution data. These results suggest that crystal packing interactions may influence their stability. C1 DANA FARBER CANC INST, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. ST JUDE CHILDRENS RES HOSP, DEPT MOL PHARMACOL, MEMPHIS, TN 38105 USA. RP Cody, V (reprint author), HAUPTMAN WOODWARD MED RES INST INC, 73 HIGH ST, BUFFALO, NY 14203 USA. FU NCI NIH HHS [CA-25394, CA-31922]; NIGMS NIH HHS [GM-51670] NR 32 TC 45 Z9 46 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 11 PY 1997 VL 36 IS 45 BP 13897 EP 13903 DI 10.1021/bi971711l PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF601 UT WOS:A1997YF60100018 PM 9374868 ER PT J AU Roberts, RW Szostak, JW AF Roberts, RW Szostak, JW TI RNA-peptide fusions for the in vitro selection of peptides and proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MESSENGER-RNA; DIRECTED EVOLUTION; ESCHERICHIA-COLI; LIBRARIES; INITIATION; TRANSLATION; RIBOSOME; PHAGE; SITES AB Covalent fusions between an mRNA and the peptide or protein that it encodes can be generated by in vitro translation of synthetic mRNAs that carry puromycin, a peptidyl acceptor antibiotic, at their 3' end. The stable linkage between the informational (nucleic acid) and functional (peptide) domains of the resulting joint molecules allows a specific mRNA to be enriched from a complex mixture of mRNAs based on the properties of its encoded peptide. Fusions between a synthetic mRNA and its encoded myc epitope peptide have been enriched from a pool of random sequence mRNA-peptide fusions by immunoprecipitation. Covalent RNA-peptide fusions should provide an additional route to the in vitro selection and directed evolution of proteins. C1 MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 34 TC 592 Z9 608 U1 6 U2 70 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 1997 VL 94 IS 23 BP 12297 EP 12302 DI 10.1073/pnas.94.23.12297 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF393 UT WOS:A1997YF39300012 PM 9356443 ER PT J AU Tan, KM Liu, JH Wang, JH Shen, S Lu, M AF Tan, KM Liu, JH Wang, JH Shen, S Lu, M TI Atomic structure of a thermostable subdomain of HIV-1 gp41 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HEMAGGLUTININ MEMBRANE GLYCOPROTEIN; RECEPTOR-MEDIATED ACTIVATION; GCN4 LEUCINE-ZIPPER; TRANSMEMBRANE GLYCOPROTEIN; INFLUENZA HEMAGGLUTININ; ENVELOPE GLYCOPROTEINS; VIRAL FUSION; SOLUBLE CD4; COILED-COIL AB Infection by HIV-1 involves the fusion of viral and cellular membranes with subsequent transfer of viral genetic material into the cell, The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 and the transmembrane subunit gp41. gp120 directs virion attachment to the cell-surface receptors, and gp41 then promotes viral-cell membrane fusion, A soluble, alpha-helical, trimeric complex within gp41 composed of N-terminal and C-terminal extraviral segments has been proposed to represent the core of the fusion-active conformation of the HIV-1 envelope, A thermostable subdomain denoted N34(L6)C28 can be formed by the N-34 and C-28 peptides connected by a flexible linker in place of the disulfide-bonded loop region, Three-dimensional structure of N34(L6)C28 reveals that three molecules fold into a six-stranded helical bundle. Three N-terminal helices within the bundle form a central, parallel, trimeric coiled coil, whereas three C-terminal helices pack in the reverse direction into three hydrophobic grooves on the surface of the N-terminal trimer, This thermostable subdomain displays the salient features of the core structure of the isolated gp41 subunit and thus provides a possible target for therapeutics designed selectively to block HIV-1 entry. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. CORNELL UNIV,DEPT BIOCHEM,COLL MED,NEW YORK,NY 10021. FU NIAID NIH HHS [AI27336] NR 56 TC 470 Z9 477 U1 0 U2 23 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 1997 VL 94 IS 23 BP 12303 EP 12308 DI 10.1073/pnas.94.23.12303 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF393 UT WOS:A1997YF39300013 PM 9356444 ER PT J AU Xu, CW Mendelsohn, AR Brent, R AF Xu, CW Mendelsohn, AR Brent, R TI Cells that register logical relationships among proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE two-hybrid; interaction trap; two-bait; biological computation; functional genomics ID CAENORHABDITIS-ELEGANS; YEAST; DECARBOXYLASE; PHOSPHATASE; EXPRESSION; SELECTION; SYSTEM; GENES; DEATH; ASSAY AB Two-hybrid methods have augmented the classical genetic techniques biologists use to assign function to genes. Here, we describe construction of a two-bait interaction trap that uses yeast cells to register more complex protein relationships than those detected in existing two-hybrid systems, We show that such cells can identify bridge or connecting proteins and peptide aptamers that discriminate between closely related allelic variants. The protein relationships detected by these cells are analogous to classical genetic relationships, but lend themselves to systematic application to the products of entire genomes and combinatorial libraries. We show that, by performing logical operations on the phenotypic outputs of these complex cells and existing two-hybrid cells, we can make inferences about the topology and order of protein interactions. Finally, we show that cells that register such relationships can perform logical operations on protein inputs, Thus these cells will be useful for analysis of gene and allele function, and may also define a path for construction of biological computational devices. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOL BIOL,BOSTON,MA 02114. NR 29 TC 47 Z9 47 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 1997 VL 94 IS 23 BP 12473 EP 12478 DI 10.1073/pnas.94.23.12473 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF393 UT WOS:A1997YF39300043 PM 9356474 ER PT J AU Chen, FL Barkett, M Ram, KT Quintanilla, A Hariharan, IK AF Chen, FL Barkett, M Ram, KT Quintanilla, A Hariharan, IK TI Biological characterization of Drosophila Rapgap1, a GTPase activating protein for Rap1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSTERIOR DETERMINANT; TYROSINE KINASE; GERM PLASM; RAS P21; GENE; MELANOGASTER; LOCALIZATION; RECEPTOR; PRODUCT; OSKAR AB The activity of Pas family proteins is modulated irt vivo by the function of GTPase activating proteins, which increase their intrinsic rate of GTP hydrolysis, We have isolated cDNAs encoding a GAP for the Drosophila Rap1 GTPase, Drosophila Rapgap1 encodes an 850-amino acid protein with a central region that displays substantial sequence similarity to human RapGAP, This domain, when expressed in Escherichia coli, potently stimulates Rap1 GTPase activity in vitro, Unlike Rap1, which is ubiquitously expressed, Rapgap1 expression is highly restricted, Rapgap1 is expressed at high levels in the developing photoreceptor cells and in the optic lobe, Rapgap1 mRNA is also localized in the pole plasm in an oskar-dependent manner, Although mutations that completely abolish Rapgap1 function display no obvious phenotypic abnormalities, overexpression of Rapgap1 induces a rough eye phenotype that is exacerbated by reducing Rap1 gene dosage, Thus, Rapgap1 can function as a negative regulator of Rap1-mediated signaling in vivo. C1 MASSACHUSETTS GEN HOSP, CTR CANC, CHARLESTOWN, MA 02129 USA. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98109 USA. NR 44 TC 21 Z9 21 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 1997 VL 94 IS 23 BP 12485 EP 12490 DI 10.1073/pnas.94.23.12485 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF393 UT WOS:A1997YF39300045 PM 9356476 ER PT J AU Li, QH Hariharan, IK Chen, FL Huang, YZ Fischer, JA AF Li, QH Hariharan, IK Chen, FL Huang, YZ Fischer, JA TI Genetic interactions with Rap1 and Ras1 reveal a second function for the Fat facets deubiquitinating enzyme in Drosophila eye development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL FATE; ACTIVATION; UBIQUITIN; PROTEINS; DIFFERENTIATION; DEGRADATION; EXPRESSION; EFFECTORS; TRAMTRACK; MUTATION AB The Drosophila fat facets gene encodes a deubiquitinating enzyme that regulates a cell communication pathway essential very early in eye development, prior to facet assembly, to limit the number of photoreceptor cells in each facet of the compound eye to eight. The Fat facets protein facilitates the production of a signal in cells outside the developing facets that inhibits neural development of particular facet precursor cells. Novel gain-of-function mutations in the Drosophila Rap1 and Ras1 genes are described herein that interact genetically with fat facets mutations. Analysis of these genetic interactions reveals that Fat facets has an additional function later in eye development involving Rap1 and Ras1 proteins. Moreover, the results suggest that undifferentiated cells outside the facet continue to influence facet assembly later in eye development. C1 UNIV TEXAS,DEPT ZOOL,INST MOL & CELLULAR BIOL,AUSTIN,TX 78712. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. FU NEI NIH HHS [R01EY11632]; NICHD NIH HHS [R29 HD030680, R29HD30680] NR 33 TC 26 Z9 26 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 1997 VL 94 IS 23 BP 12515 EP 12520 DI 10.1073/pnas.94.23.12515 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YF393 UT WOS:A1997YF39300050 PM 9356481 ER PT J AU Farber, NJ Novack, DH OBrien, MK AF Farber, NJ Novack, DH OBrien, MK TI Love, boundaries, and the patient-physician relationship SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SEXUAL CONTACT; EXPLOITATION; VIOLATIONS; PREVALENCE AB Physicians often use their relationships with patients to promote specific therapeutic goals. Because of their personal histories, values, and biases, patients may react to physicians in ways that inhibit or enhance the relationship. The feelings that are aroused may induce physicians to become overly distant, engendering patient and physician dissatisfaction, or to become overly involved emotionally, which can have serious psychological and clinical consequences. We explore how a balance between clinical objectivity and bonding with the patient is optimal and achievable. The nature and origin of personal boundaries are described. Boundary transgressions on the part of the patient are discussed, and the means of preventing transgressions by both patients and physicians through medical education, the process of self-awareness, and an exploration of family-of-origin issues are proposed. Through attention to communication with patients, the physician can maintain an empathetic yet objective relationship with the patient. C1 ALLEGHENY UNIV HLTH SCI,PHILADELPHIA,PA 19102. VET AFFAIRS MED CTR,DEPT MED,PHILADELPHIA,PA. NR 37 TC 35 Z9 35 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 10 PY 1997 VL 157 IS 20 BP 2291 EP 2294 DI 10.1001/archinte.157.20.2291 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA YE938 UT WOS:A1997YE93800001 PM 9361568 ER PT J AU Tarazi, FI Kula, NS Baldessarini, RJ AF Tarazi, FI Kula, NS Baldessarini, RJ TI Regional distribution of dopamine D-4 receptors in rat forebrain SO NEUROREPORT LA English DT Article DE autoradiography; caudate-putamen; dopamine D-4 receptor; frontal cortex; hippocampus; nemonapride; nucleus accumbens; raclopride ID SCHIZOPHRENIA; STRIATUM AB BINDING of the D-2-like (D-2/D-3/D-4) radioligand [H-3]nemonapride under selective conditions (with 300 nM S[-]-raclopride and other masking agents to occlude D-2/D-3 receptors and non-specific binding sites) revealed a subset of raclopride-insensitive binding sites considered D-4-like receptors. These sites were stereoselective to R(-)-N-n-propylnorapomorphine (NPA) over its S(+)-NPA in a similar fashion to cloned D-4 receptors expressed in cell lines. In addition, the highly D-4-selective agent L-745,870 displaced 74-83% of these sites in rat brain regions, suggesting that most were D-4 receptors. These apparent D-4 receptors represented a relatively high proportion of D-2-like receptors in hippocampus, dorsolateral frontal, medial prefrontal and entorhinal cortex, but fewer in caudate-putamen and nucleus accumbens. C1 HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA. MASSACHUSETTS GEN HOSP,MAILMAN RES CTR,MCLEAN DIV,BELMONT,MA 02178. RP Tarazi, FI (reprint author), HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115, USA. FU NIMH NIH HHS [MH-47370, MH-34006] NR 22 TC 60 Z9 60 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 10 PY 1997 VL 8 IS 16 BP 3423 EP 3426 DI 10.1097/00001756-199711100-00001 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YF197 UT WOS:A1997YF19700006 PM 9427299 ER PT J AU Khimani, AH Lim, M Graf, TG Smith, TF Ruprecht, RM AF Khimani, AH Lim, M Graf, TG Smith, TF Ruprecht, RM TI Phylogenetic relationship of the complete Rauscher murine leukemia virus genome with other murine leukemia virus genomes SO VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; LONG TERMINAL REPEAT; FOCUS-FORMING VIRUS; ENV GENE; FRIEND; RETROVIRUS; ALIGNMENT AB We report the complete nucleotide sequence of the genome of Rauscher murine leukemia virus (R-MuLV), the replication-competent helper virus present in the Rauscher virus complex, and its phylogenetic relationship with other murine leukemia virus genomes. An overall sequence identity of 97.6% was found between R-MuLV and the Friend helper virus (F-MuLV), and the two viruses were closely related on the phylogenetic trees constructed from either gag, pol, or env sequences. Moloney murine leukemia virus (Mo-MuLV) was the next closest relative to R-MuLV and F-MuLV on all trees, followed by Akv and radiation leukemia virus (RadLV). The most distantly related helper virus was Hortulanus murine leukemia virus (Ho-MuLV). Interestingly, Cas-Br-E branched with Mo-MuLV on the gag and pol trees, whereas on the env tree, it revealed the highest degree of relatedness to Ho-MuLV, possibly due to an ancient recombination with an Ho-MuLV ancestor. In summary, a phylogenetic analysis involving various MuLVs has been performed, in which the postulated close relationship between R-MuLV and F-MuLV has been confirmed, consistent with the pathobiology of the two viruses. (C) 1997 Academic Press. C1 DANA FARBER CANC INST,LAB VIRAL PATHOGENESIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. BOSTON UNIV,BMERC,BOSTON,MA 02215. FU NLM NIH HHS [P41 LM05205-14] NR 28 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 1997 VL 238 IS 1 BP 64 EP 67 DI 10.1006/viro.1997.8814 PG 4 WC Virology SC Virology GA YG860 UT WOS:A1997YG86000008 PM 9375009 ER PT J AU Asch, DA Hershey, JC AF Asch, DA Hershey, JC TI The three-salesmen conundrum in medicine SO LANCET LA English DT Editorial Material ID UNCERTAINTY; REGRET C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,WHARTON SCH,DEPT OPERAT & INFORMAT MANAGEMENT,PHILADELPHIA,PA 19104. NR 3 TC 3 Z9 3 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD NOV 8 PY 1997 VL 350 IS 9088 BP 1393 EP 1394 DI 10.1016/S0140-6736(97)04204-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YE872 UT WOS:A1997YE87200049 PM 9365467 ER PT J AU Hara, H Ayata, G Huang, PL Moskowitz, MA AF Hara, H Ayata, G Huang, PL Moskowitz, MA TI Alteration of protein kinase C activity after transient focal cerebral ischemia in mice using in vitro [H-3]phorbol-12,13-dibutyrate binding autoradiography SO BRAIN RESEARCH LA English DT Article DE autoradiography; ischemia; mouse; middle cerebral artery; nitric oxide synthase; protein kinase C; substantia nigra ID POSTISCHEMIC NEURONAL DAMAGE; RAT-BRAIN; ARTERY OCCLUSION; FOREBRAIN ISCHEMIA; PHORBOL ESTER; INDUCTION; ATROPHY; SYNAPTOSOMES; HIPPOCAMPUS; ACTIVATION AB Changes in the regional distribution of protein kinase C (PKC) after transient focal cerebral ischemia in SV-129 mice were assessed by quantitative autoradiography using [H-3]phorbol-12,13-dibutyrate ([H-3]PDBu) binding. [H-3]PDBu binding did not change up to 10 min after reperfusion of 3 h ischemia, but at 1 h after reperfusion markedly decreased to 40-50% of control (pre-ischemia) in the ipsilateral striatum and the middle cerebral artery (MCA) region of cortex in SV-129 mice. The binding decreased to 20% of control at 3-7 days after reperfusion, but did not change in the ipsilateral anterior cerebral artery (ACA) territory or the contralateral brain. In the ipsilateral substantia nigra, which lies outside the ischemic zone, [H-3]PDBu binding was not significantly changed compared to the control values (pre-ischemia) at early phase (up to 3 h after reperfusion), but marked reduction of the binding was observed 1 day after reperfusion. After 3 h ischemia followed by 3 h reperfusion, the morphological damage and the decrease in [H-3]PDBu binding in the ipsilateral striatum and the MCA region of cortex was smaller in mice lacking the expression of neuronal nitric oxide synthase (type I NOS) gene mutant mice compared to wild-type (SV-129 and C57black/6) mice. Our data suggest that postischemic alterations of PKC binding activity were observed in the ischemic and non-ischemic lesions in the mouse brain. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG & NEUROL,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828, NS2683, NS33335] NR 44 TC 10 Z9 10 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 7 PY 1997 VL 774 IS 1-2 BP 69 EP 76 DI 10.1016/S0006-8993(97)81689-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YK694 UT WOS:A1997YK69400010 PM 9452194 ER PT J AU Joyal, JL Burks, DJ Pons, S Matter, WF Vlahos, CJ White, MF Sacks, DB AF Joyal, JL Burks, DJ Pons, S Matter, WF Vlahos, CJ White, MF Sacks, DB TI Communication - Calmodulin activates phosphatidylinositol 3-kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; GLUT4 TRANSLOCATION; SIGNAL-TRANSDUCTION; 3T3-L1 ADIPOCYTES; HEXOSE-TRANSPORT; SKELETAL-MUSCLE; INSULIN; IRS-1; CELLS; PHOSPHORYLATION AB Calmodulin and phosphatidylinositol 3-kinase are vital components of a number of common intracellular events. Calmodulin, a ubiquitous Ca2+-dependent effector protein, regulates multiple processes in eukaryotic cells, including cytoskeletal organization, vesicular trafficking, and mitogenesis. Phosphatidylinositol 3-kinase participates in events downstream of the receptors for insulin and other growth factors. Here we demonstrate by coimmunoprecipitation and affinity chromatography that Ca2+/calmodulin associates with Src homology 2 domains in the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase, thereby significantly enhancing phosphatidylinositol 3-kinase activity in vitro and in intact cells. Furthermore, CGS9343B, a calmodulin antagonist, inhibited basal and Ca2+-stimulated phosphorylation of phosphatidylinositol in intact cells. These data demonstrate a novel mechanism for modulating phosphatidylinositol 3-kinase and provide a direct link between components of two fundamental signaling pathways. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 FU NIDDK NIH HHS [DK09062, DK43682, DK47308] NR 29 TC 98 Z9 99 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28183 EP 28186 DI 10.1074/jbc.272.45.28183 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900004 PM 9353264 ER PT J AU Lu, M Seufert, J Habener, JF AF Lu, M Seufert, J Habener, JF TI Pancreatic beta-cell-specific repression of insulin gene transcription by CCAAT enhancer-binding protein beta - Inhibitory interactions with basic helix-loop-helix transcription factor E47 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH GLUCOSE-CONCENTRATIONS; REGULATED NUCLEAR-PROTEIN; HOMEOBOX FACTOR STF-1; HIT CELLS; SOMATOSTATIN GENE; CHRONIC EXPOSURE; MESSENGER-RNA; C/EBP-BETA; FACTOR EXPRESSION; LEUCINE ZIPPER AB Chronic exposure of beta-cells to supraphysiologic glucose concentrations results in decreased insulin gene transcription, Here we identify the basic leucine zipper transcription factor, CCAAT/enhancer-binding protein beta (C/EBP beta), as a repressor of insulin gene transcription in conditions of supraphysiological glucose levels. C/EBP beta is expressed in primary rat islets, Moreover, after exposure to high glucose concentrations the beta-cell lines HIT-TIS and INS-1 express increased levels of C/EBP beta. The rat insulin I gene promoter contains a consensus binding motif for C/EBP beta (CEB box) that binds C/EBP beta. In non-beta-cells C/EBP beta stimulates the activity of the rat insulin I gene promoter through the CEB box. Paradoxically, in beta-cells C/EBP beta inhibits transcription, directed by the promoter of the rat insulin I gene by direct protein-protein interaction with a heptad leucine repeat sequence within activation domain 2 of the basic helix-loop-helix transcription factor E47. This interaction leads to the inhibition of both dimerization and DNA binding of E47 to the E-elements of the insulin promoter, thereby reducing functionally the transactivation potential of E47 on insulin gene transcription. We suggest that the induction of C/EBP beta in pancreatic beta-cells by chronically elevated glucose levels may contribute to the impaired insulin secretion in severe type II diabetes mellitus. C1 HARVARD UNIV,MOL ENDOCRINOL LAB,MASSACHUSETTS GEN HOSP,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02114. FU NIDDK NIH HHS [DK30834] NR 66 TC 92 Z9 94 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28349 EP 28359 DI 10.1074/jbc.272.45.28349 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900032 PM 9353292 ER PT J AU Adler, HT Nallaseth, FS Walter, G Tkachuk, DC AF Adler, HT Nallaseth, FS Walter, G Tkachuk, DC TI HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLD SHOCK DOMAINS; 11Q23 TRANSLOCATIONS; DNA-BINDING; ALL-1 GENE; MYELOID LEUKEMOGENESIS; DROSOPHILA-TRITHORAX; PUTATIVE ONCOGENE; POTENT INHIBITOR; CRUCIFORM DNA; OKADAIC ACID AB One of the most common chromosomal abnormalities in acute leukemia is a reciprocal translocation involving the HRX gene at chromosome locus 11q23, resulting in HRX fusion proteins. Using the yeast two-hybrid system, in vitro binding studies, and human cell culture coimmunoprecipitation experiments, we show here that a region of the HRX protein that is consistently retained in HRX leukemic fusion proteins interacts directly with SET, another protein implicated in leukemia. We have identified the binding sites on HRX for SET and show that these sequences are clustered near the A.T hooks that have been shown to bind DNA. We also show that carboxyl-terminal SET sequences, possibly the acidic tail of SET, bind to HRX. We have also found serine/threonine-specific protein phosphatase activity in anti-HRX coimmunoprecipitates. Using the phosphatase inhibitor okadaic acid and Western blotting, the phosphatase was identified as protein phosphatase 2A (PP2A). Mutation of a single amino acid in one of the SET binding sites of HRX resulted in lower amounts of both coimmunoprecipitated SET protein and coimmunoprecipitated PP2A. These results suggest that the leukemogenic effects of HRX fusion proteins may be related to interactions with SET and PP2A. C1 UNIV CALIF SAN DIEGO,DEPT PATHOL,LA JOLLA,CA 92093. UNIV WASHINGTON,SCH MED,DEPT PATHOL,SEATTLE,WA 98195. RP Adler, HT (reprint author), VA PUGET SOUND HLTH CARE SYST,SEATTLE DIV,1660 S COLUMBIAN WAY,RES MAIL STOP 151,SEATTLE,WA 98108, USA. NR 68 TC 84 Z9 86 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28407 EP 28414 DI 10.1074/jbc.272.45.28407 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900039 PM 9353299 ER PT J AU Emsley, J King, SL Bergelson, JM Liddington, RC AF Emsley, J King, SL Bergelson, JM Liddington, RC TI Crystal structure of the I domain from integrin alpha 2 beta 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT ADHESION; LIGAND-BINDING; A-DOMAIN; LAMININ RECEPTOR; VLA-2; IDENTIFICATION; COLLAGEN; SITE; CD11B/CD18; PLATELETS AB We have determined the high resolution crystal structure of the I domain from the alpha-subunit of the integrin alpha 2 beta 1, a cell surface adhesion receptor for collagen and the human pathogen echovirus-1. The domain, as expected, adopts the dinucleotide-binding fold, and contains a metal ion-dependent adhesion site motif with bound Mg2+ at the top of the beta-sheet. Comparison with the crystal structures of the leukocyte integrin I domains reveals a new helix (the C-helix) protruding from the metal ion-dependent adhesion site face of the domain which creates a groove centered on the magnesium ion. Modeling of a collagen triple helix into the groove suggests that a glutamic acid side chain from collagen can coordinate the metal ion, and that the C-helix insert is a major determinant of binding specificity. The binding site for echovirus-1 maps to a distinct surface of the alpha 2-I domain (one edge of the beta-sheet), consistent with data showing that virus and collagen binding occur by different mechanisms. Comparison with the homologous von Willebrand factor A3 domain, which also binds collagen, suggests that the two domains bind collagen in different ways. C1 UNIV LEICESTER,DEPT BIOCHEM,LEICESTER LE1 7RH,LEICS,ENGLAND. DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. RI emsley, jonas/A-8509-2016 OI emsley, jonas/0000-0002-8949-8030 NR 27 TC 223 Z9 226 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28512 EP 28517 DI 10.1074/jbc.272.45.28512 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900052 PM 9353312 ER PT J AU King, SL Kamata, T Cunningham, JA Emsley, J Liddington, RC Takada, Y Bergelson, JM AF King, SL Kamata, T Cunningham, JA Emsley, J Liddington, RC Takada, Y Bergelson, JM TI Echovirus 1 interaction with the human very late antigen-2 (integrin alpha 2 beta 1) I domain - Identification of two independent virus contact sites distinct from the metal, ion-dependent adhesion site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-LEVEL EXPRESSION; LIGAND-BINDING SITES; A-DOMAIN; INTERCELLULAR-ADHESION; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; VLA-2; PROTEINS; COLLAGEN AB The human integrin very late antigen (VLA)-2 (CD49b/CD29) mediates interactions with collagen and is the receptor for echovirus 1. Binding sites for both collagen and echovirus 1 have been mapped to the I domain within the alpha 2 subunit of the VLA-2 alpha 2 beta 1 heterodimer. Although murine VLA-2 interacts with collagen, it does not bind virus. We have used isolated human-murine chimeric I domains expressed as glutathione S-transferase fusion proteins in Escherichia coli to identify two groups of amino acids, 199-201 and 212-216, independently involved in virus attachment. These residues are distinct from the metal ion-dependent adhesion site previously demonstrated to be essential for VLA-2 interactions with collagen. Mutations in three metal ion-dependent adhesion site residues that abolish adhesion to collagen had no effect on virus binding. These results confirm that different sites within the I domain are responsible for VLA-2 interaction with extracellular matrix proteins and with viral ligands. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV INFECT DIS, BOSTON, MA 02115 USA. Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA. UNIV LEICESTER, DEPT BIOCHEM, LEICESTER LE1 7RH, LEICS, ENGLAND. RI emsley, jonas/A-8509-2016; OI emsley, jonas/0000-0002-8949-8030; takada, yoshikazu/0000-0001-5481-9589 FU NIAID NIH HHS [AI35667]; NIGMS NIH HHS [GM47157, GM49899] NR 32 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28518 EP 28522 DI 10.1074/jbc.272.45.28518 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900053 PM 9353313 ER PT J AU Schecter, AD Rollins, BJ Zhang, YJ Charo, IF Fallon, JT Rossikhina, M Giesen, PLA Nemerson, Y Taubman, MB AF Schecter, AD Rollins, BJ Zhang, YJ Charo, IF Fallon, JT Rossikhina, M Giesen, PLA Nemerson, Y Taubman, MB TI Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; KINASE-C ACTIVATION; SIGNAL-TRANSDUCTION; FUNCTIONAL EXPRESSION; CHEMOTACTIC PROTEIN-1; MOLECULAR-CLONING; MESSENGER-RNA; GROWTH-FACTOR; IN-VITRO; ATHEROSCLEROTIC LESIONS AB Monocyte chemoattractant protein-1 (MCP-1) is a C-C chemokine thought to play a major role in recruiting monocytes to the atherosclerotic plaque. Tissue factor (TF), the initiator of coagulation, is found in the atherosclerotic plaque, macrophages, and human aortic smooth muscle cells (SMC). The exposure of TF during plaque rupture likely induces acute thrombosis, leading to myocardial infarction and stroke. This report demonstrates that MCP-1 induces the accumulation of TF mRNA and protein in SMC and in THP-1 myelomonocytic leukemia cells. MCP-1 also induces TF activity on the surface of human SMC. The induction of TF by MCP-1 in SMC is inhibited by pertussis toxin, suggesting that the SMC MCP-1 receptor is coupled to a G(i)-protein. Chelation of intracellular calcium and inhibition of protein kinase C block the induction of TF by MCP-1, suggesting that in SMC it is mediated by activation of phospholipase C. SMC bind MCP-1 with a K-d similar to that previously reported for macrophages. However, mRNA encoding the macrophage MCP-1 receptors, CCR2A and B, is not present in SMC, indicating that they possess a distinct MCP-1 receptor. These data suggest that in addition to being a chemoattractant, MCP-I may have a procoagulant function and raise the possibility of an autocrine pathway in which MCP-1, secreted by SMC and macrophages, induces TF activity in these same cells. C1 CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,CARDIOVASC INST,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DIV THROMBOSIS RES,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT PATHOL,NEW YORK,NY 10029. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. FU NHLBI NIH HHS [HL 54469, HL09402, HL29019] NR 64 TC 161 Z9 174 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28568 EP 28573 DI 10.1074/jbc.272.45.28568 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900061 PM 9353321 ER PT J AU Tiger, CF Champliaud, MF PedrosaDomellof, F Thornell, LE Ekblom, P Gullberg, D AF Tiger, CF Champliaud, MF PedrosaDomellof, F Thornell, LE Ekblom, P Gullberg, D TI Presence of laminin alpha 5 chain and lack of laminin alpha 1 chain during human muscle development and in muscular dystrophies SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID A-CHAIN; EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; SKELETAL-MUSCLE; MOLECULAR-CLONING; MYOGENIC CELLS; MEROSIN; KIDNEY; MYOBLASTS AB There is currently a great interest in identifying laminin isoforms expressed in developing and regenerating skeletal muscle. Laminin alpha 1 has been reported to localize to human fetal muscle and to be induced in muscular dystrophies based on immunohistochemistry with the monoclonal antibody 4C7, suggested to recognize the human laminin alpha 1 chain. Nevertheless, there seems to be no expression of laminin alpha 1 protein or mRNA in developing or dystrophic mouse skeletal muscle fibers. To address the discrepancy between the results obtained in developing and dystrophic human and mouse muscle we expressed the E3 domain of human laminin alpha 1 chain as a recombinant protein and made antibodies specific for human laminin alpha 1 chain (anti-hLN-alpha 1G4/G5). We also made antibodies to the human laminin alpha 5 chain purified from placenta. In the present report we show that hLN-alpha 1G4/G5 antibodies react with a 400-kDa laminin alpha 1 chain and that 4C7 reacts with a 380-kDa laminin alpha 5 chain. Immunohistochemistry with the hLN-alpha 1G4/G5 antibody and 4C7 revealed that the two antibodies stained human kidney, developing and dystrophic muscle in distinct patterns. Our data indicate that the previously reported expression patterns in developing, adult, and dystrophic human muscle tissues with 4C7 should be re-interpreted as an expression of laminin alpha 5 chain. Our data are also consistent with earlier work in mouse, indicating that laminin alpha 1 is largely an epithelial laminin chain not present in developing or dystrophic muscle fibers. C1 UPPSALA UNIV,DEPT ANIM PHYSIOL,BMC,S-75124 UPPSALA,SWEDEN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,SCH MED,CHARLESTOWN,MA 02142. UMEA UNIV,DEPT ANAT,S-90187 UMEA,SWEDEN. RI Gullberg, Donald/H-2495-2016 OI Gullberg, Donald/0000-0002-7245-4437 NR 52 TC 183 Z9 183 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 7 PY 1997 VL 272 IS 45 BP 28590 EP 28595 DI 10.1074/jbc.272.45.28590 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YF219 UT WOS:A1997YF21900064 PM 9353324 ER PT J AU Yeghiayan, SK Andersen, SL Baldessarini, RJ AF Yeghiayan, SK Andersen, SL Baldessarini, RJ TI Lack of effect of chronic clorgyline or selegiline on dopamine and serotonin transporters in rat caudate-putamen or nucleus accumbens septi SO NEUROSCIENCE LETTERS LA English DT Article DE dopamine; serotonin; transporter; monoamine oxidase; autoradiography; striatum; accumbens ID MESSENGER-RNA; UPTAKE INHIBITORS; H-3 DOPAMINE; UPTAKE SITES; BRAIN; BINDING; COCAINE; STRIATUM; DRUGS; ANTIDEPRESSANTS AB Rats were injected intraperitoneally thrice weekly for 4 weeks with doses of selective inhibitors of monoamine oxidase type A (clorgyline, 1 mg/kg) or B ((-)-selegiline, 10 mg/kg), or saline. Both treatments produced sustained elevations of concentrations of dopamine and serotonin, and decreased their deaminated metabolites in forebrain tissue. Nevertheless, no change in binding of [H-3]GBR-12935 to the dopamine transporter or of [H-3]paroxetine to the serotonin transporter in caudate-putamen or nucleus accumbens septi was found with quantitative autoradiography. These results support the impression that transporter proteins for these monoamines are not regulated by increased ligand abundance. (C) 1997 Elsevier Science Ireland Ltd. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. FU NIMH NIH HHS [MH-14275, MH-34006, MH-47370] NR 20 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 7 PY 1997 VL 236 IS 3 BP 147 EP 150 DI 10.1016/S0304-3940(97)00777-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA YH841 UT WOS:A1997YH84100007 PM 9406758 ER PT J AU Warren, KG Catz, I Wucherpfennig, KW AF Warren, KG Catz, I Wucherpfennig, KW TI Tolerance induction to myelin basic protein by intravenous synthetic peptides containing epitope P85VVHFFKNIVTP96 in chronic progressive multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE multiple sclerosis; peptide-based tolerance; MBP autoantibody; HLA-DR2 ID MATURE T-CELLS; AUTOIMMUNE ENCEPHALOMYELITIS; FINE SPECIFICITY; SOLUBLE-ANTIGEN; RECOGNITION; APOPTOSIS; DEATH; RECEPTOR; LYMPHOCYTES; THERAPY AB Peptide-based tolerance induction may be useful for antigen-specific immunotherapy of human autoimmune diseases. Induction of tolerance to myelin basic protein (MBP) was examined in a Phase I clinical trial in multiple sclerosis (MS) patients with chronic progressive disease using a peptide that is immunodominant for MBP specific T cells and B cells. Tolerance induction was monitored by quantification of MBP specific autoantibodies in cerebrospinal fluid (CSF). The route of peptide administration was important since only intravenous but not intrathecal or subcutaneous injection induced tolerance to MBP. Following a single intravenous injection of a peptide containing epitope P85VVHFFKNIVTP96, MBP autoantibodies were undetectable for three to four months. Tolerance was more prolonged following a second injection since autoantibodies were low or undetectable after one year in the majority of patients. Duration of tolerance to MBP depended on MHC class II haplotypes of patients; tolerance was long-lived in all patients with disease associated HLA-DR2. No neurological or systemic side effects were observed, regardless of the route of peptide administration. These data demonstrate that intravenous administration of a soluble peptide can result in long-lasting tolerance to an autoantigen in humans. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP Warren, KG (reprint author), UNIV ALBERTA,DEPT MED NEUROL,EDMONTON,AB,CANADA. NR 30 TC 52 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 6 PY 1997 VL 152 IS 1 BP 31 EP 38 DI 10.1016/S0022-510X(97)00130-5 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YF258 UT WOS:A1997YF25800004 PM 9395124 ER PT J AU delaMonte, SM Sohn, YK Wands, JR AF delaMonte, SM Sohn, YK Wands, JR TI Correlates of p53- and Fas (CD95)-mediated apoptosis in Alzheimer's disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Alzheimer's disease; apoptosis; p53; Fas (CD95); tau; amyloid-beta ID PROGRAMMED CELL-DEATH; PAIRED HELICAL FILAMENTS; NEUROFIBRILLARY TANGLES; CYTOSKELETAL PATHOLOGY; DNA FRAGMENTATION; NEURITIC PLAQUES; TRANSGENIC MICE; SENILE DEMENTIA; NEURONS; PROTEIN AB Apoptosis may be an important mechanism of cell loss in Alzheimer's disease (AD). Experimentally, apoptosis is preceded by nuclear accumulation of p53, and increased expression of Fas (CD95) antigen. In the present study, quantitative Western blot analysis of postmortem frontal and temporal lobe tissue demonstrated significantly higher mean levels of p53 and Fas in AD relative to age-matched controls. Immunohistochemical staining and in situ apoptosis assays demonstrated increased p53 and Fas expression and DNA fragmentation in overlapping populations of cortical neurons, and cortical and white matter glial cells distributed in legions damaged by neurodegeneration. Double-label immunohistochemical staining studies revealed p53 immunoreactivity in: 1) cortical neurons without tau-immunoreactive neurofibrillary tangles; 2) numerous, but not all tau-immunoreactive neuropil neurites and white matter axons; 3) dystrophic fibrils surrounding amyloid-beta-immunoreactive plaques; and 4) glial cells characterized as A(2)B(5)(+) protoplasmic astrocytes or oligodendrocytes. The prominent distribution of dystrophic p53-immunoreactive processes around amyloid-beta-containing plaques suggests that amyloid deposits are associated with local neuritic degeneration. In addition, the results suggest that many tau-immunoreactive neuritic processes originate from degenerating (p53(+)) as well as regenerating neurons. Finally, apoptosis of glial cells (A(2)B(5)(+)) required to maintain the functional integrity of axons and dendrites may represent an important pathogenic mechanism of axonal loss and synaptic disconnection in AD. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DIV NEUROPATHOL,ALZHEIMERS DIS RES CTR,DEPT MED,CHARLESTOWN,MA 02129. RP delaMonte, SM (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,MGH E CANC CTR,ROOM 7308,149 13TH ST,CHARLESTOWN,MA 02129, USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169, AA-2666] NR 55 TC 204 Z9 212 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 6 PY 1997 VL 152 IS 1 BP 73 EP 83 DI 10.1016/S0022-510X(97)00131-7 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YF258 UT WOS:A1997YF25800008 PM 9395128 ER PT J AU Counter, SA Buchanan, LH Ortega, F Laurell, G AF Counter, SA Buchanan, LH Ortega, F Laurell, G TI Normal auditory brainstem and cochlear function in extreme pediatric plumbism SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE lead; auditory; brainstem; ABR; hearing; neurotoxic; cochlea; ototoxic ID STEM EVOKED-POTENTIALS; LEAD-EXPOSURE; COGNITIVE-DEVELOPMENT; MULTIPLE-SCLEROSIS; BLOOD LEAD; FOLLOW-UP; CHILDREN; PERFORMANCE; RESPONSES; NUTRITION AB Lead (Pb) intoxication in children has been associated with encephalopathy, sensory and cognitive impairments. We investigated the prevalence and neuro-sensory effects of Pb exposure in children living in Andean villages of Ecuador with high Pb contamination from discarded automobile batteries used in the local ceramics glazing industry. Venous blood samples were collected from 107 children in the Pb glazing area and from 39 children living in a geographically distant area with no known Pb contamination and measured for blood lead (PbB) levels. Auditory brainstem responses (ABR) and audiological/otological tests were conducted on children in the Pb-Glazing Group. The median PbB level for children in the Pb-Glazing Group was 40.0 mu g per dl (range: 6.2-128.2 mu g per dl) and for the non Pb-Glazing Group 6.0 mu g per dl (1.9-18.0 mu g per dl). The differences in PbB levels for children in the study and control areas were statistically significant (t-test, P<0.0001). ABR tests on the Ph-Glazing Group indicated normal wave latencies and neural transmission times, and no statistical correlation between WE level and interpeak latencies. Audiological tests showed normal cochlear function and no statistical relation between auditory thresholds and PbB level. Contrary to prevailing assumptions, elevated PbB levels in children do not invariably impair auditory brainstem neural transmission or sensory-neural cochlear function, both of which have been implicated as significant contributors to the neurodevelopmental disabilities associated with childhood plumbism. (C) 1997 Elsevier Science B.V. C1 HARVARD UNIV, DEPT AUDIOL, SHRIVER CTR, HLTH SERV, WALTHAM, MA 02154 USA. UNIV SAN FRANCISCO, DEPT MED, QUITO, ECUADOR. KAROLINSKA INST, KAROLINSKA HOSP, DEPT OTOLARYNGOL, S-17176 STOCKHOLM, SWEDEN. RP Counter, SA (reprint author), HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,DEPT NEUROL, BIOL LABS, 16 DIVIN AVE, CAMBRIDGE, MA 02138 USA. NR 43 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 6 PY 1997 VL 152 IS 1 BP 85 EP 92 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YF258 UT WOS:A1997YF25800009 PM 9395129 ER PT J AU Sattler, M Salgia, R Shrikhande, G Verma, S Choi, JL Rohrschneider, LR Griffin, JD AF Sattler, M Salgia, R Shrikhande, G Verma, S Choi, JL Rohrschneider, LR Griffin, JD TI The phosphatidylinositol polyphosphate 5-phosphatase SHIP and the protein tyrosine phosphatase SHP-2 form a complex in hematopoietic cells which can be regulated by BCR/ABL and growth factors SO ONCOGENE LA English DT Article DE BCR/ABL; SHIP; SHP-2; CBL ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; MULTIPLE CYTOKINES; RECEPTOR; ACTIVATION; BINDING; KINASE; SHC; PHOSPHORYLATION; P210(BCR/ABL); GRB2 AB We report here that interleukin-3 (IL-3) and erythropoietin (EPO) induce formation of a complex composed of two SH2-containing phosphatases, the tyrosine phosphatase SHP-2 and the SH2 containing inositol 5-phosphatase (SHIP), Both SHP-2 and SHIP are known to be involved in growth factor signal transduction, but their potential interaction in the same pathway is novel, SHIP has previously been shown to associate with SHC, and potentially to be involved in regulating apoptosis, In contrast, in some model systems, SHP-2 has been demonstrated to positively regulate cell growth, Both phosphatases in the complex were tyrosine phosphorylated, and the amount of SHIP coprecipitating with SHP-2 was inversely related to the amount of SHIP coprecipitating with SHC, In hematopoietic cells transformed by the BCR/ABL oncogene, this phosphatase complex was found to be constitutively present with both components heavily tyrosine phosphorylated, Also, other proteins were detected in the complex, including BCR/ABL itself and c-CBL, However, transformation by BCR/ABL was associated with a reduced SHIP protein expression, which could further affect the accumulation of various inositol polyphosphates in these leukemic cells, These data suggest that the function of SHIP and SHP-2 in normal cells are linked and that BCR/ABL alters the function of this signaling complex. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,DPET ADULT ONCOL,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,DIV BASIC SCI,SEATTLE,WA 98125. FU NCI NIH HHS [CA01730]; NIDDK NIH HHS [DK50654] NR 22 TC 64 Z9 69 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 6 PY 1997 VL 15 IS 19 BP 2379 EP 2384 DI 10.1038/sj.onc.1201422 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA YE157 UT WOS:A1997YE15700012 PM 9393882 ER PT J AU Anzueto, A Jubran, A Ohar, JA Piquette, CA Rennard, SI Colice, G Pattishall, EN Barrett, J Engle, M Perret, KA Rubin, BK AF Anzueto, A Jubran, A Ohar, JA Piquette, CA Rennard, SI Colice, G Pattishall, EN Barrett, J Engle, M Perret, KA Rubin, BK TI Effects of aerosolized surfactant in patients with stable chronic bronchitis - A prospective randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RECOMBINANT HUMAN DNASE; IODINATED GLYCEROL; PULMONARY-FUNCTION; CYSTIC-FIBROSIS; MUCUS; TRANSPORT; SPUTUM AB Context.-Chronic bronchitis, estimated to affect more than 13 million adults in the United States, is characterized in part by retention of airway secretions, but no approved or effective therapy for airway mucus retention in patients with chronic bronchitis has been established. Surfactant reduces sputum adhesiveness, which contributes to difficulty in clearing secretions, but surfactant has not been tested in patients with chronic bronchitis. Objective.-To examine the effects of exogenous surfactant on sputum clearance and pulmonary function in patients with stable chronic bronchitis. Design.-A prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled comparison of the effects of 2 weeks of treatment with 3 doses of aerosolized surfactant (palmitoylphosphadidylcholine [DPPC]) or saline (placebo). Setting.-Four US teaching hospitals. Participants.-A total of 87 adult patients with the diagnosis of stable chronic bronchitis. Main Outcome Measures.-Pulmonary function, respiratory symptoms, and sputum properties before treatment (day 0), after 2 weeks of treatment (day 14), and 7 days after stopping treatment (day 21). Results.-A total of 66 patients were randomized to surfactant treatment and 21 to saline treatment. Patient demographic characteristics between groups were similar at baseline, In patients who received a DPPC dose of 607.5 mg/d for 2 weeks, prebronchodilator forced expiratory volume in 1 second (FEV1) increased from 1.22 L (SEM, 0.08 L) at day 0 to 1.33 L (SEM, 0.09 L) at day 21 (P=.05), an improvement of 11.4%; postbronchodilator FEV1 improved 10.4% by days 14 and 21 (P=.02); and the ratio of residual volume to total lung capacity, a measure of thoracic gas trapping, decreased 6.2% by day 21 (P=.009). In the surfactant groups, there was a dose-dependent increase in the ability of sputum to be transported by cilia in vitro. Conclusion.-Aerosolized surfactant improved pulmonary function and resulted in a dose-related improvement in sputum transport by cilia in patients with stable chronic bronchitis. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,S TEX VET HLTH CARE SYST,SAN ANTONIO,TX 78284. LOYOLA UNIV,HINES,IL. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. ST LOUIS UNIV,HLTH SCI CTR,ST LOUIS,MO 63103. UNIV NEBRASKA,MED CTR,OMAHA,NE. 3M PHARMACEUT,ST PAUL,MN. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. E TENNESSEE PULM ASSOC,KNOXVILLE,TN. NR 32 TC 45 Z9 46 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 1997 VL 278 IS 17 BP 1426 EP 1431 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YC917 UT WOS:A1997YC91700029 PM 9356001 ER PT J AU Metlay, JP Kapoor, WN Fine, MJ AF Metlay, JP Kapoor, WN Fine, MJ TI Does this patient have community-acquired pneumonia? Diagnosing pneumonia by history and physical examination SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CONFIDENCE-INTERVALS; CLINICAL-PREDICTION; CHEST; ANTIBIOTICS; RELIABILITY; OUTPATIENTS; ADULTS AB Community-acquired pneumonia is an important cause of acute respiratory symptoms (eg, cough) in the ambulatory care setting, Distinguishing pneumonia from other causes of respiratory illnesses, such as acute bronchitis and upper respiratory tract infections, has important therapeutic and prognostic implications, The reference standard for diagnosing pneumonia is chest radiography, but it is likely that many physicians rely on the patient's history and their physical examination to diagnose or exclude this disease. A review of published studies of patients suspected of having pneumonia reveals that there are no individual clinical findings, or combinations of findings, that can rule in the diagnosis of pneumonia for a patient suspected of having this illness, However, some studies have shown that the absence of any vital sign abnormalities or any abnormalities on chest auscultation substantially reduces the likelihood of pneumonia to a point where further diagnostic evaluation may be unnecessary, This article reviews the literature on the appropriate use of the history and physical examination in diagnosing community-acquired pneumonia. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV PITTSBURGH,DEPT MED,CTR RES HLTH CARE,DIV GEN INTERNAL MED,PITTSBURGH,PA. FU BHP HRSA HHS [5 T32 PE11001-08] NR 33 TC 229 Z9 239 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 5 PY 1997 VL 278 IS 17 BP 1440 EP 1445 DI 10.1001/jama.278.17.1440 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA YC917 UT WOS:A1997YC91700032 PM 9356004 ER PT J AU Lehmann, KG vanSuylen, RJ Stibbe, J Slager, CJ Oomen, JA Maas, A diMario, C deFeyter, P Serruys, PW AF Lehmann, KG vanSuylen, RJ Stibbe, J Slager, CJ Oomen, JA Maas, A diMario, C deFeyter, P Serruys, PW TI Composition of human thrombus assessed by quantitative colorimetric angioscopic analysis SO CIRCULATION LA English DT Article DE thrombus; diagnosis; fibrin ID UNSTABLE ANGINA-PECTORIS; LEFT-VENTRICULAR THROMBI; MYOCARDIAL-INFARCTION; CORONARY ANGIOSCOPY; INTRACORONARY THROMBUS; ANGIOGRAPHIC DETECTION; ULTRASOUND; ISCHEMIA; ASPIRIN; OCCLUSION AB Background Angioscopy surpasses other diagnostic tools, such as angiography and intravascular ultrasound, in detecting arterial thrombus. This capability arises in part from the unique ability of angioscopy to assess true color during imaging. In practice, hardware-induced chromatic distortions and the subjectivity of human color perception substantially limit the theoretic potential of angioscopic color. We used a novel application of tristimulus colorimetry to quantify thrombus color to both aid in its detection and assess its composition. Methods and Results A series of human thrombus models were constructed in vitro. Spatial homogeneity was ensured by light and electron microscopy. Quantitative colorimetry angioscopic analysis demonstrated excellent measurement reproducibility (mean difference, 0.07% to 0.17%), unaffected by illuminating light intensity (coefficient of variation, 0.21% to 3.67%). Colorimetric parameters C-1 and C-2 were strongly correlated (r=.99, P<.0001) with thrombus erythrocyte concentration. Principal components analysis transformed these parameters into a single value, the thrombus erythrocyte index with little (0.06%) loss of content. Measured and predicted concentrations were similar (mean difference; 0.16 erythrocytes per 1 ng). Randomly ordered images were also subjected to visual analysis by three experienced angioscopists, with suboptimal levels of both intraobserver (mean (kappa=0.63) and interobserver (mean kappa=0.48) agreement. In addition, visual ranking resulted in a Kendall rank coefficient of 0.72 to 0.76 versus a perfect 1.00 from quantitative measurement. Conclusions Quantitative colorimetric angioscopic analysis provides a new, objective. and reproducible analytic tool for assessing angioscopic images of human thrombus. Even under ideal circumstances, experienced angioscopists do a poor job of assessing color (and therefore composition) of human thrombi. This technique can, for the first time, provide quantitative information of thrombus composition during routine diagnostic imaging. C1 VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. UNIV WASHINGTON,SCH MED,SEATTLE,WA. ERASMUS UNIV ROTTERDAM,THORAXCTR,NL-3000 DR ROTTERDAM,NETHERLANDS. NR 44 TC 11 Z9 12 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 4 PY 1997 VL 96 IS 9 BP 3030 EP 3041 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA YF295 UT WOS:A1997YF29500044 PM 9386172 ER PT J AU Gomez, AG Grimm, CT Yee, EFT Skootsky, SA AF Gomez, AG Grimm, CT Yee, EFT Skootsky, SA TI Preparing residents for managed care practice using an experience-based curriculum SO ACADEMIC MEDICINE LA English DT Article ID HEALTH-CARE; MEDICAL-EDUCATION; PHYSICIANS; SYSTEM AB Many U.S. residency graduates will practice in various types of managed care organizations, where they will be expected to arrive skilled in managed care activities such as prescribing with formularies and adhering to preauthorization processes for procedures, referrals, and hospital admissions. Residency programs must prepare their trainees to negotiate for their patients' needs within such systems. This article describes a University of California, Los Angeles, UCLA School of Medicine curriculum that teaches managed care skills to residents in two internal medicine residency training programs. The residents in one program participate in a commercial health maintenance organization plan via a group-model faculty practice. Managed care activities for residents in this program were gradually introduced beginning in 1990. This reflected previous years' gradual yet enforced introduction of managed care activities that occurred for this program's faculty and most group practice physicians in California. Residents in the other program train at a public hospital where managed care practice is simulated. Managed care activities were not required by this program's institution but were Voluntarily introduced for their educational value beginning in 1994. Responding to this program's trainee and faculty requests, these activities were rapidly implemented over two years with the goal of preparing residents for joining practices in a market with high managed care penetration. Since 1994, the centerpiece of the curriculum has been residents' participation in ambulatory utilization review and related activities. Residents learn managed care principles through problem-based learning, experiential exercises, and feedback on resource utilization. The curriculum has affected residents' attitudes toward managed care and changed their patterns of referrals and resource use. Residents trained with this curriculum perceive managed care practices as familiar and less intrusive. They submit fewer requests for referrals, perhaps with review in mind. However, precautions may be required to avoid undercare. The authors found that the reduction of referrals requested was greater than what they had expected. Residents may find scrutiny by colleagues intimidating. Also, this curriculum requires a substantial time commitment from residency training, with its already busy teaching agenda. The authors feel that initiating a managed care curriculum is an important investment in time for U.S. residency programs. Given thatmost graduates of residency programs will have their health care management decisions scrutinized while in practice, the authors feel it is important that residents' first exposure to managed care be while they are still in the supportive residency environment. They believe that early exposure will not only give residents the confidence to overcome the intimidation of colleague scrutiny, but may also give graduates the tools for involvement with the development of future managed care health policy. C1 SEPULVEDA VET HLTH ADM MED CTR,PRIMARY AMBULATORY CARE & EDUC PROGRAM,SEPULVEDA,CA. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. SEPULVEDA VET HLTH ADM MED CTR,UCLA SAN FERNANDO VALLEY PROGRAM,BEHAV MED PROGRAM,SEPULVEDA,CA. W LOS ANGELES VET AFFAIRS MED CTR,WOMENS LIFE CYCLE HLTH & EDUC CTR,LOS ANGELES,CA. SEPULVEDA VET HLTH ADM MED CTR,WOMENS LIFE CYCLE HLTH & EDUC CTR,SEPULVEDA,CA. W LOS ANGELES VET HLTH ADM MED CTR,WOMENS LIFE CYCLE HLTH & EDUC CTR,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,CTR MANAGED CARE EDUC,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DIV GEN INTERNAL MED & HLTH SERV RES,LOS ANGELES,CA 90024. NR 18 TC 14 Z9 14 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1997 VL 72 IS 11 BP 959 EP 965 DI 10.1097/00001888-199711000-00011 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA YG464 UT WOS:A1997YG46400012 PM 9387817 ER PT J AU Quan, MB Edwards, C Marks, R AF Quan, MB Edwards, C Marks, R TI Non-invasive in vivo techniques to differentiate photodamage and ageing in human skin SO ACTA DERMATO-VENEREOLOGICA LA English DT Article ID MECHANICAL-PROPERTIES AB It is important to differentiate skin changes due to the intrinsic ageing process from those due to chronic photodamage in the development of therapies to assist the latter condition, and in this study we have used instrumental techniques to differentiate between changes in a range of properties of skin due to ageing and those due to photodamage, especially with regard to elasticity. We measured three sites of differing sun exposure in a group of younger and in a group of older subjects. A pulsed A-scan ultrasound system was used to measure skin thickness, and a uniaxial extensometer was employed to assess elastic properties. Skin surface roughness measurements were made using silicone rubber impressions and a stylus profilometer. We demonstrated significant differences in skin roughness between young and old subjects at every site and differences between sun-exposed and sun-protected sites only in the older group. Parameters of the elastic properties of skin differed between the groups, and also between sites of most different sun exposure. The uniaxial extensometer can demonstrate a loss of the skin's elasticity predominantly by photodamage, and the roughness of the skin surface can be shown to increase mostly by chronological ageing but to decrease modestly by photodamage. This demonstrates that differences between the two processes can be quantified, and indeed they should be. C1 UNIV WALES COLL MED,DEPT DERMATOL,CARDIFF CF4 4XN,S GLAM,WALES. MASSACHUSETTS GEN HOSP,DERMATOL SURG UNIT,BOSTON,MA 02114. NR 12 TC 16 Z9 16 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PD NOV PY 1997 VL 77 IS 6 BP 416 EP 419 PG 4 WC Dermatology SC Dermatology GA YE324 UT WOS:A1997YE32400002 PM 9394971 ER PT J AU Chiappelli, F Kung, MA Tio, DL Tritt, SH Yirmiya, R Taylor, AN AF Chiappelli, F Kung, MA Tio, DL Tritt, SH Yirmiya, R Taylor, AN TI Fetal alcohol exposure augments the blunting of tumor necrosis factor production in vitro resulting from in vivo priming with lipopolysaccharide in young adult male but not female rats SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fetal alcohol exposure; lipopolysaccharide (LPS); tumor necrosis factor-alpha; peripheral blood mononuclear cells (PBMCs); primed PBMCs ID PROLIFERATIVE RESPONSE; ETHANOL INUTERO; IMMUNE; ALTERS; CELLS AB We previously reported altered responses of thymocytes and splenocytes to mitogen stimulation in fetal alcohol-exposed (FAE) male Sprague-Dawley rats. We also reported enhanced neuroendocrine responses to stressful stimuli in these animals. The experiments we describe herein aimed at testing whether young adult FAE rats manifest a notable dysregulation in the neuroendocrine-immune response to pathogen administration. We tested the effect of in vivo priming of the animal with a low dose of endotoxin [lipopolysaccharide (LPS), 5 mu g/kg], considered to be suboptimal from the perspective of mounting detectable levels of circulating monokines several hours after administration, upon the production of immunoreactive tumor necrosis factor (TNF-alpha) in response to a further in vitro challenge of peripheral blood mononuclear cells with 2.5 mu g/ml of LPS 90 min after priming. We show that the response to the LPS pathogen in vitro after priming is significantly blunted (p < 0.01) in male rats exposed prenatally to alcohol, compared with control male animals. FAE female rats and FAE ovariectomized female rats do not show significant differences in the priming response, compared with control animals. We also show that there is no correspondence between plasma corticosterone levels and TNF-alpha production after priming in any of the groups tested. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROBIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH DENT,LAB HUMAN ORAL & MOL IMMUNOL,LOS ANGELES,CA 90024. W LOS ANGELES DEPT VET AFFAIRS MED CTR,LOS ANGELES,CA. HEBREW UNIV JERUSALEM,DEPT PSYCHOL,IL-91905 JERUSALEM,ISRAEL. FU NIAAA NIH HHS [AA09850]; NIDA NIH HHS [DA07683] NR 18 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1997 VL 21 IS 8 BP 1542 EP 1546 PG 5 WC Substance Abuse SC Substance Abuse GA YG096 UT WOS:A1997YG09600028 PM 9394129 ER PT J AU Padial, LR Oliver, A Sagie, A Weyman, AE King, ME Levine, RA AF Padial, LR Oliver, A Sagie, A Weyman, AE King, ME Levine, RA TI Two-dimensional echocardiographic assessment of the progression of aortic root size in 127 patients with chronic aortic regurgitation: Role of the supraaortic ridge and relation to the progression of the lesion SO AMERICAN HEART JOURNAL LA English DT Article ID STRUCTURALLY NORMAL HEARTS; DOPPLER-ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; VALVE REPLACEMENT; INSUFFICIENCY; PREVALENCE; QUANTITATION; DILATATION; CHILDREN AB Although aortic root dilation has etiologic and prognostic significance in patients with chronic aortic regurgitation (AR), no information is available regarding changes over time in aortic root size in patients with the entire spectrum of AR severity or how such changes relate to progression of the AR or to left ventricular (LV) overload. To analyze-this, a total of 127 patients with chronic AR who had more than 6 months of follow-up by two-dimensional and Doppler echocardiography were included in the study (69 men and 58 women; mean age 59.3 +/- 21.2 years [range 14 to 94 years]; 67 cases of mild, 45 moderate, 15 severe, and 21 bicuspid aortic valve disease). The aortic anulus, sinuses of Valsalva, supraaortic ridge, and ascending aorta were measured in the parasternal long-axis view, LV volumes were calculated (biplane Simpson's approach), and the severity of AR was quantified based on proximal jet size and graded according to an algorithm that takes into account major color Doppler criteria. At entry to the study; significant differences between patients with mild, moderate, and severe AR were noted only in supraaortic ridge size (1.46 +/- 0.29 cm/m(2) vs 1.63 +/- 0.33 cm/m(2) [p < 0.006]; vs 1.67 +/- 0.43 cm/m(2) [p < 0.03]). A significant increase in aortic root size at all levels was observed during the follow-up period in all three groves of severity of AR. The rate of change of the supraaortic ridge, the upper support structure of the anulus and cusps, was foster in patients with more severe degrees of AR (p = 0.013); this was not the case at the other aortic levels. No differences-were observed in aortic root size or rate of progression between patients with bicuspid or tricuspid aortic valves. Patients were considered ''progressive'' if they lay on the steepest positive segment of the curve representing the rank order in the rate of aortic root progression. Compared with ''nonprogressive'' patients, patients who were progressive in suproaortic ridge size (rate >0.12 cm/yr; n = 23) had a faster rate of progression in the degree of regurgitation as assessed by the regurgitant jet area/LV outflow tract area ratio measured in the parasternal short-axis view (0.48 +/- 0.45 vs 0.24 +/- 0.5/yr; p < 0.03) and a faster rate of progression of LV end-diastolic volume (30 +/- 22.8 vs 14.4 +/- 15.6 ml/yr; p < 0.0002) and LV mass (70.8 +/- 74.4 vs 16.8 +/- 19.2 gm/yr.; p < 0.0004). In conclusion, there is progressive dilation of the aortic root at all levels, even in patients with mild AR. More rapid progression in aortic root size is associated with more rapid progression of the underlying aortic insufficiency, as well as more rapid increases in LV volume and mass. C1 MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 30 TC 19 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1997 VL 134 IS 5 BP 814 EP 821 DI 10.1016/S0002-8703(97)80004-X PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YJ247 UT WOS:A1997YJ24700004 PM 9398093 ER PT J AU Freed, LA Eagle, KA Mahjoub, ZA Gold, MR Smith, AJC Terrell, LB OGara, PT Paul, SD AF Freed, LA Eagle, KA Mahjoub, ZA Gold, MR Smith, AJC Terrell, LB OGara, PT Paul, SD TI Gender differences in presentation, management, and cardiac event-free survival in patients with syncope SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Scientific Session of the American-College-of-Cardiology Meeting CY MAR 24-28, 1996 CL ORLANDO, FL SP Amer Coll Cardiol ID SIGNAL-AVERAGED ELECTROCARDIOGRAM; AORTIC REGURGITATION; VALVE-REPLACEMENT; OPERATIVE INTERVENTION; HEALTHY-SUBJECTS; OPTIMUM TIME; WOMEN AB In a MEDLINE search of published English studies (1966 to 1996), no prior study was identified that examined gender-based differences in the management and prognosis of patients admitted with syncope. We studied 109 consecutive patients (48 women) admitted with syncope at the Massachusetts General Hospital (1989 to 1990). All patients underwent Holter monitoring, signal-averaged electrocardiography, and echocardiography according to study protocol. Follow-up was 100% complete (10 +/- 4 months). Women were older (74 +/- 2 vs 66 +/- 2 years, p < 0.01) and less likely to have premonitory symptoms when compared with men (46% vs 66%, p < 0.05). A greater proportion of men had left ventricular ejection fractions of < 0.40 (18% vs 0%, p < 0.01), abnormal signal-averaged electrocardiograms (28% vs 8%, p < 0.01), and a cardiac cause for syncope (49% vs 25%, p < 0.01). Although referral for diagnostic electrophysiologic testing was > 3 times as frequent for men compared with women (20% of men vs 6% of women, p < 0.05), this difference wets not significant after adjustment for age, ventricular arrhythmia, and referral for coronary angiography. During follow-up, 21% of men versus 6% of women (p < 0.05) had cardiac events (recurrent syncope, myocardial infarction, or sudden death). Cardiac event-free survival rates were worse for men (p = 0.045). Thus, we have identified gender-based differences in the clinical presentation of syncope for hospital admission. left ventricular dysfunction and an abnormal signal-averaged electrocardiogram occur more frequently in men. Men are more likely to have cardiac syncope and worse cardiac event-free survival when compared with women. (C) 1997 by Excerpta Medico, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MICHIGAN,DEPT MED,DIV CARDIOL,HEART CARE PROGRAM,ANN ARBOR,MI 48109. WAYNE STATE UNIV,DEPT MED,DIV CARDIOL,DETROIT,MI 48202. UNIV MARYLAND,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21201. UNIV PITTSBURGH,DEPT MED,DIV CARDIOL,PITTSBURGH,PA. UNIV MICHIGAN,MED CTR,DEPT MED,ANN ARBOR,MI 48109. BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1997 VL 80 IS 9 BP 1183 EP 1187 DI 10.1016/S0002-9149(97)00637-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YD116 UT WOS:A1997YD11600012 PM 9359547 ER PT J AU Holloman, LC Marder, SR AF Holloman, LC Marder, SR TI Management of acute extrapyramidal effects induced by antipsychotic drugs SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE akathisia; amantadine; antiparkinson agents; antipsychotic agents; basal ganglia diseases; benzodiazepines; dosage; dystonia; metoprolol; parasympatholytic agents; Parkinson's disease; propranolol; sympatholytic agents; toxicity ID NEUROLEPTIC-INDUCED AKATHISIA; CHRONIC-SCHIZOPHRENIC PATIENTS; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND CROSSOVER; D2-DOPAMINE RECEPTOR OCCUPANCY; TARDIVE-DYSKINESIA; PARKINSONS-DISEASE; CLINICAL CHARACTERISTICS; BENZTROPINE MESYLATE; INDUCED DYSTONIA AB The management of acute extrapyramidal effect (EPEs) induced by antipsychotic drugs is reviewed. EPEs associated with antipsychotics include acute dystonias, pseudoparkinsonism, and akathisia. Acute dystonias consist of abnormal muscle spasms and postures and usually occur three to five days after antipsychotic therapy begins or the dosage is increased. Acute dystonias should be treated with anticholinergic medications or benzodiazepines. Antipsychotic-induced pseudoparkinsonism has the same clinical appearance as idiopathic parkinsonism. Symptoms generally appear within the first three months. Pseudoparkinsonism is managed by lowering the anti-psychotic dosage or by adding an anticholinergic agent or a mantadine; switching to a low-potency agent or an atypical antipsychotic may also help. Akathisia is characterized by subjective feelings of restlessness and anxiety and objective signs of motor activity, such as inability to sit still. This EPE appears days to weeks after antipsychotic exposure begins and can be difficult to manage. If reduction of the antipsychotic dosage or a switch to a less potent antipsychotic is not practical or effective, an anticholinergic, P-blocker, or benzodiazepine may be added. Lipophilic beta-blockers, especially propranolol and metoprolol, appear to be the most effective treatments. Anticholinergic agents are commonly given to prevent acute dystonias, especially in high-risk patients, but long-term prophylaxis is controversial. Atypical antipsychotics may have less potential to induce EPEs. Options in the management of antipsychotic associated EPEs include using the lowest effective dosage of antipsychotic, treating the reactions with medications, and changing the antipsychotic to one with less potential for inducing EPEs. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT PHARM,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,MENTAL HLTH SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 160 TC 36 Z9 38 U1 2 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 1 PY 1997 VL 54 IS 21 BP 2461 EP 2477 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF848 UT WOS:A1997YF84800015 PM 9359953 ER PT J AU Tsou, HC Teng, DHF Ping, XL Brancolini, V Davis, T Hu, R Xie, XX Gruener, AC Schrager, CA Christiano, AM Eng, C Steck, P Ott, J Tavtigian, SV Peacocke, M AF Tsou, HC Teng, DHF Ping, XL Brancolini, V Davis, T Hu, R Xie, XX Gruener, AC Schrager, CA Christiano, AM Eng, C Steck, P Ott, J Tavtigian, SV Peacocke, M TI The role of MMAC1 mutations in early-onset breast cancer: Causative in association with Cowden syndrome and excluded in BRCA1-negative cases SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TUBEROUS SCLEROSIS; LINKAGE ANALYSIS; GENE; DISEASE; LOCALIZATION; MARKER; BRCA1 AB Cowden syndrome (CS) is an autosomal dominant disorder associated with the development of hamartomas and benign tumors in a variety of tissues, including the skin, thyroid, breast, endometrium, and brain. It has been suggested that women with CS are at increased risk for breast cancer. A locus for CS was recently defined on chromosome 10 in 12 families, resulting in the identification of the CS critical interval, between the markers D10S215 and D10S541. More recently, affected individuals in four families with CS have been shown to have germ-line mutations in a gene known as ''PTEN,'' or ''MMAC1,'' which is located in the CS critical interval on chromosome 10. In this study, we report three novel MMAC1 mutations in CS and demonstrate that MMAC1 mutations are associated with CS and breast cancer. Furthermore, we also show that certain families and individuals with CS do not have mutations in the coding sequence of MMAC1. Finally, we did not detect MMAC1 mutations in a subpopulation of individuals with early-onset breast cancer, suggesting that germ-line mutations in this gene do not appear to be common in this group. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT DERMATOL,NEW YORK,NY. ROCKEFELLER UNIV,LAB STAT GENET,NEW YORK,NY 10021. MYRIAD GENET INC,SALT LAKE CITY,UT. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT NEUROONCOL & PATHOL,BRAIN TUMOR CTR,HOUSTON,TX 77030. OI Brancolini, Valeria/0000-0003-0871-537X FU NCI NIH HHS [R0-1 CA-70519, R0-1 CA-66693]; NIA NIH HHS [K-04 AG-00694] NR 24 TC 92 Z9 95 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1997 VL 61 IS 5 BP 1036 EP 1043 DI 10.1086/301607 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YH017 UT WOS:A1997YH01700007 PM 9345101 ER PT J AU McGee, TL Devoto, M Ott, J Berson, EL Dryja, TP AF McGee, TL Devoto, M Ott, J Berson, EL Dryja, TP TI Evidence that the penetrance of mutations at the RP11 locus causing dominant retinitis pigmentosa is influenced by a gene linked to the homologous RP11 allele SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; FATAL FAMILIAL INSOMNIA; CHROMOSOME 19Q; BIMODAL EXPRESSIVITY; DNA POLYMORPHISM; LINKAGE ANALYSIS; JAPANESE FAMILY; RHODOPSIN GENE; YAC CONTIG; ONE FORM AB A subset of families with autosomal dominant retinitis pigmentosa (RP) display reduced penetrance with some asymptomatic gene carriers showing no retinal abnormalities by ophthalmic examination or by electroretinography. Here we describe a study of three families with reduced-penetrance RP. In all three families the disease gene appears to be linked to chromosome 19q13.4, the region containing the RP11 locus, as defined by previously reported linkage studies based on five other reduced-penetrance families. Meiotic recombinants in one of the newly identified RP11 families and in two of the previously reported families serve to restrict the disease locus to a 6-cM region bounded by markers D19S572 and D19S926. We also compared the disease status of RP11 carriers with the segregation of microsatellite alleles within 19q13.4 from the noncarrier parents in the newly reported and the previously reported families. The results support the hypothesis that wild-type alleles at the RP11 locus or at a closely linked locus inherited from the noncarrier parents are a major factor influencing the penetrance of pathogenic alleles at this locus. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR MOL GENET INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA. ROCKEFELLER UNIV,LAB STAT GENET,NEW YORK,NY 10021. INST G GASLINI,MOL GENET LAB,GENOA,ITALY. FU NEI NIH HHS [EY08683, EY00169, EY11655] NR 39 TC 53 Z9 54 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1997 VL 61 IS 5 BP 1059 EP 1066 DI 10.1086/301614 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA YH017 UT WOS:A1997YH01700010 PM 9345108 ER PT J AU Cody, JD Singer, FR Roodman, GD Otterund, B Lewis, TB Leppert, M Leach, RJ AF Cody, JD Singer, FR Roodman, GD Otterund, B Lewis, TB Leppert, M Leach, RJ TI Genetic linkage of Paget disease of the bone to chromosome 18q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL EXPANSILE OSTEOLYSIS; GIANT-CELL TUMOR; NUCLEAR INCLUSIONS; OSTEOCLASTS; FEATURES; REGION AB Paget disease is a common bone disease characterized by abnormal osteoclasts that are large, multinucleated, and overactive and that contain paramyxovirus-like nuclear inclusions. There is evidence for a major genetic component to Paget disease, with up to 40% of patients having affected first-degree relatives; however, the locus (loci) and-gene(s) involved are unknown. Another bone disorder, familial expansile osteolysis (FEO), although extremely rare, also is characterized by similar osteoclast abnormalities but has an earlier age at onset and a more aggressive clinical progression. The causative gene for FEO has been localized to a region of human chromosome 18q. On the basis of the presence of similar clinical findings and of viral-like nuclear inclusions in osteoclasts, we hypothesized that FEO and Paget disease are allelic versions of the same locus. Therefore, a large kindred with a high incidence of Paget disease was examined to determine if Paget disease was linked to genetic markers in the same region of chromosome 18 as that for FEO. Our analysis yielded a two-point LOD score of 3.40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX. ST JOHNS HOSP,JOHN WAYNE CANC INST,SANTA MONICA,CA. UNIV UTAH,SCH MED,ECCLES INST HUMAN GENET,DEPT HUMAN GENET,SALT LAKE CITY,UT. INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46204. FU NIA NIH HHS [1P30AG1319]; NIAMS NIH HHS [P01AR39529] NR 33 TC 107 Z9 107 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1997 VL 61 IS 5 BP 1117 EP 1122 DI 10.1086/301601 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA YH017 UT WOS:A1997YH01700017 PM 9345096 ER PT J AU Gelernter, J Kranzler, H Coccaro, E Siever, L New, A Mulgrew, CL AF Gelernter, J Kranzler, H Coccaro, E Siever, L New, A Mulgrew, CL TI D4 dopamine-receptor (DRD4) alleles and novelty seeking in substance-dependent, personality-disorder, and control subjects SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID STRUCTURED CLINICAL INTERVIEW; GENE; ASSOCIATION; ALCOHOLISM; POLYMORPHISM; POPULATION; CLOZAPINE; VARIANTS; AFRICANS; REPEAT AB Two reports have been published suggesting an association between the personality trait of novelty seeking and the DRD4*7R allele at the D4 dopamine-receptor locus (with heterozygotes or homozygotes for DRD4*7R having higher novelty seeking). We studied novelty seeking and four coding-sequence polymorphisms affecting protein structure in the D4 dopamine-receptor gene (DRD4) in a sample of 341 American subjects, of whom 224 are of primarily European ancestry and 117 are of primarily African ancestry. These subjects had diagnoses of substance dependence or personality disorder (PD) or were screened to exclude major psychiatric diagnosis. We found that, although the substance-dependent subjects had significantly higher novelty seeking than the control and PD subjects, they did not differ in DRD4*7R allele frequency. There was no association between any DRD4 polymorphism and novelty seeking in any population or diagnostic group, except for a significant association between the DRD4*7R allele and lower novelty seeking among European American females and African American substance abusers. The novelty seeking of subjects heterozygous for a null mutation did not differ from that of subjects with two functional alleles. We conclude that the most likely explanation of these results is that the DRD4 VNTR does not influence directly the trait of novelty seeking, in these samples. C1 YALE UNIV,SCH MED,DEPT PSYCHIAT,DIV MOL PSYCHIAT,W HAVEN,CT 06516. UNIV CONNECTICUT,CTR HLTH,DEPT PSYCHIAT,FARMINGTON,CT 06032. MED COLL PENN & HAHNEMANN UNIV,EASTERN PENN PSYCHIAT INST,PHILADELPHIA,PA 19129. MT SINAI SCH MED,NEW YORK,NY. BRONX VET ADM MED CTR,NEW YORK,NY. RP Gelernter, J (reprint author), VA CONNECTICUT HEALTHCARE SYST,PSYCHIAT 116A2,W HAVEN CAMPUS,950 CAMPBELL AVE,W HAVEN,CT 06516, USA. FU NIMH NIH HHS [K02-MH01387, K20-MH00931, R29-MH50859] NR 32 TC 137 Z9 142 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 1997 VL 61 IS 5 BP 1144 EP 1152 DI 10.1086/301595 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA YH017 UT WOS:A1997YH01700021 PM 9345090 ER PT J AU Glencross, PM Weinberg, JM Ibrahim, JG Christiani, DC AF Glencross, PM Weinberg, JM Ibrahim, JG Christiani, DC TI Loss of lung function among sheet metal workers: Ten-year study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE pulmonary function decline; sheet metal workers; asbestos exposure; shipyard work ID ASBESTOS INSULATION WORKERS; LONGITUDINAL DATA-ANALYSIS; DISEASE SCREENING-PROGRAM; PULMONARY-FUNCTION; PLEURAL FIBROSIS; OCCUPATIONAL EXPOSURE; CIGARETTE-SMOKING; SHIPYARD WORKERS; ABNORMALITIES; COHORT AB One hundred and twenty-two sheet metal workers in New England were examined over a 10-year interval for loss of pulmonary function and the development of asbestosis or asbestos-related pleural fibrosis. Regression models using the generalized estimating equation (GEE) approach were created to investigate the relationship between exposure and pulmonary function after adjusting for smoking status, age, height, and asbestos-related x-ray changes. A history of shipyard work was a significant contributor to the loss of forced vital capacity (FVC). Among smokers, loss in forced expiratory volume at 1 sec (FEV1) also had a significant relationship to prior shipyard work. There was a borderline significant relationship between percentage predicted FEV1 and cumulative years of asbestos exposure in smokers, as well as years-since-initial-exposure in never-smokers. This study supports previous findings of obstructive airway changes in asbestos-exposed workers and identifies shipboard work as an important predictor of loss in pulmonary function even years after shipyard exposure to asbestos has ceased. (C) 1997 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM & OCCUPAT HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PULM UNIT,OCCUPAT MED SECT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS RESP HOSP,CTR OCCUPAT & ENVIRONM MED,BRAINTREE,MA. FU CIT NIH HHS [T42/CCT110421]; NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [OH02421] NR 31 TC 15 Z9 16 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 1997 VL 32 IS 5 BP 460 EP 466 DI 10.1002/(SICI)1097-0274(199711)32:5<460::AID-AJIM5>3.0.CO;2-W PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA XY727 UT WOS:A1997XY72700005 PM 9327069 ER PT J AU Swinford, RD Baid, S Pascual, M AF Swinford, RD Baid, S Pascual, M TI Dialysis membrane adsorption during CRRT SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 2nd International Conference on Continuous Renal Replacement Therapy CY FEB 09-11, 1997 CL SAN DIEGO, CA SP Gambro Hlthcare, Cobe Renal Inten Care, Bellco DE adsorption; complement; continuous renal replacement therapies ID ACUTE-RENAL-FAILURE; COMPLEMENT FACTOR-D; HEMODIALYSIS MEMBRANES; ALTERNATIVE PATHWAY; BIOCOMPATIBILITY; ACTIVATION; POLYACRYLONITRILE; SEPSIS; POLYMETHYLMETHACRYLATE; BETA-2-MICROGLOBULIN AB Experimental and clinical studies have suggested that dialysis membrane biocompatibility may influence the morbidity and mortality of patients with acute renal failure, Complement activation by dialysis membranes may also prolong the recovery from acute renal failure, In this article, we review the concept of dialysis membrane adsorption, with particular attention to adsorption/inhihition of factor D, a highly specific serine protease of the alternative pathway of complement, The adsorptive properties of some dialysis membranes may be useful during continuous renal replacement therapies (CRRT) in critically ill patients. (C) 1997 by the National Kidney Foundation, Inc. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. UNIV TEXAS,SCH MED,DIV PEDIAT NEPHROL,HOUSTON,TX. NR 40 TC 7 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 1997 VL 30 IS 5 SU 4 BP S32 EP S37 DI 10.1016/S0272-6386(97)90540-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA YE172 UT WOS:A1997YE17200007 PM 9372977 ER PT J AU Curtin, HD AF Curtin, HD TI Rule out eighth nerve tumor: Contrast-enhanced T1-weighted or high-resolution T2-weighted MR? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE nerves, vestibulocochlear (VIII); magnetic resonance; special reports ID CEREBELLOPONTINE ANGLE; INNER-EAR; CONSTRUCTIVE INTERFERENCE; CT CISTERNOGRAPHY; ACOUSTIC NEUROMAS; SEQUENCE; LESIONS RP Curtin, HD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV PY 1997 VL 18 IS 10 BP 1834 EP 1838 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA YH894 UT WOS:A1997YH89400008 PM 9403437 ER PT J AU Friedman, E AF Friedman, E TI A hemodynamic model of the pathogenesis of age-related macular degeneration SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; BRUCHS MEMBRANE; ARTERIES; CHORIOCAPILLARIS; ATHEROSCLEROSIS; ANGIOGRAPHY; EYE RP Friedman, E (reprint author), HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 41 TC 134 Z9 139 U1 1 U2 2 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1997 VL 124 IS 5 BP 677 EP 682 PG 6 WC Ophthalmology SC Ophthalmology GA YD868 UT WOS:A1997YD86800008 PM 9372722 ER PT J AU Camacho, AE Eavey, RD Northrop, C AF Camacho, AE Eavey, RD Northrop, C TI Juvenile keratin inoculation induces chronic ear pathology SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE keratin; middle ear; granulation tissue; osteoneogesis; chronic ear pathology ID MIDDLE-EAR; AMNIOTIC-FLUID; ANIMAL-MODEL; CHOLESTEATOMA; CONTAMINATION AB Objective: Human neonatal temporal bones frequently show the formation of granulation tissue provoked by amniotic fluid keratin contents, desquamated keratinized epithelial cells and lanugo hair. Similar histopathologic findings have been produced previously in a short-term animal model. To test the hypothesis that those short-term pathologic observations could have theoretical relevance for ear disease in older patients, a longer term animal model study was necessary. Methods: Into the right bulla of 10 chinchilla pups was placed an aliquot of autogenous, nonviable epidermal scrapings and hair. Into the left bulla was placed 1 mm(2) viable autogenous epidermal tissue. Animals were killed at intervals up to 11 months and then studied by light microscopy. Results: Chronic ear histopathologic changes such as granulation tissue, osteoneogenesis, adhesions, and cholesteatoma were present. Over time, these secondary pathologic changes became more obvious than the initial keratin implant. Conclusions: The authors conclude that chronic pathologic changes resembling human ear disorders persist and that this model further extends the hypothesis that prenatally acquired keratin eventually could account for some cases of human ear disease. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. HOSP NINOS DR RICARDO GUTIERREZ,DEPT PATHOL,SAN JOSE,COSTA RICA. NR 13 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1997 VL 18 IS 6 BP 773 EP 779 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA YE751 UT WOS:A1997YE75100015 PM 9391676 ER PT J AU Wewer, UM Shaw, LM Albrechtsen, R Mercurio, AM AF Wewer, UM Shaw, LM Albrechtsen, R Mercurio, AM TI The integrin alpha 6 beta 1 promotes the survival of metastatic human breast carcinoma cells in mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; EXPRESSION; APOPTOSIS; LAMININ; CANCER; SUPPRESSION; SUBUNIT; MOLECULES; ADHESION; RECEPTOR AB The role of the integrin alpha 6 beta 1 in breast carcinoma progression was studied by targeted elimination of this integrin in MDA-MB-435 cells, a human breast carcinoma cell line that is highly metastatic in athymic mice. The strategy used is based on the finding that expression of a cytoplasmic domain deletion mutant of the beta 4-integrin subunit (beta 4-Delta CYT) in MDA-MB-435 cells eliminates formation of the alpha 6 beta 1 heterodimer. MDA-MB-435 cells that lacked alpha 6 beta 1 expression (beta 4-Delta CYT transfectants) formed tumors in athymic mice that were suppressed in their growth and that exhibited a significant increase in apoptosis in comparison to the control tumors. Unlike the control MDA-MB-435 cells, the beta 4-Delta CYT transfectants were unable to establish metastatic foci in the lungs. Also, the control transfectants grew substantially better than the beta 4-Delta CYT transfectants in the liver after intrahepatic injection because of extensive apoptosis in the beta 4-Delta CYT transfectants. These data suggest that a major function of the alpha 6 beta 1 integrin in breast carcinoma is to facilitate tumorigenesis and promote tumor cell. survival in distant organs. C1 BETH ISRAEL DEACONESS MED CTR DANA 601,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV COPENHAGEN,INST MOL PATHOL,COPENHAGEN,DENMARK. FU NCI NIH HHS [CA44704]; NIAID NIH HHS [AI39264] NR 30 TC 76 Z9 78 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1997 VL 151 IS 5 BP 1191 EP 1198 PG 8 WC Pathology SC Pathology GA YD878 UT WOS:A1997YD87800004 PM 9358743 ER PT J AU Tani, T Lumme, A Linnala, A Kivilaakso, E Kiviluoto, T Burgeson, RE Kangas, L Leivo, I Virtanen, I AF Tani, T Lumme, A Linnala, A Kivilaakso, E Kiviluoto, T Burgeson, RE Kangas, L Leivo, I Virtanen, I TI Pancreatic carcinomas deposit laminin-5, preferably adhere to laminin-5, and migrate on the newly deposited basement membrane SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; HUMAN KERATINOCYTE LOCOMOTION; SQUAMOUS-CELL CARCINOMA; MONOCLONAL-ANTIBODIES; SCATTER FACTOR; BASAL LAMINA; INTEGRIN ALPHA(6)BETA(4); DIFFERENTIAL EXPRESSION; ALPHA-3-BETA-1 INTEGRIN; CANCER-CELLS AB We studied the adhesion mechanism of pancreatic carcinoma using in vitro adhesion and migration assays of stable cell lines and tumors grown from these cell lines in nude mice. We also compared the results with the expression profiles of laminins and their receptors in pancreatic carcinomas to evaluate the relevance of these mechanisms in vivo. All of the cell Lines preferably adhered to laminin-5, irrespective of their capability to synthesize laminin-5. Cell migration was studied in the presence of hepatocyte growth factor, as it increased the speed of migration manyfold. Herbimycin A treatment and antibodies against the beta(1) and alpha(3) integrin subunits and laminin alpha(3) chain almost entirely blocked cell migration of the BxPC-3 cell line, whereas migration was nearly unaffected by RGD peptide and only moderately inhibited by antibody against the alpha(6) integrin subunit. Indirect immunofluorescence microscopy of wounded BxPC-3 cells suggested a rapid endocytosis of alpha(3) integrin subunit in the cells at the margin of the wound and a rapid, polarized rearrangement of the alpha(6) beta(4) integrin. Especially HGF-treated cultures showed a prominent cytoplasmic reaction for laminin-5 at the margin of the wound. Xenografted cells formed tumors that produced and deposited the same laminin chains as the in vitro cultures. Frozen sections of human pancreatic carcinomas showed reactivity for laminin chains suggestive for expression of laminin-1 and laminin-5. Both xenografted tumors and human pancreatic carcinomas also showed stromal reactivity for laminin-5. Electron microscopy of the human tumors suggested that this was due toan abundant reduplication the basement-membrane-like material around the nests of malignant cells. Our results suggest that pancreatic carcinomas synthesize and deposit laminin-5 in the basement membrane in an abnormal manner. Invading cells adhere to this newly produced basement membrane and migrate on it by using the alpha(3) beta(1) integrin receptor recognizing laminin-5. C1 UNIV HELSINKI,CENT HOSP,DEPT SURG 2,HELSINKI,FINLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. ORION CORP FARMOS,FARMOS RES,TURKU,FINLAND. UNIV HELSINKI,HAARTMAN INST,DEPT PATHOL,HELSINKI,FINLAND. RP Tani, T (reprint author), UNIV HELSINKI,DEPT ANAT,INST BIOMED,POB 9,FIN-00014 HELSINKI,FINLAND. NR 64 TC 87 Z9 88 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1997 VL 151 IS 5 BP 1289 EP 1302 PG 14 WC Pathology SC Pathology GA YD878 UT WOS:A1997YD87800016 PM 9358755 ER PT J AU Hanson, DB Pietrusewsky, M AF Hanson, DB Pietrusewsky, M TI Bioarchaeological research in the Mariana Islands of the western Pacific: An overview SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Editorial Material DE Mariana Islands; Marianas archipelago; bioarchaeology; skeletal biology ID PERSPECTIVE C1 UNIV HAWAII MANOA,DEPT ANTHROPOL,HONOLULU,HI 96822. RP Hanson, DB (reprint author), FORSYTH DENT CTR,DEPT BIOENGN,140 FENWAY,BOSTON,MA 02115, USA. NR 7 TC 1 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD NOV PY 1997 VL 104 IS 3 BP 267 EP 269 DI 10.1002/(SICI)1096-8644(199711)104:3<267::AID-AJPA1>3.0.CO;2-T PG 3 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA YJ900 UT WOS:A1997YJ90000001 PM 9408536 ER PT J AU Hanson, DB Butler, BM AF Hanson, DB Butler, BM TI A biocultural perspective on Marianas prehistory: Recent trends in bioarchaeological research SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article; Proceedings Paper CT Symposium on Prehistoric Skeletal Biology in Island Ecosystems, at the 64th Annual Meeting of the American-Association-of-Physical-Anthropologists CY 1995 CL OAKLAND, CA SP Amer Assoc Phys Anthropologists DE Mariana Islands; bioarchaeology; island ecosystems; skeletal biology ID 2ND METACARPAL BONE; CARBON-ISOTOPE; DIETARY CHANGE; NITROGEN; ISLANDS; CALIFORNIA; COLLAGEN; RATIOS AB Fifteen years ago, the biohistory of Micronesia was still a blank slate relative to other regions of the Pacific. Since 1980, however, the Mariana Islands, one of the largest island chains in Micronesia, have been the focus of intensive archaeological investigation and human remains have been ubiquitous components of the archaeological assemblages recovered from the islands of Guam, Rota, Tinian, and Saipan. These investigations have provided us with a wealth of new data that will contribute substantially to our understanding of population adaptation to island ecosystems in this part of the Pacific. Much of the recent bioarchaeological research in the Marianas is the product of archaeological mitigation rather than directed research. Consequently, many of our research efforts have been articulated with the needs of cultural resource management (CRM) where research designs focus on several general problem areas: 1) subsistence adaptation with emphasis on the contribution of marine vs. terrestrial resources and the role of pelagic, or deep-ocean resources in the marine component of the diet; 2) regional (upland vs. coastal; interisland) and temporal variation in subsistence/settlement; and 3) geomorphologic variation in coastal sediments, particularly as influenced by storm events. (C) 1997 Wiley-Liss, Inc. C1 SO ILLINOIS UNIV,CTR ARCHAEOL INVEST,CARBONDALE,IL 62901. RP Hanson, DB (reprint author), FORSYTH DENT CTR,DEPT BIOENGN,140 FENWAY,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES05064] NR 117 TC 11 Z9 14 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD NOV PY 1997 VL 104 IS 3 BP 271 EP 290 DI 10.1002/(SICI)1096-8644(199711)104:3<271::AID-AJPA2>3.0.CO;2-Z PG 20 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA YJ900 UT WOS:A1997YJ90000002 PM 9408537 ER PT J AU Ambrose, SH Butler, BM Hanson, DB HunterAnderson, RL Krueger, HW AF Ambrose, SH Butler, BM Hanson, DB HunterAnderson, RL Krueger, HW TI Stable isotopic analysis of human diet in the Marianas archipelago, Western Pacific SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Article; Proceedings Paper CT Symposium on Prehistoric Skeletal Biology in Island Ecosystems, at the 64th Annual Meeting of the American-Association-of-Physical-Anthropologists CY 1995 CL OAKLAND, CA SP Amer Assoc Phys Anthropologists DE paleodiet; carbon and nitrogen isotopes; collagen; apatite; Micronesia; archaeology ID CARBON-ISOTOPE; BONE-COLLAGEN; DELTA-C-13 MEASUREMENTS; TERRESTRIAL COMPONENTS; C-13/C-12 RATIOS; ORGANIC-MATTER; NITROGEN; MARINE; FOOD; FRACTIONATION AB Proportions of marine vs. terrestrial resources in prehistoric human diets in the southern Mariana Islands (Guam, Rota, Saipan), Micronesia, have been estimated by analysis of stable isotope ratios of carbon and nitrogen in bone collagen and of carbon in apatite. The isotopic composition of marine and terrestrial food resources from the Marianas have also been determined. Experimental evidence shows that collagen carbon isotopes mainly reflect those of dietary protein sources and thus overestimate the contribution of marine animal foods. Marine protein consumption apparently ranges from similar to 20% to similar to 50% on these islands. Experiments also demonstrate the carbon isotope ratio of bone apatite carbonate accurately reflects that of the whole diet. Carbonate carbon isotope data suggest some individuals consumed significant amounts of C-13-enriched (C-4) plants or seaweeds. Sugar cane is an indigenous C-4 crop and seaweeds are eaten throughout the Pacific, but they have not been considered by archaeologists to have been prehistoric dietary staples. Apatite carbon isotope analysis has apparently identified previously unrecognized prehistoric dietary adaptations in the Mariana Islands, but this must be confirmed by archaeobotanical evidence. (C) 1997 Wiley-Liss, Inc. C1 SO ILLINOIS UNIV,CTR ARCHAEOL INVEST,CARBONDALE,IL 62901. FORSYTH DENT CTR,BOSTON,MA 02115. GEOCHRON LABS,CAMBRIDGE,MA 02138. RP Ambrose, SH (reprint author), UNIV ILLINOIS,DEPT ANTHROPOL,607 S MATHEWS AVE,URBANA,IL 61801, USA. NR 72 TC 156 Z9 175 U1 2 U2 27 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PD NOV PY 1997 VL 104 IS 3 BP 343 EP 361 PG 19 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA YJ900 UT WOS:A1997YJ90000005 PM 9408540 ER PT J AU Stiens, SA Berkin, D AF Stiens, SA Berkin, D TI A clinical rehabilitation course for college undergraduates provides an introduction to biopsychosocial interventions that minimize disablement SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE rehabilitation; premedical student; medical student; consultation; education; resident ID TEACHER AB A two-credits per semester clinical medicine course was established in the Department of Physical Medicine and Rehabilitation (PM&R) in cooperation with the Johns Hopkins University undergraduate Human Biology faculty to present the variety of inpatient consultation personnel, units, patient diagnostic groups, and functional problems. College students spend 4 hr weekly on the PM&R consultation service as team members under resident supervision. The curriculum emphasizes student understanding of the roles of rehabilitation team members. Objectives include demonstration of working knowledge of the Biopsychosocial Model, the World Health Organization Model of disablement and interdisciplinary rehabilitation intervention. The course includes simulations of physical impairments, demonstrations of adaptive equipment, interactive chart reviews, readings, and audio lectures. A retrospective sequential review was made of the last 100 physical medicine and rehabilitation consultations with student attendance. The results confirm student exposure to many ward settings (surgery, 30%; neurology/neurosurgery, 28%; medicine, 24%; intensive care, 15%; oncology, 2%; and psychiatry, 1%), patient complexity (averaging 10 problems), and multiple ICD-9 diagnosis categories (circulatory, 36%; neurologic, 22%; musculoskeletal, 17%; neoplasms, 10%; injury, 5%; endocrine, 4%; infections, 3%; and others, 3%). The rehabilitation consultation service is particularly effective as an introduction to hospital-based medical practice due to the diagnostic variety of the patients, the functional approach of rehabilitation, and student exposure to multiple hospital settings. The Biopsychosocial Model of medical practice is demonstrated through multiple interdisciplinary perspectives of needs and interventions for patients with obvious functional deficits. This process develops a rudimentary understanding of the effect of illness on the person and the variety of medically effective therapeutic modalities. C1 Univ Washington, Sch Med, Dept Rehabil Med,Spinal Cord Injury Unit, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Phys Med & Rehabil, Baltimore, MD 21218 USA. Braintree Rehabil, Braintree, MA USA. Sinai Johns Hopkins PM&R Residency Training Progr, Baltimore, MD USA. RP Stiens, SA (reprint author), Univ Washington, Sch Med, Dept Rehabil Med,Spinal Cord Injury Unit, VA Puget Sound Hlth Care Syst, BB 919 Hlth Sci Bldg, Seattle, WA 98195 USA. NR 38 TC 3 Z9 3 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV-DEC PY 1997 VL 76 IS 6 BP 462 EP 470 DI 10.1097/00002060-199711000-00006 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA YP029 UT WOS:000071234100005 PM 9431264 ER PT J AU Vadakekalam, J Rabaglia, ME Metz, SA AF Vadakekalam, J Rabaglia, ME Metz, SA TI Interleukin-1 beta inhibits phospholipase C and insulin secretion at sites apart from K-ATP channel SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE pancreatic islet; calcium; exocytosis; purine nucleotides ID PANCREATIC B-CELLS; PROTEIN-KINASE-C; NITRIC-OXIDE; PHOSPHOINOSITIDE HYDROLYSIS; RAT ISLETS; GUANYLYL CYCLASE; RELEASE; LANGERHANS; MECHANISM; MOUSE AB Although interleukin-1 beta (IL-1 beta) reduces pancreatic islet content of ATP and GTP, the distal events that mediate its inhibitory effects on insulin secretion remain poorly understood. Herein, the activation of phospholipase C (PLC) was quantified during islet perifusions. An 18-h exposure to IL-1 beta (100 pM) totally vitiated activation of PLC induced by glucose, an effect that requires ATP and GTP and closure of the ATF-dependent K+ (K-ATP) channel. Surprisingly, however, when islets were depolarized directly using either of two agonists, glyburide (which does not act via generation of purine nucleotides) or 40 mM K+ (which acts distal to K-ATP channel), PLC and insulin secretion were again obliterated by IL-1 beta. IL-1 beta also reduced the labeling of phosphoinositide substrates; however, this effect was insufficient to explain the inhibition of PLC, since the effects on substrate labeling, but not on PLC, were prevented by coprovision of guanosine or adenosine. Furthermore, when IL-1 beta-treated islets piers exposed to 100 mu M carbachol (which activates PLC partially independent of extracellular Ca2+), the effects were still obliterated by IL-1 beta. These data (together with the finding that IL-1 beta inhibited Ca2+-induced insulin release) suggest that, in addition to its effects on ATP synthesis and thereby on the K-ATP channel, IL-1 beta has at least two undescribed. distal effects to block both PLC as well as Ca2+-induced exocytosis. The latter correlated best with IL-1 beta's effect to impede phosphainositide synthesis, since it also was reversed by guanosine or adenosine. C1 UNIV WISCONSIN, SCH MED, DIV ENDOCRINOL & METAB, MADISON, WI 53792 USA. UNIV WISCONSIN, SCH MED, DEPT MED, MADISON, WI 53792 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, ENDOCRINOL SECT, MADISON, WI 53705 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MED SERV, MADISON, WI 53705 USA. FU NIDDK NIH HHS [DK-37312] NR 30 TC 4 Z9 5 U1 0 U2 0 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 1997 VL 273 IS 5 BP E942 EP E950 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA YF556 UT WOS:A1997YF55600014 PM 9374680 ER PT J AU Klebanov, S Herlihy, JT Freeman, GL AF Klebanov, S Herlihy, JT Freeman, GL TI Effect of long-term food restriction on cardiac mechanics SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE isoproterenol; calcium; ventricular pressure; Langendorff preparation; diet ID SYSTOLIC PRESSURE-VOLUME; CALORIC RESTRICTION; RAT HEARTS; ELECTRICAL PERFORMANCE; FISCHER-344 RATS; METABOLIC-RATE; AGE; LONGEVITY; MYOSIN; ENERGY AB Food restriction (FR) is the only known intervention capable of increasing mammalian life span. It not only increases longevity, but reduces the incidence of a broad spectrum of age-related pathologies, including cardiomyopathy, and retards the physiological decline associated with aging. Previous work from this laboratory has shown that long-term FR affects the contractile machinery of the heart, shifting the cardiac myosin profile from the fast, V-1 isoform to the slow, V-3 isoform. The aim of the present study was to determine whether FR also induces changes in cardiac mechanics. Isolated, isovolumically beating hearts were examined from four groups of rats: 1) ad Libitum-fed rats killed at 10-13 mo of age, 2) FR rats offered only 60% of the calories consumed by ad libitum-fed rats and killed at the same age, 3) young ad Libitum-fed rats having the same heart weights as the FR rats, and 4) ad Libitum-fed rats subjected to short-term FR, i.e., for the last 3 wk of life, and also killed at 10-13 mo of age. Both short-and long-term FR profoundly and to approximately the same extent affected cardiac mechanics. Hearts from FR rats developed much higher pressures than hearts from the ad Libitum-fed rats under conditions of low-calcium perfusate. This difference disappeared, however, when contractility was enhanced by either calcium or isoproterenol. FR prolonged both contraction and relaxation times. Long-term ad libitum-fed rats (adult, 10-13 mo of age) had a lower isoproterenol sensitivity than the young ad Libitum-fed rats (10 wk of age). Both short-and long-term FR restored the sensitivity to isoproterenol. In summary, FR profoundly affects many aspects of cardiac mechanics, enhancing some age-related changes (prolongation of the contraction and relaxation times), attenuating another (increasing the isoproterenol sensitivity), and, finally, inducing some unique changes unrelated to age (increased pressure development under low-calcium perfusate). C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Freeman, GL (reprint author), Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 42 TC 25 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 1997 VL 273 IS 5 BP H2333 EP H2342 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA YF553 UT WOS:A1997YF55300031 ER PT J AU Gross, NJ Veldhuizen, R Possmayer, F Dhand, R AF Gross, NJ Veldhuizen, R Possmayer, F Dhand, R TI Surfactant convertase action is not essential for surfactant film formation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE surfactant subtype; surfactant conversion ID PULMONARY SURFACTANT; LUNG SURFACTANT; EXTRACELLULAR METABOLISM; SERINE-PROTEASE; LAMELLAR BODIES; TUBULAR MYELIN; SUBFRACTIONS; CONVERSION; SUBTYPES; INVITRO AB A serine-active enzyme, ''surfactant convertase,'' is required for the conversion of surfactant from the tubular myelin (TM) form to the small vesicular (SV) form. This transformation involves at least two steps, the conversion of TM to a surface-active film at the air-fluid interface and the reorientation of the film into the surface-inactive SV form; we asked if convertase was required for the first of these steps. Rat and mouse TMs were pretreated with diisopropyl fluorophosphate (DFP) to inactivate endogenous convertase activity or with vehicle and then were analyzed for their ability to lower surface tension in vitro as an index of the conversion of TM to a surface film. DFP pretreatment did not alter the ability of TM preparations to lower surface tension, as assessed by pulsating bubble, and it did not affect the behavior of TM in a surface balance. In an experiment designed to test the ability of TM to feed a surface film to exhaustion, TMs that had been pretreated with DFP or vehicle performed similarly. These experiments show that convertase activity is not required for the conversion of TM to a monolayer and suggest, instead, that convertase acts at a post surface film stage. C1 US DEPT VET AFFAIRS, VET AFFAIRS EDWARD HINES JR HOSP, MED SERV, HINES, IL 60141 USA. LOYOLA UNIV, STRITCH SCH MED, DEPT MED, MAYWOOD, IL 60153 USA. LOYOLA UNIV, STRITCH SCH MED, DEPT MOL & CELLULAR BIOCHEM, MAYWOOD, IL 60153 USA. UNIV WESTERN ONTARIO, LAWSON RES INST, DEPT MED, LONDON, ON N6A 5A5, CANADA. UNIV WESTERN ONTARIO, LAWSON RES INST, DEPT PHYSIOL, LONDON, ON N6A 5A5, CANADA. UNIV WESTERN ONTARIO, MRC, GRP FETAL & NEONATAL HLTH & DEV, DEPT OBSTET & GYNAECOL, LONDON, ON N6A 5A5, CANADA. UNIV WESTERN ONTARIO, MRC, GRP FETAL & NEONATAL HLTH & DEV, DEPT BIOCHEM, LONDON, ON N6A 5A5, CANADA. FU NHLBI NIH HHS [HL-45782-01] NR 18 TC 10 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 1997 VL 273 IS 5 BP L907 EP L912 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA YF568 UT WOS:A1997YF56800001 PM 9374716 ER PT J AU Rao, PM Rhea, JT Novelline, RA Mostafavi, AA Lawrason, JN McCabe, CJ AF Rao, PM Rhea, JT Novelline, RA Mostafavi, AA Lawrason, JN McCabe, CJ TI Helical CT combined with contrast material administered only through the colon for imaging of suspected appendicitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. Helical CT combined with contrast material administered by mouth and through the colon has been shown to be accurate for appendiceal imaging. This investigation was performed to determine if helical CT combined with contrast material administered only through the colon has comparable accuracy, SUBJECTS AND METHODS. One hundred patients prospectively underwent appendiceal CT imaging with thin-collimation, helical scanning limited to the lower abdomen and upper pelvis after contrast material was administered only through the colon. CT results were correlated with surgical and pathologic findings at appendectomy (56 patients), other surgery (three patients), or clinical follow-up at least 2 months after the CT scan (41 patients). RESULTS. Fifty-three CT scans were interpreted as positive for appendicitis, including 52 true-positives (with surgical-pathologic correlation) and one false-positive (with clinical follow-up). Forty-seven CT scans were interpreted as negative for appendicitis, including 40 true-negatives with clinical follow-up, three true-negatives with appendectomy and pathologic correlation, three true-negatives with other surgery and pathologic correlation, and one false-negative with appendectomy and pathologic correlation. CT had a 98% sensitivity, 98% specificity, 98% positive predictive value, 98% negative predictive value, and 98% accuracy for diagnosing or excluding appendicitis. In 47 normal appendix cases at CT, the appendix was seen in 44 cases (94%), and an alternative diagnosis was identified in 29 cases (62%). CONCLUSION. For diagnosing appendicitis, helical CT combined with contrast material administered only through the colon proved to be as accurate (98%) as helical CT combined with contrast material administered by mouth and through the colon. Helical CT with contrast material administered only through the colon also could be performed immediately and without any of the potential patient risks or discomforts of contrast material administered IV or by mouth. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP Rao, PM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 162 Z9 168 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1997 VL 169 IS 5 BP 1275 EP 1280 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YC823 UT WOS:A1997YC82300013 PM 9353441 ER PT J AU Slanetz, PJ Whitman, GJ Halpern, EF Hall, DA McCarthy, KA Simeone, JF AF Slanetz, PJ Whitman, GJ Halpern, EF Hall, DA McCarthy, KA Simeone, JF TI Imaging of fallopian tube tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PREOPERATIVE DIAGNOSIS; PRIMARY-CARCINOMA; ADENOCARCINOMA; CA-125; BREAST; APPEARANCE; ULTRASOUND; MUTATIONS; CT AB OBJECTIVE. The purposes of this study were to investigate the imaging findings in patients with primary fallopian tube neoplasms and to determine whether specific imaging features favor the preoperative diagnosis of fallopian tube tumors (FTT). MATERIALS AND METHODS, Computerized search of medical records from 1984 to 1994 identified 20 patients with a discharge diagnosis of primary fallopian tube carcinoma. Medical records, imaging studies, and pathology findings were reviewed. Eleven patients had available preoperative imaging. RESULTS. Seventeen of 20 patients with primary FTT had unilateral disease. Of these 17, preoperative imaging was available in nine, showing four solid adnexal masses, four complex cystic adnexal masses, and one normal adnexa. The preoperative imaging of these nine patients included six sonographic and five CT studies. Three patients with primary FTT had bilateral tumors, and preoperative imaging was available for two patients: Two sonographic studies and one CT study showed one complex cystic adnexal mass and three normal adnexa. CONCLUSION. Primary FTT commonly presents as an adnexal mass on preoperative imaging and mimics other pelvic malignancies, especially ovarian carcinoma. Making a specific preoperative diagnosis is difficult; however, because primary FTT is unlikely to be confused with a benign process, delay in diagnosis is rare. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DIV DIAGNOST IMAGING,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 17 TC 20 Z9 25 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1997 VL 169 IS 5 BP 1321 EP 1324 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YC823 UT WOS:A1997YC82300023 PM 9353450 ER PT J AU Grygotis, LA Chew, FS AF Grygotis, LA Chew, FS TI Radiologic-pathologic conferences of the Massachusetts General Hospital - Choroid plexus carcinoma of the lateral ventricle SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1997 VL 169 IS 5 BP 1400 EP 1400 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YC823 UT WOS:A1997YC82300041 PM 9353468 ER PT J AU Kratzer, SS Ulbright, TM Talerman, A Wahle, GR Moussa, M Stephens, JK Millos, A Young, RH AF Kratzer, SS Ulbright, TM Talerman, A Wahle, GR Moussa, M Stephens, JK Millos, A Young, RH TI Large cell calcifying Sertoli cell tumor of the testis - Contrasting features of six malignant and six benign tumors and a review of the literature SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE testicular neoplasm; Sertoli cell tumor; large cell calcifying Sertoli cell tumor; Carney syndrome; immunohistochemistry ID PEUTZ-JEGHERS SYNDROME; ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; COMPLEX; MYXOMAS AB We report six malignant and six benign large cell calcifying Sertoli cell tumors of the testis and compare the features of malignant and benign cases based on these cases and those in the literature. All the tumors in this report consisted of sheets, nests, solid tubules, and cords of eosinophilic cells, with focal calcifications, as well as a substantial neutrophilic infiltrate in 11 of them. Analysis of our cases and those in the literature showed that the malignant tumors were unilateral and solitary and occurred at a mean age of 39 years (range 28-51 years), whereas the benign neoplasms were bilateral and multifocal in 28% of cases and occurred at a mean age of 17 years (range 2-38 years). Only one malignant tumor occurred in a patient with evidence of a genetic syndrome (Carney syndrome), whereas 36% of benign tumors had various genetic syndromes or endocrine abnormalities. Most of the tumors in the latter cases were bilateral and multifocal. There were strong associations of malignant behavior with size >4 cm, extratesticular growth, gross or microscopic necrosis, high-grade cytologic atypia, vascular space invasion, and mitotic rate greater than three mitoses per 10 high-power fields. All malignant cases exhibited at least two of these features, whereas all benign cases lacked any of them. The presence of any one of these features in a solitary large cell calcifying Sertoli cell tumor, especially in a patient >25 years of age, should be viewed as suspicious for malignant behavior, whereas the presence of two or more of these features indicates a strong probability of a malignant course. ''Low'' percentages (less than or equal to 35%) of tumor cells staining for proliferating cell nuclear antigen (PCNA) also may correlate with benign behavior, but some benign tumors have high PCNA values. Ki-67 values (MIB-1 antibody) did not correlate with biologic behavior, nor did immunostains for p53 protein. C1 INDIANA UNIV,SCH MED,DEPT PATHOL & LAB MED,INDIANAPOLIS,IN 46204. INDIANA UNIV,SCH MED,DEPT UROL,INDIANAPOLIS,IN 46204. THOMAS JEFFERSON MED COLL,DEPT PATHOL,PHILADELPHIA,PA. UNIV TORONTO,TORONTO,ON,CANADA. CREDIT VALLEY HOSP,TORONTO,ON,CANADA. UNIV HOSP,LONDON,ON,CANADA. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80202. ST JOSEPH HOSP,PHILADELPHIA,PA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 29 TC 74 Z9 77 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1997 VL 21 IS 11 BP 1271 EP 1280 DI 10.1097/00000478-199711000-00002 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA YD721 UT WOS:A1997YD72100002 PM 9351565 ER PT J AU Duncan, LM LeBoit, PE AF Duncan, LM LeBoit, PE TI Are primary cutaneous immunocytoma and marginal zone lymphoma the same disease? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Editorial Material ID B-CELL LYMPHOMAS; CLASSIFICATION C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PATHOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT DERMATOL,SAN FRANCISCO,CA 94143. 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 18 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1997 VL 21 IS 11 BP 1368 EP 1372 DI 10.1097/00000478-199711000-00012 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA YD721 UT WOS:A1997YD72100012 PM 9351575 ER PT J AU Ibrahim, JG AF Ibrahim, JG TI On properties of predictive priors in linear models SO AMERICAN STATISTICIAN LA English DT Article DE Kullback-Leibler divergence; matching predictives; predictive distribution; prior distribution; variable selection AB Utilizing the notion of matching predictives as in Berger and Pericchi, we show that for the conjugate family of prior distributions in the normal linear model, the symmetric Kullback-Leibler divergence between two particular predictive densities is minimized when the prior hyperparameters are taken to be those corresponding to the predictive priors proposed in Ibrahim and Laud and Laud and Ibrahim. The main application for this result is for Bayesian variable selection. C1 DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. RP Ibrahim, JG (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0003-1305 J9 AM STAT JI Am. Stat. PD NOV PY 1997 VL 51 IS 4 BP 333 EP 337 DI 10.2307/2685901 PG 5 WC Statistics & Probability SC Mathematics GA YH217 UT WOS:A1997YH21700007 ER PT J AU Gies, EK Peters, DM Gelb, CR Knag, KM Peterfreund, RA AF Gies, EK Peters, DM Gelb, CR Knag, KM Peterfreund, RA TI Regulation of Mu opioid receptor mRNA levels by activation of protein kinase C in human SH-SY5Y neuroblastoma cells SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT 1996 Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 18-25, 1996 CL NEW ORLEANS, LA SP Amer Soc Anesthesiologists DE cell lines, SH-SY5Y neuroblastoma cells; Gene expression, mRNA; receptors, mu opioid receptor; signal transduction, protein kinase C; phorbol esters ID MESSENGER-RNA LEVELS; SOMATOSTATIN SECRETION; PROMOTER REGION; PHOSPHOLIPASE-C; GENE; MORPHINE; CLONING; INHIBITOR; BINDING; BRAIN AB Background: The mu opioid receptor (MuOR) is a member of the superfamily of G protein-coupled receptors that mediates the analgesic actions of endogenous opioid peptides and the narcotic alkaloid derivatives of morphine, Activation and translocation of protein kinase C (PKC) by N-methyl-D-aspartate receptor stimulation correlates with resistance to opioid drugs in experimental states of neuropathic pain, but the cellular mechanisms of resistance have not been identified. One possibility is that PKC activation regulates MuOR mRNA expression and thus the ability to generate functional receptors, Using a human neuroblastoma cell line, the authors tested the hypothesis that phorbol ester activation of PKC regulates MuOR mRNA levels, Methods: SH-SY5Y cells were maintained in a continuous monolayer culture and treated with phorbol esters or other agents before extraction of total cellular RNA, Slot-blot hybridization was used to measure the level of MuOR mRNA using P-32-labeled MuOR cDNA probes under high-stringency conditions. Autoradiograms were analyzed by scanning and densitometry, Results: MuOR mRNA levels decreased in a dose- and time-dependent manner after tetradecanoyl phorbol acetate (TPA) was administered to activate PKC. The nadir, a level of approximately 50% of control, was at 2-8 h, followed by gradual recovery, The actions of TPA were blocked by pretreatment with the selective PKC inhibitor bisindolylmaleimide, but not by inhibition of protein synthesis with cycloheximide or anisomycin. The combination of TPA treatment and transcription inhibition with actinomycin D was associated with a transient increase in MuOR mRNA, Conclusions: Mu opioid receptor mRNA levels are regulated by activation of PKC in a neuronal model, Protein kinase C effects which decrease MuOR mRNA levels appear largely independent of new protein synthesis, and cytotoxicity does not account for the findings, Plasticity of MuOR gene expression may contribute to variations in clinical responses to opioid analgesics in clinical states such as neuropathic pain. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA & CRIT CARE,BEECHER MEM LAB,BOSTON,MA 02114. NR 43 TC 18 Z9 18 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1997 VL 87 IS 5 BP 1127 EP 1138 DI 10.1097/00000542-199711000-00017 PG 12 WC Anesthesiology SC Anesthesiology GA YE499 UT WOS:A1997YE49900017 PM 9366465 ER PT J AU Jacobson, L Mariano, AJ Chabal, C Chaney, EF AF Jacobson, L Mariano, AJ Chabal, C Chaney, EF TI Beyond the needle - Expanding the role of anesthesiologists in the management of chronic non-malignant pain SO ANESTHESIOLOGY LA English DT Article DE anesthesiology; biomedical model; biopsychosocial model; nerve blocks; pain Clinics; multidisciplinary; pain; intractable; regional anesthesia; somatization ID SIMULTANEOUS INTERVIEW TECHNIQUE; PATIENT-PHYSICIAN RELATIONSHIP; RANDOMIZED CONTROLLED TRIAL; LOW-BACK-PAIN; ROVENSTINE LECTURE; REFRACTORY HEAD; PERSISTENT PAIN; LUMBAR SPINE; NECK PAIN; MEDICINE C1 VA PUGET SOUND HLTH CARE SYST,DEPT MENTAL HLTH,SEATTLE DIV,SEATTLE,WA 98108. UNIV WASHINGTON,SEATTLE,WA 98195. RP Jacobson, L (reprint author), VA PUGET SOUND HLTH CARE SYST,ANESTHESIOL SERV 112A,SEATTLE DIV,DEPT ANESTHESIOL,SEATTLE,WA 98108, USA. NR 84 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1997 VL 87 IS 5 BP 1210 EP 1218 DI 10.1097/00000542-199711000-00026 PG 9 WC Anesthesiology SC Anesthesiology GA YE499 UT WOS:A1997YE49900026 PM 9366474 ER PT J AU Baker, M Kwok, JBJ Kucera, S Crook, R Farrer, M Houlden, H Isaacs, A Lincoln, S Onstead, L Hardy, J Wittenberg, L Dodd, P Webb, S Hayward, N Tannenberg, T Andreadis, A Hallupp, M Schofield, P Dark, F Hutton, M AF Baker, M Kwok, JBJ Kucera, S Crook, R Farrer, M Houlden, H Isaacs, A Lincoln, S Onstead, L Hardy, J Wittenberg, L Dodd, P Webb, S Hayward, N Tannenberg, T Andreadis, A Hallupp, M Schofield, P Dark, F Hutton, M TI Localization of frontotemporal dementia with parkinsonism in an Australian kindred to chromosome 17q21-22 SO ANNALS OF NEUROLOGY LA English DT Article ID GENE; TAU; PROTEIN AB An Australian family with autosomal dominant presenile nonspecific dementia was recently described. The disease results in behavioral changes, usually disinhibition, followed by the onset of dementia accompanied occasionally by parkinsonism. Twenty-eight affected individuals were identified with an age of onset of 39 to 66 years (mean, 53 +/- 8.9 years). We mapped the disease locus to an approximately 26-cM region of chromosome 17q21-22 with a maximum two-point LOD score of 2.87. Affected individuals share a common haplotype between markers D17S783 and D17S808. This region of chromosome 17 contains the loci for several neurodegenerative diseases that lack distinctive pathological features, suggesting that these dementias, collectively referred to as frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), are caused by mutations in the same gene. The entire coding region of five genes, mapped to the FTDP-17 candidate region, were also sequenced. This analysis included the microtubule-associated protein tau that is the major component of the paired helical filaments observed in Alzheimer's disease. No pathogenic mutations were identified in either the tau gene or in any of the other genes analyzed. C1 MAYO CLIN JACKSONVILLE,JACKSONVILLE,FL 32224. UNIV TAMPA,TAMPA,FL 33606. GARVAN INST MED RES,SYDNEY,NSW,AUSTRALIA. CRC,ROYAL BRISBANE HOSP RES FDN,BRISBANE,QLD,AUSTRALIA. MATER MISERICORDIAE HOSP,DEPT ANAT PATHOL,BRISBANE,QLD,AUSTRALIA. QUEENSLAND INST MED RES,HUMAN GENET LAB,HERSTON,QLD 4006,AUSTRALIA. PRINCESS ALEXANDRA HOSP,DEPT PSYCHIAT,WOOLLOONGABBA,QLD 4102,AUSTRALIA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RI Houlden, Henry/C-1532-2008; Dodd, Peter/A-4865-2010; Hardy, John/C-2451-2009; hayward, nicholas/C-1367-2015 OI Houlden, Henry/0000-0002-2866-7777; Dodd, Peter/0000-0001-5970-0181; hayward, nicholas/0000-0003-4760-1033 NR 18 TC 62 Z9 62 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1997 VL 42 IS 5 BP 794 EP 798 DI 10.1002/ana.410420516 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA YE970 UT WOS:A1997YE97000015 PM 9392579 ER PT J AU Mandl, DL Garrison, MW Palpant, SD AF Mandl, DL Garrison, MW Palpant, SD TI Agranulocytosis induced by vancomycin or ticarcillin/clavulanate SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE vancomycin; ticarcillin/clavulanate; agranulocytosis ID INDUCED NEUTROPENIA; PATIENT; TOXICITY; THERAPY AB OBJECTIVE: To reacquaint clinicians with a reportedly rare adverse event of agranulocytosis occurring after long-term administration of vancomycin and ticarcillin/clavulanate, with a subsequent review of other reported cases in the literature. CASE SUMMARY: A 45-year-old white woman with spina bifida developed agranulocytosis (2.7 x 10(3)/mm(3) white blood cells with only 3% polymorphonuclear leukocytes and no reported eosinophils or basophils) after long-term administration of vancomycin and ticarcillin/clavulanate for decubitus ulcers and chronic osteomyelitis. Consequently, the cell counts rebounded rapidly on discontinuation of both medications and returned to normal within 1 week. DISCUSSION: The incidence of vancomycin-associated neutropenia is presumably rare, but the increased use of vancomycin may disclose a more frequent occurrence. It is suggested that the mechanism for the reaction is immunologically mediated, yet this remains unclear. Although it is difficult to determine the causative agent in this case, vancomycin was most suspect clinically. Ticarcillin/clavulanate is less likely because our patient has since been readmitted and treated with oxacillin, imipenem/cilastatin, and amoxicillin/clavulanate without affecting the white blood cell count. In that regard, it could be reasoned that an immunologic reaction to ticarcillin would have resulted in a similar outcome with other penicillins. CONCLUSIONS: This case serves as a reminder to clinicians that patients receiving long-term treatment with vancomycin should have their white blood cell count monitored at least weekly. C1 DEACONESS MED CTR,SPOKANE,WA. SACRED HEART MED CTR,SPOKANE,WA. RP Mandl, DL (reprint author), WASHINGTON STATE UNIV,COLL PHARM,601 W 1ST AVE,SPOKANE,WA 99204, USA. NR 19 TC 6 Z9 6 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 1997 VL 31 IS 11 BP 1321 EP 1324 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF306 UT WOS:A1997YF30600009 PM 9391687 ER PT J AU Drake, LA Yale, KP Lowery, BJ Dunbar, AL Gillies, R AF Drake, LA Yale, KP Lowery, BJ Dunbar, AL Gillies, R TI American Academy of Dermatology guidelines of care - Development and process SO ARCHIVES OF DERMATOLOGY LA English DT Review ID CLINICAL-PRACTICE GUIDELINES AB Medical practice guidelines are being developed at an accelerating pace, in all areas of medicine, for a wide range of uses. The field of practice guideline development is not new, but a number of important economic and health care issues have renewed interest in their creation. In 1987, in response to many ol these issues, the American Academy of Dermatology took a leadership role and began a process designed to develop guidelines for disease entities treated by dermatologists. The result was a set of clinical practice guidelines and the most comprehensive dermatology guideline development processes to date. Herein we describe the guideline development process in its current, refined form and discuss some of its unique and important characteristics. New applications of guidelines, outside of clinical practice improvement, have made their development controversial. Nevertheless, it is important for the medical profession to lead in this effort, and the American Academy of Dermatology continues to explore ways to refine and update its guidelines to reflect the latest medical science and technology. C1 UNIV OKLAHOMA,DEPT DERMATOL,OKLAHOMA CITY,OK. AMER ACAD DERMATOL,CHICAGO,IL. RP Drake, LA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BAR 604,BOSTON,MA 02114, USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 1997 VL 133 IS 11 BP 1369 EP 1374 PG 6 WC Dermatology SC Dermatology GA YF121 UT WOS:A1997YF12100007 PM 9371018 ER PT J AU Evans, DA Hebert, LE Beckett, LA Scherr, PA Albert, MS Chown, MJ Pilgrim, DM Taylor, JO AF Evans, DA Hebert, LE Beckett, LA Scherr, PA Albert, MS Chown, MJ Pilgrim, DM Taylor, JO TI Education and other measures of socioeconomic status and risk of incident Alzheimer disease in a defined population of older persons SO ARCHIVES OF NEUROLOGY LA English DT Article ID COMMUNITY POPULATION; CLINICAL-DIAGNOSIS; UNITED-STATES; SOCIAL-CLASS; DEMENTIA; PREVALENCE; OCCUPATION; AGE; ASSOCIATION; EPIDEMIOLOGY AB Objective: To assess the relations of 3 measures of socioeconomic status (education, occupational prestige, and income) to risk of incident clinically diagnosed Alzheimer disease (AD). Design: Cohort study with an average observation of 4.3 years. Setting: East Boston, Mass, a geographically defined community. Participants: A stratified random sample of 642 community residents 65 years of age and older who were free of AD at baseline. Main Outcome Measure: Clinical diagnosis of probable AD according to standard criteria, using structured uniform evaluation. Results: The relations of the 3 measures of socioeconomic status to risk of disease were assessed using logistic regression analyses. In individual analyses, fewer years of formal schooling, lower income, and lower occupational status each predicted risk of incident AD; risk of disease decreased by approximately 17% for each year of education. In an analysis including all 3 measures, the effect of education on risk for disease remained approximately the same, but the effects of the other 2 measures were somewhat less and did not attain formal statistical significance, compared with separate analysis of each measure. Conclusions: Markers of lower socioeconomic status predict risk of developing incident AD. The mechanism of this relation is uncertain, but the possibility that it reflects unidentified and potentially reversible risk factors for the disease deserves careful investigation. C1 RUSH UNIV,RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH ALZHEIMERS DIS CTR,CHICAGO,IL 60612. CTR DIS CONTROL & PREVENT,HLTH CARE & AGING STUDIES BRANCH,ATLANTA,GA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HARVARD COMMUNITY HLTH PLAN,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP Evans, DA (reprint author), RUSH INST AGING,1645 W JACKSON BLVD,SUITE 675,CHICAGO,IL 60612, USA. FU NIA NIH HHS [AG 05362, AG 06789, AG 10161] NR 52 TC 219 Z9 224 U1 2 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1997 VL 54 IS 11 BP 1399 EP 1405 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA YE501 UT WOS:A1997YE50100018 PM 9362989 ER PT J AU Compton, CC Henson, DE AF Compton, CC Henson, DE TI Protocol for the examination of specimens removed from patients with carcinoma of the exocrine pancreas - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID GIANT-CELL TUMOR; PAPILLARY-CYSTIC TUMOR; FACTORS INFLUENCING PROGNOSIS; SERUM ALPHA-FETOPROTEIN; MUCINOUS DUCTAL ECTASIA; LYMPH-NODE INVOLVEMENT; LONG-TERM SURVIVAL; ADENOSQUAMOUS CARCINOMA; DIFFERENTIAL-DIAGNOSIS; LATENT MALIGNANCY C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 147 TC 24 Z9 26 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1997 VL 121 IS 11 BP 1129 EP 1136 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YF312 UT WOS:A1997YF31200001 PM 9372738 ER PT J AU Kirby, JE Laposata, M AF Kirby, JE Laposata, M TI The nature and extent of training activities in clinical pathology required for effective consultation on laboratory test selection and interpretation SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB Objective.-The goal of this study was to identify the activities in clinical pathology training and the length of time required in each to effectively train residents as consultants on laboratory test selection and interpretation. Methods.-The information needed to address these questions was obtained from a study of 20 residents in clinical pathology at our institution between 1990 and 1996. In the survey participants were asked to assess the value of specific training activities in developing their confidence when addressing consultative questions on laboratory test use and interpretation. Participants were also asked to assess the length of time required to gain confidence in performing this role. Results.-The results of the study demonstrate that confidence in providing advice on clinical laboratory test selection and interpretation is acquired to a significant but not absolute degree after an intense 8-week experience in a single clinical laboratory subspecialty, during which time no other responsibilities are assigned. The data also indicate that interactions with clinical pathologists and formal lectures provided to the trainees during their rotations are critical components of the consultation service. There was a significant decrease in the length of time required to provide effective information on test selection and interpretation as the residents progressed through their training. Conclusions.-For all of the major subspecialties in clinical pathology, the residents gained significant confidence by 4 weeks of intense training, and by 8 weeks participants were very confident in answering consultation questions. Even after 8 weeks, however, fewer than 10% of the residents felt absolutely confident in their own decisions regarding laboratory test use and interpretation prior to discussion with senior residents and faculty. Thus, acquisition of expertise to effectively provide advice on laboratory test selection and interpretation required up to 8 weeks of focused training in each clinical laboratory subspecialty. Gaining confidence in multiple areas requires a significant commitment of full-time training. This study provides an understanding of the type and extent of training required to attain the skills necessary to effectively provide consultation in clinical pathology. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 4 TC 9 Z9 9 U1 0 U2 3 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 1997 VL 121 IS 11 BP 1163 EP 1167 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA YF312 UT WOS:A1997YF31200005 PM 9372742 ER PT J AU Schuster, MA Asch, SM McGlynn, EA Kerr, EA Hardy, AM Gifford, DS AF Schuster, MA Asch, SM McGlynn, EA Kerr, EA Hardy, AM Gifford, DS TI Development of a quality of care measurement system for children and adolescents - Methodological considerations and comparisons with a system for adult women SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HEALTH-CARE; ASTHMA; APPROPRIATENESS; PHYSICIANS; KNOWLEDGE; REFORM; IMPACT; RATES AB Objectives: To describe the development of a pediatric quality of care measurement system designed to cover multiple clinical topics that could be applied to enrollees in managed care organizations and to compare the development of this system with the concurrent development of a similar system for adult women. Design: Indicators were developed for 21 pediatric (ages 0-18 years) clinical topics and 20 adult (ages 17-50 years) women's clinical topics. Indicators were classified by the strength of evidence supporting them. A modified Delphi method was used to obtain validity and feasibility ratings from a pediatric expert panel and an adult women's expert panel. Indicators were categorized by type of care (preventive, acute, or chronic), function (screening, diagnosis, treatment, or follow up), and modality (history, physical examination, laboratory/radiology study, medication, other intervention, or other contact). Results: Of 557 pediatric and 391 adult women's proposed indicators, 453 (81%) and 340 (87%), respectively, were retained by the 2 expert panels. A lower percentage of final pediatric indicators than adult indicators were based on randomized, controlled trials and other rigorous studies (18% vs 40%, P<.001). The expert panels were more likely to retain indicators based on rigorous studies (93% retained) than on descriptive studies and expert opinion (81% retained, P<.001). A higher percentage of pediatric indicators than women's indicators were for preventive care (30% vs 11%, P<.001) and a lower percentage were for acute care (36% vs 49%, P<.001) or chronic care (34% vs 41%, P=.06). Conclusions: This study contributes to the field of pediatric quality of care assessment by providing many more indicators than have been available previously and by documenting the strength of evidence supporting these indicators. Formal consensus methods are essential for the development of pediatric quality measures because the evidence base for pediatric care is more limited than for adult care. C1 UNIV CALIF LOS ANGELES,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM HOSP,LOS ANGELES,CA. UNIV MICHIGAN,DEPT MED,ANN ARBOR,MI 48109. BROWN UNIV,WOMEN & INFANTS HOSP,PROVIDENCE,RI. ANN ARBOR VET ADM MED CTR,HLTH SERV RES & DEV FIELD PROGRAM,ANN ARBOR,MI. RP Schuster, MA (reprint author), RAND CORP,1700 MAIN ST,POB 2138,SANTA MONICA,CA 90407, USA. FU PHS HHS [18C-90315/9-02] NR 44 TC 50 Z9 52 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 1997 VL 151 IS 11 BP 1085 EP 1092 PG 8 WC Pediatrics SC Pediatrics GA YF122 UT WOS:A1997YF12200003 PM 9369869 ER PT J AU Fink, JS AF Fink, JS TI Transplantation in Parkinson's disease SO ARTIFICIAL ORGANS LA English DT Article; Proceedings Paper CT XIth World Congress of the International-Society-for-Artificial-Organs CY JUN 29-JUL 01, 1997 CL PROVIDENCE, RI SP Int Soc Artificial Organs DE Parkinson's Disease; transplantation; porcine cells; fetal cells ID FETAL MESENCEPHALIC TISSUE; ADRENAL-MEDULLA; CAUDATE-NUCLEUS; RAT MODEL; VENTRAL MESENCEPHALON; SUBSTANTIA NIGRA; GRAFTS; SURVIVAL; IMMUNOPROTECTION; REGISTRY AB The modification of nervous system function by cell replacement and the introduction of heterologous genes are being developed as possible therapeutic approaches in degenerative diseases of the nervous system. The use of cellular transplantation in the nervous system of patients with neurodegenerative diseases will be reviewed with an emphasis on Parkinson's disease. C1 MASSACHUSETTS GEN HOSP,MOVEMENT DISORDER UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP Fink, JS (reprint author), DIACRIN INC,BLDG 96,13TH ST,CHARLESTOWN,MA 02129, USA. NR 30 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD NOV PY 1997 VL 21 IS 11 BP 1199 EP 1202 PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA YC965 UT WOS:A1997YC96500016 PM 9384326 ER PT J AU Tiwari, P Reddy, V Tiwari, PK Wong, FKM Cheng, YL Yu, AW Ing, TS AF Tiwari, P Reddy, V Tiwari, PK Wong, FKM Cheng, YL Yu, AW Ing, TS TI Acid-base values of single pass, batch system, bicarbonate based hemodialysate SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 42nd Annual Conference of the American-Society-for-Artificial-Internal-Organs CY MAY 03-04, 1996 CL WASHINGTON, DC SP Amer Soc Artificial Internal Organs AB The bicarbonate, calcium, and magnesium values of a single pass, batch system, bicarbonate based hemodialysate were found to be stable during a period of 5 hours, whether the solution was extensively covered by a floating polystyrene lid or not. The pH and PCO2 of the dialysate that had been covered with a floating lid remained stable during the 5 hours, whereas the corresponding values of the dialysate that had not been so covered did show changes that were secondary to the loss of carbon dioxide. The changes were not marked enough to preclude the clinical use of the latter uncovered dialysate. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,DEPT RES,HINES,IL 60141. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,DEPT MED,HINES,IL 60141. LOYOLA UNIV,STRITCH SCH MED,MAYWOOD,IL 60153. CHINESE UNIV HONG KONG,DEPT MED,HONG KONG,HONG KONG. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1058-2916 J9 ASAIO J JI Asaio J. PD NOV-DEC PY 1997 VL 43 IS 6 BP 897 EP 899 DI 10.1097/00002480-199711000-00009 PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA YF563 UT WOS:A1997YF56300009 PM 9386839 ER PT J AU Lewis, K Hooper, DC Ouellette, M AF Lewis, K Hooper, DC Ouellette, M TI Multidrug resistance pumps provide broad defense SO ASM NEWS LA English DT Article ID LOCUS C1 TUFTS UNIV,CTR BIOTECHNOL,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DIV INFECT DIS,BOSTON,MA 02114. UNIV LAVAL,CTR HOSP,SERV INFECTIOL,QUEBEC CITY,PQ,CANADA. NR 8 TC 27 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0044-7897 J9 ASM NEWS JI ASM News PD NOV PY 1997 VL 63 IS 11 BP 605 EP 610 PG 6 WC Microbiology SC Microbiology GA YF693 UT WOS:A1997YF69300014 ER PT J AU True, WR Xian, H Eisen, SA Goldberg, J Lyons, MJ Tsuang, MT AF True, WR Xian, H Eisen, SA Goldberg, J Lyons, MJ Tsuang, MT TI Multivariate analyses of posttraumatic stress disorder and alcohol and drug dependence in 3304 twin pair members of the Vietnam Era Twin Registry. SO BEHAVIOR GENETICS LA English DT Meeting Abstract C1 St Louis Univ, Sch Publ Hlth, St Louis, MO 63108 USA. St Louis VAMC, Res Serv, St Louis, MO 63106 USA. Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA. US Dept Vet Affairs, HSRD, Hines, IL 60141 USA. Univ Illinois, Sch Publ Hlth, Program Epidemiol, Chicago, IL 60680 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02401 USA. RI Lyons, Michael/B-6119-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 1997 VL 27 IS 6 BP 608 EP 608 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA YV287 UT WOS:000071808100109 ER PT J AU Rajur, SB Roth, CM Morgan, JR Yarmush, ML AF Rajur, SB Roth, CM Morgan, JR Yarmush, ML TI Covalent protein-oligonucleotide conjugates for efficient delivery of antisense molecules SO BIOCONJUGATE CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; CELLS; ENDOCYTOSIS; EXPRESSION AB Antisense oligonucleotides have been covalently attached to asialoglycoprotein (ASGP) via disulfide bond conjugation chemistry. These conjugates were characterized extensively by an array of chemical, chromatographic, and spectroscopic means. Multiple (approximately six) oligonucleotides can be conjugated to each ASGP molecule. The molecular conjugates were used to deliver antisense oligonucleotides complementary to the mRNA of the interleukin 6 signal transduction protein (gp130) to modulate the acute phase response of hepatoma (HepG2) cells in vitro. These conjugates were biologically active, as measured by inhibition of the cytokine-stimulated up-regulation of the acute phase protein haptoglobin. The level of inhibition was comparable to that found with previous technology featuring noncovalent complexes of ASGP-poly(L-lysine) and oligonucleotide. Because of the ability to control the stoichiometry of the conjugate and its unimolecular nature (as opposed to bimolecular for the noncovalent conjugates), this methodology holds great promise for further development and application. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,CTR ENGN MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Morgan, Jeffrey/0000-0002-7546-3443; Roth, Charles/0000-0002-4924-0721 FU NIGMS NIH HHS [GM-07035] NR 18 TC 55 Z9 57 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1997 VL 8 IS 6 BP 935 EP 940 DI 10.1021/bc970172u PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA YJ099 UT WOS:A1997YJ09900022 PM 9404669 ER PT J AU Johnson, AL Bridgham, JT Witty, JP Tilly, JL AF Johnson, AL Bridgham, JT Witty, JP Tilly, JL TI Expression of bcl-2 and nr-13 in hen ovarian follicles during development SO BIOLOGY OF REPRODUCTION LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; APOPTOTIC CELL-DEATH; COMPLEMENTARY DEOXYRIBONUCLEIC-ACID; AVIAN GRANULOSA-CELLS; FOLLICULAR DEVELOPMENT; BCL-2-RELATED GENE; C-MYC; INHIBITION; ACTIVATION; BCL-X(L) AB Follicle atresia is initiated within the granulosa cell layer of ovarian follicles and is mediated via the process of apoptosis. In the hen, at least two populations of granulosa cells can be distinguished during follicle development on the basis of their inherent susceptibility or resistance to apoptosis, in vitro. Given the previously established correlation between expression of bcl-x(Long) and hen granulosa cell resistance to apoptosis, the present studies were conducted to characterize expression of bcl-2 and an avian bcl-2 homologue, nr-13, in follicles at various stages of development. Levels of nr-13 mRNA were significantly higher only in granulosa cells from the largest (F1) preovulatory follicle compared to 3- to 5-mm prehierarchal follicles. By comparison, bcl-2 mRNA levels were 5- to 9-fold higher in granulosa cells from the three largest preovulatory follicles compared to those from follicles 9 to 12 mm in diameter and prehierarchal follicles. The increase in neither nr-13 nor bcl-2 was correlated with the stage of follicle development associated with the acquisition of resistance to apoptosis in granulosa cells (e.g., at the 9- to 12-mm stage). Results from the present studies do not support a close correlation between constitutive expression of nr-13 or bcl-2 mRNA and the transition from a state of apoptosis susceptibility to apoptosis resistance in hen granulosa cells. Thus, it is proposed that nr-13 and bcl-2 play more of a supportive role in regulating additional aspects of ovarian cell function such as cell proliferation and/or differentiation. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, DEPT OBSTET GYNECOL,VINCENT CTR REPROD BIOL, BOSTON, MA 02114 USA. RP Johnson, AL (reprint author), UNIV NOTRE DAME, DEPT BIOL SCI, NOTRE DAME, IN 46556 USA. NR 45 TC 30 Z9 34 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1997 VL 57 IS 5 BP 1096 EP 1103 DI 10.1095/biolreprod57.5.1096 PG 8 WC Reproductive Biology SC Reproductive Biology GA YD114 UT WOS:A1997YD11400020 PM 9369176 ER PT J AU LambertMesserlian, G Taylor, A Leykin, L Isaacson, K Toth, T Chang, YC Schneyer, A AF LambertMesserlian, G Taylor, A Leykin, L Isaacson, K Toth, T Chang, YC Schneyer, A TI Characterization of intrafollicular steroid hormones, inhibin, and follistatin in women with and without polycystic ovarian syndrome following gonadotropin hyperstimulation SO BIOLOGY OF REPRODUCTION LA English DT Article; Proceedings Paper CT 10th Congress of the International-Society-for-Endocrinology CY JUN 12-15, 1996 CL SAN FRANCISCO, CA SP Int Soc Endocrinol ID FOLLICLE-STIMULATING-HORMONE; HUMAN MENSTRUAL-CYCLE; MESSENGER RIBONUCLEIC-ACIDS; HUMAN OOCYTES INVITRO; GRANULOSA-CELLS; LUTEINIZING-HORMONE; DIMERIC INHIBIN; EMBRYO TRANSFER; IMMUNOHISTOCHEMICAL LOCALIZATION; SUCCESSFUL FERTILIZATION AB The etiology of polycystic ovary syndrome (PCOS) is unexplained. Since no major deficiencies are reported in serum FSH or inhibin, we hypothesized that abnormal revels of a paracrine modulator of FSH action within the ovary may be associated with the arrest of follicular growth seen in the PCOS ovary. Follicular fluid aspirates were collected from women with (n = 7) or without (n = 17) PCOS during oocyte retrieval for in vitro fertilization. Aspirates were assayed for total inhibin, inhibin A (InhA), inhibin B (InhB), and follistatin (FS), as well as for estradiol, progesterone (P-4), androstenedione, and total protein. Hormone levels were compared between women with and without PCOS using all aspirates (some of which were collected from multiple follicles at once) and also between aspirates containing fluid from a single follicle only (PCOS, n = 30; non-PCOS, n=107). P-4 levels were significantly (p < 0.01) reduced in PCOS versus non-PCOS women as evidenced by analysis of all follicles as well as in single-follicle aspirates only. In addition, InhA, P-4, and FS increased with follicle volume, and InhB decreased significantly in non-PCOS, but not in PCOS, follicles. Therefore, although follicular development can be induced in PCOS patients with gonadotropins, hormonal responses within the ovary appear inappropriate in terms of concentrations or patterns of secretion. These data support the concept that PCOS is associated with a deficit in the paracrine control of folliculogenesis. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES & REPROD ENDOCRINE UNIT, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT OBSTET & GYNECOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, GEN INTERNAL MED UNIT, BOSTON, MA 02114 USA. RP LambertMesserlian, G (reprint author), BROWN UNIV, WOMEN & INFANTS HOSP, DEPT LAB MED & PATHOL, SCH MED, 101 DUDLEY ST, PROVIDENCE, RI 02905 USA. OI Messerlian, Geralyn/0000-0002-9440-3411 FU NICHD NIH HHS [HD-29164, HD-31894] NR 58 TC 31 Z9 31 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD NOV PY 1997 VL 57 IS 5 BP 1211 EP 1216 DI 10.1095/biolreprod57.5.1211 PG 6 WC Reproductive Biology SC Reproductive Biology GA YD114 UT WOS:A1997YD11400033 PM 9369189 ER PT J AU Rankin, SE Addona, GH Kloczewiak, MA Bugge, B Miller, KW AF Rankin, SE Addona, GH Kloczewiak, MA Bugge, B Miller, KW TI The cholesterol dependence of activation and fast desensitization of the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Article ID LIPID-PROTEIN INTERACTIONS; TORPEDO-CALIFORNICA; NONCOMPETITIVE INHIBITORS; RECONSTITUTED MEMBRANES; POSTSYNAPTIC MEMBRANES; CA-ATPASE; KINETICS; BINDING; INACTIVATION; MODULATION AB When nicotinic acetylcholine receptors are reconstituted into lipid bilayers lacking cholesterol, agonists no longer stimulate cation flux. The kinetics of this process are difficult to study because variations in vesicle morphology cause errors in flux measurements. We developed a new stopped-flow fluorescence assay to study activation independently of vesicle morphology. When receptors were rapidly mixed with agonist plus ethidium, the earliest fluorescence increase reported the fraction of channels that opened and their apparent rate of fast desensitization. These processes were absent when the receptor was reconstituted into dioleoylphosphatidylcholine or into a mixture of that lipid with dioleoylphosphatidic acid (12 mol%), even though a fluorescent agonist reported that resting-state receptors were still present. The agonist-induced channel opening probability increased with bilayer cholesterol, with a midpoint value of 9 +/- 1.7 mol% and a Hill coefficient of 1.9 +/- 0.69, reaching a plateau above 20-30 mol% cholesterol that was equal to the native value. On the other hand, the observed fast desensitization rate was comparable to that for native membranes from the lowest cholesterol concentration examined (5 mol%). Thus the ability to reach the open state after activation varies with the cholesterol concentration in the bilayer, whereas the rate of the open state to fast desensitized state transition is unaffected. The structural basis for this is unknown, but an interesting corollary is that the channels of newly synthesized receptors are not fully primed by cholesterol until they are inserted into the plasma membrane-a novel form of posttranslational processing. C1 MASSACHUSETTS GEN HOSP, DEPT ANESTHESIA, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOL PHARMACOL, BOSTON, MA 02114 USA. FU NIAAA NIH HHS [AA07040]; NIGMS NIH HHS [GM-15904] NR 48 TC 79 Z9 79 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 1997 VL 73 IS 5 BP 2446 EP 2455 PG 10 WC Biophysics SC Biophysics GA YD848 UT WOS:A1997YD84800018 PM 9370438 ER PT J AU Wang, JF Ganju, RK Liu, ZY Avraham, H Avraham, S Groopman, JE AF Wang, JF Ganju, RK Liu, ZY Avraham, H Avraham, S Groopman, JE TI Signal transduction in human hematopoietic cells by vascular endothelial growth factor related protein, a novel ligand for the FLT4 receptor SO BLOOD LA English DT Article ID FOCAL ADHESION KINASE; JUN ACTIVATION DOMAIN; TYROSINE-KINASE; RAS PATHWAY; SH3 DOMAIN; BINDING; PHOSPHORYLATION; IDENTIFICATION; ANGIOGENESIS; PAXILLIN AB We have recently identified a novel ligand of the vascular endothelial growth factor (VEGF) family termed VEGF-related protein (VRP), which specifically binds to the FLT4 receptor, To characterize the signaling events after VRP engagement of its cognate receptor in hematopoietic cells, a population of human erythroleukemia (HEL) cells, termed HEL-JW, expressing high levels of FLT4 receptor was isolated. Stimulation of HEL-JW cells with VRP alone and in combination with the c-kit ligand/stem cell factor increased cell growth. VRP induced tyrosine phosphorylation of various proteins, including the FLT4 receptor. Further characterization of these tyrosine phosphorylated molecules revealed that Shc, Grb2, and SOS form a complex with the activated FLT4 receptor, HEL-JW cells also expressed RAFTK, a recently identified member of the focal adhesion kinase family. RAFTK was phosphorylated and activated upon VRP treatment, and there was an enhanced association of this kinase with the adaptor protein Grb2. Furthermore, the c-Jun NH2-terminal kinase (JNK), involved in growth activation and shown to mediate RAFTK signaling in other cell types, was activated by VRP stimulation. We also observed that VRP treatment of HEL-JW cells resulted in the phosphorylation of the cytoskeletal protein paxillin. This treatment resulted in an increased association of paxillin with RAFTK, which was mediated by the C-terminal region of RAFTK. These studies indicate that VRP stimulation induced the formation of a signaling complex at: its activated receptor as well as activation of RAFTK. VRP-mediated activation of RAFTK may facilitate signal transduction to the cytoskeleton and downstream to the JNK pathway in FLT4-expressing blood cells. (C) 1997 by The American Society of Hematology. C1 HARVARD UNIV,INST MED,BIDMC,DIV EXPT MED,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BIDMC,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 43510-07, HL 53745-02, HL 55187-01] NR 45 TC 21 Z9 29 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1997 VL 90 IS 9 BP 3507 EP 3515 PG 9 WC Hematology SC Hematology GA YD108 UT WOS:A1997YD10800026 PM 9345034 ER PT J AU Tsai, T Goodman, S Saez, R Schiller, G Adkins, D Callander, N Wolff, S Freytes, CO AF Tsai, T Goodman, S Saez, R Schiller, G Adkins, D Callander, N Wolff, S Freytes, CO TI Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE BMT; relapse; second transplant; lymphoma; leukemia ID NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; COMBINATION CHEMOTHERAPY; FOLLOW-UP; DISEASE; THERAPY; CYCLOPHOSPHAMIDE; CARMUSTINE; CISPLATIN; LEUKEMIA AB Increasing numbers of patients have received autologous stem cell transplants (ASCT) for hematologic malignancies, Since only a fraction of these patients are cured, physicians are more frequently faced with the dilemma of how to manage relapse post-transplant. Potential advantages of allogeneic transplantation (alloBMT) over ASCT include lack of graft tumor contamination and presence of a graft-versus-tumor effect, For this reason, patients who relapse after ASCT are often considered candidates for allogeneic bone marrow transplantation. However, there is limited knowledge on the outcome of alloBMT in patients who relapse after ASCT, We retrospectively analyzed the outcome of 20 patients with malignant lymphoma (n = 14) and AML (n = 6) who underwent alloBMT after failing an ASCT, The median age was 30 (17-41) years and the interval from ASCT to alloBMT was 10.5 (2-25) months, Seventeen patients died between 0.3 to 11 months (median 2.0) after alloBMT, all due to BMT-related toxicities, Three patients remain alive and free of disease at 1.1, 1.2 and 2.5 years after alloBMT. Sixteen of the 18 evaluable patients (89%) developed grade II-IV acute GVHD, Patients undergoing alloBMT after ASCT have a very high treatment-related mortality and incidence of grade II-IV acute GVHD, Alternative treatments with salvage chemotherapy, radiation or investigational approaches should be considered in patients who relapse after ASCT. C1 S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX. NASHVILLE VET ADM MED CTR,NASHVILLE,TN. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. RP Tsai, T (reprint author), UNIV TEXAS,HLTH SCI CTR,DIV HEMATOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 16 TC 77 Z9 78 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 1997 VL 20 IS 10 BP 859 EP 863 DI 10.1038/sj.bmt.1700989 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA YG896 UT WOS:A1997YG89600008 PM 9404927 ER PT J AU Ross, EV Romero, R Kollias, N Crum, C Anderson, RR AF Ross, EV Romero, R Kollias, N Crum, C Anderson, RR TI Selectivity of protoporphyrin IX fluorescence for condylomata after topical application of 5-aminolaevulinic acid: implications for photodynamic treatment SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID DELTA-AMINOLEVULINIC-ACID; 5-AMINOLEVULINIC ACID; IN-VITRO; THERAPY; SKIN; PAPILLOMAVIRUS; PHOTOSENSITIZER; SENSITIZATION; INFECTIONS; PSORIASIS AB To examine the potential of using photodynamic therapy (PDT) in condylomata, we studied the distribution and kinetics of protoporphyrin IX (PpIX) formation in condylomata acuminata and adjacent normal skin after topical application of 5-aminolaevulinic acid (ALA), PpIX fluorescence spectra were measured hourly in vivo after ALA application, After grass fluorescence imaging, the lesions were biopsied, and fluorescence microscopy was performed, All three PpIX fluorescence detection modalities suggested selectivity of PpIX formation in condylomata after topical ALA application, In 17 of 25 condylomata, there was significantly greater fluorescence compared with adjacent normal skin, The greatest lesional to normal skin fluorescence ratios occurred after 2 h, The most likely mechanism for increased lesional PpIX formation in condylomata is enhanced stratum corneum permeability. Based on our results, ALA/PDT is a potential field therapy for condylomata, PpIX fluorescence imaging after ALA application may also be useful for localizing condylomata prior to treatment. C1 HARVARD UNIV, SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED, MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02115 USA. NR 31 TC 49 Z9 55 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 1997 VL 137 IS 5 BP 736 EP 742 PG 7 WC Dermatology SC Dermatology GA YG534 UT WOS:A1997YG53400012 PM 9415233 ER PT J AU Skarin, AT Dorfman, DM AF Skarin, AT Dorfman, DM TI Non-Hodgkin's lymphomas: Current classification and management SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID BONE-MARROW TRANSPLANTATION; LARGE-CELL LYMPHOMA; EUROPEAN-AMERICAN CLASSIFICATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TERM FOLLOW-UP; FOLLICULAR LYMPHOMA; LYMPHOBLASTIC LYMPHOMA; INITIAL THERAPY; CHEMOTHERAPY; DISEASE AB Considerable progress has been made in the classification of non-Hodgkin's lymphomas during the past 15 years, and the use of specific monoclonal antibodies directed against cell surface antigens has contributed to the understanding of the immunology of the disease. Early-stage indolent lymphoma is treated with radiotherapy; treatment of advanced-stage indolent lymphoma varies. Aggressive lymphomas are treated with combination chemotherapy with or without regional radiotherapy, and highly aggressive lymphomas are treated with regimens similar to those for children with leukemia. C1 DANA FARBER PARTNERS CANC CARE,ADULT ONCOL DEPT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,HEMATOL LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP Skarin, AT (reprint author), DANA FARBER PARTNERS CANC CARE,HEMATOL LAB,BOSTON,MA, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 58 TC 27 Z9 28 U1 0 U2 1 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD NOV-DEC PY 1997 VL 47 IS 6 BP 351 EP & DI 10.3322/canjclin.47.6.351 PG 23 WC Oncology SC Oncology GA YG145 UT WOS:A1997YG14500004 PM 9371057 ER PT J AU Black, PM AF Black, PM TI Hormones, radiosurgery and virtual reality: New aspects of meningioma management SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Canadian-Congress-of-Neurological-Sciences CY JUN 23, 1995 CL VICTORIA, CANADA SP Canadian Congress Neurolog Sci ID RADIATION-THERAPY; RESECTED MENINGIOMAS; RECEPTOR EXPRESSION; GROWTH AB The understanding and management of meningiomas is changing significantly today, One of the most striking features of their pathophysiology is their predominance in women. In a series of 517 patients with meningiomas seen by the Brain Tumor Group at Brigham and Women's Hospital, the female:male ratio was 2.4:1. The progesterone receptor appears to be the major candidate to explain this difference. Although meningioma cells variably express receptors for estrogen, androgen, platelet-derived growth factor, epidermal growth factor, and somatostatin, these molecules do not explain the differences because they are not differentially expressed or are not activated. Progesterone receptor can be shown to be expressed in 81% of women and 40% of men with meningiomas; it can also be shown to be activated by transfecting a construct with the progesterone responsive element and a reporter in it and using the cell's own receptors to activate this construct. Surgery remains the mainstay of meningioma management. At the Brigham and Women's Hospital three-dimensional reconstruction techniques have markedly improved the ability to visualize the tumor as well as its relation to vascular structures. With MRI reconstruction, it is possible to know the tumor's relation to the sagittal and other sinuses, to identify feeders and proximity to major arteries, and to establish its location and relation to cortex by frameless stereotaxis. These techniques can be used in a virtual reality format are some of the most powerful in neurosurgery both for teaching and for the surgical procedure itself, External beam radiation has been shown by others to be an effective adjunctive treatment to prevent meningioma recurrence. Recently, linear accelerator radiosurgery and stereotactic radiotherapy have changed the pattern of radiation at our institution. In a series of 56 skull base meningiomas, for example, 95% were controlled (i.e., showed no growth) over a four year period. Fractionated focal radiation potentially offers the same control rate with fewer complications. With increasing understanding and treatment possibilities, meningiomas remain one of the most intriguing and challenging tumors in the nervous system. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP Black, PM (reprint author), BRIGHAM & WOMENS HOSP,DIV NEUROSURG,BRAIN TUMOR CTR,NEUROSURG SERV,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 30 TC 19 Z9 20 U1 0 U2 0 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD NOV PY 1997 VL 24 IS 4 BP 302 EP 306 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA YK745 UT WOS:A1997YK74500006 PM 9398976 ER PT J AU Schwartz, GF Lagios, MD Carter, D Connolly, J Ellis, IO Eusebi, V Finkel, GC Gorstein, F Holland, R Hutter, RVP Masood, S Millis, RR OMalley, FP Palazzo, JT Patchefsky, AS Rosai, J Schnitt, SJ Schwarting, R Sloane, JP Tavassoli, FA Feig, SA Kopans, DB McCormick, B Copeland, EM Giuliano, AE Silverstein, MJ vanDongen, JA Bodian, C AF Schwartz, GF Lagios, MD Carter, D Connolly, J Ellis, IO Eusebi, V Finkel, GC Gorstein, F Holland, R Hutter, RVP Masood, S Millis, RR OMalley, FP Palazzo, JT Patchefsky, AS Rosai, J Schnitt, SJ Schwarting, R Sloane, JP Tavassoli, FA Feig, SA Kopans, DB McCormick, B Copeland, EM Giuliano, AE Silverstein, MJ vanDongen, JA Bodian, C TI Consensus conference on the classification of ductal carcinoma in situ SO CANCER LA English DT Editorial Material C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. ST MARYS HOSP,SAN FRANCISCO,CA. YALE UNIV,SCH MED,NEW HAVEN,CT. CITY HOSP NOTTINGHAM,NHS TRUST,NOTTINGHAM,ENGLAND. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. UNIV BOLOGNA,BOLOGNA,ITALY. THOMAS JEFFERSON UNIV HOSP,PHILADELPHIA,PA 19107. UNIV NIJMEGEN HOSP,NL-6500 HB NIJMEGEN,NETHERLANDS. ST BARNABAS HOSP,LIVINGSTON,NJ. UNIV FLORIDA,HLTH SCI CTR,JACKSONVILLE,AL. LONDON HLTH SCI CTR,LONDON,ENGLAND. GUYS HOSP,LONDON SE1 9RT,ENGLAND. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. ROYAL LIVERPOOL UNIV HOSP,LIVERPOOL,MERSEYSIDE,ENGLAND. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,GAINESVILLE,FL. JOHN WAYNE CANC CTR,SANTA MONICA,CA. BREAST CTR,VAN NUYS,CA 91405. NETHERLANDS CANC INST,AMSTERDAM,NETHERLANDS. MT SINAI MED CTR,NEW YORK,NY 10029. NR 0 TC 133 Z9 137 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1997 VL 80 IS 9 BP 1798 EP 1802 PG 5 WC Oncology SC Oncology GA YC306 UT WOS:A1997YC30600015 ER PT J AU Platz, EA Martinez, ME Grodstein, F Fuchs, CS Colditz, GA Stampfer, MJ Giovannucci, E AF Platz, EA Martinez, ME Grodstein, F Fuchs, CS Colditz, GA Stampfer, MJ Giovannucci, E TI Parity and other reproductive factors and risk of adenomatous polyps of the distal colorectum (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE adenoma; colorectum; menopause; oral contraceptive; parity; polyp; reproductive factors; United States; women ID LARGE BOWEL-CANCER; COLON-CANCER; HORMONAL FACTORS; BREAST-CANCER; 1ST PREGNANCY; WOMEN; AGE; FOLATE; RATS; CARCINOGENESIS AB Evidence for an effect of reproductive factors on colorectal carcinogenesis is inconsistent and little is known about their role in development of precursor adenomatous polyps, We evaluated the relation between reproductive factors and distal colorectal adenomas (n = 982) during 14 years of follow up of 26,983 participants in the Nurses' Health Study (United States), The women were free of diagnosed cancer or polyps in 1980, underwent endoscopy 1980-94, and had reported on their parity, oral contraceptive (OC) use, and ages at menarche, first term-pregnancy, and menopause, We calculated relative risks (RR) and 95 percent confidence intervals (CI) using multiple Logistic regression. Women with higher parity had an increased risk of adenomas of the distal colorectum (P trend = 0.004; 6+ cfO parity: RR = 1.3, CI = 0.9-1.8) or distal colon (P trend = 0.002, RR = 1.7, CI = 1.2-2.6). This association was significantly stronger among women with a family history of colorectal cancer (P interaction = 0.03); comparing 6+ term-pregnancies with nulliparity, among those with a family history, the RR for distal colon adenoma Nas 3.2 (CI = 1.4-7.2), while among those without a family history, the RR was 1.3 (CT = 0.8-2.2), We observed no association for distal colorectal adenoma and age at menarche, age at first term-pregnancy, ever use of OCs, or menopausal status, Further work is needed to clarify the relation of parity with colon adenoma risk. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. RP Platz, EA (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356, CA55075, T32 CA 09001-20] NR 53 TC 12 Z9 12 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 1997 VL 8 IS 6 BP 894 EP 903 DI 10.1023/A:1018420513815 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA YF740 UT WOS:A1997YF74000010 PM 9427432 ER PT J AU Herrlinger, U Kramm, CM Johnston, KM Louis, DN Finkelstein, D Reznikoff, G Dranoff, G Breakefield, XO Yu, JS AF Herrlinger, U Kramm, CM Johnston, KM Louis, DN Finkelstein, D Reznikoff, G Dranoff, G Breakefield, XO Yu, JS TI Vaccination for experimental gliomas using GM-CSF-transduced glioma cells SO CANCER GENE THERAPY LA English DT Article DE glioma; granulocyte-macrophage colony-stimulating factor; gene therapy immunotherapy; vaccination ID EXPERIMENTAL BRAIN-TUMORS; ANTITUMOR IMMUNITY; GENE-THERAPY; CANCER; IMMUNOTHERAPY; EOSINOPHILS; IMMUNOBIOLOGY; INTERLEUKIN-2; EXPRESSION; VACCINES AB Brain tumors have an immunoprivileged status wh ich contributes to their refractoriness to treatment. In th is study, immune rejection of GL261 glioma tumors in the mouse brain was achieved by subcutaneous vaccination with GM-CSF-transduced glioma cells. Cultured GL261 cells were transduced to secrete murine GM-CSF using a retrovirus vector, then irradiated, and injected subcutaneously into H-2 matched C57BL/6 mice. In prevaccination studies, the median survival time (MST) of animals vaccinated with 5 X 10(4) or 5 X 10(5) GM-CSF-transduced cells 7 days prior to intracranial injection of 10(6) nontransduced, nonirradiated GL261 cells was significantly prolonged by 45-50% compared with animals vaccinated in parallel with nontransduced, irradiated glioma cells. In treatment of established gliomas, the MST of animals, which were treated subcutaneously with 5 X 10(6) irradiated CM-CSF-transduced cells 3 days after intracranial injection of 2 X 10(4) nontransduced cells, was prolonged significantly by 36% compared with animals treated with the same number of nontransduced, irradiated cells or to sham-treated animals. in prevaccination studies, histology of brain tumors 4 days after intracranial tumor cell injection revealed infiltrates of CD8+ lymphocytes and eosinophils, the latter exclusively in animals vaccinated with GM-CSF-transduced cells. Thus, subcutaneous injection of irradiated GM-CSF-transduced glioma cells can induce a potent immune response to intracranial gliomas both as a vaccination against subsequent intracranial glioma cell implantation and for treatment of established intracranial glioma. C1 MASSACHUSETTS GEN HOSP E, PATHOL SERV, CHARLESTOWN, MA USA. MASSACHUSETTS GEN HOSP E, CTR CANC, MOL NEUROGENET UNIT, CHARLESTOWN, MA USA. MASSACHUSETTS GEN HOSP E, MOL NEUROONCOL LAB, CHARLESTOWN, MA USA. HARVARD UNIV, SCH MED, CHARLESTOWN, MA USA. DANA FARBER CANC INST, DIV HEMATOL MALIGNANCIES, BOSTON, MA 02115 USA. DANA FARBER CANC INST, DIV HUMAN CANC GENET, BOSTON, MA 02115 USA. UNIV TUBINGEN, DEPT NEUROL, D-72074 TUBINGEN, GERMANY. UNIV DUSSELDORF, CHILDRENS HOSP, D-4000 DUSSELDORF, GERMANY. MCGILL UNIV, MONTREAL GEN HOSP, DEPT NEUROSURG, MONTREAL, PQ H3G 1A4, CANADA. FU NCI NIH HHS [CA69246] NR 29 TC 79 Z9 80 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1997 VL 4 IS 6 BP 345 EP 352 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YH924 UT WOS:A1997YH92400002 PM 9408604 ER PT J AU Goldsmith, KT Dion, LD Garver, RI AF Goldsmith, KT Dion, LD Garver, RI TI Recombinant adenovirus replication in non-small cell lung cancer SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 BIRMINGHAM VAMC,DEPT MED,DIV PULM & CRIT CARE MED,BIRMINGHAM,AL. UNIV ALABAMA,BIRMINGHAM,AL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1997 VL 4 IS 6 SU S BP O39 EP O39 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YJ318 UT WOS:A1997YJ31800039 ER PT J AU Jacobs, A Tjuvajev, JG Joshi, A Joshi, R Herrlinger, U Balatoni, J Finn, R Breakefield, OX Blasberg, RG AF Jacobs, A Tjuvajev, JG Joshi, A Joshi, R Herrlinger, U Balatoni, J Finn, R Breakefield, OX Blasberg, RG TI Monitoring HSV1-tk gene delivery by a replicationconditional herpes viral vector (hrR3) in 9L gliosarcoma cells: Implications for imaging hrR3 replication in vivo SO CANCER GENE THERAPY LA English DT Meeting Abstract ID EXPRESSION C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,NEW YORK,NY 10021. NR 5 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1997 VL 4 IS 6 SU S BP O41 EP O41 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YJ318 UT WOS:A1997YJ31800041 ER PT J AU Doll, R Shankara, S Rudginsky, S Piraino, S KyostiaMoore, S Nicolette, C Kaplan, J Linette, G Haluska, F Roberts, B AF Doll, R Shankara, S Rudginsky, S Piraino, S KyostiaMoore, S Nicolette, C Kaplan, J Linette, G Haluska, F Roberts, B TI Adenoviral infection of human dendritic cells for use as antitumor vaccines SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 GENZYME CORP,FRAMINGHAM,MA 01701. MASSACHUSETTS GEN HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1997 VL 4 IS 6 SU S BP P136 EP P136 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YJ318 UT WOS:A1997YJ31800136 ER PT J AU Nguyen, J Wu, P Hlatky, L Terwilliger, EF AF Nguyen, J Wu, P Hlatky, L Terwilliger, EF TI Genetic strategies for anti-angiogenic therapy of solid tumors SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 BETH ISRAEL DEACONESS MED CTR,DEPT RADIOL SCI,BOSTON,MA 02115. BETH ISRAEL DEACONESS MED CTR,DIV EXPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1997 VL 4 IS 6 SU S BP P101 EP P101 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA YJ318 UT WOS:A1997YJ31800101 ER PT J AU Dahia, PLM Marsh, DJ Zheng, ZM Zedenius, J Komminoth, P Frisk, T Wallin, G Parsons, R Longy, M Larsson, C Eng, C AF Dahia, PLM Marsh, DJ Zheng, ZM Zedenius, J Komminoth, P Frisk, T Wallin, G Parsons, R Longy, M Larsson, C Eng, C TI Somatic deletions and mutations in the Cowden disease gene, PTEN, in sporadic thyroid tumors SO CANCER RESEARCH LA English DT Article ID RET PROTOONCOGENE; MOLECULAR CHARACTERIZATION; ENDOCRINE NEOPLASIA; CARCINOMA; ONCOGENE AB The majority of familial medullary thyroid neoplasms are associated with germ-line mutations of the RET proto-oncogene, yet very little is known about the mechanisms involved in the pathogenesis of familial and sporadic nonmedullary thyroid tumors. A subset of thyroid tumors have loss of heterozygosity of chromosome 10q22-23, a region harboring the gene responsible for Cowden disease, an autosomal dominant hamartoma syndrome associated with thyroid and breast tumors. PTEN/MMAC1/TEP1 codes for a dual-specificity phosphatase and is likely a tumor suppressor gene. We sought to determine the PTEN status in a series of epithelial thyroid neoplasms. We studied 95 sporadic thyroid tumors, of which 39 were papillary thyroid carcinomas (PTCs), 12 were follicular carcinomas, 9 were anaplastic carcinomas, 5 were Hurthle cell carcinomas, 21 were nonfunctioning follicular adenomas, and 9 were Hurthle cell adenomas. Direct sequencing of PCR-amplified products was performed for all nine exons of PTEN. Two polymorphic markers, one located in intron 8 and another, a dinucleotide repeat marker, AFMa086wg9, located within intron 2, were analyzed in paired blood-tumor DNA samples to assess hemizygous deletions of PTEN. We found a somatic frameshift mutation in one PTC, which was expected to generate a premature stop codon 2 amino acids downstream. Twenty-six % of informative benign tumors (four follicular adenomas and three Hurthle cell adenomas) and only 3 of 49 (6.1%) informative malignant tumors (one PTC, one follicular carcinoma, and one anaplastic carcinoma) showed evidence of hemizygous deletion of PTEN (P = 0.046). We conclude that a subset of thyroid tumors have somatic deletions of the PTEN gene, predominantly the benign forms, and that small intragenic mutations of PTEN are infrequent in thyroid tumors. We speculate that other mechanisms of PTEN inactivation, rather than small intragenic mutations, might occur in the hemizygously deleted samples and act as the ''Knudson second hit.'' Alternatively, other tumor suppressor genes mapping to chromosome 10q22-23 could be the actual targets for such deletions and thus represent the various hits in the pathway of multistep carcinogenesis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,HUMAN CANC GENET UNIT,BOSTON,MA 02115. KAROLINSKA HOSP,DEPT MOL MED,S-10401 STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT SURG,S-10401 STOCKHOLM,SWEDEN. UNIV ZURICH,DEPT PATHOL,CH-8091 ZURICH,SWITZERLAND. COLUMBIA UNIV,CTR CANC,DEPT PATHOL,NEW YORK,NY 10021. INST BERGONIE,DIV MOL ONCOL,F-33076 BORDEAUX,FRANCE. UNIV CAMBRIDGE,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 21 TC 229 Z9 231 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1997 VL 57 IS 21 BP 4710 EP 4713 PG 4 WC Oncology SC Oncology GA YD358 UT WOS:A1997YD35800011 PM 9354427 ER PT J AU Sherman, L Jacoby, LB Lampe, J Pelton, P Aguzzi, A Herrlich, P Ponta, H AF Sherman, L Jacoby, LB Lampe, J Pelton, P Aguzzi, A Herrlich, P Ponta, H TI CD44 expression is aberrant in benign Schwann cell tumors possessing mutations in the neurofibromatosis type 2, but not type 1, gene SO CANCER RESEARCH LA English DT Article ID HUMAN BRAIN-TUMORS; SPLICE VARIANTS; DIFFERENTIAL EXPRESSION; METASTATIC BEHAVIOR; PROGNOSTIC FACTOR; RAS PROTEINS; LYMPH-NODE; RT-PCR; MEMBRANE; ISOFORMS AB Atypical expression of CD44 splice variants has been implicated in the progression of numerous tumors. This abnormal CD44 expression is presumed to result from gene alterations that cause tumorigenic transformation. Two tumor types that have been linked to specific gene alterations are schwannomas, which have mutations in the neurofibromatosis (NF) type 2 (NF2) gene, and neurofibromas, which characteristically possess NP type I (NF1) gene mutations. We examined CD44 expression in normal sciatic nerves, in schwannomas with confirmed NF2 mutations, and in neurofibromas and malignant peripheral nerve sheath tumor tissue and cell lines from NF1 patients. Compared to normal nerves, schwannomas express higher total levels of CD44 and additional splice variants, whereas CD44 expression in neurofibromas is unaltered. Malignant peripheral nerve sheath tumor tissue and cell lines express the CD44v6 epitope, which is not expressed by normal Schwann cells or by other Schwann cell tumors. These data indicate that altered CD44 expression correlates strictly with mutations in the NF2 but not NF1 gene and suggest that CD44v6 might be a marker for the malignant transformation of Schwann cells. C1 FORSCHUNGSZENTRUM KARLSRUHE,INST GENET,D-76021 KARLSRUHE,GERMANY. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV SPITAL ZURICH,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. RP Sherman, L (reprint author), UNIV CINCINNATI,MED CTR,DEPT CELL BIOL NEUROBIOL & ANAT,231 BETHESDA AVE,CINCINNATI,OH 45267, USA. RI Aguzzi, Adriano/A-3351-2008; OI Aguzzi, Adriano/0000-0002-0344-6708 NR 48 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1997 VL 57 IS 21 BP 4889 EP 4897 PG 9 WC Oncology SC Oncology GA YD358 UT WOS:A1997YD35800038 PM 9354454 ER PT J AU Siegel, AJ Sholar, M Yang, J Dhanak, E Lewandrowski, KB AF Siegel, AJ Sholar, M Yang, J Dhanak, E Lewandrowski, KB TI Elevated serum cardiac markers in asymptomatic marathon runners after competition: Is the myocardium stunned? SO CARDIOLOGY LA English DT Article DE marathon runners; serum cardiac markers (CK-MB, cardiac troponin T, cardiac troponin I); stunned myocardium ID CREATINE-KINASE-MB; TROPONIN-T LEVELS; ISOENZYME LEVELS; INFARCTION; DIAGNOSIS; RISK; INJURY; MYOGLOBIN; EMERGENCY; NECROSIS AB Prolonged strenuous exercise may trigger acute myocardial infarction (AMI), as exemplified by the occurrence of sudden cardiac death during marathon running. Serum creatine kinase MB (CK-MB) may be elevated in asymptomatic marathon runners after competition from exertional rhabdomyolysis of skeletal muscle altered by training, limiting its utility for evaluating acute cardiac injury in such athletes. Myoglobin and CK-MB2 isoform levels are emerging as earlier markers of AMI and troponin subunits as more specific than serum CK-MB mass. We tested runners before and sequentially after the 1995 Boston Marathon for conventional and newer markers including myoglobin, CK-MB mass and isoforms, cardiac troponin T, and cardiac troponin I using standard laboratory methods and rapid format assays if available. The mean serum values for myoglobin, CK-MB mass, CK-MB/myoglobin rapid panel tests, and CK-MB2 isoforms were normal or negative pre-race and elevated or positive 4 and 24 h after competition. These markers lack specificity for acute cardiac injury in trained runners. While the mean serum values for cardiac troponins T and I remained normal, 9 of 45 runners (20%) showed an increase in subunits by first-generation assays. All runners remained asymptomatic for cardiac disease and completed subsequent marathons 1 year later, making reversible myocardial injury or stunning unlikely. Elevated values of serum markers for AMI, including first-generation assays for both troponin subunits should be interpreted with caution in trained runners. C1 MCLEAN HOSP,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT CLIN PATHOL,BOSTON,MA. NR 34 TC 63 Z9 65 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PD NOV-DEC PY 1997 VL 88 IS 6 BP 487 EP 491 DI 10.1159/000177396 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YG614 UT WOS:A1997YG61400001 PM 9397299 ER PT J AU Glickerman, DJ Hathaway, PB Hatsukami, T Daly, CP Althaus, S Kohler, TR AF Glickerman, DJ Hathaway, PB Hatsukami, T Daly, CP Althaus, S Kohler, TR TI Transluminal treatment of a celiac artery pseudoaneurysm with a stent graft occlusion device SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE stents and prostheses; arteries, therapeutic blockade; aneurysm, therapy ID ABDOMINAL AORTIC-ANEURYSMS; ENDOVASCULAR REPAIR; EMBOLIZATION; PLACEMENT; PANCREATITIS; MANAGEMENT; EXPERIENCE; COIL AB This report describes the transluminal placement of a stent graft occlusion device to treat a celiac bypass graft pseudoaneurysm which was causing biliary and duodenal obstruction. RP Glickerman, DJ (reprint author), VET AFFAIRS PUGET SOUND HLTH CARE SYST,RADIOL SERV 114,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD NOV-DEC PY 1997 VL 20 IS 6 BP 466 EP 469 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA YF148 UT WOS:A1997YF14800011 PM 9354718 ER PT J AU Kashket, S Yaskell, T AF Kashket, S Yaskell, T TI Effectiveness of calcium lactate added to food in reducing intraoral demineralization of enamel SO CARIES RESEARCH LA English DT Article DE calcium; demineralization; enamel; food; iodide penetrability; phosphate; saturation; Streptococcus mutans; sucrose ID DENTAL PLAQUE; BOVINE ENAMEL; CARIES; FLUORIDE AB Following the demonstration that rinses with solutions of soluble calcium salts reduced sucrose-induced demineralization, a study was undertaken to determine whether a similar effect could be obtained by the supplementation of a solid food with calcium lactate (CL). Subjects wore palatal appliances containing blocks of bovine enamel that were coated with Streptococcus mutans IB 1600 and ate 5-gram portions of cookies made with defined levels of CL. Determinations were made of changes in iodide penetrability (Delta Ip) of the enamel, as well as the pH, calcium and inorganic phosphate of the streptococcal plaque. CL at 3.2% (w/w) reduced Delta Ip from 12.9+/-1.7 to 6.1+/-0.9 units, i.e. by 52.7%. Plaque pH was not affected. Demineralization was reduced progressively with increasing concentrations of added CL, and CL was most effective with increasingly sweet cookies. Plaque contained 32.4+/-6.0 and 17.1+/-4.2 mM calcium after 1 and 5 min, respectively. Calculations showed that the plaque was saturated with respect to enamel during the first 5-10 minutes after food ingestion, in spite of the progressive drop in plaque pH. In conclusion, the present study demonstrated the reduction of the cariogenic potential of solid food by relatively low concentrations of CL. The effect appeared to be related to the ability of the food to maintain high levels of calcium in the streptococcal plaque during the period of active acidogenesis. C1 FORSYTH DENT CTR,CTR RES ORAL & BIOL EFFECTS FOODS,BOSTON,MA 02115. RP Kashket, S (reprint author), FORSYTH DENT CTR,NUTR SECT,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-05253] NR 26 TC 7 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD NOV-DEC PY 1997 VL 31 IS 6 BP 429 EP 433 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YB336 UT WOS:A1997YB33600005 PM 9353582 ER PT J AU Mitchel, JF McKay, RG Azrin, MA Aretz, TA Waters, DD Fram, DB AF Mitchel, JF McKay, RG Azrin, MA Aretz, TA Waters, DD Fram, DB TI Effect of low grade radiofrequency heating on arterial vasospasm in the porcine model SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE thermal energy; arteries; porcine model ID LUMINAL CORONARY ANGIOPLASTY; LASER BALLOON ANGIOPLASTY; PERIPHERAL ARTERIES; PLATELET-ADHESION; ELASTIC RECOIL; SUBENDOTHELIUM; COMPLICATIONS; ATHERECTOMY AB Nineteen pigs were studied in order to assess the effect of low grade, radiofrequency-powered, thermal balloon angioplasty on the vasoconstrictor response of peripheral arteries, A mechanical stimulus was used to induce vasospasm, Thermal angioplasty reduced the extent of inducible vasospasm from 79% to 6% compared to nonthermal control inflations, which reduced the vasoconstrictor response from 75% to 60% (P < 0.001), Histologic studies demonstrated that the extent of myocyte necrosis was significantly greater in the thermally treated arteries than in the control vessels (P < 0.01), Thermal balloon angioplasty at 60 degrees C significantly attenuates peripheral arterial vasospasm induced by mechanical trauma in the porcine model. This paralytic effect may be related to the lass of myocytes secondary to thermal necrosis. (C) 1997 Wiley-Liss, Inc. C1 HARTFORD HOSP,CARDIAC LAB,DEPT INTERNAL MED,HARTFORD,CT 06102. HARTFORD HOSP,DIV CARDIOL,HARTFORD,CT 06102. UNIV CONNECTICUT,DIV CARDIOL,FARMINGTON,CT. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 29 TC 4 Z9 4 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD NOV PY 1997 VL 42 IS 3 BP 348 EP 355 DI 10.1002/(SICI)1097-0304(199711)42:3<348::AID-CCD28>3.0.CO;2-G PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YD939 UT WOS:A1997YD93900028 PM 9367120 ER PT J AU Moskowitz, MA Dalkara, T AF Moskowitz, MA Dalkara, T TI Opportunities for collective wisdom in stroke research SO CEREBROVASCULAR DISEASES LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HACETTEPE UNIV HOSP,DEPT NEUROL,ANKARA,TURKEY. RP Moskowitz, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. RI Moskowitz, Michael/D-9916-2011 NR 7 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PD NOV-DEC PY 1997 VL 7 IS 6 BP 313 EP 314 DI 10.1159/000108212 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA YE361 UT WOS:A1997YE36100001 ER PT J AU Narula, J Kharbanda, S Khaw, BA AF Narula, J Kharbanda, S Khaw, BA TI Apoptosis and the heart SO CHEST LA English DT Review DE apoptosis; cardiomyopathy; cell death; CPP-32; cytochrome C; DNA fragmentation; myocytes; necrosis; proteases ID CELL-DEATH; PROTEASE; CARDIOMYOCYTES; CARDIOMYOPATHY; CED-3 C1 NORTHEASTERN UNIV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 24 TC 25 Z9 26 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1997 VL 112 IS 5 BP 1358 EP 1362 DI 10.1378/chest.112.5.1358 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA YF052 UT WOS:A1997YF05200034 PM 9367480 ER PT J AU Kearns, G Perrott, DH Sharma, A Kaban, LB Vargervik, K AF Kearns, G Perrott, DH Sharma, A Kaban, LB Vargervik, K TI Placement of endosseous implants in grafted alveolar clefts SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Cleft-Palate-Craniofacial-Association CY APR 22-MAY 01, 1996 CL SAN DIEGO, CALIFORNIA SP Amer Cleft Palate Craniofacial Assoc DE alveolar cleft; bone grafting; endosseous implants ID OSSEOINTEGRATED IMPLANTS; RESIDUAL ALVEOLAR; BONE; RECONSTRUCTION; MULTICENTER; DEFECTS; PALATE; JAW AB Objective: The purpose of this study was to determine the optimal timing for placement and to evaluate short-and long-term outcomes of endosseous implants in bone-grafted alveolar clefts. Design: Fourteen patients who underwent alveolar cleft bone grafting (ACBG) and closure of an oronasal fistula followed by restoration of the missing lateral incisor tooth using endosseous implants (EI) were studied. The oronasal fistulae were closed using local flaps, and the alveolus was grafted with fresh autogenous iliac marrow. Endosseous implants were placed a minimum of 4 months following ACBG. The average age at ACBG was 20.35 years (range, 12-65 yr), and at implant placement 22.2 years (range, 15-66 yr). It was necessary to regraft the alveolar cleft region in six patients to provide adequate bone volume for implant placement. Those who required alveolar regrafting had an increased mean interval between the initial ACBG and planned implant placement compared to the patients with adequate bone available for implant placement 26.4 months (range, 4-46 mo) versus 15.75 months (range, 4-36 mo). Results: Twenty-nine implants were placed in 14 patients, 9 outside of the cleft region and 20 in grafted alveolar clefts. Eighteen of 20 (90%) implants in the bone-grafted alveolar clefts have been successfully restored. The mean followup after implant placement was 39.1 months (range, 1-54 mo), and after restoration 28.5 months (range, 1-47 mo). Conclusions: Endosseous implants can be placed in bone-grafted alveolar clefts. Consideration should be given to the adequacy of graft volume and ridge morphology at the time of ACBG. The interval between ACBG and implant placement is important. The greater the interval beyond 4 months, the more likely there will be inadequate bone volume to accept an implant. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Restorat Dent, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Growth & Dev, San Francisco, CA 94143 USA. Ctr Craniofacial Anomalies, San Francisco, CA 94143 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kearns, G (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,Fruit St, Boston, MA 02114 USA. NR 22 TC 49 Z9 49 U1 0 U2 0 PU AMER CLEFT PALATE-CRANIOFACIAL ASSOC PI CHAPEL HILL PA 1829 EAST FRANKLIN ST, STE 1022, CHAPEL HILL, NC 27514 USA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD NOV PY 1997 VL 34 IS 6 BP 520 EP 525 DI 10.1597/1545-1569(1997)034<0520:POEIIG>2.3.CO;2 PG 6 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA YM080 UT WOS:000071026000009 PM 9431470 ER PT J AU Samuels, BL Hollis, DR Rosner, GL Trump, DL Shapiro, CL Vogelzang, NJ Schilsky, RL AF Samuels, BL Hollis, DR Rosner, GL Trump, DL Shapiro, CL Vogelzang, NJ Schilsky, RL TI Modulation of vinblastine resistance in metastatic renal cell carcinoma with cyclosporine a or tamoxifen: A Cancer and Leukemia Group B study SO CLINICAL CANCER RESEARCH LA English DT Article ID INTRINSIC DRUG-RESISTANCE; PHASE-II TRIAL; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; OVARIAN-CANCER; TUMOR-CELLS; EXPRESSION; INFUSION; ADRIAMYCIN; VERAPAMIL AB Multidrug resistance mediated by P-glycoprotein may be an important cause of chemotherapy failure. Renal cell carcinoma is a disease known to demonstrate a high degree of intrinsic chemotherapy drug resistance, and this has been shown to be related to intrinsic overexpression of P-glycoprotein. Cyclosporine A and tamoxifen have been shown to reverse multidrug resistance in renal cell carcinoma cell lines in vitro. Phase I studies have defined appropriate doses of cyclosporine A and tamoxifen that can be combined with continuous-infusion vinblastine and safely achieve serum levels associated in vitro with resistance reversal. A randomized Phase II study was carried out by the Cancer and Leukemia Group B to evaluate the potential of high doses of cyclosporine A or tamoxifen to modulate clinical vinblastine resistance in patients with advanced renal cell carcinoma. Patients were treated initially with continuous-infusion vinblastine alone (1.2 mg/m(2)/day for 4 days or 1.5 mg/m(2)/day for 5 days); patients with stable or progressive disease were then treated with the same vinblastine regimen, combined with a high-dose regimen of either cyclosporine A (12.5 mg/kg/day for 5 days) or tamoxifen (400 mg/m(2) as a loading dose and 300 mg/m(2)/day for 13 days). Sixty-three patients were randomized to each arm. Eighty patients on both arms were evaluable for response to vinblastine alone; of these, only one patient achieved a partial response. Thirty-three patients went on to be treated with vinblastine and high-dose cyclosporine A. No responses were observed, although four patients with progressive disease on prior vinblastine achieved stabilization of disease after cyclosporine A was added. Addition of cyclosporine resulted in more leukopenia (5% versus 25%) and in transient hyperbilirubinemia (24%) and neurocortical changes (11%). No significant azotemia was observed. Thirty-five patients received high-dose tamoxifen with continuous-infusion vinblastine. One complete remission was seen in a patient who had stable disease only with prior vinblastine alone; no other responses were observed. Leukopenia was not more severe with the addition of tamoxifen to vinblastine, nor was hyperbilirubinemia observed. However, 9% of patients developed transient ataxia with or without neurocortical changes as a result of high-dose tamoxifen therapy, and 11% developed phlebitis. We conclude that advanced renal cell carcinoma is a highly chemoresistant tumor, that continuous-infusion vinblastine has no appreciable activity in the therapy of this disease, and that addition of high doses of cyclosporine A or tamoxifen was not able to modulate this resistance in these patients. Suggestions regarding study design for future drug resistance modulation trials were made based on the design and conduct of this study. C1 CTR STAT,CANC & LEUKEMIA GRP B,DURHAM,NC 27715. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27715. DUKE UNIV,MED CTR,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV CHICAGO,MED CTR,DEPT MED,CHICAGO,IL 60637. CENT OFF,CANC & LEUKEMIA GRP B,CHICAGO,IL 60604. RP Samuels, BL (reprint author), LUTHERAN GEN HOSP,LUTHERAN GEN CANC CARE CTR,DIV HEMATOL ONCOL,1700 LUTHER LANE,PARK RIDGE,IL 60068, USA. FU NCI NIH HHS [CA32291, CA47577, CA33601] NR 57 TC 44 Z9 44 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1997 VL 3 IS 11 BP 1977 EP 1984 PG 8 WC Oncology SC Oncology GA YE927 UT WOS:A1997YE92700009 PM 9815587 ER PT J AU Urashima, M Teoh, G Ogata, A Chauhan, D Treon, SP Sugimoto, Y Kaihara, C Matsuzaki, M Hoshi, Y DeCaprio, JA Anderson, KC AF Urashima, M Teoh, G Ogata, A Chauhan, D Treon, SP Sugimoto, Y Kaihara, C Matsuzaki, M Hoshi, Y DeCaprio, JA Anderson, KC TI Characterization of p16(INK4A) expression in multiple myeloma and plasma cell leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENE; DEPENDENT KINASE INHIBITORS; HOMOZYGOUS DELETIONS; DNA METHYLATION; CPG ISLAND; P16 GENE; HUMAN CANCERS; LUNG-CANCER; INTERLEUKIN-6 AB Loss of pl6(INK4A) (p16) expression is frequently associated with the development of epithelial and lymphoid malignancies, However, the frequency and significance of p16 abnormalities in multiple myeloma (MM) and the more aggressive phase of plasma cell leukemia (PCL) have not been well defined, Accordingly, the goal of this study was to define the expression and function of p16 in fresh samples of MM and PCL, We found that p16 protein was highly expressed in primary MM cells, although it was undetectable in fresh samples of PCL. Additionally, p16 protein was also absent in four of four MM-derived cell lines, To determine the mechanism for p16 underexpression in PCL and MM-derived cell lines, we performed PCR analysis to evaluate both gene deletion and the presence of methylation, Interestingly, the p16 gene was present and methylated in all patient PCL cells and MM cell lines, whereas it was unmethylated in patient MM cells and normal B cells, Furthermore, treatment with the demethylating agent 5-deoxyazacytidine or p16 retrofection restored p16 protein expression and induced G(1), growth arrest in patient PCL cells and MM cell lines, These results suggest that inactivation of the p16 gene by methylation may be associated with decreased growth control and the development of PCL in a subset of patients with MM. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. DANA FARBER CANC INST,DEPT NEOPLAST DIS MECHANISMS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. SRL INC,RES & DEV CTR MOL BIOL & CYTOGENESIS,TOKYO,JAPAN. SRL INC,CELLULAR THERAPIES UNIT,TOKYO,JAPAN. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. FU NCI NIH HHS [CA 50947] NR 55 TC 26 Z9 26 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1997 VL 3 IS 11 BP 2173 EP 2179 PG 7 WC Oncology SC Oncology GA YE927 UT WOS:A1997YE92700034 PM 9815612 ER PT J AU Chung, DC Smith, AP Louis, DN GraemeCook, F Warshaw, AL Arnold, A AF Chung, DC Smith, AP Louis, DN GraemeCook, F Warshaw, AL Arnold, A TI Analysis of the retinoblastoma tumour suppressor gene in pancreatic endocrine tumours SO CLINICAL ENDOCRINOLOGY LA English DT Article ID ALLELIC LOSS; SUSCEPTIBILITY GENE; PITUITARY-TUMORS; BLADDER-CANCER; FREQUENT LOSS; RAS ONCOGENE; RB LOCUS; MUTATIONS; HETEROZYGOSITY; P53 AB OBJECTIVES The molecular pathogenesis of human pancreatic endocrine tumours (PETs) is largely unknown. One attractive candidate gene for involvement in pancreatic endocrine neoplasia is the retinoblastoma (Rb) tumour suppressor gene, A deletion of the Rb gene was recently described in a human insulinoma, In addition, mice harbouring a null mutation in the Rb gene bred with p53 mutant mice develop pancreatic endocrine tumours, Therefore, we sought to determine the role that allelic loss of Rb may play in a large series of human pancreatic endocrine tumours. PATIENTS AND MEASUREMENTS 46 pancreatic endocrine tumours were obtained from 41 patients, Utilizing genomic DNA isolated from the tumour samples and control normal cells, 2 highly polymorphic microsatellite loci (D13S153 and Rb 1.20) located within the Rb gene were PCR amplified and examined for loss of heterozygosity, RESULTS 2 patients were homozygous at both loci and thus uninformative, The remaining 39 had informative markers at one or both of these loci, and none of the tumours from these patients demonstrated allelic loss of Rb. CONCLUSIONS In tumours in which Rb inactivation is pathogenetically important, somatic loss of one Rb allele commonly accompanies a point mutation or microdeletion within the other allele, Thus, the absence of demonstrable allelic loss in this large series strongly suggests that Rb gene inactivation is not frequently involved in the pathogenesis of human pancreatic endocrine tumours. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Chung, DC (reprint author), MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,JACKSON 1020,55 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 55909]; NIDDK NIH HHS [DK11794, DK01410-11] NR 32 TC 37 Z9 38 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD NOV PY 1997 VL 47 IS 5 BP 523 EP 528 DI 10.1046/j.1365-2265.1997.2861110.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YG688 UT WOS:A1997YG68800004 PM 9425391 ER PT J AU Harris, WH AF Harris, WH TI Options for primary femoral fixation in total hip arthroplasty - Cemented stems for all SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LOW-FRICTION ARTHROPLASTY; YOUNG-PATIENTS; FOLLOW-UP; REPLACEMENT; FAILURE AB In considering the subject of choices for the planning of femoral fixation in total hip arthroplasty, the strength behind the argument that cementing should be preferred in all ages and all conditions comes from three major positions, all supported by excellent data, First, the long term data (15-20 years) for well performed cemented stems are excellent and unmatched. Second, with good cementing techniques, the long term results in patients younger than 50 years of age are equal to the results in patients older than 50 years of age, No longer is there validity to the prior arguments that cementing does not work well in younger patients or that younger patients should have cementless femoral stems, Third, improvements in cementing technique have been shown in nationwide studies to produce statistically significantly better results than the original techniques. RP Harris, WH (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,HIP & IMPLANT UNIT,DEPT ORTHOPAED SURG,GRJ 1126,BOSTON,MA 02114, USA. NR 41 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1997 IS 344 BP 118 EP 123 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA YF265 UT WOS:A1997YF26500013 PM 9372764 ER PT J AU DeSanctis, JT Lee, MJ Gazelle, GS Boland, GW Halpern, EF Saini, S Mueller, PR AF DeSanctis, JT Lee, MJ Gazelle, GS Boland, GW Halpern, EF Saini, S Mueller, PR TI Prognostic indicators in acute pancreatitis: CT vs APACHE II SO CLINICAL RADIOLOGY LA English DT Article ID CLASSIFICATION-SYSTEM; MANAGEMENT; ABSCESS AB Purpose: To investigate the correlation between established contrast-enhanced computed tomography (CECT) criteria of disease severity in acute pancreatitis and the APACHE (Acute Physiology and Chronic Health Evaluation) II score and to assess the utility of each as prognostic indicators in acute pancreatitis, Materials and Methods: Over a 1-year period, prospective, consensus interpretation of the CECTs of 35 consecutive inpatients was performed with determination of the CECT grade, degree of necrosis, and severity index. The APACHE II score was calculated within 24 h of CECT. Multiple clinical endpoints were recorded: local complications (pseudocyst, abscess, or acute fluid collections requiring urgent surgical or radiological intervention), systemic disease (intensive care unit admission) and duration of hospitalization. Statistical analysis was performed to determine correlations, Results: No statistically significant correlation existed between the APACHE II score and CECT grade, the degree of necrosis, or the CECT severity index, Only the CECT grade and severity index correlated significantly with the occurrence of local complications (P = 0.0035 and 0.0048, respectively), The APACHE II score was superior to the CECT grade as a predictor of the need for ICU admission (P = 0.022 vs P = 0.035), and no other CECT criteria was a significant predictor of ICU admission, Conclusion: The preferred clinical and imaging prognostic measures in acute pancreatitis, the APACHE II score and CECT criteria, do not correlate with one another in the commonly encountered, mixed primary and tertiary care population, The mathematical integration of CECT criteria and the APACHE II score fails to yield a predictor of outcome superior to the use of any one measure alone, CECT criteria best define local anatomic abnormality, and are superior to the APACHE II score as predictors of local complications, The APACHE II score is superior to all CECT criteria as an indicator of systemic disease severity (reflected in the need for ICU admission), The most effective initial triage would be immediate APACHE II calculation, Further use of imaging vs clinical assessment can then be individualized. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 9,IRELAND. ROYAL COLL SURGEONS IRELAND,DUBLIN 2,IRELAND. NR 13 TC 37 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD NOV PY 1997 VL 52 IS 11 BP 842 EP 848 DI 10.1016/S0009-9260(97)80079-7 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YF651 UT WOS:A1997YF65100005 PM 9392462 ER PT J AU Ghaemi, SN Sachs, GS Baldassano, CF Truman, CJ AF Ghaemi, SN Sachs, GS Baldassano, CF Truman, CJ TI Insight in seasonal affective disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article; Proceedings Paper CT 149th Annual Meeting of the American-Psychiatric-Association CY MAY 04-09, 1996 CL NEW YORK, NY SP Amer Psychiat Assoc ID CLINICAL-PSYCHIATRY; MOOD DISORDERS; SCHIZOPHRENIA; ILLNESS; PSYCHOSIS; PSYCHOPATHOLOGY; AWARENESS AB Lack of insight complicates the evaluation and treatment of patients with psychotic and affective disorders. No studies of insight in seasonal affective disorder (SAD) have been reported. Thirty patients with SAD diagnosed by the Structured Clinical Interview for DSM-III-R but no other axis I conditions were treated short-term with light-therapy. Insight was measured with the Scale to Assess Unawareness of Mental Disorder (SUMD) as modified by the authors to assess the self-report of insight into depressive symptoms. Increasing scores (1 to 5) indicated increasing unawareness of illness (i.e., less insight). SAD patients displayed a moderate amount of insight when depressed (mean SUMD score, 2.5), When recovered, they showed no significant change in insight into past depressive symptoms (mean SUMD score, 2.8). Greater insight into current depressive symptoms correlated with more depressive symptoms on the Hamilton Rating Scale for Depression score ([HRSD] r = .35, P < .05). In conclusion, SAD patients possess a moderate amount of insight into depressive symptoms that does not change after recovery, a result in agreement with studies of insight in psychosis and mania. Further, in SAD, increased severity of illness may be associated with increased insight into depressive symptoms, consistent with the hypothesis of depressive realism. Copyright (C) 1997 by W.B. Saunders Company. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BIPOLAR RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. RP Ghaemi, SN (reprint author), GEORGE WASHINGTON UNIV,DEPT PSYCHIAT,CTR NEUROSCI MED PROGRESS & SOC,WASHINGTON,DC 20037, USA. NR 22 TC 21 Z9 22 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 1997 VL 38 IS 6 BP 345 EP 348 DI 10.1016/S0010-440X(97)90931-7 PG 4 WC Psychiatry SC Psychiatry GA YG487 UT WOS:A1997YG48700007 PM 9406741 ER PT J AU Fusunyan, RD Walker, WA AF Fusunyan, RD Walker, WA TI Immunology SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID HEPATIC REGENERATION; EPITHELIAL-CELLS; AGE; EXPRESSION; DEFENSINS; SYSTEM RP Fusunyan, RD (reprint author), MASSACHUSETTS GEN HOSP,149 13TH ST 1493404,CHARLESTOWN,MA 02129, USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1997 VL 13 IS 6 BP 491 EP 493 DI 10.1097/00001574-199711000-00009 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YG753 UT WOS:A1997YG75300009 ER PT J AU Sanderson, IR AF Sanderson, IR TI Diet and gut inflammation SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID TOTAL PARENTERAL-NUTRITION; PEDIATRIC CROHNS-DISEASE; ULCERATIVE-COLITIS; CONTROLLED TRIAL; ACID; REMISSION; RATS; RESECTION; IMMUNITY; CHILDREN AB The interaction between diet and inflammation is complex, because of the many ways that food alters the composition of the intestinal lumen. inflammatory reactions comprise a wide variety of responses. Thus, the scope for diversity in the interactions between nutrition and inflammation is vast. Despite this, there has recently been progress in specific areas, The past year has seen the publication of controlled trials of fish oils in Crohn's disease. One study from Italy shows a benefit for the constituent oils, mainly n-3 fatty acids. However, a second study from Germany did not show similar benefit. Short-chain fatty acids have many actions on the intestine. They have been used as enemas in ulcerative colitis. Large studies have now been performed but appear less promising than earlier small studies, The review also describes progress on enteral feeds as a treatment for Crohn's disease, The effects of nutrients on the epithelial barrier are also discussed. RP Sanderson, IR (reprint author), MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,CHARLESTOWN,MA 02129, USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 23 TC 7 Z9 7 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1997 VL 13 IS 6 BP 518 EP 524 DI 10.1097/00001574-199711000-00013 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YG753 UT WOS:A1997YG75300013 ER PT J AU Chen, JN vanEeden, FJM Warren, KS Chin, A NussleinVolhard, C Haffter, P Fishman, MC AF Chen, JN vanEeden, FJM Warren, KS Chin, A NussleinVolhard, C Haffter, P Fishman, MC TI Left-right pattern of cardiac BMP4 may drive asymmetry of the heart in zebrafish SO DEVELOPMENT LA English DT Article DE laterality; looping; genetic screen; BMP4; heart; cardiac development; symmetry; zebrafish ID CENTRAL-NERVOUS-SYSTEM; FLOOR PLATE; MUTATION; XENOPUS; SPECIFICATION; INDUCTION; NOTOCHORD; REVERSAL; EMBRYOS; MOUSE AB The first evident break in left-right symmetry of the primitive zebrafish heart tube is the shift in pattern of BMP4 expression from radially symmetric to left-predominant. The midline heart tube then 'jogs' to the left and subsequently loops to the right. We examined 279 mutations, affecting more than 200 genes, and found 21 mutations that perturb this process. Some cause BMP4 to remain radially symmetric. Others randomize the asymmetric BMP4 pattern. Retention of BMP4 symmetry is associated with failure to jog: right-predominance of the BMP4 pattern is associated with reversal of the direction of jogging and looping. Raising BMP4 diffusely throughout the heart, via sonic hedgehog injection, or the blocking of its action by injection of a dominant negative BMP4 receptor, prevent directional jogging or looping. The genes crucial to directing cardiac asymmetry include a subset of those needed for patterning the dorsoventral axis and for notochord and ventral spinal cord development. Thus, the pattern of cardiac BMP4 appears to be in the pathway by which the heart interprets lateralizing signals from the midline. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MAX PLANCK INST ENTWICKLUNGSBIOL,GENET ABT,D-72076 TUBINGEN,GERMANY. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. RI Van Eeden, Freek/E-6198-2010; OI Chen, Jau-Nian/0000-0001-8807-3607; Chin, Alvin/0000-0002-0417-8653 FU NCRR NIH HHS [R01 RR08888]; NHLBI NIH HHS [R01 HL49579, T32 HL07208] NR 55 TC 217 Z9 221 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 1997 VL 124 IS 21 BP 4373 EP 4382 PG 10 WC Developmental Biology SC Developmental Biology GA YG862 UT WOS:A1997YG86200019 PM 9334285 ER PT J AU Veves, A Saouaf, R Donaghue, VM Mullooly, CA Kistler, JA Giurini, JM Horton, ES Fielding, RA AF Veves, A Saouaf, R Donaghue, VM Mullooly, CA Kistler, JA Giurini, JM Horton, ES Fielding, RA TI Aerobic exercise capacity remains normal despite impaired endothelial function in the micro- and macrocirculation of physically active IDDM patients SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; PREDICTING BODY DENSITY; FOOT ULCERATION; GENERALIZED EQUATIONS; AUTONOMIC NEUROPATHY; OXYGEN-UPTAKE; RISK; DYSFUNCTION; ACETYLCHOLINE; RESPONSES AB The aim of the present study was to examine if diabetes in the absence of neuropathy affects the exercising capacity of IDDM patients, and whether regular, intense training has a beneficial effect on endothelial function. Five groups of subjects were studied: 23 healthy control subjects who exercised regularly (age 33 +/- 6 years), 23 nonneuropathic type 1 diabetic patients who exercised regularly (age 33 +/- 6 years, IDDM duration II +/- 8 years), 7 neuropathic type 1 diabetic patients who exercised regularly (age 36 +/- 7 years, IDDM duration 22 +/- 8 years), 18 healthy subjects who did not exercise regularly (age 34 +/- 7 years), and 5 nonneuropathic type 1 diabetic patients who did not exercise regularly (age 31 +/- 4 years, IDDM duration 20 +/- 3 years). All groups mere matched for age, sex, and body weight. No differences existed in the energy expenditure per week in physical activity among the three exercising groups or between the two nonexercising groups. The maximal oxygen uptake was similar between control and diabetic nonneuropathic exercisers, and among diabetic neuropathic exercisers, control nonexercisers, and diabetic nonexercisers; however, a significant difference existed between the first two and the last three groups (P < 0.0001). A stepwise increase was found in the resting heart rate among the groups, ranging from the lowest in control exercisers to the highest in diabetic nonexercisers, but the maximal heart rate was lower only in diabetic neuropathic exercisers compared with all other groups (P < 0.05). Assessments of endothelial function in both macro-and microcirculation were performed in 12 control exercisers, 10 diabetic nonneuropathic exercisers, 5 diabetic neuropathic exercisers, 17 control nonexercisers, and 4 diabetic nonexercisers. When all diabetic patients mere considered as one group and all control subjects as another, the microcirculation endothelial function in the diabetic group was reduced compared with the control subjects (91 +/- 49 vs. 122 +/- 41% flux increase over baseline; P < 0.05). In contrast, no differences existed among the three diabetic groups or between the two control groups. Similarly, in macrocirculation, a reduced response during reactive hyperemia was observed in the diabetic patients compared with control subjects (7.0 +/- 4.5 vs. 11.2 +/- 6.6% diameter increase; P < 0.05), whereas again no difference existed among the three diabetic groups or between the two control groups. These data suggest that diabetes per se does not affect aerobic exercise capacity (Vo(2max)) in physically active individuals, but is reduced in the presence of neuropathy. In addition, regular exercise training involving the lower extremities does not improve the endothelial function in the micro-and macrocirculation of the nonexercised upper extremity in type 1 diabetic patients. C1 BETH ISRAEL DEACONESS MED CTR,DEPT MED,BOSTON,MA 02215. BETH ISRAEL DEACONESS MED CTR,DIV PODIAT,BOSTON,MA 02215. BETH ISRAEL DEACONESS MED CTR,JOSLIN DIABET CTR,BOSTON,MA 02215. BETH ISRAEL DEACONESS MED CTR,MICROCIRCULAT LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT RADIOL SCI,BOSTON,MA. BOSTON UNIV,SARGENT COLL HLTH & REHABIL SCI,DEPT HLTH SCI,BOSTON,MA. RP Veves, A (reprint author), BETH ISRAEL DEACONESS MED CTR,DEACONESS JOSLIN FOOT CTR,1 DEACONESS RD,BOSTON,MA 02215, USA. NR 36 TC 57 Z9 59 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1997 VL 46 IS 11 BP 1846 EP 1852 DI 10.2337/diabetes.46.11.1846 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YC480 UT WOS:A1997YC48000025 PM 9356035 ER PT J AU vanDijk, G Donahey, JCK Thiele, TE Scheurink, AJW Steffens, AB Wilkinson, CW Tenenbaum, R Campfield, LA Burn, P Seeley, RJ Woods, SC AF vanDijk, G Donahey, JCK Thiele, TE Scheurink, AJW Steffens, AB Wilkinson, CW Tenenbaum, R Campfield, LA Burn, P Seeley, RJ Woods, SC TI Central leptin stimulates corticosterone secretion at the onset of the dark phase SO DIABETES LA English DT Article ID OBESE GENE; WEIGHT; HYPOTHALAMUS; HUMANS; SERUM; RNA AB Leptin, a hormone secreted by adipose tissue in proportion to body adiposity, is proposed to be involved in the central nervous regulation of food intake and body weight, In addition, evidence is emerging that leptin regulates neuroendocrine and metabolic functions as well, presumably via its action in the central nervous system (CNS), To investigate this regulatory effect of leptin, we infused 3.5 mu g of human leptin directly into the third cerebral ventricle (i3vt) of lean male Long-Evans rats, 90 min before the onset of their dark phase, Before and after infusion, blood samples were withdrawn through indwelling catheters for assessment of hormonal (plasma corticosterone, insulin, leptin), autonomic (plasma norepinephrine, epinephrine), and metabolic (plasma glucose) parameters, I3vt leptin caused an increase in plasma corticosterone and plasma leptin levels relative to the control condition, The effects of i3vt leptin on corticosterone secretion became particularly apparent after the onset of the dark phase, The results of the present study indicate that i3vt leptin stimulates the hypothalamo-pituitary-adrenal (HPA) axis, particularly when rats normally encounter their largest meals, These results are consistent with the possibility that high circulating leptin levels may underlie the increased activity of the HPA axis that is generally characteristic of human obesity and most animal models of obesity. C1 UNIV WASHINGTON,DEPT PSYCHOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BEHAV NEUROSCI,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. VA PUGET SOUND HLTH CARE SYST,SEATTLE,WA. HOFFMANN LA ROCHE INC,DEPT METAB DIS,NUTLEY,NJ 07110. RP vanDijk, G (reprint author), UNIV GRONINGEN,CTR BIOL,DEPT ANIM PHYSIOL,POB 14,NL-9750 AA HAREN,NETHERLANDS. OI van Dijk, Gertjan/0000-0002-6565-4019 FU NIAAA NIH HHS [AA-07455]; NIDDK NIH HHS [DK-35816, DK-17844] NR 24 TC 64 Z9 64 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1997 VL 46 IS 11 BP 1911 EP 1914 DI 10.2337/diabetes.46.11.1911 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YC480 UT WOS:A1997YC48000037 PM 9356047 ER PT J AU Doria, A Onuma, T Warram, JH Krolewski, AS AF Doria, A Onuma, T Warram, JH Krolewski, AS TI Synergistic effect of angiotensin II type 1 receptor genotype and poor glycaemic control on risk of nephropathy in IDDM SO DIABETOLOGIA LA English DT Article DE insulin-dependent diabetes mellitus; diabetic nephropathy; angiotensin II receptor; DNA polymorphisms; genetics ID CONVERTING-ENZYME GENE; DIABETIC NEPHROPATHY; POLYMORPHISM; HYPERTENSION; SUSCEPTIBILITY; PREDISPOSITION; PROTEIN; CELLS; EXPRESSION; ISOFORMS AB We investigated the contribution of polymorphisms in the angiotensin II type 1 receptor gene (AGTR1) to renal complications in an inception cohort of 152 insulin-dependent diabetic (IDDM) patients examined 15-21 years after diabetes onset. This nested case-control study included 79 normoal-bumin-uria control subjects and 73 cases with evidence of nephropathy ranging from microalbuminuria to overt proteinuria. Subjects were genotyped for two AGTR1 polymorphisms (T-573-->C and A(1166)-->C), and an adjacent CA repeat microsatellite. Allele C-1166 and the 140 bp allele of the microsatellite were more frequent among nephropathy cases than normoalbuminuric control subjects (0.322 vs 0.247, and 0.618 vs 0.521, respectively), but these differences were not statistically significant. Although not significant by themselves, the AGTR1 polymorphisms contributed significantly to the risk of diabetic nephropathy when accompanied by poor glycaemic control. Among patients with frequent severe hyperglycaemia during the first decade of diabetes, the relative risk of nephropathy among allele C-1166 carriers was 12.1 (95% CI: 3.7-39.8), whereas it was only 1.4 (95% CI: 0.6-3.5) among allele A(1166) homozygotes. The difference between relative risks was highly significant (chi(2) = 8.25,p = 0.004 with 1 df). A similar pattern of higher risk of microalbuminuria, specifically among those carriers of allele C-1166 who had poor glycaemic control was also found in an independent study of a cross-sectional sample of 551 IDDM individuals, although the effect was smaller in magnitude. We conclude that DNA sequence differences in the AGTR1 gene may modify the noxious effects of hyperglycaemia on the kidney. Allele C-1166 carriers might especially benefit from nephropathy prevention programmes. C1 HARVARD UNIV,SCH MED,DEPT MED,JOSLIN DIABET CTR,RES DIV,SECT EPIDEMIOL & GENET,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-41 526] NR 36 TC 48 Z9 50 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 1997 VL 40 IS 11 BP 1293 EP 1299 DI 10.1007/s001250050823 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF773 UT WOS:A1997YF77300008 PM 9389421 ER PT J AU Yu, JS AF Yu, JS TI Gene therapy for brain tumors SO DRUG NEWS & PERSPECTIVES LA English DT Article ID THYMIDINE KINASE GENE; CYTOCHROME-P450 2B1 GENE; HERPES-SIMPLEX VIRUSES; RAT GLIOMA-CELLS; IN-VIVO; ANTITUMOR IMMUNITY; CANCER VACCINE; GANCICLOVIR; ADENOVIRUS; TRANSDUCTION C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 46 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD NOV PY 1997 VL 10 IS 9 BP 528 EP 534 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YN247 UT WOS:000071147800003 ER PT J AU Liepa, AM Picus, J Blanke, C John, W Clark, J Schulman, L Burris, A Thornton, D Loehrer, PJ AF Liepa, AM Picus, J Blanke, C John, W Clark, J Schulman, L Burris, A Thornton, D Loehrer, PJ TI Quality of life assessments of patients with pancreatic cancer receiving MTA (LY231514, a multi-targeted antifolate) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 ELI LILLY & CO,LILLY CORP CTR,GLOBAL HLTH ECON RES,INDIANAPOLIS,IN 46285. WASHINGTON UNIV,ST LOUIS,MO. VANDERBILT UNIV,NASHVILLE,TN. UNIV KENTUCKY,LEXINGTON,KY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CTRC RES FDN,SAN ANTONIO,TX. INDIANA UNIV,INDIANAPOLIS,IN 46204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 1997 VL 33 SU 9 BP OP19 EP OP19 PG 1 WC Oncology SC Oncology GA YK646 UT WOS:A1997YK64600019 ER PT J AU Hussain, MA AF Hussain, MA TI Polygenic models of non-insulin-dependent diabetes mellitus SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GK RAT; RESISTANCE; GLUCOSE; NIDDM; RISK RP Hussain, MA (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,LAB MOL ENDOCRINOL,BOSTON,MA 02114, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 1997 VL 137 IS 5 BP 453 EP 454 DI 10.1530/eje.0.1370453 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YJ959 UT WOS:A1997YJ95900005 PM 9405022 ER PT J AU Baird, SJS Catalano, PJ Ryan, LM Evans, JS AF Baird, SJS Catalano, PJ Ryan, LM Evans, JS TI Evaluation of effect profiles: Functional observational battery outcomes SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID TRICHLOROETHYLENE; INSECTICIDES; TOXICITY; CARBARYL AB The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects. (C) 1997 Society of Toxicology. C1 HARVARD UNIV,SCH PUBL HLTH,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP Baird, SJS (reprint author), HARVARD UNIV,SCH PUBL HLTH,HARVARD CTR RISK ANAL,PROGRAM ENVIRONM HLTH & PUBL POLICY,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES-06900] NR 34 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD NOV PY 1997 VL 40 IS 1 BP 37 EP 51 DI 10.1006/faat.1997.2357 PG 15 WC Toxicology SC Toxicology GA YK776 UT WOS:A1997YK77600004 PM 9398486 ER PT J AU Quirk, DM Barry, MJ Aserkoff, B Podolsky, DK AF Quirk, DM Barry, MJ Aserkoff, B Podolsky, DK TI Physician specialty and variations in the cost of treating patients with acute upper gastrointestinal bleeding SO GASTROENTEROLOGY LA English DT Article ID UNIVERSAL HEALTH-INSURANCE; OUTPATIENT CARE; PROMOTE QUALITY; HEMORRHAGE; SYSTEM; MEDISGROUPS; ECONOMY; ULCER; 1990S; PLAN AB Background & Aims: Upper gastrointestinal tract bleeding is a frequent cause of hospitalization. The goal of this study was to assess whether the cost of treating patients with upper gastrointestinal bleeding varies among surgeons, internists, and gastroenterologists. Methods: A retrospective study of 124 patients admitted with acute upper gastrointestinal hemorrhage was performed, Patients were stratified into three groups based on a validated risk score; length of stay and hospital costs were compared among patients primarily cared for by internists, surgeons, and gastroenterologists. Results: The median length of stay (2 days) for patients admitted to the gastroenterology service was significantly shorter than for patients admitted under the care of other physicians (P < 0.05), The median hospitalization cost ($2856) for patients admitted to the gastroenterology service was significantly lower than for patients admitted to the other services (P < 0.01), There were no significant differences in the time to endoscopy among services, Conclusions: Patients admitted to an urban teaching hospital directly under the care of a gastroenterologist had shorter hospital stays that were significantly less costly than patients under the primary care of internists or surgeons, The difference in length of stay reflects the time interval between endoscopy and discharge. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV GEN MED,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIDDK NIH HHS [T32DK07191] NR 27 TC 53 Z9 55 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1997 VL 113 IS 5 BP 1443 EP 1448 DI 10.1053/gast.1997.v113.pm9352845 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YC790 UT WOS:A1997YC79000009 PM 9352845 ER PT J AU Furuta, GT SchmidtChoudhury, A Wang, MY Wang, ZS Lu, L Furlano, RI Wershil, BK AF Furuta, GT SchmidtChoudhury, A Wang, MY Wang, ZS Lu, L Furlano, RI Wershil, BK TI Mast cell-dependent tumor necrosis factor alpha production participates in allergic gastric inflammation in mice SO GASTROENTEROLOGY LA English DT Article ID TNF-ALPHA; NEUTROPHIL RECRUITMENT; CYCLOSPORINE-A; IGE; MOUSE; PERITONITIS; HISTAMINE; RELEASE; HETEROGENEITY; DEXAMETHASONE AB Background & Aims: Immunoglobulin E-dependent gastric inflammation is characterized by neutrophil infiltration, and mast cells are required for this response. The aim of this study was to examine whether mast cell production of tumor necrosis factor (TNF)-alpha participates in the recruitment of neutrophils during this response. Methods: The levels of TNF-alpha messenger RNA (mRNA) and protein in gastric tissues were assessed by Northern blot analysis and enzyme-linked immuno-sorbent assay. In situ hybridization and histochemical staining were performed to identify the cells expressing TNF-alpha transcripts. Anti-TNF-alpha antibodies or cyclosporine A were used in an attempt to inhibit neutrophil infiltration. Results: TNF-alpha mRNA and protein were increased in gastric tissues undergoing immunoglobulin E-dependent inflammation. Mast cells were required for the development of cells expressing TNF-alpha transcripts in the stomach. Seventy-nine percent of the cells in the mucosa and 100% of the cells in the submucosa expressing TNF-alpha mRNA were identified as mast cells. Anti-TNF-alpha antibodies inhibited neutrophil infiltration in the submucosa, and cyclosporine A inhibited the tissue expression of TNF-alpha mRNA and the influx of neutrophils into the submucosa and muscularis propria. Conclusions: These findings show that mast cell-derived TNF-alpha is at least one of the mediators involved in the recruitment of neutrophils during immunoglobulin E-dependent gastric inflammation in the mouse. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,CHARLESTOWN,MA 02129. BETH ISRAEL DEACONESS MED CTR,DIV EXPT PATHOL,BOSTON,MA. CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK33506, DK40561, DK46819] NR 38 TC 44 Z9 47 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1997 VL 113 IS 5 BP 1560 EP 1569 DI 10.1053/gast.1997.v113.pm9352858 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YC790 UT WOS:A1997YC79000022 PM 9352858 ER PT J AU Jensen, DM Jutabha, R Machicado, GA Jensen, ME Cheng, S Gombein, J Hirabayashi, K Ohning, G Randall, G AF Jensen, DM Jutabha, R Machicado, GA Jensen, ME Cheng, S Gombein, J Hirabayashi, K Ohning, G Randall, G TI Prospective randomized comparative study of bipolar electrocoagulation versus heater probe for treatment of chronically bleeding internal hemorrhoids SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID OUTPATIENT TREATMENT; COAGULATION; DIATHERMY; LASER; TRIAL AB Background: Our purpose was to compare the efficacy, complications, failure rates, and crossovers of heater and bipolar probe treatments of chronically bleeding internal hemorrhoids. Methods: Eighty-one patients (31 female, 50 male) with mean age of 53 years had large (grade 2 to 3) internal hemorrhoids with bleeding for a mean of 12 years, had failed medical management, and were randomized in a prospective study of anoscopic treatments to heater versus bipolar probes. Failure was defined as a major complication or failure to reduce the size of all internal hemorrhoids with three or more treatments. Results: With similar background variables and no difference in treatment times, rectal bleeding and other symptoms were controlled in a shorter time with the heater probe than with the bipolar probe (77 versus 121 days). Five complications (fissures, bleeding, or rectal spasm) occurred with the bipolar probe, and two occurred with the heater probe. The heater probe caused more pain during treatments but had significantly fewer failures and crossovers. Conclusions: For patients who had failed medical management of chronically bleeding internal hemorrhoids, the techniques and complications of heater and bipolar probes were similar, but pain was more common, failures and crossovers were less frequent, and the time to symptom relief was shorter with the heater probe than with the bipolar probe. C1 NORTHRIDGE HOSP,LOS ANGELES,CA. RP Jensen, DM (reprint author), UNIV CALIF LOS ANGELES,CTR HLTH SCI,CURE,W LOS ANGELES VA MED CTR,ROOM 44-138 CHS,LOS ANGELES,CA 90095, USA. FU NIDDK NIH HHS [DK41301] NR 15 TC 21 Z9 25 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 1997 VL 46 IS 5 BP 435 EP 443 DI 10.1016/S0016-5107(97)70037-3 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YF762 UT WOS:A1997YF76200008 PM 9402118 ER PT J AU Inderfurth, J Wagnieres, G AF Inderfurth, J Wagnieres, G TI Photoinduction of fluorophores in the retina using a 514-nm argon ion laser SO GERMAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the German-Ophthalmologic-Society CY SEP, 1995 CL MANNHEIM, GERMANY SP German Ophthalmol Soc DE argon laser; retina; pigment epithelium; photoinduced fluorescence; lipofuscin ID PIGMENT EPITHELIUM; LIPOFUSCIN; PHOTOCOAGULATION; FLUORESCENCE AB The purpose of the present study was to elucidate the origin and spectrum of the yellow-orange fluorescence observed during standard argon-ion laser irradiation of the eye, The possibility that the fluorophores were induced by the laser was investigated. The 514.5-nm line of an argon ion laser was used to induce thermal coagulation on frozen sections of human and rabbit eyes. Specifically, the spectrum and retinal site of the fluorescence were analyzed. The fluorescence was measured with a microspectrofluorometer apparatus. The excitation wavelength was 514 nm. At the level of the retinal pigment epithelium (RPE) and choroid a fluorescence was induced that had an emission spectrum that was comparable with that of lipofuscin yet was far more intense. The fluorophores are induced by laser irradiation. Further research tc, identify the fluorophores and determine their biological behavior is necessary. C1 Stadt Kliniken Frankfurt Main Hochst, Augenklin, D-65929 Frankfurt, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Swiss Fed Inst Technol, Inst Environm Engn, CH-1015 Lausanne, Switzerland. RP Inderfurth, J (reprint author), Stadt Kliniken Frankfurt Main Hochst, Augenklin, Gotenstr 6-8, D-65929 Frankfurt, Germany. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-2921 J9 GER J OPHTHALMOL JI Ger. J. Ophthalmol. PD NOV PY 1997 VL 5 IS 6 BP 461 EP 465 PG 5 WC Ophthalmology SC Ophthalmology GA YP977 UT WOS:000071335000028 ER PT J AU Fass, R Higa, L Kodner, A Mayer, EA AF Fass, R Higa, L Kodner, A Mayer, EA TI Stimulus and site specific induction of hiccups in the oesophagus of normal subjects SO GUT LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Gastroenterological-Association CY MAY 18-23, 1996 CL SAN FRANCISCO, CA SP Amer Gastroenterol Assoc DE hiccups; oesophageal mechanoreceptors; electronic distension device; phasic distension; ramp distension; perception thresholds ID GASTROESOPHAGEAL REFLUX; INTRACTABLE HICCUPS; ESOPHAGEAL AB Background-Hiccups that are induced by a large meal have been suggested to result from gastric overdistension. The role of the oesophagus in precipitating hiccups has never been defined. Aims-To determine the involvement of oesophageal mechanoreceptors in the hiccup reflex. Methods-Ten normal healthy subjects were prospectively evaluated at a university affiliated hospital. Controlled inflation of a polyethylene bag in the proximal and distal oesophagus was carried out using slow ramp and rapid phasic distensions, by an electronic distension device. Results-Hiccups were induced in four subjects only during rapid phasic distensions and only in the proximal oesophagus. The mean (SEM) minimal volume threshold for the hiccup reflex was 32.5 (4.8) ml, which was above the perception threshold. Hiccups appeared during inflation and resolved after deflation. Conclusions-Sudden rapid stretch of the mechanoreceptors in the proximal oesophagus can trigger the hiccup reflex in normal subjects. Only rapid distensions above a determined volume threshold will predictably induce hiccups in a given subject. This mechanism may play a role in the physiological induction of hiccups. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIGEST DIS RES CTR,NEUROENTER BIOL GRP,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Fass, R (reprint author), VET ADM MED CTR,SECT GASTROENTEROL 111G 1,3601 S 6TH AVE,TUCSON,AZ 85723, USA. NR 19 TC 21 Z9 21 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD NOV PY 1997 VL 41 IS 5 BP 590 EP 593 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA YD748 UT WOS:A1997YD74800003 PM 9414962 ER PT J AU Muto, MG AF Muto, MG TI Genetic predisposition testing: Taking the lead SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material RP Muto, MG (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,FAMILIAN OVARIAN CANC CTR,BOSTON,MA 02155, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 1997 VL 67 IS 2 BP 121 EP 122 DI 10.1006/gyno.1997.4882 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA YH035 UT WOS:A1997YH03500001 PM 9367692 ER PT J AU Chedid, MG Deulofeut, H Yunis, DE Lara-Marquez, ML Salazar, M Deulofeut, R Awdeh, Z Alper, CA Yunis, EJ AF Chedid, MG Deulofeut, H Yunis, DE Lara-Marquez, ML Salazar, M Deulofeut, R Awdeh, Z Alper, CA Yunis, EJ TI Defect in Th1-like cells of nonresponders to hepatitis B vaccine SO HUMAN IMMUNOLOGY LA English DT Article ID HAPLOTYPE CONTROLS NONRESPONSIVENESS; MAJOR HISTOCOMPATIBILITY COMPLEX; STAPHYLOCOCCAL ENTEROTOXIN-B; SUPPRESSOR T-CELLS; TRANSGENIC MICE; LYMPHOCYTES-T; EXTRATHYMIC TOLERANCE; PERIPHERAL TOLERANCE; IMMUNE-RESPONSE; CLONAL DELETION AB Peripheral blood lymphocytes from nonresponders to hepatitis B vaccine (HBsAg) failed to undergo a proliferative response to recombinant HBsAg in vitro, whereas cells from responders proliferated vigorously. The lack of proliferative response was not due to defective antigen presentation in that MHC-identical responder and nonresponder antigen presenting cells were equally effective in stimulating responder T cells. Nonresponder T cells did not proliferate in response to antigen-pulsed MHC identical responder antigen presenting cells. The present study demonstrated that: 1) there were no detectable (1 in <20 X 10(4)) HBsAg-precursor T cells in any of the nonresponders, while in responders the frequency of HBsAg-precursor T cells ranged from 1 in 3.2 X 10(3) to 1 in 40 X 10(3); 2) nonresponder cell cultures did not secrete IL-2 in response to HBsAg stimulation; 3) exogenous recombinant IL-2 did not restore the proliferative response of the T cells in HBsAg-pulsed cultures of nonresponders. These results suggest chat the cellular basis for the lack of response to HBsAg is a defect in HBsAg-specific Th1-like cells; either there is an absence of the Th 1 cells or cells with TCR specificity for HBsAg are present but are unresponsive to the HBsAg peptide-MHC complex (i.e., anergy or tolerance), (C) American Society for Histocompatibility and Immunogenetics, 1997, Published by Elsevier Science Inc. C1 Dana Farber Canc Inst, Div Immunogenet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Amer Red Cross, Dedham, MA 02026 USA. RP Yunis, EJ (reprint author), Dana Farber Canc Inst, Div Immunogenet, 44 Binney St,LHRRB203, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-29583, HL-48675]; NIAID NIH HHS [AI-35630] NR 66 TC 46 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 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 1997 VL 58 IS 1 BP 42 EP 51 DI 10.1016/S0198-8859(97)00209-7 PG 10 WC Immunology SC Immunology GA YN918 UT WOS:000071221800005 PM 9438208 ER PT J AU Yang, XF Weber, GF Cantor, H AF Yang, XF Weber, GF Cantor, H TI A novel Bcl-x isoform connected to the T cell receptor regulates apoptosis in T cells SO IMMUNITY LA English DT Article ID TRANSGENIC MICE; DEFICIENT MICE; DNA-BINDING; DEATH; SURVIVAL; BCL-X(L); GENE; SUPERANTIGEN; EXPRESSION; TOLERANCE AB We define a novel Bcl-x isoform, Bcl-x gamma, that is generated by alternative splicing and characterized by a unique 47 amino acid C-terminus. Bcl-x gamma is expressed primarily in thymocytes, where it may depend on an interaction between the TCR and host MHC products, and in mature T cells, where its expression is associated with ligation of the T cell receptor. Overexpression of Bcl-x gamma in T cells inhibits activation-induced apoptosis; inhibition of Bcl-x gamma, after stable expression of Bcl-x gamma antisense cDNA, enhances activation-induced apoptosis. In contrast to other Bcl-x isoforms, cells that fail to express Bcl-x gamma after CD3 ligation undergo programmed cell death, while activated T cells that express Bcl-x gamma are spared. Identification of Bcl-x gamma helps provide a molecular explanation of T cell activation and death after antigen engagement. C1 HARVARD UNIV,SCH MED,DEPT CANC IMMUNOL & AIDS,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [R37 AI012184, AI12184, AI13600, AI37833, P01 AI037833, R01 AI013600] NR 53 TC 69 Z9 71 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1997 VL 7 IS 5 BP 629 EP 639 DI 10.1016/S1074-7613(00)80384-2 PG 11 WC Immunology SC Immunology GA YH554 UT WOS:A1997YH55400006 PM 9390687 ER PT J AU Gu, YS Seidl, KJ Rathbun, GA Zhu, CM Manis, JP vanderStoep, N Davidson, L Cheng, HL Sekiguchi, JM Frank, K StanhopeBaker, P Schlissel, MS Roth, DB Alt, FW AF Gu, YS Seidl, KJ Rathbun, GA Zhu, CM Manis, JP vanderStoep, N Davidson, L Cheng, HL Sekiguchi, JM Frank, K StanhopeBaker, P Schlissel, MS Roth, DB Alt, FW TI Growth retardation and leaky SCID phenotype of Ku70-deficient mice SO IMMUNITY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; DNA END-BINDING; PRE-B CELLS; SHORT SEQUENCE HOMOLOGIES; X-RAY RESISTANCE; V(D)J RECOMBINATION; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT AB Ku70, Ku80, and DNA-PKcs are subunits of the DNA-dependent protein kinase (DNA-PK), an enzyme implicated in DNA double-stranded break repair and V(D)J recombination. Our Ku70-deficient mice were about 50% the size of control littermates, and their fibroblasts were ionizing radiation sensitive and displayed premature senescence associated with the accumulation of nondividing cells. Ku70-deficient mice lacked mature B cells or serum immunoglobulin but, unexpectedly, reproducibly developed small populations of thymic and peripheral alpha/beta T lineage cells and had a significant incidence of thymic lymphomas. In association with B and T cell developmental defects, Ku70-deficient cells were severely impaired for joining of V(D)J coding and recombination signal sequences. These unanticipated features of the Ku70-deficient phenotype with respect to lymphocyte development and V(D)J recombination may reflect differential functions of the three DNA-PK components. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. BAYLOR COLL MED,HOWARD HUGHES MED INST,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU PHS HHS [A.I.20047, A.I.35714, A.I.36420] NR 73 TC 303 Z9 307 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 1997 VL 7 IS 5 BP 653 EP 665 DI 10.1016/S1074-7613(00)80386-6 PG 13 WC Immunology SC Immunology GA YH554 UT WOS:A1997YH55400008 PM 9390689 ER PT J AU Bonay, M Bouchonnet, F Lecossier, D Boumsell, L Soler, P Grodet, A Robertson, MJ Hance, AJ AF Bonay, M Bouchonnet, F Lecossier, D Boumsell, L Soler, P Grodet, A Robertson, MJ Hance, AJ TI Activation of T-cells through an antigen-independent alternative pathway induces precocious sensitivity to Fas-induced apoptosis SO IMMUNOLOGY LETTERS LA English DT Article DE T-lymphocyte; apoptosis; activation; Fas ID PERIPHERAL-BLOOD; DEATH; LYMPHOCYTES; EXPRESSION; LIGAND; RESPONSES; INDUCTION; NECROSIS; RECEPTOR; NAIVE AB Autoreactive T-cells can be activated inadvertently during immune responses through antigen-independent pathways. It has been suggested that Fas/Fas-ligand interactions may play a role in eliminating these cells, but the extent that cells activated through such alternative pathways are sensitive to Fas-induced apoptosis has not been extensively evaluated. Proliferation of peripheral blood T-cells from normal individuals activated for 4 days with PHA or PMA + ionophore was not influenced by the presence of anti-Fas antibody. When the same cells were activated with soluble factors produced by previously activated T-cells (lymphostimulatory activity), anti-Fas antibodies inhibited thymidine incorporation by 74+/-4%. The presence of typical morphological changes and oligonucleosomal fragmentation of DNA indicated that the reduced proliferation resulted from apoptotic death of the lymphoblasts. Fas-sensitivity of T-cells activated by lymphostimulatory activity was first detectable 4 days after activation, and at 5 days the majority of lymphoblasts bad become sensitive to Fas, whereas no evidence of sensitivity to Fas was observed for lymphoblasts generated by PHA or PMA + ionophore during the first 5 days of culture. Incubation of cells activated with PHA or PMA+ionophore in the presence of IL-2 at concentrations 10-fold higher than that present in lymphostimulatory activity did not induce early sensitivity to Fas, indicating that exposure to IL-2 could not explain the precocious development of sensitivity to Fas seen following activation by lymphostimulatory activity. These studies demonstrate that T-cells activated through an antigen-independent 'alternative' pathway develop precocious sensitivity to Fas-induced apoptosis, which may be important in permitting the elimination of autoreactive bystander cells activated in the course of immune responses. (C) 1997 Elsevier Science B.V. C1 UNIV PARIS 07,INSERM U82,F-75878 PARIS 18,FRANCE. HOP HENRI MONDOR,INSERM U448,CRETEIL,FRANCE. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. NR 31 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV PY 1997 VL 59 IS 2 BP 107 EP 113 DI 10.1016/S0165-2478(97)00108-9 PG 7 WC Immunology SC Immunology GA YD174 UT WOS:A1997YD17400007 PM 9373219 ER PT J AU Teicher, BA Kakeji, Y Ara, G Herbst, RS Northey, D AF Teicher, BA Kakeji, Y Ara, G Herbst, RS Northey, D TI Prostate carcinoma response to cytotoxic therapy: in vivo resistance SO IN VIVO LA English DT Article DE prostate carcinoma; transforming growth factor-beta; drug resistance ID GROWTH-FACTOR-BETA; CELL-LINE LNCAP; PHASE-II TRIAL; TRANSFORMING GROWTH-FACTOR-BETA-1; ANDROGEN RECEPTOR; CANCER CELLS; TRANSCRIPTION ACTIVATION; EXTRACELLULAR-MATRIX; ALKYLATING-AGENTS; GENE-EXPRESSION AB Androgen independent prostate cancer is recognized as a chemotherapy resistant disease. Human prostate carcinoma DU-145, LNCaP and PC-3 cells in monolayer in exponential growth were exposed to various concentrations of melphalan, 4-hydroperoxycyclophosphamide or adriamycin for 1 hour. These cells were all responsive to the drugs, with DU-145 cells being the least sensitive and PC-3 cells the most sensitive. When the three human prostate carcinoma cell lines were grown as xenografts in nude or SCID mice and the animals treated with single doses of melphalan, cyclophosphamide or adriamycin, the tumors were not very responsive to the drugs. The DU-145 tumors were highly resistant to each drug. The PC-3 tumors were more sensitive; however, even the PC-3 tumors were less drug responsive than several murine tumors. All three prostate cell lines secreted transforming growth factor-beta (TGF-beta) into the cell culture medium, and when grown as xenograft tumors increased the plasma levels of TGF-beta in the animals. DU-145 cells produced the most TGF-beta and LNCaP cells produced the least After administration of single doses of each of the chemotherapeutic agents to animals bearing the prostate carcinoma xenografts, there was a time dependent increase in plasma TGF-beta that was greatest in animals bearing the DU-145 tremor and least in animals bearing the LNCaP tremor. Immunohistochemical staining, showed that PC-3 tumors tended to have the most intense staining for TGF-beta and LNCaP tumors the least In situ hybridization for TGF-beta mRNA showed an increase in TGF-beta mRNA that was time independent after chemotherapy administration in all three tumors. These results support the hypothesis that the drug resistance of prostate carcinoma is manifest in vivo, and that in vivo high levels of TGF-beta may protect these tumors from cytotoxic cancer therapies. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Eli Lilly & Co, Lilly Res Labs, Lilly Corp Ctr, DC 0540, Indianapolis, IN 46285 USA. NR 57 TC 36 Z9 36 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 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 1997 VL 11 IS 6 BP 453 EP 461 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YX414 UT WOS:000072037600002 PM 9509295 ER PT J AU Teicher, BA Ikebe, M Ara, G Keyes, SR Herbst, RS AF Teicher, BA Ikebe, M Ara, G Keyes, SR Herbst, RS TI Transforming growth factor-beta 1 overexpression produces drug resistance in vivo: Reversal by decorin SO IN VIVO LA English DT Article DE transforming growth factor beta 1; decorin; drug resistance ID HUMAN BREAST-CANCER; MESSENGER-RNA ISOFORMS; FACTOR-BETA PRODUCTION; GENE-EXPRESSION; COLON-CARCINOMA; PROSTATE-CANCER; TUMOR STROMA; FACTOR-ALPHA; MCF-7 CELLS; GROWTH-FACTOR-BETA-1 AB The gene for transforming growth factor-beta 1 (TGF-beta 1) was transfected into the murine EMT-6/Parent mammary carcinoma tumor line to form the EMT6/PRK5 beta 1E tumor line. In monolayer culture the EMT-6/PRK5 beta 1E tumor line secretes about 15-times as much TGF-beta 1 into the medium as the EMT-6/Parent line. There was no difference in the response of these two cell lines to 4-hydroperoxycyclophosphamide, cisplatin, melphalan or thiotepa in monolayer culture. When the EMT-6/PRK5 beta 1E cells were grown as a solid tumor in Balb/C mice, plasma levels of TGF-beta 1 were about 5-fold higher than in animals bearing the EMT-6/Parent tumor. The EMT-6/PRK5 beta 1E tumor was markedly resistant to a dosage range of cyclophosphamide, cisplatin, melphalan and thiotepa compared with the EMT-6/Parent tumor. The bone marrow CFU-GM from the animals bearing the EMT-6/PRK5/beta 1E tumor were spared from the cytotoxicity of the drugs compared with the bone marrow CFU-GM from animals bearing the EMT-6/Parent tumor. Administration of decorin, a naturally occurring inhibitor of TGF-beta 1, to animals bearing the EMT-6/PRK5 beta 1E tumor prior to treatment of the animals with the antitumor alkylating agents restored drug sensitivity to the tumor and to the bone marrow CFU-GM. Administration of decorin prior to the antitumor alkylating agents produced very little or no increase in the response of the EMT6/Parent tumor or the bone marrow CFU-GM from those animals. The EMT6/PRK5 beta 1E tumor model allows the effect of secretion of TGF-beta 1 on therapeutic resistance. to be assessed directly compared with the EMT6/Parent tumor. In vivo resistance occurred in the presence of high levels of TGF-beta 1 and was reversed by the TGF-beta 1 inhibitor decorin. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC0540, Indianapolis, IN 46033 USA. FU NCI NIH HHS [P01-CA 38493-11] NR 54 TC 33 Z9 36 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD NOV-DEC PY 1997 VL 11 IS 6 BP 463 EP 472 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YX414 UT WOS:000072037600003 PM 9509296 ER PT J AU Smith, DJ Shoushtari, B Heschel, RL King, WF Taubman, MA AF Smith, DJ Shoushtari, B Heschel, RL King, WF Taubman, MA TI Immunogenicity and protective immunity induced by synthetic peptides associated with a catalytic subdomain of mutans group streptococcal glucosyltransferase SO INFECTION AND IMMUNITY LA English DT Article ID GLUCAN-BINDING DOMAIN; ACTIVE-SITE PEPTIDE; IMMUNOLOGICAL CHARACTERISTICS; SOBRINUS GLUCOSYLTRANSFERASE; SUBSEQUENCE PEPTIDE; NUCLEOTIDE-SEQUENCE; DENTAL-CARIES; GTFC GENE; IMMUNIZATION; INHIBITION AB We examined the immunogenicity and induction of protective immunity of two 19-mer sequences (GGY and AND) which overlapped a highly conserved region which has recently been implicated in the enzymatic activity of glucosyltransferases (GTFs) of the mutans group streptococci, These peptides were synthesized as eight-branched constructs on a lysine core. Serum immunoglobulin G (IgG) antibody, induced by subcutaneous (s.c. [salivary gland vicinity]) injection with these peptide constructs, reacted with the inciting antigen, with mutans streptococcal GTFs, and with a 21-mer peptide (CAT) containing an aspartate previously shown to covalently bind sucrose, Several of these antisera also inhibited the ability of Streptococcus sobrinus GTF to synthesize insoluble glucan, Significant levels of salivary IgA antibody were also induced by GGY and AND peptide constructs after s.c. injection, The effect of immunization with the GGY and AND peptide constructs on the cariogenicity of Streptococcus mutans was studied in three experiments by immunization of weanling Sprague-Dawley rats, twice at 7- to 14-day intervals with peptides, S. sobrinus GTF, or phosphate-buffered saline, All rats were then orally infected with S. mutans SJ. After 63-day infection periods, the GGY and AND-injected groups had significant dental caries reductions compared with sham-injected groups in most experiments, These studies support the existence of an additional catalytic subdomain within the sequence defined by the GGY and AND peptides. Furthermore, the epitopes defined in these sequences have significant immunogenicity, can induce immune responses which interfere with GTF-mediated glucan synthesis in vitro, and can protect rats from experimental dental caries. RP Smith, DJ (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733, DE-06153] NR 30 TC 32 Z9 38 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1997 VL 65 IS 11 BP 4424 EP 4430 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YD176 UT WOS:A1997YD17600009 PM 9353015 ER PT J AU Saladino, RA Stack, AM Fleisher, GR Thompson, CM Briles, DE Kobzik, L Siber, GR AF Saladino, RA Stack, AM Fleisher, GR Thompson, CM Briles, DE Kobzik, L Siber, GR TI Development of a model of low-inoculum Streptococcus pneumoniae intrapulmonary infection in infant rats SO INFECTION AND IMMUNITY LA English DT Article ID MEMBRANE PROTEIN COMPLEX; PNEUMOCOCCAL DISEASE; CONJUGATE VACCINE; POLYSACCHARIDE; IMMUNOGLOBULIN; MICE; PROTECTION; ANTIBODIES; CHILDREN AB We have developed a model of low-inoculum Streptococcus pneumoniae infection in infant rats. We challenged 4-day-old Sprague-Dawley pups via intraperitoneal or intrapulmonary injection of S. pneumoniae serotypes 1, 3, 4, 5, 6b, 7f, 9v, 14, 19f, and 23f. To achieve bacteremia with low inocula, it was necessary to passage the isolates in rats. Inocula of the 10 S. pneumoniae serotypes producing bacteremia in 50% or more animals ranged from 1 to 400 CFU. Virulence was similar by intraperitoneal and intrapulmonary routes. Lung specimens from animals challenged by the intrapulmonary route grew S. pneumoniae and demonstrated histologic evidence of focal infection. Meningitis was detected in 20 to 50% of bacteremic animals, and mortality invariably followed bacteremia within 24 to 48 h. This model of intrapulmonary infection uses low inocula of S. pneumoniae and results in bacteremia, meningitis, and death in infant rats. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. RP Saladino, RA (reprint author), CHILDRENS HOSP,DEPT MED,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 20 TC 18 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1997 VL 65 IS 11 BP 4701 EP 4704 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YD176 UT WOS:A1997YD17600047 PM 9353053 ER PT J AU Sheridan, R Driscoll, D Felsen, R AF Sheridan, R Driscoll, D Felsen, R TI Packing and temporary closure in a liver injury SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article ID TRAUMA AB As a component of a staged laparotomy for trauma, perihepatic packing can be lifesaving in the patient with exsanguinating liver injury who, due to hypothermia and coagulopathy, is unable to tolerate a more extensive procedure. However, if intra-abdominal pressure increases, the manoeuvre has been reported to compromise cardiopulmonary stability. Patients who suffer the adverse consequences of intra-abdominal hypertension are commonly managed with a loose temporary closure, frequently using an artificial material to bridge the skin defect across the incision. A case is reported where these two seemingly contradictory options were combined to achieve a successful outcome. (C) 1997 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Trauma Serv, Massachusetts Gen Hosp, Sch Med,Dept Surg, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Harvard Univ, Trauma Serv, Massachusetts Gen Hosp, Sch Med,Dept Surg, Bigelow 1302, Boston, MA 02114 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD NOV-DEC PY 1997 VL 28 IS 9-10 BP 711 EP 712 DI 10.1016/S0020-1383(97)00128-9 PG 2 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA ZJ066 UT WOS:000073176100034 PM 9624365 ER PT J AU Ghaemi, SN Sachs, GS AF Ghaemi, SN Sachs, GS TI Long-term risperidone treatment in bipolar disorder: 6-month follow up SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; risperidone; manic depressive illness; treatment resistance ID SCHIZOAFFECTIVE DISORDER; MANIA; SCHIZOPHRENIA; PREDICTORS; ILLNESS AB Antipsychotic agents, such as clozapine and risperidone, have been reported to be beneficial in the treatment of some bipolar patients. Many bipolar patients experience `breakthrough episodes' of mood disorder, with mania or depression recurring despite adequate ongoing levels of one or more mood-stabilizing medications. There are no controlled studies of breakthrough episodes, and there is little open experience to guide clinicians in pharmacotherapy of breakthrough episodes. This report describes the outcome of adjunctive risperidone treatment in breakthrough episodes of bipolar disorder. We assessed the outcome of openly adding risperidone to the medication regimen of 12 outpatients with bipolar disorder, type I, who suffered breakthrough episodes despite adequate maintenance medication (lithium, valproate, or carbamazepine, or a combination of these). Prospective ratings were made at each clinical visit using the Clinical Global Impressions and Global Assessment of Functioning scales. Patients received risperidone for a mean of 6.0 months (23.96 weeks, range 0.5-72 weeks) at a mean dose of 2.75 mg/day (range 1-4.5 mg/day). Four patients discontinued medication (two because of lack of efficacy at weeks 6 and 64, and two because of adverse events at weeks 0.5 and 23). Among the remaining eight patients, four experienced a 10-25 point improvement in Global Assessment of Functioning scores and were rated much better on the Clinical Global Impression-Improvement scale. Although one patient suffered a major depressive recurrence (at week 22), no patient experienced worsening of mania. This small open series suggests a subgroup of bipolar patients with breakthrough episodes may benefit from treatment with risperidone. C1 George Washington Univ, Dept Psychiat, Bipolar Disorder Res Program, Washington, DC 20037 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Bipolar Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Ghaemi, SN (reprint author), George Washington Univ, Dept Psychiat, Bipolar Disorder Res Program, 2150 Penn Ave NW,8th Floor, Washington, DC 20037 USA. NR 27 TC 71 Z9 77 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD NOV PY 1997 VL 12 IS 6 BP 333 EP 338 DI 10.1097/00004850-199711000-00006 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA YQ194 UT WOS:000071359000006 PM 9547135 ER PT J AU Qureshi, WA Ali, A Bhol, KC Ahmed, AR AF Qureshi, WA Ali, A Bhol, KC Ahmed, AR TI Juvenile pemphigus foliaceus treated with sublesional corticosteroids SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID DAPSONE; CHILD AB In May 1990, at the age of 16, a Caucasian non-Jewish man presented with superficial erosions on the chest, back, and neck. Examination at that time revealed superficial multiple flaccid bullae and erosions on the upper chest, upper back, and neck. There were no oral, genital, or ocular lesions. A skin biopsy of a new lesion revealed an intraepidermal vesicle with an infiltration of polymorphonuclear leukocytes, He was treated with fluorinated topical corticosteroids. On a follow-up visit in August 1990, there were no active lesions on the chest, back and neck; however, in November 1990, a recurrence of flaccid bullae was noted on the upper back, upper chest, upper arms, and abdomen. Lesions were also observed in the axillae and groin. Biopsy of a lesion on the chest wall, in November 1990, revealed an intraepidermal separation in the upper malpighian layers associated with acantholytic cells. There was a moderately dense lymphocytic infiltrate in the underlying dermis, A direct immunofluorescence study of the perilesional skin demonstrated the presence of immunoglobulin G (IgG) and C3 in the intercellular space of the upper stratum malphigii epidermis. Indirect immunofluorescence using monkey esophagus as substrate demonstrated a pemphigus antibody titer of 1:160. A serologic study by immunoblot analysis using normal human epidermis as substrate demonstrated that the patient's serum bound to a 160 kD protein. The patient was treated with saline soaks to the involved area followed by application of topical corticosteroid creams, In addition, the areas were treated with sublesional injections of triamcinalone acetonide at a concentration of 10 mg/cm(3) and a total of 2 cm(3) was injected at various sites. Two weeks later the patient was injected at sites not previously injected. Thereafter, the patient was seen at 1 or 2-month intervals; often, but not always, at each visit a maximum of 2 cm(3) of 10 mg/cm(3) of triamcinalone acetonide was injected. The volume injected depended on the number of lesions. The lesions showed healing and re-epithelialization within 10 days of injection. Most lesions responded to one injection, but some required 2-3 sessions of injections, When lesions were injected for the second or third time or subsequently, the concentration was reduced to 7.5 mg/cm(3) or 5 mg/cm(3). The frequency of sublesional corticosteroid (SLCS) injection continued to decrease with the passage of time. By June 1991, significant clearing of the lesions was observed, and, by September 1991, topical and sublesional injection therapy was discontinued, Thereafter, the patient developed scattered sporadic lesions on the torso, scalp, and extremities. These lesions were secondary to trauma suffered during sports and athletic activities. The lesions would heal spontaneously and occasionally required sublesional injection. In February 1992, a mild recurrence of lesions was observed on the scalp and trunk. The lesions were similarly treated with SLCS injections and topical therapy and promptly responded. The patient had been regularly followed at 3-3 1/2-month intervals. Occasionally, an isolated lesion has been observed. Most lesions have responded to topical and/or SLCS therapy. Since January 1993 the patient has not had any lesions. He has grown 9 in in height over the last 6 years. He has finished college education and is in overall good health. He has never received any oral corticosteroid therapy. No obvious local or systemic side-effects have been observed with SLCS injection, The areas of involvement initially showed post-inflammatory hyperpigmentation, which has subsequently disappeared. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NEI NIH HHS [EYO8379]; NIDCR NIH HHS [DEO9978] NR 24 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0NE SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD NOV PY 1997 VL 36 IS 11 BP 848 EP 850 PG 3 WC Dermatology SC Dermatology GA YL218 UT WOS:A1997YL21800009 PM 9427078 ER PT J AU Wong, JS Recht, A Beard, CJ Busse, PM Cady, B Chaffey, JT Come, S Fam, S Kaelin, C Lingos, TI Nixon, AJ Shulman, LN Troyan, S Silver, B Harris, JR AF Wong, JS Recht, A Beard, CJ Busse, PM Cady, B Chaffey, JT Come, S Fam, S Kaelin, C Lingos, TI Nixon, AJ Shulman, LN Troyan, S Silver, B Harris, JR TI Treatment outcome after tangential radiation therapy without axillary dissection in patients with early-stage breast cancer and clinically negative axillary nodes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 27-31, 1996 CL LOS ANGELES, CA SP Amer Soc Therapeut Radiol & Oncol DE breast neoplasms; regional nodal failure; radiotherapy; axillary dissection ID CONSERVATIVE SURGERY; RADICAL MASTECTOMY; LYMPH-NODES; RADIOTHERAPY; MANAGEMENT; COMPLICATIONS; CARCINOMA; TRIAL; ARM AB purpose: To determine the risk of nodal failure in patients with early-stage invasive breast cancer with clinically negative axillary lymph nodes treated with two-field tangential breast irradiation alone, without axillary lymph node dissection or use of a third nodal field, Methods and Materials: Between 1988 and 1993, 986 evaluable women with clinical Stage I or II invasive breast cancer were treated with breast-conserving surgery and radiation therapy, Of these, 92 patients with clinically negative nodes received tangential breast irradiation (median dose, 45 Gy) followed by a boost, without axillary dissection. The median age was 69 years (range, 49-87), Eighty-three percent had T1 tumors, Fifty-three patients received tamoxifen, 1 received chemotherapy, and 2 patients received both, Median follow-up time for the 79 survivors was 50 months (range, 15-96), Three patients (3%) have been lost to follow-up after 20-32 months, Results: No isolated regional nodal failures were identified, Two patients developed recurrence in the breast only (one of whom had a single positive axillary node found pathologically after mastectomy). One patient developed simultaneous local and distant failures, and six patients developed distant failures only, One patient developed a contralateral ductal carcinoma in situ, and two patients developed other cancers, Conclusion: Among a group of 92 patients with early-stage breast cancer (typically T1 and also typically elderly) treated with tangential breast irradiation alone without axillary dissection, with or without systemic therapy, there were no isolated axillary or supraclavicular regional failures, These results suggest that it is feasible to treat selected clinically node-negative patients with tangential fields alone, Prospective studies of this approach are warranted. (C) 1997 Elsevier Science Inc. C1 BETH ISRAEL DEACONESS MED CTR,DEPT SURG,BOSTON,MA. BETH ISRAEL DEACONESS MED CTR,DEPT HEMATOL ONCOL,BOSTON,MA. METROWEST MED CTR,DEPT SURG,FRAMINGHAM,MA. BRIGHAM & WOMENS HOSP,DEPT SURG,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT HEMATOL ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP Wong, JS (reprint author), HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,JOINT CTR RADIAT ONCOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 26 TC 47 Z9 47 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1997 VL 39 IS 4 BP 915 EP 920 DI 10.1016/S0360-3016(97)00456-2 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YE847 UT WOS:A1997YE84700020 PM 9369141 ER PT J AU Shipley, WU Zietman, AL Kaufman, DS Althausen, AF Heney, NM AF Shipley, WU Zietman, AL Kaufman, DS Althausen, AF Heney, NM TI Invasive bladder cancer: Treatment strategies using transurethral surgery, chemotherapy and radiation therapy with selection for bladder conservation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE bladder carcinoma; radiation therapy; combined modality therapy; chemotherapy; chemoradiotherapy ID TRANSITIONAL-CELL-CARCINOMA; 5-YEAR FOLLOW-UP; COMBINED-MODALITY PROGRAM; RADICAL RADIOTHERAPY; CISPLATIN CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; PROGNOSTIC FACTORS; NEOADJUVANT CHEMOTHERAPY; ORGAN PRESERVATION; PROSPECTIVE TRIAL AB Purpose: Combined modality therapy has become the standard oncologic approach to achieve organ preservation in many malignancies, Methods and Materials: Although radical cystectomy has been considered as standard treatment for invasive bladder carcinoma in the United States, good results have been recently reported from several centers using multimodality treatment, particularly in patients with clinical T2 and T3a disease who do not have a ureter obstructed by tumor, Results: The components of the combined treatment are usually transurethral resection of the bladder tumor (TURBT) followed by concurrent chemotherapy and radiation therapy, Following an induction course of therapy a histologic response is evaluated by cystoscopy and rebiopsy, Clinical ''complete responders'' (tumor site rebiopsy negative and urine cytology with no tumor cells present) continue with a consolidation course of concurrent chemotherapy and radiation, Those patients not achieving a clinical complete response are recommended to have an immediate cystectomy, Individually the local monotherapies of radiation, TURBT, or multidrug chemotherapy each achieve a local control rate of the primary tumor of from 20 to 40%, When these are combined, clinical complete response rates of from 65 to 80% can be achieved, Seventy-five to 85% of the clinical complete responders will remain with bladders free of recurrence of an invasive tumor, Conclusions: Bladder conservation trials using combined modality treatment approaches with selection for organ conservation by response of the tumor to initial treatment report overall 5-year survival rates of approximately 50%, and a 40-45% 5-year survival rate with the bladder intact, These modern multimodality bladder conservation approaches offer survival rates similar to radical cystectomy for patients of similar clinical stage and age, Bladder-conserving therapy should be offered to patients with invasive bladder carcinoma as a realistic alternative to radical cystectomy by experienced multimodality teams of urologic oncologists. (C) 1997 Elsevier Science Inc. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, MED ONCOL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT UROL, BOSTON, MA 02114 USA. RP Shipley, WU (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, GENITOURINARY ONCOL UNIT, BOSTON, MA 02114 USA. NR 60 TC 36 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1997 VL 39 IS 4 BP 937 EP 943 DI 10.1016/S0360-3016(97)00461-6 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YE847 UT WOS:A1997YE84700023 PM 9369144 ER PT J AU Netland, PA Siegner, SW Harris, A AF Netland, PA Siegner, SW Harris, A TI Color Doppler ultrasound measurements after topical and retrobulbar epinephrine in primate eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE color Doppler imaging; epinephrine; monkey; ocular circulation; retrobulbar injection ID OCULAR BLOOD-FLOW; ANESTHESIA; ADRENALINE AB Purpose. To determine the effects of topical epinephrine and retrobulbar anesthesia containing lidocaine with epinephrine on retrobulbar hemodynamic measurements in the primate eye, using color Doppler ultrasound. Methods. Color Doppler ultrasound measurements were performed al baseline and 90 minutes after masked administration of topical 2% epinephrine or balanced salt solution to six cynomolgus monkeys. Measurements were also performed at baseline and 30 minutes after retrobulbar injection of 2% lidocaine, with or without 1:200,000 epinephrine. Results. After topical epinephrine, color Doppler ultrasound measurements were not signifi cantly different compared with baseline measurements in the central retinal artery, posterior ciliary arteries, and superior ophthalmic vein. There were decreased systolic and diastolic veloclties in the ophthalmic artery (P < 0.03 and P < 0.02, respectively) after topical epinephrine; however, Pourcelot's ratio (resistive index) was not significantly different compared with that at baseline. In contrast, there were marked changes in the retrobulbar arterial circulation after retrobulbar injection of lidocaine with epinephrine. The systolic and diastolic velocities were decreased significantly in the central retinal artery (P < 0.02 and P < 0.01, respectively), temporal posterior ciliary artery (P < 0.05 and P < 0.03, respectively), and nasal posterior ciliary artery (P < 0.03 and P < 0.02, respectively). Pourcelot's ratio was significantly increased in the central retinal artery (P < 0.01), temporal posterior ciliary artery (P < 0.02), and nasal posterior ciliary artery (P < 0.02) after retrobulbar injection of lidocaine with epinephrine. Conclusions. These results indicate that one drop of topical epinephrine has little or no effect on the retrobulbar-circulation, whereas retrobulbar injection of anesthetic solution containing lidocaine with epinephrine significantly alters retrobulbar hemodynamics in the monkey eye. C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. FU NEI NIH HHS [R29-EY10180-01] NR 25 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1997 VL 38 IS 12 BP 2655 EP 2661 PG 7 WC Ophthalmology SC Ophthalmology GA YG139 UT WOS:A1997YG13900028 PM 9375585 ER PT J AU Goldberg, SN Gazelle, GS Debatin, JF AF Goldberg, SN Gazelle, GS Debatin, JF TI Monitoring of radio frequency tissue ablation in an interventional magnetic resonance environment - Preliminary ex vivo and in vivo results SO INVESTIGATIVE RADIOLOGY LA English DT Article DE radio frequency ablation; magnetic resonance, guidance; magnetic resonance, temperature monitoring; interventional procedures, technology ID MR-IMAGING SYSTEM; BRAIN-TUMORS; RADIOFREQUENCY; TEMPERATURE; LASER; ELECTRODE; SIZE AB RATIONALE AND OBJECTIVES. The authors evaluate the feasibility of monitoring radio frequency (RF) ablation in an interventional, open-configuration, 0.5-tesla magnetic resonance (MR) environment. METHODS. Ex vivo and in vivo RF coagulation necrosis were induced in porcine paraspinal muscle tissue using a 300 kHz monopolar RF generator applying 5 to 20 W over 3 to 9 minutes. Images were acquired simultaneous to RF application, after RF application, and in an intermittent mode (60 seconds of RF followed by 15 seconds of MR imaging). Temperature changes were monitored based on amplitude (ex vivo) and phase alterations (in vivo) of a T1-weighted graded refocused echo (GRE) sequence enabling an update every 2.5 seconds. A standardized color-coded subtraction technique enhanced signal changes. Additionally, T2- and T1-weighted spin echo (SE) images were acquired with and without intravenous contrast. Macroscopic coagulation size was compared with lesion size seen on MR images. RESULTS. Although lesion diameters were related directly to applied RF power, the application mode-had no significant impact on coagulation size (P > 0.05). As could be expected, MR imaging during RF ablation resulted in major image distortion. Radio frequency effects were seen on images acquired in the continuous and intermittent modes. Coagulation size seen on GRE images correlated well with macroscopy both ex vivo (r = 0.89) and in vivo (r = 0.92). Poorer correlation was found with postinterventional SE sequences (r = 0.78-0.84). CONCLUSIONS. Magnetic resonance monitoring of RF effects is feasible both ex vivo as well as in vivo using temperature-sensitive sequences in an open-configuration MR environment. C1 UNIV ZURICH HOSP,MR CTR,INST DIAGNOST RADIOL,DEPT MED RADIOL,CH-8091 ZURICH,SWITZERLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. RI Botnar, Rene/E-6875-2012 OI Botnar, Rene/0000-0003-2811-2509 NR 26 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 1997 VL 32 IS 11 BP 671 EP 678 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YF083 UT WOS:A1997YF08300004 ER PT J AU Duerinckx, A Atkinson, DP AF Duerinckx, A Atkinson, DP TI Coronary MR angiography during peak-systole: Work in progress SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE cardiac MRI; heart; coronary vessels, MRI; coronary angiography, MRI; systole; diastole; image quality ID MAGNETIC-RESONANCE ANGIOGRAPHY; FLOOD FLOW VELOCITY; ARTERY BLOOD-FLOW; IN-VIVO; CONTRAST; DIAMETER; RESERVE; MOTION; QUANTIFICATION; ACCURACY AB The purpose of this study is to compare the quality of images of coronary arteries obtained with two-dimensional breath-hold coronary MR angiography during peak systole and mid diastole, Two-dimensional coronary MR angiography was performed in eight normal volunteers at peak systole and in mid diastole with a commercial 1.5-T MR imager, An ultrafast gradient-echo sequence with incremented flip angle series and k-space segmentation was used. The image quality grade, length, and proximal diameter of each visualized coronary artery were measured. The highest quality images in systole and diastole were compared. Coronary MR angiography provided high quality images in systole and diastole in 14 of 16 coronary vessels (87.5%), In 8 of 14 vessels (57%), there was no visible coronary MR angiogram image degradation when comparing peak systolic with mid-diastolic images. In 4 of 14 vessels (29%), there was mild MR image degradation. There was significant MR image degradation in only one case (7%). And in one case (7%), there was mild image improvement during systole. The width and length of the visualized coronary vessels did not change significantly from diastole to systole, Existing two-dimensional breath-hold coronary MR angiography provides MR images during peak systole and mid-diastole with little or no perceptible difference in quality. C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, MRI, Los Angeles, CA 90073 USA. RP Duerinckx, A (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Radiol, MRI, Mail Rout W114,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Atkinson, Dennis/N-5238-2015 OI Atkinson, Dennis/0000-0001-7393-7505 NR 49 TC 21 Z9 21 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD NOV-DEC PY 1997 VL 7 IS 6 BP 979 EP 986 DI 10.1002/jmri.1880070608 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 102UU UT WOS:000074944300006 PM 9400840 ER PT J AU Moore, A Weissleder, R Bogdanov, A AF Moore, A Weissleder, R Bogdanov, A TI Uptake of dextran-coated monocrystalline iron oxides in tumor cells and macrophages SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE iron oxide; dextran; opsonization; endocytosis ID GLIAL-CELLS; PHAGOCYTOSIS; INVITRO; LOCALIZATION; PINOCYTOSIS; ENDOCYTOSIS; XENOGRAFTS; CARCINOMA; TRANSPORT; CULTURE AB Although several dextran-coated iron oxide preparations are in preclinical and clinical use, little Is known about the mechanism of uptake into cells, As these particles have been shown to accumulate in macrophages and tumor cells, we performed cellular uptake and inhibition studies with a prototypical monocrystalline iron oxide nanoparticle (MION). MION particles were labeled with fluorescein Isothiocyanate or radioiodinated and purified by gel permeation chromatography. Two preparations of MION particles were used in cell experiments: nontreated MION and plasma-opsonized MION purified by gradient density purification. As determined by immunoblotting, opsonization resulted in C3, vitronectin, and fibronectin association with MION. Incubation of cells with fluorescent MION showed active uptake of particles in macrophages both before and after opsonization, In C6 tumor cells, however. intracellular MION was only detectable in dividing cells, Quantitatively, I-125-labeled MION was internalized into cells with uptake values ranging from 17 ng (in 9L gliosarcoma) to 970 ng iron per million cells for peritoneal macrophages. Opsonization increased MION uptake into macrophages sixfold, whereas it increased the uptake in C6 tumor cells only twofold, Results from uptake inhibition assay suggest that cellular uptake of nonopsonized (dextran-coated) MION particles is mediated by fluid-phase endocytosis, whereas receptor-mediated endocytosis is presumably responsible for the uptake of opsonized (protein-coated) particles. C1 Massachusetts Gen Hosp, Dept Radiol, CMIR, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Dept Radiol, CMIR, 149 13th St,Room 5403, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01-CA-54886-05, R01-CA-59649-04] NR 32 TC 188 Z9 197 U1 1 U2 28 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 USA SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD NOV-DEC PY 1997 VL 7 IS 6 BP 1140 EP 1145 DI 10.1002/jmri.1880070629 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 102UU UT WOS:000074944300026 PM 9400860 ER PT J AU Yang, ZW McLachlan, RI Bremner, WJ Wreford, NG AF Yang, ZW McLachlan, RI Bremner, WJ Wreford, NG TI Quantitative (stereological) study of normal spermatogenesis in the adult monkey (Macaca fascicularis) SO JOURNAL OF ANDROLOGY LA English DT Article DE Sertoli cell; spermiogenesis; stereology; testis ID FOLLICLE-STIMULATING-HORMONE; TESTIS; CELL; RAT; RENEWAL; SERTOLI; VOLUME; NUMBER; CYCLE AB Germ cell and Sertoli cell numbers were estimated in six normal adult monkeys (Macaca fascicularis) using a contemporary unbiased and efficient stereological method-the optical disector. The data was used to assess the efficiency of spermatogenesis from type B spermatogonia to elongated spermatids. Animals underwent orchidectomy, and the right testis (volume 17.5 +/- 1.7 cm(3) [mean +/- SEM], range 13.2-25.1 cm(3)) was fixed in Bouin's fluid. Blocks were embedded in methacrylate resin and germ cells were counted in thick (25 mu m) sections using the optical disector in conjunction with a systematic uniform random-sampling protocol. The total numbers of Sertoli cells an all germ cells per testis were 566 +/- 43 (419-683) million and 12.8 +/- 1.6 (9.0-20.2) billion, respectively. On average, one Sertoli cell supported 12.4 +/- 1.9 (range 8.2-18.4) step 1-12 spermatids. 3.1 +/- 0.4 (2.3-4.5) pachytene spermatocytes, and 23.7 +/- 4.1 (15.0-39.0) total germ cells. Sertoli cell number correlated poorly with both testicular size (correlation coefficient r = -0.12) and germ cell numbers (r = -0.35 with total germ cell number), However, testicular size had a consistent and significant correlation with germ cell numbers (r = 0.97 with total germ cell number). The conversion ratio of pachytene spermatocytes to step 1-12 spermatids was 3.94 +/- 0.19, which is close to the theoretical maximum of 4. Similarly, the conversion between other cell types was consistently close to the maximum theoretical value. We conclude that the efficiency of spermatogenesis in the adult monkey is high, with stepwise conversion being consistently close to the maximal values. The capacity of Sertoli cells to support a cohort of germ cells varies widely between monkeys. Although absolute number of cells per testis is always the preferred parameter, it cannot always be obtained in an experimental situation where cost and ethical constraints mean that biopsies, rather than whole testes, are collected. Thus, if absolute data on germ cell numbers are not available, experimental outcomes impacting on cells beyond preleptonene spermatocytes may be best expressed in terms of changes in germ cell conversion rather than the traditional germ cell:Sertoli cell ratio. C1 MONASH UNIV,DEPT ANAT,CLAYTON,VIC 3168,AUSTRALIA. PRINCE HENRYS INST MED RES,MELBOURNE,VIC,AUSTRALIA. UNIV WASHINGTON,VET AFFAIRS PUGET SOUND HLTH CARE SYST,DEPT MED,SEATTLE,WA 98195. MONASH UNIV,INST REPROD & DEV,CLAYTON,VIC 3168,AUSTRALIA. NR 20 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 1997 VL 18 IS 6 BP 681 EP 687 PG 7 WC Andrology SC Endocrinology & Metabolism GA YL445 UT WOS:A1997YL44500014 ER PT J AU Imanaka, H Kimball, WR Wain, JC Nishimura, M Okubo, K Hess, D Kacmarek, RM AF Imanaka, H Kimball, WR Wain, JC Nishimura, M Okubo, K Hess, D Kacmarek, RM TI Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sonomicrometers; video-assisted thoracoscopic surgery ID UPPER ABDOMINAL-SURGERY; MUSCLE-SPARING THORACOTOMY; THORACOSCOPIC LUNG-BIOPSY; EPIDURAL-ANESTHESIA; POSTOPERATIVE PAIN; PARALYSIS; DOGS; HEMIDIAPHRAGM; VENTILATION; LAPAROTOMY AB Video-assisted thoracoscopic surgery (VATS) is replacing thoracotomy, but no study has addressed the extent or duration of VATS-induced diaphragmatic alteration. We hypothesized that VATS would impair diaphragmatic function less and return diaphragmatic function faster than thoracotomy In eight sheep, sonomicrometers were randomly implanted on the right costal diaphragm via VATS or thoracotomy. Diaphragmatic resting length, shortening fraction, and respiratory function were measured weekly during quiet breathing (QB) and CO2 rebreathing for 4 wk. For VATS, shortening fraction was smallest on postoperative days 1 (POD 1) (6.4 +/- 3.4 and 12.9 +/- 8.7% during QB and 10% CO2 rebreathing, respectively) and 7 (6.3 +/- 3.4 and 16.9 +/- 4.0% during QB and 10% CO2 rebreathing, respectively) and recovered by 3 wk (13.2 +/- 1.8 and 28.9 +/- 8.0% during QB and 10% CO2 rebreathing, respectively). For thoracotomy, shortening fraction at 10% CO2 rebreathing was smaller on PODs 1, 7, 14 (15.9 +/- 7.1, 13.6 +/- 5.4, and 19.0 +/- 6.9%) than on POD 28 (29.9 +/- 8.2%), but not during QB on POD 1 or 7 (7.5 +/- 3.8 and 3.4 +/- 2.6%) compared with POD 28 (10.7 +/- 8.7%). Shortening fraction did not differ between surgeries. There was no group difference in minute ventilation, respiratory rate, transdiaphragmatic pressure, or esophageal and gastric pressures. In conclusion, although shortening fraction recovered faster for VATS, this translated into insignificant functional differences. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT CRIT CARE,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RESP CARE,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 30 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1997 VL 83 IS 5 BP 1733 EP 1740 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA YE867 UT WOS:A1997YE86700047 PM 9375345 ER PT J AU Looker, AC Orwoll, ES Johnston, CC Lindsay, RL Wahner, HW Dunn, WL Calvo, MS Harris, TB Heyse, SP AF Looker, AC Orwoll, ES Johnston, CC Lindsay, RL Wahner, HW Dunn, WL Calvo, MS Harris, TB Heyse, SP TI Prevalence of low femoral bone density in older US adults from NHANES III SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 09-13, 1995 CL BALTIMORE, MD SP Amer Soc Bone & Mineral Res ID MEXICAN-AMERICAN WOMEN; HIP FRACTURE; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; POSTMENOPAUSAL WOMEN; SEX-DIFFERENCES; SECULAR TRENDS; PREDICTION; MASS; RISK AB Most estimates of osteoporosis in older U.S. adults have been based on its occurrence in white women, even though it is known to affect men and minority women, In the present study, we used dual-energy X-ray absorptiometry measurements of femoral bone mineral density (BMD) from the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994) to estimate the overall scope of the disease in the older U.S. population, Specifically, we estimate prevalences of low femoral BMD in women 50 years and older and explore different approaches for defining low BMD in older men ire that age range, Low BMD levels were defined in accordance with an approach proposed by an expert panel of the World Health Organization and used BMD data from 382 non-Hispanic white (NHW) men or 409 NHW women ages 20-29 years from the NHANES III dataset, For women, estimates indicate 13-18%, or 4-6 million, have osteoporosis (i.e., BMD >2.5 standard deviations [SD] below the mean of young NHW women) and 37-50%, or 13-17 million, have osteopenia (BMD between 1 and 2.5 SD below the mean of young NHW women), For men, these numbers depend on the gender of the reference group used to define cutoff values, When based on male cutoffs, 3-6% (1-2 million) of men have osteoporosis and 28-47% (8-13 million) have osteopenia; when based on female cutoffs, 1-4% (280,000-1 million) have osteoporosis and 15-33% (4-9 million) have osteopenia, Most of the older U.S. adults with low femur BMD are women, but, regardless of which cutoffs are used, the number of men is substantial. C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. HELEN HAYES HOSP,REG BONE CTR,W HAVERSTRAW,NY. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. NIA,NIH,BETHESDA,MD 20892. NIAID,NIH,BETHESDA,MD 20892. RP Looker, AC (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,6525 BELCREST RD,ROOM 900,HYATTSVILLE,MD 20782, USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 47 TC 673 Z9 697 U1 7 U2 20 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 1997 VL 12 IS 11 BP 1761 EP 1768 DI 10.1359/jbmr.1997.12.11.1761 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YE194 UT WOS:A1997YE19400001 PM 9383679 ER PT J AU Endres, M Wang, ZQ Namura, S Waeber, C Moskowitz, MA AF Endres, M Wang, ZQ Namura, S Waeber, C Moskowitz, MA TI Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; cerebral ischemia; DNA damage; energy depletion; mice; poly(ADP-ribose) polymerase ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE TOXICITY; DNA FRAGMENTATION; FOREBRAIN ISCHEMIA; ENERGY-METABOLISM; ISLET CELLS; POLYMERASE; APOPTOSIS; POLY(ADP-RIBOSYL)ATION; IDENTIFICATION AB Poly(ADP-ribose)polymerase (PARP, EC 2.4.2.30), an abundant nuclear protein activated by DNA nicks, mediates cell death in vitro by nicotinamide adenine dinucleotide (NAD) depletion after exposure to nitric oxide. The authors examined whether genetic deletion of PARP (PARP null mice) or its pharmacologic inhibition by 3-aminobenzamide (3-AB) attenuates tissue injury after transient cerebral ischemia. Twenty-two hours after reperfusion following 2 hours of filamentous middle cerebral artery occlusion, ischemic injury was decreased in PARP-/- and PARP+/- mice compared with PARP+/+ litter mates, and also was attenuated in 129/SV wildtype mice after 3-AB treatment compared with controls. Infarct sparing was accompanied by functional recovery in PARP-/- and S-AB-treated mice. Increased poly(ADP-ribose) immunostaining observed in ischemic cell nuclei 5 minutes after reperfusion was reduced by 3-AB treatment. Levels of NAD-the substrate of PARP-were reduced 2 hours after reperfusion and were 35% of contralateral levels at 24 hours. The decreases were attenuated in PARP-/- mice and in 3-AB-treated animals. Poly(ADP-ribose)polymerase cleavage by caspase-3 (CPP-32) has been proposed as an important step in apoptotic cell death. Markers of apoptosis, such as oligonucleosomal DNA damage, total DNA fragmentation, and the density of terminal deoxynucleotidyl transferase dUTP nick-end-labelled (TUNEL +) cells, however, did not differ in ischemic brain tissue of PARP-/- mice or in 3-AB-treated animals versus controls, although there were differences in the number of TUNEL-stained cells reflecting the decrease in infarct size. Thus, ischemic brain injury activates PARP and contributes to cell death most likely by NAD depletion and energy failure, although the authors have not excluded a role for PARP in apoptotic cell death at earlier or later stages in ischemic cell death. Inhibitors of PARP activation could provide a potential therapy in acute stroke. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,STROKE & NEUROVASC REGULAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,STROKE & NEUROVASC REGULAT LAB,CHARLESTOWN,MA 02129. INST MOL PATHOL,VIENNA,AUSTRIA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS10828] NR 41 TC 458 Z9 468 U1 2 U2 9 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1997 VL 17 IS 11 BP 1143 EP 1151 DI 10.1097/00004647-199711000-00002 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA YH666 UT WOS:A1997YH66600002 PM 9390645 ER PT J AU Welt, CK LambertMesserlian, G Zheng, W Crowley, WF Schneyer, AL AF Welt, CK LambertMesserlian, G Zheng, W Crowley, WF Schneyer, AL TI Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; IMMUNOREACTIVE INHIBIN; SURFACE EPITHELIUM; FOLLICULAR-FLUID; BINDING PROTEIN; ALPHA-INHIBIN; GROWTH-FACTOR; CELL-LINES; CANCER; TUMOR AB Activin induces proliferation in epithelial ovarian carcinoma cell lines, whereas follistatin (FS), an activin binding protein, inhibits this action. To test the hypothesis that activin production, in excess of inhibin and FS, results in cell proliferation in epithelial ovarian tumors, messenger RNA (mRNA) expression of the activin family of proteins, FS, and activin type I and II receptors was examined in 25 primary epithelial ovarian tumors and tumor epithelium in culture (n = 7) using RT-PCR. Activin A was measured in the serum of ovarian cancer patients, and activin A, total inhibin, and FS protein secretion was measured from primary epithelial tumors in vitro. The effect of activin and FS on cell proliferation was assessed by measuring [H-3]thymidine incorporation. All results were compared with normal ovarian epithelium. All epithelial ovarian tumors expressed mRNA for the alpha, beta A, and beta B subunits; FS 288 and 315; and the activin type IA, IB, II, and IIB receptors. beta A mRNA expression, as assessed using semiquantitative RT-PCR, was 3-fold greater in cultured tumor epithelium than in primary tumors (band density 0.86 +/- 0.17 vs. 0.28 +/- 0.09; P < 0.01). In addition, beta A mRNA was abundantly expressed in normal epithelium in culture (n = 2), whereas only trace amounts were seen in 2/9 primary epithelial samples. Activin protein was secreted by 24/25 primary epithelial ovarian tumors (range 0.2-155.8 ng/mL). In contrast, total inhibin was secreted by only 2/25 (range 0.01-0.92 ng/mL), whereas free FS was not detectable in the medium of any tumor (< 0.5 ng/mL). Treatment with activin or FS did not consistently affect cell growth. Measurement of serum activin A in a subset of subjects and in 27 additional subjects with epithelial ovarian carcinoma (n = 33) revealed preoperative activin A levels > 3 SD above the mean for pre-and postmenopausal women in 13/33 (39%) subjects. We conclude that in epithelial ovarian cancer: 1) beta A subunit mRNA is expressed, 2) activin protein is secreted more frequently than inhibin and in greater quantities than FS, 3) beta A subunit mRNA expression is greater in neoplastic and normal epithelium in culture than in the primary tissue, 4) the majority of tumors in culture do not respond to activin or FS treatment with proliferation, and 5) serum activin levels may reflect tumor secretion in some patients. Thus, activin A appears to be available as an autocrine/paracrine factor in epithelial ovarian tumors and may contribute to circulating levels, but its role in tumorigenesis has yet to be defined. C1 MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE SCI CTR, DEPT MED, BOSTON, MA 02114 USA. BROWN UNIV, WOMEN & INFANTS HOSP, DEPT PATHOL & LAB MED, PROVIDENCE, RI 02905 USA. UNIV SO CALIF, DEPT PATHOL, LOS ANGELES, CA 90033 USA. RP Welt, CK (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, DEPT MED, BOSTON, MA 02114 USA. OI Messerlian, Geralyn/0000-0002-9440-3411; Welt, Corrine/0000-0002-8219-5504 FU NICHD NIH HHS [P30-HD-28138, U54-HD-29164] NR 50 TC 69 Z9 71 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1997 VL 82 IS 11 BP 3720 EP 3727 DI 10.1210/jc.82.11.3720 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YF271 UT WOS:A1997YF27100031 PM 9360531 ER PT J AU Folli, F Kahn, CR Hansen, H Bouchie, JL Feener, EP AF Folli, F Kahn, CR Hansen, H Bouchie, JL Feener, EP TI Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels - A potential role for serine phosphorylation in insulin/angiotensin II crosstalk SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE angiotensin II; insulin receptor substrate-1; phosphatidylinositol 3-kinase; vascular smooth muscle cells; insulin resistance ID TYROSINE KINASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CONVERTING ENZYME-INHIBITION; PROTEIN-COUPLED RECEPTORS; CORONARY-ARTERY DISEASE; NITRIC-OXIDE RELEASE; VASCULAR INJURY; RISK-FACTORS; JUXTAMEMBRANE REGION AB To investigate potential interactions between angiotensin II (AII) and the insulin signaling system in the vasculature, insulin and AII regulation of insulin receptor substrate-1 (IRS-I) phosphorylation and phosphatidylinositol (PI) 3-kinase activation were examined in rat aortic smooth muscle cells. Pretreatment of cells with AII inhibited insulin-stimulated PI 3-kinase activity associated with IRS-1 by 60%. While AII did not impair insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) P-subunit, it decreased insulin-stimulated tyrosine phosphorylation of IRS-1 by 50%. AII inhibited the insulin-stimulated association between IRS-1 and the p85 subunit of PI 3-kinase by 30-50% in a dose-dependent manner. This inhibitory effect of AII on IRS-1/PI 3-kinase association was blocked by the AII receptor antagonist saralasin, but not by AT, antagonist losartan or AT(2) antagonist PD123319. AII increased the serine phosphorylation of both the IR P-subunit and IRS-1. In vitro binding experiments showed that autophosphorylation increased IR binding to IRS-1 from control cells by 2.5-fold versus 1.2-fold for IRS-l from AII-stimulated cells, suggesting that AII stimulation reduces IRS-l's ability to associate with activated IR. In addition, AII increased p85 serine phosphorylation, inhibited the total pool of p85 associated PI 3-kinase activity, and decreased levels of the p50/ p55 regulatory subunit of PI 3-kinase. These results suggest that activation of the renin-angiotensin system may lead to insulin resistance in the vasculature. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HOSP SAN RAFFAELE,DEPT MED 1,I-20132 MILAN,ITALY. HOSP SAN RAFFAELE,IRCCS,UNITA MALATTIE METAB,I-20132 MILAN,ITALY. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK 33201, DK 36836, DK 48358, P30 DK036836] NR 71 TC 311 Z9 327 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1997 VL 100 IS 9 BP 2158 EP 2169 DI 10.1172/JCI119752 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YF660 UT WOS:A1997YF66000004 PM 9410892 ER PT J AU Dunkel, L Taskinen, S Hovatta, O Tilly, JL Wikstrom, S AF Dunkel, L Taskinen, S Hovatta, O Tilly, JL Wikstrom, S TI Germ cell apoptosis after treatment of cryptorchidism with human chorionic gonadotropin is associated with impaired reproductive function in the adult SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DNA fragmentation; fertility; infertility; male reproduction ID UNDESCENDED TESTIS; MALDESCENDED TESTES; DNA FRAGMENTATION; HORMONAL-CONTROL; DEATH; SPERMATOGENESIS; FERTILITY; RATS; DEGENERATION; MALIGNANCY AB Cryptorchidism results in impaired fertility. Reduced numbers of testicular germ cells can be shown histologically during the first years of life. The process causing germ cell loss in cryptorchid prepubertal boys is unknown, but it could be the result of a form of programmed cell death known as apoptosis. 25 adult men with a history of surgically treated cryptorchidism were studied, 15 of whom had received an unsuccessful human chorionic gonadotropin (hCG) therapy before orchidopexy. Apoptotic DNA fragmentation was assayed in testis biopsies taken during orchidopexy by end-labeling, both in extracted DNA and histochemically in situ. Only a few scattered apoptotic spermatogonias were seen by end-labeling of biopsies from patients not treated with hCG, whereas more extensive labeling of spermatogonia was seen after hCG treatment. As estimated by gel electrophoresis, the amount of low molecular weight DNA was 4.3-fold higher in the hCG-treated group when compared with the level in scrotal testis of non-hCG-treated patients (P < 0.001). About 20 yr after the biopsy, the low molecular weight DNA fragmentation correlated negatively with the testis volume (r = -0.84; P < 0.001) and positively with serum FSH levels (r = 0.73; P < 0.001). Findings in the semen analysis were similar between the groups. Apoptotic loss of spermatogonia after hCG treatment of cryptorchidism warrants reevaluation of the safety of this treatment. C1 FAMILY FEDERAT FINLAND,INFERTIL CLIN,FIN-00100 HELSINKI,FINLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,VINCENT CTR REPROD BIOL,BOSTON,MA 02114. RP Dunkel, L (reprint author), UNIV HELSINKI,CHILDRENS HOSP,STENBACKINKATU 11,FIN-00290 HELSINKI,FINLAND. NR 53 TC 94 Z9 100 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV 1 PY 1997 VL 100 IS 9 BP 2341 EP 2346 DI 10.1172/JCI119773 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YF660 UT WOS:A1997YF66000025 PM 9410913 ER PT J AU Haas, J Jernick, SL Scardina, RJ Teruya, J Caliendo, AM Ruoff, KL AF Haas, J Jernick, SL Scardina, RJ Teruya, J Caliendo, AM Ruoff, KL TI Colonization of skin by Helcococcus kunzii SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GRAM-POSITIVE COCCI; FOOT INFECTIONS AB In order to investigate the role of Helcococcus kunzii as a colonizer of skin and as a possible participant in diabetic foot ulcers, we used a selective medium to culture both lower-and upper-extremity skin from a study group of podiatry patients (60 diabetics and 60 nondiabetics) and a control group of 50 healthy volunteers. Although differences in colonization were not statistically significant, a trend toward higher colonization rates in the group of podiatry patients was noted. H. kunzii appears to preferentially colonize the skin of the feet, and while its pathogenic role in diabetic foot ulcers is difficult to establish, it may be a previously unrecognized component of the polymicrobial flora characteristically isolated from patients with these infections. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,GRB526,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PODIATRY,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MICROBIOL LABS,BOSTON,MA 02114. S CTY HOSP,WAKEFIELD,RI 02879. NR 9 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 1997 VL 35 IS 11 BP 2759 EP 2761 PG 3 WC Microbiology SC Microbiology GA YD173 UT WOS:A1997YD17300008 PM 9350728 ER PT J AU Cannistra, SA AF Cannistra, SA TI ''Cancer defeated'': Not if, but when - Introducing the Biology of Neoplasia series SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID APOPTOSIS RP Cannistra, SA (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1997 VL 15 IS 11 BP 3297 EP 3298 PG 2 WC Oncology SC Oncology GA YE015 UT WOS:A1997YE01500001 PM 9363857 ER PT J AU Fuchs, CS AF Fuchs, CS TI Chemotherapy for advanced gastric cancer: Where do we stand? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PHASE-II; DOXORUBICIN; CISPLATIN; 5-FLUOROURACIL; COMBINATION; FLUOROURACIL; ETOPOSIDE; TRIAL; METHOTREXATE; MITOMYCIN RP Fuchs, CS (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 16 TC 18 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1997 VL 15 IS 11 BP 3299 EP 3300 PG 2 WC Oncology SC Oncology GA YE015 UT WOS:A1997YE01500002 PM 9363858 ER PT J AU Sellers, WR Kaelin, WG AF Sellers, WR Kaelin, WG TI Role of the retinoblastoma protein in the pathogenesis of human cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENES; E2F TRANSCRIPTION FACTOR; CELL-CYCLE CONTROL; LARGE T-ANTIGEN; HUMAN PITUITARY-TUMORS; S-PHASE ENTRY; SUSCEPTIBILITY GENE; RB PROTEIN; GROWTH SUPPRESSION; HEREDITARY RETINOBLASTOMA AB The retinoblastoma gene (RE-I)was originally identified as the gene involved in hereditary retinoblastoma. However, RB-I mutations are found in a number of common mesenchymal and epithelial malignancies. The retinoblastoma protein (pRB) acts as a transcriptional regulator of genes involved in DNA synthesis and cell-cycle control, In this regard, the functional interaction between pRB and the E2F transcription factor family appears to be critical, The pRB-E2F interaction is, in turn, regulated by a pathway that includes cyclin D1, cdk4, and p16. Mutations that affect this pathway have been documented in nearly every type of adult cancer, Thus, perturbation of pRB function may be required for the development of cancer, Insights into the biochemical functions of pRB, and its upstream regulators, may form the basis for the development of novel antineoplastic agents. (C) 1997 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 174 TC 187 Z9 190 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1997 VL 15 IS 11 BP 3301 EP 3312 PG 12 WC Oncology SC Oncology GA YE015 UT WOS:A1997YE01500003 PM 9363859 ER PT J AU Maurer, LH Herndon, JE Hollis, DR Aisner, J Carey, RW Skarin, AT Perry, MC Eaton, WL Zacharski, LL Hammond, S Green, MR AF Maurer, LH Herndon, JE Hollis, DR Aisner, J Carey, RW Skarin, AT Perry, MC Eaton, WL Zacharski, LL Hammond, S Green, MR TI Randomized trial of chemotherapy and radiation therapy with or without warfarin for limited-stage small-cell lung cancer: A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MEMBRANE GLYCOPROTEIN-IB; COAGULATION FIBRINOLYSIS; THROMBIN; CARCINOMA; SURVIVAL; ANTICOAGULATION; ACTIVATION; LOCALIZATION; PATHWAYS; TISSUES AB Purpose: Studies by the Veterans Administration Cooperative Studies program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy knight enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients and Methods: patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy, Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to ct high rate of pulmonary toxicity. Results: There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated ansi control groups, in patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07), Preamendment results, while not significant, did not have superimposable treatment survival curves. a landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with less than or equal to 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103), Conclusion: Warfarin does not appear to improve outcome significantly-in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies. (C) 1997 by American Society of Clinical Oncology. C1 LEUKEMIA GRP B STAT OFF,DURHAM,NC. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MISSOURI,COLUMBIA,MO. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. RP Maurer, LH (reprint author), DARTMOUTH COLL,HITCHCOCK MED CTR,1 MED CTR DR,LEBANON,NH 03756, USA. FU NCI NIH HHS [CA31983, CA04326, CA33601] NR 29 TC 88 Z9 93 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1997 VL 15 IS 11 BP 3378 EP 3387 PG 10 WC Oncology SC Oncology GA YE015 UT WOS:A1997YE01500013 PM 9363869 ER PT J AU Ali, RW Johannessen, AC Dahlen, G Socransky, SS Skaug, N AF Ali, RW Johannessen, AC Dahlen, G Socransky, SS Skaug, N TI Comparison of the subgingival microbiota of periodontally healthy and diseased adults in Northern Cameroon SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE subgingival microbiota; DNA probes; cultivation; Cameroon ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; DETECTION FREQUENCY; TRANSPORT MEDIA; PLAQUE SAMPLES; PATHOGENS; BACTEROIDES; PERIODONTOPATHOGENS; GINGIVALIS; MICROFLORA; POCKETS AB Our study is the Ist report on subgingival microbiota in adult Cameronians. The aim was to investigate, using the checkerboard DNA-DNA hybridization technique, the prevalence of 18 oral species in subgingival plaque samples obtained from sex- and age-matched Cameronian adults with and without periodontal destruction. We also compared cultivation and the Affirm(TM) DP test with the checkerboard technique in their capability to detect some selected species among the 18. 21 adult periodontitis patients and 21 periodontally healthy subjects were examined and the results were compared statistically. Each periodontitis patient had at least 4 pockets of greater than or equal to 6 mm depth, while the healthy subjects had no sites more than 3 mm deep. Results of the checkerboard analysis showed that significantly (p<0.05) more periodontitis patients tested positive for most of the 18 bacterial species, The Gram-positive species Actinomyces naeslundii, Streptococcus mitis and Streptococcus sanguis, known as microbiota of healthy sites, were detected significantly more frequently in the healthy group. Cultivation demonstrated P. gingivalis, B. forsythus, A. actinomycetemcomitans, P. intermedia and F. nucleatum in significantly lower %s of patients as compared to the checkerboard technique. Furthermore. the Affirm(TM) DP test detected P, gingivalis and B, forsythus in significantly feu er patients than did the checkerboard technique, A. actinomycetemcomitans was detected in 52.3% of the patients by the latter technique while the Affirm(TM) DP test failed to detect the bacterium in any of the samples. Overall, the results of the present study confirm the importance of the screening method and indicate that the prevalences of the investigated putative periodontal pathogens and beneficial species in the healthy and diseased adult Cameronians were similar to those reported for adults in the West and in some developing countries. C1 UNIV BERGEN,DEPT ORAL PATHOL & FORENS MED,N-5021 BERGEN,NORWAY. GOTHENBURG UNIV,DEPT ORAL MICROBIOL,GOTHENBURG,SWEDEN. FORSYTH DENT CTR,BOSTON,MA 02115. RP Ali, RW (reprint author), UNIV BERGEN,LAB ORAL MICROBIOL,N-5021 BERGEN,NORWAY. RI Johannessen, Anne Christine/B-8929-2017 OI Johannessen, Anne Christine/0000-0001-5403-2380 NR 32 TC 40 Z9 44 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 1997 VL 24 IS 11 BP 830 EP 835 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA YF495 UT WOS:A1997YF49500008 PM 9402505 ER PT J AU Brun, RP Spiegelman, BM AF Brun, RP Spiegelman, BM TI PPAR gamma and the molecular control of adipogenesis SO JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Argenteuil Symposium of the Princess-Lilian-Cardiology-Foundation-of-Belgium on Obesity and the Adipocyte CY OCT, 1996 CL ARGENTEUIL, FRANCE SP Princess Lilian Cardiol Fdn Belgium ID ADIPOCYTE DIFFERENTIATION; ECTOPIC EXPRESSION; ACTIVATION; CELLS; ISOFORMS; ENHANCER; PROMOTES; CASCADE; LIGAND; FAMILY C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RP Brun, RP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 15 TC 80 Z9 84 U1 1 U2 3 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 1997 VL 155 IS 2 BP 217 EP 218 DI 10.1677/joe.0.1550217 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YD776 UT WOS:A1997YD77600012 PM 9415052 ER PT J AU Silva, JA Leong, GB Weinstock, R AF Silva, JA Leong, GB Weinstock, R TI Violent behaviors associate with the antichrist delusion SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; antichrist delusion; delusional misidentification; psychosis; violence; aggression; forensic psychiatry ID MISIDENTIFICATION SYNDROMES; CAPGRAS SYNDROME; TOMOGRAPHY; ATROPHY AB Delusions involving the antichrist concept have been occasionally reported. Some cases of the antichrist delusion have been associated with violent behavior. In this article we describe the case of a man who suffered from a chronic antichrist delusion and who also displayed repeated and serious violent behaviors. We also discuss the role of the antichrist delusion as well as other psychotic symptoms in the genesis of violence in the present case. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. OHIO STATE UNIV,COLL MED,COLUMBUS,OH 43210. VET AFFAIRS OUTPATIENT CLIN,COLUMBUS,OH. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Silva, JA (reprint author), S TEXAS VET HLTH CARE SYST,PSYCHIAT SERV 116A,PSYCHIAT RES UNIT,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 44 TC 6 Z9 8 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1997 VL 42 IS 6 BP 1058 EP 1061 PG 4 WC Medicine, Legal SC Legal Medicine GA YF717 UT WOS:A1997YF71700013 PM 9397546 ER PT J AU Rossi, RA Every, NR AF Rossi, RA Every, NR TI A computerized intervention to decrease the use of calcium channel blockers in hypertension SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-03, 1997 CL WASHINGTON, DC SP Soc Gen Internal Med DE guidelines; physician's practice patterns; hypertension; calcium channel blockers ID RANDOMIZED CONTROLLED TRIAL; DRUG; MORTALITY; THERAPY; QUALITY; CARE AB OBJECTIVE: To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic. DESIGN:A randomized trial. SETTING: The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System, Seattle Division. PATIENTS/PARTICIPANTS: Clinic providers were randomized to a control group (n = 35) or intervention group (n = 36). We targeted the providers of patients being treated for hypertension with calcium channel blockers, a class of drug not recommended for initial therapy. INTERVENTION: An automated computer query identified eligible patients and their providers, A guideline reminder was placed in the charts of patients of intervention providers; the charts of patients of control providers received no reminder. MEASUREMENTS AND MAIN RESULTS: During the 5-month study period, 346 patients were seen by the 36 primary care providers (staff physicians, nurse practitioners, residents, and fellows) in the intervention group, and 373 patients were seen by the 35 providers in the control group, Intervention providers changed 39 patients (11.3%) to other medications during the study period, compared with 1 patient (<1.0%) of control providers (p < .0001). For patients whose therapy was unchanged, providers noted angina in 23.1%, indications other than those for hypertension in 9.5%, intolerable adverse effects with first-line therapy in 13.9%, and inadequate control with first-line therapy in 13.9%. Of those patients without provider-indicated contraindications, 23.6% were switched from calcium channel blockers to first-line agents during the intervention period. CONCLUSIONS: The use of a computerized, clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general, and decreased the use of calcium channel blockers for the treatment of hypertension in particular. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,HLTH SERV RES & DEV,SEATTLE,WA. NR 18 TC 51 Z9 51 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 1997 VL 12 IS 11 BP 672 EP 678 DI 10.1046/j.1525-1497.1997.07140.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA YF246 UT WOS:A1997YF24600003 PM 9383135 ER PT J AU Hajjar, RJ DiSalvo, TG Schmidt, U Thaiyananthan, G Semigran, MJ Dec, GW Gwathmey, JK AF Hajjar, RJ DiSalvo, TG Schmidt, U Thaiyananthan, G Semigran, MJ Dec, GW Gwathmey, JK TI Clinical correlates of the myocardial force-frequency relationship in patients with end-stage heart failure SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID FAILING HUMAN MYOCARDIUM; DILATED CARDIOMYOPATHY; SARCOPLASMIC-RETICULUM; EXERCISE CAPACITY; EXPRESSION; TRANSPLANTATION; PHOSPHOLAMBAN; CA2+-ATPASE; RESERVE; MODEL AB Background: This study tested the hypothesis that in patients with suspected heart failure, peak oxygen consumption was the best predictor of heart muscle failure. Failing human myocardium is characterized by an abnormal force-frequency relationship, which has been previously shown to be altered in parallel with the severity of heart failure. Methods: We examined whether seven different functional parameters of isolated electrically driven ventricular trabeculae carneae obtained from 34 explanted hearts of patients undergoing heart transplantation for end-stage heart failure correlated with any of 47 separate pretransplantation clinical parameters. The functional muscle parameters were active force at 0.33 Hz, time to 80% relaxation (RT80%) of twitch force at 0.33 Hz, optimal frequency (OF), active force at 1.0 Hz (AF(1)), diastolic force at 1.0 Hz (DF1), active force at 2.0 Hz (AF(2)), and diastolic force at 2.0 Hz (DF2). Results: Before transplantation the mean left ventricular ejection fraction was 21% +/- 10%, and all patients were in New York Heart Association class III or IV. Mean peak whole body Vo(2) was 10.9 +/- 3.3 ml/min/kg and percent body mass/age/sex-adjusted maximum Vo(2) oxygen consumption was 34.7% +/- 10.4%. Univariate analysis of Vo(2) yielded the following significant correlations: active force at 33 Hz, RT80%, OF, AF(1), DF1, AF(2), DF2; whereas univariate analysis of percent body mass/age/sex-adjusted Vo(2) yielded the following significant correlations: RT80%, OF, DF1, AF(2), DF2. Multivariate analysis showed that OF and DF, were independent predictors of peak Vo(2). Conclusion: In this study we show that peak oxygen uptake measured during cardiopulmonary exercise testing obtained before transplantation is correlated with the force-frequency behavior of isolated muscles at the time of transplantation. Peak Vo(2) seems to be a strong indicator of the severity of cardiac contractile dysfunction inpatients with heart failure. J Heart Lung Transplant 1997. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [R01 HL 49574, R44 HL 52249] NR 36 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 1997 VL 16 IS 11 BP 1157 EP 1167 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA YJ035 UT WOS:A1997YJ03500010 PM 9402516 ER PT J AU Chaudhuri, A Orme, S Eilam, S Cherayil, BJ AF Chaudhuri, A Orme, S Eilam, S Cherayil, BJ TI CD40-mediated signals inhibit the binding of TNF receptor-associated factor 2 to the CD40 cytoplasmic domain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR RECEPTOR; KAPPA-B ACTIVATION; PROTEINS; FAMILY; DEATH; IDENTIFICATION; SUPERFAMILY; TRANSDUCERS; APOPTOSIS; REGION AB TNF receptor-associated factor 2 (TRAF2) is a signal-transducing protein associated with the CD40 cytoplasmic domain, It has been hypothesized that during signal transduction, TRAF2 must be released from CD40 in order for it to interact with downstream signaling molecules. We found that CD40 and TRAF2 were constitutively associated with each other in a human B cell line. Following stimulation with an anti-CD40 Ab, a decrease in the amount of CD40-associated TRAF2 was observed that could not be explained by a change in total level of either of the proteins, These results, as well as similar findings obtained with 293 cells overexpressing CD40 and TRAF2, suggested that CD40-mediated signals inhibited the CD40-TRAF2 interaction. We then conducted binding studies using CD40 cytoplasmic domain fusion proteins and TRAF2 derived from either control or CD40-stimulated cell lines, These in vitro studies also indicated that the binding of TRAF2 to the CD40 cytoplasmic domain was inhibited by CD40 stimulation. The results of these experiments, as well as differences between the in vitro and in vivo findings, indicated that multiple mechanisms were involved in the inhibition of the CD40-TRAF2 interaction by CD40 signals. Possible mechanisms of inhibition are discussed based on mapping of the TRAF2 binding site on the CD40 cytoplasmic domain. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp E, Pediat Gastroenterol Unit, Room 3303,Bldg 149,13th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIDDK NIH HHS [T-32-DK-07477] NR 25 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1997 VL 159 IS 9 BP 4244 EP 4251 PG 8 WC Immunology SC Immunology GA YW260 UT WOS:000071914500015 PM 9379019 ER PT J AU Karras, JG Wang, ZH Huo, L Frank, DA Rothstein, TL AF Karras, JG Wang, ZH Huo, L Frank, DA Rothstein, TL TI Induction of STAT protein signaling through the CD40 receptor in B lymphocytes - Distinct STAT activation following surface Ig and CD40 receptor engagement SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; EPIDERMAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; NUCLEAR EXPRESSION; PHOSPHOLIPASE C-GAMMA-2; INDUCED APOPTOSIS; GENE-EXPRESSION; CELLS; ANTIGEN; STIMULATION AB Cross-linking CD40 mediates B lymphocyte growth and differentiation and regulates cell death pathways by an unknown mechanism. Previous reports have suggested that protein tyrosine kinase activity is critical for CD40-mediated biologic responses. We show here that CD40 engagement on murine B cells results in the rapid tyrosine phosphorylation of the STAT6 transcription factor and the trans-activation of a reporter gene containing and IFN-regulatory factor-1 STAT-binding site. In earlier studies, surface Ig engagement was found to produce rapid activation of STAT6 accompanied by later induction of STAT1, which is not observed after CD40 ligation. Thus, these results define mitogenic receptor-specific induction of STAT proteins in B cells and identify a novel and direct signal transduction pathway from the cell surface to the nucleus activated in B cells stimulated through CD40 that regulates a gene previously shown to be involved in oncogenesis and programmed cell death. C1 Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Microbiol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Evans Mem Dept Clin Res, Boston, MA 02118 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Rothstein, TL (reprint author), Boston Univ, Med Ctr, Dept Med, Room E-556,88 E Newton St, Boston, MA 02118 USA. FU NCI NIH HHS [T32-CA64070-01]; NIAID NIH HHS [T32-AI07309, AI29690] NR 51 TC 59 Z9 60 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1997 VL 159 IS 9 BP 4350 EP 4355 PG 6 WC Immunology SC Immunology GA YW260 UT WOS:000071914500027 PM 9379031 ER PT J AU Lamkhioued, B Renzi, PM Abi-Younes, S Garcia-Zepada, EA Allakhverdi, Z Ghaffar, O Rothenberg, MD Luster, AD Hamid, Q AF Lamkhioued, B Renzi, PM Abi-Younes, S Garcia-Zepada, EA Allakhverdi, Z Ghaffar, O Rothenberg, MD Luster, AD Hamid, Q TI Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MESSENGER-RNA EXPRESSION; CHEMOKINE RANTES; TISSUE EOSINOPHILIA; BRONCHIAL BIOPSIES; ACTIVATING FACTOR; GENE-EXPRESSION; HUMAN BASOPHILS; IN-VIVO; INTERLEUKIN-5 AB Presently, there is considerable evidence for the participation of eosinophils in the pathophysiology of human bronchial asthma, Although increased numbers of eosinophils are present in the airways and bronchoalveolar lavage (BAL) fluid of atopic asthmatics, the mechanisms responsible for their preferential accumulation are still largely unknown, Eotaxin is a chemokine that promotes the selective recruitment of eosinophils, We report that atopic asthmatic patients have high concentrations of eotaxin in BAL fluid and an increased expression of eotaxin mRNA and protein in the epithelium and submucosa of their airways when compared with normal controls, In the BAL cells from asthmatic patients, eotaxin immunoreactivity colocalized predominantly to macrophages (62.2%), with a lesser contribution from T cells (16.3%) and eosinophils (8.9%), BAL fluid from asthmatics contained chemotactic activity for eosinophils that was attributable in part to the presence of eotaxin, Moreover, eotaxin was more effective at inducing in vitro eosinophil chemotaxis when eosinophils were stimulated with IL-5 (a cytokine that enhances the effector capacity of mature eosinophils), These observations suggest that eotaxin contributes to the pathogenesis of asthma by the specific recruitment of eosinophils into the airways. C1 McGill Univ, Meakins Christie Labs, Montreal, PQ H2X 2P2, Canada. McGill Univ, Dept Med, Montreal, PQ H2X 2P2, Canada. McGill Univ, Dept Pathol, Montreal, PQ H2X 2P2, Canada. Univ Montreal, Notre Dame Hosp, LC Simard Res Ctr, Montreal, PQ H3C 3J7, Canada. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Hamid, Q (reprint author), McGill Univ, Meakins Christie Labs, 3626 St Urbain St, Montreal, PQ H2X 2P2, Canada. EM hamid@meakins.lan.mcgill.ca NR 47 TC 342 Z9 349 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1997 VL 159 IS 9 BP 4593 EP 4601 PG 9 WC Immunology SC Immunology GA YW260 UT WOS:000071914500057 PM 9379061 ER PT J AU Hellman, J Zanzot, EM Loiselle, PM Amato, SF Black, KM Ge, YM Kurnick, JT Warren, HS AF Hellman, J Zanzot, EM Loiselle, PM Amato, SF Black, KM Ge, YM Kurnick, JT Warren, HS TI Antiserum against Escherichia coli J5 contains antibodies reactive with outer membrane proteins of heterologous gram-negative bacteria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SALMONELLA-TYPHIMURIUM PORINS; ENDOTOXIN-ASSOCIATED PROTEIN; CROSS-REACTIVITY; RABBIT ANTISERA; ROUGH MUTANTS; OMPA PROTEIN; LIPID-A; LIPOPOLYSACCHARIDE; IMMUNIZATION; LIPOPROTEIN AB The binding of Ige in antiserum to Escherichia coli J5 to the surface of Enterobacteriaceae and to cell wall fragments released from serum-exposed bacteria was studied in a search for potentially protective epitopes other than lipopolysaccharide (LPS). IgG titers to multiple heterologous gramnegative smooth bacteria increased following incubation of the bacteria in serum and decreased following absorption with serum-exposed heterologous bacteria. IgG eluted from absorbing bacteria bound to at least three conserved bacterial outer membrane proteins (OMPs), but not LPS, as assessed by immunoblotting. The same OMPs were present in LPS-containing macromolecular cell wall fragments released by incubation of heterologous gram-negative bacteria in human serum. Part of the protection offered by J5 antiserum could be from binding of IgG to conserved OMPs at the bacterial surface or to OMPs in cell-wall fragments released from dying bacteria. C1 MASSACHUSETTS GEN HOSP,DEPT INFECT DIS,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,CHARLESTOWN,MA 02129. RP Hellman, J (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,DEPT ANESTHESIA & CRIT CARE,5TH FLOOR,149 13TH ST,CHARLESTOWN,MA 02129, USA. NR 50 TC 26 Z9 26 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1997 VL 176 IS 5 BP 1260 EP 1268 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YD809 UT WOS:A1997YD80900019 PM 9359727 ER PT J AU Ge, YM Ezzell, RM Clark, BD Loiselle, PM Amato, SF Warren, HS AF Ge, YM Ezzell, RM Clark, BD Loiselle, PM Amato, SF Warren, HS TI Relationship of tissue and cellular interleukin-1 and lipopolysaccharide after endotoxemia and bacteremia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACTERIAL LIPOPOLYSACCHARIDES; ESCHERICHIA-COLI; GENE-EXPRESSION; MACROPHAGES; KINETICS; INVITRO; CELLS; LOCALIZATION; SUPPRESSES AB Distributions of immunoreactive interleukin-l (IL-1) and lipopolysaccharide (LPS) were studied in the tissues of rats after intravenous injection of purified LPS or live Escherichia coli bacteria. IL-1 staining in the spleen peaked at 4-8 h, colocalized with LPS in marginal zone macrophages, and was undetectable 24 h after injection, whereas LPS staining peaked at 24 h and was detectable for 4 weeks, The tissue IL-1 response was similar for LPS and live bacteria. Thus, tissue IL-1 is downregulated within hours despite maintenance of LPS in the same cells for weeks, Macrophages in liver and lung had only slight IL-1 staining despite intense staining for LPS. Tissue IL-1 production appears to be differentially regulated after gram-negative bacteremia; LPS cleared by liver and lung macrophages elicit minimal IL-1, whereas there is high local IL-1 production in the marginal zone of the spleen that may increase immune responses to bacterial wall antigens. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,INFECT DIS UNIT,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT SURG,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT MED,CHARLESTOWN,MA 02129. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT PEDIAT,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. TUFTS UNIV,SCH MED,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. FU NIAID NIH HHS [AI-28943]; NIGMS NIH HHS [GM-21700, GM-50766] NR 43 TC 32 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1997 VL 176 IS 5 BP 1313 EP 1321 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YD809 UT WOS:A1997YD80900025 PM 9359733 ER PT J AU Sheridan, RL Prelack, K Szyfelbein, SK AF Sheridan, RL Prelack, K Szyfelbein, SK TI Neuromuscular blockade does not decrease oxygen consumption or energy expenditure beyond sedation in the mechanically ventilated child SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article ID TOTAL PARENTERAL-NUTRITION; CRITICALLY ILL PATIENTS; INTENSIVE-CARE UNIT; RESPIRATORY SYSTEM; MUSCLE-RELAXANTS; BLOCKING-AGENTS; NATIONAL SURVEY; PARALYSIS; INFANTS; ANESTHESIA AB Minimizing the high oxygen consumption and energy expenditure of the critically ill is an important therapeutic goal. This study was done to determine if neuromuscular blockade decreases oxygen consumption or energy expenditure more than sedation alone in the mechanically ventilated child. Twelve burned children, with an average age of 5.1 +/- 1.6 yrs, average weight of 22.8 +/- 6.5 kg, and average burn size of 28.3 +/- 5.8% of the body surface, scheduled for a planned surgical procedure under general anesthesia were enrolled in this prospective self-controlled study In conjunction with planned operative procedures and using an intravenous anesthetic technique, the children underwent expired gas collection before and after neuromuscular block ade was induced. Expired gas was collected and analyzed for the fractional concentration of oxygen and carbon dioxide. oxygen consumption (VO2), carbon dioxide production (VCO2), energy expenditure (EE), and respiratory quotient (RQ) were calculated. We found no significant difference in EE, VO2, VCO2, or RQ between the well-sedated and mechanically ventilated and the well-sedated, mechanically ventilated and paralyzed states. We therefore concluded that neuromuscular blockade does not decrease energy expenditure in the otherwise well-sedated burned child. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02138. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP Sheridan, RL (reprint author), SHRINERS BURN INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. NR 34 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD NOV-DEC PY 1997 VL 12 IS 6 BP 321 EP 323 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA YE675 UT WOS:A1997YE67500006 ER PT J AU Morrison, DA Barbiere, C AF Morrison, DA Barbiere, C TI Evolving picture of high risk coronary artery intervention SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article ID PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; REFRACTORY UNSTABLE ANGINA; CARDIOGENIC-SHOCK; SURGERY; IMMEDIATE RP Morrison, DA (reprint author), DENVER VAMC,CARDIOL SECT,1055 CLERMONT ST,DENVER,CO 80020, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD NOV-DEC PY 1997 VL 9 IS 9 BP 593 EP 600 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YJ090 UT WOS:A1997YJ09000007 ER PT J AU Gu, L Rutledge, B Fiorillo, J Ernst, C Grewal, I Flavell, R Gladue, R Rollins, B AF Gu, L Rutledge, B Fiorillo, J Ernst, C Grewal, I Flavell, R Gladue, R Rollins, B TI In vivo properties of monocyte chemoattractant protein-1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE chemokine; transgenic mice ID HISTAMINE-RELEASING FACTOR; T-LYMPHOCYTES; CHEMOTACTIC PROTEIN-1; SECRETORY PROTEIN; ENDOTHELIAL-CELLS; ACTIVATING FACTOR; GROWTH-FACTOR; GENE ENCODES; EXPRESSION; MIGRATION AB Monocyte chemoattractant protein-1 (MCP-1) attracts monocytes, memory T lymphocytes, and natural killer (NK) cells in vitro, Its expression has been documented in disorders characterized by mononuclear cell infiltrates, suggesting that it may contribute to the inflammatory component of such diseases as atherosclerosis, multiple sclerosis, or rheumatoid arthritis, To prove a causal association, the in vivo properties of MCP-1 must be understood, Several lines of transgenic mice have been constructed to address this question, A transgenic line in which MCP-1 expression is controlled by the MMTV-LTR expressed high levels of MCP-1 in multiple organs but showed no evidence for monocyte infiltration, Instead, these mice were more susceptible to infection by the intracellular pathogens, Listeria monocytogenes and Mycobacterium tuberculosis, These mice had high serum levels of MCP-1, suggesting that their circulating monocytes may have been desensitized or that MCP-1 stimulated a Th2-dominant response, In contrast, another model in which MCP-1 expression was controlled by the insulin promoter demonstrated a monocytic infiltrate in pancreatic islets, These results indicate that MCP-1 expression at low levels in an anatomically confined area results in monocyte infiltration, suggesting that when properly expressed, MCP-1's in vitro properties are reproduced in vivo, This justifies the examination of MCP-1-deficient mice in disease models in order to explore MCP-1's role in pathogenesis. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT ADULT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. PFIZER INC,PFIZER CENT RES,GROTON,CT 06340. FU NCI NIH HHS [CA53091] NR 32 TC 112 Z9 115 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1997 VL 62 IS 5 BP 577 EP 580 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YF500 UT WOS:A1997YF50000005 PM 9365111 ER PT J AU Luster, AD Rothenberg, ME AF Luster, AD Rothenberg, ME TI Role of the monocyte chemoattractant protein and eotaxin subfamily of chemokines in allergic inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokines; gene targeting; gene structure; receptor usage; asthma ID CD4+ LYMPHOCYTES-T; FUNCTIONAL EXPRESSION; CC-CHEMOKINE; MOLECULAR-CLONING; EOSINOPHIL ACCUMULATION; CHEMOTACTIC PROTEIN-3; GROWTH-FACTOR; PULMONARY EOSINOPHILIA; POTENT ACTIVATOR; MESSENGER-RNA AB Allergic inflammation is characterized by the tissue accumulation and activation of leukocytes rich in eosinophils, During these responses, there is marked induction of specific chemokines that are involved in regulating the recruitment and activation of these inflammatory cells, A subfamily of CC (or beta) chemokines composed of macrophage chemoattractant proteins (MCP) and eotaxin have emerged as cytokines involved in the recruitment and activation of the cells seen in allergic reactions, We now show that these chemokines are strikingly related in chromosomal location, gene structure, primary protein sequence, biological activity, and receptor usage, We also show that these chemokines are differentially regulated in human and animal models of allergic disease and perform distinct roles in vivo. We propose that this subfamily of chemokines plays a fundamental role in the development of allergic responses. C1 CHILDRENS HOSP,MED CTR,DEPT PEDIAT,DIV PULM MED ALLERGY & IMMUNOL,CINCINNATI,OH 45229. HARVARD UNIV,SCH MED,DEPT MED,MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,CHARLESTOWN,MA. FU NCI NIH HHS [R01-CA69212]; NIAID NIH HHS [R01-AI40618] NR 84 TC 111 Z9 112 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1997 VL 62 IS 5 BP 620 EP 633 PG 14 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YF500 UT WOS:A1997YF50000011 PM 9365117 ER PT J AU Quackenbush, EJ Aguirre, V Wershil, BK GutierrezRamos, JC AF Quackenbush, EJ Aguirre, V Wershil, BK GutierrezRamos, JC TI Eotaxin influences the development of embryonic hematopoietic progenitors in the mouse SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE embryogenesis; mast cells; CCR-3; hematopoiesis ID STEM-CELLS; IDENTIFICATION; EXPRESSION; ANTIGEN; CIRCULATION; CLONING; LINEAGE; FAMILY; FETAL AB Eotaxin is a potent chemoattractant for eosinophils during inflammation and allergic reactions in the adult, but its role during development has not been studied. We report that eotaxin and its receptor, CCR-3, are expressed by embryonic tissues responsible for blood development, including the yolk sac, fetal Liver, and fetal blood, We also found that eotaxin acts synergistically with stem cell factor (SCF) to accelerate the differentiation of embryonic mast cell progenitors and to promote the growth of Mac-1(+)/Gr-1(-) cells from progenitors isolated at 10-12 days of gestation, This response is diminished by Pertussis toxin, the G(i alpha) inhibitor, These studies suggest that eotaxin is involved in the growth of myeloid cell progenitors and the differentiation of mast cells during embryogenic development. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP,DIV CLIN GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,CAMBRIDGE,MA. BETH ISRAEL DEACONESS MED CTR,BOSTON,MA. MILLENIUM PHARMACEUT INC,CAMBRIDGE,MA. RP Quackenbush, EJ (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,200 LONGWOOD AVE,ROOM 260,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK46819, DK33506]; NIGMS NIH HHS [T32GM07748] NR 26 TC 23 Z9 24 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1997 VL 62 IS 5 BP 661 EP 666 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YF500 UT WOS:A1997YF50000015 PM 9365121 ER PT J AU Lloyd, CM Dorf, ME Proudfoot, A Salant, DJ GutierrezRamos, JC AF Lloyd, CM Dorf, ME Proudfoot, A Salant, DJ GutierrezRamos, JC TI Role of MCP-1 and RANTES in inflammation and progression to fibrosis during murine crescentic nephritis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE proteinuria; tissue damage; renal function ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; GLOMERULONEPHRITIS; MACROPHAGE; EXPRESSION; CELLS; BETA AB The involvement of chemokines inflammation is well established but their functional role in disease progression, and particularly in the development of fibrosis, is not yet understood, We have investigated the functional role that the chemokines monocyte chemotactic protein-1 (MCP-1) and RANTES play in inflammation and the progression to fibrosis during crescentic nephritis, During this disease inflammatory infiltrates are observed within glomeruli and interstitium in conjunction with increased expression of MCP-1 and RANTES and a decrease in renal function. Disease progression is marked by formation of glomerular crescents and the deposition of type I collagen, Blocking the function of MCP-1 or RANTES resulted in significant decreases in proteinuria as well as numbers of infiltrating leukocytes, indicating that both MCP-1 and RANTES play an important role in the inflammatory phase of crescentic nephritis, In particular, neutralization of MCP-1, but not RANTES, resulted in a dramatic decrease in glomerular crescent formation and deposition of type I collagen. These results highlight a novel role for MCP-1 in crescent formation and development of interstitial fibrosis and indicate that in addition to recruiting inflammatory cells this chemokine is critically involved in irreversible tissue damage. C1 MILLENNIUM PHARMACEUT INC,CAMBRIDGE,MA 02139. BOSTON UNIV,MED CTR,DEPT MED,BOSTON,MA. CTR BLOOD RES INC,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. GLAXO INST MOL BIOL SA,CH-1211 GENEVA,SWITZERLAND. FU NHLBI NIH HHS [HL148675-02]; NIDDK NIH HHS [DK30932]; Wellcome Trust [087618] NR 18 TC 75 Z9 77 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1997 VL 62 IS 5 BP 676 EP 680 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA YF500 UT WOS:A1997YF50000017 PM 9365123 ER PT J AU Ferrante, RJ Browne, SE Shinobu, LA Bowling, AC Baik, MJ MacGarvey, U Kowall, NW Brown, RH Beal, MF AF Ferrante, RJ Browne, SE Shinobu, LA Bowling, AC Baik, MJ MacGarvey, U Kowall, NW Brown, RH Beal, MF TI Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amyotrophic lateral sclerosis; neurodegeneration; free radicals; oxidative damage; superoxide dismutase ID SUPEROXIDE-DISMUTASE GENE; MOTOR-NEURON DISEASE; GLUTATHIONE-PEROXIDASE ACTIVITIES; HEME OXYGENASE-1 HO-1; LIPID-PEROXIDATION; TRANSGENIC MICE; SOD1 MUTATION; SPINAL-CORD; RAT-BRAIN; PROTEIN AB Some cases of autosomal dominant familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), suggesting that oxidative damage may play a role in ALS pathogenesis. To further investigate the biochemical features of FALS and sporadic ALS (SALS), we examined markers of oxidative damage to protein, lipids, and DNA in motor cortex (Brodmann area 4), parietal cortex (Brodmann area 40), and cerebellum from control subjects, FALS patients with and without known SOD mutations, SALS patients, and disease controls (Pick's disease, progressive supranuclear palsy, diffuse Lewy body disease). Protein carbonyl and nuclear DNA 8-hydroxy-2'-deoxyguanosine (OH(8)dG) levels were increased in SALS motor cortex but not in FALS patients, Malondialdehyde levels showed no significant changes, Immunohistochemical studies showed increased neuronal staining for hemeoxygenase-1, malondialdehyde-modified protein, and OH(8)dG in both SALS and FALS spinal cord. These studies therefore provide further evidence that oxidative damage may play a role in the pathogenesis of neuronal degeneration in both SALS and FALS. C1 MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES LAB,NEUROL SERV,BOSTON,MA 02114. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. VET ADM MED CTR,GERIATR RES EDUC CLIN CTR,BEDFORD,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [P01 AG12992, P01 AG11337, P01 AG13846] NR 60 TC 498 Z9 506 U1 4 U2 17 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1997 VL 69 IS 5 BP 2064 EP 2074 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YC168 UT WOS:A1997YC16800033 PM 9349552 ER PT J AU Edgar, MAN Pasinelli, P DeWit, M Anton, B Dokas, LA Pastorino, L DiLuca, M Cattabeni, F Gispen, WH DeGraan, PNE AF Edgar, MAN Pasinelli, P DeWit, M Anton, B Dokas, LA Pastorino, L DiLuca, M Cattabeni, F Gispen, WH DeGraan, PNE TI Phosphorylation of the casein kinase II domain of B-50 (GAP-43) in rat cortical growth cones SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE B-50/GAP-43; casein kinase II; growth cones; phosphorylation ID LONG-TERM POTENTIATION; PROTEIN-KINASE; CALMODULIN-BINDING; OKADAIC ACID; C SUBSTRATE; POLYPHOSPHOINOSITIDE METABOLISM; NORADRENALINE RELEASE; NEUROMODULIN GAP-43; HIPPOCAMPAL SLICES; PLASMA-MEMBRANES AB Growth-associated phosphoprotein B-50 is a neural protein kinase C (PKC) substrate enriched in nerve growth cones that has been implicated in growth cone plasticity. Here we investigated whether B-50 is a physiological substrate for casein kinase II (CKII) in purified rat cortical growth cone preparations. Using site-specific proteolysis and known modulators of PKC, in combination with immunoprecipitation, mass spectrometry, and phosphoamino acid analysis, we demonstrate that endogenous growth cone B-50 is phosphorylated at multiple sites, on both serine and threonine residues. Consistent with previous reports, stimulation of PKC activity increased the phosphorylation of only those proteolytic fragments containing Ser(41). Under basal conditions, however, phosphorylation was predominantly associated with fragments not containing Ser(41). Mass spectrometry of tryptic digests of B-50, which had been immunoprecipitated from untreated growth cones, revealed that in situ phosphorylation occurs within peptides B-50(181-198) and B-50(82-98). These peptides contain the major and minor in vitro CKII phosphosites, respectively. In addition, cyanogen bromide digestion of immunoprecipitated chick 8-50 generated a 4-kDa C-terminal B-50 phosphopeptide, confirming that phosphorylation of the CKII domain occurs across evolutionary diverse species. We conclude that B-50 in growth cones is not only a substrate for PKC, but also for CKII. C1 UNIV UTRECHT, DEPT MED PHARMACOL, RUDOLF MAGNUS INST NEUROSCI, NL-3508 TA UTRECHT, NETHERLANDS. MED COLL OHIO, DEPT MED, TOLEDO, OH 43699 USA. MED COLL OHIO, DEPT BIOCHEM & MOL BIOL, TOLEDO, OH 43699 USA. MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, CHARLESTOWN, MA USA. NEW ENGLAND BIOLABS INC, BEVERLY, MA 01915 USA. UNIV MILAN, INST PHARMACOL SCI, I-20122 MILAN, ITALY. RI DiLuca, Monica/A-7632-2012 OI DiLuca, Monica/0000-0003-2298-615X FU NINDS NIH HHS [NS30792] NR 55 TC 11 Z9 11 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1997 VL 69 IS 5 BP 2206 EP 2215 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YC168 UT WOS:A1997YC16800049 PM 9349568 ER PT J AU Marvizon, JCG Martinez, V Grady, EF Bunnett, NW Mayer, EA AF Marvizon, JCG Martinez, V Grady, EF Bunnett, NW Mayer, EA TI Neurokinin 1 receptor internalization in spinal cord slices induced by dorsal root stimulation is mediated by NMDA receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C-fibers; central sensitization; dorsal horn; glutamate receptor; internalization; LTP; NK1 receptor; NMDA receptor; slices; substance P ID LONG-TERM POTENTIATION; IMMUNOREACTIVE SUBSTANCE-P; HORN NOCICEPTIVE NEURONS; EXCITATORY AMINO-ACIDS; C-FIBER; RAT; GLUTAMATE; PHARMACOLOGY; ENDOCYTOSIS; TACHYKININS AB The excitability of spinal neurons that transmit pain is modulated by glutamate and substance P (SP). Glutamate is an excitatory neurotransmitter in the dorsal horn, and its effects are enhanced by SP acting on neurokinin 1 receptors (NK1Rs). We assessed activation of NK1Rs by studying their internalization in spinal cord slices. NK1Rs were localized in sections from the slices by using immunohistochemistry combined with fluorescence and confocal microscopy. Incubating the slices with SP induced internalization in most NK1R-positive neurons in laminae I, IIo, and X and in half of NK1R-positive neurons in laminae III-V. SP-induced internalization was abolished by the specific NK1R antagonist L-703,606 (1 mu M). Stimulating the dorsal root with long-duration (0.4 msec) pulses evoked EPSPs in dorsal horn neurons with latencies consistent with the conduction speed of A partial derivative- and C-fibers. High-frequency (100 Hz) stimulation of the dorsal root with these pulses induced NK1R internalization in neurons in laminae I-IIo of the stimulated side of the slice but not in the contralateral side or in other laminae. Stimulation at lower frequencies (1 and 10 Hz) failed to elicit significant internalization, suggesting that the release of SP is frequency-dependent. Internalization produced by the 100 Hz tetanus was mimicked by NMDA and blocked by an NMDA antagonist, 2-amino-5-phosphonopentanoic acid, but not by the AMPA and kainate antagonist CNQX. The NK1R antagonist L-703,606 abolished the internalization produced by 100 Hz stimulation or NMDA. Therefore, the release of SP in the dorsal horn appears to be controlled by NMDA receptors. C1 UNIV CALIF LOS ANGELES,DEPT PHYSIOL,LOS ANGELES,CA 90073. UNIV CALIF SAN FRANCISCO,DEPT SURG,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. RP Marvizon, JCG (reprint author), UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,NEUROENTER DIS PROGRAM,DEPT MED,LOS ANGELES,CA 90073, USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK40919, DK43207, DK48351] NR 43 TC 137 Z9 139 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1997 VL 17 IS 21 BP 8129 EP 8136 PG 8 WC Neurosciences SC Neurosciences & Neurology GA YC947 UT WOS:A1997YC94700007 PM 9334388 ER PT J AU Kwon, YK Bhattacharyya, A Alberta, JA Giannobile, WV Cheon, KW Stiles, CD Pomeroy, SL AF Kwon, YK Bhattacharyya, A Alberta, JA Giannobile, WV Cheon, KW Stiles, CD Pomeroy, SL TI Activation of erbB2 during Wallerian degeneration of sciatic nerve SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuregulin; erbB2; receptor tyrosine kinase; Schwann cell; Wallerian degeneration; phosphotyrosine ID GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION PATHWAYS; SCHWANN-CELLS; NEUREGULIN RECEPTOR; CARDIAC DEVELOPMENT; NEU-ONCOGENE; ARIA; SHC; AUTOPHOSPHORYLATION; HETERODIMERIZATION AB We used anti-phosphopeptide-immunodetecting antibodies as immunohistochemical reagents to define the location and activity state of p185(erbB2) during Wallerian degeneration. Nerve damage induces a phosphorylation event at Y1248, a site that couples p185(erbB2) to the Ras-Raf-MAP kinase signal transduction pathway. Phosphorylation of p185(erbB2) occurs within Schwann cells and coincides in time and space with Schwann cell mitotic activity, as measured by bromodeoxyuridine uptake. These visual images of receptor autophosphorylation link activation of p185(erbB2) to the Schwann cell proliferation that accompanies nerve regeneration. C1 KYUNGHEE UNIV,COLL ARTS & SCI,DEPT BIOL,SEOUL 130701,SOUTH KOREA. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOL GENET,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT PERIODONTOL,BOSTON,MA 02115. OI Giannobile, William/0000-0002-7102-9746 FU NICHD NIH HHS [HD18655, HD24926]; NINDS NIH HHS [NS27773] NR 36 TC 61 Z9 61 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1997 VL 17 IS 21 BP 8293 EP 8299 PG 7 WC Neurosciences SC Neurosciences & Neurology GA YC947 UT WOS:A1997YC94700023 PM 9334404 ER PT J AU Ring, D Jupiter, JB Sanders, RW Mast, J Simpson, NS AF Ring, D Jupiter, JB Sanders, RW Mast, J Simpson, NS TI Transolecranon fracture-dislocation of the elbow SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE comminution; dislocation; elbow; olecranon; trochlear notch; ulna AB Objective: To characterize the prevalence, morphology, and prognosis of anterior (transolecranon) fracture-dislocations of the elbow. Design: Retrospective case series. Setting: A consecutive series of thirteen patients from a single level-one trauma center, plus four patients from the practices of two of the senior authors. Patients: Three of seventeen patients had simple, oblique fractures of the olecranon, and fourteen had complex, comminuted fractures of the proximal ulna, including fragmentation of the olecranon in seven patients, large coronoid fragments in eight patients, and segmental fractures of the ulna in six patients. Fourteen patients were male and three were female, with an average age of thirty-eight years (range, 18 to 78 years). Intervention: All fractures were treated by open reduction and internal fixation. Two one-third tubular plates had to be revised to 3.5-millimeter dynamic compression plates within six weeks of the initial operation. Main Outcome Measure: Elbow performance rating of Broberg and Morrey. Results: At an average follow-up of twenty-five months, overall outcome was rated as excellent in seven patients, good in eight, and fair in two. Mild posttraumatic arthritis was noted in only two patients. Large coronoid fragments and extensive comminution of the trochlear notch did not preclude a good result provided that stable, anatomic fixation was achieved. Conclusions: Anterior elbow dislocations occur most often as a fracture-dislocation in which the distal humerus is driven through the olecranon, thereby causing a complex, comminuted fracture of the proximal ulna. This injury is frequently confused with anterior Monteggia lesions by virtue of the readily apparent radiocapitellar dislocation. Stable restoration of the appropriate contour and dimensions of the trochlear notch of the ulna will lead to a good result in most cases. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tampa Gen Hosp, Tampa, FL 33606 USA. Wayne State Univ, Sch Med, Detroit, MI USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 39 TC 77 Z9 85 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV PY 1997 VL 11 IS 8 BP 545 EP 550 DI 10.1097/00005131-199711000-00001 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA YQ621 UT WOS:000071406200001 PM 9415859 ER PT J AU DunussiJoannopoulos, K Weinstein, HJ Arceci, RJ Croop, JM AF DunussiJoannopoulos, K Weinstein, HJ Arceci, RJ Croop, JM TI Gene therapy with B7.1 and GM-CSF vaccines in a murine AML model SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE gene therapy; B7; GM-CSF; AML; murine models ID TUMOR-IMMUNITY; T-CELLS; ANTITUMOR IMMUNITY; MELANOMA-CELLS; ANTIGEN; COSTIMULATION; TUMORIGENICITY; LEUKEMIA; POTENT; INVIVO AB Purpose: Characterization of B7.1 and GM-CSF vaccines on the induction of anti-tumor immunity in a murine AML model. Materials and Methods: Primary AML cells were retrovirally transduced with the murine costimulatory molecule B7.1, a natural ligand for the T-cell receptors CD28 and CTLA-4, or the cytokine GM-CSF. Mice were vaccinated with irradiated AML cells expressing B7.1 or GM-CSF before or after inoculation of wild type AML cells. Results: Intravenous injection of irradiated B7.1 or GM-CSF expressing AML cells can provide long lasting systemic immunity against a subsequent challenge of wild type AML cells. Vaccination with irradiated B7.1 or GM-CSF expressing AML cells results in rejection of established leukemia when the vaccination occurs in the early stages of the disease. However, when the vaccines are administered >2 weeks after leukemic inoculation, only mice which receive the GM-CSF vaccine are cured of leukemia. Conclusions: These results suggest that tumor burden and vaccine efficiency are most likely to be the limiting factors in the curative potential of tumor vaccines. Novel approaches such as this experiment could provide improved therapeutic outcomes in patients with AML and other cancers. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CHILDRENS HOSP,DIV PEDIAT ONCOL,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,MED CTR,DIV HEMATOL ONCOL,CINCINNATI,OH 45229. NR 27 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV-DEC PY 1997 VL 19 IS 6 BP 536 EP 540 DI 10.1097/00043426-199711000-00012 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA YK292 UT WOS:A1997YK29200012 PM 9407942 ER PT J AU Jacobson, AM Hauser, ST Willett, J Wolfsdorf, JI Herman, L AF Jacobson, AM Hauser, ST Willett, J Wolfsdorf, JI Herman, L TI Consequences of irregular versus continuous medical follow-up in children and adolescents with insulin-dependent diabetes mellitus SO JOURNAL OF PEDIATRICS LA English DT Article ID METABOLIC CONTROL; ADHERENCE; IDDM; REGIMENS AB Objectives: To study the social and family characteristics of patients with insulin-dependent diabetes mellitus with irregular versus continuous clinical follow-up and to study the medical outcomes of patients with these follow-up patterns. Methods: An onset cohort of 61 children and adolescents with insulin-dependent diabetes mellitus and their parents were studied. Aspects of their social and family environment were assessed at study inception and examined in relation to frequency of follow-up early in the course of the illness. Follow-up was dichotomized so that patients with continuous follow-up were compared with patients with irregular follow-up, who were defined as those missing 1 full year of planned medical appointments during the second through fourth years after diagnosis. Patients with irregular and continuous follow-up were compared in terms of acute metabolic complications, glycemic control, and retinopathy status during a 10-year period. Results: Compared with individuals with continuous follow-up, patients with irregular clinical visits were more likely to be from families of lower socioeconomic class levels, have a parental history of separation and divorce, and were members of families that reported being least openly expressive of positive emotions. Poor glycemic control in year 1 was associated with irregular follow-up in years 2 through 4. Patients with irregular follow-up continued to have worse glycemic control in years 2 through ii than patients with continuous follow-up. However, in years 7 and 10 their glycemic control no longer differed from patients with continuous follow-up. More episodes of diabetic ketoacidosis occurred in the irregular follow-up group. Finally, retinopathy occurred more frequently among those in the irregular follow-up group. Conclusion: Early irregular clinical follow-up should be considered a risk factor for complications of insulin-dependent diabetes mellitus. C1 HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, DEPT PEDIAT, BOSTON, MA 02215 USA. JUDGE BAKER CHILDRENS CTR, BOSTON, MA 02215 USA. HARVARD UNIV, GRAD SCH EDUC, BOSTON, MA 02115 USA. RP Jacobson, AM (reprint author), HARVARD UNIV, SCH MED, JOSLIN DIABET CTR, DEPT PSYCHIAT, 1 JOSLIN PL, BOSTON, MA 02215 USA. OI Willett, John/0000-0001-7183-350X FU NIDDK NIH HHS [DK27845]; NIMH NIH HHS [5K-02-MH70178] NR 24 TC 57 Z9 58 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 1997 VL 131 IS 5 BP 727 EP 733 DI 10.1016/S0022-3476(97)70101-X PG 7 WC Pediatrics SC Pediatrics GA YJ861 UT WOS:A1997YJ86100016 PM 9403654 ER PT J AU Ibebunjo, C Nosek, MT Itani, MS Martyn, JAJ AF Ibebunjo, C Nosek, MT Itani, MS Martyn, JAJ TI Mechanisms for the paradoxical resistance to d-tubocurarine during immobilization-induced muscle atrophy SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; GASTROCNEMIUS DISUSE ATROPHY; TIBIALIS MUSCLE; SKELETAL-MUSCLE; THERMAL-INJURY; UP-REGULATION; BURN INJURY; RATS; DENERVATION; SUCCINYLCHOLINE AB This study investigated whether immobilization-induced hyposensitivity to d-tubocurarine (dTC), up-regulation of acetylcholine receptors (AChRs) and changes in fiber size and motor endplate size persist indefinitely and whether they are causally related. Unilateral disuse of the tibialis muscle was produced in adult rats by pinning the knee and ankle joints at 90 degrees flexion. The contralateral unpinned and a separate group of sham-pinned legs served as controls. After 7, 14 or 28 days of disuse, the in vivo dose of dTC that produced 50% depression of nerve-evoked twitch (ED50) in the tibialis muscle increased 3.0-, 3.2- and 2.1-fold (P < .05), and membrane AChRs increased 6.0- (P < .05), 6.3- (P > .05) and 1.2-fold (P > .395) relative to control, respectively. Disuse caused muscle fiber atrophy (P < .01) but did not affect endplate size. Hence, the ratio of endplate size to fiber size increased. There was a transient increase in gene expression of all (including de novo expression of the gamma) subunits of the AChR, peaking at day 7 and returning to normal by day 28 of immobilization. The ED50 of dTC correlated directly with AChRs (R-2 = 0.51; P < .0001) or the ratio of endplate size to fiber size (R-2 = 0.30; P < .001), and inversely with fiber size (R-2 = 0.43, P < .0001). It is proposed that acting together, but not singly, the changes in AChRs, fiber size and relative endplate size contribute to the magnitude and time course of the resistance to dTC produced by chronic disuse. C1 MASSACHUSETTS GEN HOSP, DEPT ANESTHESIA, ANESTHESIA SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT ANESTHESIOL, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, SHRINERS BURNS INST, BOSTON, MA 02114 USA. FU NIGMS NIH HHS [GM 31569-14, GM 55082A] NR 36 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1997 VL 283 IS 2 BP 443 EP 451 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF254 UT WOS:A1997YF25400004 PM 9353356 ER PT J AU Suva, LJ Flannery, MS Caulfield, MP Findlay, DM Juppner, H Goldring, SR Rosenblatt, M Chorev, M AF Suva, LJ Flannery, MS Caulfield, MP Findlay, DM Juppner, H Goldring, SR Rosenblatt, M Chorev, M TI Design, synthesis and utility of novel benzophenone-containing calcitonin analogs for photoaffinity labeling the calcitonin receptor SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HORMONE (PTH)/PTH-RELATED PEPTIDE; PARATHYROID-HORMONE; SALMON-CALCITONIN; POSTMENOPAUSAL OSTEOPOROSIS; BIOLOGICAL-ACTIVITY; ADENYLATE-CYCLASE; CELL-LINE; EXPRESSION; EPITOPE; PROTEIN AB Calcitonin (CT) is a 32-amino-acid calciotropic peptide hormone which acts on target cells via a G protein-coupled seven-transmembrane receptor (CTR). In this study, we report the design, synthesis and characterization of four potent bioactive and photoreactive CT analogs, each of which contains a single benzophenone moiety inserted at different and discrete locations within the CT molecule. Replacement of all Lys residues in salmon CT (sCT) with Arg, followed by replacement of hydrophobic residues with a Lys(epsilon-p-benzoylbenzoyl) residue [Lys(epsilon-pBz(2))] was found to preserve high biological activity. We substituted Val(8), Leu(16) and Leu(19) by Lys(epsilon-pBz(2)), and acylated the N-terminus by a pBz(2) moiety, thus distributing the photoaffinity moiety in the different analogs across a large portion of the CT sequence. With both transfected and endogenous CTRs from several species, all four benzophenone-containing analogs were shown to be virtually indistinguishable from the parent sCT analog in both receptor binding properties and stimulation of cAMP accumulation. Upon photolysis, in the presence of CTR, the radioiodinated photoreactive CT analog {[Arg(11,18),Lys(19)(epsilon-pBz(2))]sCT (K19)} covalently labels a membrane component of approximately 70 kDa. Receptor crosslinking is inhibited specifically in the presence of excess sCT. We also examined the interaction of these CT analogs with a hemagglutinin (HA) epitope-tagged CTR. The HA-CTR displayed CT binding and CT-dependent cAMP stimulation identical with native CTR. Both K19 and another bioactive analog {[Arg(11,18),Lys(8)(epsilon-pBz(2))]sCT (K8)} specifically photoaffinity cross-link to the HA-CTR. These benzophenone-containing CT analogs should facilitate studies of hormone-receptor interactions and allow the direct identification of a CT binding domain(s) within the receptor by the analysis of photochemically cross-linked conjugates. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,ARTHRIT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. NICHOLS INST LABS,SAN JUAN CAPISTRANO,CA 92690. ST VINCENTS INST MED RES,FITZROY,VIC 3065,AUSTRALIA. RP Suva, LJ (reprint author), BETH ISRAEL DEACONESS MED CTR,DIV BONE & MINERAL METAB,HARVARD INST MED,BOSTON,MA 02215, USA. FU NIAMS NIH HHS [AR-03564]; NIDDK NIH HHS [DK-46773] NR 48 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 1997 VL 283 IS 2 BP 876 EP 884 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YF254 UT WOS:A1997YF25400057 PM 9353409 ER PT J AU Yellen, G AF Yellen, G TI Molecular physiology of the HERG K+ channel and the elusive h-channel SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 1997 VL 504P SI SI BP S12 EP S12 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA YJ424 UT WOS:A1997YJ42400331 ER PT J AU Cornish, JW Metzger, D Woody, GE Wilson, D McLellan, AT Vandergrift, B O'Brien, CP AF Cornish, JW Metzger, D Woody, GE Wilson, D McLellan, AT Vandergrift, B O'Brien, CP TI Naltrexone pharmacotherapy for opioid dependent federal probationers SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE naltrexone; opioid dependence; parole; probation; substance dependence ID FOLLOW-UP; HEROIN; EXPERIENCE; EFFICACY AB Federal probationers or parolees with a history of opioid addiction were referred by them selves or their probation/parole officer for a naltrexone treatment study. Participation was voluntary and subjects could drop out of the study at any time without adverse consequences. Following orientation and informed consent, 51 volunteers were randomly assigned in a 2:1 ratio to a 6-month program of probation plus naltrexone and brief drug counseling, or probation plus counseling alone. Naltrexone subjects received medication and counseling twice a week; controls received counseling at similar intervals. All therapy and medication were administered in an office located adjacent to the federal probation department. Fifty-two percent of subjects in the naltrexone group continued for 6 months and 33% remained in the control group. Opioid use was significantly lower in the naltrexone group. The overall mean percent of opioid positive urine tests among the naltrexone subjects was 8%, versus 30% for control subjects (p < .05). Fifty-six percent of the controls and 26% of the naltrexone group (p <.05) had their probation status revoked within the 6-month study period and rearmed to prison. Treatment with naltrexone and brief drug counseling call be integrated into the Federal Probation/Parole system with favorable results on both opioid use and re-arrest rates. (C) 1997 Elsevier Science Inc. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. United State Probat Off, Philadelphia, PA 19106 USA. RP Cornish, JW (reprint author), Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. RI Metzger, David/D-9499-2012 FU NIDA NIH HHS [DA05186] NR 23 TC 118 Z9 125 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD NOV-DEC PY 1997 VL 14 IS 6 BP 529 EP 534 DI 10.1016/S0740-5472(97)00020-2 PG 6 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA YP426 UT WOS:000071275600003 PM 9437624 ER PT J AU Wozniak, J Biederman, J Faraone, SV Frazier, J Kim, J Millstein, R Gershon, J Thornell, A Cha, K Snyder, JB AF Wozniak, J Biederman, J Faraone, SV Frazier, J Kim, J Millstein, R Gershon, J Thornell, A Cha, K Snyder, JB TI Mania in children with pervasive developmental disorder revisited SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; autism; comorbidity; children ID FAMILY HISTORY; AUTISM AB Objective: Although a smalt literature of case reports suggests that mania co-occurs with pervasive developmental disorder (PDD), little is known about this overlap. The authors systematically investigated the overlap between mania and PDD in a consecutive sample of referred youths, examining its prevalence and correlates. II was hypothesized that children with PDD plus manic features have both disorders. Method: Subjects were consecutively referred children meeting diagnostic criteria on structured interview far PDD without mania (n = 52), the comorbid condition PDD+mania (n = 14), and mania without PDD (n = 114). All subjects were evaluated using a comprehensive diagnostic battery that included assessment of psychopathology (structured diagnostic interview and Child Behavior Checklist), cognition, and functioning. Results: Of the 727 referred children, 52 met criteria for PDD, 114 met criteria for mania, and 14 met criteria for both. The 14 children with both PDD+mania represented 21% of the PDD subjects and 11% of all manic subjects. Clinical characteristics of PDD were similar in PDD subjects with and without mania, and manic features were similar in manic children with and without PDD. Conclusions: Children with PDD and mania may suffer from two disorders. Comorbid mania among patients with PDD may be more common than previously thought. Identification of the comorbid condition may have important therapeutic and scientific implications. RP Wozniak, J (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT PSYCHOPHARMACOL UNIT,CHILD PSYCHIAT SERV,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 12 TC 82 Z9 84 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 1997 VL 36 IS 11 BP 1552 EP 1559 DI 10.1016/S0890-8567(09)66564-3 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA YC340 UT WOS:A1997YC34000017 PM 9394940 ER PT J AU Ross, EV Grossman, MC Duke, D Grevelink, JM AF Ross, EV Grossman, MC Duke, D Grevelink, JM TI Long-term results after CO2 laser skin resurfacing: a comparison of scanned and pulsed systems SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CARBON-DIOXIDE LASER; CO2-LASER TISSUE ABLATION; THERMAL-DAMAGE; DERMABRASION; DURATION; WRINKLES; MODEL; INCISIONS; RHYTIDES; SURGERY AB Background: New laser technology permits the use of high-energy pulsed and continuous-wave carbon dioxide (CO2) lasers with flashscanners to treat rhytides. Objective: We compared the efficacy and side effects of the two leading CO2 lasers used in skin resurfacing. Methods: A total of 28 patients with facial rhytides were treated with either the UltraPulse or SilkTouch laser systems; in five additional patients, contralateral cosmetic units were treated with one system or the other in a direct comparison of the lasers. Results: We compared photographs taken before and after treatment, and a lessening of facial wrinkling was noted in all subjects. In some subjects improvement was confirmed by optical profilometry methods. Biopsy specimens in representative patients showed that immediate thermal damage was limited to 180 mu m. Long-term postoperative specimens showed changes in the papillary dermis consistent with new collagen deposition and reduction of pretreatment solar elastosis. Posttreatment facial erythema was noted in half the patients for up to 2 months; transient hyperpigmentation was observed in one third of the treated areas. Conclusion: Although the SilkTouch system produced more immediate thermal damage, there were no significant differences in efficacy or adverse effects between the lasers. Our results suggest that both laser systems, used with appropriate settings, are capable of safely smoothing the skin surface. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DERMATOL LASER CTR,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. LASER & SKIN SURG CTR,NEW YORK,NY. NR 39 TC 82 Z9 82 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 1997 VL 37 IS 5 BP 709 EP 718 DI 10.1016/S0190-9622(97)70106-3 PN 1 PG 10 WC Dermatology SC Dermatology GA YF084 UT WOS:A1997YF08400002 PM 9366815 ER PT J AU Drake, LA Shear, NH Arlette, JP Cloutier, R Danby, FW Elewski, BE GarnisJones, S Giroux, JM Gratton, D Gulliver, W Hull, P Jones, HE Journet, M Krol, AL Leyden, JJ Maddin, SC Ross, JB Savin, RC Scher, RK Sibbald, GR Tawfik, NH Zaias, N Tolpin, M Evans, S Marsolais, C Chin, T Lin, TH Maher, T Birnbaum, JE AF Drake, LA Shear, NH Arlette, JP Cloutier, R Danby, FW Elewski, BE GarnisJones, S Giroux, JM Gratton, D Gulliver, W Hull, P Jones, HE Journet, M Krol, AL Leyden, JJ Maddin, SC Ross, JB Savin, RC Scher, RK Sibbald, GR Tawfik, NH Zaias, N Tolpin, M Evans, S Marsolais, C Chin, T Lin, TH Maher, T Birnbaum, JE TI Oral terbinafine in the treatment of toenail onychomycosis: North American multicenter trial SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DERMATOPHYTE ONYCHOMYCOSIS; GRISEOFULVIN AB Background: Onychomycosis is an increasing problem with limited therapeutic options. Objective: We evaluated the safety and efficacy of oral terbinafine, a new fungicidal antimycotic, in patients with toenail onychomycosis. Methods: A North American multicenter, double-blind, placebo-controlled study evaluated the mycologic and clinical efficacy of oral terbinafine 250 mg/day for 12 or 24 weeks in 358 patients with toenail onychomycosis. Results: A total of 74% of patients treated with 12 or 24 weeks of terbinafine achieved a successful clinical outcome. Approximately 11% of terbinafine responders showed evidence of relapse 18 to 21 months after cessation of treatment. Terbinafine was well tolerated; most adverse events were transient and mild to moderate in severity. Conclusion: The results of this study confirm that oral terbinafine is a safe and effective therapy for the treatment of onychomycosis. C1 UNIV TORONTO,TORONTO,ON,CANADA. UNIV CALGARY,CALGARY,AB,CANADA. UNIV LAVAL,QUEBEC CITY,PQ,CANADA. QUEENS UNIV,KINGSTON,ON,CANADA. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. UNIV OTTAWA,OTTAWA,ON,CANADA. UNIV MONTREAL,MONTREAL,PQ,CANADA. UNIV SASKATCHEWAN,SASKATOON,SK,CANADA. MEM UNIV NEWFOUNDLAND,ST JOHNS,NF,CANADA. THOMAS HOSP,FAIRHOPE,AK. UNIV ALBERTA,EDMONTON,AB,CANADA. HOSP UNIV PENN,PHILADELPHIA,PA 19104. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. DALHOUSIE UNIV,HALIFAX,NS,CANADA. YALE NEW HAVEN MED CTR,NEW HAVEN,CT 06504. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY. UNIV TORONTO,MISSISSAUGA,ON L5L 1C6,CANADA. UNIV MANITOBA,WINNIPEG,MB,CANADA. MT SINAI MED CTR,MIAMI BEACH,FL 33140. NOVARTIS PHARMACEUT CORP,E HANOVER,NJ. RP Drake, LA (reprint author), MASSACHUSETTS GEN HOSP,DERMATOL BAR 604,40 BLOSSOM ST,BOSTON,MA 02114, USA. RI Danby, Frederick/F-3359-2014 OI Danby, Frederick/0000-0001-7648-5081 NR 15 TC 66 Z9 70 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 1997 VL 37 IS 5 BP 740 EP 745 DI 10.1016/S0190-9622(97)70111-7 PN 1 PG 6 WC Dermatology SC Dermatology GA YF084 UT WOS:A1997YF08400007 PM 9366820 ER PT J AU Rossen, RD AF Rossen, RD TI HMG-CoA reductase inhibitors: A new class of anti-inflammatory drugs? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID MEVALONATE PATHWAY; MACROPHAGES; CHOLESTEROL; RUPTURE; CELLS C1 BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP Rossen, RD (reprint author), HOUSTON VET AFFAIRS MED CTR,ROOM 147,BLDG 109,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 8 TC 19 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1997 VL 30 IS 5 BP 1218 EP 1219 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YD802 UT WOS:A1997YD80200011 PM 9350918 ER PT J AU Wright, CD Wain, JC Lynch, TJ Choi, NC Grossbard, ML Carey, RW Moncure, AC Grillo, HC Mathisen, DJ AF Wright, CD Wain, JC Lynch, TJ Choi, NC Grossbard, ML Carey, RW Moncure, AC Grillo, HC Mathisen, DJ TI Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: A phase I and II study SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-08, 1997 CL WASHINGTON, DC SP Amer Assoc Thorac Surg ID ADENOCARCINOMA; CARCINOMA; CHEMOTHERAPY; TAXOL AB Objective: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma, We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates, Methods: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m(2)) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor), The mean age was 62 years, and 32 patients (80%) had adenocarcinoma, Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater), Results: The average hospitalization for induction treatment was 17 days, Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication, The maximum tolerated dose of paclitaxel was 100 mg/m(2). Two patients died during induction treatment, Thirty-six patients (90%) underwent resection, The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response, Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076), The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months, Conclusions: Paclitaxel at a dose of 100 mg/m(2) appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival. C1 MASSACHUSETTS GEN HOSP,SECT MED ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SECT RADIOL ONCOL,BOSTON,MA 02114. RP Wright, CD (reprint author), MASSACHUSETTS GEN HOSP,THORAC SURG SECT,BLAKE 1570,BOSTON,MA 02114, USA. NR 9 TC 49 Z9 51 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1997 VL 114 IS 5 BP 811 EP 815 DI 10.1016/S0022-5223(97)70085-0 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA YG206 UT WOS:A1997YG20600024 PM 9375611 ER PT J AU Schomacker, KT Torri, A Sandison, DR Sheridan, RL Nishioka, NS AF Schomacker, KT Torri, A Sandison, DR Sheridan, RL Nishioka, NS TI Biodistribution of indocyanine green in a porcine born model: Light and fluorescence microscopy SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the American-Burn-Association CY MAR 14-17, 1996 CL NASHVILLE, TN SP Amer Burn Assoc DE burns; burn depth; indocyanine green; fluorescence microscopy; vascular permeability; vascular occlusion ID BURN DEPTH AB Background: Infrared-excited fluorescence of intravenously administered indocyanine green (ICG) is being used as a method of early determination of burn depth. Methods: Fluorescence microscopy and tissue fluorescence were recorded in a porcine burn model and correlated to burn severity and age. Results: Recently placed superficial burns show significant fluorescence compared with adjacent normal tissue as a result of a strong inflammatory reaction in the superficial dermis with minimal vascular occlusion. The magnitude of the inflammatory reaction decreases with time. For deeper burns, vascular occlusion prevents transport of ICG into the burn and the intensity of ICG fluorescence in burn eschar is negligible. Conclusion: The intensity of ICG fluorescence measured at the surface of the wound for burns of similar age was shown to decrease exponentially with the depth of the burn. The enhanced fluorescence of partial-thickness burns is attributable to increased permeability, and the decreased signal associated with deeper injuries is attributable to vascular occlusion. These results suggest that it is possible to differentiate burns that will heal spontaneously with minimal granulation from those that will not by measuring the intensity of ICG fluorescence. C1 MASSACHUSETTS GEN HOSP,MED SERV BURNS & TRAUMA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. SANDIA NATL LABS,ALBUQUERQUE,NM 87185. RP Schomacker, KT (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BAR703,55 FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 1997 VL 43 IS 5 BP 813 EP 819 DI 10.1097/00005373-199711000-00013 PG 7 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA YK523 UT WOS:A1997YK52300014 PM 9390494 ER PT J AU McDougal, WS AF McDougal, WS TI Long-term metabolic advantages of a gastrointestinal composite urinary reservoir - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material RP McDougal, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1997 VL 158 IS 5 BP 1707 EP 1708 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA XZ996 UT WOS:A1997XZ99600016 ER PT J AU Du, ZJ Ilyinskii, PO Lally, K Desrosiers, RC Engelman, A AF Du, ZJ Ilyinskii, PO Lally, K Desrosiers, RC Engelman, A TI A mutation in integrase can compensate for mutations in the simian immunodeficiency virus att site SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; VIRAL-DNA ENDS; REVERSE TRANSCRIPTION; PRODUCTIVE INFECTION; TYPE-1 INTEGRASE; IN-VITRO; POL GENE; DOMAIN; INITIATION; SEQUENCE AB Sequences at the left terminus of U3 in the left long terminal repeat (LTR) and at the right terminus of U5 in the right LTR are important for integration of retroviral DNA, In the infectious pathogenic molecular clone of simian immunodeficiency virus strain mac239 (SIVmac239), 10 of the 12 terminal base pairs form an imperfect inverted repeat structure (5' TGGAAGGGATTT 3' [nucleotides 1 to 12] and 3' ACGATCCCTAAA 5' [nucleotides 10279 to 10268]). Nineteen different mutant forms of SIVmac239 proviral DNA with changes at one or more of the positions in each of the 12-terminal-base-pair regions were constructed. Viral replication was severely or completely compromised with nine of these mutants, Revertants appeared 40 to 50 days after transfection in two independent experiments,vith mutant 7, which contained changes of AGG to TAC at positions 5 to 7 in U3 and TCC to GAA at positions 10275 to 10273 in U5, Virus produced at these times from mutant 7 transfection replicated upon reinfection with only a slight delay when compared to the wild type. Sequence analysis of the LTR and integrase regions from infected cultures revealed two predominant changes: G to A at position 10275 in U5 and Glu to Lys at position 136 in integrase, Derivatives of clone 7 in which these changes were introduced individually and together were constructed by site-specific mutagenesis, Each change individually restored replication capacity only partially, However, the combination of both mutations restored replicative capacity to that of the original revertants. These results indicate that changes in integrase can compensate for mutations in the terminal nucleotides of the SIV LTR. The results further indicate that resistance to integrase inhibitors may include both integrase and LTR mutations. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI25328, AI39394] NR 34 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1997 VL 71 IS 11 BP 8124 EP 8132 PG 9 WC Virology SC Virology GA YB143 UT WOS:A1997YB14300006 PM 9343162 ER PT J AU Margolin, DH Reimann, KA Sodroski, J Karlsson, GB TennerRacz, K Racz, P Letvin, NL AF Margolin, DH Reimann, KA Sodroski, J Karlsson, GB TennerRacz, K Racz, P Letvin, NL TI Immunoglobulin V-H usage during primary infection of rhesus monkeys with chimeric simian-human immunodeficiency viruses SO JOURNAL OF VIROLOGY LA English DT Article ID GENE FAMILY EXPRESSION; IN-VIVO; HIV-INFECTION; MONOCLONAL-ANTIBODIES; MOLECULAR CLONE; HOMOSEXUAL MEN; AIDS; REPERTOIRE; TYPE-1; V(H)3 AB It has been suggested that naive immunoglobulins encoded by the V(H)3 gene family interact aberrantly with human immunodeficiency virus type 1 (HIV-1) gp120 via a superantigenic epitope, causing initial expansion and eventual depletion of V(H)3-expressing B cells. However, this possibility has not been prospectively assessed during an AIDS virus infection, We determined V-H family usage in rhesus monkeys during primary infection with chimeric viruses expressing HIV-1 envelopes on a simian immunodeficiency virus (SIVmac) backbone (SHIVs), Four SHIVs with different envelopes and pathogenicities were studied, V-H family usage was prospectively assessed in peripheral blood mononuclear cells and lymph node cells of these monkeys by a semiquantitative PCR technique, In the first months following SHIV infection, a period of intense viral antigenemia, representation of various V-H families increased or decreased for individual monkeys, but no single V-H family was consistently altered, In particular, the average representation of V(H)3-bearing B lymphocytes did not change, This observation suggests that the envelope glycoprotein of HIV-1 does not selectively expand or deplete the V(H)3 repertoire of primate B cells during acute AIDS virus infection, contrary to predictions of the gp120 superantigen hypothesis. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02215. BERNHARD NOCHT INST TROP MED,KORBER LAB,D-20359 HAMBURG,GERMANY. BERNHARD NOCHT INST TROP MED,DEPT PATHOL,D-20359 HAMBURG,GERMANY. RP Margolin, DH (reprint author), BETH ISRAEL DEACONESS MED CTR,DIV VIRAL PATHOGENESIS,RE113,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-20729, AI-33832, AI-35478] NR 40 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1997 VL 71 IS 11 BP 8582 EP 8591 PG 10 WC Virology SC Virology GA YB143 UT WOS:A1997YB14300060 PM 9343216 ER PT J AU Cao, HY Kanki, P Sankale, JL DiengSarr, A Mazzara, GP Kalams, SA Korber, B Mboup, S Walker, BD AF Cao, HY Kanki, P Sankale, JL DiengSarr, A Mazzara, GP Kalams, SA Korber, B Mboup, S Walker, BD TI Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: Implications for vaccine development SO JOURNAL OF VIROLOGY LA English DT Article ID CELL RECEPTOR USAGE; EX-VIVO EXPANSION; LOW VIRAL LOAD; FINE SPECIFICITY; ENVELOPE GLYCOPROTEIN; PROTECTIVE IMMUNITY; ADOPTIVE TRANSFER; INFECTION; HIV-1; RESPONSES AB Despite recent advances in antiviral therapy for human immunodeficiency virus (HIV) infection, successful global intervention will require an effective vaccine, Expanding evidence suggests that cytotoxic T-lymphocyte (CTL) responses will be an important component of such a vaccine, The varying geographic distribution of HIV type 1 (HIV-1) clades, with the relative absence of clade B HIV-1 outside the developed world, is considered a major obstacle to the development of a single efficacious vaccine, An understanding of cross-reactive CTL responses between different HIV-1 clades is crucial in the design of a vaccine which will be broadly immunogenic, In this study, we examined the ability of HIV-1 Gag-, reverse transcriptase-, and Env-specific CTL clones isolated from individuals infected in the United States to recognize non-B clade viral sequences and found that all were cross-reactive with the majority of non-B clade viral sequences tested. We next studied HIV-1-specific CTL responses in African individuals infected with clade A, C, or G virus and evaluated cross-recognition of clade B virus, Of 14 persons evaluated, all demonstrated cross-reactivity with the U.S. clade B viral constructs, We conclude that significant CTL cross-reactivity exists between clade B and non-B epitopes, suggesting that CTL cross-recognition among HIV-1 clades is more widespread than anticipated and that a vaccine based on a single clade may be broadly applicable. C1 MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. THERION BIOL,CAMBRIDGE,MA 02142. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. UNIV CHEIKH ANTA DIOP,LAB VIROL & BACTERIOL,DAKAR,SENEGAL. RP Cao, HY (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,GRAY 5,BOSTON,MA 02114, USA. OI Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [AI 28568, AI 30914, AI-35173] NR 65 TC 138 Z9 141 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1997 VL 71 IS 11 BP 8615 EP 8623 PG 9 WC Virology SC Virology GA YB143 UT WOS:A1997YB14300063 PM 9343219 ER PT J AU Nickeleit, V Vamvakas, EC Pascual, M Poletti, J Colvin, RB AF Nickeleit, V Vamvakas, EC Pascual, M Poletti, J Colvin, RB TI Histological features of cellular renal allograft rejection correlated with clinical parameters: An analysis of 111 cases. SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ST VINCENTS MED CTR,LOS ANGELES,CA. UNIV BASEL,BASEL,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 1997 VL 52 IS 5 BP 1429 EP 1430 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA YC339 UT WOS:A1997YC33900056 ER PT J AU Paietta, E Racevskis, J Neuberg, D Rowe, JM Goldstone, AH Wiernik, PH AF Paietta, E Racevskis, J Neuberg, D Rowe, JM Goldstone, AH Wiernik, PH TI Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993 SO LEUKEMIA LA English DT Article DE CD25 (interleukin-2 alpha chain receptor); Philadelphia chromosome; acute lymphoblastic leukemia ID BCR-ABL; HEMATOLOGIC MALIGNANCIES; DIAGNOSIS; THERAPY; GENES; CELLS; PCR AB Of 144 adult Eastern Cooperative Oncology Group (ECOG) patients with acute lymphoblastic leukemia (ALL) entered on study E2993 at the time of analysis, 104 had informative immunophenotypes and molecular analysis by polymerase chain reaction for BCR/ABL fusion transcripts, In 23 patients (22%), BCR/ABL transcripts were detected: the ALL-typical e1a2 alone in 12, e1a2 + b2a2/b3a2 in five, and b2a2 and/or b3a2 in six. Of BCR/ABL-positive patients, 83% had early pre-B ALL, one patient had pre-T ALL, while half of the BCR/ABL-negative patients had early pre-B ALL, 18% had CD10-negative pro-B ALL and 21% were pre-T. When antibodies to both the interleukin-2 receptor alpha (CD25) and beta chain (CD122) were tested, CD25 was expressed significantly more frequently in BCR/ABL-positive (median 23% positive blast cells, range 1-84%) than BCR/ABL-negative patients (median 3%, range 0-69%) (P=0.00006). There was no corelation with CD122 expression. Therefore, CD25 expression may serve as a surrogate marker for BCR/ABL positivity (Philadelphia chromosome), the major poor prognostic parameter in adult ALL. C1 MONTEFIORE & ALBERT EINSTEIN CANC CTR, DEPT ONCOL, BRONX, NY USA. DANA FARBER CANC INST, DIV BIOSTAT, BOSTON, MA 02115 USA. UNIV ROCHESTER, DIV MED ONCOL, ROCHESTER, NY USA. UCL HOSP, DEPT CLIN HAEMATOL, LONDON, ENGLAND. EASTERN COOPERAT ONCOL GRP, BROOKLINE, MA USA. FU NCI NIH HHS [CA14958, CA23318, CA21115] NR 20 TC 39 Z9 40 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1997 VL 11 IS 11 BP 1887 EP 1890 DI 10.1038/sj.leu.2400836 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA YE776 UT WOS:A1997YE77600014 PM 9369422 ER PT J AU Urashima, M Teoh, G Ogata, A Chauhan, D Treon, SP Hoshi, Y DeCaprio, JA Anderson, KC AF Urashima, M Teoh, G Ogata, A Chauhan, D Treon, SP Hoshi, Y DeCaprio, JA Anderson, KC TI Role of CDK4 and p16(INK4A) in interleukin-6-mediated growth of multiple myeloma SO LEUKEMIA LA English DT Article DE multiple myeloma; p16(INK4A); CDK4; interleukin-6 ID MARROW STROMAL CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; NF-KAPPA-B; P16 GENE; RETINOBLASTOMA PROTEIN; TUMOR-SUPPRESSOR; EXPRESSION; SECRETION; CYCLIN; LINES AB Interleukin-6 (IL-6) promotes growth of human multiple myeloma (MM) cells via phosphorylation of retinoblastoma protein (pRB) We therefore examined the kinetics of cyclin-dependent kinase 4 (CDK4), p16(INK4A), and pRB activation during IL-6-mediated patient MM cell growth compared with growth of IL-6 unresponsive patient plasma cell leukemia (PCL) cells. CDK4 protein was more strongly expressed in PCL cells than in MM cells. On the other hand, p16 protein was present in MM cells but undetectable in PCL cells. Interestingly, IL-6 induced peak proliferation of MM cells at days 1-3, with a return to baseline levels of DNA synthesis by days 6-9 in spite of replenishing IL-6. In these cells, IL-6 triggered a sustained increase in CDK4 by day 1 and a gradual increase in p16 to day 9, The progressive increase in p16 without further increments in CDK4 resulted in a shift from cyclin DP-CDK4/CDK6 binding at days 1-3 to p16-CDK4/CDK6 complex formation at days 6-9. Both phosphorylated pRB and dephosphorylated pRB were present initially in patient MM cells; IL-6 triggered a shift to phosphorylated pRB and G1 to S transition at days 1-3, with return to baseline levels of dephosphorylated pRB and related G1 growth arrest by day 9, No similar changes in CDK4, p16, or cell cycle profile were observed in IL-6 nonresponsive PCL cells. Our data therefore suggest a feedback mechanism in IL-6-mediated MM cell growth which is absent in IL-6 nonresponsive PCL cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. JIKEI UNIV,SCH MED,DEPT PEDIAT,TOKYO,JAPAN. FU NCI NIH HHS [CA 50947] NR 41 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1997 VL 11 IS 11 BP 1957 EP 1963 DI 10.1038/sj.leu.2400843 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA YE776 UT WOS:A1997YE77600024 PM 9369432 ER PT J AU Billman, GE Kang, JX Leaf, A AF Billman, GE Kang, JX Leaf, A TI Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs SO LIPIDS LA English DT Article ID SMOOTH-MUSCLE CELLS; VENTRICULAR-FIBRILLATION; LONG-CHAIN; ARACHIDONIC-ACID; ANTIARRHYTHMIC ACTIONS; MYOCARDIAL-INFARCTION; POTASSIUM CHANNELS; MYOCYTES; ARRHYTHMIAS; MODULATION AB The objective of this study was to obtain functional information associated with the prevention by n-3 polyunsaturated fatty acids (PUFA) of ischemia-induced fatal cardiac ventricular arrhythmias in the intact, conscious, exercising dog. Thirteen dogs susceptible to ischemia-induced ventricular fibrillation were prepared surgically by ligation of their anterior descending left coronary artery and placement of an inflatable cuff around their left circumflex artery. After 4 wk of recovery, exercise-plus-ischemia tests were performed without and then with an intravenous infusion of an emulsion of free n-3 PUFA just prior to occluding the left circumflex artery while the animals were running on a treadmill. One week later the exercise-plus-ischemia test was repeated but with a control infusion replacing the emulsion of n-3 PUFA. The infusion of the free n-3 PUFA in quantities of 1.0 to 10 g prevented ventricular fibrillation in 10 of the 13 dogs tested (P < 0.005), apparently without esterification of the PUFA into membrane phospholipids. The antiarrhythmic effect of the n-3 PUFA was associated with slowing of the heart rate, shortening of the QT-interval (electrical action potential duration), reduction of left ventricular systolic pressure, and prolongation of the electrocardiographic atrial-ventricular conduction time (P-R interval). These effects are comparable with those we have reported in studies with cultured neonatal rat cardiac myocytes. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OHIO STATE UNIV,DEPT PHYSIOL,COLUMBUS,OH 45210. RI Billman, George/E-2758-2011 FU NIDDK NIH HHS [DK38165] NR 37 TC 138 Z9 140 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD NOV PY 1997 VL 32 IS 11 BP 1161 EP 1168 DI 10.1007/s11745-997-0149-2 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA YG575 UT WOS:A1997YG57500005 PM 9397401 ER PT J AU Rooke, K BriquetLaugier, V Xia, YR Lusis, AJ Doolittle, MH AF Rooke, K BriquetLaugier, V Xia, YR Lusis, AJ Doolittle, MH TI Mapping of the gene for calreticulin (Calr) to mouse Chromosome 8 SO MAMMALIAN GENOME LA English DT Article ID MOLECULAR CHAPERONE; CALNEXIN; OLIGOSACCHARIDE; PROTEIN C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOL GENET,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90095. FU NHLBI NIH HHS [HL28481] NR 10 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1997 VL 8 IS 11 BP 870 EP 871 DI 10.1007/s003359900599 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA YC460 UT WOS:A1997YC46000019 PM 9337407 ER PT J AU Barnes, CJ Hardman, WE Lee, MK Cameron, IL AF Barnes, CJ Hardman, WE Lee, MK Cameron, IL TI Histological structure and lymphoid cell types in the distal colon aggregate of lymphoid nodules of 4-month old and 22-month old rats SO MEDICAL SCIENCE RESEARCH LA English DT Article DE rat; colon; lymphoid nodules; age ID TISSUE; PROLIFERATION; CRYPTS AB This study had two goals (1) to determine the general histological characteristics of the rat distal colonic lymphoid nodules; and (2) to characterise the immunohistochemical localisation of proliferating cells, apoptotic cells, B lymphocytes and cytotoxic T lymphocytes within the colonic lymphoid aggregates in young (i.e., 4-month old and old (i.e., 22-month old) rats. The immunohistochemical staining described in the article revealed the distal aggregates of lymphoid nodules (ALN) of the rat to be quite similar in structure and cell types to previously described intestinal lymphoid aggregates. There were no major differences in the distribution pattern of proliferating cells, apoptotic cells, B cells or cytotoxic T cells between that of the distal lymphoid aggregate and that of small intestinal Peyer's patches or that of the rat proximal colon ALN. With the techniques and markers employed here, no apparent change with age was observed in the distal ALN. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. VET AFFAIRS MED CTR,GASTROENTEROL SECT,SAN ANTONIO,TX 78284. RP Barnes, CJ (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0269-8951 J9 MED SCI RES JI Med. Sci. Res. PD NOV PY 1997 VL 25 IS 11 BP 787 EP 789 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YH335 UT WOS:A1997YH33500020 ER PT J AU Maher, ER Kaelin, WG AF Maher, ER Kaelin, WG TI von Hippel-Lindau disease SO MEDICINE LA English DT Review ID TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; FIELD GEL-ELECTROPHORESIS; FACTOR MESSENGER-RNA; GERMLINE MUTATIONS; SOMATIC MUTATIONS; FAMILIAL PHEOCHROMOCYTOMA; MOLECULAR ANALYSIS; CLINICAL-FEATURES C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Birmingham, Birmingham Womens Hosp, Dept Paediat & Child Hlth, Div Med Genet, Birmingham, W Midlands, England. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, 44 Binney St,M657, Boston, MA 02115 USA. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 107 TC 342 Z9 353 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 1997 VL 76 IS 6 BP 381 EP 391 DI 10.1097/00005792-199711000-00001 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA YM050 UT WOS:000071022900001 PM 9413424 ER PT J AU Giordano, M Castellino, P Solini, A Canessa, ML DeFronzo, RA AF Giordano, M Castellino, P Solini, A Canessa, ML DeFronzo, RA TI Na+/Li+ and Na+/H+ countertransport activity in hypertensive non-insulin-dependent diabetic patients: Role of insulin resistance and antihypertensive treatment SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID SODIUM-LITHIUM COUNTERTRANSPORT; CONVERTING ENZYME-INHIBITION; GLUCOSE DISPOSAL; PROTON EXCHANGE; ANGIOTENSIN-II; RED-CELLS; NEPHROPATHY; NIDDM; ANTAGONISTS; HYPERTROPHY AB We measured erythrocyte Na+/Li+ and Na+/H+ countertransport: (CT) activity (millimoles per liter per cell per hour) in 10 healthy control subjects (age, 38 +/- 4 years; body mass index, 25 +/- 1 kg/m(2)) and in 26 hypertensive patients with non-insulin-dependent diabetes mellitus ([NIDDM] age, 49 +/- 3 years; body mass index, 29 +/- 1 kg/m(2); fasting plasma glucose, 157 +/- 12 mg/dL) 4 weeks after discontinuation of previous antihypertensive treatment. Na+/Li+ CT was significantly increased in hypertensive NIDDM patients compared with controls (0.56 +/- 0.04 v 0.30 +/- 0.03, P < .01), whereas Na+/H+ CT was similar to control levels (21 +/- 1 v 20 +/- 2). A positive correlation was found between Na+/H+ CT and the severity of insulin resistance (r = .69, P < .01), mean arterial pressure ([MAP] r = .64, P < .01), plasma triglyceride concentration (r = .46, P < .05), and plasma total cholesterol (r = .41, P < .05). An inverse correlation was found between Na+/Li+ CT activity and plasma insulin concentration (r = -.47, P < .05). No relationship was observed between Na+/Li+ CT activity and either creatinine clearance or proteinuria. Stepwise multiple regression analysis for all metabolic variables and blood pressure showed that only the severity of insulin resistance was positively correlated with increased Na+/Li+ CT activity. Na+/H+ and Na+/Li+ CT activity were not altered by 3 hours of euglycemic physiologic hyperinsulinemia (84 +/- 3 mu U/mL). Hypertensive NIDDM subjects were treated for 3 months with captopril, nifedipine, or doxazosin. After captopril, a reduction of Na+/H+ CT was observed (22 +/- 4 v 13 +/- 2, P < .05): Na+/Li+ CT decreased after doxazosin (0.56 +/- 0.06 v 0.45 +/- 0.05, P < .05) and nifedipine (0.52 +/- 0.06 v 0.42 +/- 0.05, P < .05). In conclusion, in hypertensive NIDDM subjects, (1) Na+/Li+ CT is increased and is correlated with the level of insulin resistance and the MAP; (21 acute physiologic hyperinsulinemia does not affect Na+/Li+ or Na+/H+ CT activity; and (3) Na+/H+ CT activity is reduced by captopril, and Na+/Li+ CT is decreased by doxazosin and nifedipine. Copyright (C) 1997 by W.B. Saunders Company. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIABET DIV,SAN ANTONIO,TX 78284. S TEXAS VET HEALTHCARE SYST,AUDIE L MURPHY DIV,SAN ANTONIO,TX. BRIGHAM & WOMENS HOSP,DIV ENDOCRINE HYPERTENS,BOSTON,MA 02115. UNIV NAPLES 2,INST INTERNAL MED & NEPHROL,NAPLES,ITALY. RI Solini, Anna/K-4666-2016; OI Solini, Anna/0000-0002-7855-8253; CASTELLINO, Pietro/0000-0002-9014-2007 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [HL-35664] NR 45 TC 13 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1997 VL 46 IS 11 BP 1316 EP 1323 DI 10.1016/S0026-0495(97)90237-7 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA YE074 UT WOS:A1997YE07400014 PM 9361692 ER PT J AU Ayte, J Leis, JF DeCaprio, JA AF Ayte, J Leis, JF DeCaprio, JA TI The fission yeast protein p73(res2) is an essential component of the mitotic MBF complex and a master regulator of meiosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MATING-TYPE GENES; CELL-CYCLE GENES; SCHIZOSACCHAROMYCES-POMBE; S-PHASE; TRANSCRIPTIONAL CONTROL; START; MITOSIS; KINASE; CDC10+; ENTRY AB Depending on environmental conditions, Schizosaccharomyces pombe can remain in the stationary phase or enter into either premitotic or premeiotic DNA synthesis. This decision point is known as Start. In the mitotic cell cycle, regulation of G(1)/S-specific gene expression is dependent upon the MBF (Mlu1 binding factor) complex, known to contain p85(cdc10) and p72(res1). Here we demonstrate that p73(res2) controls cell cycle progression via its participation in the MBF complex, interacting directly with both p85(cdc10) and p72(res1). In contrast, when cells enter into meiosis, the MBF complex is disrupted, and p73(res2) shifts its regulatory function towards the transactivation of genes required for meiotic progression. These observations suggest that p73(res2) plays a pivotal role at Start and constitutes an example of a transcription factor involved in the central of both mitotic and meiotic progression. C1 DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RI Ayte, Jose/L-5217-2014 OI Ayte, Jose/0000-0002-6354-0536 NR 44 TC 13 Z9 13 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1997 VL 17 IS 11 BP 6246 EP 6254 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YC255 UT WOS:A1997YC25500005 PM 9343385 ER PT J AU MartinezMartinez, S delArco, PG Armesilla, AL Aramburu, J Luo, C Rao, A Redondo, JM AF MartinezMartinez, S delArco, PG Armesilla, AL Aramburu, J Luo, C Rao, A Redondo, JM TI Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; TRANSCRIPTION FACTOR NFAT1; COLONY-STIMULATING FACTOR; HUMAN ENDOTHELIAL-CELLS; PYRROLIDINE DITHIOCARBAMATE; REGULATORY ELEMENTS; SIGNAL-TRANSDUCTION; GENE-TRANSCRIPTION; INDUCED APOPTOSIS; CYCLOSPORINE-A AB Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappa B activation in a number of cell types. Given the role of this transcription factor an the regulation of gene expression in the inflammatory response, NF-kappa B inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappa B-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappa B, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-kappa B support a potential use of DTCs as immunosuppressants. C1 UNIV AUTONOMA MADRID,HOSP PRINCESA,SERV IMMUNOL,E-28049 MADRID,SPAIN. UNIV AUTONOMA MADRID,CSIC,CTR BIOL MOL,E-28049 MADRID,SPAIN. CTR BLOOD RES,BOSTON,MA 02115. RI Aramburu, J/G-8991-2014; Redondo, Juan Miguel/H-6351-2015; Gomez-del Arco, Pablo/L-2728-2013 OI Aramburu, J/0000-0001-9279-9523; Redondo, Juan Miguel/0000-0001-5779-9122; Gomez-del Arco, Pablo/0000-0001-6748-7157 NR 74 TC 51 Z9 51 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1997 VL 17 IS 11 BP 6437 EP 6447 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA YC255 UT WOS:A1997YC25500026 PM 9343406 ER PT J AU Chen, JN vanEeden, FJM Warren, KS NussleinVolhard, C Haffter, P Fishman, M AF Chen, JN vanEeden, FJM Warren, KS NussleinVolhard, C Haffter, P Fishman, M TI Genes for left-right asymmetry in zebrafish SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP, CARDIOVASC RES CTR, CHARLESTOWN, MA 02129 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. MAX PLANCK INST ENTWICKLUNGSBIOL, GENET ABT, D-72076 TUBINGEN, GERMANY. RI Van Eeden, Freek/E-6198-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 38 EP 38 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09600037 ER PT J AU Bates, JA Abramova, ME Michalak, M Clark, RA Valente, AJ AF Bates, JA Abramova, ME Michalak, M Clark, RA Valente, AJ TI Regulation of calreticulin transcription in HeLa cells in response to calcium depletion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. S TEXAS VET HLTH CARE SYST,SAN ANTONIO,TX 78284. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB T6G 2S2,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 172 EP 172 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09600169 ER PT J AU Goldmann, WH Galneder, R Ezzell, RM AF Goldmann, WH Galneder, R Ezzell, RM TI Quantitation of F9 cell viscosity and elasticity using cell poking. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 448 EP 448 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09600445 ER PT J AU Majumdar, A Hentschel, H Elgar, M SolnicaKrezel, L Schier, A Neuhauss, S Stemple, D Zwartkruis, F Rangini, Z Driever, W Fishman, M Drummond, I AF Majumdar, A Hentschel, H Elgar, M SolnicaKrezel, L Schier, A Neuhauss, S Stemple, D Zwartkruis, F Rangini, Z Driever, W Fishman, M Drummond, I TI Loss of epithelial cell polarity in zebrafish pronephric mutants. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. MAX PLANCK INST MOL PHYSIOL,D-44026 DORTMUND,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 516 EP 516 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09600516 ER PT J AU Dustin, ML White, R Suri, A Springer, TA SelvaRaj, P AF Dustin, ML White, R Suri, A Springer, TA SelvaRaj, P TI Principles governing the rapid organization of adhesion molecules in cell-cell contact areas. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. EMORY UNIV,ATLANTA,GA 30322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 1176 EP 1176 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09601172 ER PT J AU Mitic, LL Schneeberger, EE Fanning, AS Anderson, JM AF Mitic, LL Schneeberger, EE Fanning, AS Anderson, JM TI Interaction with ZO-1 organizes connexin-occludin chimeras at tight junctions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 YALE UNIV,SCH MED,DEPT CELL BIOL,NEW HAVEN,CT 06520. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06520. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1997 VL 8 SU S BP 1187 EP 1187 PG 1 WC Cell Biology SC Cell Biology GA YF096 UT WOS:A1997YF09601186 ER EF